Severity predictors for multisystemic inflammatory syndrome in children after SARS-CoV-2 infection in Vietnam.

Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children's Hospital from January 2022 to June 2023. The median age was 85 (range: 2-188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2-7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39-4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63-6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 109/L) (OR 2.18, 95% CI 1.29-3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38-4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28-4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 109/L) (OR 2.48, 95% CI 1.10-5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22-5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12-4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.

[Long-term outcome of 48 unoperated adult patients with Ebstein's anomaly].

Objective: To analyze the long-term outcome of unoperated Ebstein's anomaly (EA) patients aged over 18 years, and to evaluate the related factor of outcomes. Methods: The data of 48 unoperated EA patients from March 2004 to December 2008 in the First Hospital of Tsinghua University, were analyzed. The clinical data of the patients were collected, and patients received regular echocardiography, ECG and chest X-ray examinations. Septal leaflet attachment ratio (SLAr) was calculated based on transthoracic echocardiography imagines. The patients were divided into 3 groups according to SLAr: SLAr<0.45 (n=18), 0.45≤SLAr≤0.60 (n=21) and SLAr>0.60 (n=9). Chest X-ray was used for measurement of cardiothoracic ratio (CTR). Kaplan Meier survival curve was used to calculate the long-term survival rate. Cox proportional hazards regression model was used to analyze the influencing factors of death. Results: There were 19 males, and the mean age at diagnosis was (21.3±11.1) years. Forty-two patients (87.5%) were complicated with arrhythmia, including W-P-W syndrome (n=4), supraventricular tachycardia (n=16), right bundle branch block (n=37), and atrial fibrillation (n=2). The mean duration of follow-up was (148.8±16.8) months, the follow-up rate was 100% with no loss-to-follow up. Nine cases (18.8%) died during follow-up: 6 cases (12.5%) died of cardiac origin, including 3 cases of heart failure, 1 case of arrhythmia, and 2 cases of sudden death; 1 case died of accident; 2 cases died from unknown causes. During the follow-up period, the survival rates were 17/18, 19/21 (90.5%) and 3/9 in the SLAr<0.45, 0.45≤SLAr≤0.60 and SLAr>0.60 group, respectively. According to Kaplan-Meier survival curve, the 5-year survival rates among the three groups were 100%, 100% and 78%, respectively. The 10-year survival rates among the three groups were 94%, 95% and 44%, respectively. Decreased activity tolerance and heart failure were found in 7 patients (6 patients in SLAr>0.60 group and 1 patient in 0.45≤SLAr≤0.60 group). Two patients had cerebrovascular embolism. There were 3 cases with tachyarrhythmia lasting more than 24 hours. Cox regression analysis showed that the risk of death was higher in patients with SLAr>0.60 than in patients with SLAr<0.45 (HR=12.375, 95%CI 1.692-22.146, P=0.015); the risk of death in patients with CTR≥0.65 was 1.306 times higher than that in patients with CTR<0.65 (HR=1.306, 95%CI 0.417-12.754, P=0.038). Conclusions: EA patients often combines with arrhythmia. For unoperated EA patients, SLAr>0.60 and CTR≥0.65 are risk factors of death. EA patients with arrhythmia should be actively treated with drugs or radiofrequency ablation.

[Analysis of incidence and risk factors of neonatal ventilator associated pneumonia in a hospital in Hunan Province, 2016-2018].

Objective: To investigate the incidence and risk factors of ventilator-associated pneumonia (VAP) in neonatal intensive care unit (NICU), and to provide evidence for the prevention and control of VAP. Methods: A total of 1 872 neonates, who were admitted into NICU of Hunan Provincial Maternal and Child Health Hospital and subjected to mechanical ventilation from October 2016 to June 2018, were enrolled in the study. The neonates who met the diagnostic criteria of VAP were selected as the case group, and those who were treated with ventilator for 48 hours at the same time were regarded as the control group. Multivariate logistic regression model was used to analyze the related factors of VAP. Results: Of the 1 872 neonates who underwent the mechanical ventilation, the VAP occurred in 160 cases with the incidence rate of 8.5% (160 cases). The 227 specimens were collected. Gram-positive bacteria (n=116, 51.1%) were the main pathogens. The main pathogens were Staphylococcus epidermidis, Enterococcus faecalis, Acinetobacter baumannii. By Chi-square test, birth weight, birth age, Apgar score, duration of ventilator, and whether newborn mothers with pregnancy hypertension were influencing factors. The result of logistic regression analysis showed that compared with no pregnancy included hypertension, the first aid measure at birth was initial resuscitation, and the MV time ≤ 5 days, the risk factors of ventilator-associated pneumonia in neonates included: their mothers with hypertensive disorders complicating pregnancy, using of tracheal intubation and ventilator time more than 5 days. Conclusion: The incidence of VAP in neonates receiving continuous MV therapy in neonatal intensive care unit is higher. Gram-positive bacteria are the main pathogens. VAP in neonates is related to whether newborn mothers with pregnancy hypertension, MV duration and tracheal intubation.

Dusp6 is a genetic modifier of growth through enhanced ERK activity.

Like other single-gene disorders, muscular dystrophy displays a range of phenotypic heterogeneity even with the same primary mutation. Identifying genetic modifiers capable of altering the course of muscular dystrophy is one approach to deciphering gene-gene interactions that can be exploited for therapy development. To this end, we used an intercross strategy in mice to map modifiers of muscular dystrophy. We interrogated genes of interest in an interval on mouse chromosome 10 associated with body mass in muscular dystrophy as skeletal muscle contributes significantly to total body mass. Using whole-genome sequencing of the two parental mouse strains combined with deep RNA sequencing, we identified the Met62Ile substitution in the dual-specificity phosphatase 6 (Dusp6) gene from the DBA/2 J (D2) mouse strain. DUSP6 is a broadly expressed dual-specificity phosphatase protein, which binds and dephosphorylates extracellular-signal-regulated kinase (ERK), leading to decreased ERK activity. We found that the Met62Ile substitution reduced the interaction between DUSP6 and ERK resulting in increased ERK phosphorylation and ERK activity. In dystrophic muscle, DUSP6 Met62Ile is strongly upregulated to counteract its reduced activity. We found that myoblasts from the D2 background were insensitive to a specific small molecule inhibitor of DUSP6, while myoblasts expressing the canonical DUSP6 displayed enhanced proliferation after exposure to DUSP6 inhibition. These data identify DUSP6 as an important regulator of ERK activity in the setting of muscle growth and muscular dystrophy.

Management of acute Achilles tendon ruptures: A review.

OBJECTIVES: The incidence of acute Achilles tendon rupture appears to be increasing. The aim of this study was to summarize various therapies for acute Achilles tendon rupture and discuss their relative merits. METHODS: A PubMed search about the management of acute Achilles tendon rupture was performed. The search was open for original manuscripts and review papers limited to publication from January 2006 to July 2017. A total of 489 papers were identified initially and finally 323 articles were suitable for this review. RESULTS: The treatments of acute Achilles tendon rupture include operative and nonoperative treatments. Operative treatments mainly consist of open repair, percutaneous repair, mini-open repair, and augmentative repair. Traditional open repair has lower re-rupture rates with higher risks of complications. Percutaneous repair and mini-open repair show similar re-rupture rates but lower overall complication rates when compared with open repair. Percutaneous repair requires vigilance against nerve damage. Functional rehabilitation combining protected weight-bearing and early controlled motion can effectively reduce re-rupture rates with satisfactory outcomes. Biological adjuncts help accelerating tendon healing by adhering rupture ends or releasing highly complex pools of signalling factors. CONCLUSION: The optimum treatment for complete rupture remains controversial. Both mini-open repair and functional protocols are attractive alternatives, while biotherapy is a potential future development.Cite this article: X. Yang, H. Meng, Q. Quan, J. Peng, S. Lu, A. Wang. Management of acute Achilles tendon ruptures: A review. Bone Joint Res 2018;7:561-569. DOI: 10.1302/2046-3758.710.BJR-2018-0004.R2.

CD95/Fas ligand mRNA is toxic to cells.

CD95/Fas ligand binds to the death receptor CD95 to induce apoptosis in sensitive cells. We previously reported that CD95L mRNA is enriched in sequences that, when converted to si/shRNAs, kill all cancer cells by targeting critical survival genes (Putzbach et al., 2017). We now report expression of full-length CD95L mRNA itself is highly toxic to cells and induces a similar form of cell death. We demonstrate that small (s)RNAs derived from CD95L are loaded into the RNA induced silencing complex (RISC) which is required for the toxicity and processing of CD95L mRNA into sRNAs is independent of both Dicer and Drosha. We provide evidence that in addition to the CD95L transgene a number of endogenous protein coding genes involved in regulating protein translation, particularly under low miRNA conditions, can be processed to sRNAs and loaded into the RISC suggesting a new level of cell fate regulation involving RNAi.

6mer seed toxicity in tumor suppressive microRNAs.

Many small-interfering (si)RNAs are toxic to cancer cells through a 6mer seed sequence (positions 2-7 of the guide strand). Here we performed an siRNA screen with all 4096 6mer seeds revealing a preference for guanine in positions 1 and 2 and a high overall G or C content in the seed of the most toxic siRNAs for four tested human and mouse cell lines. Toxicity of these siRNAs stems from targeting survival genes with C-rich 3'UTRs. The master tumor suppressor miRNA miR-34a-5p is toxic through such a G-rich 6mer seed and is upregulated in cells subjected to genotoxic stress. An analysis of all mature miRNAs suggests that during evolution most miRNAs evolved to avoid guanine at the 5' end of the 6mer seed sequence of the guide strand. In contrast, for certain tumor-suppressive miRNAs the guide strand contains a G-rich toxic 6mer seed, presumably to eliminate cancer cells.

Efficient exon skipping of SGCG mutations mediated by phosphorodiamidate morpholino oligomers.

Exon skipping uses chemically modified antisense oligonucleotides to modulate RNA splicing. Therapeutically, exon skipping can bypass mutations and restore reading frame disruption by generating internally truncated, functional proteins to rescue the loss of native gene expression. Limb-girdle muscular dystrophy type 2C is caused by autosomal recessive mutations in the SGCG gene, which encodes the dystrophin-associated protein γ-sarcoglycan. The most common SGCG mutations disrupt the transcript reading frame abrogating γ-sarcoglycan protein expression. In order to treat most SGCG gene mutations, it is necessary to skip 4 exons in order to restore the SGCG transcript reading frame, creating an internally truncated protein referred to as Mini-Gamma. Using direct reprogramming of human cells with MyoD, myogenic cells were tested with 2 antisense oligonucleotide chemistries, 2'-O-methyl phosphorothioate oligonucleotides and vivo-phosphorodiamidate morpholino oligomers, to induce exon skipping. Treatment with vivo-phosphorodiamidate morpholino oligomers demonstrated efficient skipping of the targeted exons and corrected the mutant reading frame, resulting in the expression of a functional Mini-Gamma protein. Antisense-induced exon skipping of SGCG occurred in normal cells and those with multiple distinct SGCG mutations, including the most common 521ΔT mutation. These findings demonstrate a multiexon-skipping strategy applicable to the majority of limb-girdle muscular dystrophy 2C patients.

Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.

Trinucleotide repeat (TNR) expansions in the genome cause a number of degenerative diseases. A prominent TNR expansion involves the triplet CAG in the huntingtin (HTT) gene responsible for Huntington's disease (HD). Pathology is caused by protein and RNA generated from the TNR regions including small siRNA-sized repeat fragments. An inverse correlation between the length of the repeats in HTT and cancer incidence has been reported for HD patients. We now show that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complementary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the six members in the CAG/CUG family of related TNRs are the most toxic to both human and mouse cancer cells. siCAG/CUG TNR-based siRNAs induce cell death in vitro in all tested cancer cell lines and slow down tumor growth in a preclinical mouse model of ovarian cancer with no signs of toxicity to the mice. We propose to explore TNR-based siRNAs as a novel form of anticancer reagents.

DISE: A Seed-Dependent RNAi Off-Target Effect That Kills Cancer Cells.

Off-target effects (OTEs) represent a significant caveat for RNAi caused by substantial complementarity between siRNAs and unintended mRNAs. We now discuss the existence of three types of seed-dependent OTEs (sOTEs). Type I involves unintended targeting through the guide strand seed of an siRNA. Type II is caused by the activity of the seed on the designated siRNA passenger strand when loaded into the RNA-induced silencing complex (RISC). Both type I and II sOTEs will elicit unpredictable cellular responses. By contrast, in sOTE type III the guide strand seed preferentially targets essential survival genes resulting in death induced by survival gene elimination (DISE). In this Opinion article, we discuss DISE as a consequence of RNAi that may preferentially affect cancer cells.

Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism.

Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3'UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that specific toxic RNAi-active sequences present in the genome can kill cancer cells.

Thrombospondin expression in myofibers stabilizes muscle membranes.

Skeletal muscle is highly sensitive to mutations in genes that participate in membrane stability and cellular attachment, which often leads to muscular dystrophy. Here we show that Thrombospondin-4 (Thbs4) regulates skeletal muscle integrity and its susceptibility to muscular dystrophy through organization of membrane attachment complexes. Loss of the Thbs4 gene causes spontaneous dystrophic changes with aging and accelerates disease in 2 mouse models of muscular dystrophy, while overexpression of mouse Thbs4 is protective and mitigates dystrophic disease. In the myofiber, Thbs4 selectively enhances vesicular trafficking of dystrophin-glycoprotein and integrin attachment complexes to stabilize the sarcolemma. In agreement, muscle-specific overexpression of Drosophila Tsp or mouse Thbs4 rescues a Drosophila model of muscular dystrophy with augmented membrane residence of ßPS integrin. This functional conservation emphasizes the fundamental importance of Thbs' as regulators of cellular attachment and membrane stability and identifies Thbs4 as a potential therapeutic target for muscular dystrophy.

[Multi-centric clinical study of trial of labor after cesarean section].

OBJECTIVE: To study the feasibility and safety of trial of labor after cesarean section (TOLAC). METHODS: Retrospective analysis of five medical center of Guangdong province from January 2011 to December 2015 hospitalized delivery information, compare the same scar TOLAC (research group) with the scar pregnancy (control group) pregnancy outcomes, to study the feasibility and safety of TOLAC. RESULTS: (1) During 2011-2015, total delivery 95 600 cases in five medical center, 13 824 cases of thme with uterine scar pregnancy, including 12 027 cases elective repeat cesarean section and 1 797 cases (13.00%, 1 797/13 824) with scar uterus vaginal trial of labor. Among 1 308 cases of vaginal delivery, the success for trial of labor rate was 72.79% (1 308/1 797). From 2011 to 2015, there were increased rate of pregnancy after cesarean section, which were respectively 10.71%, 13.28%, 14.45%, 15.54% and 16.98%. The will of vaginal birth were rising and the rate were respectively 11.85%, 12.25%, 13.49%, 13.82% and 12.93%. (2) There were 489 (27.21%, 489/1 797) cases of scar uterus maternal emergency cesarean section in the trial of labor, reason for "social factors" require for cesarean delivery have 68 cases, the percentage was 13.91% (68/489), compared with control group (7.18%, 206/2 869), the difference was statistically significant difference (χ(2)=27.356, P=0.000). Doctors diagnosed as "aura uterine rupture" in the labor was 11.86% (58/489), compared with that in control group (1.43%, 41/2 869), the differences were statistically significant difference (χ(2)=1 578.223, P=0.000). (3) The incidence of uterine rupture of the research group (0.74%, 9/1 211) was significantly higher than that of control group (0.01%,2/31 200; χ(2)> 2 000, P=0.000). The incidence of postpartum hemorrhage in research group was 6.94% (84/1 211), compared with that in the control group (3.05%, 951/31 200), there was statistically significant difference (χ(2)=16.328, P=0.000). While, there were no statistical significancefor the labor time limit, birth rate of severe asphyxia and neonatal birth weight average differences between two groups (P>0.05). CONCLUSIONS: The rate of pregnancy after cesarean section is increasing year by year, and the will of vaginal birth is increasing, while it still are generally low. TOLAC is safe and feasible, but also significantly higher risk, strictly labor monitoring and can proceed fast cesarean delivery in delivery room is an important guarantee of safe delivery.

Overexpression of Latent TGFß Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFß.

Latent TGFß binding proteins (LTBPs) regulate the extracellular availability of latent TGFß. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular dystrophy, we created transgenic mice overexpressing the protective murine allele of LTBP4 specifically in mature myofibers using the human skeletal actin promoter. Overexpression of LTBP4 protein was associated with increased muscle mass and proportionally increased strength compared to age-matched controls. In order to assess the effects of LTBP4 in muscular dystrophy, LTBP4 overexpressing mice were bred to mdx mice, a model of Duchenne muscular dystrophy. In this model, increased LTBP4 led to greater muscle mass with proportionally increased strength, and decreased fibrosis. The increase in muscle mass and reduction in fibrosis were similar to what occurs when myostatin, a related TGFß family member and negative regulator of muscle mass, was deleted in mdx mice. Supporting this, we found that myostatin forms a complex with LTBP4 and that overexpression of LTBP4 led to a decrease in myostatin levels. LTBP4 also interacted with TGFß and GDF11, a protein highly related to myostatin. These data identify LTBP4 as a multi-TGFß family ligand binding protein with the capacity to modify muscle disease through overexpression.

Comparative and quantitative proteomics reveal the adaptive strategies of oyster larvae to ocean acidification.

Decreasing pH due to anthropogenic CO2 inputs, called ocean acidification (OA), can make coastal environments unfavorable for oysters. This is a serious socioeconomical issue for China which supplies >70% of the world's edible oysters. Here, we present an iTRAQ-based protein profiling approach for the detection and quantification of proteome changes under OA in the early life stage of a commercially important oyster, Crassostrea hongkongensis. Availability of complete genome sequence for the pacific oyster (Crassostrea gigas) enabled us to confidently quantify over 1500 proteins in larval oysters. Over 7% of the proteome was altered in response to OA at pHNBS 7.6. Analysis of differentially expressed proteins and their associated functional pathways showed an upregulation of proteins involved in calcification, metabolic processes, and oxidative stress, each of which may be important in physiological adaptation of this species to OA. The downregulation of cytoskeletal and signal transduction proteins, on the other hand, might have impaired cellular dynamics and organelle development under OA. However, there were no significant detrimental effects in developmental processes such as metamorphic success. Implications of the differentially expressed proteins and metabolic pathways in the development of OA resistance in oyster larvae are discussed. The MS proteomics data have been deposited to the ProteomeXchange with identifiers PXD002138 (http://proteomecentral.proteomexchange.org/dataset/PXD002138).

Correlation between single nucleotide polymorphisms in hypoxia-related genes and susceptibility to acute high-altitude pulmonary edema.

This study aimed to explore the relationship between genetic changes and high-altitude pulmonary edema (HAPE) susceptibility, and to screen for the key single nucleotide polymorphism (SNP) loci in the HAPE-susceptibility gene, by investigating the SNPs occurring in hypoxia-related genes in HAPE-susceptible and control (non-susceptible) populations. This research was conducted on Han recruits, who travelled to the Lhasa plateau (altitude, 3658 m). Ten loci located on ten genes extracted from the HAPE and healthy populations were amplified by polymerase chain reaction, and subsequently sequenced. The investigated genes included those coding for aldosterone synthase 2 (CYP11B2), angiotensin-converting enzyme (ACE), heat-shock protein 70 (HSP70), nuclear factor kappa B (NF-κB), surfactant protein A2 (SP-A2), plasminogen activator inhibitor-1 (PAI-1), nitric oxide synthetase (NOS), vascular endothelial growth factor (VEGF), prolyl hydroxylase (EGLN1), and zinc finger protein A20. The gene distribution of each SNP loci and its correlation with HAPE was analyzed. Statistical analyses of the genotype frequencies of the SNPs revealed significant differences in the ACE (rs4309), EGLN1 (rs480902), SP-A2 (rs1965708), HSP70 (rs1008438), PAI-1 (rs1799889), and NOS (rs199983) expressions between the HAPE and healthy control groups (P < 0.05); therefore, these SNP loci were believed to indicate HAPE susceptibility. HAPE is correlated with multiple- SNP loci. A correlation analysis between genetic polymorphism and HAPE susceptibility revealed that 6 hypoxia-related genes were key sites accounting for HAPE. These findings could help assess the risk of HAPE in populations expressing different genotypes, in order to reduce the occurrence of HAPE.

Reengineering a transmembrane protein to treat muscular dystrophy using exon skipping.

Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. The antisense oligonucleotides used for exon skipping are designed to bypass premature stop codons in the target RNA and restore reading frame disruption. Exon skipping is currently being tested in humans with dystrophin gene mutations who have Duchenne muscular dystrophy. For Duchenne muscular dystrophy, the rationale for exon skipping derived from observations in patients with naturally occurring dystrophin gene mutations that generated internally deleted but partially functional dystrophin proteins. We have now expanded the potential for exon skipping by testing whether an internal, in-frame truncation of a transmembrane protein γ-sarcoglycan is functional. We generated an internally truncated γ-sarcoglycan protein that we have termed Mini-Gamma by deleting a large portion of the extracellular domain. Mini-Gamma provided functional and pathological benefits to correct the loss of γ-sarcoglycan in a Drosophila model, in heterologous cell expression studies, and in transgenic mice lacking γ-sarcoglycan. We generated a cellular model of human muscle disease and showed that multiple exon skipping could be induced in RNA that encodes a mutant human γ-sarcoglycan. Since Mini-Gamma represents removal of 4 of the 7 coding exons in γ-sarcoglycan, this approach provides a viable strategy to treat the majority of patients with γ-sarcoglycan gene mutations.

The Dystrophin Complex: Structure, Function, and Implications for Therapy.

The dystrophin complex stabilizes the plasma membrane of striated muscle cells. Loss of function mutations in the genes encoding dystrophin, or the associated proteins, trigger instability of the plasma membrane, and myofiber loss. Mutations in dystrophin have been extensively cataloged, providing remarkable structure-function correlation between predicted protein structure and clinical outcomes. These data have highlighted dystrophin regions necessary for in vivo function and fueled the design of viral vectors and now, exon skipping approaches for use in dystrophin restoration therapies. However, dystrophin restoration is likely more complex, owing to the role of the dystrophin complex as a broad cytoskeletal integrator. This review will focus on dystrophin restoration, with emphasis on the regions of dystrophin essential for interacting with its associated proteins and discuss the structural implications of these approaches.

The role of 3D computed tomography (CT) imaging in the diagnosis of foreign body aspiration in children.

OBJECTIVE: The aim of this study was to improve the understanding of FBA in children and to decrease the rate of misdiagnosis, missed diagnosis and morbidity. PATIENTS AND METHODS: We analyzed the clinical features and the three-dimensional reconstructed CT images of 590 children with foreign body aspiration (FBA) in the Xuzhou area of the Jiangsu province. RESULTS: CT imaging revealed common complications of FBA including emphysema (n = 379), pneumonia (n = 174), and atelectasis (n = 26). The remaining 120 patients had no visible complications on the three-dimensional reconstructed CT images. Serious complications including pneumothorax, pneumomediastinum, subcutaneous emphysema, pneumatorrhachis could also be observed. The types of foreign bodies were diverse: the most common were peanuts and sunflower seeds. The diagnostic accuracy of the three-dimensional CT imaging was high, with a sensitivity and specificity of 99.83% and 99.89%, respectively. CONCLUSIONS: 3D CT imaging is an accurate, non-invasive technique to evaluate children with suspected FBA that can help decrease the rate of misdiagnosis and eliminate a delay in treatment for this potentially life-threatening condition.

Association between polymorphisms in the interleukin-10 gene and risk of abdominal aortic aneurysm.

In this case-control study, we attempted to investigate the role of three common single nucleotide polymorphisms (SNPs; -1082G/A rs1800896, -819T/C rs1800871, and -592A/C rs1800872) in the IL-10 gene in the development of abdominal aortic aneurysm in a Chinese population. Three hundred and eighty-one patients with abdominal aortic aneurysm and age- and gender-matched healthy controls (N = 381) were collected between March 2012 and March 2014. The IL-10 -1082G/A, -819T/C, and -592A/C polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression analyses revealed that the AA genotype of IL-10 -1082G/A was associated with an increased risk of abdominal aortic aneurysm compared to the GG genotype in a codominant model [odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.04-2.60]. Moreover, the GA+AA genotype was correlated with an elevated risk of abdominal aortic aneurysm compared to the GG genotype in a dominant model (OR = 1.34, 95%CI = 1.01-1.79). In conclusion, the results of our study suggested that the A allele of IL-10 -1082G/A is significantly associated with the development of abdominal aortic aneurysm compared to the wide-type genotype.