Oxidation of Molybdenum-Based Single-Metallic/bimetallic Carbide MXenes in Aqueous Suspensions: Mechanistic Insights.

Molybdenum carbide MXenes have garnered considerable attention in electronics, energy storage, and catalysis. However, they are prone to oxidative degradation, but the associated mechanisms have not been systematically explored. Therefore, the oxidation mechanisms of Mo-based single-metallic/bimetallic carbide MXenes including Mo2CTx, Mo2TiC2Tx, and Mo2Ti2C3Tx in aqueous suspensions were investigated for the first time in this study. Similar to Ti3C2Tx MXene, Mo-based MXenes were found to undergo oxidative degradation in their aqueous dispersions, leading to the disruption of their crystal structure and subsequent loss of optical and electronic properties. Notably, the Mo2CTx MXene deviated from this typical oxidation behavior as it produced an amorphous product with Mo ions instead of highly crystalline Mo-oxides during oxidation. Similarly, the Mo2TiC2Tx and Mo2Ti2C3Tx MXenes did not yield crystalline Mo-oxides; instead, they produced highly crystalline anatase TiO2 and a Mo-ion-containing amorphous product simultaneously. Furthermore, high-temperature annealing of the oxidized Mo2CTx MXene powder at 800 °C transformed the amorphous Mo-containing product into highly crystalline MoO2 crystals. These findings highlight the unconventional oxidation behavior of Mo-based MXenes, which suggests that the formation of crystalline Mo-based oxides requires a higher activation energy during oxidation than that of TiO2. The unique oxidative pathway reported herein can help elucidate the oxidation mechanisms of Mo-based MXene dispersions and their products. The insights from this study can pave the way for fundamental studies in academia as well as broaden the applications of Mo-based MXenes in various industries.

Lipid profile and reproductive performance of female offspring of SWISS mouse females supplemented with resveratrol or canjiqueira (Byrsonima cydoniifolia A Juss) during gestation.

This study aimed to resveratrol supplementation (at 5 or 10 mg/kg) and a hydroethanolic extract of canjiqueira fruits (150 mg/kg) on female SWISS mice. Total cholesterol, high-density lipoprotein (HDL), triglyceride levels, gestation rates, and embryonic implantation rates in their female Offspring was evaluated. In conclusion, the consumption of canjiqueira fruit extract altered the lipid profile of their female offspring, and did not impact their reproductive performance. Supplementing female SWISS mice with 10 mg/kg of resveratrol increased total cholesterol, triglycerides, and HDL levels, thereby enhancing the reproductive efficiency of their offspring.

Relationships between physical activity, sleep, and screen time with academic performance and psychological functioning among US children and adolescents with depression.

OBJECTIVE: This cross-sectional study examined the relationships between adherence to 24-HMB guidelines (including physical activity [PA], screen time [ST], and sleep) with academic performance and psychological functioning among children and adolescents with depression. METHODS: This study consists of 2165 participants aged 6-17 years with depression. Independent variables were components of 24-HMB guideline adherence, while outcomes of interest were academic performance (i.e., caring about school performance and completion of required homework) and psychological functioning (i.e., resilience and self-regulation). Logistic regression analysis was conducted while adjusting for confounding variables. RESULTS: Only 1.03 % of the participants adhered to PA + ST + Sleep guidelines. Compared to non-adherence, adherence to PA + ST guidelines was significantly linked to a greater likelihood of caring about school performance (OR = 2.17), while ST + Sleep guidelines adherence was significantly linked to a greater likelihood of caring about school performance (OR = 2.02), completing homework (OR = 2.91), resilience (OR = 2.51), and self-regulation (OR = 2.51). Furthermore, adherence to PA + ST + Sleep guidelines was significantly linked to a higher likelihood of caring about school performance (OR = 5.01), resilience (OR = 2.49), and self-regulation (OR = 2.88) among these participants with depression. CONCLUSION: Adhering to 24-HMB guidelines is positively linked to academic performance and psychological functioning among children and adolescents with depression. Thus, establishing healthy lifestyle behaviors should be promoted in school settings.

Framework for Accurate Classification of Self-Reported Stress From Multisession Functional MRI Data of Veterans With Posttraumatic Stress.

Background: Posttraumatic stress disorder (PTSD) is a significant burden among combat Veterans returning from the wars in Iraq and Afghanistan. While empirically supported treatments have demonstrated reductions in PTSD symptomatology, there remains a need to improve treatment effectiveness. Functional magnetic resonance imaging (fMRI) neurofeedback has emerged as a possible treatment to ameliorate PTSD symptom severity. Virtual reality (VR) approaches have also shown promise in increasing treatment compliance and outcomes. To facilitate fMRI neurofeedback-associated therapies, it would be advantageous to accurately classify internal brain stress levels while Veterans are exposed to trauma-associated VR imagery. Methods: Across 2 sessions, we used fMRI to collect neural responses to trauma-associated VR-like stimuli among male combat Veterans with PTSD symptoms (N = 8). Veterans reported their self-perceived stress level on a scale from 1 to 8 every 15 s throughout the fMRI sessions. In our proposed framework, we precisely sample the fMRI data on cortical gray matter, blurring the data along the gray-matter manifold to reduce noise and dimensionality while preserving maximum neural information. Then, we independently applied 3 machine learning (ML) algorithms to this fMRI data collected across 2 sessions, separately for each Veteran, to build individualized ML models that predicted their internal brain states (self-reported stress responses). Results: We accurately classified the 8-class self-reported stress responses with a mean (± standard error) root mean square error of 0.6 (± 0.1) across all Veterans using the best ML approach. Conclusions: The findings demonstrate the predictive ability of ML algorithms applied to whole-brain cortical fMRI data collected during individual Veteran sessions. The framework we have developed to preprocess whole-brain cortical fMRI data and train ML models across sessions would provide a valuable tool to enable individualized real-time fMRI neurofeedback during VR-like exposure therapy for PTSD.

Hyperbaric oxygen therapy for central retinal artery occlusion: Visual acuity and time to treatment.

Purpose: To evaluate the effectiveness of hyperbaric oxygen (HBO2) therapy as a treatment for central retinal artery occlusion (CRAO). Methods: A total of 38 patients who underwent HBO2 for non-arteritic CRAO were identified. Patients with arteritic CRAO, branch retinal artery occlusion, ophthalmic artery occlusion, and other diagnoses were excluded from the analysis. The main outcome measured was the change in visual acuity at the most recent follow-up exam compared to the visual acuity at presentation before the initiation of HBO2 therapy. Results: The overall visual acuity after HBO2 compared with the visual acuity at presentation showed a mean improvement of 0.5 logMAR from 2.2 to 1.7 logMAR (p=0.0003). Patients who presented with hand motion and light perception vision had a mean improvement of 0.4 logMAR (p=0.06) and 0.8 logMAR (p=0.004) after HBO2, respectively. An average visual acuity improvement of 0.5 logMAR (p=0.01) was observed when patients underwent HBO2 earlier than 24 hours of symptom onset. This mean improvement increased to 0.9 logMAR (p=0.009) if HBO2 was initiated within eight hours. Conclusions: HBO2 may be an effective treatment for non-arteritic CRAO, especially if patients are treated early and present with salvageable vision. The time to treatment and the presenting visual acuity may be predictive factors on the visual prognosis following HBO2. Further studies with a prospective design and more patients are necessary to determine the long-term outcomes and the optimal protocol for HBO2 in CRAO patients.

All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California.

Rationale & Objective: Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies. Study Design: Retrospective cohort study. Setting & Population: Patients aged ≥18 years with incident CKD (estimated glomerular filtration rate ≤45 mL/min/1.73 m2) with and without heart failure in a large integrated health care system in Southern California. Exposure: Heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF). Outcomes: All-cause and cardiovascular-related mortality within one year of CKD identification. Analytical Approach: HRs were estimated using Cox proportional-hazards model for risk of all-cause mortality and Fine-Gray subdistribution hazard model for risk of cardiovascular-related mortality within 1 year. Results: The study cohort included 76,688 patients with incident CKD between 2007 and 2017, of which 14,249 (18.6%) had prevalent heart failure. Among these patients, 8,436 (59.2%) had HFpEF and 3,328 (23.3%) had HFrEF. Compared with patients without heart failure, the HR for 1-year all-cause mortality was 1.70 (95% CI, 1.60-1.80) among patients with heart failure. The HRs were 1.59 (95% CI, 1.48-1.70) for patients with HFpEF and 2.43 (95% CI, 2.23-2.65) for patients with HFrEF. Compared with patients without heart failure, the 1-year cardiovascular-related mortality HR for patients with heart failure was 6.69 (95% CI, 5.93-7.54). Cardiovascular-related mortality HR was even higher among those with HFrEF (HR, 11.47; 95% CI, 9.90-13.28). Limitations: Retrospective design with a short 1-year follow-up period. Additional variables including medication adherence, medication changes, and time-varying variables were not accounted for in this intention-to-treat analysis. Conclusions: Among patients with incident CKD, heart failure was highly prevalent with HFpEF accounting for over 70% among patients with known ejection fraction. Although the presence of heart failure was associated with higher 1-year all-cause and cardiovascular-related mortality, patients with HFrEF were the most vulnerable.

Public Perception of Marijuana Use for the Treatment of Glaucoma.

The use of marijuana for the treatment of glaucoma has been widely debated amongst ophthalmologists and glaucoma specialists. Recent evidence suggests the majority of ophthalmologists do not support the use of marijuana as active treatment for glaucoma. However, there has been no investigation into understanding the public's direct perception of the efficacy of marijuana in glaucoma treatment. By using Twitter as a tool to understand the public's thoughts, tweets were analyzed over the last 2 years. Of the 700 tweets analyzed, 72% (n=503) of tweets were in favor of cannabis use in the treatment of glaucoma, whereas 18% (n=124) were evidently opposed. The majority of those in favor came from accounts of individual users (n=391; 56%) whereas those that opposed marijuana as a treatment came from accounts of health care media, ophthalmologists, and other health care workers. The discrepancy between the public and ophthalmologists and other health care professionals requires recognition and further action to better educate the public on the role of marijuana in glaucoma treatment.

Topical Dexamethasone as an Adjuvant to Mineralocorticoid Receptor Antagonists for the Treatment of Recalcitrant Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE: A previous report demonstrated efficacy of mineralocorticoid antagonist with adjuvant topical dexamethasone (MRA+DEX) in resolving subretinal fluid (SRF) in a chronic central serous chorioretinopathy (CSCR) patient. This pilot study investigates the use of MRA+DEX to treat recalcitrant, chronic CSCR patients. STUDY DESIGN: Retrospective review of chronic, recalcitrant CSCR patients unresponsive to MRA alone who were treated with MRA+DEX and followed for up to 3 months. Apical SRF thickness and visual acuity were measured. RESULTS: Ten eyes of eight chronic, recalcitrant patients were included with an average follow-up of 109 days. Mean percent reduction in apical fluid thickness at one month and at last follow-up after adding dexamethasone (DEX) was 33% and 52%, respectively. Five eyes (50%) achieved complete resolution of SRF. Three eyes (30%) showed partial response and two (20%) eyes had no response. There was no significant change in visual acuity. CONCLUSIONS: MRA+DEX decreased SRF in some recalcitrant, chronic CSCR patients. Large prospective studies are needed to evaluate the utility of MRA+DEX in these chronic CSCR patients. [Ophthalmic Surg Lasers Imaging Retina 2022;53:659-665.].

Real-world use patterns of angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) among patients with heart failure within a large integrated health system.

BACKGROUND: Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred in guidelines over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with heart failure with reduced ejection fraction (HFrEF). However, it has not been broadly adopted in clinical practice. OBJECTIVE: To characterize ARNI use within a large diverse real-world population and assess for any racial disparities. METHODS: We conducted a cross-sectional study within Kaiser Permanente Southern California. Adult patients with HFrEF who received ARNIs, ACEIs, or ARBs between January 1, 2014, and November 30, 2020, were identified. The prevalence of ARNI use among the cohort and patient characteristics by ARNIs vs ACEIs/ARBs use were described. Multivariable regression was performed to estimate odds ratios and 95% CIs of receiving ARNI by race and ethnicity. RESULTS: Among 12,250 patients with HFrEF receiving ACEIs, ARBs, or ARNIs, 556 (4.54%) patients received ARNIs. ARNI use among this cohort increased from 0.02% in 2015 to 7.48% in 2020. Patients receiving ARNIs were younger (aged 62 vs 69 years) and had a lower median ejection fraction (27% vs 32%) compared with patients receiving ACEIs/ARBs. They also had higher use of mineralocorticoid antagonists (24.1% vs 19.8%) and automatic implantable cardioverterdefibrillators (17.4% vs 13.3%). There were no significant differences in rate of ARNI use by race and ethnicity. CONCLUSIONS: Within a large diverse integrated health system in Southern California, the rate of ARNI use has risen over time. Patients given ARNIs were younger with fewer comorbidities, while having worse ejection fraction. Racial minorities were no less likely to receive ARNIs compared with White patients. DISCLOSURES: Dr Huang had stock ownership in Gilead and Pfizer. Dr Liang received support for article processing and medical writing.

USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer.

Clear cell renal cell carcinoma (ccRCC) is characterized by the loss of tumor suppressor Von Hippel Lindau (VHL) function. VHL is the component of an E3 ligase complex that promotes the ubiquitination and degradation of hypoxia inducible factor α (HIF-α) (including HIF1α and HIF2α) and Zinc Fingers And Homeoboxes 2 (ZHX2). Our recent research showed that ZHX2 contributed to ccRCC tumorigenesis in a HIF-independent manner. However, it is still unknown whether ZHX2 could be modified through deubiquitination even in the absence of pVHL. Here, we performed a deubiquitinase (DUB) complementary DNA (cDNA) library binding screen and identified USP13 as a DUB that bound ZHX2 and promoted ZHX2 deubiquitination. As a result, USP13 promoted ZHX2 protein stability in an enzymatically dependent manner, and depletion of USP13 led to ZHX2 down-regulation in ccRCC. Functionally, USP13 depletion led to decreased cell proliferation measured by two-dimensional (2D) colony formation and three-dimensional (3D) anchorage-independent growth. Furthermore, USP13 was essential for ccRCC tumor growth in vivo, and the effect was partially mediated by its regulation on ZHX2. Our findings support that USP13 may be a key effector in ccRCC tumorigenesis.

Effects of Behavioral Economics-Based Messaging on Appointment Scheduling Through Patient Portals and Appointment Completion: Observational Study.

BACKGROUND: Behavioral economics-based techniques have been an increasingly utilized method in health care to influence behavior change by modifying language in patient communication (through choice architecture and the framing of words). Patient portals are a key tool for facilitating patient engagement in their health, and interventions deployed via patient portals have been effective in improving utilization of preventive health services. OBJECTIVE: We examined the impacts of behavioral economics-based nudge health maintenance reminders on appointment scheduling through a patient portal and appointment completion for 2 preventive services: Medicare wellness visits and Pap smear. METHODS: We conducted a retrospective observational study using electronic health record data from an integrated health care system in Northern California. Nudge health maintenance reminders with behavioral economics-based language were implemented for all sites in November 2017 for Medicare wellness visits and for selected sites in February 2018 for Pap smears. We analyzed 125,369 health maintenance reminders for Medicare wellness visits, and 585,358 health maintenance reminders for Pap smear sent between January 2017 and February 2020. The primary outcomes were rate of appointments scheduled through the patient portal and appointment completion rate. We compared the outcomes between those who received the new, behavioral economics-based health maintenance reminders (the nudge group) and those who received the original, standard health maintenance reminders (the control group). We used segmented regression with interrupted time series to assess the immediate and gradual effect of the nudge for Medicare wellness visits, and we used logistic regression to assess the association of nudge health maintenance reminders, adjusting for the propensity to receive a nudge health maintenance reminder, for Pap smear. RESULTS: The rates of appointments scheduled through the patient portal were higher for nudge health maintenance reminder recipients than those for control health maintenance reminder recipients (Medicare wellness visits-nudge: 12,537/96,839, 13.0%; control: 2,769/28,530, 9.7%, P<.001; Pap smear-nudge: 8,239/287,149, 2.9%; control: 1,868/120,047, 1.6%; P<.001). Rates of appointment completion were higher for nudge health maintenance reminders for Pap smear (nudge: 67,399/287,149, 23.5% control: 20,393/120,047, 17.0%; P<.001) but were comparable for Medicare wellness visits (nudge: 49,835/96,839, 51.5% control: 14,781/28,530, 51.8%; P=.30). There was a marginally gradual effect of nudge on number of appointments scheduled through the patient portal for the overall Medicare wellness visits sample (at a monthly rate of 0.26%, P=.09), and a significant gradual effect among scheduled appointments (at a monthly rate of 0.46%, P=.04). For Pap smear, nudge health maintenance reminders were positively associated with number of appointments scheduled through the patient portal (overall sample: propensity adjusted odds ratio [OR] 1.62; 95% CI 1.50-1.74; among scheduled appointments: propensity adjusted OR 1.61, 95% CI 1.47-1.76) and with appointment completion (propensity adjusted OR 1.07; 1.04-1.10). CONCLUSIONS: Nudges, a behavioral economics-based approach to providing health maintenance reminders, increased the number of appointments scheduled through the patient portal for Medicare wellness visits and Pap smear. Our study demonstrates that a simple approach-framing and modifying language in an electronic message-can have a significant and long-term impact on patient engagement and access to care.

Barriers and Facilitators to Advance Care Planning among Chinese Patients with Advanced Cancer and Their Caregivers.

Background: Chinese American adults experience health disparities at the end of life. Culturally tailored advance care planning (ACP) may promote goal-concordant care across the continuum of serious illness. However, seriously ill Chinese Americans' preferences for ACP remain unknown. Objective: To explore barriers and facilitators to ACP among Chinese patients with advanced cancer and their caregivers. Design: Informed by socioecological theory, we conducted an exploratory qualitative study using semistructured interviews that were thematically analyzed. Setting/Participants: We recruited participants at one U.S. comprehensive cancer center. Of 27 eligible patients approached, we recruited 20 patients (74.1%) and 8 accompanying caregivers. Overall, participants were middle aged (55.6 ± 13.5 years), 60.7% female, 85.7% partnered/married, 89.3% college educated, and had low acculturation (mean Suinn-Lew Asian Self-Identify Acculturation = 2.0 ± 1.6/5.0). More patients were privately insured (35%) than self-pay (30%), Medicare (25%), and Medicaid (10%). Caregivers were split between "spouse" and "child." Results: Findings highlight participants' trust in their clinicians and the study institution as primary supports for clinicians to lead ACP. However, participants' preconceptions of clinicians' professional responsibilities and participants' belief in an uncertain future may hinder an open discussion of goals and values for future medical care. A key moderating factor in how participants view ACP may be their level of acculturation to local care, behavioral, and communication norms. Conclusions: Chinese patients may prefer a routinized clinician-led ACP approach that supports their actionable priorities in the present by leveraging patient-clinician trust, gauging acculturation level, and using indirect communication strategies. Future studies should investigate preferred communication strategies to support in-the-moment care planning.

Characterization, Antioxidant and Antitumor Activities of Oligosaccharides Isolated from Evodia lepta (Spreng) Merr. by Different Extraction Methods.

Evodia lepta (E. lepta) is a traditional Chinese herbal medicine with various biological activities. One of the active components of this widely used medicinal plant is believed to be an oligosaccharide. The extraction yields, structural characteristics, antioxidant, and antitumor activities of four oligosaccharide extracts obtained by hot water extraction (HEO), ultrasound-assisted extraction (UEO), enzyme-assisted (EEO), and microwave-assisted extraction (MEO) were investigated. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) results indicated that the extraction methods had a difference on the molecular mass distribution, structure, and morphology of the EOs. In addition, HEO and MEO showed strong antioxidant activities, which might be related to their uronic acid and protein contents. More interestingly, MEO was more active toward MDA-MB-231 cells compared to other cells, and cell growth inhibition was proposed to occur through apoptosis. Overall, microwave-assisted extraction is a promising technique for the extraction of high quality EO.

Use Characteristics and Triage Acuity of a Digital Symptom Checker in a Large Integrated Health System: Population-Based Descriptive Study.

BACKGROUND: Pressure on the US health care system has been increasing due to a combination of aging populations, rising health care expenditures, and most recently, the COVID-19 pandemic. Responses to this pressure are hindered in part by reliance on a limited supply of highly trained health care professionals, creating a need for scalable technological solutions. Digital symptom checkers are artificial intelligence-supported software tools that use a conversational "chatbot" format to support rapid diagnosis and consistent triage. The COVID-19 pandemic has brought new attention to these tools due to the need to avoid face-to-face contact and preserve urgent care capacity. However, evidence-based deployment of these chatbots requires an understanding of user demographics and associated triage recommendations generated by a large general population. OBJECTIVE: In this study, we evaluate the user demographics and levels of triage acuity provided by a symptom checker chatbot deployed in partnership with a large integrated health system in the United States. METHODS: This population-based descriptive study included all web-based symptom assessments completed on the website and patient portal of the Sutter Health system (24 hospitals in Northern California) from April 24, 2019, to February 1, 2020. User demographics were compared to relevant US Census population data. RESULTS: A total of 26,646 symptom assessments were completed during the study period. Most assessments (17,816/26,646, 66.9%) were completed by female users. The mean user age was 34.3 years (SD 14.4 years), compared to a median age of 37.3 years of the general population. The most common initial symptom was abdominal pain (2060/26,646, 7.7%). A substantial number of assessments (12,357/26,646, 46.4%) were completed outside of typical physician office hours. Most users were advised to seek medical care on the same day (7299/26,646, 27.4%) or within 2-3 days (6301/26,646, 23.6%). Over a quarter of the assessments indicated a high degree of urgency (7723/26,646, 29.0%). CONCLUSIONS: Users of the symptom checker chatbot were broadly representative of our patient population, although they skewed toward younger and female users. The triage recommendations were comparable to those of nurse-staffed telephone triage lines. Although the emergence of COVID-19 has increased the interest in remote medical assessment tools, it is important to take an evidence-based approach to their deployment.

The human resource costs of implementing autopend clinical decision support to improve health maintenance.

OBJECTIVES: Sutter Health developed a novel autopend, or automated laboratory test ordering, clinical decision support (CDS) tool to coordinate the patient and physician process of completing preventive services. This study estimated the costs of developing and implementing the autopend functionality within an existing electronic health maintenance (HM) reminder system. STUDY DESIGN: Human resource time was measured by triangulating in-depth key informant interviews with Microsoft Outlook Calendar metadata (meetings attended) for managers and hourly data from a time-based project management tool (Project Web App) for Epic programmers. Employee time spent was multiplied by the Bureau of Labor Statistics California state hourly wages. Sutter Health is an integrated health care delivery network with more than 12,000 physicians across 100 communities serving 3 million patients. METHODS: Activity-based costing methodology was used to divide the implementation into activities and the human resources required to complete them. RESULTS: Developing and implementing the autopend CDS took more than 3 years, involved 6 managers and 3 Epic programmers, and cost $201,500 (2013 US$) (2670 total hours), which excluded the costs of implementing the initial HM reminder system. Managers spent 90.5% of the total costs (86.6% of total hours) integrating autopend into the health system compared with 9.5% of the total costs (13.4% of total hours) spent programming the functionality. CONCLUSIONS: The autopend CDS might be similarly costly for other organizations to implement if their managers need to complete comparable activities. However, electronic health record vendors could include autopend as a standard package to reduce development costs and improve the uptake of this promising CDS tool.

Lipoatrophy-Associated Insulin Resistance and Hepatic Steatosis are Attenuated by Intake of Diet Rich in Omega 3 Fatty Acids.

SCOPE: Glucose homeostasis and progression of nonalcoholic fatty liver disease (NAFLD) and hepatomegaly in severe lipoatrophic mice and their modulation by intake of a diet rich in omega 3 (n-3) fatty acids (HFO) are evaluated. METHODS AND RESULTS: Severe lipoatrophic mice induced by PPAR-γ deletion exclusively in adipocytes (A-PPARγ KO) and littermate controls (A-PPARγ WT) are evaluated for glucose homeostasis and liver mass, proteomics, lipidomics, inflammation, and fibrosis. Lipoatrophic mice are heavier than controls, severely glucose intolerant, and hyperinsulinemic, and develop NAFLD characterized by increased liver glycogen, triacylglycerol, and diacylglycerol contents, mitotic index, apoptosis, inflammation, steatosis score, fibrosis, and fatty acid synthase (FAS) content and activity. Lipoatrophic mice also display liver enrichment with monounsaturated in detriment of polyunsaturated fatty acids including n-3 fatty acids, and increased content of cardiolipin, a tetracyl phospholipid exclusively found at the mitochondria inner membrane. Administration of a high-fat diet rich in n-3 fatty acids (HFO) to lipoatrophic mice enriches liver with n-3 fatty acids, reduces hepatic steatosis, FAS content and activity, apoptosis, inflammation, and improves glucose homeostasis. CONCLUSION: Diet enrichment with n-3 fatty acids improves glucose homeostasis and reduces liver steatosis and inflammation without affecting hepatomegaly in severe lipoatrophic mice.

Assessment of Accuracy and Usability of a Fee Estimator for Ambulatory Care in an Integrated Health Care Delivery Network.

Importance: Given increased enrollment in high-deductible health insurance plans and mandates from the Patient Protection and Affordable Care Act, individualized price transparency tools are needed. Objective: To assess accuracy and initial user experience of a cost estimation tool for ambulatory procedures delivered via an online patient portal and informed by real-time data feeds from third-party payers. Design, Setting, and Participants: This quality improvement study included patients aged 18 years and older at an integrated health care system in Northern California. Data from patients who used the cost estimator tool from August 21, 2018, to April 9, 2019, and who had matching explanation of benefits statements were used to assess accuracy of the tool. User experience was assessed with a brief survey completed online or via postal mail. Data were analyzed from April 15, 2019, to October 11, 2019. Main Outcomes and Measures: Tool accuracy and user experience and satisfaction. Results: As of April 30, 2019, 4610 estimates (3569 [77.4%] via internet; 1041 [22.6%] via telephone) were produced using the cost estimator tool. Among 342 individuals who had an estimate and a matching explanation of benefits statement, 287 estimates (83.9%) were accurate. All 342 individuals with an estimate and an explanation of benefits statement were invited to participate in a user survey, and 125 individuals completed the survey (36.5% response rate). Survey respondents included 92 (73.6%) women, 72 (57.6%) non-Hispanic white participants , 91 participants (72.8%) with a college degree or higher, and 55 participants (44.0%) with an income of $100 000 per year or higher. Mean (SD) age was 46.8 (13.1) years. Ninety-nine participants (79.2%) found the tool easy to use, 109 participants (87.2%) would use it again, and 100 participants (80.0%) would recommend it to others. Seven participants (5.6%) reported contacting a clinician about the estimate, and 12 participants (9.6%) changed their decision based on the estimate. Conclusions and Relevance: This quality improvement study is the first report of an online cost estimator in an integrated health care delivery network. The findings suggest that the tool, informed by real-time data feeds from third-party payers, was easy to use and provided accurate results. Increasing the number of searchable services and sharing best practices with other health care systems who share the same portal platform are the next steps for the tool.

Inner ear organoids: new tools to understand neurosensory cell development, degeneration and regeneration.

The development of therapeutic interventions for hearing loss requires fundamental knowledge about the signaling pathways controlling tissue development as well as the establishment of human cell-based assays to validate therapeutic strategies ex vivo Recent advances in the field of stem cell biology and organoid culture systems allow the expansion and differentiation of tissue-specific progenitors and pluripotent stem cells in vitro into functional hair cells and otic-like neurons. We discuss how inner ear organoids have been developed and how they offer for the first time the opportunity to validate drug-based therapies, gene-targeting approaches and cell replacement strategies.

Superior Effects of Modified Chen-Style Tai Chi versus 24-Style Tai Chi on Cognitive Function, Fitness, and Balance Performance in Adults over 55.

BACKGROUND: Cognitive decline and balance impairment are prevalent in the aging population. Previous studies investigated the beneficial effects of 24-style Tai Chi (TC-24) on either cognitive function or balance performance of older adults. It still remains largely unknown whether modified Chen-style TC (MTC) that includes 18 complex movements is more beneficial for these age-related health outcomes, as compared to TC-24. OBJECTIVE: We investigated if MTC would show greater effects than TC-24 on global cognitive function and balance-related outcomes among older adults. METHODS: We conducted a randomized trial where 80 eligible adults aged over 55 were allocated into two different styles of Tai Chi (TC) arms (sixty-minute session × three times per week, 12 weeks). Outcome assessments were performed at three time periods (baseline, Week 6, and Week 12) and included the Chinese Version of the Montreal Cognitive Assessment (MoCA) for overall cognitive function, One-leg Standing Test (LST) for static balance, Timed Up and Go Test (TUGT) for dynamic balance, chair Stand Test (CST) for leg power, and the six-meter Walk Test (6MWT) for aerobic exercise capacity. RESULTS: Compared to TC-24 arm, MTC arm demonstrated significantly greater improvements in MoCA, LST, TUGT, CST, and 6MWT (all p < 0.05). CONCLUSIONS: Both forms of TC were effective in enhancing global cognitive function, balance, and fitness. Furthermore, MTC was more effective than TC-24 in enhancing these health-related parameters in an aging population.

Are Mindful Exercises Safe and Beneficial for Treating Chronic Lower Back Pain? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic low back pain (CLBP) is a common health issue worldwide. Tai Chi, Qigong, and Yoga, as the most widely practiced mindful exercises, have promising effects for CLBP-specific symptoms. OBJECTIVE: We therefore conducted a comprehensive review investigating the effects of mindful exercises versus active and/or non-active controls while evaluating the safety and pain-related effects of mindful exercises in adults with CLBP. METHODS: We searched five databases (MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane Library) from inception to February 2019. Two investigators independently selected 17 eligible randomized controlled trials (RCT) against inclusion and exclusion criteria, followed by data extraction and study quality assessment. Standardized mean difference (SMD) was used to determine the magnitude of mindful exercises versus controls on pain- and disease-specific outcome measures. RESULTS: As compared to control groups, we observed significantly favorable effects of mindful exercises on reducing pain intensity (SMD = -0.37, 95% CI -0.5 to -0.23, p < 0.001, I2 = 45.9 %) and disability (SMD = -0.39, 95% CI -0.49 to -0.28, p < 0.001, I2 = 0 %). When compared with active control alone, mindful exercises showed significantly reduced pain intensity (SMD = -0.40, p < 0.001). Furthermore, of the three mindful exercises, Tai Chi has a significantly superior effect on pain management (SMD= -0.75, 95% CI -1.05 to -0.46, p < 0.001), whereas Yoga-related adverse events were reported in five studies. CONCLUSION: Findings of our systematic review suggest that mindful exercises (Tai Chi and Qigong) may be beneficial for CLBP symptomatic management. In particular, Tai Chi appears to have a superior effect in reducing pain intensity irrespective of non-control comparison or active control comparison (conventional exercises, core training, and physical therapy programs). Importantly, training in these mindful exercises should be implemented with certified instructors to ensure quality of movement and injury prevention.