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Studies have documented widespread academic disengagement in middle and high school students. This disengagement has been tied to a myriad of negative outcomes, including failure to graduate from high school and transition into college and meaningful vocations. Supporting adolescents in cultivating a sense of beyond-the-self purpose is one factor that may combat student disengagement. MPower is a program designed to cultivate beyond-the-self purpose in an effort to promote student engagement and completion of high school (Klein et al., 2019). In a recent quantitative study, MPower participants compared to controls demonstrated a higher GPA, BTS purpose, self-efficacy, and decreased performance approach and performance avoidance goal orientations. In the current qualitative descriptive study, 11th and 12th grade (N=25) students in the Northeastern region of the United States, described their experiences in the MPower program. Three themes associated with the transformative aspects of MPower emerged from focus group data: 1) practice in strategic goal planning, 2) engagement in mentoring relationships, and 3) increased social support within a community. Because fostering youth purpose engenders many promotive and protective factors, these findings hold important implications for implementing similar programs more widely.

Abstract Introduction The symptoms associated with Sjögren’s disease (Sjögren’s) are well-documented from the physician’s perspective. However, from the patient’s perspective, there is limited information on symptoms and their impact on health-related quality of life (HRQoL). This study aimed to provide an expanded understanding of patients’ experience of Sjögren’s and how symptoms impact HRQoL using a novel multi-method social media listening (SML) approach. Methods A total of 26,950 social media posts with relevant content on Sjögren’s posted by social media users from the USA, Canada, Australia, UK, France, Germany, Italy, Spain and China were analysed using an artificial intelligence natural language processing tool to explore patient conversations. Symptoms by level of impact on patients were characterised based on ‘commonness’ and ‘bothersomeness’. Applied concept association analysis was used to assess relationships between symptom domains and impact domains. A qualitative framework was applied to explore words and phrases patients use to describe symptoms and their impacts. Results Five of the identified symptom domains were very impactful: Pain; Dry Mouth and Throat; Fatigue, Energy and Sleep; Emotional Balance; and Dry Eye. The symptom domains Pain and Dry Mouth and Throat were the most common, while those of Emotional Balance and Fatigue, Energy and Sleep were the most bothersome. Symptom domains most closely associated with four HRQoL impact domains were Fatigue, Energy and Sleep, Dry Mouth and Throat and Dry Eye with Daily Functioning; Fatigue, Energy and Sleep with Financial Health; Emotional Balance with Psychological Wellbeing and Gynaecological Issues with Social Wellbeing. Conclusion The results of this SML study show that Sjögren's affects diverse aspects of patients’ lives, with symptoms extending beyond dry eyes and mouth and impacting daily living and functioning. Because symptoms may affect patients differently, these results highlight the importance of measuring impact on HRQoL to assess patient outcomes and treatment options in routine clinical practice and clinical trials.

This qualitative descriptive study analyzed the role that natural mentors had in cultivating a sense of purpose and meaning among 38 diverse male and female high school students. The "types" of mentoring support provided and the students' perceived "experiences" of receiving the support were considered in the analysis. Directed content analysis revealed four initial overarching types of supportive actions that were provided by mentors: emotional, instrumental, informational, and appraisal support. The types of support offered were further categorized across three dimensions of perceived support by the mentees: (a) affirmation (e.g., the experience of emotional and appraisal support), (b) cultivation (e.g., the experience of being challenged and obtaining skills), and (c) guidance (e.g., the experience of receiving information and advice). In order for mentees to perceive and accept cultivation and guidance support, they first needed to experience an affirming relationship with their mentors. Findings may inform best practices for mentoring youth toward lives of meaning and purpose.

The negative impact of discrimination on adolescent mental health is well established, but less is known about the effects of identity-based bullying (i.e., verbal or physical assaults targeting identity(ies)). The current study examined the impact of identity-based victimization (i.e., everyday discrimination and identity-based bullying) on mental health, and the protective role of teacher-student relationships, in a diverse sample of adolescents. Data from a diverse sample of 9th-12th graders (N = 986, 51% youth of Color, 52% cisgender girls, 22% sexual minorities, 41% free/reduced-price lunch status) in a semi-urban high school were analyzed using structural equation modeling analyses, including moderation and multi-group comparisons. Findings indicated that identity-based victimization is pervasive and negatively associated with mental health. Adolescents with stigmatized identities across sexual orientation, race, and gender faced a higher risk of experiencing identity-based victimization, and mental health challenges. Teacher-student relationships that were positive and autonomy-enhancing had a moderating effect on the association between identity-based victimization and mental health for many adolescents, such that they were not protective for those experiencing more severe victimization (i.e., high discrimination or identity-based bullying). Multigroup analyses indicated significant model fit differences across race and gender. Results suggest that extant school-based supports are not enough to combat the pervasive effects of identity-based victimization. Findings support the examination and implementation of changes in clinical and school-based practice and policy to better support stigmatized and victimized adolescents.

Purpose has been defined as an active engagement toward goals that are meaningful to the self (i.e., personal meaningfulness) and contribute to the world beyond the self (BTS). These BTS contributions may reflect the intention to meet a wide range of needs from family financial needs to more macro-level concerns, including social injustices. This study investigates the efficacy of a school-based program called MPOWER expressly designed by the authors to cultivate the BTS aspect of purpose. Previous research suggests that the BTS aspect of purpose has beneficial effects on school engagement, goal-setting abilities and orientations, and ultimately school performance. Ninety-four students participated in this study that utilized a randomized, pre-test-post-test between-subjects design to evaluate MPOWER (52 in MPOWER and 42 in the control group). The ANCOVA results indicated a significant increase in the BTS aspect of purpose among program participants, compared to controls. Moreover, participants had higher post-test levels of general self-efficacy and grade point averages, and decreased performance-approach (e.g., playing to be the best, comparing self to others) and performance-avoidance (e.g., avoiding risks of failure, fear of social consequences) goal orientations. Findings can be used to design programs that aim to cultivate students’ intentions to contribute to the world beyond themselves, as well as associated personal benefits (i.e., goal orientations, self-efficacy, academic performance).

Background: This study aimed to evaluate the efficacy and safety of secukinumab 150 mg compared with placebo in the management of spinal pain and disease activity in patients with axial spondyloarthritis (axSpA) at Week 8 and up to Week 24. Methods: Patients ( n = 380) with active axSpA were randomized (3:1) to secukinumab 150 mg (Group A) or placebo (Group B). At Week 8, patients from Group A with an average spinal pain score

In contrast to the focus on short-term, extrinsic goals in our society (e.g., wealth, prestige), positive youth development scholars have highlighted the need for parents and schools to help youths cultivate and plan for long-term, intrinsic, and meaningful goals (i.e., envisioning a meaningful future), arguing that envisioning a meaningful future is potentially inspiring and associated with better outcomes for youths. Envisioning a meaningful future includes being future-oriented and planful and having a sense of purpose, a life focus that provides deep meaning to life and contributes to the good of society. This study used structural equation modeling to examine the direct and indirect effects of parental and school relationships on envisioning a meaningful future and academic engagement in a diverse sample of adolescents (n = 624). Parental and school-based relationships were positively associated with academic engagement, and this association was partially mediated by envisioning a meaningful future. Analyses revealed the importance of parental and school relationships in engaging youths in developing a vision for a meaningful future toward the goal of academic engagement. Variations between African-Americans and Whites, and across grade and parental education levels are discussed.

Research-practice partnerships (RPPs) are ripe contexts for school counselors to employ data-driven practices to improve student outcomes. We leveraged an RPP between two universities and a high school to assist the latter's school counseling department in examining students' satisfaction with their counselor interactions. The RPP created the capacity for the counselors to gather and use data to implement targeted interventions for improving students' awareness and perceptions of their school counselors.

Abstract Spondyloarthritis comprises a group of inflammatory diseases, characterised by inflammation within axial joints and/or peripheral arthritis, enthesitis and dactylitis. An increasing number of biologic treatments, including biosimilars, are available for the treatment of spondyloarthritis. Although there are a growing number of randomised controlled trials assessing treatments in spondyloarthritis, there is a paucity of data from head-to-head studies. Comparative data are required so that clinicians and payers have the level of evidence required to inform clinical decision-making and health economic assessments. In the absence of head-to-head studies, statistical methods such as network meta-analyses and matching-adjusted indirect comparisons (MAICs) are used for assessing comparative effectiveness. Network meta-analysis can be used to compare treatments for trials using a common comparator (e.g. placebo); however, for those without a common comparator or where considerable heterogeneity exists between the study populations, a MAIC that controls for differences in study design and baseline patient characteristics may be used. MAICs, unlike network meta-analyses, are of value for longer-term comparisons beyond the placebo-controlled phase of clinical trials, which is important for chronic diseases requiring long-term treatment, like spondyloarthritis. At present, there are a number of limitations that restrict the effectiveness of MAIC, such as the poor availability of individual patient-level data from trials, which results in patient-level data from one trial being compared with published whole-population data from another. Despite these limitations, drug reimbursement agencies are increasingly accepting MAIC as a means of comparative effectiveness and greater methodological guidance is needed. This report highlights a number of challenges that are specific to conducting comparative studies like MAIC in spondyloarthritis, including disease heterogeneity, the paucity of biomarkers and the duration of studies required for radiographic endpoints in this slow-progressing disease.

Development of a clinically applicable liquid biopsy-based test for PD-L1 mRNA expression would be beneficial in providing complementary evidence to current immunohistochemistry assays. Hence, we report the development of a fit-for-purpose assay for detection of blood PD-L1 mRNA expression using droplet digital polymerase chain reaction (ddPCR). TaqMan® assays were selected based on coverage of the PD-L1 gene and were tested for linearity and efficiency using real-time quantitative PCR. Four reference genes were analyzed in positive control cell line (A549 treated with interferon gamma, [IFN γ]) genomic DNA. The PD-L1 primer/probe sets were also evaluated in ddPCR for limit of blank, limit of detection, and precision. Finally, thirty-five healthy volunteer samples were evaluated to establish a baseline level of PD-L1 expression. In ddPCR, the limit of blank was determined to be 0 copies and the limit of detection was determined to be less than or equal to 19 copies of PD-L1. The average intra-run coefficient of variation in the ddPCR assay was 7.44% and average inter-run CV was 7.70%. Treatment of A549 cells with IFN γ resulted in a 6.7-fold increase in PD-L1 expression (21,580 copies in untreated cDNA versus 145,000 copies in treated cDNA). Analysis of healthy human samples yielded a median value of 1659 PD-L1 copies/μL with a range of 768-7510 copies/μL. The assay was transferred to an external service provider and results from our in-house experiments and those conducted externally shows a correlation of 0.994. In conclusion, a fit-for-purpose liquid biopsy-based, purely quantitative ddPCR assay for the detection of PD-L1 mRNA expression was developed and validated using PAXgene RNA blood samples. Linearity, reproducibility, limit of blank and limit of detection were measured and deemed suitable for clinical application. This ultra-sensitive liquid biopsy ddPCR assay has promising clinical potential in screening, longitudinal monitoring and disease progression detection.

Arrigo Boito (1842-1918) is the author of the four tales presented here for the first time in English translation: The Black Ensign, Clenched Fist, Iberia, and Trapeze. Outside of Italy, he is known almost exclusively as the composer of Mefistotele, an opera for which he himself wrote the libretto. He is in fact equally esteemed as a consummate librettist, above all for the remarkable texts he created for Giuseppe Verdi’s last two masterpieces, Otello, and Falstaff. But in his homeland, he ranks rather high among the literati as a significant poet in the period when Italian political unification (1860-1870) was at long last realized, and he and a number of other young literary rebels generally referred to as the "Scapigliati" (the disheveled or disorderly ones) wrote works meant to shock the complacent insular culture of the Italian bourgeoisie into a broader European context. The chief targets of their polemic were religion – more specifically Roman Catholicism – and the prevailing maudlin romanticism of the time, so unlike the writings of Manzoni, Foscolo, and Leopardi in the earlier decades of the century.

Aims: Chronic high fat consumption has been shown to modulate nutrient transporter content in the intestine of obese mice; however it is unclear if this regulation occurs before or after the establishment of obesity, and the underlying molecular mechanism requires elucidation. Main methods: Towards this goal C57BL/6 mice were fed a low fat diet (LFD) or high fat diet (HFD), and specific protein and gene expression levels were assessed for up to 12 weeks. Similar experiments were also performed with leptin-deficient (Ob/Ob) mice. Key findings: The results showed that the HFD group presented decreased GLUT2, PEPT1, FAT/CD36 and NPC1L1, and increased NHE3, MTTP and L-FABP content. Animals fed an HFD also presented enhanced lipid transporter gene expression of Slc27a4, Npc1l1, Cd36, Mttp and L-Fabp. Additionally, FAT/CD36 and NPC1L1 protein levels were reduced in both HFD-induced obese and Ob/Ob mice. Ob/Ob mice also exhibited increased Slc2a2 and Slc15a1 mRNAs expression, but the protein expression levels remained unchanged. The HFD also attenuated PKA and PKC activities. The inhibition of PKA was associated with decreased FAT/CD36 content, whereas increased L-FABP levels likely depend on CREB activation, independent of PKA. It is plausible that the HFD-induced changes in NPC1L1, MTTP and L-FABP protein content involve regulation at the level of transcription. Moreover, the changes in GLUT2 and PEPT1 content might be associated with low PKC activity. Significance: The results indicated that an HFD is capable of reducing nutrient transporter content, possibly attenuating nutrient uptake into the intestine, and may represent a feedback mechanism for regulating body weight. Furthermore, the elevated levels of NHE3, L-FABP and MTTP may account for the increased prevalence of hypertension and dyslipidemia in obese individuals. All of these changes are potentially linked to reduced PKA or PKC activities.

Objectives: To evaluate, using musculoskeletal ultrasound (MSUS), the effects of Etanercept therapy in patients with rheumatoid arthritis (RA) over 3 months of treatment. Methods: Eighteen consecutive patients, 3 male and 15 female, affected by RA (ACR criteria) who were non-responders or partial responders to DMARDs therapy were commenced on Etanercept treatment. MSUS was performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist and knee joints, using a Philips/HP Image Point HX machine with a 7,5 MHz linear probe for knee joints and a 14 MHz probe for the hands and wrists. In addition, power Doppler was used with the following settings: PRF 700-1000Hz, gain 60-65 dB, low filter. For all the changes a semi-quantitative score (0-3) was used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis). An overall score was then calculated based on the sum of the single scores in order to obtain a comprehensive score indicative of the global pathological change. Results: The overall score significantly (p

The ban of transgenic feed and synthetic amino acids in organic chicken diets has made necessary to find protein-rich feedstuffs which do not alter productive performance. The effect of the faba bean (Vicia faba var. minor) as a partial substitute for soybean on the performance and carcass traits of slow-growing chickens of both sexes reared under the organic method was assessed. The experiment was carried out in the spring and autumn; one thousand birds per season were split into 8 groups (4 groups of males and 4 groups of females, each duplicated) and fed a double phase diet: a common starter diet for 20 days and two different growing-finisher diets containing either soybean (24%; S) or faba bean (16%; F) till the end of the rearing period (120 d). Average values of final live weight, feed intake and daily weight gain were significantly affected by sex, being higher in males than in females; the diets affected performance only in the 21-60 days of age period when the F group grew less and had poorer feed efficiency compared to the S group. Successively, the compensatory growth eliminated differences in slaughter weight. Regarding carcass traits, the diet affected only the ready- to-cook carcass percentage and the carena length, both of which were higher in S birds. Faba beans could be a valuable protein source in the diet of organic chickens when used after the critical starter period.

The aim of this study was to evaluate the accuracy and reproducibility of computed tomography (CT) image interpretation made in axial slices (2D-CT) and 3D reconstructed images (3D-CT) of patients with craniofacial anomalies. The analyses were made by undergraduate dental students, and compared with the diagnoses considered upon surgical intervention. Computed tomography of 43 patients were analyzed independently by three calibrated examiners (undergraduate students) with, respectively, one, two, and three semesters of experience in craniofacial CT training and interpretation. The analysis of 2D-CT and 3D-CT images were performed at distinct times using an independent workstation associated with a specific computer graphics software for volumetric images. The analysis of inter-examiner agreement and of the agreement between observers and the gold standard was performed using the Kappa test. The accuracy evaluation presented a progressively higher value for examiners with progressively broader experience in 2D-CT and 3D-CT image interpretation. 3D-CT analyses allowed a higher inter-examiner agreement (1 - 0.896) than 2D-CT analyses (1 - 0.614). 3D-CT was considered more precise and accurate than 2D-CT for all students' evaluations. The reproducibility and accuracy varied according to the experience in CT interpretation, and the most experienced student achieved results closer to the gold standard.O propósito desta pesquisa foi avaliar a habilidade de alunos de graduação na análise de pacientes portadores de anomalias craniofaciais usando imagens de tomografia computadorizada (TC) em cortes axiais (2D-TC) e em terceira dimensão (3D-TC). A análise foi realizada por alunos de graduação em Odontologia, em comparação com o diagnóstico efetuado no ato operatório. Tomografias computadorizadas de 43 pacientes foram analisadas, independentemente, por três alunos de graduação previamente calibrados, com respectivamente um, dois e três semestres de tempo de experiência em interpretação de TC. As análises das imagens em 2D-TC e em 3D-TC foram obtidas em tempos e ocasiões distintos por meio de uma estação de trabalho independente utilizando-se um programa específico para imagens volumétricas. Para análise de concordância entre os observadores e destes com o diagnóstico definitivo foi utilizado o teste estatístico Kappa. Os valores de acurácia foram maiores quanto maior o tempo de experiência em interpretar imagens em 2D-TC e em 3D-TC. As análises em 3D-TC apresentaram indicadores mais elevados de concordância entre os examinadores (1 - 0,896) que as análises em 2D-TC (1 - 0,614). A 3D-TC foi considerada mais precisa e acurada em relação à 2D-TC na avaliação dos três alunos. A concordância entre os examinadores e entre estes e o diagnóstico variou de acordo com o tempo de treinamento em TC, sendo o aluno mais experiente aquele que obteve resultados mais próximos ao diagnóstico.

The aim of this study was to evaluate the precision and accuracy of linear measurements of maxillary sinus made in tomographic films, by comparing with 3D reconstructed images. Linear measurements of both maxillary sinus in computed tomography CT of 17 patients, with or without lesion by two calibrated examiners independently, on two occasions, with a single manual caliper. A third examiner has done the same measurements electronically in 3D-CT reconstruction. The statistical analysis was performed using ANOVA (analyses of variance). Intra-observer percentage error was little in both cases, with and without lesion; it ranged from 1.14% to 1.82%. The inter-observer error was a little higher reaching a 2.08% value. The accuracy presented a higher value. The perceptual accuracy error was higher in samples, which had lesion compared to that which had not. CT had provided adequate precision and accuracy for maxillary sinus analyses. The precision in cases with lesion was considered inferior when compared to that without lesion, but it can't affect the method efficacy.O objetivo deste trabalho foi avaliar a precisão e acurácia de medidas lineares da região de seio maxilar realizadas em filmes tomográficos, por meio de comparação com a reconstrução da imagem em 3D. Medidas lineares de ambos os seios maxilares foram realizadas em tomografias computadorizadas (2D-TC) de 17 pacientes, normais e com lesão, por dois examinadores, calibrados, separadamente, duas vezes cada um, utilizando um compasso. Um terceiro observador realizou as mesmas medidas eletronicamente na reconstrução 3D-TC. ANOVA (análise de variância) foi utilizado para análise estatística. A porcentagem de erro intra-examinadores foi pequena em ambos os casos, com ou sem lesão, variando de 1,14% a 1,82%. O erro inter-examinadores foi maior alcançando o valor de 2,08% .O erro percentual de acurácia nas amostras com lesão foram maiores comparando-as às que não tinham lesão. A tomografia computadorizada em 2D-TC (Em filmes e estação de trabalho independente) proporcionou precisão e acurácia adequadas para análise dos seios maxilares. "O erro foi maior no caso de seios maxilares com lesão,comparando aos lados sem lesão, tanto inter quanto intra-examinadores, sem alterar, porém, a eficácia do método."

Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (Trsp(tG37) ) and/or a cancer driver TGFα transgene. The use of Trsp(tG37) altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. Trsp(tG37) transgenic and TGFα/Trsp(tG37) bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGFα transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGFα transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGFα-induced liver tumors.

The COVID-19 pandemic has dramatically impacted anaesthetic services and the delivery of anaesthetic training across the UK and internationally [1, 2]. The mean number of logbook cases recorded per trainee from March 2020 to March 2021 (during the pandemic) was compared with the aggregated mean from the same periods in the 4 years preceding the pandemic (March 2016-March 2020). 1 TableMean annual number of cases logged per trainee (excluding critical care cases) during the pandemic (2020-2021) and aggregated pre-pandemic annual mean cases (2016-2020). [Extracted from the article]

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Five years after the death of John Paul II, the Author offers a synthesis of the late Pontiff's Marian teaching, which is deepy rooted in the doctrine of the Second Vatican Ecumenical Council, in which he himself had taken part. Thus John Paul II emphasized particularly the presence of the Handmaid of the Lord in the mystery of God in Christ and in that of the Church, as related to the men and women of our time. He thus favoured a Marian spirituality solid in its contents and in harmony with the liturgy. Salient points of his teaching in this Summary sense were the Encyclical, "Redemptoris Mater" (1987), the Apostolic Letter, "Mulieris dignitatem" (1988), the Apostolic Letter, "Rosarium Virginis Mariae (2002) and the Marian chapter in the Encyclical, "Ecciesia de Eucharistia" (2003). Likewise the seventy Marian catecheses he delivered I 1995-1997 form a kind of "Life of Mary, in the light of the Word of God, Tradition and the ecclesiastical Magis- terium. But, consistent with the teaching of the Council, the references to Mary are to be found integrated everywhere in his teaching documents, just as thry are organically integrated in the four parts ofthe Catechism ofthe Catholic Church that he promulgated. Mary's is an intrinsic presence in the Christ Event, as setforth by John Paul II, with its Trinitarian and Christological perspective. Hence the appropriateness of thinking of him as the Doctor Marianus of our time. [ABSTRACT FROM AUTHOR]