Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

Cross-protective efficacy and safety of an adenovirus-based universal influenza vaccine expressing nucleoprotein, hemagglutinin, and the ectodomain of matrix protein 2.

It is necessary to develop universal vaccines that act broadly and continuously to combat regular seasonal epidemics of influenza and rare pandemics. The aim of this study was to find the optimal dose regimen for the efficacy and safety of a mixture of previously developed recombinant adenovirus-based vaccines that expressed influenza nucleoprotein, hemagglutinin, and ectodomain of matrix protein 2 (rAd/NP and rAd/HA-M2e). The vaccine efficacy and safety were measured in the immunized mice with the mixture of rAd/NP and rAd/HA-M2e intranasally or intramuscularly. The minimum dose that would be efficacious in a single intranasal administration of the vaccine mixture and cross-protective efficacy against various influenza strains were examined. In addition, the immune responses that may affect the cross-protective efficacy were measured. We found that intranasal administration is an optimal route for 107 pfu of vaccine mixture, which is effective against pre-existing immunity against adenovirus. In a study to find the minimum dose with vaccine efficacy, the 106 pfu of vaccine mixture showed higher antibody titers to the nucleoprotein than did the same dose of rAd/NP alone in the serum of immunized mice. The 106 pfu of vaccine mixture overcame the morbidity and mortality of mice against the lethal dose of pH1N1, H3N2, and H5N1 influenza infections. No noticeable side effects were observed in single and repeated toxicity studies. We found that the mucosal administration of adenovirus-based universal influenza vaccine has both efficacy and safety, and can provide cross-protection against various influenza infections even at doses lower than those previously known to be effective.

A novel vector field analysis for quantitative structure changes after macular epiretinal membrane surgery.

The aim of this study was to introduce novel vector field analysis for the quantitative measurement of retinal displacement after epiretinal membrane (ERM) removal. We developed a novel framework to measure retinal displacement from retinal fundus images as follows: (1) rigid registration of preoperative retinal fundus images in reference to postoperative retinal fundus images, (2) extraction of retinal vessel segmentation masks from these retinal fundus images, (3) non-rigid registration of preoperative vessel masks in reference to postoperative vessel masks, and (4) calculation of the transformation matrix required for non-rigid registration for each pixel. These pixel-wise vector field results were summarized according to predefined 24 sectors after standardization. We applied this framework to 20 patients who underwent ERM removal to obtain their retinal displacement vector fields between retinal fundus images taken preoperatively and at postoperative 1, 4, 10, and 22 months. The mean direction of displacement vectors was in the nasal direction. The mean standardized magnitudes of retinal displacement between preoperative and postoperative 1 month, postoperative 1 and 4, 4 and 10, and 10 and 22 months were 38.6, 14.9, 7.6, and 5.4, respectively. In conclusion, the proposed method provides a computerized, reproducible, and scalable way to analyze structural changes in the retina with a powerful visualization tool. Retinal structural changes were mostly concentrated in the early postoperative period and tended to move nasally.

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

Damage sensing through TLR9 Promotes Viral Clearance and Recovery During Influenza Infection.

Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mitochondrial DNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data show that TLR9-mediated sensing of tissue damage promotes an inflammatory response during early infection, driven by the myeloid cells and associated cytokine responses. Along with the diminished inflammatory response, the absence of damage sensing through TLR9 led to impaired viral clearance manifested as a higher and prolonged influenza burden in the lung. The absence of TLR9 led to extensive infection of myeloid cells including monocytes and macrophages rendering them highly inflammatory, despite having a low initial inflammatory response. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/- mice. Further, we show elevated circulating TLR9 ligands in the plasma samples of patients with influenza, demonstrating its clinical relevance. Overall, over data show an essential role of damage sensing through TLR9 in promoting anti-influenza immunity.

The Relationship between Perceived Organizational Support, Work Engagement, Organizational Citizenship Behavior, and Customer Orientation in the Public Sports Organizations Context.

As sports activities have recently become socio-culturally important in South Korea, the roles and functions of public sports organizations are attracting attention. In this situation, perceived organizational support is considered one of the significant variables to explain the attitudes and behaviors of employees within the organizations. Hence, the purpose of this study is to investigate the relationship between perceived organizational support of public sports organizations, work engagement, organizational citizenship behavior, and customer orientation and examine the mediating effect of work engagement. This study collected data from 248 employees working for public sports organizations, and data were analyzed with SPSS 26.0 and AMOS 26.0. The results showed the following. (1) Perceived organizational support has a significant positive effect on work engagement but does not affect organizational citizenship behavior and customer orientation. (2) Work engagement significantly positively affects organizational citizenship behavior and customer orientation. (3) Work engagement has been shown to fully mediate the relationship between perceived organizational support, organizational citizenship behavior, and customer orientation. This study suggests that public sports organizations need an efficient support strategy that can maximize employees' work engagement. For example, organizations should increase their sense of unity with employees and understand the importance of their work to strengthen perceived organizational support. Lastly, organizations need to create an environment where employees can devote themselves to and focus on their work.

Anti-inflammatory roles of type I interferon signaling in the lung.

Excessive or persistent inflammation may have detrimental effects on lung structure and function. Currently, our understanding of conserved host mechanisms that control the inflammatory response remains incompletely understood. In this study, we investigated the role of type I interferon signaling in the inflammatory response against diverse clinically relevant stimuli. Using mice deficient in type I interferon signaling (IFNAR1-/-), we demonstrate that the absence of interferon signaling resulted in a robust and persistent inflammatory response against Pseudomonas aeruginosa, lipopolysaccharide, and chemotherapeutic agent bleomycin. The elevated inflammatory response in IFNAR1-/- mice was manifested as elevated myeloid cells, such as macrophages and neutrophils, in the bronchoalveolar lavage. The inflammatory cell response in the IFNAR1-/- mice persisted to 14 days and there is impaired recovery and fibrotic remodeling of the lung in IFNAR1-/- mice after bleomycin injury. In the Pseudomonas infection model, the elevated inflammatory cell response led to improved bacterial clearance in IFNAR1-/- mice, although there was similar lung injury and survival. We performed RNA sequencing of lung tissue in wild-type and IFNAR1-/- mice after LPS and bleomycin injury. Our unbiased analysis identified differentially expressed genes between IFNAR1-/- and wild-type mice, including previously unknown regulation of nucleotide-binding oligomerization domain (NOD)-like receptor signaling, retinoic acid-inducible gene-I (RIG-I) signaling, and necroptosis pathway by type I interferon signaling in both models. These data provide novel insights into the conserved anti-inflammatory mechanisms of the type I interferon signaling.NEW & NOTEWORTHY Type I interferons are known for their antiviral activities. In this study, we demonstrate a conserved anti-inflammatory role of type I interferon signaling against diverse stimuli in the lung. We show that exacerbated inflammatory response in the absence of type I interferon signaling has both acute and chronic consequences in the lung including structural changes.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Activated somatostatin interneurons orchestrate memory microcircuits.

Despite recent advancements in identifying engram cells, our understanding of their regulatory and functional mechanisms remains in its infancy. To provide mechanistic insight into engram cell functioning, we introduced a novel local microcircuit labeling technique that enables the labeling of intraregional synaptic connections. Utilizing this approach, we discovered a unique population of somatostatin (SOM) interneurons in the mouse basolateral amygdala (BLA). These neurons are activated during fear memory formation and exhibit a preference for forming synapses with excitatory engram neurons. Post-activation, these SOM neurons displayed varying excitability based on fear memory retrieval. Furthermore, when we modulated these SOM neurons chemogenetically, we observed changes in the expression of fear-related behaviors, both in a fear-associated context and in a novel setting. Our findings suggest that these activated SOM interneurons play a pivotal role in modulating engram cell activity. They influence the expression of fear-related behaviors through a mechanism that is dependent on memory cues.

Amplification Failure of the Amelogenin X Gene Caused by a Rare Mutation in the Primer-Binding Region.

The study of gender markers is essential in forensic genetic analysis. Mutations in the X or Y homologs of the amelogenin gene can be misleading, resulting in serious mistakes in forensic genetic analysis. We recently discovered two male cases of the X homolog of the amelogenin (AMELX) allelic dropout while analyzing short tandem repeat genotypes obtained from crime scene evidence. Subsequently, we evaluated the molecular characteristics of AMELX allelic dropout in this study. We used two previously reported amelogenin primers to verify a half level of amelogenin gene amplification intensity in the two male cases, which we confirmed was caused by AMELX allelic dropout. We then characterized the point mutation using Sanger sequencing and designed mutation-specific primers that could overcome AMELX allelic dropout. Short tandem repeat genotyping analysis confirmed that the AMELX allelic dropout was recovered by the mutation-specific primer designed specifically for this case. The sequencing of the AMELX allele revealed a single-point variant from A→G at base position 7 downstream from the 3' end in the amelogenin forward primer-binding region. This point mutation was identically found in two different male cases, resulting in AMELX allelic dropout. To our knowledge, these mutations and the X homolog amplification failure of amelogenin have not been reported in the Korean population. Our study provides a reliable approach to AMELX allelic dropout due to rare case mutations and could enable the better interpretation of gender markers for forensic samples.

Diagnostic roles of PAX8 immunohistochemistry in ovarian tumors.

OBJECTIVE: This study aimed to elucidate the diagnostic roles of PAX8 immunohistochemistry in various ovarian tumors. METHODS: We searched through the PubMed database and selected the eligible studies to perform the meta-analysis. The PAX8 immunohistochemical expression rates of various ovarian tumors, including primary and metastatic carcinomas, were analyzed. In addition, the subgroup analysis based on tumor behaviors was performed. RESULTS: The PAX8 expression rates were 0.056 (95% confidence interval [CI] 0.008-0.307), 0.400 (95% CI 0.228-0.600), 0.741 (95% CI 0.578-0.857), and 0.738 (95% CI 0.666-0.799) in normal ovary and benign, borderline, and malignant ovarian tumors, respectively. The PAX8 expression rates of serous and transitional cell carcinomas were 0.937 (95% CI 0.882-0.967) and 0.918 (95% CI 0.841-0.959). In addition, the PAX8 expression rate of mucinous carcinomas was 0.393 (95% CI 0.285-0.512). However, metastatic carcinomas showed a significantly lower PAX8 expression rate than primary ovarian cancers (P < 0.001 in the meta-regression test). In cytologic specimens, PAX8 expression rates of serous and endometrioid carcinomas were 0.905 (95% CI 0.832-0.948) and 0.714 (95% CI 0.327-0.928), respectively. CONCLUSION: PAX8 expression rate was significantly higher in serous ovarian tumors than in mucinous ovarian tumors. In addition, PAX8 expression rates were significantly higher in primary ovarian cancers than in metastatic carcinomas.

Alteration of perivascular reflectivity on optical coherence tomography of branched retinal vein obstruction.

This study aimed to evaluate perivascular reflectivity in patients with branched retinal vascular obstruction (BRVO) using en-face optical coherence tomography (OCT). The study retrospectively analyzed 45 patients with recurrent BRVO, 30 with indolent BRVO, and 45 age- and sex-matched controls. Using a 3.0 × 3.0-mm deep capillary plexus slab on macular scans, OCT angiography (OCTA) and structural en-face OCT scans were divided into four quadrants. Obstructive quadrants of OCTA scans were binarized using a threshold value of mean + 2 standard deviation. The selected area of high signal strength (HSS) was applied to the structural en-face OCT scans, and the corrected mean perivascular reflectivity was calculated as the mean reflectivity on the HSS area/overall en-face OCT mean reflectivity. The same procedure was performed in the quadrants of the matched controls. Regression analysis was conducted on several factors possibly associated with corrected perivascular reflectivity. The perivascular reflectivity in the obstructive BRVO quadrant was significantly higher than in the indolent BRVO and control quadrants (P = 0.009, P = 0.003). Both univariate and multivariate regression analyses showed a significant correlation between the average number of intravitreal injections (anti-vascular endothelial growth factor or dexamethasone implant) per year and refractive errors and image binarization threshold and perivascular reflectivity (P = 0.011, 0.013, < 0.001/univariate; 0.007, 0.041, 0.005/multivariate, respectively). En-face OCT scans of the deep capillary plexus slab revealed higher perivascular reflectivity in recurrent BRVO eyes than in indolent BRVO and control eyes. The results also indicate a remarkable correlation between perivascular reflectivity and the average number of intravitreal injections, suggesting a link to recurrence rates.

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.

This study presents the development of a ß-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded ß-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus. This stimulus-responsive property was translated into the effective capture and release of model multivalent biomaterials, hDM2-gold nanoparticle conjugates. Since numerous protein interactions are mediated by α-helical peptides, these results suggest that the ß-hairpin-based MT holds great potential to be utilized in various biomedical applications, such as protein interaction inhibition and cancer biomarker (e.g., circulating tumor cells and exosomes) detection.

Suppression of TBCK enhances TRAIL-mediated apoptosis by causing the inactivation of the akt signaling pathway in human renal carcinoma Caki-1 cells.

BACKGROUND: TBC1 domain-containing kinase (TBCK) protein functions as a growth suppressor in certain cell types and as a tumor promoter in others. Although TBCK knockdown increases the responsiveness of cancer cells to anticancer drugs, the detailed mechanisms by which TBCK knockdown increases susceptibility to anticancer drugs remain unknown. OBJECTIVE: This study analyzed the role of TBCK in sensitivities to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and doxorubicin in human renal cancer cells. METHODS: Flow cytometry was employed to evaluate the extent of apoptosis. Western blotting, transient transfection, and lentiviral infection techniques were conducted to investigate the impact of TBCK on apoptosis-related protein expression and mitogen-activated protein kinase (MAPK). RESULTS: TBCK knockdown in renal cancer cells inhibits ERK and Akt signaling pathways and increases TRAIL and doxorubicin sensitivity. In TBCK-knockdown Caki-1 cells, ERK and Akt phosphorylation was suppressed compared to control cell lines, and TRAIL and doxorubicin sensitivities were increased in these cells. In addition, the phosphorylation of PDK1 was suppressed in TBCK-suppressed cells, indicating that TBCK may be involved in the PDK1 and Akt signaling pathways. The introduction of dominantly active Akt into TBCK-suppressed cells restored their sensitivity to TRAIL. In addition, TBCK downregulation enhanced TRAIL sensitivity in different renal cancer cell lines. CONCLUSIONS: These data suggest that TBCK could potentially have a crucial function in influencing the effects of anti-cancer drugs including TRAIL by modulating the signaling pathway involving Akt and PDK1 in human renal cancer cells.

Double Emulsion-Mediated Delivery of Polyphenol Mixture Alleviates Atopic Dermatitis.

Although the polyphenols have been studied to alleviate inflammation, there are still challenges to delivering the polyphenols with stabilized formulation due to their low water solubility and susceptibility to oxidation. Herein, the transdermal delivery system of polyphenol mixture (PM), including quercetin (Q), phloretin (P), and ellagic acid (E), is developed using double emulsion for applying to atopic dermatitis (AD). Through the in vitro anti-degranulation assay, the optimal molar ratio of each polyphenol (Q:P:E = 5:1:1) is obtained, and the PM shows at most a 43.6% reduction of degranulation of immune cells, which is the primary factor of AD. Moreover, the water-in-oil-in-water double emulsion (W/O/W) enhances the PM's stability and has a higher anti-degranulation effect than the oil-in-water emulsion (O/W). In the in vivo 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice AD model, PM reduces more AD symptoms than every single polyphenol. The PM-encapsulated W/O/W (PM_W/O/W) shows the most effectiveness in AD by decreasing dermatitis score, i.e., skin/ear thickness, mast cells, and serum IgE level. Finally, this suggests that the findings on the optimal ratio of PM and double emulsion-based delivery would be beneficial in treating AD and can be applied to other allergic diseases.

The Effect of Alkyl Chain Length in Organic Semiconductor and Surface Polarity of Polymer Dielectrics in Organic Thin-Film Transistors (OTFTs).

The interface between dielectric and organic semiconductor is critically important in determining organic thin-film transistor (OTFT) performance. Surface polarity of the dielectric layer can hinder charge transport characteristics, which has restricted utilization of polymeric dielectric materials containing polar functional groups. Herein, the electrical characteristics of OTFTs are analyzed depending on the alkyl chain length of organic semiconductors and surface polarity of polymer dielectrics. High-performance dibenzothiopheno[6,5-b:6',5'-f]thieno[3,2-b]thiophene (DBTTT) and newly synthesized its alkylated derivatives (C6-DBTTT and C10-DBTTT) are utilized as organic semiconductors. As dielectric layers, non-polar poly(1,3,5-trimethyl-1,3,5-trivinylcyclitrisiloxane) (pV3D3) and poly(2-cyanoethyl acrylate-co-diethylene glycol divinyl ether) [p(CEA-co-DEGDVE)] with polar cyanide functionality are utilized. The fabricated OTFTs with pV3D3 commonly exhibit the excellent charge transport characteristics. In addition, the OTFT performance is improved with lengthening the alkyl chain in organic semiconductors, which can be attributed to the molecular orientation of semiconductors. On the other hand, non-alkylated DBTTT OTFTs with polar p(CEA-co-DEGDVE) show relatively poor electrical characteristics, while their performance is drastically enhanced with the alkylated DBTTTs. The ultraviolet photoelectron spectroscopy (UPS) reveals that surface polarity of the dielectric layer can be abated with alkyl chain in organic semiconductors. It is believed that this study can provide a useful insight to optimize dielectric/semiconductor interface to achieve high-performance OTFTs.

Effect of high-dose vitamin C and E supplementation on muscle recovery and training adaptation: a mini review.

PURPOSE: This review aimed to investigate the effects of high-dose vitamins C and E supplementation combined with acute or chronic exercise on muscle recovery and training adaptation. METHODS: We used PubMed, Web of Science, and Wiley Online Library databases to perform a literature search based on the keywords 'vitamin C, vitamin E, antioxidants, muscle recovery, training adaptation, and oxidative stress'. RESULTS: Vitamin C or E supplementation has been reported to contribute to a reduction in oxidative stress and muscle damage; however, there is currently inadequate evidence of their positive effects on muscle recovery. Long-term vitamin C or E supplementation can have negative effects on physiological phenomena required for training adaptation, such as strength, muscle hypertrophy, and endurance. Numerous studies emphasized that an adequate diet consisting of fruits and vegetables is a more appropriate way of consuming antioxidants than supplementation. CONCLUSION: The effects of high-dose vitamin C and E supplementation on post-exercise muscle recovery remain unclear and ambiguous, although there is evidence of potential negative effects on training adaptation.

Pellino 3 promotes the colitis-associated colorectal cancer through suppression of IRF4-mediated negative regulation of TLR4 signalling.

The incidence of colitis-associated colorectal cancer (CAC) has increased due to a high-nutrient diet, increased environmental stimuli and inherited gene mutations. To adequately treat CAC, drugs should be developed by identifying novel therapeutic targets. E3 ubiquitin-protein ligase pellino homolog 3 (pellino 3; Peli3) is a RING-type E3 ubiquitin ligase involved in inflammatory signalling; however, its role in the development and progression of CAC has not been elucidated. In this study, we studied Peli3-deficient mice in an azoxymethane/dextran sulphate sodium-induced CAC model. We observed that Peli3 promotes colorectal carcinogenesis with increased tumour burden and oncogenic signalling pathways. Ablation of Peli3 reduced inflammatory signalling activation at the early stage of carcinogenesis. Mechanistic studies indicate that Peli3 enhances toll-like receptor 4 (TLR4)-mediated inflammation through ubiquitination-dependent degradation of interferon regulatory factor 4, a negative regulator of TLR4 in macrophages. Our study suggests an important molecular link between Peli3 and colonic inflammation-mediated carcinogenesis. Furthermore, Peli3 can be a therapeutic target in the prevention and treatment of CAC.

Risk of psychological distress by decrease in economic activity, gender, and age due to COVID-19: A multinational study.

Introduction: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2-virus. COVID-19 has officially been declared as the latest in the list of pandemics by WHO at the start of 2020. This study investigates the associations among decrease in economic activity, gender, age, and psychological distress during the COVID-19 pandemic considering the economic status and education level of countries using multinational surveys. Methods: Online self-report questionnaires were administered in 15 countries which were spontaneously participate to 14,243 respondents in August 2020. Prevalence of decrease in economic activity and psychological distress was stratified by age, gender, education level, and Human Development Index (HDI). With 7,090 of female (49.8%), mean age 40.67, 5,734 (12.75%) lost their job and 5,734 (40.26%) suffered from psychological distress. Results: Associations among psychological distress and economic status, age, and gender was assessed using multivariate logistic regression, adjusted for country and education as random effects of the mixed model. We then measured the associations between HDI and age using multivariate logistic regression. Women had a higher prevalence of psychological distress than men with 1.067 Odds ratio, and younger age was significantly associated with decrease in economic activity for 0.998 for age increasing. Moreover, countries with lower HDI showed a higher prevalence of decrease in economic activity, especially at lower education levels. Discussion: Psychological distress due to COVID-19 revealed a significant association with decrease in economic activity, women, and younger age. While the proportion of decrease in economic activity population was different for each country, the degree of association of the individual factors was the same. Our findings are relevant, as women in high HDI countries and low education level in lower HDI countries are considered vulnerable. Policies and guidelines for both financial aid and psychological intervention are recommended.

En-face optical coherence tomography hyperreflective foci of choriocapillaris in central serous chorioretinopathy.

The purpose of this study is to evaluate choroidal hyperreflective foci (HRF) changes in central serous chorioretinopathy (CSC) on en-face optical coherence tomography (OCT). Retrospective analysis of 42 patients with unilateral CSC (84 eyes, including fellow eyes for controls) and 42 age- and sex-matched controls. With 4.5 × 4.5 mm macular scans, structural en-face OCT choriocapillaris (CC) slabs were used to calculate the density and number of HRF in acute CSC eyes with serous retinal detachment (SRD), resolved CSC eyes without SRD, unaffected fellow eyes, control eyes, and 1-year follow-up eyes. Based on the 2-disc diameter (3000 µm), the en-face OCT scan was divided into foveal and perifoveal lesion and analyzed to consider the impact of SRF in HRF measurement. Regression analyses were performed on the several factors with HRF number and density in the acute and resolved CSC eyes. The perifoveal density and number of CC HRF was significantly lower in the resolved CSC eyes when compared to the acute CSC eyes (P = 0.002, both), fellow eyes (P = 0.042/density, 0.028/number), and controls (P = 0.021/density, P = 0.003/number). There was no significant difference between the acute CSC eyes, fellow eyes, controls, and 1-year follow-up eyes. As subfoveal choroidal thickness decreased and choroidal vascularity (CVI) increased, the perifoveal density and number of HRF was measured higher with a significant correlation in univariate regression analysis of the acute and resolved CSC eyes (all, P < 0.05). The authors hypothesized that stromal edema induced by choroidal congestion and hyperpermeability has the greatest influence on HRF measurement, possibly affected by inflammatory cells and materials extravasation.