Ankylosing spondylitis and sarcoidosis — Coincidence or association?

We report a 25-year-old woman presenting with sarcoidosis and bilateral sacroiliitis. Her sarcoidosis related symptoms (malaise, cough and dyspnoea) improved dramatically under treatment with steroids but severe back pain persisted. Only seven similar cases have been described over the last 40 years and the question of a possible association between the two diseases has been raised. However, prevalence data from the literature and the apparent lack of genetic links are better arguments for coincidence than for association

Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms : revival of an old drug

BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSIONSIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launche

Solar activity during Skylab: Its distribution and relation to coronal holes

Solar active regions observed during the period of Skylab observations (May 1973-February 1974) were examined for properties that varied systematically with location on the sun, particularly with respect to the location of coronal holes. Approximately 90 percent of the optical and X-ray flare activity occurred in one solar hemisphere (136-315 heliographic degrees longitude). Active regions within 20 heliographic degrees of coronal holes were below average in lifetimes, flare production, and magnetic complexity. Histograms of solar flares as a function of solar longitude were aligned with H alpha synoptic charts on which active region serial numbers and coronal hole boundaries were added

Comparison of randomized controlled trials discontinued or revised for poor recruitment and completed trials with the same research question: a matched qualitative study.

More than a quarter of randomized controlled trials (RCTs) are prematurely discontinued, mostly due to poor recruitment of patients. In this study, we systematically compared RCTs discontinued or revised for poor recruitment and completed RCTs with the same underlying research question to better understand the causes of poor recruitment, particularly related to methodological aspects and context-specific study settings. We compared RCTs that were discontinued or revised for poor recruitment to RCTs that were completed as planned, matching in terms of population and intervention. Based on an existing sample of RCTs discontinued or revised due to poor recruitment, we identified matching RCTs through a literature search for systematic reviews that cited the discontinued or revised RCT and matching completed RCTs without poor recruitment. Based on extracted data, we explored differences in the design, conduct, and study settings between RCTs with and without poor recruitment, separately for each research question using semi-structured discussions. We identified 15 separate research questions with a total of 29 RCTs discontinued or revised for poor recruitment and 48 RCTs completed as planned. Prominent research areas in the sample were cancer and acute care. The mean number of RCTs with poor recruitment per research question was 1.9 ranging from 1 to 4 suggesting clusters of research questions or settings prone to recruitment problems. The reporting quality of the recruitment process in RCT publications was generally low. We found that RCTs with poor recruitment often had narrower eligibility criteria, were investigator- rather than industry-sponsored, were associated with a higher burden for patients and recruiters, sometimes used outdated control interventions, and were often launched later in time than RCTs without poor recruitment compromising uncertainty about tested interventions through emerging evidence. Whether a multi- or single-center setting was advantageous for patient recruitment seemed to depend on the research context. Our study confirmed previously identified causes for poor recruitment, i.e., narrow eligibility criteria, investigator sponsorship, and a reduced motivation of patients and recruiters. Newly identified aspects were that researchers need to be aware of all other RCTs on a research question so that compromising effects on the recruitment can be minimized and that a larger number of centers is not always advantageous

Slowly cycling Rho kinase-dependent actomyosin cross-bridge slippage explains intrinsic high compliance of detrusor smooth muscle

Biological soft tissues are viscoelastic because they display timeindependent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+ -containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as slipping cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically

Egg excretion indicators for the measurement of soil-transmitted helminth response to treatment

BACKGROUND: Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments. METHODOLOGY: We built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14-21 and 22-45 days) after drug administration. PRINCIPAL FINDINGS: The 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14-21 days and 22-45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14-21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%. CONCLUSIONS/SIGNIFICANCE: Combining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections

The present and future system for measuring the Atlantic meridional overturning circulation and heat transport

of the global combined atmosphere-ocean heat flux and so is important for the mean climate of the Atlantic sector of the Northern Hemisphere. This meridional heat flux is accomplished by both the Atlantic Meridional Overturning Circulation (AMOC) and by basin-wide horizontal gyre circulations. In the North Atlantic subtropical latitudes the AMOC dominates the meridional heat flux, while in subpolar latitudes and in the subtropical South Atlantic the gyre circulations are also important. Climate models suggest the AMOC will slow over the coming decades as the earth warms, causing widespread cooling in the Northern hemisphere and additional sea-level rise. Monitoring systems for selected components of the AMOC have been in place in some areas for decades, nevertheless the present observational network provides only a partial view of the AMOC, and does not unambiguously resolve the full variability of the circulation. Additional observations, building on existing measurements, are required to more completely quantify the Atlantic meridional heat transport. A basin-wide monitoring array along 26.5°N has been continuously measuring the strength and vertical structure of the AMOC and meridional heat transport since March 31, 2004. The array has demonstrated its ability to observe the AMOC variability at that latitude and also a variety of surprising variability that will require substantially longer time series to understand fully. Here we propose monitoring the Atlantic meridional heat transport throughout the Atlantic at selected critical latitudes that have already been identified as regions of interest for the study of deep water formation and the strength of the subpolar gyre, transport variability of the Deep Western Boundary Current (DWBC) as well as the upper limb of the AMOC, and inter-ocean and intrabasin exchanges with the ultimate goal of determining regional and global controls for the AMOC in the North and South Atlantic Oceans. These new arrays will continuously measure the full depth, basin-wide or choke-point circulation and heat transport at a number of latitudes, to establish the dynamics and variability at each latitude and then their meridional connectivity. Modeling studies indicate that adaptations of the 26.5°N type of array may provide successful AMOC monitoring at other latitudes. However, further analysis and the development of new technologies will be needed to optimize cost effective systems for providing long term monitoring and data recovery at climate time scales. These arrays will provide benchmark observations of the AMOC that are fundamental for assimilation, initialization, and the verification of coupled hindcast/forecast climate models

Ankylosing spondylitis and sarcoidosis — Coincidence or association?

We report a 25-year-old woman presenting with sarcoidosis and bilateral sacroiliitis. Her sarcoidosis related symptoms (malaise, cough and dyspnoea) improved dramatically under treatment with steroids but severe back pain persisted. Only seven similar cases have been described over the last 40 years and the question of a possible association between the two diseases has been raised. However, prevalence data from the literature and the apparent lack of genetic links are better arguments for coincidence than for association