Recovery of Left Ventricular Function and Long-Term Outcomes in Patients With Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a form of transient left ventricular (LV) dysfunction that usually resolves within days to weeks. OBJECTIVES: We aimed to assess the predictors and prognostic impact of time-to-LV recovery after TTS. METHODS: Prospective serial imaging data from the nationwide, multicenter RETAKO (REgistry on TAKOtsubo Syndrome) were comprehensively reviewed to assess the timing of LV recovery. Multivariable logistic regression was used to assess factors associated with late (≥10 days) vs early (<10 days) recovery. The long-term risk of all-cause mortality was compared between the late and early recovery groups using fully adjusted Cox models, and using flexible parametric survival models with recovery time included as a continuous variable. RESULTS: Of 1,463 patients included (median age 73 years, 13% men), 373 (25%) had late and 1,090 (75%) had early LV recovery. Older age, history of neurological disorders, bystander coronary artery disease, active cancer, physical triggers, elevated inflammatory biomarkers, cardiogenic shock, and lower LV ejection fraction at admission were independent predictors of late recovery. At 4-year follow-up, the adjusted risk of death was significantly higher in patients with late recovery compared with those with early recovery (16.0% vs 8.6%, adjusted HR: 1.31; 95% CI: 1.12-1.60), with the risk of death increasing by 8% for every additional 10-day delay in time-to-LV recovery (adjusted HR: 1.08; 95% CI: 1.04-1.13). CONCLUSIONS: Late recovery of LV function after TTS is associated with reduced short- and long-term survival. In TTS patients without early LV recovery, closer clinical follow-up might be considered.

Development of an automated 3D high content cell screening platform for organoid phenotyping.

The use of organoid models in biomedical research has grown substantially since their inception. As they gain popularity among scientists seeking more complex and biologically relevant systems, there is a direct need to expand and clarify potential uses of such systems in diverse experimental contexts. Herein we outline a high-content screening (HCS) platform that allows researchers to screen drugs or other compounds against three-dimensional (3D) cell culture systems in a multi-well format (384-well). Furthermore, we compare the quality of robotic liquid handling with manual pipetting and characterize and contrast the phenotypic effects detected by confocal imaging and biochemical assays in response to drug treatment. We show that robotic liquid handling is more consistent and amendable to high throughput experimental designs when compared to manual pipetting due to improved precision and automated randomization capabilities. We also show that image-based techniques are more sensitive to detecting phenotypic changes within organoid cultures than traditional biochemical assays that evaluate cell viability, supporting their integration into organoid screening workflows. Finally, we highlight the enhanced capabilities of confocal imaging in this organoid screening platform as they relate to discerning organoid drug responses in single-well co-cultures of organoids derived from primary human biopsies and patient-derived xenograft (PDX) models. Altogether, this platform enables automated, imaging-based HCS of 3D cellular models in a non-destructive manner, opening the path to complementary analysis through integrated downstream methods.

Answering the Call: The Impact of Global Service-Learning on BSN Graduates.

ABSTRACT: Global migration significantly impacts demographic patterns in the United States, intensifying the need for nurses to deliver culturally competent healthcare to refugees, immigrants, and migrants. By integrating global service-learning (GSL) into nursing curricula, this study aims to provide a comprehensive understanding of GSL benefits in fostering effective intercultural communication, cultural humility, spiritual growth, and global health knowledge among nursing students. The findings suggest that GSL enhances the educational experience and equips nurses with the skills necessary to address the complex needs of a diverse patient population.

Houston, We Have AI Problem! Quality Issues with Neuroimaging-Based Artificial Intelligence in Parkinson's Disease: A Systematic Review.

In recent years, many neuroimaging studies have applied artificial intelligence (AI) to facilitate existing challenges in Parkinson's disease (PD) diagnosis, prognosis, and intervention. The aim of this systematic review was to provide an overview of neuroimaging-based AI studies and to assess their methodological quality. A PubMed search yielded 810 studies, of which 244 that investigated the utility of neuroimaging-based AI for PD diagnosis, prognosis, or intervention were included. We systematically categorized studies by outcomes and rated them with respect to five minimal quality criteria (MQC) pertaining to data splitting, data leakage, model complexity, performance reporting, and indication of biological plausibility. We found that the majority of studies aimed to distinguish PD patients from healthy controls (54%) or atypical parkinsonian syndromes (25%), whereas prognostic or interventional studies were sparse. Only 20% of evaluated studies passed all five MQC, with data leakage, non-minimal model complexity, and reporting of biological plausibility as the primary factors for quality loss. Data leakage was associated with a significant inflation of accuracies. Very few studies employed external test sets (8%), where accuracy was significantly lower, and 19% of studies did not account for data imbalance. Adherence to MQC was low across all observed years and journal impact factors. This review outlines that AI has been applied to a wide variety of research questions pertaining to PD; however, the number of studies failing to pass the MQC is alarming. Therefore, we provide recommendations to enhance the interpretability, generalizability, and clinical utility of future AI applications using neuroimaging in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Impaired Periodontitis-Induced Cytokine Production by Peripheral Blood Monocytes and Myeloid Dendritic Cells in Patients with Rheumatoid Arthritis: A Case-Control Study.

Background: Immune cells from rheumatoid arthritis (RA) patients display a reduced in vitro response to Porphyromonas gingivalis (P. gingivalis), which may have functional immune consequences. The aim of this study was to characterize, by flow cytometry, the frequency/activity of monocytes and naturally occurring myeloid dendritic cells (mDCs) in peripheral blood samples from patients with periodontitis and patients with periodontitis and RA. Methods: The relative frequency of monocytes and mDCs in the whole blood, the frequency of these cells producing TNFα or IL-6 and the protein expression levels for each cytokine, before and after stimulation with lipopolysaccharide (LPS) from Escherichia coli plus interferon-γ (IFN-γ), were assessed by flow cytometry, in peripheral blood samples from 10 healthy individuals (HEALTHY), 10 patients with periodontitis (PERIO) and 17 patients with periodontitis and RA (PERIO+RA). Results: The frequency of monocytes and mDCs producing IL-6 or TNF-α and the expression of IL-6 and TNF-α in the PERIO group were generally higher. Within the PERIO+RA group, P. gingivalis and related antibodies were negatively correlated with the monocyte and mDC expression of IL-6. A subgroup of the PERIO+RA patients that displayed statistically significantly lower frequencies of monocytes producing IL-6 after activation presented statistically significantly higher peptidylarginine deiminase (PAD)2/4 activity, anti-arg-gingipain (RgpB) IgG levels, mean probing depth (PD), periodontal inflamed surface area (PISA) and bleeding on probing (BoP). Conclusions: In the patients with PERIO+RA, innate immune cells seemed to produce lower amounts of pro-inflammatory cytokines, which are correlated with worse periodontitis-related clinical and microbiological parameters.

Advancing Parkinson's Disease Research in Canada: The Canadian Open Parkinson Network (C-OPN) Cohort.

Background: Enhancing the interactions between study participants, clinicians, and investigators is imperative for advancing Parkinson's disease (PD) research. The Canadian Open Parkinson Network (C-OPN) stands as a nationwide endeavor, connecting the PD community with ten accredited universities and movement disorders research centers spanning, at the time of this analysis, British Columbia, Alberta, Ontario, and Quebec. Objective: Our aim is to showcase C-OPN as a paradigm for bolstering national collaboration to accelerate PD research and to provide an initial overview of already collected data sets. Methods: The C-OPN database comprises de-identified data concerning demographics, symptoms and signs, treatment approaches, and standardized assessments. Additionally, it collects venous blood-derived biomaterials, such as for analyses of DNA, peripheral blood mononuclear cells (PBMC), and serum. Accessible to researchers, C-OPN resources are available through web-based data management systems for multi-center studies, including REDCap. Results: As of November 2023, the C-OPN had enrolled 1,505 PD participants. The male-to-female ratio was 1.77:1, with 83% (n = 1098) residing in urban areas and 82% (n = 1084) having pursued post-secondary education. The average age at diagnosis was 60.2±10.3 years. Herein, our analysis of the C-OPN PD cohort encompasses environmental factors, motor and non-motor symptoms, disease management, and regional differences among provinces. As of April 2024, 32 research projects have utilized C-OPN resources. Conclusions: C-OPN represents a national platform promoting multidisciplinary and multisite research that focuses on PD to promote innovation, exploration of care models, and collaboration among Canadian scientists.

Teamwork and communication between people living with Parkinson's disease (PD), physicians, health professionals, and research scientists is important for improving the lives of those living with this condition. The Canadian Open Parkinson Network (C-OPN) is a Canada-wide initiative, connecting the PD community with ten accredited universities and movement disorders research centers located in ­ at the time of this analysis­British Columbia, Alberta, Ontario, and Quebec. The aim of this paper is to showcase C-OPN as a useful resource for physician and research scientists studying PD in Canada and around the world, and to provide snapshot of already collected data. The C-OPN database comprises de-identified (meaning removal of any identifying information, such as name or date of birth) data concerning lifestyle, disease symptoms, treatments, and results from standardized tests. It also collects blood samples for further analysis. As of November 2023, C-OPN had enrolled 1,505 PD participants across Canada. Most of the participants were male (64%), living in urban areas (83%), and completed post-secondary education (82%). The average age at diagnosis was 60.2±10.3 years. In this paper, we look at environmental factors, motor and non-motor symptoms, different disease management strategies, and regional differences between provinces. In conclusion, C-OPN represents a national platform that encourages multidisciplinary and multisite research focusing on PD to promote innovation and collaboration among Canadian scientists.

Red propolis extract associated to platelet-rich plasma and stromal cells with focus in cell therapy and functional tissue regeneration.

The use of platelet-rich plasma (PRP) and adipose-derived stromal cells (ADSC) have been investigated as a form of wound healing enhancement. The objective of this work was to evaluate the association of red propolis (RP) and PRP as inducers of ADSC for application in tissue regeneration. Adipose tissue post-collection and post-cryopreservation was isolated with type II collagenase, characterized by flow cytometry, and differentiated into osteogenic, chondrogenic and adipose cell. The viability of ADSC was evaluated when exposed to different concentrations of RP using the MTT and trypan blue assay. Acridine orange and ethidium bromide (AO/EB) was performed to evaluate cell death events. Horizontal migration methods were investigated in ADSC using autologous and homologous PRP associated with RP (PRP/RP). All assays were processed in triplicate. Flow cytometry and cellular differentiation showed that type II collagenase was effective for isolating ADSC post-collection and post-cryopreservation. RP extracts at concentrations of up to 50 µg.mL-1 presented no cytotoxic effects. Association of PRP and RP at 25 and 50 µg.ml-1 influenced ADSC migration, with total closure on the seventh day after exposition. The results here presented could stimulate proliferation of ADSC cells that may contribute directly or indirectly to the reconstructive process of tissue regeneration.

Markerless three-dimensional gait analysis in healthy older adults: test-retest reliability and measurement error.

In older adults, gait analysis may detect changes that signal early disease states, yet challenges in biomechanical screening limit widespread use in clinical or community settings. Recently, a markerless method from multi-camera video data has become accessible, making screenings less challenging. This study evaluated the test-retest reliability and measurement error of markerless gait kinematics and kinetics in healthy older adults. Twenty-nine healthy older adults performed gait analysis on two occasions, at preferred walking speed, using their everyday clothes. Lower limb angles and moments were averaged from 8 gait cycles. Integrated pointwise indices [Intraclass Correlation Coefficient (ICCA,K) and Standard Error of Measurement (SEM)] were calculated for curve data, as well as ICCA,K, and SEM [95 % confidence intervals] for selected peaks. Generally, kinematic ICCs were good (>0.75) and reasonably stable throughout the gait cycle, except for the hip kinematics during the swing phase in the sagittal plane and pelvis tilt and rotation. The integrated and peaks SEM were <2.4°. The reliability of kinetics was similar (ICC>0.75), except for the transverse hip moment and abduction peak, fluctuating more during the swing than through the stance phase. SEM were < 0.07Nm/Kg. In conclusion, these results showed good overall test-retest reliability for markerless gait kinematics and kinetics for the hip, knee, and ankle joints, moderate for the pelvis angles, and error levels of ≤5°, and SEM%≤5% for the sagittal plane. This supports this method's use in assessing gait in healthy older adults, including kinetics, for which reliability data from markerless systems is difficult to find reported.

Cardiac Perforation Caused By Pectus Excavatum Metal Bar Stabilizer: A Case Report.

This paper reports the case of a female patient who underwent minimally invasive repair of pectus excavatum (MIRPE) in another service that evolved with bar rotation and cardiac perforation caused by the left stabilizer. The unique and frightening aspect of the case is that despite having the stabilizer inside the ventricle, the patient was oligosymptomatic: occasional chest pain and respiratory discomfort. Preoperative imaging showed rotation of the bar with stabilizers within the thoracic cavity. During surgery, intense ossification was observed around the prosthesis and it was noted that the left stabilizer had perforated the patient's left ventricle. Cardiac repair required a Clamshell incision and cardiopulmonary bypass. This case reinforces the validity of late radiological follow-up after MIRPE in an attempt to avoid this type of event, and the need to reevaluate the use of stabilizers perpendicular to the bar since they are not safe to prevent rotation of these implants.

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM).

A new paradigm for energy is underway demanding decarbonized energy systems. Some of them rely on emerging electrochemical devices, crucial in hydrogen technologies, including fuel cells, CO2 and water electrolysers, whose applications and performances depend on key components such as their separators/ion-exchange membranes. The most studied and already commercialized Nafion membrane shows great chemical stability, but its water content limits its high proton conduction to a limited range of operating temperatures. Here, we report the synthesis of a new series of triazinephosphonate derivatives and their use as dopants in the preparation of new modified Nafion membranes. The triazinephosphonate derivatives were prepared by substitution of chlorine atoms in cyanuric chloride. Diverse conditions were used to obtain the trisubstituted (4-hydroxyphenyl)triazinephosphonate derivatives and the (4-aminophenyl)triazinephosphonate derivatives, but with these amino counterparts, only the disubstituted compounds were obtained. The new modified Nafion membranes were prepared by casting incorporation of the synthesized 1,3,5-triazinephosphonate (TPs) derivatives. The evaluation of the proton conduction properties of the new membranes and relative humidity (RH) conditions and at 60 °C, showed that they present higher proton conductivities than the prepared Nafion membrane and similar or better proton conductivities than commercial Nafion N115, in the same experimental conditions. The Nafion-doped membrane with compound TP2 with a 1.0 wt % loading showed the highest proton conductivity with 84 mS·cm-1.

Lycopene supplementation promoted increased survival and decreased parasitemia in mice with severe malaria: comparison with N-acetylcysteine.

Oxidative stress is involved in the pathogenesis of malaria, causing anemia, respiratory complications, and cerebral malaria. To mitigate oxidative stress, we investigated the effect of nutritional supplementation whit lycopene (LYC) on the evolution of parasitemia and survival rate in mice infected with Plasmodium berghei ANKA (Pb), comparing to the effects promoted by N-acetylcysteine (NAC). Therefore, 175 mice were randomly distributed into 4 groups; Sham: untreated and uninfected animals; Pb: animals infected with Pb; LYC+Pb: animals treated with LYC and infected with Pb; NAC+Pb: animals treated with NAC and infected with Pb. The animals were followed for 12 days after infection, and survival and parasitemia rates were evaluated. There was a 40.1% increase in parasitemia in the animals of the Pb group on the 12th day, and a survival rate of 45%. LYC supplementation slowed the development of parasitemia to 19% and promoted a significative increase in the survival rate of 80% on the 12th day after infection, compared to the Pb group, effects superior to those promoted by NAC, providing strong evidence of the beneficial effect of LYC on in vivo malaria and stressing the importance of antioxidant supplementation in the treatment of this disease.

Risk Factors Associated with Musculoskeletal Injuries within the Crew of the Leopard 2 A6 Main Battle Tank Using Inertial Movement Unit Sensors: A Pilot Study.

This study aims to assess the musculoskeletal risk of military personnel on a Leopard 2 A6 main battle tank crew and to identify associated factors for future prevention and mitigation strategies. A sample of 57 Portuguese military personnel, who are or were part of the Leopard 2 A6 main battle tank crew, answered a questionnaire on their perception of task performance, considering muscle demands, comfort, posture, movements, and associated symptoms. A subsample of four soldiers from the Armoured Squadron of the Portuguese Mechanized Brigade were assessed using an inertial measurement unit system and underwent a whole-body kinematic analysis coupled with a Rapid Entire Body Assessment during a simulated two-hour mission. The results indicate that soldiers accurately perceive their roles within the crew and that, overall, there is a high risk of musculoskeletal injuries in all tasks. However, tasks directly related to the crew's primary duties carry consistently high risk when considering the time spent on their tasks. This study highlights the need for targeted preventive measures to reduce the incidence and severity of injuries among the crew of the Leopard 2 A6 main battle tank.

Multiclass Graph-Based Large Margin Classifiers: Unified Approach for Support Vectors and Neural Networks.

While large margin classifiers are originally an outcome of an optimization framework, support vectors (SVs) can be obtained from geometric approaches. This article presents advances in the use of Gabriel graphs (GGs) in binary and mul-ticlass classification problems. For Chipclass, a hyperparameter-less and optimization-less GG-based binary classifier, we discuss how activation functions and support edge (SE)-centered neurons affect the classification, proposing smoother functions and structural SV (SSV)-centered neurons to achieve margins with low probabilities and smoother classification contours We extend the neural network architecture, which can be trained with backpropagation with a softmax function and a cross-entropy loss, or by solving a system of linear equations. A new subgraph-/distance-based membership function for graph regularization is also proposed, along with a new GG recomputation algorithm that is less computationally expensive than the standard approach. Experimental results with the Friedman test show that our method was better than previous GG-based classifiers and statistically equivalent to tree-based models.

The role of AI and machine learning in the diagnosis of Parkinson's disease and atypical parkinsonisms.

Parkinson's disease is a neurodegenerative movement disorder associated with motor and non-motor symptoms causing severe disability as the disease progresses. The development of biomarkers for Parkinson's disease to diagnose patients earlier and predict disease progression is imperative. As artificial intelligence and machine learning techniques efficiently process data and can handle multiple data types, we reviewed the literature to determine the extent to which these techniques have been applied to biomarkers for Parkinson's disease and movement disorders. We determined that the most applicable machine learning techniques are support vector machines and neural networks, depending on the size and type of the data being analyzed. Additionally, more complex machine learning techniques showed increased accuracy when compared to less complex techniques, especially when multiple machine learning models were combined. We can conclude that artificial intelligence and machine learning techniques may have the capacity to significantly boost diagnostic capacity in movement disorders and Parkinson's disease.

Health-Related Quality of Life Long-Term Study in Lung Transplant Patients: A Single-Center Experience.

INTRODUCTION: Health-related quality of life (HRQL) assessment plays a crucial role in the follow-up care of lung transplanted (LTx) patients. Previous reports have indicated that the HRQL achieved by these patients is often poorer compared to that of healthy individuals. However, the factors contributing to this lower HRQL remain unclear. This prospective study aimed to assess the effectiveness of using both a generic and a disease-specific HRQL instrument in evaluating the outcomes of patients who have undergone LTx. METHODS: A total of 111 LTx patients were enrolled in the study, with 88 survivors completing the 5-year follow-up and 23 nonsurvivors identified within the first 3 y. Among the participants, 84 underwent double LTx, while 27 received a single LTx. Patients were interviewed before LTx, at 6 mo post-transplantation, and annually thereafter. Two validated instruments were utilized: the Euro quality of life five dimensions, a generic measure, and the St. George's Respiratory Questionnaire (SGRQ), a disease-specific questionnaire. RESULTS: The study showed significant improvements in Euro Quality of Life five Dimensions scores from 6 mo after LTx. Specifically, the percentage of patients without Mobility problems increased from 23% before LTx to 71% at 5 y (P = <0.001), while the ability to self-care improved from 48% to 100% (P = <0.001). The ability to carry out usual activities improved from 13% to 86% (P = <0.001), and the proportion of patients without anxiety and depression increased from 50% to 86% (P > 0.004). However, there was no significant improvement observed in Pain, with only a slight reduction from 57% to 42.8% (P = 0.22). The SGRQ also showed improvements in all dimensions (symptoms, impact, activities) (P < 0.001). However, by the fifth year, the HRQL scores remained below normal reference values. Chronic graft dysfunction was associated with a decline in SGRQ scores. Bilateral LTx patients exhibited better SGRQ scores compared to unilateral LTx patients from the first year post-transplantation. Notably, there were no differences in scores between nonsurvivors and survivors. CONCLUSIONS: The study highlights the long-term improvement in HRQL among LTx patients, with greater improvements observed in physical dimensions compared to psychological dimensions. Bilateral LTx was associated with better SGRQ scores than unilateral LTx, and chronic graft dysfunction primarily affected SGRQ scores. These findings underscore the importance of utilizing both generic and specific HRQL instruments in assessing LTx outcomes.

Multiple system atrophy with amyloid-ß-predominant Alzheimer's disease neuropathologic change.

Multiple system atrophy is a neurodegenerative disease with α-synuclein pathology predominating in the striatonigral and olivopontocerebellar systems. Mixed pathologies are considered to be of low frequency and mostly comprise primary age-related tauopathy or low levels of Alzheimer's disease-related neuropathologic change. Therefore, the concomitant presence of different misfolded proteins in the same brain region is less likely in multiple system atrophy. During the neuropathological evaluation of 21 consecutive multiple system atrophy cases, we identified four cases exhibiting an unusual discrepancy between high Thal amyloid-ß phase and low transentorhinal Braak neurofibrillary tangle stage. We mapped α-synuclein pathology, measured the size and number of glial cytoplasmic inclusions and compared the amyloid-ß peptides between multiple system atrophy and Alzheimer's disease. In addition, we performed α-synuclein seeding assay from the affected putamen samples. We performed genetic testing for APOE, MAPT, PSEN1, PSEN2 and APP. We refer to the four multiple system atrophy cases with discrepancy between amyloid-ß and tau pathology as 'amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy' to distinguish these from multiple system atrophy with primary age-related tauopathy or multiple system atrophy with typical Alzheimer's disease neuropathologic change. As most multiple system atrophy cases with mixed pathologies reported in the literature, these cases did not show a peculiar clinical or MRI profile. Three amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy cases were available for genetic testing, and all carried the APOE ɛ4 allele. The extent and severity of neuronal loss and α-synuclein pathology were not different compared with typical multiple system atrophy cases. Analysis of amyloid-ß peptides revealed more premature amyloid-ß plaques in amyloid-ß-predominant Alzheimer's disease neuropathologic change-multiple system atrophy compared with Alzheimer's disease. α-Synuclein seeding amplification assay showed differences in the kinetics in two cases. This study highlights a rare mixed pathology variant of multiple system atrophy in which there is an anatomical meeting point of amyloid-ß and α-synuclein, i.e. the striatum or cerebellum. Since biomarkers are entering clinical practice, these cases will be recognized, and the clinicians have to be informed that the prognosis is not necessarily different than in pure multiple system atrophy cases but that the effect of potential α-synuclein-based therapies might be influenced by the co-presence of amyloid-ß in regions where α-synuclein also aggregates. We propose that mixed pathologies should be interpreted not only based on differences in the clinical phenotype but also on whether protein depositions regionally overlap, potentially leading to a different response to α-synuclein-targeted therapies.

Single-cell proteomics and transcriptomics capture eosinophil development and identify the role of IL-5 in their lineage transit amplification.

The activities, ontogeny, and mechanisms of lineage expansion of eosinophils are less well resolved than those of other immune cells, despite the use of biological therapies targeting the eosinophilia-promoting cytokine interleukin (IL)-5 or its receptor, IL-5Rα. We combined single-cell proteomics and transcriptomics and generated transgenic IL-5Rα reporter mice to revisit eosinophilopoiesis. We reconciled human and murine eosinophilopoiesis and provided extensive cell-surface immunophenotyping and transcriptomes at different stages along the continuum of eosinophil maturation. We used these resources to show that IL-5 promoted eosinophil-lineage expansion via transit amplification, while its deletion or neutralization did not compromise eosinophil maturation. Informed from our resources, we also showed that interferon response factor-8, considered an essential promoter of myelopoiesis, was not intrinsically required for eosinophilopoiesis. This work hence provides resources, methods, and insights for understanding eosinophil ontogeny, the effects of current precision therapeutics, and the regulation of eosinophil development and numbers in health and disease.