PubMed · 7839678
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P J Brink. 1994. Changing values.. https://doi.org/10.1177/019394599401600601
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The association between Human Pegivirus 1 (HPgV-1, Pegivirus hominis, family Hepaciviridae) with disease etiology remains unclear, yet this virus is widely distributed among people exposed to contaminated blood. This study aimed to identify the prevalence and characterize HPgV-1 genomes obtained from acute febrile patients (n = 92 from 2019) and from blood donors (n = 633 from 2022) sampled in Mato Grosso, Brazil. The serum samples were tested by RT-qPCR for a conserved 5' UTR region of HPgV-1. Nucleic acid of 28 positive samples was converted to ds-cDNA, purified and sequenced with an Illumina NextSeq platform. The prevalence of HPgV-1 among acute febrile patients was 4.35% (4/92), who were mostly female (3/4; 75.00%) mean 28.86 (12-67) years-old; whereas among blood donors it was 3.79% (24/633), which were predominantly male (16/24; 66.67%), aged 30-45 years-old (13/24; 54.17%). Eight HPgV-1 genomic sequences (7,708-9,248) were recovered; two belong to subgenotype 2a and clustered with strains from United States, Brazil, France and Japan, while the remaining six genomes from subgenotype 2b grouped with strains from Pará, Brazil and abroad. HPgV-1 detection in acute febrile patients and in healthy blood donors highlights the necessity to investigate the epidemiological aspects of this infection, as well as the possible impact to public health in Midwestern Brazil.
BACKGROUND: Asthma is a heterogeneous disease influenced by genetic and environmental factors. Fine particulate matter (PM2.5) exacerbates asthma, likely through oxidative stress pathways, but whether genetic variation modifies this effect remains unclear. METHODS: We analysed data on 948 adults with asthma from the Severe Asthma Research Program (SARP), linking ZIP-code-level PM2.5 exposure with whole-genome sequencing data. We tested 4337 single nucleotide polymorphisms (SNPs) in 120 oxidative stress pathway genes for gene-environment (GxE) interactions with PM2.5 on lung function (forced expiratory volume in 1 s [FEV1] % predicted) using weighted linear regression. Gene expression data from bronchial epithelial cells (n = 170) were used to assess cis-expression quantitative trait loci (eQTLs). FINDINGS: Higher PM2.5 exposure was associated with lower FEV1% predicted (β per μg/m3 = -0.7, p = 0.01). We identified 20 SNPs across seven genes (OXSR1, PXDN, TPO, LRRK2, APP, MSRA, MSRB2) with significant GxE interactions after multiple-testing correction. Five SNPs were also eQTLs, linking PM2.5-modified gene expression to lung function. Minor alleles in OXSR1 and PXDN were associated with reduced gene expression and worsened FEV1% under high PM2.5 exposure. Conversely, TPO variants were associated with higher baseline expression and lower lung function, but under increasing PM2.5 exposure, minor allele carriers showed suppressed TPO expression and improved FEV1%. INTERPRETATION: This study identified 20 SNPs in oxidative stress pathway genes that modify the effect of PM2.5 on lung function in asthma. These findings highlight the importance of integrating environmental context in genetic studies and suggest potential therapeutic targets for pollution-sensitive asthma phenotypes. FUNDING: Supported by NIH grants.
STUDY DESIGN: A cross-sectional study comparing the relationship of symptoms with anatomic impairment visible on lumbar magnetic resonance imaging in 408 symptomatic subjects. OBJECTIVE: To determine how various anatomic impairments, including the magnitude and location of nerve compression visible on lumbar magnetic resonance imaging, are associated with patient reports of pain, weakness, and dysesthesia. SUMMARY AND BACKGROUND DATA: Anatomic impairments of the intervertebral disc, radicular canal, and associated soft tissues are prevalent in people with and those without low back pain or lower extremity radiculopathy. This has led to confusion in differentiating between symptom generators and benign variation visible on lumbar magnetic resonance imaging. Recent literature has suggested that the presence of nerve compression is an important finding in the prediction of symptoms. However, the threshold for meaningful nerve compression has not been described. METHODS: In this study, 408 participants undergoing a diagnostic workup for low back pain, radiculopathy, and/ or completed a survey and pain drawing. Participants underwent standardized lumbar magnetic resonance imaging using a 1.5-T scanner. Two classification systems describing the spatial distribution of symptoms were developed. An additional system to quantify the magnitude of nerve and thecal sac compression was created. All systems were assessed for reliability, after which comparisons among variables were performed using Chi2 as well as simple and multiple logistic regression analysis. RESULTS: The reliability coefficients for categorizing patients on the basis of pain drawing ranged from 0. 75 to 0.88. The S1-S2 segmental distribution was the most commonly reported location of symptoms, followed by L4-L5. The most common magnetic resonance imaging diagnosis was "unremarkable," followed by "disc impairment without nerve compression." Disc extrusion was present in 10.8% of participants. The reliability of classifying nerve compression visible on magnetic resonance imaging ranged from 0.27 to 1. Nerve compression was present in 37% of participants, and 18% had severe nerve compression. There were no significant associations between segmental distribution of symptoms and the presence of anatomic impairment. However, according to a collapsed classification scale, severe nerve compression and disc extrusion were predictive of pain distal to the knee (odds ratios, 2.72 and 3. 34). The self-report of weakness was associated mildly with severe nerve compression and disc extrusion, but not with other findings. Magnetic resonance imaging findings did not predict self-reports of dysesthesia. CONCLUSIONS: The presence of disc extrusion and/or ipsilateral, severe nerve compression at one or multiple sites is strongly associated with distal leg pain. Mild to moderate nerve compression, disc degeneration or bulging, and central spinal stenosis are not significantly associated with specific pain patterns. Although segmental distributions of pain can be determined reliably from pain drawings, this finding alone is of little use in predicting lumbar impairment. The self-report of lower extremity weakness or dysesthesia is not significantly related to any specific lumbar impairments. [Key words: back pain, diagnosis, magnetic resonance imaging, nerve compression, pain drawing, pathology]