Proximal femoral excision with interposition myoplasty for cerebral palsy patients with painful chronic hip dislocation

Purpose: Proximal femoral excision is a salvage procedure for painful chronic hip dislocation in cerebral palsy (CP) patients. The primary objective of this article is to describe our experience of an amplified interposition myoplasty, with appropriate peri-operative pain and tone management strategies, in a cohort of non-ambulatory CP patients with painful chronic hip dislocation. Our secondary objective is to present the clinical outcomes of these patients. Methods: We describe our experience in 20 CP patients (25 procedures) at mean 54-month (range 27–169) follow-up with a surgical technique that includes an augmented interposition myoplasty and tone management. The indications for surgery were pain (21 hips), poor sitting tolerance (11) and difficulty with perineal care (8). Results: The mean age was 22 years (range 10–40) with 11 patients Gross Motor Function Classification Scale (GMFCS) IV and 9 patients GMFCS V. Mean length of stay was 13 days (3–35). One procedure required revision at 12 months. Mean pain score improved from 7.8 (5–10) pre-operatively to 2.8 (1–5) post-operatively (p  <  0.001). Sitting tolerance improved in all patients and in 75 % (15) perineal care was easier. Conclusions: Our interposition myoplasty technique with individualised pain/tone management has good outcomes in this cohort of patients with multiple co-morbidities

Posteromedial bowing of the tibia: A benign condition or a case for limb reconstruction?

PURPOSE: To review the initial deformity and subsequent remodelling in posteromedial bowing of the tibia and the outcome of limb reconstruction in this condition. PATIENTS AND METHODS: In all, 38 patients with posteromedial bowing of the tibia presenting between 2000 and 2016 were identified. Mean follow-up from presentation was 78 months. A total of 17 patients underwent lengthening and deformity correction surgery, whilst three further patients are awaiting lengthening and deformity correction procedures. RESULTS: The greatest correction of deformity occurred in the first year of life, but after the age of four years, remodelling was limited. The absolute leg-length discrepancy (LLD) increased throughout growth with a mean 14.3% discrepancy in tibial length. In the lengthening group, mean length gained per episode was 45 mm (35 to 60). Mean duration in frame was 192 days, with a mean healing index of 42.4 days/cm. Significantly higher rates of recurrence in LLD were seen in those undergoing lengthening under the age of ten years (p = 0.046). Four contralateral epiphysiodeses were also performed. CONCLUSION: Posteromedial bowing of the tibia improves spontaneously during the first years of life, but in 20/38 (53%) patients, limb reconstruction was indicated for significant residual deformity and/or worsening LLD. For larger discrepancies and persistent deformity, limb reconstruction with a hexapod external fixator should be considered as part of the treatment options. Level of evidence Level IV (Case series)

Analysing the impact of rescheduling time in hybrid manufacturing control

Hybrid manufacturing control architectures merge the benefits of hierarchical and heterarchical approaches. Disturbances can be handled at upper or lower decision levels, depending on the type of disturbance, its impact and the time the control system has to react. This paper focuses particularly on a disturbance handling mechanism at upper decision levels using a rescheduling manufacturing method. Such rescheduling is more complex that the offline scheduling since the control system must take into account the current system status, obtain a satisfactory performance under the new conditions, and also come up with a new schedule in a restricted amount of time. Then, this paper proposes a simple and generic rescheduling method which, based on the satisfying principle, analyses the trade-off between the rescheduling time and the performance achieved after a perturbation. The proposed approach is validated on a simulation model of a realistic assembly cell and results demonstrate that adaptation of the rescheduling time might be beneficial in terms of overall performance and reactivity.info:eu-repo/semantics/publishedVersio

Mutational analysis of the PITX2 coding region revealed no common cause for transposition of the great arteries (dTGA)

BACKGROUND: PITX2 is a bicoid-related homeodomain transcription factor that plays an important role in asymmetric cardiogenesis. Loss of function experiments in mice cause severe heart malformations, including transposition of the great arteries (TGA). TGA accounts for 5–7% of all congenital heart diseases affecting 0.2 per 1000 live births, thereby representing the most frequent cyanotic heart defect diagnosed in the neonatal period. METHODS: To address whether altered PITX2 function could also contribute to the formation of dTGA in humans, we screened 96 patients with dTGA by means of dHPLC and direct sequencing for mutations within the PITX2 gene. RESULTS: Several SNPs could be detected, but no stop or frame shift mutation. In particular, we found seven intronic and UTR variants, two silent mutations and two polymorphisms within the coding region. CONCLUSION: As most sequence variants were also found in controls we conclude that mutations in PITX2 are not a common cause of dTGA

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients

<p>Abstract</p> <p>Background</p> <p>Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells <it>in vitro</it>.</p> <p>Methods</p> <p>RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells <it>in vitro </it>with MTT assays and matrigel transwell assay respectively.</p> <p>Results</p> <p>RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy.</p

Endocytosis of DNA-Hsp65 Alters the pH of the Late Endosome/Lysosome and Interferes with Antigen Presentation

BACKGROUND: Experimental models using DNA vaccine has shown that this vaccine is efficient in generating humoral and cellular immune responses to a wide variety of DNA-derived antigens. Despite the progress in DNA vaccine development, the intracellular transport and fate of naked plasmid DNA in eukaryotic cells is poorly understood, and need to be clarified in order to facilitate the development of novel vectors and vaccine strategies. METHODOLOGY AND PRINCIPAL FINDINGS: Using confocal microscopy, we have demonstrated for the first time that after plasmid DNA uptake an inhibition of the acidification of the lysosomal compartment occurs. This lack of acidification impaired antigen presentation to CD4 T cells, but did not alter the recruitment of MyD88. The recruitment of Rab 5 and Lamp I were also altered since we were not able to co-localize plasmid DNA with Rab 5 and Lamp I in early endosomes and late endosomes/lysosomes, respectively. Furthermore, we observed that the DNA capture process in macrophages was by clathrin-mediated endocytosis. In addition, we observed that plasmid DNA remains in vesicles until it is in a juxtanuclear location, suggesting that the plasmid does not escape into the cytoplasmic compartment. CONCLUSIONS AND SIGNIFICANCE: Taken together our data suggests a novel mechanism involved in the intracellular trafficking of plasmid DNA, and opens new possibilities for the use of lower doses of plasmid DNA to regulate the immune response