Application of different measures of skeletal maturity in initiating weaning from a brace for scoliosis: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Various measures of skeletal maturity are used to initiate weaning from a brace in patients suffering from idiopathic scoliosis, resulting in different outcomes. We present two cases with double major curves, treated with the Rigo System Cheneau brace, and weaned using different criteria.</p> <p>Case presentation</p> <p>Case 1 was a South African, Caucasian girl who was initially treated with a brace at 14.75 years and who began weaning at 16.25 years on the basis of the Greulich and Pyle Index. She was out of her brace in 6 months, at least 11 months before reaching skeletal maturity as shown by the Risser Sign. Case 2 was a South African, Caucasian girl, initially treated with a brace at 14.25 years and who began the weaning process at 17.67 years on the basis of skeletal maturity according to the Risser Sign and static height for a period of 6 months. She was out of the brace 12 months later. In Case 1, the thoracic Cobb angle progressed during weaning and scoliometer readings deteriorated. The iliac apophysis fused 11 months after the wrist. In Case 2, the therapeutic gains made during the period of bracing were maintained during weaning, that is the improvement in the lumbar Cobb angle was maintained until the brace was removed, and scoliometer readings improved. The iliac apophysis fused 8.5 months after the wrist.</p> <p>Conclusions</p> <p>In patients with idiopathic scoliosis, it would seem to be more appropriate to base the timing of weaning on the Risser Sign and static height measurements rather than on traditional methods such as the Greulich and Pyle Index.</p

The relationship between quality of life and compliance to a brace protocol in adolescents with idiopathic scoliosis: a comparative study

<p>Abstract</p> <p>Background</p> <p>Corrective bracing for adolescent idiopathic scoliosis (AIS) has favourable outcomes when patients are compliant. However, bracing may be a stressful and traumatic experience and compliance with a bracing protocol is likely to be dependent upon patients' physical, emotional and social wellbeing. The Brace Questionnaire (BrQ), a recently-developed, condition-specific tool to measure quality of life (QOL) has enabled clinicians to study relationships between QOL and compliance.</p> <p>Methods</p> <p>The BrQ was administered to 31 AIS patients after a minimum of 1 year of wearing a brace. Subjects were 13–16 year old South African girls with Cobb angles of 25–40 degrees. Participants were divided into two groups according to their level of compliance with the bracing protocol. Brace Questionnaire sub- and total scores were compared between the two groups using the t-test for comparison of means.</p> <p>Results</p> <p>Twenty participants were classified as compliant and 11 as non-compliant. Mean total BrQ scores (expressed as a percentage) were 83.7 for the compliant group and 64.4 for the non-compliant group (p < 0.001), and on analysis of the 8 domains that make up the BrQ, the compliant group scored significantly higher in the 6 domains that measured vitality and social, emotional and physical functioning.</p> <p>Conclusion</p> <p>Poor compliance with a brace protocol is associated with poorer QOL, with non-compliant patients lacking vitality and functioning poorly physically, emotionally and socially. Quality of life for adolescents with idiopathic scoliosis may relate more to psychosocial coping mechanisms than to physical deformity and its consequences. It is important to establish whether remedial programmes are capable of addressing personal, group and family issues, improving QOL and promoting compliance.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Aggression, anxiety and vocalizations in animals: GABA A and 5-HT anxiolytics

A continuing challenge for preclinical research on anxiolytic drugs is to capture the affective dimension that characterizes anxiety and aggression, either in their adaptive forms or when they become of clinical concern. Experimental protocols for the preclinical study of anxiolytic drugs typically involve the suppression of conditioned or unconditioned social and exploratory behavior (e.g., punished drinking or social interactions) and demonstrate the reversal of this behavioral suppression by drugs acting on the benzodiazepine-GABA A complex. Less frequently, aversive events engender increases in conditioned or unconditioned behavior that are reversed by anxiolytic drugs (e.g., fear-potentiated startle). More recently, putative anxiolytics which target 5-HT receptor subtypes produced effects in these traditional protocols that often are not systematic and robust. We propose ethological studies of vocal expressions in rodents and primates during social confrontations, separation from social companions, or exposure to aversive environmental events as promising sources of information on the affective features of behavior. This approach focusses on vocal and other display behavior with clear functional validity and homology. Drugs with anxiolytic effects that act on the benzodiazepine-GABA A receptor complex and on 5-HT 1A receptors systematically and potently alter specific vocalizations in rodents and primates in a pharmacologically reversible manner; the specificity of these effects on vocalizations is evident due to the effectiveness of low doses that do not compromise other physiological and behavioral processes. Antagonists at the benzodiazepine receptor reverse the effects of full agonists on vocalizations, particularly when these occur in threatening, startling and distressing contexts. With the development of antagonists at 5-HT receptor subtypes, it can be anticipated that similar receptor-specificity can be established for the effects of 5-HT anxiolytics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46351/1/213_2005_Article_BF02245590.pd

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease