Stress-induced wall motion abnormalities are a sensitive marker of myocardial ischaemia. Stress echocardiography has recently been the subject of increasing interest because of its improved ...feasibility and compatibility with new and effective alternative stresses. Transoesophageal atrial pacing (TAP) with 2-dimensional echocardiography (2-D echo) is a recently developed echo-cardiographic stress procedure that has been shown to be reliable and effective in both the diagnosis and evaluation of stress-induced myocardial ischaemia. TAP with 2-D echo was performed after treatment with placebo and intravenous gallopamil 0.03 mg/kg in 12 patients with stable, reproducible angina of effort. Compared with placebo, gallopamil treatment increased the time to 1 mm ST-segment depression (6.6 vs 5.3 minutes; p less than 0.05) and improved the ventricular wall motion score at a heart rate of 130 beats/min (17 vs 15; p less than 0.01) and 150 beats/min (13 vs 11; p = 0.07). Three patients who developed angina after placebo administration were symptom-free after gallopamil. Thus, gallopamil exerts a beneficial effect on atrial pacing-induced ischaemia, by increasing the pacing time to the ischaemic threshold and reducing the extent of dysfunctional myocardium during ischaemia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Transesophageal atrial pacing (TAP) 2D echocardiography was performed after placebo (P) and gallopamil (G) (0.03 mg/kg iv) in 12 patients with stable, reproducible, effort angina. If compared to P ...study, during G the following changes were observed: 3 out of the 12 patients did not experience angina, time to ST-1mm increased from 5.3 +/- 1.3 to 6.6 +/- 1.6 min (p less than 0.05), wall motion score was improved both at 130 b/min (15.3 +/- 4.1 drug P, 17 +/- 4.8 drug G, p less than 0.01) and at 150 b/min (10.9 +/- 5.7 drug P, 12.8 +/- 6.3 drug G, p = 0.07). In conclusion, gallopamil has a beneficial effect on atrial pacing induced ischemia: it increases pacing time to ischemic threshold and reduces during ischemia the extent of dysfunctional myocardium.
Human papillomavirus-positive oropharynx cancer incidence has increased rapidly in cohorts of US white men born during the 1930s to 1950s. It is unknown how the trajectory of the oropharynx cancer ...epidemic may be changing in the United States.
Using US cancer registry information, we investigated whether increases in oropharynx cancer have continued into recent birth cohorts and forecasted the future burden across age, sex, and race/ethnicity subgroups. Log-linear Joinpoint regression and age-period-cohort models were used to evaluate incidence trends during 1992 to 2015 and projections through 2029.
Among white men, oropharynx cancer incidence increased rapidly in individuals born during 1939 to 1955 (5.3% per 2-year birth cohort; 95% CI, 4.8% to 5.7%), but this rate of increase significantly moderated in individuals born during 1955 to 1969 (1.7% per 2-year birth cohort; 95% CI, 1.0% to 2.4%). Should these birth-cohort trends continue, from 2016 to 2029 we forecast that incidence will increase dramatically in older white men 65 to 74 years of age (from 40.7 to 71.2 per 100,000) and 75 to 84 years of age (from 25.7 to 50.1 per 100,000), moderately in white men 55 to 64 years of age (from 40.3 to 52.0 per 100,000), and remain stable in white men 45 to 54 years of age (approximately 18 per 100,000). Accounting for population growth, we project an increase in annual number of cases in the United States from 20,124 (95% CI, 19,779 to 20,469) in 2016 to 30,629 (95% CI, 29,413 to 31,845) in 2029, primarily driven by older individuals (age ≥ 65 years; from 7,976 95% CI, 7,782 to 8,172 to 18,072 95% CI, 17,271 to 18,895) and white men (from 14,453 95% CI, 14,142 to 14,764 to 22,241 95% CI, 21,119 to 23,364).
The exponential increase in oropharynx cancer incidence in young white US men has ebbed, and modest increases are occurring/anticipated in cohorts born after 1955. Continued strong increases in incidence in cohorts born before 1955, and an approximate 50% increase in size of the US population age 65 years or older through 2029, portend a substantial shift in burden to elderly white men.
Highlights • Oral tongue cancer incidence has increased in recent decades in the United States. • Increase has primarily occurred among young, white individuals. • Magnitude of increase has been ...similar across gender. • Rise in oral tongue and oropharyngeal cancer observed in similar birth cohorts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women.
We conducted a planned interim analysis of a randomized, ...double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed.
Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9–13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45–0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels.
Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims
High chromogranin-A (CgA) levels were observed in patients with heart failure but its source remained uncertain. We evaluated whether CgA is produced by myocardium and might affect myocardial ...function.
Methods and results
We measured plasma CgA levels and performed immunohistochemistry with anti-CgA antibodies on myocardial biopsies in 40 patients with dilated cardiomyopathy (DCM) and 20 patients with hypertrophic cardiomyopathy (HCM). Surgical myocardial specimens from DCM and HCM patients were used for PCR and ELISA. The presence of CgA-derived fragments in plasma was evaluated by gel-filtration HPLC and their effects on cardiac performance assessed in isolated perfused rat heart. All patients showed increased CgA plasma levels (DCM 153.7 ± 158.5 ng/mL; HCM 150.2 ± 86.7 ng/mL vs. 64.1 ± 17.9 ng/mL of controls) with a positive correlation between CgA and left ventricular end-diastolic pressure (DCM, R = 0.86; HCM, R = 0.83), and plasma brain natriuretic peptide (BNP) levels (DCM, R = 0.88; HCM, R = 0.85) (P < 0.001). Immunohistochemistry showed cytoplasmic expression of CgA and co-localization with BNP in all patients, but not in controls. PCR detected CgA mRNA in both pathologic and normal myocardium, while ELISA showed a significant amount of CgA only in pathologic myocardium (>0.5 µg/g of tissue); gel-filtration HPLC of plasma samples identified immunoreactive N-terminal CgA fragments containing vasostatin-1. Administration of vasostatin-1 to perfused rat heart produced negative inotropic and lusitropic effects counteracting isoproterenol actions.
Conclusion
We demonstrate for the first time that CgA is produced by human myocardium and exerts negative inotropic and lusitropic effects on mammalian heart. CgA may represent a key player in neuroendocrine regulation of cardiac function and a potential therapeutic target in heart failure.
•Differences in forest seasonal productivity cannot be explained by access to water or sunlight.•Equatorial climates benefit species that support high levels of dry-season photosynthesis.•PAR levels ...predicted the degree to which canopy photosynthetic capacity drives GEP.•Converted sites at Central Amazon show the disruption of the productivity cycle.
We investigated the seasonal patterns of Amazonian forest photosynthetic activity, and the effects thereon of variations in climate and land-use, by integrating data from a network of ground-based eddy flux towers in Brazil established as part of the ‘Large-Scale Biosphere Atmosphere Experiment in Amazonia’ project. We found that degree of water limitation, as indicated by the seasonality of the ratio of sensible to latent heat flux (Bowen ratio) predicts seasonal patterns of photosynthesis. In equatorial Amazonian forests (5° N–5° S), water limitation is absent, and photosynthetic fluxes (or gross ecosystem productivity, GEP) exhibit high or increasing levels of photosynthetic activity as the dry season progresses, likely a consequence of allocation to growth of new leaves. In contrast, forests along the southern flank of the Amazon, pastures converted from forest, and mixed forest-grass savanna, exhibit dry-season declines in GEP, consistent with increasing degrees of water limitation. Although previous work showed tropical ecosystem evapotranspiration (ET) is driven by incoming radiation, GEP observations reported here surprisingly show no or negative relationships with photosynthetically active radiation (PAR). Instead, GEP fluxes largely followed the phenology of canopy photosynthetic capacity (Pc), with only deviations from this primary pattern driven by variations in PAR. Estimates of leaf flush at three non-water limited equatorial forest sites peak in the dry season, in correlation with high dry season light levels. The higher photosynthetic capacity that follows persists into the wet season, driving high GEP that is out of phase with sunlight, explaining the negative observed relationship with sunlight. Overall, these patterns suggest that at sites where water is not limiting, light interacts with adaptive mechanisms to determine photosynthetic capacity indirectly through leaf flush and litterfall seasonality. These mechanisms are poorly represented in ecosystem models, and represent an important challenge to efforts to predict tropical forest responses to climatic variations.
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GEOZS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report a customized gene panel assay based on multiplex long-PCR followed by third generation sequencing on nanopore technology (MinION), designed to analyze five frequently mutated genes in ...chronic lymphocytic leukemia (CLL): TP53, NOTCH1, BIRC3, SF3B1 and MYD88. For this purpose, 12 patients were selected according to specific cytogenetic and molecular features significantly associated with their mutational status. In addition, simultaneous analysis of the targets genes was performed by molecular assays or Sanger Sequencing. Data analysis included mapping to the GRCh37 human reference genome, variant calling and annotation, and average sequencing depth/error rate analysis. The sequencing depth resulted on average higher for smaller amplicons, and the final breadth of coverage of the panel was 94.1%. The error rate was about 6% and 2% for insertions/deletions and single nucleotide variants, respectively. Our gene panel allows analysis of the prognostically relevant genes in CLL, with two PCRs per patient. This strategy offers an easy and affordable workflow, although further advances are required to improve the accuracy of the technology and its use in the clinical field. Nevertheless, the rapid and constant development of nanopore technology, in terms of chemistry advances, more accurate basecallers and analysis software, offers promise for a wide use of MinION in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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