Recent publications
Background
Platelet-rich fibrin (PRF) blood concentrates are used in oral implantology and defect surgery to promote osteoneogenesis in Bone Marrow Defects in Jawbone (BMDJ), according to the morphology of fatty-degenerative osteonecrosis also called FDOJ.
Question
Can the benefit of PRF on alveolar osteoneogenesis be confirmed by cytokine analysis?.
Methods
The cytokine expressions of the PRF samples in 26 patients undergoing BMDJ/FDOJ surgery in the same session were analysed for seven cytokines (RANTES/CCL5; FGF-2; IL-1RA; Il-6; IL-8; MCP-1; TNF-a) by multiplex (Luminex). The FDOJ samples of these 26 BMDJ/FDOJ patients were analysed for the RANTES/CCL5 expression only.
Results
Cytokine expression in PRF is compared to reference values for healthy medullary bone of the jaw and BMDJ/FDOJ and shows that the cytokine expressions of the PRF samples do not compensate or counteract prima vista for the cytokine dysregulations present in the BMDJ/FDOJ areas.
Discussion
To define the aid of cytokines studied in PRF in the restoration of the immunological dysregulation in areas of BMDJ/FDOJ, literature is reviewed comparing RANTES/CCL5, IL-1ra, TNF-α and MCP-1/CCL2 expression in PRF and BMDJ/FDOJ. Immunoregulatory properties of PRF in alveolar bone restoration are evaluated.
Summary
PRF was mistakenly thought to be a cure for bone healing, which is here shown to be incorrect. Enoral Ultrasound Sonography of bone density is available for the clinical measurement of individually developed osteoneogenesis by PRF.
Conclusion
The multiplex analysis of PRF shows a dynamic and cytokine-based interaction with osteoneogenesis that is not yet fully clarified.
Background: Vitamin D is a fat-soluble steroid that influences cardiovascular health by affecting lipid metabolism. Since dyslipidemia is a key risk factor for cardiovascular disease (CVD), our study aimed to explore the relationship between vitamin D levels and lipid parameters, considering the effects of age and gender. Methods: In this cross-sectional study of 47,778 outpatients, we analyzed correlations between two forms of vitamin D—25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D)—and lipid parameters, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC). Subgroup analyses by age and gender provided additional insights. Results: Results showed that 25(OH)D levels were negatively correlated with LDL and TC across the cohort. This association was particularly evident in men over 50, whereas women showed a positive correlation with LDL and TC before age 50 and a negative correlation after. HDL levels positively correlated with 25(OH)D across all age groups, with the strongest association in postmenopausal women. In contrast, 1,25(OH)2D showed a positive correlation only with HDL in individuals over 50, with no significant correlation with LDL or TC in any age group. Conclusions: In conclusion, findings from this cross-sectional study underscore an association between elevated levels of 25(OH)D and more favorable lipid profiles, characterized by reduced LDL and total cholesterol, as well as increased HDL levels. This association is particularly pronounced among individuals over 50 years of age and postmenopausal women.
Compromising between accuracy and rapidity is an important issue in analytics and diagnostics, often preventing timely and appropriate reactions to disease. This issue is particularly critical for infectious diseases, where reliable and rapid diagnosis is crucial for effective treatment and easier containment, thereby reducing economic and societal impacts. Diagnostic technologies are vital in disease modeling, tracking, treatment decision making, and epidemic containment. At the point-of-care level in modern healthcare, accurate diagnostics, especially those involving genetic-level analysis and nucleic acid amplification techniques, are still needed. However, implementing these techniques in remote or non-laboratory settings poses challenges because of the need for trained personnel and specialized equipment, as all nucleic acid-based diagnostic techniques, such as polymerase chain reaction and isothermal nucleic acid amplification, require temperature cycling or elevated and stabilized temperatures. However, in smart food packaging, there are approved and commercially available methods that use temperature regulation to enable autonomous heat generation without external sources, such as chemical heaters with phase change materials. These approaches could be applied in diagnostics, facilitating point-of-care, electricity-free molecular diagnostics, especially with nucleic acid-based detection methods such as isothermal nucleic acid amplification. In this review, we explore the potential interplay between self-heating elements, isothermal nucleic acid amplification techniques, and phase change materials. This paves the way for the development of truly portable, electricity-free, point-of-care diagnostic tools, particularly advantageous for on-site detection in resource-limited remote settings and for home use.
Renal fibrosis is closely related to the prognosis of chronic kidney disease (CKD). The increase in cGMP reduces renal fibrosis. Soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) are key enzymes that maintain cGMP levels. BAY 41–8543 (1 mg/kg/day) and/or BAY 73–6691 (1 mg/kg/day) were used to treat 5/6 nephrectomized rats for 13 weeks. 5/6 Nephrectomy caused an increase in cystatin C, proteinuria and glomerulosclerosis and renal interstitial fibrosis. Neither sGC stimulation nor PDE9 inhibition alone improved kidney function and morphology, whereas BAY 41–8543 in combination with BAY 73–6691 attenuated renal interstitial fibrosis. This beneficial effect could not be explained by alterations in blood pressure and the renal immune system. BAY 41–8543 in combination with BAY 73–6691 had no effect on renal macrophage, CD4 + T‐cell and CD8 + T‐cell in the late‐stage of 5/6 nephrectomy. RNA sequencing revealed BAY 41–8543 in combination with BAY 73–6691 down‐regulated the expression of fibrosis‐related genes such as Collagen Type I Alpha 1, Collagen Type III Alpha 1 Chain and Collagen Type XIV Alpha 1 Chain. sGC stimulator combined with PDE9 inhibitor attenuated renal fibrosis in 5/6 nephrectomized rats by down‐regulating fibrosis‐related gene expression. This novel approach of using low‐dose combination therapies to minimize side effects while maintaining therapeutic efficacy offers a promising strategy for the treatment of CKD.
Background/Objective
Endoprostheses might fail due to complications such as implant loosening or periprosthetic infections. The surface topography of implant materials is known to influence osseointegration and attachment of pathogenic bacteria. Laser-Induced Periodic Surface Structures (LIPSS) can improve the surface topography of orthopedic implant materials. In this preclinical in vitro study, laser pulses with a wavelength in the ultraviolet (UV) spectrum were applied for the generation of LIPSS to positively influence formation of extracellular matrix by primary human Osteoblasts (hOBs) and to reduce microbial biofilm formation in vitro.
Methods
Laser machining was employed for generating UV-LIPSS on sample disks made of Ti6Al4V and Ti6Al7Nb alloys. Sample disks with polished surfaces were used as controls. Scanning electron microscopy was used for visualization of surface topography and adherent cells. Metal ion release and cellular metal levels were investigated by inductively coupled plasma mass spectrometry. Cell culture of hOBs on sample disks with and without UV-LIPSS surface treatments was performed. Cells were investigated for their viability, proliferation, osteogenic function and cytokine release. Biofilm formation was facilitated by seeding Staphylococcus aureus on sample disks and quantified by wheat germ agglutinin (WGA) staining.
Results
UV-LIPSS modification results in topographies with a periodicity of 223 nm ≤ λ ≤ 278 nm. The release of metal ions was found increased for UV-LIPSS on Ti6Al4V and decreased for UV-LIPSS on Ti6Al7Nb, while cellular metal levels remain unaffected. Cellular adherence was decreased for hOBs on UV-LIPSS Ti6Al4V when compared to controls while proliferation rate was unaffected. Metabolic activity was lower on UV-LIPSS Ti6Al7Nb when compared to the control. Alkaline phosphatase activity was upregulated for hOBs grown on UV-LIPSS on both alloys. Less pro-inflammatory cytokines were released for cells grown on UV-LIPSS Ti6Al7Nb when compared to polished surfaces. WGA signals were significantly lower on UV-LIPSS Ti6Al7Nb indicating reduced formation of a S. aureus biofilm.
Conclusion
Our results suggest that UV-LIPSS texturing of Ti6Al7Nb positively influence bone forming function and cytokine secretion profile of hOBs in vitro. In addition, our results indicate diminished biofilm formation on UV-LIPSS treated Ti6Al7Nb surfaces. These effects might prove beneficial in the context of long-term arthroplasty outcomes.
Alzheimer’s disease (AD), characterized by severe and progressive cognitive decline, stands as one of the most prevalent and devastating forms of dementia. Based on our recent findings showing intermittent hypoxic conditioning improved neuronal function in patients with mild cognitive impairment, the present study aimed at investigating whether the neuroprotective effects of intermittent hypoxia can be replicated in a rat model of AD, which allows us to explore the underlying cellular mechanisms involving neuroinflammation, hypoxia inducible factor 1α (HIF1α), and cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Forty-one adult male Wistar rats were randomly assigned to three groups: 1) Control group: received intracerebroventricular (ICV) injection of saline; 2) STZ group: received ICV injection of streptozotocin (STZ) to induce AD-like pathology; and 3) STZ + IHHT group received ICV injection of STZ as well as 15 daily sessions of intermittent hypoxia-hyperoxia training (IHHT). We observed that ICV injection of STZ inhibited spatial learning and memory in the rats assessed with Morris Water Maze test. The cognitive function declines were accompanied by increased expression of amyloid β peptide (Aβ), HIF1α, CYP2E1, and TNFα in hippocampus. Interestingly, IHHT significantly restored the STZ-induced cognitive dysfunction, while reduced expression of Aβ, CYP2E1, HIF1α and TNFα. We conclude that IHHT with mild hypoxia-hyperoxia can enhance spatial learning and memory and reduce the AD-like pathologic changes in rats. The neuroprotective outcome of IHHT may be related to anti-inflammatory effects in hippocampus. https://authors.elsevier.com/c/1k52~1aPVmQot
Introduction
Soluble guanylate cyclase (sGC) stimulators and activators are known to enhance kidney function in various models of chronic kidney disease (CKD) by increasing cyclic guanosine monophosphate (cGMP). Their differential effects on CKD progression, particularly under conditions of oxidative stress, remain unexplored by direct comparative studies.
Methods
We conducted a side-by-side comparison using 5/6 nephrectomized rats on a high salt diet (5/6Nx+HSD) to evaluate the efficacy of the sGC stimulator BAY 41–8543 and the sGC activator BAY 60–2770 in CKD progression. BAY 41–8543 (1 mg/kg; twice daily) and BAY 60–2770 (1 mg/kg; once daily) were administered by gavage for 11 weeks.
Results
The 5/6Nx+HSD model led to increased plasma creatinine, proteinuria, and blood pressure. Both BAY 41–8543 and BAY 60–2770 significantly reduced systolic and diastolic blood pressure to a similar extent but did not improve renal function parameters. Notably, BAY 60–2770 reduced renal fibrosis, including interstitial fibrosis and glomerulosclerosis, whereas BAY 41–8543 did not. These antifibrotic effects of BAY 60–2770 were independent of blood pressure reduction. Proteomic analysis revealed that BAY 60–2770 corrected the upregulation of 9 proteins associated with apoptosis and fibrosis, including Caspase-3, MKK6 (Mitogen-Activated Protein Kinase Kinase 6), Prdx5 (Peroxiredoxin-5), in the 5/6Nx+HSD group.
Discussion
In contrast, BAY 41–8543 had no significant impact on these proteins. sGC activators were more effective than sGC stimulators in reducing renal fibrosis in 5/6 nephrectomized rats on a high salt diet, and this effect was due to modulation of apoptosis-associated proteins beyond the control of blood pressure.
A stroma a‑reactive invasion front area (SARIFA) is a new prognostic biomarker in carcinomas. Essentially, SARIFA describes the occurrence of direct contact between at least five tumor cells and adipocytes. This phenomenon is extremely easy and quick to identify, shows an extremely low interobserver variability, and does not require any additional staining as it can be identified on standard HE sections. The prognostic efficiency has now been demonstrated in gastric, colorectal, pancreatic, and prostate carcinoma.
Der Fachkräftemangel macht auch vor dem Labor nicht halt: Es fehlen sowohl Medizinische Technolog:innen als auch Fachärzt:innen für Laboratoriumsmedizin sowie Naturwissenschaftler:innen. Hier sind innovative Ansätze gefragt, um das Fachgebiet Labormedizin zu stärken. Mitglieder der AG Junge Ärztinnen und Ärzte des ALM e. V. sowie der Sektion Junges Labor der DGKL beleuchten verschiedene Ansatzpunkte und werfen einen Blick in die Zukunft.
Die Welt wandelt sich. Waren bisher die Ingenieursdisziplinen in der führenden Rolle, so sind es im 21. Jahrhundert die Software-Unternehmen, die den Ton angeben. Diese Entwicklung spielt auch bei der Automation im medizinischen Labor eine entscheidende Rolle. Während die Hardware-Automationslösungen der unterschiedlichen Hersteller relativ vergleichbar arbeiten, unterscheiden sich die Softwarelösungen für das Labor (LIS, Middleware etc.) mitunter erheblich. Kann mehr und bessere Software einen Beitrag zur Linderung des Fachkräftemangels leisten?
Background: The increasing prevalence of obesity-related glomerulopathy (ORG) poses a significant threat to public health. Sodium-glucose co-transporter-2 (SGLT2) inhibitors effectively reduce body weight and total fat mass in obese individuals and halt the progression of ORG. However, the underlying mechanisms of their reno-protective effects in ORG remain unclear. Methods: We established a high-fat diet-induced ORG model using C57BL/6J mice, which were divided into three groups: normal chow diet (NCD group), high-fat diet (HFD) mice treated with placebo (ORG group), and HFD mice treated with Empagliflozin (EMPA group). We conducted 16S ribosomal RNA gene sequencing of feces and analyzed metabolites from kidney, feces, liver, and serum samples. Results: ORG mice showed increased urinary albumin creatinine ratio, cholesterol, triglyceride levels, and glomerular diameter compared to NCD mice (all P < 0.05). EMPA treatment significantly alleviated these parameters (all P < 0.05). Multi-tissue metabolomics analysis revealed lipid metabolic reprogramming in ORG mice, which was significantly altered by EMPA treatment. MetOrigin analysis showed a close association between EMPA-related lipid metabolic pathways and gut microbiota alterations, characterized by reduced abundances of Firmicutes and Desulfovibrio and increased abundance of Akkermansia (all P < 0.05). Conclusion: The metabolic homeostasis of ORG mice, especially in lipid metabolism, was disrupted and closely associated with gut microbiota alterations, contributing to the progression of ORG. EMPA treatment improved kidney function and morphology by regulating lipid metabolism through the gut-kidney axis, highlighting a novel therapeutic approach for ORG. Keywords: obesity-related glomerulopathy, microbiota, lipid metabolism, gut-kidney axis, empagliflozin
Background: This longitudinal prospective study aimed to assess orthodontic patients’ immune system response to metal ion release in saliva. Methods: Thirty adult patients (18–35 years) were equally divided into three groups: groups at the end (G1) and beginning (G2) of multibracket appliances (MBA) treatment and a non-treated control group (G3). Participants were evaluated at four timepoints within 21 days, with saliva samples being analyzed for metal ion concentrations and blood for the lymphocyte transformation test (LTT). Results: There were no significant differences between groups or timepoints for saliva. LTT analyses revealed hypersensitivity in one-third of all patients and 50% of G2 for nickel, with three developing sensitizations after MBA insertion. All nickel-sensitized patients exhibited varying elevated saliva nickel concentrations. The most nickel-sensitized patients had low ion saliva loads. In borderline nickel-sensitization cases, saliva ion concentrations were up to 20 times higher than the reference. Hypersensitivity to palladium, gold, and mercury was also observed. Conclusions: These findings indicate that increased MBA ion release was not inherently linked to the immune response (Type-IV sensitization), as reactions occurred even with ion levels below thresholds. This underlines the need for a comprehensive evaluation of the immune response to metal ion release in orthodontic patients.
Background/Objectives: We present a software package called reflimR (Version 1.0.6), which enables rapid and transparent verification of reference intervals from routine laboratory measurements. Our method makes it easy to compare the results with specified target values and facilitates the interpretation of deviations using traffic light colors. Methods: The algorithm includes three procedural steps: (a) definition of an appropriate distribution model, based on Bowley’s quartile skewness, (b) iterative truncation, based on a modified boxplot method to obtain the central 95% of presumably inconspicuous results, and (c) extrapolation of reference limits from a truncated normal quantile–quantile plot. Results: All algorithms have been combined into one consolidated library, which can be called in the R environment with a single command reflim (x). Using an example dataset included in the package, we demonstrate that our method can be applied to mixed data containing a substantial proportion of pathological values. It leads to similar results as the direct guideline approach as well as the more sophisticated indirect refineR software package. As compared to the latter, reflimR works much faster and needs smaller datasets for robust estimates. For the interpretation of the results, we present an intuitive color scheme based on tolerance ranges (permissible uncertainty of laboratory results). We show that a relatively high number of published reference limits require careful reevaluation. Conclusions: The reflimR package closes the gap between direct guideline methods and the more sophisticated indirect refineR method. We recommend reflimR for the rapid routine verification of large amounts of reference limits and refineR for a careful analysis of unclear or doubtful results from this check.
Parental genes can influence the phenotype of their offspring through genomic-epigenomic interactions even without the direct inheritance of specific parental genotypes. Maternal genetic variations can affect the ovarian and intrauterine environments and potentially alter lactation behaviors, impacting offspring nutrition and health outcomes independently of the fetal genome. Similarly, paternal genetic changes can affect the endocrine system and vascular functions in the testes, influencing sperm quality and seminal fluid composition. These changes can initiate early epigenetic modifications in sperm, including alterations in microRNAs, tRNA-derived small RNAs, and DNA methylation patterns. These epigenetic modifications might induce further changes in target organs of the offspring, leading to modified gene expression and phenotypic outcomes without transmitting the original parental genetic alterations. This review presents clinical evidence supporting this hypothesis and discusses the potential underlying molecular mechanisms. Parental gene-offspring epigenome-offspring phenotype interactions have been observed in neurocognitive disorders as well as cardio-renal diseases.
Introduction:
Osteoimmunology recognizes the relationship between bone cells and immune cells. Chronic osteoimmune dysregulation is present in bone marrow defects of the jaw (BMDJ) as fatty-degenerative osteonecrosis (FDOJ). In comparison to samples from healthy jaw bone, the cytokine analysis of samples of BMDJ/FDOJ from 128 patients showed downregulated TNF-α and IL-6 expression and the singular overexpression of the chemokine RANTES/CCL5.
Aim and objectives:
This paper raises the question of whether the osteoimmune defects due to incomplete wound healing in BMDJ/FDOJ in 128 patients are related to dysregulation of the Th1/Th2 ratio and regulatory T cell (T-reg) expression in a control group of 197 BMDJ/FDOJ patients, each presenting with BMDJ/FJOD and one of seven different immune disorders.
Material and methods:
In the control group, serum concentrations of the cytokines IFN-y and IL-4 were determined after stimulated cytokine release and displayed as Th1/Th2 ratios.
Results:
Data show a shift in Th2 in more than 80% (n = 167) of the control cohort of 197 chronically ill patients with concomitant BMDJ/FDOJ. In these 167 subjects, the Th1/Th2 ratio was <6.1 demonstrating impaired immune regulation. Forty-seven subjects or 30% showed not only a shift in Th2 but also excessive T-reg overactivation with levels of >1.900 pg/mL, indicating strongly downregulated immune activity.
Discussion:
BMDJ/FDOJ is characterized by a lack of Th1 cytokines and an excessive expression of RANTES/CCL5 and IL-1ra and, thus, the inversion of an acute inflammatory cytokine pattern. In contrast, abdominal fat contains a very high proportion of regulatory Th1 cells and produces an inflammatory immune response through the high overexpression of TNF-α and IL-6. The lack of Th1 activation in BMDJ/FDOJ areas inhibits normal wound healing and supports the persistence of BMDJ/FDOJ.
Conclusion:
The Th1/Th2 ratio requires greater consideration, especially with respect to wound healing following dental surgical interventions, such as jaw surgery, implantation and augmentation, to avoid the emergence of the osteoimmune situation that is characteristic of BMDJ/FDOJ.
Zusammenfassung
Kardiomyopathien sind eine der wesentlichen Ursachen einer progredienten Herzinsuffizienz. Aufgrund ihrer großen klinischen Relevanz sind neue Diagnoseverfahren von eminenter Bedeutung. Neben der häufigsten Ursache von Kardiomyopathien – myokardiale Entzündung und/oder Virusinfektion – können zahlreiche andere Faktoren wie metabolische, toxische, rheumatische, endokrine, infiltrative und genetische Faktoren an der Entstehung einer Herzmuskelerkrankung beteiligt sein. Da eine korrekte Diagnose mit nicht invasiven Methoden einschließlich moderner bildgebender Verfahren nicht möglich ist, stellt die Endomyokardbiopsie weiterhin den diagnostischen Goldstandard als Voraussetzung für eine kausale, spezifische und personalisierte Therapie dar.
Künstliche Intelligenz ist als Schlagwort aus dem öffentlichen Diskurs nicht mehr wegzudenken. Auch in der Laboratoriumsmedizin wird immer mehr zum Thema geforscht und es wird untersucht, wie man KI in der täglichen Routine einsetzen kann. Doch was ist eine Künstliche Intelligenz? Haben wir es hier tatsächlich mit Intelligenz zu tun? Dieser Beitrag erläutert theoretische und technische Grundlagen, die sich hinter dem viel bemühten Wort verbergen.
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