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BACKGROUND: Lipid extraction is a major bottleneck for the commercialization of microalgae due to energy costs involved during solvent recycling. Direct transesterification offers the possibility to bypass the extraction step by immediately converting the lipids to fatty acid methyl esters (FAMEs). In this study, the efficiency of direct transesterification after pulsed electric field (PEF) treatment was evaluated. Freshly harvested Auxenochlorella protothecoides (A. protothecoides), cultivated either autotrophically or mixotrophically, was subjected to PEF. Two treatment energies were tested, 0.25 and 1.5 MJ kgdw−1, and results were compared with those for conventional two‐step transesterification. RESULTS: For autotrophically grown A. protothecoides, the percentage of the total FAMEs recovered from untreated biomass and microalgae treated with 0.25 MJ kgdw−1 was 30% for both cases, while for 1.5 MJ kgdw−1 it was 65%. A 24 h incubation step between PEF treatment and direct transesterification significantly improved the results. Untreated biomass remained stable with 30% of FAMEs, while with both treatment energies a 97% FAME recovery was achieved. However, for mixotrophic A. protothecoides the process was not as effective. Approximately 30% of FAMEs were recovered for all three conditions immediately after PEF with only a marginal increase after incubation. The reason for this different behavior of the two cultivation modes is unknown and under investigation. CONCLUSIONS: Overall, the synergy between PEF and direct transesterification was proven to have potential, in particular for autotrophic microalgae. Its implementation and further optimization in a biorefinery therefore merit further attention. © 2022 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Pulsed Electric Field (PEF) treatment was used as pre-treatment on the microalgae strain Auxenochlorella protothecoides (A.p.) prior to organic solvent extraction of lipids. Experiments were performed on fresh biomass from mixotrophic or autotrophic culture which both had an evaluated lipid content of 30–35% of cell dry weight. Lipid yield was determined gravimetrically and compared to the reference lipid content assessed by bead-milling and subsequent Soxhlet extraction. The biomass was concentrated at 10% w/w solids prior to PEF-treatment and further dewatered afterwards to approximately 25% w/w before extraction. PEF-treatment with an energy input of 1.5 MJ per kilogram of dry matter induced electropermeabilisation of the microalgae cells detected by the increase of the conductivity of the microalgae supernatant. This greatly increased the lipid yield upon subsequent monophasic solvent extraction. A mixture of Water/Ethanol/Hexane 1:18:7.3 vol/vol/vol enabled to recover 92%, and 72%, of the evaluated lipid content of mixotrophically, and autotrophically respectively, grown A.p., after 2 h of extraction. Recovery increased to 97%, and 90% respectively, after 20 h of extraction. The same extraction system on untreated biomass yielded maximum 10% of lipid content. The highest yields were obtained with 80 mL of solvent for 1 g dry biomass but solvent volume could be reduced by a factor two in case of mixotrophically grown microalgae. However, the solvent:biomass ratio still remains high, and includes a water-miscible solvent, ethanol. Total lipid extraction was confirmed by nile red staining of residual biomass combined with fluorescence microscopy imaging and flow cytometry. Gas chromatography analyses of extracted lipids after transesterification revealed that PEF- treatment did not alter their fatty acid composition. Overall PEF-treatment shows promising features for upscaling especially in a biorefinery concept since it avoids potentially harmful temperature increase and small debris problematic for further processing. [ABSTRACT FROM AUTHOR]

Novel cell-disruption combinations (autolytic incubation and hypotonic osmotic shock combined with HPH or pH12) were used to investigate the fundamental mass transfer of lipids and proteins from Nannochloropsis slurries (140 mg biomass/g slurry). Since neutral lipids exist as cytosolic globules, their mass transfer was directly dependent on disintegration of cell walls. Complete recovery was obtained with complete physical disruption. HPH combinations exerted more physical disruption and led to higher yields than pH12. In contrast, proteins exist as both cytosolic water-soluble fractions and cell-wall/membrane structural fractions and have a complex extraction behaviour. Mass transfer of cytosolic proteins was dependent on cell-wall disintegration, while that of structural proteins was governed by cell-wall disintegration and severance of protein linkage from the wall/membrane. HPH combinations exerted only physical disruption and were limited to releasing soluble proteins. pH12 combinations hydrolysed chemical linkages in addition to exerting physical disruption, releasing both soluble and structural proteins., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study reports on the use of pulsed electric field (PEF) as a pre-treatment step to enhance lipid extraction yield using extraction with ethanol-hexane blend on fresh oleaginous yeast Saitozyma podzolica. The yeasts were cultivated on nitrogen-depleted condition and had a lipid content of 26.4 ± 4.6% of dry weight. PEF-treatment was applied on the yeast suspension either directly after harvesting (unwashed route) or after a washing step (washed route) which induced a reduction of conductivity by a factor eight. In both cases, cell concentration was 20 g of biomass per liter of suspension. In the unwashed route, the lipid extraction efficiency increased from 7% (untreated) to 54% thanks to PEF-treatment. In case an additional washing step was added after PEF-treatment, up to 81% of the lipid content could be recovered. The washed route was even more efficient since lipid extraction yields increased from 26% (untreated) to 99% of total lipid. The energy input for the PEF-treatment never exceeded 150 kJ per liter of initial suspension. The best lipid recovery scenario was obtained using pulses of 1 μs, an electric field of 40 kV/cm and it required slightly less than 11 MJ/kg LIPID . This amount of energy can be further reduced by at least a factor five by optimizing the treatment and especially by increasing the concentration of the treated biomass. The process can be easily up-scaled and does not require any expensive handling of the biomass such as freezing or freeze-drying. These findings demonstrate the potential benefit of PEF-treatment in the downstream processing of oleaginous yeast. From a basic research point of view, the influence of conductivity on PEF energy requirements and extraction yields was examined, and results suggest a higher efficiency of PEF-treatment in terms of energy when treatment is performed at lower conductivity., (Copyright © 2020 Gorte, Nazarova, Papachristou, Wüstner, Leber, Syldatk, Ochsenreither, Frey and Silve.)

Background: Within the sphere of diabetes self-management, much emphasis has been placed on medication adherence. There has been a shift in thinking about medication adherence, moving from "compliance" and historically paternalistic models of care, to seeking better ways of characterizing dynamic and complex relationships that determine medication adherence and diabetes control. This study sought to understand the relationship between patient's attitudes and medication adherence for oral anti-diabetics in Thailand., Methods: In-depth interviews of patients with type 2 diabetes mellitus, taking oral anti-diabetic drugs, at the out-patient clinic run by the Department of Family Medicine, Chiang Mai University between May and December 2016. Thematic analysis followed the WHO framework for medication adherence in chronic disease to explore patient's attitudes and their influence on medication compliance., Results: Of 24 patients, 9 were men. The mean age was 62 years (SD 8.9 years). 67% had high compliance. Four themes were identified as important factors related to medication adherence: attitudes toward disease, attitudes toward treatment, attitudes toward family support and attitudes toward health care team. Specifically, symptoms at diagnosis, understanding and acceptance in taking medication, the presence of family support and the perception of concern by the doctor relate to improved medication compliance., Conclusions: Medication adherence in Thai patients with diabetes requires support from both the health care providers and the family. The patient's perception of the doctor's concern creates greater patient trust in the health care team. This trust, along with family support, helps deepen patients' understanding of the disease, accept the chronic nature of their disease, and engenders a positive attitude towards taking medication that can improve medication adherence.

Single cell oil (SCO) produced by oleaginous yeasts is considered as a sustainable source for biodiesel and oleochemicals since its production does not compete with food or feed and high yields can be obtained from a wide variety of carbon sources, e.g., acetate or lignocellulose. Downstream processing is still costly preventing the broader application of SCO. Direct transesterification of freeze-dried biomass is widely used for analytical purposes and for biodiesel production but it is energy intensive and, therefore, expensive. Additionally, only fatty acid esters are produced limiting the subsequent applications. The harsh conditions applied during direct esterification might also damage high-value polyunsaturated fatty acids. Unfortunately, universal downstream strategies effective for all yeast species do not exist and methods have to be developed for each yeast species due to differences in cell wall composition. Therefore, the aim of this study was to evaluate three industrially relevant cell disruption methods combined with three extraction systems for the SCO extraction of two novel, unconventional oleaginous yeasts, Saitozyma podzolica DSM 27192 and Apiotrichum porosum DSM 27194, based on cell disruption efficiency, lipid yield, and oil quality. Bead milling (BM) and high pressure homogenization (HPH) were effective cell disruption methods in contrast to sonification. By combining HPH (95% cell disruption efficiency) with ethanol-hexane-extraction 46.9 ± 4.4% lipid/CDW of S. podzolica were obtained which was 2.7 times higher than with the least suitable combination (ultrasound + Folch). A. porosum was less affected by cell disruption attempts. Here, the highest disruption efficiency was 74% after BM and the most efficient lipid recovery method was direct acidic transesterification (27.2 ± 0.5% fatty acid methyl esters/CDW) after freeze drying. The study clearly indicates cell disruption is the decisive step for SCO extraction. At disruption efficiencies of >90%, lipids can be extracted at high yields, whereas at lower cell disruption efficiencies, considerable amounts of lipids will not be accessible for extraction regardless of the solvents used. Furthermore, it was shown that hexane-ethanol which is commonly used for extraction of algal lipids is also highly efficient for yeasts., (Copyright © 2020 Gorte, Hollenbach, Papachristou, Steinweg, Silve, Frey, Syldatk and Ochsenreither.)

We undertook this study in light of an uncontrolled rise of melanoma incidence and mortality rates in the United Kingdom (UK). We aim to assess the effectiveness of prevention and early melanoma diagnosis in the UK's National Health Service (NHS) in comparison to the Australian system that has limited the melanoma rise. We compare the prevention campaigns against skin cancer and the stage at which melanoma is diagnosed. We analyse key drivers of early diagnosis. Overall, Australia has performed better than the UK and provides an example for the UK's NHS for better preventing melanoma and diagnosing it. Technologies under development, such as tele-dermatology and artificial intelligence applications, could aid in making melanoma early diagnosis easier, more cost-efficient, and lessen the burden on health systems. Diagnoses also provide the data to help public health officials target prevention programs.

​INTRODUCTION: Randomised controlled trials (RCTs) have shown a positive effect of early integration of palliative care (EIPC) in various advanced cancer entities regarding patients' quality of life (QoL), survival, mood, caregiver burden and reduction of aggressiveness of treatment near the end of life. However, RCTs investigating the positive effect of EIPC for patients suffering from glioblastoma multiforme (GBM) are lacking. After modelling work identifying the specific needs of GBM patients and their caregivers, the aim of this study is to investigate the impact of EIPC in this particular patient group. ​METHODS AND ANALYSIS: The recruitment period of this multicenter RCT started in May 2019. GBM patients (n=214) and their caregivers will be randomly assigned to either the intervention group (receiving proactive EIPC on a monthly basis) or the control group (receiving treatment according to international standards and additional, regular assessment of QoL ('optimised' standard care)).The primary outcome is QoL assessed by subscales of the Functional Assessment of Cancer Therapy for brain tumour (FACT-Br) from baseline to 6 months of treatment. Secondary outcomes are changes in QoL after 12 (end of intervention), 18 and 24 months (end of follow-up), the full FACT-Br scale, patients' palliative care needs, depression/anxiety, cognitive impairment, caregiver burden, healthcare use, cost-effectiveness and overall survival. ​ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki and has been approved by the local ethics committees of the University Clinics of Cologne, Aachen, Bonn, Freiburg and Munich (LMU). Results of the trial will be submitted for publication in a peer-reviewed, open access journal and disseminated through presentations at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00016066); Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pulsed Electric Field (PEF) pre-treatment, applied on fresh microalgae Auxenochlorella protothecoides, induces spontaneous release of a substantial water fraction and enables subsequent lipid extraction using ethanol-hexane blends. In this study, fresh microalgae suspensions were treated with PEF and incubated under inert conditions. Incubation promotes the release of ions and carbohydrates and increases the yields of subsequent lipid extraction thus enabling a considerable reduction of PEF-treatment energy. With a 20 h incubation period at 25 °C, almost total lipid extraction is achieved with a specific PEF-treatment energy of only 0.25 MJ/kg DW . Incubation on ice remains beneficial but less efficient than at 25 °C. Additionally, incubating microalgae cells in suspension at 100g DW /L or in a dense paste, was almost equally efficient. Correlation between the different results suggests that spontaneous release of ions and carbohydrates facilitates more successful lipid extraction. A direct causality between the two phenomena remains to be demonstrated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In 2010, Greater Manchester (GM) and London centralized acute stroke care services into a reduced number of hyperacute stroke units, with local stroke units providing on-going care nearer patients' homes., Objective: To explore the impact of centralized acute stroke care pathways on the experiences of patients., Design: Qualitative interview study. Thematic analysis was undertaken, using deductive and inductive approaches. Final data analysis explored themes related to five chronological phases of the centralized stroke care pathway., Setting and Participants: Recruitment from 3 hospitals in GM (15 stroke patients/8 family members) and 4 in London (21 stroke patients/9 family members)., Results: Participants were impressed with emergency services and initial reception at hospital: disquiet about travelling further than a local hospital was allayed by clear explanations. Participants knew who was treating them and were involved in decisions. Difficulties for families visiting hospitals a distance from home were raised. Repatriation to local hospitals was not always timely, but no detrimental effects were reported. Discharge to the community was viewed less positively., Discussion and Conclusions: Patients on the centralized acute stroke care pathways reported many positive aspects of care: the centralization of care pathways can offer patients a good experience. Disadvantages of travelling further were perceived to be outweighed by the opportunity to receive the best quality care. This study highlights the necessity for all staff on a centralized care pathway to provide clear and accessible information to patients, in order to maximize their experience of care., (© 2018 The Authors Health Expectations published by John Wiley & Sons Ltd.)

This study is the first to explore informal dementia caregivers' perceptions and outlook on written materials about all food-related processes: shopping, food preparation, and eating. The aim of the study was to develop and evaluate the content, format, and usefulness of two separate booklets (one newly developed and one existing) on food-related processes. Twenty dementia caregivers were provided with one of the two booklets, and a Think-Aloud method was used to gather information about their views on the booklets. The findings indicated that incorporating all three food processes in a new booklet could be beneficial for the participant. Shopping, purchasing food, driving, and dangers in the kitchen were addressed only in the developed booklet, and participants regarded them as important and useful areas to address. Therefore, this study has shown that tailored information may enhance caregivers' confidence and support them in making decisions to help them adapt to food-related changes.

As dementia progresses, caregivers increasingly have to manage the decline of food-related abilities with little outside information or input from support services The provision of food coping skills and knowledge can lessen the burden on caregivers. However, there is little research on caregivers' perspectives on food-related services. This paper reports on a qualitative study to investigate informal caregivers' experiences of, and views on, food-related information and support services in dementia. Twenty informal caregivers were interviewed and the transcripts from these interviews were analysed using both deductive and inductive thematic analysis. Four categories emerged. 'Direct food-related Information', covers written material, training, 'Direct food-related informal support': lunch clubs, 'Indirect non-food related formal support services' covers respite services and domestic help at home. Finally 'no services required' covers those who did not feel they needed any form of intervention due to confidence in managing food-related processes or having no change in dementia progression and food responsibility. Most caregivers will need different levels of information and support at different stages of dementia. It is necessary therefore to undertake ongoing individual assessment of food information and support needs.

Introduction: Promoting the assessment of health interventions using outcomes that matter to patients and practitioners is a key principle of Cochrane. Cochrane UK therefore commissioned the OMIPP project: Outcomes that are Most Important for Patients, Public and Practitioners to identify the outcomes they felt most important and should be evaluated in Cochrane reviews of health interventions for Chronic Rhinosinusitis (CRS)., Methodology: Using direct emailing, social media and printed cards, an online survey was distributed to a wide range of people involved in the care of patients with CRS. Patients and practitioners were asked to list the 3 outcomes from treatments most important to them. Responses were analysed through development of a thematic framework based on the data., Results: Two hundred and thirty-five people completed the survey; 155 practitioners and 80 patients. Respondents provided 653 suggestions of important outcomes. 73% concerned symptoms of CRS, (nasal discharge or drip, facial pain, nasal blockage, headache, impaired sense of smell, congestion and breathing difficulties); 9% concerned quality of life, 4% reducing the need for further treatment and 4% side effects of treatment. Objective measurements of disease formed only 3% of responses. There was high level of agreement between patients and practitioners. Of 10 current Cochrane reviews on CRS, 9 include symptomatic outcomes identified by our survey as most important to patients and healthcare practitioners., Conclusions: We have identified outcomes that both patients and their doctors consider should be included in reviews evaluating treatments of rhinosinusitis. We recommend that primary outcomes in future reviews focus on symptom-based outcomes. The ability to extract these data from relevant trials is dependent upon their inclusion in trials, and so it is important that building on this work a core outcome set for rhinosinusitis research is developed.

As dementia progresses, one area that can help maintain connection and memories with others is within the food domain. There is little research in this area particularly from the informal caregivers' perspectives. Therefore, a qualitative study was conducted to explore the impact of dementia progression on food-related processes from the perspectives of informal caregivers. The aim of the study was to document the methodology used and to disseminate the findings to researchers, care providers, and policy makers. A total of 10 men and 10 women caregivers of those with dementia underwent a semistructured interview. Transcripts were analyzed using thematic analysis. The caregivers' narratives indicated a set pattern of decline, with food shopping being the first ability to decline, followed by food preparation and the ability to eat. Caregivers adapted to their food roles, for example, by becoming responsible for financial issues. These adaptations were described as stressful yet satisfying as food care was seen as an important social time. Educating caregivers' about the likely adaptations to food processes may increase food satisfaction in both the parties.

Unlabelled: 3'-deoxy-3'-[(18)F]fluoro-L-thymidine (FLT) and 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1-25.4 months]) compared to patients with an FDG SUVmax ≥6.6 (3.1 months [95% CI 0.6-5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer survival (10.3 months (0-23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0-8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR)., Trial Registration: Clinicaltrials.gov, Identifier: NCT00568841.