Are HIV smartphone apps and online interventions fit for purpose?

Sexual health is an under-explored area of Human-Computer Interaction (HCI), particularly sexually transmitted infections such as HIV. Due to the stigma associated with these infections, people are often motivated to seek information online. With the rise of smartphone and web apps, there is enormous potential for technology to provide easily accessible information and resources. However, using online information raises important concerns about the trustworthiness of these resources and whether they are fit for purpose. We conducted a review of smartphone and web apps to investigate the landscape of currently available online apps and whether they meet the diverse needs of people seeking information on HIV online. Our functionality review revealed that existing technology interventions have a one-size-fits-all approach and do not support the breadth and complexity of HIV-related support needs. We argue that technology-based interventions need to signpost their offering and provide tailored support for different stages of HIV, including prevention, testing, diagnosis and management

Meal-derived glucagon responses are related to lower hepatic phosphate concentrations in obesity and type 2 diabetes

Aim. - Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear.Methods. - In this observational study, lean insulin-sensitive control subjects (BMI: 23.2 +/- 1.5 kg/m(2)), age-matched insulin-resistant obese subjects (BMI: 34.3 +/- 1.7 kg/m(2)) and similarly obese elderly T2D patients (BMI: 32.0 +/- 2.4 kg/m(2)) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic gamma ATP, inorganic phosphate (P-i) and lipids using P-31/H-1 magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration-time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids.Results. - MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P &lt;0.001), while glucagon concentrations were comparable across all three groups. At 260 min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r = 0.60) and postprandial hepatocellular lipid levels (160 min: r= 0.51, 240 min: r = 0.59), and negatively with adipose tissue insulin sensitivity (r = -0.73). Higher meal-induced glucagon release (iAUC(0)(-260) (min)) correlated with lower fasting (r = -0.62) and postprandial P(i )levels (160 min: r = -0.43, 240 min: r = -0.42; all P &lt;0.05). Higher meal-induced release of GIP (iAUC(0-260) (min)) correlated positively with fasting (r = 0.54) and postprandial serum triglyceride concentrations (iAUC(0-260 min, )r = 0.54; all P &lt;0.01).Conclusion. - Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic P-i suggest a role for glucagon in hepatic energy metabolism. (C) 2018 Elsevier Masson SAS. All rights reserved.</p

Sustained high prevalence of viral hepatitis and sexually transmissible infections among female sex workers in China: a systematic review and meta-analysis.

BACKGROUND: The 1980's economic boom has been associated with a rapid expansion of China's sex industry over the past three decades. Consequently, the spread of sexually transmitted infections (STIs) and hepatitis infections among female sex workers (FSW) has become an important public health issue in China. This study identifies prevalence and risks of hepatitis and STIs in Chinese FSWs. METHOD: Four electronic databases were searched for Chinese and English language peer-reviewed studies conducted between 01/2000-12/2011 that reported prevalence of hepatitis and STIs (excluding HIV) among Chinese FSW. Following the PRISMA guidelines, meta-analysis was used to estimate pooled prevalence and 95% confidence intervals for each infection. RESULT: Three hundred and thirty nine articles (34 in English and 305 in Chinese) investigating 603,647 FSWs in 29 Chinese provinces were included in this review. Over the period 2000-2011, the seroprevalence of active hepatitis B and hepatitis C among FSW were 10.7% (7.3-15.5%) and 1.0% (0.7-1.3%), respectively. The most prevalent STI was human papillomavirus (HPV, 27.0% [10.1-55.1%]), followed by herpes simplex virus-2 (HSV-2, 15.8% [11.7-20.9%]), chlamydia (13.7% [12.1-15.4%]), gonorrhoea (6.1% [5.3-7.0%]), syphilis (5.2% [4.8-5.7%]), genital warts (3.3% [2.5-4.2%]) and Trichomonas vaginitis (2.1% [1.5-24.2%]). Disease burden of both hepatitis and STI among FSW were concentrated in South Central and Southwest China. In particular, chlamydia and syphilis demonstrated a significant declining trend during the studied period (P < 0.05). Compared with the general Chinese population, FSW had significantly higher prevalence of all STIs except Trichomonas vaginitis. Further, compared to the general FSW population, HIV-positive FSW had significantly higher prevalence of syphilis, chlamydia, HSV-2 and Trichomonas vaginitis. CONCLUSION: Prevalence of hepatitis and STIs remained high and mostly stable among Chinese FSW over the period of 2000-2011. Targeted STI and hepatitis surveillance and interventions should be strengthened among Chinese FSWs, especially those who are HIV-positive

A TauP301L mouse model of dementia; development of pathology, synaptic transmission, microglial response and cognition throughout life

Background: Late stage Alzheimer's disease and other dementias are associated with neurofibrillary tangles and neurodegeneration. Here we describe a mouse (TauD35) carrying human Tau with the P301L mutation that results in Tau hyperphosphorylation and tangles. Previously we have compared gene expression in TauD35 mice to mice which develop plaques but no tangles. A similar comparison of other pathological features throughout disease progression is made here between amyloidβ and Tau mice. Methods: In vitro CA1 patch clamp and field recordings were used to investigate synaptic transmission and plasticity. Plaque load and microglia were investigated with immunohistochemistry. Cognition, locomotor activity and anxiety-related behaviours were assessed with a forced-alternation T-maze, open field and light/dark box. Results: Transgene copy number in TauD35 mice fell into two groups (HighTAU and LowTAU), allowing assessment of dose-dependent effects of overexpression and resulting in tangle load increasing 100-fold for a 2-fold change in protein levels. Tangles were first detected at 8 (HighTAU) or 13 months (LowTAU) but the effects on synaptic transmission and plasticity and behaviour were subtle. However severe neurodegeneration occurred in HighTAU mice at around 17 months preceded by considerable proliferation but little additional activation of microglia. Proliferation only started as neurodegeneration began at 13 months. Similarly to HighTau mice at 13 months of age, LowTAU mice at 24 months of age showed a comparable tangle load and microglial proliferation. However, LowTAU mice showed no neurodegeneration at this stage and considerable microglial activation, stressing the dependence of these effects on overexpression and/or age. Conclusions: Comparison of the effects of amyloidβ and plaques without tangles in a model of preclinical Alzheimer's disease to the effects of tangles without amyloidβ plaques in the late stage model described here may clarify the progressive stages of Alzheimer's disease. While Tau hyperphosphorylation and neurofibrillary tangles are eventually sufficient to cause severe neurodegeneration, initial effects on synaptic transmission and the immune response are subtle. In contrast while even with a heavy plaque load little if any neurodegeneration occurs, considerable effects on synaptic transmission and the immune system result, even before plaques are detectable

Effects of rising amyloidβ levels on hippocampal synaptic transmission, microglial response and cognition in APP_{Swe}/PSEN1_{M146V} transgenic mice

BACKGROUND: Progression of Alzheimer's disease is thought initially to depend on rising amyloidβ and its synaptic interactions. Transgenic mice (TASTPM; APP_{Swe}/PSEN1_{M146V}) show altered synaptic transmission, compatible with increased physiological function of amyloidβ, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes. METHODS: CA1 synaptic transmission and plasticity were investigated using in vitro electrophysiology. Microglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze. FINDINGS: The most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours. INTERPRETATION: The pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidβ levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition. FUNDING: GlaxoSmithKline; BBSRC; UCL; ARUK; MRC

Differential gene expression in nearly isogenic lines with QTL for partial resistance to Puccinia hordei in barley

<p>Abstract</p> <p>Background</p> <p>The barley-<it>Puccinia hordei </it>(barley leaf rust) pathosystem is a model for investigating partial disease resistance in crop plants and genetic mapping of phenotypic resistance has identified several quantitative trait loci (QTL) for partial resistance. Reciprocal QTL-specific near-isogenic lines (QTL-NILs) have been developed that combine two QTL, <it>Rphq</it>2 and <it>Rphq</it>3, the largest effects detected in a recombinant-inbred-line (RIL) population derived from a cross between the super-susceptible line L94 and partially-resistant line Vada. The molecular mechanism underpinning partial resistance in these QTL-NILs is unknown.</p> <p>Results</p> <p>An Agilent custom microarray consisting of 15,000 probes derived from barley consensus EST sequences was used to investigate genome-wide and QTL-specific differential expression of genes 18 hours post-inoculation (hpi) with <it>Puccinia hordei</it>. A total of 1,410 genes were identified as being significantly differentially expressed across the genome, of which 55 were accounted for by the genetic differences defined by QTL-NILs at <it>Rphq</it>2 and <it>Rphq</it>3. These genes were predominantly located at the QTL regions and are, therefore, positional candidates. One gene, encoding the transcriptional repressor Ethylene-Responsive Element Binding Factor 4 (<it>HvERF4</it>) was located outside the QTL at 71 cM on chromosome 1H, within a previously detected eQTL hotspot for defence response. The results indicate that <it>Rphq</it>2 or <it>Rphq</it>3 contains a <it>trans</it>-eQTL that modulates expression of <it>HvERF4</it>. We speculate that HvERF4 functions as an intermediate that conveys the response signal from a gene(s) contained within <it>Rphq</it>2 or <it>Rphq</it>3 to a host of down-stream defense responsive genes. Our results also reveal that barley lines with extreme or intermediate partial resistance phenotypes exhibit a profound similarity in their spectrum of <it>Ph</it>-responsive genes and that hormone-related signalling pathways are actively involved in response to <it>Puccinia hordei</it>.</p> <p>Conclusions</p> <p>Differential gene expression between QTL-NILs identifies genes predominantly located within the target region(s) providing both transcriptional and positional candidate genes for the QTL. Genetically mapping the differentially expressed genes relative to the QTL has the potential to discover <it>trans</it>-eQTL mediated regulatory relays initiated from genes within the QTL regions.</p

Willingness to act upon beliefs about 'treatment as prevention' among Australian gay and bisexual men

HIV 'treatment as prevention' (TasP) is highly effective in reducing HIV transmission in serodiscordant couples. There has been little examination of gay and bisexual men's attitudes towards TasP, particularly regarding men's willingness to act on beliefs about TasP. We conducted an online cross-sectional survey of Australian men in late 2012 to investigate knowledge and beliefs about new developments in HIV prevention. Amongst 839 men (mean age 39.5 years), men tended to disagree that TasP was sufficiently effective to justify reduced condom use, although HIV-positive men had more favourable attitudes. Only a minority of men were aware of any evidence for TasP; and one-quarter incorrectly believed that evidence for the effectiveness of TasP already existed for the homosexual population. One-fifth (20.5%) of men reported that they would be willing to have condomless anal intercourse with an opposite-status sexual partner when the HIV-positive partner was taking HIV treatments. Factors independently associated with such willingness were: HIV-positive serostatus, reporting any serodiscordant or serononconcordant condomless anal intercourse with a regular male partner in the previous six months, reporting any condomless anal intercourse with a casual male partner in the previous six months, and having greater beliefs in the effectiveness of TasP. This indicated that the men most willing to rely on TasP to prevent transmission were already engaging in higher risk practices. Biomedical HIV prevention represents a rapidly changing environment with new research as well as community and policy responses emerging at a fast pace. For men with serodiscordant sexual partners to successfully apply TasP to reducing transmission risk, more support and education is needed to enable better utilisation of TasP in specific relational and sexual contexts

The eClinical Care Pathway Framework: A novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England.Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway).Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation.The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council, eSTI2 Consortium (Grant Number G0901608)