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Background: can cause severe, often fatal, pneumonia in humans. Mandatory water sampling in commercially used buildings (mainly rental apartments) as regulated in the Drinking Water Ordinance () aim to protect the population against infection with Legionella. However, no data exist to date that could prove the effectiveness of the measures. At the same time, having the Public Health Department’s Infection Control Division deal with Legionalla is very time consuming.Methods: A retrospective analysis of data from the city and district of Regensburg, a selective literature search, a prospective survey of workload using an anonymous questionnaire were performed.Results: The evaluated data from the city/district of Regensburg suggest underreporting to a similar extent as shown by the RKI’s data in the compared period. Neither is the actual incidence known, nor can exposures be clearly determined in most cases. The exposure categories “travel” and “private/occupational” seem to be the most pertinent. The potential public hazard of Legionella posed by domestic plumbing systems is unclear. A connection between exceeding the technical measurement limit (, TMW) in routine tests in rental apartments and disease cases cannot be shown. A survey among non-medical personnel in the field of infection control and hygiene on the time spent on the topic of Legionella yielded a mean number of 39% of daily working hours for the observed 2-month period.Conclusion: The data on incidence, exposure, and causality are incomplete. Evidence of effective protection by the current practice of sampling in apartment buildings could not be found. For many aspects, there are no unambiguous data in the literature. Restricting mandatory monitoring to certain public/commercial institutions should be discussed, given the high workload for the Public Health Department and the unproven protective effect. Further research on this topic is necessary.

In July/August 2018, a measles outbreak occurred in a reception facility for asylum seekers in Regensburg, Bavaria, Germany. A five-year-old child and an 18-year-old man from Moldova were affected. At the time of the report, 491 people were accommodated at the facility. The outbreak was limited to the two cases mentioned by the consistent use of infection control measures. Decisive factors for successfully combating this outbreak were, in particular, the close cooperation of the local public health authority (Gesundheitsamt) with the district government officials, the institution’s management, and the general practitioners on site. The measures taken included the early information of all parties involved, the timely and repeated implementation of containment vaccinations, a consequent segregation of contagion and/or disease suspects and the critical consideration of each individual case in connection with the separate risk-adapted segregation of particularly vulnerable cohorts.

The COVID-19 pandemic required adjustments and limitations in university teaching, thereby challenging teaching concepts in anatomy requiring in-person contact, including the gross anatomy course. Therefore, the present study investigates the impact of COVID-19-associated adjustments on students' perception of the gross anatomy course's importance and quality, students' preferred learning setting and outcome, and their motivation to involve themselves in academic activities, including becoming a future peer-teacher of the course. Using paper-based questionnaires in Ulm, Germany, 397 (response rate: 82.3%) students of the winter term of 2020/2021 were surveyed using quantitative and qualitative items, which were compared with cohorts prior to the pandemic. Students reported a higher global rating on course quality during COVID-19 (pre-COVID-19: 5.3 ± 0.9, during-COVID-19: 5.6 ± 0.7, p < 0.001; 1 = very bad, 6 = very good). Students' perceived importance of the gross anatomy course showed a small but significant increase (pre-COVID-19: 4.2 ± 0.6, during-COVID-19: 4.3 ± 0.6, p < 0.001; 1 = strongly disagree, 6 = strongly agree). Students' motivation to apply as a peer-teacher remained stable, nevertheless, they reported less interest in transferring their knowledge to junior students. Finally, students reported that they spent significantly more learning time alone and their examination grades remained unchanged during the pandemic. Astonishingly, despite radical changes of the teaching environment due to COVID-19, students appreciate the offered teaching and highly valued the gross anatomy course.

Several studies reported a higher prevalence of maladaptive behaviors in children and adolescents with visual impairments (that is, those who are blind or have low vision) compared with typically developing youths. Early studies reported that up to 57% of youths with visual impairments also have mental health problems. These include problems with attention, anxiety, decreased initiative and communication, aggression, and low self-esteem. Some of the children and adolescents with visual impairments develop serious manneristic or stereotypical behaviors (eye poking or rocking) or self injurious behaviors like head hitting or self biting. Specifically, the risk of persistent problem behaviors is elevated in youths who present a combination of visual impairment and intellectual disabilities. The BPI-S is a well-established, informant based behavior-rating instrument that was designed to assess maladaptive behaviors in individuals with intellectual disabilities. A short form (Behavior Problems Inventory-- Short Form, BPI-S; Rojahn et al., 2012a, 2012b) is available. As the BPI-S includes various items that describe behaviors exhibited by youths with visual impairments, it was used in the current study. The purpose of this project was to explore the utility of the BPI-S to describe various forms of maladaptive behaviors in children and adolescents with visual impairments, and to provide data to estimate if there are differences in specific forms of stereotypical, self-injurious, or aggressive or destructive behaviors in youths who are blind as compared to youths with low vision. As an implication for clinical practice, the authors recommend the use of the BPI-S as an instrument to identify youths with visual impairments who are in need of positive behavior support. Practitioners can use the BPI-S to describe the specific form of aggressive, stereotypical, or self-injurious behavior as a target for intervention, and to evaluate the effects of behavioral interventions. However, more research is needed to provide data on the reliability of BPI-S-ratings with children and adolescents with visual impairments and the correspondence with direct observational methods. A behavior rating form like the BPI-S can be seen as a first step for assessment that must be followed by a systematic functional analysis.

The central component of the complement cascade, C3, is involved in various biological functions, including opsonization of foreign bodies, clearance of waste material, activation of immune cells, and triggering of pathways controlling development. Given its broad role in immune responses, particularly in phagocytosis and the clearance of microbes, a deficiency in complement C3 in humans is often associated with multiple bacterial infections. Interestingly, an increased susceptibility to infections appears to occur mainly in the first two years of life and then wanes throughout adulthood. In view of the well-established connection between C3 deficiency and infections, therapeutic inhibition of complement at the level of C3 is often considered with caution or disregarded. We therefore set out to investigate the immune and biochemical profile of non-human primates under prolonged treatment with the C3 inhibitor compstatin (Cp40 analog). Cynomolgus monkeys were dosed subcutaneously with Cp40, resulting in systemic inhibition of C3, for 1 week, 2 weeks, or 3 months. Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40. In fact, Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3. Overall, our data suggest that systemic C3 inhibition in healthy adult non-human primates is not associated with a weakened immune system or susceptibility to infections.

BACKGROUND:Pre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. OBJECTIVE:To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May 2017. The goal of the conference was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. METHODS:A total of 31 experts from 13 countries participated and were divided into 6 thematic working groups (WG): (1) study design, (2) humane modeling, (3) infection types, (4) organ failure/dysfunction, (5) fluid resuscitation, and (6) antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013). RESULTS:Overall, the participants reached consensus on 29 points; 20 at "recommendation" (R) and 9 at "consideration" (C) strength. This executive summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2, and 3). Detailed commentaries to all Rs and Cs are simultaneously published in three separate full-length papers. CONCLUSIONS:We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

To prevent motion artifacts in small animal positron emission tomography (PET), animals are routinely scanned under anesthesia or physical restraint. Both may potentially alter metabolism and neurochemistry. This study investigates the feasibility of fully awake acquisition and subsequent absolute quantification of dynamic brain PET data via pharmacokinetic modelling in moving rats using the glutamate 5 receptor radioligand [11C]ABP688 and point source based motion correction. Five male rats underwent three dynamic [11C]ABP688 PET scans: two test-retest awake PET scans and one scan under anesthesia for comparison. Specific radioligand binding was determined via the simplified reference tissue model (reference: cerebellum) and outcome parameters BP ND and R 1 were evaluated in terms of stability and reproducibility. Test-retest measurements in awake animals gave reliable results with high correlations of BP ND (y = 1.08 × −0.2, r = 0.99, p < 0.01) and an acceptable variability (mean over all investigated regions 15.7 ± 2.4%). Regional [11C]ABP688 BP NDs under awake and anesthetized conditions were comparable although in awake scans, absolute radioactive peak uptakes were lower and relative blood flow in terms of R 1 was higher. Awake small animal PET with absolute quantification of neuroreceptor availability is technically feasible and reproducible thereby providing a suitable alternative whenever effects of anesthesia are undesirable, e.g. in sleep research. [ABSTRACT FROM AUTHOR]

Background: Respiratory failure can be a severe complication after polytrauma. Extensive systemic inflammation due to surgical interventions, as well as exacerbated post-traumatic immune responses influence the occurrence and progression of respiratory failure. This study investigated the effect of different surgical treatment modalities as well as combined inhibition of the complement component C5 and the toll-like receptor molecule CD14 (C5/CD14 inhibition) on the pulmonary microRNA (miRNA) signature after polytrauma, using a translational porcine polytrauma model. Methods: After induction of general anesthesia, animals were subjected to polytrauma, consisting of blunt chest trauma, bilateral femur fractures, hemorrhagic shock, and liver laceration. One sham group (n=6) and three treatment groups were defined; Early Total Care (ETC, n=8), Damage Control Orthopedics (DCO, n=8), and ETC + C5/CD14 inhibition (n=4). Animals were medically and operatively stabilized, and treated in an ICU setting for 72 h. Lung tissue was sampled, miRNAs were isolated, transcribed, and pooled for qPCR array analyses, followed by validation in the individual animal population. Lastly, mRNA target prediction was performed followed by functional enrichment analyses. Results: The miRNA arrays identified six significantly deregulated miRNAs in lung tissue. In the DCO group, miR-129, miR-192, miR-194, miR-382, and miR-503 were significantly upregulated compared to the ETC group. The miRNA expression profiles in the ETC + C5/CD14 inhibition group approximated those of the DCO group. Bioinformatic analysis revealed mRNA targets and signaling pathways related to alveolar edema, pulmonary fibrosis, inflammation response, and leukocytes recruitment. Collectively, the DCO group, as well as the ETC + C5/CD14 inhibition group, revealed more anti-inflammatory and regenerative miRNA expression profiles. Conclusion: This study showed that reduced surgical invasiveness and combining ETC with C5/CD14 inhibition can contribute to the reduction of pulmonary complications. [ABSTRACT FROM AUTHOR]

In view of the rise of drug-resistant tuberculosis and difficult-to-treat related diseases caused by non-tuberculous mycobacteria, there is an urgent need for antimycobacterial drug discovery. Nα-aroyl-N-aryl-phenylalanine amides (AAPs) have been identified as antimycobacterial agents and are subject to lead optimization. The aim of the present study is to evaluate the impact of N-aryl ortho cyano substitution in a lead compound on the crystal and molecular structure and its in vitro activity against Mycobacterium abscessus. The title AAP can be conveniently synthesized from N-Boc-protected d-phenylalanine in two amide coupling steps using a previously established racemization-free method. Two polymorphic forms in the solid-state are described, as discovered by X-ray and electron diffraction. The introduction of a cyano group in the ortho position of the AAP N-aryl ring, however, leads to loss of in vitro activity against M. abscessus subsp. abscessus. [ABSTRACT FROM AUTHOR]

Previous studies indicate an implication of the terminal complement complex (TCC) in disc degeneration (DD). To investigate the functional role of TCC in trauma-induced DD in vivo, the model of endplate (EP) drilling was first applied in rabbits using a C6-deficient rabbit strain in which no TCC formation was possible. In parallel the model of needle puncture was investigated. Using a minimally invasive surgical intervention, lumbar rabbit intervertebral discs (IVDs) were treated with EP drilling or needle puncture. Degenerative effects of both surgical interventions were assessed by Pfirrmann grading and T2 quantification of the IVDs based on high-resolution MRI (11.7 T), as well as radiographic determination of disc height index. Pfirrmann grading indicated significant degenerative effects after EP drilling. Contrary to our assumption, no evidence was found that the absence of TCC formation in C6-deficient rabbits reduces the development of DD compared to C6-sufficient animals. EP drilling was proven to be suitable for application in rabbits. However, results of the present study do not provide clear evidence of a central functional role of TCC within DD and suggest that TCC deposition in DD patients may be primarily considered as a marker of complement activation during DD progression. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained mistakes.

Preclinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of preclinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling was held in Vienna in May, 2017. The goal of the conference was to identify limitations of preclinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Preclinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. A total of 31 experts from 13 countries participated and were divided into six thematic Working Groups: Study Design, Humane modeling, Infection types, Organ failure/dysfunction, Fluid resuscitation, and Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013). Overall, the participants reached consensus on 29 points; 20 at "recommendation" and nine at "consideration" strength. This Executive Summary provides a synopsis of the MQTiPSS consensus. We believe that these recommendations and considerations will serve to bring a level of standardization to preclinical models of sepsis and ultimately improve translation of preclinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. To encourage its wide dissemination, this article is freely accessible on the Intensive Care Medicine Experimental and Infection journal websites. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection, and Intensive Care Medicine Experimental.