Erythroderma (exfoliative dermatitis). Part 2: energy homeostasis and dietetic management strategies.

Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition.

Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

10-year outcome study of an early intervention program for psychosis compared with standard care service.

BACKGROUND: Despite evidence on the short-term benefits of early intervention (EI) service for psychosis, long-term outcome studies are limited by inconsistent results. This study examined the 10-year outcomes of patients with first-episode psychosis who received 2-year territory-wide EI service compared to those who received standard care (SC) in Hong Kong using an historical control design. METHOD: Consecutive patients who received the EI service between 1 July 2001 and 30 June 2002, and with diagnosis of schizophrenia-spectrum disorders, were identified and matched with patients who received SC first presented to the public psychiatric service from 1 July 2000 to 30 June 2001. In total, 148 matched pairs of patients were identified. Cross-sectional information on symptomatology and functioning was obtained through semi-structured interview; longitudinal information on hospitalization, functioning, suicide attempts, mortality and relapse over 10 years was obtained from clinical database. There were 70.3% (N = 104) of SC and 74.3% (N = 110) of EI patients interviewed. RESULTS: Results suggested that EI patients had reduced suicide rate (χ2 (1) = 4.35, p = 0.037), fewer number [odds ratio (OR) 1.56, χ2 = 15.64, p < 0.0001] and shorter duration of hospitalization (OR 1.29, χ2 = 4.06, p = 0.04), longer employment periods (OR -0.28, χ2 = 14.64, p < 0.0001) and fewer suicide attempts (χ2 = 11.47, df = 1, p = 0.001) over 10 years. At 10 years, no difference was found in psychotic symptoms, symptomatic remission and functional recovery. CONCLUSIONS: The short-term benefits of the EI service on number of hospitalizations and employment was sustained after service termination, but the differences narrowed down. This suggests the need to evaluate the optimal duration of the EI service.

Reconstitution of mitochondrial processing peptidase from the core proteins (subunits I and II) of bovine heart mitochondrial cytochrome bc(1) complex.

Mature core I and core II proteins of the bovine heart mitochondrial cytochrome bc(1) complex were individually overexpressed in Escherichia coli as soluble proteins using the expression vector pET-I and pET-II, respectively. Purified recombinant core I and core II alone show no mitochondrial processing peptidase (MPP) activity. When these two proteins are mixed together, MPP activity is observed. Maximum activity is obtained when the molar ratio of these two core proteins reaches 1. This indicates that only the two core subunits of thebc(1) complex are needed for MPP activity. The properties of reconstituted MPP are similar to those of Triton X-100-activated MPP in the bovine bc(1) complex. When Rieske iron-sulfur protein precursor is used as substrate for reconstituted MPP, the processing activity stops when the amount of product formation (subunit IX) equals the amount of reconstituted MPP used in the system. Addition of Triton X-100 to the product-inhibited reaction mixture restores MPP activity, indicating that Triton X-100 dissociates bound subunit IX from the active site of reconstituted MPP. The aromatic group, rather than the hydroxyl group, at Tyr(57) of core I is essential for reconstitutive activity.

Synthesizing two-fingered grippers for positioning and identifying objects.

Most industrial grippers now in use are two-fingered. Among them the parallel-jaw gripper is the simplest. It can partially remove the pose uncertainty of an object through grasping, such as the orientation uncertainty. This paper addresses a new type of grippers with the finger configuration of four circles instead of two parallel lines. It has a number of important advantages. Especially, it achieves form-closure and confines the object to a locally unique pose, so as to remove the pose uncertainty completely. It allows the gripped object to reach this pose freely without loss of required friction in the direction perpendicular to the grasping plane. More information can be acquired for identifying the object and its grasp mode. As a result the identification can be performed at one grasp. The key parameter of a symmetric four-pin gripper is the distance (span) between two pin centers on each finger, which depends upon the object shape and impacts the closure property, Based on a new approach to the grasp geometry, selection and limitations of the span are illustrated.