Treatment of thoraco-lumbar curves in adolescent females affected by idiopathic scoliosis with a progressive action short brace (PASB): assessment of results according to the SRS committee on bracing and nonoperative management standardization criteria

<p>Abstract</p> <p>Background</p> <p>The effectiveness of conservative treatment of scoliosis is controversial. Some studies suggest that brace is effective in stopping curve progression, whilst others did not report such an effect.</p> <p>The purpose of the present study was to effectiveness of Progressive Action Short Brace (PASB) in the correction of thoraco-lumbar curves, in agreement with the Scoliosis Research Society (SRS) Committee on Bracing and Nonoperative Management Standardisation Criteria.</p> <p>Methods</p> <p>Fifty adolescent females (mean age 11.8 ± 0.5 years) with thoraco-lumbar curve and a pre-treatment Risser score ranging from 0 to 2 have been enrolled. The minimum duration of follow-up was 24 months (mean: 55.4 ± 44.5 months). Antero-posterior radiographs were used to estimate the curve magnitude (C_M) and the torsion of the apical vertebra (T_A) at 5 time points: beginning of treatment (t₁), one year after the beginning of treatment (t₂), intermediate time between t₁and t₄(t₃), end of weaning (t₄), 2-year minimum follow-up from t₄(t₅). Three situations were distinguished: curve correction, curve stabilisation and curve progression.</p> <p>The Kruskal Wallis and Spearman Rank Correlation tests have been used as statistical tests.</p> <p>Results</p> <p>C_Mmean value was 29,30 ± 5,16 SD at t₁and 14,67 ± 7,65 SD at t₅. T_Awas 12.70 ± 6,14 SD at t₁and 8,95 ± 5,82 at t₅. The variation between measures of Cobb and Perdriolle degrees at t_1,2,3,4,5and between C_Mt₅-t₁and T_At₅-t₁were significantly different.</p> <p>Curve correction was accomplished in 94% of patients, whereas a curve stabilisation was obtained in 6% of patients.</p> <p>Conclusion</p> <p>The PASB, due to its peculiar biomechanical action on vertebral modelling, is highly effective in correcting thoraco-lumbar curves.</p

Determination of quality of life in adolescents with idiopathic scoliosis subjected to conservative treatment.

<p>Abstract</p> <p>Introduction and objectives</p> <p>Physical deformities caused by adolescent idiopathic scoliosis (AIS) coupled with conservative treatment of AIS with orthesis unavoidably impacts on patients' quality of life (QoL). The present study aimed at evaluating the QoL in patients affected by AIS treated with brace. The study also sought to determine the ability of different QoL questionnaires to monitor QoL over the course of treatment.</p> <p>Materials and methods</p> <p>Data were collected in 108 consecutive patients (96 females, 16 males) affected by AIS admitted to the outpatient orthopaedic clinic of the Catholic University of the Sacred Heart in Rome (Italy). Patients were subjected to full-time (i.e., 22 hrs per day) conservative treatment with the progressive action short brace (PASB), the Lyon brace or a combination of PASB + Lyon brace. Three instruments were used for QoL determination: the Scoliosis Research Society 22 (SRS-22), Bad Sobernheim Stress Questionnaire (BSSQ) and the Brace Questionnaire (BrQ).</p> <p>Results</p> <p>A significant correlation was detected among the 3 scores (p < 0.001). The BrQ possesses a higher capacity to detect changes in QoL in relation to the patient gender, type of brace, curve severity at baseline and at the completion of treatment, and curve type. Overall, boys displayed a higher QoL than girls. In all 3 questionnaires, higher QoL scores were determined in patients treated with the PASB compared with those using the Lyon brace. QoL scores were significantly correlated with the curve severity. Higher QoL scores were obtained by participants with thoraco-lumbar curves as compared with those with other curves.</p> <p>Conclusions</p> <p>The 3 questionnaires are effective in capturing changes in QoL in AIS patients subjected to conservative treatment. However, the BrQ possesses a higher discriminatory capacity compared with the other questionnaires tested. PASB-based treatment is associated with better QoL than the Lyon bracing.</p

Filarial Lymphedema Is Characterized by Antigen- Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells

Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Methods and Findings: To elucidate the role of CD4+ T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1–10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher production of Th1-type cytokines—IFN-c and TNF-a—in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines—IL-17A, IL-17F, IL-21, and IL-23—was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFb, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls. Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema

Insights into the Complex Formed by Matrix Metalloproteinase-2 and Alloxan Inhibitors: Molecular Dynamics Simulations and Free Energy Calculations

Matrix metalloproteinases (MMP) are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A) in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S1′ specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S1′ subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC50 = 7.06) is found for BAM, a compound exhibiting also selectivity (>20) towards MMP-2, as compared to MMP-9, the other member of the gelatinases