Positive Inclusions Research Articles

Demand Side Factors and Financial Inclusion: The Mediating Role of Financial Self-efficacy

Despite the recognized significance of achieving financial inclusion in Nigeria,there is limited studies in this area. This gap primarily arises from the prevailingfocus in existing literature on financial inclusion in Nigeria, which predominantlyemphasizes the supply side. Therefore, this study delved into the role of financial selfefficacyas a mediator in the relationship between demand-side factors and the financialinclusion of micro, small, and medium enterprises (MSMEs) in selected local governmentsin Oyo State. The study employed a cross-sectional survey design, the studygathered primary data through structured questionnaires and utilized a structuralequation model for analysis. The findings reported a significant positive link betweenfinancial attitude and financial inclusion (p-value: 0.000). Likewise, there was a noteworthypositive association between subjective norms and financial inclusion (p-value:0.001), as well as between personal experience and financial inclusion (p-value: 0.003). Intriguingly, financial self-efficacy emerged as a substantial obstacle to financial inclusion,acting as a mediating factor with a p-value of (0.002). By evaluating the mediationeffect, this study shows how financial self-efficacy enhance individuals MSMEs ownersto confidently undertake financial tasks and decisions and consequently, financial inclusion in relation to their attitude, experience and subjective norms respectively. Consequently,the study recommends the promotion of positive financial attitudes amongindividual MSMEs to facilitate continuous access to diverse financial services. Financialservice providers should prioritize the establishment of an effective and sustainablefinancial system that offers affordable services to MSMEs. Furthermore, communityleaders are encouraged to play a role in motivating their members to actively engage inthe formal financial sector.

Determinants of Participatory Intention in Autism Volunteer Work for Improving Quality of Life of Persons with Autism (PWA) and their Caregivers

Evidence-based psychosocial interventions can enhance communication and social abilities, leading to a favorable effect on the overall welfare and quality of life for individuals with autism and those who care for them. Despite the importance of volunteers in supporting individuals with autism and their families, there is limited research on the factors influencing individuals' decisions to participate in autism-related volunteer work. This study aims to bridge this gap by investigating the various factors that shape individuals' intentions to participate in volunteer activities related to autism. A cross-sectional study design with a purposive sampling technique was conducted. Data obtained from a survey questionnaire polled ninety-nine university students’ attitudes regarding the factors influencing their participatory intention in autism volunteer work. Descriptive statistics show that the participation intention level among university students was high (M=4.47, SD=0.52). There was a statistically significant strong and moderate relationship between attitude, subjective norms, perceived behavioral control, self-efficacy and religiosity toward participation intention. The regression analysis revealed that subjective norms, perceived behavior control and religiosity affected participatory intention. This study provided practical implications for designing and implementing effective interventions and programs to recruit and retain volunteers, as well as to promote positive social change and inclusion for people with autism.

A Ghanaian Approach to Disability Literature in Picture Books

In this study, we examined how Ghanaian picture books present disabilities. Using a content-analysis approach, the primary goal was to deduce how picture books serve to promote positive attitudes and inclusion of students with disabilities in schools in Ghana. Data included the text and visuals of seven picture books published in 2016 by Curriculum Research and Development Division of Ghana Education Services (now known as the National Council for Curriculum and Assessment), a branch of the Ghana Ministry of Education. The findings show that picture books provide an opportunity to address issues of stigma related to learning and physical disabilities, while explaining disability to non-disabled readers and disabled readers, who identify with stories about children who are like them. The process of reading stories to and with children can act as a cultural-awareness indicator. This study of children’s literature, and others like it, serve as an educational support for the inclusion of students with disabilities in inclusive classroom settings. Picture books can help to increase disability awareness in young people.

Workforce diversity in Cambodia: Does it make differences in employees' perceptions?

AbstractThis study explored the dynamics of workforce diversity and employees' perceptions of inclusion, fairness, organization support, and leader‐member exchange (LMX) in Cambodia. The survey was conducted with 90 participants in international non‐profit organizations. Data was analyzed using the nonparametric tests. Among diversity characteristics, gender and religion were associated with differences in interactional fairness and LMX. Marital status and educational level produced differences in LMX and distributive fairness, respectively. Further, higher job positions were found to be associated with positive inclusion and LMX. This study points to the necessity of establishing a culture of diversity and inclusion in Cambodian workplaces.

Workplace inclusion in higher education philanthropy

Positive workplace inclusion is important for any business today, but especially so for higher education philanthropy. Higher education philanthropy suffers from high turnover and lack of diversity, making successful workplace inclusion urgent. Higher education philanthropy exacerbates low diversity and high turnover through education bias, compensation and opportunity imbalance, work culture expectations that favour in-group members, low task interdependency, isolation from co-workers, low support from leadership, and burnout. To address the primary challenge of turnover, this paper proposes unit-level measures that higher education philanthropy offices might use to increase inclusion, promote diversity and improve work group performance and morale.

The Racialized American Dream: Predictors for the 21st Century

ABSTRACT The American Dream has long been understood as a “shorthand summary of a nation’s collective aspirations” (Hauhart 2015:65). What determines optimism about the Dream? This paper uses nationally representative data collected at a critical historical juncture to advance research which has connected the American Dream to America’s racial history. We find faith in the American Dream was racialized into the 21st-Century, both in the sense that our data show different levels of optimism toward the Dream by race and in that predictors of belief vary by racialized experiences and ideologies. We find that most Americans continued to believe in the American Dream, but contrary to prominent 20th-Century understandings, whites became less optimistic than persons of color, and that this remaining white belief was complex, with racial attitudes being central. Predictors of belief in the Dream were different by race in ways that may vitally reflect how collective aspirations are conceived from within unfolding American racial civic histories and 21st-Century racial hierarchies, patterns we discuss as privileged multiculturalism (whites), meritocratic incorporation (Hispanics), and positive social inclusion (Blacks). Ultimately, these findings suggest that the socio-cultural significance of the American Dream is not just tied to material position but intertwined with racialized cultural expectations, outlooks, and status concerns.

Sex Diversity and Equity Among Fellows of the American Orthopaedic Association.

We hypothesized that women are underrepresented among fellows of the American Orthopaedic Association (AOA) relative to their prevalence among faculty at departments of orthopaedic surgery. Clinical faculty at departments of orthopaedic surgery that are affiliated with residency training programs were analyzed for AOA membership. Participation-to-prevalence ratios (PPRs) were calculated for men and women with AOA membership relative to their prevalence among orthopaedic surgeon faculty. A PPR of <0.8 or >1.2 indicated under- or overrepresentation, respectively. PPR values between 0.8 and 1.2 indicated equivalent representation. Sex disparities in AOA membership were explored by academic rank and orthopaedic subspecialty. There were 4,310 orthopaedic surgery faculty, and 998 (23.2%) had AOA membership. Overall, women formed the minority of members in the AOA study cohort (11.4%), but they had equivalent representation relative to their prevalence among faculty (10.0%, PPR = 1.14, p = 0.210). In the AOA study cohort, women were the minority at each academic rank, including assistant professor (20.2% versus 79.8%, p < 0.001), associate professor (16.8% versus 83.2%, p < 0.001), and full professor (7.0% versus 93.0%, p < 0.001). However, women had greater representation in the AOA study cohort at each academic rank than would be expected based on their prevalence among faculty, including the assistant (PPR = 1.45), associate (PPR = 1.56), and full (PPR = 1.27) professor levels. Similarly, in the AOA study cohort, women were the minority in each orthopaedic subspecialty, but were only underrepresented in pediatric orthopaedics (PPR = 0.74). Women had greater representation in the AOA study cohort than would be expected by their prevalence among faculty in hand surgery (PPR = 1.51) and orthopaedic sports medicine (PPR = 1.33). In contrast, men had equivalent representation in each orthopaedic subspecialty. Women form a minority group in the AOA, but they exhibit greater representation in the AOA than would be expected based on their prevalence among faculty at each academic rank, and they have greater representation than men, who exhibit equivalent representation across all academic ranks. Collectively, these results disproved our hypothesis, and suggest that women are participating in the AOA at rates that are greater than their prevalence among faculty. Equitable participation of women in orthopaedic surgery is necessary to promote diversity and inclusion in the specialty. The AOA may be an important catalyst for future positive diversity and inclusion efforts within orthopaedic surgery.

Altered expression of human myxovirus resistance protein A in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. The etiology of sporadic ALS (sALS) has not yet been clarified. An increasing body of evidence suggests the involvement of viral infections and interferons (IFNs). Human myxovirus resistance protein A (MxA) is an IFN-induced dynamin-like GTPase that acts as a potent antiviral factor. This study examined MxA expression in ALS patient spinal cords using immunohistochemistry. Thirty-two cases of sALS (pathologically proven ALS-TDP), 10 non-ALS, other neurological disease control cases were examined. In most ALS cases, MxA cytoplasmic condensates were observed in the remaining spinal anterior horn neurons. The ALS group had a significantly higher rate of MxA-highly expressing neurons than the non-ALS group. Colocalization of MxA cytoplasmic condensate and transactive response DNA-binding protein 43 kDa (TDP-43)-positive inclusions was rarely observed. Because MxA has antiviral activity induced by IFNs, our results suggest that IFNs are involved in the pathogenesis of ALS in spinal cord anterior horn neurons. Our study also suggests that monitoring viral infections and IFN activation in patients with ALS may be critically important.

Comparative analysis of brain language templates with primary language areas detected from presurgical fMRI of brain tumor patients.

Functional brain templates are often used in the analysis of clinical functional MRI (fMRI) studies. However, these templates are mostly built based on anatomy or fMRI of healthy subjects, which have not been fully vetted in clinical cohorts. Our aim was to evaluate language templates by comparing with primary language areas (PLAs) detected from presurgical fMRI of brain tumor patients. Four language templates (A-D) based on anatomy, task-based fMRI, resting-state fMRI, and meta-analysis, respectively, were compared with PLAs detected by fMRI with word generation and sentence completion paradigms. For each template, the fraction of PLA activations enclosed by the template (positive inclusion fraction, [PIF]), the fraction of activations within the template but that did not belong to PLAs (false inclusion fraction, [FIF]), and their Dice similarity coefficient (DSC) with PLA activations were calculated. For anterior PLAs, Template A had the greatest PIF (median, 0.95), whereas Template D had both the lowest FIF (median, 0.074), and the highest DSC (median, 0.30), which were all significant compared to other templates. For posterior PLAs, Templates B and D had similar PIF (median, 0.91 and 0.90, respectively) and DSC (both medians, 0.059), which were all significantly higher than that of Template C. Templates B and C had significantly lower FIF (median, 0.061 and 0.054, respectively) compared to Template D. This study demonstrated significant differences between language templates in their inclusiveness of and spatial agreement with the PLAs detected in the presurgical fMRI of the patient cohort. These findings may help guide the selection of language templates tailored to their applications in clinical fMRI studies.

High-fat diet consumption promotes adolescent neurobehavioral abnormalities and hippocampal structural alterations via microglial overactivation accompanied by an elevated serum free fatty acid concentration

Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.

Consensus-Derived Recommended Skills for Transition to Residency Courses.

Transition to residency (TTR) courses facilitate the medical student-residency transition and are an integral part of senior medical student training. The authors established a common set of skills for TTR courses, and an expected level of entrustment students should demonstrate in each skill on TTR course completion. A modified Delphi approach was used with 3 survey iterations between 2020 and 2022 to establish skills to be included in a TTR course. Nine TTR experts suggested general candidate skills and conducted a literature search to ensure no vital skills were missed. A stakeholder panel was solicited from email lists of TTR educators, residency program directors, and residents at the panelists' institutions. Consensus was defined as more than 75% of participants selecting a positive inclusion response. An entrustment questionnaire asked panelists to assign a level of expected entrustment to each skill, with 1 indicating observation only and 6 indicating perform independently. The stakeholder panel initially consisted of 118 respondents with representation across educational contexts and clinical specialties. Response rates were 54% in iteration 2, 42% in iteration 3, and 33% on the entrustment questionnaire. After 3 iterations, 54 skills met consensus and were consolidated into 37 final skills categorized into 18 clinical skills (e.g., assessment and management of inpatient concerns), 14 communication skills (e.g., delivering serious news or having difficult conversations), 4 personal and professional skills (e.g., prioritization of clinical tasks), and 1 procedural skill (mask ventilation). Median entrustment levels were reported for all skills, with 19 skills having a level of expected entrustment of 4 (perform independently and have all findings double-checked). These consensus skills can serve as the foundation of a standardized national TTR curriculum framework. Entrustment guidance may help educational leaders optimize training and allocation of resources for TTR curriculum development and implementation.

Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase

Comorbid proteinopathies are observed in many neurodegenerative disorders including Alzheimer’s disease (AD), increase with age, and influence clinical outcomes, yet the mechanisms remain ill-defined. Here, we show that reduction of progranulin (PGRN), a lysosomal protein associated with TDP-43 proteinopathy, also increases tau inclusions, causes concomitant accumulation of α-synuclein and worsens mortality and disinhibited behaviors in tauopathy mice. The increased inclusions paradoxically protect against spatial memory deficit and hippocampal neurodegeneration. PGRN reduction in male tauopathy attenuates activity of β-glucocerebrosidase (GCase), a protein previously associated with synucleinopathy, while increasing glucosylceramide (GlcCer)-positive tau inclusions. In neuronal culture, GCase inhibition enhances tau aggregation induced by AD-tau. Furthermore, purified GlcCer directly promotes tau aggregation in vitro. Neurofibrillary tangles in human tauopathies are also GlcCer-immunoreactive. Thus, in addition to TDP-43, PGRN regulates tau- and synucleinopathies via GCase and GlcCer. A lysosomal PGRN–GCase pathway may be a common therapeutic target for age-related comorbid proteinopathies.

The impact of microboards on social and community inclusion of adults with intellectual and developmental disabilities: “To not just exist, but to truly live”

Social relationships and community networks have received significant attention for enhancing positive quality of life and inclusion among people with intellectual and developmental disabilities. One community-based initiative that has the potential to promote and strengthen community inclusion of people with intellectual and developmental disabilities is through a MicroboardTM. Utilizing a qualitative descriptive approach, this study explored the experiences of people involved in microboards to learn if and how microboards may influence and strengthen social and community connections. In-depth, semi-structured interviews were conducted with 23 participants involved in microboards in British Columbia, Canada; and data were analysed using thematic analysis. The findings suggest three key roles of microboards including being (i) person-centered, (ii) empowering, and (iii) facilitating collective participation. These key roles and ways to enhance them are important to consider for initiatives designed to strengthen positive social connections and community inclusion outcomes for people with intellectual and developmental disabilities.

Priority populations’ experiences of the accessibility and inclusion of recreation centres: a qualitative study

BackgroundAlthough the health benefits of physical activity are well documented, certain priority populations are often disproportionately insufficiently active and at higher risk of poor health. Recreation centres have the potential to provide accessible and supportive environments for physical activity for all. However, little is known about priority populations’ experiences of these venues and their views of how accessibility and inclusion can be optimised. This study aimed to gain in-depth insights of recreation centre experiences and potential strategies for improving inclusion and accessibility amongst priority populations (women, older adults, ethnic minorities, persons living with disabilities/additional needs, individuals identifying as LGBTQIA+, low socio-economic position).MethodsThis qualitative study (2021–2022) involved 18 semi-structured individual interviews with adult priority population users of recreation centres (50% 65 + years, 61.2% female) in one Melbourne municipality. Participants were asked to discuss their positive and negative experiences at the centres and to identify strategies for enhancing accessibility and inclusion. Interviews were audio-recorded and transcribed verbatim. Content analysis was performed for data analysis.ResultsWhile many participants had positive views of the facilities and programs at the centres, as they met their needs, they also had suggestions for improving accessibility and inclusion. Similarly, most participants were happy with the communications, felt included, and perceived the culture positively. Those who did not feel included at the centres offered many potential strategies for changing the culture, modifying communications (e.g., signage), and establishing partnerships for better access and inclusion.ConclusionsThe present study adds to essential knowledge concerning priority populations’ experiences of recreation centres. For recreation facilities that were generally perceived as having positive inclusion and accessibility, the findings nonetheless highlighted suggestions for further enhancement. These strategies may be useful more broadly for improving accessibility and inclusion, thereby promoting physical activity and ultimately health for all.

Beyond the consultation and the medication: collective activities and resocialization in a CAPS I.

to evaluate the collective and resocialization activities developed in a CAPS I, from the perspective of users, family members and service professionals. evaluative research, anchored in the theoretical-methodological framework of the Fourth Generation Evaluation, conducted with 11 users, six family members and 10 professionals from a Psychosocial Care Center I. It took place from September 2021 to August 2022, using prior ethnography, interviews and negotiation, with data analysis using the Constant Comparative Method. participants pointed out that therapeutic workshops, support groups and collective meetings are held, which take place mainly in the physical space of the service, with adequate operationalization and frequency, facilitated by the professionals' attitude and the provision of transportation and food. It was assessed that these actions had an impact on the psychosocial care offered, resulting in treatment adherence, improved interpersonal relationships within the service and community, emergence of positive feelings, social inclusion and support for coping with difficulties. The challenges are the support group schedule and the participation of children and adolescents. collective and resocialization activities were evaluated as essential for the psychosocial care offered at CAPS, providing significant benefits to users, promoting interaction, social inclusion, interpersonal relationships and coping with adversities.

Nutritional Quality, Amino Acid Profile and Phytochemicals of High Protein-fibre Cookies Produced from Whole Wheat, Orange-fleshed Sweet Potato, Defatted Peanut and Rice Bran Composite Flour

This study evaluated the nutritional qualities of cookies from whole wheat (WW), orange-fleshed sweet potato (OFSP), defatted peanut (DPN) and rice bran (RB) composite flour. The flours (WPRG 1, 2 and 3) were formulated at different ratios (5.00-37.50%) and 100% WW flour (as control). The improved protein (13.54 ̵ 18.91%) and fibre (2.96 ̵ 8.65%) of the cookies depicted the positive inclusion of OFSP, DPN and RB flours. However, the essential minerals were significantly (p≤0.05) high in the composite cookies with no traces of heavy metals. Besides, the hydrophobic amino acids (24.10 ̵ 28.91%) and biological value (74.07 ̵ 89.77%) of the cookies showcased their potential bio-availability in some cardio-disease management. Their phenol (100.28-220.35 mg/100g) and tannin (53.40-76.50 mg/100 g) contents significantly (p≤0.05) enhanced their antioxidative power. The cookies produced from 56.25% WW, 18.75% OFSP, 5% RB and 20% DPN composite flour were mostly preferred by the consumers’ ratings. Finally, the added peanut and rice bran flours showed no significant (p&lt;0.05) effect on the physical properties, acceptability and preference of the cookie samples. Hence, we conclude that it is possible to produce better and high nutritional (protein, fibre, etc.) cookies from whole wheat, OFSP, defatted peanut and rice bran composite flours.

The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.

TAR DNA binding protein of 43 kDa (TDP-43)-positive inclusions in neurons are a hallmark of several neurodegenerative diseases including familial amyotrophic lateral sclerosis (fALS) caused by pathogenic TARDBP variants as well as more common non-Mendelian sporadic ALS (sALS). Here we report a G376V-TDP-43 missense variant in the C-terminal prion-like domain of the protein in two French families affected by an autosomal dominant myopathy but not fulfilling diagnostic criteria for ALS. Patients from both families presented with progressive weakness and atrophy of distal muscles, starting in their fifth to seventh decade. Muscle biopsies revealed a degenerative myopathy characterized by accumulation of rimmed (autophagic) vacuoles, disruption of sarcomere integrity and severe myofibrillar disorganization. The G376V variant altered a highly conserved amino acid residue and was absent in databases on human genome variation. Variant pathogenicity was supported by in silico analyses and functional studies. The G376V mutant increased the formation of cytoplasmic TDP-43 condensates in cell culture models, promoted assembly into high molecular weight oligomers and aggregates in vitro, and altered morphology of TDP-43 condensates arising from phase separation. Moreover, the variant led to the formation of cytoplasmic TDP-43 condensates in patient-derived myoblasts and induced abnormal mRNA splicing in patient muscle tissue. The identification of individuals with TDP-43-related myopathy, but not ALS, implies that TARDBP missense variants may have more pleiotropic effects than previously anticipated and support a primary role for TDP-43 in skeletal muscle pathophysiology. We propose to include TARDBP screening in the genetic work-up of patients with late-onset distal myopathy. Further research is warranted to examine the precise pathogenic mechanisms of TARDBP variants causing either a neurodegenerative or myopathic phenotype.

The AppNL‐G‐F/MAPT mouse model of Alzheimer’s Disease demonstrates increased levels of ptau217 in CSF, changes that correlate with increased cerebral p‐tau depositions

AbstractBackgroundCerebrospinal fluid (CSF) biomarkers reflecting the neuropathological hallmarks of Alzheimer’s disease (AD) have during the two last decades been developed and are commonly used to diagnose patients with AD patients. Previous studies have shown that CSF p‐tau217 particularly well can separate AD patients from healthy controls and that CSF levels of ptau217 correlate significantly with the amyloid burden and tau pathology in the brain (determined by PET). However, more studies are needed to fully understand the temporal relationship between CSF p‐tau217 changes and the accumulation tau in the brain. In this current study, we aim to investigate these temporal associations by the use of a novel knock‐in mouse model, AppNL‐G‐F expressing all six isoforms of human MAPT.MethodCerebrospinal fluid (CSF) and brain tissue will be collected from 3‐22 months old AppNL‐G‐F /MAPT and MAPT knock‐in mice. A pilot study of a subset of mice at different ages has been performed where levels of CSF ptau217 were analyzed using Mesoscale Discovery developed by Eli Lilly and Company. Mouse brain sections were immunostained against Aß and ptau181/217/231 to determine the cerebral p‐tau distribution.ResultIn CSF from our AppNL‐G‐F /MAPT double knock‐in (dKi) mouse model, we found age‐related increases in ptau217 levels compared to MAPT Ki mice. These changes in CSF ptau217 were associated with an increase of cerebral accumulation of p‐tau positive inclusions in the cortex and hippocampus of these mice. Additionally, we also found temporal differences in co‐localization between Aß plaques and the investigated phosphorylation sites of tau.ConclusionOur preliminary results from the AppNL‐G‐F/MAPT double knock‐in model, show early alterations in CSF ptau217 levels, changes that correlate in time with cerebral p‐tau positive accumulation as well as formation of Aß plaques. These findings indicate that alterations in CSF and cerebral p‐tau occurs early in the disease, when Aß pathology is widespread but no tau tangles are present. Furthermore, our preliminary data suggest temporal differences in phosphorylation sites of tau associated with Aß pathology. Additional CSF analysis and immunostainings will be performed before the AAIC conference.

Learning Deliberative Capacities in Brazilian Schools

What are the impacts of teaching deliberation on students’ attitudes in practical discussions? This study presents research findings from a field experiment involving more than 500 students from five public schools in the Brazilian cities of Belo Horizonte and Belém. We found a small effect of deliberative training on students’ justifications of their views and telling personal stories. However, much larger effects emerged when data were analysed separately by schools’ socioeconomic contexts, suggesting that middleclass students benefited more from training than disadvantaged students. Respect did not vary between groups and school contexts. Overall participation in discussion increased, and the effect was significantly greater in treatment groups, with positive inclusion of female students. The results support the view that learning deliberation is not a unidimensional process, but a complex combination of different components, and some capacities are more easily achieved than others.

Expression of expanded GGC repeats within NOTCH2NLC causes cardiac dysfunction in mouse models

BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5′ untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain.ResultsIn this study, we utilized two transgenic mouse models, expressing NOTCH2NLC-(GGC)98 ubiquitously or specifically in cardiomyocytes, and identified p62 (also known as sequestosome 1, SQSTM1)-positive intranuclear NOTCH2NLC-polyG inclusions in cardiomyocytes in two mouse models. We observed that both models exhibited cardiac-related pathological and echocardiographic changes, albeit exhibiting varying degrees of severity. Transcriptomic analysis revealed shared downregulation of genes related to ion channels and mitochondria in both models, with the cardiomyocyte-specific mice showing a more pronounced downregulation of mitochondria and energy metabolism-related pathways. Further investigations revealed decreased expression of mitochondria-related genes and electron transport chain activity. At last, we conducted a retrospective review of cardiac-related examination results from NIID patients at our hospital and also identified some cardiac abnormalities in NIID patients.ConclusionsOur study provided the first in vivo evidence linking GGC repeat expansions within NOTCH2NLC to cardiac abnormalities and highlighted the contribution of mitochondrial dysfunction in the development of cardiac abnormalities.