Community-Based Participatory Research to Adapt Health Measures for Use by People with Developmental Disabilities

Background: People with developmental disabilities (DD) are often not included as participants in research owing to a variety of ethical and practical challenges. One major challenge is that traditional measurements instruments may not be accessible to people with DD. Participatory research approaches promise to increase the participation of marginalized communities in research, but few partnerships have successfully used such approaches to conduct quantitative studies people with DD. Objective: To use a community-based participatory search (CBPR) approach to create an accessible, computer-assisted survey about violence and health in people with DD, and to psychometrically test adapted health instruments. Methods: Our academic-community partnership, composed of academic researchers, people with DD, and supporters, collaboratively selected and modified data collection instruments, conducted cognitive interviews and pilot tests, and then administered the full survey to 350 people with DD. Results: Although team members sometimes had opposing accommodation needs and adaption recommendations, academic and community partners were able to work together successfully to adapt instruments to be accessible to participants with a wide range of DD. Results suggest the adapted health instruments had strong content validity and all but one had good to excellent internal consistency reliability (alpha, 0.81-0.94). The majority of participants (75%) responded that all or most of the questions were easy to understand. Conclusions: Researchers should consider using participatory approaches to adapting instruments so people with DD can be validly included in research

Rampant gene rearrangement and haplotype hypervariation among nematode mitochondrial genomes

Rare syntenic conservation, sequence duplication, and the use of both DNA strands to encode genes are signature architectural features defining mitochondrial genomes of enoplean nematodes. These characteristics stand in contrast to the more conserved mitochondrial genome sizes and transcriptional organizations of mitochondrial DNAs (mtDNAs) derived from chromadorean nematodes. To address the frequency of gene rearrangement within nematode mitochondrial DNA (mtDNA), mitochondrial genome variation has been characterized within a more confined enoplean taxonomic unit, the family Mermithidae. The complete nucleotide sequences of the mosquito parasitic nematodes Romanomermis culicivorax, R. nielseni, and R. iyengari mtDNA have been determined. Duplicated expanses encompassing different regions of the mitochondrial genomes were found in each of these congeners. These mtDNA shared few rRNA and protein gene junctions, indicating extensive gene rearrangement within the Romanomermis lineage. Rapid structural changes are also observed at the conspecific level where no two individual nematodes carry the same haplotype. Rolling circle amplification was used to isolate complete mitochondrial genomes from individuals in local populations of Thaumamermis cosgrovei, a parasite of terrestrial isopods. Mitochondrial DNA length variants ranging from 19 to 34 kb are observed, but haplotypes are not shared between any two individuals. The complete nucleotide sequences of three haplotypes have been determined, revealing a constant region encoding most mitochondrial genes and a hypervariable segment that contains intact and pseudogene copies of several mitochondrial genes, duplicated to different copy numbers, resulting in mtDNA size variation. Constant rearrangement generates new T. cosgrovei mtDNA forms

How accurate is an LCD screen version of the Pelli–Robson test?

Purpose: To evaluate the accuracy and repeatability of a computer-generated Pelli–Robson test displayed on liquid crystal display (LCD) systems compared to a standard Pelli–Robson chart. Methods: Two different randomized crossover experiments were carried out for two different LCD systems for 32 subjects: 6 females and 10 males (40.5 ± 13.0 years) and 9 females and 7 males (27.8 ± 12.2 years), respectively, in the first and second experiment. Two repeated measurements were taken with the printed Pelli–Robson test and with the LCDs at 1 and 3 m. To test LCD reliability, measurements were repeated after 1 week. Results: In Experiment 1, contrast sensitivity (CS) measured with LCD1 resulted significantly higher than Pelli–Robson both at 1 and at 3 m of about 0.20 log 1/C in both eyes (p < 0.01). Bland–Altman plots showed a proportional bias for LCD1 measures. LCD1 measurements showed reasonable repeatability: ICC was 0.83 and 0.65 at 1 and 3 m, respectively. In Experiment 2, CS measured with LCD2 resulted significantly lower than Pelli–Robson both at 1 and at 3 m of about 0.10 log 1/C in both eyes (p < 0.01). Bland–Altman plots did not show any proportional bias for LCD2 measures. LCD2 measurements showed sufficient repeatability: ICC resulted 0.51 and 0.65 at 1 and 3 m, respectively. Conclusions: Computer-generated versions of Pelli–Robson test, displayed on LCD systems, do not provide accurate results compared to classic Pelli–Robson printed version. Clinicians should consider that Pelli–Robson computer-generated versions could be non-interchangeable to the printed version

An effector from the Huanglongbing-associated pathogen targets citrus proteases

The citrus industry is facing an unprecedented challenge from Huanglongbing (HLB). All cultivars can be affected by the HLB-associated bacterium ‘Candidatus Liberibacter asiaticus’ (CLas) and there is no known resistance. Insight into HLB pathogenesis is urgently needed in order to develop effective management strategies. Here, we use Sec-delivered effector 1 (SDE1), which is conserved in all CLas isolates, as a molecular probe to understand CLas virulence. We show that SDE1 directly interacts with citrus papain-like cysteine proteases (PLCPs) and inhibits protease activity. PLCPs are defense-inducible and exhibit increased protein accumulation in CLas-infected trees, suggesting a role in citrus defense responses. We analyzed PLCP activity in field samples, revealing specific members that increase in abundance but remain unchanged in activity during infection. SDE1-expressing transgenic citrus also exhibit reduced PLCP activity. These data demonstrate that SDE1 inhibits citrus PLCPs, which are immune-related proteases that enhance defense responses in plants

European Code against Cancer 4th Edition: Alcohol drinking and cancer.

Alcohol consumption is the third leading risk factor for disease and mortality in Europe. As evaluated by the International Agency for Research on Cancer (IARC) Monographs, a causal relationship is established for consumption of alcoholic beverages and cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colorectum and female breast, even at low and moderate alcohol intakes. The higher the amount of alcohol consumed, the higher the risk of developing cancer. In Europe, an estimated 10% (95% CI: 7%-13%) of all cancer cases in men and 3% (95% CI: 1%-5%) of all cancer cases in women are attributable to alcohol consumption. Several biological mechanisms explain the carcinogenicity of alcohol; among them, ethanol and its genotoxic metabolite, acetaldehyde, play a major role. Taking all this evidence into account, a recommendation of the 4th edition of European Code against Cancer is: "If you drink alcohol of any type, limit your intake. Not drinking alcohol is better for cancer prevention.

Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modelling Study

Hallett et al use a mathematical model to examine the long-term impact and cost-effectiveness of different pre-exposure prophylaxis (PrEP) strategies for HIV prevention in serodiscordant couples

Corresponding Functional Dynamics across the Hsp90 Chaperone Family: Insights from a Multiscale Analysis of MD Simulations

Understanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of the full length protein are available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are studied in complex with the natural ligands ATP, ADP and in the Apo state. Common key aspects of their functional dynamics are elucidated with a novel multi-scale comparison of their internal dynamics. Starting from the atomic resolution investigation of internal fluctuations and geometric strain patterns, a novel analysis of domain dynamics is developed. The results reveal that the ligand-dependent structural modulations mostly consist of relative rigid-like movements of a limited number of quasi-rigid domains, shared by the three proteins. Two common primary hinges for such movements are identified. The first hinge, whose functional role has been demonstrated by several experimental approaches, is located at the boundary between the N-terminal and Middle-domains. The second hinge is located at the end of a three-helix bundle in the Middle-domain and unfolds/unpacks going from the ATP- to the ADP-state. This latter site could represent a promising novel druggable allosteric site common to all chaperones

Role of genetic polymorphisms in tumour angiogenesis

Angiogenesis plays a crucial role in the development, growth and spread of solid tumours. Pro- and anti-angiogenic factors are abnormally expressed in tumours, influencing tumour angiogenesis, growth and progression. Polymorphisms in genes encoding angiogenic factors or their receptors may alter protein expression and/or activity. This article reviews the literature to determine the possible role of angiogenesis-related polymorphisms in cancer. Further research studies in this potentially crucial area of tumour biology are proposed

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus genus and several species of this family are pathogenic to humans. The viruses are classified as potential agents of biological warfare and terrorism and sensitive detection as well as effective prophylaxis and antiviral therapies are required

Tm1: A Mutator/Foldback Transposable Element Family in Root-Knot Nematodes

Three closely related parthenogenetic species of root-knot nematodes, collectively termed the Meloidogyne incognita-group, are economically significant pathogens of diverse crop species. Remarkably, these asexual root-knot nematodes are capable of acquiring heritable changes in virulence even though they lack sexual reproduction and meiotic recombination. Characterization of a near isogenic pair of M. javanica strains differing in response to tomato with the nematode resistance gene Mi-1 showed that the virulent strain carried a deletion spanning a gene called Cg-1. Herein, we present evidence that the Cg-1 gene lies within a member of a novel transposable element family (Tm1; Transposon in Meloidogyne-1). This element family is defined by composite terminal inverted repeats of variable lengths similar to those of Foldback (FB) transposable elements and by 9 bp target site duplications. In M. incognita, Tm1 elements can be classified into three general groups: 1) histone-hairpin motif elements; 2) MITE-like elements; 3) elements encoding a putative transposase. The predicted transposase shows highest similarity to gene products encoded by aphids and mosquitoes and resembles those of the Phantom subclass of the Mutator transposon superfamily. Interestingly, the meiotic, sexually-reproducing root-knot nematode species M. hapla has Tm1 elements with similar inverted repeat termini, but lacks elements with histone hairpin motifs and contains no elements encoding an intact transposase. These Tm1 elements may have impacts on root-knot nematode genomes and contribute to genetic diversity of the asexual species