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.

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.

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.

Analogs of the abortifacient aminoglutethimide.

PIP: The abortifacient properties of analogs of aminoglutethimide were tested in rats. Aminoglutethimide is nonsteroidal and nonestrogenic, and induces abortion in pregnant rats by interfering with the conversion of cholesterol to delta5-pregnenolone. However, the spread between efficacy (100 mg/kg) and toxicity (200 mg/kg) is not large, thus limiting its potential use in humans. A series of derivatives, Schiff b ases and an unsaturated ring system were prepared. None of the prepared analogs demonstrated the abortifacient activity of aminoglutethimide. It is concluded that the abortifacient activity of aminoglutethimide is highly specific, and that all changes made caused the activity to be lost. The experimental procedures involved in preparing the analogs are described.^ieng

Noninvasive grading of musculoskeletal tumors using PET.

Twenty-five patients with mass lesions involving the musculoskeletal system were studied with positron emission tomography (PET) in order to determine if a relationship exists between histologic grade and tumor uptake of [fluorine-18]2-deoxy-2-fluoro-D-glucose (FDG). There were 6 benign lesions and 19 malignant lesions of various grades. A high correlation (Rho = 0.83) was found between the normalized uptake of tracer and the NCl grade. The high-grade malignancies had significantly greater (p = 0.0091) uptake of FDG than the combination of benign lesions and low-grade malignancies. All lesions with a normalized uptake value of 1.6 or greater were high-grade, while all lesions less than 1.6 represented either benign tumors or low grade malignancies. This strong relationship between FDG uptake and grade among neoplasms from a wide variety of cell types within a single organ system suggests that the technique may be useful in predicting grade even when the cell type is unknown.

Rapid determination of X/V growth requirements of Haemophilus species in broth.

A broth system was developed for rapid identification of the requirement for X factor (hemin), or V factor (NAD), or both for growth of Haemophilus species. This system was compared to growth around paper discs/strips impregnated with factors X and/or V. The broth system consisted of three tubes, each containing brain-heart infusion broth supplemented with V factor, X factor, or both. Each tube was inoculated with a saline suspension of an Haemophilus isolate, and the broths were shaken for aeration at 37 degrees C. Under these conditions turbidity or clumping was usually evident after 4-5 hr only in the broth(s) containing the required supplement(s). A few strains requiring only V factor required overnight incubation. One hundred fifty-six Haemophilus isolates were tested for growth around supplemented discs/strips or in supplemented broths: 129 were H. influenzae/aegypticus, 25 were of various species that required only V factor, and 2 were H. aphrophilus. Ten of 89 H. influenzae isolates from the respiratory tract were misidentified by satellitism. All isolates were correctly identified by growth in supplemented broths. The cost of the broth assay was about 60 cents/test, whereas the satellite assay cost about 120 cents/test. Serotyping and antibiotic sensitivity testing could be performed directly from the broth culture. Determination of X and/or V requirement by Haemophilus species with supplemented broths was sensitive, rapid, and inexpensive.

A survey of potential virulence factors in clinical and environmental isolates of Serratia marcescens.

One hundred and forty seven isolates of Serratia marcescens were collected from diverse clinical and environmental sources in south-east Texas. Natural isolates were compared with hospital strains for the occurrence of 12 potential virulence determinants. Their overall frequency was as follows: haemolytic activity 48%; lecithinase 95%; lipase 95%; motility 99%; pigmentation 24%; plasmid carriage 46%; proteolytic activity 98%; siderophore activity 99%; urease activity 5%; mannose-sensitive haemagglutination 96%; mannose-resistant haemagglutination 61%; and mannose-resistant type-K haemagglutination (MR/K-HA) 68%. Clinical strains demonstrated a significantly higher occurrence of MR/K-HA (p less than 0.001) and non-pigmentation (p less than 0.01) than environmental isolates.

Osmotic flow caused by chondroitin sulfate proteoglycan across well-defined nuclepore membranes.

Osmotic flows generated by solutions of Swarm rat chondrosarcoma proteoglycan subunit have been analysed using Nuclepore membranes of well-defined straight-through cylindrical pores of known radius rp. Membranes with rp in the range of 27-500 nm were studied. For semipermeable membranes, which are impermeable to the proteoglycan, the flows were consistently related to r2p and not to r4p (Poiseuille's Law) which demonstrates that the flow is a diffusion-controlled process as described previously (R.P.W. Williams and W.D. Comper, J. Phys. Chem. 91 (1987) 3443). We have also identified a characteristic distance, approx. 50% of the average interparticle spacing, out from the pore surface of the membrane over which the proteoglycan has to move to generate flow. The proteoglycan generates similar osmotic permeability coefficients with membranes up to 125 nm in pore diameter which is significantly larger than the average intermolecular distance. These results have been interpreted in terms of the membrane pore recognising dynamic transient aggregates in the proteoglycan solution.

Osmotic flow caused by polyelectrolytes.

Osmotic flow of water caused by high concentrations of anionic polyelectrolytes across semipermeable membranes, permeable only to solvent and simple electrolyte, has been measured in a newly designed flow cell. The flow cell features small solution and solvent compartments and an efficient stirring mechanism. We have demonstrated that, while the osmotic pressure of the anionic polyelectrolytes is determined primarily by micro-counterions, the osmotic flow is determined by solution-dependent properties as embodied in the hydrodynamic frictional coefficient which is determined by the polymer backbone segment of the polyelectrolyte. The variation of the osmotic permeability coefficient, L(p)(o), with concentration and osmotic pressure closely correlated with the concentration dependence of this frictional coefficient. These studies confirm previous work that the kinetics of osmotic flow across a membrane impermeable to the osmotically active solute is primarily determined by the diffusive mobility of the solute.

Weak reflection of a wave by a one-dimensional array of randomly spaced elements, with reference to the scattering of ultrasound by blood.

The mean reflection coefficient is deduced for a line of elements each of the same thickness, placed at random between two fixed ends, where the reflection coefficient of each element is very small. This theory is applied to the problem of the scattering of ultrasound by blood, and some qualitative agreement with experimental data is found. A simplified theory is also presented, from which the variance of the reflection coefficient is given.

Structure-activity studies with chlorohydrins as orally active male antifertility agents.

PIP: Some analogs of alpha-chlorohydrin were studied as an effort to improve the activity and to determine structure-activity relationships. The structural analogs were prepared and their activities in male rats were studied. Several were slightly active but only 1-amino-3-chloro-2-propanol hydrochloride was strongly active (effective dose-99 was 7-8 mg/kg/day; lethal dose-50 was 500 mg/kg). The rest were all derivatives whose activity could be rationalized by in vivo hydrolysis to give 1-amino-3-chloro-2-propanol or alpha-chlorohydrin. On resolving the amino compound an excellent separation of activity and acute toxicity was achieved. Details of these synthesis will published elsewhere.^ieng

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.

Weak reflection of ultrasound by elements arranged in the steps of a one-dimensional random walk, with reference to backscatter by blood.

Blood backscatters ultrasound primarily because the erythrocytes (red blood corpuscles) have a specific acoustic impedance slightly different from that of the surrounding plasma. In an attempt to explain some of the main results concerning such scatter, a one-dimensional model is set up and analysed. The results computed from it are in qualitative agreement with, and contribute a partial explanation of, the variation of reflection coefficient with erythrocyte concentration and the noise in the backscattered signal.