What matters to you? An observational field study of patient and care provider expectations for health care relationships.

Therapeutic connections (TC) between patients and providers are foundational to patient-centered care, which is co-produced between patients and care providers. This necessitates that we understand what patients expect from TCs, the extent to which providers know what patients expect, and what providers expect. The purpose of this study was to examine nine TC dimensions and determine which are most important to patients, which dimensions providers believe are most important to patients, and which are most important to providers. An online survey of patients (n = 388) and care providers (n = 433) was conducted in the USA in March 2021. Respondents rated the extent to which the nine TC dimensions were important to them, followed by open-ended questions to expand upon what matters. The quantitative responses were rank-ordered and rankings were compared across groups. All groups ranked "having the patient's best interest in mind no matter what" as the top expectation. Patients also ranked "caring commitment" and being "on the same page" as highly important. Providers were relatively accurate in ranking what they believed was most important to patients. Respondents affirmed the TC dimensions in the qualitative results, adding nuance and context, such as patients feeling "heard" and noting providers that go "above and beyond." Providers ranked dimensions differently for themselves, prioritizing "full presence" and "emotional support" of patients. This study is among the first to examine expectations for TC. TC could play an explanatory role in understanding variation in patient experience ratings and other outcomes.

"Nothing Is More Powerful than Words:" How Patient Experience Narratives Enable Improvement.

BACKGROUND AND OBJECTIVES: Patient experience narratives (narratives) are an increasingly important element of both measurement approaches and improvement efforts in healthcare. Prior studies show that narratives are considered by both clinicians and staff to be an appealing, meaningful, and credible form of evidence on performance. They also suggest that making concrete use of narratives within organizational settings to improve care can be complex and challenging. Our qualitative study was designed to explore how middle managers working in a health system's outpatient clinics value and use written narratives in their day-to-day work. METHODS: We conducted qualitative interviews with 20 middle managers working in 8 outpatient clinics. Interviews were fully transcribed, loaded into MAX-QDA software, and coded using thematic analysis techniques. Code reports were extracted and reanalyzed for subthemes related to the objectives of this paper. RESULTS: Middle managers across sites described valuing narratives as a tool to: enable better patient experience assessment by augmenting data from patient experience scores; deepen understanding of and relationships with patients; provide insight about operational issues; identify areas for needed improvement and potential solutions; and facilitate strategic work. They reported using narratives for a range of activities related to their roles as supervisors, such as focusing attention on positive practices and needed improvements, promoting deeper group learning, motivating change, reinforcing sense of purpose for staff, recognizing staff strengths and training needs, and inspiring transformational thinking. Finally, interviewees reported numerous specific quality improvement projects (both short- and longer-term) that were informed by narratives-for example, by identifying an issue to be addressed or by suggesting a workable solution. Together, these interviews suggest a collective "narrative about narratives" woven by these organizational actors-a story which illustrates how narratives are highly relevant for how middle managers derive meaning from their work, put organizational values such as responsive service provision into practice, and enact their roles as supervisors. CONCLUSIONS: Our results add to the nascent literature a detailed description of how narratives can be used both as a tool for middle managers in their leadership and supervisory roles, and as a blueprint for improvement work within outpatient settings. They also illuminate why patient experience scores may improve when narrative data are collected and used. Finally, our results suggest that for middle managers, perhaps "nothing is more powerful than words" because narratives function as both an insight provider and a compelling tool that adds direction and meaning to workplace endeavors.

Evaluation of the root dentin bond strength and intratubular biomineralization of a premixed calcium aluminate-based hydraulic bioceramic endodontic sealer.

PURPOSE: This study evaluated the dentin bonding strength and biomineralization effect of a recently developed premixed calcium aluminate-based endodontic sealer (Dia-Root Bio Sealer) in comparison with existing calcium silicate-based sealers. METHODS: The root canals of 80 mandibular premolars were filled with Dia-Root Bio Sealer, Endoseal MTA, EndoSequence BC Sealer, and AH Plus Bioceramic Sealer. Medial and apical specimens were then obtained by sectioning. The push-out bond strength was measured using the medial specimens, and the failure mode was recorded. Intratubular biomineralization in the apical specimens was analyzed using scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS). The data were analyzed using one-way analysis of variance followed by the Tukey test (P < 0.05). RESULTS: The push-out bond strength of Dia-Root Bio Sealer was significantly higher than that of the other tested materials, and a cohesive failure pattern was observed in all groups. Dia-Root Bio Sealer also exhibited a significantly higher degree of biomineralization than the other groups, and EDS analysis indicated that the biomineralized precipitates were amorphous calcium phosphate. CONCLUSION: The results of this study indicate that Dia-Root Bio Sealer has the potential to be used as an adequate root canal sealer due to its favorable bonding performance.

Contrast-enhanced ultrasonography-CT/MRI fusion guidance for percutaneous ablation of inconspicuous, small liver tumors: improving feasibility and therapeutic outcome.

BACKGROUND: Percutaneous radiofrequency ablation (RFA) is pivotal for treating small malignant liver tumors, but tumors often remain inconspicuous on B-mode ultrasound (US). This study evaluates the potential of CEUS-CT/MRI fusion imaging (FI) to improve tumor visibility and the associated RFA outcomes for small (≤ 3 cm) malignant liver tumors that were inconspicuous on US. METHODS: Between January 2019 and April 2021, a prospective study enrolled 248 patients with liver malignancies (≤ 3 cm) that were poorly visible on B-mode US. Tumor visibility and ablation feasibility were assessed using B-mode US, US-CT/MRI FI, and CEUS-CT/MRI FI, and graded on a 4-point scale. CEUS was employed post-registration of US and CT/MRI images, utilizing either SonoVue or Sonazoid. Comparisons between US-based and CEUS-based fusion visibility and feasibility scores were undertaken using the Friedman test. Moreover, rates of technical success, technique efficacy, local tumor progression (LTP), and major complications were assessed. RESULTS: The cohort included 223 hepatocellular carcinomas (HCCs) (89.9%) and 23 metastases (9.3%), with an average tumor size of 1.6 cm. CEUS-CT/MRI FI demonstrated a significant advantage in tumor visibility (3.4 ± 0.7 vs. 1.9 ± 0.6, P < 0.001) and technical feasibility (3.6 ± 0.6 vs. 2.9 ± 0.8, P < 0.001) compared to US-FI. In 85.5% of patients, CEUS addition to US-FI ameliorated tumor visibility. Technical success was achieved in 99.6% of cases. No severe complications were reported. One and two-year post CEUS-CT/MRI FI-guided RFA estimates for LTP were 9.3% and 10.9%, respectively. CONCLUSIONS: CEUS-CT/MRI FI significantly improves the visualization of tumors not discernible on B-mode US, thus augmenting percutaneous RFA success and delivering improved therapeutic outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05445973. Registered 17 June 2022 - Retrospectively registered, http://clinicaltrials.gov/study/NCT05445973?id=NCT05445973&rank=1 .

Leveraging Patients' Creative Ideas for Innovation in Health Care.

Policy Points Patients' creative ideas may inform learning and innovation that improve patient-centered care. Routinely collected patient experience surveys provide an opportunity to invite patients to share their creative ideas for improvement. We develop and assess a methodological strategy that validates question wording designed to elicit creative ideas from patients. Health care organizations should consider how to report and use these data in health care delivery and quality improvement, and policymakers should consider promoting the use of narrative feedback to better understand and respond to patients' experiences. CONTEXT: Learning health systems (LHSs) have been promoted for a decade to achieve high-quality, patient-centered health care. Innovation driven by knowledge generated through day-to-day health care delivery, including patient insights, is critical to LHSs. However, the pace of translating patient insights into innovation is slow and effectiveness inadequate. This study aims to evaluate a method for systematically eliciting patients' creative ideas, examine the value of such ideas as a source of insight, and examine patients' creative ideas regarding how their experiences could be improved within the context of their own health systems. METHODS: The first stage of the study developed a survey and tested strategies for elicitation of patients' creative ideas with 600 patients from New York State. The second stage deployed the survey with the most generative open-ended question sequence within a health care system and involved analysis of 1,892 patients' responses, including 2,948 creative ideas. FINDINGS: Actionable, creative feedback was fostered by incorporating a request for transformative feedback into a sequence of narrative elicitation questions. Patients generate more actionable and creative ideas when explicitly invited to share such ideas, especially patients with negative health care experiences, those from minority racial/ethnic backgrounds, and those with chronic illness. The most frequently elicited creative ideas focused on solving challenges, proposing interventions, amplifying exceptional practices, and conveying hopes for the future. CONCLUSIONS: A valid and reliable method for eliciting creative ideas from patients can be deployed as part of routine patient experience surveys that include closed-ended survey items and open-ended narrative items in which patients share their experiences in their own words. The elicited creative ideas are promising for patient engagement and innovation efforts. This study highlights the benefits of engaging patients for quality improvement, offers a rigorously tested method for cultivating innovation using patient-generated knowledge, and outlines how creative ideas can enable organizational learning and innovation.

Assessing an innovative method to promote learning from patient narratives: Findings from a field experiment in ambulatory care.

OBJECTIVE: To assess whether an online interactive report designed to facilitate interpretation of patients' narrative feedback produces change in ambulatory staff learning, behavior at the individual staff and practice level, and patient experience survey scores. DATA SOURCES AND SETTING: We studied 22 ambulatory practice sites within an academic medical center using three primary data sources: 333 staff surveys; 20 in-depth interviews with practice leaders and staff; and 9551 modified CG-CAHPS patient experience surveys augmented by open-ended narrative elicitation questions. STUDY DESIGN: We conducted a cluster quasi-experimental study, comparing 12 intervention and 10 control sites. At control sites, narratives were delivered free-form to site administrators via email; at intervention sites, narratives were delivered online with interactive tools for interpretation, accompanied by user training. We assessed control-versus-intervention site differences in learning, behavior, and patient experience scores. DATA COLLECTION: Staff surveys and interviews were completed at intervention and control sites, 9 months after intervention launch. Patient surveys were collected beginning 4 months pre-launch through 9 months post-launch. We used control-versus-intervention and difference-in-difference analyses for survey data and thematic analysis for interview data. PRINCIPAL FINDINGS: Interviews suggested that the interface facilitated narrative interpretation and use for improvement. Staff survey analyses indicated enhanced learning from narratives at intervention sites (29% over control sites' mean of 3.19 out of 5 across eight domains, p < 0.001) and greater behavior change at staff and practice levels (31% and 21% over control sites' means of 3.35 and 3.39, p < 0.001, respectively). Patient experience scores for interactions with office staff and wait time information increased significantly at intervention sites, compared to control sites (3.7% and 8.2%, respectively); however, provider listening scores declined 3.3%. CONCLUSIONS: Patient narratives presented through structured feedback reporting methods can catalyze positive changes in staff learning, promote behavior change, and increase patient experience scores in domains of non-clinical interaction.

Research Note: Comparative evaluation of pathogenicity in SPF chicken between different subgroups of H5N6 high pathogenicity avian influenza viruses.

Since 2014, periodic outbreaks of high pathogenicity avian influenza (HPAI) caused by clade 2.3.4.4 H5 HPAI virus (HPAIV) have resulted in huge economic losses in the Korean poultry industry. During the winter season of 2016-2017, clade 2.3.4.4e H5N6 HPAIVs classified into 5 subgroups (C1-5) were introduced into South Korea. Interestingly, it was revealed that the subgroup C2 and C4 viruses were predominantly distributed throughout the country, whereas detection of the subgroup C3 viruses was confined in a specific local region. In the present study, we conducted comparative evaluation of the pathogenicity of viruses belonging to subgroups C2 and C3 (H15 and HN1 strains) in specific pathogen-free (SPF) chickens, and further compared them with previously determined pathogenicity of subgroup C4 (ES2 strain) virus. The HN1 strain showed lower viral replication in tissues, less transmissibility, and higher mean chicken lethal dose than the H15 and ES2 strains in SPF chickens. Considering that the HN1 strain has a different NS gene segment from the H15 and ES2 strains, the reassortment of the NS gene segment likely affects their infectivity and transmissibility in chickens. These findings emphasize the importance of monitoring the genetic characteristics and pathogenic features of HPAIVs to effectively control their outbreaks in the field.

Learning from patients: The impact of using patients' narratives on patient experience scores.

BACKGROUND: Enthusiasm has grown about using patients' narratives-stories about care experiences in patients' own words-to advance organizations' learning about the care that they deliver and how to improve it, but studies confirming association have not been published. PURPOSE: We assessed whether primary care clinics that frequently share patients' narratives with their staff have higher patient experience survey scores. APPROACH: We conducted a 1-year study of 5,545 adult patients and 276 staff affiliated with nine clinics in one health system. We used multilevel models to analyze survey data from patients about their experiences and from staff about exposure to useful narratives. We examined staff confidence in own knowledge as a moderator because confidence can influence use of new information sources. RESULTS: Frequency of sharing useful narratives with staff was associated with patient experience scores for all measures, conditional on staff confidence in own knowledge ( p < .01). For operational measures (e.g., care coordination), increased sharing correlated with subsequently higher performance for more confident staff and lower performance or no difference for less confident staff, depending on measure. For relational measures (e.g., patient-provider communication), increased sharing correlated with higher scores for less confident staff and lower scores for more confident staff. CONCLUSION: Sharing narratives with staff frequently is associated with better patient experience survey scores, conditional on confidence in knowledge. PRACTICE IMPLICATIONS: Frequently sharing useful patient narratives should be encouraged as an organizational improvement strategy. However, organizations need to address how narrative feedback interacts with their staff's confidence to realize higher experience scores across domains.

Better outcomes through patient - Provider therapeutic connections? An exploratory study of proposed mediating variables.

BACKGROUND: Patient-provider therapeutic connections (TCs) have been theorized to enhance patient outcomes as well as care provider job satisfaction and to reduce burnout. High-quality TCs may result in better matching of health care to patient needs, and thus, better care quality and patient outcomes. For care providers, work environments that enable high-quality TCs may make the work more motivating and facilitate resilience. METHOD: We surveyed patients (n = 346) and care providers (n = 341) about their experiences of TCs, and how TCs related to outcomes. We tested parallel mediation models to examine relations. RESULTS: TCs predicted better patient health status, mental health status, and satisfaction, and predicted greater care provider job satisfaction and lower burnout. TCs were theorized to operate through two sets of mechanisms (health self-efficacy and activation for patients; meaningfulness of work and psychological safety for providers). Results revealed significant indirect associations between TCs and outcomes for both groups. CONCLUSIONS: TCs are associated with patient and provider outcomes; however, these relations appear to be explained by several mediating variables. It appears that TCs are associated with better outcomes for patients through health self-efficacy and activation, and TCs are associated with better outcomes for care providers through meaningfulness of work and psychological safety.

Prenatal and postnatal exposure to polychlorinated biphenyls alter follicle numbers, gene expression, and a proliferation marker in the rat ovary.

Polychlorinated biphenyls (PCBs) were used in industrial applications until they were banned in the 1970s, but they still persist in the environment. Little is known about the long-term effects of exposure to PCB mixtures on the rat ovary during critical developmental periods. Thus, this study tested whether prenatal and postnatal exposures to PCBs affect follicle numbers and gene expression in the ovaries of F1 offspring. Sprague-Dawley rats were treated with vehicle or Aroclor 1221 (A1221) at 1 mg/kg/day during embryonic days 8-18 and/or postnatal days (PND) 1-21. Ovaries from F1 rats were collected for assessment of follicle numbers and differential expression of estrogen receptor 1 (Esr1), estrogen receptor 2 (Esr2), androgen receptor (Ar), progesterone receptor (Pgr), and Ki-67 (Ki67) at PNDs 8, 32, and 60. Sera were collected for measurement of estradiol concentrations. Prenatal exposure to A1221 significantly decreased the number of primordial follicles and the total number of follicles at PND 32 compared to control. Postnatal PCB exposure borderline increased Ki67 gene expression and significantly increased Ki67 protein levels (PND 60) compared to control. Combined prenatal and postnatal PCB exposure borderline decreased Ar expression (PND 8) compared to control. However, PCB exposure did not significantly affect the expression of Pgr, Esr1, and Esr2 or serum estradiol concentrations compared to control at any time point. In conclusion, these data suggest that PCB exposure affects follicle numbers and levels of the proliferation marker Ki67, but it does not affect expression of some sex steroid hormone receptors in the rat ovary.

Genetic Characterization and Pathogenesis of H5N1 High Pathogenicity Avian Influenza Virus Isolated in South Korea during 2021-2022.

High pathogenicity avian influenza (HPAI) viruses of clade 2.3.4.4 H5Nx have been circulating in poultry and wild birds worldwide since 2014. In South Korea, after the first clade 2.3.4.4b H5N1 HPAI viruses were isolated from wild birds in October 2021, additional HPAIV outbreaks occurred in poultry farms until April 2022. In this study, we genetically characterized clade 2.3.4.4b H5N1 HPAIV isolates in 2021-2022 and examined the pathogenicity and transmissibility of A/mandarin duck/Korea/WA585/2021 (H5N1) (WA585/21) in chickens and ducks. Clade 2.3.4.4b H5N1 HPAI viruses caused 47 outbreaks in poultry farms and were also detected in multiple wild birds. Phylogenetic analysis of HA and NA genes indicated that Korean H5N1 HPAI isolates were closely related to Eurasian viruses isolated in 2021-2022. Four distinct genotypes of H5N1 HPAI viruses were identified in poultry, and the majority were also found in wild birds. WA585/21 inoculated chickens showed virulent pathogenicity with high mortality and transmission. Meanwhile, ducks infected with the virus showed no mortality but exhibited high rates of transmission and longer viral shedding than chickens, suggesting that they may play an important role as silent carriers. In conclusion, consideration of both genetic and pathogenic traits of H5N1 HPAI viruses is required for effective viral control.

The spectrum of imaging manifestations of Gorham-Stout disease: a novel dynamic contrast-enhanced MR lymphangiography.

BACKGROUND: To describe the radiological features of Gorham-Stout disease (GSD) as evaluated using plain radiography and dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) imaging techniques. METHODS: Clinical and conventional imaging data were retrospectively reviewed for 15 patients with GSD between January 2001 and December 2020. After December 2018, DCMRL examinations were performed for lymphatic vessel evaluation in patients with GSD and reviewed in four patients. RESULTS: The median age at diagnosis was 9 years (range: 2 months-53 years). The clinical manifestations were dyspnea in seven patients (46.7%), sepsis in 12 (80.0%), orthopedic problems in seven (46.7%), and bloody chylothorax in seven (46.7%). The common sites of osseous involvement were the spine (73.3%) and pelvic bone (60.0%). Among the non-osseous involvements, peri-osseous infiltrative soft-tissue abnormalities adjacent to the area of bone involvement were the most common (86.7%), followed by splenic cysts (26.7%) and interstitial thickening (26.7%). DCMRL demonstrated weak central conducting lymphatic flow in two patients with abnormal giant tortuous thoracic ducts and no flow in one patient. All patients who underwent DCMRL in this study presented with altered anatomical lymphatics and functional flow with collateralization. CONCLUSION: DCMRL imaging and plain radiography are very useful for determining the extent of GSD. DCMRL is a novel imaging tool for the visualization of abnormal lymphatics in patients with GSD, which helps in further treatment. Therefore, in patients with GSD, it might be necessary to obtain not only plain radiographs but also MR and DCMRL images.

Bronchial and non-bronchial systemic artery embolization with transradial access in patients with hemoptysis.

PURPOSE We aimed to determine the safety and feasibility of transradial access (TRA) in bronchial artery and non-bronchial systemic artery (NBSA) embolization in patients with non-massive hemoptysis. METHODS This retrospective study was approved by the Institutional Review Board. Among the 300 patients treated for hemoptysis with bronchial artery and NBSA embolization between April 2018 and July 2019, 19 procedures in 19 patients were conducted by TRA and were retrospectively analyzed. TRA was considered when the bronchial artery or NBSA originated from the arch vessel or its tributaries. The exclusion criteria of TRA included Barbeau C or D waveform and a radial artery diameter of less than 1.8 mm on ultrasound. TRA was also avoided in cases of the high-origin bronchial artery (i.e., T4 or higher level of the aorta). The hemoptysis-free time was estimated using the Kaplan-Meier method. RESULTS The technical success (i.e., embolization of all target artery with TRA) rate was 94.7% (18 out of 19 patients). In terms of the target arteries, embolization with TRA was technically successful in treating 47 out of 48 arteries (97.9%). The 1-month and 6-month hemoptysis-free rates were 89.5% (17/19) and 73.7% (14/19), respectively. The only adverse event was iatrogenic dissection of the bronchial artery with little clinical significance in 1 patient. No access site complications were identified on post-procedure day 1 ultrasonography. CONCLUSION With proper patient selection, TRA offers a safe and effective approach to embolize the bronchial arteries and NBSAs in patients with hemoptysis.

Evolution, Transmission, and Pathogenicity of High Pathogenicity Avian Influenza Virus A (H5N8) Clade 2.3.4.4, South Korea, 2014-2016.

During 2014-2016, clade 2.3.4.4 H5N8 high pathogenicity avian influenza virus (HPAIV) caused the largest known avian influenza epidemic in South Korea. Based on data from earlier H5N8 outbreaks, primitive H5N8 virus in South Korea was classified into five subgroups: C1, C2, C3, C4, and C5. The present study investigated the pathogenic and molecular epidemiologic characteristics of H5N8 viruses obtained from 388 cases of poultry farms and 85 cases of wild bird infections in South Korea during 2014-2016. Representative viruses of subgroups C1, C2, and C4 showed significant pathobiological differences in specific pathogen-free (SPF) chickens, with the H1731 (C1) virus showing substantially lower infectivity, transmissibility, and pathogenicity than the H2102 (C2) and H1924 (C4) viruses. Full genome sequence analysis showed the number of mutations that significantly increased in domestic duck-origin H5N8 HPAIVs compared to the viruses from gallinaceous poultry. These differences may have been due to the long-term circulation of viruses in domestic duck farms. The same mutations, at positions 219 and 757 of PB1, independently evolving in the C0, C1, and C2 subgroups may have been positively selected, resulting in convergent evolution at the amino acid level. Bayesian discrete trait phylodynamic analysis (DTA) indicated multiple introductions of H5N8 HPAIV from wild birds into domestic poultry in various regions in South Korea. Following initial viral introduction into domestic duck farms in the western part of Korea, domestic ducks played a major role in viral transmission and maintenance. These findings highlight the need for continued genomic surveillance and pathobiological characterization of HPAIV in birds. Enhanced biosecurity in poultry farms should be implemented to prevent the introduction, maintenance, and spread of HPAIV.

Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations.

Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy. [BMB Reports 2022; 55(9): 453-458].

In Vitro and in Silico Analyses of the Adiponectin Receptor Agonistic Action of Soybean Tripeptides.

The Tyr-Pro (YP) dipeptide can serve as an adiponectin receptor 1 (AdipoR1) agonist. We thus investigated the AdipoR1-agonistic potential of YP-related tripeptides in the soybean protein sequence. Among the 17 soybean candidate tripeptides, those elongated at the C-terminus of YP (0.1 µM YPG, 140 ± 16%; 0.1 µM YPE, 141 ± 22%; 0.1 µM YPP, 145 ± 19%; 0.1 µM YPQ, 143 ± 20%; p < 0.05) significantly promoted glucose uptake by L6 muscle myotubes, comparable to the effect of 0.1 µM AdipoRon (163 ± 52%, p < 0.05). The knockdown of AdipoR1 expression in L6 cells abrogated this effect of YPG and YPP, indicating that the two tripeptides had an AdipoR1 agonistic effect. CHARMM-GUI-aided molecular dynamics simulation in a virtual phospholipid membrane revealed that YPG and YPP were stably positioned at the binding pockets of AdipoR1 (binding free energy < -10 kcal/mol). These findings demonstrate that the tripeptides YPG and YPP, with AdipoR1 agonistic YP sequences, have alternative adiponectin-like potential via their preferential binding to AdipoR1.

Creativity in problem solving to improve complex health outcomes: Insights from hospitals seeking to improve cardiovascular care.

Introduction: Improving performance often requires health care teams to employ creativity in problem solving, a key attribute of learning health systems. Despite increasing interest in the role of creativity in health care, empirical evidence documenting how this concept manifests in real-world contexts remains limited. Methods: We conducted a qualitative study to understand how creativity was fostered during problem solving in 10 hospitals that took part in a 2-year collaborative to improve cardiovascular care outcomes. We analyzed interviews with 197 hospital team members involved in the collaborative, focusing on work processes or outcomes that participants self-identified as creative or promoting creativity. We sought to identify recurrent patterns across instances of creativity in problem solving. Results: Participants reported examples of creativity at both stages typically identified in problem solving research and practice: uncovering non-obvious problems and finding novel solutions. Creativity generally involved the assembly of an "ecological view" of the care process, which reflected a more complete understanding of relationships between individual care providers, organizational sub-units, and their environment. Teams used three prominent behaviors to construct the ecological view: (a) collecting new and diverse information, (b) accepting (rather than dismissing) disruptive information, and (c) employing empathy to understand and share feelings of others. Conclusions: We anticipate that findings will be useful to researchers and practitioners who wish to understand how creativity can be fostered in problem solving to improve clinical outcomes and foster learning health systems.

Emergence of clade 2.3.4.4b novel reassortant H5N1 high pathogenicity avian influenza virus in South Korea during late 2021.

High pathogenicity H5N1 avian influenza viruses pose a threat to both animal and human health worldwide. In late 2020, outbreaks of H5 high pathogenicity avian influenza viruses belonging to clade 2.3.4.4b emerged in Europe, following on from outbreaks in East Asia in earlier years. However, very recent studies show that clade 2.3.4.4b H5N1, rather than 2.3.4.4b H5N8, has become predominant in wild birds and has infected poultry in several countries. In this study, we describe isolation of a novel H5N1 virus from a captured mandarin duck in South Korea, and another H5N1 virus from a quail farm. We performed genetic analysis of these two viruses to identify their origin and to determine their relationship with the clade 2.3.4.4b H5N1 viruses currently circulating in Europe. Based on our results, it is presumed that the novel H5N1 virus isolated in Korea originated from an unknown reassortant between clade 2.3.4.4b H5N8 viruses circulating from 2020 and other Eurasian viruses, with additional reassortment of genes and point mutations that discriminate them from the recently reported H5N1 virus in Europe.

Ribes fasciculatum Ameliorates High-Fat-Diet-Induced Obesity by Elevating Peripheral Thermogenic Signaling.

Ribes fasciculatum has been consumed as a food and as a traditional medicine for treating autoimmune diseases and aging in diverse countries. A previous study showed that a mixture of Ribes fasciculatum and Cornus officinalis prohibited adipocyte differentiation and lipid accumulation in preadipocytes and suppressed diet-induced obesity. Nevertheless, the mechanism of R. fasciculatum to regulate energy homeostasis solely through thermogenic signaling remains unclear. Thus, we investigated its effects on energy homeostasis using R. fasciculatum fed to C57BL/6 mice with a 45% high-fat diet. Chronic consumption of R. fasciculatum decreased the body weight of obese mice with increasing food intakes and improved metabolic-syndrome-related phenotypes. Therefore, we further tested its thermogenic effects. Cold chamber experiments and qPCR studies indicated that R. fasciculatum elevated thermogenic signaling pathways, demonstrated by increased body temperature and uncoupling protein 1 (UCP1) signaling in the white and brown adipose tissues. Afzelin is one major known compound derived from R. fasciculatum. Hence, the isolated compound afzelin was treated with preadipocytes and brown adipocytes for cell viability and luciferase assay, respectively, to further examine its thermogenic effect. The studies showed that the response of afzelin was responsible for cell viability and the increased UCP1. In conclusion, our data indicated that R. fasciculatum elevated peripheral thermogenic signaling through increased UCP1 via afzelin activation and ameliorated diet-induced obesity.

Perfluorooctanoic Acid Disrupts Ovarian Steroidogenesis and Folliculogenesis in Adult Mice.

Perfluorooctanoic acid (PFOA) is a synthetic fluorosurfactant used in the manufacturing of fluorotelomers. Although PFOA is no longer produced in the United States, it is environmentally persistent and found in imported food packaging, cookware, and textiles. Previous studies have identified developmental toxicity of PFOA, but little is known about the effects of PFOA on the adult ovary. Thus, this study examined the effects of PFOA on hormone levels, ovarian steroidogenic gene expression, and folliculogenesis in mice in vitro and in vivo. For the in vitro studies, antral follicles from adult female mice were cultured with vehicle control or 1, 10, or 100 µg/ml PFOA for 96 h. For the in vivo studies, adult CD-1 female mice were orally dosed with vehicle control or 1, 5, 10, or 20 mg/kg/day PFOA for 10 days. Gene expression of steroidogenic enzymes, levels of sex steroid hormones, and follicle counts were analyzed. In vitro, PFOA (100 µg/ml) significantly decreased follicle growth, estradiol and estrone levels, and gene expression of StaR, Cyp11a1, and Hsd3b1 compared with controls. In vivo, exposure to PFOA significantly decreased progesterone and pregnenolone levels (5 mg/kg), increased testosterone levels (1 mg/kg), and increased gene expression of Cyp19a1 (1 mg/kg) compared with controls. Exposure to PFOA also significantly altered follicle counts by decreasing primordial follicles and increasing preantral and antral follicles (5 and 10 mg/kg) compared with controls. Collectively, these data show that PFOA disrupts adult ovarian function in a nonmonotonic matter and may pose a risk for premature ovarian failure.