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Background: Persisting symptoms after concussion (PSaC) are a pathological manifestation of head injuries that present with symptoms after the acute phase of head trauma has subsided. Insufficient research about PSaC has led to gaps in knowledge and incorrect terminology being applied. Furthermore, gaps exist in standardised assessment protocols and understanding of mental health symptoms associated with sports. Objectives: The study aimed to; 1) Determine expert consensus on appropriate terminology for symptoms lasting >4 weeks, 2) Investigate associations with mental health and postural stability symptoms, 3) Evaluate experts’ views on quantitative balance and electroencephalogram (EEG) testing. Methods: A Delphi-like survey was designed in REDCap and sent to identified experts in the field of sports-related concussions (SRC). Expert consensus was defined as ≥ 75% agreement. Results: Expert consensus identified the following mood and motor control symptoms being associated with PSaC: increases in emotional state (80%), irritability (87%), nervousness (87%), sadness (80%), balance impairment (80%), dizziness (87%) and feeling slow (80%). Numbness and tingling were not considered longer-term effects (80%). Additionally, 93% of respondents acknowledged mental health symptoms as potential longer-term effects, with 80% agreeing on inadequate current management. Respondents indicated PSaC are only somewhat adequately managed (73%) or not managed well enough (27%). The use of EEG and quantitative balance testing remains open for debate. The survey response rate was 21%. Conclusion: Improving mental health management for athletes with PSaC and standardising terminology is crucial. Future research is required to establish effective diagnosis and treatment methods. Addressing these issues may result in better care and safer return to play for athletes. [ABSTRACT FROM AUTHOR]

The case sets the foundation for clinical protocols to incorporate mobile EEG and qEEG techniques, instrumental balance testing, and mood symptom screening in athletes who have suffered a sports-related concussion. The protocol provides a framework for clinicians to monitor a patient's recovery progress in terms of brainwave activity, general cognition, moods, and motor control. Objective data obtained through the protocol may assist in developing personalized treatment plans, improving follow-up care, and identifying residual brain function deficits that may be missed in standardized clinical exams. Finally, this case highlights a need for more thorough communication and testing procedures that screen for mood symptoms and provide an opportunity for athletes to discuss their mental health after suffering from an SRC., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Business management training is essential for success in the modern era. Health and medical professionals are exposed to knowledge that allows them to treat pathologies. However, their training does not prepare them to manage their practices as businesses and in a sustainable, effective, and efficient manner., Objectives: To investigate the business management training needs of registered South African Biokineticists., Methods: A quantitative and descriptive research design was used. Sixty-nine registered Biokineticists answered the emailed survey. The survey was sent out on two separate days, two weeks apart. Participants could only answer the survey once. The survey was sent out by the Biokinetics Association of South Africa (BASA). The sample in this study consisted of both male and female participants who graduated between the years of 1985-2019. The survey consisted of demographic questions about their study methods. It also included a 5-point Likert Scale where a score of 1 indicated an exceptionally low need and a score of 5 indicated a very high need for corresponding business processes. The business processes included accounting, business sustainability, corporate social responsibility, ethics, financial management, human resource management, leadership and managerial decision-making, marketing, operational management, and strategic management. A final open-ended question on what other business management training the participant needed was asked at the end of the survey., Results: Combined high to very high needs (X≥4 on the Likert Scale) for the business management processes explored were: accounting: 28%, business sustainability: 33%, corporate social responsibility: 23%, ethics: 55%, financial management: 35%, human resource management: 29%, leadership and managerial decision-making: 43%, marketing: 41%, operational management: 39%, and strategic management: 33%. Seventy-one percent of the participants who took part in the study suggested that they needed other business management training needs, providing suggestions in the final question. Of the 71% of participants who answered this question, the most important requests identified included information technology (17%), tax-related management and knowledge (19%) and medical aid training for ICD-10 coding (13%). The other 51% of the participants that answered the final question provided suggestions that could be categorised into the areas of business already reported on in the Likert Scale. Sixty-nine out of a possible ±1600 registered Biokineticists who were BASA members completed the survey. This represents a response rate of about 4%., Conclusion: Business management training needs exist for South African Biokineticists. By addressing these needs, it may lead to improvements in overall patient care, practice management and small business growth which in return can lead to the socioeconomic stimulation of the country., Competing Interests: Conflict of interest and source of funding: The authors declare no conflict of interest and no source of funding., (Copyright © 2021 South African Journal of Sports Medicine.)

The autosomal recessive disorder primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific pyridoxal-phosphate-dependent enzyme alanine:glyoxylate aminotransferase (AGT). Numerous mutations and polymorphisms in the gene encoding AGT have been identified, but in only a few cases has the causal relationship between genotype and phenotype actually been demonstrated. In this study, we have determined the effects of the most common naturally occurring amino acid substitutions (both normal polymorphisms and disease-causing mutations) on the properties, especially specific catalytic activity, of purified recombinant AGT. The results presented in this paper show the following: 1) normal human His-tagged AGT can be expressed at high levels in Escherichia coli and purified in a correctly folded, dimerized and catalytically active state; 2) presence of the common P11L polymorphism decreases the specific activity of purified recombinant AGT by a factor of three; 3) AGTs containing four of the most common PH1-specific mutations (G41R, F152I, G170R, and I244T) are all soluble and catalytically active in the absence of the P11L polymorphism, but in its presence all lead to protein destabilization and aggregation into inclusion bodies; 4) naturally occurring and artificial amino acid substitutions that lead to peroxisome-to-mitochondrion AGT mistargeting in mammalian cells also lead to destabilization and aggregation in E. coli; and 5) the PH1-specific G82E mutation abolishes AGT catalytic activity by interfering with cofactor binding, as does the artificial K209R mutation at the putative site of cofactor Shiff base formation. These results are discussed in the light of the high allelic frequency ( approximately 20%) of the P11L polymorphism and its importance in determining the phenotypic manifestations of mutations in PH1.

The molecular basis of the variable species-specific peroxisomal and/or mitochondrial targeting of the enzyme alanine-glyoxylate aminotransferase 1 (AGT) has been studied in human fibroblasts by confocal immunofluorescence microscopy after intranuclear microinjection of various human, rabbit, marmoset, and feline AGT cDNA constructs. The expression of full-length human and rabbit AGT cDNA led to an exclusively peroxisomal distribution of AGT. However, the distribution of feline and marmoset AGT depended on the cDNA construct injected. In both species, injection of the short cDNAs (from transcripts that occur naturally in marmoset liver but not in feline liver) led to an exclusively peroxisomal distribution. However, injection of the long cDNAs (from transcripts that occur naturally in both species) led to most of the AGT being targeted to the mitochondria and only a small, yet significant, fraction to the peroxisomes. Reintroduction of the 'ancestral' first potential translation initiation site into human AGT cDNA led to an 'ancestral' distribution of AGT (i.e. both mitochondrial and peroxisomal). Deletion of the second potential translation start site from the long feline cDNA led to a distribution that was almost entirely mitochondrial, which suggests that most peroxisomal AGT encoded by the long cDNA results from internal translation initiation from this site with the consequent loss of the N-terminal mitochondrial targeting sequence. Expression of rabbit cDNA and the short marmoset and feline cDNAs in cells selectively deficient in the import of peroxisomal matrix proteins showed that peroxisomal AGT in all these species is imported via the peroxisomal targeting sequence type 1 (PTS1) import pathway. The almost complete functional dominance of the N-terminal mitochondrial targeting sequence over the C-terminal PTS. which was not due to any direct interference of the former with peroxisomal import, was maintained even when the unusual PTS1 of AGT (KKL in human) was replaced by the prototypical PTS1 SKL. The results demonstrate that the major determinant of alanine-glyoxylate aminotransferase subcellular distribution in mammals is the presence or absence of the mitochondrial targeting sequence rather than the peroxisomal targeting sequence. Various strategies have arisen during the evolution of mammals to enable the exclusion of the mitochondrial targeting sequence from the newly synthesised polypeptide, all of which involve the use of alternative transcription and/or translation initiation sites.

The autosomal recessive disease primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate amino-transferase (AGT). This paper concerns the identification, characterization and clinical use of an unusual discretely polymorphic tandem repeat sequence in the fourth intron of the human AGT gene (gene locus designation AGXT). In a random Caucasian population, three alleles could be clearly recognized that consisted of either 12 (type III), 17 (type II) or approximately 38 (type I) tandemly repeated copies of a highly conserved 29/32-bp sequence with frequencies of 33%, 7% and 60%, respectively. In a random Japanese population, the allelic frequencies were markedly different (i.e. 31%, 45% and 19%, respectively). In addition, a fourth allele was identified, consisting of approximately 32 repeats (type IV), with an allelic frequency of approximately 5% in Japanese. The repetitive sequence was similar to previously identified mammalian sequences with homology to the Epstein-Barr virus IR3 repetitive element involving a 12/15-bp region GCA(GGN)GGAGGAGGG within the repeat unit. This IR3-like sequence was interspersed with a 17-bp sequence with no similarity to any currently known repetitive element. The type I and type III alleles were judged to be equivalent to a previously identified TaqI polymorphism. Two polymorphisms previously shown to be associated with the peroxisome-to-mitochondrion mistargeting of AGT in PH1 (a C154-->T point substitution in exon 1 and a 74-bp duplication in intron 1) were found to segregate exclusively with the type I intron 4 polymorphism in Caucasians, but not in Japanese. The polymorphic nature of the intron 4 tandem repeats makes them of potential use in the prenatal diagnosis of PH1, especially when coupled with the exon 1 C154-->T substitution or intron 1 duplication polymorphisms. A PH1 family, in which a fetus had been predicted previously to be either normal or a carrier by AGT enzymic analysis of a fetal liver biopsy, but who had been shown to be only partially informative with respect to the C154-->T/intron 1 polymorphisms, was analysed retrospectively. The family was completely informative for the intron 4 tandem repeat polymorphism and the carrier status of the fetus was confirmed.

The subcellular distribution of hepatic alanine:glyoxylate aminotransferase 1 (AGT) has changed, under the influence of dietary selection pressure, on several o occasions during the evolution of mammals. In some species (e.g. human and rabbit) AGT is entirely peroxisomal; in other species (e.g. marmoset and rat) this enzyme is found in similar amounts in peroxisomes and mitochondria; in yet other species (e.g. cat) it is mainly mitochondrial. The molecular basis of the species-specific dual intracellular targeting of AGT has been partially elucidated in the human and rabbit (as examples of the first group), and in the rat and marmoset (as examples of the second group). As part of a wider study on the molecular evolution of AGT intracellular targeting, we report in the present paper the results of an investigation into the molecular basis of the subcellular distribution of AGT in the cat (as an example of the third group). Cat liver AGT cDNA has been cloned and sequenced, and shown to have a high degree of similarity to AGT from human, rabbit, marmoset and rat. Southern-blotting analysis showed that AGT in the cat is probably encoded by a single gene, as it is in other species. Transcript analysis by RNase protection indicated that almost all of the AGT mRNA would possess an open reading frame encoding a polypeptide of 414 amino acids and a molecular mass of 45,508 Da. The N-terminal 22 amino acids comprised the putative mitochondrial-targeting sequence (by analogy with the equivalent sequence in marmoset and rat pre-mitochondrial AGT). The very low level of peroxisomal AGT in cat liver is compatible with the absence of any RNase-protected transcripts initiating downstream of the first putative translation initiation codon (i.e. absence of any transcripts in which the mitochondrial-targeting sequence is excluded from the open reading frame). In vitro studies showed that the 45 kDa polypeptide was imported into rat liver mitochondria and processed to a mature protein of approximately 43 kDa, compatible with the cleavage of the N-terminal 22 amino acids, as is also the case in rat and marmoset. A polypeptide in which the N-terminal 22 amino acids was absent could not be imported into mitochondria in vitro.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Three unrelated PH1 patients, who possess a novel complex phenotype, are described. At the enzymological level, this phenotype is characterized by a complete, or nearly complete, absence of AGT catalytic activity and reduced AGT immunoreactivity. Unlike normal individuals in whom the AGT is confined to the peroxisomal matrix, the immunoreactive AGT in these three patients was distributed approximately equally between the peroxisomes and mitochondria. The peroxisomal AGT appeared to be aggregated into amorphous core-like structures in which no other peroxisomal enzymes could be identified. Mutational analysis of the AGT gene showed that two of the three patients were compound heterozygotes for two previously unrecognized point mutations which caused Gly41-->Arg and Phe152-->Iso amino acid substitutions. The third patient was shown to be a compound heterozygote for the Gly41-->Arg mutation and a previously recognized Gly170-->Arg mutation. All three patients were homozygous for the Pro11-->Leu polymorphism that had been found previously with a high allelic frequency in normal populations. It is suggested that the Phe152-->Iso and Gly170-->Arg substitutions, which are only eighteen residues apart and located in the same highly conserved internal region of 58 amino acids, might be involved in the inhibition of peroxisomal targeting and/or import of AGT and, in combination with the Pro11-->Leu polymorphism, be responsible for its aberrant mitochondrial compartmentalization. On the other hand, the Gly41-->Arg substitution, either in combination with the Pro11-->Leu polymorphism or by itself, is predicted to be responsible for the intraperoxisomal aggregation of the AGT protein.

In mammals, the subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT) is species dependent, with the proportion of AGT targeted to mitochondria varying between 0% and greater than 90%, the remainder being located in the peroxisome. In order to extend our studies on the molecular evolution of intracellular targeting of AGT, we have investigated the organization and expression of the AGT genes of rabbit, which has all of its AGT located in the peroxisome, and marmoset, which has approximately 50% of its AGT located in the peroxisome and 50% in the mitochondrion. Southern-blot analysis indicates that, in both of these species, AGT is encoded by a single-copy gene, as has previously been shown for human (all AGT in the peroxisome) and rat (50% AGT in the peroxisome and 50% in the mitochondrion). Comparison of the cDNA sequences encoding marmoset, rabbit, human and rat AGT, combined with transcript mapping and in vitro mitochondrial protein-import analysis, has provided a molecular explanation for the differential targeting of AGT in these species. As in the rat, marmoset AGT is synthesized in two forms, via the use of alternative transcription and translation-initiation sites. These two forms of AGT differ only in the presence or absence of a 22-amino-acid amino-terminal peptide, which acts as a cleavable mitochondrial-targeting sequence, directing the longer form of AGT to mitochondria. The shorter form of AGT, lacking the mitochondrial-targeting sequence, is presumed to be localized in the peroxisomes. In humans and rabbits, similar but distinct evolutionary mutational events within the AGT gene have resulted in exclusion of the region encoding the mitochondrial-targeting sequence from the open reading frame, explaining the exclusive peroxisomal localization of AGT in these species. We discuss the impact of these results on our understanding of both the evolution of species dependence of AGT subcellular distribution and the recent identification of amino acid changes in human AGT which result in mistargeting of this protein to mitochondria.

We have synthesized and sequenced alanine:glyoxylate aminotransferase (AGT; HGMW-approved symbol for the gene--AGXT) cDNA from the liver of a primary hyperoxaluria type 1 (PH1) patient who had normal levels of hepatic peroxisomal immunoreactive AGT protein, but no AGT catalytic activity. This revealed the presence of a single point mutation (G----A at cDNA nucleotide 367), which is predicted to cause a glycine-to-glutamate substitution at residue 82 of the AGT protein. This mutation is located in exon 2 of the AGT gene and leads to the loss of an AvaI restriction site. Exon 2-specific PCR followed by AvaI digestion showed that this patient was homozygous for this mutation. In addition, three other PH1 patients, one related to and two unrelated to, but with enzymological phenotype similar to that of the first patient, were also shown to be homozygous for the mutation. However, one other phenotypically similar PH1 patient was shown to lack this mutation. The mechanism by which the glycine-to-glutamate substitution at residue 82 causes loss of catalytic activity remains to be resolved. However, the protein sequence in this region is highly conserved between different mammals, and the substitution at residue 82 is predicted to cause significant local structural alterations.

We report here the identification of a duplication within the first intron of the gene encoding human alanine:glyoxylate aminotransferase (AGT); this duplication is closely linked to two point mutations associated with peroxisome-to-mitochondrion mistargeting of AGT in primary hyperoxaluria type 1 (PH1) patients. Polymerase chain reaction amplification of regions of the AGT gene including the insertion site from individuals heterozygous for this duplication, produces allele-specific fragments of different sizes. We have taken advantage of this to identify a nonsense mutation within a non-expressed allele of a compound heterozygote PH1 patient with mitochondrial AGT.

We have previously reported the isolation of a genomic clone encoding human liver-specific peroxisomal alanine:glyoxylate aminotransferase (AGT, EC 2.6.1.44), the deficient enzyme in primary hyperoxaluria type 1 (PH1) (P. E. Purdue, Y. Takada, and C. J. Danpure, J. Cell Biol. 111: 2341-2351, 1990). This clone has now been characterized, revealing that the coding sequence is distributed among 11 exons covering 10 kb. The nucleotide sequences of each exon have been determined, confirming that this clone corresponds to previously characterized AGT cDNA (Y. Takada, N. Kaneko, H. Esumi, P. E. Purdue, and C. J. Danpure, Biochem. J. 268: 517-520, 1990). In addition, to provide sequence data for the design of exon-specific PCR primers, the intron sequences immediately flanking each exon have been determined. Furthermore, in an attempt to identify putative transcriptional control sequences we have determined the sequence of 1.25 kb directly upstream of the cDNA 5' end. The results of genomic Southern blotting indicate that human AGT is probably encoded by a single copy gene, and a combination of in situ hybridization and PCR analysis of rodent/human somatic cell hybrids suggests that this gene is located on chromosome 2q36-q37. The gene symbol AGXT has been assigned for this locus.

The Sprague-Dawley rat was used to demonstrate the effect of nitrous oxide, with and without folinic pretreatment, on reproductive indices and fetal development. One of the objectives of the investigation was to test the hypothesis that at least some of the teratogenic effect of nitrous oxide is related to interference with folate metabolism. Groups of animals were exposed to 70-75% nitrous oxide on day 9 of pregnancy with or without folinic acid 0.1 mg i.p. 12 h before, and immediately before, exposure. Subsequent fetal development was compared with that of various control groups. There were no significant differences in fetal survival, but fetal weights were reduced in both groups exposed to nitrous oxide. Of the indices of skeletal maturity, the number of ossified sternebrae was reduced only in the nitrous oxide group not receiving folinic acid. The incidence of major skeletal abnormalities in the untreated nitrous oxide group was significantly increased to five times that of the control groups, whereas the incidence in the nitrous oxide group receiving folinic acid was not significantly different from control. It is concluded that pretreatment with folinic acid can at least partially reduce the teratogenic effects of nitrous oxide in the rat.