[Current Research Activities on Person-Centered Medicine in Academic Institutes of General Practice in Germany and Austria]. / Aktuelle Forschungsaktivitäten zur personenzentrierten Medizin in akademischen Instituten für Allgemeinmedizin in Deutschland und Österreich.

AIM OF STUDY: Person-centered medicine (PCM) with its focus on humanistic-biographical-oriented medicine and integrated, positive-salutogenic health is a central aspect in the patient-physician relationship in general practice. The objective of this analysis is to assess the prevalence and type of research project in academic institutions of general practice in Germany (Ger) and Austria (At) and the thematic priorities of the projects in the areas PCM, health promotion (HP), prevention (PRE) and conventional medicine (CM). METHODS: A search was conducted (September-December 2015) on the websites of 30 institutes and divisions of general medicine for their current research projects. The retrieved projects were assigned to five categories: PCM, HP, PRE, CM and others. Subsequently, we identified the targeted patient groups of the projects as well as the thematic focus in the categories PCM, HP, PRE and CM with focus on PCM and HP. RESULTS: 541 research projects were identified, 452 in Germany and 89 in Austria. Research projects were only included if they were explicitly indicated as research-oriented. Seventy projects addressed PCM aspects, 15 projects HP aspects, 32 projects PRE aspects and 396 projects CM aspects. The most frequently target groups in the categories PCM (24 of 70) and HP (7 of 15) were chronically ill patients. The most common thematic focus in PCM was communication (13 of 70) and in HP, physical activity (6 of 15). CONCLUSION: The vast majority of research projects investigated conventional medical topics. The percentage of research activities in the field of PCM (13%) or PCM including HP (16%) in Ger and At is below the European average of 20%. From our point of view, PCM and HP need to be implemented to a greater extent in general practice.

Gratitude mediates quality of life differences between fibromyalgia patients and healthy controls.

PURPOSE: Despite a growing literature on the benefits of gratitude for adjustment to chronic illness, little is known about gratitude in medical populations compared to healthy populations, or the degree to which potential deficits in gratitude might impact quality of life. The purpose of the present study was to (1) examine levels of gratitude and quality of life in fibromyalgia patients and healthy controls and (2) consider the role of gratitude in explaining quality of life differences between fibromyalgia patients and healthy controls. METHODS: Participants were 173 fibromyalgia patients and 81 healthy controls. All participants completed measures of gratitude, quality of life, and socio-demographics. RESULTS: Although gratitude was positively associated with quality of life, levels of gratitude and quality of life were lower in the fibromyalgia sample relative to the healthy controls. This difference in gratitude partially mediated differences in quality of life between the two groups after controlling for socio-demographic variables. CONCLUSIONS: Our findings suggest that gratitude is a valuable positive psychological trait for quality of life in people with fibromyalgia. Interventions to improve gratitude in this patient population may also bring enhancement in quality of life.

Structural basis of furan-amino acid recognition by a polyspecific aminoacyl-tRNA-synthetase and its genetic encoding in human cells.

The site-selective introduction of photo-crosslinking groups into proteins enables the discovery and mapping of weak and/or transient protein interactions with high spatiotemporal resolution, both in vitro and in vivo. We report the genetic encoding of a furan-based, photo-crosslinking amino acid in human cells; it can be activated with red light, thus offering high penetration depths in biological samples. This is achieved by activation of the amino acid and charging to its cognate tRNA by a pyrrolysyl-tRNA-synthetase (PylRS) mutant with broad polyspecificity. To gain insights into the recognition of this amino acid and to provide a rationale for its polyspecificity, we solved three crystal structures of the PylRS mutant: in its apo-form, in complex with adenosine 5'-(ß,γ-imido)triphosphate (AMP-PNP) and in complex with the AMP ester of the furan amino acid. These structures provide clues for the observed polyspecificity and represent a promising starting point for the engineering of PylRS mutants with further increased substrate scope.

Mechanistic analysis of the pump cycle of the KdpFABC P-type ATPase.

The high-affinity potassium uptake system KdpFABC is a unique type Ia P-type ATPase, because it separates the sites of ATP hydrolysis and ion transport on two different subunits. KdpFABC was expressed in Escherichia coli. It was then isolated and purified to homogeneity to obtain a detergent-solubilized enzyme complex that allowed the analysis of ion binding properties. The electrogenicity and binding affinities of the ion pump for K(+) and H(+) were determined in detergent-solubilized complexes by means of the electrochromic styryl dye RH421. Half-saturating K(+) concentrations and pK values for H(+) binding could be obtained in both the unphosphorylated and phosphorylated conformations of KdpFABC. The interaction of both ions with KdpFABC was studied in detail, and the presence of independent binding sites was ascertained. It is proposed that KdpFABC reconstituted in vesicles translocates protons at a low efficiency opposite from the well-established import of K(+) into the bacteria. On the basis of our results, various mechanistic pump cycle models were derived from the general Post-Albers scheme of P-type ATPases and discussed in the framework of the experimental evidence to propose a possible molecular pump cycle for KdpFABC.

The Physical, Psychological, and Social Day-to-Day Experience of Women Living With Endometriosis Compared to Healthy Age-Matched Controls-A Mixed-Methods Study.

Background: Endometriosis is characterized by lesions of endometrial tissue outside the uterus. Chronic pain is considered as main symptom, but challenges can relate to various physical, mental, and social aspects of the women's lives. The aim of our study was to gain a holistic understanding of the everyday reality of women with endometriosis compared to healthy controls. Methods: The total sample comprised 12 hormone-free endometriosis patients (EP) and 11 age-matched healthy women (HC). A mixed-methods design was used comprising semi-structured interviews, standardized questionnaires and a comprehensive diary to assess pain ratings and various mental and physical symptoms over the course of a menstrual cycle. Interviews were recorded, transcribed, and evaluated according to phenomenological analysis using the MAXQDA software. Results: Interviews showed that living with endometriosis was associated with an impairment in everyday life. Physical strains, especially pain, high levels of psychological distress, and social limitations have been reported. Living with endometriosis affected the patients' personality and they "no longer felt like themselves." Physical and psychological symptoms were reported to interfere with social interaction and participation. Evaluation of the standardized questionnaires revealed significant impairments in EP compared to HC in regard to anxiety and depression scores (both p < 0.001; Hospital Anxiety and Depression Scale), mental and physical quality of life (both p < 0.001; Short-Form Health Survey-12), stress ratings (p < 0.001; Patient Health Questionnaire-15) and functional well-being (p < 0.001; Functional Well-being-7). The highest levels of mean pelvic pain and dyschezia were observed in EP during menstruation, but mean pain ratings and dyschezia were increased in EPs compared to HP during the whole cycle. EP reported mental symptoms (e.g., depressed mood or anxiety) mainly during menstruation, while HC did not show any mental symptoms during the cycle. In addition, physical symptoms were elevated during the entire cycle in EPs (all p < 0.01). Discussion: The mixed-methods approach enabled to interpret the interviews, the standardized questionnaires, and the symptom diary in a broader context of everyday life. The symptoms do not appear to act independently, but rather influence each other. This leads to a complex interplay of physical, mental, and social impairments, with pain often being the starting point.

[Effects of lifestyle interventions for arterial hypertension in primary care: A systematic review]. / Effekte von Lebensstiländerungen bei arterieller Hypertonie in der Primärversorgung - ein systematisches Review.

BACKGROUND: The proportion of adults suffering from hypertension worldwide was estimated at 31.1 % in 2010. The aim of this study was to evaluate the effects of lifestyle changes in patients with arterial hypertension (AH) in primary care. MATERIAL AND METHODS: Systematic literature search in the online databases PubMed, Embase, Cochrane and Opengrey. Only randomized controlled trials of the years 2005 to 2017 in German or English were considered. RESULTS: 11 studies out of 458 identified references were evaluated. The patient groups investigated were very heterogeneous and underwent different types of intervention. Educating patients about the clinical picture, regular self-measurements of blood pressure, or patient memories of maintaining a healthy lifestyle have been used most frequently. CONCLUSION: There is a need for further studies focusing on primary care. However, many lifestyle interventions seem to show very good effects in patients with pre-existing AH (secondary prophylaxis), so these measures should form the basis of antihypertensive therapy in all patients with AH. In addition, it is important to maintain advice on a healthy lifestyle during drug therapy.

Hugh E. Huxley: birth of the filament sliding model of muscle contraction.

Hugh E. Huxley used a combination of X-ray diffraction and electron microscopy to define the structural basis for muscle contraction. He developed the entirely new concept of movement based on the relative motion of two elongated protein polymers powered by the action of independent molecular motors. The concept applies to a large number of cell motility mechanisms.

Anger rumination mediates differences between fibromyalgia patients and healthy controls on mental health and quality of life.

The present study examined differences between fibromyalgia patients and healthy controls on anger rumination, mental health and quality of life and tested anger rumination as a mediator of patient-control differences in mental health and quality of life. Participants were a propensity score-matched sample of 58 fibromyalgia patients and 58 healthy controls. Participants completed measures of anger rumination, depression and anxiety and quality of life. Patients were higher than controls on all anger rumination scales and depression and anxiety and lower on quality of life. All anger rumination scales were related to poorer mental health and quality of life. Patient-control differences on mental health and quality of life were mediated by anger rumination. In multiple mediator models, the only subscale with unique mediating effects was anger memories. Anger rumination has potent associations with mental health and quality of life, and differences between patients and controls on mental health and quality of life are partially mediated by differences in anger rumination. Addressing tendencies to ruminate on anger experiences in the care of fibromyalgia patients may offer an important avenue to improved health and quality of life. © 2019 John Wiley & Sons, Ltd.

Genetically encoded fluorophenylalanines enable insights into the recognition of lysine trimethylation by an epigenetic reader.

Fluorophenylalanines bearing 2-5 fluorine atoms at the phenyl ring have been genetically encoded by amber codon. Replacement of F59, a phenylalanine residue that is directly involved in interactions with trimethylated K9 of histone H3, in the Mpp8 chromodomain recombinantly with fluorophenylalanines significantly impairs the binding to a K9-trimethylated H3 peptide.

The proline-rich domain of TonB possesses an extended polyproline II-like conformation of sufficient length to span the periplasm of Gram-negative bacteria.

TonB from Escherichia coli and its homologues are critical for the uptake of siderophores through the outer membrane of Gram-negative bacteria using chemiosmotic energy. When different models for the mechanism of TonB mediated energy transfer from the inner to the outer membrane are discussed, one of the key questions is whether TonB spans the periplasm. In this article, we use long range distance measurements by spin-label pulsed EPR (Double Electron-Electron Resonance, DEER) and CD spectroscopy to show that the proline-rich segment of TonB exists in a PPII-like conformation. The result implies that the proline-rich segment of TonB possesses a length of more than 15 nm, sufficient to span the periplasm of Gram-negative bacteria.

Intraobserver and interobserver variability of transesophageal echocardiography in aortic arch atheroma measurement.

BACKGROUND: The risk of stroke associated with aortic arch atheroma is proportional to plaque thickness, the accurate measurement of which may influence future therapeutic decisions. Transesophageal echocardiography is the procedure of choice for plaque measurement. This study examines the reproducibility of such measurements within the context of the Aortic Arch Related Cerebral Hazard Trial of antithrombotic therapy. METHODS: Atheroma images were remeasured by 3 independent blinded observers of varying expertise. Intraobserver and interobserver variability were calculated using Lin's concordance correlation coefficient (rho-c), the Bland-Altman method, and the kappa statistic. RESULTS: A total of 160 images were obtained from 96 patients (68% male; mean age 74 +/- 9 years). Mean plaque thickness was 5.1 +/- 2.3 mm, range 1.2 to 19.3 mm. For intraobserver variability, rho-c = 0.95, mean difference = 0.01 mm, and kappa = 0.71. For interobserver variability, rho-c ranged from 0.80 to 0.91; mean difference was 0.13 to 0.48 mm; and kappa was 0.61 to 0.69. By all statistical methods, agreement was at least substantial, although lower at greater plaque thicknesses. For the clinically relevant 4 mm, agreement was 84% to 88%. CONCLUSIONS: Transesophageal echocardiography measurement of aortic plaque is substantially reproducible across a range of observer experience and, thus, is a widely applicable, adequately reliable tool for clinical and research purposes.