| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 3. |
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| 4. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 5. |
- Karlsson, Matilda, 1981-, et al.
(författare)
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Sprayed cultured autologous keratinocytes in the treatment of severe burns : a retrospective matched cohort study.
- 2020
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Ingår i: Annals of burns and fire disasters. - Palermo, Italy : Mediterranean Council for Burns and Fire Disasters. - 1592-9558. ; 33:2, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- The standard treatment of burns is early excision followed by autologous skin grafting. The closure of extensive deep burns poses a considerable challenge. Cultured autologous keratinocytes have been used since 1981 in an effort to improve healing. However, the time required to culture the cells and the lack of a dermal component limit the expectations of outcome. Our aim was to compare the duration of hospital stay between patients who were treated with autologous skin grafts and cultured autologous keratinocytes and those who were treated with autologous skin grafting without cultured autologous keratinocytes. In this retrospective study all patients treated with cultured autologous keratinocytes between 2012 and 2015 were matched by size and depth of burn with patients not treated with cultured autologous keratinocytes. Multivariable regression was used to analyse associations between duration of hospital stay and treatment adjusted for age, mortality, size and depth of the burn. Then, we investigated the possibility of differentiation of human bone marrow stem cell line to keratinocyte- like cells as a future direction. The regression analysis showed a coefficient of 17.36 (95% CI -17.69 to 52.40), p= 0.32, for hospital stay in the treatment group, compared with the matched group. Our results showed no difference in the duration of hospital stay between the two treatments. Autologous stem cells should be considered as a future modality of burn management, although further studies are needed.
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| 6. |
- Nugud, Ahmed, et al.
(författare)
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Biomaterials as a Vital Frontier for Stem Cell-Based Tissue Regeneration
- 2022
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media SA. - 2296-634X. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Biomaterials and tissue regeneration represent two fields of intense research and rapid advancement. Their combination allowed the utilization of the different characteristics of biomaterials to enhance the expansion of stem cells or their differentiation into various lineages. Furthermore, the use of biomaterials in tissue regeneration would help in the creation of larger tissue constructs that can allow for significant clinical application. Several studies investigated the role of one or more biomaterial on stem cell characteristics or their differentiation potential into a certain target. In order to achieve real advancement in the field of stem cell-based tissue regeneration, a careful analysis of the currently published information is critically needed. This review describes the fundamental description of biomaterials as well as their classification according to their source, bioactivity and different biological effects. The effect of different biomaterials on stem cell expansion and differentiation into the primarily studied lineages was further discussed. In conclusion, biomaterials should be considered as an essential component of stem cell differentiation strategies. An intense investigation is still required. Establishing a consortium of stem cell biologists and biomaterial developers would help in a systematic development of this field.
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| 7. |
- Pompermaier, Laura, et al.
(författare)
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Impact of COVID-19 on global burn care
- 2022
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Ingår i: Burns. - : Elsevier Science Ltd. - 0305-4179 .- 1879-1409. ; 48:6, s. 1301-1310
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worldwide, different strategies have been chosen to face the COVID-19-patient surge, often affecting access to health care for other patients. This observational study aimed to investigate whether the standard of burn care changed globally during the pan-demic, and whether country acute accent s income, geographical location, COVID-19-transmission pat-tern, and levels of specialization of the burn units affected reallocation of resources and access to burn care.Methods: The Burn Care Survey is a questionnaire developed to collect information on the capacity to provide burn care by burn units around the world, before and during the pandemic. The survey was distributed between September and October 2020. McNemar`s test analyzed differences between services provided before and during the pandemic, chi 2 or Fishers exact test differences between groups. Multivariable logistic regression analyzed the independent effect of different factors on keeping the burn units open during the pandemic.Results: The survey was completed by 234 burn units in 43 countries. During the pandemic, presence of burn surgeons did not change (p = 0.06), while that of anesthetists and dedi-cated nursing staff was reduced (< 0.01), and so did the capacity to manage patients in all age groups (p = 0.04). Use of telemedicine was implemented (p < 0.01), collaboration be-tween burn centers was not. Burn units in LMICs and LICs were more likely to be closed, after adjustment for other factors.Conclusions: During the pandemic, most burn units were open, although availability of standard resources diminished worldwide. The use of telemedicine increased, suggesting the implementation of new strategies to manage burns. Low income was independently associated with reduced access to burn care.(c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 8. |
- Abd El-Daim, Islam Ahmed Moustafa, et al.
(författare)
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Bacillus velezensis 5113 Induced Metabolic and Molecular Reprogramming during Abiotic Stress Tolerance in Wheat
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Abiotic stresses are main limiting factors for agricultural production around the world. Plant growth promoting rhizobacteria (PGPR) have been shown to improve abiotic stress tolerance in several plants. However, the molecular and physiological changes connected with PGPR priming of stress management are poorly understood. The present investigation aimed to explore major metabolic and molecular changes connected with the ability of Bacillus velezensis 5113 to mediate abiotic stress tolerance in wheat. Seedlings treated with Bacillus were exposed to heat, cold/freezing or drought stress. Bacillus improved wheat survival in all stress conditions. SPAD readings showed higher chlorophyll content in 5113-treated stressed seedlings. Metabolite profiling using NMR and ESI-MS provided evidences for metabolic reprograming in 5113-treated seedlings and showed that several common stress metabolites were significantly accumulated in stressed wheat. Two-dimensional gel electrophoresis of wheat leaves resolved more than 300 proteins of which several were differentially expressed between different treatments and that cold stress had a stronger impact on the protein pattern compared to heat and drought. Peptides maps or sequences were used for database searches which identified several homologs. The present study suggests that 5113 treatment provides systemic effects that involve metabolic and regulatory functions supporting both growth and stress management.
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| 9. |
- Abd El-Daim, Islam Ahmed Moustafa, et al.
(författare)
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Identifying potential molecular factors involved in Bacillus amyloliquefaciens 5113 mediated abiotic stress tolerance in wheat
- 2018
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Ingår i: Plant Biology. - : Wiley. - 1435-8603 .- 1438-8677. ; 20, s. 271-279
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Tidskriftsartikel (refereegranskat)abstract
- Abiotic stressors are main limiting factors for agricultural production around the world. Plant growth-promoting bacteria have been successfully used to improve abiotic stress tolerance in several crops including wheat. However, the molecular changes involved in the improvement of stress management are poorly understood. The present investigation addressed some molecular factors involved in bacterially induced plant abiotic stress responses by identifying differentially expressed genes in wheat (Triticum aestivum) seedlings treated with the beneficial bacterium Bacillus amyloliquefaciens subsp. plantarum UCMB5113 prior to challenge with abiotic stress conditions such as heat, cold or drought. cDNA-AFLP analysis revealed differential expression of more than 200 transcript-derived fragments (TDFs) in wheat leaves. Expression of selected TDFs was confirmed using RT-PCR. DNA sequencing of 31 differentially expressed TDFs revealed significant homology with both known and unknown genes in database searches. Virus-induced gene silencing of two abscisic acid-related TDFs showed different effects upon heat and drought stress. We conclude that treatment with B.amyloliquefaciens 5113 caused molecular modifications in wheat in order to induce tolerance against heat, cold and drought stress. Bacillus treatment provides systemic effects that involve metabolic and regulatory functions supporting both growth and stress management.
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| 10. |
- Abd El-Daim, Islam Ahmed Moustafa, et al.
(författare)
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Impact of bacterial priming on some stress tolerance mechanisms and growth of cold stressed wheat seedlings
- 2013
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Ingår i: International Journal of Plant Biology. - : MDPI AG. - 2037-0156 .- 2037-0164. ; 4, s. 29-33
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Tidskriftsartikel (refereegranskat)abstract
- The potential to enhance growth of cold stressed wheat by seed treatment (priming) with the beneficial bacteria Bacillus amyloliquefaciens 5113 and Azospirillum brasilense NO40 were tested. Results showed an improved ability of bacteria-treated seedlings to survive at −5°C up to 12 h. Cold stress increased transcript levels of three stress marker genes and increased activity for the ascorbate-glutathione redox enzymes. However, primed and stressed seedlings generally showed smaller effects on the stress markers correlating with better growth and improved stress tolerance. Bacterial priming to improve crop plant performance at low temperature seems a useful strategy to explore further.
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| 11. |
- Abd El-Daim, Islam Ahmed Moustafa, et al.
(författare)
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Improved heat stress tolerance of wheat seedlings by bacterial seed treatment
- 2014
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Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 379, s. 337-350
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate if rhizosphere bacteria can improve heat tolerance of wheat. MethodsWheat (Triticum aestivum) seeds of the cultivars Olivin and Sids1 were treated with Bacillus amyloliquefaciens UCMB5113 or Azospirillum brasilense NO40 and young seedlings tested for management of short term heat stress. ResultsBacterial treatment improved heat stress management of wheat. Olivin showed higher heat tolerance than Sids1 both with non-inoculated and inoculated seeds. Heat increased transcript levels of several stress related genes in the leaves, while expression was lower in inoculated plants but elevated compared with the control. Enzymes of the ascorbate-glutathione redox cycle were activated in leaves after heat challenge but showed a lower response in inoculated plants. Metabolite profiling distinguished different treatments dependent on analysis technique with respect to primary and secondary metabolites. Analysis of some plant stress regulatory genes showed that bacterial treatment increased transcript levels while effects of heat treatment varied. Conclusions: The improvement of heat tolerance by bacteria seems associated with reduced generation of reactive oxygen species (and consequently less cell damage), small changes in the metabolome while preactivation of certain heat shock transcription factors seems important. Seed inoculation with beneficial bacteria seems a promising strategy to improve heat tolerance of wheat.
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| 12. |
- Abd El-Daim, Islam Ahmed Moustafa, et al.
(författare)
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Paenibacillus polymyxa A26 Sfp-type PPTase inactivation limits bacterial antagonism against Fusarium graminearum but not of F. culmorum in kernel assay
- 2015
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fusarium graminearum and F. culmorum are the causing agents of a destructive disease known as Fusarium head blight (FHB). FHB is a re-emerging disease in small grain cereals which impairs both the grain yield and the quality. Most serious consequence is the contamination of grain with Fusarium mycotoxins that are severe threat to humans and animals. Biological control has been suggested as one of the integrated management strategies to control FHB. Paenibacillus polymyxa is considered as a promising biocontrol agent due to its unique antibiotic spectrum. P. polymyxa A26 is an efficient antagonistic agent against Fusarium spp. In order to optimize strain A26 production, formulation and application strategies traits important for its compatibility need to be revealed. Here we developed a toolbox, comprising of dual culture plate assays and wheat kernel assays, including simultaneous monitoring of FHB causing pathogens, A26, and mycotoxin production. Using this system we show that, besides generally known lipopeptide antibiotic production by P. polymyxa, biofilm formation ability may play a crucial role in the case of stain A26 F. culmorum antagonism. Application of the system for effective strain selection and maintenance is discussed.
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| 13. |
- Abd El-Daim, Islam Ahmed Moustafa
(författare)
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Use of rhizobacteria for the alleviation of plant stress
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Plant growth promoting rhizobacteria are beneficial microbes able to induce plant stress tolerance and antagonise plant pathogens. The present study showed that wheat seedlings pre-treated with Bacillus thuringiensis AZP2 had better tolerance to severe drought stress and showed 78% greater plant biomass and five-fold higher survivorship compared to wheat seedlings not treated with the bacterium. The effect of B. thuringiensis AZP2 also resulted in improved net assimilation and reduced emission of stress volatiles. The study investigated the effect of the inactivation of sfp-type phosphopantetheinyl transferase in plant growth promoting bacterium Paenibacillus polymyxa A26. The inactivation of the sfp gene resulted in loss of NRP/PK production such fusaricidins and polymyxins. In contrast to the former Bacillus spp. model the mutant strain compared to wild type showed greatly enhanced biofilm formation ability. Its biofilm promotion is directly mediated by NRP/PK, as exogenous addition of the wild type metabolite extracts restores its biofilm formation level. Further, increased biofilm formation was connected with enhanced ability of the sfp inactivated strain to remarkably protect wheat seedlings by improving its survival and biomass under severe drought stress conditions compared to wild type. Fusarium graminearum and F. culmorum are the causing agents of a destructive disease known as Fusarium head blight (FHB). The disease is the leading cause of contamination of grain with Fusarium mycotoxins that are severe threat to humans and animals. Biological control has been suggested as one of the integrated management strategies to control FHB causing agents. The present study showed that P. polymyxa A26 is a potent antagonistic agent against F. graminearum and F. culmorum. In order to optimize strain A26 production, formulation and application strategies traits important for its compatibility need to be revealed. Hence, a toolbox comprising of dual culture plate assays and wheat kernel assays including simultaneous monitoring of the FHB causing pathogens, A26 and mycotoxins produced was developed in the present study. Using this system results showed that, besides the involvement of lipopeptide antibiotic production by P. polymyxa in the antagonism process, biofilm formation ability may play a crucial role in the case of A26 F. culmorum antagonism.
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| 14. |
- Aboelnaga, Ahmed, et al.
(författare)
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Microbial cellulose dressing compared with silver sulphadiazine for the treatment of partial thickness burns: A prospective, randomised, clinical trial
- 2018
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Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 44:8, s. 1982-1988
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe current treatment for partial thickness burns at the trial site is silver sulphadiazine, as it minimises bacterial colonisation of wounds. Its deleterious effect on wound healing, together with the need for repeated, often painful, procedures, has brought about the search for a better treatment. Microbial cellulose has shown promising results that avoid these disadvantages. The aim of this study was therefore to compare microbial cellulose with silver sulphadiazine as a dressing for partial thickness burns.MethodAll patients who presented with partial thickness (superficial and deep dermal) burns from October 2014 to October 2016 were screened for this randomised clinical trial. Twenty patients were included in each group: the cellulose group was treated with microbial cellulose sheets and the control group with silver sulphadiazine cream 10 mg/g. The wound was evaluated every third day. Pain was assessed using the Face, Legs, Activity, Cry, Consolability (FLACC) scale during and after each procedure. Other variables recorded were age, sex, percentage total body surface area burned (TBSA%), clinical signs of infection, time for epithelialisation and hospital stay. Linear multivariable regression was used to analyse the significance of differences between the treatment groups by adjusting for the size and depth of the burn, and the patient’s age.ResultsMedian TBSA% was 9% (IQR 5.5–12.5). The median number of dressing changes was 1 (IQR 1–2) in the cellulose group, which was lower than that in the control group (median 9.5, IQR 6–16) (p < 0.001). Multivariable regression analysis showed that the group treated with microbial cellulose spent 6.3 (95% CI 0.2–12.5) fewer days in hospital (p = 0.04), had a mean score that was 3.4 (95% CI 2.5–4.3) points lower during wound care (p < 0.001), and 2.2 (95% CI 1.6–2.7) afterwards (p < 0.001). Epithelialisation was quicker, but not significantly so.ConclusionThese results suggest that the microbial cellulose dressing is a better first choice for treatment of partial thickness burns than silver sulphadiazine cream. Fewer dressings of the wound were done and, combined with the low pain scores, this is good for both the patients and the health care system. The differences in randomisation of the area of burns is, however, a concern that needs to be included in the interpretation of the results.
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| 15. |
- Arumugam, Ashokan, et al.
(författare)
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Sedentary and physical activity time differs between self-reported ATLS-2 physical activity questionnaire and accelerometer measurements in adolescents and young adults in the United Arab Emirates
- 2023
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most young adults and adolescents in the United Arab Emirates (UAE) do not meet the established internationally recommended physical activity levels per day. The Arab Teen Lifestyle Study (ATLS) physical activity questionnaire has been recommended for measuring self-reported physical activity of Arab adolescents and young adults (aged 14 years to mid-twenties). The first version of the ATLS has been validated with accelerometers and pedometers (r ≤ 0.30). The revised version of the questionnaire (ATLS-2, 2021) needs further validation. The aim of this study was to validate the self-reported subjective sedentary and physical activity time of the ATLS-2 (revised version) physical activity questionnaire with that of Fibion accelerometer-measured data.METHODS: In this cross-sectional study, 131 healthy adolescents and young adults (aged 20.47 ± 2.16 [mean ± SD] years (range 14-25 years), body mass index 23.09 ± 4.45 (kg/m2) completed the ATLS-2 and wore the Fibion accelerometer for a maximum of 7 days. Participants (n = 131; 81% non-UAE Arabs (n = 106), 13% Asians (n = 17) and 6% Emiratis (n = 8)) with valid ATLS-2 data without missing scores and Fibion data of minimum 10 h/day for at least 3 weekdays and 1 weekend day were analyzed. Concurrent validity between the two methods was assessed by the Spearman rho correlation and Bland-Altman plots.RESULTS: The questionnaire underestimated sedentary and physical activity time compared to the accelerometer data. Only negligible to weak correlations (r ≤ 0.12; p > 0.05) were found for sitting, walking, cycling, moderate intensity activity, high intensity activity and total activity time. In addition, a proportional/systematic bias was evident in the plots for all but two (walking and moderate intensity activity time) of the outcome measures of interest.CONCLUSIONS: Overall, self-reported ATLS-2 sedentary and physical activity time had low correlation and agreement with objective Fibion accelerometer measurements in adolescents and young adults in the UAE. Therefore, sedentary and physical activity assessment for these groups should not be limited to self-reported measures.
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| 16. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 17. |
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| 18. |
- Dogan, Sinan, et al.
(författare)
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A prospective dual-centre intra-individual controlled study for the treatment of burns comparing dermis graft with split-thickness skin auto-graft
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- To investigate if donor and recipient site morbidity (healing time and cosmesis) could be reduced by a novel, modified split-thickness skin grafting (STSG) technique using a dermal component in the STSG procedure (DG). The STSG technique has been used for 150 years in surgery with limited improvements. Its drawbacks are well known and relate to donor site morbidity and recipient site cosmetic shortcomings (especially mesh patterns, wound contracture, and scarring). The Dermal graft technique (DG) has emerged as an interesting alternative, which reduces donor site morbidity, increases graft yield, and has the potential to avoid the mesh procedure in the STSG procedure due to its elastic properties. A prospective, dual-centre, intra-individual controlled comparison study. Twenty-one patients received both an unmeshed dermis graft and a regular 1:1.5 meshed STSG. Aesthetic and scar assessments were done using The Patient and Observer Scar Assessment Scale (POSAS) and a Cutometer Dual MPA 580 on both donor and recipient sites. These were also examined histologically for remodelling and scar formation. Dermal graft donor sites and the STSG donor sites healed in 8 and 14 days, respectively (p < 0.005). Patient-reported POSAS showed better values for colour for all three measurements, i.e., 3, 6, and 12 months, and the observers rated both vascularity and pigmentation better on these occasions (p < 0.01). At the recipient site, (n = 21) the mesh patterns were avoided as the DG covered the donor site due to its elastic properties and rendered the meshing procedure unnecessary. Scar formation was seen at the dermal donor and recipient sites after 6 months as in the standard scar healing process. The dermis graft technique, besides potentially rendering a larger graft yield, reduced donor site morbidity, as it healed faster than the standard STSG. Due to its elastic properties, the DG procedure eliminated the meshing requirement (when compared to a 1:1.5 meshed STSG). This promising outcome presented for the DG technique needs to be further explored, especially regarding the elasticity of the dermal graft and its ability to reduce mesh patterns. Trial registration: ClinicalTrials.gov Identifier (NCT05189743) 12/01/2022. © 2022, The Author(s).
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| 19. |
- El-Serafi, Ahmed T., et al.
(författare)
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A Systematic Review of Keratinocyte Secretions : A Regenerative Perspective
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:14
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Forskningsöversikt (refereegranskat)abstract
- Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in the skin, are difficult to obtain without the creation of another wound. Stem cell differentiation towards keratinocytes is a challenging process, and it is difficult to reproduce in chemically defined media. Nevertheless, a co-culture of keratinocytes with stem cells usually achieves efficient differentiation. This systematic review aims to identify the secretions of normal human keratinocytes reported in the literature and correlate them with the differentiation process. An online search revealed 338 references, of which 100 met the selection criteria. A total of 80 different keratinocyte secretions were reported, which can be grouped mainly into cytokines, growth factors, and antimicrobial peptides. The growth-factor group mostly affects stem cell differentiation into keratinocytes, especially epidermal growth factor and members of the transforming growth factor family. Nevertheless, the reported secretions reflected the nature of the involved studies, as most of them focused on keratinocyte interaction with inflammation. This review highlights the secretory function of keratinocytes, as well as the need for intense investigation to characterize these secretions and evaluate their regenerative capacities.
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| 20. |
- El-Serafi, Ahmed T., et al.
(författare)
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Skin regeneration in three dimensions, current status, challenges and opportunities
- 2017
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Ingår i: Differentiation. - : Elsevier. - 0301-4681 .- 1432-0436. ; 96, s. 26-29
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Forskningsöversikt (refereegranskat)abstract
- Skin regeneration is a life-saving need for many patients, whom list is stretched from burn victims to motor-car accidents. Spraying cells, either keratinocytes or stem cells, were associated with variable results and, in many cases, unfavorable outcomes. As the spatial configuration of the skin is distinctive, many trials investigated the bio-printing or the construction of three dimensional skin models where different layers of the skin were preserved. Although some of these models showed the histological configuration of the skin, their acceptance by the wound was questionable as a consequence of delayed vascularization. In this mini-review, different models for three dimensional regeneration of the skin will be discussed with their main points of strength and challenges as well as their possible opportunities.
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| 21. |
- Ellabban, Mohamed A., et al.
(författare)
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Virtual planning of the anterolateral thigh free flap for heel reconstruction
- 2022
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Ingår i: Microsurgery. - : WILEY. - 0738-1085 .- 1098-2752. ; 42:5, s. 460-469
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Tidskriftsartikel (refereegranskat)abstract
- Purpose three dimensional (3-D) virtual planning is an example of computer assisted surgery that improved management of composite tissue defects. However, converting the 3-D construct into two dimensional format is challenging. The purpose of this study was to assess 3-D virtual planning of complex heel defects for better optimized reconstruction. Patients and methods a prospective analysis of 10 patients [9 male and 1 female; mean age = 27.9 years] with post-traumatic heel defects was performed. Heel defects comprised types II (three patients) or III (seven patients) according to Hidalgo and Shaw and were managed using anterolateral thigh (ALT) free flap adopting 3-D virtual planning of the actual defect which was converted into a silicone two dimensional mold. The mean definitive size of the defects was 63.4 cm(3). Functional, aesthetic, and sensory evaluations of both donor and recipient sites were performed 1 year after surgery. Results Six patients received thinned ALT (mean size = 139 cm(3)) while four patients received musculofasciocutaneous ALT flap (mean size = 199 cm(3)). One flap exhibited partial skin flap necrosis. Another flap was salvaged after re-exploration secondary to venous congestion. The mean follow-up was 20.2 months. The Maryland foot score showed 4 excellent, 5 good, and 1 fair cases. The mean American Orthopedic Foot and Ankle hind foot scoring was 76.3 (range: 69-86). All patients regained their walking capability. Conclusions 3-D virtual planning of complex heel defects facilitates covering non-elliptical defects while harvesting a conventional elliptical flap with providing satisfactory functional outcomes and near-normal contour, volume, and sensibility.
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| 22. |
- Hamid Muhammed, Hamed, 1967-, et al.
(författare)
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Skin Cancer Detection Using Temperature Variation Analysis
- 2013
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Ingår i: Engineering. - 1947-394X. ; 5:10B
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Tidskriftsartikel (refereegranskat)abstract
- In the medical field, new technologies are incorporated for the sole purpose of enhancing the quality of life for the patients and even for the normal healthy people. Infrared technology is one of the technologies that have some applications in both the medical and biological fields. In this work, the thermal infrared (IR) measurement is used to investigate the potential of skin cancer detection. IR enjoys non-invasive and non-contact advantages as well as favorable cost, apparently. It is also very well developed regarding the technological and methodological aspects. IR per se is an electro-metric radiation that all objects emit when their temperature is above the absolute zero. And the human body is not different in this regard. The IR range extends, ideally, to cover wavelengths from 800 nanometer to few hundred micrometer. Cancer, in modern life, has grown tangibly due to many factors, such as life expectancies increase, personal habits and ultraviolet radiation exposures among others. Moreover, the significant enhancement of technologies has helped identifying more types of cancers than before. The sole purpose of this work is to investigate further IR technology methods and applications not yet matured in skin cancer detection to enhance the detection ability with higher safety level.
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| 23. |
- Hegazy, Mohamed-Elamir F., et al.
(författare)
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Cytotoxic Cembranoids from the Red Sea Soft Coral Sarcophyton glaucum
- 2011
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Ingår i: Natural Product Communications. - 1934-578X .- 1555-9475. ; 6:12, s. 1809-1812
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Tidskriftsartikel (refereegranskat)abstract
- One new cembrane diterpene, 2R,7R,8R-dihydroxydeepoxysarcophine (1), together with three known compounds, 7 alpha,8 beta-dihydroxydecpoxysarcophine (2), 7 beta-acetoxy-8 alpha-hydroxydeepoxysarcophine (3), and sarcophine (4), have been isolated from the Red Sea soft coral Sarcophyton glaucum. Their structures were determined using 1D and 2D NMR spectroscopy. 7 beta-Acetoxy-8 alpha-hydroxydeepoxysarcophine (3) exhibits cytotoxic activity against HepG2, HCT-116, and HeLa cells with IC(50) values of 3.6, 2.3, and 6.7 mu g/mL, respectively.
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| 24. |
- Lagerwall, Cathrine, et al.
(författare)
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Xeno-free workflow exhibits comparable efficiency and quality of keratinocytes isolated from human skin biopsies
- 2021
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Ingår i: Regenerative Therapy. - : Elsevier. - 2352-3204. ; 18, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Regenerative solutions of the skin represent a hope for burn victims with extensive skin loss and chronic wound patients. The development of xeno-free workflow is crucial for clinical application in compliance with the directives of the European Medicines Agency. This study aimed at evaluating the outcome of the xeno-free isolation workflow of keratinocytes from human skin biopsy. Methods Skin biopsies were obtained from volunteers. The epidermis was digested with TrypLEâ„¢ Select, which was deactivated by dilution or with trypsin, deactivated by media with fetal bovine serum. Freshly isolated cells were compared for total cell number, viability, activity of caspase 3, gene expression and the presence of the keratinocyte surface markers cytokeratin 14. The cells were cultured in xeno-free conditions for one week and characterized regarding the number and viability as well as the metalloproteinase secretion. Results The number of obtained cells was similar in both workflows. The cell viability was less in the TrypLE group, with slight reduction of the cell surface marker cytokeratin 14. Caspase 3 activity was comparable as well as the gene expression of the apoptotic markers BAX, BCL2 and SLUG, as well as the keratinocyte markers cytokeratin 14, stratifin and filaggrin. Upon culture, the number of keratinocytes, their viability and secretion of matrix metalloproteinases 1 and 10 were equal in both groups. Conclusion This study reports the possibility of isolating functioning and viable keratinocytes through a xeno-free workflow for clinical application.
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| 25. |
- Meijer, Johan, et al.
(författare)
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Control of Drought Stress in Wheat Using Plant-Growth-Promoting Bacteria
- 2013
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Ingår i: Journal of Plant Growth Regulation. - : Springer Science and Business Media LLC. - 0721-7595 .- 1435-8107. ; 32, s. 122-130
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Tidskriftsartikel (refereegranskat)abstract
- Abiotic stress conditions are the main limiting factors for crop cultivation around the world. In the present study we aimed to improve wheat growth under drought stress conditions through priming with beneficial bacteria considered as plant-growth promoting bacteria (PGPB). Two bacterial strains, Bacillus amyloliquefaciens 5113 and Azospirillum brasilense NO40, were used to prime the wheat cv. Sids1. To generate drought stress for 12-day-old seedlings, water was withheld for 4, 5, or 7 days while growth and survival were recorded. Furthermore, several stress markers were examined by molecular and biochemical assays to study the role of priming on different stress tolerance mechanisms. Priming significantly alleviated the deleterious effect of drought stress on wheat. Drought resulted in the upregulation of some stress-related genes (APX1, SAMS1, and HSP17.8) in the leaves and increased activity of enzymes involved in the plant ascorbate-glutathione redox cycle. Bacteria-treated plants showed attenuated transcript levels suggesting improved homeostatic mechanisms due to priming. The present study reports on the ability of certain PGPB to attenuate several stress consequences in plants which strongly supports the potential of such an approach to control drought stress in wheat.
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| 26. |
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| 27. |
- Partiyan, Arthur, et al.
(författare)
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Fracture resistance of three-unit zirconia fixed partial denture with modified framework
- 2017
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Ingår i: Odontology. - : Springer. - 1618-1247 .- 1618-1255. ; 105:1, s. 62-67
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Tidskriftsartikel (refereegranskat)abstract
- Obtaining ideal prosthetic framework design is at times hindered by anatomical limitations in the posterior region that might increase the risk for zirconia restoration fracture. Modification such as increasing the bulk thickness especially in the connector region could result in strengthening the zirconia framework. Three-unit zirconia fixed partial dentures replacing mandibular molars were fabricated using the following two techniques: CAD/CAM technology and manual copy milling. Modified framework with unveneered full thickness connectors were designed and fabricated with the aforementioned methods. Conventional frameworks (0.5 mm thick with rounded 3 mm connectors) served as control (N = 20). After cementation on epoxy dies, the frameworks were loaded to fracture in a universal testing machine. Fractured surfaces were prepared for examination using scanning electron microscopy. Statistical analysis revealed significant differences in fracture resistance between conventional and modified framework design for both fabrication techniques tested. SEM examination indicated that critical crack originated at the tensile surface of the connectors for conventional frameworks. The critical crack for modified frameworks occurred on the axial wall of the abutments. The modification of the zirconia framework design presented significant improvement of the fracture resistance compared to the conventional design.
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| 28. |
- Rayyan, Mohammad M., et al.
(författare)
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Comparison of interim restorations fabricated by CAD/CAM with those fabricated manually
- 2015
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Ingår i: The Journal of prosthetic dentistry (Print). - : Mosby. - 0022-3913 .- 1097-6841. ; 114:3, s. 414-419
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Tidskriftsartikel (refereegranskat)abstract
- Statement of problem. Interim restorations represent an essential treatment step; however, the optimal resin material for long-term interim restorations requires investigation. Purpose. The purpose of this in vitro study was to compare the color stability, water sorption, wear resistance, surface hardness, fracture resistance, and microleakage of computer-aided design/computer-aided manufacturing-(CAD/CAM) fabricated interim restorations with those of manually fabricated interim restorations. Material and methods. Epoxy replicas were made from a prepared maxillary first premolar. On the replicas, interim crowns were fabricated and divided into the following groups: CAD/CAM poly(methyl methacrylate) (PMMA) blocks (CC), autopolymerizing temporary resin (AP), automix temporary resin (AM), and thermoplastic resin (TP). After cementation, all specimens were subjected to thermocycling and dynamic fatigue. The CIE Laboratory color coordinates were then recorded before and after immersion in coffee, tea, carbonated cola, and red wine. Water sorption was evaluated by using an immersion technique. Wear resistance was measured in a surface abrasion device. Vickers microhardness was measured on polished specimens. Fracture resistance was evaluated by axial loading with a universal testing machine. Marginal dye penetration was evaluated by sectioning the interim restorations after immersion in methylene blue (alpha=.05). Results. Colorimetric analysis revealed a large degree of color alteration (SE) in the manually fabricated interim restorations: AP = Delta E of 6.7 +/- 2); AM = Delta E of 7.1 +/- 1.5), and TP = Delta E of =5.4 +/- 3.1. The CC group demonstrated color stability (Delta E=2.1 +/- 0.2). CAD/CAM interim restorations demonstrated significantly lower water sorption, higher wear resistance, higher surface hardness, and significantly higher fracture resistance (1 289 +/- 56N) compared with manually fabricated interim restorations (AP=996 +/- 45, AM=899 +/- 37, and TP=1179 +/- 41). The stereomicroscopic examination of sectioned specimens demonstrated the absence of dye penetration in all tested specimens. Conclusions. CAD/CAM interim crowns presented stable physical and mechanical properties and may be used for long-term interim restorations.
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| 29. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 30. |
- Shahin, Hady, et al.
(författare)
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Human serum albumin as a clinically accepted cell carrier solution for skin regenerative application
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The rules governing Medicinal Products in the European Union necessitates the production of cell-based therapy in good manufacturing practice facilities. The produced cells may need several hours in transportation to reach the application sites. In this study, we investigated four candidate solutions for transporting human keratinocytes. The solutions are (1) normal saline, (2) saline with 2.5% human serum albumin (Saline + HSA), (3) chemically defined, xeno-free keratinocyte media and (4) keratinocyte media with pituitary bovine extract (PBE-media). One million keratinocytes from three donors were suspended in each solution and kept at 4 °C for up to 24 h. Cells kept in Saline + HSA showed higher viability after 1, 3 and 24 h. Then, equal number of viable cells were seeded on collagenous matrix and cultured for 48 h. The adhesion and colonization were higher in the cells kept in PBE-media, while the keratinocyte surface marker, cytokeratin 14, was present in all studied groups. These results confirmed the suitability of Saline + HSA as a cell transportation solution for clinical use, which will be the choice for the planned clinical trial. Keratinocyte PBE-media can be an alternative for cells transported for research purpose, if the same media type is going to be used in the following experiments.
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| 31. |
- Shahin, Hady, 1989-
(författare)
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Keratinocytes and Adipose-derived mesenchymal stem cells : The heir and the spare to regenerative cellular therapies for difficult-to-heal skin wounds
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cell-based therapy is considered as Advanced Therapy Medicinal Product, (ATMP), which had increasingly stricter regulations in the last decade. The cells must be produced according to the ‘Guidelines on Good Manufacturing Practice (GMP) specific to Advanced Therapy Medicinal Products’, adopted by the European Medicines Agency (EMA). A fully compliant autologous keratinocyte-based ATMP certified for clinical use remains an unmet challenge in Europe. This necessitates the development of a comprehensive bio-production workflow to tackle key technical bottlenecks along this procedure. On the other hand, adipose-derived mesenchymal stem cells (AD-MSCs) hold promise as an effective alternative to primary keratinocytes in treating difficult-to-heal wounds, particularly for patients with extensive skin wounds. The overall aim of this thesis is to provide a bio-production workflow addressing the challenges associated with developing an autologous keratinocyte-based ATMP. Additionally, the thesis aims to elucidate the molecular and functional mechanisms that modulate the wound healing capabilities of keratinocytes and AD-MSCs. In papers I-III the bio-production procedure for an autologous keratinocyte-based ATMP to treat difficult-to-heal wounds was divided into 3 main stages; keratinocytes extraction, expansion, and transportation. Paper I validated the use of an animal-origin-free enzymatic workflow for the extraction of keratinocytes from the epidermis, compared to the classical workflow containing animal-derived products. Both workflows proved comparable in efficiency in terms of the final cell yield from skin samples, in addition to the purity and functionality of the keratinocytes following cultivation. This report confirms the feasibility of an entirely xeno-free workflow for acquiring GMP-compliant epidermal cells suitable for clinical application without altering key features of keratinocytes. Paper II evaluates an expansion approach for keratinocytes on three culture substrates (1) glass (2) conventional polystyrene (plastic) and (3) animal-derived collagen I ECM matrix. Keratinocytes cultured on glass showed better colonization and survival during the first 3 days of culture. Further molecular characterization revealed evidence of accelerated epidermal differentiation in keratinocytes cultured on glass. Henceforth, functional characterization revealed that glass enhanced the temporal angiogenic and migratory capabilities of keratinocytes. Our findings provided evidence that glass can be a promising substrate capable of supporting keratinocyte cultures, with enhanced wound repair characteristics favourable for transplantation applications. In paper III, we evaluated four candidate solutions for transporting keratinocytes in suspension at 4°C for 24h, namely (1) normal saline; (2) saline with 2.5% human serum albumin; (3) chemically defined, xenofree keratinocyte media; and (4) keratinocyte media with bovine pituitary extract. The tested conditions showed that 2.5% HSA preserved keratinocyte viability, colonization as well as phenotype. This study helped the research team to implement the use of human serum albumin as transportation solution for the proposed keratinocyte-ATMP approach. In paper IV, a direct co-culture model for human keratinocytes and AD-MSCs was proposed to investigate the ability of keratinocytes to enhance AD-MSCs’ differentiation toward the epidermal lineage. Furthermore, miRNA and protein content of human keratinocytes and AD-MSCs were analysed and bioinformatically analysed to identify possible regulations between differentially expressed miRNAs and proteins. This study predicted two potential miRNA-mediated gene regulations with strong implications in AD-MSCs-to-epidermal differentiation; the first was centred on epidermal growth factor (EGF) through miR-485-5p, miR-6765-5p and miR-4459. The second was the regulation of interleukin 1 alpha (IL-1α) by four isomers of miR-30-5p and miR-181a-5p. Paper V evaluates the regenerative potential of autologous AD-MSCs in-vivo using an excisional full-thickness porcine wound model. The data generated from miRNA and protein screening of AD-MSCs was re-analysed with a focus on possible regulations of AD-MCSs in wound healing. Our computational analyses predicted that miR-155 mediates multiple gene regulations of fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and vascular cell adhesion molecule 1. The predicted model was verified experimentally and revealed a positive regulation between miR-155 and the identified four factors. Each of these factors carries out key functions within the wound healing process including vascularization, inflammation, proliferation, and remodelling. In summary, the core of the work presented in this thesis provides a complete, in-vitro validated, and EMA-compliant bio-production procedure for autologous keratinocyte as an ATMP. We also presented novel miRNA-mediated epigenetic regulations in human keratinocytes and AD-MSCs. These models can serve as a valuable tool to develop novel hypotheses aiming to elucidate the biology of stem cell differentiation and wound healing.
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| 32. |
- Shahin, Hady, et al.
(författare)
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MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration
- 2024
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : FRONTIERS MEDIA SA. - 2296-4185. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds.Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data.Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection.Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.
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| 33. |
- Shahin, Hady, et al.
(författare)
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miRNome and Proteome Profiling of Human Keratinocytes and Adipose Derived Stem Cells Proposed miRNA-Mediated Regulations of Epidermal Growth Factor and Interleukin 1-Alpha
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- Wound healing is regulated by complex crosstalk between keratinocytes and other cell types, including stem cells. In this study, a 7-day direct co-culture model of human keratinocytes and adipose-derived stem cells (ADSCs) was proposed to study the interaction between the two cell types, in order to identify regulators of ADSCs differentiation toward the epidermal lineage. As major mediators of cell communication, miRNome and proteome profiles in cell lysates of cultured human keratinocytes and ADSCs were explored through experimental and computational analyses. GeneChip(R) miRNA microarray, identified 378 differentially expressed miRNAs; of these, 114 miRNAs were upregulated and 264 miRNAs were downregulated in keratinocytes. According to miRNA target prediction databases and the Expression Atlas database, 109 skin-related genes were obtained. Pathway enrichment analysis revealed 14 pathways including vesicle-mediated transport, signaling by interleukin, and others. Proteome profiling showed a significant upregulation of the epidermal growth factor (EGF) and Interleukin 1-alpha (IL-1 alpha) compared to ADSCs. Integrated analysis through cross-matching the differentially expressed miRNA and proteins suggested two potential pathways for regulations of epidermal differentiation; the first is EGF-based through the downregulation of miR-485-5p and miR-6765-5p and/or the upregulation of miR-4459. The second is mediated by IL-1 alpha overexpression through four isomers of miR-30-5p and miR-181a-5p.
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| 34. |
- Shahin, Hady, et al.
(författare)
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Vascularization is the next challenge for skin tissue engineering as a solution for burn management
- 2020
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Ingår i: Burns & trauma. - : Oxford University Press. - 2321-3868 .- 2321-3876. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Skin regeneration represents a promising line of management for patients with skin loss, including burn victims. The current approach of spraying single cells over the defective areas results in variable success rates in different centers. The modern approach is to synthesize a multilayer skin construct that is based on autologous stem cells. One of the main complications with different types of transplants is sloughing due to the absence of proper vascularization. Ensuring proper vascularization will be crucial for the integration of skin constructs with the surrounding tissues. Combination of the right cells with scaffolds of proper physico-chemical properties, vascularization can be markedly enhanced. The material effect, pore size and adsorption of certain proteins, as well as the application of appropriate growth factors, such as vascular endothelial growth factors, can have an additive effect. A selection of the most effective protocols is discussed in this review.
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| 35. |
- Sjöberg, Folke, 1956-, et al.
(författare)
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The impact and validity of the Berlin criteria on burn-induced ARDS : Examining mortality rates, and inhalation injury influences. A single center observational cohort study.
- 2024
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Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As several recent studies have shown low mortality rates in burn injury induced ARDS early (≤7 days) after the burn, the Berlin criteria for the ARDS diagnosis in this setting may be disputed. Related to this issue, the present study investigated the incidence, trajectory and risk factors of early Acute Respiratory Distress Syndrome (ARDS) and outcome in burn patients, as per the Berlin criteria, along with the concurrent prevalence and influence of inhalation injury, and ventilator-acquired pneumonia (VAP).METHODS: Over a 2.5-year period, burn patients with Total Burn Surface Area (TBSA) exceeding 10% admitted to a national burn center were included. The subgroup of interest comprised patients with more than 48 h of ventilatory support. This group was assessed for ARDS, inhalation injury, and VAP.RESULTS: Out of 292 admissions, 62 sustained burns > 10% TBSA. Of these, 28 (45%) underwent ventilatory support for over 48 h, almost all, 24 out of 28, meeting the criteria for ARDS early, within 7 days post-injury and with a PaO2/FiO2 (PF) ratio nadir at day 5. The mortality rate for this early ARDS group was under 10%, regardless of PF ratios (mean TBSA% 34,8%). Patients with concurrent inhalation injury and early ARDS showed significantly lower PF ratios (p < 0.001), and higher SOFA scores (p = 0.004) but without impact on mortality. Organ failure, indicated by SOFA scores, peaked early (day 3) and declined in the first week, mirroring PF ratio trends (p < 0.001).CONCLUSIONS: The low mortality associated with early ARDS in burn patients in this study challenges the Berlin criteria's for the early ARDS diagnosis, which for its validity relies on that higher mortality is linked to worsening PF ratios. The finding suggests alternative mechanisms, leading to the early ARDS diagnosis, such as the significant impact of inhalation injury on early PF ratios and organ failure, as seen in this study. The concurrence of early organ failure with declining PF ratios, supports, as expected, the hypothesis of trauma-induced inflammation/multi-organ failure mechanisms contributing to early ARDS. The study highlights the complexity in differentiating between the contributions of inhalation injury to early ARDS and the related organ dysfunction early in the burn care trajectory. The Berlin criteria for the ARDS diagnosis may not be fully applicable in the burn care setting, where the low mortality significantly deviates from that described in the original Berlin ARDS criteria publication but is as expected when considering the actual not very extensive burn injury sizes/Baux scores as in the present study.
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| 36. |
- Steinvall, Ingrid, 1959-, et al.
(författare)
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ABO blood group and effects on ventilatory time, length of stay and mortality in major burns a retrospective observational outcome study
- 2022
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Ingår i: Burns. - Oxford, United Kingdom : Elsevier. - 0305-4179 .- 1879-1409. ; 48:4, s. 785-790
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Tidskriftsartikel (refereegranskat)abstract
- Blood group has been found to be important in the development of many diseases and the outcome of several disease processes, especially cardiovascular morbidity and mortality, such as caused by trauma and sepsis. The main reason is claimed to be related to glycobiology and effects mediated through the endothelium. This study investigated the possible effect of blood group (ABO) on burn care outcome. Burn outcome prediction models are extremely accurate and as such can be used to identify outcome effects even in single centre settings. In this retrospective risk adjusted observational study, we investigated the effect of ABO blood group on ventilatory time, length of hospital stay (LOS), and 90 day mortality among patients with burns. RESULTS: A total of 225 patients were included (2008-2019) with median TBSA of 26%; interquartile range (IQR) of 20-37%; median age 45 years (IQR 22-65 years); median Baux score (age + TBSA%); 76 (IQR 53- 97); 168 (75%) were male; median duration of hospital stay was 31 days (IQR 19-56); a total of 138 (61%) received treatment with mechanical ventilation; and 29 (13%) died. In a multivariable regression model, we were unable to isolate any significant effect of any blood group (O, A, B, AB) on the outcome measures studied (ventilatory time, LOS, and mortality). IN SUMMARY: contrary to many other major areas of disease in which ABO blood groups affect outcome, we were unable to find any such effect on patients with burns. Given the precision of the outcome models presented (AUC 0.93) any such an effect, if missed due to the limited study cohort, may be considered limited and to have only a minor clinical impact.
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| 37. |
- Steinvall, Ingrid, 1959-, et al.
(författare)
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Addition of admission lactate levels to Baux score improves mortality prediction in severe burns.
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Risk adjustment and mortality prediction models are central in optimising care and for benchmarking purposes. In the burn setting, the Baux score and its derivatives have been the mainstay for predictions of mortality from burns. Other well-known measures to predict mortality stem from the ICU setting, where, for example, the Simplified Acute Physiology Score (SAPS 3) models have been found to be instrumental. Other attempts to further improve the prediction of outcome have been based on the following variables at admission: Sequential Organ Failure Assessment (aSOFA) score, determinations of aLactate or Neutrophil to Lymphocyte Ratio (aNLR). The aim of the present study was to examine if estimated mortality rate (EMR, SAPS 3), aSOFA, aLactate, and aNLR can, either alone or in conjunction with the others, improve the mortality prediction beyond that of the effects of age and percentage total body surface area (TBSA%) burned among patients with severe burns who need critical care. This is a retrospective, explorative, single centre, registry study based on prospectively gathered data. The study included 222 patients with median (25th-75th centiles) age of 55.0 (38.0 to 69.0) years, TBSA% burned was 24.5 (13.0 to 37.2) and crude mortality was 17%. As anticipated highest predicting power was obtained with age and TBSA% with an AUC at 0.906 (95% CI 0.857 to 0.955) as compared with EMR, aSOFA, aLactate and aNLR. The largest effect was seen thereafter by adding aLactate to the model, increasing AUC to 0.938 (0.898 to 0.979) (p < 0.001). Whereafter, adding EMR, aSOFA, and aNLR, separately or in combinations, only marginally improved the prediction power. This study shows that the prediction model with age and TBSA% may be improved by adding aLactate, despite the fact that aLactate levels were only moderately increased. Thereafter, adding EMR, aSOFA or aNLR only marginally affected the mortality prediction.
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| 38. |
- Timmusk, Salme, et al.
(författare)
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Drought-Tolerance of Wheat Improved by Rhizosphere Bacteria from Harsh Environments: Enhanced Biomass Production and Reduced Emissions of Stress Volatiles
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Water is the key resource limiting world agricultural production. Although an impressive number of research reports have been published on plant drought tolerance enhancement via genetic modifications during the last few years, progress has been slower than expected. We suggest a feasible alternative strategy by application of rhizospheric bacteria coevolved with plant roots in harsh environments over millions of years, and harboring adaptive traits improving plant fitness under biotic and abiotic stresses. We show the effect of bacterial priming on wheat drought stress tolerance enhancement, resulting in up to 78% greater plant biomass and five-fold higher survivorship under severe drought. We monitored emissions of seven stress-related volatiles from bacterially-primed drought-stressed wheat seedlings, and demonstrated that three of these volatiles are likely promising candidates for a rapid non-invasive technique to assess crop drought stress and its mitigation in early phases of stress development. We conclude that gauging stress by elicited volatiles provides an effectual platform for rapid screening of potent bacterial strains and that priming with isolates of rhizospheric bacteria from harsh environments is a promising, novel way to improve plant water use efficiency. These new advancements importantly contribute towards solving food security issues in changing climates.
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| 39. |
- Timmusk, Salme, et al.
(författare)
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Sfp-type PPTase inactivation promotes bacterial biofilm formation and ability to enhance wheat drought tolerance
- 2015
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Paenibacillus polymyxa is a common soil bacterium with broad range of practical applications. An important group of secondary metabolites in P polymyxa are non-ribosomal peptide and polyketide derived metabolites (NRPs/PKs). Modular non-ribosomal peptide synthetases catalyze main steps in the biosynthesis of the complex secondary metabolites. Here we report on the inactivation of an A26 Sfp-type 4'-phosphopantetheinyl transferase (Sfp-type PPTase). The inactivation of the gene resulted in loss of NRPs/PKs production. In contrast to the former Bacillus spp. model the mutant strain compared to wild type showed greatly enhanced biofilm formation ability. A26 Delta sfp biofilm promotion is directly mediated by NRPs/PKs, as exogenous addition of the wild type metabolite extracts restores its biofilm formation level. Wheat inoculation with bacteria that had lost their Sfp-type PPTase gene resulted in two times higher plant survival and about three times increased biomass under severe drought stress compared to wild type. Challenges with P. polymyxa genetic manipulation are discussed.
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| 40. |
- Yosri, Nermeen, et al.
(författare)
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Anti-Viral and Immunomodulatory Properties of Propolis : Chemical Diversity, Pharmacological Properties, Preclinical and Clinical Applications, and In Silico Potential against SARS-CoV-2
- 2021
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Ingår i: Foods. - : MDPI AG. - 2304-8158. ; 10:8
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Forskningsöversikt (refereegranskat)abstract
- Propolis, a resin produced by honeybees, has long been used as a dietary supplement and folk remedy, and more recent preclinical investigations have demonstrated a large spectrum of potential therapeutic bioactivities, including antioxidant, antibacterial, anti-inflammatory, neuroprotective, immunomodulatory, anticancer, and antiviral properties. As an antiviral agent, propolis and various constituents have shown promising preclinical efficacy against adenoviruses, influenza viruses, respiratory tract viruses, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 300 chemical components have been identified in propolis, including terpenes, flavonoids, and phenolic acids, with the specific constituent profile varying widely according to geographic origin and regional flora. Propolis and its constituents have demonstrated potential efficacy against SARS-CoV-2 by modulating multiple pathogenic and antiviral pathways. Molecular docking studies have demonstrated high binding affinities of propolis derivatives to multiple SARS-CoV-2 proteins, including 3C-like protease (3CL(pro)), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), the receptor-binding domain (RBD) of the spike protein (S-protein), and helicase (NSP13), as well as to the viral target angiotensin-converting enzyme 2 (ACE2). Among these compounds, retusapurpurin A has shown high affinity to 3CL(pro) (Delta G = -9.4 kcal/mol), RdRp (-7.5), RBD (-7.2), NSP13 (-9.4), and ACE2 (-10.4) and potent inhibition of viral entry by forming hydrogen bonds with amino acid residues within viral and human target proteins. In addition, propolis-derived baccharin demonstrated even higher binding affinity towards PLpro (-8.2 kcal/mol). Measures of drug-likeness parameters, including metabolism, distribution, absorption, excretion, and toxicity (ADMET) characteristics, also support the potential of propolis as an effective agent to combat COVID-19.
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- Zielinski, Brian L., et al.
(författare)
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Patterns of Transcript Abundance of Eukaryotic Biogeochemically-Relevant Genes in the Amazon River Plume
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- The Amazon River has the largest discharge of all rivers on Earth, and its complex plume system fuels a wide array of biogeochemical processes, across a large area of the western tropical North Atlantic. The plume thus stimulates microbial processes affecting carbon sequestration and nutrient cycles at a global scale. Chromosomal gene expression patterns of the 2.0 to 156 mu m size-fraction eukaryotic microbial community were investigated in the Amazon River Plume, generating a robust dataset (more than 100 million mRNA sequences) that depicts the metabolic capabilities and interactions among the eukaryotic microbes. Combining classical oceanographic field measurements with metatranscriptomics yielded characterization of the hydrographic conditions simultaneous with a quantification of transcriptional activity and identity of the community. We highlight the patterns of eukaryotic gene expression for 31 biogeochemically significant gene targets hypothesized to be valuable within forecasting models. An advantage to this targeted approach is that the database of reference sequences used to identify the target genes was selectively constructed and highly curated optimizing taxonomic coverage, throughput, and the accuracy of annotations. A coastal diatom bloom highly expressed nitrate transporters and carbonic anhydrase presumably to support high growth rates and enhance uptake of low levels of dissolved nitrate and CO2. Diatom-diazotroph association (DDA: diatoms with nitrogen fixing symbionts) blooms were common when surface salinity was mesohaline and dissolved nitrate concentrations were below detection, and hence did not show evidence of nitrate utilization, suggesting they relied on ammonium transporters to aquire recently fixed nitrogen. These DDA blooms in the outer plume had rapid turnover of the photosystem D1 protein presumably caused by photodegradation under increased light penetration in clearer waters, and increased expression of silicon transporters as silicon became limiting. Expression of these genes, including carbonic anhydrase and transporters for nitrate and phosphate, were found to reflect the physiological status and biogeochemistry of river plume environments. These relatively stable patterns of eukaryotic transcript abundance occurred over modest spatiotemporal scales, with similarity observed in sample duplicates collected up to 2.45 km in space and 120 minutes in time. These results confirm the use of metatranscriptomics as a valuable tool to understand and predict microbial community function.
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