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The burden of disease relating to undiagnosed HIV infection is significant in the UK. BHIVA (British HIV Association) recommends population screening in high prevalence areas, expanding outside traditional antenatal/GUM settings. RUClear 2011-12 piloted expanding HIV testing outside traditional settings using home-sampling kits (dry-blood-spot testing) ordered online. Greater Manchester residents (≥age 16) could request testing via an established, online chlamydia testing service (www.ruclear.co.uk). Participant attitudes towards this new service were assessed. Qualitative methods (thematic analysis) were used to analyse free-text data submitted by participants via hard copy questionnaires issued in all testing kits. 79.9% (2447/3062) participants completed questionnaires, of which 30.9% (756/2447) provided free-text data. Participants overwhelmingly supported the service, valuing particularly accessibility and convenience, allowing individuals to order tests any time of day and self-sample comfortably at home; avoiding the invasive nature of venipuncture and avoiding the need for face-to-face interaction with health services. The pilot was also clinically and cost-effective. Testing via home-sampling kits ordered online (dry-blood-spot testing) was felt to be an acceptable and convenient method for accessing a HIV test. Many individuals undertook HIV testing where they would otherwise not have been tested at all. Expansion of similar services may increase the uptake of HIV testing.

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in β-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of β-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired β-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.

Neutral endopeptidase 24.11 (NEP) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). We report that NEP expression and catalytic activity are lost in vitro in androgen-independent but not androgen-dependent PC cell lines. In vivo , NEP protein expression is commonly decreased in cancer cells of metastatic PC specimens from patients with androgen-independent but not androgen-dependent PC. Overexpression of NEP in androgen-independent PC cells or incubation with recombinant NEP inhibits PC cell growth. Furthermore, in androgen-dependent PC cells, expression of NEP is transcriptionally regulated by androgen and decreases with androgen withdrawal. These data suggest that decreased NEP expression, common in androgen-independent PCs, is facilitated by the elimination of androgens, and that NEP loss plays an important role in the development of androgen-independent PC by allowing PC cells to use mitogenic neuropeptides as an alternate source to androgen in order to stimulate cell proliferation.

As specific genes are identified that are associated with behavior, it becomes increasingly important for behavioral geneticists to be able to incorporate these genes in their research. Rather than using blood, DNA can be extracted from cheek swabs, which makes it possible to obtain DNA inexpensively by mail from large, widely dispersed individuals. The purpose of this paper is to recommend this technique to the behavioral genetics community and to present results of our use of this technique to obtain DNA by mail for 114 2-year-olds and 116 adults.

A review of Kawasaki disease (KD)-like syndromes (KDLS) in patients with human immunodeficiency virus (HIV) raised the question whether vasculitis in children and KDLS in immunocompromised adults might be etiologically related. We describe a 42-year-old white man with AIDS and Kaposi sarcoma who presented with KDLS, which was diagnosed on the basis of clinical criteria for KD. Analysis of a conjunctival tissue sample revealed endothelial cell damage with fibrin deposition and infiltration of immunoglobulin A-secreting plasma cells.

Intervertebral disc disease is a common cause of pain and neurological deficits and is known to be associated with degeneration and calcification. Here we analysed samples of herniated disc material and compared it to material taken from non-herniated discs following surgical treatment in dogs. Our clinical approach to these cases allows collection of samples providing a unique opportunity for a case-controlled study such as this, an opportunity which is not available to the human neurosurgeon. We analysed all samples using Fourier transform infrared (FTIR) spectroscopy, as well as a proportion with X-ray diffraction (XRD) and transmission electron microscopy (TEM). FTIR spectra of the majority of herniated samples were consistent with the presence of crystalline hydroxyapatite, whereas most of the non-herniated discs showed spectra consistent with amorphous phosphate material. XRD analysis and TEM confirmed these findings and identified the amorphous material as amorphous calcium phosphate nanoparticle clusters of ∼ 20 nm diameter and the crystalline hydroxyapatite material as needles up to 100 nm in length. The differences between the herniated and non-herniated discs indicate that the degenerative process involves a conversion of amorphous calcium phosphate into crystalline hydroxyapatite which precedes and may predispose the disc to herniate.

The sterilization by radiation of disposable medical items has been investigated. Various vegetative and spore-bearing bacteria have been irradiated and results indicate that 2·5 Mrad can be recommended to give a high degree of sterility. Spores of B. pumilus (E.601) showed such resistance that it might be a suitable test organism for determining the efficiency of a radiation treatment. A high standard of packaging must be demanded for pre-sterilized products.