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- Ademuyiwa, Adesoji O., et al.
(author)
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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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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)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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- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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- Drake, TM, et al.
(author)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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In: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Journal article (peer-reviewed)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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- El-Sayed, Ashraf S. A., et al.
(author)
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Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants : Genome Mining and Metabolic Manipulation
- 2020
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In: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:13
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Research review (peer-reviewed)abstract
- Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids "Taxol" is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree,Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark ofT. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi fromTaxusspp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceaeand Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.
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- Mahmoud, Sara H., et al.
(author)
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Immunogenicity and Cross-Protective Efficacy Induced by an Inactivated Recombinant Avian Influenza A/H5N1 (Clade 2.3.4.4b) Vaccine against Co-Circulating Influenza A/H5Nx Viruses
- 2023
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In: Vaccines. - : MDPI. - 2076-393X. ; 11:9
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Journal article (peer-reviewed)abstract
- Controlling avian influenza viruses (AIVs) is mainly based on culling of the infected bird flocks or via the implementation of inactivated vaccines in countries where AIVs are considered to be endemic. Over the last decade, several avian influenza virus subtypes, including highly pathogenic avian influenza (HPAI) H5N1 clade 2.2.1.2, H5N8 clade 2.3.4.4b and the recent H5N1 clade 2.3.4.4b, have been reported among poultry populations in Egypt. This demanded the utilization of a nationwide routine vaccination program in the poultry sector. Antigenic differences between available avian influenza vaccines and the currently circulating H5Nx strains were reported, calling for an updated vaccine for homogenous strains. In this study, three H5Nx vaccines were generated by utilizing the reverse genetic system: rgH5N1_2.3.4.4, rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2. Further, the immunogenicity and the cross-reactivity of the generated inactivated vaccines were assessed in the chicken model against a panel of homologous and heterologous H5Nx HPAIVs. Interestingly, the rgH5N1_2.3.4.4 induced high immunogenicity in specific-pathogen-free (SPF) chicken and could efficiently protect immunized chickens against challenge infection with HPAIV H5N1_2.3.4.4, H5N8_2.3.4.4 and H5N1_2.2.1.2. In parallel, the rgH5N1_2.2.1.2 could partially protect SPF chickens against infection with HPAIV H5N1_2.3.4.4 and H5N8_2.3.4.4. Conversely, the raised antibodies to rgH5N1_2.3.4.4 could provide full protection against HPAIV H5N1_2.3.4.4 and HPAIV H5N8_2.3.4.4, and partial protection (60%) against HPAIV H5N1_2.2.1.2. Compared to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2 vaccines, chickens vaccinated with rgH5N1_2.3.4.4 showed lower viral shedding following challenge infection with the predefined HPAIVs. These data emphasize the superior immunogenicity and cross-protective efficacy of the rgH5N1_2.3.4.4 in comparison to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2.
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- Sayed Ali Sayed, Mahmoud
(author)
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Microbial and enzymatic syntheses of polymer building blocks through selective transformations of polyols and furans
- 2018
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Doctoral thesis (other academic/artistic)abstract
- AbstractTransition from fossil- to bio-based economy is a critical step towards reduction of greenhouse gas emissions and climate change, and hence for achievement of sustainable communities and environment. In order to be fossil-free, the chemical and material industry is in need of carbon-neutral building blocks from renewable resources for the diverse array of products that are currently produced from olefins and aromatics. Hence, new pathways for producing the same or novel chemical structures are needed. Industrial biotechnology offers a key technology area for transformation of biomass components or derivatives to chemical building blocks by the use of microorganisms or their enzymes. The thesis introduces new routes for microbial and enzymatic biotransformations of trimethylolpropane (TMP) and 5-hydroxymethyl furfural (HMF) to building blocks for polymers. TMP is an important industrial polyol with three hydroxyl groups produced from butyraldehyde and formaldehyde that can be potentially biobased, while HMF, a dehydration product of sugar, is totally biobased. The building block molecules produced from TMP include 2,2-bis(hydroxymethyl)butyric acid (BHMB), six membered cyclic carbonates, and from HMF are 5-hydroxymethyl-2-furan carboxylic acid (HMFCA), 5 formyl-2-furan carboxylic acid (FFCA) and 2,5-furan carboxylic acid (FDCA). Growing cells of Mycobacterium sp. MS1601 (previously Corynebacterium sp. ATCC 21245) was the only bacteria that showed the ability to selectively oxidize only one hydroxyl group of TMP to form BHMB at high yield. After optimization of the process parameters and employing high cell density cultivations in a sequential batch mode with cell recycling and cell bleeding, the volumetric productivity of BHMB was improved from 0.02 g/L.h to 0.2 g/L.h to yield 21 g/L BHMB, the highest amount reported so far. Moreover, BHMB was recovered from the reaction medium by anion exchange resin at 78% yield. Transesterification of TMP with methacrylic acid and its derivatives including methyl, ethyl vinyl and dimethyl carbonate (DMC) was investigated using immobilized lipase (Novozym435) in solvent free medium in order to produce methacrylate functionalized six-membered cyclic carbonates. The results obtained from the experimental part and in-silico analysis indicate that methyl and ethyl methacrylate were preferable substrates for the enzyme to give the product with 61.3 % yield and 73% selectivity after 9 hours reaction. Also, the functionalized cyclic carbonate was purified from the reaction solution using silica chromatography at 60.5% yield. Even the production of bio-based TMP under mild conditions was demonstrated by condensation of bio-based butyraldehyde with formaldehyde produced by oxidation of the corresponding alcohols using Gluconobacter oxydans cells and alcohol oxidase, respectively. Oxidation of crude 5-HMF to HMFCA at 100 % selectivity and yield was achieved using resting cells of G. oxydans DSM 50049. The bacteria show the ability to oxidize 31.5 g/L of crude HMF completely to HMFCA after only 6 h of the reaction, indicating that the bacteria is tolerant to the antimicrobial activity and high concentration of HMFCA. The product was recovered from the reaction with 98% purity using a simple liquid-liquid extraction step. On the other hand, Mycobacterium sp. MS1601 cells activated by growth in glycerol, oxidized HMF to FDCA and HMFCA with 60% and 40% yield, respectively. A gene sequence encoding HMF oxidase (HMFO) like enzyme was identified in the genome sequence of Mycobacterium sp. MS1601, cloned and expressed in E.coli BL21 (DE3), and the enzyme was purified and characterized. The enzyme oxidized HMF to diformyl furan (DFF) followed by conversion to FFCA at 100 % yield without further conversion to FDCA. In-silico analysis of the HMFO-Myc1 indicated that catalytic histidine is positioned at 445 and tyrosine 444 and 443 residues, which are directing the substrate into the right position in the active site, hinders FFCA from being accommodated in the right position, which motivates further studies on engineering the enzyme to enable conversion of FFCA to FDCA.
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10. |
- Sayed, Mahmoud, et al.
(author)
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Enhanced selective oxidation of trimethylolpropane to 2,2-bis(hydroxymethyl)butyric acid using Corynebacterium sp. ATCC 21245
- 2017
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In: Process Biochemistry. - : Elsevier BV. - 1359-5113. ; 63, s. 1-7
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Journal article (peer-reviewed)abstract
- 2,2-Bis(hydroxymethyl)butyric acid (BHMB) is an important multifunctional chemical for the emerging bio-based polymer industry. It can be produced from trimethylolpropane (TMP) by selective oxidation using growing cells of Corynebacterium sp. ATCC 21245. However, this process is limited by the low volumetric productivity and low concentration of the final product. In the present study, we performed sequential batch operation with cell recycling in media containing glycerol, acetic acid, and increasing concentrations of yeast extract. This approach enhanced the conversion of 10 and 15g/L TMP to 11.0 and 16.3g/L BHMB at rates of 0.50 and 0.20g/L.h, respectively. Applying a cell bleeding strategy resulted in an overall 10-fold improvement in productivity. The consequently prolonged biocatalyst viability resulted in a quantitative conversion of 20g/L TMP to 22.3g/L BHMB and a yield of 1.10gBHMB/gTMP (100% molar yield). This work facilitates further studies of the selective oxidation on other industrially important polyols.
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