Effect of Supination Versus Pronation in the Non-Operative Treatment of Pediatric Supracondylar Humerus Fractures

Background: Supracondylar fracture of the humerus is the most common elbow injury that requires reduction and immobilization in the proper position to union. There are a few reports regarding the position of the forearm immobilization on elbow cosmetic outcome. Objectives: This study aimed to compare two modes of the forearm, supination and pronation in elbow deformity incidence after closed reduction and casting of this fracture. Patients and Methods: This prospective and descriptive study was carried out on children with supracondylar fracture of the humerus treated with closed reduction and cast immobilization in one of the two modes of either supination or pronation for a period of three weeks. Twenty-nine patients were immobilized in supination and 35 in pronation. Follow-up lasted for 8 months. Re-displacement was defined as the criteria and subsequent deformities of the elbow in patients, were assessed by clinical and radiographic examination. Results: A total of 64 patients, 50 boys and 14 girls, with the mean age of 4.8 years (3.1 to 8.5 years) participated. All fractures were closed and of the extension type. Forty-five cases had Gartland type II and 19 had type III fracture. Deformity of the elbow had occurred in seven cases (10.94%). Four cases of cubitus varus (CA 5 º - 16º) were observed in the supination group, of these, three patients had type III and one other had a type II fracture. In the pronation group, two cases of cubitus varus (CA 6 º - 14º) and one case of cubitus valgus (CA 17º) were observed, with type III initial fracture in all 3 cases. Conclusions: In regard to elbow malunion deformity, no obvious difference was observed between the two methods of supination and pronation in the closed treatment of supracondylar humerus fracture. However, as cubitus varus and valgus had occurred in both groups with unstable type III fractures, to prevent this complication, operative fixation is advised rather than closed reduction and position of the forearm immobilization

Rps27a might act as a controller of microglia activation in triggering neurodegenerative diseases

Neurodegenerative diseases (NDDs) are increasing serious menaces to human health in the recent years. Despite exhibiting different clinical phenotypes and selective neuronal loss, there are certain common features in these disorders, suggesting the presence of commonly dysregulated pathways. Identifying causal genes and dysregulated pathways can be helpful in providing effective treatment in these diseases. Interestingly, in spite of the considerable researches on NDDs, to the best of our knowledge, no dysregulated genes and/or pathways were reported in common across all the major NDDs so far. In this study, for the first time, we have applied the three-way interaction model, as an approach to unravel sophisticated gene interactions, to trace switch genes and significant pathways that are involved in six major NDDs. Subsequently, a gene regulatory network was constructed to investigate the regulatory communication of statistically significant triplets. Finally, KEGG pathway enrichment analysis was applied to find possible common pathways. Because of the central role of neuroinflammation and immune system responses in both pathogenic and protective mechanisms in the NDDs, we focused on immune genes in this study. Our results suggest that "cytokine-cytokine receptor interaction" pathway is enriched in all of the studied NDDs, while "osteoclast differentiation" and "natural killer cell mediated cytotoxicity" pathways are enriched in five of the NDDs each. The results of this study indicate that three pathways that include "osteoclast differentiation", "natural killer cell mediated cytotoxicity" and "cytokine-cytokine receptor interaction" are common in five, five and six NDDs, respectively. Additionally, our analysis showed that Rps27a as a switch gene, together with the gene pair Il-18, Cx3cl1 form a statistically significant and biologically relevant triplet in the major NDDs. More specifically, we suggested that Cx3cl1 might act as a potential upstream regulator of Il-18 in microglia activation, and in turn, might be controlled with Rps27a in triggering NDDs. © 2020 Khayer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Efficient inhibition of human immunodeficiency virus replication using novel modified microRNA-30a targeting 3'-untranslated region transcripts

RNA interference (RNAi)-based gene therapy is currently considered to be a combinatorial anti-human immunodeficiency virus-1 (HIV-1) therapy. Although arti­ficial polycistronic microRNAs (miRs) can reduce HIV-1 escape mutant variants, this approach may increase the risk of side effects. The present study aimed to optimize the efficiency of anti-HIV RNAi gene therapy in order to reduce the cell toxicity induced by multi-short hairpin RNA expression. An artificial miR-30a-3'-untranslated region (miR-3'-UTR) obtained from a single RNA polymerase II was used to simultaneously target all viral transcripts. The results of the present study demonstrated that HIV-1 replication was signifi­cantly inhibited in the cells with the miR-3'-UTR construct, suggesting that miR-3'-UTR may serve as a promising tool for RNAi-based gene therapy in the treatment of HIV-1. © 2016, Spandidos Publications. All Rights Reserved

Phenotypic Identification and Genotypic Characterization of Plasmid‑Mediated AmpC β‑Lactamase‑Producing Escherichia coli and Klebsiella pneumoniae Isolates in Iran

One of the mechanisms of Klebsiella pneumoniae and Escherichia coli resistance to β-lactam antibiotics is the production of β-lactamase enzymes. Among these are the AmpC β-lactamases, which confer resistance to a class of antibiotics. However, little is known about the AmpC β-lactamases of K. pneumoniae and E. coli clinical isolates in Qazvin, Iran. This study was designed to assess the AmpC β-lactamases-producing strains and also identify the prevalence of AmpC β-lactamases genes. Antimicrobial susceptibility tests were performed on 435 K. pneumoniae and E. coli isolates using disk difusion technique. Plasmid-mediated AmpC genes were studied using a multiplex PCR assay. The AmpC β-lactamase-producer isolates were studied by employing cefoxitin disk difusion test, AmpC induction test, AmpC cefoxitin-EDTA test, and boronic acid disk test. Our results showed that of 46 (18.4%) cefoxitin-insensitive E. coli isolates, 10 (21.7%) were positive for AmpC β-lactamase genes, among them 4 (8.69%) isolates were positive for blaDHA genes and 6 (13%) for blaCIT genes. Of 57 (30.4%) cefoxitin-insensitive K. pneumoniae isolates, 10 (17.5%) were positive for AmpC gene with 4 (6.34%) and 6 (9.5%) isolates positive for blaDHA and blaCIT genes, respectively. However, no MOX, ACC, FOX, or EBC genes were detected in the isolates. Considering the results of diferent confrmatory phenotypic tests, the AmpC cefoxitin-EDTA test showed a higher discriminatory power for detecting AmpC β-lactamase-producing strains. The specifcity and sensitivity of AmpC cefoxitin-EDTA were 77%, 100% for K. pneumonia and 70%, 90% for E. coli higher than the other two tests, respectively. Also, the authors demonstrated high prevalence rate for resistance to certain antibiotics, such as cefuroxime, trimethoprim-sulfamethoxazole, ampicillin, and cefotaxime. In conclusion, our study provided valuable information regarding the plasmid-mediated AmpC β-lactamase gene content, antibiotic resistance, and confrmatory phenotypic tests for AmpC β-lactamases in E. coli and K. pneumoniae isolates from clinical sources

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Enhancing clinical decision support with genomic tools in breast cancer: a Scottish perspective

Introduction: The Oncotype DX Breast RS test has been adopted in Scotland and has been the subject of a large population-based study by a Scottish Consensus Group to assess the uptake of the recurrence score (RS), evaluate co-variates associated with the RS and to analyse the effect it may have had on clinical practice. Materials & Methods: Pan-Scotland study between August 2018–August 2021 evaluating 833 patients who had a RS test performed as part of their diagnostic pathway. Data was extracted retrospectively from electronic records and analysis conducted to describe change in chemotherapy administration (by direct comparison with conventional risk assessment tools), and univariate/multivariate analysis to assess relationship between covariates and the RS. Results: Chemotherapy treatment was strongly influenced by the RS (p < 0.001). Only 30 % of patients received chemotherapy treatment in the intermediate and high risk PREDICT groups, where chemotherapy is considered. Additionally, 55.5 % of patients with a high risk PREDICT had a low RS and did not receive chemotherapy. There were 17 % of patients with a low risk PREDICT but high RS who received chemotherapy. Multivariate regression analysis showed the progesterone receptor Allred score (PR score) to be a strong independent predictor of the RS, with a negative PR score being associated with high RS (OR 4.49, p < 0.001). Increasing grade was also associated with high RS (OR 3.81, p < 0.001). Classic lobular pathology was associated with a low RS in comparison to other tumour pathology (p < 0.01). Nodal disease was associated with a lower RS (p = 0.012) on univariate analysis, with menopausal status (p = 0.43) not influencing the RS on univariate or multivariate analysis. Conclusions: Genomic assays offer the potential for risk-stratified decision making regarding the use of chemotherapy. They can help reduce unnecessary chemotherapy treatment and identify a subgroup of patients with more adverse genomic tumour biology. A recent publication by Health Improvement Scotland (HIS) has updated guidance on use of the RS test for NHS Scotland [1].It suggests to limit its use to the intermediate risk PREDICT group. Our study shows the impact of the RS test in the low and high risk PREDICT groups. The implementation across Scotland has resulted in a notable shift in practice, leading to a significant reduction in chemotherapy administration in the setting of high risk PREDICT scores returning low risk RS. There has also been utility for the test in the low risk PREDICT group to detect a small subgroup with a high RS. We have found the PR score to have a strong independent association with high risk RS. This finding was not evaluated by the key RS test papers, and the potential prognostic information provided by the PR score as a surrogate biomarker is an outstanding question that requires more research to validate

Fast splice site detection using information content and feature reduction

Background: Accurate identification of splice sites in DNA sequences plays a key role in the prediction of gene structure in eukaryotes. Already many computational methods have been proposed for the detection of splice sites and some of them showed high prediction accuracy. However, most of these methods are limited in terms of their long computation time when applied to whole genome sequence data. Results: In this paper we propose a hybrid algorithm which combines several effective and informative input features with the state of the art support vector machine (SVM). To obtain the input features we employ information content method based on Shannon\u27s information theory, Shapiro\u27s score scheme, and Markovian probabilities. We also use a feature elimination scheme to reduce the less informative features from the input data. Conclusion: In this study we propose a new feature based splice site detection method that shows improved acceptor and donor splice site detection in DNA sequences when the performance is compared with various state of the art and well known method

Approaches to link RNA secondary structures with splicing regulation

In higher eukaryotes, alternative splicing is usually regulated by protein factors, which bind to the pre-mRNA and affect the recognition of splicing signals. There is recent evidence that the secondary structure of the pre-mRNA may also play an important role in this process, either by facilitating or by hindering the interaction with factors and small nuclear ribonucleoproteins (snRNPs) that regulate splicing. Moreover, the secondary structure could play a fundamental role in the splicing of yeast species, which lack many of the regulatory splicing factors present in metazoans. This review describes the steps in the analysis of the secondary structure of the pre-mRNA and its possible relation to splicing. As a working example, we use the case of yeast and the problem of the recognition of the 3-prime splice site.Comment: 21 pages, 7 figure

Connected by sea, disconnected by tuna? Challenges to regionalism in the Southwest Indian Ocean

Madagascar, Mauritius and Seychelles are at the center of industrial tuna extraction in the Southwest Indian Ocean (SWIO). In this paper, we show that, while a discourse of regionalism between the three islands is prominent, the possibilities of regionalism face deep challenges in relation to the tuna industry. This is due to three factors. First, local perceptions, especially amongst those working in and on the tuna industry, are in disconnection with an ‘Indianoceania’ vision. Second, the geopolitics between coastal states and distant water fishing nations create various entanglements including through fishing access revenue and foreign aid. Finally, the materiality of tuna can at times create competition as countries seek to individually maximize benefits from the industry. We argue that the active reinforcement of regional identity and collaboration around this resource is necessary to sustain local benefits into the future