Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

Psychosocial functioning and intelligence both partly explain socioeconomic inequalities in premature death. A population-based male cohort study

The possible contributions of psychosocial functioning and intelligence differences to socioeconomic status (SES)-related inequalities in premature death were investigated. None of the previous studies focusing on inequalities in mortality has included measures of both psychosocial functioning and intelligence.The study was based on a cohort of 49 321 men born 1949-1951 from the general community in Sweden. Data on psychosocial functioning and intelligence from military conscription at ∼18 years of age were linked with register data on education, occupational class, and income at 35-39 years of age. Psychosocial functioning was rated by psychologists as a summary measure of differences in level of activity, power of initiative, independence, and emotional stability. Intelligence was measured through a multidimensional test. Causes of death between 40 and 57 years of age were followed in registers.The estimated inequalities in all-cause mortality by education and occupational class were attenuated with 32% (95% confidence interval: 20-45%) and 41% (29-52%) after adjustments for individual psychological differences; both psychosocial functioning and intelligence contributed to account for the inequalities. The inequalities in cardiovascular and injury mortality were attenuated by as much as 51% (24-76%) and 52% (35-68%) after the same adjustments, and the inequalities in alcohol-related mortality were attenuated by up to 33% (8-59%). Less of the inequalities were accounted for when those were measured by level of income, with which intelligence had a weaker correlation. The small SES-related inequalities in cancer mortality were not attenuated by adjustment for intelligence.Differences in psychosocial functioning and intelligence might both contribute to the explanation of observed SES-related inequalities in premature death, but the magnitude of their contributions likely varies with measure of socioeconomic status and cause of death. Both psychosocial functioning and intelligence should be considered in future studies

Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report

Background: “Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. &lt;p/&gt;Aims: To identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. &lt;p/&gt;Methodology: A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. &lt;p/&gt;Results: 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7mg/day during days 1-15 to 346.9mg/day during days 16-30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. &lt;p/&gt;Conclusions: Rapid dose escalation occurred in less than half of this case series (n=5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS

Sibling relationships and family functioning in siblings of early adolescents, adolescents and young adults with autism spectrum disorder

The purpose of the study was to investigate how family functioning (defined as the ability that family members hold to manage stressful events, and intimate and social relationships), the degree to which family members feel happy and fulfilled with each other (called family satisfaction), and the demographical characteristics of siblings (age and gender) impacted on sibling relationships. The Circumplex Model of Marital and Family Systems and Behavioral Systems constituted the theoretical frameworks that guided our study. Eighty-six typically developing adolescents and young adults having a sister or a brother with autism spectrum disorder were enrolled. Results indicated that the youngest age group (early adolescents) reported to engage more frequently in negative behaviors with their siblings with ASD than the two older age groups (middle adolescents and young adults). No significant differences were found among the three age groups regarding behaviors derived from attachment, caregiving and affiliative systems. Family satisfaction and age significantly predicted behaviors during sibling interactions. Suggestions on prevention and intervention programs were discussed in order to prevent parentification among typically developing siblings and decrease episodes of quarrels and overt conflicts between brothers and sisters with and without AS

Climate Change and invasibility of the Antarctic benthos

Benthic communities living in shallow-shelf habitats in Antarctica (&lt;100-m depth) are archaic in their structure and function. Modern predators, including fast-moving, durophagous (skeleton-crushing) bony fish, sharks, and crabs, are rare or absent; slow-moving invertebrates are the top predators; and epifaunal suspension feeders dominate many soft substratum communities. Cooling temperatures beginning in the late Eocene excluded durophagous predators, ultimately resulting in the endemic living fauna and its unique food-web structure. Although the Southern Ocean is oceanographically isolated, the barriers to biological invasion are primarily physiological rather than geographic. Cold temperatures impose limits to performance that exclude modern predators. Global warming is now removing those physiological barriers, and crabs are reinvading Antarctica. As sea temperatures continue to rise, the invasion of durophagous predators will modernize the shelf benthos and erode the indigenous character of marine life in Antarctica

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

North American carbon dioxide sources and sinks: magnitude, attribution, and uncertainty

North America is both a source and sink of atmospheric carbon dioxide (CO2). Continental sources - such as fossil-fuel combustion in the US and deforestation in Mexico - and sinks - including most ecosystems, and particularly secondary forests - add and remove CO2 from the atmosphere, respectively. Photosynthesis converts CO2 into carbon as biomass, which is stored in vegetation, soils, and wood products. However, ecosystem sinks compensate for only similar to 35% of the continent's fossil-fuel-based CO2 emissions; North America therefore represents a net CO2 source. Estimating the magnitude of ecosystem sinks, even though the calculation is confounded by uncertainty as a result of individual inventory- and model-based alternatives, has improved through the use of a combined approach. Front Ecol Environ 2012; 10(10): 512-519, doi:10.1890/12006

Scientific principles for the identification of endocrine-disrupting chemicals: a consensus statement

Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation. Twenty-three international scientists from different disciplines discussed principles and open questions on ED identification as outlined in a draft consensus paper at an expert meeting hosted by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11-12 April 2016. Participants reached a consensus regarding scientific principles for the identification of EDs. The paper discusses the consensus reached on background, definition of an ED and related concepts, sources of uncertainty, scientific principles important for ED identification, and research needs. It highlights the difficulty in retrospectively reconstructing ED exposure, insufficient range of validated test systems for EDs, and some issues impacting on the evaluation of the risk from EDs, such as non-monotonic dose-response and thresholds, modes of action, and exposure assessment. This report provides the consensus statement on EDs agreed among all participating scientists. The meeting facilitated a productive debate and reduced a number of differences in views. It is expected that the consensus reached will serve as an important basis for the development of regulatory ED criteria

Improved Glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy ((1)H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA(1c) reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (-59.3, -16.5%). The relative reduction in IHL correlated with that in HbA(1)c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism