Epidermal biomarkers of the skin barrier in atopic and contact dermatitis.

Dysfunction of the skin barrier plays a critical role in the initiation and progression of inflammatory skin diseases, such as atopic dermatitis and contact dermatitis. Epidermal biomarkers can aid in evaluating the functionality of the skin barrier and understanding the mechanisms that underlay its impairment. This narrative review provides an overview of recent studies on epidermal biomarkers associated with the function and integrity of the skin barrier, and their application in research on atopic dermatitis and contact dermatitis. The reviewed studies encompass a wide spectrum of molecular, morphological and biophysical biomarkers, mainly obtained from stratum corneum tape strips and biopsies. Lipids, natural moisturizing factors, and structural proteins are the most frequently reported molecular biomarkers. Additionally, corneocyte surface topography and elasticity show potential as biomarkers for assessing the physical barrier of the skin. In contact dermatitis studies, biomarkers are commonly employed to evaluate skin irritation and differentiate between irritant and allergic contact dermatitis. In atopic dermatitis, biomarkers are primarily utilized to identify differences between atopic and healthy skin, for predictive purposes, and monitoring response to therapies. While this overview identifies potential biomarkers for the skin barrier, their validation as epidermal biomarkers for atopic dermatitis and contact dermatitis has yet to be established.

Influence of subscapularis tendon reattachment after reverse shoulder arthroplasty: clinical findings and ultrasonographic evaluation of the subscapularis at 89 months mean follow-up.

BACKGROUND: Reverse shoulder arthroplasty (RSA) is commonly used to treat rotator cuff arthropathy. In the deltopectoral approach for RSA, the subscapularis tendon is (partly) detached. The clinical effects of subscapularis reattachment are still under debate. An observational study was performed to evaluate the clinical effects of subscapularis tendon reattachment on the mid- to long-term following RSA. METHODS: In this study, 40 patients for a total of 46 shoulders with a reverse shoulder prosthesis participated. Constant Murley Score (CMS), Oxford Shoulder Score (OSS), Range of Motion (ROM) and abduction and internal rotation strength were measured. The integrity of the subscapularis tendon at follow-up was assessed using ultrasound. Outcomes were compared between three groups: repair and intact at follow-up, repair and not intact, and no repair. RESULTS: Mean follow-up was 89 months with a minimum of three years. CMS, OSS, ROM and strength did not differ between groups. One-third of the initially reattached subscapularis tendons were still present at follow-up. No dislocations were reported. CONCLUSION: This study showed no clinical effects of subscapularis reattachment after reverse shoulder arthroplasty on the mid- to long-term.

Invasive fungal infections in patients treated with Bruton's tyrosine kinase inhibitors.

Bruton's tyrosine kinase (BTK) inhibitors are increasingly used in untreated and previously treated chronic lymphocytic leukaemia (CLL) patients. Invasive fungal infections (IFI) were rarely observed in patients treated for CLL in the pre-BTK era. In this article, we describe two patients with CLL who developed an IFI during treatment with the BTK inhibitor ibrutinib. The atypical presentation and the serious course of this complication are described.

Characterization of the Scattering and Absorption of Colored Zein Colloids in Optically Dense Dispersions.

In this research, we model the color of optically dense colloidal dispersions of dyed and undyed zein particles using results from multiple light scattering theory. These particles, as well as monodisperse silica colloids, were synthesized and characterized to obtain particle properties such as particle size, particle size distribution, refractive index, and absorption spectrum of the dye. This information was used to model the diffuse transmission of concentrated particle dispersions, which was measured using a specially designed variable path length quartz glass cuvette. For the nonabsorbing silica dispersions, a transport mean-free path throughout the visible range was obtained. Results showed a difference of less than 5% from the values calculated with a multiple scattering model using the single-particle properties as an input. For undyed zein particles, which are off-white, the deviation between the model and the experiment was about 30% because of slight absorption at wavelengths below 550 nm but <7% at higher wavelengths. From these results, it was concluded that the model correctly describes diffuse transmission and that the measurements are sensitive to absorption. Finally, this method was applied to dispersions of dyed zein particles. Here, the transport mean-free path was first determined for wavelengths at which there is no absorption, which agreed with the theory better than 4%. The modeled transport mean-free path was then used to extract the reciprocal absorption mean-free path in the remaining parts of the visible spectrum, and a reasonable agreement with the absorption spectrum of the dye solution was obtained.

White zein colloidal particles: synthesis and characterization of their optical properties on the single particle level and in concentrated suspensions.

Growing interest in using natural, biodegradable ingredients for food products leads to an increase in research for alternative sources of functional ingredients. One alternative is zein, a water-insoluble protein from corn. Here, a method to investigate the optical properties of white zein colloidal particles is presented in both diluted and concentrated suspensions. The particles are synthesized, after purification of zein, by anti-solvent precipitation. Mean particle diameters ranged from 35 to 135 nm based on dynamic light scattering. The value of these particles as white colorant is examined by measuring their optical properties. Dilute suspensions are prepared to measure the extinction cross section of individual particles and this was combined with Mie theory to determine a refractive index (RI) of 1.49 ± 0.01 for zein particles dispersed in water. This value is used to further model the optical properties of concentrated suspensions. To obtain full opacity of the suspension, comparable to 0.1-0.2 wt% suspensions of TiO2, concentrations of 2 to 3.3 wt% of zein particles are sufficient. The optimal size for maximal scattering efficiency is explored by modeling dilute and concentrated samples with RI's matching those of zein and TiO2 particles in water. The transport mean free path of light was determined experimentally and theoretically and the agreement between the transport mean free path calculated from the model and the measured value is better than 30%. Such particles have the potential to be an all-natural edible alternative for TiO2 as white colorant in wet food products.

Chemotherapy-induced exacerbations of thyroid orbitopathy in a patient with B-cell lymphoma.

A 55-year-old woman with concurrent active thyroid orbitopathy and B-cell lymphoma developed acute exacerbation of thyroid orbitopathy after receiving Rituximab, cyclophosphamide, hydroxydaunorubicin, Prednisone (R-CHOP) chemotherapy, presenting with subtotal loss of vision and severe eyelid edema. Intravenous methylprednisolone was fully effective within several hours. Further exacerbations of her orbitopathy were seen following every subsequent chemotherapeutic treatment, but responded well to oral prednisone. This case shows that thyroid orbitopathy may severely and acutely progress after chemotherapy for concurrent B-cell lymphoma. Clinical awareness of this potential complication may prevent blindness in this rare subset of patients.

International practices in the dietary management of fructose 1-6 biphosphatase deficiency.

BACKGROUND: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. METHODS: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians. RESULTS: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: <1y, 36% (n = 46); 1-10y, 59% (n = 74); 11-16y, 3% (n = 4); and >16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than ≤16y were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11-16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management. CONCLUSIONS: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency.

Dietary practices in propionic acidemia: A European survey.

BACKGROUND: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance. AIM: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines. METHODS: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. RESULTS: Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of centres, providing a median of 44% (14-83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m, 7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds. CONCLUSIONS: There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking.

Dietary practices in isovaleric acidemia: A European survey.

BACKGROUND: In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management. AIM: To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014). METHODS: A cross-sectional questionnaire was sent to all European dietitians who were either members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG) or whom had responded to previous questionnaires on dietetic practice (n = 53). The questionnaire comprised 27 questions about the dietary management of IVA. RESULTS: Information on 140 patients with IVA from 39 centres was reported. 133 patients (38 centres) were given a protein restricted diet. Leucine-free amino acid supplements (LFAA) were routinely used to supplement protein intake in 58% of centres. The median total protein intake prescribed achieved the WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Centres that prescribed LFAA had lower natural protein intakes in most age groups except 1 to 10 y. In contrast, when centres were not using LFAA, the median natural protein intake met WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Enteral tube feeding was rarely prescribed. CONCLUSIONS: This survey demonstrates wide differences in dietary practice in the management of IVA across European centres. It provides unique dietary data collectively representing European practices in IVA which can be used as a foundation to compare dietary management changes as a consequence of the first E-IMD IVA guidelines availability.

Is there any influence of humeral component retroversion on range of motion and clinical outcome in reverse shoulder arthroplasty? A clinical study.

PURPOSE: Reverse shoulder arthroplasty becomes more widely used as treatment for patients with complex cuff arthropathy. Theoretically, a higher retroversion of the humeral component leads to an increase in external rotation ROM and a decrease in internal rotation ROM. There is no consensus in optimal retroversion orientation. We retrospectively describe the effect of retroversion of the humeral component. We hypothesize that 20° humeral retroversion improves postoperative ROM, strength or clinical outcome scores compared to neutral retroversion. METHODS: A retrospective clinical study is performed. An Aequalis reverse shoulder prosthesis was placed in 65 shoulders from 58 patients with a mean age of 73.8 years (95% CI 72.0-75.6). Between October 2006 and May 2012, the humeral component was placed in neutral retroversion in 36 shoulders (55%). From June 2012 to June 2014, it was placed in 20° retroversion in 29 shoulders (45%). After a mean follow-up of 36 months with a minimum of 12 months, patients were invited for a study visit. ROM, strength, Constant-Murley and Oxford Scores were measured. RESULTS: ROM, strength and Constant-Murley and Oxford Scores did not differ significantly between both groups. CONCLUSIONS: With the Aequalis prosthesis, no significant effect of 0° or 20° retroversion on external and internal rotation ROM, strength or functional outcome scores was found.

The influence of subscapularis tendon reattachment on range of motion in reversed shoulder arthroplasty: a clinical study.

PURPOSE: Reverse shoulder arthroplasty becomes more widely used as a treatment for patients with painful cuff arthropathy. As a part of the deltopectoral approach, the subscapularis tendon, if present, is (partly) detached. There is no consensus on repair of the tendon after placement of the prosthesis. We retrospectively describe the clinical effects of subscapularis tendon reattachment. Our hypothesis was that subscapularis repair has no clinical effects on range of motion and functional outcome scores. METHODS: A retrospective clinical study is performed. An Aequalis reverse shoulder prosthesis (Tornier, Montbonnot, France) was placed in 65 patients with a mean age of 73.8 years (range 47-90). In 40 patients (61.5 %), the quality of the tendon was initially insufficient for repair. The subscapularis was repaired in 25 patients (38.5 %). After a mean follow-up of 36 months with a minimum of 12 months, an ultrasound examination of the subscapularis was performed in patients with a repaired tendon. Range of motion, strength, Constant-Murley and Oxford scores were measured. RESULTS: On ultrasound examination, 10 (40 %) out of 25 repaired subscapularis tendons were still sufficient. Postoperatively, range of motion, strength, Constant-Murley and Oxford scores did not differ significantly between repair with present tendon, repair with absent tendon or no repair. CONCLUSION: In reverse shoulder arthroplasty, no significant differences on range of motion, functional outcome scores or strength were found between subscapularis repair or no repair, whether the tendon healed at follow-up or not.

Vitamin D deficiency in childhood obesity is associated with high levels of circulating inflammatory mediators, and low insulin sensitivity.

HYPOTHESIS: Childhood obesity is accompanied by low-grade systemic inflammation, which contributes to the development of insulin resistance and cardiovascular complications later in life. As vitamin D exhibits profound immunomodulatory functions and vitamin D deficiency is highly prevalent in childhood obesity, we hypothesized that vitamin D deficiency in childhood obesity coincides with enhanced systemic inflammation and reduced insulin sensitivity. METHODS: In a cross-sectional study of 64 obese and 32 healthy children aged 6-16 years, comprehensive profiling of 32 circulating inflammatory mediators was performed, together with assessment of 25-hydroxyvitamin D (25(OH)D) levels and measures for insulin sensitivity. RESULTS: Severe vitamin D insufficiency, which is further referred to as vitamin D deficiency, was defined as a 25(OH)D level ≤37.5 nmol l(-1), and was highly prevalent in obese (56%) versus healthy control children (16%). Throughout the study, 25(OH)D-deficient children were compared with the other children, including 25(OH)D insufficient (37.5-50 nmol l(-1)) and 25(OH)D sufficient children (≥50 nmol l(-1)). First, 25(OH)D-deficient obese children showed a lower insulin sensitivity than other obese children, as measured by a lower quantitative insulin sensitivity check index. Second, the association between 25(OH)D deficiency and insulin resistance in childhood obesity was confirmed with multiple regression analysis. Third, 25(OH)D-deficient obese children showed higher levels of the inflammatory mediators cathepsin S, chemerin and soluble vascular adhesion molecule (sVCAM), compared with the other obese children. Finally, hierarchical cluster analysis revealed an over-representation of 25(OH)D deficiency in obese children expressing inflammatory mediator clusters with high levels of cathepsin S, sVCAM and chemerin. CONCLUSION: 25(OH)D deficiency in childhood obesity was associated with enhanced systemic inflammation and reduced insulin sensitivity. The high cathepsin S and sVCAM levels may reflect activation of a pro-inflammatory, pro-diabetic and atherogenic pathway, which could be inhibited by vitamin D supplementation.

Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14++ monocytes.

AIMS/HYPOTHESIS: In adults, circulating inflammatory mediators and activated CD14(++) monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis of circulating inflammatory mediators, monocyte populations and their function in childhood obesity. METHODS: In lean and obese children aged 6 to 16 years (n = 96), 35 circulating inflammatory mediators including adipokines were measured. Hierarchical cluster analysis of the inflammatory mediator profiles was performed to investigate associations between inflammatory mediator clusters and clinical variables. Whole-blood monocyte phenotyping and functional testing with the toll-like receptor 4 ligand, lipopolysaccharide, were also executed. RESULTS: First, next to leptin, the circulating mediators chemerin, tissue inhibitor of metalloproteinase 1, EGF and TNF receptor 2 were identified as novel inflammatory mediators that are increased in childhood obesity. Second, cluster analysis of the circulating mediators distinguished two obesity clusters, two leanness clusters and one mixed cluster. All clusters showed distinct inflammatory mediator profiles, together with differences in insulin sensitivity and other clinical variables. Third, childhood obesity was associated with increased CD14(++) monocyte numbers and an activated phenotype of the CD14(++) monocyte subsets. CONCLUSIONS/INTERPRETATION: Inflammatory mediator clusters were associated with insulin resistance in obese and lean children. The activation of CD14(++) monocyte subsets, which is associated with increased development of atherosclerosis in obese adults, was also readily detected in obese children. Our results indicate that inflammatory mechanisms linking obesity to its metabolic and cardiovascular complications are already activated in childhood obesity.

A high-field magnetization study of a Nd(2)Fe(14)Si(3) single crystal.

Magnetization study of a single crystal of Nd(2)Fe(14)Si(3) (with the rhombohedral Th(2)Zn(17)-type structure) reveals that the compound is a ferromagnet with a spontaneous magnetic moment of 32.3µ(B) per formula unit (at T = 2 K) and a Curie temperature equal to 495 K. The easy-magnetization direction lies close to the b-axis, tilting slightly towards the c-axis. (The b-axis [120] is not a high-symmetry direction in the crystallographic class D(3d).) The observed strong magnetic anisotropy is attributed almost entirely to the Nd sublattice, as concluded from comparison with a Y(2)Fe(14)Si(3) single crystal. A magnetic field applied along the c-axis induces a first-order spin reorientation transition at B(FOMP) = 20 T. In the process of magnetization the Nd and Fe sublattices behave as essentially non-collinear. This is manifest particularly in the downward curvature of the first (pre-FOMP) stage of the magnetization curve. It is proposed to regard this curvature as a validity criterion for the single-sublattice approximation.

Improved ECG signal analysis using wavelet and feature extraction.

OBJECTIVES: Automatic detection of arrhythmias is important for diagnosis of heart problems. However, in ECG signals, there is significant variation of waveforms in both normal and abnormal beats. It is this phenomenon, which makes it difficult to analyse ECG signals. The aim of developing methodology is to distinguish between normal beats and abnormal beats in an ECG signal. METHODS: ECG signals were first decomposed using wavelet transform. The feature vectors were then extracted from these decomposed signals as normalised energy and entropy. To improve the classification of the feature vectors of normal and abnormal beats, the normal beats which occur before and after the abnormal beats were eliminated from the group of normal beats. RESULTS: With our proposed methods, the normal beats and abnormal beats formed different clusters of vector points. By eliminating normal beats which occur before and after the abnormal beats, the clusters of different types of beats showed more apparent separation. CONCLUSIONS: The combination of wavelet decomposition and the classification using feature vectors of the beats in ECG signals separate abnormal beats from normal beats. The elimination of the normal beats which occur before and after the abnormal beats succeeded in minimising the size of normal beats cluster.