To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors.
An Expert Panel ...conducted targeted systematic literature reviews to identify new studies.
The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update.
The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.
Model organisms have played an important role in the elucidation of multiple genes and cellular processes that regulate aging. In this study we utilized the budding yeast, Saccharomyces cerevisiae, ...in a large-scale screen for genes that function in the regulation of chronological lifespan, which is defined by the number of days that non-dividing cells remain viable. A pooled collection of viable haploid gene deletion mutants, each tagged with unique identifying DNA "bar-code" sequences was chronologically aged in liquid culture. Viable mutants in the aging population were selected at several time points and then detected using a microarray DNA hybridization technique that quantifies abundance of the barcode tags. Multiple short- and long-lived mutants were identified using this approach. Among the confirmed short-lived mutants were those defective for autophagy, indicating a key requirement for the recycling of cellular organelles in longevity. Defects in autophagy also prevented lifespan extension induced by limitation of amino acids in the growth media. Among the confirmed long-lived mutants were those defective in the highly conserved de novo purine biosynthesis pathway (the ADE genes), which ultimately produces IMP and AMP. Blocking this pathway extended lifespan to the same degree as calorie (glucose) restriction. A recently discovered cell-extrinsic mechanism of chronological aging involving acetic acid secretion and toxicity was suppressed in a long-lived ade4Delta mutant and exacerbated by a short-lived atg16Delta autophagy mutant. The identification of multiple novel effectors of yeast chronological lifespan will greatly aid in the elucidation of mechanisms that cells and organisms utilize in slowing down the aging process.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myths, Presumptions, and Facts about Obesity Casazza, Krista; Fontaine, Kevin R; Astrup, Arne ...
New England journal of medicine/The New England journal of medicine,
01/2013, Volume:
368, Issue:
5
Journal Article
Peer reviewed
Open access
This commentary reviews common myths and presumptions about obesity and also provides some useful evidence-based concepts about overweight and obesity.
Passionate interests, the human tendency to ...seek explanations for observed phenomena, and everyday experience appear to contribute to strong convictions about obesity, despite the absence of supporting data. When the public, mass media, government agencies, and even academic scientists espouse unsupported beliefs, the result may be ineffective policy, unhelpful or unsafe clinical and public health recommendations, and an unproductive allocation of resources. In this article, we review some common beliefs about obesity that are not supported by scientific evidence and also provide some useful evidence-based concepts. We define myths as beliefs held to be true despite substantial refuting evidence, presumptions . . .
Recent studies have suggested a role for epigenetic mechanisms in the complex etiology of various neurodegenerative diseases. In this review, we discuss advances that have been made toward ...understanding the role of epigenetic processes in neurodegenerative disorders, with a particular focus on Alzheimer's disease, where the most extensive studies have been undertaken to date. We provide a brief overview of DNA modifications, followed by a summarization of studies of DNA modifications in Alzheimer's disease and other neurodegenerative diseases.
Epigenetic mechanisms have been hypothesized to play a role in a number of different neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, we provide an overview of current studies performed in the field, with a focus on DNA methylation, before discussing the potential direction of future studies.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To investigate the variations in body weight, food intake, and body composition of both male and female C57BL/6J mice during a diet‐induced obesity model with high‐fat diet (HFD) feeding.
...Methods
Mice were individually housed and fed ad libitum either a low‐fat diet (LFD, 10% calories from fat; n = 15 male, n = 15 female) or HFD (45% calories from fat; n = 277 male, n = 278 female) from 8 to 43 weeks of age. Body weight, food intake, and body composition were routinely measured.
Results
Body weight was significantly increased with HFD (vs. LFD) in males from week 14 (P = 0.0221) and in females from week 27 (P = 0.0076). Fat mass and fat‐free mass of all groups were significantly increased over time (all P < 0.0001), with a large variation observed in fat mass. Baseline fat mass, fat‐free mass, and daily energy intake were significant predictors of future body weight for both sexes (P < 0.0001). Baseline fat mass was a significant predictor of future body fat (P < 0.0001).
Conclusions
Both males and females have large variations in fat mass, and this variability increases over time, while that of fat‐free mass remains relatively stable. Sex differences exist in HFD responses and multivariate predicting models of body weight.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We present a reconfigurable, dynamic beam steering holographic metasurface aperture to synthesize a microwave camera at K-band frequencies. The aperture consists of a 1D printed microstrip ...transmission line with the front surface patterned into an array of slot-shaped subwavelength metamaterial elements (or meta-elements) dynamically tuned between "ON" and "OFF" states using PIN diodes. The proposed aperture synthesizes a desired radiation pattern by converting the waveguide-mode to a free space radiation by means of a binary modulation scheme. This is achieved in a holographic manner; by interacting the waveguide-mode (reference-wave) with the metasurface layer (hologram layer). It is shown by means of full-wave simulations that using the developed metasurface aperture, the radiated wavefronts can be engineered in an all-electronic manner without the need for complex phase-shifting circuits or mechanical scanning apparatus. Using the dynamic beam steering capability of the developed antenna, we synthesize a Mills-Cross composite aperture, forming a single-frequency all-electronic microwave camera.
Summary
Calorie restriction (CR) extends the mean and maximum lifespan of a wide variety of organisms ranging from yeast to mammals, although the molecular mechanisms of action remain unclear. For ...the budding yeast Saccharomyces cerevisiae reducing glucose in the growth medium extends both the replicative and chronological lifespans (CLS). The conserved NAD+‐dependent histone deacetylase, Sir2p, promotes replicative longevity in S. cerevisiae by suppressing recombination within the ribosomal DNA locus and has been proposed to mediate the effects of CR on aging. In this study, we investigated the functional relationships of the yeast Sirtuins (Sir2p, Hst1p, Hst2p, Hst3p and Hst4p) with CLS and CR. SIR2, HST2, and HST4 were not major regulators of CLS and were not required for the lifespan extension caused by shifting the glucose concentration from 2 to 0.5% (CR). Deleting HST1 or HST3 moderately shortened CLS, but did not prevent CR from extending lifespan. CR therefore works through a Sirtuin‐independent mechanism in the chronological aging system. We also show that low temperature or high osmolarity additively extends CLS when combined with CR, suggesting that these stresses and CR act through separate pathways. The CR effect on CLS was not specific to glucose. Restricting other simple sugars such as galactose or fructose also extended lifespan. Importantly, growth on nonfermentable carbon sources that force yeast to exclusively utilize respiration extended lifespan at nonrestricted concentrations and provided no additional benefit when restricted, suggesting that elevated respiration capacity is an important determinant of chronological longevity.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Weight loss is a predictor of shorter survival in amyotrophic lateral sclerosis (ALS). We performed serial measures of body composition using Dual-energy X-ray Absorptiometry (DEXA) in ALS patients ...to explore its utility as a biomarker of disease progression.
DEXA data were obtained from participants with ALS (enrollment, at 6- and 12- months follow ups) and Parkinson's disease (enrollment and at 4-month follow up) as a comparator group. Body mass index, total lean mass index, appendicular lean mass index, total fat mass index, and percentage body fat at enrollment were compared between the ALS and PD cohorts and age-matched normative data obtained from the National Health and Nutrition Examination Survey database. Estimated monthly changes of body composition measures in the ALS cohort were compared to those of the PD cohort and were correlated with disease progression measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).
The ALS cohort (N = 20) had lower baseline total and appendicular lean mass indices compared to the PD cohort (N = 20) and general population. Loss in total and appendicular lean masses were found to be significantly associated with follow-up time. Low baseline percentage body fat (r = 0.72, p = 0.04), loss of percentage body fat (r = 0.81, p = 0.01), and total fat mass index (r = 0.73, p = 0.04) during follow up correlated significantly with monthly decline of ALSFRS-R scores in ALS cohort who had 2 or more follow-ups (N = 8).
Measurement of body composition with DEXA might serve as a biomarker for rapid disease progression in ALS.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several evolutionary theories predict that rates of morphological change should be positively associated with the rate at which new species arise. For example, the theory of punctuated equilibrium ...proposes that phenotypic change typically occurs in rapid bursts associated with speciation events. However, recent phylogenetic studies have found little evidence linking these processes in nature. Here we demonstrate that rates of species diversification are highly correlated with the rate of body size evolution across the 30,000+ living species of ray-finned fishes that comprise the majority of vertebrate biological diversity. This coupling is a general feature of fish evolution and transcends vast differences in ecology and body-plan organization. Our results may reflect a widespread speciational mode of character change in living fishes. Alternatively, these findings are consistent with the hypothesis that phenotypic 'evolvability'-the capacity of organisms to evolve-shapes the dynamics of speciation through time at the largest phylogenetic scales.
PDF
