| 1. |
- Aspholm, Emelie E., et al.
(author)
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Keeping α-synuclein at bay: A more active role of molecular chaperones in preventing mitochondrial interactions and transition to pathological states?
- 2020
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In: Life. - : MDPI AG. - 2075-1729. ; 10:11, s. 1-19
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Journal article (peer-reviewed)abstract
- The property of molecular chaperones to dissolve protein aggregates of Parkinson-related α-synuclein has been known for some time. Recent findings point to an even more active role of molecular chaperones preventing the transformation of α-synuclein into pathological states subsequently leading to the formation of Lewy bodies, intracellular inclusions containing protein aggregates as well as broken organelles found in the brains of Parkinson’s patients. In parallel, a short motif around Tyr39 was identified as being crucial for the aggregation of α-synuclein. Interestingly, this region is also one of the main segments in contact with a diverse pool of molecular chaperones. Further, it could be shown that the inhibition of the chaperone:α-synuclein interaction leads to a binding of α-synuclein to mitochondria, which could also be shown to lead to mitochondrial membrane disruption as well as the possible proteolytic processing of α-synuclein by mitochondrial proteases. Here, we will review the current knowledge on the role of molecular chaperones in the regulation of physiological functions as well as the direct consequences of impairing these interactions—i.e., leading to enhanced mitochondrial interaction and consequential mitochondrial breakage, which might mark the initial stages of the structural transition of α-synuclein towards its pathological states. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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| 2. |
- Avram, Vlad Florian, et al.
(author)
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Improvement of platelet respiration by cell-permeable succinate in diabetic patients treated with statins
- 2021
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In: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:4
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Journal article (peer-reviewed)abstract
- Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first-line lipid- lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM- and statin-induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell-permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.
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| 3. |
- Barbara Sahlin, K., et al.
(author)
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Short-term effect of induced alterations in testosterone levels on fasting plasma amino acid levels in healthy young men
- 2021
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In: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:11
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Journal article (peer-reviewed)abstract
- Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term T alterations were induced. We designed a human model of 30 healthy young males with pharmacologically induced T changes, which resulted in three time points for blood collection: (A) baseline, (B) low T (3 weeks post administration of gonadotropin releasing hormone antagonist) and (C) restored T (2 weeks after injection of T undecanoate). The influence of T on AAs was analyzed by spectrophotometry on plasma samples. Levels of 9 out of 23 AAs, of which 7 were essential AAs, were significantly increased at low T and are restored upon T supplementation. Levels of tyrosine and phenylalanine were most strongly associated to T changes. Short-term effect of T changes suggests an increased protein breakdown that is restored upon T supplementation. Fasting AA levels are able to monitor the early metabolic changes induced by the T fluctuations.
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| 4. |
- Blyth, Colette, et al.
(author)
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Genomic, Habitat, and Leaf Shape Analyses Reveal a Possible Cryptic Species and Vulnerability to Climate Change in a Threatened Daisy
- 2021
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In: Life. - : MDPI. - 2075-1729. ; 11:6
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Journal article (peer-reviewed)abstract
- Olearia pannosa is a plant species listed as vulnerable in Australia. Two subspecies are currently recognised (O. pannosa subsp. pannosa (silver daisy) and O. pannosa subsp. cardiophylla (velvet daisy)), which have overlapping ranges but distinct leaf shape. Remnant populations face threats from habitat fragmentation and climate change. We analysed range-wide genomic data and leaf shape variation to assess population diversity and divergence and to inform conservation management strategies. We detected three distinct genetic groupings and a likely cryptic species. Samples identified as O. pannosa subsp. cardiophylla from the Flinders Ranges in South Australia were genetically distinct from all other samples and likely form a separate, range-restricted species. Remaining samples formed two genetic clusters, which aligned with leaf shape differences but not fully with current subspecies classifications. Levels of genetic diversity and inbreeding differed between the three genetic groups, suggesting each requires a separate management strategy. Additionally, we tested for associations between genetic and environmental variation and carried out habitat suitability modelling for O. pannosa subsp. pannosa populations. We found mean annual maximum temperature explained a significant proportion of genomic variance. Habitat suitability modelling identified mean summer maximum temperature, precipitation seasonality and mean annual rainfall as constraints on the distribution of O. pannosa subsp. pannosa, highlighting increasing aridity as a threat for populations located near suitability thresholds. Our results suggest maximum temperature is an important agent of selection on O. pannosa subsp. pannosa and should be considered in conservation strategies. We recommend taxonomic revision of O. pannosa and provide conservation management recommendations.
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| 5. |
- Camartin, C, et al.
(author)
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Palliative Sedation-The Last Resort in Case of Difficult Symptom Control: A Narrative Review and Experiences from Palliative Care in Switzerland
- 2022
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In: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:2
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Journal article (peer-reviewed)abstract
- Palliative sedation can be considered as “the last resort” in order to treat unbearable, refractory symptoms or suffering in end-of-life patients. The aim is symptom relief and not to induce death as in the case of euthanasia. The treatment might be one of the most challenging therapeutic options in the field of palliative care, involving both ethical and practical issues. Still, studies have shown that it is a safe and valuable treatment and in general does not shorten the life of the patient. Since patients in Switzerland have the legal option of assisted suicide, palliative sedation is an alternative that has become increasingly important. The use of palliative sedation was reported in 17.5% of all patients admitted to palliative care in Switzerland, making the country of those with the highest use of this treatment. The aim of this narrative review is to discuss ethical and practical issues in palliative sedation, with specific focus on experiences from Switzerland. Indications, ethical considerations, drugs of choice and duration are discussed. Decision making should be based on solid guidelines. When used correctly, palliative sedation is an important and useful tool in palliative care in order to provide good symptom relief.
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| 6. |
- Choi, Seong Il, et al.
(author)
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A Conceptual Framework for Integrating Cellular Protein Folding, Misfolding and Aggregation
- 2021
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In: Life. - : MDPI AG. - 2075-1729. ; 11:7
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Research review (peer-reviewed)abstract
- How proteins properly fold and maintain solubility at the risk of misfolding and aggregation in the cellular environments still remains largely unknown. Aggregation has been traditionally treated as a consequence of protein folding (or misfolding). Notably, however, aggregation can be generally inhibited by affecting the intermolecular interactions leading to aggregation, independently of protein folding and conformation. We here point out that rigorous distinction between protein folding and aggregation as two independent processes is necessary to reconcile and underlie all observations regarding the combined cellular protein folding and aggregation. So far, the direct attractive interactions (e.g., hydrophobic interactions) between cellular macromolecules including chaperones and interacting polypeptides have been widely believed to mainly stabilize polypeptides against aggregation. However, the intermolecular repulsions by large excluded volume and surface charges of cellular macromolecules can play a key role in stabilizing their physically connected polypeptides against aggregation, irrespective of the connection types and induced conformational changes, underlying the generic intrinsic chaperone activity of cellular macromolecules. Such rigorous distinction and intermolecular repulsive force-driven aggregation inhibition by cellular macromolecules could give new insights into understanding the complex cellular protein landscapes that remain uncharted.
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| 7. |
- Demi, Selina, et al.
(author)
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Doctor at your fingertips : An exploration of digital visits from stakeholders’ perspectives
- 2021
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In: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 11:1
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Journal article (peer-reviewed)abstract
- Technological advances and the evolution of mobile technologies enable patients to meet their doctors through their smartphones. While offering the opportunity of digital visits to patients, there are also challenges for this development. The purpose of this study is to enhance the understanding of digital visits, as perceived by experts working in telemedicine companies. To serve this purpose, the authors conducted semi-structured interviews with managers and employees in eight telemedicine companies. The analysis of the empirical data confirmed the importance of digital visits and their efficiency. The potential of digital visits is expected to increase significantly, should they make use of remote devices to transfer real-time data from patients to physicians. In such a case, digital visits are expected to cover approximately 70–75% of medical cases. However, the use of remote devices must be taken with caution and specific conditions need to be taken into account. We encourage researchers to perform research on promising technologies such as artificial intelligence and remote diagnostic devices, which could make more diagnoses and conditions possible to be treated by digital visits. This is even more important in light of the ongoing Covid-19 pandemic.
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| 8. |
- Frankling, MH, et al.
(author)
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Successful Strategies and Areas of Improvement-Lessons Learned from Design and Conduction of a Randomized Placebo-Controlled Trial in Palliative Care, 'Palliative-D'
- 2021
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In: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:11
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Journal article (peer-reviewed)abstract
- Clinical trials in palliative care are challenging to design and conduct. Burden on patients should be minimized, while gatekeeping by professionals and next-of kin needs to be avoided. Clinical deterioration due to disease progression affects attrition unrelated to intervention, and different care settings complicate comparisons and reduce the generalizability of the results. The aim of this review is to provide advice for colleagues planning to perform clinical trials in palliative care based on our own experiences from performing the Palliative-D study and by a thorough literature review on this topic. The Palliative-D study was a double-blind trial with 244 randomized patients comparing the effect of vitamin D3 to placebo in patients with advanced or metastatic cancer in the palliative phase of their disease trajectory who were enrolled in specialized palliative home care teams. Endpoints were opioid and antibiotic use, fatigue, and QoL. Recruitment was successful, but attrition rates were higher than expected, and we did not reach targeted power. For the 150 patients who completed the study, the completeness of the data was exceptionally high. Rather than patient reported pain, we choose the difference in the mean change in opioid dose between groups after twelve weeks compared to baseline as the primary endpoint. In this paper we discuss challenges in palliative care research based on lessons learned from the “Palliative-D” trial regarding successful strategies as well as areas for improvement.
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| 9. |
- Godman, B, et al.
(author)
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Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing Countries
- 2021
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In: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 11:6
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Journal article (peer-reviewed)abstract
- Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.
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| 10. |
- Goodrose-Flores, C, et al.
(author)
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Weight Loss in Advanced Cancer: Sex Differences in Health-Related Quality of Life and Body Image
- 2022
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In: Life (Basel, Switzerland). - : MDPI AG. - 2075-1729. ; 12:1
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Journal article (peer-reviewed)abstract
- Weight maintenance is a priority in cancer care, but weight loss is common and a serious concern. This study explores if there are sex differences in the perception of weight loss and its association to health-related quality of life (HRQoL) and body image. Cancer patients admitted to Advanced Medical Home Care were recruited to answer a questionnaire, including characteristics, the HRQoL-questionnaire RAND-36, and a short form of the Body Image Scale. Linear regression analyses stratified by sex and adjusted for age were performed to examine associations between percent weight loss and separate domains of HRQoL and body image score in men and women separately. In total, 99 participants were enrolled, of which 80 had lost weight since diagnosis. In men, an inverse association between weight loss and the HRQoL-domain physical functioning, β = −1.34 (95%CI: −2.44, −0.24), and a positive association with body image distress, β = 0.22 (95%CI: 0.07, 0.37), were found. In women, weight loss was associated with improvement in the HRQoL-domain role limitations due to physical health, β = 2.02 (95%CI: 0.63, 3.41). Following a cancer diagnosis, men appear to experience weight loss more negatively than women do. Recognizing different perceptions of weight loss may be of importance in clinical practice.
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