LINC01013 Is a Determinant of Fibroblast Activation and Encodes a Novel Fibroblast-Activating Micropeptide.

Myocardial fibrosis confers an almost threefold mortality risk in heart disease. There are no prognostic therapies and novel therapeutic targets are needed. Many thousands of unannotated small open reading frames (smORFs) have been identified across the genome with potential to produce micropeptides (< 100 amino acids). We sought to investigate the role of smORFs in myocardial fibroblast activation.Analysis of human cardiac atrial fibroblasts (HCFs) stimulated with profibrotic TGFß1 using RNA sequencing (RNA-Seq) and ribosome profiling (Ribo-Seq) identified long intergenic non-coding RNA LINC01013 as TGFß1 responsive and containing an actively translated smORF. Knockdown of LINC01013 using siRNA reduced expression of profibrotic markers at baseline and blunted their response to TGFß1. In contrast, overexpression of a codon-optimised smORF invoked a profibrotic response comparable to that seen with TGFß1 treatment, whilst FLAG-tagged peptide associated with the mitochondria.Together, these data support a novel LINC01013 smORF micropeptide-mediated mechanism of fibroblast activation. TGFß1 stimulation of atrial fibroblasts induces expression of LINC01013, whose knockdown reduces fibroblast activation. Overexpression of a smORF contained within LINC01013 localises to mitochondria and activates fibroblasts.

Impact of PI-QUAL on PI-RADS and cancer yield in an MRI-TRUS fusion biopsy population.

PURPOSE: To test the inter-reader agreement of the Prostate Imaging Quality (PI-QUAL) score for multiparametric prostate MRI and its impact on diagnostic performance in an MRI-ultrasound fusion biopsy population. PATIENTS AND METHODS: Pre-biopsy multiparametric (T2-weighted, DWI, and DCE) prostate MRIs (mpMRI) of 50 patients undergoing transrectal ultrasound-guided MRI-fusion (MRI-TRUS) biopsy were included. Two radiologists independently assigned a PI-QUAL score to each patient and assessed the diagnostic quality of individual sequences. PI-RADS categories were assigned to six regions per prostate (left and right: base/mid-glandular/apex). Inter-reader agreement was calculated using Cohen's kappa and diagnostic performance was compared by the area under the receiver operating characteristics curve (AUC). RESULTS: In 274 diagnostic areas, the malignancy rate was 62.7% (22.5% clinically significant prostate cancer, ISUP ≥ 2). Inter-reader agreement for the diagnostic quality was poor for T2w (kappa 0.19), fair for DWI and DCE (kappa 0.23 and 0.29) and moderate for PI-QUAL (kappa 0.51). For PI-RADS category assignments, inter-reader agreement was very good (kappa 0.86). Overall diagnostic performance did not differ between studies with a PI-QUAL score > 3 compared to a score ≤ 3 (p = 0.552; AUC 0.805 and 0.839). However, the prevalence of prostate cancer was significantly lower when the PI-QUAL score was ≤ 3 (16.7% vs. 30.2%, p = 0.008). CONCLUSION: PI-QUAL has only a limited impact on PI-RADS diagnostic performance in patients scheduled for MRI-TRUS fusion biopsy. However, the lower cancer prevalence in the lower PI-QUAL categories points out a risk of false-positive referrals and unnecessary biopsies if prostate imaging quality is low.

[Influencing factors on stress management in medical students-with special consideration of depression]. / Einfluss- und Wirkfaktoren auf Stressbewältigung im Medizinstudium ­ unter besonderer Berücksichtigung der Depressivität.

BACKGROUND: Due to high levels of stress, a practical course on stress management in medical school was offered to preclinical medical students at the Justus-Liebig University in Giessen up to 2019. In addition to autogenic training with specific resolution formulas, learning strategies, examination anxiety, and stress management were taught. OBJECTIVE: The aim was to determine the factors influencing the efficacy of the course as well as predictive factors favoring the success of preventive strategies for medical students. METHODS: A total of 81 medical students with an average age of M = 25.4 years participated in this study, with 32.1% being male. The pre-post surveys were conducted anonymously with PSQ, BDI, PHQ­9, HADS, SF-12 and the STQL­S. RESULTS: With respect to satisfaction, stress, anxiety, and depression, a significant improvement was achieved at high effect levels (Cohen's d > 1). Initially, 35% of the students suffered from clinically relevant depression; these also showed a significantly higher stress level at the end of the course. This also applies to students with low study or life satisfaction. There were significant interactions of stress reduction depending on the existence of adequate learning techniques as well as anxiety symptoms but less often due to the existence of adequate stress management strategies. CONCLUSION: As predictive factors against a high stress level in medical students, a high study satisfaction and a high life satisfaction as well as low depression values could be confirmed. Relevant factors contributing to the efficacy of the course are learning strategies and coping with examination phobia. Theoretical information concerning stress management was found to be less helpful.

Extensively-drug-resistant Klebsiella pneumoniae ST307 outbreak strain from north-eastern Germany does not show increased tolerance to quaternary ammonium compounds and chlorhexidine.

BACKGROUND: An outbreak of extensively-drug-resistant Klebsiella pneumoniae strain ST307 in a cluster of hospitals in north-east Germany gave rise to the assumption that the epidemiological success of the strain could be based on increased tolerance to biocides. METHODS: The tolerance of the outbreak strain was compared with epidemiologically unrelated clinical isolates of K. pneumoniae, and reference strains of Pseudomonas aeruginosa (ATCC 15442) and Escherichia coli K12 (NCTC 10538). Tests were performed in a miniaturized assay based on European Standard EN 1040. The widely used biocides benzalkonium chloride (BAC) and didecyl dimethyl ammonium chloride (DDAC), their commercial formulation Descosept spezial (DS), and the antiseptic agent chlorhexidine digluconate (CHG) were selected as test substances. These biocides are used regularly in the hospitals involved in the outbreak. FINDINGS: All biocides had a bactericidal effect against all tested strains in the quantitative suspension test within 5 min at typically used concentrations and dilutions. The effectiveness of BAC and DDAC alone and in combination, and CHG antisepsis were not impaired under tested conditions. CONCLUSION: The outbreak strain did not show significantly increased tolerance towards biocides regarding the antiseptic. Thus, the epidemiological success of the strain has to be ascribed to other causes, such as inadequate hand hygiene of visitors.

Infection control measures and prevalence of multidrug-resistant organisms in non-hospital care settings in northeastern Germany: results from a one-day point prevalence study.

BACKGROUND: Much of the existing literature on the epidemiology of multidrug-resistant bacterial organisms (MDROs) and infection control measures still concentrates on hospital care settings. AIM: To pilot a cross-sectional survey in long-term care facilities (LTCFs), rehabilitation clinics, and homecare services to assess the prevalence of MDROs, structural data on infection control, and referral links between care settings in the state of Mecklenburg-West Pomerania, Germany, in 2015. METHODS: A voluntary, anonymous, point prevalence survey, using routine microbiological and structural data (MDRO screening strategies) and the compliance of referring facilities with MRDO patient transfer sheets that are mandatory in Germany. Data from 39 facilities including 24 LTCFs, nine rehabilitation clinics, and six homecare services were analysed. FINDINGS: The most reported pathogen was meticillin-resistant Staphylococcus aureus (MRSA) with a prevalence of 2.09% in homecare services, 1.43% in LTCFs, and 0.53% in rehabilitation clinics. Missing information on the MRDO status in the referral documents was a relevant problem in all facility types. CONCLUSION: Our results imply strong epidemiological links between acute care hospitals and non-clinical care settings. This underlines that successful efforts to curb antimicrobial resistance must not be limited to single facilities but include different settings that are linked by referral networks. Compared to surveys in clinical settings that used the same approach, the prevalence of MRSA is comparable to that of hospitals. By contrast, care facilities lack the infection control resources of hospitals.

Attitudes and perceptions of health care workers in Northeastern Germany about multidrug-resistant organisms.

There were 256 health care workers in 39 facilities who were interviewed about their perceptions of the quality of care of patients with and without multidrug-resistant organisms based on a standardized questionnaire. There are remarkable differences in the responses between facility types (acute care hospitals, long-term care hospitals, rehabilitation hospitals, and home care services). Hygiene management must be specifically tailored to the requirements of each facility.

[Use of Reusable Textile Undergloves for Medical Procedures: A Feasibility Study]. / Einsatz wiederaufbereitbarer textiler Unterziehhandschuhe für medizinische Tätigkeiten: eine Machbarkeitsstudie.

OBJECTIVE: Undergloves are a way to reduce moisture-related skin damage. The aim of this feasibility study was to gain experience with logistics, applicability, acceptability and cost of the routine use of reusable textile undergloves in a hospital setting. METHODS: Undergloves were tested with 18 health-care workers on an intensive care unit over three months. Data on usage as well as logistics were recorded. At baseline, personal data and knowledge and use of cotton undergloves, existing skin problems and the nursing behaviour of the hands by the subjects were determined by means of an input questionnaire. After each wearing, data on usage were collected by a questionnaire. Participants were interviewed by means of a questionnaire with respect to their experience with the use of the undergloves. RESULTS: Acceptance and compliance with the use of undergloves was remarkably good. This was partly due to the properties of the gloves, and partly to the reduction of sweating and very positive effect on the skin of the hands. In the study period 2165 underglove uses were documented, resulting in an average daily consumption of four pairs per person per day. The average wearing time was 28.6 min. The undergloves were suitable for application as well as reprocessing. Reprocessment-related fatigue was relatively low and did not lead to the loss of the properties, only few gloves had to be sorted out. Even if one assumes a complete write-off of the gloves with end of the study, costs for reprocessing were about 0.46 € or 64 % less than the single use. CONCLUSION: The routine use of textile, reprocessable undergloves is feasible. Major challenges for broad usage are within logistics and acceptance by the user.

[Principles of hygiene in ENT endoscopy]. / Grundsätze der Hygiene bei der HNO-Endoskopie.

This article gives a report on principles of reprocessing of rigid and flexible endoscopes used in ENT units including structural and spatial requirements based on the general and also ENT-specific risks of infection associated with diagnostic and therapeutic endoscopy. The underlying legal principles as well as recommendations from scientific societies will be exemplified in order to give the otorhinolaryngologist a practical guidance.Preliminary results of a nation-wide survey on infection control standards based on data of 29 ENT practices in Germany reveal actual deficits of varying degree concerning infection control management including reprocessing of endoscopes. The presented review aims to give support to the establishment of a structured infection control management program including the evaluation of results by means of a prospective surveillance.

[On the relevance of the official lists for notified products and measures for disinfection, disinfestation and control of vertebrate pests ordered by an authority on the legal basis of § 18 IfSG (German Protection against Infection Act)]. / Zur Bedeutung der Listen bekannt gemachter Mittel und Verfahren für behördlich angeordnete Entseuchungen, Entwesungen und zur Bekämpfung von Wirbeltieren auf Grundlage des § 18 Infektionsschutzgesetz.

In order to protect human health against communicable diseases, the German Protection against Infection Act (IfSG) requires the use of officially approved products and methods for officially ordered disinfection, disinfestation (control of arthropods) as well as measures for the management of vertebrate pests that spread pathogens. Official approval is granted by registration in lists published by the responsible federal health authorities and only for products and methods that have been tested and found to be sufficiently effective and do not have an unacceptable impact on health and the environment (§ 18 IfSG). It is not compulsory for manufacturers to have their products and methods listed in accordance with § 18 IfSG. In particular listing is not a prerequisite for access to the German market. Users are free to choose a product as long as no officially ordered measure, i.e. disinfection, disinfestation or measures against vertebrate pests, according to § 18 IfSG applies. However, it is highly recommended to use approved products included in the abovementioned lists even for routine application, as these registered products and methods have been tested, i.e. the efficacy has been proven by means of specific, recognized and quality assured testing procedures or by expert reports which have been confirmed by independent institutions.

Analysis of MRSA-attributed costs of hospitalized patients in Germany.

Infections with methicillin-resistant Staphylococcus aureus (MRSA) are assumed to have a high economic impact due to increased hygienic measures and prolonged hospital length of stay. However, surveys on the real expenditure for the prevention and treatment of MRSA are scarce, in particular with regard to the German Diagnosis-Related Groups (G-DRG) payment system. The aim of our study is to empirically assess the additional cost for MRSA management measures and to identify the main cost drivers in the whole process from the hospital's point of view. We conducted a one-year retrospective analysis of MRSA-positive cases in a German university hospital and determined the cost of hygienic measures, laboratory costs, and opportunity costs due to isolation time and extended lengths of stay. A total of 182 cases were included in the analysis. The mean length of hospital stay was 22.75 days and the mean time in isolation was 17.08 days, respectively. Overall, the calculated MRSA-attributable costs were 8,673.04 per case, with opportunity costs making up, by far, the largest share (77.45 %). Our study provides a detailed up-to-date analysis of MRSA-attributed costs in a hospital. It allows a current comparison to previous studies worldwide. Moreover, it offers the prerequisites to investigate the adequate reimbursement of MRSA burden in the DRG payment system and to assess the efficiency of targeted hygienic measures in the prevention of MRSA.

Efficacy of different carrier gases for barrier discharge plasma generation compared to chlorhexidine on the survival of Pseudomonas aeruginosa embedded in biofilm in vitro.

Because of its antimicrobial properties, nonthermal plasma could serve as an alternative to chemical antisepsis in wound treatment. Therefore, this study investigated the inactivation of biofilm-embedded Pseudomonas aeruginosa SG81 by a surface barrier-discharged (SBD) plasma for 30, 60, 150 and 300 s. In order to optimize the efficacy of the plasma, different carrier gases (argon, argon admixed with 1% oxygen, and argon with increased humidity up to approx. 80%) were tested and compared against 0.1% chlorhexidine digluconate (CHG) exposure for 600 s. The antimicrobial efficacy was determined by calculating the difference between the numbers of colony-forming units (CFU) of treated and untreated biofilms. Living bacteria were distinguished from dead by fluorescent staining and confocal laser scanning microscopy. Both SBD plasmas and CHG showed significant antimicrobial effects compared to the untreated control. However, plasma treatment led to a higher antimicrobial reduction (argon plasma 4.9 log10 CFU/cm(2), argon with admixed oxygen 3 log10 CFU/cm(2), and with increased gas humidity 2.7 log10 CFU/cm(2) after 300 s) compared to CHG. In conclusion, SBD plasma is suitable as an alternative to CHG for inactivation of Pseudomonas aeruginosa embedded in biofilm. Further development of SBD plasma sources and research on the role of carrier gases and humidity may allow their clinical application for wound management in the future.

Impact of health campaign on hand hygiene with alcohol-based hand rubs in a non-clinical setting.

BACKGROUND: Hand hygiene has been acknowledged as the single most important measure to prevent nosocomial infections. Likewise, for non-clinical settings, hand hygiene is recognized as a key element to prevent the spread of infectious diseases, nevertheless poor compliance has been documented. The feasibility of hand hygiene interventions in open-community settings with adults is mostly unclear. AIM: To investigate the acceptability and feasibility of a health campaign to promote hand hygiene with alcohol-based hand disinfectants at workplaces in a non-clinical setting. METHODS: The surveys were conducted as part of a prospective, controlled intervention study with volunteers from the administration of the Ernst-Moritz-Arndt-University Greifswald, the municipality of Greifswald and the state of Mecklenburg-West Pomerania. Participants in the intervention group were provided with alcohol-based hand disinfection; the control group was unchanged. Eleven volunteers filled out an initial survey at the beginning of the intervention regarding demographic and health-related questions as well as questions about the type of work, and a survey after completion of the intervention to evaluate the study's impact on the participants' attitudes toward hand hygiene. Participants in the experimental group filled out a monthly questionnaire regarding their compliance with hand hygiene measures, feasibility of hand disinfection and possible side-effects. FINDINGS: From 850 employees asked to participate, 134 were included in the study, and surveys from 129 participants (intervention: 64 vs control: 65) were accepted for analysis. Overall, datasets of 1230 person-months (79.46% of total possible follow-up surveys) were collected. Return rate and compliance remained high during the study period. Hand disinfection did not lead to skin problems in the majority of person-months. After the intervention, a majority of participants would favour a further use of hand disinfectants. CONCLUSION: Campaigns that enforce the use of alcohol-based hand disinfectants can have a sustainable effect on the compliance with hand hygiene measures in non-clinical settings. Campaigns have been shown to be feasible and effective in the prevention of transmissible diseases, therefore employers should consider whether hand hygiene campaigns to introduce waterless hand rubs could be included in companies' health programmes.

Clinical use of the antiseptic polihexanide for genital tract infections.

BACKGROUND: In clinical practice, treatment of genital tract infections is based on administration of either antibiotics or antiseptics. While antibiotics may be applied systemically or topically, antiseptics may be applied only topically. In case of bacterial vaginosis (BV), antibiotic therapy may often be limited and side effects due to systemic administration may develop. Polihexanide (PHMB) is a promising option for the topical treatment of genital tract infections, in particular BV and vaginitis. METHOD: A systematic search for publications on the use of PHMB for the treatment of genital infections in two electronic databases was performed. Titles, abstracts and citations were imported into a reference database. Duplicates were removed and two reviewers assessed each identified publication separately. RESULTS: Among a total of 204 references, 3 prospective randomized trials were identified. Two trials treated BV infections with PHMB in comparison to clindamycin as antibiotic standard therapy with no significant differences either in safety or in efficacy. The third controlled trial investigated the clinical efficacy of PHMB compared to placebo in the treatment of human papilloma virus. Patients treated with PHMB daily for up to 16-weeks showed significantly higher (52%) clearance of genital warts as compared to patients treated with placebo (4%). CONCLUSION: PHMB may be a clinically effective alternative for the treatment of BV and human papilloma virus. Although PHMB-based antiseptics are available since the late 90s, controlled trials to investigate its clinical potential for antiseptic treatment are scant. Clinical use of antiseptics for the treatment of infectious diseases should be explored and supported further.

Cost-analysis of PCR-guided pre-emptive antibiotic treatment of Staphylococcus aureus infections: an analytic decision model.

The aim of this study is to examine whether rapid polymerase chain reaction (PCR)-based screening is a cost-efficient tool to optimize pre-emptive antibiotic therapy of methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA, respectively) infections. A decision analytic cost model was developed, based on data from the peer-reviewed literature. Sensitivity analyses were undertaken to investigate the impact of variation in the MRSA rate, cost ratio of the cost of inappropriate antibiotic therapy to the cost of appropriate antibiotic therapy, PCR test cost, and total hospital costs per case. At a current MRSA rate of 24.5 % in Germany, PCR-guided treatment regimens are cost-efficient compared to empirical strategies. The costs of alternative treatment strategies differ, on average, up to 1,780 per case. An empirical MRSA treatment strategy is least costly when the cost ratio is less than 1.06. When the total hospital cost per MRSA case is increased, pre-emptive MSSA treatment with PCR tests achieves the lowest average cost. Early verification and adaptation of an initial pre-emptive antibiotic treatment of S. aureus infections using PCR-based tests are advantageous in Germany and other European countries. PCR tests, accordingly, should be considered as elements in antimicrobial stewardship programs.

Transmission rates, screening methods and costs of MRSA--a systematic literature review related to the prevalence in Germany.

Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a serious challenge for health care institutions, which is inherent in the combination of prevalence, transmission rates and costs. Furthermore, performing an MRSA screening requires information on the complex system of effectiveness, accuracy and costs of different screening methods. The purpose of this study was to give an overview of parameters with decisive significance for the burden of MRSA and the selection of a specific MRSA screening strategy. A systematic literature search for peer-reviewed health economic studies associated with MRSA was performed (from 1995 to the present). Eighty-seven different studies met all inclusion and exclusion criteria. Primary outcomes included the prevalence of MRSA, MRSA transmission rates, performance characteristics of MRSA screening methods, costs for pre-emptive isolation precautions and costs per MRSA case. The prevalence rates reported for all inpatients (1.2-5.3 %) as well as for inpatients with risk factors or patients in risk areas (3.85-20.6 %) vary greatly. The range of cross-transmission rates per day reported for patients with MRSA in isolation is 0.00081-0.009 and for carriers not in isolation is 0.00137-0.140, respectively. For polymerase chain reaction (PCR) methods, the mean sensitivity and specificity were 91.09 and 95.79 %, respectively. Culture methods show an average sensitivity of 89.01 % and an average specificity of 93.21 %. The turn-around time for PCR methods averages 15 h, while for the culture method, it can only be estimated as 48-72 h. This review filtered important parameters and cost drivers, and covered them with literature-based averages. These findings serve as an ideal evidence base for further health economic considerations of the cost-effectiveness of different MRSA screening methods.

Antimicrobial efficacy of the silver wound dressing Biatain Ag in a disc carrier test simulating wound secretion.

AIM: The efficacy of antimicrobial compounds included in wound dressings has been determined using the quantitative suspension test according to EN 13727 before. However, as suspension tests are not an accurate reflection of the conditions under which wound antiseptics are used, it was investigated if a disc carrier test would yield results simulating practical conditions on wound surfaces. A silver-leaching foam wound dressing was used for evaluation of the disc carrier test method. METHOD: The disc carriers consisted of circular stainless-steel discs measuring 2 cm in diameter and 1.5 mm in thickness, complying with the requirements of EN 10088-2. Carriers were contaminated with Staphylococcus aureus, methicillin-resistant S. aureus or Pseudomonas aeruginosa, respectively, together with an artificial wound secretion and left to dry at room temperature for 30 min. The wound dressings being tested were placed on the discs for the length of the exposure time, and after neutralization by thioglycolate in phosphate-buffered saline the number of surviving test organisms was then counted. The logarithmic reduction factor was calculated from the difference between the initial inoculum and the number of recovered test organisms. RESULTS: The disc carrier test allowed determination of an antimicrobial efficacy in a realistic setting. It also imposed more stringent requirements on efficacy over time than the quantitative suspension test. The silver foam wound dressing showed a time-dependent antimicrobial efficacy. After 24-hour application time, the reduction factors against S. aureus, P. aeruginosa and the methicillin-resistant S. aureus were 1.9 ± 0.15, 2.1 ± 0.14 and 3.1 ± 0.18, respectively. CONCLUSION: The disc carrier test was a useful method for testing the antimicrobial efficacy of a foam silver dressing. The antimicrobial dressing exhibited an antimicrobial effect after 3 h and achieved a reduction >2 log against the tested bacterial strains in the presence of a simulated wound secretion after 24 h.

Efficacy of five alcohol-based skin antiseptics on sebaceous skin used at shorter application times than the current recommendation of 10 minutes.

Alcohol-based skin antiseptics are recommended with a minimum application time of 10 min on skin containing high numbers of sebaceous glands. In clinical practice, a 10-min application time is often too long. Therefore, we determined the efficacy of skin antiseptics on the forehead and lower back using shorter application times. Five alcoholic solutions were tested in a double-blind trial for their colony-forming units (cfu) reduction after 3, 4, 5 and 10 min on the forehead of 20 healthy volunteers and the lower back of 10 healthy volunteers and 10 patients against the reference alcohol 70% propan-2-ol, 10 min. After an application time of 3 min, 3/5 (forehead) and 5/5 (lower back) preparations were at least equally as effective compared to the reference alcohol and an application time of 10 min. Alcohol-based skin antiseptics do not require a 10-min application time. For all of the tested antiseptics, a minimum application time of 3 min on sebaceous skin can be recommended.