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Πέμπτη 17 Δεκεμβρίου 2020

JBI Evidence Synthesis

Assessing impact: does sample size matter?
No abstract available

Barriers and facilitators to physical activity among ethnic Chinese children: a qualitative systematic review
imageObjective: The review aimed to synthesize the barriers and facilitators from the available studies that explored physical activity among ethnic Chinese children and uncover any differences or similarities in these barriers and facilitators. Introduction: Physical activity promotes overall health, fitness, and well-being in children, yet prevalence of this has been low among ethnic Chinese children who reside in either Chinese and non-Chinese territories. Research has been conducted to explore the barriers and facilitators to physical activity among ethnic Chinese children. However, no qualitative systematic review has been conducted to synthesize these barriers and facilitators. Inclusion criteria: Studies were considered for inclusion if they explored the barriers and facilitators to physical activity among ethnic Chinese children aged six to 17 years in either Chinese or non-Chinese territories, or among people who had responsibility for them in school, home, and community settings. The review included studies that focused on their views, experiences, attitudes, understandings, perceptions, and perspectives. Studies were included if they focused on qualitative data including, but not limited to, designs such as phenomenology, ethnography, grounded theory and action research. In addition, the authors considered cross-sectional surveys to find any free text relating to the review question. Methods: MEDLINE, Embase, CINAHL, PsycINFO, BNI, AMED, Web of Science, Scopus, CNKI, Wanfang and VIP databases were searched to identify published studies. The search for unpublished studies included EThOS, OpenGrey, ProQuest Dissertations and Theses, CNKI and Wanfang. Databases were searched from their inception dates to 10 December 2018 and no language restrictions were applied. The JBI guidelines for qualitative systematic reviews were followed in conducting the review. The JBI process of meta-aggregation was used to identify categories and synthesize findings. Results: Out of 9460 records identified, 11 qualitative studies met the eligibility criteria and were included in the review. Using the JBI checklist for qualitative research (10 criteria), the critical appraisal scores of the majority of studies ranged from a moderate score of 6 (n = 1) to a high score of 7 and above (n = 9). Seven studies were from China, two from Australia, one each from the United Kingdom and the United States. The sample size ranged from 12 to 115 participants. A total of 56 findings were extracted and aggregated into 21 categories, based on the similarity of meaning. From studies conducted in the Chinese territories, four synthesized findings (personal, socio-cultural, environmental, and policy- and program-related barriers and facilitators) were aggregated from 37 extracted findings and 14 aggregated categories. From studies conducted in the non-Chinese territories, only two synthesized findings (personal and socio-cultural barriers and facilitators) were derived from 19 extracted findings and seven aggregated categories. Based on the ConQual scores, confidence in the synthesized findings was moderate. Conclusions: Four broad themes emerged from the participants' accounts, namely personal, socio-cultural, environmental, and policy- and program-related factors. Barriers and facilitators at the personal and socio-cultural level (e.g., parents and teachers) were most frequently cited, reflecting the importance of children's self-influence and the role of adults. Future interventions are needed to address the identified barriers and enhance the facilitators. Systematic review registration number: PROSPERO CRD42018097124

Characteristics of Indigenous healing strategies in Canada: a scoping review
imageObjective: The objective of this review was to identify the characteristics of Indigenous healing strategies in Canada and culturally relevant approaches within Indigenous contexts. Introduction: In responding to the Canadian Truth and Reconciliation Commission's Calls to Action, there is increasing interest in Indigenous healing strategies across clinical, policy, and community sectors. The high relevance of Indigenous healing has also encouraged exploration of new approaches to research that are responsive to, and inclusive of, Indigenous contexts. To date, there is no clear understanding of what characterizes Indigenous healing strategies in Canada. Inclusion criteria: This review considered healing strategies for First Nations, Inuit, and Métis in Canada. Strategies examined included those related to health services and programs, policies and guidelines, models and frameworks, and Indigenous narratives and expert opinion in any service setting. Methods: This review employed the JBI approach to scoping reviews. Searches were performed in CINAHL Full Text, Sociological Abstracts, PsycINFO, MEDLINE, and Academic Search Premier in December 2018. Searches for gray literature were conducted in iPortal, Canadian Electronic Library, and a list of Canadian government and Indigenous organization websites in February 2019. This review was limited to publications from 2008 onward. Non-English articles and theses and dissertations were excluded. Results: Among the 59 articles included in this review, 41 were journal articles and 28 were published within the previous five years (i.e., 2014 and onward). The healing strategies were most frequently implemented in Ontario (n = 13), British Columbia (n = 8), and Manitoba (n = 5). The majority of strategies were utilized in the health settings (n = 37), which included mainstream treatment modalities as well as community-based healing initiatives. Services and programs (n = 24) were the predominant type of healing strategies, followed by models and frameworks (n = 9), policies and guidelines (n = 8), Indigenous narratives and expert opinion (n = 7), and others (n = 11). The most frequent guiding principles were identified as Honoring Cultures and Traditions (n = 14), Medicine Wheel (n = 12), and Strength-Based/Empowerment (n = 12). The most widely used main components were Artistic Expression (n = 16), Ceremonies (n = 15), and Games and Exercises (n = 12). As for human resources, Community Members (n = 19) were most frequently engaged, followed by Local Agencies (n = 12) and Knowledge Keepers (n = 12). Eight culturally relevant approaches were identified from 29 primary research studies, with the most popular being Consultation/Participatory Research (n = 20) and Indigenous Protocols (n = 5). Conclusions: The findings of this review collectively support a decolonizing approach that upholds Indigenous knowledge, respects Indigenous rights to self-determination, and recognizes Indigenous resilience and agency. More research is needed with a focus on Inuit or Métis healing, and innovative knowledge synthesis methods inclusive of diverse Indigenous ways of knowing.

Effectiveness of non-pharmacological interventions to treat orthostatic hypotension in elderly people and people with a neurological condition: a systematic review
imageObjective: The objective of this review was to summarize the best available evidence regarding the effectiveness of non-pharmacological interventions to treat orthostatic hypotension (OH) in elderly people and people with a neurological condition. Introduction: Orthostatic hypotension is common in elderly people and people with a neurological condition and can interfere with or limit rehabilitation. Non-pharmacological interventions to treat OH could allow for longer and earlier mobilization, which is recommended in national clinical guidelines for rehabilitation in the acute or sub-acute phase following stroke or other neurological conditions. Inclusion criteria: The review considered people aged 50 years and older, and people aged 18 years and elderly people with a neurological condition. Non-pharmacological interventions to treat OH included compression garments, neuromuscular stimulation, physical counter-maneuvers, aerobic or resistance exercises, sleeping with head tilted up, increasing fluid and salt intake, and timing and size of meals. The comparator was usual care, no intervention, pharmacological interventions, or other non-pharmacological interventions. Outcome measures included systolic blood pressure, diastolic blood pressure, heart rate, cerebral blood flow, observed/perceived symptoms, duration of standing or sitting in minutes, tolerance of therapy, functional ability, and adverse events/effects. Methods: Databases for published and unpublished studies available in English up to April 2018 with no lower date limit were searched. Critical appraisal was conducted using standardized instruments from JBI. Data were extracted using standardized tools designed for quantitative studies. Where appropriate, studies were included in a meta-analysis; otherwise, data were presented in a narrative form due to heterogeneity. Results: Forty-three studies – a combination of randomized controlled trials (n = 13), quasi-experimental studies (n = 28), a case control study (n = 1), and a case report (n = 1) – with 1069 participants were included. Meta-analyses of three interventions (resistance exercise, electrical stimulation, and lower limb compression bandaging) showed no significant effect of these interventions. Results from individual studies indicated physical maneuvers such as leg crossing, leg muscle pumping/contractions, and bending forward improved orthostatic hypotension. Abdominal compression improved OH. Sleeping with head up in combination with pharmacological treatment was more effective than sleeping with head up alone. Eating smaller, more frequent meals was effective. Drinking 480 mL of water increased blood pressure. Conclusions: The review found mixed results for the effectiveness of non-pharmacological interventions to treat OH in people aged 50 years and older, and people with a neurological condition. There are several non-pharmacological interventions that may be effective in treating OH, but not all have resulted in clinically meaningful changes in outcome. Some may not be suitable for people with moderate to severe disability; therefore, it is important for clinicians to consider the patient's abilities and impairments when considering which non-pharmacological interventions to implement.

Efficacy of group social skills interventions on social competency and participation in adolescents with acquired and developmental disabilities: a systematic review protocol
Objective: The objective of this review is to evaluate the efficacy of group social skills interventions in improving social knowledge, social competency, and social participation in adolescents with acquired and developmental disabilities. Introduction: Difficulties with social functioning and participation are commonly experienced by adolescents with a range of acquired and developmental disabilities. There is evidence for the use of group social skills interventions in youth with autism spectrum disorder, although less is known about their efficacy with youth with other disabilities. Inclusion criteria: This review will include studies that evaluate group social skills interventions in adolescents with an acquired or developmental disability, excluding a primary mental health disorder. Randomized controlled trials will be the only experimental design included and group social skills interventions must have an available intervention manual to allow use in clinical practice. Primary outcomes will include measures of social knowledge, social competence, and social participation. Methods: PubMed, CINAHL, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Web of Science will be searched for eligible studies published in English. Clinical Trials Registry, Google Scholar, and ProQuest Dissertations and Theses will also be searched. Screening, study selection, critical appraisal, and data extraction will be conducted by two independent reviewers using standardized tools. Studies will be pooled, where possible, with statistical meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings presented. Systematic review registration number: PROSPERO CRD42020158189.

Effects of reading media on reading comprehension in health professional education: a systematic review protocol
Objective: To evaluate the effect of digital-based reading versus paper-based reading on reading comprehension among students, trainees, and residents participating in health professional education. Introduction: Several reviews have examined the effects of reading media on reading comprehension; however, none have considered health professional education specifically. The growing use of electronic media in health professional education, as well as recent data on the consequences of digital-based reading on learning, justify the necessity to review the current literature to provide research and educational recommendations. Inclusion criteria: Studies conducted with health professions students, trainees, and residents individually receiving educational material written in their first language in a paper-based or a digital-based format will be considered. Studies conducted among participants with cognitive impairment or reading difficulties will be excluded. Observational, experimental and quasi-experimental studies that assess reading comprehension measured by previously validated or researcher-generated tests will be considered. Methods: Relevant studies will be sought from CINAHL, Embase, ERIC, Google Scholar, MEDLINE, PsycINFO, and Web of Science (SCI and SSCI), without date or language restrictions. Two independent reviewers will perform title and abstract screening, full-text review, critical appraisal, and data extraction. Disagreements will be resolved through discussion or with a third independent reviewer. Synthesis will occur at four levels (i.e., study, participant, intervention, and outcome levels) in a table format. Data will be synthesized descriptively and with meta-analyses if appropriate. Systematic review registration number: PROSPERO CRD42020154519

Experiences of Widening Participation students in undergraduate medical education in the United Kingdom: a qualitative systematic review protocol
Objective: The objective of this review is to characterize the experiences of Widening Participation students in undergraduate medical education in the United Kingdom (UK). Introduction: Most Widening Participation research in the UK is focused on medical school recruitment. Although this is important, there is a paucity of research examining whether the experience of medical school itself is an equal experience for both traditional and Widening Participation students. The aim of this review is to explore and to characterize the experiences of Widening Participation students within medical education during their studies in the UK. Inclusion criteria: This review will include qualitative research conducted in the UK examining any aspect of the lived experience of undergraduate medical education according to Widening Participation students, including identity formation, learning experience in pre-clinical environments and clinical placements, and the relation to social, cultural, and financial capital. Methods: The study will consider articles found through searching the databases MEDLINE, PubMed, Web of Science, CINAHL, Embase, PsycINFO, and ERIC, as well as gray literature. Studies published from 2000 onwards in the English language will be included. Studies will be assessed against the inclusion criteria at all stages by two independent reviewers. Eligible studies will be critically appraised for methodological quality. Regardless of methodological quality, all studies retrieved will be included in the review. The final synthesized findings will be graded according to the ConQual approach. Systematic review registration number: Submitted and awaiting registration on PROSPERO (ID 167879)

Prevalence of tobacco smoking among European migrants residing in EU 15 countries: a quantitative systematic review protocol
Objectives: The objective of this systematic review is to summarize the prevalence of tobacco smoking in European migrants residing in EU 15 countries. Introduction: Most of the migration within the World Health Organization European Region is intracontinental. The prevalence of smoking varies greatly across the European Region. Migrants may choose to adopt the smoking behaviors of their host countries or retain the smoking behaviors of their countries of origin. Several studies have identified the high prevalence of smoking of some migrant groups in comparison to their host countries, but no systematic reviews have been completed on intracontinental migrants within the European Region. Inclusion criteria: Epidemiological studies, which include data on the prevalence of tobacco smoking in European migrants aged ≥ 15 years of age living in the following EU 15 countries host countries for ≥ 1 year: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Portugal, Spain, Sweden, and the United Kingdom. Methods: MEDLINE, Embase, CINAHL, PsycINFO, ASSIA, and Web of Science will be searched to identify published studies. General gray literature (eg, Open Grey) as well as gray literature for migrants (Migrant Health Research Portal) and tobacco will be searched. The JBI methodology for systematic reviews of prevalence will be used in this review. Data synthesis will use meta-analysis where appropriate and narrative synthesis.

Effectiveness of nitric oxide agents in preventing the early onset of pre-eclampsia and possible modification of metabolic factors in high-risk pregnancies: a systematic review protocol
Objectives: To determine the effectiveness of nitric oxide agents in modifying the metabolic factors of pre-eclampsia and its effectiveness in preventing the onset of pre-eclampsia in high-risk pregnancies. Introduction: Pre-eclampsia is a major cause of maternal death during the prenatal and neonatal periods. Nitric oxide is a vasodilator and platelet aggregation inhibitor responsible for the vascular adaptation of the placenta. Although various studies have established that nitric oxide is effective in preventing complications from pre-eclampsia, there is limited evidence to show that administering nitric oxide agents to high-risk women before 20 weeks' gestation will prevent the onset of pre-eclampsia. Inclusion criteria: This review will consider randomized controlled trials that compare nitric oxide donors and precursors with a placebo or no intervention on pregnant women (18 to 44 years) with ≤ 20-week gestational age that are at high risk of pre-eclampsia. The primary outcome of interest will be the onset of pre-eclampsia. Secondary outcomes include increased systolic and diastolic blood pressure, elevated asymmetric dimethylarginine levels, decreased endothelial nitric oxide synthase activity, reduced maternal placental vasculature, and abnormal Doppler ultrasound waveforms. Methods: Data sources will be drawn up from MEDLINE, CINAHL, ProQuest (Health and Medicine), and Web of Science from inception till current date. No language restrictions will be applied in the search strategy. Selected studies will be assessed against the JBI critical appraisal checklist, and the certainty of evidence and strength of recommendations from findings will also be ascertained. Systematic review registration number: PROSPERO CRD42018099298

Participation-focused interventions for stroke rehabilitation: a scoping review protocol
Objective: The objectives of this scoping review are to i) identify adaptive stroke rehabilitation interventions using metacognitive or self-management approaches targeting participation as an outcome; ii) determine the explicit and implicit theories underlying these interventions; and iii) ascertain the elements in each intervention. This review will develop a catalogue of these interventions, improving the understanding of how these interventions work, thereby facilitating efficient development and testing of participation-focused interventions. Introduction: Stroke rehabilitation interventions can be categorized as those aiming to correct impairment and those seeking participation improvement despite impairment. Impairment-focused interventions include a relatively small number of well-defined elements, generally based on motor learning or other types of learning theory. Participation-focused interventions span a large group of diverse interventions. The underlying theory is typically varied and often implicit, but many of these interventions are based on metacognitive or self-management approaches. An examination of the underlying theory and elements of participation-focused interventions would allow researchers to more effectively advance the science of these approaches. Inclusion criteria: The review will include published papers describing rehabilitation interventions using metacognitive or self-management approaches to improve participation among adults who have experienced a stroke. Methods: The search will include JBI Evidence-Based Practice Database, MEDLINE, Embase, CINAHL, PsycINFO, OTSeeker, and PEDro databases. Studies will be selected according to a three-step process, including i) managing search results and removing duplicates, ii) title and abstract screening, and iii) full text screening. The extracted data will be presented in table form and narrative summary, aligning with the objectives and scope of this review.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Telephone consultation 11855 int 1193,

Ophthalmology Clinics

COVID-19 and the Eye: A Comprehensive Review of the Literature
No abstract available

A Review and Update on Surgical Management of Intraocular Lens Dislocation
imageNo abstract available

Updates in the Management of Corneal Ectasia
No abstract available

Review: Optimizing DMEK Technique, 2018-2020
No abstract available

Recent Advances in Pediatric Endothelial Keratoplasty
imageNo abstract available

Recent Updates in Femtosecond Laser-assisted Cataract Surgery
imageNo abstract available

Alpha-Gal Syndrome in Ophthalmology and Medicine: Erratum
No abstract available

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Telephone consultation 11855 int 1193,

Cancers, Vol. 12, Pages 3823: An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

Alexandros G.Sfakianakis shared this article with you from Inoreader
Μέσω Cancers

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Cancers, Vol. 12, Pages 3823: An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

Cancers doi: 10.3390/cancers12123823

Authors: Rong-Zong Liu Roseline Godbout

Treatment for early stage and localized prostate cancer (PCa) is highly effective. Patient survival, however, drops dramatically upon metastasis due to drug resistance and cancer recurrence. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. It is therefore crucial to decipher the key genetic alterations and relevant molecular pathways driving PCa metastatic progression so that predictive biomarkers and precise therapeutic targets can be developed. Through PCa cohort analysis, we found that a fatty acid-binding protein (FABP) gene cluster (containing five FABP family members) is preferentially amplified and overexpressed in metastatic PCa. All five FABP genes reside on chromosome 8 at 8q21.13, a chromosomal region frequently amplified in PCa. There is emerging evidence that these FABPs promote metastasis through distinct biological actions and molecular pathways. In this review, we discuss how these FABPs may serve as drivers/promoters for PCa meta static transformation using patient cohort analysis combined with a review of the literature.

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Cancers, Vol. 12, Pages 3821: Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients

Alexandros G.Sfakianakis shared this article with you from Inoreader
Μέσω Cancers

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Cancers, Vol. 12, Pages 3821: Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients

Cancers doi: 10.3390/cancers12123821

Authors: Hanna A. Zielinska Carl S. Daly Ahmad Alghamdi Amit Bahl Muhammed Sohail Paul White Sarah R. Dean Jeff M. P. Holly Claire M. Perks

Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan–Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients.

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Plasma proteomic data can contain personally identifiable, sensitive information and incidental findings [Research]

Alexandros G.Sfakianakis shared this article with you from Inoreader

The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics.

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Cardiac and sudden death after chronic total occlusion percutaneous coronary intervention: Prognostic role of the target vessel

Alexandros G.Sfakianakis shared this article with you from Inoreader

Abstract

Background

The role of the target vessel in percutaneous revascularization of chronic total occlusion (CTO) is unclear.

Objective

We sought to assess the long‐term results of percutaneous coronary intervention (PCI) for CTO lesions in each coronary artery and to investigate the impact of successful revascularization and previous myocardial infarction (MI) in the territory of the target vessel.

Methods and Results

Cohort observational study on 1,124 patients who have undergone CTO PCI attempt: 371 on left anterior descending artery (LAD), 485 right coronary artery, and 268 left circumflex. Patients were further stratified by successfully revascularized and not‐revascularized CTO (CTO‐NR). Vessels affected by a previous MI were defined as infarct‐related artery (IRA). The primary endpoint was cardiac death; the secondary endpoint was the combined rate of sudden cardiac‐death and sustained ventricular‐arrhythmias (SCD/SVAs). Propensity score‐matching was performed to evaluate LAD versus NON‐LAD CTO. Up to 12‐year follow‐up, the clinical benefit associated with successful PCI was consistent across the three groups. CTO‐NR had the greatest association with cardiac death and SCD/SVAs in each coronary artery and in IRA‐CTO patients.

Conclusions

Unsuccessful percutaneous CTO revascularization was associated with lower cardiac survival and freedom from SCD/SVAs, irrespective of the vessel treated. This result was mainly driven by patients with an IRA CTO.

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Is Candida auris sexual?

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journal.ppat.1009094.g001&size=inline

by Zoe K. Ross, Alexander Lorenz

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The Synergistic Effect of Hyperthermia and Chemotherapy in Magnetite Nanomedicine-Based Lung Cancer Treatment

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A conscious choice: Is it ethical to aim for unconsciousness at the end of life?

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Μέσω Bioethics

Abstract

One of the most commonly referenced ethical principles when it comes to the management of dying patients is the doctrine of double effect (DDE). The DDE affirms that it is acceptable to cause side effects (e.g. respiratory depression) as a consequence of symptom‐focused treatment. Much discussion of the ethics of end of life care focuses on the question of whether actions (or omissions) would hasten (or cause) death, and whether that is permissible. However, there is a separate question about the permissibility of hastening or causing unconsciousness in dying patients. Some authors have argued that the DDE would not permit end of life care that directly aims to render the patient unconscious. The claim is that consciousness is an objective human good and therefore doctors should not intentionally (and permanently) suppress it. Three types of end of life care (EOLC) practices will be explored in this article. The first is symptom‐based management (e.g. analgesia); the second is proportional terminal sedation as a means of relieving suffering (also referred to as palliative sedation or continuous deep sedation); and finally, deliberate and rapid sedation to unconsciousness until death (a practice we call terminal anaesthesia in this paper). After examining the common arguments for the various types of symptom‐based management and sedation, we apply the DDE to the latter two types of EOLC practices. We argue that aiming at unconsciousness, contrary to some claims, can be morally good or at least morally neutral in some dying patients.

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The role of gene dosage in budding yeast centrosome scaling and spontaneous diploidization

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journal.pgen.1008911.g005&size=inline

by Jingjing Chen, Zhiyong Xiong, Danny E. Miller, Zulin Yu, Scott McCroskey, William D. Bradford, Ann M. Cavanaugh, Sue L. Jaspersen

Ploidy is the number of whole sets of chromosomes in a species. Ploidy is typically a stable cellular feature that is critical for survival. Polyploidization is a route recognized to increase gene dosage, improve fitness under stressful conditions and promote evolutionary diversity. However, the mechanism of regulation and maintenance of ploidy is not well characterized. Here, we examine the spontaneous diploidization associated with mutations in components of the Saccharomyces cerevisiae centrosome, known as the spindle pole body (SPB). Although SPB mutants are associated with defects in spindle formation, we show that two copies of the mutant in a haploid yeast favors diploidization in some cases, leading us to speculate that the increased gene dosage in diploids 'rescues' SPB duplication defects, allowing cells to successfully propagate with a stable diploid karyotype. This copy number-based rescue is linked to SPB scaling: certain SPB subcomplexes do not scale or only minimally scale with ploidy. We hypothesize that lesions in structures with incompatible allometries such as the centrosome may drive changes such as whole genome duplication, which have shaped the evolutionary landscape of many eukaryotes.
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