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1.
J Plast Reconstr Aesthet Surg ; 99: 88-95, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39357139

RESUMO

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.

2.
J Sch Psychol ; 106: 101349, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39251310

RESUMO

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.


Assuntos
Emoções , Aprendizado Social , Estudantes , Humanos , Feminino , Haiti , Masculino , Projetos Piloto , Criança , Estudantes/psicologia , Instituições Acadêmicas , Habilidades Sociais , Currículo , COVID-19/psicologia , COVID-19/prevenção & controle , Avaliação de Programas e Projetos de Saúde
3.
Best Pract Res Clin Gastroenterol ; 71: 101931, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39209418

RESUMO

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.


Assuntos
Neoplasias Gastrointestinais , Humanos , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/patologia , Endoscopia Gastrointestinal/métodos , Ressecção Endoscópica de Mucosa/métodos , Resultado do Tratamento , Mucosa Intestinal/cirurgia , Mucosa Intestinal/patologia
4.
Elife ; 132024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028260

RESUMO

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.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Movimento Celular , Via de Sinalização Wnt , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas Wnt/metabolismo , Proteínas Wnt/genética , Receptores Frizzled/metabolismo , Receptores Frizzled/genética
5.
Eur J Investig Health Psychol Educ ; 14(7): 1996-2012, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39056648

RESUMO

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.

6.
J Sch Psychol ; 104: 101311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38871420

RESUMO

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.


Assuntos
Etnicidade , Instituições Acadêmicas , Habilidades Sociais , Estudantes , Criança , Feminino , Humanos , Masculino , Desenvolvimento Infantil/fisiologia , Emoções , Etnicidade/estatística & dados numéricos , Fatores Sexuais , Disparidades Socioeconômicas em Saúde , Fatores Socioeconômicos , Estudantes/psicologia , Estados Unidos , Negro ou Afro-Americano , Brancos , Hispânico ou Latino
7.
J Gen Virol ; 105(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38787366

RESUMO

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.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Degradação Associada com o Retículo Endoplasmático , Proteínas de Membrana , Ubiquitina-Proteína Ligases , Replicação Viral , Humanos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Vírus da Encefalite Japonesa (Espécie)/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Células HeLa , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Interações Hospedeiro-Patógeno , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/virologia , Proteínas/metabolismo , Proteínas/genética , Antígenos de Diferenciação
8.
Genetics ; 227(3)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717968

RESUMO

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.


Assuntos
Secretases da Proteína Precursora do Amiloide , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Células Germinativas , Receptores Notch , Transdução de Sinais , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Células Germinativas/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética
9.
Sci Rep ; 14(1): 9571, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671086

RESUMO

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.


Assuntos
Receptores de Antígenos de Linfócitos B , Humanos , Receptores de Antígenos de Linfócitos B/metabolismo , Glicosilação , Linhagem Celular Tumoral , Neoplasias da Retina/genética , Neoplasias da Retina/metabolismo , Neoplasias da Retina/patologia , Neoplasias da Retina/imunologia , Autoantígenos/imunologia , Autoantígenos/metabolismo , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/metabolismo , Feminino , Masculino , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia , Pessoa de Meia-Idade , Idoso
11.
Methods ; 225: 20-27, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38471600

RESUMO

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.


Assuntos
Cromatina , Nucleossomos , Humanos , Cromatina/genética , Cromatina/metabolismo , Nucleossomos/genética , Nucleossomos/metabolismo , Nylons/química , Nylons/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Animais , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Montagem e Desmontagem da Cromatina/genética , Genômica/métodos
12.
Front Surg ; 11: 1309202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533092

RESUMO

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.

13.
Front Med (Lausanne) ; 11: 1368858, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500950

RESUMO

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.

14.
Res Sq ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38260335

RESUMO

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.

15.
Neurochem Res ; 49(1): 117-128, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37632637

RESUMO

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.


Assuntos
Neuroblastoma , Doença de Parkinson , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Luteolina/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Regulação para Cima , Oxidopamina/toxicidade , Morte Celular , Proteínas/metabolismo , Ubiquitina/metabolismo
16.
Rheumatology (Oxford) ; 63(4): 1058-1067, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37449908

RESUMO

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.


Assuntos
Gota , Estomatite , Adulto , Humanos , Urato Oxidase/uso terapêutico , Urato Oxidase/efeitos adversos , Supressores da Gota/efeitos adversos , Ácido Úrico , Resultado do Tratamento , Exacerbação dos Sintomas , Polietilenoglicóis/efeitos adversos , Uricosúricos/uso terapêutico , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico
17.
Appl Psychol Health Well Being ; 16(1): 235-253, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37539776

RESUMO

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.


Assuntos
Emoções , Instituições Acadêmicas , Criança , Humanos , Cognição , Inquéritos e Questionários , Autorrelato
18.
Protein Sci ; 33(3): e4889, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160319

RESUMO

Legionella are freshwater Gram-negative bacteria that in their normal environment infect protozoa. However, this adaptation also allows Legionella to infect human alveolar macrophages and cause pneumonia. Central to Legionella pathogenesis are more than 330 secreted effectors, of which there are nine core effectors that are conserved in all pathogenic species. Despite their importance, the biochemical function of several core effectors remains unclear. To address this, we have taken a structural approach to characterize the core effector of unknown function LceB, or Lpg1356, from Legionella pneumophila. Here, we solve an X-ray crystal structure of LceB using an AlphaFold model for molecular replacement. The experimental structure shows that LceB adopts a Sel1-like repeat (SLR) fold as predicted. However, the crystal structure captured multiple conformations of LceB, all of which differed from the AlphaFold model. A comparison of the predicted model and the experimental models suggests that LceB is highly flexible in solution. Additionally, the molecular analysis of LceB using its close structural homologs reveals sequence and structural motifs of known biochemical function. Specifically, LceB harbors a repeated KAAEQG motif that both stabilizes the SLR fold and is known to participate in protein-protein interactions with eukaryotic host proteins. We also observe that LceB forms several higher-order oligomers in solution. Overall, our results have revealed that LceB has conformational flexibility, self-associates, and contains a molecular surface for binding a target host-cell protein. Additionally, our data provides structural insights into the SLR family of proteins that remain poorly studied.


Assuntos
Legionella pneumophila , Humanos , Legionella pneumophila/genética , Legionella pneumophila/química , Proteínas de Bactérias/química
19.
Aging (Albany NY) ; 15(22): 13150-13162, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37993256

RESUMO

BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear. METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting. RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more. CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Neoplasias Renais/genética , Fatores de Transcrição/genética
20.
Front Psychol ; 14: 1229653, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868591

RESUMO

Introduction: Despite increasing interest in measuring social and emotional learning (SEL), there is a lack of European-validated tools for assessing the efficacy of SEL programs. The aim of this study was to validate an Italian version of the social skills improvement system (SSIS) SEL brief scales-student form. Methods: Participants were 1,175 students (mean age: 11.02 years; SD: 2.42; range: 8-16 years; males: 46.8%) recruited at schools in Northern Italy. Statistical analyses and results: Initial confirmatory factor analysis encountered a series of challenges, implying non-convergence of the original five-factor measurement model (self-awareness, self-management, social awareness, relationship skills, and responsible decision-making) based on the Collaborative on Academic Social Emotional Learning (CASEL) competency framework established with students in the United States. Further exploratory and confirmatory analyses supported a four-factor model that remained partially invariant across gender groups. The Italian version of the SSIS SEL brief scales was thus shown to be an efficient measurement tool for estimating social and emotional learning in students. Discussion: We discuss the implications of findings in relation to selecting valid and reliable instruments for assessing children's and adolescents' SEL competencies, while considering the culturally-situated nature of the constructs under study.

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