Reduction in stiffness of proximal leg muscles during the first 6 months of glucocorticoid therapy for giant cell arteritis: A pilot study using shear wave elastography.

Aim: To investigate muscle stiffness changes in patients treated for giant cell arteritis (GCA) with high‐dose oral glucocorticoids. Methods: Using ultrasound elastography, shear wave velocity (SWV) was measured in the quadriceps, hamstrings and biceps brachii muscles of 14 patients with GCA (4 male, mean age ± SD, 68.2 ± 4.3 years) within the first 2 weeks of initiating glucocorticoid treatment (baseline) and repeated after 3 and 6 months treatment. Muscle strength and performance tests were performed at each visit. Baseline measures were compared with those from 14 healthy controls. Linear mixed models were used to test for change in patient measures over time. Results: At baseline, muscle SWV in patients was not significantly different from controls. With glucocorticoid treatment, there was a reduction in SWV in the leg but not the arm muscles. SWV decreased by a mean of 14% (range 8.3%‐17.3%; P = .001) after 3 months and 18% (range 10.2%‐25.3%; P < .001) after 6‐months in the quadriceps and hamstrings during the resting position. The baseline, 3 and 6 months mean SWV (±SD) for the vastus lateralis were 1.62 ± 0.16 m/s, 1.40 ± 0.10 m/s and 1.31 ± 0.06 m/s, respectively (P < .001). In the patient group as a whole, there was no significant change in muscle strength. However, there were moderate correlations (r = .54‐.69) between exhibiting weaker muscle strength at follow‐up visits and a greater reduction in SWV. Conclusion: Glucocorticoid therapy in patients with GCA was associated with a significant reduction in proximal leg muscle stiffness during the first 6 months. Future research should study a larger sample of patients for a longer duration to investigate if diminished muscle stiffness precedes signs of glucocorticoid‐induced myopathy

Identification of type III secretion inhibitors for plant disease management

Bacterial plant pathogens are among the most devastating threats to agriculture. To date, there are no effective means to control bacterial plant diseases due to the restrictions in the use of antibiotics in agriculture. A novel strategy under study is the use of chemical compounds that inhibit the expression of key bacterial virulence determinants. The type III secretion system is essential for virulence of many Gram-negative bacteria because it injects into the plant host cells bacterial proteins that interfere with their immune system. Here, we describe the methodology to identify bacterial type III secretion inhibitors, including a series of protocols that combine in planta and in vitro experiments. We use Ralstonia solanacearum as a model because of the number of genetic tools available in this organism and because it causes bacterial wilt, one of the most threatening plant diseases worldwide. The procedures presented can be used to evaluate the effect of different chemical compounds on bacterial growth and virulence

Melasma and its association with different types of nevi in women: A case-control study

<p>Abstract</p> <p>Background</p> <p>Very little is known about possible association of nevi and melasma. The study objective was to determine if there is an association between melasma and existence of different kinds of nevi.</p> <p>Methods</p> <p>In a case-control study, 120 female melasma patients referred to dermatology clinic of Ardabil and 120 patients referred to other specialty clinics who lacked melasma were enrolled after matching for age. Number of different types of nevi including lentigines and melanocytic nevi were compared between case and control group patients. Data were entered into the computer and analyzed by SPSS 13 statistical software.</p> <p>Results</p> <p>Mean number of lentigines was 25.5 in melasma group compared to 8 in control group(P < 0.01). Mean number of melanocytic nevi was 13.2 in cases compared to 2.8 in control group(P < 0.001). Multivariate analysis showed that existence of freckles, lentigines and more than three melanocytic nevi were positively related to developing melasma. The chance of melasma increased up to 23 times for patients having more than three melanocytic nevi. Congenital nevi were observed among 10% both in case and control groups. Campbell de morgan angiomas were seen among 26 patients(21.8%) in case group compared to 6 patients(5%) in control group.</p> <p>Conclusion</p> <p>Existence of lentigines and melanocytic nevi increases chance of having melasma</p

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

The Search for Invariance: Repeated Positive Testing Serves the Goals of Causal Learning

Positive testing is characteristic of exploratory behavior, yet it seems to be at odds with the aim of information seeking. After all, repeated demonstrations of one’s current hypothesis often produce the same evidence and fail to distinguish it from potential alternatives. Research on the development of scientific reasoning and adult rule learning have both documented and attempted to explain this behavior. The current chapter reviews this prior work and introduces a novel theoretical account—the Search for Invariance (SI) hypothesis—which suggests that producing multiple positive examples serves the goals of causal learning. This hypothesis draws on the interventionist framework of causal reasoning, which suggests that causal learners are concerned with the invariance of candidate hypotheses. In a probabilistic and interdependent causal world, our primary goal is to determine whether, and in what contexts, our causal hypotheses provide accurate foundations for inference and intervention—not to disconfirm their alternatives. By recognizing the central role of invariance in causal learning, the phenomenon of positive testing may be reinterpreted as a rational information-seeking strategy

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

&lt;p&gt;&lt;b&gt;Background&lt;/b&gt; Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, &#8805;2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 &#8804; P &#8804; .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 &#8804; P &#8804; .04), hair color (.006 &#8804; P &#8804; .06), and number of nevi (6.9 × 10−6 &#8804; P &#8804; .02).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion&lt;/b&gt; Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.&lt;/p&gt

Translational research into gut microbiota: new horizons on obesity treatment: updated 2014

Obesity is currently a pandemic of worldwide proportions affecting millions of people. Recent studies have proposed the hypothesis that mechanisms not directly related to the human genome could be involved in the genesis of obesity, due to the fact that, when a population undergoes the same nutritional stress, not all individuals present weight gain related to the diet or become hyperglycemic. The human intestine is colonized by millions of bacteria which form the intestinal flora, known as gut flora. Studies show that lean and overweight human may present a difference in the composition of their intestinal flora; these studies suggest that the intestinal flora could be involved in the development of obesity. Several mechanisms explain the correlation between intestinal flora and obesity. The intestinal flora would increase the energetic extraction of non-digestible polysaccharides. In addition, the lipopolysaccharide from intestinal flora bacteria could trigger a chronic sub-clinical inflammatory process, leading to obesity and diabetes. Another mechanism through which the intestinal flora could lead to obesity would be through the regulation of genes of the host involved in energy storage and expenditure. In the past five years data coming from different sources established causal effects between intestinal microbiota and obesity/insulin resistance, and it is clear that this area will open new avenues of therapeutic to obesity, insulin resistance and DM2

Skeletal carbonate mineralogy of Scottish bryozoans

This paper describes the skeletal carbonate mineralogy of 156 bryozoan species collected from Scotland (sourced both from museum collections and from waters around Scotland) and collated from literature. This collection represents 79% of the species which inhabit Scottish waters and is a greater number and proportion of extant species than any previous regional study. The study is also of significance globally where the data augment the growing database of mineralogical analyses and offers first analyses for 26 genera and four families. Specimens were collated through a combination of field sampling and existing collections and were analysed by X-ray diffraction (XRD) and micro-XRD to determine wt% MgCO3 in calcite and wt% aragonite. Species distribution data and phylogenetic organisation were applied to understand distributional, taxonomic and phylo-mineralogical patterns. Analysis of the skeletal composition of Scottish bryozoans shows that the group is statistically different from neighbouring Arctic fauna but features a range of mineralogy comparable to other temperate regions. As has been previously reported, cyclostomes feature low Mg in calcite and very little aragonite, whereas cheilostomes show much more variability, including bimineralic species. Scotland is a highly variable region, open to biological and environmental influx from all directions, and bryozoans exhibit this in the wide range of within-species mineralogical variability they present. This plasticity in skeletal composition may be driven by a combination of environmentally-induced phenotypic variation, or physiological factors. A flexible response to environment, as manifested in a wide range of skeletal mineralogy within a species, may be one characteristic of successful invasive bryozoans

Resistance to penicillin of Staphylococcus aureus isolates from cows with high somatic cell counts in organic and conventional dairy herds in Denmark

BACKGROUND: Quarter milk samples from cows with high risk of intramammary infection were examined to determine the prevalence of Staphylococcus aureus (SA) and penicillin resistant SA (SAr) in conventional and organic dairy herds and herds converting to organic farming in a combined longitudinal and cross-sectional study. METHODS: 20 conventional herds, 18 organic herds that converted before 1995, and 19 herds converting to organic farming in 1999 or 2000 were included in the study. Herds converting to organic farming were sampled three times one year apart; the other herds were sampled once. Risk of infection was estimated based on somatic cell count, milk production, breed, age and lactation stage. RESULTS: The high-risk cows represented about 49 % of the cows in the herds. The overall prevalence of SA and SAr among these cows was 29% (95% confidence interval: 24%–34%) and 4% (95% confidence interval: 2%–5%) respectively. The prevalence of penicillin resistance among SA infected cows was 12% (95% confidence interval: 6%–19%) when calculated from the first herd visits. No statistically significant differences were observed in the prevalence of SAr or the proportion of isolates resistant to penicillin between herd groups. CONCLUSION: The proportion of isolates resistant to penicillin was low compared to studies in other countries except Norway and Sweden. Based on the low prevalence of penicillin resistance of SA, penicillin should still be the first choice of antimicrobial agent for treatment of bovine intramammary infection in Denmark