Self-image, self-esteem, anxiety, and functional capacity in patients undergoing open-structure rhinoplasty.

BACKGROUND: Rhinoplasty may improve negative psychological aspects, such as mild to moderate body dysmorphic disorder; however, the repercussions on the self-image and quality of life of patients after the procedure are unknown. OBJECTIVE: To evaluate self-image, self-esteem, anxiety, and functional capacity of patients undergoing open-structure rhinoplasty. METHODS: A primary, analytical, clinical, longitudinal, and prospective study was conducted, which included 30 female patients, aged between 18 and 50 years with elongated nose and nasal hump, who underwent open and structured rhinoplasty. All procedures were performed by a team from the Rhinology DCP/Unifesp. The Rosenberg Self-Esteem Scale - EPM, BDSS, BDD-YBOCS, SF-36, SRQ-20, and STAI (T/E) questionnaires were administered before the surgery and at 6, 12, and 18 months after surgery. RESULTS: The results showed statistically significant differences in the Rosenberg scale - EPM (p = 0.017), BDSS (p < 0.001), BDD (p = 0.006), SF-36 (p = 0.041), SRQ-20 (p = 0.012), and STAI-T (p = 0.001) scores in general analyses. Additionally, the statistically significant changes persisted in various stratified postoperative periods. In the qualitative analysis, there was only statistical significance for the classification of the BDSS score, where the "Absent" (absence of body dysmorphism) index increased from 70.0% in the preoperative state to 96.7% in 18 months postoperatively. The "Present" (presence of body dysmorphism) index fell from 30.0% to 3.3% in the same period (p = 0.001). CONCLUSION: Open-structure rhinoplasty improved the patients' self-image, self-esteem, anxiety, and mental health.

Role of SEL1L in the progression of solid tumors, with a special focus on its recent therapeutic potential.

Since suppressor/enhancer of Lin-12-like (SEL1L) was cloned in 1997, various pieces of evidence from lower species suggest it plays a significant role in protein degradation via the ubiquitin-proteasome system. The relevance of SEL1L in many aspects of malignant transformation and tumorigenic events has been the subject of research, which has shown compelling in vitro and in vivo findings relating its altered expression to changes in tumor aggressiveness. The Endoplasmic Reticulum (ER) in tumor cells is crucial for preserving cellular proteostasis by inducing the unfolded protein response (UPR), a stress response. A crucial component of the UPR is ER-associated degradation (ERAD), which guards against ER stress-induced apoptosis and the removal of unfolded or misfolded proteins by the ubiquitin-proteasome system. As a protein stabilizer of HMG-CoA reductase degradation protein 1 (HRD1), one of the main components of ERAD, SEL1L plays an important role in ER homeostasis. Notably, the expression levels of these two proteins fluctuate independently in various cancer types, yet changes in their expression affect the levels of other associated proteins during cancer pathogenesis. Recent studies have also outlined the function of SEL1L in cancer medication resistance. This review explores the value of targeting SEL1L as a novel treatment approach for cancer, focusing on the molecular processes of SEL1L and its involvement in cancer etiology.

Characterizing the underwater soundscape at the site of a proposed port in northeast Iceland.

Finnafjörður is a small fjord in northeast Iceland, where the planned construction of a large port has the potential to meaningfully change the marine soundscape and ecosystem. In this study, we used one year (2021/22) of passive acoustic recordings to characterize the pre-construction soundscape, including broadband and decidecade sound pressure levels (SPL), frequency-weighted sound exposure levels, seasonal and diel variability and identified regular types of sound. Finnafjörður is relatively quiet with median decidecade levels centered between 25 Hz and 50 kHz of 74.5 to 86.3 dB re 1 µPa. Wind and rain dominate ambient SPL, while anthropogenic sources only occasionally contributed to the soundscape. Regular biological sound sources include humpback whales, toothed whales, and fish. This baseline soundscape description can be used for noise management during port construction, to monitor future changes in the region, and to act as a framework for comprehensive impact assessments as ports are developed globally.

The effectiveness of a contextually grounded social emotional learning program in Haiti: A pilot cluster randomized control trial.

Social emotional learning (SEL) has a robust evidence basis, but there remains a large gap in literature on the effectiveness of programs across educational settings in low- and middle-income countries and conflict-affected settings. The present study was a pilot trial aimed at evaluating the effects of a classroom based SEL program on dimensions of classroom climate and individual student social emotional skills. In the present study, fourth through sixth grade classrooms in 10 schools (N = 39 teachers, 75.68% female; N = 1048 students, 62.3% female) were randomly allocated to the SEL or wait-list control condition. The SEL program was associated with significant improvements in teacher reports of student achievement orientation (dr = 1.21) and responsible decision-making (dr = 0.49). There were no significant differences between conditions on peer sensitivity, teacher-pupil interactions, student interpersonal skills, or overall social emotional skills. Findings suggest that this community-developed, contextually relevant SEL curriculum may hold promise even in the context of ongoing adversity, including the COVID-19 pandemic and heightened insecurity due to political violence.

Endoscopic removal of gastrointestinal lesions by using third space endoscopy techniques.

The concept of submucosal space, or rather the "third space", located between the intact mucosal flap and the muscularis propria layer of the gastrointestinal tract, represents a tunnel that the endoscopist could use to perform interventions in the muscularis propria layer or breech it to enter the mediastinum or the peritoneal cavity without full thickness perforation. The tunnel technique can be used both for the removal of mucosal tumours, called endoscopic submucosal tunnel dissection (ESTD), for the removal of subepithelial tumours (SELs), called submucosal tunnelling endoscopic resection (STER), and for the removal of extra-luminal lesions (for example in the mediastinum or in the rectum), called submucosal tunnelling endoscopic resection for extraluminal tumours (STER-ET). Aim of this updated narrative review, is to summarize the evidences that analyses indications, and outcomes of tunnelling techniques for the treatment of above mentioned lesions.

The Effect of a SEL (Social-Emotional Learning) Intervention Program Based on Emotional Regulation and Metacognitive Awareness for Special Education Preservice Teachers Experiencing Adapted Teaching in Mathematics.

This study's aim was to examine the influence of a unique intervention program based on emotional self-awareness and the development of emotional regulation as an important component of SEL combined with metacognitive awareness. Seventy-two third-year preservice teachers participated for one year, tutoring a mathematically challenged student. This intervention was applied to an experimental group where each participant learned to assess his/her emotional state using a special ruler prior to teaching a lesson, and according to the ruler's assessment results, the preservice teacher was assisted by a variety of emotional regulations as well as metacognitive strategies. A control group learned only metacognitive strategies. This study's results indicated that experimental group participants showed notable improvement in cognitive reappraisal post-intervention compared to the control group, which showed no change. For metacognitive awareness, in both research groups, an increase was apparent post-intervention. Nevertheless, a comparison of the effect size of differences between the two measurement points indicated that the experimental group exhibited a greater improvement in metacognitive regulation compared to the control group. A significant positive correlation was found in the experimental group between cognitive reappraisal and metacognitive regulation. Assimilation and training of emotional skills among preservice teachers during training are necessary.

Caenorhabditis elegans SEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity.

During Caenorhabditis elegans development, multiple cells migrate long distances or extend processes to reach their final position and/or attain proper shape. The Wnt signalling pathway stands out as one of the major coordinators of cell migration or cell outgrowth along the anterior-posterior body axis. The outcome of Wnt signalling is fine-tuned by various mechanisms including endocytosis. In this study, we show that SEL-5, the C. elegans orthologue of mammalian AP2-associated kinase AAK1, acts together with the retromer complex as a positive regulator of EGL-20/Wnt signalling during the migration of QL neuroblast daughter cells. At the same time, SEL-5 in cooperation with the retromer complex is also required during excretory canal cell outgrowth. Importantly, SEL-5 kinase activity is not required for its role in neuronal migration or excretory cell outgrowth, and neither of these processes is dependent on DPY-23/AP2M1 phosphorylation. We further establish that the Wnt proteins CWN-1 and CWN-2, together with the Frizzled receptor CFZ-2, positively regulate excretory cell outgrowth, while LIN-44/Wnt and LIN-17/Frizzled together generate a stop signal inhibiting its extension.

Gender, racial-ethnic, and socioeconomic disparities in the development of social-emotional competence among elementary school students.

Social-emotional competence (SEC) has been demonstrated to be a crucial factor for student mental health and is malleable through the high-quality implementation of effective school-based social and emotional learning (SEL) programs. SEL is now widely practiced in the United States as a Tier 1 strategy for the entire student body, yet it remains unclear whether disparities exist in the development of SEC across socio-culturally classified subgroups of students. Also, despite the field's widespread concern about teacher bias in assessing SEC within diverse student bodies, little evidence is available on the measurement invariance of the SEC assessment tools used to explore and facilitate SEC development. Based on a sociocultural view of student SEC development, this study aimed to measure and examine the extent to which gender, racial-ethnic, and socioeconomic disparities exist in SEC developmental trajectories during elementary school years. Specifically, using 3 years of SEC assessment data collected from a districtwide SEL initiative (N = 5452; Grades K-2 at baseline; nine measurement occasions), this study (a) tested the measurement invariance of a widely-used, teacher-rated SEC assessment tool (DESSA-Mini) across student gender, race and ethnicity, and socioeconomic status (SES); and (b) examined the extent to which multiyear SEC growth trajectories differed across these subgroups under a routine SEL practice condition. The invariance testing results supported strict factorial invariance of the DESSA-Mini across all the examined subgroups, thereby providing a foundation for valid cross-group comparisons of student SEC growth. The piecewise latent growth modeling results indicated that boys (vs. girls), Black students (vs. White students), Hispanic students (vs. White students), and low-income students (vs. middle-to-high-income students) started with a lower level of SEC, with these gaps being sustained or slightly widened throughout 3 elementary school years. Based on these findings, this study calls for future research that can inform practice efforts to ensure equitable SEC assessments and produce more equitable SEL outcomes, thereby promoting equity in school mental health.

Notch signaling without the APH-2/nicastrin subunit of gamma secretase in Caenorhabditis elegans germline stem cells.

The final step in Notch signaling activation is the transmembrane cleavage of Notch receptor by γ secretase. Thus far, genetic and biochemical evidence indicates that four subunits are essential for γ secretase activity in vivo: presenilin (the catalytic core), APH-1, PEN-2, and APH-2/nicastrin. Although some γ secretase activity has been detected in APH-2/nicastrin-deficient mammalian cell lines, the lack of biological relevance for this activity has left the quaternary γ secretase model unchallenged. Here, we provide the first example of in vivo Notch signal transduction without APH-2/nicastrin. The surprising dispensability of APH-2/nicastrin is observed in Caenorhabditis elegans germline stem cells (GSCs) and contrasts with its essential role in previously described C. elegans Notch signaling events. Depletion of GLP-1/Notch, presenilin, APH-1, or PEN-2 causes a striking loss of GSCs. In contrast, aph-2/nicastrin mutants maintain GSCs and exhibit robust and localized expression of the downstream Notch target sygl-1. Interestingly, APH-2/nicastrin is normally expressed in GSCs and becomes essential under conditions of compromised Notch function. Further insight is provided by reconstituting the C. elegans γ secretase complex in yeast, where we find that APH-2/nicastrin increases but is not essential for γ secretase activity. Together, our results are most consistent with a revised model of γ secretase in which the APH-2/nicastrin subunit has a modulatory, rather than obligatory role. We propose that a trimeric presenilin-APH-1-PEN-2 γ secretase complex can provide a low level of γ secretase activity, and that cellular context determines whether or not APH-2/nicastrin is essential for effective Notch signal transduction.

Japanese encephalitis virus hijacks ER-associated degradation regulators for its replication.

Flaviviruses target their replication on membranous structures derived from the ER, where both viral and host proteins play crucial structural and functional roles. Here, we have characterized the involvement of the ER-associated degradation (ERAD) pathway core E3 ligase complex (SEL1L-HRD1) regulator proteins in the replication of Japanese encephalitis virus (JEV). Through high-resolution immunofluorescence imaging of JEV-infected HeLa cells, we observe that the virus replication complexes marked by NS1 strongly colocalize with the ERAD adapter SEL1L, lectin OS9, ER-membrane shuttle factor HERPUD1, E3 ubiquitin ligase HRD1 and rhomboid superfamily member DERLIN1. NS5 positive structures also show strong overlap with SEL1L. While these effectors show significant transcriptional upregulation, their protein levels remain largely stable in infected cells. siRNA mediated depletion of OS9, SEL1L, HERPUD1 and HRD1 significantly inhibit viral RNA replication and titres, with SEL1L depletion showing the maximum attenuation of replication. By performing protein translation arrest experiments, we show that SEL1L, and OS9 are stabilised upon JEV infection. Overall results from this study suggest that these ERAD effector proteins are crucial host-factors for JEV replication.

Hyper-N-glycosylated SEL1L3 as auto-antigenic B-cell receptor target of primary vitreoretinal lymphomas.

Primary vitreoretinal lymphoma (PVRL) is a rare subtype of DLBCL and can progress into primary central nervous system lymphoma (PCNSL). To investigate the role of chronic antigenic stimulation in PVRL, we cloned and expressed B-cell receptors (BCR) from PVRL patients and tested for binding against human auto-antigens. SEL1L3, a protein with multiple glycosylation sites, was identified as the BCR target in 3/20 PVRL cases. SEL1L3 induces proliferation and BCR pathway activation in aggressive lymphoma cell lines. Moreover, SEL1L3 conjugated to a toxin killed exclusively lymphoma cells with respective BCR-reactivity. Western Blot analysis indicates the occurrence of hyper-N-glycosylation of SEL1L3 at aa 527 in PVRL patients with SEL1L3-reactive BCRs. The BCR of a PVRL patient with serum antibodies against SEL1L3 was cloned from a vitreous body biopsy at diagnosis and of a systemic manifestation at relapse. VH4-04*07 was used in both lymphoma manifestations with highly conserved CDR3 regions. Both BCRs showed binding to SEL1L3, suggesting continued dependence of lymphoma cells on antigen stimulation. These results indicate an important role of antigenic stimulation by post-translationally modified auto-antigens in the genesis of PVRL. They also provide the basis for a new treatment approach targeting unique lymphoma BCRs with ultimate specificity.

Using synthetic genome readers/regulators to interrogate chromatin processes: A brief review.

Aberrant gene expression underlies numerous human ailments. Hence, developing small molecules to target and remedy dysfunctional gene regulation has been a long-standing goal at the interface of chemistry and medicine. A major challenge for designing small molecule therapeutics aimed at targeting desired genomic loci is the minimization of widescale disruption of genomic functions. To address this challenge, we rationally design polyamide-based multi-functional molecules, i.e., Synthetic Genome Readers/Regulators (SynGRs), which, by design, target distinct sequences in the genome. Herein, we briefly review how SynGRs access chromatin-bound and chromatin-free genomic sites, then highlight the methods for the study of chromatin processes using SynGRs on positioned nucleosomes in vitro or disease-causing repressive genomic loci in vivo.

Case Report: Technical description and clinical evaluation of three cases of unilateral biportal endoscopic decompression for symptomatic spinal epidural lipomatosis.

Objective: To investigate the clinical characteristics and outcomes of three patients with symptomatic Spinal epidural lipomatosis (SEL) treated using Unilateral Biportal Endoscopic (UBE) surgery. Methods: This report retrospectively analyzed the clinical data of three patients with SEL admitted to our hospital. The analysis covers onset characteristics, clinical manifestations, and the most recent radiologic grading system of neural compression (Manjila classification). Furthermore, it details the decompression accomplished through the application of a minimally invasive UBE surgical technique, specifically targeting the removal of proliferated fat responsible for nerve and spinal cord compression. Results: This technique was performed successfully in 3 patients with SEL. Radiating pain was reduced, and the functional disability and radiologic compression were improved in all three patients. Postoperative spinal instability and surgical complications related to the procedure were not observed. Conclusions: For SEL, timely diagnosis and appropriate intervention can prevent the progression of neurological disability. UBE is a minimally invasive muscle-preserving technique that achieves neural decompression directly by the removal of excessive intraspinal adipose tissue buildup.

Tickling the heart: integrating social emotional learning into medical education to cultivate empathetic, resilient, and holistically developed physicians.

Objectives: Advancements in technology have improved healthcare quality but shifted the focus to efficiency, negatively impacting patient- doctor relationships. This study proposes integrating social-emotional learning (SEL) into medical education to address this issue. Key arguments: Social-emotional learning (SEL) is based on social learning theory and has a focus on emotion management, stress management, empathy, and social skills. Through SEL, students can develop social and emotional skills by observing, interacting with, and imitating others. Incorporating SEL into medical education would ensure that physicians develop the social and emotional skills necessary to form positive relationships with patients and to cope with the emotional demands of medical work. SEL comprises six domains, namely, the cognitive, emotion, social, values, perspective, and identity domains. These six domains are closely related to the six core competencies the Accreditation Council for Graduate Medical Education (ACGME) indicated every doctor should possess, which indicates that the domains of SEL are highly relevant within the context of medical education. Furthermore, SEL can lead to the development of empathy, which can improve physicians' ability to understand patients' perspectives and emotions, and resilience, which can enable physicians to more effectively cope with the demands of their work, and it can lead to holistic development, with doctors gaining an understanding of both the technical and humanistic aspects of their work. Conclusion: Incorporating SEL in medical education would enable doctors to develop key social and emotional skills that would improve their ability to provide holistic medical services and therefore would improve overall medical systems.

SEL1L-HRD1 ER-associated degradation regulates leptin receptor maturation and signaling in POMC neurons in diet-induced obesity.

Endoplasmic reticulum (ER) homeostasis in the hypothalamus has been implicated in the pathogenesis of certain patho-physiological conditions such as diet-induced obesity (DIO) and type 2 diabetes; however, the significance of ER quality control mechanism(s) and its underlying mechanism remain largely unclear and highly controversial in some cases. Moreover, how the biogenesis of nascent leptin receptor in the ER is regulated remains largely unexplored. Here we report that the SEL1L-HRD1 protein complex of the highly conserved ER-associated protein degradation (ERAD) machinery in POMC neurons is indispensable for leptin signaling in diet-induced obesity. SEL1L-HRD1 ERAD is constitutively expressed in hypothalamic POMC neurons. Loss of SEL1L in POMC neurons attenuates leptin signaling and predisposes mice to HFD-associated pathologies including leptin resistance. Mechanistically, newly synthesized leptin receptors, both wildtype and disease-associated human mutant Cys604Ser (Cys602Ser in mice), are misfolding prone and bona fide substrates of SEL1L-HRD1 ERAD. Indeed, defects in SEL1L-HRD1 ERAD markedly impair the maturation of these receptors and causes their ER retention. This study not only uncovers a new role of SEL1L-HRD1 ERAD in the pathogenesis of diet-induced obesity and central leptin resistance, but a new regulatory mechanism for leptin signaling.

A social emotional learning intervention to reduce psychosocial difficulties among rural children in central China.

Programmes based on social emotional learning (SEL) have been effective in reducing psychosocial difficulties in a number of countries. In Mainland China, there has been no empirical research on the prevention of children's psychosocial difficulties using the SEL approach. This study aimed to assess whether an adapted version of the SEL programme can reduce psychosocial difficulties of primary school children in rural China. The intervention consisted of 16 weekly 90-min class sessions, conducted among 206 children aged 8-12 years (with 290 controls) in a poor rural area of Central China. Self-report questionnaires were administered at baseline, post-intervention and 5-month follow-up. The results suggested that the programme (1) can reduce children's total difficulties (measured using the Strength and Difficulties Questionnaire) at post-intervention (d = -0.18) and 5-month follow-up (d = -0.19), (2) was more effective among children experiencing verbal abuse (d = -0.21) or physical abuse (d = -0.24) from caregivers and (3) was popular among more than 90% of the participants. The programme is cheap, easy to implement and can be delivered in school hours. Therefore, it has clear potential for replicability and sustainability.

The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout.

OBJECTIVES: Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase. METHODS: COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety. RESULTS: During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only. CONCLUSIONS: SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase. CLINICAL TRIAL REGISTRATION: NCT03905512.

Luteolin Protects Against 6-Hydoroxydopamine-Induced Cell Death via an Upregulation of HRD1 and SEL1L.

Parkinson's Disease (PD) is caused by many factors and endoplasmic reticulum (ER) stress is considered as one of the responsible factors for it. ER stress induces the activation of the ubiquitin-proteasome system to degrade unfolded proteins and suppress cell death. The ubiquitin ligase 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation 1 (HRD1) and its stabilizing molecule, the suppressor/enhancer lin-12-like (SEL1L), can suppress the ER stress via the ubiquitin-proteasome system, and that HRD1 can also suppress cell death in familial and nonfamilial PD models. These findings indicate that HRD1 and SEL1L might be key proteins for the treatment of PD. Our study aimed to identify the compounds with the effects of upregulating the HRD1 expression and suppressing neuronal cell death in a 6-hydroxydopamine (6-OHDA)-induced cellular PD model. Our screening by the Drug Gene Budger, a drug repositioning tool, identified luteolin as a candidate compound for the desired modulation of the HRD1 expression. Subsequently, we confirmed that low concentrations of luteolin did not show cytotoxicity in SH-SY5Y cells, and used these low concentrations in the subsequent experiments. Next, we demonsrated that luteolin increased HRD1 and SEL1L mRNA levels and protein expressions. Furthermore, luteolin inhibited 6-OHDA-induced cell death and suppressed ER stress response caused by exposure to 6-OHDA. Finally, luteolin did not reppress 6-OHDA-induced cell death when expression of HRD1 or SEL1L was suppressed by RNA interference. These findings suggest that luteolin might be a novel therapeutic agent for PD due to its ability to suppress ER stress through the activation of HRD1 and SEL1L.

Experience of Overseas Research on Electronic Health Literacy and Its Enlightenment to China in Public Health Emergencies / 中国医学伦理学

The Internet has become an important carrier of medical information.Good electronic health literacy can enhance the public’s ability to obtain correct medical and health information with the help of electronic resources,which is helpful for the public to use health information to prevent diseases,avoid drug abuse,reduce the waste of medical resources and strengthen the self-management of chronic diseases.The improvement of electronic health literacy is of great value to the healthy development of citizens’ health literacy and healthy behavior.In view of the late start and slow development in the field of electronic health literacy in China,by combing the theoretical and practical research experience of electronic health literacy outside the region and combining with the COVID-19,this paper put forward new thinking on electronic health literacy in China,in order to provide useful reference for improving electronic health literacy of Chinese citizens,realizing self-care,self-management and disease prevention.