Background
The purpose of this study was to compare general health‐related quality of life (HR‐QOL) of thyroid cancer survivors with a normative sample stratified by age at diagnosis (adolescents and ...young adults 18‐35 years; middle‐aged adults 36‐64 years; elderly 65‐84 years), and to compare general HR‐QOL and disease‐specific symptoms among adolescents and young adults, middle‐aged adults, and elderly thyroid cancer survivors in an exploratory population‐based cross‐sectional study.
Methods
All patients diagnosed with thyroid cancer between 1990 and 2008, who were registered in the Eindhoven Cancer Registry, received a survey. Our final sample included 293 thyroid cancer survivors.
Results
Compared with a normative sample, adolescents and young adult thyroid cancer survivors showed statistically significant and clinically meaningfully worse physical, role, cognitive, and social functioning, and more fatigue and financial problems. Adolescents and young adult thyroid cancer survivors scored statistically significant and clinically meaningfully better on physical functioning and interest in sex compared with the elderly and had less sympathetic and throat/mouth problems compared with middle‐aged adults.
Conclusion
Thyroid cancer seems to have a greater impact on younger than older thyroid cancer survivors and the lower HR‐QOL in older compared to younger thyroid cancer survivors is probably caused mostly by their age and not the cancer.
Introduction
The aim of this study was to compare second-generation cryoballoon and contact-force radiofrequency point-by-point pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients ...with regard to pulmonary vein reconnection and arrhythmia-free survival.
Methods and results
Altogether, 269 consecutive patients with drug-refractory AF undergoing PVI were included and randomly allocated to second-generation cryoballoon or contact-force point-by-point radiofrequency ablation. Median follow-up duration was 389 days (interquartile range 219–599). Mean age was 59 years (71% male); 136 patients underwent cryoballoon and 133 patients underwent radiofrequency ablation. Acute electrical PVI was 100% for both techniques. Procedure duration was significantly shorter in cryoballoon vs radiofrequency (166.5 vs 184.13 min
P
= 0.016). Complication rates were similar (6.0 vs 6.7%,
P
= 1.00). Single procedure freedom of atrial arrhythmias was significantly higher in cryoballoon as compared to radiofrequency (75.2 vs 57.4%,
P
= 0.013). In multivariate analysis, persistent AF, AF duration, and cryoballoon ablation were associated with freedom of atrial tachyarrhythmias. The number of repeat ablation procedures was significantly lower in the cryoballoon compared to radiofrequency (15.0 vs 24.3%,
P
= 0.045). At repeat ablation, pulmonary vein reconnection rate was significantly lower after cryoballoon as compared to radiofrequency ablation (36.8 vs 58.1%,
P
= 0.003).
Conclusions
Improved arrhythmia-free survival and more durable pulmonary vein isolation is seen after PVI using second-generation cryoballoon as compared to contact-force radiofrequency, in patients with drug-refractory paroxysmal AF. Complication rates for both ablation techniques are low.
Alternative splicing is a biological mechanism that enables the synthesis of several isoforms with different or even opposite functions. This process must be tightly regulated to prevent unwanted ...isoform expression favoring pathological processes. Some isoforms of interleukin 32 (IL-32) are reported to be more potent in inducing inflammation, however the role in cell death remains to be investigated. This study demonstrates that IL-32γ and IL-32β can induce caspase-8-dependent cell death whereas this was not observed for IL-32α. Overexpression of IL-32β or IL-32γ but not IL-32α, resulted in enhanced expression of the survival cytokine IL-8. Furthermore, restoring the IL-8 signaling pathway by overexpressing CXCR1 in HEK293 cells, rescued IL-32β but not IL-32γ-induced cell death. Interestingly, IL-32γ was able to downregulate CXCR1 and thereby induce cell death. Subsequent studies into the role of IL-32 in thyroid cancer (TC) revealed that several IL-32 isoforms, IL-8, and CXCR1 are expressed in TC cell lines and specimens. Remarkably, TC cell lines were found to produce high concentrations of IL-8, indicating an important role for IL-8 in the survival-signaling pathway in these cells. Intriguingly, a significant correlation between the IL-8 receptor CXCR1 and IL-32γ was observed in TC specimens, while this was not observed for the other IL-32 splice variants. Blocking IL-32 alternative splicing by Isoginkgetin resulted in predominant expression of IL-32γ splice variants and cell death in TC cell lines. All together, modulation of IL-32 alternative splicing could represent a novel strategy for the treatment of malignancies, in particular thyroid cancer.
Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized ...circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subjects, as well as their relationship with coagulation and metabolic control.
Microparticles were isolated from plasma, stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. Microparticle numbers and origin were comparable in the two groups, but the median number of TF-positive microparticles was twice as high in patients than in controls (P=0.018). Patients had higher percentages of TF-positive microparticles from T-helper cells (P=0.045), granulocytes (P=0.004), and platelets (P=0.002). Subpopulations of TF-positive microparticles from platelets and T-helper cells exposed granulocytic markers. Correlations were found between the numbers of various TF-positive microparticle subpopulations and body mass index, fasting plasma glucose and insulin, or tumor necrosis factor-alpha and serum HDL cholesterol. Microparticles from patients generated less thrombin in vitro (P=0.007). Microparticle numbers did not correlate with in vivo coagulation markers prothrombin fragment F(1+2) and thrombin-antithrombin complexes.
TF, possibly of granulocytic origin, is exposed on microparticle subpopulations in asymptomatic patients with well-regulated type 2 diabetes. TF-positive microparticles are associated with components of the metabolic syndrome but not with coagulation. Thus, TF on microparticles may be involved in processes other than coagulation, including transcellular signaling or angiogenesis.
The mass extinction at the Cretaceous–Paleogene boundary, ∼66 Ma, is thought to be caused by the impact of an asteroid at Chicxulub, present-day Mexico. Although the precise mechanisms that led to ...this mass extinction remain enigmatic, most postulated scenarios involve a short-lived global cooling, a so-called “impact winter” phase. Here we document a major decline in sea surface temperature during the first months to decades following the impact event, using TEX ₈₆ paleothermometry of sediments from the Brazos River section, Texas. We interpret this cold spell to reflect, to our knowledge, the first direct evidence for the effects of the formation of dust and aerosols by the impact and their injection in the stratosphere, blocking incoming solar radiation. This impact winter was likely a major driver of mass extinction because of the resulting global decimation of marine and continental photosynthesis.
It is critically important to correctly identify persons with a lifetime history (LTH) of suicide attempts (SA) from both a clinical and research perspective. Face-to-face interviews are often the ...best available method for researchers to collect data about a complex phenomenon like a LTH of SA. However, extensive survey methodology research has shown that probing sensitive topics like a LTH of SA are sensitive for interviewer-related errors or interviewer effects. Studies investigating these interviewer effects are scarce in the field of suicide studies. This study presents a possible roadmap for study of interviewerrelated measurement error and an exploration of role-dependent behaviour of interviewers by assessing the LTH of SA through an epidemiological design. Data from the baseline assessment of the Netherlands Study of Depression and Anxiety (N = 2981) was used to illustrate the proposed roadmap to study interviewer effects. Results show: : (1) that it was possible to identify the existence of interviewer effects in assessing a LTH of SA; (2) that interviewer effects occurred by probing and clarification activities of the interviewer but not with inadequate formulation of the original question and so give a possible explanation for these effects; and (3) that it was possible to study the impact of these effects on the association between a well-known risk factor and LTH of SA. Applying the Measurement Error framework for systematically examining errors in data collection on suicidality seems a promising method.
Mental health smartphone apps could increase the safety and self-management of patients at risk of suicide, but it is still unclear whether it is feasible to integrate such apps into routine mental ...healthcare. This study reports on the feasibility of using a safety planning app (BackUp) and a self-monitoring app (mEMA) as components of the routine treatment of depressed outpatients with suicidal ideation. Clinicians were trained in working with both of the apps, and they invited their eligible patients with suicidal ideation for study participation. Patients used the apps for 3 months and discussed these with their clinician during treatment. Patients completed assessments at baseline (T
0
), 4 weeks (T
1
) and post-test (T
2
, 12 weeks after baseline). Both patients and clinicians also participated in telephone interviews. Feasibility was assessed in terms of
usability
(score > 70 on System Usability Scale, SUS),
acceptability
(score > 20 on Client Satisfaction Questionnaire-8, CSQ-8), and
uptake
(sufficient rates of component completion and app usage in treatment). The sample included 17 adult outpatients (52.9% male, age range 20–50 years) diagnosed with a depressive disorder and suicidal ideation at baseline. BackUp was rated by patients at above the cut-off scores for usability (SUS mean score at T
1
75.63 and at T
2
77.71) and acceptability (CSQ-8 mean score at T
1
23.42 and at T
2
23.50). mEMA was similarly rated (SUS mean score at T
1
75.83 and at T
2
76.25; CSQ-8 mean score at T
1
23.92 and at T
2
22.75). Telephone interviews with patients and clinicians confirmed the usability and acceptability. The uptake criteria were not met. Our findings suggest that mobile safety planning and mobile self-monitoring can be considered acceptable and usable as treatment components for depressed suicidal outpatients, but the integration of apps into routine treatment needs to be further explored.
Highlights • PI3K/Akt/mTOR pathway is a key player in pathogenesis of thyroid cancer (TC). • Activation of PI3K/Akt/mTOR promotes tumor cell proliferation and dedifferentiation. • Antitumorigenic ...mechanisms are inhibited, including apoptosis and autophagy. • PI3K/Akt/mTOR inhibition is promising strategy for systemic therapy in advanced TC. • PI3K/Akt/mTOR influences RAI uptake and is target for redifferentiation strategies.
Genome-wide association studies of psychiatric disorders have been criticized for their lack of explaining a considerable proportion of the heritability established in twin and family studies. ...Genome-wide association studies of major depressive disorder in particular have so far been unsuccessful in detecting genome-wide significant single nucleotide polymorphisms (SNPs). Using two recently proposed methods designed to estimate the heritability of a phenotype that is attributable to genome-wide SNPs, we show that SNPs on current platforms contain substantial information concerning the additive genetic variance of major depressive disorder. To assess the consistency of these two methods, we analyzed four other complex phenotypes from different domains. The pattern of results is consistent with estimates of heritability obtained in twin studies carried out in the same population.
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