Laminin mimetic peptide nanofibers regenerate acute muscle defect

Skeletal muscle cells are terminally differentiated and require the activation of muscle progenitor (satellite) cells for their regeneration. There is a clinical need for faster and more efficient treatment methods for acute muscle injuries, and the stimulation of satellite cell proliferation is promising in this context. In this study, we designed and synthesized a laminin-mimetic bioactive peptide (LM/E-PA) system that is capable of accelerating satellite cell activation by emulating the structure and function of laminin, a major protein of the basal membrane of the skeletal muscle. The LM/E-PA nanofibers enhance myogenic differentiation in vitro and the clinical relevance of the laminin-mimetic bioactive scaffold system was demonstrated further by assessing its effect on the regeneration of acute muscle injury in a rat model. Laminin mimetic peptide nanofibers significantly promoted satellite cell activation in skeletal muscle and accelerated myofibrillar regeneration following acute muscle injury. In addition, the LM/E-PA scaffold treatment significantly reduced the time required for the structural and functional repair of skeletal muscle. This study represents one of the first examples of molecular- and tissue-level regeneration of skeletal muscle facilitated by bioactive peptide nanofibers following acute muscle injury. Significance Statement Sports, heavy lifting and other strength-intensive tasks are ubiquitous in modern life and likely to cause acute skeletal muscle injury. Speeding up regeneration of skeletal muscle injuries would not only shorten the duration of recovery for the patient, but also support the general health and functionality of the repaired muscle tissue. In this work, we designed and synthesized a laminin-mimetic nanosystem to enhance muscle regeneration. We tested its activity in a rat tibialis anterior muscle by injecting the bioactive nanosystem. The evaluation of the regeneration and differentiation capacity of skeletal muscle suggested that the laminin-mimetic nanosystem enhances skeletal muscle regeneration and provides a suitable platform that is highly promising for the regeneration of acute muscle injuries. This work demonstrates for the first time that laminin-mimetic self-assembled peptide nanosystems facilitate myogenic differentiation in vivo without the need for additional treatment. © 2017 Acta Materialia Inc

Accuracy and clinical utility of comprehensive dysphagia screening assessments in acute stroke: A systematic review and meta‐analysis

IntroductionNurses and other nonspecialists in dysphagia are often trained to screen swallowing poststroke. There are many basic tools that test water only, they are usually conservative, and patients that fail the test remain nil by mouth until a speech and language therapy assessment. More comprehensive tests also allow nonspecialists to recommend modified oral intake. Little is known about the accuracy, clinical utility and cost‐effectiveness of these tests.MethodsFollowing PRISMA guidelines, a systematic review was conducted to describe comprehensive swallowing tests that are available for use in acute stroke by nurses or other nonspecialists in dysphagia. A meta‐analysis was performed to evaluate accuracy and the clinical utility of the tests was considered. Searches and analyses, conducted by two reviewers, included MEDLINE, Embase, trial registries and grey literature up to December 2018. Validated studies were assessed for quality and risk of bias using QUADAS‐2.ResultsTwenty studies were included, describing five different tests, three of which had undergone validation. The tests varied in content, recommendations and use. There was no test superior in accuracy and clinical utility. Three studies validating the Gugging Swallow Screen provided sufficient data for meta‐analysis, demonstrating high sensitivity; 96% (95% CI 0.90–0.99), but low specificity, 65% (95% CI 0.47–0.79), in line with many water swallow tests. Results should be interpreted with caution as study quality and applicability to the acute stroke population was poor.ConclusionsThere is no comprehensive nurse dysphagia assessment tool that has robustly demonstrated good accuracy, clinical utility and cost‐effectiveness in acute stroke.Relevance to Clinical PracticeNurses and other clinicians can develop competencies in screening swallowing and assessing for safe oral intake in those with poststroke dysphagia. It is important to use a validated assessment tool that demonstrates good accuracy, clinical utility and cost‐effectiveness

RASOnD - A comprehensive resource and search tool for RAS superfamily oncogenes from various species

<p>Abstract</p> <p>Background</p> <p>The Ras superfamily plays an important role in the control of cell signalling and division. Mutations in the Ras genes convert them into active oncogenes. The Ras oncogenes form a major thrust of global cancer research as they are involved in the development and progression of tumors. This has resulted in the exponential growth of data on Ras superfamily across different public databases and in literature. However, no dedicated public resource is currently available for data mining and analysis on this family. The present database was developed to facilitate straightforward accession, retrieval and analysis of information available on Ras oncogenes from one particular site.</p> <p>Description</p> <p>We have developed the RAS Oncogene Database (RASOnD) as a comprehensive knowledgebase that provides integrated and curated information on a single platform for oncogenes of Ras superfamily. RASOnD encompasses exhaustive genomics and proteomics data existing across diverse publicly accessible databases. This resource presently includes overall 199,046 entries from 101 different species. It provides a search tool to generate information about their nucleotide and amino acid sequences, single nucleotide polymorphisms, chromosome positions, orthologies, motifs, structures, related pathways and associated diseases. We have implemented a number of user-friendly search interfaces and sequence analysis tools. At present the user can (i) browse the data (ii) search any field through a simple or advance search interface and (iii) perform a BLAST search and subsequently CLUSTALW multiple sequence alignment by selecting sequences of Ras oncogenes. The Generic gene browser, GBrowse, JMOL for structural visualization and TREEVIEW for phylograms have been integrated for clear perception of retrieved data. External links to related databases have been included in RASOnD.</p> <p>Conclusions</p> <p>This database is a resource and search tool dedicated to Ras oncogenes. It has utility to cancer biologists and cell molecular biologists as it is a ready source for research, identification and elucidation of the role of these oncogenes. The data generated can be used for understanding the relationship between the Ras oncogenes and their association with cancer. The database updated monthly is freely accessible online at <url>http://202.141.47.181/rasond/</url> and <url>http://www.aiims.edu/RAS.html</url>.</p

Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

EUROPEAN GERIATRIC MEDICINE

Key summary pointsAimOur aim was to investigate which swallowing difficulty of food consistency in older people who did not have any disease that might affect swallowing functions, and which symptoms were most likely related to oropharyngeal dysphagia (OD) risk.FindingsWe have found that the eating/drinking difficulty of thick liquids was the highest predictive value with respect to OD risk and the eating difficulty of mixed content food had the highest diagnostic ratio.MessageThe present study reports that even in older person who do not go to the hospital with the complaints of swallowing difficulty, the difficulty of swallowing thick liquids and especially the mixed content food should be questioned. AbstractPurposeThe present study aimed to investigate which swallowing difficulty of food consistency in participants over 65years of age who did not have any disease that might affect swallowing functions, and which symptoms were most likely related to oropharyngeal dysphagia (OD).MethodsThe cross-sectional and multicenter study was conducted at 12 hospitals including 883 participants aged >= 65years who were fed orally and who were admitted to the physical medicine and rehabilitation outpatient clinics between September 2017 and December 2018. Demographic characteristics were recorded. Katz Daily Living Activities Index (KDLAI), swallowing-related quality of life scale (Swal-QoL) and 10-item Eating Assessment Tool (EAT-10) were used. The participants were asked the yes or no questions including swallowing difficulty of various types of food consistency with the face-to-face interview.ResultsParticipants were divided into two groups as normal swallowing (EAT-10= 3 group) (n=244) according to the EAT-10 scores. While there was no difference related to number of teeth and KDLAI scores between groups (p=0.327 and p=0.221, respectively), the significant difference was found between groups in terms of yes/no questions and Swal-QoL scores (p<0.05). Receiver operating characteristic analysis revealed that eating difficulty of mixed content food provided maximum sensitivity (99%) and eating/drinking difficulty of thick liquid had maximum specificity (77%). The higher area under curve was in eating/drinking difficulty of thick liquid (0.891), and higher positive likelihood ratio (LR) was eating/drinking difficulty of thick liquid (4.26) as well as lower negative LR was eating difficulty of mixed content food (0.01). The higher diagnostic odds ratio was eating difficulty of mixed content food (367.0), and the higher posttest probability was eating/drinking difficulty of thick liquid (0.211).ConclusionWhile eating difficulty of hard solid food is the most common symptom in healthy participants over 65years of age, the eating difficulty of thick liquids is the highest predictive value related to oropharyngeal dysphagia risk. Also, the eating difficulty of mixed content food had the highest diagnostic ratio

EUROPEAN GERIATRIC MEDICINE

Purpose Dysphagia is known to be a disorder of the swallowing function, and is a growing health problem in aging populations. Swallowing screening tests have mostly been studied in comorbidities such as stroke associated with old age. There is no simple, quick and easy screening test to best determine the risk of oropharyngeal dysphagia in geriatric guidelines. We aimed to evaluate whether the Gugging Swallowing Screen (GUSS) test is an effective method for evaluating swallowing difficulty in healthy older people. Methods This cross-sectional and multicenter study was conducted at 13 hospitals between September 2017 and February 2019. The study included 1163 participants aged >= 65 years and who had no secondary dysphagia. Reliability was evaluated for data quality, scaling assumptions, acceptability, reliability, and validity as well as cutoff points, specificity and sensitivity. Results The age distribution of 773 (66.5%) patients was between 65 and 74 years and 347 (29.8%) of them were male and 767 (66%) patients were female. The average total GUSS score was 18.57 +/- 1.41. The Cronbach's alpha was 0.968. There was a moderate statistically significant negative correlation between the total GUSS and 10-item Eating Assessment Tool scores as well as between the total GUSS score and quality of life. The cutoff point of the total GUSS score was 18.50, sensitivity was 95.5% and specificity was 94.4%. Conclusions The GUSS test is a valid and reliable test to identify possible oropharyngeal dysphagia risk in healthy older people who had no secondary dysphagia. It is suitable as a screen test for clinical practice. Key summary pointsAim We aimed to evaluate whether the Gugging Swallowing Screen (GUSS) test is an effective method for evaluating swallowing difficulty in healthy older people. Findings Total GUSS score sensitivity was 95.5% and its specificity was 94.4%. Message The GUSS test is a valid and reliable test to identify possible oropharyngeal dysphagia risk in healthy older person who had no secondary dysphagia. It is suitable as a screen test for clinical practice

Views Of Elementary Mathematics Teachers About Mental Games Course

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Relationship between MTHFR gene polymorphisms (C677T and A1298C) and chronic lymphocytic leukemia in the Turkish population

Objective: Chronic lymphocytic leukemia (CLL) is a neoplastic disease that influences B cell lymphocytes. CLL is the most common kind of leukemia accounting for approximately 30% of all hematological malignancies. The functions of MTHFR enzyme are a critical juncture in the DNA synthesis, and in methylation of metabolic reactions. Two common genetic polymorphisms, C677T and A1298C, are associated with reduced enzyme activity. We evaluated the association between MTHFR gene polymorphisms and the CLL risk. Materials and methods: In the present study, MTHFR gene polymorphisms were investigated in a case-control study of 91 patients with CLL and 101 healthy control subjects using real time polymerase chain reaction (RT-PCR) assay in the Turkish population. Results & conclusion: The patients carrying 1298C allele or 1298CC genotype had a higher risk of CLL (P =.04, P =.005, respectively). Moreover, the patients carrying 677TT genotype had a lower risk of CLL than the other patients carrying 677CC and 677CT genotypes in recessive model (P =.03). Additionally, the CA haplotype block showed a protective effect against the risk of CLL (the C677/A1298, P =.0013). In conclusion, our results demonstrate for the first time MTHFR gene C677T and A1298C polymorphisms, especially A1298C, have a major effect on the risk of CLL in the Turkish patients. We suggest that considering the first contradictory results in Caucasians, further additional studies are necessary to elucidate the relationship of these polymorphisms with the risk of CLL disease in Caucasian populations. © 2018 Elsevier B.V.Çukurova Üniversitesi: FEF2013D17This study was supported by ÇUKUROVA UNIVERSITY SCIENTIFIC RESEARCH PROJECTS UNIT ( FEF2013D17 )

An unusual late complication in traumatic brain injury: Persistent dysphagia due to tracheoesophageal fistula

Traumatic brain injury (TBI), which leads to cognitive, physical, emotional and behavioral deficits according to the severity of trauma, is a disability with high morbidity and mortality. In addition to primary effects of TBI, direct trauma to the face, neck, and chest also contributes to increased morbidity. Recovery in swallowing functions in TBI patients is often parallel with recovery in functional daily activities. Herein, contrary to that expectation, we present a TBI case with persistent dysphagia symptoms lasting for even 1.5 years after trauma, despite the fact that she gained independence in dailylife activities under supervision