| 1. |
- Goubet, AG, et al.
(författare)
-
Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis
- 2021
-
Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 28:12, s. 3297-3315
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
|
|
| 2. |
- Dent, E., et al.
(författare)
-
Physical Frailty : ICFSR International Clinical Practice Guidelines for Identification and Management
- 2019
-
Ingår i: The Journal of Nutrition, Health & Aging. - : SPRINGER FRANCE. - 1279-7707 .- 1760-4788. ; 23:9, s. 771-787
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults.Methods: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care.Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation).Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
|
|
| 3. |
- Algora, A., et al.
(författare)
-
Pronounced Shape Change Induced by Quasiparticle Alignment
- 2000
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813 .- 1089-490X. ; 61:3
-
Tidskriftsartikel (refereegranskat)abstract
- Mean lifetimes of high-spin states of Kr-74 have been determined using the Doppler-shift attenuation method. The high-spin states were studied using the Ca-40(Ca-40, alpha 2p) reaction at a beam energy of 160 MeV with the GASP gamma-ray spectrometer. The ground-state band and negative parity side band show the presence of three different configurations in terms of transitional quadrupole deformations. A dramatic shape change was found along the ground-state band after the S-band crossing. The deduced quadrupole deformation changes are well reproduced by cranked Woods-Saxon Strutinsky calculations.
|
|
| 4. |
- de, Angelis G, et al.
(författare)
-
T=0 pairing correlations and band crossing phenomena in N=Z nuclei
- 1998
-
Ingår i: NUCLEAR PHYSICS A. - : ELSEVIER SCIENCE BV. ; 630:1-2, s. 426C-433C
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The structure of the N=Z nuclei Zn-60, Ga-62, Ge-64 and Kr-72 has been investigated at GASP spectrometer through the S-32 + Ca-40 and Ca-40 + Ca-40 reactions at 140 and 160 MeV, respectively, using reaction channel selection with the ISIS Si-ball. The hig
|
|
| 5. |
- Schlegel, C, et al.
(författare)
-
K-isomers in very neutron-rich nuclei around mass 180
- 2000
-
Ingår i: Physica Scripta. Topical Issues. - 0281-1847. ; T88, s. 72-76
-
Tidskriftsartikel (refereegranskat)abstract
- gamma-spectroscopy methods have been used to search for microsecond isomers among the fragmentation products of a 1 GeV/nucleon Pb-208 beam. In particular the population of the known K-pi = 35/2(-) isomer in W-179 has been investigated and several new isomeric decays have been found for neutron rich nuclei in the A approximate to 180-200 mass region. The ground state band of the neutron rich N = 116 system of W-190 has been identified for the first time and we discuss its structure in comparison to neighboring systems.
|
|
| 6. |
- de, Angelis G, et al.
(författare)
-
Band crossing phenomena in N = Z nuclei - A probe to T = 0 pairing correlations?
- 1997
-
Ingår i: ACTA PHYSICA HUNGARICA NEW SERIES-HEAVY ION PHYSICS. - : AKADEMIAI KIADO. ; 6:1-4, s. 269-273
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The structure of the N = Z nuclei Zn-60, Ga-62, Ge-64 and Kr-72 has been investigated at GASP. Total Routhian surface (TRS) calculations have been performed for the N = 36, 38 and 40 Kr isotones. In the case of Kr-72 the four quasi-particle g(9/2) alignme
|
|
| 7. |
- Dent, E., et al.
(författare)
-
International Clinical Practice Guidelines for Sarcopenia (ICFSR) : Screening, Diagnosis and Management
- 2018
-
Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 22:10, s. 1148-1161
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR).Methods: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process.Recommendations: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
|
|
| 8. |
- Caamano, M, et al.
(författare)
-
Isomers in neutron-rich A approximate to 190 nuclides from Pb-208 fragmentation
- 2005
-
Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 23:2, s. 201-215
-
Tidskriftsartikel (refereegranskat)abstract
- Relativistic projectile fragmentation of Pb-208 has been used to produce isomers in neutron-rich, A approximate to 190 nuclides. A forward-focusing spectrometer provided ion-by-ion mass and charge identification. The detection of gamma-rays emitted by stopped ions has led to the assignment of isomers in Ta-188, W-190, Re-192, Re-193, Os-195, Ir-197, Ir-198, Pt-200, Pt-201, Pt-202 and Au-203, with half-lives ranging from approximately 10 ns to 1 ms. Tentative isomer information has been found also for Er-174, Er-175, Hf-185, Re-191, Re-194 and Ir-199. In most cases, time-correlated, singles gamma-ray events provided the first spectroscopic data on excited states for each nuclide. In Pt-200 and Pt-201. the assignments are supported by gamma-gamma coincidences. Isomeric ratios provide additional information, such as half-life and transition energy constraints in particular cases. The level structures of the platinum isotopes are discussed, and comparisons are made with isomer systematics.
|
|
| 9. |
- Carmona-Gutierrez, D, et al.
(författare)
-
The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 651-
-
Tidskriftsartikel (refereegranskat)abstract
- Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.
|
|
| 10. |
- Castoldi, F, et al.
(författare)
-
Autophagy-mediated metabolic effects of aspirin
- 2020
-
Ingår i: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 6:1, s. 129-
-
Tidskriftsartikel (refereegranskat)abstract
- Salicylate, the active derivative of aspirin (acetylsalicylate), recapitulates the mode of action of caloric restriction inasmuch as it stimulates autophagy through the inhibition of the acetyltransferase activity of EP300. Here, we directly compared the metabolic effects of aspirin medication with those elicited by 48 h fasting in mice, revealing convergent alterations in the plasma and the heart metabolome. Aspirin caused a transient reduction of general protein acetylation in blood leukocytes, accompanied by the induction of autophagy. However, these effects on global protein acetylation could not be attributed to the mere inhibition of EP300, as determined by epistatic experiments and exploration of the acetyl-proteome from salicylate-treated EP300-deficient cells. Aspirin reduced high-fat diet-induced obesity, diabetes, and hepatosteatosis. These aspirin effects were observed in autophagy-competent mice but not in two different models of genetic (Atg4b−/− or Bcln1+/−) autophagy-deficiency. Aspirin also improved tumor control by immunogenic chemotherapeutics, and this effect was lost in T cell-deficient mice, as well as upon knockdown of an essential autophagy gene (Atg5) in cancer cells. Hence, the health-improving effects of aspirin depend on autophagy.
|
|
