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Introduction: Social prescribing (SP) is a holistic and collaborative approach to help individuals access community-based supports and services for their nonmedical social needs. The aim of this study was to assess the needs and priorities of Canadian older adults (aged 55 years and older), with a focus on optimizing SP programs for those who are systemically disadvantaged and socially marginalized., Methods: Semistructured focus groups (N = 10 groups, 43 participants) were conducted online via Zoom with participants from across Canada. Data transcription and thematic analysis were completed in NVivo. Analyses were informed by self-determination theory., Results: Our results suggest that older adults desire SP programs that respect their ability to maintain their autonomy and independence, aid and facilitate the development of connectedness and belonging, are built on a foundation of trust and relationship-building in interactions with providers and link workers, and prioritize the person and thus personalize SP to the unique needs of each individual., Conclusion: SP programs should be informed by the values of older adults. As work is currently underway to formalize and scale SP in Canada, personalizing these programs to the unique circumstances, needs and priorities of participants should be a top priority., Competing Interests: The authors declare there are no conflicts of interest.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of dementia globally. Although the direct cause of AD remains under debate, neuroinflammation and oxidative stress are critical components in its pathogenesis and progression. As a result, compounds like cannabidiol (CBD) are being increasingly investigated for their ability to provide antioxidant and anti-inflammatory neuroprotection. CBD is the primary non-psychotropic phytocannabinoid derived from Cannabis sativa. It has been found to provide beneficial outcomes in a variety of medical conditions and is gaining increasing attention for its potential therapeutic application in AD. CBD is not psychoactive and its lipophilic nature allows its rapid distribution throughout the body, including across the blood-brain barrier (BBB). CBD also possesses anti-inflammatory, antioxidant, and neuroprotective properties, making it a viable candidate for AD treatment. This review outlines CBD's mechanism of action, the role of oxidative stress and neuroinflammation in AD, and the effectiveness and limitations of CBD in preclinical models of AD.

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP's potential as a novel therapeutic target., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that debilitates over 55 million individuals worldwide. Currently, treatments manage and alleviate its symptoms; however, there is still a need to find a therapy that prevents or halts disease progression. Since AD has been labeled as "type 3 diabetes" due to its similarity in pathological hallmarks, molecular pathways, and comorbidity with type 2 diabetes mellitus (T2DM), there is growing interest in using anti-diabetic drugs for its treatment. Rosiglitazone (RSG) is a peroxisome proliferator-activated receptor-gamma agonist that reduces hyperglycemia and hyperinsulinemia and improves insulin signaling. In cellular and rodent models of T2DM-associated cognitive decline and AD, RSG has been reported to improve cognitive impairment and reverse AD-like pathology; however, results from human clinical trials remain consistently unsuccessful. RSG has also been reported to modulate the expression of brain-derived neurotrophic factor (BDNF), a protein that regulates neuroplasticity and energy homeostasis and is implicated in both AD and T2DM. The present review investigates RSG's limitations and potential therapeutic benefits in pre-clinical models of AD through its modulation of BDNF expression.

Web archives, such as the Internet Archive, preserve the web and allow access to prior states of web pages. We implicitly trust their versions of archived pages, but as their role moves from preserving curios of the past to facilitating present day adjudication, we are concerned with verifying the fixity of archived web pages, or mementos, to ensure they have always remained unaltered. A widely used technique in digital preservation to verify the fixity of an archived resource is to periodically compute a cryptographic hash value on a resource and then compare it with a previous hash value. If the hash values generated on the same resource are identical, then the fixity of the resource is verified. We tested this process by conducting a study on 16,627 mementos from 17 public web archives. We replayed and downloaded the mementos 39 times using a headless browser over a period of 442 days and generated a hash for each memento after each download, resulting in 39 hashes per memento. The hash is calculated by including not only the content of the base HTML of a memento but also all embedded resources, such as images and style sheets. We expected to always observe the same hash for a memento regardless of the number of downloads. However, our results indicate that 88.45% of mementos produce more than one unique hash value, and about 16% (or one in six) of those mementos always produce different hash values. We identify and quantify the types of changes that cause the same memento to produce different hashes. These results point to the need for defining an archive-aware hashing function, as conventional hashing functions are not suitable for replayed archived web pages., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Aturban et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Comprehensive medication reviews (CMRs) are offered to eligible Medicare beneficiaries to improve patient medication knowledge, identify, and address medication concerns, and empower medication self-management. However, the specific content of real-world CMRs is unclear., Objective: To qualitatively assess CMR content and delivery among telephonic CMR providers., Methods: This qualitative thematic analysis used transcriptions of audio-recorded patient interactions during CMRs from 3 telephonic medication therapy management provider organizations. Data were qualitatively analyzed using the inductive saturation model to code emergent themes by independent reviewers who met to agree themes through consensus. Intercoder reliability was calculated using Krippendorf alpha., Results: Overall, 32 CMR transcripts from 3 organizations were analyzed in 13 rounds of coding. Intercoder reliability was >95%. A total of 21 themes were identified across 4 stages: call opening (4 themes), medication reconciliation (5 themes), clinical assessments and guidance (8 themes), and call closing (4 themes). The call opening stage included: service explanation; insurance coverage/cost; identity/privacy/recording; and patient's medication management. Medication reconciliation included: drug name, dose, frequency, and indication; medication deletion and addition; over-the-counter and vaccination assessment; drug efficacy assessment; and prescribing provider assessment. Clinical assessments and guidance included 4 core clinical assessments: allergy assessment; drug therapy problem assessment; drug-related adverse events; and medication modification; and 4 additional assessments: clinical/therapeutic guidance; cost savings guidance; diet/exercise/lifestyle guidance; and optional clinical and behavioral assessments. Call closing included: documentation; primary care provider confirmation; patient satisfaction; and call transfer. There were variations among organizations in the depth that CMR components were covered., Conclusion: These findings suggest provider organizations are including components that meet Centers for Medicare and Medicaid Services goals for CMRs. Yet, variations among organizations indicate a need for standardization and patient-centered measures to ensure appropriate CMR components are covered, while maintaining flexibility for pharmacists to provide patient-oriented CMRs that meet patients' clinical needs., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The unjamming of elastic concentrated nanoemulsions into viscous dilute nanoemulsions, through dilution with the continuous phase, offers interesting opportunities for a pulsed-field gradient (PFG) NMR, particularly if the nanoemulsion is designed to take advantage of the nuclear specificity offered by NMR. Here, we make and study size-fractionated oil-in-water nanoemulsions using a perfluorinated copolymer silicone oil that is highly insoluble in the aqueous continuous phase. By studying these nanoemulsions using ^{19}F stimulated-echo PFG-NMR, we avoid any contribution from the aqueous continuous phase, which contains a nonfluorinated ionic surfactant. We find a dramatic change in the ^{19}F PFG-NMR decays at high field-gradient strengths as the droplet volume fraction, ϕ, is lowered through dilution. At high ϕ, observed decays as a function of field-gradient strength exhibit decay-to-plateau behavior indicating the jamming of nanodroplets, which contain ^{19}F probe molecules, in an elastic material reminiscent of a nanoporous solid. In contrast, at lower ϕ, only a simple decay is observed, indicating that the nanodroplets have unjammed and can diffuse over much larger distances. Through a comparison with bulk mechanical rheometry, we show that this dramatic change coincides with the loss of low-frequency shear elasticity of the nanoemulsion.

The calculation of tensile mechanical properties from stress-strain curves is a fundamental step in characterizing material behavior, yet no standardized method exists to perform these calculations for soft tissue. To address this deficiency, we developed a free web application called Dots-on-Plots2 that fully automates the calculation of tensile mechanical properties from stress-strain curves. The analyzed mechanical properties include the strength, strain, and energy at four points of interest (transition, yield, ultimate, and rupture), and the linear modulus. Users of Dots-on-Plots can upload multiple files, view and download results, and adjust threshold settings. This study determined a threshold setting that minimized error when calculating the transition point, where the stress-strain curve "transitions" from a nonlinear "toe" region to a linear region. Using the optimal threshold (2% stress deviation from a linear region fit), Dots-on-Plots calculated the transition strains from twenty tensile experiments of human meniscus to be 0.049 ± 0.007, which nearly matched the known transition strain values of 0.050 ± 0.006 (determined using finite element parameter optimization). The sensitivity of the calculated transition strain to the shape of various stress-strain curves was analyzed using sets of model-generated synthetic data. This free web application offers a convenient and reliable tool to systematically enhance the speed, transparency, and consistency of mechanical analysis across biomedical research groups., (Copyright © 2023 by ASME.)

Mitohormesis defines the increase in fitness mediated by adaptive responses to mild mitochondrial stress. Tetracyclines inhibit not only bacterial but also mitochondrial translation, thus imposing a low level of mitochondrial stress on eukaryotic cells. We demonstrate in cell and germ-free mouse models that tetracyclines induce a mild adaptive mitochondrial stress response (MSR), involving both the ATF4-mediated integrative stress response and type I interferon (IFN) signaling. To overcome the interferences of tetracyclines with the host microbiome, we identify tetracycline derivatives that have minimal antimicrobial activity, yet retain full capacity to induce the MSR, such as the lead compound, 9-tert-butyl doxycycline (9-TB). The MSR induced by doxycycline (Dox) and 9-TB improves survival and disease tolerance against lethal influenza virus (IFV) infection when given preventively. 9-TB, unlike Dox, did not affect the gut microbiome and also showed encouraging results against IFV when given in a therapeutic setting. Tolerance to IFV infection is associated with the induction of genes involved in lung epithelial cell and cilia function, and with downregulation of inflammatory and immune gene sets in lungs, liver, and kidneys. Mitohormesis induced by non-antimicrobial tetracyclines and the ensuing IFN response may dampen excessive inflammation and tissue damage during viral infections, opening innovative therapeutic avenues.

Background: Alternative payment models are common for both primary care providers and pharmacies. These models rely on quality measures to determine reimbursement, and pharmacists and primary care providers can contribute to performance on a similar set of medication-related measures. Therefore, payers need to decide which provider to incentivize for which measures when both are included in alternative payment models., Objectives: To explore the relative contribution of pharmacies and primary care group practices to a range of quality measures., Methods: This retrospective cross-sectional study used Medicare Part A, B, and D claims for a 20% random sample of Medicare beneficiaries for 2014-2016. Eight quality measures were selected from the Merit-based Incentive Payment System and Medicare Part D Stars Ratings. Measures included medication adherence measures, appropriate prescribing measures such as high-risk medication use in the elderly, statin use in persons with diabetes (SUPD), and others. The residual intraclass correlation coefficient (RICC) was used to estimate the contribution of pharmacists and primary care providers to measure variation. To estimate the relative contribution across provider types, the pharmacy RICC was divided by the group practice RICC to yield a RICC ratio., Results: Due to varying measure eligibility requirements, the number of patients per measure ranged from 179,430 to 2,226,129. Across all measures, the RICC values were low, ranging from 0.013 for SUPD to 0.145 for adult sinusitis. Adherence measures had the highest RICC ratios (1.15-1.44), and the annual influenza vaccination measure had the lowest (0.56)., Discussion and Conclusions: The relative contributions of pharmacists and primary care providers vary across quality measures. As payers design payment models with measures to which pharmacists and primary care providers can contribute, the RICC ratio may be useful in aligning incentives to the providers with the greatest relative contributions. Additional research is needed to validate this method and extend it to additional sets of providers., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (© 2022 Published by Elsevier Inc.)

Background: Comprehensive medication reviews (CMRs) are provided by providers such as pharmacists to eligible beneficiaries. Although CMRs have been shown to provide value to patients, little is known about the service uniformity, quality, and content of CMRs., Objective: This study aimed to characterize the current state of CMR services from diverse stakeholder perspectives and describe variation in responses to content and delivery of telephonic CMR services., Methods: Semistructured interviews were conducted with 10 key informants. The interview guide contained 6 key questions with additional probing questions. Transcripts were analyzed using the inductive saturation model and phenomenological approach to code emergent themes, which were iteratively refined until saturation was achieved., Results: Key informants included CMR payers (n = 3), providers (n = 5), and standards-setting organizations (n = 2). Ten themes about CMRs emerged from qualitative analysis: (1) definition, (2) organizational goals, (3) content, (4) eligibility, (5) frequency, (6) acceptance and completion, (7) process and personnel, (8) quality assurance, (9) preparation, and (10) future directions. CMR content descriptions were consistent across perspectives. Key informants described scenarios appropriate for expanded CMR eligibility criteria, although none were consistently reported. Providers emphasized patient CMR acceptance rates whereas payers and standard-setting organizations emphasized completion rates. Completion rates and adherence to Centers for Medicare and Medicaid Services standards were characterized as core organizational goals (n = 8), whereas patient satisfaction was less frequently identified (n = 4). A lack of incentive for CMR providers to follow-up with patients was a barrier to expanded services. Overall, key informants were dissatisfied with the CMR completion rate measure and would prefer measures focused on service quality and outcomes., Conclusions: CMR services largely met perceived guidelines, with variation in value-added services. Key informants desired adoption of an actionable measure that is focused on quality rather than completion rate. To inform a quality measure, future research should analyze completed CMRs to determine the extent of variation in content and delivery., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

BACKGROUND: It is well known that medication accessibility reduces morbidity and mortality and increases health-related quality of life; however, despite efforts to improve health care access, many Americans still face challenges in accessing medications. Several health care access and utilization conceptual frameworks have been created and used for decades to illustrate key relationships and interdependencies between elements of the system. However, none of these frameworks have focused exclusively on medication access and associated factors. Medication access is a complex, multidimensional issue that must consider not only patient-specific challenges, but also health system limitations, among others. A better understanding of medication access, beyond the proxy marker of adherence, is needed to identify opportunities to improve accessibility. OBJECTIVE: To develop a conceptual framework that defines a patient's medication access journey and characterizes barriers frequently encountered while seeking medication access. METHODS: A multistakeholder roundtable composed of 15 experts from across the health care continuum was convened in 2018 by the Pharmacy Quality Alliance to develop a conceptual framework for medication access. The roundtable participants were convened through in-person and telephonic meetings. To inform their work, 2 literature reviews and an environmental scan were conducted to identify medication access barriers, interventions affecting medication access, and medication access quality measures. RESULTS: The resulting framework included 7 nodes that represent the major access points encountered by patients when attempting to access medications: perceived need, help seeking, encounter, prescribing, prescription adjudication, prescription dispensing, and adherence. Also, 18 barriers were identified. Patient health literacy, cost, insurance, and organizational health literacy were predominant barriers across multiple nodes. CONCLUSIONS: The framework that was developed provides a patient-focused, holistic view of medication access, incorporating access nodes and corresponding barriers. It also provides a structure to consider key opportunities for interventions and measurement to address medication access challenges. DISCLOSURES: This study was conducted with grant support from the National Pharmaceutical Council, which served as a collaborator in the study. Westrich is employed by the National Pharmaceutical Council. Nelson is employed by the Pharmacy Quality Alliance, which was contracted to conduct this study. Pickering, Campbell, and Holland were employed by the Pharmacy Quality Alliance at the time of this study. This research was presented as a professional poster at the American Public Health Association Annual Meeting in October 2019, Philadelphia, PA.

Reduced protein levels of SMARCB1 (also known as BAF47, INI1, SNF5) have long been observed in synovial sarcoma. Here, we show that combined Smarcb1 genetic loss with SS18-SSX expression in mice synergized to produce aggressive tumors with histomorphology, transcriptomes, and genome-wide BAF-family complex distributions distinct from SS18-SSX alone, indicating a defining role for SMARCB1 in synovial sarcoma. Smarcb1 silencing alone in mesenchyme modeled epithelioid sarcomagenesis. In mouse and human synovial sarcoma cells, SMARCB1 was identified within PBAF and canonical BAF (CBAF) complexes, coincorporated with SS18-SSX in the latter. Recombinant expression of CBAF components in human cells reconstituted CBAF subcomplexes that contained equal levels of SMARCB1 regardless of SS18 or SS18-SSX inclusion. In vivo , SS18-SSX expression led to whole-complex CBAF degradation, rendering increases in the relative prevalence of other BAF-family subtypes, PBAF and GBAF complexes, over time. Thus, SS18-SSX alters BAF subtypes levels/balance and genome distribution, driving synovial sarcomagenesis. SIGNIFICANCE: The protein level of BAF component SMARCB1 is reduced in synovial sarcoma but plays a defining role, incorporating into PBAF and SS18-SSX-containing canonical BAF complexes. Reduced levels of SMARCB1 derive from whole-complex degradation of canonical BAF driven by SS18-SSX, with relative increases in the abundance of other BAF-family subtypes. See related commentary by Maxwell and Hargreaves, p. 2375 . This article is highlighted in the In This Issue feature, p. 2355 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Zeolites are known to be effective catalysts in biomass converting processes. Understanding the mesoporous structure and dynamics within it during such reactions is important in effectively utilizing them. Nuclear magnetic resonance (NMR) T 2 relaxation and diffusion measurements, using a high-power radio frequency probe, are shown to characterize the dynamics of water in mesoporous commercially made 5A zeolite beads before and after the introduction of xylose. Xylose is the starting point in the dehydration into furfural. The results indicate xylose slightly enhances rotational mobility while it decreases translational motion through altering the permeability, K , throughout the porous structure. The measurements show xylose inhibits pure water from relocating into larger pores within the zeolite beads where it eventually is expelled from the bead itself.