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Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma
(2016)
Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.
A range-wide synthesis and timeline for phylogeographic events in the red fox (Vulpes vulpes)
(2013)
Background: Many boreo-temperate mammals have a Pleistocene fossil record throughout Eurasia and North America, but only few have a contemporary distribution that spans this large area. Examples of Holarctic-distributed carnivores are the brown bear, grey wolf, and red fox, all three ecological generalists with large dispersal capacity and a high adaptive flexibility. While the two former have been examined extensively across their ranges, no phylogeographic study of the red fox has been conducted across its entire Holarctic range. Moreover, no study included samples from central Asia, leaving a large sampling gap in the middle of the Eurasian landmass.
Results: Here we provide the first mitochondrial DNA sequence data of red foxes from central Asia (Siberia), and new sequences from several European populations. In a range-wide synthesis of 729 red fox mitochondrial control region sequences, including 677 previously published and 52 newly obtained sequences, this manuscript describes the pattern and timing of major phylogeographic events in red foxes, using a Bayesian coalescence approach with multiple fossil tip and root calibration points. In a 335 bp alignment we found in total 175 unique haplotypes. All newly sequenced individuals belonged to the previously described Holarctic lineage. Our analyses confirmed the presence of three Nearctic- and two Japan-restricted lineages that were formed since the Mid/Late Pleistocene.
Conclusions: The phylogeographic history of red foxes is highly similar to that previously described for grey wolves and brown bears, indicating that climatic fluctuations and habitat changes since the Pleistocene had similar effects on these highly mobile generalist species. All three species originally diversified in Eurasia and later colonized North America and Japan. North American lineages persisted through the last glacial maximum south of the ice sheets, meeting more recent colonizers from Beringia during postglacial expansion into the northern Nearctic. Both brown bears and red foxes colonized Japan’s northern island Hokkaido at least three times, all lineages being most closely related to different mainland lineages. Red foxes, grey wolves, and brown bears thus represent an interesting case where species that occupy similar ecological niches also exhibit similar phylogeographic histories.
Diversity-oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS-compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)-catalyzed coupling of dithiols to diazo building blocks. The synthetized library was probed against metallo-β-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity.
Treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute leukemia (Ph+ ALL) has been revolutionized with the advent of tyrosine kinase inhibitors (TKIs). Most patients with CML achieve long-term survival similar to individuals without CML due to treatment with TKIs not only in frontline but also in further lines of therapy. The third-generation TKI ponatinib has demonstrated efficacy in patients with refractory CML and Ph+ ALL. Ponatinib is currently the most potent TKI in this setting demonstrating activity against T315I mutant clones. However, ponatinib’s safety data revealed a dose-dependent, increased risk of serious cardiovascular (CV) events. Guidance is needed to evaluate the benefit–risk profile of TKIs, such as ponatinib, and safety measures to prevent treatment-associated CV events. An expert panel of German hematologists and cardiologists summarize current evidence regarding ponatinib’s efficacy and CV safety profile. We propose CV management strategies for patients who are candidates for ponatinib.
Objective: To assess the influence of biphasic calcium phosphate materials with different surface topographies on bone formation and osseointegration of titanium implants in standardized alveolar ridge defects.
Materials and methods: Standardized alveolar ridge defects (6 × 6 mm) were created in the mandible of 8 minipigs and filled with three biphasic calcium phosphate materials (BCP1–3, 90% tricalcium phosphate/10% hydroxyapatite) with different surface properties (micro- and macroporosities) as well as a bovine-derived natural bone mineral (NBM) as a control. At 12 weeks, implants were placed into the augmented defects. After further 8 weeks of healing, dissected blocks were processed for histological analysis (e.g., mineralized (MT), residual bone graft material (BS), bone-to-implant contact (BIC)).
Results: All four biomaterials showed well-integrated graft particles and new bone formation within the defect area. MT values were comparable in all groups. BS values were highest in the NBM group (21.25 ± 13.52%) and markedly reduced in the different BCP groups, reaching statistical significance at BCP1-treated sites (9.2 ± 3.28%). All test and control groups investigated revealed comparable and statistically not significant different BIC values, ranging from 73.38 ± 20.5% (BCP2) to 84.11 ± 7.84% (BCP1), respectively.
Conclusion* All bone graft materials facilitated new bone formation and osseointegration after 12 + 8 weeks of healing.
Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in mice and other model organisms. Modifications of traditional gene trap cassettes, including addition of conditional features in the form of Flip-excision (FlEx) arrays to enable directional gene trap cassette inversions by Cre and Flpe site-specific recombinases, greatly enhanced their experimental potential. By taking advantage of these conditional gene trap cassettes, we developed a generic strategy for generating conditional mutations and validated this strategy in mice carrying a multipurpose allele of the Prdm16 transcription factor gene. We demonstrate that the gene trap insertion creates a null mutation replicating the Pierre Robin sequence-type cleft palate phenotype of other Prdm16 mutant mice. Consecutive breeding to Flpe and Emx1IREScre deleter mice spatially restricted Prdm16 loss to regions of the forebrain expressing the homeobox gene Emx1, demonstrating the utility of the technology for the analysis of tissue-specific gene functions.
Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.
Background & Aims: Phosphodiesterase‐5 inhibitors (PDE‐5‐I) are used for treatment of erectile dysfunction (ED), which is common in patients with cirrhosis. They may improve portal hypertension (PH), but contradictory data on efficacy and side‐effects have been reported. Non‐selective beta blockers (NSBB) reduce portal pressure, but might aggravate ED. Thus, we evaluated the combination of PDE‐5‐I with NSBB and its impact on PH and ED in experimental cirrhosis.
Methods: ED was assessed in cirrhotic patients (n = 86) using standardized questionnaire. Experimental cirrhosis was induced by bile‐duct‐ligation or carbon‐tetrachloride intoxication in rats. Corpus cavernosum pressure – a surrogate of ED ‐, as well as systemic and portal haemodynamics, were measured in vivo and in situ after acute administration of udenafil alone or in combination with propranolol. mRNA and protein levels of PDE‐5 signalling were analysed using PCR and western Blot.
Results: ED in humans was related to severity of liver disease and to NSBB treatment. PDE‐5 was mainly expressed in hepatic stellate cells and upregulated in human and experimental cirrhosis. Propranolol reduced corpus cavernosum pressure in cirrhotic rats and it was restored by udenafil. Even though udenafil treatment improved PH, it led to a reduction of mean arterial pressure. The combination of udenafil and propranolol reduced portal pressure and hepatic resistance without systemic side‐effects.
Conclusions: ED is common with advanced cirrhosis and concomitant NSBB treatment. The combination of PDE‐5‐I and NSBB improves ED and PH in experimental cirrhosis.
Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially,thedevelopmentoffibrosisandportalhypertensioninNAFLDpatientsrequirestreatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. Asexpected,WDinducedobesityandliverfibrosisasconfirmedbySiriusRedandOilRed O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increasedduringfeedingofWD,indicatinginfiltrationofmacrophagesintotheliver,eventhoughthis increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.
Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis
(2020)
Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.
Background: The present study aimed to assess the three‐dimensional changes following soft tissue augmentation using free gingival grafts (FGG) at implant sites over a 3‐month follow‐up period.
Methods: This study included 12 patients exhibiting deficient keratinized tissue (KT) width (i.e., <2 mm) at the vestibular aspect of 19 implants who underwent soft tissue augmentation using FGG at second stage surgery following implant placement. Twelve implants were considered for the statistical analysis (n = 12). The region of interest (ROI) was intraorally scanned before surgery (S0), immediately post‐surgery (S1), 30 (S2) and 90 (S3) days after augmentation. Digital scanned files were used for quantification of FGG surface area (SA) and converted to standard tessellation language (STL) format for superimposition and evaluation of thickness changes between the corresponding time points. FGG shrinkage (%) in terms of SA and thickness was calculated between the assessed time points.
Results: Mean FGG SA amounted to 91 (95% CI: 63 to 119), 76.2 (95% CI: 45 to 106), and 61.3 (95% CI: 41 to 81) mm2 at S1, S2, and S3, respectively. Mean FGG SA shrinkage rate was 16.3% (95% CI: 3 to 29) from S1 to S2 and 33% (95% CI: 19 to 46) from S1 to S3. Mean thickness gain from baseline (S0) to S1, S2, and S3 was 1.31 (95% CI: 1.2 to 1.4), 0.82 (95% CI: 0.5 to 1.12), and 0.37 (0.21 to 0.5) mm, respectively. FGG thickness shrinkage was of 38% (95% CI: 17.6 to 58) from S1 to S2 and 71.8% (95% CI: 60 to 84) from S1 to S3. Dimensional changes from S1 to S3 were statistically significant, P <0.017. Soft tissue healing was uneventful in all patients.
Conclusions: The present three‐dimensional assessment suggests that FGG undergo significant dimensional changes in SA and thickness over a 3‐month healing period.
Background: Recent advances in 3D printing technology have enabled the emergence of new educational and clinical tools for medical professionals. This study provides an exemplary description of the fabrication of 3D‐printed individualised patient models and assesses their educational value compared to cadaveric models in oral and maxillofacial surgery.
Methods: A single‐stage, controlled cohort study was conducted within the context of a curricular course. A patient's CT scan was segmented into a stereolithographic model and then printed using a fused filament 3D printer. These individualised patient models were implemented and compared against cadaveric models in a curricular oral surgery hands‐on course. Students evaluated both models using a validated questionnaire. Additionally, a cost analysis for both models was carried out. P‐values were calculated using the Mann‐Whitney U test.
Results: Thirty‐eight fourth‐year dental students participated in the study. Overall, significant differences between the two models were found in the student assessment. Whilst the cadaveric models achieved better results in the haptic feedback of the soft tissue, the 3D‐printed individualised patient models were regarded significantly more realistic with regard to the anatomical correctness, the degree of freedom of movement and the operative simulation. At 3.46 € (compared to 6.51 €), the 3D‐printed patient individualised models were exceptionally cost‐efficient.
Conclusions: 3D‐printed patient individualised models presented a realistic alternative to cadaveric models in the undergraduate training of operational skills in oral and maxillofacial surgery. Whilst the 3D‐printed individualised patient models received positive feedback from students, some aspects of the model leave room for improvement.
After removal of a dental implant or extraction of a tooth in the upper jaw, the closure of an oroantral fistula (OAF) or oroantral communication (OAC) can be a difficult problem confronting the dentist and surgeon working in the oral and maxillofacial region. Oroantral communication (OAC) acts as a pathological pathway for bacteria and can cause infection of the antrum, which further obstructs the healing process as it is an unnatural communication between the oral cavity and the maxillary sinus. There are different ways to perform the surgical closure of the OAC. The decision-making in closure of oroantral communication and fistula is influenced by many factors. Consequently, it requires a combination of knowledge, experience, and information gathering. Previous narrative research has focused on assessments and comparisons of various surgical techniques for the closure of OAC/OAF. Thus, the decision-making process has not yet been described comprehensively.
The present study aims to illustrate all the factors that have to be considered in the management of OACs and OAFs that determine optimal treatment.
Background and Objective: Macrophages’ cytokine expression and polarization play a substantial role in the host's “destructive” inflammatory response to periodontal and peri‐implant pathogens. This study aimed to evaluate cell viability, anti‐inflammatory activity, and macrophage polarization properties of different cranberry concentrates.
Methods: THP‐1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB‐G cell line), osteosarcoma‐derived osteoblasts (SAOS‐2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti‐inflammatory analysis, induced macrophages exposed to cranberry concentrates (A‐type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)‐8, IL‐1 ß, IL‐6, and IL‐10 expression of LPS‐stimulated macrophages, and macrophage polarization markers were evaluated through determination of live‐cell protease activity, enzyme‐linked immunosorbent assay, and immunofluorescence staining semi‐quantification.
Results: Cranberry concentrates (A‐type PACs) did not reduce HGF, SAOS‐2, and macrophage viability after 24 hours of exposure. Pro‐inflammatory cytokine expression (ie IL‐8 and IL‐6) was downregulated in LPS‐stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti‐inflammatory IL‐10 expression was significantly upregulated in LPS‐stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS‐stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS‐stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours.
Conclusion: Cranberry‐derived proanthocyanidins may have the potential to act as an anti‐inflammatory component in the therapy of periodontal and peri‐implant diseases.
The prevalence of peri-implant diseases around subcrestally placed implants: a cross-sectional study
(2021)
Objectives: To evaluate the prevalence of peri-implant health, peri-implant mucositis or periimplantitis for subcrestally placed implants (1–3 mm) on the short-, medium- and long term.
Material and Methods: Two hundred patients were enrolled in this cross-sectional study that were treated and screened during regular maintenance visits at one university center. A total of 657 implants were evaluated. Peri-implant health and diseases were assessed according to predefined case definitions. Binary logistic regression was used to assess the correlation with local and systemic factors.
Results: After a median function time of 9.36 ± 6.44 years (range: 1–26 years), the prevalence of peri-implant mucositis and peri-implantitis was 66.5% and 15.0%, at the patient level, corresponding to 62.6% and 7.5%, at the implant level, respectively. Peri-implantitis was significantly associated with patients’ history of periodontitis (odds ratio, OR 5.33).
Conclusion: Peri-implant diseases were a common finding around subcrestally placed implants.
Objectives: A conometric concept was recently introduced in which conical implant abutments hold the matching crown copings by friction alone, eliminating the need for cement or screws. The aim of this in vitro study was to assess the presence of microgap formation and bacterial leakage at the Acuris conometric restorative interface of three different implant abutment systems. Material and methods: A total of 75 Acuris samples of three implant-abutment systems (Ankylos, Astra Tech EV, Xive) were subjected to microbiological (n = 60) and scanning electron microscopic (SEM) investigation (n = 15). Bacterial migration into and out of the conical coupling system were analyzed in an anaerobic workstation for 48, 96, 144, and 192 h. Bacterial DNA quantification using qrt-PCR was performed at each time point. The precision of the conometric coupling and internal fit of cemented CAD/CAM crowns on corresponding Acuris TiN copings were determined by means of SEM. Results: qrt-PCR results failed to demonstrate microbial leakage from or into the Acuris system. SEM analysis revealed minute punctate microgaps at the apical aspect of the conometric junction (2.04 to 2.64 µm), while mean cement gaps of 12 to 145 µm were observed at the crown-coping interface. Conclusions: The prosthetic morse taper connection of all systems examined does not allow bacterial passage. Marginal integrity and internal luting gap between the ceramic crown and the coping remained within the clinically acceptable limits. Clinical relevance: Conometrically seated single crowns provide sufficient sealing efficiency, relocating potential misfits from the crown-abutment interface to the crown-coping interface.
Aims: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.
Methods and results: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.
Conclusion: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.
Background: Health care accessibility is known to differ geographically. With this study we focused on analysing accessibility of general and specialized obstetric units in England and Germany with regard to urbanity, area deprivation and neonatal outcome using routine data.
Methods: We used a floating catchment area method to measure obstetric care accessibility, the degree of urbanization (DEGURBA) to measure urbanity and the index of multiple deprivation to measure area deprivation.
Results: Accessibility of general obstetric units was significantly higher in Germany compared to England (accessibility index of 16.2 vs. 11.6; p < 0.001), whereas accessibility of specialized obstetric units was higher in England (accessibility index for highest level of care of 0.235 vs. 0.002; p < 0.001). We further demonstrated higher obstetric accessibility for people living in less deprived areas in Germany (r = − 0.31; p < 0.001) whereas no correlation was present in England. There were also urban–rural disparities present, with higher accessibility in urban areas in both countries (r = 0.37–0.39; p < 0.001). The analysis did not show that accessibility affected neonatal outcomes. Finally, our computer generated model for obstetric care provider demand in terms of birth counts showed a very strong correlation with actual birth counts at obstetric units (r = 0.91–0.95; p < 0.001).
Conclusion: In Germany the focus of obstetric care seemed to be put on general obstetric units leading to higher accessibility compared to England. Regarding specialized obstetric care the focus in Germany was put on high level units whereas in England obstetric care seems to be more balanced between the different levels of care with larger units on average leading to higher accessibility.
Objective: About 2% of all pregnancies are complicated by the implantation of the zygote outside the uterine cavity and termed ectopic pregnancy. Whereas a multitude of guidelines exists and related research is constantly growing, no thorough assessment of the global research architecture has been performed yet. Hence, we aim to assess the associated scientific activities in relation to geographical and chronological developments, existing research networks and socioeconomic parameters.
Design: Retrospective, descriptive study.
Setting: On the basis of the NewQIS platform, scientometric methods were combined with novel visualising techniques such as density-equalising mapping to assess the scientific output on ectopic pregnancy. Using the Web of Science, we identified all related entries from 1900 to 2012.
Results: 8040 publications were analysed. The USA and the UK were dominating the field in regard to overall research activity (2612 and 723 publications), overall citation numbers and country-specific H-Indices (US: 80, UK: 42). Comparison to economic power of the most productive countries demonstrated that Israel invested more resources in ectopic pregnancy-related research than other nations (853.41 ectopic pregnancy-specific publications per 1000 billlion US$ gross domestic product (GDP)), followed by the UK (269.97). Relation to the GDP per capita index revealed 49.3 ectopic pregnancy-specific publications per US$1000 GDP per capita for the USA in contrast to 17.31 for the UK. Semiqualitative indices such as country-specific citation rates ranked Switzerland first (24.7 citations per ectopic pregnancy-specific publication), followed by the Scandinavian countries Finland and Sweden. Low-income countries did not exhibit significant research activities.
Conclusions: This is the first in-depth analysis of global ectopic pregnancy research since 1900. It offers unique insights into the global scientific landscape. Besides the USA and the UK, Scandinavian countries and Switzerland can also be regarded as leading nations with regard to their relative socioeconomic input.
Smoking cigarettes throughout pregnancy is one of the single most important avoidable causes of adverse pregnancy outcomes and it represents the first major environmental risk of the unborn. If compared with other risk factors in the perinatal period, exposure to tobacco smoke is considered to be amongst the most harmful and it is associated with high rates of long and short term morbidity and mortality for mother and child. A variety of adverse pregnancy outcomes are linked with cigarette consumption before and during pregnancy. Maternal prenatal cigarette smoke disturbs the equilibrium among the oxidant and antioxidant system, has negative impact on the genetic and cellular level of both mother and fetus and causes a large quantity of diseases in the unborn child. These smoking-induced damages for the unborn offspring manifest themselves at various times in life and for most only a very limited range of causal treatment exists. Education, support and assistance are of high importance to decrease maternal and fetal morbidity and mortality, as there are few other avoidable factors which influence a child's health that profoundly throughout its life. It is imperative that smoking control should be seen as a public health priority.
Background: Despite the numerous associations of vitamin D with health and disease, vitamin D deficiency is still common from a global perspective. While basic research, clinical and preventive activities grow constantly in vitamin D research, there is no in-depth analysis of the related global scientific productivity available so far.
Methods: Density equalizing mapping procedures (DEMP) were combined with socioeconomic benchmarks using the NewQIS platform.
Results: A total of 25,992 vitamin D-related research articles were identified between 1900 to 2014 with a significant increase (r2 = .6541) from 1900 to 2014. Authors located in Northern America – especially in the USA – distributed the majority of global vitamin D research, followed by their Western European counterparts. DEMP-analysis illustrates that Africa and South America exhibit only minor scientific productivity. Among high-income group countries, Scandinavian nations such as Denmark or Finland (2147.9 and 1607.7 vitamin D articles per GDP in 1000 billion USD) were highly active with regard to socioeconomic figures.
Conclusion: Networks dedicated to vitamin D research are present around the world. Overall, the Northern American and Western European nations occupy prominent positions. However, South American, African and Asian countries apart from Japan only play a minor role in the global research production related to vitamin D. Since vitamin D deficiency is currently increasing in the Americas, Europe and parts of the Middle East, research in these regions may need to be encouraged.
Background: School attendance during the COVID-19 pandemic is intensely debated.
Aim: In November 2020, we assessed SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany.
Methods: We collected oro-nasopharyngeal swabs and blood samples, examining SARS-CoV-2 infection and IgG antibodies by RT-PCR and ELISA. Household members self-swabbed. We assessed individual and institutional prevention measures. Classes with SARS-CoV-2 infection and connected households were retested after 1 week.
Results: We examined 1,119 participants, including 177 primary and 175 secondary school students, 142 staff and 625 household members. SARS-CoV-2 infection occurred in eight classes, affecting each 1–2 individuals. Infection prevalence was 2.7% (95% confidence interval (CI): 1.2–5.0; 9/338), 1.4% (95% CI: 0.2–5.1; 2/140), and 2.3% (95% CI: 1.3–3.8; 14/611) among students, staff and household members. Six of nine infected students were asymptomatic at testing. We detected IgG antibodies in 2.0% (95%CI: 0.8–4.1; 7/347), 1.4% (95% CI: 0.2–5.0; 2/141) and 1.4% (95% CI: 0.6–2.7; 8/576). Prevalence increased with inconsistent facemask-use in school, walking to school, and case-contacts outside school. For three of nine households with infection(s), origin in school seemed possible. After 1 week, no school-related secondary infections appeared in affected classes; the attack rate in connected households was 1.1%.
Conclusion: School attendance under rigorously implemented preventive measures seems reasonable. Balancing risks and benefits of school closures need to consider possible spill-over infection into households. Deeper insight is required into the infection risks due to being a schoolchild vs attending school.
Background: School attendance during the SARS-CoV-2 pandemic is intensely debated. Modelling studies suggest that school closures contribute to community transmission reduction. However, data among school-attending students and staff are scarce. In November 2020, we examined SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany.
Methods: Students and school staff were examined, oro-nasopharyngeal swabs and blood samples collected, and SARS-CoV-2 infection and IgG antibodies detected by RT-PCR and ELISA. Household members performed self-swabs. Individual and institutional infection prevention and control measures were assessed. Classes with SARS-CoV-2 infection and connected household members were re-tested after one week.
Findings: 1119 participants were examined, including 177 primary and 175 secondary school students, 142 staff, and 625 household members. Participants reported mainly cold symptoms (19·4%). SARS-CoV-2 infection occurred in eight of 24 classes affecting each 1-2 individuals. Infection prevalence was 2·7% (95%CI; 1·2-5·0%; 9/338), 1·4% (0·2-5·1%; 2/140), and 2·3% (1·3-3·8%; 14/611) among students, staff and household members, respectively, including quarantined persons. Six of nine infected students were asymptomatic. Prevalence increased with inconsistent facemask use in school, way to school on foot, and case-contacts outside school. IgG antibodies were detected in 2·0% (0·8-4·1%; 7/347), 1·4% (0·2-5·0%; 2/141) and 1·4% (0·6-2·7%; 8/576), respectively. For three of nine households with infection(s) detected at cross-sectional assessment, origin in school seemed possible. After one week, no school-related, secondary infections appeared in affected classes; the attack rate in connected households was 1·1%.
Interpretation: These data suggest that school attendance under preventive measures is feasible, provided their rigorous implementation. In balancing threats and benefits of open versus closed schools during the pandemic, parents and society need to consider possible spill-overs into their households. Deeper insight is needed into the infection risks due to being a schoolchild as compared to attending school.
Wastewater-based epidemiology (WBE) has demonstrated its importance to support SARS-CoV-2 epidemiology complementing individual testing strategies. Due to their immune-evasive potential and the resulting significance for public health, close monitoring of SARS-CoV-2 variants of concern (VoC) is required to evaluate the regulation of early local countermeasures. In this study, we demonstrate a rapid workflow for wastewater-based early detection and monitoring of the newly emerging SARS-CoV-2 VoCs Omicron in the end of 2021 at the municipal wastewater treatment plant (WWTP) Emschermuendung (KLEM) in the Federal State of North-Rhine-Westphalia (NRW, Germany).
Initially, available primers detecting Omicron-related mutations were rapidly validated in a central laboratory. Subsequently, RT-qPCR analysis of purified SARS-CoV-2 RNA was performed in a decentral PCR laboratory in close proximity to KLEM. This decentralized approach enabled the early detection of K417N present in Omicron in samples collected on 8th December 2021 and the detection of further mutations (N501Y, Δ69/70) in subsequent biweekly sampling campaigns. The presence of Omicron in wastewater was confirmed by next generation sequencing (NGS) in a central laboratory with samples obtained on 14th December 2021. Moreover, the relative increase of the mutant fraction of Omicron was quantitatively monitored over time by dPCR in a central PCR laboratory starting on 12th December 2021 confirming Omicron as the dominant variant by the end of 2021.
In conclusions, WBE plays a crucial role in surveillance of SARS-CoV-2 variants and is suitable as an early warning system to identify variant emergence. In particular, the successive workflow using RT-qPCR, RT-dPCR and NGS demonstrates the strength of WBE as a versatile tool to monitor variant spreading.
Objectives: To assess and compare the efficacy and safety of autogenous tooth roots (TRs) and autogenous bone blocks (ABs) for combined vertical and horizontal alveolar ridge augmentation and two-stage implant placement.
Materials and Methods: A total of 28 patients in need of implant therapy and vertical ridge augmentation were allocated to parallel groups receiving either healthy autogenous tooth roots (e.g., retained wisdom teeth) (n = 14, n = 15 defects) or cortical autogenous bone blocks harvested from the retromolar area (n = 14, n = 17 defects). After 26 weeks of submerged healing, the clinical reduction in ridge height (RH) deficiency was defined as the primary outcome.
Results: Both surgical procedures were associated with a similar mean reduction in RH deficiency values, amounting to 4.48 ± 2.42 mm (median: 4.25; 95% CI: 3.08–5.88) in the TR group and 4.46 ± 3.31 mm (median: 3.00; 95% CI: 2.54–6.38) in the AB group (p = .60, Mann–Whitney U-test). In all patients investigated, the reduction in RH deficiency values allowed for an adequate implant placement at the respective sites. The frequency of complications (e.g., soft tissue dehiscences) was low (TR: n = 4; AB: n = 0).
Conclusions: Up to staged-implant placement, both TR and AB grafts appeared to be associated with comparable efficacy and safety for combined vertical and horizontal alveolar ridge augmentation.
Efficacy of platelet-rich fibrin in promoting the healing of extraction sockets: a systematic review
(2021)
Purpose: To address the focused question: in patients with freshly extracted teeth, what is the efficacy of platelet-rich fibrin (PRF) in the prevention of pain and the regeneration of soft tissue and bone compared to the respective control without PRF treatment?
Methods: After an electronic data search in PubMed database, the Web of Knowledge of Thomson Reuters and hand search in the relevant journals, a total of 20 randomized and/or controlled studies were included.
Results: 66.6% of the studies showed that PRF significantly reduced the postoperative pain, especially in the first 1–3 days after tooth extraction. Soft tissue healing was significantly improved in the group of PRF compared to the spontaneous wound healing after 1 week (75% of the evaluated studies). Dimensional bone loss was significantly lower in the PRF group compared to the spontaneous wound healing after 8–15 weeks but not after 6 months. Socket fill was in 85% of the studies significantly higher in the PRF group compared to the spontaneous wound healing.
Conclusions: Based on the analyzed studies, PRF is most effective in the early healing period of 2–3 months after tooth extraction. A longer healing period may not provide any benefits. The currently available data do not allow any statement regarding the long-term implant success in sockets treated with PRF or its combination with biomaterials. Due to the heterogeneity of the evaluated data no meta-analysis was performed.
Background & Aims: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients.
Methods: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort.
Results: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly.
Conclusions: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.
Wastewater-based SARS-CoV-2 epidemiology (WBE) has been established as an important tool to support individual testing strategies. The Omicron sub-variants BA.4/BA.5 have spread globally, displacing the preceding variants. Due to the severe transmissibility and immune escape potential of BA.4/BA.5, early monitoring was required to assess and implement countermeasures in time. In this study, we monitored the prevalence of SARS-CoV-2 BA.4/BA.5 at six municipal wastewater treatment plants (WWTPs) in the Federal State of North Rhine-Westphalia (NRW, Germany) in May and June 2022. Initially, L452R-specific primers/probes originally designed for SARS-CoV-2 Delta detection were validated using inactivated authentic viruses and evaluated for their suitability for detecting BA.4/BA.5. Subsequently, the assay was used for RT-qPCR analysis of RNA purified from wastewater obtained twice a week at six WWTPs. The occurrence of L452R carrying RNA was detected in early May 2022, and the presence of BA.4/BA.5 was confirmed by variant-specific single nucleotide polymorphism PCR (SNP-PCR) targeting E484A/F486V and NGS sequencing. Finally, the mutant fractions were quantitatively monitored by digital PCR, confirming BA.4/BA.5 as the majority variant by 5 June 2022. In conclusion, the successive workflow using RT-qPCR, variant-specific SNP-PCR, and RT-dPCR demonstrates the strength of WBE as a versatile tool to rapidly monitor variants spreading independently of individual test capacities.
Wastewater-based SARS-CoV-2 epidemiology (WBE) has been established as an important tool to support individual testing strategies. Omicron sub-variants BA.4/5 have spread globally displacing the predeceasing variants. Due to the severe transmissibility and immune escape potential of BA.4/5, early monitoring was required to asses and implement countermeasures in time.
In this study, we monitored the prevalence of SARS-CoV-2 BA.4/5 at six municipal wastewater treatment plants (WWTPs) in the Federal State of North-Rhine-Westphalia (NRW, Germany) in May and June 2022. Initially, L452R-specific primers/probes originally designed for SARS-CoV-2 Delta detection were validated using inactivated authentic viruses and evaluated for their suitability to detect BA.4/5. Subsequently, the assay was used for RT-qPCR analysis of RNA purified from wastewater obtained twice a week at six WWTPs. The occurrence of L452R carrying RNA was detected in early May 2022 and the presence of BA.4/5 was confirmed by variant-specific single nucleotide polymorphism PCR (SNP-PCR) targeting E484A/F486V. Finally, the mutant fractions were quantitatively monitored by digital PCR confirming BA.4/5 as the majority variant by 5th June 2022.
In conclusions, the successive workflow using RT-qPCR, variant-specific SNP-PCR, and RT-dPCR demonstrates the strength of WBE as a versatile tool to rapidly monitor variant spreading independent of individual test capacities.
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
Conclusion: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients
Background: Cirrhosis is known to have a high prevalence and mortality worldwide. However, in Europe, the epidemiology of cirrhosis is possibly undergoing demographic changes, and etiologies may have changed due to improvements in standard of care. The aim of this population-based study was to analyze the trends and the course of liver cirrhosis and its complications in recent years in Germany.
Methods: We analyzed the data of all hospital admissions in Germany within diagnosis-related groups from 2005 to 2018. The diagnostic records of cirrhosis and other categories of diseases were based on ICD-10-GM codes. The primary outcome measurement was in-hospital mortality. Trends were analyzed through Poisson regression of annual number of admissions. The impact of cirrhosis on overall in-hospital mortality were assessed through the multivariate multilevel logistic regression model adjusted for age, sex, and comorbidities.
Findings: Of the 248,085,936 admissions recorded between 2005 and 2018, a total of 2,302,171(0•94%) were admitted with the diagnosis of cirrhosis, mainly as a comorbidity. Compared with other chronic diseases, patients admitted with cirrhosis were younger, mainly male and had the highest in-hospital mortality rate. Diagnosis of cirrhosis was an independent risk factor of in-hospital mortality with the highest odds ratio (OR:6•2[95%CI:6.1-6•3]) among all diagnoses. The prevalence of non-alcoholic fatty liver disease has increased four times from 2005 to 2018, while alcoholic cirrhosis is 20 times than other etiologies. Bleeding was found to be decreasing over time, but ascites remained the most common complication and was increasing.
Interpretation: This nationwide study demonstrates that cirrhosis represents a considerable healthcare burden, as shown by the increasing in-hospital mortality, also in combination with other chronic diseases. Alcohol-related cirrhosis and complications are on the rise. More resources and better management strategies are warranted.
Einleitung: In dem vorliegenden Artikel wird die persönliche Studien- und Lebenssituation von Studierenden mit Kindern am Fachbereich Medizin der Goethe-Universität Frankfurt am Main beleuchtet. Der spezielle Fokus liegt auf den Themen "Studium mit Kind" sowie "familiengerechte Hochschule", welche in Deutschland in der letzten Dekade sehr präsent sowohl in der Hochschulforschung als auch im akademischen Alltag sind. Hier versucht die Arbeitsstelle "Individuelle Studienbegleitung" am FB Medizin der Goethe-Universität durch ein neues Beratungs- und Servicekonzept mit wissenschaftlicher Begleitforschung den individuellen Studienverläufen gerecht zu werden und den Studienerfolg zu fördern.
Methoden: In erster Linie stammen die hier beschriebenen Erfahrungen der Medizinstudierenden mit Kind aus qualitativen Leitfadeninterviews (Stand April 2010), die im Rahmen des Modellprojektes Teilzeitstudium Medizin durchgeführt wurden. Ergänzend wurden die Studienergebnisse des Fachbereichs Medizin der Goethe-Universität Frankfurt am Main herangezogen und eine Literaturanalyse einbezogen.
Ergebnisse: Als Ergebnis kann festgehalten werden, dass die bereits seit mehreren Jahren erhobenen Forderungen und gewünschten Unterstützungsleistungen zwar zum Teil umgesetzt, aber noch nicht ausreichend an allen Fachbereichen implementiert wurden. Somit ist die aktuelle Situation von Studierenden mit Kindern in der Medizin nach wie vor schwierig und stellt für alle Beteiligten eine große Herausforderung dar.
Lösungsansatz: Im Rahmen der Arbeitsstelle "Individuelle Studienbegleitung" konnte im November 2009 das "Modellprojekt Teilzeitstudium Medizin" aufgebaut werden. Nur durch neue, unkonventionelle und innovative Ideen kann man die Sicherstellung der medizinischen Ausbildung erreichen und die heutige heterogene Studierendenschaft adäquat ansprechen sowie Studierende erfolgreich durch ihr Studium begleiten.
Due to the increasingly heterogeneous trajectories of aging, gerontology requires theoretical models and empirical methods that can meaningfully, reliably, and precisely describe, explain, and predict causes and effects within the aging process, considering particular contexts and situations. Human behavior occurs in contexts; nevertheless, situational changes are often neglected in context-based behavior research. This article follows the tradition of environmental gerontology research based on Lawton’s Person-Environment-Interaction model (P-E model) and the theoretical developments of recent years. The authors discuss that, despite an explicit time component, current P-E models could be strengthened by focusing on detecting P-E interactions in various everyday situations. Enhancing Lawton’s original formula via a situationally based component not only changes the theoretical perspectives on the interplay between person and environment but also demands new data collection approaches in empirical environmental research. Those approaches are discussed through the example of collecting mobile data with smartphones. Future research should include the situational dimension to investigate the complex nature of person environment interactions.
RP1 (synonym: MAPRE2, EB2) is a member of the microtubule binding EB1 protein family, which interacts with APC, a key regulatory molecule in the Wnt signalling pathway. While the other EB1 proteins are well characterized the cellular function and regulation of RP1 remain speculative to date. However, recently RP1 has been implicated in pancreatic cancerogenesis. CK2 is a pleiotropic kinase involved in adhesion, proliferation and anti-apoptosis. Overexpression of protein kinase CK2 is a hallmark of many cancers and supports the malignant phenotype of tumor cells. In this study we investigate the interaction of protein kinase CK2 with RP1 and demonstrate that CK2 phosphorylates RP1 at Ser236 in vitro. Stable RP1 expression in cell lines leads to a significant cleavage and down-regulation of N-cadherin and impaired adhesion. Cells expressing a Phospho-mimicking point mutant RP1-ASP236 show a marked decrease of adhesion to endothelial cells under shear stress. Inversely, we found that the cells under shear stress downregulate endogenous RP1, most likely to improve cellular adhesion. Accordingly, when RP1 expression is suppressed by shRNA, cells lacking RP1 display significantly increased cell adherence to surfaces. In summary, RP1 phosphorylation at Ser236 by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association.
Memory Concerns, Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment
(2014)
Background: Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer's dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).
Methods: We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.
Results: Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.
Conclusions: Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.
Radiographic outcomes following lateral alveolar ridge augmentation using autogenous tooth roots
(2018)
Background: To assess and compare the radiographic outcomes following lateral alveolar ridge augmentation using autogenous tooth roots (TR) and autogenous bone (AB) blocks.
Methods: In a total of 30 patients, lateral ridge augmentation was conducted in parallel groups using either (1) healthy autogenous tooth roots (e.g., retained wisdom or impacted teeth) (n = 15) or (2) cortical autogenous bone blocks harvested from the retromolar area. Cone-beam computed tomographic (CBCT) scans taken at 26 weeks of submerged healing were analyzed for the basal graft integration (i.e., contact between the graft and the host bone in %) (BI26) and the cross-sectional grafted area (mm2) (SA26).
Results: Both groups revealed a comparable clinical width of the alveolar ridge at baseline (CWb). Mean BI26 and SA26 values amounted to 69.26 ± 26.01% (median 72.44) and 22.07 ± 12.98 mm2 (median 18.83) in the TR group and 79.67 ± 15.66% (median 78.85) and 12.42 ± 10.11 mm2 (median 11.36) in the AB group, respectively. Between-group differences in mean SA26 values were statistically significant (p = 0.031). Linear regression analysis failed to reveal any significant correlations between BI26 and CWb/SA26 values in either group.
Conclusions: TR grafts may be associated with improved SA26 values following lateral alveolar ridge augmentation.
Trial registration: DRKS00009586. Registered 10 February 2016.
An oroantral fistula (OAF) is a pathological abnormal communication between the oral cavity and the maxillary sinus which may arise as a result of failure of primary healing of an OAF, dental infections, osteomyelitis, radiation therapy, trauma, or iatrogenic complications. With the presence of a fistula, the maxillary sinus is permanently open. Microbial flora passes from the oral cavity into the maxillary sinus, and the inflammation of the sinus occurs with all potential consequences. In literature, various techniques have been proposed for closure of OAFs. Due to the heterogeneity of the data and techniques found, we opted for a narrative review to highlight the variety of techniques discussed in the literature. Techniques of particular interest include the bone sandwich with resorbable guided tissue regeneration (GTR) membrane and platelet-rich fibrin (PRF) used alone as both a clot and a membrane. The great advantage of these techniques is that no donor site surgery is necessary, making the outcome valuable in terms of time savings, cost and, more importantly, less discomfort to the patient. Additionally, both bony and soft tissue closure is performed for OAF, in contrast to flaps, which are typically used for procedures in the sinus area. The reconstructed bony tissue regenerated from these techniques will also be appropriate for endosseous dental implantation.
Objectives: To evaluate peri-implant tissue dimensions following nonsurgical (NS) and surgical therapy (S) employing different decontamination protocols of advanced ligature-induced peri-implantitis in dogs.
Material & Methods: Peri-implantitis defects (n = 5 dogs, n = 30 implants) were randomly and equally allocated in a split-mouth design to NS or S treatment using either an Er:YAG laser (ERL), an ultrasonic device (VUS), or plastic curettes + local application of metronidazole gel (PCM), respectively. Horizontal bone thickness (hBT) and soft tissue thickness (hMT) were measured at different reference points: (v0) at the marginal portion of the peri-implant mucosa (PM); (v1) at 50% of the distance from PM to bone crest (BC); (v2) at the BC; (v3) at the most coronal extension of the bone-to-implant contact. Vertical peri-implant tissue height was calculated from PM to BC.
Results: All of the treatment groups showed a gradual hMT increase from v0 to the v2 reference point, followed by a reduction from v2 to the v3 region. The S-VUS subgroup tended to be associated with higher hMT values at the v0 region than the NS-VUS subgroup (0.44 mm versus 0.31 mm). PM-BC distance varied from 2.22 to 2.83 mm in the NS group, and from 2.07 to 2.38 in the S group.
Conclusion: Vertical and horizontal peri-implant tissue dimensions were similar in different treatment groups.
Objectives: To assess the short‐term clinical outcomes of lateral augmentation of deficient extraction sockets and two‐stage implant placement using autogenous tooth roots (TR).
Material and methods: A total of n = 13 patients (13 implants) were available for the analysis. At the time of tooth extraction, each subject had received lateral augmentation using the respective non‐retainable but non‐infected tooth root where the thickness of the buccal bone was <0.5 mm or where a buccal dehiscence‐type defect was present. Titanium implants were placed after a submerged healing period of 6 months and loaded after 20 ± 2 weeks (V8). Clinical parameters (e.g., bleeding on probing—BOP, probing pocket depth—PD, mucosal recession—MR, clinical attachment level—CAL) were recorded at V8 and after 26 ± 4 weeks (V9) of implant loading.
Results: At V9, all patients investigated revealed non‐significant changes in mean BOP (−19.23 ± 35.32%), PD (0.24 ± 0.49 mm), MR (0.0 ± 0.0 mm) and CAL (0.24 ± 0.49 mm) values, respectively. There was no significant correlation between the initial gain in ridge width and changes in BOP and PD values.
Conclusions: The surgical procedure was associated with stable peri‐implant tissues on the short‐term.
Low-to-moderate quality meta-analytic evidence shows that motor control stabilisation exercise (MCE) is an effective treatment of non-specific low back pain. A possible approach to overcome the weaknesses of traditional meta-analyses would be that of a prospective meta-analyses. The aim of the present analysis was to generate high-quality evidence to support the view that motor control stabilisation exercises (MCE) lead to a reduction in pain intensity and disability in non-specific low back pain patients when compared to a control group. In this prospective meta-analysis and sensitivity multilevel meta-regression within the MiSpEx-Network, 18 randomized controlled study arms were included. Participants with non-specific low back pain were allocated to an intervention (individualized MCE, 12 weeks) or a control group (no additive exercise intervention). From each study site/arm, outcomes at baseline, 3 weeks, 12 weeks, and 6 months were pooled. The outcomes were current pain (NRS or VAS, 11 points scale), characteristic pain intensity, and subjective disability. A random effects meta-analysis model for continuous outcomes to display standardized mean differences between intervention and control was performed, followed by sensitivity multilevel meta-regressions. Overall, 2391 patients were randomized; 1976 (3 weeks, short-term), 1740 (12 weeks, intermediate), and 1560 (6 months, sustainability) participants were included in the meta-analyses. In the short-term, intermediate and sustainability, moderate-to-high quality evidence indicated that MCE has a larger effect on current pain (SMD = −0.15, −0.15, −0.19), pain intensity (SMD = −0.19, −0.26, −0.26) and disability (SMD = −0.15, −0.27, −0.25) compared with no exercise intervention. Low-quality evidence suggested that those patients with comparably intermediate current pain and older patients may profit the most from MCE. Motor control stabilisation exercise is an effective treatment for non-specific low back pain. Sub-clinical intermediate pain and middle-aged patients may profit the most from this intervention.
Treatment‐related complications contribute substantially to morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Although AML patients are susceptible to fluid overload (FO) (e.g., in the context of chemotherapy protocols, during sepsis treatment or to prevent tumor lysis syndrome), little attention has been paid to its role in AML patients undergoing induction chemotherapy. AML patients receiving induction chemotherapy between 2014 and 2019 were included in this study. FO was defined as ≥5% weight gain on day 7 of induction chemotherapy compared to baseline weight determined on the day of admission. We found FO in 23 (12%) of 187 AML patients undergoing induction chemotherapy. Application of >100 ml crystalloid fluids/kg body weight until day 7 of induction chemotherapy was identified as an independent risk factor for FO. AML patients with FO suffered from a significantly increased 90-day mortality rate and FO was demonstrated as an independent risk factor for 90-day mortality. Our data suggests an individualized, weight-adjusted calculation of crystalloid fluids in order to prevent FO-related morbidity and mortality in AML patients during induction chemotherapy. Prospective trials are required to determine the adequate fluid management in this patient population.
Wastewater-based SARS-CoV-2 epidemiology (WBE) has been established as an important tool to support individual testing strategies. Omicron sub-variants BA.4/5 have spread globally displacing the predeceasing variants. Due to the severe transmissibility and immune escape potential of BA.4/5, early monitoring was required to asses and implement countermeasures in time.
In this study, we monitored the prevalence of SARS-CoV-2 BA.4/5 at six municipal wastewater treatment plants (WWTPs) in the Federal State of North-Rhine-Westphalia (NRW, Germany) in May and June 2022. Initially, L452R-specific primers/probes originally designed for SARS-CoV-2 Delta detection were validated using inactivated authentic viruses and evaluated for their suitability to detect BA.4/5. Subsequently, the assay was used for RT-qPCR analysis of RNA purified from wastewater obtained twice a week at six WWTPs. The occurrence of L452R carrying RNA was detected in early May 2022 and the presence of BA.4/5 was confirmed by variant-specific single nucleotide polymorphism PCR (SNP-PCR) targeting E484A/F486V. Finally, the mutant fractions were quantitatively monitored by digital PCR confirming BA.4/5 as the majority variant by 5th June 2022.
In conclusions, the successive workflow using RT-qPCR, variant-specific SNP-PCR, and RT-dPCR demonstrates the strength of WBE as a versatile tool to rapidly monitor variant spreading independent of individual test capacities.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
The growth of aerosol due to the aqueous phase oxidation of sulfur dioxide by ozone was measured in laboratory-generated clouds created in the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN). Experiments were performed at 10 and −10 °C, on acidic (sulfuric acid) and on partially to fully neutralised (ammonium sulfate) seed aerosol. Clouds were generated by performing an adiabatic expansion – pressurising the chamber to 220 hPa above atmospheric pressure, and then rapidly releasing the excess pressure, resulting in a cooling, condensation of water on the aerosol and a cloud lifetime of approximately 6 min. A model was developed to compare the observed aerosol growth with that predicted using oxidation rate constants previously measured in bulk solutions. The model captured the measured aerosol growth very well for experiments performed at 10 and −10 °C, indicating that, in contrast to some previous studies, the oxidation rates of SO2 in a dispersed aqueous system can be well represented by using accepted rate constants, based on bulk measurements. To the best of our knowledge, these are the first laboratory-based measurements of aqueous phase oxidation in a dispersed, super-cooled population of droplets. The measurements are therefore important in confirming that the extrapolation of currently accepted reaction rate constants to temperatures below 0 °C is correct.
The growth of aerosol due to the aqueous phase oxidation of sulfur dioxide by ozone was measured in laboratory-generated clouds created in the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN). Experiments were performed at 10 and −10 °C, on acidic (sulfuric acid) and on partially to fully neutralised (ammonium sulfate) seed aerosol. Clouds were generated by performing an adiabatic expansion – pressurising the chamber to 220 hPa above atmospheric pressure, and then rapidly releasing the excess pressure, resulting in a cooling, condensation of water on the aerosol and a cloud lifetime of approximately 6 min. A model was developed to compare the observed aerosol growth with that predicted using oxidation rate constants previously measured in bulk solutions. The model captured the measured aerosol growth very well for experiments performed at 10 and −10 °C, indicating that, in contrast to some previous studies, the oxidation rates of SO2 in a dispersed aqueous system can be well represented by using accepted rate constants, based on bulk measurements. To the best of our knowledge, these are the first laboratory-based measurements of aqueous phase oxidation in a dispersed, super-cooled population of droplets. The measurements are therefore important in confirming that the extrapolation of currently accepted reaction rate constants to temperatures below 0 °C is correct.
Objective: The aim of this study was to evaluate and compare the efficacy of single-treatment cooled and uncooled microwave ablation in thyroid nodules.
Methods: Eighteen patients (11 women) with an average age of 62 years (range: 41–80) with 18 cold, mainly solid or solid thyroid nodules were treated with cooled or uncooled microwave ablation. Pain during the treatment was measured on a 10-point score. Side effects revealed by ultrasound or patients’ complaints were documented. Laboratory data was evaluated before, 24 h and three months after MWA. Nodule volumes were measured before and three months after MWA.
Results: Cooled MWA was better tolerated than uncooled MWA. A significant reduction of thyroid nodule volume was observed in all cases. The reduction after cMWA was higher (40%) than after uMWA (29%). Pain intensity during cMWA was significantly lower than after uMWA. CMWA and uMWA led to a significant decrease of nodule blood circulation and echogenicity and to a significant increase of nodule elasticity. Thyroid function remained intact in all cases. The energy (kJ/s) administered into the nodules in relation to the ablation time during cMWA was higher than during uMWA.
Conclusions: CMWA leads to a slightly higher but statistically not significant nodule volume reduction than uMWA. Patient comfort during cMWA is higher than during uMWA. The risk of unintended side effects is less in cMWA. A Single-treatment provides sufficient results.