| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Rajkumar, T, et al.
(författare)
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Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies - International collaboration of epidemiological studies of cervical cancer
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 118:6, s. 1481-1495
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Tidskriftsartikel (refereegranskat)abstract
- Tobacco smoking has been classified as a cause of cervical cancer, but the effect of different patterns of smoking on risk is unclear. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 13,541 women with and 23,017 women without cervical carcinoma, from 23 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of carcinoma of the cervix in relation to tobacco smoking were calculated with stratification by study, age, sexual partners, age at first intercourse, oral contraceptive use and parity. Current smokers had a significantly increased risk of squamous cell carcinoma of the cervix compared to never smokers (RR = 1.60 (95% CI: 1.48-1.73), p < 0.001). There was increased risk for past smokers also, though to a lesser extent (RR = 1.12 (1.01-1.25)), and there was no clear trend with time since stopping smoking (p-trend = 0.6). There was no association between smoking and adenocarcinoma of the cervix (RR = 0.89 (0.74-1.06) and 0.89 (0.72-1.10) for current and past smokers respectively), and the differences between the RRs for smoking and squamous cell and adenocarcinoma were statistically significant (current smoking p < 0.001 and past smoking p = 0.01). In current smokers, the RR of squamous cell carcinoma increased with increasing number of cigarettes smoked per day and also with younger age at starting smoking (p < 0.001 for each trend), but not with duration of smoking (p-trend = 0.3). Eight of the studies had tested women for cervical HPV-DNA, and in analyses restricted to women who tested positive, there was a significantly increased risk in current compared to never smokers for squamous cell carcinoma (RR = 1.95 (1.43-2.65)), but not for adenocarcinoma (RR = 1.06 (0.14-7.96)). In summary, smokers are at an increased risk of squamous cell but not of adenocarcinoma of the cervix. The risk of squamous cell carcinoma increases in current smokers with the number of cigarettes smoked per day and with younger age at starting smoking.
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| 5. |
- Tajkumar, T, et al.
(författare)
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Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies
- 2009
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 18:4, s. 1060-1069
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Tidskriftsartikel (refereegranskat)abstract
- High-risk human papillomavirus (HPV) types cause most cervical carcinomas and are sexually transmitted. Sexual behavior therefore affects HPV exposure and its cancer sequelae. The International Collaboration of Epidemiological Studies of Cervical Cancer has combined data on lifetime number of sexual partners and age at first sexual intercourse from 21 studies, or groups of studies, including 10,773 women with invasive cervical carcinoma, 4,688 women with cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, and 29,164 women without cervical carcinoma. Relative risks for invasive cancer and CIN3 were estimated by conditional logistic regression. Risk of invasive cervical carcinoma increased with lifetime number of sexual partners (P for linear trend <0.001). The relative risk for > or =6 versus 1 partner, conditioned on age, study, and age at first intercourse, was 2.27 [95% confidence interval (95% CI), 1.98-2.61] and increased to 2.78 (95% CI, 2.22-3.47) after additional conditioning on reproductive factors. The risk of invasive cervical carcinoma increased with earlier age at first intercourse (P for linear trend <0.001). The relative risk for age at first intercourse < or =14 versus > or =25 years, conditioned on age, study, and lifetime number of sexual partners was 3.52 (95% CI, 3.04-4.08), which decreased to 2.05 (95% CI, 1.54-2.73) after additional conditioning on reproductive factors. CIN3/carcinoma in situ showed a similar association with lifetime number of sexual partners; however, the association with age at first intercourse was weaker than for invasive carcinoma. Results should be interpreted with caution given the strong correlation between sexual and reproductive factors and the limited information on HPV status.
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| 6. |
- Garnier, P., et al.
(författare)
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The detection of energetic electrons with the Cassini Langmuir probe at Saturn
- 2012
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117, s. A10202-
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Tidskriftsartikel (refereegranskat)abstract
- The Cassini Langmuir probe, part of the Radio and Plasma Wave Science (RPWS) instrument, has provided a wealth of information about the cold and dense plasma in the Saturnian system. The analysis of the ion side current (current for negative potentials) measured by the probe from 2005 to 2008 reveals also a strong sensitivity to energetic electrons (250-450 eV). These electrons impact the surface of the probe, and generate a detectable current of secondary electrons. A broad secondary electrons current region is inferred from the observations in the dipole L Shell range of similar to 6-10, with a peak full width at half maximum (FWHM) at L = 6.4-9.4 (near the Dione and Rhea magnetic dipole L Shell values). This magnetospheric flux tube region, which displays a large day/night asymmetry, is related to the similar structure in the energetic electron fluxes as the one measured by the onboard Electron Spectrometer (ELS) of the Cassini Plasma Spectrometer (CAPS). It corresponds spatially to both the outer electron radiation belt observed by the Magnetosphere Imaging Instrument (MIMI) at high energies and to the low-energy peak which has been observed since the Voyager era. Finally, a case study suggests that the mapping of the current measured by the Langmuir probe for negative potentials can allow to identify the plasmapause-like boundary recently identified at Saturn, and thus potentially identify the separation between the closed and open magnetic field lines regions.
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| 7. |
- Leo, P. J., et al.
(författare)
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Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study
- 2017
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately > 7.1% risk, and those in the highest 5% have approximately > 21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.
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| 8. |
- Lindh, Christina, et al.
(författare)
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Trabecular pattern in intraoral radiographs as a sign of osteoporosis : the OSTEODENT study
- 2006
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Konferensbidrag (refereegranskat)abstract
- Objectives: The aim of this study was to investigate if the trabecular pattern in intraoral radiographs, assessed by five observers, could serve as an indicator of osteoporosis. Methods: Six hundred and seventy one women (45 - 70 yrs) from four European centers were included in the study and examined with intraoral radiographs in the right upper and lower premolar region. The patients also underwent examinations with central dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. Five observers assessed the trabecular pattern in the intraoral radiographs into one of three classes: dense, heterogeneous or sparse trabecular pattern. The assessments were made with the aid of reference images and the observers underwent a calibration procedure before starting their assessments. The classifications were compared with the true diagnosis of osteoporosis measured using DXA. Results: The sensitivity and specificity for five observers’ assessments of the intraoral radiographs with sparse trabecular pattern as indicative of osteoporosis at either hip or spine are given in the table below. The values are calculated for patients diagnosed as having osteoporosis at any of the examined sites. Upper jaw Lower jaw Observer Sensitivity Specificity Sensitivity Specificity 1 22.2 90.2 13.2 94.5 2 22.6 94.8 15.8 94.2 3 26.5 91.6 28.1 86.7 4 36.3 87.4 30.2 82.4 5 35.3 93.7 39.1 95.6 If the cut-off included either “heterogeneous” or “sparse” trabeculation then a higher sensitivity was achieved (90.6 – 73.7) but a lower specificity (49.4 – 26.2). Conclusion: Assessment of sparse trabecular pattern on intraoral radiographs offered a combination of low sensitivity but high specificity for osteoporosis diagnosis. If it is assumed that high specificity is preferred for osteoporosis assessment by dentists, then this method may have potential for clinical use, although inter-observer variability may be a problem. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 9. |
- Nijs, Jo, et al.
(författare)
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Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria
- 2023
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 130:5, s. 611-621
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Tidskriftsartikel (refereegranskat)abstract
- Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.
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| 10. |
- Nwaru, Bright I, et al.
(författare)
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Furry Animal Allergen Component Sensitization and Clinical Outcomes in Adult Asthma and Rhinitis
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 7:4, s. 1230-1238.e4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sensitization to allergen components has been linked to asthma in children, but studies in adults are lacking.Objective: To study the relation of sensitization to furry animal allergen components to risk of asthma, rhinitis, and markers of asthma severity in adults.Methods: From the West Sweden Asthma Study, a random population-representative sample of adults aged 16 to 75 years, 2006 participants were clinically examined; 1872 were analyzed for serum IgE level to a mix of aeroallergens. Those with an IgE level of more than 0.35 kUA/L to cat, dog, or horse allergen components were analyzed for specific cat (Felis domesticus [Fel d 1, Fel d 2, and Fel d 4]), dog (Canis familiaris [Can f 1, Can f 2, Can f 3, and Can f 5]), and horse (Equus caballus [Equ c 1]) allergen components. We defined monosensitization, double sensitization, and polysensitization (>2 components) patterns and applied cluster analysis to derive distinct sensitization clusters.Results: Sensitization to each allergen component, lipocalins, each sensitization pattern, and each sensitization cluster (nonsensitized, Fel d 1–driven sensitized, and multisensitized clusters) was associated with substantial increased risk of asthma, rhinitis, concomitant asthma and rhinitis, and Asthma Control Test–controlled asthma. Fel d 1, Can f 1, Can f 2, Can f 3, polysensitization, and multisensitized cluster were further associated with increased fractional exhaled nitric oxide and eosinophil levels, but with lower PD20 methacoline (provocative dose of methacholine causing a 20% drop in FEV1) values. There was no association with asthma exacerbations, FEV1 predicted values, emergency visits or regular oral steroid use, and neutrophil levels.Conclusions: Sensitization to furry animal allergen components is an important predictor of asthma, rhinitis, and markers of asthma severity with increased blood eosinophils, fractional exhaled nitric oxide, and airway hyperreactivity.
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