To evaluate the efficacy of photodynamic therapy (PDT) with half-dose verteporfin for treating acute central serous chorioretinopathy (CSC).
Prospective, double-masked, placebo-controlled, randomized ...clinical trial.
Sixty-three eyes of 63 patients with acute symptomatic CSC of 3 months' duration or less were recruited. Forty-three eyes were randomized to indocyanine green angiography (ICGA)-guided PDT with half-dose (3 mg/m(2)) verteporfin and 21 eyes were randomized to placebo.
Patients in the verteporfin group received an infusion of half-dose verteporfin over 8 minutes, followed by ICGA-guided PDT 10 minutes from the start of infusion. Laser was applied for 83 seconds covering the choroidal abnormalities observed in ICGA, with a maximum laser spot size of 4500 mum.
The primary outcome measure was the proportion of eyes with absence of subretinal fluid at the macula at 12 months. Secondary outcome measures included changes in mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), subjective symptoms, optical coherence tomography (OCT) results, central foveal thickness (CFT), and angiographic findings during the 12-month study period.
Thirty-nine patients in the verteporfin group and 19 patients in the placebo group completed 12 months of follow-up. Thirty-seven (94.9%) eyes in the verteporfin group compared with 11 (57.9%) eyes in the placebo group showed absence of subretinal fluid at the macula at 12 months (P = 0.001). The mean logMAR BCVA at 12 months was significantly better in the verteporfin group compared with the placebo group: -0.05 and 0.05, respectively (P = 0.008). All 39 (100%) verteporfin-treated eyes had stable or improved vision, compared with 15 (78.9%) eyes in the placebo group (P = 0.009). The mean OCT CFT for the verteporfin group also was significantly lower compared with the placebo group at 12 months (P = 0.001). No ocular or systemic adverse event was encountered in the study.
Photodynamic therapy with half-dose verteporfin is effective in treating acute symptomatic CSC, resulting in a higher proportion of patients with absence of exudative macular detachment and better visual acuity compared with placebo.
We present a comprehensive map of over 1 million polyadenylation sites and quantify their usage in major cancers and tumor cell lines using direct RNA sequencing. We built the Expression and ...Polyadenylation Database to enable the visualization of the polyadenylation maps in various cancers and to facilitate the discovery of novel genes and gene isoforms that are potentially important to tumorigenesis. Analyses of polyadenylation sites indicate that a large fraction (∼30%) of mRNAs contain alternative polyadenylation sites in their 3' untranslated regions, independent of the cell type. The shortest 3' untranslated region isoforms are preferentially upregulated in cancer tissues, genome-wide. Candidate targets of alternative polyadenylation-mediated upregulation of short isoforms include POLR2K, and signaling cascades of cell-cell and cell-extracellular matrix contact, particularly involving regulators of Rho GTPases. Polyadenylation maps also helped to improve 3' untranslated region annotations and identify candidate regulatory marks such as sequence motifs, H3K36Me3 and Pabpc1 that are isoform dependent and occur in a position-specific manner. In summary, these results highlight the need to go beyond monitoring only the cumulative transcript levels for a gene, to separately analysing the expression of its RNA isoforms.
In the real world, learning often proceeds in an unsupervised manner without explicit instructions or feedback. In this study, we employed an experimental paradigm in which subjects explored an ...immersive virtual reality environment on each of two days. On day 1, subjects implicitly learned the location of 39 objects in an unsupervised fashion. On day 2, the locations of some of the objects were changed, and object location recall performance was assessed and found to vary across subjects. As prior work had shown that functional magnetic resonance imaging (fMRI) measures of resting-state brain activity can predict various measures of brain performance across individuals, we examined whether resting-state fMRI measures could be used to predict object location recall performance. We found a significant correlation between performance and the variability of the resting-state fMRI signal in the basal ganglia, hippocampus, amygdala, thalamus, insula, and regions in the frontal and temporal lobes, regions important for spatial exploration, learning, memory, and decision making. In addition, performance was significantly correlated with resting-state fMRI connectivity between the left caudate and the right fusiform gyrus, lateral occipital complex, and superior temporal gyrus. Given the basal ganglia's role in exploration, these findings suggest that tighter integration of the brain systems responsible for exploration and visuospatial processing may be critical for learning in a complex environment.
•Modified Ti64 alloys with improved ductility and oxidation resistance are developed.•B improves the ductility by refining grain size and enhancing boundary cohesion.•Y enhances the oxidation ...resistance by possibly slowing down the oxidation kinetics.
The effects of B and Y on the mechanical properties and oxidation behavior of cast Ti–6Al–4V alloys were systematically investigated, and the new alloys with improved ductility and oxidation resistance are developed by the microalloying approach. The results indicate that boron is beneficial for improving the ductility by not only grain-size refinement but also grain-boundary enhancement, while yttrium is effective in increasing the oxidation resistance through possibly slowing down the oxidation kinetics. The improved properties, together with their high strength, make the microalloyed cast Ti–6Al–4V alloys competitive for practical engineering applications.
Purpose
To predict biological effects of targeted alpha therapy (TAT) in preclinical studies, dosimetry calculations based on the micro‐level distributions of emitters are essential. Due to the ...saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha‐immuno‐conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly nonuniform and unsteady distributions of irradiation sources. Since the micro‐level distribution of emitters cannot be measured and obtained in patients with current technology, a modeling toolset to give more insight of the internal dose could be an alternative.
Methods
A multi‐physics model based on a Monte Carlo microdosimetry technique and computational fluid dynamics (CFD) modeling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time‐dependent absorbed dose to the target.
Results
The conceptual model is capable of handling complex nonuniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios.
Conclusion
Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future.
Summary
Osteoporosis is linked to age-related decline of melatonin production; however, the direct effects of melatonin on osteoclastogenesis remain unknown. Our study demonstrates that melatonin at ...pharmacological concentrations, rather than at physiological concentrations, significantly inhibits osteoclastogenesis. Melatonin-mediated anti-osteoclastogenesis involves a reactive oxygen species (ROS)-mediated but not a silent information regulator type 1 (SIRT1)-independent pathway.
Introduction
Osteoporosis is a bone disorder linked to impaired bone formation and excessive bone resorption. Melatonin has been suggested to treat osteoporosis due to its beneficial actions on osteoblast differentiation. However, the direct effects of melatonin on osteoclastogenesis in bone marrow monocytes (BMMs) remain unknown. This study was to investigate whether melatonin at either physiological or pharmacological concentrations could affect osteoclast differentiation.
Methods
Primary BMMs were isolated from the femurs and tibias of C57BL/6 mice and were induced toward multinucleated osteoclasts, in the presence of melatonin at either physiological (0.01 to 10 nM) or pharmacological (1 to 100 μM) concentrations. Tartrate-resistant acid phosphatase (TRAP) staining was used to label multinucleated osteoclasts and the levels of osteoclast-specific genes were evaluated. To further explore the underlying mechanisms, the roles of silent information regulator type 1 (SIRT1) and reactive oxygen species (ROS) were evaluated.
Results
We found that melatonin at pharmacological concentrations, rather than at physiological concentrations, significantly inhibited osteoclast formation in a dose-dependent manner. The number of TRAP-positive cells and the gene expression of osteoclast-specific markers were significantly downregulated in melatonin-treated BMMs. The melatonin-mediated repression of osteoclast differentiation involved the inhibition of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. The treatment with SIRT1 inhibitors did not affect osteoclast differentiation but, when supplemented with exogenous hydrogen peroxide, a partial rescue of melatonin-suppressed osteoclastogenesis was observed.
Conclusion
Melatonin at pharmacological doses directly inhibited osteoclastogenesis of BMMs by a ROS-mediated but not a SIRT1-independent pathway.
Objective
To assess the possible relationship between serum levels of 25OHD (25‐hydroxyvitamin D) collected 24 hours after delivery and postpartum depression in a Chinese cohort sample.
Design
Cohort ...study.
Setting
One city hospital in Beijing, China.
Population
Women delivering a full‐term, singleton, live‐born infant at one city hospital in Beijing between August 2013 and November 2013.
Methods
Women were enrolled immediately postpartum. A blood sample was obtained 24–48 hours after childbirth to test serum levels of 25OHD. Participation consisted of a visit to an obstetric unit 3 months after delivery.
Main outcome measure
At 3 months' postpartum, women were screened for depression using the Edinburgh Postnatal Depression Scale (EPDS). The primary outcome measure was a prespecified EPDS score of ≥12.
Results
During the study period, 323 women were admitted. In all, 248 agreed to enrol and 213 completed 3 months' follow‐up (21 were lost to follow‐up and 14 withdrew). Of the 213 women who were included, 26 (12.2%) were considered to meet criteria for postpartum depression. Serum 25OHD levels in women with no postpartum depression were significantly higher than those in women with postpartum depression (P < 0.0001). Based on the receiver operating characteristic curve, the optimal cutoff value for serum 25OHD level as an indicator for screening for postpartum depression was estimated to be 10.2 ng/ml, with an area under the curve of 0.801 (95%CI 0.704–0.896). In multivariate analysis, there was an increased risk of postpartum depression associated with 25OHD levels ≤10.2 ng/ml (OR 7.17, 95%CI 3.81–12.94; P < 0.0001) after adjusting for possible confounders.
Conclusion
Our study demonstrated that lower serum 25OHD levels were associated with postpartum depression. This association was independent of other possible variables.
Considerable support exists establishing a relationship between childhood adversities and adult depression. Consistent evidence has emerged linking early life adversities with a more chronic course ...for depression, as well as to poorer treatment outcomes. What remain decidedly less clear, however, are the moderators and mediating mechanisms underlying this association. This article provides a review of the existing research relating early adversities to adult depression, as well as recent studies suggestive of potential mediators and moderators of this relation. Advances in these areas are important for their potential to lead to the identification of new targets for clinical intervention for adults with a history of childhood adversities, as well as to the development of individually tailored prevention and treatment strategies.
Full text
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UL
To establish a surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin, so as to provide insights into creation ...of a sensitive and highly efficient surveillance and early warning system for schistosomiasis.
National and international publications, documents, laws and regulations pertaining to schistosomiasis control were retrieved with keywords including schistosomiasis, surveillance, early warning and control interventions from 2008 to 2022, and a thematic panel discussion was held to preliminarily construct surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin. The index system was then comprehensively scored and screened using the Delphi method, and the weight of each index was determined using analytic hierarchy process and the modified proportional allocation method. In addition, the credibility of the Delphi method was evaluated
To examine the association of alcohol consumption with risk of incident knee osteoarthritis (OA) in a large prospective cohort study.
In the Osteoarthritis Initiative, 2,846 participants aged 45–79 ...years and free from radiographic knee OA in at least one knee at baseline were followed up to 96 months. Information on baseline alcohol consumption was obtained from the Block Brief Food Frequency Questionnaire. Incident cases of radiographic knee OA (ROA) were defined as Kellgren–Lawrence grade changing from zero or one to ≥ two during the follow-up time. Incident symptomatic OA (SxOA) was defined as ROA with knee pain worsening. The Cox proportional hazards models were used to assess the independent association between alcohol consumption and risk of knee.
During 96 months’ follow-up, we identified 691 knees with incident ROA, and 496 knees with incident SxOA among 2,846 subjects. Compared to non-drinkers, excessive alcohol consumption was significantly associated with increased risk of ROA (HR ≥ 30 g/d vs none = 1.93, 95% CI: 1.28–2.89) and SxOA (HR ≥ 30 g/d vs none = 1.61, 95% CI: 1.04–2.48). Similar association was observed for liquor consumption (HR liquor≥15 g/d vs none = 1.71, 95% CI: 1.16–2.52 for ROA; HR liquor≥15 g/d vs none = 1.59, 95% CI: 1.04–2.39 for SxOA). Light to moderate alcohol consumption was not associated with knee OA risk.
Our results suggest that excessive alcohol drinking was associated with an increased risk of knee OA. Further studies are needed in other populations.
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