Evaluation of the reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index and the Cutaneous Assessment Tool-Binary Method in juvenile dermatomyositis among paediatric dermatologists, rheumatologists and neurologists.

BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and Cutaneous Assessment Tool-Binary Method (CAT-BM) have been shown to be reliable and valid outcome measures to assess cutaneous disease in adult dermatomyositis (DM) and juvenile DM (JDM), respectively. OBJECTIVES: This study compared the CDASI and CAT-BM for use by paediatric dermatologists, paediatric rheumatologists and paediatric neurologists in patients with JDM. METHODS: Five paediatric dermatologists, five paediatric rheumatologists and five paediatric neurologists each evaluated 14 patients with JDM using the CDASI, CAT-BM, and skin Physician Global Assessment (PGA) scales. Inter-rater reliability, intra-rater reliability, construct validity and completion time were compared. RESULTS: Inter-rater reliability for CDASI activity and damage scores was good to moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists. The inter-rater reliability for CAT-BM activity scores was moderate for paediatric dermatologists and rheumatologists, but poor for paediatric neurologists and poor across all specialties for damage scores. Intra-rater reliability for the CDASI and CAT-BM activity and damage scores was moderate to excellent for paediatric dermatologists, rheumatologists and neurologists. Strong associations were found between skin PGA activity and damage scores and CDASI or CAT-BM activity and damage scores, respectively (P < 0·002). The CDASI had a mean completion time of 5·4 min compared with that for the CAT-BM of 3·1 min. CONCLUSIONS: Our data confirm the reliability of the CDASI activity and damage scores and the CAT-BM activity scores when used by paediatric dermatologists and rheumatologists in assessing JDM. Significant variation existed in the paediatric neurologists' scores.

The new classification of seizures: an overview for the general physician.

The International League Against Epilepsy Classification of the Epilepsies, first presented in 1981, has been widely adopted across the globe. In 2017 it was revised to allow for more robust, specific, flexible and logical classification of seizures. A number of new seizure types are recognised. Classification should be timely as it plays a vital role in the diagnosis and management of patients with epilepsy. Accurate classification also underpins epilepsy research from pathophysiology to public health. Here we review the basic and extended forms of the classification. Semiology (symptoms and signs) is used as the foundation for grouping seizures under focal, generalised or of unknown onset. Focal seizures can be further classified by the presence or absence of awareness and motor signs. Generalised seizures engage bilateral networks from the onset and these can be either motor or non-motor. Seizures of unknown onset can be classified as motor, non-motor, tonic-clonic, epileptic spasms, or behaviour arrest.

Leveraging genetically simple traits to identify small-effect variants for complex phenotypes.

BACKGROUND: Polymorphisms underlying complex traits often explain a small part (less than 1 %) of the phenotypic variance (σ2P). This makes identification of mutations underling complex traits difficult and usually only a subset of large-effect loci are identified. One approach to identify more loci is to increase sample size of experiments but here we propose an alternative. The aim of this paper is to use secondary phenotypes for genetically simple traits during the QTL discovery phase for complex traits. We demonstrate this approach in a dairy cattle data set where the complex traits were milk production phenotypes (fat, milk and protein yield; fat and protein percentage in milk) measured on thousands of individuals while secondary (potentially genetically simpler) traits are detailed milk composition traits (measurements of individual protein abundance, mineral and sugar concentrations; and gene expression). RESULTS: Quantitative trait loci (QTL) were identified using 11,527 Holstein cattle with milk production records and up to 444 cows with milk composition traits. There were eight regions that contained QTL for both milk production and a composition trait, including four novel regions. One region on BTAU1 affected both milk yield and phosphorous concentration in milk. The QTL interval included the gene SLC37A1, a phosphorous antiporter. The most significant imputed sequence variants in this region explained 0.001 σ2P for milk yield, and 0.11 σ2P for phosphorus concentration. Since the polymorphisms were non-coding, association mapping for SLC37A1 gene expression was performed using high depth mammary RNAseq data from a separate group of 371 lactating cows. This confirmed a strong eQTL for SLC37A1, with peak association at the same imputed sequence variants that were most significant for phosphorus concentration. Fitting any of these variants as covariables in the association analysis removed the QTL signal for milk production traits. Plausible causative mutations in the casein complex region were also identified using a similar strategy. CONCLUSIONS: Milk production traits in dairy cows are typical complex traits where polymorphisms explain only a small portion of the phenotypic variance. However, here we show that these mutations can have larger effects on secondary traits, such as concentrations of minerals, proteins and sugars in the milk, and expression levels of genes in mammary tissue. These larger effects were used to successfully map variants for milk production traits. Genetically simple traits also provide a direct biological link between possible causal mutations and the effect of these mutations on milk production.

Incorporating mixed rations and formulated grain mixes into the diet of grazing cows: Effects on milk composition and coagulation properties, and the yield and quality of Cheddar cheese.

Effects of different strategies for feeding supplements to grazing dairy cows on the composition and coagulation properties of milk and the subsequent yield and quality of Cheddar cheese were measured. The experiment used milk from 72 Holstein-Friesian cows, averaging 45d in milk, fed according to 1 of 3 feeding strategies: (1) cows grazed a restricted allowance of perennial ryegrass pasture [approximately 14kg of dry matter (DM)/cow per day, to ground level] supplemented with milled wheat grain fed in the milking parlor and alfalfa hay offered in the paddock (control); (2) same pasture and allowance as control, supplemented with a formulated grain mix containing wheat grain, corn grain, and canola meal fed in the parlor and alfalfa hay fed in the paddock (FGM); or (3) same pasture and allowance as control, supplemented with a partial mixed ration comprising the same formulated grain mix but mixed with alfalfa hay and presented on a feed pad after each milking (PMR). For all strategies, supplements provided the same metabolizable energy and grain:forage ratio (78:22, DM basis). Within each feeding strategy, milk was sampled from cows receiving either 8 or 16kg (DM) of supplement/cow per day. There were 2 replicated groups of 6 cows per supplement amount per dietary strategy; approximately 250L of milk was sampled from each for analyses of composition and coagulation properties and the manufacture of Cheddar cheese. The experiment had a 14-d adaptation period and a 14-d measurement period. For cows fed according to the control strategy, those fed 16kg/cow per day produced milk with lower concentrations of milk fat than cows fed 8kg/cow per day. This effect was not observed for cows fed according to the FGM and PMR strategies. Milk from cows fed 16kg of DM/cow per day according to the control strategy yielded less Cheddar cheese than milk from cows fed according to the PMR strategy, with cheese yields from FGM cows being intermediate. Amount of supplement offered had minor effects on percentages of some fatty acids. We observed few other effects of feeding strategy on milk composition, types of milk protein, milk coagulation properties, or the composition and quality of the resultant Cheddar cheese. These data show that, compared with the traditional control strategy, feeding PMR or FGM may increase milk fat concentration and the subsequent yield of Cheddar cheese without compromising cheese composition or quality.

Casein polymorphism heterogeneity influences casein micelle size in milk of individual cows.

Milk samples from individual cows producing small (148-155 nm) or large (177-222 nm) casein micelles were selected to investigate the relationship between the individual casein proteins, specifically κ- and ß-casein phenotypes, and casein micelle size. Only κ-casein AA and ß-casein A1A1, A1A2 and A2A2 phenotypes were found in the large casein micelle group. Among the small micelle group, both κ-casein and ß-casein phenotypes were more diverse. κ-Casein AB was the dominant phenotype, and 3 combinations (AA, AB, and BB) were present in the small casein micelle group. A considerable mix of ß-casein phenotypes was found, including B and I variants, which were only found in the small casein micelle group. The relative amount of κ-casein to total casein was significantly higher in the small micelle group, and the nonglycosylated and glycosylated κ-casein contents were higher in the milks with small casein micelles (primarily with κ-casein AB and BB variants) compared with the large micelle group. The ratio of glycosylated to nonglycosylated κ-casein was higher in the milks with small casein micelles compared with the milks with large casein micelles. This suggests that although the amount of κ-casein (both glycosylated and nonglycosylated) is associated with micelle size, an increased proportion of glycosylated κ-casein could be a more important and favorable factor for small micelle size. This suggests that the increased spatial requirement due to addition of the glycosyl group with increasing extent of glycosylation of κ-casein is one mechanism that controls casein micelle assembly and growth. In addition, increased electrostatic repulsion due to the sialyl residues on the glycosyl group could be a contributory factor.

The effect of sodium chloride substitution with potassium chloride on texture profile and microstructure of Halloumi cheese.

The effect of partial substitution of NaCl with KCl on texture profile and microstructure of Halloumi cheese was investigated. Four batches of Halloumi cheese were made and kept in 4 different brine solutions (18%, wt/wt), including A) NaCl only, B) 3NaCl:1KCl, C) 1NaCl:1KCl, and D) 1NaCl:3KCl and then stored at 4°C for 56 d. The texture profile was analyzed using an Instron universal machine, whereas an environmental scanning electron microscope was used to investigate the effect of NaCl substitution on the microstructure of cheeses. No significant difference was found in hardness, cohesiveness, adhesiveness, and gumminess among experimental cheeses at the same storage day. Hardness, cohesiveness, and gumminess decreased significantly during storage period with the same salt treatment, whereas adhesiveness significantly increased. Environmental scanning electron microscope micrographs showed a compact and closed texture for cheeses at the same storage period. The microstructure of all cheeses became more closed and compact with storage period. Calcium content negatively correlated with hardness and Na and K contents during storage with the same salt treatment.

Composition, coagulation properties, and cheesemaking potential of milk from cows undergoing extended lactations in a pasture-based dairying system.

Extending the lactation length of dairy cows beyond the traditional 10 mo toward lactations of up to 22 mo has attracted interest in the pasture-based seasonal dairying systems of Australia and New Zealand as a way of alleviating the need for cows to conceive during peak lactation, such as is required to maintain seasonally concentrated calving systems. Lactation lengths longer than 10 mo instead provide cows with more time to cycle and conceive after parturition and may therefore be more suitable systems for high-producing Holstein-Friesian cows. Before recommending such systems there is a need to evaluate the effects of long lactations on the suitability of milk for manufacture of high-quality dairy products. In the current experiment, the composition of milk from cows entering the second half of a 22-mo lactation was examined in detail and compared with that from cows undergoing a traditional 10-mo lactation. On 2 occasions, coagulation properties were measured using low amplitude strain oscillation rheometry, and Cheddar cheese was made in 250-L pilot-scale vats. Results showed that milk from extended lactations had higher concentrations of fat and protein than cows undergoing 10-mo lactations under similar management conditions and at the same time of year. The ratio of casein to true protein was not affected by lactation length and neither were the proportions of individual caseins. The increase in milk solids during extended lactations translated into a more rapid rate of coagulation and ultimately a firmer curd on one of the two occasions. Milk from extended lactations yielded more cheese per 100 kg of milk, and there were few differences in the composition or organoleptic properties of the cheese. These data are the first to show that pasture-based dairy industries could embrace the use of extended lactations without compromising the core business of producing high-quality dairy products.

'No going back' to institutional care for people with severe disability: reflections on practice through an interpretive study.

PURPOSE: This paper evaluated quality of life for people with a disability with high health and high support needs following a move from a congregate care institution to community housing. The study explored residents' perceptions of the service, level of community involvement, lifestyle choices, and input into decision-making. METHOD: An exploratory interpretative study was conducted using semi structured interviews with nine community house residents, ten community house staff and five family members. RESULTS: Participants were clear they definitely would not go back to the institution, but the relocation experience was not without difficulties. These issues related to 'site', 'staff' & 'skills'. CONCLUSIONS: Direct support staff hold considerable power to increase or diminish residents' quality of life. A targeted programme addressing specific site, staff & skill issues would strengthen quality of life for these very dependent residents.

Comparison of casein micelles in raw and reconstituted skim milk.

During the manufacture of skim milk powder, many important alterations to the casein micelles occur. This study investigates the nature and cause of these alterations and their reversibility upon reconstitution of the powders in water. Samples of skim milk and powder were taken at different stages of commercial production of low-, medium-, and high-heat powders. The nature and composition of the casein micelles were analyzed using a variety of analytical techniques including photon correlation spectroscopy, transmission electron microscopy, turbidity, and protein electrophoresis. It was found that during heat treatment, whey proteins are denatured and become attached to the casein micelles, resulting in larger micelles and more turbid milk. The extent of whey protein attachment to the micelles is directly related to the severity of the heat treatment. It also appeared that whey proteins denatured during heat treatment may continue to attach to casein micelles during water removal (evaporation and spray-drying). The process of water removal causes casein and Ca in the serum to become increasingly associated with the micelles. This results in much larger, denser micelles, increasing the turbidity while decreasing the viscosity of the milk. During reconstitution, the native equilibrium between colloidal Ca and serum Ca is slowly reestablished. The reequilibration of the caseins and detachment of the whey proteins occur even more slowly. The rate of reequilibration does not appear to be influenced by shear or temperature in the range of 4 to 40 degrees C.

CT-based classification of long spinal allograft fusion.

Anterior column reconstruction of the thoracolumbar spine by structural allograft has an increased potential for biological fusion when compared to synthetic reconstructive options. Estimation of cortical union and trabecular in-growth is, however, traditionally based on plain radiography, a technique lacking in sensitivity. A new assessment method of bony union using high-speed spiral CT imaging is proposed which reflects the gradually increasing biological stability of the construct. Grade I (complete fusion) implies cortical union of the allograft and central trabecular continuity. Grade II (partial fusion) implies cortical union of the structural allograft with partial trabecular incorporation. Grade III (unipolar pseudarthrosis) denotes superior or inferior cortical non-union of the central allograft with partial trabecular discontinuity centrally and Grade IV (bipolar pseudarthrosis) suggests both superior and inferior cortical non-union with a complete lack of central trabecular continuity. Twenty-five patients underwent anterior spinal reconstruction for a single level burst fracture between T4 and L5. At a minimum of two years follow up the subjects underwent high-speed spiral CT scanning through the reconstructed region of the thoracolumbar spine. The classification showed satisfactory interobserver (kappa score = 0.91) and intraobserver (kappa score = 0.95) reliability. The use of high-speed CT imaging in the assessment of structural allograft union may allow a more accurate assessment of union. The classification system presented allows a reproducible categorization of allograft incorporation with implications for treatment.

Liposclerosing myxofibrous tumour: a traumatized variant of fibrous dysplasia? Report of four cases and review of the literature.

AIMS: To describe the pathological and radiological features of four cases of liposclerosing myxofibrous tumour (LSMFT). LSMFT is a benign fibro-osseous lesion of bone with a marked predilection for the intertrochanteric region of the proximal femur. It is characterized by a complex mixture of histological elements including fibrous dysplasia-like bony trabeculae, myxofibrous tissue, lipomatous areas, xanthoma cells and pseudo-Paget's bone. This lesion is not a universally accepted pathological entity and often appears in the literature under variants of fibrous dysplasia or other benign lytic bone lesions. METHODS AND RESULTS: All lesions exhibited histological and/or radiological overlap with fibrous dysplasia. A relationship to trauma was noted in three of the cases. The hypothesis that these lesions represent a traumatized variant of fibrous dysplasia was explored. After reviewing the biomechanics of the proximal femur, a possible relationship between predilection of LSFMT for this anatomical region and increased susceptibility to fracture was noted. CONCLUSIONS: We hypothesize that when fibrous dysplasia involves the proximal femur, it makes the bone more susceptible to fatigue fracture, thereby altering its histological appearance. The wide variety of histological patterns in LSMFT could represent the end result of repeated reaction to fatigue stresses.

An appraisal of research utilization across the United States.

The success of research utilization (RU) is a function of how well it has been incorporated into the cultural norm of the organization. The authors describe current and future nursing research utilization activities in various clinical agencies across the United States and identify barriers and facilitators to those activities. The most frequent RU projects focused on pressure ulcers and pain management. Barriers included lack of resources, organizational culture, change, and nurses' education. Facilitators were leadership commitment, available resources, and a supportive organizational culture.

Lumbar foot innervation of the medial foot and ankle region.

BACKGROUND: Differences in the dermatomal maps appearing in standard anatomic texts which are in common use may lead to diagnostic confusion in the assessment of patients who suffer from nerve root deficiency. This is particularly evident in the variable depiction of the L4 nerve root dermatome which is carried distally in the saphenous nerve. The purpose of this study is to establish the distal limit of L4 nerve root innervation in the foot by performing cadaveric dissection of the saphenous nerve. METHODS: Dissection of the dorsum of the medial foot and ankle was performed on 20 cadaveric specimens. RESULTS: The saphenous nerve was found to enter the dermis of the medial ankle region (mean = 14.75 mm) distal to the tip of the medial malleolus in the direction of the hallux. In three cases the nerve terminated proximal to the medical malleolus. In all cases the medial forefoot and hallux were supplied by the most medial branch of the superficial peroneal nerve. CONCLUSIONS: These findings suggest that the sensory component of the L4 nerve root terminates in most cases near the medical malleolus, well proximal to the bunion area of the forefoot.

Factors influencing wound healing after surgery for metastatic disease of the spine.

STUDY DESIGN: The study group consisted of 53 patients who underwent 75 operations for spine metastases. Patient and tumor demographic factors, preoperative nutritional status, and perioperative adjunctive therapy were retrospectively reviewed. OBJECTIVE: To determine the risk factors for wound breakdown and infection in patients undergoing surgery for spinal metastases. SUMMARY OF BACKGROUND DATA: Spinal fusion using spine implants may be associated with an infection rate of 5% or more. Surgery for spine metastases is associated with an infection rate of more than 10%. Factors other than the type of surgery performed may account for the greater infection rate. METHODS: Data were obtained by reviewing patient records. Age, sex, and neurologic status of the patient; tumor type and site; and surgical details were noted. Adjunctive treatment with corticosteroids and radiotherapy was recorded. Nutritional status was evaluated by determining serum protein and serum albumin concentrations and by total lymphocyte count. RESULTS: Wound breakdown and infection occurred in 15 of 75 wounds. No patient or tumor demographic factors other than intraoperative blood loss (P < 0.1) were statistically associated with infection. The correlation between preoperative protein deficiency (P < 0.01) or perioperative corticosteroid administration (P < 0.10) and wound infection was significant. There was no statistical correlation between lymphocyte count or perioperative radiotherapy and wound infection. CONCLUSIONS: The results indicate that preoperative protein depletion and perioperative administration of corticosteroids are risk factors for wound infection in patients undergoing surgery for spine metastases. Perioperative correction of nutritional depletion and cessation of steroid therapy may reduce wound complications.

Partners in quality.

A university system counters funding cutbacks for nursing education by partnering with a hospital system. The partnership benefits both institutions.

Systemic reactions in U.S. Marine Corps personnel who received Japanese encephalitis vaccine.

The overall hypersensitivity reaction rate among 14,249 U.S. Marine Corps personnel who received 36,850 doses of an investigational Japanese encephalitis vaccine was 10.3 per 10,000 doses; reaction rates were 16.1 and 10.3 per 10,000 doses for the first two doses, and 2.0 per 10,000 doses for the third. The reaction rate was 26.7 per 10,000 vaccinees. Of 38 reactors, 26 had urticaria and/or angioedema, and 11 had pruritus. Vaccine reaction intervals clustered within 48 hours for dose 1, but the median reaction interval for dose 2 was 96 hours. A history of urticaria or allergic rhinitis was associated with an increased probability of a vaccine reaction.

Comparison of the mechanical performance of trochanteric fixation devices.

The transtrochanteric surgical approach to the hip is commonly used, especially for revision hip surgery. Failure of the trochanter to heal can lead to hardware failure, persistent pain, and limp. Rigid internal fixation is needed in this approach to achieve an adequate rate of healing. Newer cable and cable grip systems have been designed to improve trochanteric fixation, but have not been compared to the older Charnley wire fixation techniques. In this study, an in vitro mechanical method previously used to test wire fixation methods was used to compare wire, cable, and cable grip fixation methods. A quasistatic mechanical distraction device was used to compare structural stiffness, load to clinical failure, energy to clinical failure, and maximum load resisted by the fixation devices. The cable grip system was found to be stiffer, to resist a larger load to mechanical failure at 1-cm displacement, and to absorb a greater amount of energy to clinical failure when compared with the other systems. These data suggest that use of the cable grip fixation method should result in improved clinical success compared with the Charnley wire technique.

Characterisation of the tumour-associated carbohydrate epitope recognised by monoclonal antibody 4D3.

The tumour-associated epitope recognised by monoclonal antibody (MAb) 4D3 is expressed on a high m.w. mucin glycoprotein preparation known as small intestinal mucin antigen (SIMA). This epitope is detected in tissue from a high proportion of patients with colorectal cancer, and elevated levels occur in serum from a significant number of such patients, highlighting the potential clinical utility of MAb 4D3. In the present study, insight into the composition and structure of the carbohydrate epitope recognised by MAb 4D3 was gained following characterisation of 2 glycopeptides that co-purified with SIMA. Sequence analysis of 1 of these glycopeptides revealed that it was identical to the glycoprotein alpha-1-anti-chymotrypsin. This glycoprotein was subsequently deglycosylated to yield 5 forms corresponding to alpha-1-anti-chymotrypsin substituted with 4, 3, 2, 1 or no branched glycans. MAb 4D3 was reactive with each of the glycosylated forms, including the form carrying only 1 branched glycan, but did not react with fully deglycosylated alpha-1-anti-chymotrypsin. MAb 4D3 also reacted to different extents with ovine, bovine or porcine submaxillary mucins, each of which has a different amount of the O-linked sialylated disaccharide known as sialosyl Tn. Of these mucins, MAb 4D3 was most reactive with ovine submaxillary mucin, in which almost all of the carbohydrate chains are sialosyl Tn. Reactivity of MAb 4D3 towards isolated glycans, sialosyl Tn and related structures led to the conclusion that the preferred MAb 4D3 epitope involves the sialylated N-acetyl galactosamine disaccharide as well as an additional monosaccharide present on a neighbouring carbohydrate chain. Although the preferred epitope recognised by MAb 4D3 involves this sialylated disaccharide, the specificity of MAb 4D3 was different from that of other MAbs with a reported specificity for sialosyl Tn.