Exploring Flood Response Challenges, Training Needs, and the Impact of Online Flood Training for Lifeguards and Water Safety Professionals in South Africa.

Flooding is a significant cause of human and economic loss in the African region, including in South Africa. Flood mitigation and response in South Africa is challenging due to a range of environmental, infrastructure, and policy constraints. Lifeguards represent a potential additional workforce to bolster flood mitigation and response. This study aimed to explore the feasibility and acceptability of online flood safety training for water safety professionals in South Africa, as well as assess the current flood response capacity and future needs of this group. Online surveys were completed by a convenience sample of South African water safety professionals (including lifeguards) pre-and post a series of four online flood training workshops. Free text responses were thematically coded and flood knowledge was compared between the pre-and post-workshop survey respondents. Sixty-eight responses were analysed (64.7% pre-workshop phase; 63.2% male, 29.4% aged 50-59 years). A range of challenges in flood mitigation and response were identified including equipment, training, and a lack of government support. However, positives were also identified including respondents' willingness to assist in flood emergencies and good cooperation with neighbouring countries and across the region. Opportunities for better cross-municipal and government communication were discussed. In times of crisis, or in resource poor settings, water safety professionals can bolster traditional flood mitigation and response capacity. Opportunities exist to harness this willingness, but also improve cross-governmental and municipal knowledge sharing to improve future flood mitigation and response efforts in South Africa.

Application of an in silico approach identifies a genetic locus within ITGB2, and its interactions with HSPG2 and FGF9, to be associated with anterior cruciate ligament rupture risk.

We developed a Biomedical Knowledge Graph model that is phenotype and biological function-aware through integrating knowledge from multiple domains in a Neo4j, graph database. All known human genes were assessed through the model to identify potential new risk genes for anterior cruciate ligament (ACL) ruptures and Achilles tendinopathy (AT). Genes were prioritised and explored in a case-control study comparing participants with ACL ruptures (ACL-R), including a sub-group with non-contact mechanism injuries (ACL-NON), to uninjured control individuals (CON). After gene filtering, 3376 genes, including 411 genes identified through previous whole exome sequencing, were found to be potentially linked to AT and ACL ruptures. Four variants were prioritised: HSPG2:rs2291826A/G, HSPG2:rs2291827G/A, ITGB2:rs2230528C/T and FGF9:rs2274296C/T. The rs2230528 CC genotype was over-represented in the CON group compared to ACL-R (p < 0.001) and ACL-NON (p < 0.001) and the TT genotype and T allele were over-represented in the ACL-R group and ACL-NON compared to CON (p < 0.001) group. Several significant differences in distributions were noted for the gene-gene interactions: (HSPG2:rs2291826, rs2291827 and ITGB2:rs2230528) and (ITGB2:rs2230528 and FGF9:rs2297429). This study substantiates the efficiency of using a prior knowledge-driven in silico approach to identify candidate genes linked to tendon and ACL injuries. Our biomedical knowledge graph identified and, with further testing, highlighted novel associations of the ITGB2 gene which has not been explored in a genetic case control association study, with ACL rupture risk. We thus recommend a multistep approach including bioinformatics in conjunction with next generation sequencing technology to improve the discovery potential of genomics technologies in musculoskeletal soft tissue injuries.HighlightsA biomedical knowledge graph was modelled for musculoskeletal soft tissue injuries to efficiently identify candidate genes for genetic susceptibility analyses.The biomedical knowledge graph and sequencing data identified potential biologically relevant variants to explore susceptibility to common tendon and ligament injuries. Specifically genetic variants within the ITGB2 and FGF9 genes were associated with ACL risk.Novel allele combinations (HSPG2-ITGB2 and ITGB2-FGF9) showcase the potential effect of ITGB2 in influencing risk of ACL rupture.

Factors which affect the application and implementation of a spinal motion restriction protocol by prehospital providers in a low resource setting: A scoping review.

Introduction: The safety and effectiveness of prehospital clinical c-spine clearance or spinal motion restriction (SMR) decision support tools are unclear. The present study aimed to examine the available literature on clinical cervical spine clearance and selective SMR decision support tools to identify possible barriers to implementation, safety, and effectiveness when used by emergency medical service (EMS) practitioners. Method: We performed a focused scoping review of published literature on the prehospital use of clinical c-spine clearance and SMR decision tools in adult blunt trauma patients. The Medline, Embase, Cochrane Library, Cumulative Index of Nursing and Allied Health Literature, Web of Science, Turning Research into Practice and EBSCOhost online databases were searched (February 2021). The type of decision support tool and facilitators and barriers to its use were extracted from each included publication in accordance with a modified descriptive-analytical framework. Extracted data were subjected to thematic analysis. Results: Following screening, forty-two articles were included in this scoping review. No studies conducted specifically in low resource settings were found. The majority of articles (57%) evaluated the use of specific SMR decision support tools, such as the National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian C-spine Rule (CCR). Potential facilitators of safe and effective use were identified in 60%, and potential barriers to safe and effective use in 55% of included articles. Only one study evaluated the CCR when used by EMS practitioners, making it difficult to determine its appropriateness for implementation in the prehospital setting. Conclusion: This is the first scoping review, to our knowledge, that has attempted to identify the possible barriers and facilitators to their implementation, safety, and effectiveness when used by EMS practitioners. Key issues identified included terminology, guideline compliance and implementation, and a lack of context-specific evidence. These may provide important considerations for future guideline development.

Exploring new genetic variants within COL5A1 intron 4-exon 5 region and TGF-ß family with risk of anterior cruciate ligament ruptures.

Variants within genes encoding structural and regulatory elements of ligaments have been associated with musculoskeletal soft tissue injury risk. The role of intron 4-exon 5 variants within the α1 chain of type V collagen (COL5A1) gene and genes of the transforming growth factor-ß (TGF-ß) family, TGFBR3 and TGFBI, was investigated on the risk of anterior cruciate ligament (ACL) ruptures. A case-control genetic association study was performed on 210 control (CON) and 249 participants with surgically diagnosed ruptures (ACL), of which 147 reported a noncontact mechanism of injury (NON). Whole-exome sequencing data were used to prioritize variants of potential functional relevance. Genotyping for COL5A1 (rs3922912 G>A, rs4841926 C>T, and rs3124299 C>T), TGFBR3 (rs1805113 G>A and rs1805117 T>C), and TGFBI (rs1442 G>C) was performed using Taqman SNP genotyping assays. Significant overrepresentation of the G allele of TGFBR3 rs1805113 was observed in CON vs ACL (P = .014) and NON groups (P = .021). Similar results were obtained in a female with the G allele (CON vs ACL: P = .029; CON vs NON: P = .016). The TGFBI rs1442 CC genotype was overrepresented in the female ACL vs CON (P = .013). Associations of inferred allele combinations were observed in line with the above results. COL5A1 intron 4-exon 5 genomic interval was not associated with the risk of ACL ruptures. Instead, this novel study is the first to use this approach to identify variants within the TGF-ß signaling pathway to be implicated in the risk of ACL ruptures. A genetic susceptibility interval was identified to be explored in the context of extracellular matrix remodeling.

Defining the molecular signatures of Achilles tendinopathy and anterior cruciate ligament ruptures: A whole-exome sequencing approach.

Musculoskeletal soft tissue injuries are complex phenotypes with genetics being one of many proposed risk factors. Case-control association studies using the candidate gene approach have predominately been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to further define the genetic profile of these injuries using an integrated omics approach involving whole exome sequencing and a customised analyses pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. Approximately 200 000 variants were identified in the sequenced samples. Previous research was used to guide a targeted analysis of the genes encoding the tenascin-C (TNC) glycoprotein and the α1 chain of type XXVII collagen (COL27A1) located on chromosome 9. Selection of variants within these genes were; however, not predetermined but based on a tiered filtering strategy. Four variants in TNC (rs1061494, rs1138545, rs2104772 and rs1061495) and three variants in the upstream COL27A1 gene (rs2567706, rs2241671 and rs2567705) were genotyped in larger Achilles tendinopathy and anterior cruciate ligament (ACL) rupture sample groups. The CC genotype of TNC rs1061494 (C/T) was associated with the risk of Achilles tendinopathy (p = 0.018, OR: 2.5 95% CI: 1.2-5.1). Furthermore, the AA genotype of the TNC rs2104772 (A/T) variant was significantly associated with ACL ruptures in the female subgroup (p = 0.035, OR: 2.3 95% CI: 1.1-5.5). An inferred haplotype in the TNC gene was also associated with the risk of Achilles tendinopathy. These results provide a proof of concept for the use of a customised pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries.

The interaction of polymorphisms in extracellular matrix genes and underlying miRNA motifs that modulate susceptibility to anterior cruciate ligament rupture.

OBJECTIVES: Variants within genes that encode proteins regulating fibrillogenesis such as BGN (rs1126499 C>T, rs1042103 C>T), COL5A1 (rs12722 C>T) and DCN (rs516115 C>T) have been associated with susceptibility to anterior cruciate ligament (ACL) ruptures. A miRNA mediated transcript instability was proposed for the COL5A1 association. The study aims were: (i) to investigate the association of inferred allele combinations across the COL5A1 3'-UTR, BGN and DCN genes with susceptibility to ACL rupture; and (ii) to use an in silico approach to identify miRNA binding sites common to these risk associated allele combinations. DESIGN: Case-control association study METHODS: Allele combinations were generated from the genotype data of the BGN (rs1126499, rs1042103), COL5A1 (rs12722) and DCN (rs516115) loci for 227 participants with surgically diagnosed ACL ruptures and 234 asymptomatic controls. Statistical analyses between the CON and ACL groups as well as sex-specific interactions were investigated. Significance was accepted at p<0.05. miRNA binding sites within these genes were identified using DIANA tools. RESULTS: Several sex-specific inferred allele combinations were associated with altered susceptibility and miRNA (miR-22, miR-27b, miR-140, miR-199a, miR-199b, miR-299, miR-338 and miR-484) recognition motifs were identified in range of these susceptibility loci. CONCLUSIONS: In conclusion, this study has implicated inferred allele combinations across BGN (rs1126499, rs1042103), COL5A1 (rs12722) and DCN (rs516115) as well as eight miRNA recognition sequences in susceptibility to ACL rupture. The biological significance of these genomic signatures needs to be explored to understand their effect on the ligaments functional capacity.

Semantic interrogation of a multi knowledge domain ontological model of tendinopathy identifies four strong candidate risk genes.

Tendinopathy is a multifactorial syndrome characterised by tendon pain and thickening, and impaired performance during activity. Candidate gene association studies have identified genetic factors that contribute to intrinsic risk of developing tendinopathy upon exposure to extrinsic factors. Bioinformatics approaches that data-mine existing knowledge for biological relationships may assist with the identification of candidate genes. The aim of this study was to data-mine functional annotation of human genes and identify candidate genes by ontology-seeded queries capturing the features of tendinopathy. Our BioOntological Relationship Graph database (BORG) integrates multiple sources of genomic and biomedical knowledge into an on-disk semantic network where human genes and their orthologs in mouse and rat are central concepts mapped to ontology terms. The BORG was used to screen all human genes for potential links to tendinopathy. Following further prioritisation, four strong candidate genes (COL11A2, ELN, ITGB3, LOX) were identified. These genes are differentially expressed in tendinopathy, functionally linked to features of tendinopathy and previously implicated in other connective tissue diseases. In conclusion, cross-domain semantic integration of multiple sources of biomedical knowledge, and interrogation of phenotypes and gene functions associated with disease, may significantly increase the probability of identifying strong and unobvious candidate genes in genetic association studies.

Extracellular matrix proteins interact with cell-signaling pathways in modifying risk of achilles tendinopathy.

The aim of this study was to investigate interactions between variants within genes encoding components of the collagen fibril and components of cell-signaling pathways within the extracellular matrix, and determine the relative contribution of these variants to Achilles tendinopathy risk in a polygenic model. A total of 339 asymptomatic control participants and 179 participants clinically diagnosed with Achilles tendinopathy were genotyped for variants within six genes encoding components of the collagen fibril and three genes encoding components of cell-signaling pathways. Logistic regression, stepwise selection, and receiver operating characteristic curve (ROC) analysis was used to select and evaluate genetic interactions and determine the relative contribution of these variants to overall genetic risk. The strongest, best fit polygenic risk model included the variables sex, three COL27A1 variants (rs4143245; rs1249744; rs946053), COL5A1 rs12722, CASP8 rs1045485, and CASP8 rs2824129 with an area under the ROC curve of 0.737 and the maximum sum of sensitivity and specificity indicators equal to 134%. Significant interactions between genes encoding components of the collagen fibril and genes encoding components of the cell-signaling pathways modify risk of Achilles tendinopathy.

A variant within the AQP1 3'-untranslated region is associated with running performance, but not weight changes, during an Ironman Triathlon.

The objective of this study was to test the association of the rs1049305 (G > C) variant within the 3'-untranslated region of the aquaporin 1 gene, AQP1, with changes in body weight, post-race serum sodium concentration and performance in Ironman triathletes. Five hundred and four male Ironman triathletes were genotyped for the rs1049305 variant within the AQP1 gene. Change in pre- and post-race body weight was calculated for 470 triathletes and used as a proxy for changes in body fluid during the race, as well as to divide triathletes into biologically relevant weight-loss groups (0-3%, 3-5% and >5%). There were no rs1049305 genotype effects on post-race serum sodium concentrations (P = 0.647), pre-race weight (P = 0.610) nor relative weight change during the Ironman Triathlons (P = 0.705). In addition, there were no significant differences in genotype (P = 0.640) nor allele (P = 0.643) distributions between the weight loss groups. However, triathletes who carry a C-allele were found to complete the 42.2-km run stage faster (mean 286, s = 49 min) than triathletes with a GG genotype (mean 296, s = 47 min; P = 0.032). The AQP1 rs1049305 variant is associated with running performance, but not relative body weight change, during the 2000, 2001 and 2006 South African Ironman Triathlons.

Variants within the COMP and THBS2 genes are not associated with Achilles tendinopathy in a case-control study of South African and Australian populations.

Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell-matrix interactions. Recent studies have shown that genetic variation is a significant risk factor for Achilles tendinopathy, and the genes encoding cartilage oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as good candidate genes for association with Achilles tendinopathy. This study aimed to test the association of sequence variants within these candidate genes with the risk of Achilles tendinopathy in participants from South Africa (SA) and Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants clinically diagnosed with Achilles tendinopathy were genotyped for five single nucleotide polymorphisms within the COMP and THBS2 genes in this case-control study. There was no difference in genotype distributions between control and tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS populations. As the selection of COMP and THBS2 as candidate genes was hypothesis driven, based on biological function, the possibility that other variants within these genes are associated with Achilles tendinopathy cannot be excluded.

Investigation of variants within the COL27A1 and TNC genes and Achilles tendinopathy in two populations.

The TNC gene has previously been associated with Achilles tendinopathy (AT) in a South African population. The aims of this study were (i) to investigate the association of single nucleotide polymorphisms within the TNC gene, and the additional candidate gene, COL27A1, with AT in two populations, and (ii) to identify if there is a risk haplotype for AT in both populations. Three hundred and thirty nine healthy control participants (CON) and 179 participants clinically diagnosed with AT (TEN) from South Africa and Australia, were genotyped for variants: rs4143245, rs1249744, rs753085, rs946053 (COL27A1) and rs13321, rs2104772, rs1330363 (TNC). Haplotypes were inferred using the genotype data. The rs2104772 (p = 0.017) and rs1330363 (p = 0.020) variants within TNC showed a significant allele association with AT. The GCA haplotype (rs946053-rs13321-rs2104772) occurred significantly more frequently in TEN participants compared to CON (27% vs. 18%; p = 0.019). This study further implicates the genomic region containing the TNC and COL27A1 genes in influencing risk of AT, and maps the potential risk allele to a genetic interval flanked by rs946053 and rs2104772. This region may have functional effects on the transcription, structure and properties of tenascin-C and the alpha-1 chain of type XXVII collagen.

Dipsogenic genes associated with weight changes during Ironman Triathlons.

Thirst is regulated by a complex interaction of signalling pathways within the central nervous system, including components of the renin-angiotensin and kalikrein kinin systems, as well as the serotonergic pathways. The aim of this study was to determine whether there were any associations between polymorphisms within the ACE, BDKRB2, NOS3 and/or 5-HTT genes with weight changes during the 2000 and 2001 226 km South African Ironman Triathlons. Pre- and post-race serum [Na(+)] and body weights, as well as genotype data, were collected from 428 (61.1%) Caucasian male triathletes who were divided into three groups according to their relative weight loss during the triathlon (0-3, 3-5 and >5%). There was a significant linear trend for the distribution of both the BDKRB2 +9/+9 genotype and the 5-HTT SS genotype between the three weight loss groups, with the >5% group having the highest percentage of athletes with the +9/+9 genotype (chi(2)=5.3, P=0.021) and the highest percentage of athletes with the SS genotype (chi(2)=5.8, P=0.016). Likewise, the >5% group had the highest percentage of athletes with the combined SS 5-HTT and/or +9/+9 BDKRB2 genotypes (chi(2)=7.4, P=0.007). In conclusion, the functional SS genotype of the serotonin transporter-linked polymorphic region (5-HTTLPR) within the 5-HTT gene and the functional +9/+9 genotype of the BDKBR2 gene were associated with larger weight losses during the Ironman Triathlons. These findings suggest the involvement of the serotonergic pathways in the control of thirst and drinking behaviour and provide further evidence for the dipsogenic effect of circulating bradykinin.

The bradykinin beta 2 receptor (BDKRB2) and endothelial nitric oxide synthase 3 (NOS3) genes and endurance performance during Ironman Triathlons.

We have previously shown that the insertion allele of the angiotensin-converting enzyme (ACE) gene was over-represented in the fastest South-African-born finishers of the South African Ironman Triathlons. As ACE is a component of the skeletal muscle kallikrein-kinin system (KKS), the aim of this study is to determine if there are any further associations between polymorphisms within the BDKRB2 and NOS3 genes, which encode for the KKS components, bradykinin beta(2) receptor and nitric oxide synthase, respectively, and ultra-endurance performance during the Ironman Triathlons. Four-hundred and forty-three male Caucasian triathletes who completed the 2000 and/or 2001 South African Ironman Triathlons and 203 healthy Caucasian male control subjects were genotyped for the functional -9/+9 polymorphism within exon 1 of the BDKRB2 gene and the G894T NOS3 gene polymorphisms. The BDKRB2 -9/-9 genotype occurred at a significantly higher frequency when the triathlete group (27.0%) was compared with the control group (19.3%, P=0.035). When divided into tertiles, there was also a significant linear trend for the NOS3 GG genotype distribution among the fastest (35.0%), middle (40.4%) and slowest (46.9%) finishers (P=0.039). The overall finishing times of the triathletes with an NOS3 GG genotype together with a BDKRB2 +9 allele were significantly slower than those with other genotype combinations (P=0.001). The NOS3/BDKRB2 genotype (beta=-0.150, B=-31.48, P=0.002), together with body mass index and age, accounted for 14.6% of the variance in the overall race time for the triathlon. In conclusion, both the NOS3 and BDKRB2 genes are associated with the actual performance during the Ironman Triathlons.