Background: High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, ...retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC. Methods: Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5–9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis. Results: HPV was detected in 62 (25%) of 253 cases (95% confidence interval CI = 19%–30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio OR = 2.4; 95% CI = 1.2– 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1–12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05–0.61) and smokers (OR = 0.16; 95% CI = 0.02–1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1–167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01–0.36), and had improved disease-specific survival (hazard ratio HR = 0.26; 95% CI = 0.07–0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4– 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4–4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8–2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20–0.88). Conclusions: These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.
In order to understand the aging and processing of organic aerosols (OA), an intensive field campaign (Campaign of Air Pollution at Typical Coastal Areas IN Eastern China, CAPTAIN) was conducted ...March–April at a receptor site (a Changdao island) in central eastern China. Multiple fast aerosol and gas measurement instruments were used during the campaign, including a high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) that was applied to measure mass concentrations and non-refractory chemical components of submicron particles (PM1nr). The average mass concentration of PM1(PM1nr+black carbon) was 47 ± 36 μg m−3 during the campaign and showed distinct variation, depending on back trajectories and their overlap with source regions. Organic aerosol (OA) is the largest component of PM1 (30%), followed by nitrate (28%), sulfate (19%), ammonium (15%), black carbon (6%), and chloride (3%). Four OA components were resolved by positive matrix factorization (PMF) of the high-resolution spectra, including low-volatility oxygenated organic aerosol (LV-OOA), semi-volatile oxygenated OA (SV-OOA), hydrocarbon-like OA (HOA) and a coal combustion OA (CCOA). The mass spectrum of CCOA had high abundance of fragments from polycyclic aromatic hydrocarbons (PAHs) (m/z 128, 152, 178, etc.). The average atomic ratio of oxygen to carbon in OA (O / C) at Changdao was 0.59, which is comparable to other field studies reported at locations downwind of large pollution sources, indicating the oxidized nature of most OA during the campaign. The evolution of OA elemental composition in the van Krevelen diagram (H / C vs. O / C) showed a slope of −0.63; however, the OA influenced by coal combustion exhibits a completely different evolution that appears dominated by physical mixing. The aging of organic aerosols vs. photochemical age was investigated. It was shown that OA / ΔCO, as well as LV-OOA / ΔCO and SV-OOA / ΔCO, positively correlated with photochemical age. LV-OOA accounted for 73% of the OA secondary formation (SOA) in the oldest plumes (photochemical age of 25 h). The kOH at Changdao, by assuming SOA formation and aging as a first-order process proportional to OH, was calculated to be 5.2 × 10−12 cm3 molec.−1 s−1, which is similar to those determined in recent studies of polluted air in other continents.
Global satellite observations of temperature and geopotential height (GPH) from the Microwave Limb Sounder (MLS) on the EOS Aura spacecraft are discussed. The precision, resolution, and accuracy of ...the data produced by the MLS version 2.2 processing algorithms are quantified, and recommendations for data screening are made. Temperature precision is 1 K or better from 316 hPa to 3.16 hPa, degrading to ∼3 K at 0.001 hPa. The vertical resolution is 3 km at 31.6 hPa, degrading to 6 km at 316 hPa and to ∼13 km at 0.001 hPa. Comparisons with analyses (Goddard Earth Observing System version 5.0.1 (GEOS‐5), European Centre for Medium‐range Weather Forecasts (ECMWF), Met Office (MetO)) and other observations (CHAllenging Minisatellite Payload (CHAMP), Atmospheric Infrared Sounder/Advanced Microwave Sounder Unit (AIRS/AMSU), Sounding of the Atmosphere using Broadband Radiometry (SABER), Halogen Occultation Experiment (HALOE), Atmospheric Chemistry Experiment (ACE), radiosondes) indicate that MLS temperature has persistent, pressure‐dependent biases which are between −2.5 K and +1 K between 316 hPa and 10 hPa. The 100‐hPa MLS v2.2 GPH surface has a bias of ∼150 m relative to the GEOS‐5 values. These biases are compared to modeled systematic uncertainties. GPH biases relative to correlative measurements generally increase with height owing to an overall cold bias in MLS temperature relative to correlative temperature measurements in the upper stratosphere and mesosphere.
Aims The purpose of this study was to determine the relationship between subclinical hypothyroidism and prevalence of retinopathy and nephropathy, incident cardiovascular disease, and mortality in ...Type 2 diabetic patients without taking thyroid medication.
Methods Serum thyrotropin and free thyroxine concentrations were measured in 588 Type 2 diabetic subjects in Taipei Veterans General Hospital, Taiwan. In a cross‐sectional study, we examined the prevalence of retinopathy and nephropathy. In a longitudinal study, we examined the risk of cardiovascular disease events, cardiovascular mortality and total mortality in the 4‐year follow‐up.
Results In the cross‐sectional analysis, subclinical hypothyroidism was associated with a greater prevalence of diabetic nephropathy (odds ratio, 3.15 95% CI, 1.48–6.69) and did not show a high prevalence of diabetic retinopathy (odds ratio, 1.15 95% CI, 0.59–2.26) compare to euthyroid diabetics. During the 44.0 ± 7.4 months of follow‐up, 51 participants had cardiovascular events. The risk of cardiovascular events was significantly increased in Type 2 diabetics with subclinical hypothyroidism after adjustment for age, sex, A1C, other standard cardiovascular risk factors and medication (hazard ratio, 2.93; 95% CI, 1.15–7.48; P = 0.024), but it became nonsignificant after additional adjustment for urinary albumin‐to‐creatinine ratio (hazard ratio, 2.06; 95% CI, 0.67–6.36; P = 0.211). The rates of cardiovascular‐related and total mortality did not significantly differ by thyroid status.
Conclusions Type 2 diabetic patients with subclinical hypothyroidism are associated with an increased risk of nephropathy and cardiovascular events, but not with retinopathy. Our data suggest that the higher cardiovascular events in subclinical hypothyroidism with Type 2 diabetes may be mediated with nephropathy.
The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias.
We evaluated the associations of inhalable ...particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM
) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM
) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived.
On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM
concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval CI, 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM
concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations.
Our data show independent associations between short-term exposure to PM
and PM
and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).
Purpose
To review current knowledge of elevated lipoprotein(a) Lp(a) levels in relation to atherosclerotic cardiovascular disease (ASCVD) and discuss their potential use as biomarkers and therapeutic ...approaches in clinical practice.
Methods
We summarized the current understanding and recent advances in the structure, metabolism, atherogenic mechanisms, standardized laboratory measurement, recommended screening populations, and prognostic value of Lp(a), with a special focus on the current potential treatment approaches for hyperlipoprotein(a)emia in patients with ASCVD.
Results
Lp(a) is composed of LDL-like particle and characteristic apolipoprotein(a) apo(a) connected by a disulfide bond. Substantial evidence shows that elevated plasma Lp(a) level is a heritable, independent, and possibly causal risk factor for ASCVD through its proatherogenic, proinflammatory, and potentially prothrombotic properties. Current guidelines recommend Lp(a) measurement for patients with an intermediate-high risk of ASCVD, familial hypercholesterolemia, a family history of early ASCVD or elevated Lp(a), and progressive ASCVD despite receiving optimal therapy. Traditional Lp(a)-lowering approaches such as niacin, PCSK9 inhibitors, mipomersen, lomitapide, and lipoprotein apheresis were associated with a non-specific and limited reduction of Lp(a), intolerable side effects, invasive procedure, and high expense. The phase 2 randomized controlled trial of antisense oligonucleotide against the apo(a) encoding gene LPA mRNA showed that IONIS-APO(a)-L
RX
could specifically reduce the level of Lp(a) by 90% with good tolerance, which may become a promising candidate for the prevention and treatment of ASCVD in the future.
Conclusions
It is reasonable to measure Lp(a) levels to reclassify ASCVD risk and manage individuals with elevated Lp(a) to further reduce the residual risk of ASCVD, especially with IONIS-APO(a)-L
RX
.
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