Bedbugs: how to diagnose and manage cases of infestations.

Bedbugs are on the rise in urban populations across the world, perhaps reflecting the ban on the use of organophosphates in many countries worldwide. They are flat obligate haematophagous insects, preferring humans, and as a consequence the bedbug bites lack toxins and can often go unnoticed for some time. Bites can, however, cause weals, purpura, petechiae, vesicles, pustules, papular urticaria, localized infection and rarely anaphylaxis. Infestations have to be confirmed by finding the bugs, usually around the bed of the person being bitten. Eradication usually requires a combination of physical (for example high temperature, mattresses protectors, traps, cold) and chemical methods (for example chrysanthemic acid derivatives plus potentiators such as geraniol and piperonyl butoxide or acetylcholine esterase inhibitors).

Real-world experience of SARS-CoV-2 antibody assays in UK healthcare workers.

BACKGROUND: The seroprevalence of antibodies to SARS-CoV-2 in healthcare workers is variable throughout the world. This study compares the use of two antibody assays among large cohorts of healthcare workers in southern England. METHODS: This cohort study includes data obtained from staff at Western Sussex Hospitals NHS Foundation Trust (WSHT) and Brighton and Sussex University Hospitals (BSUH) during voluntary antibody testing, using Abbott and Roche SARS-CoV-2 antibody assays at each Trust respectively. RESULTS: The observed seroprevalence level was 7.9% for the WSHT/Abbott cohort versus 13% for the BSUH/Roche cohort. Based on a previous positive PCR, we find that the false-negative rate of the Abbott and Roche assays were 60.2% and 19% respectively, implying sensitivity levels of 39.8% and 81%. Within these cohorts, seropositivity was most strongly associated with those of South Asian ethnicity, allied health professionals and male sex (p<0.0001). CONCLUSIONS: In this real-world study, neither antibody test performed to the specification level stated by the manufacturer. More rigorous testing of these and other assays in target populations is recommended prior to widespread usage if they are to provide data that might be useful to control the pandemic.

Arginine and methylated arginines in human plasma and urine measured by tandem mass spectrometry without the need for chromatography or sample derivatisation.

A method for the simultaneous analysis of asymmetric dimethylarginine, symmetric dimethylarginine, monomethylarginine and arginine in human plasma and urine, with short analysis time and isotopic internal standardisation for each analyte is described. The method requires neither sample derivatisation nor the need for chromatographic separation of analytes. The method described shows good precision and accuracy and is suited for both research purposes and implementation in the busy, routine clinical laboratory. In addition the synthesis and utilisation of isotopically labelled symmetric dimethylarginine and monomethylarginine is described for the first time, avoiding the use of surrogates such as homoarginine for internal standardisation.

Age and sex variation in serum albumin concentration: an observational study.

BACKGROUND: In the UK, a common reference interval for serum albumin is widely used irrespective of age or sex. Implicit in this is that laboratories produce analytically similar results. This paper challenges the validity of this approach. METHODS: A three-week collection of results sent to all primary care centres in England has been analysed by age, sex and laboratory. In all, 1,079,193 serum albumin reports were included in this analysis. RESULTS: The mean population serum albumin concentration increases to peak at around age 20 years and then decreases with increasing age. Values in females decrease more rapidly but become close to male values at 60 years. The variation between laboratories was large and potentially clinically significant. CONCLUSIONS: Reference intervals for serum albumin should be stratified by age and sex. Until there is greater methodological standardization, laboratories should determine their own reference intervals and not accept a single consensus reference interval.

Impaired renal function and biomarkers of vascular disease in Alzheimer's disease.

Renal disease is a risk factor for vascular diseases and for dementia, and renal insufficiency can be a feature of Alzheimer's disease (AD). Evidence has suggested that vascular mechanisms mediate the link between renal disease and dementia. Our study sought to test this hypothesis by examining renal and vascular functioning in AD by investigating estimated glomerular filtration rates (eGFR), calculated from serum creatinine concentrations, and established biomarkers of vascular functioning, asymmetrical dimethylarginine (ADMA) and plasma homocysteine (Hcy), in individuals with mild to moderate AD (n = 34) and a group of older adult controls (n = 34). We found significantly reduced eGFR, indicative of impaired renal functioning, in individuals with AD (M = 62.9, SD = 15.2) compared with controls (M = 73.6, SD = 11.8). However, concentrations of ADMA and Hcy did not differ between patient and control groups (ADMA: M = 0.47; M = 0.50; Hcy: M = 17.2; M = 14.9; patients and controls). The criteria for a mediation analysis were not met, as concentrations of ADMA and Hcy did not predict AD, indicating that these biomarkers of vascular functioning did not mediate a relationship between renal functioning and AD. This study indicated that renal insufficiency may independently contribute to AD pathology, and other vascular mechanisms may influence a relationship between renal impairment and AD.

Pro-inflammatory cytokines IL-1ß and TNF-α are not associated with plasma homocysteine concentration in Alzheimer's disease.

Increased concentrations of pro-inflammatory blood cytokines and plasma homocysteine (Hcy) are frequently reported in Alzheimer's disease (AD). Hcy appears to have immunomodulating and pro-inflammatory activities. Further, emerging evidence from animal and non-AD human studies implicates Hcy in potentiating the activities of proinflammatory cytokines; Hcy toxicity may also, in part, be mediated by these cytokines. As little is known about the potential relationship between these inflammatory markers specific to AD, the aim of this study was to assess potential impact of Hcy on the widely reported increases in cytokine concentrations in AD. Blood concentrations of two proinflammatory cytokines, IL-1ß and TNF-α, along with Hcy were assessed in 40 AD patients and 30 cognitively intact controls. Mean blood concentrations of IL-1ß and TNF-α differed significantly between the AD and control groups (p=0.001 and p<0.001 resp). This difference survived adjustment for age and gender on logistic regression. Hcy was significantly correlated with age only in the patient (r(s)=0.38, p=0.02) but not the control group. There was no significant correlation between IL-1ß and Hcy, and between TNF-α, and Hcy in either the AD or the control group. Hence, our AD data did not replicate results obtained from animal and non-AD human studies which have linked pro-inflammatory cytokines concentrations to Hcy. A different inflammatory focus may exist in AD which may be influenced at least in a significant part by non-vascular pathogenesis. However, these results indirectly support the notion that the observed mild hyperhocysteinemia in AD may be due to non-inflammatory factors.

Plasma fetuin-A is associated with the severity of cognitive impairment in mild-to-moderate Alzheimer's disease.

The significance of vascular risk factors in the development and progression of Alzheimer's disease (AD) is now widely recognized. Fetuin-A is an abundant plasma protein that predicts vascular risk in a variety of clinical settings. In the context of cerebral ischemia, fetuin-A appears to be anti-inflammatory. Given the apparent importance of neuroinflammation in cognitive decline, we analyzed fetuin-A concentrations and pro-inflammatory cytokine levels in a cohort of 34 patients with mild-to-moderate AD, and compared these to age-matched controls. Further, we analyzed the relationship between plasma fetuin-A concentration and a measure of cognitive impairment using multivariate regression modeling. Plasma fetuin-A concentrations were lower in the patient group (p = 0.006) compared with controls and were significantly correlated with Mini-Mental State Examination (MMSE) score (r = 0.504, p = 0.002). Fetuin-A concentration was also significantly and inversely correlated with plasma TNF-α concentration (r = -0.496, p = 0.003). The association between MMSE performance and fetuin-A was maintained even after multivariate adjustment for other risk factors including TNF-α (adjusted R² total = 0.371). Using this model, plasma fetuin-A concentration explained 21% of the variance in MMSE scores. Further studies are needed to evaluate whether fetuin-A is related to the progression and pathogenesis of AD.

Instability of fibroblast growth factor-23 (FGF-23): implications for clinical studies.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a bone secreted hormone that regulates phosphate homeostasis and calcitriol levels. FGF-23 concentrations are elevated in chronic kidney disease (CKD), oncogenic osteomalcia and a number of rare hereditary disorders. Studies systematically evaluating the pre-analytical stability of intact FGF-23 are lacking. METHODS: The stability of FGF-23 was assessed in timed experiments using blood taken into K2-EDTA plasma specimen tubes from a group of healthy participants and from a group with mild-to-moderate CKD. We evaluated the use of aprotinin, a serine protease inhibitor, and a commercially available protease inhibitor cocktail to preserve intact FGF-23 after blood collection. FGF-23 measurements were made using both intact and C-terminal assays. RESULTS: Both whole blood and separated sample studies demonstrated a rapid loss of intact FGF-23 within 2 h, while concentrations increased using the C-terminal assay. The addition of protease inhibitor cocktail stabilised FGF-23 concentrations for 4 h after blood collection. Intact and C-terminal assay FGF-23 measurements showed poor correlation in both healthy and CKD cohorts. CONCLUSION: K2-EDTA plasma samples, even when promptly separated, are unsuitable for measurement of FGF-23 unless stabilised with a protease inhibitor cocktail.