Central Hypothesis Research Articles

Testing the Goodwin Model: Can Distribution Battles Trigger Business Cycles? Evidence from a Behavioral Experiment

AbstractThe Goodwin model provides an important explanation for business cycles with its investment decisions based on pro-cyclical wage fluctuations. The purpose of this paper is to test the central hypothesis of the Goodwin model, namely that wage developments influence investments, which creates business cycles. The model used to test this hypothesis was that of a simplified company, where labor demand is related to investments. Thus, more investments lead to higher wages and vice versa. In the behavioral experiment the test subjects played the manager of a company who maximizes their profits through investments. The central assumptions and conclusions of the Goodwin model are supported by behavioral science.

POLÍTICAS PÚBLICAS EDUCACIONAIS NO AMAZONAS: UM ESTUDO DAS ESPECIFICIDADES REGIONAIS

This article discusses the implementation of Public Educational Policies in the State of Amazonas, addressing its particularities and the challenges faced in one of the richest regions in diversity, but also marked by educational inequalities. Although the Federal Constitution of Brazil, in articles 6 and 205, guarantees the right to education, the Amazonian reality reveals the need for a more in-depth look at the quality of education. The research investigates whether secretariats and technical teams are properly prepared to create and implement policies that transcend mere access to education. The central hypothesis is that the lack of qualified professionals in the State compromises the effectiveness of these policies, which requires an approach that prioritizes the interests of the school community and students, promoting quality education that meets local specificities.

DEMOCRATIZAÇÃO DO ENSINO DE DIREITOS HUMANOS NO ENSINO FUNDAMENTAL: DESAFIOS E OPORTUNIDADES PARA A FORMAÇÃO DE CIDADÃOS CONSCIENTES

This article investigates the challenges and opportunities in democratizing human rights education in elementary school, highlighting its role in shaping socially responsible and conscious citizens. The absence of a structured human rights education limits students' ability to develop a culture of respect for diversity and otherness, contributing to the perpetuation of inequalities. The central hypothesis is that the integration of a comprehensive and transversal human rights curriculum can transform the school environment and reduce discriminatory behaviors. Based on a bibliographical analysis of legal documents and recent studies, including the Universal Declaration of Human Rights (UDHR) and the National Plan for Human Rights Education (PNEDH), this study examines initiatives implemented in Brazil, such as the "Direito na Escola" and "OAB Vai à Escola" programs. The results indicate that, despite barriers such as the lack of teacher training and pedagogical resources, human rights education from elementary school is crucial to building a more just and equitable society. The article concludes that the democratization of human rights education requires effective public policies and an integrated approach involving the state, school, family, and civil society.

Impressions about harm are formed rapidly and then refined, modulated by serotonin.

Attributing motives to others is a crucial aspect of mentalizing, can be biased by prejudice, and is affected by common psychiatric disorders. It is therefore important to understand in depth the mechanisms underpinning it. Toward improving models of mentalizing motives, we hypothesized that people quickly infer whether other's motives are likely beneficial or detrimental, then refine their judgment (classify-refine). To test this, we used a modified Dictator game, a game theoretic task, where participants judged the likelihood of intent to harm vs. self-interest in economic decisions. Toward testing the role of serotonin in judgments of intent to harm, we delivered the task in a week-long, placebo vs. citalopram study. Computational model comparison provided clear evidence for the superiority of classify-refine models over traditional ones, strongly supporting the central hypothesis. Further, while citalopram helped refine attributions about motives through learning, it did not induce more positive initial inferences about others' motives. Finally, model comparison indicated a minimal role for racial bias within economic decisions for the large majority of our sample. Overall, these results support a proposal that classify-refine social cognition is adaptive, although relevant mechanisms of serotonergic antidepressant action will need to be studied over longer time spans.

A Survey on Female Employment and the Quality of Their Family Relationships in Mahabad, Iran (2017–2018)

Abstract The primary objective of this descriptive survey is to examine the correlation between women’s employment and the quality of their family relationships in Mahabad, a Kurdish city in the northwest of Iran. This locale has distinct cultural norms and perspectives concerning female employment. The statistical sample consists of all married women aged between 20 and 60 years and employed within the urban areas of Mahabad from 2017 to 2018. This group encompasses a total of 2,995 individuals (N = 2995). Employing Cochran’s formula, the sample size was determined to be n = 350. Participants were selected through multi-stage clustering and systematic random sampling methodologies. Data were collected through a researcher-designed questionnaire, with a Cronbach’s alpha coefficient estimated at 0.89, indicating satisfactory reliability. Descriptive and inferential statistical techniques were employed for data analysis, including the chi-square test and percentage frequency distribution tables. The study’s central hypothesis was validated using the chi-square test at a 5% significance level. Consequently, the research findings substantiate that, within the context of Mahabad, employed women exhibit a higher quality of family relationships than their unemployed counterparts. Given the historically limited discourse on the circumstances of Kurdish women in smaller regions, and the prevailing tendency to focus primarily on the challenges faced by women at the lower strata of society, this research serves as a valuable contribution towards a more comprehensive understanding of the lives of this particular cohort of Kurdish women residing in the modest city of Mahabad. By delving into the dimensions of employment and the quality of their marital relationships, this study strives toward shedding light on the positive impacts of women’s participation on their family dynamics. The insights gleaned from this research hold the potential to serve as a model that can be extrapolated to benefit women in other regions across the Middle East in the future.

Tau load in select brainstem neurons predicts the severity and nature of balance deficits in the absence of cell death.

Patients with tauopathies present with profoundly different clinical symptoms 1 , even within the same disorder 2 . A central hypothesis in the field, well-supported by biomarker studies 3,4 and post-mortem pathology 5-7 , is that clinical heterogeneity reflects differential degeneration of vulnerable neuronal populations responsible for specific neurological functions. Recent work has revealed mechanisms underlying susceptibility of particular cell types 8-10 , but relating tau load to disrupted behavior - es- pecially before cell death - requires a targeted circuit-level approach. Here we studied two distinct balance behaviors in larval zebrafish 11 expressing a human 0N/4R-tau allele 12 in select populations of evolutionarily-conserved and well-characterized brainstem vestibular circuits 13,14 . We observed that human tau load predicted the severity of circuit-specific deficits in posture and navigation in the ab- sence of cell death. Targeting expression to either mid- or hindbrain balance neurons recapitulated these particular deficits in posture and navigation. By parametrically linking tau load in specific neu- rons to early behavioral deficits, our work moves beyond cell type to close the gap between pathological and neurological conceptions of tauopathy.

A Comparative Analysis of Independent Audit Sectors in Turkiye And Uzbekistan

The independent audit sector consists of independent auditing companies and professionals providing auditing services to businesses and organizations. The sector has a critical importance for developing countries to provide and sustain qualitative operations of enterprises and organizations. A strong independent audit sector helps to improve the operations of entire private sector and hence provides better integration to international markets In this context, due to the importance of the subject, a research on the audit sector is carried out in this study. The main axis of the study is the comparative analysis of the independent audit sectors in Uzbekistan and Türkiye. Since there is no other study comparing these two countries in terms of this sector, this paper tries to make a contribution to the related literature. The study’s central hypothesis is that Uzbekistan has a significant potential to catch international auditing standards. A comparative analysis is conducted for independent audit sector of two counties in order to test this hypothesis

Dielectric Signatures of Late Carcinoma Immune Cells Using MMTV-PyMT Mammary Carcinoma Models.

Peripheral blood mononuclear cells (PBMCs) are specialized immune cells produced from hematopoietic stem cells (HSC). They actively surveil for any signs of infection, foreign invaders, and abnormal or aberrant cells associated with diseases. Numerous inherent interactions between PBMCs and proliferating cancer cells facilitate cellular communication, inducing alterations in the composition of the PBMCs. These subtle alterations can be detected by using dielectrophoresis (DEP). The ultimate objective is to apply this knowledge in a clinical setting to achieve noninvasive early detection of breast cancer while minimizing the occurrence of false positives and negatives commonly associated with standard screening methods like mammography. To realize our long-term goal, we are probing the dielectric properties of the PBMCs from FVB/N MMTV-PyMT+ (late carcinoma, PyMT+ PBMC) and FVB/N (wild-type, WT-PBMC) age-matched mice at 14+ weeks using dielectrophoresis on a microfluidic platform. The central hypothesis of this research is that the changes triggered in the subcellular components, such as the cytoskeleton, lipid bilayer membrane, cytoplasm, focal adhesion proteins, and extracellular matrix (ECM) at the onset of carcinoma, regulate dielectric properties (conductivity, σ; and permittivity, ε), thus affecting the bioelectric signals that aid in the detection of breast cancer. The ANOVA results suggest a significant difference in PyMT+ PBMCs crossover frequencies at 0.01 and 0.05 S/m medium conductivity levels. Post hoc pairwise analysis of WT-PBMCs showed that the crossover frequencies are distinct across the medium conductivity ranges from 0.01 to 0.05 S/m. This study revealed that on average, PyMT+ PBMCs have increased crossover frequency, polarizability, higher membrane capacitance, and a folding factor compared with the age-matched wild-type PBMCs.

Is there a ubiquitous spectrolaminar motif of local field potential power across primate neocortex?

Mendoza-Halliday, Major et al., 2024 ("The Paper")1 advocates a local field potential (LFP)-based approach to functional identification of cortical layers during "laminar" (simultaneous recordings from all cortical layers) multielectrode recordings in nonhuman primates (NHPs). The Paper describes a "ubiquitous spectrolaminar motif" in the primate neocortex: 1) 75-150 Hz power peaks in the supragranular layers, 2) 10-19 Hz power peaks in the infragranular layers and 3) the crossing point of their laminar power gradients identifies Layer 4 (L4). Identification of L4 is critical in general, but especially for The Paper as the "motif" discovery is couched within a framework whose central hypothesis is that gamma activity originates in the supragranular layers and reflects feedforward activity, while alpha-beta activity originates in the infragranular layers and reflects feedback activity. In an impressive scientific effort, The Paper analyzed laminar data from 14 cortical areas in 2 prior macaque studies and compared them to marmoset, mouse, and human data to further bolster the canonical nature of the motif. Identification of such canonical principles of brain operation is clearly a topic of broad scientific interest. Similarly, a reliable online method for L4 identification would be of broad scientific value for the rapidly increasing use of laminar recordings using numerous evolving technologies. Despite The Paper's strengths, and its potential for scientific impact, a series of concerns that are fundamental to the analysis and interpretation of laminar activity profile data in general, and local field potential (LFP) signals in particular, led us to question its conclusions. We thus evaluated the generality of The Paper's methods and findings using new sets of data comprised of stimulus-evoked laminar response profiles from primary and higher-order auditory cortices (A1 and belt cortex), and primary visual cortex (V1). The rationale for using these areas as a test bed for new methods is that their laminar anatomy and physiology have already been extensively characterized by prior studies, and there is general agreement across laboratories on key matters like L4 identification. Our analyses indicate that The Paper's findings do not generalize well to any of these cortical areas. In particular, we find The Paper's methods for L4 identification to be unreliable. Moreover, both methodological and statistical concerns, outlined below and in the supplement, question the stated prevalence of the motif in The Paper's published dataset. After summarizing our findings and related broader concerns, we briefly critique the evidence from biophysical modeling studies cited to support The Paper's conclusions. While our findings are at odds with the proposition of a ubiquitous spectrolaminar motif in the primate neocortex, The Paper already has, and will continue to spark debate and further experimentation. Hopefully this countervailing presentation will lead to robust collegial efforts to define optimal strategies for applying laminar recording methods in future studies.

Kin investment biases of aunts and uncles: associations with phenotypic resemblance and sociodemographic characteristics.

Higher investment in maternal than paternal aunts and uncles is explained by the "paternity uncertainty hypothesis". Regardless of laterality, however, aunts show a greater degree of investment than uncles, which is attributed to sex-specific reproductive strategies. Resemblance cues can be used as indicators of genetic relatedness. The central hypothesis of the current study was that perceived phenotypic resemblance between aunts/uncles and niblings would be associated with aunts' and uncles' investment. The association was predicted to be stronger with respect to patrilateral than matrilateral aunts and uncles and stronger with respect to patrilateral aunts than patrilateral uncles. 243 Iranians aged between 15 and 50 participated in a retrospective analysis and filled out a 52-item questionnaire focusing on the solicitude, emotional closeness, and contact frequency between aunts/uncles and their nephews/nieces. In addition, the participants had to rate their phenotypic resemblance with their aunts and uncles. Aunts' and uncles' solicitude, emotional closeness, and contact frequency were differentially expressed according to sex and laterality. Maternal aunts showed the significantly highest emotional closeness, contact frequency, and investment, while the opposite was true for paternal uncles. Moreover, investment was correlated with phenotypic resemblance. Such association was stronger for patrilateral than matrilateral aunts and uncles, and concerning solicitude it was stronger for patrilateral aunts than patrilateral uncles. The resemblance-based kin recognition mechanism among aunts and uncles was self- rather than family-referent. In conclusion, phenotypic similarity can be used as a cue to genetic kinship and is correlated with the investment of aunts and uncles. However, such associations also depend on the degree of genetic relatedness and the differential kin investment provided by each sex.

Abstract B002: Cancer health equity and research advocacy program among immigrant communities

Abstract Introduction: In an effort to ensure an all-inclusive initiative that would close the disparity gap among the immigrant communities in Florida, we developed a pilot project under the Inclusive Cancer Care Research Equity (iCCaRE) for Black Men Consortium with generous support from the Mayo Clinic Comprehensive Cancer Center (MCCCC). The objective is to train cancer advocates to engage their communities and develop and implement cancer prevention and screening navigation programs. The central hypothesis for this program is that community-driven cancer advocacy will significantly improve cancer awareness, knowledge, prevention, risk reduction, screening uptake, and early detection among Black immigrants. Methods: We collaborated with immigrant communities’ leaders to brainstorm on the current state of healthcare access and disparities experienced by Black immigrants and to set program and research priorities through listening sessions. Cancer advocates were trained to engage their communities to (1) develop and implement cancer risk reduction and education programs using train-the-trainer approach, (2) mobilize the resources within the community for cancer health promotion, prevention, and screening strategies, (3) partner with key stakeholders to accomplish targeted objectives; (4) raise funds to support advocacy activities; and (5) develop and successfully organize community-centered programs. Results: We are currently working with 10 Black immigrant organizations, including immigrant churches across different ethnicities, including Nigeria, Ghana, Cameroon, Liberia, South Africa, Haiti, Jamaica, and across different cities in the United States. Eighteen community cancer advocates, including breast and prostate cancer survivors, caregivers, and community influencers, were trained to engage the immigrant communities in cancer risk reduction and research in Florida using multiple channels, including in-person community programs and online engagement approaches. We have engaged 720 immigrants in cancer risk reduction education and the need to participate in research during advocate-led in-person community outreaches. We currently have 26 immigrants who have volunteered in the Mayo Clinic Community Research Registry. The program is ongoing, and we anticipate that more than 750 will be engaged, and 100 will volunteer to be registered in the Mayo Clinic Community Research Registry. Conclusion: Advocate-led advocacy in immigrant communities will provide evidence for compelling arguments about the feasibility and availability of the Black immigrant population for robust and sustainable research and program engagements to eliminate disparity and advance cancer health equity. Citation Format: Opeyemi O. Bolajoko, Caleb Ramirez, Shannon Pressey, Noreen A. Stephenson, Vinessa A. Gordon, Binta Onyibe, Kingsley Efe, Austin Okaiwele, Mubo Oloruntobo, Brittany M. Norris, Folakemi T. Odedina. Cancer health equity and research advocacy program among immigrant communities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B002.

Interaction of motor behaviour, cortical oscillations and deep brain stimulation in Parkinson disease

Abstract Recent progress in the study of Parkinson's disease (PD) has highlighted the pivotal role of beta oscillations within the basal ganglia-thalamo-cortical network in modulating motor symptoms. Predominantly manifesting as transient bursts, these beta oscillations are central to the pathophysiology of PD motor symptoms, especially bradykinesia. Our central hypothesis is that increased bursting duration in cortex, coupled with kinematics of movement, disrupts the typical flow of neural information, leading to observable changes in motor behavior in PD. To explore this hypothesis, we employed an integrative approach, analyzing the interplay between moment-to-moment brain dynamics and movement kinematics, and the modulation of these relationships by therapeutic deep brain stimulation (DBS). Local field potentials were recorded from the hand motor (M1) and premotor cortical (PM) areas, and internal Globus Pallidus (GPi) in 26 PD patients undergoing DBS implantation surgery. Participants executed rapid alternating hand movements in 30-second blocks, both with and without therapeutic pallidal stimulation. Behaviorally, the analysis revealed bradykinesia, with hand movement cycle width increasing linearly over time during DBS-OFF blocks. Crucially, there was a moment-to-moment correlation between M1 low beta burst duration and movement cycle width, a relationship that dissipated with therapeutic DBS. Further analyses suggest that high gamma activity correlates with enhanced motor performance with DBS-ON. Regardless of the nature of coupling, DBS’s modulation of cortical bursting activity appeared to amplify the brain signals’ informational content regarding instantaneous movement changes. Our findings underscore that DBS significantly reshapes the interaction between motor behavior and neural signals in PD, not only modulating specific bands but also expanding the system's capability to process and relay information for motor control. These insights shed light on the possible network mechanisms underlying DBS therapeutic effects, suggesting a profound impact on both neural and motor domains.

Youth and Education: Past, Present and Future Inequalities in Argentina

Abstract Within the framework of the post-pandemic and in the educational context that has been experienced in Argentina in recent years, inequalities appear, with new aspects to debate about youth and education in the current young generations. With this idea, the article presents past, present and future debates on the opportunities and aspects of youth that have been recorded during longitudinal research carried out in the last twenty years with different cohorts of young people. In particular, it presents the results of an ongoing investigation into the young population and secondary education in different areas of Argentina. The main objective is to debate the aspects and contexts that occurred and caused inequalities in youth transitions. The central hypothesis of the article is that the processes and effects of inequality in each of the generations studied are explained and described both within the circumstances and conjunctures in which the youth trajectories occur.

Abstract A075: Establishing the interaction mechanism of oncoprotein, Mucin1, and extracellular vesicle marker protein, Alix, in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with devastating mortality rates largely due to a poor understanding of its progression mechanism. Small extracellular vesicles (sEVs) are used by cancer cells to aid in their progression, and tumor-derived EVs (TEVs) show a distinct protein cargo composition potentially contributing to this rapid progression and metastasis of PDAC. To investigate this phenomenon, we isolated sEVs from conditioned media of pancreatic cancer cell lines using ultracentrifugation and characterized them by transmission electron microscopy (TEM), nanoparticle tracking analysis, and immunoblotting. These sEVs were then used in several studies to investigate critical TEV cargo sorting machinery. For instance, PDAC-derived sEVs have selective enrichment of the oncogenic transmembrane protein Mucin1 (MUC1). Preliminary MUC1KO studies from our lab revealed that MUC1 potentially regulates sEV formation, where we saw a clear impact on sEV cargo in the absence of MUC1. Additional studies found that the cytoplasmic adaptor protein ALG-2-Interacting Protein X (Alix), a protein known to play a critical role during TEV formation, regulates MUC1’s presence in sEVs. From this discovery, we then identified a novel MUC1-Alix interaction, which was confirmed using several techniques, including co-immunoprecipitation (CoIP). To define the Alix-interacting domain of MUC1, we utilized in silico modeling and localized surface plasmon resonance (LSPR) of MUC1.CT and Alix to quantify the interaction. This revealed the cytoplasmic tail of MUC1 (MUC1.CT) as the Alix-interacting domain. Moving forward, our central hypothesis for this study is that this MUC1.CT-Alix interaction utilizes a conserved binding motif that targets Alix to the endosomal membrane and contributes to the formation of MUC1+ sEVs. While a distinct sEV biogenesis pathway employed by cancer cells has not yet been defined, our studies will provide insight into the potential sEV sorting mechanism of MUC1 and other cancer biomarkers and advance the understanding of PDAC progression. Citation Format: Kristine V Hoagstrom, Ying Huang, Gloria E Borgstahl, Michael A Hollingsworth. Establishing the interaction mechanism of oncoprotein, Mucin1, and extracellular vesicle marker protein, Alix, in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A075.

High-speed railways reduces carbon emissions: mediating effects of green innovation and the resilience of environmental investment

High-speed rails (HSRs) are a sustainable approach in many cities. Although some studies recognize that introducing HSR is negatively related to carbon emissions, explorations of the mechanisms underlying this relationship remain scarce. The main purpose of this study is to investigate whether introducing HSR reduces carbon emissions through increasing green innovation (GI) and the resilience of environmental investment (REI). Employing signal theory and fault tolerance theory, among others, we propose models that illuminate how inaugurating HSRs reduces carbon emissions through GI and REI. Our proposed central hypothesis is that GI and REI mediate carbon emission reduction by introducing HSR. In this study, we used the data from 284 China’s cities during 2000-2021 and examined our hypothesis via a difference-in-differences (DID) model. The results show that introducing HSR reduces carbon emissions through GI and REI. On the basis of the current status of China’s economic and social development, we further analyze several critical moderating effects, such as the digital economy, the urban‒rural gap, and whether it is a resource-based city. In 2023, China’s Central Economic Work Conference (CEWC) explicitly proposed “developing the digital economy.” We find that the digital economy strengthens the negative relationship between introducing HSRs and carbon emissions. The digital economy also strengthens the positive correlation between the introduction of HSR and GI. Additionally, this strengthens the positive correlation between HSRs and REI. In addition, the urban‒rural disparity is a manifestation of China’s uneven development. We find that the urban‒rural disparity weakens the relationship between HSRs and carbon emissions. In addition, China’s resource-based cities lag behind other cities. Our findings suggest that, in contrast to other cities, high-speed rails increase carbon emissions in resource-based cities.

Abstract 23: Cognitive impairment during chronic i.c.v. angiotensin II is associated with increased tau phosphorylation in the cortex and hippocampus

Cardiovascular risk factors, such as hypertension, are recognized as important contributors to cognitive impairment and dementia, including Alzheimer’s disease (AD). However, the mechanisms underlying the detrimental effects of hypertension on the brain remain to be fully established. Angiotensin II (Ang II) has known detrimental effects on the brain, including cerebrovascular damage, sympathetic activation, and neuroinflammation. Ang II activates neuronal glycogen synthase 3b (GSK-3b), a major kinase involved in the phosphorylation of the microtubule associated protein tau. Hyperphosphorylated tau and the subsequent formation of neurofibrillary tangles are a hallmark of AD and related dementias (tauopathies). Here, we tested the central hypothesis that brain Ang II leads to cognitive impairment by increasing tau hyperphosphorylation. 3-month old male C57BL6 mice were implanted with a s.c. osmotic minipump connected to an i.c.v. cannula delivering low dose Ang II (6ng/hr) or saline for 4 weeks. Blood pressure was monitored twice weekly using tail-cuff plethysmography. During the 4 th week of infusion, mice underwent a battery of neurobehavioral testing assessing various cognitive domains including novel object recognition (recognition and short-term memory), Y-maze (spatial working memory), Barnes maze (spatial learning and long-term memory), and hippocampal/executive function (nest building). Tau phosphorylation was assessed in the cortex and hippocampus by Western blotting. Systolic blood pressure increased slightly by week 3 prior to start of behavioral tests (control: 115.3 ± 4.1 mmHg vs Ang II: 130.8 ± 4.7; n=10). We did not observe significant differences during novel object recognition (discrimination index: control: 0.49 ± 0.08 vs Ang II: 0.35 ± 0.23; n=5) or Y-maze (spontaneous alternations: control: 62.4 ± 6.1% vs Ang II: 59.0 ± 4.3%). Mice receiving i.c.v. Ang II had significantly delayed latency to find the escape hole during the Barnes maze learning trials (Treatment p=0.0006, Time p=0.0039, interaction: p=0.3028; two-way repeated measures ANOVA). The impairment in spatial learning was associated with an increase in tau phosphorylation in the cortex assessed by AT8 antibody. Ongoing studies are investigating whether this increase is mediated by activation of neuronal GSK-3b. We conclude that Ang II-mediated hyperphosphorylation of tau is a potential novel molecular mechanism driving the detrimental effects of hypertension on cognitive health.

The Physical Sensation of Precordial Pain as a Signal of Psychiatric Relevance of Anguish

Anguish is a sensation of precordial chest tightness or oppression that has an emotional origin. Unlike anxiety which is focused on the future, anguish is experienced in the present as a state of pain and mental agony. Furthermore, distress is supposed to have different autonomic, physiological and biochemical reactions when compared to anxiety and depression. The main objective of this work is to investigate whether depression is more related to anguish than anxiety, and also to identify which variables or symptoms are most predictive of the state of anguish. A binomial logistic regression model was adjusted and statistically significant evidence was found that depression may be more related to distress than anxiety. An important depression diagnostic variable (MINI Depression) was selected in the model (at the 10% level) and its interpretation corroborates the central hypothesis of the study mentioned above. Correspondence analysis also points to clues in the direction of the research hypothesis. As for the second objective, under the same logistic model, the following variables were shown to be related to the state of distress: Gender, Reduced Hamilton Score, BSI Somatization, BSI Hostility, BSI Obsession Compulsion, Age and MINI Depression.

Heterozygous loss of Engrailed-1 and α-synucleinopathy (En1/SYN): A dual-hit preclinical mouse model of Parkinson's disease, analyzed with artificial intelligence

In this study, we develop and validate a new Parkinson's disease (PD) mouse model that can be used to better understand how the disease progresses and to test the effects of new, potentially disease-modifying, PD therapies. Our central hypothesis is that mitochondrial dysfunction intercalates with misfolded α-synuclein (α-syn) accumulation in a vicious cycle, leading to the loss of nigral neurons. Our hypothesis builds on the concept that PD involves multiple molecular insults, including mitochondrial dysfunction and aberrant α-syn handling. We predicted that mitochondrial deficits, due to heterozygous loss of Engrailed-1 (En1+/−), combined with bilateral injections of pathogenic α-syn fibrils (PFFs), will act to generate a highly relevant PD model – the En1/SYN model. Here, En1+/− mice received bilateral intrastriatal stereotaxic injections of either PBS or α-syn fibrils and were analyzed using automated behavioral tests and deep learning-assisted histological analysis at 2, 4, and 6 months post-injection. We observed significant and progressive Lewy body-like inclusion pathology in the amygdala, motor cortex, and cingulate cortex, as well as the loss of tyrosine hydroxylase-positive (TH+) cells in the substantia nigra. The En1/SYN model also exhibited significant motor impairments at 6 months post-injection, which were however not exacerbated as we had expected. Still, this model has a comprehensive number of PD-like phenotypes and is therefore superior when compared to the α-syn PFF or En1+/− models alone.

Reducing asthma attacks in disadvantaged school children with asthma: study protocol for a type 2 hybrid implementation-effectiveness trial (Better Asthma Control for Kids, BACK)

BackgroundAsthma is a leading cause of children’s hospitalizations, emergency department visits, and missed school days. Our school-based asthma intervention has reduced asthma exacerbations for children experiencing health disparities in the Denver Metropolitan Area, due partly to addressing care coordination for asthma and social determinants of health (SDOH), such as access to healthcare and medications. Limited dissemination of school-based asthma programs has occurred in other metropolitan and rural areas of Colorado. We formed and engaged community advisory boards in socioeconomically diverse regions of Colorado to develop two implementation strategy packages for delivering our school-based asthma intervention — now termed “Better Asthma Control for Kids (BACK)" — with tailoring to regional priorities, needs and resources.MethodsIn this proposed type 2 hybrid implementation-effectiveness trial, where the primary goal is equitable reach to families to reduce asthma disparities, we will compare two different packages of implementation strategies to deliver BACK across four Colorado regions. The two implementation packages to be compared are: 1) standard set of implementation strategies including Tailor and Adapt to context, Facilitation and Training termed, BACK-Standard (BACK-S); 2) BACK-S plus an enhanced implementation strategy, that incorporates network weaving with community partners and consumer engagement with school families, termed BACK-Enhanced (BACK-E). Our evaluation will be guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, including its Pragmatic Robust Implementation Sustainability Model (PRISM) determinants of implementation outcomes. Our central hypothesis is that our BACK-E implementation strategy will have significantly greater reach to eligible children/families than BACK-S (primary outcome) and that both BACK-E and BACK-S groups will have significantly reduced asthma exacerbation rates (“attacks”) and improved asthma control as compared to usual care.DiscussionWe expect both the BACK-S and BACK-E strategy packages will accelerate dissemination of our BACK program across the state – the comparative impact of BACK-S vs. BACK-E on reach and other RE-AIM outcomes may inform strategy selection for scaling BACK and other effective school-based programs to address chronic illness disparities.Trial registrationClinicaltrials.gov identifier: NCT06003569, registered on August 22, 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06003569.

Perspectives on the comparative benefits of body-powered and myoelectric upper limb prostheses

BackgroundPatient access to body-powered and myoelectric upper limb prostheses in the United States is often restricted by a healthcare system that prioritizes prosthesis prescription based on cost and perceived value. Although this system operates on an underlying assumption that design differences between these prostheses leads to relative advantages and disadvantages of each device, there is limited empirical evidence to support this view.Main textThis commentary article will review a series of studies conducted by our research team with the goal of differentiating how prosthesis design might impact user performance on a variety of interrelated domains. Our central hypothesis is that the design and actuation method of body-powered and myoelectric prostheses might affect users’ ability to access sensory feedback and account for device properties when planning movements. Accordingly, other domains that depend on these abilities may also be affected. While our work demonstrated some differences in availability of sensory feedback based on prosthesis design, this did not result in consistent differences in prosthesis embodiment, movement accuracy, movement quality, and overall kinematic patterns.ConclusionCollectively, our findings suggest that performance may not necessarily depend on prosthesis design, allowing users to be successful with either device type depending on the circumstances. Prescription practices should rely more on individual needs and preferences than cost or prosthesis design. However, we acknowledge that there remains a dearth of evidence to inform decision-making and that an expanded research focus in this area will be beneficial.