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A shared problem in psychology, psychiatry, and philosophy is how to define mental disorders. Various theories have been proposed, ranging from naturalism to social constructionism. In this article, I first briefly introduce the current landscape of such theories, before concentrating on one of the most influential approaches today: The harmful dysfunction theory developed by Jerome Wakefield. It claims that mental disorders are hybrid phenomena since they have a natural basis in dysfunctional mental mechanisms, but also a cultural component in the harm experienced by human beings. Although the theory is well thought through, I will raise a critical question: Is it possible to isolate mental mechanisms as naturally evolved from cultural factors? I will argue that it is not, but that the theory could still be helpful in an understanding of mental disorders, albeit on a new footing that does not operate with a natural and a cultural component as two separate factors. I argue that we need to develop a "naturecultural" approach to psychopathology that avoids mentalism, based on the fact that human beings are irreducibly persons., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Acquired resistance to platinum-derived cytostatics poses major challenges in ovarian carcinoma therapy. In this work, we show a shift in the epithelial-mesenchymal transition (EMT) process towards an "ectodermal" conversion of ovarian carcinoma cells in response to cisplatin treatment, a progression we have termed epithelial-mesenchymal-ectodermal transition (EMET). EMET appears to occur via the classical EMT as judged by a) the downregulation of several epithelial markers and b) upregulation of Vimentin, accompanied by various embryonal transcription factors and, importantly, a plethora of neuronal markers, consistent with ectodermal differentiation. Moreover, we isolated cells from ovarian carcinoma cultures exhibiting a dual neural/stemness signature and multidrug resistance (MDR) phenotype. We also found that the epithelial cells differentiate from these neural/stem populations, indicating that the cell of origin in this tumor must in fact be a neural cell type with stemness features. Notably, some transcription factors like PAX6 and PAX9 were not localized in the nucleoplasm of these cells, hinting at altered nuclear permeability. In addition, the neuronal morphology was rapidly established when commercially available and primary ovarian carcinoma cells were cultured in the form of organoids. Importantly, we also identified a cell type in regular ovarian tissues, which possess similar neural/stemness features as observed in 2D or 3D cultures. The signature of this cell type is amplified in ovarian carcinoma tumors, suggesting a neuroepithelial origin of this tumor type. In conclusion, we propose that ovarian carcinomas harbor a small population of cells with an intrinsic neuronal/stemness/MDR phenotype, serving as the cradle from which ovarian carcinoma evolves., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Real-world evidence on the management of chronic kidney disease (CKD) with and without type 2 diabetes (T2D) is limited. This study described the characteristics, treatment, and disease burdenin patients with stage 3-4 CKD with and without T2D in Finland., Methods: This cohort study used data from primary and hospital care in five municipalities in Finland to identify adults with stage 3-4 CKD, defined as having either one estimated glomerular filtration rate (eGFR) measurement of 15-59 ml/min/1.73m2 followed by a second measurement taken ≥ 90 days apart, or a registered CKD diagnosis. Prevalence was determined on 31 December 2022, and a cohort of incident stage 3-4 CKD patients was followed from the first date fulfilling eligibility criteria since 01 January 2016 (index) until death or 31 December 2022, and analyzed by T2D status., Results: The prevalence of stage 3-4 CKD was 6.3%. Among the 12 474 incident stage 3-4 CKD patients, the majority were non-T2D (73%). The median age was similar for non-T2D and T2D CKD patients, respectively. Baseline albuminuria screening was 9% among non-T2D and 53% among T2D. The use of kidney-protective treatments at index was also lower in non-T2D patients (47%), compared with T2D patients (69%). The use of kidney-protective treatments remained unchanged during 12 months after index. Healthcare resource utilization was high, and CKD or heart failure contributed considerably more to the all-cause healthcare costs than atherosclerotic diseases, regardless of T2D status. In both CKD subgroups, 10% had died within one year., Conclusions: In Finland, CKD is highly prevalent and associated with high risks and low use of albuminuria testing and kidney-protective medications. Most CKD patients were non-T2D, which showed lower use of preventive management and similar risks compared with T2D patients. These findings call for an urgent need for improved awareness and risk management, especially in non-T2D CKD patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Filamentous microorganisms exhibit a complex macro-morphology constituted of branched and cross-linked hyphae. Fully resolved mechanical models of such mycelial compounds rely heavily on accurate input data for mechanical properties of individual hyphae. Due to their irregular shape and high adaptability to environmental factors, the measurement of these intrinsic properties remains challenging. To overcome previous shortcomings of microfluidic bending tests, a novel system for the precise measurement of the individual bending stiffness of fungal hyphae is presented in this study. Utilizing two-photon polymerization, microfluidic molds were fabricated with a multi-material approach, enabling the creation of 3D cell traps for spore immobilization. Unlike previous works applying the methodology of microfluidic bending tests, the hyphae were deflected in the vertical center of the microfluidic channel, eliminating the adverse influence of nearby walls on measurements. This lead to a significant increase in measurement yield compared to the conventional design. The accuracy and reproducibility of bending tests was ensured through validation of the measurement flow using micro-particle image velocimetry. Our results revealed that the bending stiffness of hyphae of Aspergillus niger is approximately three to four times higher than that reported for Candida albicans hyphae. At the same time, the derived longitudinal Young's Modulus of the hyphal cell wall yields a comparable value for both organisms. The methodology established in this study provides a powerful tool for studying the effects of cultivation conditions on the intrinsic mechanical properties of single hyphae. Applying the results to resolved numerical models of mycelial compounds promises to shed light on their response to hydrodynamic stresses in biotechnological cultivation, which influences their expressed macro-morphology and in turn, product yields., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Brinkmann, Schrader, Meinen, Kampen, Kwade and Dietzel.)

Microbioreactors increase information output in biopharmaceutical screening applications because they can be operated in parallel without consuming large quantities of the pharmaceutical formulations being tested. A capillary wave microbioreactor (cwMBR) has recently been reported, allowing cost-efficient parallelization in an array that can be activated for mixing as a whole. Although impedance spectroscopy can directly distinguish between dead and viable cells, the monitoring of cells in suspension within bioreactors is challenging because the signal is influenced by the potentially varying properties of the culture medium. In order to address this challenge, an impedance sensor consisting of two sets of microelectrodes in a cwMBR is presented. Only one set of electrodes was covered by a two-photon cross-linked hydrogel to become insensitive to the influence of cells while remaining sensitive to the culture medium. With this impedance sensor, the biomass of Saccharomyces cerevisiae could be measured in a range from 1 to 20 g L -1 . In addition, the sensor can compensate for a change in the conductivity of the suspension of 5 to 15 mS cm -1 . Moreover, the two-photon cross-linking of hydroxyethyl starch methacrylate hydrogel, which has been studied in detail, recommends itself for even much broader sensing applications in miniaturized bioreactors and biosensors.

Background: Accurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women., Methods: We compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates., Results: Self-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data., Conclusion: This study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jacob et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Volatile methylsiloxanes (VMS) are man-made, nonbiodegradable chemicals produced at a megaton-per-year scale, which leads to concern over their potential for environmental persistence, long-range transport, and bioaccumulation. We used directed evolution to engineer a variant of bacterial cytochrome P450 BM3 to break silicon-carbon bonds in linear and cyclic VMS. To accomplish silicon-carbon bond cleavage, the enzyme catalyzes two tandem oxidations of a siloxane methyl group, which is followed by putative [1,2]-Brook rearrangement and hydrolysis. Discovery of this so-called siloxane oxidase opens possibilities for the eventual biodegradation of VMS.

Percutaneous drainage is a first-line therapy for abscesses and other fluid collections. However, experimental data on the viscosity of body fluids are scarce. This study analyses the apparent viscosity of serous, purulent and biliary fluids to provide reference data for the evaluation of drainage catheters. Serous, purulent and biliary fluid samples were collected during routine drainage procedures. In a first setup, the apparent kinematic viscosity of 50 fluid samples was measured using an Ubbelohde viscometer. In a second setup, the apparent dynamic viscosity of 20 fluid samples obtained during CT-guided percutaneous drainage was measured using an in-house designed capillary extrusion experiment. The median apparent kinematic viscosity was 0.96 mm 2 /s (IQR 0.90-1.15 mm 2 /s) for serous samples, 0.98 mm 2 /s (IQR 0.97-0.99 mm 2 /s) for purulent samples and 2.77 mm 2 /s (IQR 1.75-3.70 mm 2 /s) for biliary samples. The median apparent dynamic viscosity was 1.63 mPa*s (IQR 1.27-2.09 mPa*s) for serous samples, 2.45 mPa*s (IQR 1.69-3.22 mPa*s) for purulent samples and 3.50 mPa*s (IQR 2.81-3.90 mPa*s) for biliary samples (all differences p < 0.01). Relative to water, dynamic viscosities were increased by a factor of 1.36 for serous fluids, 2.26 for purulent fluids, and 4.03 for biliary fluids. Serous fluids have apparent viscosities similar to water, but biliary and purulent fluids are more viscous. These data can be used as a reference when selecting the drainage catheter size, with 8F catheters being appropriate for most percutaneous drainage cases., (© 2023. The Author(s).)

The relationship between biology and the psy disciplines (psychology, psychiatry, and psychotherapy) is a complex one. Many scholars have criticized how these disciplines have been biologized in the 20th century, especially since the emergence of psychopharmacology, neuroscience, and genetic research. However, biology is not just a laboratory-based science of chemical compounds, scanners, and DNA sequencing, but also a field science based on observations of organisms in their milieus. In this paper, we draw a contrast between laboratory-based biology with a focus on brains and genes, and an ecology-based biology with a focus on lives and niches. Our argument is philosophical in nature - building partly on Wittgenstein as a "philosopher of life" - to the effect that the psy sciences need not just less biologization of the former kind, but also more biologization of the latter kind to avoid a prevalent mentalism. Not least when it comes to an understanding of psychological distress, which can favorably be viewed situationally and coupled to human lives in ecological niches., (© 2023. The Author(s).)

Background: Intensive Care Unit (ICU) survivors often experience several impairments in their physical, cognitive, and psychological health status, which are labeled as post-intensive care syndrome (PICS). The aim of this work is to develop a multidisciplinary and -professional guideline for the rehabilitative therapy of PICS., Methods: A multidisciplinary/-professional task force of 15 healthcare professionals applied a structured, evidence-based approach to address 10 scientific questions. For each PICO-question (Population, Intervention, Comparison, and Outcome), best available evidence was identified. Recommendations were rated as "strong recommendation", "recommendation" or "therapy option", based on Grading of Recommendations, Assessment, Development and Evaluation principles. In addition, evidence gaps were identified., Results: The evidence resulted in 12 recommendations, 4 therapy options, and one statement for the prevention or treatment of PICS., Recommendations: early mobilization, motor training, and nutrition/dysphagia management should be performed. Delirium prophylaxis focuses on behavioral interventions. ICU diaries can prevent/treat psychological health issues like anxiety and post-traumatic stress disorders. Early rehabilitation approaches as well as long-term access to specialized rehabilitation centers are recommended. Therapy options include additional physical rehabilitation interventions. Statement: A prerequisite for the treatment of PICS are the regular and repeated assessments of the physical, cognitive and psychological health in patients at risk for or having PICS., Conclusions: PICS is a variable and complex syndrome that requires an individual multidisciplinary, and multiprofessional approach. Rehabilitation of PICS should include an assessment and therapy of motor-, cognitive-, and psychological health impairments., (© 2023. The Author(s).)

Background: This methodological essay discusses the following question: How can researchers' competences in exploring existential aspects related to healthcare be enhanced? Exploring this novel perspective on caring practice may help us better understand and communicate about experiences and issues that matter to others (e.g. patients/users). Two things are needed: firstly, a vocabulary mirroring an "aesthetic-holistic" research approach allowing us to capture the essence of "what it is like" and secondly, the development of skills and competences allowing us to understand complex aspects of caring that are embodied, ethically sensitive and sustainable., Aim: To identify personal competences and approaches underpinning research exploring "what it is like"-understanding human existence., Discussion: The discussion addresses three questions: (A) What does human science exploring human existence search for? (B) Which researcher competences are required? (C) Which theoretical and practical approaches and dimensions may enhance the researchers' competences? We argue that we should find "ourselves" not only grasped through language and a qualitative research-methodological approach but also in what is reflected in the relation between self, language (dialogue) and the other. It is crucial to listen to the world in an ontological way. Emotions, feelings and bodily sensed understandings can, in some situations, bar us from stepping further into meta-physical listening and from adopting a being-in-the-world stance. In this relational perspective, the researcher may adopt an attentive pace and aesthetical attunement that transcend what cannot be reached through the language of logical, rigorous, precise and rational words, tuning into the ontological mood that exists as the tacit backdrop of our existence. This approach we dub "Embodied Relational Research.", Conclusion: Researchers who explore humanity may benefit from cultivating awareness, sensitivity and understanding while displaying openness towards the other (the patients' or users' experiences). In this context, contemplative and creative dimensions are important to apply., (© 2022 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Purpose: Rectosigmoid resection rectopexy has been established as an effective therapy for obstructive defecation syndrome. The addition of the NOSE-technique provides an even less invasive approach avoiding minilaparotomy, but can be technically challenging. Application of a robotic platform has been proposed to facilitate the specimen extraction and fashioning of the intracorporeal anastomosis and has been proven to be effective in left-sided colectomies., Methods: After establishing laparoscopic rectosigmoid-resection-rectopexy with NOSE, we modified our technique by addition of the robotic platform. Whenever robotic capacity was available, elective patients scheduled for rectosigmoid resection rectopexy for obstructive defecation syndrome were operated robotically assisted. Demographic and intraoperative data were prospectively collected. Follow up was assessed using the Wexner constipation score, Wexner incontinence score, and Altomare ODS score., Results: The NOSE-RRR technique was completed in all 31 patients. The mean operative time was 166 min (range 67-230). No conversion was required. The median hospital stay was 5 days (range 3-28). Four patients had minor complications (Clavien I). Two patients were reoperated (Clavien IIIb). Functional scores improved significantly postoperatively. Mean Wexner incontinence score was 7.1 preoperatively, 6.9 after 1 month, and decreased significantly to 3.93 after 3 months (p < 0.001). Mean Altomare ODS score was 17.47 preoperatively and 6.93/5.03 after 1/3 months (p < 0.001). Wexner constipation score (12.83) also showed a significant improvement after 1/3 months (6.97/6.67; p < 0.001)., Conclusion: NOSE-RRR can be performed safely with a low rate of manageable complications. The technique provides a significant improvement for ODS-Symptoms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Common mental health problems are a substantial burden in many western countries. Studies have pointed out that work related factors can both increase and decrease the risk of developing mental health problems. Influence at work is a key factor relating the psychosocial work environment to employees mental health. However, little is known regarding how contemporary employees experience and understand influence at work. The purpose of this study is to explore this in depth., Methods: We conducted semi-structured interviews with 59 employees in knowledge and relational work and analysed the data using principles from Interpretative Phenomenological Analysis (IPA)., Findings: TWe identified three themes each consisting of two interrelated parts, where the second part describes the consequences of the identified type of influence for employees: 1) work tasks and performance, 2) relations and belonging, 3) identity and becoming., Conclusions: The interviewed employees had a multifaceted understanding of influence at work and that influence at work mattered to them in different but important ways. Our hope is that managers, employees and consultants will be inspired by the three themes when designing work tasks, organizations and interventions in order to increase the level of influence and thereby help enhance the mental well-being of employees.

Background: An increasing body of qualitative and quantitative research suggests that choir singing can improve mental and physical health and wellbeing. A recurring phenomenon is social agency and social and emotional competences. However, there is little consensus about the underlying impact mechanisms and the special nature of music as a medium for music-based social-emotional competence., Aim: This research was carried out to explore how the participants experienced engaging and singing in the choir A Song for the Mind in order to understand the social and emotional aspects in relation to choir singing and mental health., Method: Six women and two men were interviewed. The study involved open-ended interviews and applied Paul Ricoeur's phenomenological-hermeneutic theory of interpretation in processing the collected data., Findings: Two themes emerged-The Singing Me and Cultivating Us. Joining the choir, singing and engaging with the lyrics, helped the participants get in contact with complex feelings and visualise and express challenges. This formed feelings of connecting to oneself and opening up to become aware of the world such as nature, the other person and the choir. Songs, melodies, tones, lyrics-singing together-formed a relation between the participants and the other and the group. This was a meaningful, and to some, a life-changing experience, and an important learning process to the professionals. As the participants are sensing and connecting to themselves, there is an opening for growing a nascent presence and awareness., Conclusion: Joining the initiative A Song for the Mind instils an attention to the other person(s). The singing process seems to evoke presence, leading to awareness towards relational aspects and solidarity. In a choir singing perspective, and health care practice in general, this can be seen as a budding and ground-breaking formation of cultural activities holding learning and empowering potentials instilling mental health., (© 2022 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

With progress in genome sequencing and data sharing, 1,000s of bacterial genomes are publicly available. Genome mining-using bioinformatics tools in terms of biosynthetic gene cluster (BGC) identification, analysis, and rating-has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing the genetic potential of the phylum Bacteroidetes revealed Chitinophaga as the most talented genus in terms of BGC abundance and diversity. Guided by the computational predictions, we conducted a metabolomics and bioactivity driven NP discovery program on 25 Chitinophaga strains. High numbers of strain-specific metabolite buckets confirmed the upfront predicted biosynthetic potential and revealed a tremendous uncharted chemical space. Mining this data set, we isolated the new iron chelating nonribosomally synthesized cyclic tetradeca- and pentadecalipodepsipeptide antibiotics chitinopeptins with activity against Candida , produced by C. eiseniae DSM 22224 and C. flava KCTC 62435, respectively. IMPORTANCE The development of pipelines for anti-infectives to be applied in plant, animal, and human health management are dried up. However, the resistance development against compounds in use calls for new lead structures. To fill this gap and to enhance the probability of success for the discovery of new bioactive natural products, microbial taxa currently underinvestigated must be mined. This study investigates the potential within the bacterial phylum Bacteroidetes. A combination of omics-technologies revealed taxonomical hot spots for specialized metabolites. Genome- and metabolome-based analyses showed that the phylum covers a new chemical space compared with classic natural product producers. Members of the Bacteroidetes may thus present a promising bioresource for future screening and isolation campaigns.

Covering: up to end of January 2022Bacteria representing the phylum Bacteroidetes produce a diverse range of natural products, including polyketides, peptides and lactams. Here, we discuss unique aspects of the bioactive compounds discovered thus far, and the corresponding biosynthetic pathways if known, providing a comprehensive overview of the Bacteroidetes as a natural product reservoir.

Termites live in a dynamic environment where colony health is strongly influenced by surrounding microbes. However, little is known about the mycobiomes of lower termites and their nests, and how these change in response to disease. Here we compared the individual and nest mycobiomes of a healthy subterranean termite colony (Coptotermes testaceus) to one infected and ultimately eradicated by a fungal pathogen. We identified Trichoderma species in the materials of both nests, but they were also abundant in the infected termites. Methanolic extracts of Trichoderma sp. FHG000531, isolated from the infected nest, were screened for secondary metabolites by UHPLC-HR MS/MS-guided molecular networking. We identified many bioactive compounds with potential roles in the eradication of the infected colony, as well as a cluster of six unknown peptides. The novel peptide FE011 was isolated and characterized by NMR spectroscopy. The function of this novel peptide family as well as the role of Trichoderma species in dying termite colonies therefore requires further investigation., (© 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Minimally invasive resection techniques for the treatment of various pathologies of the pancreas are potentially advantageous for the treated patients in terms of restitution time and postoperative morbidity, but are a technical challenge for the responsible surgeon. The introduction of robotic assistance in visceral surgery offers a possibility for further distribution of minimally invasive procedures in pancreatic surgery.The aim of this study was to examine the possibilities for developing robotic pancreatic surgery in Germany. The data are based on the quality reports of the hospitals for the years 2015-2019 combined with a selective literature search.The number of quality reports available decreased from 1635 to 1594 between 2015 and 2019. A median of 96 clinics performed 11-20, 56 clinics 21-50 and 15 clinics more than 50 pancreaticoduodenectomies. For distal resections, there were 35 clinics with 11-20, 14 clinics with 21-50 and two clinics with more than 50 procedures. In relation to all clinics with at least five distal resections per year, minimally invasive procedures were performed at only 29 clinics; a ratio to laparoscopic left resections of over 50% was reported in only seven clinics.According to the literature, the learning curves for robotic pancreatic distal resection and pancreaticoduodenectomy diverge. While the learning curve for robotic distal resection is completed after around 20 procedures, the learning curve for robotic pancreaticoduodenectomy has several plateaus, which are reached after around 30, 100 and 250 procedures.Due to the decentralised structure of pancreatic surgery in Germany, a nationwide introduction of robotic pancreatic surgery is unlikely. The routine use of robotic pancreaticoduodenectomy will probably be restricted to high volume centres in the foreseeable future., Competing Interests: Torben Glatz, Sebastian Brinkmann, Omar Thaher, Jamal Driouch und Dirk Bausch haben Zuwendungen in Form von Reisestipendien von Intuitive Surgical Systems erhalten., (Thieme. All rights reserved.)

Protease inhibitors represent a promising therapeutic option for the treatment of parasitic diseases such as malaria and human African trypanosomiasis. Falcitidin was the first member of a new class of inhibitors of falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum . Using a metabolomics dataset of 25 Chitinophaga strains for molecular networking enabled identification of over 30 natural analogues of falcitidin. Based on MS/MS spectra, they vary in their amino acid chain length, sequence, acyl residue, and C-terminal functionalization; therefore, they were grouped into the four falcitidin peptide families A-D. The isolation, characterization, and absolute structure elucidation of two falcitidin-related pentapeptide aldehyde analogues by extensive MS/MS spectrometry and NMR spectroscopy in combination with advanced Marfey's analysis was in agreement with the in silico analysis of the corresponding biosynthetic gene cluster. Total synthesis of chosen pentapeptide analogues followed by in vitro testing against a panel of proteases revealed selective parasitic cysteine protease inhibition and, additionally, low-micromolar inhibition of α-chymotrypsin. The pentapeptides investigated here showed superior inhibitory activity compared to falcitidin.

Purpose: Esophageal perforation is associated with high morbidity and mortality. In addition to surgical treatment, endoscopic endoluminal stent placement and endoscopic vacuum therapy (EVT) are established methods in the management of this emergency condition. Although health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic intervention, not much is known about HRQoL, particularly in the long-term follow-up of patients treated for non-neoplastic esophageal perforation with different treatment strategies. The aim of this study was to evaluate patients' outcome after non-neoplastic esophageal perforation with focus on HRQoL in the long-term follow-up., Methods: Patients treated for non-neoplastic esophageal perforation at the University Hospital Cologne from January 2003 to December 2014 were included. Primary outcome and management of esophageal perforation were documented. Long-term quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI), the Health-Related Quality of Life Index (HRQL) for patients with gastroesophageal reflux disease (GERD), and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires for general and esophageal specific QoL (QLQ-C30 and QLQ-OES18)., Results: Fifty-eight patients were included in the study. Based on primary treatment, patients were divided into an endoscopic (n = 27; 46.6%), surgical (n = 20; 34.5%), and a conservative group (n = 11; 19%). Short- and long-term outcome and quality of life were compared. HRQoL was measured after a median follow-up of 49 months. HRQoL was generally reduced in patients with non-neoplastic esophageal perforation. Endoscopically treated patients showed the highest GIQLI overall score and highest EORTC general health status, followed by the conservative and the surgical group., Conclusion: HRQoL in patients with non-neoplastic esophageal perforation is reduced even in the long-term follow-up. Temporary stent or EVT is effective and provides a good alternative to surgery, not only in the short-term but also in the long-term follow-up., (© 2021. The Author(s).)

High-throughput platforms facilitating screening campaigns of environmental samples are needed to discover new products of natural origin counteracting the spreading of antimicrobial resistances constantly threatening human and agricultural health. We applied a combination of droplet microfluidics and fluorescence-activated cell sorting (FACS)-based technologies to access and assess a microbial environmental sample. The cultivation performance of our microfluidics workflow was evaluated in respect to the utilized cultivation media by Illumina amplicon sequencing of a pool of millions of droplets, respectively. This enabled the rational selection of a growth medium supporting the isolation of microbial diversity from soil (five phyla affiliated to 57 genera) including a member of the acidobacterial subgroup 1 (genus Edaphobacter). In a second phase, the entire diversity covered by 1071 cultures was used for an arrayed bioprospecting campaign, resulting in > 6000 extracts tested against human pathogens and agricultural pests. After redundancy curation by using a combinatorial chemical and genomic fingerprinting approach, we assigned the causative agents present in the extracts. Utilizing UHPLC-QTOF-MS/MS-guided fractionation and microplate-based screening assays in combination with molecular networking the production of bioactive ionophorous macrotetrolides, phospholipids, the cyclic lipopetides massetolides E, F, H and serratamolide A and many derivatives thereof was shown., (© 2021 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Miniaturization of biomedical and chemical research areas is performed using microfluidic techniques. Droplet-based microfluidic applications are of high interest for various applications, e.g., high-throughput screening assays. Many of them are based on simple water-in-oil (w/o) or oil-in-water (o/w) emulsions that are easily to produce. More complex assays based on separate compartments require the use of multiple emulsions, such as water-in-oil-in-water (w/o/w) or oil-in-water-in-oil (o/w/o) emulsions. In this study an easy, fast to establish method to generate agarose-solidified (w/w/o) double emulsions with ∼55 µm in diameter, in which both agarose-phases are not separated by a surfactant stabilized oil is described. An off-chip emulsion-breaking and washing step of the inner agarose droplets based on density gradient centrifugation was designed, offering new possibilities for high-throughput assays on picoliter scale. In brief, this paper reports:•the protocol to generate agarose-solidified (w/w/o) double emulsions non-seperated by surfactant stabilized oil;•an off-chip washing protocol of agarose-solidified emulsions based on density gradient centrifugation., (© 2021 The Authors. Published by Elsevier B.V.)

In 1911, the city of São Paulo decided to modernize its milk supply system by opening up the import market for industrially pasteurized milk. But the industrial product was widely rejected, creating even more demand for raw milk produced in small barns under potentially unsafe conditions. This study examines how public authorities handled the double challenge of both minimizing the health risks of raw milk and helping to improve the industrial product, over the course of three decades. The article ends with an analysis of the effects of mandatory pasteurization, introduced in 1939, which equated to a ban on the sale of raw milk in the city of São Paulo.

Background: The coronavirus disease 2019 (COVID-19) pandemic led to far-reaching restrictions of social and professional life, affecting societies all over the world. To contain the virus, medical schools had to restructure their curriculum by switching to online learning. However, only few medical schools had implemented such novel learning concepts. We aimed to evaluate students' attitudes to online learning to provide a broad scientific basis to guide future development of medical education., Methods: Overall, 3286 medical students from 12 different countries participated in this cross-sectional, web-based study investigating various aspects of online learning in medical education. On a 7-point Likert scale, participants rated the online learning situation during the pandemic at their medical schools, technical and social aspects, and the current and future role of online learning in medical education., Results: The majority of medical schools managed the rapid switch to online learning (78%) and most students were satisfied with the quantity (67%) and quality (62%) of the courses. Online learning provided greater flexibility (84%) and led to unchanged or even higher attendance of courses (70%). Possible downsides included motivational problems (42%), insufficient possibilities for interaction with fellow students (67%) and thus the risk of social isolation (64%). The vast majority felt comfortable using the software solutions (80%). Most were convinced that medical education lags behind current capabilities regarding online learning (78%) and estimated the proportion of online learning before the pandemic at only 14%. In order to improve the current curriculum, they wish for a more balanced ratio with at least 40% of online teaching compared to on-site teaching., Conclusion: This study demonstrates the positive attitude of medical students towards online learning. Furthermore, it reveals a considerable discrepancy between what students demand and what the curriculum offers. Thus, the COVID-19 pandemic might be the long-awaited catalyst for a new "online era" in medical education., Competing Interests: The authors have declared that no competing interests exist.

The 'core' metabolome of the Bacteroidetes genus Chitinophaga was recently discovered to consist of only seven metabolites. A structural relationship in terms of shared lipid moieties among four of them was postulated. Here, structure elucidation and characterization via ultra-high resolution mass spectrometry (UHR-MS) and nuclear magnetic resonance (NMR) spectroscopy of those four lipids (two lipoamino acids (LAAs), two lysophosphatidylethanolamines (LPEs)), as well as several other undescribed LAAs and N -acyl amino acids (NAAAs), identified during isolation were carried out. The LAAs represent closely related analogs of the literature-known LAAs, such as the glycine-serine dipeptide lipids 430 ( 2 ) and 654. Most of the here characterized LAAs ( 1 , 5 - 11 ) are members of a so far undescribed glycine-serine-ornithine tripeptide lipid family. Moreover, this study reports three novel NAAAs ( N -(5-methyl)hexanoyl tyrosine ( 14 ) and N -(7-methyl)octanoyl tyrosine ( 15 ) or phenylalanine ( 16 )) from Olivibacter sp. FHG000416, another Bacteroidetes strain initially selected as best in-house producer for isolation of lipid 430. Antimicrobial profiling revealed most isolated LAAs ( 1 - 3 ) and the two LPE 'core' metabolites ( 12 , 13 ) active against the Gram-negative pathogen M. catarrhalis ATCC 25238 and the Gram-positive bacterium M. luteus DSM 20030. For LAA 1 , additional growth inhibition activity against B. subtilis DSM 10 was observed.

Minimally invasive donor nephrectomy has become the standard procedure in most transplant centres over the past two decades and has contributed to a reduction in postoperative morbidity for the donor. Robot-assisted technology is an alternative to conventional (hand-assisted) laparoscopic technology and will find increasing use in the future. In this review article, we address technical aspects of robotic-assisted donor nephrectomy, in accordance with our own experience and will provide an overview of the currently available literature. Robot-assisted living kidney donation is a safe procedure with a very low postoperative complication rate. The procedure offers advantages over the open surgical technique with respect to the reduction in the postoperative need for analgesia and the duration of hospital stay, with longer operating times and warm ischemia times, but without a measurable effect on transplant function. The postoperative outcome parameters are comparable to those of the laparoscopic technique, indicating a further acceleration of postoperative convalescence. The advantages of robot-assisted technology, due to the better exposure options, are most relevant in patients with a high BMI and multiple renal arteries, as well as in right-sided nephrectomies in which a longer transplant artery can be obtained. Robot-assisted living kidney donation will play a major role in the future of transplant surgery and is a serious alternative to conventional laparoscopic technology., Competing Interests: Dirk Bausch und Torben Glatz haben Zuwendungen in Form von Reisestipendien von Intuitive Surgical Systems erhalten. Sebastian Brinkmann hat keinen Interessenkonflikt angegeben., (Thieme. All rights reserved.)

Background: There is growing concern regarding the implications of miscommunication in health care settings, the results of which can have serious detrimental impacts on patient safety and health outcomes. Effective communication between nurses and patients is integral in the delivery of timely, competent, and safe care. In a hospital environment where care is delivered 24 hours a day, interpreters are not always available. In 2014, we developed a communication app to support patients' interactions with allied health clinicians when interpreters are not present. In 2017, we expanded this app to meet the needs of the nursing workforce. The app contains a fixed set of phrases translated into common languages, and communication is supported by text, images, audio content, and video content., Objective: This study aims to evaluate the efficacy of the communication app to support nursing staff during the provision of standard care to patients from non-English-speaking backgrounds when an interpreter is not available., Methods: This study used a one-group pretest-posttest sequential explanatory mixed methods research design, with quantitative data analyzed using inferential statistics and qualitative data analyzed via thematic content analysis. A total of 134 observation sessions (82 pretest and 52 posttest) of everyday nurse-patient interactions and 396 app use sessions were recorded. In addition, a total of 134 surveys (82 pretest and 52 posttest) with nursing staff, 7 interviews with patients, and 3 focus groups with a total of 9 nursing staff participants were held between January and November 2017., Results: In the absence of the app, baseline interactions with patients from English-speaking backgrounds were rated as more successful (t 80 =5.69; P<.001) than interactions with patients from non-English-speaking backgrounds. When staff used the app during the live trial, interactions with patients from non-English-speaking backgrounds were rated as more successful than interactions without the app (F 2,119 =8.17; P<.001; η 2 =0.37). In addition, the level of staff frustration was rated lower when the app was used to communicate (t 80 =2.71; P=.008; r=0.29). Most participants indicated that the app assisted them in communicating., Conclusions: Through the use of the app, a number of patients from non-English-speaking backgrounds experienced better provision of standard care, similar to their English-speaking peers. Thus, the app can be seen as contributing to the delivery of equitable health care., (©David Silvera-Tawil, Courtney Pocock, DanaKai Bradford, Andrea Donnell, Jill Freyne, Karen Harrap, Sally Brinkmann. Originally published in JMIR Nursing (https://nursing.jmir.org), 30.07.2021.)

Cholangiocarcinoma (CCA) is an aggressive malignancy with a 5-year-survival rate of <10%, mainly due to diagnosis in advanced stages and limited therapeutic options in case of progressive disease. Recently, evidence has indicated that alterations in the SWI/SNF-complex (SWI/SNF) may have an important role in the tumorigenesis of CCA. SWI/SNF-related chromatin remodeling has been reported to be crucial for differentiation and tumor suppression, and loss-of-function mutations of SWI/SNF are present in 20% of human malignancies; however, at present, little is known about its relevance in CCA. In the present study, a cohort of 52 patients with the diagnosis of primary CCA was retrospectively collected. All patients underwent surgery with curative intent. Tissue microarray analysis was performed on each tumor for immunohistochemical loss-of-protein analysis of the SWI/SNF core subunits ARID1A, INI-1, BRG1, PBRM-1 and BRM, corresponding to the following CCA subtypes: Extrahepatic CCA (ECCA), small duct or large duct intrahepatic CCA (ICCA). Kaplan-Meier analysis was used to determine survival distribution and survival differences were evaluated by log-rank test. In total, 14 of 52 patients (~35%) exhibited protein-loss of any tested SWI/SNF core subunit. Notably, 17% of patients exhibited a loss of ARID1a; this was the protein loss with the highest frequency. Patients with small and large duct ICCA with protein-loss of any tested SWI/SNF subunit exhibited significantly worse survival compared with the wild-type cohort with proficient protein expression (P=0.013 and P=0.002), whereas no significant survival difference was detected for patients with ECCA. SWI/SNF and its core subunits may be considered promising predictive and therapeutic targets, and require further investigation in patients with CCA., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Wagner et al.)

Sample components can not only be changed but also activated or inactivated via enzymatic or metabolic reactions. Identifying such activity conversions is the challenge. Up to now, the instrumental complexity and required bioanalytical effort have hindered progress in understanding such mechanisms. The newly developed all-in-one nanoGIT +active system substantially extends, and at the same time, miniaturizes the state-of-the-art technology. It combines all relevant steps on the same adsorbent surface. On-surface metabolization, immediate separation, multi-imaging, and effect-directed detection is performed as all-in-one system. Such a compact, miniaturized nanomolar system was exemplarily developed for well-known food systems. The proof-of-concept showed not only the miniaturized simulation of the coordinated processes of all digestion segments, but also bioactivity changes. The results presented as images were easily understandable. The conversions on surface were verified by comparison with state-of-the-art in vitro assays (analyzed by the same method). With new bioanalytical tools, new insights will open up. Activity changes and effects on metabolization pathways can now be identified more comprehensively and cost-/time-efficiently, if compared to status quo procedures (requiring in vitro digestion assays, column chromatographic separation systems, multiple detectors and in vitro effect-directed assays). This is attractive for nutritional, health and pharmaceutical science, drug development, medicinal research and for lean laboratories., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The goal of the present study was to classify the most common types of plain radiographs using a neural network and to validate the network's performance on internal and external data. Such a network could help improve various radiological workflows., Methods: All radiographs from the year 2017 (n = 71,274) acquired at our institution were retrieved from the PACS. The 30 largest categories (n = 58,219, 81.7% of all radiographs performed in 2017) were used to develop and validate a neural network (MobileNet v1.0) using transfer learning. Image categories were extracted from DICOM metadata (study and image description) and mapped to the WHO manual of diagnostic imaging. As an independent, external validation set, we used images from other institutions that had been stored in our PACS (n = 5324)., Results: In the internal validation, the overall accuracy of the model was 90.3% (95%CI: 89.2-91.3%), whereas, for the external validation set, the overall accuracy was 94.0% (95%CI: 93.3-94.6%)., Conclusions: Using data from one single institution, we were able to classify the most common categories of radiographs with a neural network. The network showed good generalizability on the external validation set and could be used to automatically organize a PACS, preselect radiographs so that they can be routed to more specialized networks for abnormality detection or help with other parts of the radiological workflow (e.g., automated hanging protocols; check if ordered image and performed image are the same). The final AI algorithm is publicly available for evaluation and extension., Key Points: • Data from one single institution can be used to train a neural network for the correct detection of the 30 most common categories of plain radiographs. • The trained model achieved a high accuracy for the majority of categories and showed good generalizability to images from other institutions. • The neural network is made publicly available and can be used to automatically organize a PACS or to preselect radiographs so that they can be routed to more specialized neural networks for abnormality detection.

Background: Ivor-Lewis esophagectomy (ILE) is the standard surgical care for esophageal cancer patients but postoperative morbidity impairs quality of life and reduces long-term oncological outcome. Two-stage ILE separating the abdominal and thoracic phase into two distinct surgical procedures has proven to enhance microcirculation of the gastric conduit and therefore most likely reduces complications. However, two-stage ILE has not been evaluated systematically in selected groups of patients scheduled for this procedure. This investigation aims to demonstrate the feasibility of two-stage ILE in high-risk patients., Patients and Methods: In this retrospective analysis of data obtained from a prospective database, a consecutive series of 275 hybrid ILE (hILE) were included. Patients were divided into two groups based on one- or two-stage hILE. Postoperative complications were assessed according to ECCG (Esophageal Complication Consensus Group) criteria and compared using the Clavien-Dindo score. Indication for two-stage esophagectomy was classified as pre- or intraoperative decision., Results: 34 out of 275 patients (12.7%) underwent two-stage hILE. Patients of the two-stage group were significantly older. In 21 of 34 patients (61.8%) the decision for a two-stage procedure was made prior to esophagectomy, in 13 (38.2%) patients intraoperatively after completion of the laparoscopic gastric mobilization. The most frequent preoperative reason to select the two-stage procedure was a stenosis of the coeliac trunc and superior mesenteric artery (n = 10). The predominant cause for an intraoperative change of strategy was a laparoscopically diagnosed hepatic fibrosis/cirrhosis (n = 5).Overall morbidity and major' complications (CD > IIIa) were comparable for both groups (11.7% in both groups). The overall anastomotic leak rate was 12.4% and was non-significant lower for the two-stage procedure., Conclusion: Two-stage hILE is a feasible concept to individualize the surgical treatment of patients with well-defined clinical risk factors for postoperative morbidity. It can also be applied after completion of the abdominal phase of IL esophagectomy without compromising the patient safety.

Compared to the biological world's rich chemistry for functionalizing carbon, enzymatic transformations of the heavier homologue silicon are rare. We report that a wild-type cytochrome P450 monooxygenase (P450 BM3 from Bacillus megaterium, CYP102A1) has promiscuous activity for oxidation of hydrosilanes to give silanols. Directed evolution was applied to enhance this non-native activity and create a highly efficient catalyst for selective silane oxidation under mild conditions with oxygen as the terminal oxidant. The evolved enzyme leaves C-H bonds present in the silane substrates untouched, and this biotransformation does not lead to disiloxane formation, a common problem in silanol syntheses. Computational studies reveal that catalysis proceeds through hydrogen atom abstraction followed by radical rebound, as observed in the native C-H hydroxylation mechanism of the P450 enzyme. This enzymatic silane oxidation extends nature's impressive catalytic repertoire., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Zagaria, Andò and Zennaro have provided a useful analysis of the theoretical precariousness of psychology by looking at a number of its core concepts. They propose that evolutionary psychology could be a unifying approach for the otherwise fragmented discipline. In this response, I argue that although evolutionary psychology provides many interesting perspectives on the mental life of human beings, it is much too soon to jump to a unifying conclusion for psychology on its basis. Before beginning the work of explaining the functioning of the mind in evolutionary terms, we need illuminating descriptions of mental life as such. Phenomenological description should precede evolutionary explanation, and the former will reveal that mental life is intentional and normative - something that evolutionary and other explanatory perspectives have difficulties accommodating. When the subject matter is human mental life, it might be better to live with conceptual confusion than obtaining consensus on a misguided foundation. I agree with the authors that psychology stands on feet of clay, but instead of lamenting the "unsteady building" of the discipline, I suggest we embrace a more nomadic life for psychology - moving about on our feet - given the fact that humans perpetually and historically seem to reflect on their own lives, which is a process that should be kept open rather than terminated.

Objective: In this work, we propose a new care concept for dementia patients in their own apartments: interconnected living in a quarter. We describe a technical setup that is comprised of a safety system and an activity detection system. The latter detects, processes and illustrates activities of daily living to help the quarter managers to provide appropriate interventions for persons with dementia in the quarter., Participants: The nine-month field study reported in this work was conducted in two quarters with eight participants., Methods: We evaluated different possibilities to determine activity indicators with the aim of providing information that enables the quarter managers to offer exactly the level of support needed by each individual patient. To evaluate the usefulness and the perception of the technical infrastructure, qualitative interviews with the dementia patients and the quarter managers were conducted., Results: The results indicate that the interconnected living concept helps to increase the safety of the dementia patients. Additionally, several activity indicators that help the quarter managers to offer the appropriate level of support to the dementia patients have been identified., Conclusion: The presented concept, which has been evaluated in a real-world-setting, constitutes a new holistic and cross-disciplinary dementia care approach.

Background: HIV diagnosis in South Africa is based on a point-of-care testing (PoCT) algorithm with paper-based record-keeping. Aggregated testing data are reported routinely. To facilitate improved HIV case-based surveillance, the Western Cape Province implemented a unique pilot intervention to digitise PoCT results, at an individual level, and generate an electronic register using the newly developed Provincial Health Data Centre (PHDC). We describe the intervention (phased) and present an evaluation of the operational feasibility of the intervention. We also offer implementation insights into establishing electronic capture of individual level testing data., Methods: Cross-sectional analyses were conducted on records of all patients attending a local Community Health Centre who had an HIV-PoCT during the study period. Data from the intervention were linked to the PHDC using a unique identifier and compared with aggregate data from the paper-based register. Correlation coefficients were calculated to quantify the correlation between the two monthly datasets. To support an understanding of the findings, the Department of Health project management team generated reflections on the implementation process, which were then grouped thematically into implementation lessons., Results: In total, 11,337 PoCT records were digitised (70% (7954) during Phase I; and 30% (3383) during Phase II). Linkage of forms to the PHDC was 96% in Phase I and 98% in Phase II. Comparison with aggregate data showed high correlation during Phase I, but notable divergence during Phase II. Divergence in Phase II was due to stringent data quality requirements and high clinical staff turnover. Factors supporting implementation success in Phase I included direct oversight of data capturing by a manager with clinical and operational insight. Implementation challenges included operational, health system, and high cost-related issues., Conclusions: We demonstrate that rapid digitisation of HIV PoCT data, without compromising currently collected aggregate data, is operationally feasible, and can contribute to person-level longitudinal HIV case-based surveillance. To take to scale, we will need to improve PoCT platforms and clerical and administrative systems. Although we highlight challenges, we demonstrate that electronic HIV testing registers can successfully replace manual registers and improve efforts to monitor and evaluate HIV testing strategies.

Background: This study was conducted to validate a pretreatment (i.e. prior to neoadjuvant chemoradiotherapy) pathological staging system in the resection specimen after neoadjuvant chemoradiotherapy for esophageal cancer. The study investigated the prognostic value of pretreatment pathological T and N categories (prepT and prepN categories) in both an independent and a combined patient cohort., Methods: Patients with esophageal cancer treated with neoadjuvant chemotherapy and esophagectomy between 2012 and 2015 were included. PrepT and prepN categories were estimated based on the extent of tumor regression and regressional changes of lymph nodes in the resection specimen. The difference in Akaike's information criterion (ΔAIC) was used to assess prognostic performance. PrepN and ypN categories were combined to determine the effect of nodal sterilization on prognosis. A multivariable Cox regression model was used to identify combined prepN and ypN categories as independent prognostic factors., Results: The prognostic strength of the prepT category was better than the cT and ypT categories (ΔAIC 7.7 vs. 3.0 and 2.9, respectively), and the prognostic strength of the prepN category was better than the cN category and similar to the ypN category (ΔAIC 29.2 vs. - 1.0 and 27.9, respectively). PrepN + patients who became ypN0 had significantly worse survival than prepN0 patients (2-year overall survival 69% vs. 86% in 137 patients; p = 0.044). Similar results were found in a combined cohort of 317 patients (2-year overall survival 62% vs. 85%; p = 0.002). Combined prepN/ypN stage was independently associated with overall survival., Conclusions: These results independently confirm the prognostic value of prepTNM staging. PrepTNM staging is of additional prognostic value to cTNM and ypTNM. PrepN0/ypN0 patients have a better survival than prepN +/ypN0 patients.

Background: Journal hand searching offers the possibility to complement a literature search as part of systematic reviews and other evidence syntheses. Hand searching is indicated in cases where scientific journals with potentially relevant publications addressing the research question are not indexed in a literature database. However, it is often unclear whether these journals are actually indexed, and when they are, in which literature databases. In many cases, it is also unknown which journals should be searched by hand in addition to systematic literature search after databases to be searched have been specified. Therefore, the project aimed to investigate the indexation of selected scientific health science journals and to provide an overview of indexation in order to facilitate the hand search planning process., Methods: Journals from German-speaking countries covering eight professional fields (medical laboratory assistance, occupational therapy, midwifery, logopedics, nursing, physiotherapy, public health and rehabilitation) were considered that publish original research papers or systematic reviews or other review types in German and/or English. Two researchers per field identified relevant journals and independently analyzed the indexing locations using the journal websites. In case of missing information, we contacted the editors., Results: A total of 70 journals were included: from 1 to 17 journals per field. These journals are indexed in 1 to 29 databases. Twelve journals are not indexed or do not offer information concerning indexation. Indexation is distributed across n=74 different literature databases. Most journals are indexed in LIVIVO (n=55) and bibnet.org (n=33). Other common indexing databases are Scopus (n=18), Web of Science Core Collection (n=16), PSYNDEX (n=13), and Embase (n=10)., Conclusions: The results indicate a heterogeneous indexation of the included journals. Only a small number is indexed in common international literature databases such as MEDLINE or CINAHL. On the other hand, only a few journals are not indexed in any database. The results can be used as a basis to define databases for literature searches as part of systematic reviews. In addition, the findings might guide the selection of journals for hand searching after literature databases have been defined., (Copyright © 2020. Published by Elsevier GmbH.)

Qualitative interview styles have been guided by precedent within academic disciplines. The nature of information sought, and the role of interviewer and interviewee are key determinants across styles, which range from doxastic (focused on understanding interviewees' experiences or behaviors) to epistemic (focused on co-constructing knowledge). In this article, we position common interview styles along a doxastic-epistemic continuum, and according to the role of the interviewee (from respondent to equal partner). Through our typology and critique of interview styles, we enhance epistemic interviewing by introducing "deliberative interviews," which are more debate oriented and closer to equality in the interviewee and interviewer relationship than existing interview styles. Deliberative interviews require a comprehensive, pre-interview briefing on the subject matter followed by interactive deliberation wherein complex issues are debated across viewpoints in an effort to devise solutions. The effectiveness of this interview style in generating new knowledge warrants empirical testing across academic disciplines., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2018.)

Purpose : The aim of this article is to explore, theoretically and empirically, the reciprocity of care afforded by writing courses as community interventions for older adults. Methods : We narratively analyzed 209 excerpts of the anthology "I´m the one who has written this" written by teachers and participants of courses organized by the Church City Mission in Norway. Results : The reciprocity that appeared in the writing courses is grounded in the sense of vulnerability that both teachers and participants embraced, and that is experienced in three main relational movements that these writing courses convey: self-exploration, otherness and togetherness. In addition, the data suggests that these courses promote affective processing and existential meaning-making, motivation, as well as improvements of memory and attention. However, more research is needed to confirm these preliminary findings, and their possible effects in older adults with and without symptoms of dementia. Conclusion : Even though these writing courses for older adults are not explicitly therapeutic, they can have therapeutic effects, given the reciprocity afforded in these cultural community interventions. A theoretical exploration upon reciprocity in eldercare is hereby provided. These findings could shape improvements in aging and health care policies that are person-centered and focus on reciprocity.

Background: Micronutrient supplementation is recommended in Ebola virus disease (EVD); however, there are limited data on therapeutic impacts of specific micronutrients., Objective: To evaluate the association between vitamin A supplementation and mortality in EVD., Methods: This retrospective cohort included patients with EVD admitted to 5 International Medical Corps Ebola Treatment Units (ETUs) in 2 countries during 2014-2015. Protocolized treatments with micronutrients were used at all ETUs: however, because of resource constraints, only a subset of patients received vitamin A. Standardized data on demographics, clinical characteristics, malaria status, and Ebola viral loads (cycle threshold values) were collected. The outcome of interest was mortality between cases treated with 200,000 IU of vitamin A on care days 1 and/or 2, and those not. Propensity scores based on the first 48 h of care were derived using covariates of age, ETU duration, malaria status, cycle threshold values, and clinical symptoms. Patients were matched 1:1 using nearest neighbors with replacement. Mortality between cases treated and not treated with vitamin A was compared using generalized estimating equations to calculate RR with associated 95% CI., Results: There were 424 cases analyzed, of which 330 (77.8%) were treated with vitamin A. The mean age was 30.5 y and 40.3% were men. The most common symptoms were diarrhea (85.6%), anorexia (80.7%), and abdominal pain (76.9%). Mortality proportions among cases treated and not treated with vitamin A were 55.0% and 71.9%, respectively. In the propensity-matched analysis, mortality was significantly lower among cases receiving vitamin A (RR = 0.77, 95% CI: 0.59, 0.99; P = 0.041). In a subgroup analysis of patients treated with multivitamins already containing vitamin A, additional vitamin A supplementation did not impact mortality., Conclusion: Early vitamin A supplementation was associated with reduced mortality in patients with EVD, and should be further studied and considered for use in future epidemics., (Copyright © American Society for Nutrition 2019.)

Transthoracic esophagectomy with gastric tube formation is the surgical treatment of choice for esophageal cancer. The surgical reconstruction induces changes of gastric microcirculation, which are recognized as potential risk factors of anastomotic leak. This prospective observational study investigates the association of celiac trunk (TC) stenosis with postoperative anastomotic leak. One hundred fifty-four consecutive patients with esophageal cancer scheduled for Ivor-Lewis esophagectomy were included. Preoperative staging computed tomography (CT) was used to identify TC stenosis. Any narrowing of the lumen due to atherosclerotic changes was classified as stenosis. Percentage of stenotic changes was calculated using the North American Symptomatic Carotid Endarterectomy Trial formula. Multivariable analysis was used to identify possible risk factors for leak. The overall incidence of TC stenosis was 40.9%. Anastomotic leak was identified in 15 patients (9.7%). Incidence of anastomotic leak in patients with stenosis was 19.4% compared to 2.3% in patients without stenosis. Incidence of stenosis in patients with leak was 86.7% (13 of 15 patients) and significantly higher than 38.8% (54 of 139 patients) in patients without leak (P < 0.001). There was a significant difference in median degree of TC stenosis (50.0% vs 39.4%; P = 0.032) in patients with and without leak. In the multivariable model, TC stenosis was an independent risk factor for anastomotic leak (odds ratio: 5.98, 95% CI: 1.58-22.61). TC stenosis is associated with postoperative anastomotic leak after Ivor-Lewis esophagectomy. Routine assessment of TC for possible stenosis is recommended to identify patients at risk., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Noncanonical amino acids (ncAAs) with dual stereocenters at the α and β positions are valuable precursors to natural products and therapeutics. Despite the potential applications of such bioactive β-branched ncAAs, their availability is limited due to the inefficiency of the multistep methods used to prepare them. Herein we report a stereoselective biocatalytic synthesis of β-branched tryptophan analogues using an engineered variant of Pyrococcus furiosus tryptophan synthase (PfTrpB), PfTrpB 7E6 . PfTrpB 7E6 is the first biocatalyst to synthesize bulky β-branched tryptophan analogues in a single step, with demonstrated access to 27 ncAAs. The molecular basis for the efficient catalysis and broad substrate tolerance of PfTrpB 7E6 was explored through X-ray crystallography and UV/Vis spectroscopy, which revealed that a combination of active-site and remote mutations increase the abundance and persistence of a key reactive intermediate. PfTrpB 7E6 provides an operationally simple and environmentally benign platform for the preparation of β-branched tryptophan building blocks., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: This study aims to assess the feasibility of 4D flow MRI measurements in complex vascular territories; namely, the celiac artery (CA) and superior mesenteric artery (SMA)., Materials and Methods: In this prospective study, 22 healthy volunteers and 10 patients were scanned at 3 T. Blood flow parameters were compared between healthy volunteers and patients with stenosis of the CA and/or SMA as a function of stenosis grade characterized by prior contrast-enhanced computed tomography (CE-CT). The 4D flow MRI acquisition covered the CA, SMA and adjusting parts of the abdominal aorta (AO). Measurements of velocity- (peak velocity [PV], average velocity [AV]) and volume-related parameters (peak flow [PF], stroke volume [SV]) were conducted. Further, stenosis grade and wall shear stress in the CA, SMA and AO were evaluated., Results: In patients, prior evaluation by CE-CT revealed 11 low- and 5 mid-grade stenoses of the CA and/or SMA. PV and AV were significantly higher in patients than in healthy volunteers [PV: p < 0.0001; AV: p = 0.03, p < 0.001]. PF and SV did not differ significantly between healthy volunteers and patients; however, a trend towards lower PF and SV could be detected in patients with mid-grade stenoses. Comparison of 4D flow MRI with CE-CT revealed a strong positive correlation in estimated degree of stenosis (CA: r = 0.86, SMA: r = 0.98). Patients with mid-grade stenoses had a significantly higher average WSS magnitude (AWM) than healthy volunteers (p = 0.02)., Conclusion: This feasibility study suggests that 4D flow MRI is a viable technique for the evaluation of complex flow characteristics in small vessels such as the CA and SMA. 4D flow MRI approves comparable to the morphologic assessment of complex vascular territories using CE-CT but, in addition, offers the functional evaluation of flow parameters that goes beyond the morphology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims and Objectives: To develop a communication app to support nursing staff during the provision of standard care of patients from non-English-speaking backgrounds (NESBs), when an interpreter is not available. This paper reports on the user needs analysis phase that informed the development, content and functionality of the app., Background: In 2014 we developed CALD Assist, a communication app to support patient interactions with allied health clinicians when interpreters are not present. It includes 95 commonly used phrases professionally interpreted into 10 languages and grouped by discipline. This work expands upon our previous app to meet the needs of the nursing workforce., Design: Qualitative through focus groups, observations and interviews, with a quantitative component from observational data and staff surveys., Methods: Four focus groups with hospital staff, ten interviews with patients from NESBs and 85 observation sessions of everyday patient-staff interactions followed by staff surveys (n = 85) were held between January and June 2017., Results: Baseline data prior to app development revealed that staff confidence of the patients' level of understanding and the success of the interaction were significantly greater for English-speaking (ES) patients, than for non-English-speaking patients. A total of 143 phrases were identified and subdivided into 16 categories for inclusion in the new app., Conclusion: Staff participants highlighted that patients from NESBs are a challenging patient group to interact with. Patient and staff participants identified a range of areas where the nursing app could benefit, including pain management, mobility, hygiene and nutrition., Relevance to Clinical Practice: The proposed app can be used to reduce variances in practice and provide a timely and positive patient experience for patients from NESBs who are unable to communicate in English during hospital admissions., (© 2018 John Wiley & Sons Ltd.)

Much theorizing in psychology and related disciplines begins with a given model of the mind that is then applied in research projects to study concrete phenomena. Sometimes psychological research can be theory-driven in quite an explicit way, approaching the logic of the hypothetico-deductive method. Others reject this and prefer to work inductively, and, in the extreme case of positivism, perhaps try to avoid theorizing altogether. In this article I shall suggest another way to think of the relationship between psychological theories and psychological phenomena. My suggestion is not simply to replace the hypothetico-deductive model with an inductive one, but to argue that the most direct route to theories of the human mind that grasp its complexity is to begin with the Kantian question of transcendental philosophy: X exists - how is X possible? In the context of this article, I apply this questioning to the phenomenon of grief: Grief exists - what general psychological theory of the mind do we need in order to account for its possibility? I attempt to extract three general psychological points from the existence of grief, viz. (1) the deep relationality of the self, (2) the limitations of evolutionary accounts, and (3) the normativity of psychological phenomena. I shall argue that these are general psychological lessons to be learned from grief, although they could also be arrived at by considering several other significant psychological phenomena.

Purpose: Anastomotic leakage is a major surgical complication following esophagectomy and gastric pull-up. Specific risk factors such as celiac trunk (TC) stenosis and high calcification score of the aorta have been identified, but no data are available on their relative prognostic values. This retrospective study aimed to compare and evaluate calcification score versus stenosis quantification with regards to prognostic impact on anastomotic leakage., Patients and Methods: Preoperative contrast-enhanced computed tomography scans of 164 consecutive patients with primary esophageal cancer were evaluated by two radiologists to apply a calcification score (0-3 scale) assessing the aorta, the celiac axis and the right and left postceliac arteries. Concurrently, the presence and degree of stenosis of TC and superior mesenteric artery were recorded for stenosis quantification., Results: Anastomotic leakage was noted in 14/164 patients and 12/14 showed stenosis of TC (n=11). The presence of TC stenosis was found to have a significant impact on anastomotic healing ( p =0.004). The odds ratio for the prediction of anastomotic leakage by the degree of stenosis was 1.04 (95% CI, 1.02-1.07). Ten of 14 patients had aortic calcification scores of 1 or 2, but calcification scores of the aorta, the celiac axis and the right and left postceliac arteries did not correlate with the corresponding TC stenosis values and showed no influence on patient outcome as defined by the occurrence of anastomotic insufficiency ( p =0.565, 0.855, 0.518 and 1.000, respectively). Inter-reader reliability of computed tomography analysis and absolute agreement on calcium scoring was mostly over 90%. No significant differences in preoperative comorbidities and patient characteristics were found between those with and without anastomotic leakage., Conclusion: Measurement of TC stenosis in preoperative contrast-enhanced computed tomography scans proved to be more reliable than calcification scores in predicting anastomotic leakage and should, therefore, be used in the risk assessment of patients undergoing esophagectomy and gastric pull-up., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Perforation of the esophagus is the most severe complication of transesophageal echocardiography (TEE) and can lead to mediastinitis, pleural empyema, or peritonitis. Currently, the majority of patients receive operative treatment with only 6% treated endoscopically. We report our experience with endoscopic and conservative approaches., Methods: We retrospectively reviewed all patients treated for esophageal perforation and included all patients with perforation caused by TEE. All patients with perforation of the esophagus by TEE probe underwent conservative or endoscopic treatment, drainage of pleural and mediastinal retentions, and adjusted to antibiotic therapy., Results: From January 2004 to December 2014 a total of 109 patients were treated for esophageal perforation in our department. In 6 patients (5.5%) the perforation was caused by TEE. Location was cervical and midthoracic in 2 and 4 cases, respectively. All patients underwent successful endoscopic treatment and no further surgical procedure, such as esophageal suture or resection was necessary. The mean time between TEE and therapy of the perforation was 7.3 days. In all patients closure of the leakage could be achieved within 30 days. Mortality rate was 0%., Conclusions: Esophageal perforations caused by TEE are typically small, in the cervical and mid esophagus, and minimally contaminated. These are good prognostic factors for successful endoscopic treatment with preservation of the esophagus. Operative treatment should only be considered in cases of failed endoscopic treatment.