The impact of a corrective tether on a scoliosis porcine model: a detailed 3D analysis with a 20 weeks follow-up

Purpose

Non-fusion treatment for adolescent idiopathic scoliosis generates interest due to the potential for growth preservation and mobility. Using an established porcine scoliotic model, this study aims to evaluate the global alignment and the morphology of the spine with and without application of a non-fusion corrective tether.

Methods

At 12 weeks of age, 21 immature Yorkshire pigs had an induction of scoliosis. Once a 50° Cobb angle was obtained; animals were placed into one of the following groups: a scoliosis model group (SM, n = 11) where animals were euthanized, tether release group (TR, n = 5) where the inducing tether was removed, and an anterior correction group (AC, n = 5) where the inducing tether was removed and non-fusion corrective tether was applied. TR and AC were observed for a further 20 weeks and then euthanized. Post-mortem CT scans were used to create 3D spinal reconstructions to obtain global and morphologic parameters.

Results

Maximal Cobb angle of the scoliotic deformity was significantly lower for AC (27.9° ± 12.0°) than for the two other groups (TR 52.7° ± 10.0°, SM 48.3° ± 7.6°). AC experienced an increase in kyphosis (24.2° ± 15.9°) compared to TR (7.1° ± 6.4°). Correction in the axial plane was also observed in AC versus TR. Correction of vertebral wedging was found for AC compared to SM and TR in the three apical vertebrae.

Conclusions

3D realignment of scoliotic curves was observed with application of the corrective tether. The correction was the product of both mechanical action and growth modulation. These findings are encouraging for future development of a non-fusion device for the treatment of immature scoliotic curves.     

Double dissociation of a latent working memory process

Background. The study explored the construct validity of a computational model of working memory (WM) by determining whether model parameters manifested double dissociations of lesion laterality with type of material studied. The data set modeled involved psychometrically matched verbal and figural WM tasks on which a double dissociation between test version and lesion laterality failed to emerge when total test scores were used as the laterality marker. Method. This re-analysis of a previously published study involved investigating the WM performance of 15 demographically matched controls with 15 adult patients with left-hemispheric (LH) lesions and 15 adult patients with right-hemispheric (RH) lesions. Each participant was given verbal and figural versions of a continuous paired associates test (CPAT). The two versions had previously been psychometrically matched in a larger sample of healthy individuals. A WM model composed of encoding, displacement, and episodic memory parameters was fit to each individual’s performance profiles for both versions of the CPAT. Results. Replicating the previous results for raw scores, rank transformed values of total score performance failed to reveal a double dissociation. Nonetheless an absolute double dissociation was observed for the model’s displacement parameter: RH patients demonstrated deficits on the figural but not verbal WM displacement parameter, whereas LH patients demonstrated deficits on the verbal but not figural WM displacement parameter. Additionally, both LH and RH patients were impaired on the figural encode parameter, perhaps explaining the absence of a double dissociation in total score performance. Conclusions. By combining different patterns of profile and level data into theoretically motivated model parameters, computational models of neurocognition can enhance the construct validity of interpretations of neuropsychological performance.     

Fabry disease: a review

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result is intralysosomal accumulation of glycosphingolipids. In males who carry the mutation (1/40,000), severe multisystem disease develops in childhood or adolescence. Attacks of acute pain lasting a few minutes to a few days occur in the hands and feet, joints, muscles, and abdomen, sometimes with a fever. Highly suggestive skin lesions called angiokeratomas develop, as well as cornea verticillata characterized by corneal deposits without visual impairment. Stroke, seizures, heart disorders (conduction disturbances, valve disease, and left heart failure) and kidney disorders (proteinuria and chronic renal failure) develop in the third or fourth decade of life. Women who are heterozygous for the Gal gene can transmit the disease to their sons but are usually free of symptoms, although many have cornea verticillata. However, they may have moderate or severe disease related to uneven chromosome X inactivation. Late-onset variants with predominant neurological, cardiac, or renal manifestations have been described. The diagnosis is difficult when the family history is negative for Fabry disease. Tests on plasma and leukocytes show very low levels of alpha GalA activity in affected men, confirming the diagnosis. The Gal gene mutation should be looked for to detect heterozygous women. Symptomatic treatments include analgesics, antihypertensives, antiplatelet agents or anticoagulants to treat ischemic events, and hemodialysis or kidney transplantation to treat chronic renal failure. The recent introduction of enzyme replacement therapy with recombinant agalsidase alpha or beta has been a major breakthrough in the treatment of Fabry disease. Enzyme replacement therapy relieves the pain and decreases the risk of complications. The safety profile is good. Given the high cost of agalsidase therapy (about 160,000 euro/year/patient) and the low incidence of Fabry disease, patients should be referred to highly specialized centers (see addresses on the France Orphanet web site).     

Effect of the TNF-alpha-promoter polymorphism on cardiac allograft rejection.

BACKGROUND: A polymorphism exists in the tumor necrosis factor alpha (TNF-alpha) promoter (position -308, G/A = TNFA1/TNFA2). The TNFA2 allele is associated with increased TNF-alpha production in vitro and has been reported to increase the risk of allograft rejection in pediatric recipients of cardiac transplantation. We examined the effect of the TNFA2 allele on the risk of allograft rejection in adult cardiac transplant recipients. METHODS: We prospectively analyzed 57 subjects (aged 54 +/- 11 years, 84% men, 49% ischemic) who underwent cardiac transplantation between October 1996 and July 2001. Patients were observed after transplantation (mean, 910 +/- 605 days) and the frequency of allograft rejection (biopsy Grade > or =2) in patients with the TNFA2 allele (Group A, n = 15) was compared with TNFA1 homozygotes (Group B, n = 42). Overall survival and time to rejection episodes also were compared between groups. RESULTS: The frequency of allograft rejection was similar between groups (Group A, 8/15 [56%]; Group B, 22/42 [52%]; p = 0.77). Time to rejection also was comparable (Group A, 17 +/- 11 days; Group B, 20 +/- 20 days, p = 0.74). Overall post-transplant survival was similar between groups (1- and 2-year percentage survival: Group A, 87% and 78%, Group B, 88% and 82%, p = 0.35). CONCLUSION: The TNFA2 allele was not associated with increased risk of rejection in adult cardiac transplant recipients. The impact of this polymorphism on overall post-transplant outcomes will require investigation in larger multicenter studies.     

Early prediction of IgA nephropathy progression: proteinuria and AOPP are strong prognostic markers

BACKGROUND: Inflammation and oxidative stress have been incriminated in the pathogenesis of IgA nephropathy (IgAN). The aim of the present study was to assess whether markers reflecting these pathophysiologic processes, namely C-reactive protein (CRP) and advanced oxidation protein products (AOPP), would allow-in conjunction with clinical and histopathologic parameters-to predict disease progression. METHODS: Between 1994 and 1997, 120 adult patients with biopsy-proven IgAN were included in a prospective cohort study, and followed until the end of 2002 or start of dialysis. In every patient, we determined plasma levels of CRP and AOPP. These parameters were included, together with clinical data, in a multivariate Cox proportional hazard regression analysis, with halving of baseline creatinine clearance as the primary renal end point. RESULTS: A total of 51 patients reached the renal end point, including 30 who had to start dialysis. With multivariate analysis, the most potent independent risk factors of poor renal outcome were proteinuria > or =1 g/day [proportional hazard risk (HR) = 23.7, P= 0.0001], hypertension (HR = 8.13, P= 0.008), and AOPP plasma level (HR = 1.09 per 10 micromol/L, P= 0.042), whereas angiotensin II inhibitors were protective (HR = 0.19, P= 0.001). CONCLUSION: Our data support the role of oxidative stress in the pathogenesis of IgAN and suggest that patients with proteinuria > or =1 g/day should be eligible for early implemented antioxidant and/or anti-inflammatory therapeutic strategies, with AOPP plasma level as a surrogate marker to evaluate their effects.     

Alterations in neural systems mediating cognitive flexibility and inhibition in mood disorders

Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task‐switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto‐parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed. Hum Brain Mapp 37:1335‐1348, 2016. © 2016 Wiley Periodicals, Inc.     

A total ban on alcohol advertising: presenting the public health case

Evidence from burden of disease and economic costing studies amply indicate that the public health burden from hazardous and harmful use of alcohol in South Africa warrants drastic action. Evidence that banning alcohol advertising is likely to be an effective intervention is reflected in WHO strategy documents on non-communicable diseases and harmful use of alcohol. Studies on young people furthermore support arguments refuting the claim that advertising only influences brand choice. Given the weakness of relying on industry self-regulation, the government is considering legislation to ban alcohol advertising, resulting in heated debate. Tobacco control and studies investigating the effect of alcohol advertising bans on consumption and alcohol-related deaths point to the effectiveness of such action - ideally supplemented by other policy interventions. Arguments against an advertising ban include possible communication sector job losses, but these are likely to have been exaggerated. Banning alcohol advertising will necessitate greater scrutiny of digital media, satellite television and merchandising to reduce the likelihood of subverting the ban.