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Epidermal growth factor (EGF) has important effects in the renal collecting duct to regulate salt and water transport. To identify elements of EGF-mediated signaling in the rat renal inner medullary collecting duct (IMCD), we carried out phosphoproteomics analysis. Biochemically isolated rat IMCD suspensions were treated with 1 μM of EGF or vehicle for 30 min. We performed comprehensive quantitative phosphoproteomics using TMT-labeling of tryptic peptides followed by protein mass spectrometry. We present a data resource reporting all detected phosphorylation sites and their changes in response to EGF. For a total of 29,881 unique phosphorylation sites, 135 sites were increased and 119 sites were decreased based on stringent statistical analysis. The data are provided to users at https://esbl.nhlbi.nih.gov/Databases/EGF-phospho/. Analysis demonstrated that EGF signals through canonical EGF pathways in the renal IMCD. Analysis of KEGG pathways in which EGF-regulated phosphoproteins are over-represented in native rat IMCD cells confirmed mapping to RAF-MEK-ERK signaling, but also pointed to a role for EGF in the regulation of protein translation. A large number of phosphoproteins regulated by EGF contained PDZ domains that are key elements of epithelial polarity determination. We also provide a collecting duct EGF-network map as a user accessible web resource at https://esbl.nhlbi.nih.gov/Databases/EGF-network/. Overall, the phosphoproteomic data presented provide a useful resource for experimental design and modeling of signaling in the renal collecting duct.

Objectives: The appearance of early lithic industries has been associated with the gradual development of unique biomechanical and cognitive abilities in hominins, including human-like precision grasping and basic learning and/or communicating capacities. These include tools used for activities exclusively associated with hominin contexts (cutting flakes) and hammerstones utilized for behaviors shared with non-human primates (e.g., nut-cracking). However, no previous experimental research has focused on comparing the factors affecting efficiency between these two key behavioral patterns and their evolutionary implications., Materials and Methods: Here, we address this gap with an experimental design involving participants with varying tool-related experience levels (i.e., no experience, theoretical-only experience, and extensive practical knapping expertise) to monitor their success rates, biometrics, and surface electromyography (sEMG) recordings from eight important hand and forearm muscles., Results: Our results showed that practical experience had a substantial impact on flake-cutting efficiency, allowing participants to achieve greater success rates with substantially less muscle effort. This relationship between success rates and muscle effort was not observed for the nut-cracking task. Moreover, even though practical experience did not significantly benefit nut-cracking success, experts exhibited increased rates of self-improvement in that task., Discussion: Altogether, these experimental findings suggest that the ability to practice and retain tool-using knowledge played a fundamental role in the subsistence strategies and adaptability of early hominins, potentially providing the cognitive basis for conceptualizing the first intentional tool production strategies., (© 2024 The Author(s). American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

Objective: Explore factors influencing patient comfort with and perceived helpfulness of screening for health-related social needs., Methods: In a parallel secondary mixed-methods analysis of data from three primary care clinics, we used logistic regression to examine effects of practice- and patient-level factors on comfort with and perceived helpfulness of social needs screening. We applied narrative analysis to 20 patient interviews to further understand how patients' lived experiences influenced their perceptions of screening., Results: Among 511 patients, receiving an explanation about screening was associated with increased odds of comfort (OR 2.1, 95% CI [1.1-4.30]) and perceived helpfulness (OR 4.7 [2.8-7.8]). Those experiencing more needs were less likely to report comfort (3 + needs vs. 0: OR 0.2 [0.1-0.5]). Narratives elucidated how a history of stigmatizing experiences increased discomfort disclosing needs and captured how relationship quality with healthcare teams influenced perceptions of screening for patients with extensive needs., Conclusion: Practice-level (screening explanation and therapeutic rapport) and patient-level factors (history and extent of needs) are key influences on comfort with and perceived helpfulness of screening., Practice Implications: Good communication about screening benefits all patients. Patients with extensive social needs may require additional sensitivity to their past experiences., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Approximately 20% of adults in Vietnam have hypertension, and management of this chronic condition remains challenging. This study aimed to assess the effectiveness of a multicomponent intervention in reducing blood pressure (BP) in adults with uncontrolled hypertension., Methods: This cluster randomised controlled trial was conducted in sixteen communities (8 intervention and 8 comparison) in a rural setting in Vietnam (2017-2022). Consenting adults (aged ≥ 18 years) with uncontrolled hypertension were enrolled. Sixteen communities were equally randomised to an intervention or comparison group stratified by district. Consenting adults were assigned to study groups by community. The comparison arm received training sessions about hypertension prevention and management for health workers, and patient education materials. The intervention arm received training sessions about hypertension prevention and management for health workers, and patient education materials and three enhancement components including a storytelling intervention, home BP self-monitoring, and expanded community health worker services. The primary outcome was the difference in changes in patient's levels of systolic BP between the study groups over a 12-month follow-up period. Patients and outcome assessors were masked., Findings: A total of 671 patients (340: intervention, 331: comparison) were enrolled in the trial. The mean age was 66 years and 45% were men. At the 12-month follow-up, the mean systolic BP declined by 18.4 mmHg in the intervention group and 3.7 mmHg in the comparison group (differential decline of 14.7 mmHg [95% CI: 11.8-17.6]). The intervention group also achieved better BP control and medication adherence than the comparison group. There were no serious adverse events related to study participation., Interpretation: The results of this trial demonstrate that a multicomponent intervention can effectively reduce elevated BP in individuals with uncontrolled hypertension in Vietnam. Trial registration: This trial was registered at ClinicalTrials.gov, NCT03590691., Funding: National Heart, Lung, and Blood Institute., Competing Interests: We declare no competing interests., (© 2024 The Authors.)

Background and Objectives: There are growing numbers of older adults with long-term vision impairment who are likely to experience everyday activity challenges from their impairment in conjunction with age-related changes. Technology has potential to support activity engagement. To develop effective technologies and interventions, we need to understand the context of activity challenges and identify unmet support needs., Research Design and Methods: The Aging Concerns, Challenges, and Everyday Solution Strategies (ACCESS) study is a mixed-method approach to explore everyday challenges of people aging with long-term disabilities. Participants included 60 adults aging with long-term vision impairment (63% female; M age = 67, SD = 4.6) who completed in-depth, structured interviews exploring the nature of everyday challenges and their unmet support needs for activity engagement. We conducted a content analysis using a deductive and inductive approach to build a detailed coding scheme of challenge codes and subcodes., Results: The analyses provided detailed insights about the nature of challenges people aging with vision impairment experience when performing specific instrumental activities of daily living (IADLs) in the context of home maintenance, transportation, shopping/finance, and managing health. Vision-related challenges and participation restrictions were identified for several activities that require reading, navigation, and identification (e.g., shopping, medication management, public transportation). Emergent challenge themes for performing IADLs included personal limitations (e.g., physical, cognitive, financial) and environmental barriers (e.g., accessibility, technology, transportation)., Discussion and Implications: Contextual examples of IADL challenges among individuals aging with vision impairment highlight opportunities for technology design and innovation to support participation in everyday activities., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

The following hypothesis proposes non-diffusive, environmental bacteriophage (phage) motion. (1) Some phage-hosting, motile bacteria undergo chemotaxis down ATP concentration gradients to escape lysis-inducing conditions, such as phage infection. (2) Some phages respond by non-infective binding to the motile bacteria. (3) When the bacteria reach a lower ATP concentration, which is a condition that signals increased density of phage-susceptible bacteria, the phage converts, Trojan-horse-like, to productive binding and infection. This hypothesis was previously proposed for Bacillus thuringiensis siphophage 0105phi7-2. It is tested here and confirmed with the following observations. (1) B. thuringiensis is found, macroscopically, preferentially located at low ATP concentrations when propagated in-gel after inoculation in the center of an artificially generated ATP concentration gradient. (2) Inoculating phage 0105phi7-2 at the bacteria inoculation site, 2-3 h after inoculation of bacteria, results in cell lysing activity that moves with the bacteria, without a visible trail of lysis. Trojan-horse-like behavior is consistent with only biofilm-inhabiting phages because environmental selection for this behavior requires limited fluid flows. We propose using artificial ATP concentration gradients to instigate Trojan-horse-like phage behavior during phage therapy of bacterial biofilms.

Membrane-spanning portions of proteins' polypeptide chains are commonly known as their transmembrane domains (TMDs). The structural organisation and dynamic behaviour of TMDs from proteins of various families, be that receptors, ion channels, enzymes etc., have been under scrutiny on the part of the scientific community for the last few decades. The reason for such attention is that, apart from their obvious role as an "anchor" in ensuring the correct orientation of the protein's extra-membrane domains (in most cases functionally important), TMDs often actively and directly contribute to the operation of "the protein machine". They are capable of transmitting signals across the membrane, interacting with adjacent TMDs and membrane-proximal domains, as well as with various ligands, etc. Structural data on TMD arrangement are still fragmentary at best due to their complex molecular organisation as, most commonly, dynamic oligomers, as well as due to the challenges related to experimental studies thereof. Inter alia, this is especially true for viral fusion proteins, which have been the focus of numerous studies for quite some time, but have provoked unprecedented interest in view of the SARS-CoV-2 pandemic. However, despite numerous structure-centred studies of the spike (S) protein effectuating target cell entry in coronaviruses, structural data on the TMD as part of the entire spike protein are still incomplete, whereas this segment is known to be crucial to the spike's fusogenic activity. Therefore, in attempting to bring together currently available data on the structure and dynamics of spike proteins' TMDs, the present review aims to tackle a highly pertinent task and contribute to a better understanding of the molecular mechanisms underlying virus-mediated fusion, also offering a rationale for the design of novel efficacious methods for the treatment of infectious diseases caused by SARS-CoV-2 and related viruses.

The Dietary Inflammatory Index (DII) is designed to assess the inflammatory potential of the diet. While previous research has utilized DII among college-aged women, no study to date has validated it in this population. We conducted a construct validation of DII among 393 healthy women aged 18-31 years against a robust panel of 14 inflammatory biomarkers, including CRP, IL-1β, IL-4, IL-6, IL-10, and TNF-α, which were used in the development of DII. Three linear regression models were constructed: (1) an age-adjusted model, (2) the most parsimonious model based on likelihood ratio tests, and (3) a fully adjusted model for age, race, body mass index, waist circumference, physical activity, smoking status, and nonsteroidal anti-inflammatory drug use. DII was derived from the Harvard food frequency questionnaire and categorized into quartiles. Consistent with our hypothesis, DII was negatively and significantly associated with back-transformed IL-10 levels, confirming that a more pro-inflammatory diet was associated with lower levels of an anti-inflammatory cytokine (Model 3: Q4 vs. Q1 β = 0.62; 95% CI: 0.42, 0.93; p -trend = 0.04). While validated in other populations, DII may not be a suitable tool for assessing the inflammatory potential of the diet among college-aged women.

To assess the association of serum tetranectin levels with cardiac remodeling parameters and to evaluate its prognostic role in women with anthracycline-related cardiac dysfunction (ARCD) and without previous cardiovascular diseases (CVD) during 24-month follow-up period. A total of 362 women with primary diagnosed breast cancer who were planned to be treated with anthracyclines were examined. At 12 months after chemotherapy completion, all women were examined and ARCD was diagnosed in 114 patients. After 24 months of follow-up, all patients with ARCD were divided into 2 groups: group 1 comprised women with the adverse course of ARCD (n = 54), group 2 comprised those without it (n = 60). In group 1, the levels of tetranectin were lower than group 2 by 27.6% (p < 0.001) and the patients without ARCD by 33.7% (p < 0.001). In group 1, the levels of tetranectin decreased (p < 0.001) from 11.8 (7.1; 14.3) to 9.02 (5.3; 14.6) pg/mL at 24 months. Moreover, in group 2 (p = 0.871) and in patients without ARCD (p = 0.716), they did not change. The tetranectin values were the independent predictor (odds ratio 7.08; p < 0.001) and its levels ≤ 15/9 ng/mL (AUC = 0.764; p < 0.001) were identified as the predictors for the adverse course of ARCD. NT-proBNP levels did not show the prognostic role, but the addition of NT-proBNP improved prognostic value of analysis (AUC = 0.954; p = 0.002). The cut-off values of tetranectin were established as predictor for adverse course of ARCD, when NT-proBNP was not. The combined use of tetranectin and NT-proBNP demonstrated higher diagnostic value for prediction of adverse outcomes., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Background: There is a paucity of data on enteral and parenteral (EN and PN) nutrition support (NS) provided by nutrition and dietetic practitioners in adult acute care settings in Ghana. Furthermore, gray literature suggests that Ghanaian clinical nutrition professionals (CNPs) are seldom involved in advanced nutrition care teams., Objectives: To assess the knowledge, attitudes, and practices of Ghanaian CNPs regarding EN and PN., Methods: An online cross-sectional survey was administered to Ghanaian CNPs ahead of a professional development workshop on EN and PN Support. Participants were asked questions about initiation and timing of NS, and knowledge on availability of commercial formula. A 5-point Likert scale was used to assess self-efficacy in using EN and PN. To assess practical knowledge on EN and PN, participants were asked to identify whether EN or PN was indicated for seven short case scenarios. Open-ended questions were used to assess reasons for participant self-ratings., Results: A total of 76 dietitians, nutritionists, students, and interns completed the survey. For EN, self-efficacy scores were lowest for the calculation of enteral goal rate, and goal volume (mean 3.20 ± 1.27), and writing of EN prescriptions (mean 3.07 ± 1.29). Self-efficacy scores for the formulation of alternative formulas in lieu of commercial formula were the highest (3.63 ± 1.36). For PN, self-efficacy scores for all domains were lower than 3, with the lowest scores observed for writing PN prescriptions (2.19 ± 1.14) and determining micronutrient additives (2.12 ± 1.04). We identified limited training and lack of practical exposure to NS, limited ability to effectively monitor tube feeds, and prohibitive cost and limited availability of EN and PN formula among the barriers impacting self-efficacy scores., Conclusion: Given the vital role that CNPs play in the delivery of EN and PN, it is important to develop professional training programs especially focused on PN to bridge knowledge and practice gaps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ayande, Agordoh, Salino, Webster-Ariyan, Collier, Asante and Carbone.)

Diversity of phage propagation, physical properties, and assembly promotes the use of phages in ecological studies and biomedicine. However, observed phage diversity is incomplete. Bacillus thuringiensis siphophage, 0105phi-7-2, first described here, significantly expands known phage diversity, as seen via in-plaque propagation, electron microscopy, whole genome sequencing/annotation, protein mass spectrometry, and native gel electrophoresis (AGE). Average plaque diameter vs. plaque-supporting agarose gel concentration plots reveal unusually steep conversion to large plaques as agarose concentration decreases below 0.2%. These large plaques sometimes have small satellites and are made larger by orthovanadate, an ATPase inhibitor. Phage head-host-cell binding is observed by electron microscopy. We hypothesize that this binding causes plaque size-increase via biofilm evolved, ATP stimulated ride-hitching on motile host cells by temporarily inactive phages. Phage 0105phi7-2 does not propagate in liquid culture. Genomic sequencing/annotation reveals history as temperate phage and distant similarity, in a virion-assembly gene cluster, to prototypical siphophage SPP1 of Bacillus subtilis . Phage 0105phi7-2 is distinct in (1) absence of head-assembly scaffolding via either separate protein or classically sized, head protein-embedded peptide, (2) producing partially condensed, head-expelled DNA, and (3) having a surface relatively poor in AGE-detected net negative charges, which is possibly correlated with observed low murine blood persistence.

This study addresses a joint nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy approach to provide a platform for dynamic assessment of kidney viability and metabolism. On porcine kidney models, ROS production, oxidative damage kinetics, and metabolic changes occurring both during the period between organ retrieval and implantation and after kidney graft were examined. The 1H-NMR metabolic profile—valine, alanine, acetate, trimetylamine-N-oxide, glutathione, lactate, and the EPR oxidative stress—resulting from ischemia/reperfusion injury after preservation (8 h) by static cold storage (SCS) and ex vivo machine perfusion (HMP) methods were monitored. The functional recovery after transplantation (14 days) was evaluated by serum creatinine (SCr), oxidative stress (ROS), and damage (thiobarbituric-acid-reactive substances and protein carbonyl enzymatic) assessments. At 8 h of preservation storage, a significantly (p < 0.0001) higher ROS production was measured in the SCS vs. HMP group. Significantly higher concentration data (p < 0.05−0.0001) in HMP vs. SCS for all the monitored metabolites were found as well. The HMP group showed a better function recovery. The comparison of the areas under the SCr curves (AUC) returned a significantly smaller (−12.5 %) AUC in the HMP vs. SCS. EPR-ROS concentration (μmol·g−1) from bioptic kidney tissue samples were significantly lower in HMP vs. SCS. The same result was found for the NMR monitored metabolites: lactate: −59.76%, alanine: −43.17%; valine: −58.56%; and TMAO: −77.96%. No changes were observed in either group under light microscopy. In conclusion, a better and more rapid normalization of oxidative stress and functional recovery after transplantation were observed by HMP utilization.

Background: Health literacy (HL) has shown its important role on reducing the burden of heart diseases. However, no study has provided a comprehensive worldwide view of the data regarding HL and heart diseases. The study aimed to provide insight into: (1) the intellectual structure, (2) research trends, and (3) research gaps on HL and heart diseases; and (4) to explore HL scales commonly utilized in heart studies., Materials and Methods: Studies related to HL and heart diseases were retrieved from Web of Science, Scopus, and PubMed. All publications published between 2000 and 2021 were included after conducting keyword searches on "heart diseases" in general or on specific types of heart diseases (e.g., "heart failure") and "health literacy". Bibliometric analyses were carried out using the Bibliometrix R package and VOSviewer 1.6.14., Findings: A total of 388 original research articles and reviews on HL and heart diseases were included in our study. The studies were primarily conducted in the United States and developed countries. A total of 337 studies (86.9%) focused on heart failure (200 studies, 51.5%) and ischemic heart diseases (137 studies, 35.3%). Sixty-two studies (16.0%) focused on other heart diseases (e.g., valvular diseases and rheumatic heart diseases). The number of interventional studies was limited (52 studies, 13.4%) and fluctuated from 2000 to 2021. The most common questionnaires measuring health literacy among patients with heart diseases were the Test of Functional Health Literacy in Adults (TOFHLA), Short Test of Functional Health Literacy in Adults (STOFHLA), and Brief Health Literacy Screen (BHLS). Use of the eHealth Literacy Scale (eHEALS) has become the latest trend among patients with heart diseases., Conclusion: Health literacy and heart diseases were most often studied in the United States and developed countries. Several HL tools were used; eHEALS has been lately used in this field. These findings suggest the need to conduct more empirical studies on HL and heart diseases in different settings (e.g., developing or poor countries) and with different types of heart diseases (e.g., valvular and rheumatic disorders). Additionally, it is necessary to develop heart disease-specified HL scales for research and practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huy, Truong, Hoang, Nguyen, Nguyen, Dang, Hsu, Huang, Chang, Shih, Carbone, Yang and Duong.)

Objective: To evaluate role of molecular (endothelin-1, soluble Fas-L, NT-proBNP, TNF-α, interleukin-1β,) and genetic factors (NOS3 (rs1799983), EDNRA (C + 70G, rs5335), NADPH oxidase (C242T, rs4673), p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522), NOS3 (Glu298Asp, rs1799983), Caspase 8 (CASP8, rs3834129 and rs1045485), interleukin-1β gene (Il-1β, rs1143634), TNF-α gene (rs1800629), SOD2 (rs4880), GPX1 (rs1050450) in development of anthracycline-induced cardiotoxicity (AIC) in women without cardiovascular diseases., Methods: A total of 176 women with breast cancer and without cardiovascular diseases who received anthracyclines were enrolled in the study. After the 12 months of chemotherapy (CT), all patients were divided into two groups: group 1 ( n  = 52) comprised patients with AIC, group 2 ( n  = 124) comprised those without it., Results: Based on ROC-analysis, levels of endothelin-1 of ≥9.0 pg/mL (AUC of 0.699), sFas-L of ≥98.3 ng/mL (AUC of 0.990), and NT-proBNP of ≥71.5 pg/mL (AUC of 0.994;) were identified as a cut-off values predicting AIC during 12 months after CT. Whereas, NT-proBNP and sFas-L were more significant predictors than endothelin-1 ( p  < 0.001). The development of AIC was significantly related to Arg/Arg of p53 protein gene (OR = 2.972; p  = 0.001), T/T of NOS3 gene (OR = 3.059, p  = 0.018), T/T of NADPH oxidase gene (OR = 2.753, p  = 0.008), and C/C of GPX1 (OR = 2.345; p  = 0.007)., Conclusion: Evaluation of polymorphisms genes of p53 (rs1042522), NOS3 (rs1799983), GPX1 (rs1050450), and NADPH oxidase (rs4673) can be recommended before CT for the risk assessment of AIC development. The serum levels of NT-proBNP and soluble Fas-L after CT may be considered as non-invasive biomarkers for prediction of AIC development during the 12 months.

Introduction: Health-related social needs are associated with poor health outcomes. Many primary care practices now screen and refer patients with health-related social needs to assistance organizations, but some patients decline screening or assistance. Improving communication about health-related social needs screening and referral could increase screening response and assistance acceptance rates., Study Design: This is a pragmatic, nonrandomized 3-stage trial of messages and communication strategies for health-related social needs screening and referral. Messages and strategies were informed by qualitative analysis of stakeholder interviews and were developed through an iterative, patient-, and stakeholder-engaged process., Setting/participants: Settings included 3 primary care clinics serving primarily low-income patients in western Colorado., Intervention: Stage 1 includes usual clinic processes for health-related social needs screening (form given to patients at the front desk without additional explanation), Stage 2 includes adding written patient-friendly messages regarding the purpose of health-related social needs screening and referral to usual clinic processes, and Stage 3 includes adding verbal messages delivered by a medical assistant (form given to patients by a medical assistant during the rooming process)., Main Outcome Measures: Primary outcomes include (1) screening form response rate and (2) acceptance of referral for assistance rate among patients with health-related social needs. Secondary outcomes include (1) comfort with screening, (2) perceived helpfulness of screening, and (3) receipt of explanation about screening., Results: All data collection and analysis occurred in 2021. Study Stage 2 was not associated with significant changes in any outcomes. Stage 3 was associated with decreased odds of screening form response at 2 of the 3 clinics relative to those of Stage 1 (OR=0.1, 95% CI=0.1, 0.3; OR=0.4, 95% CI=0.2, 0.7) but with increased odds of assistance acceptance (OR=2.1, 95% CI=1.1, 4.0) among patients with needs who responded to the screening form. Stage 3 was also associated with higher odds of patients perceiving screening as helpful and receiving an explanation about screening., Conclusions: Altering practice workflows to provide verbal explanations of health-related social needs screening may reduce response rates but may encourage responders to accept assistance referrals. Optimal communication strategies and workflows will likely differ depending on the intended goals of health-related social needs screening and referral., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Social determinants profoundly impact health. Many primary care practices now seek to screen their patients for health-related social needs (HRSN) and refer them to resources in the community. However, there is little empirical evidence to guide communication with patients in order to ensure their comfort with the process and increase the likelihood that it results in positive outcomes. This paper describes the first phase of the Improving Messaging Around Gaps in Needs and rEfferals (IMAGINE) study-a multi-phase study aiming to develop and test patient-centred messages about screening and referral for HRSN. In this initial qualitative phase, our objective was to identify communication strategies that might make western Colorado primary care patients more comfortable with the HRSN screening and referral process. From May to July 2020 we interviewed 10 staff members responsible for HRSN screening from primary care practices participating in the western Colorado Accountable Health Communities (AHC) initiative and 20 patients from 2 of these practices. We used a rapid qualitative analysis process that involved summarising interview transcripts across key domains of interest and then identifying emergent themes within each domain using a data matrix. Through this process, we examined current communication about HRSN screening, as well as suggestions for messages and other strategies that could improve communication. In most practices, the AHC Screening Tool was handed to patients by front desk staff at check-in with little explanation as to its purpose. Patients and staff alike recommended that patients be provided with information that: normalises the screening and referral process; assures privacy; clarifies that the purpose is to help and support rather than judge or report; emphasises community benefits; and respects patient autonomy. Interviewees also suggested broader strategies to support more effective communication, such as practice staff and clinicians building trusting relationships with patients and understanding and acknowledging the complex structural barriers that often prevent patients from accessing meaningful assistance. These findings provide actionable suggestions for improving communication about HRSN screening and referral in primary care settings. The next steps include developing specific messages based on these findings and testing their impact on screening tool completion rate, referral uptake, and patient-reported comfort with the process., (© 2022 John Wiley & Sons Ltd.)

Understanding fusion mechanisms employed by SARS-CoV-2 spike protein entails realistic transmembrane domain (TMD) models, while no reliable approaches towards predicting the 3D structure of transmembrane (TM) trimers exist. Here, we propose a comprehensive computational framework to model the spike TMD only based on its primary structure. We performed amino acid sequence pattern matching and compared the molecular hydrophobicity potential (MHP) distribution on the helix surface against TM homotrimers with known 3D structures and selected an appropriate template for homology modeling. We then iteratively built a model of spike TMD, adjusting "dynamic MHP portraits" and residue variability motifs. The stability of this model, with and without palmitoyl modifications downstream of the TMD, and several alternative configurations (including a recent NMR structure), was tested in all-atom molecular dynamics simulations in a POPC bilayer mimicking the viral envelope. Our model demonstrated unique stability under the conditions applied and conforms to known basic principles of TM helix packing. The original computational framework looks promising and could potentially be employed in the construction of 3D models of TM trimers for a wide range of membrane proteins.

Telehealth holds much potential for supporting older adults' physical and social health. In particular, telewellness interventions to support the physical and social wellness of older adults are needed to overcome participation barriers with in-person programs. This paper presents guidelines for delivering telewellness interventions to older adults, which were informed by a human factors approach to developing a Tele Tai Chi intervention for older adults with mobility disabilities, including reviewing user needs literature and conducting user-centered needs assessment research. From these findings, we developed a protocol and support materials for delivering a telewellness intervention and conducted a feasibility study. We also established an adaptation committee to provide recommendations on the intervention. The outcome of our human factors approach was the establishment of research-driven design guidelines for delivering group exercise programs to older adults using videoconferencing. The guidelines provide direction for designing a telewellness protocol, supporting remote participation, and promoting socialization and engagement. These guidelines can be used to deliver interventions that increase access to socially-engaging, physical activity programs for older adults, which can ultimately help support their physical health, mental health, and quality of life.

During their lifetime, 20% of US women experience depression. Studies have indicated that a high Dietary Inflammatory Index (DII) score is associated with high C-reactive protein (CRP) levels and depression. No previous study has compared the association of the DII with different measures of depression (e.g., somatic, cognitive) among pre- and post-menopausal women. We used data from 2512 pre-menopausal and 2392 post-menopausal women from the National Health and Nutrition Examination Survey (NHANES) 2005−2010 database. We ran linear and logistic regression models to compare the association of the DII with survey-measured depression among pre- and post-menopausal women. We further assessed the mediation effect of CRP on the association of the DII and depression, using structural equation modeling. The odds of experiencing depression among pre-menopausal women was higher for all DII quartiles compared to the reference group (i.e., DII Q1), with an odds ratio (OR) of 3.2, 5.0, and 6.3 for Q2, Q3, and Q4, respectively (p < 0.05). Among post-menopausal women, only Q4 had 110% higher odds of experiencing depression compared to Q1 (p = 0.027). No mediation effect of CRP was found between DII and any of our depression outcome measures. Our findings suggest that lifestyle habits, such as diet, may have a stronger influence on mental health among pre-menopausal women than post-menopausal women.

The protective effects of recombinant human lactoferrin rhLF (branded "CAPRABEL™") on the cognitive functions of rat offspring subjected to prenatal hypoxia (7% O 2 , 3 h, 14th day of gestation) have been analyzed. About 90% of rhLF in CAPRABEL was iron-free (apo-LF). Rat dams received several injections of 10 mg of CAPRABEL during either gestation (before and after the hypoxic attack) or lactation. Western blotting revealed the appearance of erythropoietin (EPO) alongside the hypoxia-inducible factors (HIFs) in organ homogenates of apo-rhLF-treated pregnant females, their embryos (but not placentas), and in suckling pups from the dams treated with apo-rhLF during lactation. Apo-rhLF injected to rat dams either during pregnancy or nurturing the pups was able to rescue cognitive deficits caused by prenatal hypoxia and improve various types of memory both in young and adult offspring when tested in the radial maze and by the Novel Object Recognition (NOR) test. The data obtained suggested that the apo-form of human LF injected to female rats during gestation or lactation protects the cognitive functions of their offspring impaired by prenatal hypoxia.

Objective: To evaluate the role of matrix metalloproteinases (MMP)-2 and 9 and the gene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) in the course of anthracycline-induced cardiotoxicity (AIC) in women without previous cardiovascular diseases (CVD) during 24-months., Methods: A total of 114 women (47.0 [44.0; 52.0] years old) with AIC of NYHA class I-III who received doxorubicin for breast cancer were enrolled., Results: After 24 months patients had breast cancer remission and were divided into 2 groups: group 1 comprised women with adverse course of AIC (n = 54), group 2 comprised those without it (n = 60). Serum levels of MMP-2 were higher by 8% (p = 0.017) MMP9 by 18.4% (p < 0.001) in group 1 than in group 2. In group 1 the levels of MMP-2 increased (p < 0.001) from 376.8 (329.5; 426.7) to 481.4 (389.8; 518.7) pg/mL, and MMP-9 increased (p < 0.001) from 23.6 (21.4; 24.6) to 26.0 (23.3; 27.0) pg/mL at 24 months. In group 2 the both MMP-2 and MMP-9 level decreased at 24 months. Based on ROC-analysis, the levels of MMP2 ≥ 388.2 pg/mL (AUС = 0.64; р = 0.013) and MMP-9 ≥ 21.25 pg/mL (AUС = 0.9; р < 0.001) were identified as predictors for adverse course of AIHF. The presence of C/C genotype of MMP2 (OR = 4.76; p = 0.029) and C/C genotype of MMP-9 (OR = 15.2; p < 0.0001) were related with adverse course of AIHF and higher levels of MMP-2 and MMP-9., Conclusion: Gene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) and serum levels of MMP-2 and MMP-9 levels in women without previous CVD were associated with adverse course of AIC during 24 months., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Protein amyloid-β (Aβ) oligomers with β-sheet-like backbone (β-structured) form extracellular amyloid plaques associated with Alzheimer's disease (AD). However, the relationship to AD is not known. Some investigations suggest that the toxic Aβ component has α-sheet-like backbone (α-structured) subsequently detoxified by intracellular α-to-β conversion before plaque formation. Our objective is to compare this latter hypothesis with observations made by electron microscopy of thin sections of AD-cerebral cortex. We observe irregular, 200-2,000 nm, intracellular, lipofuscin-like inclusions. Some are light-staining and smooth. Others are dark-staining and made granular by fibers that are usually overlapping and are sometimes individually seen. Aspects unusual for lipofuscin include 1) dark and light inclusions interlocking as though previously one inclusion, 2) dark inclusion-contained 2.6 nm thick sub-fibers that are bent as though α-structured, and 3) presence of inclusions in lysosomes and apparent transfer of dark inclusion material to damaged, nearby lysosomal membranes. These data suggest the following additions to α-structure-based hypotheses: 1) Lipofuscin-associated, α-structured protein toxicity to lysosomal membranes is in the chain of AD causation; 2) α-to-β detoxification of α-structured protein occurs in lipofuscin and causes dark-to-light transition that, when incomplete, is the origin of cell-to-cell transmission essential for development of AD.

Optimal management of Type 2 diabetes mellitus (Type 2 DM) is impeded by widespread nonadherence to efficacious medication regimens. Cardiovascular disease (CVD) is the most common cause of morbidity and mortality among persons with Type 2 DM. In this work we evaluated the relationship between CVD and medication adherence to antihypertensives, oral hypoglycemic agents, and antidepressants among patients with Type 2 DM. We also sought to understand how patients perceived barriers to and facilitators of adherence to medications. Adherence to medications was measured in 72 primary care patients from the West Philadelphia area using electronic monitoring (Medication Event Monitoring System caps) over 12 weeks. Standard questions assessed the presence of CVD. Participants answered open-ended questions about barriers to and facilitators of medication adherence. Participants who had CVD were significantly less likely to achieve ≥80% adherence to an antidepressant, oral hypoglycemic agent, and antihypertensive medications at 12 weeks. Participants identified four themes related to medication adherence: Interference from Psychosocial Demands, Need for Technological Innovation, Awareness of Disease Severity, and Integrating Community Linkages. Interventions to improve medication adherence among persons with Type 2 DM in underserved communities may aim to address social determinants of health, create community linkages, emphasize disease severity and utilize apps which are integrated with existing primary care services.

Depression affects 8% of adults in America and is one of the leading causes of disability in Western countries. The dietary inflammatory index (DII) has previously been reported to be associated with inflammation and depression. However, no study to date has looked at the potential mediating effect of inflammation on the association of DII and depression. We hypothesized that the association of DII and depression would be both statistically and clinically mediated substantially by inflammation. We assessed these associations using the cross-sectional National Health and Nutrition Examination Survey (NHANES) 2005-2010 database. Our analysis included 10,022 participants aged 20 years and older. Inflammation was assessed with C-reactive protein (CRP) levels. Diet was measured using two 24 hour dietary recalls. Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9), which has a score range of 0 to 27, with the higher score showing more severe depressive symptoms. Comparing the highest to lowest DII quartiles, the mean score difference for depression was 0.47 units (95% CI 0.24-0.70, P-trend <.001) in the multivariable adjusted model. In the sex-stratified models, the results remained significant only among females, with the mean score difference of 0.72 (95% CI 0.34-1.10, P-trend <.001). CRP mediated 3.6% of the association between DII and depression in the total population in the fully adjusted model, which was statistically significant (P-trend <.001) but not clinically significant. No mediation association was found in the sex-stratified models. Further studies are needed to assess the associations with various inflammatory biomarkers in larger and more diverse populations., (Published by Elsevier Inc.)

Background: Persons aging with mobility disability (PAwMD) experience transportation barriers, which can hinder their ability to fully participate in society. Despite a vast infrastructure of federal laws and programs designed to ensure access to transportation, PAwMD remain a transportation-disadvantaged population., Objectives: This paper presents detailed insights on transportation challenges experienced by PAwMD along with recent Federal programmatic initiatives designed to enhance access and mobility for transportation for older adults and people with disabilities. To identify policy gaps and opportunities to improve transportation services, we compared individual-level challenges from PAwMD to national survey data about barriers associated with delivering transportation services at state and local levels., Methods: To assess individual-level transportation challenges, we conducted in-depth, structured interviews with sixty older adult participants with self-identified mobility disabilities for at least 10 years. We also conducted a content analysis of end-user transportation challenges and agency-level transportation coordination barriers to identify correspondences., Results: Participants reported challenges utilizing public and private modes of transportation, related to availability; accessibility; safety; advanced planning; as well as societal attitudes. Barriers to the availability, delivery, and coordination of access and mobility services are linked directly or indirectly to the PAwMD reports of experiencing a shortage of accessible transportation options., Conclusions: Findings highlight the complexity of federal transportation policies and programmatic initiatives designed to support older adults and people with disabilities, which contribute to implementation barriers and transportation challenges. Results highlight the importance of integrating end-user and state and local provider input into transportation policy development and program implementation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Social determinants of health (SDOH) influence health outcomes. Food insecurity (FI) is the most common need related to SDOH. Many primary care practices and health systems have begun to screen for FI and refer patients to resources. How this process is viewed by multiple stakeholders, including patients, health care workers, and staff at food assistance organizations (FAOs), will influence its impact., Methods: In this mixed-methods study, we completed 42 interviews with individuals from the 3 stakeholder groups. We then conducted a survey with 126 respondents using questions developed from the qualitative results., Results: All stakeholders recognized the impact FI has on health outcomes, but perspectives varied on the value of sharing information through referrals to FAOs and concerning receipt of services, including privacy concerns and that the process would require significant work and not necessarily improve FI., Discussion: Stakeholders agree that FI impacts health but have differences in perceptions around screening and referral done in health care settings. Perspectives of multiple stakeholders need to be considered when designing these systems., Conclusion: Successfully designing systems to address FI through referral to FAOs requires input of multiple stakeholders because perspectives on the value and work required for this process vary., Competing Interests: Conflict of interest: none., (© Copyright 2022 by the American Board of Family Medicine.)

Introduction: Practice-based research networks (PBRNs) have long sought to engage with communities and address questions relevant to multiple stakeholders and real-world primary care practice. Topic-generating processes that involve these stakeholders are crucial for identifying these questions. PBRNs often focus on certain populations or geographic areas. We are forming a new PBRN to address the health concerns and research interests of people in communities in Western Colorado., Methods: To engage with and determine the questions important to multiple stakeholders in communities in western Colorado, we conducted community meetings at which we used Photovoice followed by Nominal Group Technique in group discussions across the region. We then conducted a survey to develop a list of priority research topics., Results: Multiple stakeholders were ready and eager to engage with us to form a PBRN. Across all communities, many of the topics that emerged were related to the social determinants of health. Mental health-specifically, lack of access to services and high suicide incidence-was the most important topic according to community members. This was consistent across groups of stakeholders and corroborated other community work such as Community Health Needs Assessments., Discussion: Using participatory methods increased our stakeholder engagement and helped build strong community-academic partnerships for our PBRN-related research. Use of Photovoice allowed all participants to express their thoughts and ideas and led to a clear path forward for this new research network., Competing Interests: Conflict of interest: None., (© Copyright 2022 by the American Board of Family Medicine.)

Collagens play important roles in development and homeostasis in most higher organisms. In order to function, collagens require the specific chaperone HSP47 for proper folding and secretion. HSP47 is known to bind to the collagen triple helix, but the exact positions and numbers of binding sites are not clear. Here, we employed a collagen II peptide library to characterize high-affinity binding sites for HSP47. We show that many previously predicted binding sites have very low affinities due to the presence of a negatively charged amino acid in the binding motif. In contrast, large hydrophobic amino acids such as phenylalanine at certain positions in the collagen sequence increase binding strength. For further characterization, we determined two crystal structures of HSP47 bound to peptides containing phenylalanine or leucine. These structures deviate significantly from previously published ones in which different collagen sequences were used. They reveal local conformational rearrangements of HSP47 at the binding site to accommodate the large hydrophobic side chain from the middle strand of the collagen triple helix and, most surprisingly, possess an altered binding stoichiometry in the form of a 1:1 complex. This altered stoichiometry is explained by steric collisions with the second HSP47 molecule present in all structures determined thus far caused by the newly introduced large hydrophobic residue placed on the trailing strand. This exemplifies the importance of considering all three sites of homotrimeric collagen as independent interaction surfaces and may provide insight into the formation of higher oligomeric complexes at promiscuous collagen-binding sites., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic stress is implicated in behavioral and health issues in cats, but methods for recognition, evaluation, and measurement of stress are lacking. Cortisol concentration is typically used as an indicator of stress., Objectives: To evaluate use of an enzyme immunoassay to quantitate hair and nail cortisol concentrations (HCC and NCC) in cats and evaluate associations between HCC and NCC and behavioral, physical, and environmental correlates of chronic stress in cats., Animals: Forty-eight adult, owned or community cats., Methods: Cross-sectional study. Nail clippings and hair were collected from cats. Medical history and cat daily lifestyle questionnaires were completed by owners or caretakers. A commercial laboratory performed cortisol extraction and quantification using a validated enzyme immunoassay kit. Correlational and regression analyses were used to evaluate associations between HCC and NCC and behavioral, environmental, and medical factors., Results: Hair and nail cortisol concentrations were significantly associated (r s  = 0.70; P < .001), but HCCs varied widely within and among cats. Cats with litterbox issues had significantly increased HCC (P = .02) and NCC (P = .001) as compared to cats without litterbox issues. Cats with groomed coats had lower HCCs (P = .02) as compared to cats without groomed coats, whereas cats with dander and mats had higher NCCs (P = .01) as compared to cats without dander and mats., Conclusions and Clinical Importance: The quantification of NCCs might improve identification and evaluation of chronic stress in cats. The variability of HCCs in individual cats warrants caution using this measurement in chronic stress studies., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Phage G is recognized as having a remarkably large genome and capsid size among isolated, propagated phages. Negative stain electron microscopy of the host-phage G interaction reveals tail sheaths that are contracted towards the distal tip and decoupled from the head-neck region. This is different from the typical myophage tail contraction, where the sheath contracts upward, while being linked to the head-neck region. Our cryo-EM structures of the non-contracted and contracted tail sheath show that: (1) The protein fold of the sheath protein is very similar to its counterpart in smaller, contractile phages such as T4 and phi812; (2) Phage G's sheath structure in the non-contracted and contracted states are similar to phage T4's sheath structure. Similarity to other myophages is confirmed by a comparison-based study of the tail sheath's helical symmetry, the sheath protein's evolutionary timetree, and the organization of genes involved in tail morphogenesis. Atypical phase G tail contraction could be due to a missing anchor point at the upper end of the tail sheath that allows the decoupling of the sheath from the head-neck region. Explaining the atypical tail contraction requires further investigation of the phage G sheath anchor points.

Background: The physical and social environments surrounding food, whether perceived or observed, can influence consumers' food choices by changing food access, and affordability, or by changing settings where food-related behaviors occur., Aim: To describe older adults' perceived food environment, identify the most important sites and factors that enable healthy eating, and explore older adults' recommendations for communities to facilitate fruit and vegetable consumption., Methods: Participants aged 60 and older from metropolitan areas in Massachusetts, Iowa, and Illinois completed a researcher-administered survey to rate the perceived environment including accessibility, availability, and affordability of fruits and vegetables, and perceived importance of factors and establishments related to fruit and vegetable consumption. Participants also suggested changes for establishments to facilitate fruit and vegetable consumption., Results: The majority of the 142 participants perceived their food environment for fruits and vegetables as not difficult to access (85.2%) with good or excellent availability (90.1%). Education, marital status, and race were associated with some aspects of the perceived food environment. Perceived accessibility and supermarkets were rated as the most important factor and establishment, respectively, to facilitate fruit and vegetable consumption across all study sites. Participants proposed recommendations to address the availability, quality, accessibility and affordability of fruits and vegetables., Conclusion: Interventions promoting accessible, affordable, quality fruits and vegetables may improve older adult consumers' perceptions of their food environment. Communities may also use undervalued resources such as mobile markets more strategically to provide additional support for healthy eating in older adults.

Blood-borne therapeutic phages and phage capsids increasingly reach therapeutic targets as they acquire more persistence, i.e., become more resistant to non-targeted removal from blood. Pathogenic bacteria are targets during classical phage therapy. Metastatic tumors are potential future targets, during use of drug delivery vehicles (DDVs) that are phage derived. Phage therapy has, to date, only sometimes been successful. One cause of failure is low phage persistence. A three-step strategy for increasing persistence is to increase (1) the speed of lytic phage isolation, (2) the diversity of phages isolated, and (3) the effectiveness and speed of screening phages for high persistence. The importance of high persistence-screening is illustrated by our finding here of persistence dramatically higher for coliphage T3 than for its relative, coliphage T7, in murine blood. Coliphage T4 is more persistent, long-term than T3. Pseudomonas chlororaphis phage 201phi2-1 has relatively low persistence. These data are obtained with phages co-inoculated and separately assayed. In addition, highly persistent phage T3 undergoes dispersal to several murine organs and displays tumor tropism in epithelial tissue (xenografted human oral squamous cell carcinoma). Dispersal is an asset for phage therapy, but a liability for phage-based DDVs. We propose increased focus on phage persistence-and dispersal-screening.

Background: Healthcare workers play an important role in responding to the needs of the millions of children and adolescents who experience sexual abuse around the globe. A supportive child and adolescent-centered initial response is crucial for the physical and emotional wellbeing of survivors., Objective: In 2017, the World Health Organization (WHO) published clinical guidelines for responding to child and adolescent sexual abuse. The review described in this paper informed the development of good practice statements on how best to deliver health care to survivors., Participants and Setting: This review examined the values and preferences of children and adolescents who were sexually abused, and of their caregivers and healthcare workers, regarding: 1) initial response to children and adolescents who have been sexually abused; and 2) obtaining medical history, conducting physical examination, and documenting examination findings., Methods: Searches were conducted in Scopus, Pubmed, and the WHO's Global Index Medicus (1 January, 1995-15 July 2016). All articles in English that indicated preferences of survivors, caregivers and/or healthcare workers in ensuring empathetic and trauma-informed care were included., Results: Sixty-two articles were included and analyzed thematically. Key findings included the importance of providing care to survivors in a manner that respects the child or adolescent's autonomy and wishes, ensures privacy and confidentiality, and makes services and facilities appropriate and welcoming., Conclusions: Findings indicate how evidence-based recommendations can be delivered in a child or adolescent-centred and trauma-informed manner., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The report presents the results of the development of dental films with ketorolac trometamine based on the natural biodegradable polymers from the groups of sodium alginates and xanthan gums in combination with lightly crosslinked acrylic polymer carbopol. Physicochemical properties, such as moisture, mucoadhesion, thickness, tensile strength, disintegration in phosphate buffer were determined in obtained samples of this dosage form. A comparison of physicochemical properties of experimental samples and commercial model of dental film has allowed establishing the perspective composition of complex matrix of films with ketorolac trometamine for use in dentistry., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

There is a paucity of qualitative research on children's and adolescents' perceptions of their sexual abuse experiences. This paper aims to describe the narrative types and consequences of sexual abuse stories among ten female Filipino children and adolescents. Data were collected through semi-structured interviews and analyzed using dialogical narrative analysis. Results show that three narrative types appear in the stories of the survivors. These are the tragic resistance narrative, rescued slave narrative, and heroic saga narrative, and each of these narratives has idiosyncratic effects on the identities, affiliations, disclosure, and adjustment processes of the participants. The results show how symbolic cultural structures can have far-reaching consequences on sexually abused children and adolescents., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021.)

Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases., (© 2021 S. Karger AG, Basel.)

Background: There are growing numbers of adults aging with long-term mobility disabilities. Very little is known about the challenges this population experiences with everyday activities, and such challenges are likely to be greater and more complex than those of older adults who experience mobility declines later in life., Objectives: The current manuscript presents in-depth insights on the specific activity challenges experienced by older adults with long-term mobility disabilities, and the response strategies they employ to overcome those challenges., Methods: In-depth, structured interviews designed to assess challenges and response strategies for a range of daily activities were conducted with sixty older adult participants (ages 60-79) who self-identified as having a mobility disability for a minimum of 10 years. A coding scheme was developed to classify emerging themes. We identify the most common challenges and responses reported across all 6 broad categories as well as for a single activity category as an exemplar of an in-depth activity analysis., Results: A needs taxonomy revealed challenges and response themes in relation to the most difficult activities identified by the participants. Frequently reported challenges included physical limitations and accessibility challenges. Common response strategies (e.g., utilizing tools or technologies, obtaining assistance from others, or modifying the approach to the task) were successfully mapped onto the Selection, Optimization, and Compensation model., Conclusions: Findings reveal the unique challenges individuals face when engaging in everyday activities, and the potential of affordable and effective supports to promote aging-in-place, functional independence, and community engagement for adults aging with long-term mobility disability., (Copyright © 2020. Published by Elsevier Inc.)

The production of volatile organic compounds (VOCs) during programmed cell death (PCD) is still insufficiently studied and their implication in the process is not well understood. The present study demonstrates that the release of VOSCs with presumed antioxidant capacity (methanethiol, dimethylsulfide and dimethyldisulfide) accompanies the cell death in chemical-stressed tobacco BY-2 suspension cultured cells. The cells were exposed to cell death inducers of biotic nature mastoparan (MP, wasp venom) and camptothecin (CPT, alkaloid), and to the abiotic stress agent CdSO 4 . The VOCs emission was monitored by proton-transfer reaction mass spectrometry (PTR-MS). The three chemicals induced PCD expressing apoptotic-like phenotype. The identified VOSCs were emitted in response to MP and CPT but not in presence of Cd. The VOSCs production occurred within few hours after the administration of the elicitors, peaked up when 20-50 % of the cells were dead and further levelled off with cell death advancement. This suggests that VOSCs with antioxidant activity may contribute to alleviation of cell death-associated oxidative stress at medium severity of cell death in response to the stress factors of biotic origin. The findings provide novel information about cell death defence mechanisms in chemical-challenged BY-2 cells and show that PCD related VOSCs synthesis depends on the type of inducer., Competing Interests: Declaration of Competing Interest There are no commercial links or other connections for each of the authors that could pose a conflict of interest in any way., (Copyright © 2020. Published by Elsevier GmbH.)

Background: People with disabilities acquired in early to mid-life are living longer, contributing to growing numbers of older adults who are aging with disability, an understudied population likely to be underserved., Objectives: This paper demonstrates the usefulness of the TechSAge Minimum Battery as a holistic assessment of health for people aging with disabilities., Methods: Survey data of socio-demographic and health characteristics were collected from 176 older adults with long-term vision, hearing, and/or mobility disabilities. A series of descriptive and bivariate analyses were conducted to illustrate the heterogeneity of the sample. An in-depth analysis of the subsample with vision difficulty was conducted to highlight the tool's value in assessing detailed contextual information for a specific disability., Results: Prevalence of health conditions (M = 4.1; SD = 2.5), prescription medications (M = 4.1; SD = 3.9), and serious functional difficulties (M = 1.6; SD = 0.85) indicated a fair degree of comorbidity, but with considerable variation in number and type among individuals. Subjective health ratings were high overall, but lower scores were correlated with additional comorbidities (r = -0.31-0.40, p =<.001). Analyses of the subsample with vision difficulty demonstrated heterogeneity in functional capacity, degree of impairment, duration, and use of supportive aids., Conclusions: Findings highlighted the heterogeneity among people aging with disability and demonstrated the importance of capturing multi-dimensional factors inclusive of an individual's capacity, context, and personal factors, which the Minimum Battery provides in an integrated assessment. Potential healthcare applications of the tool are discussed with implications for bridging aging and disability services., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Empowerment has been described as a prerequisite for health and the ultimate goal of health literacy in both clinical practice and health promotion. Improving health literacy and empowerment is central to national and international public health and healthcare policies. While initially merged in the construct of critical health literacy, and currently linked without question in policy and discourse, health literacy and empowerment have been dichotomized - treated as two separate fields of study and practice - and partitioned further into condition-based lines of inquiry. Few studies have addressed both concepts. Indeed, references to empowerment in health literacy studies have decreased over the last decade. This chapter summarizes and interprets the significance of these fault lines for current and future research. Divergent clinical and health promotion perceptions of health empowerment, its expected outcomes, processes, interventions and measures are reviewed. Gaps in the literature are identified and recommendations are suggested to build a more robust science around health literacy and empowerment by addressing those limitations. The chapter reinforces recent calls for increased attention to empowerment in health literacy research and the reintegration of the critical health literacy concept to better reflect policy, achieve global public health goals, advance healthcare delivery, and foster multidisciplinary career opportunities for students, researchers, and practitioners.

We review some aspects of the rapid isolation of, screening for and characterization of jumbo phages, i.e., phages that have dsDNA genomes longer than 200 Kb. The first aspect is that, as plaque-supporting gels become more concentrated, jumbo phage plaques become smaller. Dilute agarose gels are better than conventional agar gels for supporting plaques of both jumbo phages and, prospectively, the even larger (>520 Kb genome), not-yet-isolated mega-phages. Second, dilute agarose gels stimulate propagation of at least some jumbo phages. Third, in-plaque techniques exist for screening for both phage aggregation and high-in-magnitude, negative average electrical surface charge density. The latter is possibly correlated with high phage persistence in blood. Fourth, electron microscopy of a thin section of a phage plaque reveals phage type, size and some phage life cycle information. Fifth, in-gel propagation is an effective preparative technique for at least some jumbo phages. Sixth, centrifugation through sucrose density gradients is a relatively non-destructive jumbo phage purification technique. These basics have ramifications in the development of procedures for (1) use of jumbo phages for phage therapy of infectious disease, (2) exploration of genomic diversity and evolution and (3) obtaining accurate metagenomic analyses.

Background: A home-based record (HBR) is a health document kept by the patient or their caregivers, rather than by the health care facility. HBRs are used in 163 countries, but they have not been implemented universally or consistently. Effective implementation maximizes both health impacts and cost-effectiveness. We sought to examine this research-to-practice gap and delineate the facilitators and barriers to the effective implementation and use of maternal and child health HBRs especially in low- and middle-income countries (LMICs)., Methods: Using a framework analysis approach, we created a framework of implementation categories in advance using subject expert inputs. We collected information through 2 streams. First, we screened 69 gray literature documents, of which 18 were included for analysis. Second, we conducted semi-structured interviews with 12 key informants, each of whom had extensive experience with HBR implementation. We abstracted the relevant data from the documents and interviews into an analytic matrix. The matrix was based on the initial framework and adjusted according to emergent categories from the data., Results: We identified 8 contributors to successful HBR implementation. These include establishing high-level support from the government and ensuring clear communication between all ministries and nongovernmental organizations involved. Choice of appropriate contents within the record was noted as important for alignment with the health system and for end user acceptance, as were the design, its physical durability, and timely redesigns. Logistical considerations, such as covering costs sustainably and arranging printing and distribution, could be potential bottlenecks. Finally, end users' engagement with HBRs depended on how the record was initially introduced to them and how its importance was reinforced over time by those in leadership positions., Conclusions: This framework analysis is the first study to take a more comprehensive and broad approach to the HBR implementation process in LMICs. The findings provide guidance for policy makers, donors, and health care practitioners regarding best implementation practice and effective HBR use, as well as where further research is required., (© Mahadevan and Broaddus-Shea.)

Animal source foods (ASF) provide nutrients essential to child growth and development yet remain infrequently consumed in rural Nepal. Agriculture and nutrition programs aim to increase ASF intake among children through small-scale animal husbandry projects. The relationship between livestock ownership and children's consumption of ASF, however, is not well established. This study examined associations between livestock ownership and the frequency with which Nepali children consume eggs, dairy, and meat. We analyzed longitudinal 7-day food frequency data from sentinel surveillance sites of the Policy and Science of Health, Agriculture and Nutrition (PoSHAN) study. Data consisted of surveys from 485 Nepali farming households conducted twice per year for two years (a total of 1449 surveys). We used negative binomial regression analysis to examine the association between the number of cattle, poultry, and meat animals (small livestock) owned and children's weekly dairy, egg, and meat intakes, respectively, adjusting for household expenditure on each food type, mother's education level, caste/ethnicity, agroecological region, season, and child age and sex. We calculated predicted marginal values based on model estimates. Children consumed dairy 1.4 (95% CI 1.1-2.0), 2.3 (1.7-3.0) and 3.0 (2.1-4.2) more times per week in households owning 1, 2-4 and >4 cattle, respectively, compared to children in households without cattle. Children consumed eggs 2.8 (2.1-3.7) more times per week in households owning 1 or 2 chickens compared to children in households without chickens. Child intake of meat was higher only in households owning more than seven meat animals. Children's intakes of dairy, eggs, and meat rose with household expenditure on these foods. Small-scale animal production may be an effective strategy for increasing children's consumption of eggs and dairy, but not meat. Increasing household ability to access ASF via purchasing appears to be an important approach for raising children's intakes of all three food types., Competing Interests: The authors declare no conflict of interest.

Increased knowledge of virus assembly-generated particles is needed for understanding both virus assembly and host responses to virus infection. Here, we use a phage T3 model and perform electron microscopy (EM) of thin sections (EM-TS) of gel-supported T3 plaques formed at 30 °C. After uranyl acetate/lead staining, we observe intracellular black particles, some with a difficult-to-see capsid. Some black particles (called LBPs) are larger than phage particles. The LBP frequency is increased by including proflavine, a DNA packaging inhibitor, in the growth medium and increasing plaque-forming temperature to 37 °C. Acidic phosphotungstate-precipitate (A-PTA) staining causes LBP substitution by black rings (BRs) that have the size and shape expected of hyper-expanded capsid containers for LBP DNA. BRs are less frequent in liquid cultures, suggesting that hyper-expanded capsids evolved primarily for in-gel (e.g., in-biofilm) propagation. BR-specific A-PTA staining and other observations are explained by α-sheet intense structure of the major subunit of hyper-expanded capsids. We hypothesize that herpes virus triggering of neurodegenerative disease occurs via in-gel propagation-promoted (1) generation of α-sheet intense viral capsids and, in response, (2) host production of α-sheet intense, capsid-interactive, innate immunity amyloid protein that becomes toxic. We propose developing viruses that are therapeutic via detoxifying interaction with this innate immunity protein.

Objective: To conduct a comprehensive mapping of published indicators for monitoring and evaluation (M&E) of sexual and reproductive health (SRH) services and outcomes in humanitarian settings., Methods: A systematic search of the peer-reviewed and grey literature published between January 2008 and May 2018 was conducted to identify all references describing indicator sets for M&E of SRH services and outcomes in humanitarian settings. The databases MEDLINE, Web of Science, and Global Health, as well as 85 websites of relevant organizations involved in humanitarian response were searched. Characteristics of identified indicator sets and data from individual indicators was extracted., Findings: Of 3278 records identified, 20 met the review's inclusion criteria and 9 existing indicator sets were identified. A total of 179 relevant indicators were included in the mapping, and removal of duplicates yielded 132 unique indicators. Twenty-seven percent fell within the maternal health domain, followed by the HIV/AIDS domain (26%) and the gender-based violence domain (23%). The distribution of indicators by type (process/output, outcome, impact) was balanced overall but varied substantially across domains. The most commonly used data collection platforms were facility-based systems or population-based surveys. Domains covered and indicator definitions were inconsistent across indicator sets., Conclusion: Results demonstrate the need to standardize data collection efforts for M&E of SRH services and outcomes in humanitarian settings and to critically appraise the extent to which different domains should be covered. A core list of indicators is essential for assessing response status over time as well as across countries., Competing Interests: Competing interestsThe authors declare that they have no competing interests. The authors alone are responsible for the views expressed in this [article] and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated., (© The Author(s). 2019.)

Objective: Our immediate objective is to determine whether infectivity of lytic podophage T3 has a relatively high persistence in the blood of a mouse, as suggested by previous data. Secondarily, we determine whether the T3 surface has changed during this mouse passage. The surface is characterized by native agarose gel electrophoresis (AGE). Beyond our current data, the long-term objective is optimization of phages chosen for therapy of all bacteremias and associated sepsis., Results: We find that the persistence of T3 in mouse blood is higher by over an order of magnitude than the previously reported persistence of (1) lysogenic phages lambda and P22, and (2) lytic phage T7, a T3 relative. We explain these differences via the lysogenic character of lambda and P22, and the physical properties of T7. For the future, we propose testing a new, AGE-based strategy for rapidly screening for high-persistence, lytic, environmental podophages that have phage therapy-promoting physical properties.