Vascular endothelial growth factor (VEGF) has been shown to stimulate angiogenesis and myocardial perfusion. The short-term safety of VEGF gene therapy is excellent. However, there are only limited ...results regarding the long-term effects. The Kuopio Angiogenesis Trial (KAT) studied the efficiency and short-term safety of the local VEGF-A(165) gene transfer in 103 patients with coronary artery disease. Three patient groups received either VEGF as an adenoviral (n=37), or as a plasmid/liposome vector (n=28), or as a placebo (n=38), during coronary angioplasty and stenting (percutaneous coronary intervention, PCI)AQ1. The aim of this study was to examine the long-term effects and safety of VEGF gene therapy. Patients were interviewed by telephone or with a questionnaire on their current status of health, coronary and other cardiovascular events and symptoms, working ability, exercise tolerance, other diseases, such as cancer and diabetes, as well as their personal experience of the treatment. Causes of death were clarified from hospital records. The total follow-up time was 8.1 years (range 6.9-9.7 years). Overall 82% of the patients were reached across the study. Eight (7.5%) of the patients died during the follow-up, but there was no significant difference in mortality between the groups (3/32 vs 2/26 vs 3/31 VEGF-adenovirus vs VEGF-plasmid/liposome vs placebo, respectively; P=0.88). The incidence of major adverse cardiovascular events (MACEs) (10 vs 11 vs 15; P=0.85), cancer (1 vs 4 vs 2; P=0.38) or diabetes (2 vs 2 vs 2; P=0.97) did not differ between the groups. Local intracoronary VEGF gene transfer is safe and does not increase the risk of MACE, arrhythmias, cancer, diabetes or other diseases.
•Data from multiple stellar occultations are used to study waves in Saturn’s B ring.•Different parts of the Janus 2:1 wave appear to have different pattern speeds.•The B-ring’s typical surface mass ...density appears to be between 40 and 140 g/cm2.•The B-ring’s surface mass density is not strongly correlated with optical depth.
Saturn’s B ring is the most opaque ring in our Solar System, but many of its fundamental parameters, including its total mass, are not well constrained. Spiral density waves generated by mean-motion resonances with Saturn’s moons provide some of the best constraints on the rings’ mass density, but detecting and quantifying such waves in the B ring has been challenging because of this ring’s high opacity and abundant fine-scale structure. Using a wavelet-based analyses of 17 occultations of the star γ Crucis observed by the Visual and Infrared Mapping Spectrometer (VIMS) onboard the Cassini spacecraft, we are able to examine five density waves in the B ring. Two of these waves are generated by the Janus 2:1 and Mimas 5:2 Inner Lindblad Resonances at 96,427 km and 101,311 km from Saturn’s center, respectively. Both of these waves can be detected in individual occultation profiles, but the multi-profile wavelet analysis reveals unexpected variations in the pattern speed of the Janus 2:1 wave that might arise from the periodic changes in Janus’ orbit. The other three wave signatures are associated with the Janus 3:2, Enceladus 3:1 and Pandora 3:2 Inner Lindblad Resonances at 115,959 km, 115,207 km and 108,546 km. These waves are not visible in individual profiles, but structures with the correct pattern speeds can be detected in appropriately phase-corrected average wavelets. Estimates of the ring’s surface mass density derived from these five waves fall between 40 and 140 g/cm2, even though the ring’s optical depth in these regions ranges from ∼1.5 to almost 5. This suggests that the total mass of the B ring is most likely between one-third and two-thirds the mass of Saturn’s moon Mimas.
Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism ...of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect.
Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand 11CAZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10 mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale.
We observed a significant reduction in 11CAZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS 11CAZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment.
Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.
Astronomy An object in the distant Solar System has been shown to have a ring that is unusually far from its host - prompting speculation about how the ring material has avoided clumping together to ...form moons. ...all the other giant planets (Jupiter, Uranus and Neptune) are surrounded by rings too, and these can be seen with sufficiently powerful telescopes, such as the Keck Telescope in Hawaii or theJames Webb Space Telescope. Narrow rings have also been found around a few non-planetary bodies in the outer Solar System, such as Chariklo and Haumea3,4.
More Kronoseismology with Saturn's rings Hedman, M. M; Nicholson, P. D
Monthly Notices of the Royal Astronomical Society,
10/2014, Letnik:
444, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In a previous paper, we developed tools which allowed us to confirm that several of the waves in Saturn's rings were likely generated by resonances with fundamental sectoral normal modes inside ...Saturn itself. Here we use these same tools to examine eight additional waves that are probably generated by structures inside the planet. One of these waves appears to be generated by a resonance with a fundamental sectoral normal mode with azimuthal harmonic number m = 10. If this attribution is correct, then the m = 10 mode must have a larger amplitude than the modes with m = 5–9, since the latter do not appear to generate strong waves. We also identify five waves with pattern speeds between 807° and 834° d−1. Since these pattern speeds are close to the planet's rotation rate, they probably are due to persistent gravitational anomalies within the planet. These waves are all found in regions of enhanced optical depth known as plateaux, but surprisingly the surface mass densities they yield are comparable to the surface mass densities of the background C-ring. Finally, one wave appears to be a one-armed spiral pattern whose rotation rate suggests it is generated by a resonance with a structure inside Saturn, but the nature of this perturbing structure remains unclear. Strangely, the resonant radius for this wave seems to be drifting inwards at an average rate of 0.8 km yr−1 over the last 30 yr, implying that the relevant planetary oscillation frequency has been steadily increasing.
Background
Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. ...However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.
Methods
In this nationwide population‐based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.
Results
We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal‐related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.
Conclusions
The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.
Scalable and effective treatments are needed for children with functional abdominal pain disorders (FAPDs). We performed a randomized controlled trial of the efficacy and cost effectiveness of ...cognitive behavioral therapy delivered online (Internet-CBT) compared with usual therapy.
We studied children (age, 8–12 y) diagnosed with FAPDs, based on the Rome IV criteria, in Sweden from September 2016 through April 2017. The patients were assigned randomly to groups that received 10 weeks of therapist-guided, internet-delivered cognitive behavioral therapy (Internet-CBT, n = 46) or treatment as usual (treatments within the health care and school systems, including medications and visits to doctors and other health care professionals; n = 44). The primary outcome was global child-rated gastrointestinal symptom severity assessed using the Pediatric Quality of Life Gastrointestinal Symptom scale. All outcomes were collected from September 2016 through January 2018. Secondary outcomes included quality of life, gastrointestinal-specific anxiety, avoidance behaviors, and parental responses to children’s symptoms. Societal costs and costs for health care consumption were collected during the treatment.
Children who received Internet-CBT had a significantly larger improvement in gastrointestinal symptom severity with a medium effect size (Cohen’s d = 0.46; 95% CI, 0.05–0.88; number needed to treat, 3.8) compared with children who received the treatment as usual. The children’s quality of life, gastrointestinal-specific anxiety, avoidance behaviors, and parental responses to children’s symptoms also improved significantly in the Internet-CBT group compared with the treatment as usual group. The effects of Internet-CBT persisted through 36 weeks of follow-up evaluation. Children who received Internet-CBT had significantly less health care use than children who received treatment as usual, with an average cost difference of US $137 (P = .011). We calculated a cost savings of US $1050 for every child treated with Internet-CBT compared with treatment as usual.
In a randomized trial of pediatric patients with FAPDs, we found Internet-CBT to be clinically cost effective compared with treatment as usual. Internet-CBT has the potential to increase the availability of treatment for a number of patients and reduce health care costs. ClinicalTrials.gov: NCT02873078.
Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker ...discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.
Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained ...through studies of epigenetic modifications.
To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (
<1.08E-07) and replicated 33 (at Bonferroni-corrected
<0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglycerides and high-density lipoprotein cholesterol (HDL-C; cg27243685;
=8.1E-26 and 9.3E-19) was associated with
-expression of a reverse cholesterol transporter (
=7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66;
=0.0007). We found significant
-methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels (
=0.004,
=0.008 and
=0.00003) and coronary heart disease (
=0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at
were
-methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus.
We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events.
Internet interventions are assumed to be cost-effective. However, it is unclear how strong this evidence is, and what the quality of this evidence is.
A comprehensive literature search (1990-2014) in ...Medline, EMBASE, the Cochrane Central Register of Controlled Trials, NHS Economic Evaluations Database, NHS Health Technology Assessment Database, Office of Health Economics Evaluations Database, Compendex and Inspec was conducted. We included economic evaluations alongside randomized controlled trials of Internet interventions for a range of mental health symptoms compared to a control group, consisting of a psychological or pharmaceutical intervention, treatment-as-usual (TAU), wait-list or an attention control group.
Of the 6587 abstracts identified, 16 papers met the inclusion criteria. Nine studies featured a societal perspective. Results demonstrated that guided Internet interventions for depression, anxiety, smoking cessation and alcohol consumption had favourable probabilities of being more cost-effective when compared to wait-list, TAU, group cognitive behaviour therapy (CBGT), attention control, telephone counselling or unguided Internet CBT. Unguided Internet interventions for suicide prevention, depression and smoking cessation demonstrated cost-effectiveness compared to TAU or attention control. In general, results from cost-utility analyses using more generic health outcomes (quality of life) were less favourable for unguided Internet interventions. Most studies adhered reasonably to economic guidelines.
Results of guided Internet interventions being cost-effective are promising with most studies adhering to publication standards, but more economic evaluations are needed in order to determine cost-effectiveness of Internet interventions compared to the most cost-effective treatment currently available.
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