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Background and Objectives
Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established.
Methods
Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature.
Results
A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs.
Conclusion
The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.
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.
Background
Postoperative delirium (POD) is a frequent and serious complication after surgery. Evidence of a relationship between anticholinergic medication and the development of delirium is inconclusive, but studies on POD are rare.
Objectives
The objective of this study was to evaluate the anticholinergic load of preoperative medication in older adult patients and its association with the development of POD.
Methods
This investigation was part of the European BioCog project (http://www.biocog.eu), a prospective multicenter observational study in older adult surgical patients (ClinicalTrials.gov identifier: NCT02265263, 15 October 2014). Patients with a Mini–Mental State Examination score ≤ 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. The preoperative anticholinergic load was calculated using the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Cognitive Burden Scale (ACBS), and associations with POD were analyzed using logistic regression analysis adjusting for age, comorbidities, duration of anesthesia and number of drugs used.
Results
In total, 837 participants were included for analysis, and 165 patients (19.7%) fulfilled the criteria of POD. After adjusting for confounders, we found no association between preoperative anticholinergic load and the development of POD (ADS [points] odds ratio [OR] 0.928; 95% confidence interval [CI] 0.749–1.150; ARS [points] OR 0.832; 95% CI 0.564–1.227; ACBS [points] OR 1.045; 95% CI 0.842–1.296).
Conclusion
This study found no association between the anticholinergic load of drugs used preoperatively and the development of POD in older adult patients without severe preexisting cognitive impairment. Future analyses should examine the influence of intra- and postoperative administration of anticholinergic drugs as well as dosages of and interactions between medications.
Background
There is no consensus on the instruments for diagnosis of post-intensive care syndrome (PICS). We present a proposal for a set of outcome measurement instruments of PICS in outpatient care.
Methods
We conducted a three-round, semi-structured consensus-seeking process with medical experts, followed each by exploratory feasibility investigations with intensive care unit survivors (n1 = 5; n2 = 5; n3 = 7). Fourteen participants from nine stakeholder groups participated in the first and second consensus meeting. In the third consensus meeting, a core group of six clinical researchers refined the final outcome measurement instrument set proposal.
Results
We suggest an outcome measurement instrument set used in a two-step process. First step: Screening with brief tests covering PICS domains of (1) mental health (Patient Health Questionnaire-4 (PHQ-4)), (2) cognition (MiniCog, Animal Naming), (3) physical function (Timed Up-and-Go (TUG), handgrip strength), and (4) health-related quality of life (HRQoL) (EQ-5D-5L). Single items measure subjective health before and after the intensive care unit stay. If patients report new or worsened health problems after intensive care unit discharge and show relevant impairment in at least one of the screening tests, a second extended assessment follows: (1) Mental health (Patient Health Questionnaire-8 (PHQ-8), Generalized Anxiety Disorder Scale-7 (GAD-7), Impact of Event Scale – revised (IES-R)); (2) cognition (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT) A and B); (3) physical function (2-Minute Walk Test (2-MWT), handgrip strength, Short Physical Performance Battery (SPPB)); and (4) HRQoL (EQ-5D-5L, 12-Item WHO Disability Assessment Schedule (WHODAS 2.0)).
Conclusions
We propose an outcome measurement instrument set used in a two-step measurement of PICS, combining performance-based and patient-reported outcome measures. First-step screening is brief, free-of-charge, and easily applicable by health care professionals across different sectors. If indicated, specialized healthcare providers can perform the extended, second-step assessment. Usage of the first-step screening of our suggested outcome measurement instrument set in outpatient clinics with subsequent transfer to specialists is recommended for all intensive care unit survivors. This may increase awareness and reduce the burden of PICS.
Background
A pre-existing neurocognitive disorder (NCD) is a relevant factor for the outcome of surgical patients. To improve understanding of these conditions, we investigated the association between parameters of the cholinergic system and NCD.
Method
This investigation is part of the BioCog project (www.biocog.eu), which is a prospective multicenter observational study including patients aged 65 years and older scheduled for elective surgery. Patients with a Mini-Mental State Examination (MMSE) score ≤23 points were excluded. Neurocognitive disorder was assessed according to the fifth Diagnostic and Statistical Manual of Mental Disorders criteria. The basal forebrain cholinergic system volume (BFCSV) was assessed with magnetic resonance imaging, the peripheral cholinesterase (ChE) activities with point-of-care measurements, and anticholinergic load by analyzing the long-term medication with anticholinergic scales (Anticholinergic Drug Scale [ADS], Anticholinergic Risk Scale [ARS], Anticholinergic Cognitive Burden Scale [ACBS]). The associations of BFCSV, ChE activities, and anticholinergic scales with NCD were studied with logistic regression analysis, adjusting for confounding factors.
Results
A total of 797 participants (mean age 72 years, 42% females) were included. One hundred and eleven patients (13.9%) fulfilled criteria for mild NCD and 82 patients (10.3%) for major NCD criteria. We found that AcetylChE activity was associated with major NCD (odds ratio [95% confidence interval]: [U/gHB] 1.061 [1.010, 1.115]), as well as ADS score ([points] 1.353 [1.063, 1.723]) or ARS score, respectively ([points] 1.623 [1.100, 2.397]) with major NCD. However, we found no association between BFCSV or ButyrylChE activity with mild or major NCD.
Conclusions
AcetylChE activity and anticholinergic load were associated with major NCD. Future research should focus on the association of the cholinergic system and the development of postoperative delirium and postoperative NCD.
Background: In longitudinal studies, observations are made over time. Hence, the single observations at each time point are dependent, making them a repeated measurement. In this work, we explore a different, counterintuitive setting: At each developmental time point, a lethal observation is performed on the pregnant or nursing mother. Therefore, the single time points are independent. Furthermore, the observation in the offspring at each time point is correlated with each other because each litter consists of several (genetically linked) littermates. In addition, the observed time series is short from a statistical perspective as animal ethics prevent killing more mother mice than absolutely necessary, and murine development is short anyway. We solve these challenges by using multiple contrast tests and visualizing the change point by the use of confidence intervals.
Results: We used linear mixed models to model the variability of the mother. The estimates from the linear mixed model are then used in multiple contrast tests.There are a variety of contrasts and intuitively, we would use the Changepoint method. However, it does not deliver satisfying results. Interestingly, we found two other contrasts, both capable of answering different research questions in change point detection: i) Should a single point with change direction be found, or ii) Should the overall progression be determined? The Sequen contrast answers the first, the McDermott the second. Confidence intervals deliver effect estimates for the strength of the potential change point. Therefore, the scientist can define a biologically relevant limit of change depending on the research question.
Conclusion: We present a solution with effect estimates for short independent time series with observations nested at a given time point. Multiple contrast tests produce confidence intervals, which allow determining the position of change points or to visualize the expression course over time. We suggest to use McDermott’s method to determine if there is an overall significant change within the time frame, while Sequen is better in determining specific change points. In addition, we offer a short formula for the estimation of the maximal length of the time series.
The effect of pulsed electric field (PEF) and ultrasound (US) on the frying behavior of potato chips was investigated. For this purpose, a special fryer with a window was designed to enable the investigation of water evaporation by the characterization of bubble formation during frying. The number of water vapor bubbles and the bubble volume distribution were analyzed in order to gain an insight into heat and mass transfer affected by PEF and US treatment. Quality parameters of the potato chips such as moisture, fat and acrylamide content were measured. Overall, the results of this study show for the first time impacting effects on the frying process that can be achieved by combining PEF as a volumetric cell disintegration technology and ultrasound as a mean to affect interface phenomena. The obtained results can be used to further optimize frying processes used for the production of chips and other products.
While the Food and Biotechnology industries often use unit operations that have been known for some time, sometimes these processes are not efficient or sustainable. The need to develop more efficient processing lines to obtain higher quality products is of utmost importance. Over the last years, pulsed electric fields (PEF) processing has attracted the interest of numerous researchers and companies due to its ability to reduce processing time, preserve thermolabile compounds, which are responsible for the aroma, nutritional and bioactive properties of food products.
Therefore, in this article, some of the most important studies regarding the application of PEF technology in food and biotechnology processing is discussed.
Äpfel besitzen mehrere Allergene, die beim Essen innerhalb von 5–10 min zu Symptomen im Mundbereich führen – und deshalb von Apfelallergikern nicht gegessen werden können. In Deutschland haben rund 7,5 Mio. Menschen spezifische Antikörper gegen das Hauptallergen (Mal d 1) in Äpfeln entwickelt und sind damit sensibilisiert. Mindestens 3,5 Mio. von ihnen entwickeln die teilweise erheblichen allergischen Symptome als Ausdruck eines Oralen Allergie-Syndroms. Es gibt bisher keine medikamentöse Therapie gegen diese Allergie.
Apfelallergiker können daher nur auf Äpfel ganz verzichten, oder vorher erhitzte Äpfel essen oder Sorten suchen, die wenig Allergene enthalten und deshalb als allergikerfreundliche Apfelsorten bezeichnet werden können.
Alleinige Bestimmungen von Allergenen im Labor können nicht voraussagen, ob ein Apfel ohne allergische Symptome von Apfelallergikern gegessen werden kann; dazu bedarf es klinischer Prüfungen.
Wir beschreiben eine standardisierte klinische, orale Provokationstestung, die zur Charakterisierung eines allergenarmen, allergikerfreundlichen Apfels bzw. Apfelsorte benutzt werden kann.. Die Ergebnisse solcher mindestens dreijährigen Tests können zur Verleihung des ECARF-Siegels für allergikerfreundliche Produkte genutzt werden.
Background:
Etomidate is typically used as an induction agent in cardiac surgery because it has little impact on hemodynamics. It is a known suppressor of adrenocortical function and may increase the risk for post-operative infections, sepsis, and mortality. The aim of this study was to evaluate whether etomidate increases the risk of postoperative sepsis (primary outcome) and infections (secondary outcome) compared to propofol.
Methods:
This was a retrospective before–after trial (IRB EA1/143/20) performed at a tertiary medical center in Berlin, Germany, between 10/2012 and 01/2015. Patients undergoing cardiac surgery were investigated within two observation intervals, during which etomidate and propofol were the sole induction agents.
Results:
One-thousand, four-hundred, and sixty-two patients, and 622 matched pairs, after caliper propensity-score matching, were included in the final analysis. Sepsis rates did not differ in the matched cohort (etomidate: 11.5% vs. propofol: 8.2%, p = 0.052). Patients in the etomidate interval were more likely to develop hospital-acquired pneumonia (etomidate: 18.6% vs. propofol: 14.0%, p = 0.031).
Conclusion:
Our study showed that a single-dose of etomidate is not statistically associated with higher postoperative sepsis rates after cardiac surgery, but is associated with a higher incidence of hospital-acquired pneumonia. However, there is a notable trend towards a higher sepsis rate.
Background:
Cardiac surgery patients represent a high-risk cohort in intensive care units (ICUs). Central venous pressure (CVP) measurement seems to remain an integral part in hemodynamic monitoring, especially in cardio-surgical ICUs. However, its value as a prognostic marker for organ failure is still unclear. Therefore, we analyzed postoperative CVP values after adult cardiac surgery in a large cohort with regard to its prognostic value for morbidity and mortality.
Methods:
All adult patients admitted to our ICUs between 2006 and 2019 after cardiac surgery were eligible for inclusion in the study (n = 11,198). We calculated the median initial CVP (miCVP) after admission to the ICU, which returned valid values for 9802 patients. An ROC curve analysis for optimal cut-off miCVP to predict ICU mortality was conducted with consecutive patient allocation into a (a) low miCVP (LCVP) group (≤11 mmHg) and (b) high miCVP (HCVP) group (>11 mmHg). We analyzed the impact of high miCVP on morbidity and mortality by propensity score matching (PSM) and logistic regression.
Results:
ICU mortality was increased in HCVP patients. In addition, patients in the HCVP group required longer mechanical ventilation, had a higher incidence of acute kidney injury, were more frequently treated with renal replacement therapy, and showed a higher risk for postoperative liver dysfunction, parametrized by a postoperative rise of ≥ 10 in MELD Score. Multiple regression analysis confirmed HCVP has an effect on postoperative ICU-mortality and intrahospital mortality, which seems to be independent.
Conclusions:
A high initial CVP in the early postoperative ICU course after cardiac surgery is associated with worse patient outcome. Whether or not CVP, as a readily and constantly available hemodynamic parameter, should promote clinical efforts regarding diagnostics and/or treatment, warrants further investigations.
Preoperative medication use and development of postoperative delirium and cognitive dysfunction
(2021)
Postoperative delirium (POD) and postoperative (neuro-)cognitive disorder (POCD) are frequent and serious complications after operations. We aim to investigate the association between pre-operative polypharmacy and potentially inappropriate medications and the development of POD/POCD in elderly patients. This investigation is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental State Examination score less than or equal to 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method (for the intensive care unit [ICU]), and a patient chart review. POCD was assessed 3 months after surgery with a neuropsychological test battery. Pre-operative long-term medication was evaluated in terms of polypharmacy (≥5 agents) and potentially inappropriate medication (defined by the PRISCUS and European list of potentially inappropriate medications [EU(7)-PIM] lists), and associations with POD and POCD were analyzed using logistic regression analysis. Eight hundred thirty-seven participants were included for analysis of POD and 562 participants for POCD. Of these, 165 patients (19.7%) fulfilled the criteria of POD and 60 (10.7%) for POCD. After adjusting for confounders, pre-operative polypharmacy and intake of potentially inappropriate medications could not be shown to be associated with the development of POD nor POCD. We found no associations between pre-operative polypharmacy and potentially inappropriate medications and development of POD and POCD. Future studies should focus on the evaluation of drug interactions to determine whether patients benefit from a pre-operative adjustment.
The benzodiazepine, midazolam, is one of the most frequently used sedatives in intensive care medicine, but it has an unfavorable pharmacokinetic profile when continuously applied. As a consequence, patients are frequently prolonged and more deeply sedated than intended. Due to its distinct pharmacological features, including a cytochrome P450-independent metabolization, intravenous lormetazepam might be clinically advantageous compared to midazolam. In this retrospective cohort study, we compared patients who received either intravenous lormetazepam or midazolam with respect to their survival and sedation characteristics. The cohort included 3314 mechanically ventilated, critically ill patients that received one of the two drugs in a tertiary medical center in Germany between 2006 and 2018. A Cox proportional hazards model with mortality as outcome and APACHE II, age, gender, and admission mode as covariates revealed a hazard ratio of 1.75 [95% CI 1.46–2.09; p < 0.001] for in-hospital mortality associated with the use of midazolam. After additionally adjusting for sedation intensity, the HR became 1.04 [95% CI 0.83–1.31; p = 0.97]. Thus, we concluded that excessive sedation occurs more frequently in critically ill patients treated with midazolam than in patients treated with lormetazepam. These findings require further investigation in prospective trials to assess if lormetazepam, due to its ability to maintain light sedation, might be favorable over other benzodiazepines for sedation in the ICU.
Objective:
The cervical mucus plugs are enriched with proteins of known immunological functions. We aimed to characterize the anti-HIV-1 activity of the cervical mucus plugs against a panel of different HIV-1 strains in the contexts of cell-free and cell-associated virus.
Design:
A cohort of consenting HIV-1-negative and HIV-1-positive pregnant women in labour was recruited from Mthatha General Hospital in the Eastern Cape province of South Africa, from whom the cervical mucus plugs were collected in 6 M guanidinium chloride with protease inhibitors and transported to our laboratories at −80 °C.
Methods:
Samples were centrifuged to remove insoluble material and dialysed before freeze--drying and subjecting them to the cell viability assays. The antiviral activities of the samples were studied using luminometric reporter assays and flow cytometry. Time-of-addition and BlaM-Vpr virus-cell fusion assays were used to pin-point the antiviral mechanisms of the cervical mucus plugs, before proteomic profiling using liquid chromatography-tandem mass spectrometry.
Results:
The proteinaceous fraction of the cervical mucus plugs exhibited anti-HIV-1 activity with inter-individual variations and some degree of specificity among different HIV-1 strains. Cell-associated HIV-1 was less susceptible to inhibition by the potent samples whenever compared with the cell-free HIV-1. The samples with high antiviral potency exhibited a distinct proteomic profile when compared with the less potent samples.
Conclusion:
The crude cervical mucus plugs exhibit anti-HIV-1 activity, which is defined by a specific proteomic profile.
Background
In DNA methylation analyses like epigenome-wide association studies, effects in differentially methylated CpG sites are assessed. Two kinds of outcomes can be used for statistical analysis: Beta-values and M-values. M-values follow a normal distribution and help to detect differentially methylated CpG sites. As biological effect measures, differences of M-values are more or less meaningless. Beta-values are of more interest since they can be interpreted directly as differences in percentage of DNA methylation at a given CpG site, but they have poor statistical properties. Different frameworks are proposed for reporting estimands in DNA methylation analysis, relying on Beta-values, M-values, or both.
Results
We present and discuss four possible approaches of achieving estimands in DNA methylation analysis. In addition, we present the usage of M-values or Beta-values in the context of bioinformatical pipelines, which often demand a predefined outcome. We show the dependencies between the differences in M-values to differences in Beta-values in two data simulations: a analysis with and without confounder effect. Without present confounder effects, M-values can be used for the statistical analysis and Beta-values statistics for the reporting. If confounder effects exist, we demonstrate the deviations and correct the effects by the intercept method. Finally, we demonstrate the theoretical problem on two large human genome-wide DNA methylation datasets to verify the results.
Conclusions
The usage of M-values in the analysis of DNA methylation data will produce effect estimates, which cannot be biologically interpreted. The parallel usage of Beta-value statistics ignores possible confounder effects and can therefore not be recommended. Hence, if the differences in Beta-values are the focus of the study, the intercept method is recommendable. Hyper- or hypomethylated CpG sites must then be carefully evaluated. If an exploratory analysis of possible CpG sites is the aim of the study, M-values can be used for inference.
BACKGROUND:
Intraoperative electroencephalography (EEG) signatures related to the development of postoperative delirium (POD) in older patients are frequently studied. However, a broad analysis of the EEG dynamics including preoperative, postinduction, intraoperative and postoperative scenarios and its correlation to POD development is still lacking. We explored the relationship between perioperative EEG spectra-derived parameters and POD development, aiming to ascertain the diagnostic utility of these parameters to detect patients developing POD.
METHODS:
Patients aged ≥65 years undergoing elective surgeries that were expected to last more than 60 minutes were included in this prospective, observational single center study (Biomarker Development for Postoperative Cognitive Impairment [BioCog] study). Frontal EEGs were recorded, starting before induction of anesthesia and lasting until recovery of consciousness. EEG data were analyzed based on raw EEG files and downloaded excel data files. We performed multitaper spectral analyses of relevant EEG epochs and further used multitaper spectral estimate to calculate a corresponding spectral parameter. POD assessments were performed twice daily up to the seventh postoperative day. Our primary aim was to analyze the relation between the perioperative spectral edge frequency (SEF) and the development of POD.
RESULTS:
Of the 237 included patients, 41 (17%) patients developed POD. The preoperative EEG in POD patients was associated with lower values in both SEF (POD 13.1 ± 4.6 Hz versus no postoperative delirium [NoPOD] 17.4 ± 6.9 Hz; P = .002) and corresponding γ-band power (POD −24.33 ± 2.8 dB versus NoPOD −17.9 ± 4.81 dB), as well as reduced postinduction absolute α-band power (POD −7.37 ± 4.52 dB versus NoPOD −5 ± 5.03 dB). The ratio of SEF from the preoperative to postinduction state (SEF ratio) was ~1 in POD patients, whereas NoPOD patients showed a SEF ratio >1, thus indicating a slowing of EEG with loss of unconscious. Preoperative SEF, preoperative γ-band power, and SEF ratio were independently associated with POD (P = .025; odds ratio [OR] = 0.892, 95% confidence interval [CI], 0.808–0.986; P = .029; OR = 0.568, 95% CI, 0.342–0.944; and P = .009; OR = 0.108, 95% CI, 0.021–0.568, respectively).
CONCLUSIONS:
Lower preoperative SEF, absence of slowing in EEG while transitioning from preoperative state to unconscious state, and lower EEG power in relevant frequency bands in both these states are related to POD development. These findings may suggest an underlying pathophysiology and might be used as EEG-based marker for early identification of patients at risk to develop POD.
Background
Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent and serious complications after surgery. We aim to investigate the association between genetic variants in cholinergic candidate genes according to the Kyoto encyclopedia of genes and genomes - pathway: cholinergic neurotransmission with the development of POD or POCD in elderly patients.
Methods
This analysis is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental-State-Examination score ≤ 23 points were excluded. POD was assessed up to seven days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. POCD was assessed three months after surgery with a neuropsychological test battery. Genotyping was performed on the Illumina Infinium Global Screening Array. Associations with POD and POCD were analyzed using logistic regression analysis, adjusted for age, comorbidities and duration of anesthesia (for POCD analysis additionally for education). Odds ratios (OR) refer to minor allele counts (0, 1, 2).
Results
745 patients could be included in the POD analysis, and 452 in the POCD analysis. The rate of POD within this group was 20.8% (155 patients), and the rate of POCD was 10.2% (46 patients). In a candidate gene approach three genetic variants of the cholinergic genes CHRM2 and CHRM4 were associated with POD (OR [95% confidence interval], rs8191992: 0.61[0.46; 0.80]; rs8191992: 1.60[1.22; 2.09]; rs2067482: 1.64[1.10; 2.44]). No associations were found for POCD.
Conclusions
We found an association between genetic variants of CHRM2 and CHRM4 and POD. Further studies are needed to investigate whether disturbances in acetylcholine release and synaptic plasticity are involved in the development of POD.
Background
In mucosal barrier interfaces, flexible responses of gene expression to long-term environmental changes allow adaptation and fine-tuning for the balance of host defense and uncontrolled not-resolving inflammation. Epigenetic modifications of the chromatin confer plasticity to the genetic information and give insight into how tissues use the genetic information to adapt to environmental factors. The oral mucosa is particularly exposed to environmental stressors such as a variable microbiota. Likewise, persistent oral inflammation is the most important intrinsic risk factor for the oral inflammatory disease periodontitis and has strong potential to alter DNA-methylation patterns. The aim of the current study was to identify epigenetic changes of the oral masticatory mucosa in response to long-term inflammation that resulted in periodontitis.
Methods and results
Genome-wide CpG methylation of both inflamed and clinically uninflamed solid gingival tissue biopsies of 60 periodontitis cases was analyzed using the Infinium MethylationEPIC BeadChip. We validated and performed cell-type deconvolution for infiltrated immune cells using the EpiDish algorithm. Effect sizes of DMPs in gingival epithelial and fibroblast cells were estimated and adjusted for confounding factors using our recently developed “intercept-method”. In the current EWAS, we identified various genes that showed significantly different methylation between periodontitis-inflamed and uninflamed oral mucosa in periodontitis patients. The strongest differences were observed for genes with roles in wound healing (ROBO2, PTP4A3), cell adhesion (LPXN) and innate immune response (CCL26, DNAJC1, BPI). Enrichment analyses implied a role of epigenetic changes for vesicle trafficking gene sets.
Conclusions
Our results imply specific adaptations of the oral mucosa to a persistent inflammatory environment that involve wound repair, barrier integrity, and innate immune defense.
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.
This study reported the impact of electron beam (e-beam) treatment on microbiota and mycotoxins naturally present in red pepper powder and physicochemical quality changes. Treatment at 6 kGy indicated significant (p < 0.05) decontamination of yeasts and molds by 3.0 and 4.4 log CFU/g, respectively. A reduction of 4.5 log CFU/g of total plate counts (TPC) was observed at 10 kGy for 23 s. Fungal inactivation followed first-order kinetics while TPC better fitted with Gompertz function (R2 = 0.9912). E-beam treatment was not efficient for the degradation of aflatoxins but indirectly controlled their production by inactivation of mycotoxigenic molds. Indeed, reduction of 25% ochratoxin A was recorded at 30 kGy retaining >85% of total phenols, carotenoids and antioxidants activity. Moreover, treatment impact on total color difference (ΔE*) indicated ‘slight differences’. Overall, e-beam treatments up to 10 kGy were efficient in decontaminating the natural microbiota without detrimental effects on the physicochemical qualities of red pepper powder.
The study aimed for the analysis of the impact of pulsed electric field (PEF) pre-treatment on convection (CD) and microwave (MW-CD) assisted air drying. Drying kinetics acceleration and retention of bioactive compounds of PEF pre-treated carrots and apples has been demonstrated. Moreover, the direct and indirect environmental energy impacts of CD and MW-CD technologies with consideration of bioactive compounds preservation has been evaluated. PEF assisted CD and MW-CD demonstrated lower energy use, especially for indirect energy consumption, in the case of carotenoids preservation in dried carrots.
The influence of oil content and droplet size of oil-in-water emulsions on the heat development in an ohmic heating system was investigated. The setup was run with constant power or voltage. Emulsions consisted of sunflower oil (10–50 wt%), aqua dest. (90–50 wt%) and whey protein isolate (1.25/ 2.5/ 3.75/ 5.0 and 6.25 wt%) Two different droplet size distributions were produced, large (d0.5 ≈ 2.0 μm) and small (d0.5 ≈ 0.3 μm), for each oil mass fraction. The emulsions were ohmically heated from 10 to 80 °C at a constant power of 3.0 kW and constant voltage of 15 V/cm. The electrical conductivity decreased with an increasing oil content, resulting in longer or shorter heating time for constant voltage or constant power input, respectively. The droplet size only affected the heating process at the highest oil content.
Industrial relevance
Emulsions occur in a wide range of food products (e.g. sauces, dressings, desserts) and have properties giving structure to the food system. Ohmic heating is an emerging thermal process with improved (e.g. faster or less energy required) heating characteristics. The influence of physical changes due to different droplet sizes are of interest because these might also affect the heating characteristic. In addition, the direct comparison of two different process regulations (constant power and constant voltage) indicate which set up is expedient to a successful heating process. This study aims to identify the influence of emulsion-induced structural changes and process changes on the heating rates, which is of interest for the food industry and the related machine building industry.
Red pepper (Capsicum annuum L.) is one of the major spices consumed globally, recognized for its aroma and nutrient properties, and it has a major economic value for high producing countries. However, characterization of its techno-functional properties and in-depth understanding of oxidative stability is needed to produce food of high quality and stability. Thus, this work focused on the chemical, functional, thermal, oxidative stability and rheological properties of red pepper powder and paste. Experiment was designed in a Completely Randomized Design (CRD) fashion. The red pepper powder contained 14.50 g/100 g, 44.00 g/100 g and 7.57 g/100 g of crude fat, crude fiber and ash, respectively. The concentration of total phenols, carotenoids and antioxidants activity of the powder were 1.04 g GAE/100 g, 374 mg βc/100 g and 38.61 μmol TE/g, respectively. Functional properties showed lower bulk density (395.1 kg/m3) and higher tapped density (583.4 kg/m3) indicating the higher compressibility of the powder. In contrast, Hausner ratio (1.48), Carr’s index (32%) and angle of repose (45°) indicated poor flowability of the powder. Particle size distribution also indicated that the volume weighted mean values D[4,3] of the powder and paste were 262.20 and 201.46, respectively. Emulsifying capacity of the powder was 47.5%. Oil and water absorption capacities varied from 1.41 to 1.73 and 0.86 to 2.29 g/g of initial weight, respectively. Higher glass transition temperature was observed for the powder (62.54°C) than the paste (45.64°C). The induction period indicated that red pepper was more stable against oxidation in powder (5.2 h) than in the paste form (3.2 h). Rheological analysis revealed that the paste exhibited shear-thinning behavior. Overall, understanding of the properties of red pepper could contribute to enhance quality.
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%.
Shockwaves are mechanical pressure pulses generated in liquids and gases. Based on the principles of acoustics, shockwavescan propagate through fluids such as water. At interfaces of materials with different acoustic impedances, mechanical energy is dissipated, and disintegration of biological tissue can be achieved. Physical properties as well as technical requirements for shockwave generation by electrohydraulic, electromagnetic or piezoelectric energy conversion have been reported in the literature. The use of electrohydraulic shockwaves for food treatment is an emerging food processing technology, where a lack of scientific and technical knowledge has limited further advancements in process and equipment design. In scientific literature, single aspects required for process description are available, e.g., in metallurgy, mining, air purification or particle accelerators, but their combination toward a combined model is required to characterize underlying mechanisms of action. In food, most of the studies have focused on shockwave technology for treatment of meat cuts with the purpose of reducing aging time, softening of tissue and improving its tenderness. Other applications of the shockwave technology could expand to biological inactivation, targeted texture modifications and improving extractive and refining processes in agriculture industries. Total processing costs are estimated in a range of a few Euros per ton of product. Despite being a promising alternative to existing processes used for these purposes, the application of shockwave in the food industry is limited to date to research on pilot-scale prototypes.
PEF is an innovative technology to extend the shelf life of fresh liquid food products, mainly juices, with minor impact on the quality. Many lab scale studies have been published, indicating the great potential of PEF for the juice industry. For industrial realization, the PEF systems have been adapted to the industrial requirements, establishing HACCP and hygienic design concept. Important process parameters have been identified from research and integrated in industrial PEF processes. Juice producers are now able to use PEF for their production lines.
This chapter presents the mechanism of the enhancement of freezing by means of ultrasound (US). It has been demonstrated that the effects of US are a rather complex issue. In theory, ultrasound creates cavitation bubbles throughout the volume of the product, which promotes nucleation of the ice and crushes the crystals already present in food. They can also enhance convective heat transfer to the cooling media, thereby accelerating freezing. Moreover, it has been shown that ultrasound reduces the degree of supercooling before nucleation in frozen food. Additionally, numerous experimental studies indicate that ultrasound assisted freezing is a good method to achieve homogenous crystallizations, reduce the deteriorating effect of freezing on food, and thus improve quality after thawing.
"The limits of my language are the limits of my mind. All I know is what I have words for" (Wittgenstein). When learning something completely new, we connect the unknown term to an already existing part of our knowledge. We can only build new ideas and insights upon an existing conceptual foundation. In the field of statistics, we educators frequently find ourselves met with great confusion when teaching novices. These students, entirely unfamiliar with even basic statistics, must connect the introduced statistical terms within their personal existing networks of largely non-statistical knowledge. Lecturers, on the other hand, who are well versed in statistics, have deeply internalized the content to be taught and its relevant context. The juxtaposition of the two roles may produce amusement in a lecturer upon gaining insight into the word associations made by the statistical novices. For example, a ‘logistic regression’ does not involve the ‘shipping of goods in economically difficult times,’ though this might seem entirely reasonable and intuitive to the statistics learner. Other times, these different perspectives can lead to headaches and frustration for both learners and their lecturers. In this article, we illustrate how simple statistical terms are initially connected to a student’s pre-exiting knowledge and how these associations change after completing an introductory course in applied statistics. Furthermore, we emphasize the important difference between “term”, “approach”, and “context”. Understanding this fundamental distinction may help improve the communication between the lecturer and the learner. We offer a collection of practical tools for instructors to help promote students’ conceptual understanding in a supportive, mutually-beneficial learning environment.
In diesem Buch sind Lehrbeispiele gesammelt, die Dozierenden wertvolle Anregungen für ihre eigene Lehre liefern: Es werden Ideen für einzelne Übungen, Unterrichtseinheiten, Prüfungen oder ganze Kurse vorgestellt. Die benötigten Materialien sind für die Nutzer online frei verfügbar, um die Anwendung zu vereinfachen.
Alle Beiträge dieses Buches wurden 2020 für den Preis für das beste Health-Data-Science-Lehrmaterial eingereicht, der von der Arbeitsgruppe Lehre und Didaktik der Biometrie der Deutschen Region der Internationalen Biometrischen Gesellschaft und der GMDS ausgeschrieben wurde. So entstand ein breiter Querschnitt an Beiträgen für lebendige Lehre in Biometrie, Epidemiologie, Public Health und ähnlichen Gebieten.
Das Buch knüpft damit an die beiden Bände Zeig mir Biostatistik! und Zeig mir mehr Biostatistik! an, denen ähnliche Ausschreibungen vorausgingen.
Die Herausgeber unterrichten Biometrie als Haupt- oder Nebenfach an verschiedenen Universitäten bzw. Hochschulen. Es verbindet sie das gemeinsame Ziel, den Austausch von Ideen und ausgereiftem Unterrichtsmaterial im Bereich Health Data Science zu fördern.
Fütterung von Zuchtstuten
(2021)
Shredlage für Mastbullen?
(2021)
Shredlage in der Bullenmast?
(2021)
Mehr Milchleistung
(2021)
Flüssigfutter bei Milchkühen
(2021)
Ist die TMR zu feucht?
(2021)
Zu viel Wasser in der TMR?
(2021)
Ursachen von Kotwasser
(2021)
Wasser dosiert zusetzen
(2021)
Duckweed is a promising resource for future feed and food production as well as wastewater treatment. However, diseases and pests can critically limit the performance of the production systems. Patches of discolored and bleached duckweed (Lemna minor L.) appeared in hydroponic systems and spread rapidly through the crop. Pythium myriotylum was confirmed as the causing pathogen by microbiological and molecular biological analysis. This is the first report of P. myriotylum on duckweed in Germany. The result and possible countermeasures are discussed.
Wasser
(2021)
Neue Futtermittel
(2021)
Ganzpflanzensilage
(2021)
Maniok und Tapioka
(2021)
Fütterung von Zuchtstuten
(2021)
Fütterung von Jungpferden
(2021)
Shredlage in der Bullenmast
(2021)
Fütterung von Sportpferden
(2021)
Piglets experience a high level of stress upon weaning due to changes in social structures and feeding. Incorporation of flavors in the maternal diet might be a promising tool to prenatally modulate flavor preferences of the offspring and prevent neophobia. This study aimed to evaluate if the supplementation of the maternal diet with Spicemaster GH 501, an intense, plant-based herbal flavor, could affect feed preferences of early-weaned piglets and thus improve feed intake, performance, and overall health conditions. On approx. day 95 of gestation, 59 pregnant sows (DanZucht) were separated into two groups. The control group received commercial gestation and lactation feeds without flavor, while the trial group received diets with added flavor (400 g/t Spicemaster GH 501). After weaning, 272 piglets from both groups were rehoused and given an early-grower feed, which was consistently supplemented in both groups with 400 g/t Spicemaster GH 501 throughout the whole trial. Strikingly, the trial group, which was prenatally exposed to the flavor, gained significantly more weight during the initial phase after weaning. Moreover, the trial group was less prone to develop ear tip necrosis and displayed an improved general health condition, which was reflected in a reduced number of antibiotic treatments during the duration of the trial. Collectively, the incorporation of flavoring compounds in the maternal diet provides a powerful mechanism to shape taste preferences in early-weaned piglets and conse-quently reduce stress levels and susceptibility to infections.
Piglets experience a high level of stress during the onset of the fattening phase due to changes in social structures and feeding. Incorporation of flavors in the feed supports constant levels of feed intake thus avoiding drops in performance. This study aimed to evaluate if a combination of vanilla and fruity flavors could maintain high interest in variable feeds across different ages. 384 crossbred (Topigs 20 x Piétrain) piglets were separated at weaning into two groups (eight pens per group: four pens with females and four pens with uncastrated males; 24 animals per pen), according to gender and weight. The control group received commercial starter feeds without flavor, while the other group received diets with added flavor (500 g/t Cuxarom Fruit 210, a sweetish, berry multifruit note combined with creamy vanilla). After 49 days, 264 animals from both groups were rehoused and given an early-grower feed with or without added flavor for 7 days. Consequently, animals from the trial group again received flavor-supplemented feed and vice versa. During the early-grower phase, the feed intake of the trial group was 11.2% higher than that of the control group. Moreover, the trial group gained significantly more weight during the early-grower phase (+12.2%) in comparison to the control group. This indicates that the animals prefer the flavor they were familiarized with during the starter phase. This memory effect leads to an increased feed intake and weight gain in early-grower pigs and can counteract drops in performance, particularly when mixing animals or transitioning.
Das 23. gehölzkundliche Winterseminar der Arbeitsgruppe Junge Dendrologen in der DDG fand im Herzen Deutschlands in der Lutherstadt Wittenberg statt. Wie in den vergangenen Jahren war als Tagungsort eine Jugendherberge gewählt worden. Ursprünglich sollte Quartier in der Jugendherberge in der Bauhaus-Stadt Dessau bezogen werden. Da diese bereits ausgebucht war, wurde nach Wittenberg ausgewichen, was für die Programmgestaltung vorteilhaft war.
Die Fütterung von Zuchtstuten ist ein wichtiger Faktor, der für die Geburt eines gesunden und voll entwickelten Fohlens und für die Fruchtbarkeit der Stute verantwortlich ist. Die Versorgung der Stuten ist aufgrund der Schwankungen in der Futteraufnahme rund um die Geburt durch den Einsatz von hochwertigen Futtermitteln zu sichern.
Der Versuch überprüfte den Einfluss der Fütterung von Shredlage-Maissilage auf die Futterqualität, Mastleistung, Gesundheit und den Schlachtkörperwert von Fleckviehbullen. Die Ergebnisse zeigten, dass die Fütterung von Shredlage keinen negativen Einfluss auf die obigen Parameter ausübte. Im Gegenteil, der Einsatz von Shredlage zeigt Potential einen Beitrag zu einer wiederkäuergerechten Fütterung zu leisten und Produktionsmerkmale zu verbessern.
Die vollständig überarbeitete Neuauflage des Lehrbuchklassikers jetzt ergänzt durch ein zusätzliches Kapitel und mit neuem Layout.
Dieses Standardwerk umfasst sämtliche Themengebiete der Lebensmittelphysik und behandelt u. a. die thermischen, rheologischen, akustischen und elektrischen Eigenschaften sowie die Dichte und Textur von Lebensmitteln. Zudem wird ausführlich auf die Funktion von online-Sensoren und deren Bedeutung für die Prozessautomatisierung in der Lebensmittelindustrie eingegangen.
Für Studierende der Lebensmittelwissenschaften und der Lebensmitteltechnologie ist dieses Lehrbuch mit vielen vorgerechneten Beispielen die Basis für ein grundlegendes Verständnis der Lebensmittelphysik. Ingenieure, Technologen und Techniker in der Lebensmittelproduktion können die aufgelisteten Anwendungsbeispiele am Ende jedes Kapitels nutzen, um ihre Kenntnisse für zukünftige physikalische Verfahren zu vertiefen.
Die Analyse der kommunalen Planungspraxis zur Auswahl und Bewertung von Siedlungsflächen in der Flächennutzungsplanung zeigt auf, welchen Einfluss Forschungsergebnisse auf die aktuelle Planungspraxis haben. Aufbauend auf einer Analyse des Forschungsstandes und der rechtlichen Rahmenbedingungen wird die Bewertung von Siedlungsflächen in 29 verschiedenen Flächennutzungsplänen untersucht. Als Ergebnis wurde ermittelt, dass in der Planungspraxis die Anzahl der Bewertungskriterien und die Komplexität der Bewertung in den letzten Jahren stark zugenommen hat. Außerdem kann gezeigt werden, dass und wie stark sich die Planungsmethodik und die verwendeten Kriterien zur Auswahl und Bewertung von Siedlungsflächen zwischen den einzelnen Gemeinden unterscheiden. Trotz umfangreicher anwendungsorientierter Forschung seit den 1990er Jahren zur Bewertung und Auswahl von Siedlungsflächen lassen sich jedoch nur indirekte Einflüsse der Forschungsergebnisse auf die Planungspraxis identifizieren. Teilweise wurde allerdings festgestellt, dass auch von den Gemeinden selbst neue Kriterien und Vorgehensweisen entwickelt werden.
In order to produce protein-rich duckweed for human and animal consumption, a stable cultivation process, including an optimal nutrient supply for each species, must be implemented. Modified nutrient media, based on the N-medium for duckweed cultivation, were tested on the relative growth rate (RGR) and crude protein content (CPC) of Lemna minor and Wolffiella hyalina, as well as the decrease of nitrate-N and ammonium-N in the media. Five different nitrate-N to ammonium-N molar ratios were diluted to 10% and 50% of the original N-medium concentration. The media mainly consisted of agricultural fertilizers. A ratio of 75% nitrate-N and 25% ammonium-N, with a dilution of 50%, yielded the best results for both species. Based on the dry weight (DW), L. minor achieved a RGR of 0.23 ± 0.009 d−1 and a CPC of 37.8 ± 0.42%, while W. hyalina’s maximum RGR was 0.22 ± 0.017 d−1, with a CPC of 43.9 ± 0.34%. The relative protein yield per week and m2 was highest at this ratio and dilution, as well as the ammonium-N decrease in the corresponding medium. These results could be implemented in duckweed research and applications if a high protein content or protein yield is the aim.