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Background and Purpose The cation channel transient receptor potential canonical ( TRPC) 6 has been associated with several pathologies including focal segmental glomerulosclerosis, pulmonary hypertension and ischaemia reperfusion-induced lung oedema. We set out to discover novel inhibitors of TRPC6 channels and investigate the therapeutic potential of these agents. Experimental Approach A library of potential TRPC channel inhibitors was designed and synthesized. Activity of the compounds was assessed by measuring intracellular Ca2+ levels. The lead compound SAR7334 was further characterized by whole-cell patch-clamp techniques. The effects of SAR7334 on acute hypoxic pulmonary vasoconstriction ( HPV) and systemic BP were investigated. Key Results SAR7334 inhibited TRPC6, TRPC3 and TRPC7-mediated Ca2+ influx into cells with IC50s of 9.5, 282 and 226 nM, whereas TRPC4 and TRPC5-mediated Ca2+ entry was not affected. Patch-clamp experiments confirmed that the compound blocked TRPC6 currents with an IC50 of 7.9 nM. Furthermore, SAR7334 suppressed TRPC6-dependent acute HPV in isolated perfused lungs from mice. Pharmacokinetic studies of SAR7334 demonstrated that the compound was suitable for chronic oral administration. In an initial short-term study, SAR7334 did not change mean arterial pressure in spontaneously hypertensive rats ( SHR). Conclusions and Implications Our results confirm the role of TRPC6 channels in hypoxic pulmonary vasoregulation and indicate that these channels are unlikely to play a major role in BP regulation in SHR. SAR7334 is a novel, highly potent and bioavailable inhibitor of TRPC6 channels that opens new opportunities for the investigation of TRPC channel function in vivo. [ABSTRACT FROM AUTHOR]

Introduction: The German Guideline Program in Oncology (GGPO) comprises guidelines aiming at epidemiology, prevention, diagnosis, treatment and aftercare of different types of cancer. As many patients in Germany use complementary and alternative medicine (CAM), the aim of our study was to assess the information on CAM presented in these guidelines compared to conventional, supportive and psychosocial therapy. Methods: We assessed all recommendations and statements from guidelines published from 2010 to 2012 from the program according to level of evidence (LoE) as given in the guideline. We differentiated between conventional cancer treatment, conventional supportive treatment, psychosocial interventions and complementary treatment. Results: A total of 9 guidelines (ovarian, colorectal, pancreatic, gastric, breast, prostate, oral cancer, melanoma and Hodgkin lymphoma) were included in our analysis. The total number of statements is highly diverse, ranging from 35 to 150. Only few statements and recommendations are given regarding supportive, psychosocial or complementary therapy. Regarding conventional treatments, only two guidelines (ovarian and oral cancer) have more than 50 % statements and recommendations on level 1. Considering supportive treatments, the LoE is lower, except the guideline on pancreatic cancer (40 % level 1). In breast cancer, all statements are based on expert consensus. Four guidelines do not include any statement at all. All guidelines beside that on Hodgkin lymphoma include at least one statement or recommendation on psychosocial therapy. Most recommendations are GCP.CAM is discussed in 8 guidelines; LoE is low with GCP statements dominating. Discussion: There may be different reasons for the low number of statements and recommendations on supportive, psychosocial and CAM therapies. Often, these topics are considered less important, and evidence is assumed as being low. In the GGPO, guidelines focusing on psychosocial and supportive therapy are under development. Thus, cancer-specific guidelines will be able to refer to these guidelines and only include recommendations on psychosocial care and supportive therapy which are specific for the type of cancer. A national guideline on CAM would close the gap of information for physicians and patients. In case of missing or low evidence, a transparent description of this uncertainty would be valuable information to professionals and patients. [ABSTRACT FROM AUTHOR]

Aims: Assessment of the safety, efficacy and effectiveness of growth factors alone or in combination with other technologies in the treatment of DFU including medical, economical, social, ethical and juridical aspects. Methods: We systematically searched relevant data bases limited to English and German language and publications since 1990. Review and assessment of the quality of publications followed methods conforming to widely accepted standards for evidence-based medicine and health economics. Results: We identified 25 studies comparing becaplermin, rhEGF, bFGF and the metabolically active skin grafts Dermagraft and Apligraf with standard wound care (SWC) alone or extracellular wound matrix. Study duration ranged from 12 to 20 weeks and the study population comprised between 17 and 382 patients. Treatment with becaplermin, rhEGF, Dermagraft and Apligraf resulted in a higher incidence of complete wound closure and shorter time to complete wound healing with statistically signifi cant differences. Regarding the proportion of adverse events there was no diff erence betweentreatment groups. The methodological quality of the studies was affected by significant deficiencies. Economic evaluations showed becaplermin being cost-effective. Conclusions: Add-on therapy with growth factors and active skin substitutes for treating uncomplicated DFU could be an alternative to SWC alone. For explicit recommendations further studies with stronger evidence are necessary. [ABSTRACT FROM AUTHOR]

Many phenolic compounds show high boiling points, low molecular weights, moderate polarities or high toxicities. Therefore, conventional wastewater treatment is limited or expensive. Recycling of the separated compounds is often not possible. But, if liquid-liquid reactive extraction is linked to a non-porous membrane, some or all of the above mentioned limitations may be overcome. The key element is a composite membrane with a dense, hydrophobic top layer which avoids the mixing of the two aqueous fluid streams. The dilute phenol stream is one of them, the other is caustic soda as stripping solvent. Since the basics of this technology have been discussed before, the scope of this study is to facilitate process implementation and integration. To this end, a life cycle assessment framework is used to identify the optimal equipment size for the treatment of wastewater that may, for example, originate from the production of polycarbonate. Limiting for this application is not the environmental performance though, but most likely process economics. [ABSTRACT FROM AUTHOR]

Background: To investigate awareness, use, and perceptions of the patient guidelines (PGs) of the German Guideline Program in Oncology (GGPO) and to explore general preferences regarding cancer information among patients and healthcare providers (HCPs). Methods: Two cross-sectional surveys among patients with cancer (November 2020—May 2021) and among HCPs (April -June 2021) were set up as anonymised, self-administered, semi-structured online surveys, including open-ended questions. Data were analysed with descriptive statistics and qualitative thematic analysis. Patients were recruited from national self-help organisations and certified cancer centres located all over Germany. HCPs were recruited from cancer centres, scientific medical societies and guideline groups. Results: Of 816 participating patients, 45% were aware of the GGPO-PGs, while 55% of the 455 participating HCPs were aware of them. Of those aware of the GGPO-PGs, 65% of patients and 86% of HCPs perceived them as helpful, while 95% in both groups saw them as comprehensive. Seventy-five percent of patients and 85% of HCPs were satisfied with the GGPO-PGs, 22%/13% were partially satisfied, and 3%/2% were rather/not at all satisfied. In addition to self-help organisations, physicians and hospitals were perceived as central in distributing the GGPO-PGs. More patients (78%) than HCPs (56%) stated a preference for detailed information, although the wish for concise information – e.g. decision aids – was concurrently expressed by the majority of all participants. Thematic analysis showed that up-to-dateness, trustworthiness, and supportive messaging are important properties for PGs. Conclusions: HCPs found the GGPO-PGs helpful, but awareness was low, which suggests that dissemination should be improved. This is also true for patients; however, further research needs to be done to increase the helpfulness of PGs for patients. Oncological PGs seem to be needed in different formats according to patients’ situational needs. Theory-driven research should investigate how to best frame patient information in a supportive way. [ABSTRACT FROM AUTHOR]

Background: The success of abdominal cancer surgery depends not only on the surgery itself but is influenced by the overall perioperative management. Given the multitude of perioperative measures and the ever-increasing number of studies on perioperative management, it is difficult to keep track and provide evidence-based perioperative management. The planned guideline on perioperative management will review the existing evidence and derive treatment recommendations. Methods: The processing of the evidence is carried out by 6 working groups according to an 8-step scheme: after drafting the guideline questions in PICO format (1), a systematic literature search is carried out (2), and the records found are screened by two independent reviewers from the coordination team. Subsequently, the full texts of the potentially relevant articles are made available to the working groups for full text screening (3). All articles to be included are reviewed for methodological quality (4) before summary of findings tables are generated (5). In line with the GRADE approach, confidence in the evidence is assessed (6) before a recommendation is derived from the evidence, using a modified GRADE Evidence to Decision Framework (7). Finally, all recommendations are compiled and agreed within the guideline group (8). Discussion: Guidelines serve as foundation for therapy decisions in everyday clinical practice and should therefore be based on up-to-date research results. However, while primary studies and systematic reviews are critically reviewed for their methodological quality, the process of guideline development is often not comprehensible. A protocol with predefined methodology should therefore create transparency and strengthen confidence in the recommendations. Trial registration: The guideline is registered in the AWMF (Association of the Scientific Medical Societies) Guideline Register (088—010OL). [ABSTRACT FROM AUTHOR]

Abstract: A technical and economic analysis of gas sweetening processes for natural gas with amine absorption and membrane technology has been conducted. Amine absorption is still considered a state of the art technology for gas sweetening but membranes have shown a great potential in this area, if the flux and selectivity for CO2 is high enough. The PVAm/PVA (polyvinyl amine and polyvinyl alcohol) membrane, developed at NTNU shows such qualities. For two different feed gas cases a simulation analysis with Aspen Hysys for amine absorption and a membrane model interfaced within Aspen Hysys was performed. Further, an economical analysis was also conducted to evaluate the total capital investment and gas processing cost for both technologies. [Copyright &y& Elsevier]

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, ; or ). [ABSTRACT FROM AUTHOR]