A qualitative study of stakeholders' experiences with and acceptability of a technology-supported health coaching intervention (SHARE-S) delivered in coordination with cancer survivorship care.

PURPOSE: Healthy cancer survivorship involves patients' active engagement with preventative health behaviors and follow-up care. While clinicians and patients have typically held dual responsibility for activating these behaviors, transitioning some clinician effort to technology and health coaches may enhance guideline implementation. This paper reports on the acceptability of the Shared Healthcare Actions & Reflections Electronic systems in survivorship (SHARE-S) program, an entirely virtual multicomponent intervention incorporating e-referrals, remotely-delivered health coaching, and automated text messages to enhance patient self-management and promote healthy survivorship. METHODS: SHARE-S was evaluated in single group hybrid implementation-effectiveness pilot study. Patients were e-referred from the clinical team to health coaches for three health self-management coaching calls and received text messages to enhance coaching. Semi-structured qualitative interviews were conducted with 21 patient participants, 2 referring clinicians, and 2 health coaches to determine intervention acceptability (attitudes, appropriateness, suitability, convenience, and perceived effectiveness) and to identify important elements of the program and potential mechanisms of action to guide future implementation. RESULTS: SHARE-S was described as impactful and convenient. The nondirective, patient-centered health coaching and mindfulness exercises were deemed most acceptable; text messages were less acceptable. Stakeholders suggested increased flexibility in format, frequency, timing, and length of participation, and additional tailored educational materials. Patients reported tangible health behavior changes, improved mood, and increased accountability and self-efficacy. CONCLUSIONS: SHARE-S is overall an acceptable and potentially effective intervention that may enhance survivors' self-management and well-being. Alterations to tailored content, timing, and dose should be tested to determine impact on acceptability and outcomes.

A Multidisciplinary Curriculum to Standardize Chest Procedures Training for Trainees in General Surgery, Emergency Medicine, and Critical Care.

Introduction: Critical care, emergency medicine, and surgical trainees frequently perform surgical and Seldinger-technique tube thoracostomy, thoracentesis, and thoracic ultrasound. However, approaches to teaching these skills are highly heterogeneous. Over 10 years, we have developed a standardized, multidisciplinary curriculum to teach these procedures. Methods: Emergency medicine residents, surgical residents, and critical care fellows, all in the first year of their respective programs, underwent training in surgical and Seldinger chest tube placement and securement, thoracentesis, and thoracic ultrasound. The curriculum included preworkshop instructional videos and 45-minute in-person practice stations (3.5 hours total). Sessions were co-led by faculty from emergency medicine, thoracic surgery, and pulmonary/critical care who performed real-time formative assessment with standardized procedural steps. Postcourse surveys assessed learners' confidence before versus after the workshop in each procedure, learners' evaluations of faculty by station and specialty, and the workshop overall. Results: One hundred twenty-three trainees completed course evaluations, demonstrating stable and positive responses from learners of different backgrounds taught by a multidisciplinary group of instructors, as well as statistically significant improvement in learner confidence in each procedure. Over time, we have made incremental changes to our curriculum based on feedback from instructors and learners. Discussion: We have developed a unique curriculum designed, revised, and taught by a multidisciplinary faculty over many years to teach a unified approach to the performance of common chest procedures to surgical, emergency medicine, and critical care trainees. Our curriculum can be readily adapted to the needs of institutions that desire a standardized, multidisciplinary approach to thoracic procedural education.

Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.

Background: Blood-based biomarkers are gaining grounds for Alzheimer's disease (AD) detection. However, two key obstacles need to be addressed: the lack of methods for multi-analyte assessments and the need for markers of neuroinflammation, vascular, and synaptic dysfunction. Here, we evaluated a novel multi-analyte biomarker platform, NULISAseq CNS disease panel, a multiplex NUcleic acid-linked Immuno-Sandwich Assay (NULISA) targeting ~120 analytes, including classical AD biomarkers and key proteins defining various disease hallmarks. Methods: The NULISAseq panel was applied to 176 plasma samples from the MYHAT-NI cohort of cognitively normal participants from an economically underserved region in Western Pennsylvania. Classical AD biomarkers, including p-tau181 p-tau217, p-tau231, GFAP, NEFL, Aß40, and Aß42, were also measured using Single Molecule Array (Simoa). Amyloid pathology, tau pathology, and neurodegeneration were evaluated with [11C] PiB PET, [18F]AV-1451 PET, and MRI, respectively. Linear mixed models were used to examine cross-sectional and Wilcoxon rank sum tests for longitudinal associations between NULISA biomarkers and AD pathologies. Spearman correlations were used to compare NULISA and Simoa. Results: NULISA concurrently measured 116 plasma biomarkers with good technical performance, and good correlation with Simoa measures. Cross-sectionally, p-tau217 was the top hit to identify Aß pathology, with age, sex, and APOE genotype-adjusted AUC of 0.930 (95%CI: 0.878-0.983). Fourteen markers were significantly decreased in Aß-PET+ participants, including TIMP3, which regulates brain Aß production, the neurotrophic factor BDNF, the energy metabolism marker MDH1, and several cytokines. Longitudinally, FGF2, IL4, and IL9 exhibited Aß PET-dependent yearly increases in Aß-PET+ participants. Markers with tau PET-dependent longitudinal changes included the microglial activation marker CHIT1, the reactive astrogliosis marker CHI3L1, the synaptic protein NPTX1, and the cerebrovascular markers PGF, PDGFRB, and VEFGA; all previously linked to AD but only reliably measured in cerebrospinal fluid. SQSTM1, the autophagosome cargo protein, exhibited a significant association with neurodegeneration status after adjusting age, sex, and APOE ε4 genotype. Conclusions: Together, our results demonstrate the feasibility and potential of immunoassay-based multiplexing to provide a comprehensive view of AD-associated proteomic changes. Further validation of the identified inflammation, synaptic, and vascular markers will be important for establishing disease state markers in asymptomatic AD.

Sex-biasing influence of autism-associated Ube3a gene overdosage at connectomic, behavioral, and transcriptomic levels.

Genomic mechanisms enhancing risk in males may contribute to sex bias in autism. The ubiquitin protein ligase E3A gene (Ube3a) affects cellular homeostasis via control of protein turnover and by acting as transcriptional coactivator with steroid hormone receptors. Overdosage of Ube3a via duplication or triplication of chromosomal region 15q11-13 causes 1 to 2% of autistic cases. Here, we test the hypothesis that increased dosage of Ube3a may influence autism-relevant phenotypes in a sex-biased manner. We show that mice with extra copies of Ube3a exhibit sex-biasing effects on brain connectomics and autism-relevant behaviors. These effects are associated with transcriptional dysregulation of autism-associated genes, as well as genes differentially expressed in 15q duplication and in autistic people. Increased Ube3a dosage also affects expression of genes on the X chromosome, genes influenced by sex steroid hormone, and genes sex-differentially regulated by transcription factors. These results suggest that Ube3a overdosage can contribute to sex bias in neurodevelopmental conditions via influence on sex-differential mechanisms.

CsPbBr3 Perovskite Crack Platelet Nanocrystals and Their Biexciton Generation.

Lead halide perovskite nanocrystals have been extensively studied in recent years as efficient optical materials for their bright and color-tunable emissions. However, these are mostly confined to their 3D nanocrystals and limited to the anisotropic nanostructures. By exploring the Cs-sublattice-induced metal(II) ion exchange with Pb(II), crack CsPbBr3 perovskite platelet nanocrystals having polar surfaces in all three directions are reported here, which remained different than reported standard square platelets. The crack platelets are also passivated with halides to enhance their brightness. Further, as these crack and passivated crack platelets have defects and polar surfaces, the exciton and biexciton generation in these platelets is investigated using femtosecond photoluminescence and transient absorption measurement at ambient as well as cryogenic temperatures, correlated with time-resolved single-particle photoluminescence spectroscopy, and compared with standard square platelets having nonpolar facets. These investigations revealed that the crack platelets and passivated crack platelets possess enhanced biexciton emission compared to square platelets due to the presence of polar surfaces in all three directions. These results provide insights into not only the design of the anisotropic nanostructures of ionic nanocrystals but also the possibility of tuning the single exciton to biexciton generation efficiency, which has potential applications in optoelectronic systems.

Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression.

While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-ß (Aß) progression - a central feature of AD - remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aß accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aß progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aß-positive status in the Atherosclerosis Risk in Communities (ARIC) study. Genetic variation that influenced plasma levels of CAT, CD36 and KRT19 predicted rates of Aß accumulation, including causal relationships with Aß PET levels identified with two-sample Mendelian randomization. In addition to associations with tau PET and plasma AD biomarker changes, as well as expression patterns in human microglia subtypes and neurovascular cells in AD brain tissue, we showed that 31 % of candidate proteins were related to mid-life (20-year) or late-life (8-year) dementia risk in ARIC. Our findings reveal plasma proteins associated with longitudinal Aß accumulation, and identify specific peripheral immune mediators that may contribute to the progression of AD pathophysiology.

Prevalence of Self-Reported COVID-19 Infection in Persons with Complicated Mild to Severe Traumatic Brain Injury (TBI): A TBI Model Systems Study.

OBJECTIVE: To describe the incidence of self-reported COVID-19 history in a longitudinal cohort of individuals with complicated mild to severe traumatic brain injury (TBI) and describe demographic, injury and functional differences based on history of COVID-19 infection. DESIGN: Individuals with complicated mild to severe TBI aged 16 or older at time of injury who were enrolled in the TBI Model Systems longitudinal cohort study, completed a baseline or follow-up interview between October 1, 2021-March 31, 2023, and provided information about COVID-19 history and timing of COVID-19 infection was collected. RESULTS: Of the 3,627 individuals included in the analysis, 29.5% reported a history of COVID-19 infection. Those with reported COVID-19 history tended to be younger, not of a racial/ethnic minority background, and greater functional status at follow up based on the Glasgow Outcome Scale-Extended scale compared to those with no reported COVID-19 history (p < 0.05). Among those with COVID-19 history, 61.8% did not receive medical care, 27.6% received medical care but no hospitalization, and 10.5% were hospitalized. Of those hospitalized, 21.4% required ventilator use. CONCLUSION: Incidence of COVID-19 diagnosis and related hospitalization characteristics in persons with complicated mild to severe TBI was similar to national incidence between March 2020-2023. Secondary effects of the COVID-19 pandemic on persons with TBI require investigation.

Invasive Group A Streptococcal Infections in Europe After the COVID-19 Pandemic.

BACKGROUND: The incidence of airborne respiratory infections fell as a result of the protective measures taken during the COVID-19 pandemic and rose again when these were stopped. In 2022, there was a notable rise in invasive group A streptococcal (iGAS) infections in many countries, including Germany. This rise was also reflected in the data of the university otorhinolaryngology department in Ulm, Germany. METHODS: This review is based on publications retrieved by a selective literature search on the rise of iGAS infections in Europe, with particular attention to the timing of disease onset, clinical presentation, pathogenic strains, and potential causes and risk factors. RESULTS: The rise in infections after the pandemic was especially marked among children up to age 10 and in older adults; in Germany, it affected all age groups equally. Rising prevalence figures were seen in Germany and elsewhere as early as the fall of 2022, outside the usual season, and peaked mainly in the first and second quarters of 2023. The increased incidence of iGAS-associated pneumonia was paralleled by that of viral airway infections and led to greater use of intensive-care measures for children. The main bacterial strain identified was emm1; a new variant (M1DK) played a role in Denmark, and an emm4 variant (M4NL22) became increasingly important in the Netherlands. In Germany, initial evidence suggested the predominance of M1UK. Increased antibiotic resistance was not found. CONCLUSION: The reduced confrontation of the immune system with pathogens during the pandemic, along with the increased incidence of viral airway infections immediately after it, apparently accounted for the exceptionally high post-pandemic rise in iGAS infections and the increase in invasive pulmonary diseases in Europe. Consistent vaccination programs against coincident respiratory viruses could reduce the burden of iGAS infections. The further extension of multinational surveillance programs with obligatory participation could aid in the detection of factors affecting the course of disease and the spread of new bacterial strains.

Single-cell topographical profiling of the immune synapse reveals a biomechanical signature of cytotoxicity.

Immune cells have intensely physical lifestyles characterized by structural plasticity and force exertion. To investigate whether specific immune functions require stereotyped mechanical outputs, we used super-resolution traction force microscopy to compare the immune synapses formed by cytotoxic T cells with contacts formed by other T cell subsets and by macrophages. T cell synapses were globally compressive, which was fundamentally different from the pulling and pinching associated with macrophage phagocytosis. Spectral decomposition of force exertion patterns from each cell type linked cytotoxicity to compressive strength, local protrusiveness, and the induction of complex, asymmetric topography. These features were validated as cytotoxic drivers by genetic disruption of cytoskeletal regulators, live imaging of synaptic secretion, and in silico analysis of interfacial distortion. Synapse architecture and force exertion were sensitive to target stiffness and size, suggesting that the mechanical potentiation of killing is biophysically adaptive. We conclude that cellular cytotoxicity and, by implication, other effector responses are supported by specialized patterns of efferent force.

Evaluation and Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity in Traumatic Brain Injury.

OBJECTIVE: Paroxysmal sympathetic hyperactivity (PSH) can occur in up to 10% of severe traumatic brain injury (TBI) patients and is associated with poorer outcomes. A consensus regarding management is lacking. We provide a practical guide on the multi-faceted clinical management of PSH, including pharmacological, procedural and non-pharmacological interventions. In addition to utilizing a standardized assessment tool, the use of medications to manage sympathetic and musculoskeletal manifestations (including pain) is highlighted. Recent studies investigating new approaches to clinical management are included in this review of pharmacologic treatment options. CONCLUSION: While studies regarding pharmacologic selection for PSH are limited, this paper suggests a clinical approach to interventions based on predominant symptom presentation (sympathetic hyperactivity, pain and/or muscle hypertonicity) and relevant medication side effects.

Adaptive sampling method to monitor low-risk pathways with limited surveillance resources.

The rise of globalization has led to a sharp increase in international trade with high volumes of containers, goods, and items moving across the world. Unfortunately, these trade pathways also facilitate the movement of unwanted pests, weeds, diseases, and pathogens. Each item could contain biosecurity risk material, but it is impractical to inspect every item. Instead, inspection efforts typically focus on high-risk items. However, low risk does not imply no risk. It is crucial to monitor the low-risk pathways to ensure that they are and remain low risk. To do so, many approaches would seek to estimate the risk to some precision, but increasingly lower risks require more samples. On a low-risk pathway that can be afforded only limited inspection resources, it makes more sense to assign fewer samples to the lower risk activities. We approach the problem by introducing two thresholds. Our method focuses on letting us know whether the risk is below certain thresholds, rather than estimating the risk precisely. This method also allows us to detect a significant change in risk. Our approach typically requires less sampling than previous methods, while still providing evidence to regulators to help them efficiently and effectively allocate inspection effort.

Cerebrospinal fluid p-tau181, 217, and 231 in definite Creutzfeldt-Jakob disease with and without concomitant pathologies.

INTRODUCTION: The established cerebrospinal fluid (CSF) phosphorylated tau181 (p-tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age-related tauopathy (PART) found in Creutzfeldt-Jakob disease (CJD) at autopsy. METHODS: We investigated CSF N-terminal p-tau181, p-tau217, and p-tau231 with in-house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post-mortem examination performed in patients with CJD 1.3 (0.3-14.3) months after CSF collection revealed no co-pathology in 10, concomitant AD in 8, PART in 8, and other co-pathologies in 3 patients. RESULTS: N-terminal p-tau was increased in CJD versus SCD (p < 0.0001) and correlated with total tau (t-tau) in the presence of AD and PART co-pathology (rho = 0.758-0.952, p ≤ 001). Concentrations in CJD+AD were indistinguishable from AD dementia, with the largest fold-change in p-tau217 (11.6), followed by p-tau231 and p-tau181 (3.2-4.5). DISCUSSION: Variable fold-changes and correlation with t-tau suggest that p-tau closely associates with neurodegeneration and concomitant AD in CJD. HIGHLIGHTS: N-terminal phosphorylated tau (p-tau) biomarkers are increased in Creutzfeldt-Jakob disease (CJD) with and without concomitant AD. P-tau217, p-tau231, and p-tau181 correlate with total tau (t-tau) and increase in the presence of amyloid beta (Aß) co-pathology. N-terminal p-tau181 and p-tau231 in Aß-negative CJD show variation among PRNP genotypes. Compared to mid-region-targeting p-tau181, cerebrospinal fluid (CSF) N-terminal p-tau has greater potential to reflect post-mortem neuropathology in the CJD brain.

Stellungnahme der Wissenschaftlichen Fachgesellschaft und des Berufsverbandes zur Notfallversorgung in der Hals-Nasen-Ohren-Heilkunde.

Clinics and practices in the field of ear, nose and throat medicine (ENT) are experiencing a significant increase in the number of emergency patients, which has multiple reasons. There is broad consent that a reform of emergency structures is necessary.The government commission for modern and needs-based hospital care has made recommendations with statements on the reform of emergency and acute care in the areas of "emergency services and financing" and "integrated emergency centers and integrated control centers". For this purpose a reliable foundation will be created with participation of specialist societies and professional associations, also linked to the hope of initiating the urgently needed relief of medical staff in clinics and practices.The present manuscript describes the health policy history and current problems in emergency care, focusing on proposed solutions with reference to the special features of ENT medicine. This position paper is linked to an appeal to self-administration and politicians to quickly implement a sustainable concept for emergency care, as financing and staff availability are becoming increasingly critical and the unregulated wave of emergency patients must be given a helping hand.

Drinking contexts, coping motive, simultaneous cannabis use, and high-intensity drinking among adults in the United States.

AIMS: High-intensity drinking (HID), extreme drinking considerably above the level of heavy episodic drinking (HED), is associated with long-term health and social consequences. There is limited understanding of HID beyond young adulthood. This study aims to identify concurrent risk factors for HID, comparing age differences among all adults. METHODS: Multinomial logistic and linear regression modeling was performed using a nationally-representative sample of adults (analytic n = 7956) from the 2015 and 2020 National Alcohol Surveys. The outcomes were any HID of 8-11 drinks and 12+ drinks for men, and 8+ drinks for women, and corresponding frequencies. Concurrent risk factors included coping motive, sensation seeking, simultaneous use of alcohol and cannabis (SAC), and drinking at a bar or party. Analyses were stratified by age (18-29 vs. older) and sex. RESULTS: For younger men, sensation-seeking was significantly associated with HID (vs. no HED) at both levels and frequency of HID 8-11 drinks, while drinking to cope was only significant for 12+ drinks. For older men, drinking to cope was a consistent predictor for both HID level and its frequency, but sensation-seeking was not significant. Both coping and sensation-seeking were significantly associated with any HID for all women, while coping was significant for HID frequency for younger women. Frequent drinking at bars and parties were associated with greater odds of HID for all adults. With HED as referent, similar patterns of (though fewer significant) associations were observed. CONCLUSIONS: Younger and older adults share similar risk factors for HID, with coping more consistent for older men.

Geriatric conditions and healthcare utilization among older adults living in subsidized housing.

BACKGROUND: Nearly 2.9 million older Americans with lower incomes live in subsidized housing. While regional and single-site studies show that this group has higher rates of healthcare utilization compared to older adults in the general community, little is known about healthcare utilization nationally nor associated risk factors. METHODS: We conducted a retrospective cohort study of Medicare beneficiaries aged ≥65 enrolled in the National Health and Aging Trends Study in 2011, linked to Medicare claims data, including individuals living in subsidized housing and the general community. Participants were followed annually through 2020. Outcomes were hospitalization, short-term skilled nursing facility (SNF) utilization, long-term care utilization, and death. Fine-Gray competing risks regression analysis was used to assess the association of subsidized housing residence with hospitalization and nursing facility utilization, and Cox proportional hazards regression analysis was used to assess the association with death. RESULTS: Among 6294 participants (3600 women, 2694 men; mean age, 75.5 years [SD, 7.0]), 295 lived in subsidized housing at baseline and 5999 in the general community. Compared to older adults in the general community, those in subsidized housing had a higher adjusted subdistribution hazard ratio [sHR] of hospitalization (sHR 1.21; 95% CI, 1.03-1.43), short-term SNF utilization (sHR 1.49; 95% CI, 1.15-1.92), and long-term care utilization (sHR 2.72; 95% CI, 1.67-4.43), but similar hazard of death (HR, 0.86; 95% CI, 0.69-1.08). Individuals with functional impairment had a higher adjusted subdistribution hazard of hospitalization and short-term SNF utilization and individuals with dementia and functional impairment had a higher hazard of long-term care utilization. CONCLUSIONS: Older adults living in subsidized housing have higher hazards of hospitalization and nursing facility utilization compared to those in the general community. Housing-based interventions to optimize aging in place and mitigate risk of nursing facility utilization should consider risk factors including functional impairment and dementia.

Injection Laryngoplasty for Children with Dysphagia after Cardiac Surgery.

Objective: To determine whether injection laryngoplasty (IL) resolves thin liquid aspiration among children with unilateral vocal cord paralysis (UVCP) after cardiac surgery. Study Design: Retrospective case-control. Setting: Tertiary children's hospital. Methods: Consecutive children (<5 years) between 2012 and 2022 with UVCP after cardiac surgery were included. Resolution of thin liquid aspiration after IL versus observation was determined for children obtaining videofluoroscopic swallow studies (VFSS). Results: A total of 32 children with left UVCP after cardiac surgery met inclusion. Initial surgeries were N = 9 (28%) patent ductus arteriosus ligations, N = 7 (22%) aortic arch surgeries, N = 9 (28%) surgeries for hypoplastic left heart syndrome, and N = 7 (22%) other cardiac surgeries. The mean age at initial surgery was 1.8 months (SD: 3.7). All children had a VFSS obtained after surgery that confirmed aspiration. There were 17 children that obtained an IL at 33.6 months (SD: 20.9) after cardiac surgery and 15 children observed without IL procedure. No surgical complications after IL were noted. The rate of aspiration resolution based on postoperative VFSS was N = 14 (82%) for the IL group and N = 9 (60%) for the control group P = .24. Documented VFSS aspiration resolution after cardiac surgery occurred by 9.6 months (SD: 10.0) in the observation group and 47.4 months (SD: 24.1) in the IL group (P < .001). Conclusion: IL can help treat aspiration in children with UVCP after cardiac surgery but the benefit beyond observation remains unclear. Future studies should continue to explore the utility for IL in managing dysphagia in this pediatric population.

High Density Loading and Collisional Loss of Laser-Cooled Molecules in an Optical Trap.

We report optical trapping of laser-cooled molecules at sufficient density to observe molecule-molecule collisions for the first time in a bulk gas. SrF molecules from a red-detuned magneto-optical trap (MOT) are compressed and cooled in a blue-detuned MOT. Roughly 30% of these molecules are loaded into an optical dipole trap with peak number density n_{0}≈3×10^{10} cm^{-3} and temperature T≈40 µK. We observe two-body loss with rate coefficient ß=2.7_{-0.8}^{+1.2}×10^{-10} cm^{3} s^{-1}. Achieving this density and temperature opens a path to evaporative cooling towards quantum degeneracy of laser-cooled molecules.