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- Bouffet-Halle, Alix, et al.
(författare)
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Characterisation and cross-amplification of sex-specific genetic markers in Australasian Egerniinae lizards and their implications for understanding the evolution of sex determination and social complexity
- 2022
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Ingår i: Australian Journal of Zoology. - 0004-959X. ; 69:2, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Sex is a pervasive factor that underpins functional phenotypic variation across a range of traits. Although sex can usually be distinguished morphologically, in some species this is not possible. The development of genetic markers for sex identification is, thus, key if we are to incorporate sex into an understanding of ecological or evolutionary process. Here we develop genetic markers for the identification of sex within an iconic Australian lizard group, the Egernia group, which is notable for its complex social behaviour. We used restriction-site associated DNA sequencing to characterise sex-specific genetic sequences for a key member of the group, Liopholis whitii, and designed primers for four of these putative sex-specific sequences. These primers amplified across some, but not all, species of the group. Our results provided several important insights. They suggest conservatism of a XX/XY sex determination system within the group as well as sex-specific genomic regions that appear independent of the conserved genomic regions identified in other skink species. More broadly, the development of sex markers for the Egernia group opens up a range of potential research questions related to the role that sex plays in the mediation of social behaviour and, through this, the emergence and stability of social life.
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| 8. |
- Danielsson, D., et al.
(författare)
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Brachytherapy and osteoradionecrosis in patients with base of tongue cancer
- 2023
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 143:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Background: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. Aims: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. Material and Methods: We used data from the Swedish Head and Neck Cancer Register between 2008–2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. Results: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p =.012), whereas overall survival did not differ (HR = 0.95, p =.782). Conclusions and Significance: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.
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| 9. |
- Danielsson, Daniel, et al.
(författare)
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Influence of genetic background and oxidative stress response on risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer
- 2016
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 38:3, s. 387-393
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteoradionecrosis (ORN) of the mandible is a severe complication of head and neck radiotherapy (RT) treatment, where the impact of individual radiosensitivity has been a suggested explanation. Methods: A cohort of patients with stage II/III ORN was compared to matched controls. Blood was collected and irradiated in vitro to study the capacity to handle radiation-induced oxidative stress. Patients were also genotyped for 8 single-nucleotide polymorphisms (SNPs) in genes involved in the oxidative stress response. Results: A difference in 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) levels was found between the patient cohorts (p = 0.01). The SNP rs1695 in glutathione s-transferase p1 (GSTP1) was also found to be more frequent in the patients with ORN (p = .02). Multivariate analysis of the clinical and biological factors revealed concomitant brachytherapy plus the 2 biomarkers to be significant factors which influense risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer. Conclusion: The current study indicates that oxidative stress response contributes to individual radiosensitivity and healthy tissue damage caused by RT and may be predicted by biomarker analysis.
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- Danielsson, Daniel, et al.
(författare)
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Reduced oxidative stress response as a risk factor for normal tissue damage after radiotherapy: a study on mandibular osteoradionecrosis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe use of radiotherapy (RT) to treat cancer involves exposure of normal tissues. Factors that promote the development of normal tissue damage are poorly understood. An increased individual sensitivity to ionizing radiation is a likely candidate, but general phenotypes for late adverse effects of RT are difficult to define. We have found osteoradionecrosis (ORN) in the mandible as a well-defined model phenotype for an in-depth study of clinical and biological risk factors for developing late adverse effects to RT.MethodsA cohort of patients with stage 2/3 ORN following RT for head and neck cancer (HCN) was studied and compared to a closely matched control group. Blood samples from the patients were collected and irradiated in vitro and the capacity to handle radiation-induced oxidative stress was investigated by measuring the level of 8-oxo-dG in serum 60 min post exposure. The patients were also genotyped for eight SNPs in genes involved in the oxidative stress response and previously studied in the context of individual radiosensitivity. Results from these endpoints were analyzed in conjunction with clinical data using multivariate analysis and an ORN risk model was constructed. FindingsA significant difference in 8-oxo-dG levels was found between the patient cohorts, indicating a heterogeneous response to oxidative stress induced by the in vitro γ-radiation. The SNP rs1695 in GSTP1 was found to be significantly more frequent in the ORN+ compared to ORN- group. Multivariate analysis of the clinical and biological factors revealed concomitant brachytherapy plus the two biomarkers to be the most significant. Interpretation: The current study indicates that patient-related factors are a major source of individual variation in normal tissue response to RT. Two of the studied genetic biomarkers are strong factors in the described risk model of ORN.
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| 11. |
- Drobin, Kimi, et al.
(författare)
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Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depending on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.
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| 12. |
- Halle, Martin
(författare)
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Vascular inflammation : implications for microvascular reconstructive surgery after irradiation
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Better treatment has led to a rapidly increasing population of cancer survivors. A growing body of clinical evidence has shown that radiotherapy is associated with adverse effects on the cardiovascular system, such as myocardial infarction and stroke, depending on the previous treatment site. However, there is a paucity of experimental evidence linked to these clinical findings since the pathology, not evident until years after exposure, precludes adequate investigation through cell- and animal-experiments. We present a differential global gene expression strategy, by comparing irradiated with nonirradiated conduit arteries and veins, harvested simultaneously from the same patient during microvascular free tissue transfers for cancer reconstruction. We could thereby benefit from the true advantages of microarray technology, bypassing the common problem of inter-individual variability and furthermore exclude the influence of other risk factors and study the effect of irradiation only. Surgery at different time-points after radiotherapy did furthermore give us the opportunity to study temporal aspects, a key-factor for the understanding of delayed vascular disease. Temporal aspects of vascular alterations caused by irradiation are furthermore of importance for the timing of surgery in relation to radiotherapy, since there has been a debate about treatment order and timing between the two. In paper I, we could demonstrate that preoperative, compared to postoperative, radiotherapy was associated with microvascular occlusion after autologous free tissue transfers for head and neck reconstructions, and furthermore increased with the time elapsed from last radiotherapy session to surgery. In paper II, we utilized Affymetrix® microarray technology to unravel gene expression patterns in irradiated, compared to non-irradiated, arteries. Based on Gene Ontology Tree Machine®- analysis, target genes were selected and further confirmed with RT-PCR and immunohistochemistry. A major part of differentially expressed genes related to increased NF-kappaB activation, confined to cells within the arterial wall. The observed NF-kappaB activation, together with invading macrophages and T-cells, was evident even years after radiation exposure. Since microvascular occlusions after free tissue transfers are more likely to occur on the venous side, further analyses were performed in veins in paper III, utilizing a Taqman® tissue low density array, including 45 selected target-genes involved in inflammation and coagulation. An acute NF-kappaB activation was detected in irradiated veins, confined to the endothelium, whereas in contrast to arteries, no sustained NF-kappaB activity was observed more than 15 weeks from last radiotherapy session. Neither was any detectable invasion of inflammatory cells observed. Immunohistochemistry indicated decreased staining of endothelial nitric oxide synthase (eNOS) in irradiated veins, compared to controls, in further support for an endothelial dysfunction caused by irradiation. A sustained activation was detected for plasminogen activator-1 (PAI-1) in irradiated veins. In study IV, we detected a decreased eNOS activity in endothelial cells after incubation with the free fatty acids (FFAs) palmitic and oleic, but not linolenic, acid, whereas a triglyceride-rich fat emulsion increased the eNOS activity. This is interesting since FFAs are markedly elevated during surgery. With support from clinical and experimental data, we clearly advocate postoperative radiotherapy for microvascular reconstructive surgery, whenever possible for oncological reasons. Vascular inflammation may, together with increased PAI-1 gene expression observed in radiated veins, explain the increased risk for vascular complications when radiotherapy is administered prior to microvascular surgery. Moreover, the finding of a sustained NF-kappaB activation, together with presence of macrophages and T-cells, in irradiated arteries supports radiotherapy as an independent risk factor for cardiovascular disease and contributes to the search for therapeutic adjuncts to cope with the adverse effects of radiotherapy.
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- Mont, Lluís, et al.
(författare)
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Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death: Position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE.
- 2017
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Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 19:1, s. 139-163
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Tidskriftsartikel (refereegranskat)
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- Piepoli, Massimo F., et al.
(författare)
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Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology
- 2022
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:1, s. 143-168
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Tidskriftsartikel (refereegranskat)abstract
- The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.
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| 19. |
- Piepoli, Massimo F., et al.
(författare)
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Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology
- 2022
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Ingår i: European Journal of Preventive Cardiology. - : OXFORD UNIV PRESS. - 2047-4873 .- 2047-4881. ; 29:1, s. 275-300
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Tidskriftsartikel (refereegranskat)abstract
- The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.
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| 20. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 21. |
- Sjöström, Mats, et al.
(författare)
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Mandibular resection in patients with head and neck cancer : acute and long-term complications after reconstruction
- 2022
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Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis Group. - 0001-6489 .- 1651-2251. ; 142:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Background: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient.Aims/Objectives: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions.Material and Methods: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24).Results: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien–Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication.Conclusions: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien–Dindo grade IIIa–V events was significantly lower for patients treated with primary closure without grafts. Significance: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.
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| 22. |
- Sjöström, Mats, et al.
(författare)
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Mandibular resection in patients with head and neck cancer : acute and long-term complications after reconstruction
- 2022
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Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis Group. - 0001-6489 .- 1651-2251. ; 142:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Background The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient.Aims/Objectives This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions.Material and Methods We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24).Results Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien-Dindo >= IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication.Conclusions A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien-Dindo grade IIIa-V events was significantly lower for patients treated with primary closure without grafts Significance The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.
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