Photodynamic therapy (PDT) is a clinical treatment in which a light‐absorbing drug called a photosensitizer (PS) is combined with light and molecular oxygen to generate cytotoxic singlet oxygen. PDT ...provides additional tissue selectivity compared to conventional chemotherapy as singlet oxygen is generated only in areas in which PS accumulates and that are simultaneously illuminated by a light source with sufficient irradiance and dose. Early PDT beacons built on this concept by adding an analyte‐responsive element that simultaneously turns on PDT and fluorescence, providing both an additional layer of selectivity and real‐time feedback of the PS′s activation state. More recent PDT beacons have expanded this idea, with new methods now available for sensing analytes, generating singlet oxygen, and reporting treatment status. In this Minireview, we consider developments in advanced activation strategies implemented in therapeutic and theranostic beacons.
Extreme specificity: Photodynamic therapy beacons are phototoxic drugs that are only cytotoxic upon tissue accumulation, analyte‐driven activation, and external illumination. Moreover, their cytotoxic state simultaneously provides optical feedback to monitor treatment. In this Minireview, recent developments on how these beacons are becoming smarter still are discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Oncology has come a long way in addressing patients' quality of life, together with developing surgical, radio-oncological and medical anticancer therapies. However, the multiple and varying needs of ...patients are still not being met adequately as part of routine cancer care. Supportive and palliative care interventions should be integrated, dynamic, personalised and based on best evidence. They should start at the time of diagnosis and continue through to end-of-life or survivorship. ESMO is committed to excellence in all aspects of oncological care during the continuum of the cancer experience. Following the 2003 ESMO stand on supportive and palliative care (Cherny N, Catane R, Kosmidis P. ESMO takes a stand on supportive and palliative care. Ann Oncol 2003; 14(9): 1335–1337), this position paper highlights the evolving and growing gap between the needs of cancer patients and the actual provision of care. The concept of patient-centred cancer care is presented along with key requisites and areas for further work.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Conventional antidepressants require 2-8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act ...within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small molecules capable of resetting and stabilizing clock genes to evaluate if they can rapidly relieve symptoms and sustain improvement.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Purspose The prevention of youth violence is a public health priority in many countries. We examined the prevalence of bullying victimization and physical fighting in youths in 79 high- and ...low-income countries and the relations between structural determinants of adolescent health (country wealth, income inequality, and government spending on education) and international differences in youth violence. Methods Cross-sectional surveys were administered in schools between 2003 and 2011. These surveys provided national prevalence rates of bullying victimization (n = 334,736) and four or more episodes of physical fighting in the past year (n = 342,312) in eligible and consenting 11–16 year olds. Contextual measures included per capita income, income inequality, and government expenditures on education. We used meta-regression to examine relations between country characteristics and youth violence. Results Approximately 30% of adolescents reported bullying victimization and 10.7% of males and 2.7% of females were involved in frequent physical fighting. More youth were exposed to violence in African and Eastern Mediterranean countries than in Europe and Asia. Violence directly related to country wealth; a 1 standard deviation increase in per capita income corresponded to less bullying (−3.9% in males and −4.2% in females) and less fighting (−2.9% in males and −1.0% in females). Income inequality and education spending modified the relation between country wealth and fighting; where inequality was high, country wealth related more closely to fighting if education spending was also high. Conclusions Country wealth is a robust determinant of youth violence. Fighting in affluent but economically unequal countries might be reduced through increased government spending on education.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lithium–oxygen (Li–O2) batteries have the highest theoretical energy density of all the Li-based energy storage systems, but many challenges prevent them from practical use. A major obstacle is the ...sluggish performance of the air cathode, where both oxygen reduction (discharge) and oxygen evolution (charge) reactions occur. Recently, there have been significant advances in the development of graphene-based air cathode materials with a large surface area and catalytically active for both oxygen reduction and evolution reactions, especially with additional catalysts or dopants. However, most studies reported so far have examined air cathodes with a limited areal mass loading rarely exceeding 1 mg/cm2. Despite the high gravimetric capacity values achieved, the actual (areal) capacities of those batteries were far from sufficient for practical applications. Here, we present the fabrication, performance, and mechanistic investigations of high-mass-loading (up to 10 mg/cm2) graphene-based air electrodes for high-performance Li–O2 batteries. Such air electrodes could be easily prepared within minutes under solvent-free and binder-free conditions by compression-molding holey graphene materials because of their unique dry compressibility associated with in-plane holes on the graphene sheet. Li–O2 batteries with high air cathode mass loadings thus prepared exhibited excellent gravimetric capacity as well as ultrahigh areal capacity (as high as ∼40 mAh/cm2). The batteries were also cycled at a high curtailing areal capacity (2 mAh/cm2) and showed a better cycling stability for ultrathick cathodes than their thinner counterparts. Detailed post-mortem analyses of the electrodes clearly revealed the battery failure mechanisms under both primary and secondary modes, arising from the oxygen diffusion blockage and the catalytic site deactivation, respectively. These results strongly suggest that the dry-pressed holey graphene electrodes are a highly viable architectural platform for high-capacity, high-performance air cathodes in Li–O2 batteries of practical significance.
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IJS, KILJ, NUK, PNG, UL, UM
Angiogenesis and inflammation are closely integrated processes in osteoarthritis (OA) and may affect disease progression and pain. Inflammation can stimulate angiogenesis, and angiogenesis can ...facilitate inflammation. Angiogenesis can also promote chondrocyte hypertrophy and endochondral ossification, contributing to radiographic changes in the joint. Inflammation sensitizes nerves, leading to increased pain. Innervation can also accompany vascularization of the articular cartilage, where compressive forces and hypoxia may stimulate these new nerves, causing pain even after inflammation has subsided. Inhibition of inflammation and angiogenesis may provide effective therapeutics for the treatment of OA by improving symptoms and retarding joint damage. This review aims to summarize (i) the evidence that angiogenesis and inflammation play an important role in the pathophysiology of OA and (ii) possible directions for future research into therapeutics that could effectively treat this disease.
Background
People with dementia can have feeding and swallowing difficulties (dysphagia). Modification of the consistency of food or fluids, or both, is a common management strategy. However, diet ...modification can affect quality of life and may lead to dehydration and malnutrition. Evidence on the benefits and risks of modifying food and fluids is mandatory to improve the care of people with dementia and dysphagia.
Objectives
To determine the effectiveness and adverse effects associated with modifying the consistency of food and fluids in improving oral intake and eliminating aspiration in adults with dysphagia and dementia.
Search methods
We searched ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), the Cochrane Library, MEDLINE via Ovid SP, Embase via Ovid SP, PsycINFO via Ovid SP, CINAHL via EBSCOhost, LILACS via BIREME, ClinicalTrials.gov and the World Health Organization (WHO) Portal on 9 May 2018. We also checked the reference lists of relevant articles to identify any additional studies.
Selection criteria
We included randomised controlled trials (RCTs), quasi‐RCTs and cluster‐RCTs published in any language that measured any of the outcomes of interest. We included trials with adults with a clinical diagnosis of dementia with symptoms and signs of dysphagia confirmed on instrumental assessment. We included participants with all types, stages and severities of dementia. Control groups received either no intervention or interventions not involving diet modification or modification to sensory properties of food.
Data collection and analysis
Two review authors independently assessed for inclusion all potential studies identified. Data were extracted independently along with assessment of methodological quality using standard Cochrane methods. We contacted study authors for additional unpublished information.
Main results
No trials on modification of food met the inclusion criteria. We included two studies that examined modification to fluids. Both were part of the same large multicentre trial and included people with dementia and people with or without dementia and Parkinson's disease. Participation in the second trial was determined by results from the first trial. With unpublished data supplied by study authors, we examined data from participants with dementia only. The first study, a cross‐over trial, investigated the immediate effects on aspiration of two viscosities of liquids (nectar thick and honey thick) compared to regular liquids in 351 participants with dementia using videofluoroscopy. Regular liquids with a chin down head posture, as well as regular liquids without any intervention were also compared. The sequence of interventions during videofluoroscopy may have influenced response to intervention. The second study, a parallel designed RCT, compared the effect of nectar and honey thick liquids with a chin down head posture over a three‐month period in a subgroup of 260 participants with dementia. Outcomes were pneumonia and adverse intervention effects. Honey thick liquids, which are more consistent with descriptors for 'spoon thick' or 'extremely thick' liquids, showed a more positive impact on immediate elimination of aspiration during videofluoroscopy, but this consistency showed more adverse effects in the second follow‐up study. During the second three‐month follow‐up trial, there were a greater number of incidents of pneumonia in participants receiving honey thick liquids than those receiving nectar thick liquids or taking regular liquids with a chin down posture. There were no deaths classified as 'definitely related' to the type of fluids prescribed. Neither trial addressed quality of life. Risk of bias for both studies is high. The overall quality of evidence for outcomes in this review is low.
Authors' conclusions
We are uncertain about the immediate and long‐term effects of modifying the consistency of fluid for swallowing difficulties in dementia as too few studies have been completed. There may be differences in outcomes depending on the grade of thickness of fluids and the sequence of interventions trialled in videofluoroscopy for people with dementia. Clinicians should be aware that while thickening fluids may have an immediate positive effect on swallowing, the long‐term impact of thickened fluids on the health of the person with dementia should be considered. Further high‐quality clinical trials are required.
Chronic wasting disease (CWD) is a highly contagious, fatal neurodegenerative disease caused by infectious prions (PrP
) affecting wild and captive cervids. Although experimental feeding studies have ...demonstrated prions in feces of crows (Corvus brachyrhynchos), coyotes (Canis latrans), and cougars (Puma concolor), the role of scavengers and predators in CWD epidemiology remains poorly understood. Here we applied the real-time quaking-induced conversion (RT-QuIC) assay to detect PrP
in feces from cervid consumers, to advance surveillance approaches, which could be used to improve disease research and adaptive management of CWD. We assessed recovery and detection of PrP
by experimental spiking of PrP
into carnivore feces from 9 species sourced from CWD-free populations or captive facilities. We then applied this technique to detect PrP
from feces of predators and scavengers in free-ranging populations. Our results demonstrate that spiked PrP
is detectable from feces of free-ranging mammalian and avian carnivores using RT-QuIC. Results show that PrP
acquired in natural settings is detectable in feces from free-ranging carnivores, and that PrP
rates of detection in carnivore feces reflect relative prevalence estimates observed in the corresponding cervid populations. This study adapts an important diagnostic tool for CWD, allowing investigation of the epidemiology of CWD at the community-level.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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