Factors associated with cytomegalovirus serostatus in young people in England:A cross-sectional study

BACKGROUND: Human cytomegalovirus (CMV) is a common herpesvirus which is estimated to infect 83% of the global population. Whilst many infections are asymptomatic, it is an important cause of morbidity and mortality, particularly for immunocompromised people and for infants who are congenitally infected. A vaccine against CMV has been stated as a public health priority, but there are gaps in our understanding of CMV epidemiology. To guide potential future vaccination strategies, our aim was to examine risk factors for CMV seropositivity in young people in England. METHODS: The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected through questionnaires, and blood samples are taken. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for CMV antibodies. We undertook descriptive and regression analyses of CMV seroprevalence and risk factors for infection. RESULTS: Demographic data and serostatus were available for 732 individuals, of whom 175 (23.7%) were CMV-seropositive. CMV seroprevalence was associated with age, with 18.3% seropositive at 11-14 years compared to 28.3% at 22-24 years. CMV serostatus was also higher in people of non-white ethnicity (adjusted odds ratio [aOR] 6.22, 95% confidence interval [CI] 3.47-11.14), and in adults who were seropositive for EBV (aOR 2.08 [1.06-4.09]). There was no evidence that smoking status, occupation, body mass index and region of England were associated with CMV serostatus. CONCLUSIONS: CMV seroprevalence is strongly associated with ethnicity, and modestly increases with age in 11-24-year-olds. A greater understanding of the transmission dynamics of CMV, and the impact of this on CMV-associated morbidity and mortality, is necessary to inform effective vaccination strategies when a vaccine for CMV becomes available

Predicting blunt cerebrovascular injury in pediatric trauma: Validation of the Utah Score

Risk factors for blunt cerebrovascular injury (BCVI) may differ between children and adults, suggesting that children at low risk for BCVI after trauma receive unnecessary computed tomography angiography (CTA) and high-dose radiation. We previously developed a score for predicting pediatric BCVI based on retrospective cohort analysis. Our objective is to externally validate this prediction score with a retrospective multi-institutional cohort. We included patients who underwent CTA for traumatic cranial injury at four pediatric Level I trauma centers. Each patient in the validation cohort was scored using the “Utah Score” and classified as high or low risk. Before analysis, we defined a misclassification rate <25% as validating the Utah Score. Six hundred forty-five patients (mean age 8.6 ± 5.4 years; 63.4% males) underwent screening for BCVI via CTA. The validation cohort was 411 patients from three sites compared with the training cohort of 234 patients. Twenty-two BCVIs (5.4%) were identified in the validation cohort. The Utah Score was significantly associated with BCVIs in the validation cohort (odds ratio 8.1 [3.3, 19.8], p < 0.001) and discriminated well in the validation cohort (area under the curve 72%). When the Utah Score was applied to the validation cohort, the sensitivity was 59%, specificity was 85%, positive predictive value was 18%, and negative predictive value was 97%. The Utah Score misclassified 16.6% of patients in the validation cohort. The Utah Score for predicting BCVI in pediatric trauma patients was validated with a low misclassification rate using a large, independent, multicenter cohort. Its implementation in the clinical setting may reduce the use of CTA in low-risk patients

Reversion of FMR1 Methylation and Silencing by Editing the Triplet Repeats in Fragile X iPSC-Derived Neurons

SummaryFragile X syndrome (FXS) is the most common form of inherited intellectual disability, resulting from a CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Here, we report a strategy for CGG repeat correction using CRISPR/Cas9 for targeted deletion in both embryonic stem cells and induced pluripotent stem cells derived from FXS patients. Following gene correction in FXS induced pluripotent stem cells, FMR1 expression was restored and sustained in neural precursor cells and mature neurons. Strikingly, after removal of the CGG repeats, the upstream CpG island of the FMR1 promoter showed extensive demethylation, an open chromatin state, and transcription initiation. These results suggest a silencing maintenance mechanism for the FMR1 promoter that is dependent on the existence of the CGG repeat expansion. Our strategy for deletion of trinucleotide repeats provides further insights into the molecular mechanisms of FXS and future therapies of trinucleotide repeat disorders

IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease

Macrophages (Mø) are integral in ischemia/reperfusion injury–incited (I/R-incited) acute kidney injury (AKI) that leads to fibrosis and chronic kidney disease (CKD). IL-34 and CSF-1 share a receptor (c-FMS), and both cytokines mediate Mø survival and proliferation but also have distinct features. CSF-1 is central to kidney repair and destruction. We tested the hypothesis that IL-34–dependent, Mø-mediated mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. In renal I/R, the time-related magnitude of Mø-mediated AKI and subsequent CKD were markedly reduced in IL-34–deficient mice compared with controls. IL-34, c-FMS, and a second IL-34 receptor, protein-tyrosine phosphatase ζ (PTP-ζ) were upregulated in the kidney after I/R. IL-34 was generated by tubular epithelial cells (TECs) and promoted Mø-mediated TEC destruction during AKI that worsened subsequent CKD via 2 distinct mechanisms: enhanced intrarenal Mø proliferation and elevated BM myeloid cell proliferation, which increases circulating monocytes that are drawn into the kidney by chemokines. CSF-1 expression in TECs did not compensate for IL-34 deficiency. In patients, kidney transplants subject to I/R expressed IL-34, c-FMS, and PTP−ζ in TECs during AKI that increased with advancing injury. Moreover, IL-34 expression increased, along with more enduring ischemia in donor kidneys. In conclusion, IL-34-dependent, Mø-mediated, CSF-1 nonredundant mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD

SRAO CO Observation of 11 Supernova Remnants in l = 70 to 190 deg

We present the results of 12CO J = 1-0 line observations of eleven Galactic supernova remnants (SNRs) obtained using the Seoul Radio Astronomy Observatory (SRAO) 6-m radio telescope. The observation was made as a part of the SRAO CO survey of SNRs between l = 70 and 190 deg, which is intended to identify SNRs interacting with molecular clouds. The mapping areas for the individual SNRs are determined to cover their full extent in the radio continuum. We used halfbeam grid spacing (60") for 9 SNRs and full-beam grid spacing (120") for the rest. We detected CO emission towards most of the remnants. In six SNRs, molecular clouds showed a good spatial relation with their radio morphology, although no direct evidence for the interaction was detected. Two SNRs are particularly interesting: G85.4+0.7, where there is a filamentary molecular cloud along the radio shell, and 3C434.1, where a large molecular cloud appears to block the western half of the remnant. We briefly summarize the results obtained for individual SNRs.Comment: Accepted for publication in Astrophysics & Space Science. 12 pages, 12 figures, and 3 table

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

Solid variant of aneurysmal bone cyst of the thoracic spine: a case report

<p>Abstract</p> <p>Introduction</p> <p>The solid variant of aneurysmal bone cyst is rare, and only 13 cases involving the spine have been reported to date, including seven in the thoracic vertebrae. The diagnosis is difficult to secure radiographically before biopsy or surgery.</p> <p>Case report</p> <p>An 18-year-old Hispanic man presented to our facility with a one-year history of left chest pain without any significant neurological deficits. An MRI scan demonstrated a 6 cm diameter enhancing multi-cystic mass centered at the T6 vertebral body with involvement of the left proximal sixth rib and extension into the pleural cavity; the spinal cord was severely compressed with evidence of abnormal T2 signal changes. Our patient was taken to the operating room for a total spondylectomy of T6 with resection of the left sixth rib from a single-stage posterior-only approach. The vertebral column was reconstructed in a 360° manner with an expandable titanium cage and pedicle screw fixation. Histologically, the resected specimen showed predominant solid fibroblastic proliferation, with minor foci of reactive osteoid formation, an area of osteoclastic-like giant cells, and cyst-like areas filled with erythrocytes and focal hemorrhage, consistent with a predominantly solid variant of aneurysmal bone cyst. At 16 months after surgery, our patient remains neurologically intact with resolution of his chest and back pain.</p> <p>Conclusions</p> <p>Because of its rarity, location, and radical treatment approach, we considered this case worthy of reporting. The solid variant of aneurysmal bone cyst is difficult to diagnose radiologically before biopsy or surgery, and we hope to remind other physicians that it should be included in the differential diagnosis of any lytic expansile destructive lesion of the spine.</p

Atlantoaxial subluxation as an early manifestation in an adolescent with undifferentiated spondyloarthritis: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Atlantoaxial instability has been described as a manifestation of ankylosing spondylitis (juvenile and adult onset), reactive arthritis, juvenile idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been reported as an early manifestation of these disorders. We present this case report to increase awareness of the condition in the hope that earlier recognition of this disease may prevent further serious injury.</p> <p>Case presentation</p> <p>We report the case of a 17-year-old Hispanic adolescent woman who was initially diagnosed with undifferentiated spondyloarthritis due to peripheral arthritis, enthesitis, a positive human leukocyte antigen B27 result, and inflammatory spinal pain lasting two months. Our patient experienced persistent and worsening occipitocervical pain and signs of myelopathy three months after diagnosis; consequently, we found atlantoaxial instability along with cervical spine bone erosion and pannus formation. She was treated surgically with a C1-2 posterior instrumented fusion and at six weeks post-operatively was started on tumor necrosis factor α blockade. Her occipitocervical symptoms subsided following surgery and initiation of immunomodulation.</p> <p>Conclusions</p> <p>Our report serves to emphasize to pediatric and adult general practitioners, pediatricians, internists, family physicians, pediatric and adult rheumatologists and spine surgeons that atlantoaxial subluxation may be an early manifestation of spondyloarthritis, and that the condition is treatable by surgical intervention and immunomodulation.</p

Transmission of NS5A-Inhibitor Resistance-Associated Substitutions among Men Who Have Sex with Men Recently Infected with Hepatitis C Virus Genotype 1a

The transmission of direct-acting antiviral resistance-associated substitutions (RAS) could hamper hepatitis C virus (HCV) cure rates and elimination efforts. A phylogenetic analysis of 87 men who have sex with men recently infected with HCV genotype 1a placed one-third (28/87) in a large cluster, in which 96% harbored NS5A M28V RAS.</p