Wnt/β-Catenin Signaling Pathway Is Necessary for the Specification but Not the Maintenance of the Mouse Retinal Pigment Epithelium

β-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1dm), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1Y654E, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb1∆ex3 mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium.</p

Wnt/β-Catenin Signaling Pathway Is Necessary for the Specification but Not the Maintenance of the Mouse Retinal Pigment Epithelium

β-Catenin (Ctnnb1) has been shown to play critical roles in the development and maintenance of epithelial cells, including the retinal pigment epithelium (RPE). Ctnnb1 is not only a component of intercellular junctions in the epithelium, it also functions as a transcriptional regulator in the Wnt signaling pathway. To identify which of its functional modalities is critically involved in mouse RPE development and maintenance, we varied Ctnnb1 gene content and activity in mouse RPE lineage cells and tested their impacts on mouse eye development. We found that a Ctnnb1 double mutant (Ctnnb1$^{dm}$), which exhibits impaired transcriptional activity, could not replace Ctnnb1 in the RPE, whereas Ctnnb1$^{Y654E}$, which has reduced affinity for the junctions, could do so. Expression of the constitutively active Ctnnb$^{1∆ex3}$ mutant also suppressed the development of RPE, instead facilitating a ciliary cell fate. However, the post-mitotic or mature RPE was insensitive to the loss, inactivation, or constitutive activation of Ctnnb1. Collectively, our results suggest that Ctnnb1 should be maintained within an optimal range to specify RPE through transcriptional regulation of Wnt target genes in the optic neuroepithelium

Cupping for Treating Pain: A Systematic Review

The objective of this study was to assess the evidence for or against the effectiveness of cupping as a treatment option for pain. Fourteen databases were searched. Randomized clinical trials (RCTs) testing cupping in patients with pain of any origin were considered. Trials using cupping with or without drawing blood were included, while trials comparing cupping with other treatments of unproven efficacy were excluded. Trials with cupping as concomitant treatment together with other treatments of unproven efficacy were excluded. Trials were also excluded if pain was not a central symptom of the condition. The selection of studies, data extraction and validation were performed independently by three reviewers. Seven RCTs met all the inclusion criteria. Two RCTs suggested significant pain reduction for cupping in low back pain compared with usual care (P < .01) and analgesia (P < .001). Another two RCTs also showed positive effects of cupping in cancer pain (P < .05) and trigeminal neuralgia (P < .01) compared with anticancer drugs and analgesics, respectively. Two RCTs reported favorable effects of cupping on pain in brachialgia compared with usual care (P = .03) or heat pad (P < .001). The other RCT failed to show superior effects of cupping on pain in herpes zoster compared with anti-viral medication (P = .065). Currently there are few RCTs testing the effectiveness of cupping in the management of pain. Most of the existing trials are of poor quality. Therefore, more rigorous studies are required before the effectiveness of cupping for the treatment of pain can be determined

Industry portfolio allocation with asymmetric correlations

We develop a new framework of optimal consumption and portfolio choice at industry portfolio level under dynamic and asymmetric correlations between industry and market portfolios. We derive in closed-form the optimal consumption and investment strategies under regime-dependent correlations environment. Overall, we find that ignoring time-varying and asymmetric correlations between portfolios can be costly to investors when applied to a construction of the optimal portfolio. Finally, we empirically test the performance of the model-based investment strategy

Identification and Interpretation: A Framework of Naturalistic Epistemology Perceived by Korean Pre-Service Science Teachers

Abstract The epistemology of science and teachers&apos; perspectives on it have been major lines of investigation in science education research. The role that epistemology should play in science education has become increasingly relevant because of its incorporation within some important curriculum reform movements around the world. Improving teachers&apos; perspectives and designing advanced teaching-learning sequences along them have been substantial parts of the science education reform. Such efforts are having been active when a new epistemological position emerged. The present inquiry has been conducted at the interface of these two lines of research. The main focus of the study is analyzing the way Korean pre-service teachers interpret epistemological aspects of scientific knowledge. A questionnaire to explore pre-service teachers&apos; epistemological beliefs was developed for developing frameworks of naturalized epistemology. The questionnaire is composed of items using Likert scale and open-ended items. Two groups of pre-service teachers participated in this exploration: in an elementary teacher education universities and a secondary science teacher education university. Epistemological beliefs of prospective elementary teachers were identified through qualitative analysis of the answers to the open ended questions as well. Suggestions for curricula change and teaching-learning strategies being involved in the incorporation of scientific epistemology are considered

Ginseng for Erectile Dysfunction: A Cochrane Systematic Review

The objectives of this study were to assess the effects of ginseng on erectile dysfunction. We searched multiple electronic databases from their inceptions to 30 January 2021 without restrictions by language. We included randomized or quasirandomized controlled trials that evaluated the use of any type of ginseng as a treatment for erectile dysfunction compared to placebo or conventional treatment. The authors independently screened the literature, extracted data, assessed risk of bias, and rated the certainty of evidence (CoE) according to the GRADE approach. We included nine studies, and all compared ginseng to placebo. Ginseng appears to have a trivial effect on erectile dysfunction when compared to placebo based on the Erectile Function Domain of the International Index of Erectile Function (IIEF)-15 instrument (mean difference [MD] 3.52, 95% confidence interval [CI] 1.79 to 5.25; I2=0%; 3 studies; low CoE). Ginseng may have little to no effect on adverse events compared to placebo (risk ratio [RR] 1.45, 95% CI 0.69 to 3.03; I2=0%; 7 studies; low CoE). While ginseng may improve men's self-reported ability to have intercourse (RR 2.55, 95% CI 1.76 to 3.69; I2=23%; 6 studies; low CoE), it may have a trivial effect on men's satisfaction with intercourse based on the Intercourse Satisfaction Domain of the IIEF-15 (MD 1.19, 95% CI 0.41 to 1.97; I2=0%; 3 studies; low CoE). No study reported quality of life as an outcome.publishedVersio

Effects of education on low-phosphate diet and phosphate binder intake to control serum phosphate among maintenance hemodialysis patients: A randomized controlled trial.

Background:For phosphate control, patient education is essential due to the limited clearance of phosphate by dialysis. However, well-designed randomized controlled trials about dietary and phosphate binder education have been scarce. Methods:We enrolled maintenance hemodialysis patients and randomized them into an education group (n = 48) or a control group (n = 22). We assessed the patients' drug compliance and their knowledge about the phosphate binder using a questionnaire. Results:The primary goal was to increase the number of patients who reached a calcium-phosphorus product of lower than 55. In the education group, 36 (75.0%) patients achieved the primary goal, as compared with 16 (72.7%) in the control group (P = 0.430). The education increased the proportion of patients who properly took the phosphate binder (22.9% vs. 3.5%, P = 0.087), but not to statistical significance. Education did not affect the amount of dietary phosphate intake per body weight (education vs. control: -1.18 ± 3.54 vs. -0.88 ± 2.04 mg/kg, P = 0.851). However, the dietary phosphate-to-protein ratio tended to be lower in the education group (-0.64 ± 2.04 vs. 0.65 ± 3.55, P = 0.193). The education on phosphate restriction affected neither the Patient-Generated Subjective Global Assessment score (0.17 ± 4.58 vs. -0.86 ± 3.86, P = 0.363) nor the level of dietary protein intake (-0.03 ± 0.33 vs. -0.09 ± 0.18, P = 0.569). Conclusion:Education did not affect the calcium-phosphate product. Education on the proper timing of phosphate binder intake and the dietary phosphate-to-protein ratio showed marginal efficacy

Acupuncture for the treatment of tinnitus: a systematic review of randomized clinical trials

BACKGROUND: Complementary and alternative medicine (CAM) has frequently been used to treat tinnitus, and acupuncture is a particularly popular option. The objective of this review was to assess the evidence concerning the effectiveness of acupuncture as a treatment for tinnitus. METHODS: Fourteen databases were searched from the dates of their creation to July 4th, 2012. Randomized clinical trials (RCTs) were included if acupuncture was used as the sole treatment. The Cochrane risk of bias tool was used to assess the risk of bias. RESULTS: A total of 9 RCTs met all the inclusion criteria. Their methodological quality was mostly poor. Five RCTs compared the effectiveness of acupuncture or electroacupuncture with sham acupuncture for treating tinnitus. The results failed to show statistically significant improvements. Two RCTs compared a short one-time scalp acupuncture treatment with the use of penetrating sham acupuncture at non-acupoints in achieving subjective symptom relief on a visual analog scale; these RCTs demonstrated significant positive effects with scalp acupuncture. Two RCTs compared acupuncture with conventional drug treatments. One of these RCTs demonstrated that acupuncture had statistically significant effects on the response rate in patients with nervous tinnitus, but the other RCT did not demonstrate significant effects in patients with senile tinnitus. CONCLUSIONS: The number, size and quality of the RCTs on the effectiveness of acupuncture for the treatment of tinnitus are not sufficient for drawing definitive conclusions. Further rigorous RCTs that overcome the many limitations of the current evidence are warranted

Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one of the leading causes of women's death worldwide. It is important to discover a reliable biomarker for the detection of breast cancer. Plasma is the most ideal source for cancer biomarker discovery since many cells cross-communicate through the secretion of soluble proteins into blood.</p> <p>Methods</p> <p>Plasma proteomes obtained from 6 breast cancer patients and 6 normal healthy women were analyzed by using the isotope-coded affinity tag (ICAT) labeling approach and tandem mass spectrometry. All the plasma samples used were depleted of highly abundant 6 plasma proteins by immune-affinity column chromatography before ICAT labeling. Several proteins showing differential abundance level were selected based on literature searches and their specificity to the commercially available antibodies, and then verified by immunoblot assays.</p> <p>Results</p> <p>A total of 155 proteins were identified and quantified by ICAT method. Among them, 33 proteins showed abundance changes by more than 1.5-fold between the plasmas of breast cancer patients and healthy women. We chose 5 proteins for the follow-up confirmation in the individual plasma samples using immunoblot assay. Four proteins, α1-acid glycoprotein 2, monocyte differentiation antigen CD14, biotinidase (BTD), and glutathione peroxidase 3, showed similar abundance ratio to ICAT result. Using a blind set of plasmas obtained from 21 breast cancer patients and 21 normal healthy controls, we confirmed that BTD was significantly down-regulated in breast cancer plasma (Wilcoxon rank-sum test, <it>p </it>= 0.002). BTD levels were lowered in all cancer grades (I-IV) except cancer grade zero. The area under the receiver operating characteristic curve of BTD was 0.78. Estrogen receptor status (<it>p </it>= 0.940) and progesterone receptor status (<it>p </it>= 0.440) were not associated with the plasma BTD levels.</p> <p>Conclusions</p> <p>Our study suggests that BTD is a potential serological biomarker for the detection of breast cancer.</p