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Abstract Root exudates contain specialised metabolites that shape the plant’s root microbiome. How host-specific microbes cope with these bioactive compounds, and how this ability affects root microbiomes, remains largely unknown. We investigated how maize root bacteria metabolise benzoxazinoids, the main specialised metabolites of maize. Diverse and abundant bacteria metabolised the major compound in the maize rhizosphere MBOA (6-methoxybenzoxazolin-2(3H)-one) and formed AMPO (2-amino-7-methoxy-phenoxazin-3-one). AMPO forming bacteria were enriched in the rhizosphere of benzoxazinoid-producing maize and could use MBOA as carbon source. We identified a gene cluster associated with AMPO formation in microbacteria. The first gene in this cluster, bxdA encodes a lactonase that converts MBOA to AMPO in vitro. A deletion mutant of the homologous bxdA genes in the genus Sphingobium, did not form AMPO nor was it able to use MBOA as a carbon source. BxdA was identified in different genera of maize root bacteria. Here we show that plant-specialised metabolites select for metabolisation-competent root bacteria. BxdA represents a benzoxazinoid metabolisation gene whose carriers successfully colonize the maize rhizosphere and thereby shape the plant’s chemical environmental footprint.

Abstract Background Managing genetic diversity is critically important for maintaining species fitness. Excessive homozygosity caused by the loss of genetic diversity can have detrimental effects on the reproduction and production performance of a breed. Analysis of genetic diversity can facilitate the identification of signatures of selection which may contribute to the specific characteristics regarding the health, production and physical appearance of a breed or population. In this study, breeds with well-characterized traits such as fine wool production (Rambouillet, N = 745), parasite resistance (Katahdin, N = 581) and environmental hardiness (Dorper, N = 265) were evaluated for inbreeding, effective population size (N e ), runs of homozygosity (ROH) and Wright’s fixation index (FST) outlier approach to identify differential signatures of selection at 36,113 autosomal single nucleotide polymorphisms (SNPs). Results Katahdin sheep had the largest current N e at the most recent generation estimated with both the GONe and NeEstimator software. The most highly conserved ROH Island was identified in Rambouillet with a signature of selection on chromosome 6 containing 202 SNPs called in an ROH in 50 to 94% of the individuals. This region contained the DCAF16, LCORL and NCAPG genes that have been previously reported to be under selection and have biological roles related to milk production and growth traits. The outlier regions identified through the FST comparisons of Katahdin with Rambouillet and Dorper contained genes with known roles in milk production and mastitis resistance or susceptibility, and the FST comparisons of Rambouillet with Katahdin and Dorper identified genes related to wool growth, suggesting these traits have been under natural or artificial selection pressure in these populations. Genes involved in the cytokine-cytokine receptor interaction pathways were identified in all FST breed comparisons, which indicates the presence of allelic diversity between these breeds in genomic regions controlling cytokine signaling mechanisms. Conclusions In this paper, we describe signatures of selection within diverse and economically important U.S. sheep breeds. The genes contained within these signatures are proposed for further study to understand their relevance to biological traits and improve understanding of breed diversity.

Johann Lechner,1 Volker von Baehr,2 Florian Notter,1 Fabian Schick1 1Clinic for Integrative Dentistry, Munich, Germany; 2Department of Immunology and Allergology, Institute for Medical Diagnostics, Berlin, GermanyCorrespondence: Johann Lechner, Gruenwalder Str. 10A, Munich, 81547, Germany, Tel +49 89 697 0129, Fax +49 89 692 5830, Email drlechner@aol.comIntroduction: Osteoimmunology recognizes the relationship between bone cells and immune cells. Chronic osteoimmune dysregulation is present in bone marrow defects of the jaw (BMDJ) as fatty-degenerative osteonecrosis (FDOJ). In comparison to samples from healthy jaw bone, the cytokine analysis of samples of BMDJ/FDOJ from 128 patients showed downregulated TNF-α and IL-6 expression and the singular overexpression of the chemokine RANTES/CCL5.Aim and Objectives: This paper raises the question of whether the osteoimmune defects due to incomplete wound healing in BMDJ/FDOJ in 128 patients are related to dysregulation of the Th1/Th2 ratio and regulatory T cell (T-reg) expression in a control group of 197 BMDJ/FDOJ patients, each presenting with BMDJ/FJOD and one of seven different immune disorders.Material and Methods: In the control group, serum concentrations of the cytokines IFN-y and IL-4 were determined after stimulated cytokine release and displayed as Th1/Th2 ratios.Results: Data show a shift in Th2 in more than 80% (n = 167) of the control cohort of 197 chronically ill patients with concomitant BMDJ/FDOJ. In these 167 subjects, the Th1/Th2 ratio was < 6.1 demonstrating impaired immune regulation. Forty-seven subjects or 30% showed not only a shift in Th2 but also excessive T-reg overactivation with levels of > 1.900 pg/mL, indicating strongly downregulated immune activity.Discussion: BMDJ/FDOJ is characterized by a lack of Th1 cytokines and an excessive expression of RANTES/CCL5 and IL-1ra and, thus, the inversion of an acute inflammatory cytokine pattern. In contrast, abdominal fat contains a very high proportion of regulatory Th1 cells and produces an inflammatory immune response through the high overexpression of TNF-α and IL-6. The lack of Th1 activation in BMDJ/FDOJ areas inhibits normal wound healing and supports the persistence of BMDJ/FDOJ.Conclusion: The Th1/Th2 ratio requires greater consideration, especially with respect to wound healing following dental surgical interventions, such as jaw surgery, implantation and augmentation, to avoid the emergence of the osteoimmune situation that is characteristic of BMDJ/FDOJ. Keywords: osteoimmunology, T-cells, Th1/Th2 shift, jawbone, osteoclastogenesis, RANTES/CCL5

We present a review of the latest framework achievements in geoarchaeological sciences applied to microstratigraphic and biomolecular studies of prehistoric archaeological contexts, highlighting the importance of musealized archaeological stratigraphies. We assess how today's scientific and technological accomplishments can be tailored for archaeological human ecology studies with analytical ensembles that provide unprecedented results. Sampling and processing workflows originating from resin consolidation and thin section micromorphology of undisturbed blocks of archaeological soils and sediments, guarantee subsampling accuracy at the micrometre scale granting access to individual components otherwise impossible to target: the achievable information yield makes even the smallest soil samples potential sources of pioneering discoveries. Yet, archaeological excavations are still the primary mode of retrieving new soil samples. We argue that, when dealing with archaeological sites that were excavated and partially musealised in the past, the exploration of related museum collections should be prioritized as perspective source of new study samples. Analysing old and potentially very informative samples, with an approach that we define as “Green Archaeology”, may represent a source of well-structured primary data as well as a means for planning new excavations, delivering novel discoveries while safeguarding site integrity and promoting Third Mission valorisation of sites and heritage dormant collections.

The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants. Of these pairs, 12 were found to have an effect on VL. Furthermore, 28/58 pairs were validated by time-to-event analyses and 48/92 by computational HLA-epitope predictions. Our diversity-based approach allows a powerful and systematic investigation of the interaction between the virus and cellular immunity, revealing a notable subset of such interaction effects. From an evolutionary perspective, these observations underscore the complexity of HLA-mediated selection pressures on the virus that shape viral evolution and pathogenesis.

Infections with Campylobacter species mainly cause gastrointestinal disease and are usually self-limiting. Systemic complications such as bacteremia and osteoarticular infections are rare. Here we report a very rare case of a vertebral osteomyelitis due to C. jejuni, and we reviewed the literature for similar cases, identifying six other cases. Therapy should be guided on resistance testing if available due to emerging resistance rates, especially to fluoroquinolones. Azithromycin may be a treatment option for C. jejuni spondylodiscitis.

Joana Vasconcelos e Cruz,1,2 Florian Notter,3 Fabian Schick,3 Johann Lechner4 1Dental Materials, Egas Moniz School of Health & Science, Caparica, Portugal; 2Dental Materials, Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Caparica, Portugal; 3Dental Surgeon, Clinic for Integrative Dentistry, Munich, Germany; 4Head, Clinic for Integrative Dentistry, Munich, GermanyCorrespondence: Johann Lechner, Gruenwalder Str. 10A, Munich, 81547, Germany, Tel +49 89 697 0129, Fax +49 89 692 5830, Email drlechner@aol.comBackground: Apical periodontitis (AP) is one of the most common endodontic diseases associated with osteo destructive cytokine production. The literature also reports cytokine studies in fatty degenerative osteonecrotic bone marrow defects (BMDJ/FDOJ) independent of AP.Objective: We compare the RANTES/CCL5 (R/C) chemokine production between AP and BMDJ/FDOJ. For both pathologies, the R/C expression was also compared to radiographic diagnosis in 2D-OPG, 3D-CBCT/DVT.Material and Methods: Postoperative samples were collected and divided in three different groups: HB (healthy jawbone) (n=19), APs (n=19), and BMDJ/FDOJ (n=7). The R/C expression was evaluated using multiplex analysis. In addition, two clinical cases from AP and BMDJ/FDOJ groups were randomly selected and radiographic diagnosis in 2D-OPG and 3D-CBCT/DVT was compared to TAU measurements and R/C expression in AP and in BMDJ/FDOJ.Results: BMDJ/FDOJ showed the highest R/C expression (2498.71 pg/mL), followed by AP (841.85 pg/mL) and HB (149.85 pg/mL) (AP vs BMDJ/FDOJ = p=0.01; AP vs HB = p=< 0.01; BMDJ/FDOJ vs HB = p=< 0.01). In both clinical cases, the radiographic findings depict the AP areas in OPG and CBCT/DVT, in contrast to the BMDJ/FDOJ areas. Conversely, the systemic immunological R/C expressions are threefold and fivefold excessive in both cases.Discussion: AP is recognized as a pathology requiring treatment, while the pathogenesis of BMDJ/FDOJ is controversially discussed in the literature, despite stronger potential systemic immunological effects (breast cancer (case 1) and multiple sclerosis (case 2)). The inadequate radiographic representation of reduced bone density in BMDJ/FDOJ areas could be a reason for this contradiction.Conclusion: The data presented provide the first quantitative analysis of R/C expression in AP and BMDJ/FDOJ. BMDJ/FDOJ showed high R/C expression than AP, besides the diagnostic through radiographs being extremely poor. To cover this imprecision, a radiation-free TAU device is available. Keywords: bone marrow, RANTES/CCL5, apical periodontitis, osteonecrosis, dental radiography, ultrasonography

AbstractPurpose To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials.Methods In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT.Results We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40–43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry.Discussion There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects.Conclusions The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Many people use satellite images in their professional and everyday lives, and school curricula often require their use. Yet, the ways teachers actually use satellite images in the classroom is often limited, if they use them at all. The YCHANGE project trained teachers to use remote sensing data by themselves and to use it in their classrooms. The project partners created a remote sensing curriculum which suggests how teachers can develop their students' skills in this area of geography. This curriculum is based on existing research and school curricula. The project partners created and published sample learning units, and the project webpage also offered the possibility for teachers to publish student-created projects. YCHANGE training event participants in Switzerland and Germany filled out an online survey. Most participants said they improved their ability to read satellite images and use them in the classroom. However, participants' evaluation of the YCHANGE materials and training events was mixed. The study shows some differences among the Swiss language regions, and significant differences between Germany and Switzerland. For example, our training events introduced the participants to the web application BLIF. On average, the German participants liked BLIF, but the participants in Switzerland rated BLIF significantly worse. We therefore recommend that future research compare remote sensing, as well as other areas of geography education, among different countries and language regions.

Objective Bone marrow defects of the jaw (BMDJ) surrounding dental implants, in combination with impaired bone-to-implant contact (BIC), are difficult to detect in X-rays. This study evaluated BMDJ surrounding titanium (Ti-Impl) and ceramic (Cer-Impl) dental implants and incomplete BIC using a new trans-alveolar ultrasonography device (TAU) with numerical scaling for BIC. Methods The titanium stimulation test (Ti-Stim) was used to detect immune overactivation in response to titanium. Bone density surrounding implants was measured using TAU. We also validated osteoimmune dysregulation. Results TAU values showed reduced BIC and decreased osseointegration for Ti-Impl. Moreover, TAU values in the Cer-Impl group were more than twice those in the Ti-Impl cohort. The multiplex analysis of C-C motif chemokine 5 (CCL5, also known as RANTES) expression revealed a 20-fold increase in BMDJ surrounding Ti-Impl. Higher levels of CCL5 inflammation were present in the positive Ti-Stim group. Conclusions Our data indicate that Cer-Impl have an osteoimmune advantage over Ti-Impl. The key determinant for osteoimmune sustainability appears to be the absence of inflammation at the implant site. We therefore recommend the use of TAU to assess the implant site prior to implantation.

Abstract Both respiratory muscle endurance training (RMET) and inspiratory resistive training (IMT) seem to increase whole-body exercise performance, but direct comparisons between the two are scarce. We hypothesized that the similarity of RMET to exercise-induced ventilation would induce larger improvements compared to IMT. Twenty-six moderately-trained men performed either 4 weeks of RMET, IMT or SHAM training. Before and after the interventions, respiratory muscle endurance, 3-km running time-trial performance and leg muscle fatigue after intense constant-load cycling (assessed with femoral nerve magnetic stimulation) were measured. Both RMET (+ 59%) and IMT (+ 38%) increased respiratory muscle endurance (both p

Automated tumor segmentation tools for glioblastoma show promising performance. To apply these tools for automated response assessment, longitudinal segmentation, and tumor measurement, consistency is critical. This study aimed to determine whether BraTumIA and HD-GLIO are suited for this task. We evaluated two segmentation tools with respect to automated response assessment on the single-center retrospective LUMIERE dataset with 80 patients and a total of 502 post-operative time points. Volumetry and automated bi-dimensional measurements were compared with expert measurements following the Response Assessment in Neuro-Oncology (RANO) guidelines. The longitudinal trend agreement between the expert and methods was evaluated, and the RANO progression thresholds were tested against the expert-derived time-to-progression (TTP). The TTP and overall survival (OS) correlation was used to check the progression thresholds. We evaluated the automated detection and influence of non-measurable lesions. The tumor volume trend agreement calculated between segmentation volumes and the expert bi-dimensional measurements was high (HD-GLIO: 81.1%, BraTumIA: 79.7%). BraTumIA achieved the closest match to the expert TTP using the recommended RANO progression threshold. HD-GLIO-derived tumor volumes reached the highest correlation between TTP and OS (0.55). Both tools failed at an accurate lesion count across time. Manual false-positive removal and restricting to a maximum number of measurable lesions had no beneficial effect. Expert supervision and manual corrections are still necessary when applying the tested automated segmentation tools for automated response assessment. The longitudinal consistency of current segmentation tools needs further improvement. Validation of volumetric and bi-dimensional progression thresholds with multi-center studies is required to move toward volumetry-based response assessment.

Summary: Background: Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. Methods: We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. Findings: Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50–10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35–73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18–10.52; p = 0.024). Interpretation: Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. Funding: This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation.

Abstract Publicly available Glioblastoma (GBM) datasets predominantly include pre-operative Magnetic Resonance Imaging (MRI) or contain few follow-up images for each patient. Access to fully longitudinal datasets is critical to advance the refinement of treatment response assessment. We release a single-center longitudinal GBM MRI dataset with expert ratings of selected follow-up studies according to the response assessment in neuro-oncology criteria (RANO). The expert rating includes details about the rationale of the ratings. For a subset of patients, we provide pathology information regarding methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter status and isocitrate dehydrogenase 1 (IDH1), as well as the overall survival time. The data includes T1-weighted pre- and post-contrast, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) MRI. Segmentations from state-of-the-art automated segmentation tools, as well as radiomic features, complement the data. Possible applications of this dataset are radiomics research, the development and validation of automated segmentation methods, and studies on response assessment. This collection includes MRI data of 91 GBM patients with a total of 638 study dates and 2487 images.

Abstract Background Neuropsychiatric disorders, such as schizophrenia (SZ) and autism spectrum disorder (ASD), are common, multi-factorial and multi-symptomatic disorders. Ample evidence implicates oxidative stress, deficient repair of oxidative DNA lesions and DNA damage in the development of these disorders. However, it remains unclear whether insufficient DNA repair and resulting DNA damage are causally connected to their aetiopathology, or if increased levels of DNA damage observed in patient tissues merely accumulate as a consequence of cellular dysfunction. To assess a potential causal role for deficient DNA repair in the development of these disorders, we behaviourally characterized a mouse model in which CaMKIIa-Cre-driven postnatal conditional knockout (KO) of the core base-excision repair (BER) protein XRCC1 leads to accumulation of unrepaired DNA damage in the forebrain. Results CaMKIIa-Cre expression caused specific deletion of XRCC1 in the dorsal dentate gyrus (DG), CA1 and CA2 and the amygdala and led to increased DNA damage therein. While motor coordination, cognition and social behaviour remained unchanged, XRCC1 KO in the forebrain caused increased anxiety-like behaviour in males, but not females, as assessed by the light–dark box and open field tests. Conversely, in females but not males, XRCC1 KO caused an increase in learned fear-related behaviour in a cued (Pavlovian) fear conditioning test and a contextual fear extinction test. The relative density of the GABA(A) receptor alpha 5 subunit (GABRA5) was reduced in the amygdala and the dorsal CA1 in XRCC1 KO females, whereas male XRCC1 KO animals exhibited a significant reduction of GABRA5 density in the CA3. Finally, assessment of fast-spiking, parvalbumin-positive (PV) GABAergic interneurons revealed a significant increase in the density of PV+ cells in the DG of male XRCC1 KO mice, while females remained unchanged. Conclusions Our results suggest that accumulation of unrepaired DNA damage in the forebrain alters the GABAergic neurotransmitter system and causes behavioural deficits in relation to innate and learned anxiety in a sex-dependent manner. Moreover, the data uncover a previously unappreciated connection between BER deficiency, unrepaired DNA damage in the hippocampus and a sex-specific anxiety-like phenotype with implications for the aetiology and therapy of neuropsychiatric disorders.

BackgroundEchinacea purpurea has clinical antiviral activity against respiratory viruses and modulates immune functions. In this study, we compared higher doses of new Echinacea formulations with conventional formulations at lower, preventive doses for therapy of respiratory tract infections (RTIs).MethodsIn this randomized, blinded, controlled trial, healthy adults (n = 409) were randomized between November 2018 and January 2019 to one of four Echinacea formulations, which were taken in case of an RTI for up to 10 days. New formulations A (lozenges) and B (spray) delivered an increased dose of 16,800 mg/d Echinacea extract during days 1–3 and 2,240–3,360 mg/d afterward; as controls, conventional formulations C (tablets) and D (drops) delivered a lower daily dose of 2,400 mg, usually taken for prevention. The primary endpoint was time to clinical remission of first RTI episodes based on the Kaplan–Meier analysis of patient-reported, investigator-confirmed, respiratory symptoms assessed for up to 10 days. In a sensitivity analysis, the mean time to remission beyond day 10 was calculated by extrapolating the treatment effects observed on days 7 to 10.ResultsA total of 246 participants (median age 32 years, 78% female participants) were treated for at least one RTI. Recovery by day 10 (complete absence of symptoms) was achieved in 56 and 44% of patients with the new and conventional formulations, respectively, showing a median time to recovery of 10 and 11 days, respectively (p = 0.10 in intention-to-treat analysis, p = 0.07 in per-protocol analysis). In the extrapolated sensitivity analysis, new formulations resulted in a significantly shorter mean time to remission (9.6 vs. 11.0 days, p < 0.001). Among those with an identified respiratory virus, viral clearance until day 10 based on real-time PCR from nasopharyngeal swabs was more frequent with new formulations (70 vs. 53%, p = 0.046). Tolerability and safety (adverse events: 12 vs. 6%, p = 0.19) were good and similar between formulations. There was one severe adverse event with a potential hypersensitivity reaction in a recipient of the novel spray formulation.ConclusionIn adults with acute RTI, new Echinacea formulations with higher doses resulted in faster viral clearance than conventional formulations in prophylactic dosages. The trend for faster clinical recovery was not significant by day 10 but became so upon extrapolation. A dose increase during acute respiratory symptoms might improve the clinical benefits of orally administered Echinacea formulations.Trial registrationThe study was registered in the Swiss National Clinical Trials Portal (SNCTP000003069) and on ClinicalTrials.gov (NTC03812900; URL https://clinicaltrials.gov/ct2/show/NCT03812900?cond=echinacea&draw=3&rank=14).

Fabian Schick, Johann Lechner, Florian Notter Clinic for Integrative Dentistry, Munich, GermanyCorrespondence: Fabian Schick, Clinic for Integrative Dentistry, Gruenwalder Str. 10A, Munich, 81547, Germany, Tel +49 89 697 00 55, Email drfabischick@outlook.deBackground: This case report demonstrates the value of ultrasound measurements, and immunological and toxicological diagnostics in addition to current x-ray imaging procedures to diagnose hidden oral and maxillofacial infections. Using a clear scheme shows the procedure of the authors’ steps. The positive impact on the patient’s dermatological clinical picture is shown. Functional regeneration using metal-free ceramic implants and autologous bone augmentation is demonstrated. After a healing period, a postoperative control took place.Question: Are chronic inflammatory and chronic toxic stressors from the oral region affecting the patient’s state of health and dermatological symptoms?Patients and Methods: A 52 year old female suffering from neurodermatitis, who had been therapy-resistant for several years, was rehabilitated by oral surgery and prosthetics. Radiological examinations with orthopantomogram (OPG) and three-dimensional imaging (DVT/CBCT) were inconclusive for possible jawbone inflammatory sites. Immunological, toxicological diagnostics and trans-alveolar bone densitometry with ultrasound (TAU), were able to show immunological and toxicological stressors and areas of reduced bone density. Bone densitometry with ultrasound raised the suspicion of silent inflammations in the jawbone with potentially increased cytokine levels.Results: For the patient incompatible materials, teeth with increased toxin exposure and surrounding softened, fatty, ischaemic bone was removed. Histologies and cytokine profiles were obtained. The resulting defects were functionally regenerated using ceramic implants and autologous augmentation. The cytokine profiles showed significantly elevated RANTES/CCL5, confirming the need for surgical intervention. The patient’s atopic dermatitis improved significantly in this case.Summary: Individualized immunological and toxicological diagnostics and trans-alveolar bone density bone densitometry with ultrasound (TAU) identified immunological and toxicological stressors as well as reduced bone density with increased cytokine levels. A therapy-resistant neurodermatitis improved significantly after treatment.Conclusion: This case report illustrates the need for patient-specific and individualized examinations that link dentistry more closely with other medical conditions in order to clarify possible interactions.Graphical Abstract: Keywords: atopic dermatitis, CCL5/RANTES, osteoimmunology, ceramic implants, autologous augmentation, silent inflammation, FDOJ, trans alveolar ultrasonography

As whole genome sequence (WGS) data sets have become abundant and widely available, so has the need for variant detection and scoring. The aim of this study was to compare the accuracy of commonly used variant calling programs, Freebayes and GATK HaplotypeCaller (GATK-HC), and to use U.S. sheep WGS data sets to identify novel breed-associated SNPs. Sequence data from 145 sheep consisting of 14 U.S. breeds were filtered and biallelic single nucleotide polymorphisms (SNPs) were retained for genotyping analyses. Genotypes from both programs were compared to each other and to genotypes from bead arrays. The SNPs from WGS were compared to the bead array data with breed heterozygosity, principal component analysis and identifying breed associated SNPs to analyze genetic diversity. The average sequence read depth was 2.78 reads greater with 6.11% more SNPs being identified in Freebayes compared to GATK-HC. The genotype concordance of the variant callers to bead array data was 96.0% and 95.5% for Freebayes and GATK-HC, respectively. Genotyping with WGS identified 10.5 million SNPs from all 145 sheep. This resulted in an 8% increase in measured heterozygosity and greater breed separation in the principal component analysis compared to the bead array analysis. There were 1,849 SNPs identified in only the Romanov sheep where all 10 rams were homozygous for one allele and the remaining 135 sheep from 13 breeds were homozygous for the opposite allele. Both variant calling programs had greater than 95% concordance of SNPs with bead array data, and either was suitably accurate for ovine WGS data sets. The use of WGS SNPs improved the resolution of PCA analysis and was critical for identifying Romanov breed-associated SNPs. Subsets of such SNPs could be used to estimate germplasm composition in animals without pedigree information.

Abstract Background Data on antimicrobial resistance mechanisms are scanty for Cedecea spp., with very variable antibiotic resistance patterns documented. Here we report the first in vivo resistance evolution of a C. davisae clinical isolate in a patient with a complex hand trauma and provide insight in the resistance mechanism, leading to therapeutic implications for this pathogen. Case presentation Cedecea davisae was isolated from a patient with hand trauma during a first surgical debridement. Six days after primary surgical treatment and under antimicrobial treatment with amoxicillin-clavulanic acid and later cefepime, follow up cultures yielded C. davisae which demonstrated a resistance development. The susceptible parental isolate and its resistant derivative were characterized by whole genome sequencing, ampC, ompC and ompF by RT- PCR. The resistant derivative demonstrated an A224G SNP in ampD, the transcriptional regulator of ampC, leading to a His75Arg change in the corresponding AmpD protein. AmpC transcription of the resistant derivative was 362-times higher than the susceptible isolate. Transcription levels of ompF and ompC were 8.5-fold and 1.3-fold lower, respectively, in the resistant derivative. Downregulation of OmpF putatively resulted from a mutation in the presumed promoter region upstream of the dusB-Fis operon, a proposed regulator for ompF. Conclusions This case demonstrates the in vivo resistance development of C. davisae within 7 days similar to that of the members of the Enterobacter cloacae complex. Our findings add valuable information for future therapeutic management of these opportunistic pathogens as they warrant the same empirical treatment as AmpC producers.