Current treatment practice of Guillain-Barré syndrome

Objective: To define the current treatment practice of Guillain-Barré syndrome (GBS). Methods: The study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account. Results: We excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE. Conclusions: In current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations

Do Bat Gantries and Underpasses Help Bats Cross Roads Safely?

Major roads can reduce bat abundance and diversity over considerable distances. To mitigate against these effects and comply with environmental law, many European countries install bridges, gantries or underpasses to make roads permeable and safer to cross. However, through lack of appropriate monitoring, there is little evidence to support their effectiveness. Three underpasses and four bat gantries were investigated in northern England. Echolocation call recordings and observations were used to determine the number of bats using underpasses in preference to crossing the road above, and the height at which bats crossed. At gantries, proximity to the gantry and height of crossing bats were measured. Data were compared to those from adjacent, severed commuting routes that had no crossing structure. At one underpass 96% of bats flew through it in preference to crossing the road. This underpass was located on a pre-construction commuting route that allowed bats to pass without changing flight height or direction. At two underpasses attempts to divert bats from their original commuting routes were unsuccessful and bats crossed the road at the height of passing vehicles. Underpasses have the potential to allow bats to cross roads safely if built on pre-construction commuting routes. Bat gantries were ineffective and used by a very small proportion of bats, even up to nine years after construction. Most bats near gantries crossed roads along severed, pre-construction commuting routes at heights that put them in the path of vehicles. Crossing height was strongly correlated with verge height, suggesting that elevated verges may have some value in mitigation, but increased flight height may be at the cost of reduced permeability. Green bridges should be explored as an alternative form of mitigation. Robust monitoring is essential to assess objectively the case for mitigation and to ensure effective mitigation

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer

Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan–Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR=1.82; 95% CI=1.19–2.79) and disease-free survival (HR=1.56; 95% CI=1.05–2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR=2.85; 95% CI=1.43–5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer

Genus Paracoccidioides: Species Recognition and Biogeographic Aspects

Background: Paracoccidioidomycosis is a systemic mycosis caused by Paracoccidioides brasiliensis (species S1, PS2, PS3), and Paracoccidioides lutzii. This work aimed to differentiate species within the genus Paracoccidioides, without applying multilocus sequencing, as well as to obtain knowledge of the possible speciation processes. Methodology/Principal Findings: Single nucleotide polymorphism analysis on GP43, ARF and PRP8 intein genes successfully distinguished isolates into four different species. Morphological evaluation indicated that elongated conidia were observed exclusively in P. lutzii isolates, while all other species (S1, PS2 and PS3) were indistinguishable. To evaluate the biogeographic events that led to the current geographic distribution of Paracoccidioides species and their sister species, Nested Clade and Likelihood Analysis of Geographic Range Evolution (LAGRANGE) analyses were applied. The radiation of Paracoccidioides started in northwest South America, around 11–32 million years ago, as calculated on the basis of ARF substitution rate, in the BEAST program. Vicariance was responsible for the divergence among S1, PS2 and P. lutzii and a recent dispersal generated the PS3 species, restricted to Colombia. Taking into account the ancestral areas revealed by the LAGRANGE analysis and the major geographic distribution of L. loboi in the Amazon basin, a region strongly affected by the Andes uplift and marine incursions in the Cenozoic era, we also speculate about the effect of these geological events on the vicariance between Paracoccidioides and L. loboi. Conclusions/Significance: The use of at least 3 SNPs, but not morphological criteria, as markers allows us to distinguish among the four cryptic species of the genus Paracoccidioides. The work also presents a biogeographic study speculating on how these species might have diverged in South America, thus contributing to elucidating evolutionary aspects of the genus Paracoccidioides

Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy

Heritable changes in gene expression that are not based upon alterations in the DNA sequence are defined as epigenetics. The most common mechanisms of epigenetic regulation are the methylation of CpG islands within the DNA and the modification of amino acids in the N-terminal histone tails. In the last years, it became evident that the onset of cancer and its progression may not occur only due to genetic mutations but also because of changes in the patterns of epigenetic modifications. In contrast to genetic mutations, which are almost impossible to reverse, epigenetic changes are potentially reversible. This implies that they are amenable to pharmacological interventions. Therefore, a lot of work in recent years has focussed on the development of small molecule enzyme inhibitors like DNA-methyltransferase inhibitors or inhibitors of histone-modifying enzymes. These may reverse misregulated epigenetic states and be implemented in the treatment of cancer or other diseases, e.g., neurological disorders. Today, several epigenetic drugs are already approved by the FDA and the EMEA for cancer treatment and around ten histone deacetylase (HDAC) inhibitors are in clinical development. This review will give an update on recent clinical trials of the HDAC inhibitors used systemically that were reported in 2009 and 2010 and will present an overview of different biomarkers to monitor the biological effects

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

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