Longitudinal Analysis of Mitochondrial Function in a Choline-Deficient L-Amino Acid-Defined High-Fat Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis Mouse Model.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. Some patients with MAFLD develop metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver fibrosis. However, the molecular mechanisms underlying this progression remain unknown, and no effective treatment for MASH has been developed so far. In this study, we performed a longitudinal detailed analysis of mitochondria in the livers of choline-deficient, methionine-defined, high-fat-diet (CDAHFD)-fed mice, which exhibited a MASH-like pathology. We found that FoF1-ATPase activity began to decrease in the mitochondria of CDAHFD-fed mice prior to alterations in the activity of mitochondrial respiratory chain complex, almost at the time of onset of liver fibrosis. In addition, the decrease in FoF1-ATPase activity coincided with the accelerated opening of the mitochondrial permeability transition pore (PTP), for which FoF1-ATPase might be a major component or regulator. As fibrosis progressed, mitochondrial permeability transition (PT) induced in CDAHFD-fed mice became less sensitive to cyclosporine A, a specific PT inhibitor. These results suggest that episodes of fibrosis might be related to the disruption of mitochondrial function via PTP opening, which is triggered by functional changes in FoF1-ATPase. These novel findings could help elucidate the pathogenesis of MASH and lead to the development of new therapeutic strategies.

Designing and Evaluating a Hierarchical Framework for Matching Food Outlets across Multi-sourced Geospatial Datasets: a Case Study of San Diego County.

Research on retail food environment (RFE) relies on data availability and accuracy. However, the discrepancies in RFE datasets may lead to imprecision when measuring association with health outcomes. In this research, we present a two-tier hierarchical point of interest (POI) matching framework to compare and triangulate food outlets across multiple geospatial data sources. Two matching parameters were used including the geodesic distance between businesses and the similarity of business names according to Levenshtein distance (LD) and Double Metaphone (DM). Sensitivity analysis was conducted to determine thresholds of matching parameters. Our Tier 1 matching used more restricted parameters to generate high confidence-matched POIs, whereas in Tier 2 we opted for relaxed matching parameters and applied a weighted multi-attribute model on the previously unmatched records. Our case study in San Diego County, California used government, commercial, and crowdsourced data and returned 20.2% matched records from Tier 1 and 18.6% matched from Tier 2. Our manual validation shows a 100% matching rate for Tier 1 and up to 30.6% for Tier 2. Matched and unmatched records from Tier 1 were further analyzed for spatial patterns and categorical differences. Our hierarchical POI matching framework generated highly confident food POIs by conflating datasets and identified some food POIs that are unique to specific data sources. Triangulating RFE data can reduce uncertain and invalid POI listings when representing food environment using multiple data sources. Studies investigating associations between food environment and health outcomes may benefit from improved quality of RFE.

Mapping environmentally sustainable urban development within six US cities through object-based image change analysis of aerial orthoimagery.

The rapid expansion of cities and continuous urban population growth underscores a need for sustainable urban development. Sustainable development is that which addresses human needs, contributes to well-being, is economically viable, and utilizes natural resources at a degree sustainable by the surrounding environmental systems. Urban green spaces, green roofs, and solar panels are examples of environmentally sustainable urban development (ESUD), or development that focuses on environmental impact, but also presents the potential to achieve social and economic sustainability. The aim of this study was to map and compare amounts of ESUD c. 2010 and c. 2019 through an object-based image analysis (OBIA) approach using National Agricultural Imagery Program (NAIP) aerial orthoimagery for six mid- to large-size cities in the USA. The results of this study indicate a hybrid OBIA and manual interpretation approach applied to NAIP orthoimagery may allow for reliable mapping and areal estimation of urban green space and green roof changes in urban areas. The reliability of OBIA-only mapping and estimation of areal extents of existing green roofs, and new and existing solar panels, is inconclusive due to low mapping accuracy and coarse spatial resolution of aerial orthoimagery relative to some ESUD features. The three urban study areas in humid continental climate zones (Dfa) were estimated to have greater areal extent of new and existing urban green space and existing green roofs, but less areal extent of new green roofs and existing solar panels compared to the three study areas in humid subtropical climate zones (Cfa).

The impact of patient travel time on disparities in treatment for early stage lung cancer in California.

BACKGROUND: Travel time to treatment facilities may impede the receipt of guideline-concordant treatment (GCT) among patients diagnosed with early-stage non-small cell lung cancer (ES-NSCLC). We investigated the relative contribution of travel time in the receipt of GCT among ES-NSCLC patients. METHODS: We included 22,821 ES-NSCLC patients diagnosed in California from 2006-2015. GCT was defined using the 2016 National Comprehensive Cancer Network guidelines, and delayed treatment was defined as treatment initiation >6 versus ≤6 weeks after diagnosis. Mean-centered driving and public transit times were calculated from patients' residential block group centroid to the treatment facilities. We used logistic regression to estimate risk ratios and 95% confidence intervals (CIs) for the associations between patients' travel time and receipt of GCT and timely treatment, overall and by race/ethnicity and neighborhood socioeconomic status (nSES). RESULTS: Overall, a 15-minute increase in travel time was associated with a decreased risk of undertreatment and delayed treatment. Compared to Whites, among Blacks, a 15-minute increase in driving time was associated with a 24% (95%CI = 8%-42%) increased risk of undertreatment, and among Filipinos, a 15-minute increase in public transit time was associated with a 27% (95%CI = 13%-42%) increased risk of delayed treatment. Compared to the highest nSES, among the lowest nSES, 15-minute increases in driving and public transit times were associated with 33% (95%CI = 16%-52%) and 27% (95%CI = 16%-39%) increases in the risk of undertreatment and delayed treatment, respectively. CONCLUSION: The benefit of GCT observed with increased travel times may be a 'Travel Time Paradox,' and may vary across racial/ethnic and socioeconomic groups.

A Spatio-Demographic Perspective on the Role of Social Determinants of Health and Chronic Disease in Determining a Population's Vulnerability to COVID-19.

INTRODUCTION: During the COVID-19 pandemic, health and social inequities placed racial and ethnic minority groups at increased risk of severe illness. Our objective was to investigate this health disparity by analyzing the relationship between potential social determinants of health (SDOH), COVID-19, and chronic disease in the spatial context of San Diego County, California. METHODS: We identified potential SDOH from a Pearson correlation analysis between socioeconomic variables and COVID-19 case rates during 5 pandemic stages, from March 31, 2020, to April 3, 2021. We used ridge regression to model chronic disease hospitalization and death rates by using the selected socioeconomic variables. Through the lens of COVID-19 and chronic disease, we identified vulnerable communities by using spatial methods, including Global Moran I spatial autocorrelation, local bivariate relationship analysis, and geographically weighted regression. RESULTS: In the Pearson correlation analysis, we identified 26 socioeconomic variables as potential SDOH because of their significance (P ≤ .05) in relation to COVID-19 case rates. Of the analyzed chronic disease rates, ridge regression most accurately modeled rates of diabetes age-adjusted death (R2 = 0.903) and age-adjusted hospitalization for hypertensive disease (hypertension, hypertensive heart disease, hypertensive chronic kidney disease, and hypertensive encephalopathy) (R2 = 0.952). COVID-19 and chronic disease rates exhibited positive spatial autocorrelation (0.304≤I≤0.561, 3.092≤Z≤6.548, 0.001≤P≤ .002), thereby justifying spatial models to highlight communities that are vulnerable to COVID-19. CONCLUSION: Novel spatial analysis methods reveal relationships between SDOH, COVID-19, and chronic disease that are intuitive and easily communicated to public health decision makers and practitioners. Observable disparity patterns between urban and rural areas and between affluent and low-income communities establish the need for spatially differentiated COVID-19 response approaches to achieve health equity.

Quantitative analysis of mitochondrial calcium uniporter (MCU) and essential MCU regulator (EMRE) in mitochondria from mouse tissues and HeLa cells.

Mitochondrial calcium homeostasis plays critical roles in cell survival and aerobic metabolism in eukaryotes. The calcium uniporter is a highly selective calcium ion channel consisting of several subunits. Mitochondrial calcium uniporter (MCU) and essential MCU regulator (EMRE) are core subunits of the calcium uniporter required for calcium uptake activity in the mitochondria. Recent 3D structure analysis of the MCU-EMRE complex reconstituted in nanodiscs revealed that the human MCU exists as a tetramer forming a channel pore, with EMRE bound to each MCU at a 1 : 1 ratio. However, the stoichiometry of MCU and EMRE in the mitochondria has not yet been investigated. We here quantitatively examined the protein levels of MCU and EMRE in the mitochondria from mouse tissues by using characterized antibodies and standard proteins. Unexpectedly, the number of EMRE molecules was lower than that of MCU; moreover, the ratios between MCU and EMRE were significantly different among tissues. Statistical calculations based on our findings suggest that a MCU tetramer binding to 4 EMREs may exist, but at low levels in the mitochondrial inner membrane. In brain mitochondria, the majority of MCU tetramers bind to 2 EMREs; in mitochondria in liver, kidney, and heart, MCU tetramers bind to 1 EMRE; and in kidney and heart, almost half of MCU tetramers bound to no EMRE. We propose here a novel stoichiometric model of the MCU-EMRE complex in mitochondria.

An Interaction-Based Bayesian Network Framework for Surgical Workflow Segmentation.

Recognizing and segmenting surgical workflow is important for assessing surgical skills as well as hospital effectiveness, and plays a crucial role in maintaining and improving surgical and healthcare systems. Most evidence supporting this remains signal-, video-, and/or image-based. Furthermore, casual evidence of the interaction between surgical staff remains challenging to gather and is largely absent. Here, we collected the real-time movement data of the surgical staff during a neurosurgery to explore cooperation networks among different surgical roles, namely surgeon, assistant nurse, scrub nurse, and anesthetist, and to segment surgical workflows to further assess surgical effectiveness. We installed a zone position system (ZPS) in an operating room (OR) to effectively record high-frequency high-resolution movements of all surgical staff. Measuring individual interactions in a closed, small area is difficult, and surgical workflow classification has uncertainties associated with the surgical staff in terms of their varied training and operation skills, patients in terms of their initial states and biological differences, and surgical procedures in terms of their complexities. We proposed an interaction-based framework to recognize the surgical workflow and integrated a Bayesian network (BN) to solve the uncertainty issues. Our results suggest that the proposed BN method demonstrates good performance with a high accuracy of 70%. Furthermore, it semantically explains the interaction and cooperation among surgical staff.

Twitter Communication During an Outbreak of Hepatitis A in San Diego, 2016-2018.

Objectives. To examine how and what information is communicated via social media during an infectious disease outbreak.Methods. In the context of the 2016 through 2018 hepatitis A outbreak in San Diego County, California, we used a grounded theory-based thematic analysis that employed qualitative and quantitative approaches to uncover themes in a sample of public tweets (n = 744) from Twitter, a primary platform used by key stakeholders to communicate to the public during the outbreak.Results. Tweets contained both general and hepatitis A-specific information related to the outbreak, restatements of policy and comments critical of government responses to the outbreak, information with the potential to shape risk perceptions, and expressions of concern regarding individuals experiencing homelessness and their role in spreading hepatitis A. We also identified misinformation and common channels of content driving themes that emerged in our sample.Conclusions. Public health professionals may identify real-time public risk perceptions and concerns via social media during an outbreak and target responses that fulfill the informational needs of those who seek direction and reassurance during times of uncertainty.

[Long-Term Survival of a Patient with Advanced Recurrent Rectal Cancer Treated with a Multidisciplinary Therapy including Five Operations-A Case Report].

A 68-year-old female with rectal cancer underwent low anterior resection with regional lymph node dissection. The final pathological diagnosis was Stage Ⅲa, and an adjuvant therapy(S-1)was provided for 6 months. One year after the surgery, an anastomotic recurrence was detected. Therefore, pelvic chemoradiotherapy with folinic acid and 5-fluorouracil(FL)was provided, and resection was performed with the Hartmann procedure. Following the second surgery, chemotherapy with bevacizumab(BV)and capecitabine plus oxaliplatin(CapeOX)was provided, and the patient showed no signs of recurrence for several years. However, lung metastasis appeared, which was resected. A year later, the patient underwent hepatectomy and radiofrequency ablation for liver metastasis. Another year later, she underwent lung resection again because of new lung metastasis. During the periods between the surgeries, various chemotherapy regimens were followed continuously, however, the patient died of progressive recurrence 8 years and 4 months after the initial surgery. Recurrences and distant metastases are poor prognostic factors for rectal cancers. However, combined effective chemotherapy and radiotherapy with surgery may improve the patient's chances of survival.

[A Case Report of Gastric Cancer Excised after Neoadjuvant Chemotherapy and Long-Term Survival Achieved after NivolumabAdministration for Peritoneal Dissemination].

The patient was a 64-year-old man with Type 3 advanced cancer in the upper body of the stomach. The preoperative tumor marker value of CA19-9 was abnormally high, but there was no proof of distant metastasis or peritoneal dissemination. The first operation was an exploratory laparotomy due to direct tumor invasion to the pancreas. Systemic chemotherapy was performed for tumor reduction. First, S-1 plus cisplatin therapy was administered for 4 courses but discontinued because of renal dysfunction and thrombocytopenia. In the second-line therapy, ramucirumabplus paclitaxel therapy was administered for 7 courses. Since the tumor invasion to the pancreas turned to be clear based on a CT scan, total gastrectomy with regional lymphadenectomy was performed. However, 5 months after surgery, a single nodule appeared in the upper abdomen that was suspected to be peritoneal dissemination. Nivolumab therapy was administered for 16 months without tumor enlargement or any adverse effect. Recently, there has been a marked development in chemotherapy for gastric cancer. Unresectable cases became operable after the administration of appropriate chemotherapy. In our case, nivolumab therapy had no adverse effect. However, serious adverse effects have been reported by several authors which suggests that regular examinations for interstitial pneumonia, hypothyroidism, and other adverse effects are important.

Functional analysis of coiled-coil domains of MCU in mitochondrial calcium uptake.

The mitochondrial calcium uniporter (MCU) complex is a highly-selective calcium channel. This complex consists of MCU, mitochondrial calcium uptake proteins (MICUs), MCU regulator 1 (MCUR1), essential MCU regulator element (EMRE), etc. MCU, which is the pore-forming subunit, has 2 highly conserved coiled-coil domains (CC1 and CC2); however, their functional roles are unknown. The yeast expression system of mammalian MCU and EMRE enables precise reconstitution of the properties of the mammalian MCU complex in yeast mitochondria. Using the yeast expression system, we here showed that, when MCU mutant lacking CC1 or CC2 was expressed together with EMRE in yeast, their mitochondrial Ca2+-uptake function was lost. Additionally, point mutations in CC1 or CC2, which were expected to prevent the formation of the coiled coil, also disrupted the Ca2+-uptake function. Thus, it is essential for the Ca2+ uptake function of MCU that the coiled-coil structure be formed in CC1 and CC2. The loss of function of those mutated MCUs was also observed in the mitochondria of a yeast strain lacking the yeast MCUR1 homolog. Also, in the D. discoideum MCU, which has EMRE-independent Ca2+-uptake function, the deletion of either CC1 or CC2 caused the loss of function. These results indicated that the critical functions of CC1 and CC2 were independent of other regulatory subunits such as MCUR1 and EMRE, suggesting that CC1 and CC2 might be essential for pore formation by MCUs themselves. Based on the tetrameric structure of MCU, we discussed the functional roles of the coiled-coil domains of MCU.

Twitter-based measures of neighborhood sentiment as predictors of residential population health.

Several studies have recently applied sentiment-based lexicons to Twitter to gauge local sentiment to understand health behaviors and outcomes for local areas. While this research has demonstrated the vast potential of this approach, lingering questions remain regarding the validity of Twitter mining and surveillance in local health research. First, how well does this approach predict health outcomes at very local scales, such as neighborhoods? Second, how robust are the findings garnered from sentiment signals when accounting for spatial effects? To evaluate these questions, we link 2,076,025 tweets from 66,219 distinct users in the city of San Diego over the period of 2014-12-06 to 2017-05-24 to the 500 Cities Project data and 2010-2014 American Community Survey data. We determine how well sentiment predicts self-rated mental health, sleep quality, and heart disease at a census tract level, controlling for neighborhood characteristics and spatial autocorrelation. We find that sentiment is related to some outcomes on its own, but these relationships are not present when controlling for other neighborhood factors. Evaluating our encoding strategy more closely, we discuss the limitations of existing measures of neighborhood sentiment, calling for more attention to how race/ethnicity and socio-economic status play into inferences drawn from such measures.

Language Services In Hospitals Vary By Ownership And Location.

Twenty-four million people in the United States have limited English proficiency. They experience barriers to health care because of their inability to communicate effectively with providers. Hospitals are required to provide language services that reflect the needs of people in their communities, but these services are not available systematically.

GIS-based multielement source analysis of dustfall in Beijing: A study of 40 major and trace elements.

Dust, as an important carrier of inorganic and organic pollutants, daily exposes to human without any protection. It affects our health adversely, especially its chemical elements and ions. In this research, we investigated the chemical characteristics of dustfall in Beijing, specifically in terms of 40 major and trace elements, and presented semi-quantitative evaluations of the relative local and remote contributions. In total, 58 samples were collected in Beijing and nearby cities during 2013-2014 "the winter heating period". Using multiple statistical methods and GIS techniques, we obtained the relative similarities among certain elements and identified their pollution sources (from local or nearby cities). And more interestingly, the relative contributions of nearby cities can be calculated by the Hysplit4 backward-trajectory model. In addition, the correlation analysis for the 40 elements in dust and soil indicated that traffic restricted interchange between them; the city center, with the heaviest traffic, had the most significant influence. Finally, the resulting source apportionment was examined and modified using land use data and terrain information. We hope it can provide a strong basis for the environmental protection and risk assessment.