Search Results (190)

Individuals with post-traumatic stress disorder (PTSD) are at increased risk for hazardous drinking, which often complicates treatment and affects trauma-focused psychotherapy outcomes. The present study is an exploratory, secondary analysis investigating differential effects of prolonged exposure (PE) among those with and without hazardous drinking and whether treatment outcomes varied across these groups as a function of PE format. Data used were from a randomized controlled trial that examined two daily, compressed formats of PE treatment for PTSD (massed and intensive outpatient program) in military personnel and veterans (N = 234). Individuals without hazardous drinking had greater PTSD symptom reductions compared to those with hazardous drinking (d = 0.42, p = 0.001). However, the hazardous drinking group also demonstrated significant reductions in PTSD (d = 1.46, p < 0.001) following treatment, as well as in the number of drinks per week (d = 0.63, p = 0.025) at the 6-month follow-up. There was no significant difference in treatment engagement based on drinking classification and outcomes did not vary based on PE format. The findings suggest that PE is an appropriate treatment for individuals with PTSD and hazardous drinking. However, group differences in PTSD symptom reductions indicate concurrent hazardous drinking reduces treatment benefits of PE. Full article

Background/Objectives: Osteosarcoma is the most common malignant bone tumor in children, characterized by a high degree of genomic instability, resulting in copy number alterations and genomic rearrangements without disease-defining recurrent mutations. Clinical trials based on molecular characterization have failed to find new effective therapies or improve outcomes over the last 40 years. Methods: To better understand the immune microenvironment of osteosarcoma, we performed single-cell RNA sequencing on six tumor biopsy samples, combined with a previously published cohort of six samples. Additional osteosarcoma samples were profiled using spatial transcriptomics for the validation of discovered subtypes and to add spatial context. Results: Analysis revealed immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs), regulatory and exhausted T cells, and LAMP3+ dendritic cells. Conclusions: Using cell–cell communication modeling, we identified robust interactions between MDSCs and other cells, leading to NF-κB upregulation and an immunosuppressive microenvironment, as well as interactions involving regulatory T cells and osteosarcoma cells that promoted tumor progression and a proangiogenic niche. Full article

Background: Individuals with neuromuscular diseases (NMDs) have low physical activity levels and an increased risk of cardiovascular and pulmonary diseases. Respiratory gas kinetics obtained during cardiopulmonary exercise testing (CPET) may provide valuable insights into disease mechanisms and cardiorespiratory fitness in individuals with NMD. Recovery from exercise is an important marker of exercise performance and overall physical health, and impaired recovery is strongly associated with poor health outcomes. This study evaluates recovery metrics in individuals with NMD after performing maximal exertion during CPET. Methods: A total of 34 individuals with NMD and 15 healthy volunteers were recruited for the study. CPET was performed using a wearable metabolic system and a wheelchair-accessible total body trainer to peak exertion. Recovery metrics assessed were (i) the time to reach 50% O₂ recovery compared with peak exercise and (ii) the ratios of ventilation and respiratory gases between peak exercise and the highest values observed during recovery (overshoot). Results: The NMD group had a significantly longer time to reach 50% O₂ recovery (T1/2 VO₂: 105 ± 43.4 vs. 76 ± 36.4 s, p = 0.02), lower respiratory overshoot (17.1 ± 13.0% vs. 28.8 ± 9.03%), and lower ventilation/VO₂ (31.9 ± 28.3 vs. 52.2 ± 23.5) compared to the control group. Conclusions: This study observes significantly impaired recovery metrics following peak exercise in individuals with NMD compared to controls. These insights may improve the understanding of exercise recovery and mechanics, thus improving prognostication and optimizing exercise prescriptions for individuals with NMD. Full article

Alzheimer’s disease (AD) is the third leading cause of death among older adults with nearly 6 million diagnosed annually. In the race for a cure, one thing is certain—exercise can reduce your risk. However, the mechanisms responsible for this reduced risk are unknown. Several studies have linked exercise to improved memory, reduced amyloid beta plaques, and tau hyperphosphorylation in AD. Background/Objectives: By utilizing a novel rat model of AD, TgF344-AD, we evaluated the time course of behavioral shifts as well as the protective effect of exercise. Methods: TgF344-AD animals (61 total, 31 females and 30 males) were assessed every 3 months from 3 to 12 months of age and then assessments were increased to monthly until they reached 18 months of age. A progressive treadmill protocol was administered at 12 months of age and continued until 18 months. Pre-intervention and post-intervention data were analyzed. Results: Females had greater grip strength relative to body mass compared to males and exercise attenuated the age-related and AD-induced decline. Also, female AD-impaired memory was rescued with exercise, while males had no exercise-induced improvements. Conclusions: There is a sex difference present in the TgF344-AD rat model of Alzheimer’s disease and this should be studied further; in addition, sex differences across all models of AD and the human pathology need to be evaluated. Exercise neuroprotection, while more prominent in females, is an important factor in AD research, and further work to understand the mechanisms of neuroprotection is warranted. Full article

Background/Objectives: Persistent breathlessness impacts people living with advanced chronic obstructive pulmonary disease (COPD) and carers. Accessible services are limited. This translational pilot study evaluated the feasibility, impacts on patient and carer-reported outcomes, and hospital use of a home-based breathlessness intervention service (BLIS). Methods: People with stable COPD, ≥1 COPD-related hospital admissions in the previous year, and persistent breathlessness participated in a pre–post study. The BLIS program involved home visits/phone contacts by a nurse/physiotherapist (average 8 contacts, 7 weeks). Uptake, retention, and fidelity were recorded prospectively, and participant experience was explored (post-program interviews). Breathing discomfort (Multidimensional Dyspnea Profile A1 scale), threat (Brief Illness Perception Questionnaire), and carer stress/strain (Zarit Burden Interview) were compared pre- and post-program (week 9, 3 and 6 months) using mean difference and 95% confidence intervals (CIs). Hospital use for COPD-related causes in 12 months before/after participation was reported. Results: A total of 16/19 eligible people agreed to participate, and 15/16 completed the program. In participants with COPD (73 [9] years, FEV1%pred 42% [15], mean [SD]; a median of 3 COPD-related hospital admissions in the previous year) and carers (n = 6), BLIS was highly (in 95%) acceptable. Compared to pre-program, breathing discomfort was reduced in week 9 and 6 months; breathlessness threat was reduced in week 9 and 3 months; and carer burden was reduced at 6 months. Compared to the 12 months prior, hospital admissions decreased in the 12 months post-program. Conclusions: Translation of this service to the local setting was feasible, with high program uptake and retention. Post-program improvements in key patient- and carer-reported outcomes and a reduction in public hospital admissions support the implementation of the BLIS program for this cohort in this setting. Full article

Purpose: Adjuvant trastuzumab therapy has improved outcomes in HER2-positive breast cancer, but the impact of the timing of its initiation remains unclear. This study evaluates the effect of time to adjuvant trastuzumab-based therapy (TTAT) after surgery on survival in HER2-positive breast cancer. Methods: In this retrospective study, HER2-positive breast cancer patients treated with surgery followed by adjuvant trastuzumab without prior neoadjuvant therapy were analyzed. Patients were grouped by TTAT ≤ 42 days or >42 days post-surgery. Key endpoints included overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), evaluated through Kaplan–Meier and Cox regression analyses. Results: Patients with TTAT greater than 42 days had significantly worse OS, DFS, and DMFS (p = 0.036, p = 0.045, and p = 0.048, respectively, log-rank test) than those initiating trastuzumab within 42 days. On multivariate analysis, delays beyond 42 days were associated with a significantly increased risk of recurrence and mortality, showing reduced DFS (HR 2.52; p = 0.027) and OS (HR 4.48; p = 0.004). These findings indicate that even moderate delays in trastuzumab initiation can adversely affect survival. Conclusions: Delaying trastuzumab initiation beyond 42 days post-surgery negatively impacts survival in HER2-positive breast cancer, emphasizing the need for timely treatment. These results support clinical guidelines advocating prompt initiation of adjuvant therapy to improve long-term outcomes for HER2-positive patients. Full article

Black/African American individuals experience high rates of posttraumatic stress disorder (PTSD), which is frequently chronic and undertreated in this population. Intimate relationships are a salient resource for Black/African American adults’ psychological well-being. To help advance health equity, this study serves as an initial, proof-of-concept investigation of patient outcomes among Black/African American adults who received a disorder-specific couple therapy for PTSD. Participants were a subsample of seven Black/African American adults (mean age = 40.56 years, SD = 10.18; 85.7% male) who participated in an uncontrolled trial of an abbreviated, intensive, multi-couple group version of cognitive-behavioral conjoint therapy for PTSD with 24 military dyads. Treatment was delivered over 2 days in a weekend retreat format. Assessments were administered at baseline, 1 month post-retreat, and 3 months post-retreat. There were large and significant decreases in patients’ PTSD symptoms based on clinicians’ and patients’ ratings (ds −1.37 and −1.36, respectively) by the 3-month follow-up relative to baseline. There were also large and significant decreases in patients’ depressive, anxiety, and anger symptoms (ds −1.39 to −1.93) and a large, marginally significant decrease in patients’ insomnia (d = −0.85; p = 0.083). Patients reported a medium, non-significant increase in relationship satisfaction (d = 0.68; p = 0.146) and a large, marginally significant increase in joint dyadic coping (d = 0.90; p = 0.069). Findings offer preliminary evidence that treating PTSD within a couple context is a relevant strategy to reduce PTSD and comorbid symptoms among partnered Black/African American adults and a promising approach to enhance relationships. Full article

Background/Objectives: The aim of this study was to determine the optimal ventilation mode during cardiopulmonary resuscitation (CPR) by comparing the effects of chest compression-synchronized ventilation (CCSV) and intermittent positive-pressure ventilation (IPPV) on arterial blood gases. Methods: This prospective randomized controlled study included patients presenting with out-of-hospital cardiac arrest who were randomly assigned to the CCSV or IPPV groups. Arterial blood gas analysis was performed at the start of CPR and 10 min after initiating mechanical ventilation. Primary outcomes included changes in the arterial oxygen and carbon dioxide pressures. Results: Of the 144 patients with out-of-hospital cardiac arrest, 30 were included in the study, with 15 each assigned to the CCSV and IPPV groups. The median arterial oxygen pressure in the CCSV group was 76.1 [22.8; 260.3 interquartile range], compared with 8.8 [−1.6; 113.9 interquartile range] in the IPPV group (p = 0.250). The change in carbon dioxide pressure was −10.3 [−18.3; −2.7 interquartile range] in the CCSV group and −11.5 [−39.5; 5.6 interquartile range] in the IPPV group (p = 0.935). Wilcoxon signed-rank test results revealed significant differences in arterial oxygen and carbon dioxide pressure levels before and after treatment in the CCSV group (p = 0.026 and 0.048, respectively). However, in the IPPV group, changes in arterial partial pressure of oxygen and carbon dioxide before and after treatment were non-significant (p = 0.095 and 0.107, respectively). Conclusions: Although CCSV significantly improved oxygenation and ventilation in patients undergoing CPR, it cannot be considered superior to IPPV. Full article

In this article, we introduce a novel framework for learning spatial concepts within a human-in-the-loop (HITL) context, highlighting the critical role of explainability in AI systems. By incorporating human feedback, the approach enhances the learning process, making it particularly suitable for applications where user trust and interpretability are essential, such as AiTR. Namely, we introduce a new parametric similarity measure for spatial relations expressed as histograms of forces (HoFs). Next, a spatial concept is represented as a spatially attributed graph and HoF bundles. Last, a process is outlined for utilizing this structure to make decisions and learn from human feedback. The framework’s robustness is demonstrated through examples with diverse user types, showcasing how varying feedback strategies influence learning efficiency, accuracy, and ability to tailor the system to a particular user. Overall, this framework represents a promising step toward human-centered AI systems capable of understanding complex spatial relationships while offering transparent insights into their reasoning processes. Full article

The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression of self-renewal factors and CSCs population. O-GlcNAcylation of GATAD2B at the C-terminus protects GATAD2B from ubiquitination and proteasomal degradation in breast cancer cells. We identify ITCH as a novel E3 ligase for GATAD2B and show that targeting ITCH genetically increases GATAD2B levels and increases CSCs phenotypes. Lastly, we show that overexpression of wild-type GATAD2B, but not the mutant lacking C-terminal O-GlcNAc sites, promotes mammosphere formation, expression of CSCs factors and drug resistance. Together, we identify a key role of GATAD2B and ITCH in regulating CSCs in breast cancer and GATAD2B O-GlcNAcylation as a mechanism regulating breast cancer stem-like populations and promoting chemoresistance. Full article

Magnetic nanoparticles are extensively utilized as markers/signal labelling in various biomedical applications. Detecting and distinguishing magnetic signals from similarly sized moving magnetic nanoparticles in microfluidic systems is crucial yet challenging for biosensing. In this study, we have developed an original method to detect and differentiate magnetic signals from moving superparamagnetic (SPM) and ferrimagnetic (FM) nanoparticles of comparable sizes. Our approach utilizes a highly sensitive magnetic-coil-based sensor that harnesses the combined effects of giant magnetoimpedance (GMI) and an LC-resonance circuit, offering performance superior to that of conventional GMI sensors. Iron oxide nanoparticles, which have similar particle sizes but differing coercivities (zero for SPM and non-zero for FM) or similar zero coercivities but differing particle sizes, flow through the magnetic coil at controlled velocities. Their distinct effects are analyzed through changes in the complex impedance of the sensing system. Our findings provide a unique pathway for utilizing SPM and FM nanoparticles as innovative magnetic markers to identify specific biological entities, thereby expanding their potential applications. Full article

Older adults with serious mental illness (SMI) (i.e., schizophrenia, schizoaffective disorder, bipolar disorder) have compromised physical function that adversely affects their quality of life. Exercise is an effective intervention to improve function in older persons; however, older people with SMI experience barriers to exercise engagement. This study sought to obtain feedback on an exercise program in development for older people with SMI that comprised home-based exercise delivery, individualized exercise prescription, and motivational health coaching calls. Individual interviews and focus groups were conducted with older Veterans with SMI (n = 3) and clinical staff serving this population (directors: n = 3; clinicians: n = 15, k = 3) to elicit feedback on the perceived feasibility and acceptability of the preliminary program and recommendations for modifications to the program. Rapid analysis was used to summarize transcripts of audio-recorded interviews and focus groups. Results indicated a strong perceived feasibility and acceptability of the preliminary intervention because of how the individualized exercise prescription component (i.e., exercise plan) would be personalized to the Veteran’s preferences and abilities. Clinical staff participants expressed concerns about how the lack of real-time supervision would negatively affect exercise completion. Participants recommended tailoring the home-based exercise delivery and motivational health coaching calls components to each Veteran’s unique context. Full article

Flaxseed meal, rich in water-soluble gums, improves the texture of gluten-free (GF) products. Bioactive antioxidant peptides from flaxseed, known as linusorbs (LOs) or cyclolinopeptides, may provide health benefits. However, the stability of flaxseed-derived LOs during dough preparation, baking, and storage remains unclear. To investigate this, GF bread dough and bread were prepared with flaxseed meal, and the LO content was determined in the flaxseed meal, the bread flour with the flaxseed meal, the dough, and the bread. The LO levels were also monitored during storage at various temperatures (−18 °C, 4 °C, and 22–23 °C) for 0, 1, 2, and 4 weeks using high-performance liquid chromatography–diode array detection (HPLC-DAD). The levels of oxidized LOs, such as [1–9-NαC],[1-(R_s,S_s)-MetO]-linusorb B2 (LO14), remained relatively stable in the flaxseed meal and the flour derived from it across under all conditions for up to 4 weeks. Due to microbial contamination, the dough could not be stored at either 4 or 21 °C, and the bread could only be stored at 21 °C for one week. However, the bread and dough could be stored for up to 4 weeks at −18 °C, and the bread at 4 °C, without a significant loss of LOs. The main changes in LOs occurred during processing rather than storage. Reduced LOs were found in higher concentrations in the flour and meal compared to the dough and bread, without a corresponding increase in oxidized LOs. The flaxseed meal-fortified bread maintained oxidative stability when stored at low temperatures. This is the first study to investigate the effect of baking conditions on LO content and antioxidant properties. Full article

Aeromonas species are enteropathogens that cause gastroenteritis with a unique three-peak infection pattern related to patient age. The contributions of individual Aeromonas species to age-related infections remain unknown. Multi-locus sequence typing (MLST) was performed to determine the species of Aeromonas strains from Australian patients with gastroenteritis. Public database searches were conducted to collect strains of enteric Aeromonas species, identified by either MLST or whole genome sequencing with known patient age. Violin plot analysis was performed to assess Aeromonas infection distribution across patients of different ages. Generalized additive model (GAM) analysis was employed to investigate the relationship between Aeromonas species and patient age. A total of 266 strains of seven Aeromonas species met the selection criteria, which were used for analyses. The violin plots revealed distinct patterns among individual Aeromonas species in relation to patient age. The GAM analyses identified a significant association between Aeromonas species and patient age (p = 0.009). Aeromonas veronii (153 strains) showed the highest probability of infection in most ages, particularly among young adults. Aeromonas caviae (59 strains) is more common in young children and adults over 60 years of age. The probability of infection for Aeromonas hydrophila (34 strains) and Aeromonas dhakensis (9 strains) was generally low, there was a slight increase in individuals aged 50–60 for A. hydrophila and over 60 years for A. dhakensis. These findings provide novel evidence of the varied contributions of different Aeromonas species to human enteric infections related to patient age, offering valuable insights for epidemiology and clinical management. Full article

Background/Objective: Research shows that obesity has risen among rehabilitation patients. Despite this, nutrition care in subacute rehabilitation wards focuses primarily on preventing and treating protein-energy malnutrition. The continued provision of energy-dense meals during lengthy rehabilitation admissions may present a risk of overnutrition for some patients, which can adversely affect functional outcomes. However, overnutrition is not routinely monitored in practice. This study summarizes the initial findings of a multi-site investigation of overnutrition incidence across five rehabilitation wards to scope the need for future research. Methods: A retrospective audit was conducted, including all inpatients admitted over 3 months to the study wards with a complete dataset (total sample n = 199). Data were collected from the medical record and menu management system to determine overnutrition, defined as an average daily energy intake equal to or greater than 1000 kJ above estimated requirements and weight gain of equal to or greater than 1 kg over the admission. Results: The incidence of overnutrition in the total sample was 12.1%. Of those patients deemed at low risk of malnutrition (n = 124), 19.4% developed overnutrition during their rehabilitation admission. Those who developed overnutrition during their admission gained an average of 2.9 kg, with a mean excess energy intake of 2456 kJ/day above estimated requirements. They also consumed a high intake of discretionary items (mean of 3156 kJ/day). Conclusions: The findings suggest that further research is needed to investigate the etiology and impact of the overlooked problem of overnutrition in subacute rehabilitation settings. Future investigation is essential to ensure that the planning and delivery of subacute dietetic and food services meet the nutrition needs of patients in longer-stay inpatient settings. Full article