'With or without you': associations between noteworthy events and cognitive complaints across 100 days.

OBJECTIVES: Daily noteworthy events have implications for physical and mental health, but less is known about the role daily events have for self-reported cognition and whether the involvement of close social partners differentiates these associations. The current study examined how daily positive and negative noteworthy events relate to subjective memory and attentional difficulties and whether close social partners moderated associations. METHOD: We used data from a 100-day microlongitudinal web-based study of 104 older adults (Nobservations=7,051; Mage=63.13 years, SDage=7.81, 88.46% Female). Participants reported on exposure to and valence of noteworthy events, involvement of close social partners, and subjective cognitive complaints at the end of each day. RESULTS: Logistic multilevel models revealed that days with a negative event were associated with increased odds of forgetting something and trouble concentrating whereas days with positive events were associated with decreased odds of trouble concentrating. Close social partner involvement did not moderate within-person associations. CONCLUSION: Our results suggest that day-to-day events are correlates of cognitive complaints regardless of close social partner involvement in the events. Research should clarify the role of daily positive and negative events in personalized interventions and determine whether this person-centered approach to self-reported cognitive health helps inform diagnostic practices.

Reconstructing Nasal Defects With Acellular Dermal Matrix After Mohs Micrographic Surgery: A 12-year Experience.

BACKGROUND AND OBJECTIVE: Large defects of the nose after Mohs surgery pose a significant reconstructive challenge to both dermatologic and reconstructive surgeons. The authors present their 12-year experience utilizing acellular dermal matrices for nasal reconstruction. METHODS: A retrospective review of patients undergoing Mohs surgery and alloplastic nasal reconstruction with acellular dermal matrices between 2010 and 2022 was performed. Patients who underwent single-stage reconstruction and dual-stage reconstruction with skin graft with at least 90 days of follow-up were included. RESULTS: Fifty-one patients met criteria with a median age of 77 years. Fifty-three lesions were reconstructed with acellular dermal matrices. The most common lesion location was nasal sidewall (50%) with a mean defect size of 10.8 cm 2 . 30.8% underwent same-day acellular dermal matrix reconstruction, with 69.2% undergoing two-stage reconstruction. Acellular dermal matrices successfully reconstructed acquired defects in 94.2% of lesions. Average time to re-epithelialization was 27.6 + 6.2 days. Average time to repigmentation was 145.35 + 86 days. No recurrences were recorded. Total complication rate was 9.62%. Average size for successful healing was 10.8 cm 2 . Average defect size for complication or failure was 14.7 cm 2 . Seven sites (13.46%) underwent aesthetic improvement procedures. CONCLUSION: Acellular bilayer wound matrix is an adequate reconstructive option for single or dual-stage reconstruction of the nose with low complication and revision rates.

Outbreak of Highly Pathogenic Avian Influenza A(H5N1) Virus in Seals, St. Lawrence Estuary, Quebec, Canada1.

We describe an unusual mortality event caused by a highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b involving harbor (Phoca vitulina) and gray (Halichoerus grypus) seals in the St. Lawrence Estuary, Quebec, Canada, in 2022. Fifteen (56%) of the seals submitted for necropsy were considered to be fatally infected by HPAI H5N1 containing fully Eurasian or Eurasian/North American genome constellations. Concurrently, presence of large numbers of bird carcasses infected with HPAI H5N1 at seal haul-out sites most likely contributed to the spillover of infection to the seals. Histologic changes included meningoencephalitis (100%), fibrinosuppurative alveolitis, and multiorgan acute necrotizing inflammation. This report of fatal HPAI H5N1 infection in pinnipeds in Canada raises concerns about the expanding host of this virus, the potential for the establishment of a marine mammal reservoir, and the public health risks associated with spillover to mammals.Nous décrivons un événement de mortalité inhabituelle causé par un virus de l'influenza aviaire hautement pathogène A(H5N1) clade 2.3.4.4b chez des phoques communs (Phoca vitulina) et gris (Halichoerus grypus) dans l'estuaire du Saint-Laurent au Québec, Canada, en 2022. Quinze (56%) des phoques soumis pour nécropsie ont été considérés comme étant fatalement infectés par le virus H5N1 de lignées eurasiennes ou de réassortiment eurasiennes/nord-américaines. Un grand nombre simultané de carcasses d'oiseaux infectés par le H5N1 sur les sites d'échouement a probablement contribué à la contamination de ces phoques. Les changements histologiques associés à cette infection incluaient : méningo-encéphalite (100%), alvéolite fibrinosuppurée et inflammation nécrosante aiguë multi-organique. Cette documentation soulève des préoccupations quant à l'émergence de virus mortels, à la possibilité d'établissement de réservoirs chez les mammifères marins, et aux risques pour la santé publique associés aux propagations du virus chez les mammifères.

Discovery of Protease-Activated Receptor 4 (PAR4)-Tethered Ligand Antagonists Using Ultralarge Virtual Screening.

Here, we demonstrate a structure-based small molecule virtual screening and lead optimization pipeline using a homology model of a difficult-to-drug G-protein-coupled receptor (GPCR) target. Protease-activated receptor 4 (PAR4) is activated by thrombin cleavage, revealing a tethered ligand that activates the receptor, making PAR4 a challenging target. A virtual screen of a make-on-demand chemical library yielded a one-hit compound. From the single-hit compound, we developed a novel series of PAR4 antagonists. Subsequent lead optimization via simultaneous virtual library searches and structure-based rational design efforts led to potent antagonists of thrombin-induced activation. Interestingly, this series of antagonists was active against PAR4 activation by the native protease thrombin cleavage but not the synthetic PAR4 agonist peptide AYPGKF.

The SocialVidStim: a video database of positive and negative social evaluation stimuli for use in social cognitive neuroscience paradigms.

This paper describes the SocialVidStim-a database of video stimuli available to the scientific community depicting positive and negative social evaluative and neutral statements. The SocialVidStim comprises 53 diverse individuals reflecting the demographic makeup of the USA, ranging from 9 to 41 years old, saying 20-60 positive and 20-60 negative social evaluative statements (e.g. 'You are a very trustworthy/annoying person'), and 20-60 neutral statements (e.g. 'The sky is blue'), totaling 5793 videos post-production. The SocialVidStim are designed for use in behavioral and functional magetic resonance imaging paradigms, across developmental stages, in diverse populations. This study describes stimuli development and reports initial validity and reliability data on a subset videos (N = 1890) depicting individuals aged 18-41 years. Raters perceive videos as expected: positive videos elicit positively valenced ratings, negative videos elicit negatively valenced ratings and neutral videos are rated as neutral. Test-retest reliability data demonstrate intraclass correlations in the good-to-excellent range for negative and positive videos and the moderate range for neutral videos. We also report small effects on valence and arousal that should be considered during stimuli selection, including match between rater and actor sex and actor believability. The SocialVidStim is a resource for researchers and we offer suggestions for using the SocialVidStim in future research.

The Impact of Disability and Assistive Technology Use on Well-Being in Later Life: Findings From the National Health and Aging Trends Study.

BACKGROUND AND OBJECTIVES: Although assistive technologies have the potential to bridge the gap between personal capabilities and environmental demands, they may not always fully accommodate disability. This study examined the implications of change in the extent of accommodation provided by assistive technology for well-being in older adulthood. RESEARCH DESIGN AND METHODS: Data from 5 waves (2015-2019) of the National Health and Aging Trends Study provided information on disability and assistive technology use among older adults aged 65 and older in the United States (n = 7,057). An eight-level index that jointly characterized the spectrum of disability and assistive technology use was applied to 7 activities of daily living (ADLs). Fixed-effects panel model assessed within-person associations between well-being and the extent of assistive technology accommodation along different levels of the disability spectrum. RESULTS: At baseline, bathing (28.7%; 95% confidence interval [CI]: 27.6, 29.8) and toileting (37.9%; 95% CI: 36.2, 39.6) were the 2 activities in which most older adults successfully accommodated their limitations with assistive technologies. Longitudinally, the level of support provided by assistive technology changed widely across activities and over time. Within-person analyses showed that for all ADLs except for eating, there was a significant decline in well-being when the adopted assistive technology no longer supported users' needs and successfully resolved their disabilities. DISCUSSION AND IMPLICATIONS: Our findings highlight the utility of technology-based interventions and underscore the imperative that assistive technologies attend to the specific needs of older adults and support independence in everyday activities.

Who feels like they belong? Personality and belonging in college.

Having a secure sense of belonging at school supports students' academic achievement and well-being. However, little research has examined how students' personalities relate to their feelings of school belonging. We address this gap in the literature by leveraging data from a large sample of first-year college students (N = 4,753) from a diverse set of North American colleges and universities (N = 12). We found that both extraversion and agreeableness were positively associated with belonging, while neuroticism was negatively associated with belonging. In an exploratory analysis, we examined differences between large and small schools. Students who were more extraverted, less neurotic, and less open were more likely to attend large schools. Additionally, the association between extraversion and belonging was stronger for students at large schools. These findings advance our understanding of who comes to feel like they belong at college and how school context may influence these relationships. We emphasize the need for continued research on the relationship between personality and belonging. Additionally, we highlight the implications of these results for higher education institutions.

Groebke Blackburn Bienaymé-mediated multi-component synthesis of selective HDAC6 inhibitors with anti-inflammatory properties.

Histone deacetylases (HDACs) are a class of enzymes that cleave acyl groups from lysine residues of histone and non-histone proteins. There are 18 human HDAC isoforms with different cellular targets and functions. Among them, HDAC6 was found to be overexpressed in different types of cancer. However, when used in monotherapy, HDAC6 inhibition by selective inhibitors fails to show pronounced anti-cancer effects. The HDAC6 enzyme also addresses non-histone proteins like α-tubulin and cortactin, making it important for cell migration and angiogenesis. Recently, the NLRP3 inflammasome was identified as an important regulator of inflammation and immune responses and, importantly, HDAC6 is critically involved the activation of the inflammasome. We herein report the design, synthesis and biological evaluation of a library of selective HDAC6 inhibitors. Starting from the previously published crystal structure of MAIP-032 in complex with CD2 of zHDAC6, we performed docking studies to evaluate additional possible interactions of the cap group with the L1-loop pocket. Based on the results we synthesized 13 novel HDAC6 inhibitors via the Groebke-Blackburn-Bienaymé three component reaction as the key step. Compounds 8k (HDAC1 IC50: 5.87 µM; HDAC6 IC50: 0.024 µM; selectivity factor (SF1/6): 245) and 8m (HDAC1 IC50: 3.07 µM; HDAC6 IC50: 0.026 µM; SF1/6: 118) emerged as the most potent and selective inhibitors of HDAC6 and outperformed the lead structure MAIP-032 (HDAC1 IC50: 2.20 µM; HDAC6 IC50: 0.058 µM; SF1/6: 38) both in terms of inhibitory potency and selectivity. Subsequent immunoblot analysis confirmed the high selectivity of 8k and 8m for HDAC6 in a cellular environment. While neither 8k and 8m nor the selectivity HDAC6 inhibitor tubastatin A showed antiproliferative effects in the U-87 MG glioblastoma cell line, compound 8m attenuated cell migration significantly in wound healing assays in U-87 MG cells. Moreover, in macrophages compounds 8k and 8m demonstrated significant inhibition of LPS-induced IL1B mRNA expression and TNF release. These findings suggest that our imidazo[1,2-a]pyridine-capped HDAC6 inhibitors may serve as promising candidates for the development of drugs to effectively treat NLRP3 inflammasome-driven inflammatory diseases.

Using Integra for Reconstruction of Facial Defects after Mohs Micrographic Surgery.

Background: We aimed to identify how Integra bilayer wound matrix has expanded facial reconstruction options after Mohs surgery due to its reliability in both single- and dual-stage reconstruction. Methods: A retrospective review of patients undergoing Mohs surgery and alloplastic facial reconstruction with Integra between 2012 and 2022 was performed. Patients who underwent single-stage reconstruction and dual-stage reconstruction with skin graft with at least 90 days of follow-up were included. Results: One hundred thirty patients with a median age of 76 years were included. Basal cell carcinoma was the most common malignancy (39%). One hundred forty-two lesions were treated and reconstructed same-day with Integra. Lesions most commonly involved the nose (34%) and forehead (22%). The mean postoperative defect size was 26.9 cm2. An estimated 45.5% (n = 60) of defect sites underwent single-stage reconstruction with healing by secondary intention, whereas 54.5% (n = 72) underwent dual-stage reconstruction with skin graft. Integra success rate was 90.2%. Average time to re-epithelialization was 32.2 + 7.3 days. Average time to repigmentation was 169.5 + 14.6 days. The complication rate was 12.8% (n = 17), with 12 undergoing debridement, three needing new Integra graft, and seven needing new skin grafts. Average size for successful healing without complication was 26.6 cm2. Nineteen sites (13.2%) underwent aesthetic improvement procedures, with the majority occurring after dual-stage reconstruction (n = 13). Conclusions: Integra is a reliable outpatient reconstructive option for facial Mohs defects that can increase the threshold for autologous tissue harvesting and successfully reconstruct large defects of 26.6 cm2 on average with low complication and reoperation rates.

Capturing multiple assistive technology use and its impact in later life: lessons learned from distinct measurement approaches.

PURPOSE: Assistive technology (AT) use is prevalent in older adulthood and can accommodate activity difficulties to support well-being. However, within the context of multiple activity difficulties and multiple technology use, it is unclear how to best assess their combined effects on older adults' health outcomes. This study proposed four distinct approaches to quantify multiple AT use and examined their respective impact in later life. MATERIAL AND METHODS: Using data from the 2015 round of the National Health and Aging Trends Study (n = 6,936), we compared four indices to summarize the state of multiple AT use among the U.S. older population: binary, item-specific, cumulative, and accommodative. Separate regression analyses tested the impact of each index on older adults' well-being and restricted participation in meaningful activities. RESULTS: In 2015, 59.9% of the respondents were identified as AT users. Among these users, 53.8% reported using two or more technologies when performing daily self-care and mobility activities. The implications of multiple AT use for health outcomes varied across the four indices. Approaches that captured elements of person-technology fit provided the most nuanced and actionable insights on the benefits of using AT to support well-being. CONCLUSIONS: ATs were commonly adopted by older adults in everyday activities. Overall, findings suggest that there are multiple approaches to conceptualize the independent, cumulative, or balanced effects of multiple AT use. Each measurement approach has unique implications for understanding the impacts of using ATs on older adults' health outcomes.

Multiple assistive technology (AT) use is observed and prevalent in later life, highlighting that there is great need for older adults to deploy different technologies to help with different daily activities.The concept of multiple AT use can be approached in various ways (e.g., where effects of each AT are independent, cumulative, or dependent on fit), with each conceptualization based on distinct assumptions and capable of serving different purposes in rehabilitation research.This study demonstrates that information on person-technology fit plays a critical role in helping rehabilitation engineers and clinical practitioners assess the effects of AT use on health and well-being outcomes among older adults.

The Microwave Temperature and Humidity Profiler: Description and Preliminary Results.

This manuscript presents the Microwave Temperature and Humidity Profiler (MTHP), a dual-band spectroradiometer designed for measuring multi-incidence angle temperature and humidity atmospheric profiles from an aircraft platform. The MTHP bands are at 60 GHz for measuring the oxygen complex lines, therefore at this band, MTHP has a hyperspectral radiometer able to provide 2048 channels over an 8 GHz bandwidth, and 183 GHz for measuring water vapor, which only uses four channels since this absorption band's spectral richness is simpler. The MTHP builds upon the Microwave Temperature Profiler (MTP) with the inclusion of the hyperspectral radiometer. The instrument's design, components, and calibration methods are discussed in detail, with a focus on the three-point calibration scheme involving internal calibration loads and static air temperature readings. Preliminary results from the Technological Innovation into Iodine and GV aircraft Environmental Research (TI3GER) campaign are presented, showcasing the instrument's performance during flights across diverse geographical regions. The manuscript presents successful antenna temperature measurements at 60 GHz and 183 GHz. The hyperspectral measurements are compared with a simulated antenna temperature using the Atmospheric Radiative Transfer Simulator (ARTS) showing an agreement better than R2 > 0.88 for three of the flights analyzed. Additionally, the manuscript draws attention to potential Radio Frequency Interference (RFI) effects observed during a specific flight, underscoring the instrument's sensitivity to external interference. This is the first-ever airborne demonstration of a broadband and hyperspectral multi-incidence angle 60 GHz measurement. Future work on the MTHP could result in an improved spatial resolution of the atmospheric temperature vertical profile and, hence, help in estimating the Planetary Boundary Layer (PBL) with better accuracy. The MTHP and its hyperspectral multi-incidence angle at 60 GHz have the potential to be a valuable tool for investigating the PBL's role in atmospheric dynamics, offering insights into its impact on Earth's energy, water, and carbon cycles.

Patient Preferences for Pain Control After Mohs Micrographic Surgery: A Single-Center Discrete Choice Experiment.

Importance: Patient preferences for pain medications after Mohs micrographic surgery are important to understand and have not been fully studied. Objective: To evaluate patient preferences for pain management with only over-the-counter medications (OTCs) or OTCs plus opioids after Mohs micrographic surgery given varying levels of theoretical pain and opioid addiction risk. Design, Setting, and Participants: This prospective discrete choice experiment was conducted in a single academic medical center from August 2021 to April 2022 among patients undergoing Mohs surgery and their accompanying support persons (≥18 years). A prospective survey was administered to all participants using the Conjointly platform. Data were analyzed from May 2022 to February 2023. Main outcome and measure: The primary outcome was the pain level at which half of the respondents chose OTCs plus opioids equally to only OTCs for pain management. This pain threshold was determined for varying opioid addiction risk profiles (low, 0%; low-moderate, 2%; moderate-high, 6%; high, 12%) and measured via a discrete choice experiment and linear interpolation of associated parameters (pain levels and risk of addiction). Results: Of the 295 respondents (mean [SD] age, 64.6 [13.1] years; 174 [59%] were female; race and ethnicity were not considered) who completed the discrete choice experiment, 101 (34%) stated that they would never consider opioids for pain management regardless of the pain level experienced, and 147 (50%) expressed concern regarding possible opioid addiction. Across all scenarios, 224 respondents (76%) preferred only OTCs vs OTCs plus opioids after Mohs surgery for pain control. When the theoretical risk of addiction was low (0%), half of the respondents expressed a preference for OTCs plus opioids given pain levels of 6.5 on a 10-point scale (90% CI, 5.7-7.5). At higher opioid addiction risk profiles (2%, 6%, 12%), an equal preference for OTCs plus opioids and only OTCs was not achieved. In these scenarios, patients favored only OTCs despite experiencing high levels of pain. Conclusion and relevance: The findings of this prospective discrete choice experiment indicate that the perceived risk of opioid addiction affects the patient's choice of pain medications after Mohs surgery. It is important to engage patients undergoing Mohs surgery in shared decision-making discussions to determine the optimal pain control plan for each individual. These findings may encourage future research on the risks associated with long-term opioid use after Mohs surgery.

4D Bioprinting via Molecular Network Contraction for Membranous Tissue Fabrication.

Generation of thin membranous tissues (TMT), such as the cornea, epidermis, and periosteum, presents a difficult fabrication challenge in tissue engineering (TE). TMTs consist of several cell layers that are less than 100 µm in thickness per layer. While traditional methods provide the necessary resolution for TMT fabrication, they require significant handling and incorporation of several layers is limited. Extrusion bioprinting offers precise control over deposition of different biomaterials and cell populations within the same construct but lacks the resolution to generate biomimetic TMTs. For the first time, a 4D bioprinting strategy that allows for the generation of cell-laden TMTs is developed. Anionic gelatin methacrylate (GelMA) hydrogels are treated with cationic poly-l-lysine (PLL), which induces charge attraction, microscale network collapse, and macroscale hydrogel shrinking. The impact of shrinking on hydrogel properties, print resolution, and cell viability is presented. Additionally, this work suggests that a novel mechanism is occurring, where PLL exhibits a contractile force on GelMA and PLL molecular weight drives GelMA shrinking capabilities. Finally, it is shown that this phenomenon can occur while maintaining an encapsulated cell population. These findings address a critical barrier by generating macroscale tissue structures with their microscale TMT counterparts in the same print.

Personalized Pre-clinic Nursing Telemedicine Visit: An Efficient and Efficacious Approach for Bowel and Bladder Dysfunction in Children.

OBJECTIVES: To evaluate the effectiveness and efficacy of a Registered Nurse (RN) led educational pre-clinic telephone call on compliance and outcomes in children with bowel and bladder dysfunction (BBD). METHODS: A retrospective chart review of a prospectively applied protocol in a single academic institution was performed for children aged 4-17 presenting with BBD. All children underwent a pre-clinic RN telemedicine visit where they were educated on pathophysiology of BBD, provided personalized urotherapy and bowel recommendations and instructed to complete pre-clinic questionnaires and voiding diaries. Patients were evaluated by a provider 4weeks following RN call. Data collected included compliance with forms, bowel management and need for imaging/testing, medications, and biofeedback. Patients were considered to improve with urotherapy alone if they were discharged from urology without the need for medications and/or biofeedback. RESULTS: In total, 277 patients completed an RN call and 224 patients attended a provider visit between December 2020 and June 2022. Mean age was 9.4years (3:1 Female to Male ratio). During the RN call, 154 (56%) patients had bowel management initiated. Of the 224 patients seen by a provider, 69% (n = 154) had symptom improvement or resolution with urotherapy alone. Thirty-eight patients (17%) enrolled in biofeedback with 7 (3%) completing all 8 sessions. Thirty-two patients (14%) required medication for daytime bladder symptoms. CONCLUSION: Our novel RN-led pre-clinic telemedicine visit demonstrates excellent compliance and patient outcomes for children with BBD and can reduce the use of unnecessary imaging, medications, and time-consuming treatments such as biofeedback.

Everyday Experiences of Physical Function and Awareness of Fall Risk in Older Adulthood.

Background and Objectives: Falls, the leading cause of death and disability among older adults, occur in daily life when the demands of daily activities surpass the ability to maintain balance. An estimated 30% of older adults misestimate their physical function, placing them at greater risk of falling. This study examined how experiences of physical function are linked to awareness of fall risk in daily life. Research Design and Methods: For 30 consecutive days following a fall-risk assessment, 41 older adults (observations = 1,135; 56% women; age: 65-91) self-assessed objective and subjective fall risk using a custom smartphone application. Alignment of objective and subjective fall risk was indexed as awareness of fall risk. Postural sway was measured by the application. Physical and mobility symptoms and fear of falling were reported daily. Results: At baseline, 49% of participants misestimated their fall risk. Awareness of fall risk varied from day to day and fall risk was misestimated on 40% of days. Multilevel multinomial models showed individual differences in the level of daily symptoms to increase the tendency to misestimate fall risk. Daily symptoms and fear of falling increased awareness of high fall risk, but daily symptoms threatened awareness of low fall risk. Discussion and Implications: Findings suggest that misestimation of fall risk is common in older adulthood and informed by appraisals of physical function. Fall prevention strategies could support older adults in understanding their everyday physical function and provide tools to adjust the demands of activities in daily life.

Multi-stage optimal dynamic treatment regimes for survival outcomes with dependent censoring.

We propose a reinforcement learning method for estimating an optimal dynamic treatment regime for survival outcomes with dependent censoring. The estimator allows the failure time to be conditionally independent of censoring and dependent on the treatment decision times, supports a flexible number of treatment arms and treatment stages, and can maximize either the mean survival time or the survival probability at a certain time-point. The estimator is constructed using generalized random survival forests and can have polynomial rates of convergence. Simulations and analysis of the Atherosclerosis Risk in Communities study data suggest that the new estimator brings higher expected outcomes than existing methods in various settings.

Where and with whom does a brief social-belonging intervention promote progress in college?

A promising way to mitigate inequality is by addressing students' worries about belonging. But where and with whom is this social-belonging intervention effective? Here we report a team-science randomized controlled experiment with 26,911 students at 22 diverse institutions. Results showed that the social-belonging intervention, administered online before college (in under 30 minutes), increased the rate at which students completed the first year as full-time students, especially among students in groups that had historically progressed at lower rates. The college context also mattered: The intervention was effective only when students' groups were afforded opportunities to belong. This study develops methods for understanding how student identities and contexts interact with interventions. It also shows that a low-cost, scalable intervention generalizes its effects to 749 4-year institutions in the United States.