Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation

by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Mental health and risk of death and hospitalization in COVID–19 patients. Results from a large-scale population-based study in Spain

by Aida Moreno-Juste, Beatriz Poblador-Plou, Cristina Ortega-Larrodé, Clara Laguna-Berna, Francisca González-Rubio, Mercedes Aza-Pascual-Salcedo, Kevin Bliek-Bueno, María Padilla, Concepción de-la-Cámara, Alexandra Prados-Torres, Luis A. Gimeno-Feliú, Antonio Gimeno-Miguel

The COVID–19 pandemic has created unprecedented challenges for health care systems globally. This study aimed to explore the presence of mental illness in a Spanish cohort of COVID-19-infected population and to evaluate the association between the presence of specific mental health conditions and the risk of death and hospitalization. This is a retrospective cohort study including all individuals with confirmed infection by SARS-CoV-2 from the PRECOVID (Prediction in COVID–19) Study (Aragon, Spain). Mental health illness was defined as the presence of schizophrenia and other psychotic disorders, anxiety, cognitive disorders, depression and mood disorders, substance abuse, and personality and eating disorders. Multivariable logistic regression models were used to examine the likelihood of 30-day all-cause mortality and COVID–19 related hospitalization based on baseline demographic and clinical variables, including the presence of specific mental conditions, by gender. We included 144,957 individuals with confirmed COVID–19 from the PRECOVID Study (Aragon, Spain). The most frequent diagnosis in this cohort was anxiety. However, some differences were observed by sex: substance abuse, personality disorders and schizophrenia were more frequently diagnosed in men, while eating disorders, depression and mood, anxiety and cognitive disorders were more common among women. The presence of mental illness, specifically schizophrenia spectrum and cognitive disorders in men, and depression and mood disorders, substance abuse, anxiety and cognitive and personality disorders in women, increased the risk of mortality or hospitalization after COVID–19, in addition to other well-known risk factors such as age, morbidity and treatment burden. Identifying vulnerable patient profiles at risk of serious outcomes after COVID–19 based on their mental health status will be crucial to improve their access to the healthcare system and the establishment of public health prevention measures for future outbreaks.

Validation of a web-based self-administered test for cognitive assessment in a Swedish geriatric setting

by Einar Rystedt, Jakob Morén, Johan Lindbäck, Vitor Tedim Cruz, Martin Ingelsson, Lena Kilander, Nuno Lunet, Joana Pais, Luis Ruano, Gabriel Westman

Computerized cognitive tests have the potential to cost-effectively detect and monitor cognitive impairments and thereby facilitate treatment for these conditions. However, relatively few of these tests have been validated in a variety of populations. Brain on Track, a self-administered web-based test, has previously been shown to have a good ability to differentiate between healthy individuals and patients with cognitive impairment in Portuguese populations. The objective of this study was to validate the differential ability and evaluate the usability of Brain on Track in a Swedish memory clinic setting. Brain on Track was administered to 30 patients with mild cognitive impairment/mild dementia and 30 healthy controls, all scheduled to perform the test from home after one week and after three months. To evaluate the usability, the patient group was interviewed after completion of the testing phase. Patients scored lower than healthy controls at both the first (median score 42.4 vs 54.1, p

Distress, multimorbidity, and complex multimorbidity among Chinese and Korean American older adults

by Hannah Oh, Brittany N. Morey, Yuxi Shi, Sunmin Lee

Background

Studies suggest that distress is associated with various health conditions such as hypertension, asthma, diabetes, and coronary heart disease. However, only few studies focused on Asian Americans and little is known about the association with multiple comorbidity.

Methods

We conducted a cross-sectional analysis among 400 Chinese and Korean American participants (aged 50–75 years) of the STOP CRC randomized controlled trial. Perceived distress was assessed using the distress thermometer scale (range 0–10). Disease diagnosis was self-reported by the participants. Multimorbidity (MM) was defined as having ≥2 chronic conditions. Complex multimorbidity (CMM) was defined as having ≥3 of the following body system disorders: circulation disorder, endocrine-metabolic disorder, cancer, anxiety or depression, breathing problem, and other health problems. We performed logistic regression for CMM and Poisson regression with robust error variance for MM to estimate associations with distress, adjusting for potential confounders.

Results

The mean age was 58.4 years and mean distress score was 3.65. One-unit increase in distress score was associated with a 1.22-fold increase in the odds of having CMM (95% CI: 1.04–1.42). The magnitude of association slightly increased after additional adjustment for socioeconomic factors and health insurance status (OR: 1.29; 95% CI: 1.10–1.52). Higher distress score was positively associated with MM but the association was only marginally significant (PR: 1.04; 95% CI: 0.99–1.10), adjusting for socioeconomic factors and health insurance status.

Conclusion

Our data suggest that higher perceived distress may be associated with simultaneous dysfunction of multiple distinct body systems among Chinese and Korean American older adults.

A comparative analysis of depressive-like behavior: Exploring sex-related differences and insights

by Ana Carolina Cavalcante Rodrigues, Caroline Vitória de Lima Moreira, Camila Carlos Prado, Luan Silvestro Bianchini Silva, Rafael Fernandes Costa, Adesina Paul Arikawe, Gustavo Rodrigues Pedrino, Elson Alves Costa, Osmar Nascimento Silva, Hamilton Barbosa Napolitano, Iranse Oliveira-Silva, James Oluwagbamigbe Fajemiroye

Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels [CORT] and behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter [CORT], FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated [CORT], but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence [CORT] as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.

Ethical inclusion: Risks and benefits of research from the perspective of perinatal people with opioid use disorders who have experienced incarceration

by Julia Reddy, Kristel Black, Keia Bazemore, Kiva Jordan, Jamie B. Jackson, Andrea K. Knittel

Background

Research ethics guidelines and emphasis on representation in research guide the inclusion of marginalized groups, including people with perinatal opioid use disorders (OUD) and people experiencing incarceration in the United States. However, insights from participants regarding the risks and benefits of participation are not adequately considered. The aim of this study was to examine the risks and benefits of research participation from the perspective of pregnant/postpartum people with OUD who have experienced incarceration.

Design

We recruited people who had experience with perinatal incarceration and were either currently pregnant or postpartum, and at least 18 years old. All participants met the clinical criteria for OUD. Our study did not have exclusion criteria based on gender, race, or ethnicity.

Setting

Participants were either currently incarcerated at the North Carolina Correctional Institute for Women in Raleigh, North Carolina, United States or had previously experienced perinatal incarceration and were recruited from a perinatal substance use disorder treatment program located in North Carolina.

Participants

Between 9/2021-4/2022, we completed 12 interviews with pregnant/postpartum people with OUD, approximately half who were currently incarcerated and half with a recent history of perinatal incarceration.

Intervention/measurement

Interviews were conducted via Webex phone or video. The interviews followed a scripted interview guide and lasted one hour on average. Interview transcripts were analyzed using the Rigorous and Accelerated Data Reduction technique to produce an overarching thematic framework.

Findings

Our analysis identified benefits, including the personal advantage of self-expression, helping others and contributing to change, and financial incentives. Risks included stigma and breach of confidentiality, misunderstanding of the distinction between research and advocacy, and limited ability to share their whole experience.

Conclusions

Participant-identified benefits of research mirrored those from other marginalized populations, though participant-identified risks were novel and nuanced. Recruitment and consent should move beyond normative research ethics committees protocol language to consider the perspectives of participants.

Robust cardiac segmentation corrected with heuristics

by Alan Cervantes-Guzmán, Kyle McPherson, Jimena Olveres, Carlos Francisco Moreno-García, Fabián Torres Robles, Eyad Elyan, Boris Escalante-Ramírez

Cardiovascular diseases related to the right side of the heart, such as Pulmonary Hypertension, are some of the leading causes of death among the Mexican (and worldwide) population. To avoid invasive techniques such as catheterizing the heart, improving the segmenting performance of medical echocardiographic systems can be an option to early detect diseases related to the right-side of the heart. While current medical imaging systems perform well segmenting automatically the left side of the heart, they typically struggle segmenting the right-side cavities. This paper presents a robust cardiac segmentation algorithm based on the popular U-NET architecture capable of accurately segmenting the four cavities with a reduced training dataset. Moreover, we propose two additional steps to improve the quality of the results in our machine learning model, 1) a segmentation algorithm capable of accurately detecting cone shapes (as it has been trained and refined with multiple data sources) and 2) a post-processing step which refines the shape and contours of the segmentation based on heuristics provided by the clinicians. Our results demonstrate that the proposed techniques achieve segmentation accuracy comparable to state-of-the-art methods in datasets commonly used for this practice, as well as in datasets compiled by our medical team. Furthermore, we tested the validity of the post-processing correction step within the same sequence of images and demonstrated its consistency with manual segmentations performed by clinicians.