Publications - Publikationer

Factors Causing Incomplete Colonoscopy Reported by the Endoscopist

Grode, L. B., Dragnes Brix, L. — Thu, 01 May 2025 04:22:12 +0200

Colonoscopy is a primary diagnostic method for colorectal cancer screening. Ensuring completeness is critical for its effectiveness. The aim of this study is to explores patient and procedure-related contributors to incomplete colonoscopy in a Danish high volume endoscopy unit. A population-based register study was conducted, using data from electronic health records from a Danish hospital was analyzed, covering all colonoscopies performed between July 2015 and August 2019. The primary outcome assessed was the completeness of the index colonoscopy, with incomplete cases further classified based on the causes for incompleteness that were assessed and documented in real-time by the endoscopist. Data also included patient demographics and comorbidities, and profession of the endoscopist. Among 33,128 colonoscopies, prevalence of incomplete colonoscopies was 6.55%, with inadequate bowel preparation as the leading cause (60.3%). Men were more prone to inadequate bowel preparation, while procedural pain, non-passability, and stenosis were associated with women. Physician endoscopists exhibited higher incomplete colonoscopy rates compared to nurse endoscopists, and patients with higher comorbidity scores were more likely to have incomplete colonoscopy. This study highlights the prevalence of incomplete colonoscopy and recognizes modifiable risk factors like inadequate bowel preparation and procedural pain. Findings underscore the need for personalized interventions, stressing ongoing endoscopist education and targeted strategies to improve colonoscopy effectiveness.

Reactivity-based metabolomics reveal cysteine has glyoxalase 1-like and glyoxalase 2-like activities

Daniel Opfermann, M., Bøgelund Søndergård, M., Vase Bech, L., et al. — Wed, 01 Jan 2025 04:22:12 +0100

Methylglyoxal (MG) is a reactive metabolite involved in diabetes and aging through the formation of protein adducts. Less is known about the extent that MG and its metabolic product S-d-lactoylglutathione (LGSH) form adducts with cell metabolites. Using a ‘symmetric’ isotope-labeled and reactivity-based metabolomics approach in living cells, we found over 200 adducts and, surprisingly, discovered that 10 of the most abundant are lactoylated amino acids mainly derived from LGSH. The most abundant adduct d-Lac-Cys is formed rapidly between LGSH and cysteine, whereas the diastereoisomer l-Lac-Cys is formed directly from MG and cysteine, assigning cysteine with both glyoxalase 1-like and glyoxalase 2-like activity. Cellular cysteine and MG dynamically regulate d-Lac-Cys and l-Lac-Cys levels and the adducts are increased in diabetes, suggesting their use as novel biomarkers. Lastly, cysteine amides, as proxies for protein cysteines, also undergo lactoylation by MG and LGSH, suggesting the existence of two additional pathways for nonenzymatic lactoylation of proteins. (Figure presented.)

LC-MS/MS based quantitative metabolite profiling of the ischemic heart and toxicological investigation of sexual assault cases in the Aarhus area

Birkler, R. I. D. — Sun, 01 Jan 2012 04:22:12 +0100

Hyperthermic and Oxidative Stress in sudden infant death. Investigation of human fibroblast cultures and evaluation of infant death in a forensic setting

Rohde, M. C. — Sat, 01 Jan 2011 04:22:12 +0100

Phenolic acids in rye and rye bread: Occurrence, antioxidant activity and bioavailabity

Andreasen, M. F. — Tue, 01 Jan 2002 04:22:12 +0100

Homicide in Denmark 1992-2016

Thomsen, A. H. — Thu, 01 Oct 2020 04:22:12 +0200

Afhandlingen omhandler dødsmåden “drab”, som den tager sig ud fra et retsmedicinsk perspektiv. Gennem tre forskningsstudier undersøges drab, først med en overordnet undersøgelse af alle drabsmetoder (Studie I), derefter med en afgrænset undersøgelse af drab ved skarp vold (Studie II) og hvordan udviklingen i behandling har påvirket gruppen af drabsofre udsat for stiklæsioner (Studie III). Studierne er baseret på obduktionserklæringer fra ofre for drab i Danmark i perioden 1992-2016.

Studie I: Drab - overordnet
Der var 1.417 drabsofre. De hyppigste drabsmetoder var skarp vold (33,2%), skud (22,2%), stump vold (21,9%) og kvælning (17,6%). Der var et signifikant fald i det årlige antal drab ved alle de fire hyppigste
drabsmetoder, samt i drabsepisoder med både et enkelt drabsoffer og flere drabsofre. To ud af tre drabsofre var mænd, og ni ud af ti gerningspersoner var mænd. Der var tydelige forskelle mellem mandlige og kvindelige ofre, idet en stor andel af kvindelige drabsofre blev dræbt i familien, og en stor andel af mandlige ofre blev dræbt af en ven/bekendt i forbindelse med fuldskab/i nattelivet.

Studie II: Drab ved skarp vold
471 drabsofre blev slået ihjel ved skarp vold, den hyppigste drabsmetode. De fleste drab ved skarp vold blev begået indendørs, ofte med en køkkenkniv. Kvindelige ofre havde flere skarprandede læsioner, stiklæsioner og afværgelæsioner end mandlige ofre. Der var tydelige forskelle i antallet af skader ved de forskellige
drabstyper, hvilket forklarer forskellene mellem mandlige og kvindelige drabsofre. Brystkassen var den hyppigst skadede region, ofte med skade på lunger og hjerte.

Studie III: Drab ved stik vs. bedre behandling
428 drabsofre blev dræbt med stiklæsioner. Faldet i det årlige antal drab med stiklæsioner skyldtes et fald i antallet af drab med en enkelt stiklæsion og ikke drab med flere stiklæsioner. Drabsofre med en enkelt stiklæsion adskilte sig fra drabsofre med flere stiklæsioner med hensyn til alvorlighed af skader, behandlingsniveau og overlevelsestid. På trods af faldet i antallet af drab med en enkelt stiklæsion er overlevelsestiden steget fra den første halvdel af perioden til den sidste halvdel og andelen af drabsofre, der er nået på operationsbordet er tredoblet. Dette tyder på, at hurtigere og bedre lægebehandling kunne være årsag til faldet i drab med et enkelt knivstik og derfor muligt også for faldet i drab med stiklæsioner i det hele taget.
De tre studier viser, at drabsepidemiologi er foranderlig og følger den generelle samfundsudvikling. Den overordnede undersøgelse (Studie I) kan forhåbentlig give anledning til yderligere retsmedicinske forsknings-
studier og danne grundlag for offentlig debat og politikudvikling relateret til vold. De afgrænsede undersøgelser (Studie II og III) kan bruges som støtte i efterforskning af dødsfald og obduktionsarbejde, men også som en uddybning af de underliggende forhold, der påvirker drabsstatistikkerne.

A coordinated community response to rape and sexual assault

Nielsen, L. H. — Thu, 08 Feb 2018 04:22:12 +0100

Sudden unexpected death on the basis of genetic heart disease

Larsen, M. K. — Sun, 01 Jan 2012 04:22:12 +0100

QT-prolonging Drugs in Cardiac Tissue from Mentally Ill Patients

Mikkelsen, C. R. — Sun, 01 Jan 2017 04:22:12 +0100

Energy Metabolism and Proteins - Development of Chemical Tools for Exploration of Post-Translational Modifications

Sibbersen, C. — Wed, 01 Jan 2014 04:22:12 +0100

Morphology and pathoanatomy of the cervical spine facet joints in road traffic crash fatalities with emphasis on whiplash - a pathoanatomical and diagnostic imaging study

Uhrenholt, L. — Mon, 01 Jan 2007 04:22:12 +0100

General and Site-Specific Features of Atherosclerosis

Dalager, S. — Mon, 01 Jan 2007 04:22:12 +0100

Cardiopulmonary remodeling following repetitive acute pulmonary emboli and inhibition of endogenous fibrinolysis in a porcine model

Kirk, M. E., Dragsbaek, S. J., Merit, V. T., et al. — Mon, 15 Sep 2025 04:22:12 +0200

Background: The underlying pathophysiology of chronic thromboembolic pulmonary disease (CTEPD) with or without sustained pulmonary hypertension (pH) remains unclear, but repetitive pulmonary emboli (PE) and impaired fibrinolysis are known risk factors. We hypothesized that repetitive PE and inhibition of endogenous fibrinolysis would induce CTEPD with PH (CTEPH). Methods: Twenty-four Danish female slaughter pigs of ∼60 kg (4 groups of 6 pigs) were included in the study. Pigs received either autologous PE (PE group), PE plus tranexamic acid (PE + TXA), repetitive PE (day 0, 3, 7, and 10) plus tranexamic acid (REP PE + TXA), or saline infusion (SHAM). Pigs were evaluated at baseline and on day 30 using computed tomography pulmonary angiography (CTPA), invasive hemodynamics, and tissue samples. Results: CTPA showed increased pulmonary obstruction score on day 30 in REP PE + TXA group compared to remaining groups (0 ± 0 SHAM vs 31 ± 21 PE vs 42 ± 12 PE + TXA vs 69 ± 17 % REP PE + TXA, P = 0.004). Mean pulmonary arterial pressure was higher in REP PE + TXA group on day 30 than remaining groups (12 ± 2 SHAM vs 13 ± 1 PE vs 12 ± 2 PE + TXA vs 16 ± 2 mmHg REP PE + TXA, P = 0.002) yet none of the groups developed PH and right ventricular function was normalized after 30 days. In histological samples, we found chronic thromboembolic lesions with organized fibrotic thrombi, revascularization, and neointima formation, but no microvascular remodeling. Conclusions: Autologous repetitive PE and inhibited fibrinolysis caused chronic thrombi without PH in a porcine model. Our findings suggest that a repetitive PE and impaired endogenous fibrinolysis alone are insufficient to develop CTEPH. Translational aspect: This porcine model using autologous pulmonary emboli presents a realistic large animal model of chronic thromboembolic pulmonary disease particularly suitable to further investigate the vascular remodeling after acute PE. Future research should examine the role of inflammation, endothelial dysfunction and angiogenesis-driven clot resolution to improve understanding of the pathophysiological mechanisms.

Arabinoxylan Concentrate from Wheat as a Functional Food Ingredient to Improve Glucose Homeostasis

Knudsen, K. E. B., Lærke, H. N., Hedemann, M. S., et al. — Thu, 01 May 2025 04:22:12 +0200

Background: Arabinoxylan (AX) concentrates from wheat can be produced from co-products from the starch and gluten industries. These fractions are rich in AX, have high solubility, can be incorporated into bread and breakfast cereals, and have the potential to enhance functional and nutritional effects beyond what is possible with cereal species. Methods: The aim of this review is to summarize the available literature on AX concentrates from wheat in terms of production, incorporation in breads, and influence on glucose homeostasis in human subjects and animals. Results: Breads enriched in AX fiber have been found to increase the viscosity of digesta from the small intestine but with no effect on the digestibility of starch. In the large intestine, AX is, to a large extent, degraded, producing short-chain fatty acids. Across acute human and animal studies, the intake of AX concentrates has been shown to reduce the rate and extent of glucose absorption and insulin responses in a dose-dependent fashion. No general influence of AX on incretins has been identified, and the role of AX-enriched diets in appetite sensation is unclear. Medium- and long-term human and animal intervention studies demonstrated improved glucose homeostasis (fructosamine and glycated hemoglobin A1c) during the consumption of AX-enriched diets compared to placebo. Although AX concentrates across studies improved glucose homeostasis, a confounding factor to be further investigated is to what extent protein being present in relatively high concentrations in some of the produced AX-rich wheat fractions, partly or fully, is responsible for the observed homeostatic effects.

Enhanced autopsy triage (EA-Triage) in drug-related deaths

Kisbye, L. W., Rickert, A., Hasselstrøm, J. B., et al. — Sat, 01 Mar 2025 04:22:12 +0100

The objective was to assess the diagnostic accuracy of an enhanced autopsy triage (EA-Triage) setup consisting of postmortem computed tomography (PMCT), simulated quick toxicological analysis (sQTA), external examination, and case information in determining cause of death (COD) in persons with past or current use of illegal drugs (drug-related deaths). Information on drug-related deaths selected for medico-legal autopsy in 2020–2021 at the Department of Forensic Medicine, Aarhus University, Denmark, was analyzed retrospectively. The included cases underwent conventional autopsy, PMCT, and systematic toxicological analysis. A board-certified forensic pathologist, who was blinded to the internal examination and COD from the medico-legal autopsy, determined COD based on the EA-Triage setup. 154 cases with a median age of 40.6 years (range 17–70 years, 82% males) were included. The COD determined by medico-legal autopsy and that determined by EA-Triage matched in 113 cases (73%), including those with an unknown COD. EA-Triage and medico-legal autopsy determined unknown COD in 45 (29%) and 5 cases (3%), respectively. Excluding cases with an unknown COD, EA-Triage predicted COD in 109 cases (71%); of those, 72 (66%) had no unexplained case circumstances or suspicion of a criminal act. In these 72 cases, the CODs determined by EA-Triage and medico-legal autopsy matched in 71 cases (99%), and the sensitivity and specificity for detecting lethal intoxication were 100% and 90%, respectively. EA-Triage showed strong diagnostic accuracy for determining COD in drug-related deaths. This method may be suitable for enhancing preautopsy triage and guiding police investigations at an early stage.

Butyrate increases cardiac output and causes vasorelaxation in a healthy porcine model

Larsen, A. M., Christensen, L. J., Homilius, C., et al. — Wed, 01 Jan 2025 04:22:12 +0100

Background
Butyrate, a short-chain fatty acid, has shown potential to improve left ventricular (LV) function and induce vasorelaxation in rodents. Butyrate may either be produced by the microbiome in the colon, be ingested or administered intravenously. This study aimed to evaluate effects of butyrate on cardiac output (CO) and associated hemodynamic variables in a porcine model.

Methods
In a randomized, blinded crossover study, ten healthy 60-kg pigs were given three-hour infusions of 600 mM butyrate and equimolar sodium chloride (control). CO was measured by thermodilution via a pulmonary artery catheter. LV contractility was assessed using pressure-volume admittance catheterization. Additionally, isolated porcine coronary arteries were exposed to butyrate in a wire myograph to evaluate vasorelaxation.

Results
Butyrate infusion increased plasma butyrate concentration to 0.53 mM (95% confidence interval (CI): 0.49 to 0.58 mM, P<0.001) and CO by 1.6 L/min (95% CI: 1.0 to 2.1 L/min, P<0.001) compared with the control. Heart rate, LV ejection fraction, cardiac efficiency and dP/dtmax rose, while systemic vascular resistance, arterial elastance, mean arterial pressure and LV ends-systolic volume decreased. Load-independent LV contractility and stroke volume did not significantly differ. In the myograph, porcine coronary arteries relaxed in response to butyrate in a concentration-dependent manner.

Conclusion
Butyrate increased CO by lowering systemic vascular tone and raising heart rate. Although load-independent contractility remained stable, increased dP/dtmax and ejection fraction, preserved stroke volume and decreased LV end-systolic volume indicated an enhanced cardiac contractile performance. These cardiovascular effects of butyrate warrant further clinical investigation.

Injectable sustained local release doxorubicin depot technology– a promising adjuvant to systemic treatment?

Jørgensen, A. R., Hansen, A. E., Henriksen, J. R., et al. — Wed, 01 Jan 2025 04:22:12 +0100

Drug depot technologies that release chemotherapeutics locally in cancerous tissues present an intriguing strategy. This study aimed to assess the feasibility, delivery capacity, and therapeutic efficacy of a thin needle injectable doxorubicin-loaded carbohydrate-ester-based (CarboCell) depot technology. CarboCell was evaluated in three experimental setups: (A) In non-tumorous mice, release kinetics were evaluated 24 h and 48 h after a subcutaneous depot injection. (B) In mice with syngeneic CT 26 colorectal cancer, efficacy was evaluated based on tumour growth control and survival. This was done by two intratumoral injections of 50 µl CarboCell containing 1 mg/mL or 4 mg/mL doxorubicin at 5 days intervals. (C) In ten female pigs, local and distant release of doxorubicin from a 2 mg/mL doxorubicin CarboCell (2 or 4 mL) injected into tibial metaphysis was evaluated using microdialysis in nine tissue compartments. (A) Subcutaneous CarboCell depots demonstrated a sustained release of doxorubicin with (mean ± SEM) 36 ± 13% and 48 ± 20% of the loaded dose being released at 24 h and 48 h time points, respectively. (B) Intratumoral injection effectively controlled tumour growth and markedly extended the median survival time compared to the control group. (C) Doxorubicin peak drug concentrations in the metaphysis were > 0.3 µg/mL and could be quantified at least 10 mm from the application site. The systemic spill-over was minimal. Doxorubicin-loaded CarboCell proved easily administrable, maintaining antitumoral activity, good metaphyseal distribution and providing much higher local concentrations in metaphyseal bone providing high local concentrations in metaphyseal bone with a good distribution and limited systemic exposure.

Hospitalisations for physical abuse in infants and children less than 5 years, 2013–2021

Quantin, C., Cottenet, J., Chambers, C., et al. — Thu, 01 May 2025 04:22:12 +0200

Background: Child physical abuse (CPA) is a global public health problem associated with lifelong negative consequences, yet reliable epidemiologic data are lacking. This multinational cohort study analyses trends in CPA hospitalisations from 2013 to 2021. Methods: We used medico-administrative databases to identify children aged one month to five years hospitalised in Denmark, England, France, Ireland, and Wales. We identified CPA using a validated algorithm based on ICD-10 codes. We calculated the number, proportion, and incidence rate of children hospitalised for CPA, and the number and proportion of total hospitalisations for CPA, by year and age group (<1 and <5). We determined the proportion of CPA hospitalisations recorded using different ICD-10 codes, by country. Findings: The pooled incidence rate of infants <1 year hospitalised for CPA was stable over time (around 42/100,000 per year), ranging on average from 33 to 48/100,000 between countries. The pooled proportion of infant hospitalisations for CPA was around 0.17% (N = 750) per year (range 0.15–0.21%, N range 674–785), increasing significantly during the COVID-19 pandemic in 2020 (0.21%, N = 674). In children <5, the incidence rate (around 18/100,000 per year) and proportion of CPA hospitalisations (around 0.11% per year (N = 1600), range 0.10–0.14% (N range 1341–1657) were lower than in infants, but also increased in 2020 (0.14%, N = 1341). There were national differences in the distribution of ICD-10 codes used to record CPA and differences in year-on-year trends between countries. Interpretation: Comparing temporal trends in CPA hospitalisations between countries is feasible. Hospital data are one of several valuable sources for CPA surveillance. Funding: European COST Action EURO-CAN. European Union (HORIZON Europe SERENA project).

Pain, Quality of Life and Mental Health in Adults With X-Linked Hypophosphatemia

Wed, 19 Feb 2025 04:22:12 +0100

OBJECTIVE: Hereditary hypophosphatemic disorders such as X-linked hypophosphatemia (XLH) are rare phosphate wasting disorders that cause abnormal bone mineralization, which manifests as bone deformities and dental problems. Pain, stiffness, and fatigue are the main symptoms reported by adult patients with XLH, interfering with their quality of life and activities of daily living. Here, we provide a comprehensive evaluation of pain and health related quality of life in patients with XLH.

DESIGN AND METHODS: In this cross-sectional study, forty-nine adult patients with XLH and forty-two healthy sex- and age- matched control participants underwent pressure algometry to determine pain sensitivity. In addition, we collected patient reported outcome data on pain, quality of life and mental health through the following questionnaires: (i) brief pain inventory- short form, (ii) SF-36v2™ Health Survey, (iii) painDETECT, (iv) Functional Assessment of Cancer Therapy- Bone Pain, (iv) Pain Catastrophizing Scale, (v) Generalized Anxiety Disorder 7 and (vi) Patient Health Questionnaire 9.

RESULTS: Patients with XLH present altered skin, but not bone mechanical pressure pain thresholds, which may suggest referred pain through sensitization mechanisms. Questionnaire data highlight significantly higher pain scores in patients with XLH, which correlate with depression scores. Additionally, patients with XLH report decreased quality of life and mental health, increased pain catastrophizing thinking and anxiety.

CONCLUSION: Our results suggest that using patient-reported outcomes is important to understand the pain phenotype and mental health in patients with XLH and can be helpful to dictate treatment aimed at improving their pain and quality of life.

Senescence profiling of monoclonal gammopathies reveals paracrine senescence as a crucial defense against disease progression

Borges, G. A., Diaz-delCastillo, M., Guilatco, A. J., et al. — Thu, 01 May 2025 04:22:12 +0200

Multiple myeloma (MM) is a plasma cell (PC) malignancy that is preceded by monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). MGUS and SMM PCs exhibit the same primary oncogenic abnormalities as MM but lack the end-organ damage that defines proliferative disease, suggesting that clonal PCs in these precursor conditions could exhibit senescence or senescence-like growth arrest. Herein we identified monoclonal gammopathy patient-derived PCs that exhibit senescence features and found that senescent PCs were significantly increased in MGUS patients compared to SMM or MM. Spatial analysis of senescent PCs in stable MGUS and SMM patient biopsies demonstrated the activation of local paracrine senescence in the bone marrow microenvironment. Stable MGUS and SMM patients also exhibited disease-specific senescence-associated secretory phenotype (SASP) signatures that significantly correlated with PC burden and clonal antibody. In contrast, progressing MGUS, SMM, and new MM patients lacked local paracrine senescence responses and robust activation of disease specific SASP signatures. Overall, these data suggest that failure to activate tumor-specific paracrine senescence responses is key to disease progression in monoclonal gammopathies.

3D dental similarity quantification in forensic odontology identification

Kofod Petersen, A., Forgie, A., Villesen, P., Staun Larsen, L. — Thu, 01 May 2025 04:22:12 +0200

Forensic odontology identification largely depends on comparing dental work like fillings and crowns with the dental records of potential victims. This process can be challenging, especially regarding victims with minimal or no dental work. Alternatively, 3D tooth morphology can be used for identification by automated dental surface similarity scoring. However, high-resolution 3D intraoral photo scans contain hundreds of thousands of datapoints from each individual jaw, making database searches difficult and slow. Here, we reduce full 3D scans to keypoints, which are small points located in areas of high curvature on tooth surfaces. We use Difference of Curvature (DoC) for robust keypoint detection and evaluate different keypoint representation methods to distinguish between scans of the same individual and scans of different individuals, assigning them a similarity score.The results demonstrate that combining DoC with the Signature of Histograms of OrienTations (SHOT) representation method effectively separates matches from mismatches. This indicates the potential for automatic scoring of dental surface similarity. This can be valuable for forensic odontology identification, especially in cases where traditional methods are limited by the lack of dental work.

Metabolic profiles associate with mortality and neurological outcomes in out-of-hospital cardiac arrest patients

Berg-Hansen, K., Wiggers, H., Møller, N., et al. — Tue, 01 Apr 2025 04:22:12 +0200

Background: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and poor neurological outcome, with significant metabolic changes upon return of spontaneous circulation (ROSC). This study aimed to investigate the association of metabolic derangements with outcomes in patients resuscitated from OHCA. Methods: Blood samples from 156 consecutive unconscious OHCA patients in the Targeted Temperature Management trial were analyzed at hospital admission. Metabolic parameters including free fatty acids (FFAs), glucose, lactate, 3-hydroxybutyrate (3-OHB), and insulin were measured. Hierarchical clustering categorized patients based on metabolic response patterns. Thirty-day mortality and neurological outcomes were compared across these clusters. Results: The median age was 62 years (IQR 54–68) and 87% were male. Hierarchical clustering identified three distinct metabolic profiles. Cluster A showed severe metabolic distress with elevated lactate, high insulin resistance, and modest FFA/3-OHB levels. Cluster B had low FFA/3-OHB levels while Cluster C showed high FFA/3-OHB levels; both were associated with lower lactate and insulin resistance compared with Cluster A. Cluster A was linked to greater cardiac arrest severity, including longer time to ROSC, increased defibrillations, and higher adrenaline use. Thirty-day mortality rates were: Cluster A, 68%; B, 33%; C, 21% (log-rank P < 0.001). Neurological deaths were lowest in Clusters C. Baseline FFA levels were independently associated with neurological death. Conclusion: This study identifies distinct metabolic profiles associated with neurological recovery after cardiac arrest, suggesting a potential link between metabolic states and outcomes that may reflect adaptive brain resilience. These findings highlight the need for further research to explore whether metabolic-targeted interventions could enhance recovery.

Effect of repeated bolus and continuous doxorubicin administration on bone and soft tissue concentrations– a randomized study evaluated in a tumour-free porcine model

Jørgensen, A. R., Bue, M., Hanberg, P., et al. — Mon, 01 Dec 2025 04:22:12 +0100

Purpose: The aim of this study was to evaluate plasma and bone- and soft-tissue concentrations of doxorubicin following two administrations of either bolus or continuous infusion administered at a three-week interval. The achievement of adequate concentration at target sites is believed to be positively correlated to effect, and it has been suggested that concentrations are affected by the number of administrations. Methods: Eighteen female pigs were included in the study and randomized into two groups of nine receiving either a bolus or continuous infusion. The animals received a dosage of 2 mg/kg on day 1 and on day 22. From day 1 to 10, doxorubicin concentrations, as well as kidney and liver function, were monitored with plasma samples (total concentrations). On day 22, doxorubicin was measured in plasma samples (total concentration) and microdialysates (unbound concentrations) from subcutaneous tissue, muscle, synovial fluid of the knee joint, cancellous bone, and intravenously. Results: On day 22, the pharmacokinetic profiles were comparable between the two groups except for plasma AUC_{0 − 12 h}, which was higher after continuous infusion, and intravenous C_max, which was higher after bolus infusion. Bone- and soft tissue concentrations were below 0.10 µg/mL. Except for mean plasma (total) concentration at the 6 h timepoint on day 1 and 22 in the continuous group, which was higher after the first administration (p = 0.037), no differences in plasma concentrations were found between the two administrations. Conclusion: Low mean tissue doxorubicin concentrations and similar pharmacokinetic profiles were found between the bolus and continuous infusion groups. Thus, similar anti-neoplastic efficacy is to be expected with both administration types.

Metabolic changes during cardiac regeneration in the axolotl

Dittrich, A., Andersson, S. A., Busk, M., et al. — Sat, 01 Mar 2025 04:22:12 +0100

Background
The axolotl is a prominent model organism of heart regeneration due to its ability to anatomically and functionally repair the heart after an injury that mimics human myocardial infarction. In humans, such an injury leads to permanent scarring. Cardiac regeneration has been linked to metabolism and the oxygenation state, but so far, these factors remain to be detailed in the axolotl model. In this descriptive study, we have investigated metabolic changes that occurred during cardiac regeneration in the axolotl.

Results
We describe systemic and local cardiac metabolic changes after injury involving an early upregulation of glucose uptake and nucleotide biosynthesis followed by a later increase in acetate uptake. We detect several promising factors and metabolites for future studies and show that, unlike other popular animal models capable of intrinsic regeneration, the axolotl maintains its cardiac regenerative ability under hyperoxic conditions.

Conclusions
Axolotls undergo dynamic metabolic changes during the process of heart regeneration and display a robust reparative response to cardiac cryo-injury, which is unaffected by hyperoxia.

Glyoxalase 2 Coordinates de Novo Serine Metabolism

Trujillo, M. N., Jennings, E. Q., Farrera, D. O., et al. — Tue, 01 Apr 2025 04:22:12 +0200

Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme in de novo Ser biosynthesis. Numerous metabolic pathways rely on Ser as a precursor, most notably one-carbon metabolism, glutathione biosynthesis, and de novo nucleotide biosynthesis. To facilitate proliferation, many cancer cells shunt glycolytic flux through this pathway, placing PHGDH as a metabolic liability and feasible therapeutic target for the treatment of cancer. Herein, we demonstrate the post-translational modification (PTM) of PHGDH by lactoylLys. These PTMs are generated through a non-enzymatic acyl transfer from the glyoxalase cycle intermediate, lactoylglutathione (LGSH). Knockout of the primary LGSH regulatory enzyme, glyoxalase 2 (GLO2), results in increased LGSH and resulting lactoylLys modification of PHGDH. These PTMs reduce enzymatic activity, resulting in a marked reduction in intracellular Ser. Using stable isotope tracing, we demonstrate reduced flux through the de novo Ser biosynthetic pathway. Collectively, these data identify PHGDH as a target for modification by lactoylLys, resulting in reduced enzymatic activity and reduced intracellular Ser.

Role of Intestinal Microbiome in Potentiating Inflammation and Predicting Outcomes in Alcohol-associated Cirrhosis

Støy, S., Schnabl, B. — Sun, 01 Jun 2025 04:22:12 +0200

Bloodletting as Medical Child Abuse Revealed by Lack of Iron Accumulation Despite Multiple Erythrocyte Transfusions

Hasle, H., Frost, L., Johansen, K. B., Jørgensen, G. H. — Thu, 01 May 2025 04:22:12 +0200

The central venous line was used for feeding an infant with failure to thrive. He later developed unexplained severe transfusion-dependent anemia. Ferritin remained low despite more than 100 transfusions. The medical arguments mainly based upon iron physiology provided strong suspicion for intended bloodletting, which was documented by covert video. The mother was very active on social media lacking behavioral signs of Munchhausen by proxy during hospital contacts. Despite clear medical evidence of medical child abuse, the diagnosis was delayed by several years.

Lactate orchestrates metabolic hemodynamic adaptations through a unique combination of venocontraction, artery relaxation, and positive inotropy

Thu, 01 May 2025 04:22:12 +0200

Aim: H⁺ facilitates metabolic blood flow regulation while negatively impacting cardiac contractility. Cardiovascular consequences of conjugate bases accumulating alongside H⁺ remain unclear. Here, we evaluate the cardiovascular effects of nine prominent carboxylates—particularly lactate, 3-hydroxybutyrate, and butyrate—linked to metabolic and microbial activity. Methods: Comparing the actions of pH-adjusted Na-carboxylates to equiosmolar NaCl, we study arteries and veins isolated from healthy rats and humans with ischaemic heart disease, isolated perfused rat hearts, and rat cardiovascular function in vivo. Results: The tested carboxylates generally relax arteries and veins. L-lactate relaxes human and rat arteries up to 70% (EC₅₀ = 10.1 mM) and rat brachial and mesenteric veins up to 30% of pre-contractions, yet stands out by augmenting contractions of rat femoral, saphenous, and lateral marginal veins and human internal thoracic and great saphenous veins up to 50%. D-lactate shows only minor actions. In isolated perfused hearts, 10 mM L-lactate increases coronary flow (17.1 ± 7.7%) and left ventricular developed pressure (10.1 ± 3.0%) without affecting heart rate. L-lactate infusion in rats—reaching 3.7 ± 0.3 mM in the circulation—increases left ventricular end-diastolic volume (11.3 ± 2.8%), stroke volume (22.6 ± 3.0%), cardiac output (23.4 ± 3.5%), and ejection fraction (10.6 ± 2.0%), and lowers systemic vascular resistance (34.1 ± 3.7%) without influencing blood pressure or heart rate. The ketone body 3-hydroxybutyrate causes lactate accumulation and elevates left ventricular end-diastolic volume in vivo. Conclusion: Carboxylate metabolites generally relax arteries and veins. L-lactate relaxes arteries, lowering systemic vascular resistance, causes preferential venocontraction with increased ventricular diastolic filling, and elevates cardiac contractility and cardiac output. We propose that L-lactate optimizes cardiovascular function during metabolic disturbances.

Pediatric cardiac arrest registries and survival outcomes

Markel, F., Djakow, J., Biarent, D., et al. — Sat, 01 Mar 2025 04:22:12 +0100

Objective: The epidemiology of pediatric cardiac arrest in Europe is largely unknown. We aimed to characterize pediatric cardiac arrest registries and obtain the first survival outcome data on pediatric cardiac arrest in Europe. Design: This is a prospective multinational survey. Setting: We surveyed all 53 countries in Europe asking about: the existence registries for pediatric out-of-hospital cardiac arrest (pOHCA) and/or in-hospital cardiac arrest (pIHCA)), the data collected, and the structure of the registries. Subsequently, we investigated outcomes (number of pOHCA/pIHCA since start of the registry, return of spontaneous circulation (ROSC), survival to hospital discharge/30-day survival) from the countries with active registries. Patients and interventions: We obtained information from 33 countries including 25 of the 27 European Union states. Measurements and main results: Thirteen countries (39%) have an ongoing pediatric cardiac arrest registry (pOHCA: 11 countries, pIHCA: 8 countries). All use the Utstein template for data collection. Five countries (15%) collect data about CPR quality. Eleven countries (33%) expressed interest in European collaboration on registry data. Overall, 13 countries reported data on outcomes from a total of 17,708 pOHCAs and 2,743 pIHCAs. The ROSC rate after pOHCA ranges from 10% to 72% as compared to 60% to 72% after pIHCA. Survival to hospital discharge ranges from 16% to 39% after pOHCA as compared to 32% to 57% after pIHCA. Conclusions: Less than 40% of the European countries have a pOHCA and/or pIHCA registry, reporting a wide variety in survival rates, especially after pOHCA. More systematic data collection is needed to identify the real incidence and outcomes from pediatric cardiac arrest, ideally through a joint European registry.

Pharmacokinetics and Side Effects of Δ⁹-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD

Sønderskov, M. B., Khatir, D. S., Kjærgaard, K. D., et al. — Sat, 01 Mar 2025 04:22:12 +0100

Introduction: Chronic kidney disease (CKD) affects approximately 10% of the global population and is associated with a large symptom burden. Medicinal cannabis is advised against in patients with severe CKD. However, pharmacokinetic and pharmacodynamic knowledge regarding their use in patients with CKD is lacking. Methods: We aimed to investigate the pharmacokinetics and side effects of a single dose of Sativex, corresponding to 5.4 mg Δ⁹-tetrahydrocannabinol (THC) and 5 mg cannabidiol (CBD), in patients with CKD stages 4 and 5 compared with healthy volunteers (controls). The study was a nonrandomized and unblinded clinical study. Results: Twenty controls and 29 patients with CKD completed the study. The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77–3.48), 4.16 (3.35–5.28), and 4.31 (3.16–5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls. AUC for CBD and metabolites, and other pharmacokinetic parameters, such as maximum concentration (C_max) and excretion of metabolites in urine were also significantly different between patients with CKD and controls. After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1). Conclusion: Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects may be more pronounced; however, the intersubject variability was high. If cannabis products are administered to patients with severe CKD, caution is needed.

Reliability of the OMERACT Giant cell arteritis Ultrasonography Score (OGUS)

Duftner, C., Redlinger, N., Bruyn, G. A., et al. — Wed, 01 Jan 2025 04:22:12 +0100

Objective To test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography. Methods Six GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2. Ultrasonography was conducted on temporal arteries (common superficial, frontal and parietal branches) and axillary arteries bilaterally to calculate the OGUS, the Southend score and the Halo count. Inter-reader and intra-reader reliability were assessed by intraclass correlation coefficient (ICC). Results Mean age of GCA patients was 78±5.1 years, 2 (33.3%) were women, and all were in clinical remission. Expert inter-reader ICC of the OGUS was 0.60 in both rounds, 0.40 in round 1 and 0.51 in round 2 for the Southend score and 0.45 and 0.52, respectively, for the Halo count. Median ICCs for intra-reader reliability were 0.86, 0.73 and 0.65 for the OGUS, Southend score and Halo count, respectively. For non-experts, inter-reader ICCs in round 1 were 0.20 for the OGUS, 0.20 for a normalised Southend score (=score divided by available segments) and 0.35 for a normalised Halo count. After training, inter-reader reliability ICCs improved to 0.52, 0.29 and 0.54, respectively. Conclusion Inter-reader reliability was fair to moderate, and intra-reader reliability was good for OGUS, Southend score and Halo count among experts. Inter-reader reliability of non-experts in vascular ultrasonography improved after the training.

Fatal poisonings in Nordic countries in 2022 among people who use drugs

Kriikku, P., Edvardsen, H. M. E., Thelander, G., et al. — Tue, 01 Jul 2025 04:22:12 +0200

The present study is a survey of fatal poisonings occurring in 2022 among people who use drugs (PWUD) in the Nordic countries. This is the eighth report in a series of studies on PWUD conducted about every fifth year since 1984 by a working group representing Denmark, Finland, Iceland, Norway and Sweden.Data on the number of deaths, gender, age, place of death, main intoxicant, and drugs detected in blood were recorded. National data were compared between the Nordic countries as well as with the earlier studies. The death rate (number of deaths per 100,000 inhabitants) among PWUD in 2022 was highest in Norway (8.03), followed by Iceland (7.20) and Finland (5.95), and lowest in Denmark (5.09). This rate increased in all countries compared to 2017, except in Sweden, which saw a decrease from 6.46 to 5.91. The change was only statistically significant in Norway. Most deaths occurred among men, with women accounting for 16–23 %. The median age at the time of death among PWUD was 40–43 years in Denmark, Norway and Sweden, while it was about ten years younger in Finland and Iceland (median age 33 years). Opioids were the main cause of PWUD death in all countries. The proportion of opioid deaths amounted to 73–89 % and was lowest in Denmark and highest in Iceland. New psychoactive substances (NPS) were sporadically detected in all countries but were rarely the main intoxicant. The largest diversity of NPS was detected in Finland and Sweden.

Trabecular bone structural units and their cement lines change with age, bone volume fraction, structure, and strength in female human vertebrae

Wed, 01 Jan 2025 04:22:12 +0100

A lifetime of successive bone remodeling events leads to trabeculae which are composed of a patchwork of bone structural units (BSUs) called hemi-osteons or trabecular packets. Traditionally, only intact surface BSUs have been studied, which are those that have been created most recently. Accordingly, the complex changes in the size and distribution of BSU throughout the trabeculae have been overlooked. In this study, the BSUs within the trabeculae of the second lumbar vertebrae were manually traced, using ImageJ software, in osteopontin immunostained sections of eight young women (aged 19-38 yr) and eight older women (aged 69-96 yr). A series of BSU profile properties including area, width, length, and perimeter were quantified, along with properties of each trabecular profile such as the number of BSU and cement line length. The relationships between these properties and age, as well as selected trabecular microstructural properties assessed with microcomputed tomography, and bone strength assessed on the neighboring third lumbar vertebrae, were investigated. The median BSU profile length and perimeter decreased with age, while the median BSU profile area and width was unchanged. Moreover, age was associated with an increase in the number of BSU profiles and cement line length per trabecular profile area. However, changes in BSU profile geometry, the number of BSU profiles, and the cement line length per trabecular profile were strongly correlated with trabecular bone volume fraction, structure model index, and bone strength. Further research is needed to understand how these changes in BSU properties affect the mechanical and failure properties of trabecular bone.

Firearm Homicides in Europe

Krüsselmann, K., Aarten, P., Granath, S., et al. — Sun, 01 Jan 2023 04:22:12 +0100

Detailed, comparative research on firearm violence in Europe is rare. Using data from the European Homicide Monitor, this paper presents the prevalence and characteristics of firearm homicides in Denmark, Finland, the Netherlands, Sweden and Switzerland between 2001 and 2016. Furthermore, we compare firearm to non-firearm homicides to assess the degree of uniqueness of firearms as modus operandi. We find that the firearm homicide rate varies across our sample of countries. We also identify two country profiles: in Denmark, the Netherlands and Sweden, most firearm homicides take place in public and urban areas, involving male victims and perpetrators. In these countries, the use of firearms in homicides is largely concentrated in the criminal milieu. In Finland and Switzerland, firearms are mostly used in domestic homicides, with a higher share of female victims. We explore these findings in relation to firearm availability in each country.

Metabolic Differences in Neuroimaging with [¹⁸F]FDG in Rats Under Isoflurane and Hypnorm–Dormicum

Alstrup, A. K. O., Simonsen, M., Hansen, K. V., Real, C. C. — Wed, 01 Jan 2025 04:22:12 +0100

Background: Anesthesia can significantly impact positron emission tomography (PET) neuroimaging in preclinical studies. Therefore, understanding these effects is crucial for accurate interpretation of the results. In this experiment, we investigate the effect of [¹⁸F]-labeled glucose analog fluorodeoxyglucose ([¹⁸F]FDG) uptake in the brains of rats anesthetized with two commonly used anesthetics for rodents: isoflurane, an inhalation anesthetic, and Hypnorm–Dormicum, a combination injection anesthetic. Materials and Methods: Female adult Sprague Dawley rats were randomly assigned to one of two anesthesia groups: isoflurane or Hypnorm–Dormicum. The rats were submitted to dynamic [¹⁸F]FDG PET scan. The whole brain [¹⁸F]FDG standard uptake value (SUV) and the brain voxel-based analysis were performed. Results: The dynamic [¹⁸F]FDG data revealed that the brain SUV was 38% lower in the isoflurane group after 40 min of image (2.085 ± 0.3563 vs. 3.369 ± 0.5577, p = 0.0008). In voxel-based analysis between groups, the maps collaborate with SUV data, revealing a reduction in [¹⁸F]FDG uptake in the isoflurane group, primarily in the cortical regions, with additional small increases observed in the midbrain and cerebellum. Discussion and Conclusions: The observed differences in [¹⁸F]FDG uptake in the brain may be attributed to variations in metabolic activity. These results underscore the necessity for careful consideration of anesthetic choice and its impact on neuroimaging outcomes in future research.

Environmental aspects of dental filling materials

Bindslev, D. A. — Wed, 01 Apr 1998 04:22:12 +0200

In recent years, the possible environmental impact caused by certain routines
in dental practice has attracted attention among regulators. As part of point
source reduction strategies, the discharge of mercury/amalgam-contaminated
wastes has been regulated in a number of countries, even though it has been
documented that by adopting appropriate mercury hygiene measures,
including installation of amalgam-separating devices, the environmental
impact of amalgam use in dentistry is minimal. There are, so far, no data
indicating the environmental impact of methacrylate-based dental filling
materials. As to the occupational environment, recent reports have stated that
when normal occupational recommendations for proper mercury hygiene
routines are followed (e.g., water spray coolant and high vacuum suction
during removal of amalgam restorations), no occupational health risk can be
assumed. An increasing number of reports on occupational allergic reactions
to components of polymer-based dental filling materials call for attention to
the sensitizing potential of certain ingredients in these products.

The effect of tumor promotors on cell morphology, population kinetics and differentiation

Bindslev, D. A. — Mon, 01 Oct 1984 04:22:12 +0100

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) accelerates expression of differentiation markers in cultures of rat palatal epithelial cells

Bindslev, D. A., Dabelsteen, E. — Thu, 01 Jan 1987 04:22:12 +0100

Cultures of rat palatal epithelium grown on collagen rafts were treated with
different doses of the potent tumor promoter 12-O-tetradecanoylphorbol-13-
acetate (TPA). Sections from biopsies taken 1, 6, 24, and 48 hr after the
addition of TPA were examined for the localization of staining by blood
group antigen H antibody and antikeratin antibody AE1. In contrast to control
cultures, where antigen H was seen exclusively at the cell membranes of the
second and third cell layer, several antigen H-positive cells, some appearing
in groups, were found in the basal cell layer of TPA-treated specimens.
Staining for keratins with the AE1 antikeratin antibody showed no staining of
basal cells but only suprabasal cells in controls, whereas several cells of the
basal cell layer of TPA-treated cultures stained positively with this antibody.
The results support the theory that TPA, by forcing a part of the basal cell
population to terminal differentiation, strongly affects the composition of the
basal cell population.

Chemically unrelated tumor promoters induce identical morphological changes in cultured rat oral epithelium

Bindslev, D. A., Philipsen, H.P., Nikai, H., Andersen, L., Jepsen, A. — Fri, 23 Jan 1987 04:22:12 +0100

By use of phase contrast microscopy, transmission and scanning electron
microscopy the cytomorphological effects of different known tumor
promoters (TPA, teleocidin, mezerein and anthralin) were studied and
compared to the cytomorphological effects of a variety of non- or weak
promoting irritants (ethylphenylpropiolate (EPP), phorbol, acetone, ethanol
and dimethyl sulfoxide (DMSO]. The studies were conducted in cultures of
stratifying rat tongue epithelial cells. It was demonstrated that the tumor
promoters induce characteristic cytomorphological alterations, the most
striking changes being elongation of the cells and formation of long
cytoplasmic extensions together with induction of so-called "dark cells". The
non-promoting irritants exerted well-known cytotoxic reactions like cell
rounding and cell sloughing. It is suggested that the characteristic tumor
promotor induced cytomorphological effects partly reflects a block of the
intercellular communication and thus should be paid more attention as an
important characteristic event among the pleiotropic effects exerted by tumor
promoters

Protein targets of reactive metabolites

Hansen, J. — Fri, 22 Jul 2022 04:22:12 +0200

Endogenous compounds as well as drugs and other xenobiotics usually undergo a range
of enzyme catalyzed transformations. This may lead to chemically reactive metabolites
with unknown biological functions and targets.
Metabolites may be biologically active and act as intracellular signaling molecules or
affect or modify the function of enzymes or other essential macromolecules and thus
exert unwanted effects.
Using a chemical probe of MDMA as a proxy we have illustrated a workflow enabling
identification of protein targets of reactive metabolites. We have subsequently
successfully used this workflow to identify novel targets of endogenous metabolites and
pinpointed interesting biological effects.

Genetically determined cardiomyopathies at autopsy

Sheppard, M. N., van der Wal, A. C., Banner, J., et al. — Sat, 01 Apr 2023 04:22:12 +0200

Cardiomyopathies (CMP) comprise a heterogenous group of diseases affecting primarily the myocardium, either genetic and/or acquired in origin. While many classification systems have been proposed in the clinical setting, there is no internationally agreed pathological consensus concerning the diagnostic approach to inherited CMP at autopsy. A document on autopsy diagnosis of CMP is needed because the complexity of the pathologic backgrounds requires proper insight and expertise. In cases presenting with cardiac hypertrophy and/or dilatation/scarring with normal coronary arteries, a suspicion of inherited CMP must be considered, and a histological examination is essential. Establishing the actual cause of the disease may require a number of tissue-based and/or fluid-based investigations, be it histological, ultrastructural, or molecular. A history of illicit drug use must be looked for. Sudden death is frequently the first manifestation of disease in case of CMP, especially in the young. Also, during routine clinical or forensic autopsies, a suspicion of CMP may arise based on clinical data or pathological findings at autopsy. It is thus a challenge to make a diagnosis of a CMP at autopsy. The pathology report should provide the relevant data and a cardiac diagnosis which can help the family in furthering investigations, including genetic testing in case of genetic forms of CMP. With the explosion in molecular testing and the concept of the molecular autopsy, the pathologist should use strict criteria in the diagnosis of CMP, and helpful for clinical geneticists and cardiologists who advise the family as to the possibility of a genetic disease.

Butyrate increases cardiac output and causes vasorelaxation in a healthy porcine model

Christensen, L. J., Larsen, A. M., Homilius, C., et al. — Sat, 15 Feb 2025 04:22:12 +0100

Background: Butyrate, a short-chain fatty acid, has shown potential to improve left ventricular (LV) function and induce vasorelaxation in rodents. Butyrate may either be produced by the microbiome in the colon, be ingested or administered intravenously. This study aimed to evaluate effects of butyrate on cardiac output (CO) and associated hemodynamic variables in a porcine model. Methods: In a randomized, blinded crossover study, ten healthy 60-kg pigs were given three hour infusions of 600 mM butyrate and equimolar sodium chloride (control). CO was measured by thermodilution via a pulmonary artery catheter. LV contractility was assessed using pressure-volume admittance catheterization. Additionally, isolated porcine coronary arteries were exposed to butyrate in a wire myograph to evaluate vasorelaxation. Results: Butyrate infusion increased plasma butyrate concentration to 0.53 mM (95 % confidence interval (CI): 0.49 to 0.58 mM, P < 0.58 mM, P < 0.001) and CO by 1.6 L/min (95 % CI: 1.0 to 2.1 L/min, P < 0.001) compared with the control. Heart rate, LV ejection fraction, cardiac efficiency and dP/dt_max rose, while systemic vascular resistance, arterial elastance, mean arterial pressure and LV end-systolic volume decreased. Load-independent LV contractility and stroke volume did not significantly differ. In the myograph, porcine coronary arteries relaxed in response to butyrate in a concentration-dependent manner. Conclusion: Butyrate increases cardiac output and lowers vascular resistance in a large animal model, through increased HR and systemic vasorelaxation. Load-independent LV contractility was not significantly altered. We observed indices of increased end-organ perfusion. These potentially beneficial cardiovascular properties of butyrate should be further studied.

Palatinale rugae til human identifikation:

Kofod Petersen, A., Bindslev, D. A., Villesen, P., Staun Larsen, L. — Fri, 08 Nov 2024 04:22:12 +0100

Background
The human palatal rugae (folds) comprise a detailed pattern in the hard palate. They are described to be very constant during an individual’s lifetime, comparable with a fingerprint, and, importantly within a forensic setting, can serve as an important supplement in odontological identification of deceased.
Aim
The aim of this study was to test two methods of superimposition in correctly distinguishing between matches (from same individual) and mismatches (from different individuals) of digital scans of rugae.
Methods
We used an existing research database holding digital intraoral scans of 51 individuals from two points in time approximately 6 months apart. The palatal rugae area was cut manually from the digital scans without regards to teeth position. Two superimposition methods (Iterative Closest Point (ICP) and Random Sample Consensus (RANSAC)) were tested in an all-vs-all manner. Similarity was reported as fitness and inlier Root Mean Squared Error (RMSE).
Results
For both ICP and RANSAC none of the similarity measures were able to unambiguously distinguish between matches (rugae from same individual at two time points) and mismatches (rugae from different individuals).
Conclusion
The results imply that the two superimposition methods are not applicable for matching rugae scans. Further exploration of possible methods to distinguish between matches and mismatches are needed to fully exploit the great potential within forensic odontology identification of these digital palatal 3D ‘fingerprints’.

Intimate Partner Homicide

Leth, P. M., Thomsen, A. H. — Wed, 01 Jan 2025 04:22:12 +0100

Intimate partner homicide (IPH) is defined as a homicide committed against a current or former partner, whether the couple is married, cohabitating or companions such as a girlfriend or a boyfriend and irrespective of gender. Women are predominantly the victims of IPH, and the perpetrators are predominantly males. The World Health Organization has declared that violence against women, including intimate partner violence is a major public health problem globally and a violation of women's human rights. In this chapter the important risk factors are described. We further describe IPH followed by perpetrator suicide, the significance of alcohol and drug abuse, mental health issues, so-called mercy killings, epidemiology, homicide methods and prevention.

Det er professionelt at være i tvivl, men uprofessionelt ikke at handle

Frost, L. — Wed, 01 May 2024 04:22:12 +0200

Det kaster lange skygger ind i et liv, når man som barn bliver udsat for mishandling. Vi skal i almen praksis handle, når vi får mistanken. Der er hjælp at hente i børnehusene og på de højtspecialiserede børneafdelinger.

Ny metode til analyse af fingeraftryk har store perspektiver

Frisch, K. — Wed, 11 Sep 2024 04:22:12 +0200

The potential of using keel bone fracture in laying hens to investigate bone pain in a high mineral turnover, late mineralizing bone – a research plan.

Sun, 10 Mar 2024 04:22:12 +0100

A novel CCL3-HMGB1 signaling axis regulating osteocyte RANKL expression in multiple myeloma

Anloague, A., Sabol, H. M., Kaur, J., et al. — Tue, 01 Apr 2025 04:22:12 +0200

Multiple myeloma (MM) is a clonal plasma cell proliferative malignancy characterized by a debilitating bone disease. Osteolytic destruction, a hallmark of MM, is driven by increased osteoclast number and exacerbated bone resorption, primarily fueled by the excessive production of RANKL, the master regulator of osteoclast formation, within the tumor niche. We previously reported that osteocytes, the most abundant cells in the bone niche, promote tumor progression and support MM bone disease by overproducing RANKL. However, the molecular mechanisms underlying RANKL dysregulation in osteocytes in the context of MM bone disease are not entirely understood. Here, we present evidence that MM-derived CCL3 induces upregulation of RANKL expression in both human and murine osteocytes. Through a combination of in vitro, ex vivo, and in vivo models and clinical data, we demonstrate that genetic or pharmacologic inhibition of CCL3 prevents RANKL upregulation in osteocytes and attenuates the bone loss induced by MM cells. Mechanistic studies revealed that MM-derived CCL3 triggers the secretion of HMGB1 by osteocytes, a process required for osteocytic RANKL upregulation by MM cells. These findings identify a previously unknown CCL3-HMGB1 signaling axis in the MM tumor niche that drives bone resorption by promoting RANKL overproduction in osteocytes.

Determination of endogenous GHB in ante-mortem whole blood, urine, and oral fluid by LC–MS/MS

Sørensen, L. K., Faldborg, K. B., Andersen, C. U., Hasselstrøm, J. B. — Sun, 01 Dec 2024 04:22:12 +0100

Two challenges in detecting γ-hydroxybutyric acid (GHB) intake are its endogenous presence and in vitro production after sampling. This study developed an LC–MS/MS method for selective GHB determination in human antemortem blood, urine, and oral fluid at endogenous concentrations. Furthermore, the stability of GHB in blood samples and its endogenous concentrations in samples taken under controlled circumstances were investigated. Samples were extracted in methanol/acetonitrile and processed by anion exchange solid-phase extraction. GHB was separated from structural isomers using a reversed–phase LC column with anion properties. The validated limit of quantification was 0.005 µg/mL in blood and 0.010 µg/mL in urine and oral fluid, at which the relative reproducibility standard deviation and bias were <15 %. The mean extraction recovery was ≥90 %. The average GHB concentration increased by 1.2 µg/mL in fluoride/citrate- preserved blood after 28 days of storage at 4°C; however, in fluoride/oxalate (FX)-preserved blood, the mean concentration increased by only 0.055 µg/mL. No change was observed at −20°C. In 105 randomly selected samples of FX-preserved blood collected for forensic antemortem toxicological analysis, all concentrations were <0.066 µg/mL, even after long-term storage at −20°C. In blood, urine, and oral fluid samples from a clinical study of GHB intake, endogenous baseline levels from 30 participants ranged from 0.0069–0.050, 0.024–0.38, and 0.034–0.93 µg/mL, respectively. These results demonstrate that the current cut-off level of 5 µg/mL for discriminating between endogenous and exogenous GHB in antemortem blood could be considerably lower for FX-preserved blood stored at −20°C.

Mapping RANKL- and OPG-expressing cells in bone tissue

El-Masri, B. M., Andreasen, C. M., Laursen, K. S., et al. — Sun, 01 Dec 2024 04:22:12 +0100

Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway. ISH was performed across species, skeletal sites, and following recombinant OPG (OPG:Fc) and parathyroid hormone 1–34 (PTH) treatment of mice. OPG:Fc treatment in mice induced an increased expression of RANKL mRNA mainly in trabecular, but not endocortical bone surface cells. Additionally, a decreased expression of OPG mRNA was detected in bone surface cells and osteocytes of both compartments. A similar but more pronounced effect on RANKL and OPG expression was seen one hour after PTH treatment. These findings suggest that bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis, and that OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data from murine bone marrow stromal cells revealed that Tnfsf11⁺ cells expressed high levels of Mmp13, Limch1, and Wif1, confirming their osteoprogenitor status. ISH confirmed co-expression of Mmp13 and Tnfsf11 in bone surface cells of both vehicle- and OPG:Fc-treated mice. Under physiological conditions of human/mouse bone, RANKL is expressed mainly by osteoprogenitors proximate to the osteoclasts, while OPG is expressed mainly by osteocytes and bone-forming osteoblasts.

Publications - Publikationer

Factors Causing Incomplete Colonoscopy Reported by the Endoscopist

Reactivity-based metabolomics reveal cysteine has glyoxalase 1-like and glyoxalase 2-like activities

LC-MS/MS based quantitative metabolite profiling of the ischemic heart and toxicological investigation of sexual assault cases in the Aarhus area

Hyperthermic and Oxidative Stress in sudden infant death. Investigation of human fibroblast cultures and evaluation of infant death in a forensic setting

Phenolic acids in rye and rye bread: Occurrence, antioxidant activity and bioavailabity

Homicide in Denmark 1992-2016

A coordinated community response to rape and sexual assault

Sudden unexpected death on the basis of genetic heart disease

QT-prolonging Drugs in Cardiac Tissue from Mentally Ill Patients

Energy Metabolism and Proteins - Development of Chemical Tools for Exploration of Post-Translational Modifications

Morphology and pathoanatomy of the cervical spine facet joints in road traffic crash fatalities with emphasis on whiplash - a pathoanatomical and diagnostic imaging study

General and Site-Specific Features of Atherosclerosis

Cardiopulmonary remodeling following repetitive acute pulmonary emboli and inhibition of endogenous fibrinolysis in a porcine model

Arabinoxylan Concentrate from Wheat as a Functional Food Ingredient to Improve Glucose Homeostasis

Enhanced autopsy triage (EA-Triage) in drug-related deaths

Butyrate increases cardiac output and causes vasorelaxation in a healthy porcine model

Injectable sustained local release doxorubicin depot technology– a promising adjuvant to systemic treatment?

Hospitalisations for physical abuse in infants and children less than 5 years, 2013–2021

Pain, Quality of Life and Mental Health in Adults With X-Linked Hypophosphatemia

Senescence profiling of monoclonal gammopathies reveals paracrine senescence as a crucial defense against disease progression

3D dental similarity quantification in forensic odontology identification

Metabolic profiles associate with mortality and neurological outcomes in out-of-hospital cardiac arrest patients

Effect of repeated bolus and continuous doxorubicin administration on bone and soft tissue concentrations– a randomized study evaluated in a tumour-free porcine model

Metabolic changes during cardiac regeneration in the axolotl

Glyoxalase 2 Coordinates de Novo Serine Metabolism

Role of Intestinal Microbiome in Potentiating Inflammation and Predicting Outcomes in Alcohol-associated Cirrhosis

Bloodletting as Medical Child Abuse Revealed by Lack of Iron Accumulation Despite Multiple Erythrocyte Transfusions

Lactate orchestrates metabolic hemodynamic adaptations through a unique combination of venocontraction, artery relaxation, and positive inotropy

Pediatric cardiac arrest registries and survival outcomes

Pharmacokinetics and Side Effects of Δ9-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD

Reliability of the OMERACT Giant cell arteritis Ultrasonography Score (OGUS)

Fatal poisonings in Nordic countries in 2022 among people who use drugs

Trabecular bone structural units and their cement lines change with age, bone volume fraction, structure, and strength in female human vertebrae

Firearm Homicides in Europe

Metabolic Differences in Neuroimaging with [18F]FDG in Rats Under Isoflurane and Hypnorm–Dormicum

Environmental aspects of dental filling materials

The effect of tumor promotors on cell morphology, population kinetics and differentiation

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) accelerates expression of differentiation markers in cultures of rat palatal epithelial cells

Chemically unrelated tumor promoters induce identical morphological changes in cultured rat oral epithelium

Protein targets of reactive metabolites

Genetically determined cardiomyopathies at autopsy

Butyrate increases cardiac output and causes vasorelaxation in a healthy porcine model

Palatinale rugae til human identifikation:

Intimate Partner Homicide

Det er professionelt at være i tvivl, men uprofessionelt ikke at handle

Ny metode til analyse af fingeraftryk har store perspektiver

The potential of using keel bone fracture in laying hens to investigate bone pain in a high mineral turnover, late mineralizing bone – a research plan.

A novel CCL3-HMGB1 signaling axis regulating osteocyte RANKL expression in multiple myeloma

Determination of endogenous GHB in ante-mortem whole blood, urine, and oral fluid by LC–MS/MS

Mapping RANKL- and OPG-expressing cells in bone tissue

Pharmacokinetics and Side Effects of Δ⁹-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD

Metabolic Differences in Neuroimaging with [¹⁸F]FDG in Rats Under Isoflurane and Hypnorm–Dormicum