Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases.

BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function. METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types. RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs. CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism. TRIAL REGISTRATION: Trial registration number NCT01701869

Bioavailability, Antipsoriatic Efficacy and Tolerability of a New Light Cream with Mometasone Furoate 0.1%

Mometasone furoate, a potent glucocorticoid (class III) with a favorable benefit/risk ratio, has emerged as a standard medication for the treatment of inflammatory skin disorders. The purpose of the investigation presented here was to determine the noninferiority of a topical mometasone formulation, a light cream (O/W 60/40 emulsion) with mometasone furoate 0.1% (water content of 33%) versus marketed comparators. Using the vasoconstrictor assay, a strong blanching effect of the new cream (called Mometasone cream) comparable to that of a mometasone comparator, a fatty cream with mometasone furoate 0.1%, could be demonstrated. Thus, the topical bioavailability of the active ingredient mometasone furoate (0.1%) was regarded to be similar for Mometasone cream and the mometasone comparator. Using the psoriasis plaque test, a strong antipsoriatic effect comparable to that of the mometasone comparator was found for Mometasone cream after 12 days of occlusive treatment. A nearly identical reduction in the mean infiltrate thickness and similar mean AUC values were noted with both formulations confirmed by clinical assessment data. The noninferiority of Mometasone cream to its active comparator with re-spect to the AUC of change to baseline in infiltrate thickness was demonstrated. Both medications were well tolerated. Overall, Mometasone cream and the mometasone comparator showed similar efficacy and tolerability. Mometasone cream, in addition to its high potency and good tolerability, provides the properties of a light cream, which might make this new medication particularly suitable for application on acutely inflamed and sensitive skin. Copyright (C) 2012 S. Karger AG, Base

The Milliarcsecond Structure of Radio Galaxies and Quasars

Hybrid maps of the nuclei of radio galaxies and quasars show a variety of morphologies. Among compact sources, two structures are common: an asymmetric, “core-jet” morphology (eg, 3C 273), and an “equal double” morphology with two separated, similar components (eg, CTD 93). The nuclei of extended, double radio galaxies generally have a core-jet morphology with the jet directed toward one of the outer components

A Prospective Longitudinal Study of the Clinical Outcomes from Cryptococcal Meningitis following Treatment Induction with 800 mg Oral Fluconazole in Blantyre, Malawi

Introduction: Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data. Methods: From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation. Results: Sixty patients were recruited. 26/60 (43%) died by 4 weeks. 35/60 (58.0%) and 43/56 (77%) died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score ,14 of 15), moderate/severe neurological disability (modified Rankin Score .3 of 5) and confusion (Abbreviated Mental Test Score ,8 of 10) were all common at baseline and associated with death or treatment failure. ART prior to recruitment was not associated with better outcomes. Conclusions: Mortality and treatment failure from cryptococcal meningitis following initiation of treatment with 800 mg oral fluconazole is unacceptably high. To improve outcomes, there is an urgent need for better therapeutic strategies and point-of-care diagnostics, allowing earlier diagnosis before development of neurological deficit

Apparent Temperature and Cause-Specific Emergency Hospital Admissions in Greater Copenhagen, Denmark

One of the key climate change factors, temperature, has potentially grave implications for human health. We report the first attempt to investigate the association between the daily 3-hour maximum apparent temperature (Tappmax) and respiratory (RD), cardiovascular (CVD), and cerebrovascular (CBD) emergency hospital admissions in Copenhagen, controlling for air pollution. The study period covered 1 January 2002−31 December 2006, stratified in warm and cold periods. A case-crossover design was applied. Susceptibility (effect modification) by age, sex, and socio-economic status was investigated. For an IQR (8°C) increase in the 5-day cumulative average of Tappmax, a 7% (95% CI: 1%, 13%) increase in the RD admission rate was observed in the warm period whereas an inverse association was found with CVD (−8%, 95% CI: −13%, −4%), and none with CBD. There was no association between the 5-day cumulative average of Tappmax during the cold period and any of the cause-specific admissions, except in some susceptible groups: a negative association for RD in the oldest age group and a positive association for CVD in men and the second highest SES group. In conclusion, an increase in Tappmax is associated with a slight increase in RD and decrease in CVD admissions during the warmer months

Overwintering Hosts for the Exotic Leafroller Parasitoid, Colpoclypeus florus: Implications for Habitat Manipulation to Augment Biological Control of Leafrollers in Pome Fruits

Thirty sites of managed and native habitats were surveyed for leafrollers (Lepidoptera: Tortricidae) in the apple producing region of central Washington State and northern Oregon from September through November 1997–2000 to discover species that supported overwintering by the parasitoid Colpoclypeus florus (Walker) (Hymenoptera: Eulophidae). C. florus, a species introduced from Europe, requires medium to large host larvae late in autumn on which to overwinter, and few leafroller species display this biology. Over the four years, five potential C. florus hosts were collected, including: Ancylis comptana (Froelich), Xenotemna pallorana (Robinson), and Syndemis sp. (Tortricidae), Filatima sp. (Gelechiidae), and Caloptilia burgessiellia (Zeller) (Gracillariidae). Of these, A. comptana, Syndemis sp., and Filatima sp. have been confirmed as overwintering hosts for C. florus. During the four years, the Syndemis sp. was rare and observed at only one location feeding on redosier dogwood, Cornus sericea L. (Cornales: Cornaceae) although, at this location, many of the larvae collected were parasitized by C. florus. Filatima sp. was common in the Yakima valley feeding on balsam poplar, Populus balsamifera L. ssp. trichocarpa (Torr. & Gray ex Hook) Brayshaw (Malpighiales: Salicaceae) but was rarely parasitized. A. comptana, however, was collected at many locations in central Washington and was frequently found as an overwintering host for C. florus. A. comptana was found feeding on two Rosaceae: Wood's rose, Rosa woodsii Lindl., and strawberry, Fragaria ananassa Duchesne (Rosales: Rosaceae). Based on the number of host larvae collected, A. comptana appears to be the primary overwintering host for C. florus in Washington. Introduction of A. comptana populations to near-orchard habitats may facilitate biological control of leafrollers that are orchard pests

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

Ethnicity and attitudes to deceased kidney donation: a survey in Barbados and comparison with Black Caribbean people in the United Kingdom

<p>Abstract</p> <p>Background</p> <p>Black minority ethnic groups in the UK have relatively low rates of deceased donation and report a higher prevalence of beliefs that are regarded as barriers to donation. However there is little data from migrants' countries of origin. This paper examines community attitudes to deceased kidney donation in Barbados and compares the findings with a survey conducted in a disadvantaged multi-ethnic area of south London.</p> <p>Methods</p> <p>Questionnaires were administered at four public health centres in Barbados and at three private general practices. Adjusted odds ratios were calculated to compare attitudinal responses with a prior survey of 328 Caribbean and 808 White respondents in south London.</p> <p>Results</p> <p>Questionnaires were completed by 327 respondents in Barbados (93% response); 42% men and 58% women, with a mean age of 40.4 years (SD 12.6). The main religious groups were Anglican (29%) and Pentecostal (24%). Educational levels ranged from 18% not completing 5th form to 12% with university education. Attitudes to the notion of organ donation were favourable, with 73% willing to donate their kidneys after their death and only 5% definitely against this. Most preferred an opt-in system of donation. Responses to nine attitudinal questions identified 18% as having no concerns and 9% as having 4 or more concerns. The highest level of concern (43%) was for lack of confidence that medical teams would try as hard to save the life of a person who has agreed to donate organs. There was no significant association between age, gender, education or religion and attitudinal barriers, but greater knowledge of donation had some positive effect on attitudes. Comparison of attitudes to donation in south London and Barbados (adjusting for gender, age, level of education, employment status) indicated that a significantly higher proportion of the south London Caribbean respondents identified attitudinal barriers to donation.</p> <p>Conclusions</p> <p>Community attitudes in Barbados are favourable to deceased donation based on a system of informed consent. Comparison with south London data supports the hypothesis that the relatively high prevalence of negative attitudes to deceased donation among disadvantaged ethnic minorities in high income countries may reflect feelings of marginalisation and lack of belonging.</p

Association of Typical versus Atypical Antipsychotics with Symptoms and Quality of Life in Schizophrenia

BACKGROUND: Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL) and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. METHODOLOGY AND PRINCIPAL FINDINGS: The Hasegawa Dementia Scale-Revised (HDS-R), Brief Psychiatric Rating Scale (BPRS), the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ)-equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. CONCLUSION AND SIGNIFICANCE: These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia