Community based multi-disease health screening as an opportunity for early detection of HIV cases and linking them to care.

BACKGROUND: The 95-95-95 UNAIDS global strategy was adapted to end the AIDS epidemic by 2030. The target is based on the premise that early detection of HIV-infected persons and linking them to treatment regardless of their CD4 counts will lead to sustained viral suppression. HIV testing strategies to increase uptake of testing in Western and Central Africa remain inadequate. Hence, a high proportion of people living with HIV in this region do not know their status. This report describes the implementation of a community based multi-disease health screening (also known as "Know Your Status" -KYS), as part of basic science research, in a way that contributed to achieving public health goals. METHODS: A community based multi-disease health screening was conducted in 7 communities within the Eastern region of Ghana between November 2017 and April 2018, to recruit and match HIV seronegative persons to HIV seropositive persons in a case-control HIV gut microbiota study. Health assessments included blood pressure, body mass index, blood sugar, Hepatitis B virus, syphilis, and HIV testing for those who consented. HIV seronegative participants who consented were consecutively enrolled in an ongoing HIV gut microbiota case-control study. Descriptive statistics (percentages) were used to analyze data. RESULTS: Out of 738 people screened during the exercise, 700 consented to HIV testing and 23 (3%) were HIV positive. Hepatitis B virus infection was detected in 4% (33/738) and Syphilis in 2% (17/738). Co-infection of HIV and HBV was detected in 4 persons. The HIV prevalence of 3% found in these communities is higher than both the national prevalence of 1.7% and the Eastern Regional prevalence of 2.7 in 2018. CONCLUSION: Community based multi-disease health screening, such as the one undertaken in our study could be critical for identifying HIV infected persons from the community and linking them to care. In the case of HIV, it will greatly contribute to achieving the first two 95s and working towards ending AIDS by 2030.

Insecticidal Activity of Jatropha Extracts Against the Azalea Lace Bug, Stephanitis pyrioides (Hemiptera: Tingidae).

We assessed bioactivity of ethanolic extracts from 35 species of Jatropha L. against an ornamental plant pest, the azalea lace bug, Stephanitis pyrioides (Scott). Jatropha extracts were prepared by air-drying stem, root, or whole plant material, grinding the tissue into a fine powder, adding 70% ethanol, and then vacuum filtering the contents. Emulsions included the extract diluted to the desired concentration in de-ionized water and 10% dimethyl sulfoxide (DMSO). Treatments involved pipetting 20 µl of emulsion onto three adult lace bugs in each well of a 96-well microtiter plate. Treated wells served as replicates for each of six extract concentrations and were arranged according to a RCBD. Extracts of Jatropha clavuligera Müll. Arg. and J. ribifolia (Pohl) Ballion from 0.06 to 0.50% were the most acutely bioactive with bug mortality exceeding that of the positive control - azadirachtin, a terpenoid and chief active ingredient in neem oil. At 1.00%, extracts of J. clavuligera, J. ribifolia and azadirachtin killed 100% of bugs within 3 hr. Jatropha clavuligera induced the lowest LC50 and ranked first in insecticidal potency based on ≥98% of bugs dying within 3 hr. Extracts of J. curcas L., J. gossypiifolia L., J. excisa Griseb, and azadirachtin were equally bioactive; although after 3 hr, the three Jatropha species killed bugs faster. When compared with DMSO, all extract emulsions were bioactive against adult bugs. Thus, active ingredients in a new biopesticide could be sourced from the stem, root, or whole plant extracts of at least five Jatropha species.

Super high-resolution single-molecule sequence-based typing of HLA class I alleles in HIV-1 infected individuals in Ghana.

Polymorphisms in human leukocyte antigen (HLA) class I loci are known to have a great impact on disease progression in HIV-1 infection. Prevailing HIV-1 subtypes and HLA genotype distribution are different all over the world, and the HIV-1 and host HLA interaction could be specific to individual areas. Data on the HIV-1 and HLA interaction have been accumulated in HIV-1 subtype B- and C-predominant populations but not fully obtained in West Africa where HIV-1 subtype CRF02_AG is predominant. In the present study, to obtain accurate HLA typing data for analysis of HLA association with disease progression in HIV-1 infection in West African populations, HLA class I (HLA-A, -B, and -C) four-digit allele typing was performed in treatment-naïve HIV-1 infected individuals in Ghana (n = 324) by a super high-resolution single-molecule sequence-based typing (SS-SBT) using next-generation sequencing. Comparison of the SS-SBT-based data with those obtained by a conventional sequencing-based typing (SBT) revealed incorrect assignment of several alleles by SBT. Indeed, HLA-A*23:17, HLA-B*07:06, HLA-C*07:18, and HLA-C*18:02 whose allele frequencies were 2.5%, 0.9%, 4.3%, and 3.7%, respectively, were not determined by SBT. Several HLA alleles were associated with clinical markers, viral load and CD4+ T-cell count. Of note, the impact of HLA-B*57:03 and HLA-B*58:01, known as protective alleles against HIV-1 subtype B and C infection, on clinical markers was not observed in our cohort. This study for the first time presents SS-SBT-based four-digit typing data on HLA-A, -B, and -C alleles in Ghana, describing impact of HLA on viral load and CD4 count in HIV-1 infection. Accumulation of these data would facilitate high-resolution HLA genotyping, contributing to our understanding of the HIV-1 and host HLA interaction in Ghana, West Africa.

Human Leukocyte Antigen-Associated HIV-1 CRF02_AG gag and vif Polymorphisms in Ghana.

In human immunodeficiency virus type-1 (HIV-1) infections, cytotoxic T-lymphocyte (CTL) responses targeting human leukocyte antigen (HLA)-restricted viral epitopes exert strong suppressive pressure on viral replication and frequently select for mutations resulting in viral escape from CTL recognition. Numerous data on these HLA-associated mutations in HIV-1 subtypes B and C have been amassed with few reports described in other subtypes. In the present study, we investigated the HLA-associated mutations in HIV-1 subtype CRF02_AG prevailing in Ghana, Western Africa. We determined viral gag sequences in 246 out of 324 HIV-1-infected Ghanaians. Phylogeny analysis revealed that 200 (81.3%) individuals were infected with HIV-1 CRF02_AG. Full gag and vif sequences were obtained from 199 and 138, respectively, out of the 200 individuals infected with CRF02_AG and subjected to determination of HLA-associated mutations. The analysis found HLA-associated HIV-1 CRF02_AG non-synonymous polymorphisms at 19 sites; 13 in gag and six in vif, including those that were newly determined. Generation of this data is an important contribution to our understanding of HIV-1 CRF02_AG and host T cell interaction.

Analysis of soluble or titanium dioxide derived titanium levels in human whole blood: consensus from an inter-laboratory comparison.

Exposure to titanium (Ti), via the ingestion of pigment grade Ti dioxide (TiO2), is commonplace for westernised populations. It may also occur as a consequence of metal ion leaching in subjects bearing Ti-containing implants. Accurate exposure analysis requires fit-for-purpose analytical methodology, especially for true measures of baseline levels. Inductively coupled plasma (ICP) techniques are, mainly, now used for bio-analysis of Ti. Since whole blood reference materials, certified for natural low levels of Ti, are not currently available, we undertook an inter-laboratory comparison of pooled human blood from fasted volunteers ±low level (+∼2.5 µg L-1) or high level (+10-20 µg L-1) spikes of soluble Ti or TiO2 particles. Seven established laboratories were enrolled to analyse the samples using ICP based techniques, which included at least one of ICP optical emission spectrometry (ICP-OES), high resolution ICP mass spectrometry (HR-ICP-MS), triple quadrupole ICP-MS (ICP-MS/MS) or single quadrupole ICP-MS (SQ-ICP-MS). Five laboratories diluted the blood for analysis whilst two performed acid digestion. Overall, we showed that the laboratories could, mostly, quantitatively detect modest levels of spiked Ti in blood. Markedly varying levels of Ti, however, were reported for the same baseline pooled sample (0.4-24.6 µg L-1) and, in this study, specificity was poor for SQ-ICP-MS. Digestion of samples caused sample contamination compromising limits of detection and accuracy, whilst simple dilution had no such problem, and remained linear in response for spikes with ionic and TiO2 particles. We conclude that measuring baseline levels of Ti in whole blood is challenging but should be readily achievable down to 0.5-1.5 µg L-1, if sample preparation avoids contamination and instrument techniques are used that negate polyatomic or isobaric interferences from the sample matrix. We also remind those relying upon Ti bio-analytical data for their experimental outcomes that (a) spiking and recovery experiments provide information only on linearity of detection but not at all on accuracy as this will not detect constant positive errors and that (b) biological standard materials for Ti generally contain high levels of the analyte and tend to mask baseline analytical errors. Caution may be required in interpreting the findings of some published Ti/TiO2 bio-exposure studies.

Erythritol and Lufenuron Detrimentally Alter Age Structure of Wild Drosophila suzukii (Diptera: Drosophilidae) Populations in Blueberry and Blackberry.

We report on the efficacy of 0.5 M (61,000 ppm) erythritol (E) in Truvia Baking Blend, 10 ppm lufenuron (L), and their combination (LE) to reduce egg and larval densities of wild populations of Drosophila suzukii (Matsumura) infesting fields of rabbiteye blueberries (Vaccinium virgatum) and blackberries (Rubus sp.). Formulations included the active ingredients (lufenuron, erythritol, or both), sugar (in control and erythritol treatments), and Dawn hand-soap applied to plants with pressurized 3-gallon garden spray tanks. The three chemical treatments (E, L, and LE) had no effect on D. suzukii ovipositing in blackberry and blueberry fruit, but they did reduce larval infestation by 75%, particularly densities of first and second instars. Erythritol and lufenuron were equally efficacious compounds as a D. suzukii ovicide and larvicide, but they did not display additive or synergistic activity. Extremely high larval mortality in control fruits show an age structure heavily skewed toward egg output.

Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease.

BACKGROUND: Adult Refsum's Disease (ARD) is caused by defects in the pathway for alpha-oxidation of phytanic acid (PA). Treatment involves restricting the dietary intake of phytanic acid by reducing the intake of dairy-derived fat. The adequacy of micronutrient intake in patients with ARD is unknown. METHODS: Patients established on the Chelsea low-PA diet had general diet macronutrients, vitamins and trace elements assessed using 7-day-weighed intakes and serial 24-h recalls. Intakes were compared with biochemical assessments of nutritional status for haematinics (ferritin), trace elements (copper, zinc, iron, selenium), water- (vitamin B6 , B12 and folate) and fat-soluble vitamins (A, D, E and K). RESULTS: Eleven subjects (four women, seven men) were studied. Body mass index was 27 ± 5 kg/m(2) (range 19-38). All subjects had high sodium intakes (range 1873-4828 mg). Fat-soluble vitamin insufficiencies occurred in some individuals (vitamin A, n = 2; vitamin D, n = 6; vitamin E, n = 3; vitamin K, n = 10) but were not coincident. Vitamin B6 levels were normal or elevated (n = 6). Folate and 5-methyltetrahydrofolate concentrations were normal. Metabolic vitamin B12 insufficiency was suspected in four subjects based on elevated methylmalonic acid concentrations. Low copper and selenium intakes were noted in some subjects (n = 7, n = 2) but plasma levels were adequate. Iron, ferritin and zinc intakes and concentrations were normal. CONCLUSION: Subjects with ARD can be safely managed on the Chelsea low PA without routine micronutrient supplementation. Sodium intake should be monitored and reduced. Periodic nutritional screening may be necessary for fat-soluble vitamins, vitamin B12 , copper or selenium.

Phenotypic Variation in Fitness Traits of a Managed Solitary Bee, Osmia ribifloris (Hymenoptera: Megachilidae).

We investigated fitness in natural populations of a managed solitary bee Osmia ribifloris Cockerell (Hymenoptera: Megachilidae) from sites separated from 400 to 2,700 km. Parental wild bees originated in central Texas (TX), central-northern Utah (UT), and central California (CA). They were then intercrossed and raised inside a mesh enclosure in southern Mississippi (MS). Females from all possible mated pairs of O. ribifloris produced F1 broods with 30-40% female cocoons and outcrossed progeny were 30% heavier. Mitochondrial (COI) genomes of the four populations revealed three distinct clades, a TX-CA clade, a UT clade, and an MS clade, the latter (MS) representing captive progeny of CA and UT bees. Although classified as separate subspecies, TX and CA populations from 30° N to 38° N latitude shared 98% similarity in COI genomes and the greatest brood biomass per nest straw (600- to 700-mg brood). Thus, TX and CA bees show greater adaptation for southern U.S. sites. In contrast, UT-sourced bees were more distantly related to TX and CA bees and also produced ∼50% fewer brood. These results, taken together, confirm that adult O. ribifloris from all trap-nest sites are genetically compatible, but some phenotypic variation exists that could affect this species performance as a commercial blueberry pollinator. Males, their sperm, or perhaps a substance in their sperm helped stabilize our captive bee population by promoting legitimate nesting over nest usurpation. Otherwise, without insemination, 50% fewer females nested (they nested 14 d late) and 20% usurped nests, killing 33-67% of brood in affected nests.

Retained drugs in the gastrointestinal tracts of deceased victims of oral drug overdose.

CONTEXT: The extent of non-absorbed drug burden in the GI tract following overdose is unknown. Patients who present with clinical signs of toxicity may not undergo decontamination due to assumption that the drug has already been completely absorbed and because of limited scientific evidence of benefit for routine GI decontamination in poisoned patients. OBJECTIVE: The goal of this study was to assess whether people who die of an oral overdose have unabsorbed drug present in the GI tract. The secondary goal was to analyze pharmacologic characteristics of retained drugs when present. MATERIALS AND METHODS: Retrospective review of autopsy reports from 2008 to 2010, whose cause of death was determined as "intoxication" or "overdose, was performed at the Office of Chief Medical Examiner of the City of New York (OCME NYC)." Decedents of all ages were identified via electronic OCME database. Inclusion criteria were as follows: 1) cause of death "intoxication" or "overdose" noted by forensic autopsy, 2) ingestion of a solid drug formulation. RESULTS: 92 out of 1038 autopsies (9%) that met inclusion criteria had documentation of retained pill fragments, granules, paste, sludge, slurry, or whole pills in the GI tract. The most common drugs found were opioids and anticholinergics. Ninety-eight percent (98%) of the retained drugs were either modified-release preparations or drugs known to slow GI transit. Most decedents were dead on arrival; there were twelve in-hospital deaths and eleven patients died in the Emergency Department. Bupropion and venlafaxine were responsible for four deaths in those who received medical care. One person died in the ICU following bupropion ingestion. DISCUSSION AND CONCLUSION: Overdose of an oral drug that either has modified-release properties or slows GI tract motility may result in substantial unabsorbed drug burden remaining in the GI tract.

Surveillance of Patients with Metal-on-Metal Hip Resurfacing and Total Hip Prostheses: A Prospective Cohort Study to Investigate the Relationship Between Blood Metal Ion Levels and Implant Failure.

BACKGROUND: We designed a prospective, single-center study to assess whether blood metal ion levels could predict implant failure in patients managed with unilateral metal-on-metal hip resurfacing or total hip arthroplasty. METHODS: Five hundred and ninety-seven patients who had received unilateral Articular Surface Replacement prostheses at least twelve months earlier were recruited. Blood metal ion levels were compared between the group of patients with failed implants and the group with non-failed implants. Implant failure was defined as prostheses associated with revision, an intention to revise, or poor patient-reported hip function (Oxford Hip Score, <31 of 48). Specificity, sensitivity, area under the curve, positive and negative predictive values, and odds ratios were calculated. Logistic regression analysis was used to identify other risk factors for implant failure. RESULTS: Patients with failed arthroplasty had significantly higher blood cobalt and chromium ion levels than did patients with non-failed arthroplasty (p < 0.01). Blood cobalt ion levels were disproportionately raised in patients with failed total hip arthroplasty (8.2 µg/L) compared with patients with failed hip resurfacing (2.5 µg/L) (p = 0.018). Blood chromium ion levels were not significantly different in patients with failed total hip arthroplasty and failed hip resurfacing (p = 0.058). The maximum value of either metal ion had good discriminant ability to predict implant failure (area under the curve, 0.76). A 7-µg/L cutoff had a positive predictive value of 0.75 (95% confidence interval, 0.66 to 0.82) and a negative predictive value of 0.82 (95% confidence interval, 0.78 to 0.86). In patients managed with total hip arthroplasty, for each increase of 1 µg/L there was a 23% (p < 0.001) increase in the odds of them being in the failed group. For patients managed with hip resurfacing, the increase in odds was 5% (p < 0.001). CONCLUSIONS: Raised levels of blood metal ions were associated with failed metal-on-metal hip resurfacings and total hip arthroplasties. A threshold level of 7 µg/L had inadequate sensitivity to be used in isolation as a screening test for implant failure, but it provided nearly optimal misclassification rates. No level had a perfect positive predictive value, and so we discourage surgeons from performing revision surgery based on blood metal ion levels alone. Levels of cobalt ions were raised out of proportion to levels of chromium ions in failed total hip arthroplasty and may reflect a different mechanism for metal ion generation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

HIV-1 drug-resistance surveillance among treatment-experienced and -naïve patients after the implementation of antiretroviral therapy in Ghana.

BACKGROUND: Limited HIV-1 drug-resistance surveillance has been carried out in Ghana since the implementation of antiretroviral therapy (ART). This study sought to provide data on the profile of HIV-1 drug resistance in ART-experienced and newly diagnosed individuals in Ghana. METHODS: Samples were collected from 101 HIV-1-infected patients (32 ART-experienced cases with virological failure and 69 newly diagnosed ART-naïve cases, including 11 children), in Koforidua, Eastern region of Ghana, from February 2009 to January 2010. The pol gene sequences were analyzed by in-house HIV-1 drug-resistance testing. RESULTS: The most prevalent HIV-1 subtype was CRF02_AG (66.3%, 67/101) followed by unique recombinant forms (25.7%, 26/101). Among 31 ART-experienced adults, 22 (71.0%) possessed at least one drug-resistance mutation, and 14 (45.2%) had two-class-resistance to nucleoside and non-nucleoside reverse-transcriptase inhibitors used in their first ART regimen. Importantly, the number of accumulated mutations clearly correlated with the duration of ART. The most prevalent mutation was lamivudine-resistance M184V (n = 12, 38.7%) followed by efavirenz/nevirapine-resistance K103N (n = 9, 29.0%), and zidovudine/stavudine-resistance T215Y/F (n = 6, 19.4%). Within the viral protease, the major nelfinavir-resistance mutation L90M was found in one case. No transmitted HIV-1 drug-resistance mutation was found in 59 ART-naïve adults, but K103N and G190S mutations were observed in one ART-naïve child. CONCLUSIONS: Despite expanding accessibility to ART in Eastern Ghana, the prevalence of transmitted HIV-1 drug resistance presently appears to be low. As ART provision with limited options is scaled up nationwide in Ghana, careful monitoring of transmitted HIV-1 drug resistance is necessary.

High precision isotope measurements reveal poor control of copper metabolism in parkinsonism.

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable (65)Cu isotope tracer. The analyses of blood serum (65)Cu/(63)Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.

Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement.

Blood metal ions have been widely used to investigate metal-on-metal hip replacements, but their ability to discriminate between well-functioning and failed hips is not known. The Medicines and Healthcare products Regulatory Agency (MHRA) has suggested a cut-off level of 7 parts per billion (ppb). We performed a pair-matched, case-control study to investigate the sensitivity and specificity of blood metal ion levels for diagnosing failure in 176 patients with a unilateral metal-on-metal hip replacement. We recruited 88 cases with a pre-revision, unexplained failed hip and an equal number of matching controls with a well-functioning hip. We investigated the 7 ppb cut-off level for the maximum of cobalt or chromium and determined optimal mathematical cut-off levels from receiver-operating characteristic curves. The 7 ppb cut-off level for the maximum of cobalt or chromium had a specificity of 89% and sensitivity 52% for detecting a pre-operative unexplained failed metal on metal hip replacement. The optimal cut-off level for the maximum of cobalt or chromium was 4.97 ppb and had sensitivity 63% and specificity 86%. Blood metal ions had good discriminant ability to separate failed from well-functioning hip replacements. The MHRA cut-off level of 7 ppb provides a specific test but has poor sensitivity.

An analysis of metal ion levels in the joint fluid of symptomatic patients with metal-on-metal hip replacements.

We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial fluid and whole blood taken from a group of 92 patients with failed current-generation metal-on-metal hip replacements. We applied acid oxidative digestion to our trace metal analysis protocol, which found significantly higher levels of metal ion concentrations in blood and synovial fluid than a non-digestive method. Patients were subcategorised by mode of failure as either 'unexplained pain' or 'defined causes'. Using this classification, chromium and cobalt ion levels were present over a wider range in synovial fluid and not as strongly correlated with blood ion levels as previously reported. There was no significant difference between metal ion concentrations and manufacturer of the implant, nor femoral head size below or above 50 mm. There was a moderately positive correlation between metal ion levels and acetabular component inclination angle as measured on three-dimensional CT imaging. Our results suggest that acid digestion of samples of synovial fluid samples is necessary to determine metal ion concentrations accurately so that meaningful comparisons can be made between studies.

Generation of HIV-1 primary isolates representative of plasma variants using the U87.CD4 cell line.

In order to obtain HIV-1 primary isolates in settings with limited access to donor PBMCs, a culture method was developed where patient PBMCs infected with HIV-1 were cultured together with U87.CD4 cells. Using this non-laborious method, it is possible to harvest virus solely on the basis of syncytia formation and circumventing monitoring of viral replication by CA-p24 ELISA. Primary isolates from 23 out of 33 patients (70%) were isolated successfully. From PCR amplification and sequencing of the V1V5 region of the viral gp120 envelope gene, primary isolates were compared with variants obtained from plasma and PBMCs of 13 patients. The primary isolates of seven patients (54%) resembled closely the plasma viral quasispecies, whereas different variants were isolated from the other patients (46%). Three patients harboured a dual infection, while this remained unnoticed from sequencing the plasma or PBMC compartment. The primary isolates were highly infectious for TZM-bl cells and could infect CD4-enriched lymphocytes. This study demonstrates that it is possible to grow viral isolates using a non-laborious and simple method. These isolates may be used in the field for studies on antiretroviral therapy or for vaccine trials.

The painful metal-on-metal hip resurfacing.

We carried out metal artefact-reduction MRI, three-dimensional CT measurement of the position of the component and inductively-coupled plasma mass spectrometry analysis of cobalt and chromium levels in whole blood on 26 patients with unexplained pain following metal-on-metal resurfacing arthroplasty. MRI showed periprosthetic lesions around 16 hips, with 14 collections of fluid and two soft-tissue masses. The lesions were seen in both men and women and in symptomatic and asymptomatic hips. Using three-dimensional CT, the median inclination of the acetabular component was found to be 55 degrees and its positioning was outside the Lewinnek safe zone in 13 of 16 cases. Using inductively-coupled plasma mass spectrometry, the levels of blood metal ions tended to be higher in painful compared with well-functioning metal-on-metal hips. These three clinically useful investigations can help to determine the cause of failure of the implant, predict the need for future revision and aid the choice of revision prostheses.

Metabolic syndrome and renal sodium handling in three ethnic groups living in England.

AIM/HYPOTHESIS: Increased proximal renal sodium re-absorption is associated with central adiposity and insulin resistance in white men. Our study examined whether this association also exists in other ethnic groups with different prevalences of insulin resistance and associated metabolic abnormalities. METHODS: We studied the association between fractional renal excretion of endogenous lithium (FELi) and metabolic syndrome in a population study of 1190 randomly selected men and women who where 40 to 59 years of age (426 white, 397 of African and 367 of South Asian origin). Anthropometric values, blood pressure, biochemical values, questionnaire data and timed urine collections were obtained with standardised techniques. Endogenous lithium in serum and urine was measured by absorption spectrophotometry. Metabolic markers were the homeostasis model assessment (HOMA) index, waist circumference, serum triglycerides, serum HDL cholesterol and metabolic syndrome as defined by Adult Treatment Panel III criteria. RESULTS: In white men and women a higher rate of proximal sodium re-absorption was inversely associated with higher waist circumference, serum triglycerides and HOMA index, and with lower serum HDL cholesterol (all p< or =0.001). No associations were found in people of African or South Asian origin. The former had lower FELi than the other groups. White people with the metabolic syndrome had a lower FELi than those without (15.9% vs 19.0%; p=0.003). No difference was found in people of African or South Asian origin. CONCLUSIONS/INTERPRETATION: Increased proximal sodium re-absorption is associated with the metabolic syndrome in white men and women. This relationship is not seen in people of African or South Asian origin, despite a greater degree of insulin resistance.

A novel mouse model of experimental asthma.

BACKGROUND: Animal models that mimic the pulmonary features observed in human asthma are important tools to study the mechanism(s) of allergen-induced asthma. Cockroach and dust mite allergens are two common allergens found in the 'inner city' environment. In this study, we examined the interaction between recombinant cockroach (r Bla g 2) and dust mite (r Der f 1) allergens in inbred mouse strain (A/J). The tested hypothesis was that there are enhanced effects of exposure to r Bla g 2 and r Der f 1 allergens in the airway inflammatory response in A/J mice. METHODS: Five groups of mice (male, 6-8 weeks) were examined: vehicle (saline) controls; adjuvant (alum) controls; r Bla g 2 immunized (0.01-10 microg/mouse), r Der f 1 immunized (0.01-10 microg/mouse), and combined immunization with r Der f 1 (0.05 microg/mouse) and r Bla g 2 (0.0 5 microg/mouse). Mice were immunized at days 0 and 7, challenged by oro-tracheal inhalation with r Der f 1 and/or r Bla g 2 allergen at day 14, and were studied and sacrificed on day 17. Airway hyperreactivity was measured by peak airway pressure and airway pressure time index (APTI). Differential cell analysis and total proteins in bronchoalveolar lavage returns were used to assess airway inflammation and epithelial injury. RESULTS: Dose-related statistically significant increases in peak pressure, APTI, total cells, eosinophils, epithelial cells, but not total proteins, were induced by r Bla g 2 challenge in r Bla g 2-immunized mice. Similar allergen-induced dose-related increases in airway total cells, eosinophils, epithelial cells and total proteins were observed in r Der f 1 immunized mice. Compared to either allergen alone, enhanced airway inflammation and epithelial damage, but not airway reactivity, were detected in the combined group. CONCLUSION: This novel mouse model will allow investigation of the immunopathogenesis of human asthma and should provide insight into the common form of 'inner city asthma'.