HIV positive patient with GBS-like syndrome

Introduction. Guillain–Barré Syndrome (GBS) is an acute demyelinating polyneuropathy which can occur post-infection. Criteria of diagnosis of GBS include areflexia with progressive bilateral weakness in arms and legs. GBS can lead to severe respiratory and cardiac complications. The fatality rate can be up to 5 % in patients, depending on the severity of the symptoms. HIV can cause a range of neurological disorders including, on rare occasions, GBS. GBS can occur at any stage of HIV infection, highlighting the complexity of diagnosis of GBS within HIV patients. Case presentation. A 57 year old female with lumbar back pain radiating to the legs, poor mobility and tiredness, with reports of a viral-like illness four days previously, was initially diagnosed with a lower respiratory tract infection and discharged. Seventeen days later the patient was readmitted to hospital with progressive lower and upper limb weakness, areflexia and sensory loss. She was diagnosed with GBS and was unexpectedly discovered to be HIV-positive. HIV avidity was low indicating a recently acquired HIV infection. The patient was treated with intravenous immunoglobulin for five days for the GBS and commenced antriretrovirals for HIV. The patient was discharge from hospital 53 days after admission with walking aids and regular physiotherapy follow-up. Conclusion. This case highlighted the need for all clinicians to be aware that patients with symptoms of GBS, regardless of clinical history should be offered an HIV test. GBS can be the first sign a patient is HIV-positive

Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a Scottish cohort

Background: Protease inhibitors (PI) including boceprevir, telaprevir and simeprevir have revolutionised HCV genotype 1 treatment since their introduction. A number of pre-treatment resistance associated amino acid variants (RAVs) and polymorphisms have been associated with reduced response to treatment. Objectives: We measured the prevalence of RAVs/polymorphisms in a PI treatment-naïve HCV genotype 1 Scottish cohort using Sanger sequencing. Study design: Chronically infected, treatment-naïve, HCV genotype 1 patients (n = 146) attending NHS Greater Glasgow and Clyde clinics were investigated for RAVs/polymorphisms to the PIs boceprevir, telaprevir and simeprevir. The NS3/4A region was amplified by nested polymerase chain reaction. The 1.4 kb amplified product was sequenced using an ABI 3710XL DNA sequencer. Sequence analysis was performed using web-based ReCall (beta 2.10). Amino acid positions 36, 41, 43, 54, 55, 80, 109, 122, 155, 156, 168 and 170 were analysed for RAVs/polymorphisms. Results: Overall, 23.29% (34/146) of patients had an RAV or polymorphism detected. Overall, 13.69% (20/146) of patients had HCV virus that contained the Q8 K polymorphism. Other RAVs detected were: V36 M 0.70% (1/146), V36L 0.70% (1/146), T54S 6.85% (10/146), V55A 3.42% (5/146) and V/I170A 0.68% (1/146). Four patients had dual combinations of mutations (T54S + V36L; T54S + V55A and 2 patients with T54S + Q80K). Conclusions: Q80K was the most prevalent baseline polymorphism detected in the Scottish cohort. Simeprevir treatment is not recommended in patients infected with the Q80K genotype 1a variant. This highlights the need for baseline sequencing prior to administration of this drug in this population

Increased risk of HIV and other drug-related harms associated with injecting in public places: national bio-behavioural survey of people who inject drugs

Background: Whilst injecting drugs in public places is considered a proxy for high risk behaviour among people who inject drugs (PWID), studies quantifying its relationship with multiple drug-related harms are lacking and none have examined this in the context of an ongoing HIV outbreak (located in Glasgow, Scotland). We aimed to: 1) estimate the prevalence of public injecting in Scotland and associated risk factors; and 2) estimate the association between public injecting and HIV, current HCV, overdose, and skin and soft tissue infections (SSTI). Methods: Cross-sectional, bio-behavioural survey (including dried blood spot testing to determine HIV and HCV infection) of 1469 current PWID (injected in last 6 months) recruited by independent interviewers from 139 harm reduction services across Scotland during 2017–18. Primary outcomes were: injecting in a public place (yes/no); HIV infection; current HCV infection; self-reported overdose in the last year (yes/no) and SSTI the last year (yes/no). Multi-variable logistic regression was used to determine factors associated with public injecting and to estimate the association between public injecting and drug-related harms (HIV, current HCV, overdose and SSTI). Results: Prevalence of public injecting was 16% overall in Scotland and 47% in Glasgow city centre. Factors associated with increased odds of public injecting were: recruitment in Glasgow city centre (aOR=5.45, 95% CI 3.48–8.54, p<0.001), homelessness (aOR=3.68, 95% CI 2.61–5.19, p<0.001), high alcohol consumption (aOR=2.42, 95% CI 1.69–3.44, p<0.001), high injection frequency (≥4 per day) (aOR=3.16, 95% CI 1.93–5.18, p<0.001) and cocaine injecting (aOR=1.46, 95% CI 1.00 to 2.13, p = 0.046). Odds were lower for those receiving opiate substitution therapy (OST) (aOR=0.37, 95% CI 0.24 to 0.56, p<0.001) and older age (per year increase) (aOR=0.97, 95% CI 0.95 to 0.99, p = 0.013). Public injecting was associated with an increased risk of HIV infection (aOR=2.11, 95% CI 1.13–3.92, p = 0.019), current HCV infection (aOR=1.49, 95% CI 1.01–2.19, p = 0.043), overdose (aOR=1.59, 95% CI 1.27–2.01, p<0.001) and SSTI (aOR=1.42, 95% CI 1.17–1.73, p<0.001). Conclusions: These findings highlight the need to address the additional harms observed among people who inject in public places and provide evidence to inform proposals in the UK and elsewhere to introduce facilities that offer safer drug consumption environments

IDENTIFICATION OF TRANSCRIPTION FACTORS ASSOCIATED WITH DOWN SYNDROME SKELETAL ABNORMALITIES

poster abstractIndividuals with Down syndrome (DS) exhibit a variety of phenotypes, including craniofacial and skeletal dysmorphologies. It is believed that trisomic genes initiate phenotypes associated with Down syndrome, though specific gene-phenotype relationships for DS are largely unknown. We hypothesize that the altered expression of genes in three copies will also affect the expression of downstream genes, including non-trisomic genes and play an important role in DS phenotypes. Transcription factors, which encode proteins that bind to specific DNA sequences controlling the flow of transcription, are among the genes that may be affected by trisomy. We have identified genetic and phenotypic alterations in craniofacial precursors as early as embryonic dayE9.5of the Ts65Dn mouse model of human DS. This mouse model is trisomic for orthologs of approximately half of the genes on human chromosome 21. Previous microarray data from the developing mandible have shown dysregulation of multiple non-trisomic genes. We will test the expression of the Six2, Gata3, Gata6, Pth, Hoxb4, Runx2, Ets2, and Osterix transcription factors at two developmental time points, E9.5 and E13.5, to determine which are dysregulated in the Ts65Dn DS mouse model. Understanding the effect of trisomy on non-trisomic transcription factors will help identify links between trisomy and specific DS phenotypes

Rapid Decline in HCV Incidence among People Who Inject Drugs Associated with National Scale-Up in Coverage of a Combination of Harm Reduction Interventions

BACKGROUND: Government policy has precipitated recent changes in the provision of harm reduction interventions - injecting equipment provision (IEP) and opiate substitution therapy (OST) - for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID. METHODS AND FINDINGS: We used a framework to triangulate different types of evidence: 'group-level/ecological' and 'individual-level'. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1-2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1-20.1) in 2008-09 to 7.3 (3.0-12.9) in 2011-12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11-0.74) and weighted for frequency of injecting (AORw 0.05, 95%CI 0.01-0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008-2012. CONCLUSIONS: This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions

A hepatitis C avidity test for determining recent and past infections in both plasma and dried blood spots

DBS testing has been used successfully to detect HCV antibody positive individuals. Determining how long someone has been infected is important for surveillance initiatives. Antibody avidity is a method that can be used to calculate recency of infection. A HCV avidity assay was evaluated for both plasma and DBS. Study design: To measure antibody avidity a commercial HCV ELISA was modified using 7 M urea. The plasma samples were split into: group 1 (recently infected N = 19), group 2 (chronic carrier N = 300) and group 3 (resolved infection N = 82). Mock DBS made from group 1 (N = 12), group 2 (N = 50), group 3 (N = 25) and two seroconverter panels were evaluated. 133 DBS taken from patients known to have a resolved infection or be a chronic carrier were also tested. The avidity assay cut-off was set at AI ≤ 30 for a recent infection. Using sequential samples the assay could detect a recent infection in the first 4–5 months from the point of infection. Most of the false positive results (AI < 30 among cases known not to have had recent infection) were detected among known resolved infections, in both the plasma and DBS; as a result, a testing algorithm has been designed incorporating both PCR and two dilution factors. The sensitivity and specificity of the assay on plasma was 100% and 99.3%, respectively, while DBS had 100% sensitivity and 98.3% specificity. The HCV avidity assay can be used to distinguish between chronic and recent infection using either plasma or DBS as the sample type

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services:REAL WORLD DATA

BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population

Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands

Organometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including topoisomerase I/II and thioredoxin reductase inhibition and induction of reactive oxygen species. DNA damage induction was consistent with cytotoxicity observed against proliferating cells and Ag8 induced cell death by apoptosis. Ag8 also inhibited DNA repair enzyme PARP1, showed preferential activity against cisplatin resistant A2780 cells and potentiated the activity of temozolomide. Ag8 was substantially less active against non-proliferating non-cancer cells and selectively inhibited glycolysis in cancer cells. Ag8 also induced significant anti-tumour effects against cells implanted intraperitoneally in hollow fibres but lacked activity against hollow fibres implanted subcutaneously. Thus, Ag8 targets multiple pathways of importance in cancer biology, is less active against non-cancer cells and shows activity in vivo in a loco-regional settin

Solidarity and Strife After the Atlanta Spa Shootings: A Mixed Methods Study Characterizing Twitter Discussions by Qualitative Analysis and Machine Learning

Background: On March 16, 2021, a white man shot and killed eight victims, six of whom were Asian women at Atlanta-area spa and massage parlors. The aims of the study were to: (1) qualitatively summarize themes of tweets related to race, ethnicity, and racism immediately following the Atlanta spa shootings, and (2) examine temporal trends in expressions hate speech and solidarity before and after the Atlanta spa shootings using a new methodology for hate speech analysis. Methods: A random 1% sample of publicly available tweets was collected from January to April 2021. The analytic sample included 708,933 tweets using race-related keywords. This sample was analyzed for hate speech using a newly developed method for combining faceted item response theory with deep learning to measure a continuum of hate speech, from solidarity race-related speech to use of violent, racist language. A qualitative content analysis was conducted on random samples of 1,000 tweets referencing Asians before the Atlanta spa shootings from January to March 15, 2021 and 2,000 tweets referencing Asians after the shooting from March 17 to 28 to capture the immediate reactions and discussions following the shootings. Results: Qualitative themes that emerged included solidarity (4% before the shootings vs. 17% after), condemnation of the shootings (9% after), racism (10% before vs. 18% after), role of racist language during the pandemic (2 vs. 6%), intersectional vulnerabilities (4 vs. 6%), relationship between Asian and Black struggles against racism (5 vs. 7%), and discussions not related (74 vs. 37%). The quantitative hate speech model showed a decrease in the proportion of tweets referencing Asians that expressed racism (from 1.4% 7 days prior to the event from to 1.0% in the 3 days after). The percent of tweets referencing Asians that expressed solidarity speech increased by 20% (from 22.7 to 27.2% during the same time period) (p \u3c 0.001) and returned to its earlier rate within about 2 weeks. Discussion: Our analysis highlights some complexities of discrimination and the importance of nuanced evaluation of online speech. Findings suggest the importance of tracking hate and solidarity speech. By understanding the conversations emerging from social media, we may learn about possible ways to produce solidarity promoting messages and dampen hate messages