Incidence and significance of elevated platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios among hospitalised HIV-positive adult patients

There is increasing interest in the peripheral blood platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation. We audited records of unselected hospitalised HIV-positive adults to identify the frequency of elevated PLR and NLR, potential associations with specific diagnoses, and outcome. Of 259 patients audited, their median age was 47 years (interquartile range = 41–54); 188 (73%) were men. An elevated PLR occurred in 87 patients (33.6%); 67 (25.9%) had an elevated NLR; 200 (77%) had an elevated C-reactive protein (CRP). Elevated PLR and NLR was associated with a variety of infectious, inflammatory, and malignant conditions similar to conditions described in the general non-HIV-infected adult population. Additionally, elevated PLR and NLR occurred both in patients in receipt of antiretroviral therapy (with undetectable viral loads), as well as in those with newly-diagnosed and poorly-controlled infection. Fourteen patients with infectious and inflammatory conditions had an elevated PLR and normal CRP, with/without elevated NLR. There was no association between elevated PLR or NLR and ICU admission, p = 0.1001 and p = 0.605, respectively. Elevated NLR, but not PLR was associated with death, p = 0.0405 and p = 1.000, respectively: two-tailed Fisher’s exact test. The single site nature of the audit and relatively small number of patients limits these observations

Incidence and significance of an elevated red blood cell distribution width among hospitalised HIV-infected adult patients

We audited the records of unselected hospitalised HIV-positive adults admitted to a University-affiliated inner London hospital to identify the frequency of elevated red blood cell distribution width (RDW), and potential associations with specific diagnoses, and with outcome. Of 259 patients audited, 188 (73%) were men. Patients' median age was 47 years (interquartile range = 41-54). An elevated RDW was seen in 50 patients (19%); 200 (77%) had an elevated C-reactive protein (CRP), and 77 (30%) had a low haemoglobin. Only five patients had an elevated RDW without an elevated CRP and/or low haemoglobin. An elevated RDW was associated with a wide range of infectious, inflammatory, and malignant conditions similar to observed associations reported in the general non-HIV infected adult population. Additionally an elevated RDW occurred both in patients with well-controlled HIV infection and in receipt of antiretroviral therapy, as well as in those with newly diagnosed and poorly-controlled infection. Five (10%) of 50 patients with an elevated RDW needed intensive care unit (ICU) admission and two (4%) died. Two (0.95%) of 209 patients with a normal RDW needed ICU admission and four (1.9%) died. The findings of this audit are limited by the relatively small number of patients and the single site nature of the audit

Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression

The ABCG2 membrane protein is a key xeno- and endobiotic transporter, modulating the absorption and metabolism of pharmacological agents and causing multidrug resistance in cancer. ABCG2 is also involved in uric acid elimination and its impaired function is causative in gout. Analysis of ABCG2 expression in the erythrocyte membranes of healthy volunteers and gout patients showed an enrichment of lower expression levels in the patients. By genetic screening based on protein expression, we found a relatively frequent, novel ABCG2 mutation (ABCG2-M71V), which, according to cellular expression studies, causes reduced protein expression, although with preserved transporter capability. Molecular dynamics simulations indicated a stumbled dynamics of the mutant protein, while ABCG2-M71V expression in vitro could be corrected by therapeutically relevant small molecules. These results suggest that personalized medicine should consider this newly discovered ABCG2 mutation, and genetic analysis linked to protein expression provides a new tool to uncover clinically important mutations in membrane proteins. © 2018 The Author(s)

Whole Genome Resequencing Reveals Natural Target Site Preferences of Transposable Elements in Drosophila melanogaster

Transposable elements are mobile DNA sequences that integrate into host genomes using diverse mechanisms with varying degrees of target site specificity. While the target site preferences of some engineered transposable elements are well studied, the natural target preferences of most transposable elements are poorly characterized. Using population genomic resequencing data from 166 strains of Drosophila melanogaster, we identified over 8,000 new insertion sites not present in the reference genome sequence that we used to decode the natural target preferences of 22 families of transposable element in this species. We found that terminal inverted repeat transposon and long terminal repeat retrotransposon families present clade-specific target site duplications and target site sequence motifs. Additionally, we found that the sequence motifs at transposable element target sites are always palindromes that extend beyond the target site duplication. Our results demonstrate the utility of population genomics data for high-throughput inference of transposable element targeting preferences in the wild and establish general rules for terminal inverted repeat transposon and long terminal repeat retrotransposon target site selection in eukaryotic genomes

Gout. Epidemiology of gout

Gout is the most prevalent form of inflammatory arthropathy. Several studies suggest that its prevalence and incidence have risen in recent decades. Numerous risk factors for the development of gout have been established, including hyperuricaemia, genetic factors, dietary factors, alcohol consumption, metabolic syndrome, hypertension, obesity, diuretic use and chronic renal disease. Osteoarthritis predisposes to local crystal deposition. Gout appears to be an independent risk factor for all-cause mortality and cardiovascular mortality and morbidity, additional to the risk conferred by its association with traditional cardiovascular risk factors

Mutation of the glucagon receptor gene and diabetes mellitus in the UK: association or founder effect?

Recent evidence suggests that a mutation of the glucagon receptor (GCG-R) gene is involved in the development of type 2 diabetes in French patients. We have examined patients from three geographically distinct regions in the UK and found the GGT40 (Gly) to AGT40 (Ser) mutation to be present in 15/691 (2.2%) of patients with type 2 (non-insulin dependent) diabetes and 1/425 (0.2%) of geographically matched controls and have therefore replicated association of the GCG-R mutation with classical type 2 diabetes (Fisher's exact test p = 0.008). An increased frequency of the mutation of the GCG-R gene was also found in probands of type 1 (insulin dependent) diabetic multiplex (affected sib pair) families, (10/404, 2.5%). However, a lack of preferential transmission from parents heterozygous for the mutation, to affected type 1 diabetic sibs may suggest population stratification. This in turn cannot be excluded as an alternative explanation for the difference in frequency of the GCG-R gene mutation between subjects with type 2 diabetes and normal controls