### Recent Submissions

• Journal Article

#### Ostarine and Ligandrol Improve Muscle Tissue in an Ovariectomized Rat Model ﻿

Frontiers in Endocrinology 2020; 11 p.1-12: Art. 556581
In postmenopausal women, hormonal decline changes muscle function and structure. The non-steroidal selective androgen receptor modulators (SARMs) Ostarine (OS) and Ligandrol (LG) have been shown to increase muscle mass and physical function while showing a relative low risk profile. Information about their effects on muscle structure and metabolism is lacking. To analyze this, two experiments were performed using ovariectomized rats as a standard model for postmenopausal conditions. In each experiment, 3-month old Sprague-Dawley rats were divided into five groups (n = 12 to 15). One group remained intact (Non-OVX), the other four groups were ovariectomized (OVX) and remained untreated for eight (OS Experiment) or nine (LG Experiment) weeks. Thereafter, rats of three of the four OVX groups were treated with OS or LG (with doses of 0.04, 0.4, or 4 mg/kg body weight/day) for 5 weeks. Then, uterus, gastrocnemius, and soleus muscles were weighed, fiber size, capillary density, and enzyme activity (lactate dehydrogenase [LDH], citrate synthase [CS], and complex I) were analyzed. In the LG experiment, intramuscular fat content was determined in the quadriceps femoris muscle. All OS treatments resulted in a higher capillary density in the gastrocnemius and longissimus muscles compared with the Non-OVX and the OVX rats, whereas all LG treatments showed a higher capillary density compared with the Non-OVX group. Muscle fiber size and distribution patterns were not changed under either SARM. The CS activity was higher in the longissimus muscle under OS treatment. LG resulted in a higher activity of CS in the gastrocnemius and of LDH in the longissimus muscle. Both SARMs showed an uterotrophic effect, OS at 4 and 0,4 mg dosages, LG at 4 mg dosage. In sum, beneficial effect on muscle vascularization was observed for both SARMs with a stronger impact for OS. LG showed more effect on muscle metabolism. However, a higher muscle weight and intramuscular fat content observed after LG treatment (4 mg) as well as an uterotrophic effect of both SARMs at higher dosages could be considered as an unfavorable side effects and might be a limitation for their application at these dosages.
• Journal Article

#### Critical Care Echocardiography as a Routine Procedure for the Detection and Early Treatment of Cardiac Pathologies ﻿

Diagnostics 2020; 10(9) p.1-12: Art. 671
Transthoracic and transesophageal echocardiography are important investigations in the intensive care unit (ICU) to diagnose acute cardiac pathologies and assess the haemodynamic status. Recommendations for critical care echocardiography (CCE) have been published recently, but these still lack an evidence-based foundation. It is not known if performing transthoracic echocardiography (TTE) on a routine basis instead of only when required in acute cases is feasible or clinically useful. In this single-centre prospective observational study, we routinely performed TTE on 111 consecutive non-cardiological, non-cardiothoracic surgical ICU patients in two surgical ICUs in a tertiary care facility. Significant cardiac pathologies were detected in 82 (76.6%) and critical cardiac pathologies in 33 (30.8%) of the 107 patients. The most common critical cardiac pathologies were sPAP > 50 mmHg (19.63%), tricuspid annular plane systolic excursion ≤ 13 mm (9.4%), grade III diastolic dysfunction (8.4%), severe tricuspid valve insufficiency (5.6%) and left ventricular ejection fraction (LV-EF) ˂ 30% (4.7%). Some of the most commonly found cardiac pathologies are not well emphasised in current recommendations and training programs. We observed a progression of the cardiac pathologies previously described in 41 of the patients (91.1%). Patients with echocardiographic abnormalities had a significant survival disadvantage in the ICU. By performing CCE routinely, we observed the range and prevalence of cardiac pathologies that can be detected by echocardiography in critically ill patients. We recommend routine transthoracic CCE in ICU patients for early detection of cardiac pathologies and to help inform early intervention regimens, since cardiac conditions carry a significant survival disadvantage for the ICU patient.
• Journal Article

#### Development and Technical Validation of an Immunoassay for the Detection of APP$_{669–711}$ (Aβ$_{−3–40}$) in Biological Samples ﻿

International Journal of Molecular Sciences 2020; 21(18) p.1-25: Art. 6564
The ratio of amyloid precursor protein (APP)$_{669–711}$ (Aβ$_{−3–40}$)/Aβ$_{1–42}$ in blood plasma was reported to represent a novel Alzheimer’s disease biomarker. Here, we describe the characterization of two antibodies against the N-terminus of Aβ$_{−3–x}$ and the development and “fit-for-purpose” technical validation of a sandwich immunoassay for the measurement of Aβ$_{−3–40}$. Antibody selectivity was assessed by capillary isoelectric focusing immunoassay, Western blot analysis, and immunohistochemistry. The analytical validation addressed assay range, repeatability, specificity, between-run variability, impact of pre-analytical sample handling procedures, assay interference, and analytical spike recoveries. Blood plasma was analyzed after Aβ immunoprecipitation by a two-step immunoassay procedure. Both monoclonal antibodies detected Aβ$_{−3–40}$ with no appreciable cross reactivity with Aβ$_{1–40}$ or N-terminally truncated Aβ variants. However, the amyloid precursor protein was also recognized. The immunoassay showed high selectivity for Aβ$_{−3–40}$ with a quantitative assay range of 22 pg/mL–7.5 ng/mL. Acceptable intermediate imprecision of the complete two-step immunoassay was reached after normalization. In a small clinical sample, the measured Aβ$_{42}$/Aβ$_{−3–40}$ and Aβ$_{42}$/Aβ$_{40}$ ratios were lower in patients with dementia of the Alzheimer’s type than in other dementias. In summary, the methodological groundwork for further optimization and future studies addressing the Aβ$_{42}$/Aβ$_{−3–40}$ ratio as a novel biomarker candidate for Alzheimer’s disease has been set.
• Journal Article

#### JCSM Rapid Communications: from basic science to clinical research ﻿

JCSM Rapid Communications 2020; 3(2) p.41-43
• Journal Article

#### In vivo Imaging With $^{18}$F-FDG- and $^{18}$F-Florbetaben-PET/MRI Detects Pathological Changes in the Brain of the Commonly Used 5XFAD Mouse Model of Alzheimer's Disease ﻿

Frontiers in Medicine 2020; 7 p.1-12: Art. 529
Imaging biomarkers of Alzheimer's disease (AD) that are able to detect molecular changes in vivo and transgenic animal models mimicking AD pathologies are essential for the evaluation of new therapeutic strategies. Positron-emission tomography (PET) using either $^{18}$F-Fluorodeoxyglucose ($^{18}$F-FDG) or amyloid-tracers is a well-established, non-invasive tool in the clinical diagnostics of AD assessing two major pathological hallmarks. $^{18}$F-FDG-PET is able to detect early changes in cerebral glucose metabolism and amyloid-PET shows cerebral amyloid load. However, the suitability of $^{18}$F-FDG- and amyloid-PET in the widely used 5XFAD mouse model of AD is unclear as only a few studies on the use of PET biomarkers are available showing some conflicting results. The aim of this study was the evaluation of $^{18}$F-FDG-PET and amyloid-PET in 5XFAD mice in comparison to neurological deficits and neuropathological changes. Seven- and 12-month-old male 5XFAD mice showed a significant reduction in brain glucose metabolism in $^{18}$F-FDG-PET and amyloid-PET with $^{18}$F-Florbetaben demonstrated an increased cerebral amyloid deposition (n = 4–6 per group). Deficits in spatial reference memory were detected in 12-month-old 5XFAD mice in the Morris Water Maze (n = 10–12 per group). Furthermore, an increased plaque load and gliosis could be proven immunohistochemically in 5XFAD mice (n = 4–6 per group). PET biomarkers $^{18}$F-FDG and $^{18}$F-Florbetaben detected cerebral hypometabolism and increased plaque load even before the onset of severe memory deficits. Therefore, the 5XFAD mouse model of AD is well-suited for in vivo monitoring of AD pathologies and longitudinal testing of new therapeutic approaches.
• Journal Article

#### Long-term opioid therapy for chronic noncancer pain: second update of the German guidelines ﻿

PAIN Reports 2020; 5(5) p.1-9: Art. e840
Introduction: The opioid epidemic in North America challenges national guidelines worldwide to define the importance of opioids for the management of chronic noncancer pain (CNCP). Methods: The second update of the German guidelines on long-term opioid therapy for CNCP was developed by 26 scientific associations and 2 patient self-help organizations. A systematic literature search in CENTRAL, Medline, and Scopus (to May 2019) was performed. Meta-analyses of randomized controlled trials and open-label extension studies with opioids for CNCP were conducted. Levels of evidence were assigned according to the Oxford Centre for Evidence-Based Medicine classification system. The formulation and strength of recommendations were established by multistep formalized procedures to reach a consensus according to German Association of the Medical Scientific Societies regulations. The guidelines underwent external review by 4 experts and public commentary. Results: Opioids are one drug-based treatment option for short- (4–12 weeks), intermediate- (13–26 weeks), and long-term (>26 weeks) therapy of chronic pain in osteoarthritis, diabetic polyneuropathy, postherpetic neuralgia, and low back pain. Contraindications are primary headaches, functional somatic syndromes, and mental disorders with the (cardinal) symptom of pain. For specified other clinical pain conditions, short- and long-term therapy with opioids should be evaluated on an individual basis. Long-term therapy with opioids is associated with relevant risks. Conclusion: Responsible application of opioids requires consideration of possible indications and contraindications, as well as regular assessment of clinical response and adverse effects. Neither uncritical opioid prescription nor general rejection of opioids is justified in patients with CNCP.
• Journal Article

#### Use of symptom-focused oncological cancer therapies in hospices: a retrospective analysis ﻿

BMC Palliative Care. 2020 Sep 12;19(1):140
Abstract Background There is controversy regarding the practical implementation of symptom-focused oncological cancer therapies to hospice residents. In this study, we aim to analyse the use and indication of supportive-oncological cancer therapies in hospices. Methods We conducted a retrospective survey of all residents of two hospice centres in the government district of Lower Bavaria, Germany. Hospice 1 (H1) was a member of an oncological–palliative medical network, and hospice 2 (H2) was independently organized. The evaluation period was the first 40 months after the opening of the respective hospice care centre. Demographical and epidemiological data as well as indications and type of supportive-oncological cancer therapies were recorded. A descriptive analysis and statistical tests were performed. Results Of the 706 residents, 645 had an underlying malignant disease. The average age was 72 years and the mean residence time was 28 days. The most frequent cancer types were gastrointestinal cancers, gynaecological cancers and bronchial carcinomas. Overall 39 residents (33 in H1 and 6 in H2, p < 0.01) received symptom-focused oncological cancer therapy. The average age of these residents was 68 years, and the mean residence time was 55 days. The most common therapeutic indications were dyspnoea and pain. The most common symptom-focused oncological cancer therapies were bisphosphonates, transfusions (erythrocyte- and platelet- concentrates), radiotherapy and anti-proliferative drugs (chemotherapy, anti-hormonal- and targeted- therapies). Patients with therapy lived significantly longer than patients without therapy (p < 0.01). Conclusions Symptom-focused oncological cancer therapies can be implemented in hospices; however, their implementation seems to require certain structural and organizational prerequisites as well as careful patient selection. As a palliative medical approach, the focus is to ameliorate the symptoms and not prolong life. Symptom-focused oncology treatment could be a further and important part for the therapy of hospice patients in the future.
• Journal Article

#### There is no intraocular affection on a SARS-CoV-2 - Infected ocular surface ﻿

American Journal of Ophthalmology Case Reports 2020; 20 p.1-2: Art. 100884
Purpose The presence of SARS-CoV-2 RNA in anterior chamber fluid and/or the vitreous in patients with SARS-CoV-2 RNA on the ocular surface is unclear. Knowledge about the infectious state of intraocular structures could influence the daily work of ophthalmic surgeons. Observations We analyzed ocular samples from a patient who had succumbed to COVID-19 pneumonia for the prevalence of SARS-CoV-2 RNA. We detected viral RNA in the ocular-surface samples on one swab and in one excidate from the conjunctiva. Samples from the anterior chamber and vitreous revealed no SARS-CoV-2 RNA. Conclusions SARS-CoV-2 can effectively be inactivated with standard disinfection agents. The now proven absence of SARS-CoV-2 in intraocular fluids could influence how ophthalmic surgeons work. Without having to account for the risk of a contagion via the anterior chamber and/or vitreous body, the surgical staff would require no additional, more elaborate protection.
• Journal Article

#### Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients ﻿

Journal of Neuroinflammation. 2020 Sep 03;17(1):261
Abstract Background New-generation cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD). Objective To describe systematically the CSF profile in MOG-EM. Material and methods Cytological and biochemical findings (including white cell counts and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgA/IgM fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster (MRZ) reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF l-lactate) from 163 lumbar punctures in 100 adult patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively. Results Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in almost 90% of samples (N = 151), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 62). If present, intrathecal IgG (and, more rarely, IgM) synthesis was low, often transient and mostly restricted to acute attacks. CSF WCC was elevated in > 50% of samples (median 31 cells/μl; mostly lymphocytes and monocytes; > 100/μl in 12%). Neutrophils were present in > 40% of samples; activated lymphocytes were found less frequently and eosinophils and/or plasma cells only very rarely (< 4%). Blood–CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 48% of all samples and at least once in 55% of all patients (N = 88) tested. The frequency and degree of CSF alterations were significantly higher in patients with acute myelitis than in patients with acute ON and varied strongly depending on attack severity. CSF l-lactate levels correlated significantly with the spinal cord lesion load in patients with acute myelitis (p < 0.0001). Like pleocytosis, blood–CSF barrier dysfunction was present also during remission in a substantial number of patients. Conclusion MOG-IgG-positive EM is characterized by CSF features that are distinct from those in MS. Our findings are important for the differential diagnosis of MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.
• Journal Article

#### Thoracic radiotherapy plus Durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy - employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy: study protocol of the TRADE-hypo trial ﻿

BMC Cancer. 2020 Aug 26;20(1):806
• Journal Article

#### Phenotypic Variability in a Coinfection With Three Independent Candida parapsilosis Lineages ﻿

Frontiers in Microbiology 2020; 11 p.1-10: Art. 1994
The human pathogenic yeast Candida parapsilosis has gained significant importance over the past decades as one of the principal causes of fungal bloodstream infections. Isolates of C. parapsilosis are known to be able to switch between several different colony morphologies in vitro, which are correlated with different cell shapes, altered cell surface properties, and thus different capacities to form biofilms on indwelling medical devices. In a set of six clinical specimens from a single surgery patient yielding stable smooth- as well as crepe-morphology isolates, we investigated the differences between five of them on a phenotypic and genomic level. In contrast to the initial assumption that they were switched forms of a clonal strain, karyotyping and genome sequencing showed that the patient was colonized by at least three distinct linages. Statistical analysis placed these groups distantly across the population of C. parapsilosis. Interestingly the single blood culture isolate was of smooth morphology and matched with an isolate from the patient’s nose of similar morphology. Strong variation between the isolates was seen in adhesin-encoding genes, where repeat regions showed significant variation in length and repeat-numbers, most strikingly in HWP$_1$ of the smooth isolates. Although no differences in drug susceptibility were evident, the high phylogenetic distance separating the individual strains highlights the need for testing of multiple colonies in routine practice. The absence of biofilm formation in the blood stream isolate indicates a lack of respective adhesins in the cell wall, in turn pointing toward lack of adhesion as a positively contributing factor for dissemination.
• Journal Article

#### A “groovy” diagnosis: Eosinophilic fasciitis ﻿

Clinical Case Reports 2020; 00 p.1-2
Clinical examination can be the key to pursuing a diagnosis, even in rare diseases. The “groove sign” is a typical finding in eosinophilic fasciitis and can be elicited by elevation of the arm to allow for venous return with visible “grooving” of the veins due to skin thickening.
• Journal Article

#### Inherited and Acquired Determinants of Hepatic CYP3A Activity in Humans ﻿

Frontiers in Genetics 2020; 11 p.1-13: Art. 944
Human CYP3A enzymes (including CYP3A4 and CYP4A5) metabolize about 40% of all drugs and numerous other environmental and endogenous substances. CYP3A activity is highly variable within and between humans. As a consequence, therapy with standard doses often results in too low or too high blood and tissue concentrations resulting in therapeutic failure or dose-related adverse reactions. It is an unanswered question how much of the big interindividual variation in CYP3A activity is caused by genetic or by environmental factors. This question can be answered by the twin study approach. Using midazolam as CYP3A probe drug, we studied 43 monozygotic and 14 dizygotic twins and measured midazolam and its metabolite 1-OH-midazolam. In addition, endogenous biomarkers of CYP3A activity, 4ß-OH-cholesterol and 6ß-OH-cortisol, were analyzed. Additive genetic effects accounted for only 15% of the variation in midazolam AUC, whereas 48% was attributed to common environmental factors. In contrast, 73, 56, and 31% of 1-OH-midazolam, 4ß-OH-cholesterol and 6ß-OH-cortisol variation was due to genetic effects. There was a low phenotypic correlation between the four CYP3A biomarkers. Only between midazolam and its 1-OH-metabolite, and between midazolam and 6ß-OH-cortisol we found significant bivariate genetic correlations. Midazolam AUC differed depending on the CYP3A4$^∗$22 variant (p = 0.001) whereas plasma 4ß-OH-cholesterol was significantly lower in homozygous carriers of CYP3A5$^∗$3 (p = 0.02). Apparently, non-genomic factors played a dominant role in the inter-individual variation of the CYP3A probe drug midazolam. A small intra-individual pharmacokinetic variation after repeated administration of midazolam was rated earlier as indication of high heritability of CYP3A activity, but according to present data that could also largely be due to constant environmental factors and/or heritability of liver blood flow. The higher heritabilities of 4ß-OH-cholesterol and of 1-OH-midazolam may deserve further research on the underlying factors beyond CYP3A genes.
• Journal Article

#### Cone-beam-computed-tomography of the symmetry of root canal anatomy in mandibular incisors ﻿

Journal of Oral Science 2020; 62(2) p.180-183
• Journal Article

#### Sensitivity of conventional radiographs and cone-beam computed tomography in detecting the remaining root-canal filling material ﻿

Journal of Oral Science 2020; 62(3) p.271-274
This study aimed to compare the sensitivity of radiographs and flat-panel volume-computed tomography (fpVCT) in detecting the remaining root-canal filling material. Thirty-two root canals in extracted human mandibular molars were prepared and obturated with gutta-percha and sealer. The filling material was removed, and the teeth were split longitudinally. Radiographs and fpVCT scans were obtained and digitized. Virtual images were developed using reconstruction software and then superimposed, and the remaining filling material was outlined. Direct observation of the split root halves using flatbed scans served as a control. The presence and extension of the remaining filling material were evaluated. Statistical analysis was conducted using chi-squared test (P < 0.05). A total of 116 remnants were detected in the flatbed scans, 81 in the fpVCT scans, and 90 in the radiographs, with no significant difference between the radiograph (78%) and fpVCT (70%) results (P = 0.18). In the fpVCT scans, 42% of the remnants exhibited the same dimensions as the control, whereas 27% appeared larger and 30% appeared smaller. In the radiographs, the dimensions of the remnants were identical to the control in 64% of cases, smaller in 29%, and larger in 7%. FpVCT did not exhibit better performance than dental radiographs in detecting the remaining root-canal-filling material: the extension of remnants was indicated correctly in the fpVCT in fewer than 50% of the samples.
• Journal Article

#### The kinesin motor Klp98A mediates apical to basal Wg transport ﻿

Development 2020; 147(15) p.1-15: Art. dev186833
Development and tissue homeostasis rely on the tight regulation of morphogen secretion. In the Drosophila wing imaginal disc epithelium, Wg secretion for long-range signal transduction occurs after apical Wg entry into the endosomal system, followed by secretory endosomal transport. Although Wg release appears to occur from the apical and basal cell sides, its exact post-endocytic fate and the functional relevance of polarized endosomal Wg trafficking are poorly understood. Here, we identify the kinesin-3 family member Klp98A as the master regulator of intracellular Wg transport after apical endocytosis. In the absence of Klp98A, functional mature endosomes accumulate in the apical cytosol, and endosome transport to the basal cytosol is perturbed. Despite the resulting Wg mislocalization, Wg signal transduction occurs normally. We conclude that transcytosis-independent routes for Wg trafficking exist and demonstrate that Wg can be recycled apically via Rab4-recycling endosomes in the absence of Klp98A.
• Journal Article

#### Quantification of Symptom Load by a Disease‐Specific Questionnaire HPQ 28 and Analysis of Associated Biochemical Parameters in Patients With Postsurgical Hypoparathyroidism ﻿

JBMR Plus 2020; 4(7) p.1-10: Art. e10368
In hypoparathyroidism (HypoPT), patients suffer severely from reduced quality of life. The complexity of HypoPT demands a disease‐specific control instrument to characterize symptom load. We employed a newly developed disease‐specific Hypoparathyroid Patient Questionnaire (the HPQ 40/28) to investigate and quantify HypoPT patients' complaints and contributing factors. In this cross‐sectional, two‐center study, patients with postsurgical HypoPT (n = 49) were matched for gender and age and compared with patients having undergone thyroid surgery without HypoPT (n = 39) and patients with primary hyperparathyroidism (n = 35). The HPQ 40/28 was completed when patients visited the respective center. Clinical background information, blood tests, and current medication were documented by the physician. Serum calcium lay within the reference range in 87% of HypoPT patients, serum phosphate in 95.7%, and calcium–phosphate product (CPP) in 100%. HPQ 40/28 scores for the scales “pain and cramps” (PaC), “neurovegetative symptoms” (NVS), “numbness or tingling,” and “heart palpitations” were significantly elevated in comparison with control groups. Correlations between complaints and laboratory parameters could be demonstrated in the HypoPT group, with serum calcium correlating with NVS (r = 0.309, p < 0.05) and serum phosphate with loss of vitality (r = 0.349, p < 0.05). CPP was the main contributor to symptom load with an influence on PaC (r = 0.295, p < 0.05), loss of vitality (r = 0.498, p < 0.001), numbness or tingling (r = 0.328, p < 0.05), and memory problems (r = 0.296, p < 0.05). In conclusion, the newly developed HPQ 40/28 successfully identified and quantified symptoms typical in HypoPT patients. Using the HPQ 40/28, the CPP was identified as the predominant factor in the severity of complaints in HypoPT.
• Journal Article

#### Antimicrobial Resistance Patterns in Clostridioides difficile Strains Isolated from Neonates in Germany ﻿

Antibiotics 2020; 9(8) p.1-7: Art. 481
Young children are frequently colonized with Clostridioides (C.) difficile. Depending on their resistance patterns, antibiotic treatment can facilitate gastrointestinal spreading in colonized individuals, potentially leading to transmission to others. C. difficile was isolated from stool samples from infants born in two hospitals in Göttingen and Darmstadt, Germany. All isolates were subjected to phenotypic antimicrobial resistance testing, PCR-based screening for toxin genes and mass spectrometry-based exclusion of ribotypes 027 and 176. Within an initial cohort of 324 neonates with a longitudinal survey of C. difficile, 137 strains were isolated from 48 individuals. Antimicrobial resistance was recorded against metronidazole in one (0.7%), erythromycin in 16 (11.7%) and moxifloxacin in 2 (1.5%) of the strains, whereas no resistance was observed against vancomycin (0.0%) or rifampicin (0.0%). Newly observed resistance against erythromycin in children with detection of previously completely sensitive isolates was reported for C. difficile isolates from 2 out of 48 children. In 20 children (42%), non-toxigenic strains were detected, and from 27 children (56%), toxigenic strains were isolated, while both toxigenic and non-toxigenic strains were recorded for 1 child (2%). Ribotypes 027 or 176 were not observed. In conclusion, the German C. difficile strains isolated from the children showed mild to moderate resistance with predominance of macrolide resistance, a substance class which is frequently applied in children. The observed switches to the dominance of macrolide-resistant isolates suggests likely selection of resistant C. difficile strains already in children.
• Journal Article

#### Case Report: The Role of Neuropsychological Assessment and Imaging Biomarkers in the Early Diagnosis of Lewy Body Dementia in a Patient With Major Depression and Prolonged Alcohol and Benzodiazepine Dependence ﻿

Frontiers in Psychiatry 2020; 11 p.1-8: Art. 684
Dementia with Lewy bodies (DLB) is the second most common form of dementia and is assumed to be often under- or misdiagnosed, especially in early stages. Here we present a complex case of probable DLB with major depression and alcohol and benzodiazepine dependence in which DLB was ruled out initially. This case highlights the challenging diagnostic workup of DLB patients. Core clinical features can be missing and indicative biomarkers can be negative, especially in early stages of the disease. Initially, Fluorodeoxyglucose positron emission tomography as well as neuropsychological assessment were suspicious for a possible DLB diagnosis in our patient while core clinical criteria were missing and the indicative biomarker 123I-FP-CIT SPECT was negative. Follow up was performed two years later and the patients showed several core and supportive clinical features of DLB and 123I-FP-CIT SPECT showed a pathological pattern. Extensive neuropsychological assessment in combination with PET imaging might provide crucial evidence for DLB even in early stages. If neuropsychology and PET imaging point to an early DLB diagnosis careful follow-up should be performed as core symptoms and indicative biomarkers might appear in later stages of the disease.
• Journal Article

#### Laser Ablated Periodic Nanostructures on Titanium and Steel Implants Influence Adhesion and Osteogenic Differentiation of Mesenchymal Stem Cells ﻿

Materials 2020; 13(16) p.1-16: Art. 3526
Metal implants used in trauma surgeries are sometimes difficult to remove after the completion of the healing process due to the strong integration with the bone tissue. Periodic surface micro- and nanostructures can directly influence cell adhesion and differentiation on metallic implant materials. However, the fabrication of such structures with classical lithographic methods is too slow and cost-intensive to be of practical relevance. Therefore, we used laser beam interference ablation structuring to systematically generate periodic nanostructures on titanium and steel plates. The newly developed laser process uses a special grating interferometer in combination with an industrial laser scanner and ultrashort pulse laser source, allowing for fast, precise, and cost-effective modification of metal surfaces in a single step process. A total of 30 different periodic topologies reaching from linear over crossed to complex crossed nanostructures with varying depths were generated on steel and titanium plates and tested in bone cell culture. Reduced cell adhesion was found for four different structure types, while cell morphology was influenced by two different structures. Furthermore, we observed impaired osteogenic differentiation for three structures, indicating reduced bone formation around the implant. This efficient way of surface structuring in combination with new insights about its influence on bone cells could lead to newly designed implant surfaces for trauma surgeries with reduced adhesion, resulting in faster removal times, reduced operation times, and reduced complication rates.