An efficient pyrrolysyl-tRNA synthetase for economical production of MeHis-containing enzymes.

Genetic code expansion has emerged as a powerful tool in enzyme design and engineering, providing new insights into sophisticated catalytic mechanisms and enabling the development of enzymes with new catalytic functions. In this regard, the non-canonical histidine analogue Nδ-methylhistidine (MeHis) has proven especially versatile due to its ability to serve as a metal coordinating ligand or a catalytic nucleophile with a similar mode of reactivity to small molecule catalysts such as 4-dimethylaminopyridine (DMAP). Here we report the development of a highly efficient aminoacyl tRNA synthetase (G1PylRSMIFAF) for encoding MeHis into proteins, by transplanting five known active site mutations from Methanomethylophilus alvus (MaPylRS) into the single domain PylRS from Methanogenic archaeon ISO4-G1. In contrast to the high concentrations of MeHis (5-10 mM) needed with the Ma system, G1PylRSMIFAF can operate efficiently using MeHis concentrations of ∼0.1 mM, allowing more economical production of a range of MeHis-containing enzymes in high titres. Interestingly G1PylRSMIFAF is also a 'polyspecific' aminoacyl tRNA synthetase (aaRS), enabling incorporation of five different non-canonical amino acids (ncAAs) including 3-pyridylalanine and 2-fluorophenylalanine. This study provides an important step towards scalable production of engineered enzymes that contain non-canonical amino acids such as MeHis as key catalytic elements.

Evaluation of Kinect 3D Sensor for Healthcare Imaging.

Microsoft Kinect is a three-dimensional (3D) sensor originally designed for gaming that has received growing interest as a cost-effective and safe device for healthcare imaging. Recent applications of Kinect in health monitoring, screening, rehabilitation, assistance systems, and intervention support are reviewed here. The suitability of available technologies for healthcare imaging applications is assessed. The performance of Kinect I, based on structured light technology, is compared with that of the more recent Kinect II, which uses time-of-flight measurement, under conditions relevant to healthcare applications. The accuracy, precision, and resolution of 3D images generated with Kinect I and Kinect II are evaluated using flat cardboard models representing different skin colors (pale, medium, and dark) at distances ranging from 0.5 to 1.2 m and measurement angles of up to 75°. Both sensors demonstrated high accuracy (majority of measurements <2 mm) and precision (mean point to plane error <2 mm) at an average resolution of at least 390 points per cm2. Kinect I is capable of imaging at shorter measurement distances, but Kinect II enables structures angled at over 60° to be evaluated. Kinect II showed significantly higher precision and Kinect I showed significantly higher resolution (both p < 0.001). The choice of object color can influence measurement range and precision. Although Kinect is not a medical imaging device, both sensor generations show performance adequate for a range of healthcare imaging applications. Kinect I is more appropriate for short-range imaging and Kinect II is more appropriate for imaging highly curved surfaces such as the face or breast.

ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children.

The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available genetic testing, and to review newer methods for evaluating pancreatitis.

How often does the operating list follow the planned order? An analysis of elective maxillofacial operating lists.

OBJECTIVES: The authors explored consistency of the observed running order in operating sequence compared with prior scheduled listing. We analysed potential variables felt to be predictive in the chances of a patient having their procedure as previously scheduled. METHODS: Data were retrospectively collected for a consecutive group of patients who underwent elective maxillofacial procedures over a four week period. The consistency of scheduled and observed running order was documented. We considered four independent variables (original list position, day of week, morning or afternoon list, seniority of surgeon) and analysed their relationship to the probability of a patient undergoing their operation as per listing. Logistic regression analysis was used to determine significant associations between predictor variables with an altered list order. RESULTS: Data were available for 35 lists (n = 133). 49% of lists were found to run according to prior given order, the remainder subject to some alteration. Logistic regression analysis showed a statistically significant association between original scheduled position and day of week, with list position consistency. Patients listed first were twelve times more likely to have their operation as listed compared to those placed fourth (OR 12.7, 95% CI 3.7-43, p < 0.05). Operating lists at the start of a week were subject to less alteration (p < 0.05). There was no demonstrated relationship between the grade of surgeon operating and alteration in operating sequence. CONCLUSION: Approximately half of lists showed some alteration to the previously printed order. It appears that being first on an elective list offers the greatest guarantee that a patient will have their operation as per prior schedule. It may be reasonable for clinicians to be mindful of potential operating list alterations when preparing their patients for elective surgery.

Engineering enzyme activity using an expanded amino acid alphabet.

Enzyme design and engineering strategies are typically constrained by the limited size of nature's genetic alphabet, comprised of only 20 canonical amino acids. In recent years, site-selective incorporation of non-canonical amino acids (ncAAs) via an expanded genetic code has emerged as a powerful means of inserting new functional components into proteins, with hundreds of structurally diverse ncAAs now available. Here, we highlight how the emergence of an expanded repertoire of amino acids has opened new avenues in enzyme design and engineering. ncAAs have been used to probe complex biological mechanisms, augment enzyme function and, most ambitiously, embed new catalytic mechanisms into protein active sites that would be challenging to access within the constraints of nature's genetic code. We predict that the studies reviewed in this article, along with further advances in genetic code expansion technology, will establish ncAA incorporation as an increasingly important tool for biocatalysis in the coming years.

Engineering mutually orthogonal PylRS/tRNA pairs for dual encoding of functional histidine analogues.

The availability of an expanded genetic code opens exciting new opportunities in enzyme design and engineering. In this regard histidine analogues have proven particularly versatile, serving as ligands to augment metalloenzyme function and as catalytic nucleophiles in designed enzymes. The ability to genetically encode multiple functional residues could greatly expand the range of chemistry accessible within enzyme active sites. Here, we develop mutually orthogonal translation components to selectively encode two structurally similar histidine analogues. Transplanting known mutations from a promiscuous Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRSIFGFF ) into a single domain PylRS from Methanomethylophilus alvus (MaPylRSIFGFF ) provided a variant with improved efficiency and specificity for 3-methyl-L-histidine (MeHis) incorporation. The MaPylRSIFGFF clone was further characterized using in vitro biochemical assays and x-ray crystallography. We subsequently engineered the orthogonal MmPylRS for activity and selectivity for 3-(3-pyridyl)-L-alanine (3-Pyr), which was used in combination with MaPylRSIFGFF to produce proteins containing both 3-Pyr and MeHis. Given the versatile roles played by histidine in enzyme mechanisms, we anticipate that the tools developed within this study will underpin the development of enzymes with new and enhanced functions.

The influence of measurement location on reliability of quantitative nailfold videocapillaroscopy in patients with SSc.

OBJECTIVES: Nailfold videocapillaroscopy is being increasingly used as a marker of SSc-related microvascular disease, including in response to treatment. However, it requires further validation. Our aim was to assess the inter-observer, intra-observer and test-retest variability of semi-automated measurement of capillary features as well as of a manual density measurement. METHODS: All capillary apexes in images from 58 patients with SSc were marked up independently by two trained observers (inter-observer variability). The first observer then re-marked the images (intra-observer variability), and finally, the first observer marked up a second image of the same nailfold (test-retest). Mark-up of capillaries was carried out on cropped mosaic images (cropped independently by the observers to a fixed width, to allow the same length of nail bed to be studied for each patient) and on whole mosaic images (examining the whole nail bed). RESULTS: Reproducibility of independently cropped mosaic images was poor and was due to the variation in the positioning of the cropped area. However, quantification of whole mosaic images was highly reproducible, e.g. for inter-capillary distance, the intra-class correlation coefficient for inter-observer, intra-observer and test-retest reliability was 0.95, 0.98 and 0.90 (compared with 0.88, 0.79 and 0.89 for cropped mosaic images), respectively. Intra-observer limits of agreement for whole mosaic images were better than inter-observer reproducibility. CONCLUSION: Quantitative assessment of SSc-related change in nailfold capillaries is unreliable if examination of the same set of capillaries cannot be guaranteed. Conversely a wide-field, high-magnification system that allows visualization of the whole nail bed offers a highly reproducible approach for quantitative assessment and therefore has potential as an outcome measure.

Preliminary clinical evaluation of semi-automated nailfold capillaroscopy in the assessment of patients with Raynaud's phenomenon.

OBJECTIVES: Nailfold capillaroscopy is well established in screening patients with Raynaud's phenomenon for underlying SSc-spectrum disorders, by identifying abnormal capillaries. Our aim was to compare semi-automatic feature measurement from newly developed software with manual measurements, and determine the degree to which semi-automated data allows disease group classification. METHODS: Images from 46 healthy controls, 21 patients with PRP and 49 with SSc were preprocessed, and semi-automated measurements of intercapillary distance and capillary width, tortuosity, and derangement were performed. These were compared with manual measurements. Features were used to classify images into the three subject groups. RESULTS: Comparison of automatic and manual measures for distance, width, tortuosity, and derangement had correlations of r=0.583, 0.624, 0.495 (p<0.001), and 0.195 (p=0.040). For automatic measures, correlations were found between width and intercapillary distance, r=0.374, and width and tortuosity, r=0.573 (p<0.001). Significant differences between subject groups were found for all features (p<0.002). Overall, 75% of images correctly matched clinical classification using semi-automated features, compared with 71% for manual measurements. CONCLUSIONS: Semi-automatic and manual measurements of distance, width, and tortuosity showed moderate (but statistically significant) correlations. Correlation for derangement was weaker. Semi-automatic measurements are faster than manual measurements. Semi-automatic parameters identify differences between groups, and are as good as manual measurements for between-group classification.

Outcome in poor grade subarachnoid hemorrhage patients treated with acute endovascular coiling of aneurysms and aggressive intensive care.

BACKGROUND: Patients with poor grade (World Federation of Neurosurgeons (WFNS) Grades 4 and 5) subarachnoid hemorrhage (SAH) were historically considered to have a poor neurological outcome and therefore not traditionally offered aggressive treatment. In recent years there has been increasing evidence that early aggressive treatment of this patient group can result in a good outcome. Aim of this study is to identify the outcome of patients with WFNS Grade-4 and -5 SAH treated acutely with endovascular detachable coil embolization (DCE) and aggressive neurocritical care within our institution. METHODS: We retrospectively reviewed the records of patients with SAH WFNS Grades 4 and 5 treated with DCE within 7 days of admission between 1st January 2004 and 1st January 2008. Data collected included age, sex, grade SAH, position/number of Aneurysms, coiling complications, time spent on the neurosurgical critical care unit (NCCU), and 6-month outcome assessed by Glasgow outcome scale (GOS). GOS was dichotomized into good outcome (good recovery/moderate disability) and poor outcome (severe disability, vegetative, dead). RESULTS: A total of 193 acute SAH patients were admitted and treated within this time period, of these, 47 patients were classified as poor grade and included: 70% were female and 30% were male. The mean age was 56 years (33-88 years range). A total of 56 aneurysms were noted at angiography, 52 aneurysms were coiled. Complications of SAH Vasospasm was noted in 18 patients (38%), cerebral infarction in 13 patients (28%), seizures in 7 patients (15%), hydrocephalus in 25 patients (53%). Complications of DCE occurred in 2 patients (4% of total) these were an aneurysmal rupture and a peri-procedure thrombosis. Incomplete coiling occurred in another 5 patients (10.6% of total) due to technical difficulties. The median length of stay on the NCCU was 12 days (1-52 days range). Of the 47 poor grade patients coiled, 25 (53%) had a good outcome (good recovery/moderate disability) and 22 (47%) had a poor outcome (severe disability, vegetative, dead) by the time of the 6-month follow-up. CONCLUSION: Potentially, more than half the patients with WFNS Grade-4 and -5 SAH who are treated aggressively with coil embolization in association with supportive neurocritical care can achieve a good quality neurological outcome. However, it should be anticipated that these patients will spend a significant period of time in neurocritical care.

Functional splinting of upper limb injuries with gauze-based topical negative pressure wound therapy.

Complex hand injuries can be difficult to dress effectively and achieve adequate splintage of the hand in a functional position. During the past 7 years, we have had a great deal of success with topical negative-pressure dressings in the management of complex blast-related extremity war injuries. We have more recently changed to using a gauze-based system and have found this particularly useful in dressing complex hand injuries. We have been able to use this vacuum dressing system to splint the hand in a position of function. This provides an easily applied dressing that, through topical negative pressure, promotes wound healing and ensures a resting functional position, thus minimizing postoperative stiffness. We have not been able to achieve this as efficiently with standard dressings and plaster-of-Paris casts. This article details the technique of functional splinting of complex hand injuries using a gauze-based, topical negative-pressure dressing system.

Noncovalent interactions in the gas-phase conformers of anionic iduronate (methyl 2-o-sulfo-α-L-iduronate): variation of subconformer versus ring conformer energetics for a prototypical anionic monosaccharide studied using computational methods.

The conformational preferences of the prototypical anionic monosaccharide (methyl 2-O-sulfo-α-L-iduronate) have been studied at various computational levels to investigate the energetic variation of 17 subconformers associated with the (4)C(1), (2)S(0), (5)S(1), and (1)C(4) ring conformers. These calculations include the first fully optimized MP2 calculations that have been performed for an anionic sugar system, and therefore allow an assessment of the performance of a group of DFT functionals (B3LYP, PW91PW91, and M05-2X) for treating the noncovalent dispersion and anomeric effects that are present in this system. We find that the recently developed M05-2X functional of Truhlar and co-workers [Y. Zhao, N. E. Schultz, D. G. Truhlar, J. Chem. Theory Comput., 2006, 2, 364] reproduces the MP2 results most closely, thus indicating that it may well be suitable for computational studies of larger ionic saccharides. Most importantly, the results presented indicate that it is crucial to consider the subconformers (which correspond to rearrangements of the sugar-ring side-chains) of the main ring-conformers in order to obtain a reliable overview of the potential energy surface of such systems. We find that the lowest isolated (gas-phase) conformer corresponds to a (4)C(1) chair conformer, which displays a pair of strong C(3)-OH···SO(3)(-) and OMe···SO(3)(-) electrostatic hydrogen-bonding interactions, coupled with a looser C(4)-OH···SO(3)(-) interaction. Overall, the relative energies of the subconformers appear to be straightforwardly related to the number of hydrogen-bonding interactions that each conformer displays among its pendant functional groups.

The formation of the cAMP/protein kinase A-dependent annexin 2-S100A10 complex with cystic fibrosis conductance regulator protein (CFTR) regulates CFTR channel function.

Cystic fibrosis results from mutations in the cystic fibrosis conductance regulator protein (CFTR), a cAMP/protein kinase A (PKA) and ATP-regulated Cl(-) channel. CFTR is increasingly recognized as a component of multiprotein complexes and although several inhibitory proteins to CFTR have been identified, protein complexes that stimulate CFTR function remain less well characterized. We report that annexin 2 (anx 2)-S100A10 forms a functional cAMP/PKA/calcineurin (CaN)-dependent complex with CFTR. Cell stimulation with forskolin/3-isobutyl-1-methylxanthine significantly increases the amount of anx 2-S100A10 that reciprocally coimmunoprecipitates with cell surface CFTR and calyculin A. Preinhibition with PKA or CaN inhibitors attenuates the interaction. Furthermore, we find that the acetylated peptide (STVHEILCKLSLEG, Ac1-14), but not the nonacetylated equivalent N1-14, corresponding to the S100A10 binding site on anx 2, disrupts the anx 2-S100A10/CFTR complex. Analysis of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and CFTR(inh172)-sensitive currents, taken as indication of the outwardly rectifying Cl(-) channels (ORCC) and CFTR-mediated currents, respectively, showed that Ac1-14, but not N1-14, inhibits both the cAMP/PKA-dependent ORCC and CFTR activities. CaN inhibitors (cypermethrin, cyclosporin A) discriminated between ORCC/CFTR by inhibiting the CFTR(inh172)-, but not the DIDS-sensitive currents, by >70%. Furthermore, peptide Ac1-14 inhibited acetylcholine-induced short-circuit current measured across a sheet of intact intestinal biopsy. Our data suggests that the anx 2-S100A10/CFTR complex is important for CFTR function across epithelia.

Rectal Perforation following High-Pressure Distal Colostogram.

In patients with anorectal malformations and a colostomy, the high-pressure distal colostogram is the technique of choice to determine the type of malformation and thus to plan the surgical repair. Perforations associated with high-pressure distal colostograms are very rare. The aim of our study was to identify pitfalls to prevent perforation secondary to high-pressure distal colostogram. The study included two male patients and was complicated with rectal perforations secondary to high-pressure distal colostogram. Both patients had an imperforate anus without a fistula. One patient had extraperitoneal rectal perforation with progressive contrast spillage into the peritoneum and demised. The other patient developed an extraperitoneal perforation and an associated necrotizing fasciitis of his perineum and scrotum, but he recovered well after debridement. Two further cases of rectal perforation have been described in the literature. Rectal perforation, although rare, is a described life-threatening complication secondary to high-pressure distal colostogram. The cause is excessive contrast pressure. Injection of contrast should be stopped once the distal end of the colon has a convex shape. Intraperitoneal perforation may cause hypovolemic/septic shock, and patients need to be appropriately resuscitated and should undergo laparotomy. Extraperitoneal perforation requires close monitoring for possible local complications, which may necessitate early debridement.

A Surgical Technique to Repair Perineal Body Disruption Secondary to Sexual Assault.

Perineal trauma is uncommon in the pediatric population and it is estimated that 5 to 21% is secondary to sexual abuse. We aim to present a proposed surgical technique to repair perineal injuries secondary to sexual assault in female children. The technique is based on the posterior sagittal anorectoplasty (PSARP) for repairing anorectal malformations and, between 2017 and 2019, it was used to treat three girls (2 months, 2 years, and 8 years of age) with fourth-degree perineal injuries secondary to sexual assault. One of them underwent laparotomy and Hartmann's colostomy for an acute abdomen. Two underwent wound debridement and suturing and only had a stoma fashioned at 5 days and 6 weeks posttrauma, respectively. The perineal repair was performed 2, 6, and 7 weeks postinjury and done as follows: with the child prone in jack-knife position, stay-sutures are placed on the common wall between the rectum and the vagina. Using a needle tip diathermy, a transverse incision is performed below the sutures lifting the anterior rectal wall up. Stay sutures are then positioned on the posterior wall of the vaginal mucosa. The incision between the walls is deepened until the rectum and the vagina are completely separated. The deep and superficial perineal body is then reconstructed using absorbable sutures and an anterior anoplasty and an introitoplasty are performed. The stoma in each was closed 6 weeks postreconstruction. At follow-up, now 1 year or more postrepair, all patients have an excellent cosmetic outcome and are fully continent for stools.

Characterization of imine reductases in reductive amination for the exploration of structure-activity relationships.

Imine reductases (IREDs) have shown great potential as catalysts for the asymmetric synthesis of industrially relevant chiral amines, but a limited understanding of sequence activity relationships makes rational engineering challenging. Here, we describe the characterization of 80 putative and 15 previously described IREDs across 10 different transformations and confirm that reductive amination catalysis is not limited to any particular subgroup or sequence motif. Furthermore, we have identified another dehydrogenase subgroup with chemoselectivity for imine reduction. Enantioselectivities were determined for the reduction of the model substrate 2-phenylpiperideine, and the effect of changing the reaction conditions was also studied for the reductive aminations of 1-indanone, acetophenone, and 4-methoxyphenylacetone. We have performed sequence-structure analysis to help explain clusters in activity across a phylogenetic tree and to inform rational engineering, which, in one case, has conferred a change in chemoselectivity that had not been previously observed.

Assessment of hyperpolarized 3He lung MRI for regional evaluation of interventional therapy: a pilot study in pediatric cystic fibrosis.

PURPOSE: To determine whether regional changes in lung ventilation in a group of pediatric cystic fibrosis (CF) patients following a course of chest physiotherapy could be detected with (3)He MRI. MATERIALS AND METHODS: The reproducibility of lung ventilation volume measurements obtained with (3)He lung magnetic resonance imaging (MRI) was established in a group of five children with CF age 6-15 years. The same methodology was then used to evaluate whether standard chest physiotherapy (percussion and drainage) had any immediate effect on regional ventilated lung volumes in a further group of nine age-matched CF children (5-15 years). RESULTS: Global lung ventilation volumes remained the same within the limits of sensitivity derived from the reproducibility study; however, regional lung ventilation was observed to change in most patients after therapy. CONCLUSION: (3)He MRI can be successfully used in children with CF, and has the sensitivity to detect regional quantitative changes in lung ventilation following chest physiotherapy.

Genetic modifiers of liver disease in cystic fibrosis.

CONTEXT: A subset (approximately 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension. OBJECTIVE: To assess whether any of 9 polymorphisms in 5 candidate genes (alpha(1)-antitrypsin or alpha(1)-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2], and transforming growth factor beta1 [TGFB1]) are associated with severe liver disease in patients with CF. DESIGN, SETTING, AND PARTICIPANTS: Two-stage case-control study enrolling patients with CF and severe liver disease with portal hypertension (CFLD) from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America, with the University of North Carolina at Chapel Hill as the coordinating site. In the initial study, 124 patients with CFLD (enrolled January 1999-December 2004) and 843 control patients without CFLD were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 patients with CFLD (enrolled January 2005-February 2007) and 1088 with no CFLD. MAIN OUTCOME MEASURES: Differences in distribution of genotypes in patients with CFLD vs patients without CFLD. RESULTS: The initial study showed CFLD to be associated with the SERPINA1 Z allele (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.31-9.61; P = 3.3 x 10(-6)) and with TGFB1 codon 10 CC genotype (OR, 1.53; 95% CI, 1.16-2.03; P = 2.8 x 10(-3)). In the replication study, CFLD was associated with the SERPINA1 Z allele (OR, 3.42; 95% CI, 1.54-7.59; P = 1.4 x 10(-3)) but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (OR, 5.04; 95% CI, 2.88-8.83; P = 1.5 x 10(-8)). CONCLUSIONS: The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater risk (OR, approximately 5) of developing severe liver disease with portal hypertension.

Effects of response preference on resistance to change.

Treatments based on differential reinforcement of alternative behavior, such as functional communication training, are widely used. Research regarding the maintenance of related treatment effects is limited. Nevin and Wacker (2013) provided a conceptual framework, rooted in behavioral momentum theory, for the study of treatment maintenance that addressed two components: (a) reemergence of problem behavior, and (b) continued expression of appropriate behavior. In the few studies on this topic, focus has been on variables impacting the reemergence of problem behavior, with fewer studies evaluating the persistence of appropriate behavior. Given the findings from applied research related to functional communication training, variables related to response topography, such as response preference, may impact this aspect of maintenance. In the current study, the impact of response preference on persistence was evaluated in the context of functional communication training for individuals who did not exhibit problem behavior (Experiment 1) and for individuals with a history of reinforcement for problem behavior (Experiment 2). High-preferred mands were more persistent than low-preferred mands. These findings suggest that response related variables, such as response preference, impact response persistence and further suggest that response related variables should be considered when developing interventions such as functional communication training.

Improved wrist pannus volume measurement from contrast-enhanced MRI in rheumatoid arthritis using shuffle transform.

BACKGROUND: Contrast-enhanced MRI is of value in assessing rheumatoid pannus in the hand, but the images are not always easy to quantitate. OBJECTIVE: To develop and evaluate an improved measurement of volume of enhancing pannus (VEP) in the hand in human rheumatoid arthritis (RA). METHODS: MR images of the hand and wrist were obtained for 14 patients with RA at 0, 1 and 13 weeks. Volume of enhancing pannus was measured on images created by subtracting precontrast T1-weighted images from contrast-enhanced T1-weighted images using a shuffle transformation technique. Maximum intensity projection (MIP) and 3D volume rendering of the images were used as a guide to identify the pannus and any contrast-enhanced veins. RESULT: Visualisation of pannus was much improved following the shuffle transform. Between 0 weeks and 1 week, the mean value of the within-subject coefficient of variation (CoV) was 0.13 and the estimated total CoV was 0.15. There was no evidence of significant increased variability within the 13-week interval for the complete sample of patients. CONCLUSION: Volume of enhancing pannus can be measured reproducibly in the rheumatoid hand using 3D contrast-enhanced MRI and shuffle transform.

Cystic Fibrosis & disorders of the large intestine: DIOS, constipation, and colorectal cancer.

Since 1966 when the Cystic Fibrosis Foundation Patient Registry (CFFPR) was founded, clinicians have witnessed significant advances in both the quality and quantity of life for patients living with Cystic Fibrosis (CF). As patients with CF live longer and fuller lives, increasing encumbrances from gastrointestinal manifestations of CF will be observed. This article serves to discuss "below the diaphragm" concerns involving the large intestine (Distal Intestinal Obstruction Syndrome, Constipation, and Colorectal Cancer). Avenues for development and implementation of clinical care protocols, particularly regarding proactive management of known associated conditions and cancer screening, will continue to be refined in the coming years. It falls to the multidisciplinary CF care team to be actively engaged in addressing these concerns effectively as priority shifts from relative acuity (typically related to early nutrition and lung function) to the travails of longevity as the CF population continues to age.