Genetic studies indicate that protein homeostasis is a major contributor to metazoan longevity. Collapse of protein homeostasis results in protein misfolding cascades and the accumulation of ...insoluble protein fibrils and aggregates, such as amyloids. A group of small molecules, traditionally used in histopathology to stain amyloid in tissues, bind protein fibrils and slow aggregation in vitro and in cell culture. We proposed that treating animals with such compounds would promote protein homeostasis in vivo and increase longevity. Here we show that exposure of adult Caenorhabditis elegans to the amyloid-binding dye Thioflavin T (ThT) resulted in a profoundly extended lifespan and slowed ageing. ThT also suppressed pathological features of mutant metastable proteins and human β-amyloid-associated toxicity. These beneficial effects of ThT depend on the protein homeostasis network regulator heat shock factor 1 (HSF-1), the stress resistance and longevity transcription factor SKN-1, molecular chaperones, autophagy and proteosomal functions. Our results demonstrate that pharmacological maintenance of the protein homeostatic network has a profound impact on ageing rates, prompting the development of novel therapeutic interventions against ageing and age-related diseases.
PURPOSEThe number of cancer survivors worldwide is growing, with over 15.5 million cancer survivors in the United States alone—a figure expected to double in the coming decades. Cancer survivors face ...unique health challenges as a result of their cancer diagnosis and the impact of treatments on their physical and mental well-being. For example, cancer survivors often experience declines in physical functioning and quality of life while facing an increased risk of cancer recurrence and all-cause mortality compared with persons without cancer. The 2010 American College of Sports Medicine Roundtable was among the first reports to conclude that cancer survivors could safely engage in enough exercise training to improve physical fitness and restore physical functioning, enhance quality of life, and mitigate cancer-related fatigue.
METHODSA second Roundtable was convened in 2018 to advance exercise recommendations beyond public health guidelines and toward prescriptive programs specific to cancer type, treatments, and/or outcomes.
RESULTSOverall findings retained the conclusions that exercise training and testing were generally safe for cancer survivors and that every survivor should “avoid inactivity.” Enough evidence was available to conclude that specific doses of aerobic, combined aerobic plus resistance training, and/or resistance training could improve common cancer-related health outcomes, including anxiety, depressive symptoms, fatigue, physical functioning, and health-related quality of life. Implications for other outcomes, such as peripheral neuropathy and cognitive functioning, remain uncertain.
CONCLUSIONSThe proposed recommendations should serve as a guide for the fitness and health care professional working with cancer survivors. More research is needed to fill remaining gaps in knowledge to better serve cancer survivors, as well as fitness and health care professionals, to improve clinical practice.
ABSTRACT
Metal-poor stars are important tools for tracing the early history of the Milky Way, and for learning about the first generations of stars. Simulations suggest that the oldest metal-poor ...stars are to be found in the inner Galaxy. Typical bulge surveys, however, lack low metallicity ($\rm {Fe/H} \lt -1.0$) stars because the inner Galaxy is predominantly metal-rich. The aim of the Pristine Inner Galaxy Survey (PIGS) is to study the metal-poor and very metal-poor (VMP, $\rm {Fe/H} \lt -2.0$) stars in this region. In PIGS, metal-poor targets for spectroscopic follow-up are selected from metallicity-sensitive CaHK photometry from the CFHT. This work presents the ∼250 deg2 photometric survey as well as intermediate-resolution spectroscopic follow-up observations for ∼8000 stars using AAOmega on the AAT. The spectra are analysed using two independent tools: ULySS with an empirical spectral library, and FERRE with a library of synthetic spectra. The comparison between the two methods enables a robust determination of the stellar parameters and their uncertainties. We present a sample of 1300 VMP stars – the largest sample of VMP stars in the inner Galaxy to date. Additionally, our spectroscopic data set includes ∼1700 horizontal branch stars, which are useful metal-poor standard candles. We furthermore show that PIGS photometry selects VMP stars with unprecedented efficiency: 86 per cent/80 per cent (lower/higher extinction) of the best candidates satisfy $\rm {Fe/H} \lt -2.0$, as do 80 per cent/63 per cent of a larger, less strictly selected sample. We discuss future applications of this unique data set that will further our understanding of the chemical and dynamical evolution of the innermost regions of our Galaxy.
Mpox: What Practicing Gastroenterologists Need to Know Sultan, Shahnaz; Zucker, Jason; Weinberg, David S.
Gastroenterology (New York, N.Y. 1943),
April 2023, 2023-04-00, 20230401, Letnik:
164, Številka:
4
Journal Article
ABSTRACT
The most metal-deficient stars hold important clues about the early buildup and chemical evolution of the Milky Way, and carbon-enhanced metal-poor (CEMP) stars are of special interest. ...However, little is known about CEMP stars in the Galactic bulge. In this paper, we use the large spectroscopic sample of metal-poor stars from the Pristine Inner Galaxy Survey (PIGS) to identify CEMP stars ($\rm {C/Fe} \geqslant +0.7$) in the bulge region and to derive a CEMP fraction. We identify 96 new CEMP stars in the inner Galaxy, of which 62 are very metal-poor ($\rm {Fe/H} \lt -2.0$); this is more than a 10-fold increase compared to the seven previously known bulge CEMP stars. The cumulative fraction of CEMP stars in PIGS is $42^{\, +14\, }_{\, -13} {{\ \rm per\ cent}}$ for stars with $\rm {Fe/H} \lt -3.0$, and decreases to $16^{\, +3\, }_{\, -3} {{\ \rm per\ cent}}$ for $\rm {Fe/H} \lt -2.5$ and $5.7^{\, +0.6\, }_{\, -0.5} {{\ \rm per\ cent}}$ for $\rm {Fe/H} \lt -2.0$. The PIGS inner Galaxy CEMP fraction for $\rm {Fe/H} \lt -3.0$ is consistent with the halo fraction found in the literature, but at higher metallicities, the PIGS fraction is substantially lower. While this can partly be attributed to a photometric selection bias, such bias is unlikely to fully explain the low CEMP fraction at higher metallicities. Considering the typical carbon excesses and metallicity ranges for halo CEMP-s and CEMP-no stars, our results point to a possible deficiency of both CEMP-s and CEMP-no stars (especially the more metal-rich) in the inner Galaxy. The former is potentially related to a difference in the binary fraction, whereas the latter may be the result of a fast chemical enrichment in the early building blocks of the inner Galaxy.
The relevance of cancer rehabilitation as a public health issue grows steadily as cancer incidence, survival, and mean patient age increase. Reported rates of physical impairment and disability are ...already high, prior to the anticipated influx of aged cancer survivors. Despite the high prevalence of cancer-related disablement, treatment rates, even for readily remediable physical impairments, are as low as 1-2%. In addition to low referral rates, a challenge to patient-centric cancer rehabilitation is a fractured system that requires multiple visits to a range of specialists to address even a single issue, and cancer survivors generally have several. Effective solutions must acknowledge the limited cancer rehabilitation clinical work force and its clustering in tertiary centers, as well as the lack of consensus regarding the essential and effective components of a cancer rehabilitation program. A number of models of cancer rehabilitation service delivery have been developed, but, as yet, none have been empirically validated. This paper describes these models and proposes a taxonomy for stratifying the needs of cancer survivors. Modalities used to preserve or restore function among survivors range from simple, relatively intuitive activities to complex, integrated programs that include diagnostic and multi-modal pharmacological, manual, and even procedural interventions. Criteria for determining a survivor's needs across this spectrum are proposed, and the role of the physiatrist as a vital advocate and champion discussed.
Background
Measuring function with valid and responsive tools in patients with cancer is essential for driving clinical decision‐making and for the end points of clinical trials. Current ...patient‐reported outcome measurements of function fall short for many reasons. This study evaluates the responsiveness of the Patient‐Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile, a novel measure of function across multiple domains.
Methods
Two hundred nine participants across five geographically distinct tertiary care centers completed the assessment and pain rating at two outpatient cancer rehabilitation clinic visits. Patients and providers completed a global rating of change measure at the second visit to indicate whether the patient was improving or worsening in function. Multiple response indices and linear models measured whether the measure was responsive to self‐reported and clinician‐rated changes over time. Correlations between changes in function and changes in anchors (pain rating and performance status) were also calculated.
Results
Function as measured by the PROMIS Cancer Function Brief 3D Profile changed appropriately as both patients and clinicians rated change. Small to moderate effect sizes supported the tool's responsiveness. Function was moderately correlated with pain and more strongly correlated with performance status, and changes in function corresponded with changes in anchor variables. No floor/ceiling effect was found.
Conclusions
The PROMIS Cancer Function Brief 3D Profile is sensitive to changes over time in patients with cancer. The measure may be useful in clinical practice and as an end point in clinical trials.
Lay summary
We gave patients a questionnaire by which they told their physicians how well they were functioning, including how fatigued they were.
This study tested that questionnaire to see whether the scores would change if patients got better or worse.
Lay summary
We gave patients a questionnaire by which they told their physicians how well they were functioning, including how fatigued they were.
This study tested that questionnaire to see whether the scores would change if patients got better or worse.
Short
The PROMIS Cancer Function Brief 3D Profile was found to be responsive to measuring change in function in patients with cancer. The changes were correlated with changes in performance status, pain, and both patient‐ and physician‐reported global ratings of change.
This article presents a clinical screening and referral framework to enable health care professionals to guide individuals with cancer to safe and effective exercise programs.
ABSTRACT
We present a comprehensive metallicity analysis of the Sagittarius dwarf spheroidal galaxy (Sgr dSph) using Pristine CaHK photometry. We base our member selection on Gaia EDR3 astrometry, ...applying a magnitude limit at G0 = 17.3, and our population study on the metallicity-sensitive photometry from the Pristine Inner Galaxy Survey (PIGS). Working with photometric metallicities instead of spectroscopic metallicities allows us to cover an unprecedented large area (∼100 square degrees) of the dwarf galaxy, and to study the spatial distribution of its members as function of metallicity with little selection effects. Our study compares the spatial distributions of a metal-poor population of 9719 stars with Fe/H <−1.3 and a metal-rich one of 30 115 stars with Fe/H >−1.0. The photometric Sgr sample also allows us to assemble the largest sample of 1150 very metal-poor Sgr candidates (Fe/H <−2.0). By investigating and fitting the spatial properties of the metal-rich and metal-poor population, we find a negative metallicity gradient which extends up to 12 degrees from the Sgr centre (or ∼5.5 kpc at the distance of Sgr), the limit of our footprint. We conclude that the relative number of metal-poor stars increases in the outer areas of the galaxy, while the central region is dominated by metal-rich stars. These findings suggest an outside-in formation process and are an indication of the extended formation history of Sgr, which has been affected by the tidal interaction between Sgr and the Milky Way.
PDF
