Individualised and health-related quality of life of persons with spinal cord injury

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Gamma-Glutamyltransferase is a Reliable Marker for Tubular Effects of Contrast Media

The aim of this study was to evaluate the usefulness of the measurement of urinary excretion of the brush-border enzyme gamma glutamyl-transferase (GGT), in comparison with that of alanine aminopeptidase (AAP), as a marker for tubular toxicity due to contrast media (CM). Urinary activities of AAP and GGT were measured prior to the administration of CM and 1, 3 and 5 days after in forty-nine adult renal patients undergoing a radiological examination with intravascular administration of CM. The behavior of GGT was similar to that of AAP. In fact, urinary activities of both AAP and GGT increased greatly after CM. This effect was maximal on the 1st day and statistically significant for both enzymes. Furthermore, on the 1st day a relevant increase of enzyme activity (at least +50% over the basal value) was observed in the same number of patients (67%) for AAP and GGT. The concordance between GGT and AAP variations was high and statistically significant. Finally, different variables (osmolarity, dose of CM, and baseline renal function of the patients) had a similar effect on urinary excretion of AAP and GGT. The repeatability of duplicated determinations of GGT resulted better than that of AAP. In conclusion, the good concordance of the results of GGT with those of AAP justifies the use of GGT as a marker for tubular effects due to CM. Furthermore, the measurement of GGT has a better repeatability than that of AAP

The multifaceted role of vitamin b6 in cancer: drosophila as a model system to investigate dna damage

A perturbed uptake of micronutrients, such as minerals and vitamins, impacts on different human diseases, including cancer and neurological disorders. Several data converge towards a crucial role played by many micronutrients in genome integrity maintenance and in the establishment of a correct DNA methylation pattern. Failure in the proper accomplishment of these processes accelerates senescence and increases the risk of developing cancer, by promoting the formation of chromosome aberrations and deregulating the expression of oncogenes. Here, the main recent evidence regarding the impact of some B vitamins on DNA damage and cancer is summarized, providing an integrated and updated analysis, mainly centred on vitamin B6. In many cases, it is difficult to finely predict the optimal vitamin rate that is able to protect against DNA damage, as this can be influenced by a given individual's genotype. For this purpose, a precious resort is represented by model organisms which allow limitations imposed by more complex systems to be overcome. In this review, we show that Drosophila can be a useful model to deeply understand mechanisms underlying the relationship between vitamin B6 and genome integrity

Molecular characterization of pyridoxine 5′-phosphate oxidase and its pathogenic forms associated with neonatal epileptic encephalopathy

Defects of vitamin B6 metabolism are responsible for severe neurological disorders, such as pyridoxamine 5′-phosphate oxidase deficiency (PNPOD; OMIM: 610090), an autosomal recessive inborn error of metabolism that usually manifests with neonatal-onset severe seizures and subsequent encephalopathy. At present, 27 pathogenic mutations of the gene encoding human PNPO are known, 13 of which are homozygous missense mutations; however, only 3 of them have been characterised with respect to the molecular and functional properties of the variant enzyme forms. Moreover, studies on wild type and variant human PNPOs have so far largely ignored the regulation properties of this enzyme. Here, we present a detailed characterisation of the inhibition mechanism of PNPO by pyridoxal 5′-phosphate (PLP), the reaction product of the enzyme. Our study reveals that human PNPO has an allosteric PLP binding site that plays a crucial role in the enzyme regulation and therefore in the regulation of vitamin B6 metabolism in humans. Furthermore, we have produced, recombinantly expressed and characterised several PNPO pathogenic variants responsible for PNPOD (G118R, R141C, R225H, R116Q/R225H, and X262Q). Such replacements mainly affect the catalytic activity of PNPO and binding of the enzyme substrate and FMN cofactor, leaving the allosteric properties unaltered

The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism

Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism

Epidemiología de las quemaduras pediátricas: seis años de experiencia en una unidad especializada de alta complejidad

Introducción: Las lesiones por quemaduras son una patología grave, que pueden conducir a una gran morbilidad y una mortalidad significativa, pero también tienen un impacto sanitario-económico considerable. El objetivo de este estudio fue describir epidemiológicamente la población hospitalizada en la Unidad de Quemados del Hospital de Pediatría “Prof. Dr. Juan P. Garrahan” entre los años 2015 y 2020. Material y métodos: Estudio observacional, descriptivo- analítico, transversal, con evaluación y análisis de datos registrados en base de datos de historias clínicas digitalizadas. Resultados: La serie incluyó 214 pacientes, 60,3% sexo masculino, mediana de edad 4.6 años (0-16,6), 63% provenientes de la provincia de Buenos Aires, 78% de traslados se hicieron por vía terrestre con tiempo promedio de 55,6 minutos (DS 81,9), 52,8% ingresaron en los meses de otoño-invierno, 80% carecían de cobertura social. La etiología lesional fue fuego y variantes (69,2%) y escaldaduras (25,7%). El 49% reunieron criterios de lesión inhalatoria. La mediana de superficie corporal quemada (SCQ) fue 30% (0-100%), lesiones tipo B (profundas) 16,2% (0-100%) y gravedad crítica (37,4%) y grave (19,2%), requiriendo una mediana de 5 actos quirúrgicos (0-55). El 87,3% de los ingresos fue en Cuidados Intensivos, con mediana de estancia hospitalaria de 33 días (1-243) y relación promedio %SCQ/días internación 1,9 (DS 2,1). El uso de Asistencia Respiratoria Mecánica (ARM) fue 68,7% con una mediana de 7.5 días (1-100). La mortalidad de la serie fue 9,8% y estuvo asociada estadísticamente a lesión inhalatoria (p=0,0001), profundidad lesional B (p=0,00001) y uso de ARM (p=0,0011). Conclusion: Los resultados de este estudio concluyen que el sexo masculino, la franja etaria < 5 años, los ingresos en otoño-invierno, las lesiones por fuego, el grupo de gravedad crítico y la utilización de ARM son datos epidemiológicos predominantes correspondientes a una Unidad de Quemados de Alta Complejidad y deben ser tenidos en cuenta para la planificación y adecuación de los recursos asistenciales.Burn injuries are a serious pathology, which can lead to high morbidity and significant mortality, but also have a considerable health-economic impact. The objective of this study was to epidemiologically describe the population hospitalized in the Burn Unit of the Pediatric Hospital “Prof. Dr. Juan P. Garrahan” between 2015 and 2020. Material and method: Observational, descriptive-analytical, cross-sectional study, with evaluation and analysis of data recorded in a database of digitized medical records. Results: The series included 214 patients, 60,3% male, median age 4,6 years (0-16,6), 63% from the province of Buenos Aires, 78% of transfers were made by land with an average time of 55,6 minutes (DS 81,9), 52,8% entered in the fall-winter months, 80% lacked social coverage. The lesional etiology was fire and variants (69,2%) and scalds (25,7%). 49% met criteria for inhalation injury. The median body surface area burned (SCQ) was 30% (0-100%), type B (deep) injuries 16,2% (0-100%) and critical (37,4%) and severe (19,2%) severity, requiring a median of 5 surgical acts (0-55). 87,3% of the admissions were in Intensive Care, with a median hospital stay of 33 days (1-243) and average ratio %SCQ/days hospitalization 1,9 (DS 2,1). The use of Mechanical Respiratory Assistance (MRA) was 68,7% with a median of 7,5 days (1-100). Mortality in the series was 9,8% and was statistically associated with inhalation injury (p=0,0001), injury depth B (p=0,00001) and use of MRA (p=0,0011). Conclusion: The results of this study conclude that male sex, the age group <5 years, admissions in autumn-winter, fire injuries, the critical severity group and the use of MRA are predominant epidemiological data corresponding to a Unit of High Complexity Burns and must be taken into account for the planning and adaptation of care resources

Pointing in cervical dystonia patients

IntroductionThe normal hemispheric balance can be altered by the asymmetric sensorimotor signal elicited by Cervical Dystonia (CD), leading to motor and cognitive deficits.MethodsDirectional errors, peak velocities, movement and reaction times of pointing towards out-of-reach targets in the horizontal plane were analysed in 18 CD patients and in 11 aged-matched healthy controls.ResultsCD patients displayed a larger scatter of individual trials around the average pointing direction (variable error) than normal subjects, whatever the arm used, and the target pointed. When pointing in the left hemispace, all subjects showed a left deviation (constant error) with respect to the target position, which was significantly larger in CD patients than controls, whatever the direction of the abnormal neck torsion could be. Reaction times were larger and peak velocities lower in CD patients than controls.DiscussionDeficits in the pointing precision of CD patients may arise from a disruption of motor commands related to the sensorimotor imbalance, from a subtle increase in shoulder rigidity or from a reduced agonists activation. Their larger left bias in pointing to left targets could be due to an increased right parietal dominance, independently upon the direction of head roll/jaw rotation which expands the left space representation and/or increases left spatial attention. These deficits may potentially extend to tracking and gazing objects in the left hemispace, leading to reduced skills in spatial-dependent motor and cognitive performance

The path from trigeminal asymmetry to cognitive impairment: a behavioral and molecular study

Trigeminal input exerts acute and chronic effects on the brain, modulating cognitive functions. Here, new data from humans and animals suggest that these effects are caused by trigeminal influences on the Locus Coeruleus (LC). In humans subjects clenching with masseter asymmetric activity, occlusal correction improved cognition, alongside with reductions in pupil size and anisocoria, proxies of LC activity and asymmetry, respectively. Notably, reductions in pupil size at rest on the hypertonic side predicted cognitive improvements. In adult rats, a distal unilateral section of the trigeminal mandibular branch reduced, on the contralateral side, the expression of c-Fos (brainstem) and BDNF (brainstem, hippocampus, frontal cortex). This counterintuitive finding can be explained by the following model: teeth contact perception loss on the lesioned side results in an increased occlusal effort, which enhances afferent inputs from muscle spindles and posterior periodontal receptors, spared by the distal lesion. Such effort leads to a reduced engagement of the intact side, with a corresponding reduction in the afferent inputs to the LC and in c-Fos and BDNF gene expression. In conclusion, acute effects of malocclusion on performance seem mediated by the LC, which could also contribute to the chronic trophic dysfunction induced by loss of trigeminal input