Development and validation of a severity scale for leprosy Type 1 Reactions

Objectives: To develop a valid and reliable quantitative measure of leprosy Type 1 reactions.Methods: A scale was developed from previous scales which had not been validated. The face and content validity were assessed following consultation with recognised experts in the field. The construct validity was determined by applying the scale to patients in Bangladesh and Brazil who had been diagnosed with leprosy Type 1 reaction. An expert categorized each patient's reaction as mild or moderate or severe. Another worker applied the scale. This was done independently. In a subsequent stage of the study the agreement between two observers was assessed.Results: The scale had good internal consistency demonstrated by a Cronbach's alpha &gt;0.8. Removal of three items from the original scale resulted in better discrimination between disease severity categories. Cut off points for Type 1 reaction severities were determined using Receiver Operating Characteristic curves. A mild Type 1 reaction is characterized using the final scale by a score of 4 or less. A moderate reaction is a score of between 4.5 and 8.5. A severe reaction is a score of 9 or more.Conclusions: We have developed a valid and reliable tool for quantifying leprosy Type 1 reaction severity and believe this will be a useful tool in research of this condition, in observational and intervention studies, and in the comparison of clinical and laboratory parameters.<br/

Behavioral Inhibition as a Risk Factor for the Development of Childhood Anxiety Disorders: A Longitudinal Study

This longitudinal study examined the additive and interactive effects of behavioral inhibition and a wide range of other vulnerability factors in the development of anxiety problems in youths. A sample of 261 children, aged 5 to 8 years, 124 behaviorally inhibited and 137 control children, were followed during a 3-year period. Assessments took place on three occasions to measure children’s level of behavioral inhibition, anxiety disorder symptoms, other psychopathological symptoms, and a number of other vulnerability factors such as insecure attachment, negative parenting styles, adverse life events, and parental anxiety. Results obtained with Structural Equation Modeling indicated that behavioral inhibition primarily acted as a specific risk factor for the development of social anxiety symptoms. Furthermore, the longitudinal model showed additive as well as interactive effects for various vulnerability factors on the development of anxiety symptoms. That is, main effects of anxious rearing and parental trait anxiety were found, whereas behavioral inhibition and attachment had an interactive effect on anxiety symptomatology. Moreover, behavioral inhibition itself was also influenced by some of the vulnerability factors. These results provide support for dynamic, multifactorial models for the etiology of child anxiety problems

An enhanced regimen as post-exposure chemoprophylaxis for leprosy:PEP+

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted)

Current European Labyrinthula zosterae Are Not Virulent and Modulate Seagrass (Zostera marina) Defense Gene Expression

Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype×genotype interactions of host and pathogen from different regions (10–100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist×eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence

The genome of the seagrass Zostera marina reveals angiosperm adaptation to the sea

Seagrasses colonized the sea(1) on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet(2). Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes(3), genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae(4) and that is important for ion homoeostasis, nutrient uptake and O-2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming(5,6), to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants(7)

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted)

The genome of the seagrass Zostera marina reveals angiosperm adaptation to the sea.

Seagrasses colonized the sea on at least three independent occasions to form the basis of one of the most productive and widespread coastal ecosystems on the planet. Here we report the genome of Zostera marina (L.), the first, to our knowledge, marine angiosperm to be fully sequenced. This reveals unique insights into the genomic losses and gains involved in achieving the structural and physiological adaptations required for its marine lifestyle, arguably the most severe habitat shift ever accomplished by flowering plants. Key angiosperm innovations that were lost include the entire repertoire of stomatal genes, genes involved in the synthesis of terpenoids and ethylene signalling, and genes for ultraviolet protection and phytochromes for far-red sensing. Seagrasses have also regained functions enabling them to adjust to full salinity. Their cell walls contain all of the polysaccharides typical of land plants, but also contain polyanionic, low-methylated pectins and sulfated galactans, a feature shared with the cell walls of all macroalgae and that is important for ion homoeostasis, nutrient uptake and O2/CO2 exchange through leaf epidermal cells. The Z. marina genome resource will markedly advance a wide range of functional ecological studies from adaptation of marine ecosystems under climate warming, to unravelling the mechanisms of osmoregulation under high salinities that may further inform our understanding of the evolution of salt tolerance in crop plants