Active animal health surveillance in European Union Member States: gaps and opportunities

Animal health surveillance enables the detection and control of animal diseases including zoonoses. Under the EU-FP7 project RISKSUR, a survey was conducted in 11 EU Member States and Switzerland to describe active surveillance components in 2011 managed by the public or private sector and identify gaps and opportunities. Information was collected about hazard, target population, geographical focus, legal obligation, management, surveillance design, risk-based sampling, and multi-hazard surveillance. Two countries were excluded due to incompleteness of data. Most of the 664 components targeted cattle (26·7%), pigs (17·5%) or poultry (16·0%). The most common surveillance objectives were demonstrating freedom from disease (43·8%) and case detection (26·8%). Over half of components applied risk-based sampling (57·1%), but mainly focused on a single population stratum (targeted risk-based) rather than differentiating between risk levels of different strata (stratified risk-based). About a third of components were multi-hazard (37·3%). Both risk-based sampling and multi-hazard surveillance were used more frequently in privately funded components. The study identified several gaps (e.g. lack of systematic documentation, inconsistent application of terminology) and opportunities (e.g. stratified risk-based sampling). The greater flexibility provided by the new EU Animal Health Law means that systematic evaluation of surveillance alternatives will be required to optimize cost-effectiveness

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C–Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living culture

Importance of incomplete lineage sorting and introgression in the origin of shared genetic variation between two closely related pines with overlapping distributions

Genetic variation shared between closely related species may be due to retention of ancestral polymorphisms because of incomplete lineage sorting (ILS) and/or introgression following secondary contact. It is challenging to distinguish ILS and introgression because they generate similar patterns of shared genetic diversity, but this is nonetheless essential for inferring accurately the history of species with overlapping distributions. To address this issue, we sequenced 33 independent intron loci across the genome of two closely related pine species (Pinus massoniana Lamb. and Pinus hwangshanensis Hisa) from Southeast China. Population structure analyses revealed that the species showed slightly more admixture in parapatric populations than in allopatric populations. Levels of interspecific differentiation were lower in parapatry than in allopatry. Approximate Bayesian computation suggested that the most likely speciation scenario explaining this pattern was a long period of isolation followed by a secondary contact. Ecological niche modeling suggested that a gradual range expansion of P. hwangshanensis during the Pleistocene climatic oscillations could have been the cause of the overlap. Our study therefore suggests that secondary introgression, rather than ILS, explains most of the shared nuclear genomic variation between these two species and demonstrates the complementarity of population genetics and ecological niche modeling in understanding gene flow history. Finally, we discuss the importance of contrasting results from markers with different dynamics of migration, namely nuclear, chloroplast and mitochondrial DNA

Epidemiology, comorbidities, and healthcare utilization of patients with chronic urticaria in Germany

Abstract Background Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary. Objectives To investigate the epidemiology of CU, overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database. Methods Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin [InGef] (01 January 2015–30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD‐10‐GM codes). Twelve‐month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthcare utilization by patients with CU were investigated. Results Of 4 693 772 individuals of all ages listed in the database, 3 538 540 were observable during 2017. Overall, 17 524 patients (˜0.5%) were diagnosed with CU; chronic spontaneous urticaria (CSU: 71.2%), chronic inducible urticaria (CIndU: 19.7%), CSU+CIndU (9.1%). Females, vs. males, had higher diagnosed prevalence (0.62% vs. 0.37%) and diagnosed incidence (0.18% vs. 0.11%) of CU among all patients. Patients most frequently visited general practitioners (41.3% of total visits). Hypertensive diseases (43.5%), lipoprotein metabolism disorders (32.1%) and affective disorders (26.0%) were the most frequently reported comorbidities of special interest. Rates of most comorbidities of special interests were similar to atopic dermatitis and psoriasis patients, and all higher vs. overall population. More than half (54.1%) of all CU patients were not prescribed any treatment. Second‐generation H 1 ‐antihistamines were the most commonly prescribed medication for adult (17.9%) and paediatric (27.9%) patients. Patients with CIndU (paediatric, 15.5%; adult, 7.8%) were more often hospitalized versus patients with CSU (paediatric, 9.9%; adult, 4.6%). Conclusions In Germany, prevalence of CU along with multiple comorbidities may pose increased burden on the healthcare system. Awareness of adhering to treatment guidelines, and aiming for complete control of urticaria, needs to be driven and may improve outcomes

Epidemiology, comorbidities, and healthcare utilization of patients with chronic urticaria in Germany

Background: Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary. Objectives: To investigate the epidemiology of CU, overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database. Methods: Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin [InGef] (01 January 2015-30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD-10-GM codes). Twelve-month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthcare utilization by patients with CU were investigated. Results: Of 4 693 772 individuals of all ages listed in the database, 3 538 540 were observable during 2017. Overall, 17 524 patients (˜0.5%) were diagnosed with CU; chronic spontaneous urticaria (CSU: 71.2%), chronic inducible urticaria (CIndU: 19.7%), CSU+CIndU (9.1%). Females, vs. males, had higher diagnosed prevalence (0.62% vs. 0.37%) and diagnosed incidence (0.18% vs. 0.11%) of CU among all patients. Patients most frequently visited general practitioners (41.3% of total visits). Hypertensive diseases (43.5%), lipoprotein metabolism disorders (32.1%) and affective disorders (26.0%) were the most frequently reported comorbidities of special interest. Rates of most comorbidities of special interests were similar to atopic dermatitis and psoriasis patients, and all higher vs. overall population. More than half (54.1%) of all CU patients were not prescribed any treatment. Second-generation H1 -antihistamines were the most commonly prescribed medication for adult (17.9%) and paediatric (27.9%) patients. Patients with CIndU (paediatric, 15.5%; adult, 7.8%) were more often hospitalized versus patients with CSU (paediatric, 9.9%; adult, 4.6%). Conclusions: In Germany, prevalence of CU along with multiple comorbidities may pose increased burden on the healthcare system. Awareness of adhering to treatment guidelines, and aiming for complete control of urticaria, needs to be driven and may improve outcomes

Chances and Limitations of Wild Bird Monitoring for the Avian Influenza Virus H5N1 — Detection of Pathogens Highly Mobile in Time and Space

Highly pathogenic influenza virus (HPAIV) H5N1 proved to be remarkably mobile in migratory bird populations where it has led to extensive outbreaks for which the true number of affected birds usually cannot be determined. For the evaluation of avian influenza monitoring and HPAIV early warning systems, we propose a time-series analysis that includes the estimation of confidence intervals for (i) the prevalence in outbreak situations or (ii) in the apparent absence of disease in time intervals for specified regional units. For the German outbreak regions in 2006 and 2007, the upper 95% confidence limit allowed the detection of prevalences below 1% only for certain time intervals. Although more than 25,000 birds were sampled in Germany per year, the upper 95% confidence limit did not fall below 5% in the outbreak regions for most of the time. The proposed analysis can be used to monitor water bodies and high risk areas, also as part of an early-warning system. Chances for an improved targeting of the monitoring system as part of a risk-based approach are discussed with the perspective of reducing sample sizes

A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy

Background: Basal cell carcinoma (BCC) represents the most common non-melanoma skin cancer worldwide affecting mainly adult, fair-skinned individuals. The WHO distinguishes aggressive and non-aggressive forms of which prototypical variants of the latter are primary nodular and superficial BCC.Objectives: To demonstrate non-inferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared to MAL (a cream containing methyl-aminolevulinate) in the treatment of non-aggressive BCC with photodynamic therapy (PDT). Non-inferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of Δ = -15%.Patients/Methods: The study was a randomized, phase III trial performed in Germany and the UK with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA, 143 with MAL. Patients received two PDT sessions one week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J/cm2). Results shown include clinical endpoints as well as patients' reassessment 12 months after the last PDT.Results: Of the BF-200 ALA-treated patients, 93.4% were complete responders compared to 91.8% in the MAL group. The difference of means was 1.6 with a one-sided 97.5% CI of -6.5, establishing non-inferiority (p&lt;0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%.Conclusions: Treatment of non-aggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven non-inferiority to MAL-PDT and demonstrates low recurrence rates after 1-year follow-up.</p

Characterizing the secretome of licensed hiPSC-derived MSCs

Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. RNA sequencing confirmed high resemblance, with average Pearson correlation of 0.88 and Jaccard similarity index of 0.99, and similar to hBMSCs the hiMSCs released extracellular vesicles with in vitro immunomodulatory properties. Potency assay with TNF alpha and IFN gamma demonstrated an increase in well-known immunomodulatory genes such as IDO1, CXCL8/IL8, and HLA-DRA which was also highlighted by enhanced secretion in the media. Notably, expression of 125 genes increased more than 1000-fold. These genes were predicted to be regulated by NFKB signaling, known to play a central role in immune response. Altogether, our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.Molecular Epidemiolog

Perception and Impact of COVID-19 Pandemic in Psoriasis Patients: Data from the German PsoBest and the CoronaBest Registries

María José Valencia López,1,&ast; Brigitte Stephan,1,&ast; Anna Meineke,1 Sandra Wolf,1 Diamant Thaci,2 Ulrich Mrowietz,3 Valerie Andrees,1 Stephan Jeff Rustenbach,1 Kristian Reich,1 Linus Thalmann,1 Henriette Bogena,1 Petra Staubach,4 Ralph Michael von Kiedrowski,5 Matthias Augustin1 1Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; 2Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 3Psoriasis-Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany; 4Department of Dermatology and Allergy, University Medical Center Mainz, Mainz, Germany; 5Dermatological Practice Selters, Selters, Germany&ast;These authors contributed equally to this workCorrespondence: Matthias Augustin, Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, Hamburg, 20246, Germany, Tel +49 040 7410 55428, Fax +49 040 7410 55348, Email [email protected]: Limited data are available characterizing the impact of the SARS-CoV-2 pandemic on psoriasis care for patients in Germany.Objective: To analyze patient perception and impact of the pandemic on well-being and psoriasis management of German patients with moderate-to-severe psoriasis or psoriasis arthritis under systemic therapies.Methods: The CoronaBest registry captures events of SARS-CoV-2 infections and analyzes the impact of the pandemic on patients with psoriasis or psoriasis arthritis. In June 2020, and independently in February 2022, patients with psoriasis or psoriasis arthritis received a standardized questionnaire for current treatment, protective measures, well-being, and individual risks for COVID-19, among others.Results: Included were 4,194 patients in 2020 (mean age of 47.7 years and 41.8% women) and 4,818 patients in 2022 (mean age of 56.4 and 42.9% women). Treatment discontinuations were observed in 2.7% and 1.7% of patients in 2020 and 2022, respectively. In the vast majority of the cases (> 92%), no additional measures were taken concerning the management of psoriasis treatments in either 2020 or 2022. Those patients with changes reported most frequently: telephone calls instead of face-to-face visits (80.2%, in 2020 vs 40.5% in 2022) or more frequent controls (27.1%, 2020 vs 22.0%, 2022). A majority (66.7%, 2020, and 70.6%, 2022) did not perceive the virus as a considerable threat. The proportion of patients feeling well informed about COVID-19 by physicians increased from 42.6% in 2020 to 51.8% in 2022. About 81.1% of patients in 2020 and 67.5% in 2022 stated that their overall personal condition was not affected due to the pandemic. Physicians attributed no special risk of contracting SARS-CoV-2 in most of the patients.Conclusion: A high rate of systemic treatment persistence and awareness of risks and protective measures indicate that health care for psoriasis largely followed current national and international recommendations during the COVID-19 pandemic.Keywords: psoriasis, COVID-19, SARS-CoV-2, pandemic, patient perception, risk factor