Libyan Boy with Autosomal Recessive Trait (P22-phox Defect) of Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a primary immune deficiency disorder of the phagocytes. In this disorder, phagocytic cells (polymorphonuclear leukocytes and monocytes) cannot produce active oxygen metabolites and, therefore, cannot destroy the ingested intracellular bacteria. Clinically, patients with CGD usually have recurrent bacterial and fungal infections causing abscess and granuloma formation in the skin, lymph nodes and visceral organs

Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B

In 2016, two research groups independently identified microdeletions and pathogenic variants in the lysine-specific histone methyltransferase 2B gene, KMT2B in patients with early-onset progressive dystonia. KMT2B-dystonia (DYT28) is emerging as an important and frequent cause of childhood-onset progressive generalised dystonia and is estimated to potentially account for up to 10% of early-onset generalised dystonia. Herein, we review variants in KMT2B associated with dystonia, as well as the clinical phenotype, treatment and underlying disease mechanisms. Furthermore, in context of this newly identified condition, we summarise our approach to the genetic investigation of paediatric dystonia

Usability and Psychosocial Impact of Decision Support to Increase Sexual Health Education in American Indian and Alaska Native Communities

Despite sexual and reproductive health disparities, few evidence-based sexual health education programs exist for American Indian/Alaska Native (AI/AN) youth, with even fewer tools available to assist AI/AN communities in adopting, implementing, and maintaining such programs. iCHAMPSS (Choosing And Maintaining effective Programs for Sex education in Schools) is a theory- and web-based decision-support-system designed to address dissemination barriers and increase the reach and fidelity of evidence-based programs (EBPs), specifically sexual health education programs. To investigate the potential of iCHAMPSS in AI/AN communities, we pilot-tested iCHAMPSS with adult stakeholders (N = 36) from agencies across the country that serve AI/AN communities. Stakeholders were recruited to review selected iCHAMPSS tools over two weeks in spring 2016. Pre- and post-surveys were administered to assess usability constructs, short-term psychosocial outcomes, and perceived feasibility. Data were analyzed using descriptive and non-parametric statistics. iCHAMPSS was perceived as acceptable, easy to use, credible, appealing, more helpful than current resources, and impactful of EBP adoption, implementation, and maintenance. Conversely, using iCHAMPSS significantly increased participants’ perceived barriers to adopting an EBP (p = 0.01). Overall, AI/AN stakeholders responded positively to iCHAMPSS, indicating the potential for adaptation to support the dissemination and implementation of evidence-based sexual health education in AI/AN communities

Kelvin-Helmholtz Instability Associated With Reconnection and Ultra Low Frequency Waves at the Ground: A Case Study

The Kelvin-Helmholtz instability (KHI) and its effects relating to the transfer of energy and mass from the solar wind into the magnetosphere remain an important focus of magnetospheric physics. One such effect is the generation of Pc4-Pc5 ultra low frequency (ULF) waves (periods of 45–600 s). On July 3, 2007 at ∼ 0500 magnetic local time the Cluster space mission encountered Pc4 frequency Kelvin-Helmholtz waves (KHWs) at the high latitude magnetopause with signatures of persistent vortices. Such signatures included bipolar fluctuations of the magnetic field normal component associated with a total pressure increase and rapid change in density at vortex edges; oscillations of magnetosheath and magnetospheric plasma populations; existence of fast-moving, low-density, mixed plasma; quasi-periodic oscillations of the boundary normal and an anti-phase relation between the normal and parallel components of the boundary velocity. The event occurred during a period of southward polarity of the interplanetary magnetic field according to the OMNI data and THEMIS observations at the subsolar point. Several of the KHI vortices were associated with reconnection indicated by the Walén relation, the presence of deHoffman-Teller frames, field-aligned ion beams observed together with bipolar fluctuations in the normal magnetic field component, and crescent ion distributions. Global magnetohydrodynamic simulation of the event also resulted in KHWs at the magnetopause. The observed KHWs associated with reconnection coincided with recorded ULF waves at the ground whose properties suggest that they were driven by those waves. Such properties were the location of Cluster’s magnetic foot point, the Pc4 frequency, and the solar wind conditions.publishedVersio

Native IYG: Improving Psychosocial Protective Factors for HIV/STI and Teen Pregnancy Prevention among Youth in American Indian/Alaska Native Communities

Background: Few HIV/STI and pregnancy prevention programs for youth in American Indian and Alaska Native (AI/AN) communities have been rigorously evaluated despite sexual health disparities in this population. This study reports the evaluation of a culturally adapted Internet-based HIV/STI and pregnancy prevention program for AI/AN youth, Native It’s Your Game (Native IYG). Methods: A randomized study was conducted with 523 youth (12 to 14 years old), recruited from 25 tribal sites in Alaska, Arizona, and the Pacific Northwest. Participants were surveyed at baseline and upon completion of treatment or comparison interventions. Multivariable linear regression models were used to assess impact on short term psychosocial determinants of sexual initiation. Results: A sample of 402 intervention (n=290) and comparison (n=112) youth completed the post-intervention survey (76.9% retention) from 1 to 462 days post-baseline (mean = 114, SD = ±96.67). Participants were 55.5% female, mean age of 13.0 (± 0.97) years with 86.1% self-reporting as AI/AN. Reasons not to have sex, STI knowledge, condom knowledge, condom availability self-efficacy, and condom use self-efficacy were significantly impacted (all P ≤ .01). Limitations included variability in intervention exposure and time between data collection time points. Conclusions: Native IYG demonstrated efficacy to impact short-term psychosocial determinants of sexual behavior in a sample of predominantly AI/AN middle school youth

Using honey to heal diabetic foot ulcers

Diabetic ulcers seem to be arrested in the inflammatory/proliferative stage of the healing process, allowing infection and inflammation to preclude healing. Antibiotic-resistant bacteria have become a major cause of infections, including diabetic foot infections. It is proposed here that the modern developments of an ancient and traditional treatment for wounds, dressing them with honey, provide the solution to the problem of getting diabetic ulcers to move on from the arrested state of healing. Honeys selected to have a high level of antibacterial activity have been shown to be very effective against antibiotic-resistant strains of bacteria in laboratory and clinical studies. The potent anti-inflammatory action of honey is also likely to play an important part in overcoming the impediment to healing that inflammation causes in diabetic ulcers, as is the antioxidant activity of honey. The action of honey in promotion of tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells, and its insulin-mimetic effect, would also be of benefit in stimulating the healing of diabetic ulcers. The availability of honey-impregnated dressings which conveniently hold honey in place on ulcers has provided a means of rapidly debriding ulcers and removing the bacterial burden so that good healing rates can be achieved with neuropathic ulcers. With ischemic ulcers, where healing cannot occur because of lack of tissue viability, these honey dressings keep the ulcers clean and prevent infection occurring

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

The global status of insect resistance to neonicotinoid insecticides

This document is the Accepted Manuscript version of the following article: Chris Bass, Ian Denholm, Martin S. Williamson, and Ralf Nauen, ‘The global status of insect resistance to neonicotinoid insecticides’, Pesticide Biochemistry and Physiology, Vol. 121, pp. 78-87, June 2015. The Version of Record is available online at doi: https://doi.org/10.1016/j.pestbp.2015.04.004. Published by Elsevier Copyright © 2015 Elsevier Inc.The first neonicotinoid insecticide, imidacloprid, was launched in 1991. Today this class of insecticides comprises at least seven major compounds with a market share of more than 25% of total global insecticide sales. Neonicotinoid insecticides are highly selective agonists of insect nicotinic acetylcholine receptors and provide farmers with invaluable, highly effective tools against some of the world's most destructive crop pests. These include sucking pests such as aphids, whiteflies, and planthoppers, and also some coleopteran, dipteran and lepidopteran species. Although many insect species are still successfully controlled by neonicotinoids, their popularity has imposed a mounting selection pressure for resistance, and in several species resistance has now reached levels that compromise the efficacy of these insecticides. Research to understand the molecular basis of neonicotinoid resistance has revealed both target-site and metabolic mechanisms conferring resistance. For target-site resistance, field-evolved mutations have only been characterized in two aphid species. Metabolic resistance appears much more common, with the enhanced expression of one or more cytochrome P450s frequently reported in resistant strains. Despite the current scale of resistance, neonicotinoids remain a major component of many pest control programmes, and resistance management strategies, based on mode of action rotation, are of crucial importance in preventing resistance becoming more widespread. In this review we summarize the current status of neonicotinoid resistance, the biochemical and molecular mechanisms involved, and the implications for resistance management.Peer reviewedFinal Accepted Versio

Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor

<p>Abstract</p> <p>Background</p> <p>Myxoma virus is a member of the <it>Poxviridae </it>and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy.</p> <p>Results</p> <p>An unusually large number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over 70% of the clinical samples submitted for laboratory confirmation. Unexpectedly, further analysis revealed that a high proportion of these viral DNA preparations contained a frame-shift mutation within the M135R gene that has previously been identified as a virulence factor. This frame-shift mutation results in expression of a greatly truncated product. The same frame-shift mutation has also been found recently within an avirulent strain of myxoma virus (6918). However, three other frame-shift mutations found in this strain (in the genes M009L, M036L and M148R) were not shared with the Danish viruses but a single nucleotide deletion in the M138R/M139R intergenic region was a common feature.</p> <p>Conclusions</p> <p>It appears that expression of the full-length myxoma virus M135R protein is not required for virulence in rabbits. Hence, the frame-shift mutation in the M135R gene in the nonpathogenic 6918 virus strain is not sufficient to explain the attenuation of this myxoma virus but one/some of the other frame-shift mutations alone or in conjunction with one/some of the thirty two amino acid substitutions must also contribute. The real time PCR assay for myxoma virus is a useful diagnostic tool for laboratory confirmation of suspected cases of myxomatosis.</p