Carbapenemase-producing Gram-negative bacteria in hospital wastewater, wastewater treatment plants and surface waters in a metropolitan area in Germany, 2020.

Carbapenemase-producing bacteria (CPB) such as Klebsiella pneumoniae and Escherichia coli are causing hospital outbreaks worldwide. An important transfer route into the aquatic environment is the urban water cycle. We aimed to determine the presence of CPB in hospital wastewater, wastewater treatment plants (WWTPs) and surface waters in a German metropolitan area and to characterise these bacteria by whole-genome comparisons. During two periods in 2020, 366 samples were collected and cultivated on chromogenic screening media. Bacterial colonies were selected for species identification and PCR-based carbapenemase gene screening. Genomes of all detected CPB were sequenced and analysed for resistance gene content, followed by multilocus sequence typing (MLST) and core genome MLST (cgMLST) for K. pneumoniae and E. coli isolates. Carbapenemase genes were detected in 243 isolates, most of which belonged to genera/species Citrobacter spp. (n = 70), Klebsiella spp. (n = 57), Enterobacter spp. (n = 52) and E. coli (n = 42). Genes encoding KPC-2 carbapenemase were detected in 124 of 243 isolates. K. pneumoniae produced mainly KPC-2 and OXA-232 whereas E. coli harboured various enzymes (KPC-2, VIM-1, OXA-48, NDM-5, KPC-2 + OXA-232, GES-5, GES-5 + VIM-1, IMP-8 + OXA-48). Eight and twelve sequence types (STs) were identified for K. pneumoniae and E. coli, respectively, forming different clusters. The detection of numerous CPB species in hospital wastewater, WWTPs and river water is of concern. Genome data highlight a hospital-specific presence of distinct carbapenemase-producing K. pneumoniae and E. coli strains belonging to "global epidemic clones" in wastewater samples representing local epidemiology. The various detected CPB species including E. coli ST635, which is not known to cause human infections, could serve as reservoirs/vectors for the spread of carbapenemase genes in the environment. Therefore, effective pretreatment of hospital wastewater prior to discharge into the municipal wastewater system may be required, although swimming lakes do not appear to be a relevant risk factor for CPB ingestion and infection.

[Hyperbaric oxygen therapy : Selected indications in the discipline of otorhinolaryngology]. / Hyperbare Sauerstofftherapie : Ausgewählte Indikationen im Fachgebiet HNO-Heilkunde.

Hyperbaric oxygenation (HBO) represents the controlled exposure to positive pressure with simultaneous inhalation of pure oxygen. It is considered to be an effective treatment option for diseases with restricted blood flow as oxygen not only binds chemically to hemoglobin but also physically dissolves in blood plasma. With the help of a hyperbaric chamber the ambient pressure of a patient can be modified and the physiological characteristics in positive pressure can be medically used. The indications relevant to otorhinolaryngology are necrotizing otitis externa and skull base osteomyelitis, other forms of osteomyelitis, gangrene, wound healing disorders and sudden loss of hearing. When choosing a treatment, not only the availability and costs of HBO treatment play a role but also the patient's tolerance of overpressure. The risks of treatment, e.g., due to oxygen toxicity or barotrauma of the middle ear or the paranasal sinuses, must be weighed up against the potential benefits.

Preclinical development of a miR-132 inhibitor for heart failure treatment.

Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound's therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.

Green exercise and mg-ca-SO4 thermal balneotherapy for the treatment of non-specific chronic low back pain: a randomized controlled clinical trial.

BACKGROUND: Non-specific chronic low back pain (nscLBP) has a high socio-economic relevance due to its high incidence, prevalence and associated costs. Therefore, it is essential to evaluate effective therapeutic strategies. This study examines the effects of moderate mountain exercise and spa therapy on orthopedic and psychophysiological parameters. Based on a three-armed randomized controlled trial, guided mountain hiking tours and balneotherapy in thermal water were compared to a control group. METHODS: Eighty patients with diagnosed nscLBP were separated into three groups: The two intervention groups GE (green exercise) and GEBT (green exercise and balneotherapy) undertook daily mountain hiking tours, whereas the GEBT group got an additional treatment with baths in Mg-Ca-SO4 thermal water. The third group (CO) received no intervention. GE and GEBT group were treated for 6 days; all groups were followed up for 120 days. RESULTS: Compared to GE and CO group, the GEBT treatment showed significant improvements of pain, some orthopedic parameters, health-related quality of life and mental well-being in patients with nscLBP. CONCLUSIONS: The results of this study confirmed a benefit of mountain hiking combined with Mg-Ca-SO4 spa therapy as a multimodal treatment of patients with nscLBP. Further studies should focus on long-term-effects of this therapeutic approach. TRIAL REGISTRATION: ISRCTN, ISRCTN99926592 . Registered 06. July 2018 - Retrospectively registered.

Potential role of host-derived quorum quenching in modulating bacterial colonization in the moon jellyfish Aurelia aurita.

Multicellular organisms can be regarded as metaorganisms, comprising of a macroscopic host interacting with associated microorganisms. Within this alliance, the host has to ensure attracting beneficial bacteria and defending against pathogens to establish and maintain a healthy homeostasis. Here, we obtained several lines of evidence arguing that Aurelia aurita uses interference with bacterial quorum sensing (QS) - quorum quenching (QQ) - as one host defense mechanism. Three A. aurita-derived proteins interfering with bacterial QS were identified by functionally screening a metagenomic library constructed from medusa-derived mucus. Native expression patterns of these host open reading frames (ORFs) differed in the diverse life stages (associated with different microbiota) pointing to a specific role in establishing the developmental stage-specific microbiota. Highly increased expression of all QQ-ORFs in germ-free animals further indicates their impact on the microbiota. Moreover, incubation of native animals with pathogenic bacteria induced expression of the identified QQ-ORFs arguing for a host defense strategy against confronting bacteria by interference with bacterial QS. In agreement, immobilized recombinant QQ proteins induced restructuring of polyp-associated microbiota through changing abundance and operational taxonomic unit composition. Thus, we hypothesize that additional to the immune system host-derived QQ-activities potentially control bacterial colonization.

Willing to go the extra mile: Prospective evaluation of an intensified non-surgical treatment for patients with morbid obesity.

BACKGROUND & AIMS: Bariatric surgery has been well established and considered the treatment of choice in morbid obesity. However, some patients refuse surgery because long-term effects have not been fully elucidated, quality of life might change and lifelong supplementation with vitamins and trace elements may be required. Our aim was to exhaust non-surgical treatment modalities and to evaluate such an intensified treatment alternative. METHODS: A total of 206 patients (mean age = 46 years; BMI = 49 kg/m2) enrolled since 2013 into a non-surgical multimodality obesity treatment program covered by major health insurances were prospectively evaluated over a three year period. The 12-month treatment course comprised 57 h cognitive-behavioral therapy, 53.5 h physical exercise training, and 43.5 h nutritional therapy offered in small groups. Weight loss was induced by a formula-based, very low-calorie diet for 12 weeks in combination with a gastric balloon. The primary outcome was relative weight loss (RWL). Secondary outcome measures were waist-to-hip ratio, blood pressure, antihypertensive drug treatment, anti-diabetic medication, HbA1c, and quality of life. RESULTS: 166 Patients (81%) completed treatment. Mean (±SD) weight loss after 12 months for women and men were 28.8 kg (±14.7) and 33.7 kg (±19.5), respectively, among completers. RWL was 21.9% (±10.0) and excess weight loss (EWL) was 46.9% (±22.2), whereas intention-to-treat analysis revealed a RWL of 20.0% (±10.4) and an EWL of 42.9% (±22.9). Weight loss was accompanied by improved quality of life, lowered HbA1c values, and a significantly reduced need of antihypertensive and diabetes medications over the study period. Three year follow-up data from the first 78 patients (76% follow-up rate) revealed a RWL of 13% (±13.1) and an EWL of 27.2% (±28.8). The majority of patients (51%) maintained a RWL of 10% or more, and 44% had an EWL > 30%. CONCLUSIONS: In patients with morbid obesity, an intensified non-surgical multimodality treatment program may achieve significant and sustained weight loss accompanied by improvement of disease markers as well as quality of life for at least three years.

EBIO Does Not Induce Cardiomyogenesis in Human Pluripotent Stem Cells but Modulates Cardiac Subtype Enrichment by Lineage-Selective Survival.

Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca2+-activated potassium channels (SKs 1-4). Investigating EBIO in human pluripotent stem cells (PSCs), we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency. Equivalent to mPSCs, timed EBIO supplementation during hPSC differentiation resulted in dose-dependent enrichment of up to 80% CMs, including an increase in nodal- and atrial-like phenotypes. However, our study revealed extensive EBIO-triggered cell loss favoring cardiac progenitor preservation and, subsequently, CMs with shortened action potentials. Proliferative cells were generally more sensitive to EBIO, presumably via an SK-independent mechanism. Together, EBIO did not promote cardiogenic differentiation of PSCs, opposing previous findings, but triggered lineage-selective survival at a cardiac progenitor stage, which we propose as a pharmacological strategy to modulate CM subtype composition.

Pupillometry: the eyes shed fresh light on the mind.

Recent studies provide promising methodological advances in the use of pupillometry as on-line measurement of cognitive processes and show that visual attention allocation, mind-wandering, mental imagery, and even rhyme expectations can influence the size of the human pupil.

Developing and analysing a curriculum map in Occupational- and Environmental Medicine.

BACKGROUND: During the last 5 years a fundamental curriculum reform was realized at the medical school of the Ludwig-Maximilians-University. In contrast to those efforts, the learning objectives were not defined consistently for the curriculum and important questions concerning the curriculum could not be answered. This also applied to Occupational and Environmental Medicine where teachers of both courses were faced with additional problems such as the low number of students attending the lectures.The aims of the study were to develop and analyse a curriculum map for Occupational and Environmental Medicine based on learning objectives using a web-based database.Furthermore we aimed to evaluate student perception about the curricular structure. METHODS: Using a web-based learning objectives database, a curriculum map for Occupational and Environmental Medicine was developed and analysed. Additionally online evaluations of students for each course were conducted. RESULTS: The results show a discrepancy between the taught and the assessed curriculum. For both curricula, we identified that several learning objectives were not covered in the curriculum. There were overlaps with other content domains and redundancies within both curricula. 53% of the students in Occupational Medicine and 43% in Environmental Medicine stated that there is a lack of information regarding the learning objectives of the curriculum. CONCLUSIONS: The results of the curriculum mapping and the poor evaluation results for the courses suggest a need for re-structuring both curricula.

Fitts's Law violation and motor imagery: are imagined movements truthful or lawful?

Fitts's Law for the timing of targeted movements states that, when target width is held constant, movement time (MT) will increase as the travelled distance increases. Even imagined movements, mentally simulated actions without actual actions, obey Fitts's Law. Recently, a violation of Fitts's Law has been reported; when targets occur in a structured array, MT to the farthest target is shorter than that predicted by Fitts's Law. We conducted two experiments to determine if the violation also occurs for imagined movements. Results showed a close correspondence between real and imaginary MTs across target locations, including the Fitts's violation for the farthest target. We conclude that the violation of Fitts's Law occurs in motor imagery and that the locus of the violation is in the planning stage of action.