Assessment of paediatric head shape and management of craniosynostosis.

BACKGROUND: The presentation of a child with an abnormal head shape can be challenging and should be met with an appropriate clinical approach. Craniosynostosis is a common cause of paediatric skull deformity and is best managed by a multispecialty tertiary referral unit with regular follow-up. As craniosynostosis frequently requires time-sensitive surgery, it is important to differentiate between craniosynostosis and common self-limiting conditions such as deformational plagiocephaly. OBJECTIVE: The aim of this article is to outline the clinical approach to paediatric skull deformity in the general practice setting, and to highlight the importance of early referral if there is clinical suspicion of craniosynostosis. DISCUSSION: Parental concern regarding infant head shape is common. General practitioners (GPs) have an important role in assessment, diagnosis and referral for paediatric skull deformities. GPs are well placed to clinically differentiate between deformational plagiocephaly and craniosynostosis and provide timely referrals to optimise patient outcomes.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas Advancement in Molecular Diagnostics and Signal Readout Approaches.

Discovery of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has greatly improved the gene editing technology. Their applications in the area of diagnostic innovation are gaining much attention. The key characteristics of CRISPR/Cas system that allowed its extensive exploitation in the detection platform are their programmable and highly selective target recognition scheme. Herein, this review presents the major three Cas effectors (Cas9, Cas12, and Cas13) and their significance in various detection assays. The CRISPR/Cas detection strategies, based on their target hybridization, cleavage activity, sensor capabilities, and signal readout methods, are discussed. Some of the recent progressions, challenges, and improvement strategies of CRISPR/Cas technology are highlighted and their biosensing detection platforms toward the development of simple, sensitive, and portable point-of-care diagnostic devices are presented.

Comparison of glottic views and intubation times in the supine and 25 degree back-up positions.

BACKGROUND: We explored whether positioning patients in a 25° back-up sniffing position improved glottic views and ease of intubation. METHODS: In the first part of the study, patients were intubated in the standard supine sniffing position. In the second part, the back of the operating table was raised 25° from the horizontal by flexion of the torso at the hips while maintaining the sniffing position. The best view obtained during laryngoscopy was assessed using the Cormack and Lehane classification and Percentage of Glottic Opening (POGO) score. The number of attempts at both laryngoscopy and tracheal intubation, together with the use of ancillary equipment and manoeuvres were recorded. The ease of intubation was indirectly assessed by recording the time interval between beginning of laryngoscopy and insertion of the tracheal tube. RESULTS: Seven hundred eighty one unselected surgical patients scheduled for non-emergency surgery were included. In the back-up position, ancillary laryngeal manoeuvres, which included cricoid pressure, backwards upwards rightward pressure and external laryngeal manipulation, were required less frequently (19.6 % versus 24.6 %, p = 0.004). The time from beginning of laryngoscopy to insertion of the tracheal tube was 14 % shorter (median time 24 versus 28 s, p = 0.031) in the back-up position. There was no significant difference in glottic views. CONCLUSIONS: The 25° back-up position improved the ease of intubation as judged by the need for fewer ancillary manoeuvres and shorter time for intubation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02934347 registered retrospectively on 14th Oct 2016.

Molecular responses of brain endothelial cells to radiation in a mouse model.

Although most small arteriovenous malformations (AVM) are curable, over 90% of large lesions are untreatable with current surgery or radiosurgery. Endothelial cells (EC) are believed to be pivotal in the resulting vascular changes after AVM are irradiated, although their role is not fully understood. Elucidating the molecular effects of radiation on EC may allow development of new therapies that modulate the response of AVM to radiation. Cultured murine cerebral EC (bEnd.3) were exposed to a single 25 Gy dose of ionising radiation from a linear accelerator. Expression of the membrane proinflammatory and thrombotic molecules E-selectin, tissue factor (TF) and thrombomodulin (TM) were examined by immunofluorescent staining at times up to three weeks post irradiation. We found that E-selectin is significantly down regulated in the first 24 hours after irradiation. Later there is no significant difference in expression of this molecule between irradiated and non-irradiated groups. TM expression was significantly increased at all times, and the staining intensity of TF remained unchanged three weeks post irradiation. These results contribute to a greater understanding of the proinflammatory and thrombotic changes caused by irradiating normal brain EC.

Transmembrane helix prediction using amino acid property features and latent semantic analysis.

BACKGROUND: Prediction of transmembrane (TM) helices by statistical methods suffers from lack of sufficient training data. Current best methods use hundreds or even thousands of free parameters in their models which are tuned to fit the little data available for training. Further, they are often restricted to the generally accepted topology "cytoplasmic-transmembrane-extracellular" and cannot adapt to membrane proteins that do not conform to this topology. Recent crystal structures of channel proteins have revealed novel architectures showing that the above topology may not be as universal as previously believed. Thus, there is a need for methods that can better predict TM helices even in novel topologies and families. RESULTS: Here, we describe a new method "TMpro" to predict TM helices with high accuracy. To avoid overfitting to existing topologies, we have collapsed cytoplasmic and extracellular labels to a single state, non-TM. TMpro is a binary classifier which predicts TM or non-TM using multiple amino acid properties (charge, polarity, aromaticity, size and electronic properties) as features. The features are extracted from sequence information by applying the framework used for latent semantic analysis of text documents and are input to neural networks that learn the distinction between TM and non-TM segments. The model uses only 25 free parameters. In benchmark analysis TMpro achieves 95% segment F-score corresponding to 50% reduction in error rate compared to the best methods not requiring an evolutionary profile of a protein to be known. Performance is also improved when applied to more recent and larger high resolution datasets PDBTM and MPtopo. TMpro predictions in membrane proteins with unusual or disputed TM structure (K+ channel, aquaporin and HIV envelope glycoprotein) are discussed. CONCLUSION: TMpro uses very few free parameters in modeling TM segments as opposed to the very large number of free parameters used in state-of-the-art membrane prediction methods, yet achieves very high segment accuracies. This is highly advantageous considering that high resolution transmembrane information is available only for very few proteins. The greatest impact of TMpro is therefore expected in the prediction of TM segments in proteins with novel topologies. Further, the paper introduces a novel method of extracting features from protein sequence, namely that of latent semantic analysis model. The success of this approach in the current context suggests that it can find potential applications in other sequence-based analysis problems. AVAILABILITY: http://linzer.blm.cs.cmu.edu/tmpro/ and http://flan.blm.cs.cmu.edu/tmpro/

Increasing heel skin perfusion by elevation.

OBJECTIVE: To determine the efficacy of elevation in the primary prevention and treatment of pressure ulcers by studying the blood flow in tissue at risk of ulceration. DESIGN: A prospective study was used to compare different preventative devices with an elevating prosthesis. SETTING: : Wollongong Hospital Wollongong, New South Wales, Australia. PARTICIPANTS: Normal subjects and subjects with vasculopathy were tested with their heel resting on a hospital bed, medical-grade lamb's wool, or a viscoelastic gel overlay, with or without the test prosthesis. Skin perfusion was measured throughout using a laser Doppler monitor. INTERVENTION: A device designed to elevate the heel off the bed and distribute the weight of the leg and foot on the calf. MAIN OUTCOME MEASURE: Heel capillary blood perfusion. MAIN RESULTS: Perfusion in the heel was significantly greater when elevated than when using the other devices tested. The differences in mean red blood cell flux were significant, with P < .0001 for bed-normals, ie, subjects with no peripheral vascular disease on an alpha Xcell mattress overlay as the control with flux increasing from 7.6 to 163.1 arbitrary units (AU); P < .005 bed-vasculopathy, ie, subjects with peripheral vascular disease on an alpha Xcell mattress overlay as the control with flux increasing from 31.6 to 224.7 AU; P < .0001 viscoelastic overlay subjects where the viscoelastic overlay was the control with flux increasing from 26.6 to 291.4 AU; and P < .01 lamb's wool subjects where the lamb's wool was the control with flux increasing from 27.7 AU to 169.2 AU. CONCLUSION: In this study, when the heels were elevated, tissue perfusion to that area was substantially increased. When the heel was transferred to the elevating splint, the heel capillary bed underwent reactive hyperemia, indicating the alleviation of tissue hypoxia. Elevation is therefore an important technique in pressure ulcer prevention and treatment and should be incorporated into health care practice.

Evolutionary insights from suffix array-based genome sequence analysis.

Gene and protein sequence analyses, central components of studies in modern biology are easily amenable to string matching and pattern recognition algorithms. The growing need of analysing whole genome sequences more efficiently and thoroughly, has led to the emergence of new computational methods. Suffix trees and suffix arrays are data structures, well known in many other areas and are highly suited for sequence analysis too. Here we report an improvement to the design of construction of suffix arrays. Enhancement in versatility and scalability, enabled by this approach, is demonstrated through the use of real-life examples. The scalability of the algorithm to whole genomes renders it suitable to address many biologically interesting problems. One example is the evolutionary insight gained by analysing unigrams, bi-grams and higher n-grams, indicating that the genetic code has a direct influence on the overall composition of the genome. Further, different proteomes have been analysed for the coverage of the possible peptide space, which indicate that as much as a quarter of the total space at the tetra-peptide level is left un-sampled in prokaryotic organisms, although almost all tri-peptides can be seen in one protein or another in a proteome. Besides, distinct patterns begin to emerge for the counts of particular tetra and higher peptides, indicative of a 'meaning' for tetra and higher n-grams. The toolkit has also been used to demonstrate the usefulness of identifying repeats in whole proteomes efficiently. As an example, 16 members of one COG,coded by the genome of Mycobacterium tuberculosis H37Rv have been found to contain a repeating sequence of 300 amino acids.

Surgical treatment of hallux valgus: the Gibson-Piggott technique revisited.

More than 130 surgical procedures have been described to treat hallux valgus deformity. The "spike" first distal metatarsal osteotomy was first described by Gibson and Piggott in 1962. Despite having the advantage of using only patient's "material", this technique has been abandoned by most orthopaedic surgeons, due to fear of complications such as breaking of the bony peg and loosening of fixation at the osteotomy site. A group of surgeons at our hospital have performed 422 Gibson-Piggott procedures between 1985 and 2005 with consistently good results. This fact convinced us to "revisit" the procedure. Thirty seven consecutive patients (43 feet) who had surgery between July 2000 and December 2002 were randomly selected as "sample". A Questionnaire based on the American Orthopaedic Foot and Ankle Society (AFOS) Score was used for evaluation. Thirty three patients (36 feet), i.e. 89% responded to our survey. Average follow-up after surgery was 47 months (between 31 and 63 months). Results showed that 30 patients (91%) had no or only mild pain, 29 patients (88%) had no or only slight limitation in activities of daily living and 31 patients (94%) were able to use fashionable or comfortable shoes with no problems. When using numerical evaluation, 28 patients (85%) scored 65 or more points (from a total of 95 points), representing a good postoperative result, comparable with other "modern" distal metatarsal osteotomies. In conclusion, the Gibson-Piggott procedure was shown to be a valuable technique in the treatment of mild or moderate hallux valgus deformity.

Detection of IL-13, IL-10, and IL-6 in the leprosy skin lesions of patients during prednisolone treatment for type 1 (T1R) reactions.

This study demonstrates the presence of IL-10 and IL-6, by immunohistochemistry, in the skin lesions of patients with Type 1 reactions. Fifteen patients with Type 1 reaction from Hyderabad, India were included in this study. They were all receiving standardized treatment for Type 1 reactions: a reducing course of daily oral prednisolone for 6 months. Biopsies were taken before treatment and during treatment at weeks 1, 4, and 6 months. IL-13 was observed in the lesions of most patients. By week 4 of treatment, the presence of IL-13, IL-10, and IL-6 in the lesions had decreased significantly. Although some patients showed significant clinical skin sign improvement within one week of therapy, no concomitant decrease or increase in any of the cytokines was observed at this time point. Interestingly, some cytokine activity within the lesions was observed after 6 months of treatment.

Comparison of hepatic resection and hepatic transplantation in the treatment of hepatocellular carcinoma among cirrhotic patients.

BACKGROUND: The benefits of hepatic transplantation (HT) compared with hepatic resection (HR) in treating hepatocellular carcinoma (HCC) in patients with cirrhosis are controversial. The aim of this study was to compare the results of these therapeutic options. METHODS: The charts of all patients with cirrhosis who underwent HR or HT for HCC between 1997 and 2000 were analyzed. RESULTS: The cohort included 44 patients who underwent HR compared with 65 with HT. All patients in the HR group had Child's A disease, in contrast to the HT group, which included 23% Child's A and 77% Child's B and C patients. Whereas all HT patients spent at least three nights in the intensive care unit, 41% of the HR group never required critical care. Perioperative mortality was 7% in both groups. Pathologic analysis revealed T1/T2 disease in 43% of the HR group compared with 75% of the HT group. After 36 months of follow-up, there was no significant difference in overall survival (57% vs. 66%) or disease-free survival (36% vs. 66%) between the two groups. CONCLUSIONS: With overall survival and disease-free survival as the main outcomes, the results of HR versus HT are comparable in Child's A patients with HCC. In this patient subset, HR not only is an effective form of therapy, but is also associated with quicker recovery.