关键词： Apert syndrome   Acrocephalosyndactyly   Complex syndactyly   soft tissue distraction   external fixator   synostosis   functional hand assessment   craniosynostosis  

摘要： Background: The complex syndactyly in Apert syndrome hands is challenging to operate. The synostosis and tightness of skin between third and fourth digits lead to severe coverage problems during ray release. A soft tissue distractor can simplify the release with the aim to keep all 10 fingers. Methods: A retrospective follow-up of 12 patients/24 hands, median age 8 years (6 to 17 y), 6 boys and 6 girls, operated between 2000 and 2013 was done from 2015 to 2016. The surgical management started with syndactyly release of the first and fourth web, and later of the second. The third stage was placing a soft tissue distractor on the third and fourth finger after osteotomy on the synostosis between them. Four weeks of distraction and 2 weeks of rest resulted in regenerated skin between the digits giving much better coverage of the released digits at time of separation 6 weeks later. Assessment of hand function, grip strength and completion of the Patient Reported Outcome Measure CHEQ was performed. Results: Soft tissue coverage at the time of digit separation was considerably facilitated. We experienced 2 infections in 2 hands. In 18/24 hands median 2 (1 to 3) small full thickness skin grafts were needed, usually for coverage of the base of the digits. All wounds healed well. The children managed different practical tasks well, alternating between best functioning grip depending on the activity. According to CHEQ, the children did median 19 (13 to 27) activities independently and median 8 (2 to 15) nonindependently, of a total of 29. Peak strength values for 10/12 children were for the right hand median 17.8% (9.6% to 40.6%) of normative data and for left hand median 13.6% (2.4% to 20.5%) of normative data. Conclusion: Soft tissue distraction facilitates the treatment of acrocephalosyndactyly hands, giving 5-fingered hands. Apert children manage many activities independently but struggled with fine motor skills demanding strength.

关键词： alternative splicing   transcriptome   RNA-seq   RT-PCR   visualization  

摘要： (1) Background: A simplistic understanding of the central dogma falls short in correlating the number of genes in the genome to the number of proteins in the proteome. Post-transcriptional alternative splicing contributes to the complexity of the proteome and is critical in understanding gene expression. mRNA-sequencing (RNA-seq) has been widely used to study the transcriptome and provides opportunity to detect alternative splicing events among different biological conditions. Despite the popularity of studying transcriptome variants with RNA-seq, few efficient and user-friendly bioinformatics tools have been developed for the genome-wide detection and visualization of alternative splicing events. (2) Results: We propose AS-Quant, (Alternative Splicing Quantitation), a robust program to identify alternative splicing events from RNA-seq data. We then extended AS-Quant to visualize the splicing events with short-read coverage plots along with complete gene annotation. The tool works in three major steps: (i) calculate the read coverage of the potential spliced exons and the corresponding gene;(ii) categorize the events into five different categories according to the annotation, and assess the significance of the events between two biological conditions;(iii) generate the short reads coverage plot for user specified splicing events. Our extensive experiments on simulated and real datasets demonstrate that AS-Quant outperforms the other three widely used baselines, SUPPA2, rMATS, and diffSplice for detecting alternative splicing events. Moreover, the significant alternative splicing events identified by AS-Quant between two biological contexts were validated by RT-PCR experiment. (3) Availability: AS-Quant is implemented in Python 3.0. Source code and a comprehensive user's manual are freely available online.

摘要： Background Endoluminal therapy either by dilatation, scar tissue resection or stent insertion is an established treatment for non-malignant airway stenosis although the surgical approach is still considered the "gold standard." No clear consensus exists on the structured role of each modality. Aims We aimed to investigate the role of bronchoscopic management in non-operable tracheal stenosis cases, evaluating the effectiveness and safety of each procedure based on a structured algorithmic approach. Patients and methods This prospective study was carried out on (40) consecutive patients diagnosed between March 2017 and March 2020 with tracheal stenosis not amenable to surgery. All strictures were first evaluated by flexible bronchoscopy and classified as simple or complex. Patients were treated following a standardised therapeutic algorithm approach based on published evidence and our own expertise. Results The mean age of the study population was 45.25 +/- 18.79;lesions were classified as simple (14) and complex (24), while two patients had mixed type stenosis. Long term success rate was 100% in simple stenosis and 87.5% in the complex ones. Stents were deployed in 24 cases, most of which were of the complex type and only two of the simple type. Post-procedural mild to moderate complications were detected overall in 70% of the patients. All complications were non-life threatening, mostly stent-related and were effectively managed. Conclusion We conclude that after accurate classification and a structured algorithmic approach, interventional bronchoscopic management may play a crucial role in the effective treatment of benign tracheal stenosis.

关键词： alternative splicing (AS)   genotype‐   specific RNA splicing (GSS)   prioritisation   rice (Oryza sativa)   salt stress   splice site mutation   splicing quantitative trait locus (sQTL)  

摘要： Pre-mRNA splicing is an essential step for the regulation of gene expression. In order to specifically capture splicing variants in plants for genome-wide association studies (GWAS), we developed a software tool to quantify and visualise Variations of Splicing in Population (VaSP). VaSP can quantify splicing variants from short-read RNA-seq datasets and discover genotype-specific splicing (GSS) events, which can be used to prioritise causal pre-mRNA splicing events in GWAS. We applied our method to an RNA-seq dataset with 328 samples from 82 genotypes from a rice diversity panel exposed to optimal and saline growing conditions. In total, 764 significant GSS events were identified in salt stress conditions. GSS events were used as markers for a GWAS with the shoot Na+ accumulation, which identified six GSS events in five genes significantly associated with the shoot Na+ content. Two of these genes, OsNUC1 and OsRAD23 emerged as top candidate genes with splice variants that exhibited significant divergence between the variants for shoot growth under salt stress conditions. VaSP is a versatile tool for alternative splicing analysis in plants and a powerful tool for prioritising candidate causal pre-mRNA splicing and corresponding genomic variations in GWAS.

关键词： c-KIT   Cloning   Coat color   Gene expression   Gene structure   Skin pigmentation   Splicing  

摘要： c-KIT, a type III receptor protein tyrosine kinase, plays an essential role in melanocyte development, migration, and survival. Mutations within the c-KIT gene are previously shown to cause the white coat color phenotypes in pigs, mice, goats, and humans. However, up so far, the splicing isoform(s), genomic architecture of c-KIT have not been characterized well in merino sheep. Reverse transcriptase (RT)-PCR analysis with molecular prediction identified two basic splice variants: Transcript Variant-1, 2 for 12 bp insertion coding sequences (CDS) corresponding to the four amino acids 'GNSK', respectively. Using 5 ' RACE, here we report for the first time a novel c-KIT 'Transcript Variant-3' from the skin of merino sheep by comparative genome analyses at exon(1)-intron(1)-exon(2) boundaries. In contrast, a single product of 795 bp was characterized by 3' RACE. We also demonstrated that the c-KIT gene expression at the transcript level is not mediated via an intron-9 splicing event. Overall, beyond what was observed in other mammals, our data provide novel insights into the molecular structure of the c-KIT gene in sheep.

摘要： After a medical student prompted medical faculty to tell their stories of depression and related mental health issues, the author wrote this article with the aim of decreasing the stigma of mental illness and encouraging treatment, as needed, in the medical profession. The professional culture of the house of medicine not only mimics society in attributing stigma to people with mental health issues but may also contribute to high rates of suicide in the ranks of health care professionals by leading to a delay in seeking treatment. Acculturation accelerates in the first year of medical school such that medical students experience an increase in burnout and depressive symptoms from prematriculation levels. It follows that faculty have a responsibility to improve the learning environment. Survey data from medical faculty at the author's institution showed that depression decreased respondents' willingness to seek mental health treatment because of the stigma and issues of access to help. Faculty attitudes toward mental health issues, including reluctance to admit having such issues, may be conveyed to medical students in the hidden curriculum that teaches them to keep depression hidden. Moreover, the fear of mental disorders is manifested in licensing and privileging applications under the guise of patient safety, contributing to a culture of shame and silence. As creators and guardians of this professional culture, medical faculty and other physicians must be the ones who change it. The same faculty who play a part in causing and perpetuating stigma related to mental health issues have the power to derive and enact some of the solutions. In addition to giving voice to a personal experience of mental health issues, this article offers suggestions for normalizing moderate to severe depression as a medical disorder, decreasing the stigma of mental health issues, and encouraging faculty to seek treatment.

关键词： Complementary and aAlternativeMedicine   Children   Asthma  

摘要： Objective: Complementary and Alternative Medicine (CAM) is increasingly used in the treatment of asthma in children. In the studies conducted, it was stated that there was a standardization problem in CAM methods. Moreover, this situation raises the question of ?Which is the most widely used CAM method?? in asthma treatment. This study aimed to determine the use of CAM methods in children who are followed up with the diagnosis of asthma. Material and methods: The patients aged 4?10 years who were diagnosed with asthma by a physician in the past and who admitted to the Child Health and Diseases Polyclinic of a hospital issuing tertiary health service in Turkey were included in the study. The demographic data of patients and CAM methods used were examined. Results: The median age of a total of 164 asthmatic children included in the study was 6.3 (4?10) years, and 58.3% of them were observed to be male. The median time to diagnosis of the patients was 2.0 (1;105) months, mostly having multiple cough attacks per day (33.1%), and the rate of children with cough attacks at least once a month to awaken from sleep at night was 47.6%. Honey (36.6%) was found to be one of the most preferred biological-based therapies for families and was followed by molasses (16.9%), which were derived from herbal and natural products. Conclusions: There are varying rates of CAM use in asthmatic children all over the world, and it was found that honey was used the most in our study. Atopy can be found in the etiology of asthmatic patients. Therefore, it should not be forgotten that using different CAM methods at the same time may pose a risk.

关键词： radius and ulna fractures   orthopedic trauma   fracture brace   nonoperative management  

摘要： Background: One of the most common pediatric fractures is a midshaft both bone forearm fracture. The preferred nonoperative treatment is cast immobilization for 6 to 8 weeks;however, 4% to 8% refracture within 6 months. There are no comparative studies evaluating the efficacy of bracing after cast immobilization. We hypothesized that children treated with prolonged functional bracing would have a lower rate of refracture than casting alone or short-term bracing. Methods: This is a retrospective review of children younger than 15 years of age treated nonoperatively following radius and ulnar shaft fractures treated at 3 tertiary pediatric hospitals. We excluded distal radius/ulna fractures, isolated fractures of the radius/ulna, and fractures near the elbow. Logistic regression analysis on casting plus functional bracing was run to determine if age, translation, or the number of days in brace were associated with refracture. The incidence of refracture was compared between groups. Results: A total of 1549 patients were screened and 426 were included in the study [111 casting only (CO), 259 casting plus functional brace <8 wk (CFB <8 wk), 56 casting plus functional brace >= 8 wk (CFB >= 8 wk)]. In comparing the groups, CO was the youngest (4.4 y vs. 6.3 and 8.4 y). The initial translation and angulation of the radius and ulna were significantly greater in the CFB >= 8 weeks group. Regression analyses shows no association between refracture and initial fracture characteristics including age, translation, or the number of days in brace. The CO group had 3 refractures (2.7%), the CFB <8 weeks group had 13 (5%) and the CFB >= 8 weeks group had 1 (1.8%);demonstrating no statistical significance. Conclusion: Extended fracture bracing, following a period of cast immobilization, did not lead to a statistically significant difference in refracture rate. Contrary to previous cases series, the benefit of bracing seems nominal. Larger, prospective studies are needed to better und