Long-term exposure to fine particulate matter, lung function and cognitive performance:A prospective Dutch cohort study on the underlying routes

Background Exposure to fine particulate matter and black carbon is related to cognitive impairment and poor lung function, but less is known about the routes taken by different types of air pollutants to affect cognition. Objectives We tested two possible routes of fine particulate matter (PM2.5) and black carbon (BC) in impairing cognition, and evaluated their importance: a direct route over the olfactory nerve or the blood stream, and an indirect route over the lung. Methods We used longitudinal observational data for 31232 people aged 18+ from 2006 to 2015 from the Dutch Lifelines cohort study. By linking current and past home addresses to air pollution exposure data from ELAPSE, long-term average exposure (≥ ten years) to PM2.5 and BC was calculated. Lung function was assessed by spirometry and Global Initiative (GLI) z-scores of forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were calculated. Cognitive performance was measured by cognitive processing time (CPT) assessed by the Cogstate Brief Battery. Linear structural equation modeling was performed to test the direct/indirect associations. Results Higher exposure to PM2.5 but not BC was directly related to higher CPT and thus slower cognitive processing speed [18.33 (×10−3) SD above the mean (95% CI: 6.84, 29.81)]. The direct association of PM2.5 constituted more than 97% of the total effect. Mediation by lung function was low for PM2.5 with a mediated proportion of 1.78% (FEV1) and 2.62% (FVC), but higher for BC (28.49% and 46.22% respectively). Discussion Our results emphasize the importance of the lung acting as a mediator in the relationship between both exposure to PM2.5 and BC, and cognitive performance. However, higher exposure to PM2.5 was mainly directly associated with worse cognitive performance, which emphasizes the health-relevance of fine particles due to their ability to reach vital organs directly

Survival of MUTYH-Associated Polyposis Patients With Colorectal Cancer and Matched Control Colorectal Cancer Patients

Background: MUTYH-associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH-associated polyposis colorectal cancers might influence tumor behavior and patient survival, we compared survival between patients with MUTYH-associated polyposis colorectal cancer and matched control patients with colorectal cancer from the general population. Method:s In this retrospective multicenter cohort study from Europe, 147 patients with MUTYH-associated polyposis colorectal cancer were compared with 272 population-based control patients with colorectal cancer who were matched for country, age at diagnosis, year of diagnosis, stage, and subsite of colorectal cancer. Kaplan–Meier survival and Cox regression analyses were used to compare survival between patients with MUTYH-associated polyposis colorectal cancer and control patients with colorectal cancer. All statistical tests were two-sided. Results: Five-year survival for patients with MUTYH-associated polyposis colorectal cancer was 78% (95% confidence interval [CI] = 70% to 84%) and for control patients was 63% (95% CI = 56% to 69%) (log-rank test, P = .002). After adjustment for differences in age, stage, sex, subsite, country, and year of diagnosis, survival remained better for MUTYH-associated polyposis colorectal cancer patients than for control patients (hazard ratio of death = 0.48, 95% CI = 0.32 to 0.72). Conclusions: In a European study cohort, we found statistically significantly better survival for patients with MUTYH-associated polyposis colorectal cancer than for matched control patients with colorectal cancer

Myocarditis related to Campylobacter jejuni infection: A case report

BACKGROUND: Myocarditis can develop as a complication of various infections and is most commonly linked to enterovirus infections. Myocarditis is rarely associated with bacterial infections; salmonellosis and shigellosis have been the most frequently reported bacterial cause. We report a case of myocarditis related to Campylobacter jejuni enteritis. CASE PRESENTATION: A 30-year-old previously healthy man presented with a history of prolonged chest pain radiating to the jaw and the left arm. Five days prior to the onset of chest pain, he developed bloody diarrhea, fever and chills. Creatine kinase (CK) and CK-MB were elevated to 289 U/L and 28.7 μg/L. Troponin I was 30.2 μg/L. The electrocardiogram (ECG) showed T wave inversion in the lateral and inferior leads. The chest pain resolved within 24 hours of admission. The patient had a completely normal ECG stress test. The patient was initiated on ciprofloxacin 500 mg po bid when Campylobacter jejuni was isolated from the stool. Diarrhea resolved within 48 hours of initiation of ciprofloxacin. The diagnosis of Campylobacter enteritis and related myocarditis was made based on the clinical and laboratory results and the patient was discharged from the hospital in stable condition. CONCLUSION: Myocarditis can be a rare but severe complication of infectious disease and should be considered as a diagnosis in patients presenting with chest pain and elevated cardiac enzymes in the absence of underlying coronary disease. It can lead to cardiomyopathy and congestive heart failure. There are only a few reported cases of myocarditis associated with Campylobacter infection

The correlation potential of magnetic susceptibility and outcrop gamma-ray logs at Tournaisian-Viséan boundary sections in western Europe

We have measured five deep-water carbonate and carbonate-siliciclastic sections at the Tournaisian-Visean (Tn/V) boundary in western Europe, using petrophysical outcrop logging techniques (gamma-ray spectrometry /GRS/ and magnetic susceptibility /MS/). The aim was to trace correlatable log patterns across the flanks of the London-Brabant Massif from eastern Ireland to western Germany. Both GRS and MS logging proved useful for long-distance (up to similar to 1000 km) correlation. The log patterns can be interpreted in terms of sea-level fluctuations. A late Tournaisian regression, a sequence boundary at the Tn/V boundary, early Visean lowstand systems tract and an overlying transgressive to regressive succession can be identified from the GRS and MS logs. The Tn/V sequence boundary can be correlated with exposure features and karstic surfaces in the up-dip shallow-water settings at the boundary between sequence 4 and 5 of Hance et al. (2001, 2002). This indicates that sea-level fluctuations around the Tn/V boundary were synchronous and traceable on the flanks of the London-Brabant Massif. The GRS-based logging has a greater correlation potential than MS as it can be applied in a broad spectrum of facies and depositional settings. In certain sections, the MS signal shows an increasing trend during transgression and a decreasing during regression, which is opposite to the MS paradigm from shallow-water carbonate platform settings. These trends are assumed to result from landward/basinward facies shifts of low-productivity carbonate ramp systems. Lowstand shedding of carbonate tempestites and turbidites results in low MS values while during sea-level rise the ramp systems backstep, developing retrograding facies successions in their distal parts, which are associated with upward-increasing MS values

NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy

Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes

Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects

BACKGROUND: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations. An attenuated form of polyposis (AFAP) is characterized by less than 100 adenomas and later onset of the disease. METHODS: Here, we analyzed the APC gene for germline mutations in 59 Czech and 15 Slovak FAP patients. In addition, 50 apparently APC mutation negative Czech probands and 3 probands of Slovak origin were screened for large deletions encompassing the APC gene. Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. Screening for large deletions was performed by multiplex ligation dependent probe amplification. The extent of deletions was analyzed using following microsatellite markers: D5S299, D5S82, D5S134 and D5S346. RESULTS: In the set of Czech and Slovak patients, we identified 46 germline mutations among 74 unrelated probands. Total mutation capture is 62,2% including large deletions. Thirty seven mutations were detected in 49 patients presenting a classical FAP phenotype (75,5%) and 9 mutations in 25 patients with attenuated FAP (36%). We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. CONCLUSION: The results of the molecular genetic testing are used both in the establishment of the predictive diagnosis and in the clinical management of patients. In some cases this study has also shown the difficulty to classify clinically between the classical and the attenuated form of FAP according to the established criteria. Interfamilial and/or intrafamilial phenotype variability was also confirmed in some cases which did not fit well with predicted genotype-phenotype correlation. All these findings have to be taken into consideration both in the genetic counselling and in the patient care