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1.
Ann Surg Open ; 5(1): e384, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38883944

ABSTRACT

Background: Perioperative data are essential to improve the safety of surgical care. However, surgical outcome research (SOR) from low- and middle-income countries (LMICs) is disproportionately sparse. We aimed to assess practices, barriers, facilitators, and perceptions influencing the collection and use of surgical outcome data (SOD) in LMICs. Methods: An internet-based survey was developed and disseminated to stakeholders involved in the care of surgical patients in LMICs. The Performance of Routine Information Systems Management framework was used to explore the frequency and relative importance of organizational, technical, and behavioral barriers. Associations were determined using χ 2 and ANOVA analyses. Results: Final analysis included 229 surgeons, anesthesia providers, nurses, and administrators from 36 separate LMICs. A total of 58.1% of individuals reported that their institution had experience with collection of SOD and 73% of these reported a positive impact on patient care. Mentorship and research training was available in <50% of respondent's institutions; however, those who had these were more likely to publish SOD (P = 0.02). Sixteen barriers met the threshold for significance of which the top 3 were the burden of clinical responsibility, research costs, and accuracy of medical documentation. The most frequently proposed solutions were the availability of an electronic data collection platform (95.3%), dedicated research personnel (93.2%), and access to research training (93.2%). Conclusions: There are several barriers and facilitators to collection of SOD that are common across LMICs. Most of these can be addressed through targeted interventions and are highlighted in this study. We provide a path towards advancing SOR in LMICs.

2.
World J Surg ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844403

ABSTRACT

BACKGROUND: Despite a glaring need and proven efficacy, prospective surgical registries are lacking in low- and middle-income countries. The objective of this study was to design and implement a comprehensive prospective perioperative registry in a low-income country. METHODS: This study was conducted at Hawassa University Comprehensive Specialized Hospital in Hawassa, Ethiopia. Design of the registry occurred from June 2021 to May 2022 and pilot implementation from May 2022 to May 2023. All patients undergoing elective or emergent general surgery were included. Following one year, operability and fidelity of the registry were analyzed by assessing capture rate, incidence of missing data, and accuracy. RESULTS: A total of 67 variables were included in the registry including demographics, preoperative, operative, post-operative, and 30-day data. Of 440 eligible patients, 226 (51.4%) were successfully captured. Overall incidence of missing data and accuracy was 5.4% and 90.2% respectively. Post pilot modifications enhanced capture rate to 70.5% and further optimized data collection processes. CONCLUSION: The establishment of a low-cost electronic prospective perioperative registry in a low-income country represents a significant step forward in enhancing surgical care in under-resourced settings. The initial success of this registry highlights the feasibility of such endeavors when strong partnerships and local context are at the center of implementation. Continuous efforts to refine this registry are ongoing, which will ultimately lead to enhanced surgical quality, research output, and expansion to other sites.

3.
J Surg Res ; 290: 188-196, 2023 10.
Article in English | MEDLINE | ID: mdl-37269802

ABSTRACT

INTRODUCTION: Systematic collection and analysis of surgical outcomes data is a cornerstone of surgical quality improvement. Unfortunately, there remains a dearth of surgical outcomes data from low- and middle-income countries (LMICs). To improve surgical outcomes in LMICs, it is essential to have the ability to collect, analyze, and report risk-adjusted postoperative morbidity and mortality data. This study aimed to review the barriers and challenges to developing perioperative registries in LMIC settings. METHODS: We conducted a scoping review of all published literature on barriers to conducting surgical outcomes research in LMICs using PubMed, Embase, Scopus, and GoogleScholar. Keywords included 'surgery', 'outcomes research', 'registries', 'barriers', and synonymous Medical Subject Headings derivatives. Articles found were subsequently reference-mined. All relevant original research and reviews published between 2000 and 2021 were included. The performance of routine information system management framework was used to organize identified barriers into technical, organizational, or behavioral factors. RESULTS: Twelve articles were identified in our search. Ten articles focused specifically on the creation, success, and obstacles faced during the implementation of trauma registries. Technical factors reported by 50% of the articles included limited access to a digital platform for data entry, lack of standardization of forms, and complexity of said forms. 91.7% articles mentioned organizational factors, including the availability of resources, financial constraints, human resources, and lack of consistent electricity. Behavioral factors highlighted by 66.6% of the studies included lack of team commitment, job constraints, and clinical burden, which contributed to poor compliance and dwindling data collection over time. CONCLUSIONS: There is a paucity of published literature on barriers to developing and maintaining perioperative registries in LMICs. There is an immediate need to study and understand barriers and facilitators to the continuous collection of surgical outcomes in LMICs.


Subject(s)
Developing Countries , General Surgery , Treatment Outcome , Humans , Registries
4.
Eur J Pediatr ; 182(7): 3203-3209, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37129615

ABSTRACT

Gastroschisis mortality is 75-100% in low-resource settings. In Rwanda, late deaths are often due to sepsis. We aimed to understand the effect of antimicrobial use on survival. We conducted a retrospective review of gastroschisis patients at a tertiary hospital in Kigali, Rwanda between January 2016-June 2019. Demographics, antimicrobial use, microbiology, and outcomes were abstracted. Descriptive and univariate analyses were conducted to assess factors associated with improved survival. Among 92 gastroschisis patients, mortality was 77%(n = 71); 23%(n = 21) died within 48 h. 98%(n = 90) of patients received antibiotics on arrival. Positive blood cultures were obtained in 41%(n = 38). Patients spent 86%(SD = 20%) of their hospital stay on antibiotics and 38%(n = 35) received second-line agents. There was no difference in age at arrival, birth weight, gestational age, silo complications, or antimicrobial selection between survivors and non-survivors. Late death patients spent more total hospital days and post-abdominal closure days on antibiotics (p < 0.001) compared to survivors. There was no difference in the proportion of hospital stay on second-line antibiotics (p = 0.1). CONCLUSION: We identified frequent late deaths, prolonged antibiotic courses, and regular use of second-line antibiotic agents in this retrospective cohort of Rwandan gastroschisis patients. Future studies are needed to evaluate antimicrobial resistance in pediatric surgical patients in Rwanda. WHAT IS KNOWN: • Global disparities in gastroschisis outcomes are extreme, with <4% mortality in high-income settings and 75-100% mortality in low-income settings. • Antimicrobial surveillance data is sparse across Africa, but existing evidence suggests high levels of resistance to first-line antibiotics in Rwanda. WHAT IS NEW: • In-hospital survival for gastroschisis was 23% from 2016-2019 and most deaths occurred late (>48hrs after admission) due to sepsis. • Rwandan gastroschisis patients received prolonged courses of antibiotics and second-line antibiotics were frequently used without culture data, raising concern for antimicrobial resistance.


Subject(s)
Gastroschisis , Humans , Child , Gastroschisis/complications , Gastroschisis/drug therapy , Retrospective Studies , Rwanda/epidemiology , Inpatients , Anti-Bacterial Agents/therapeutic use
5.
Lancet Digit Health ; 5(5): e295-e315, 2023 05.
Article in English | MEDLINE | ID: mdl-37100544

ABSTRACT

An increasing number of digital health interventions (DHIs) for remote postoperative monitoring have been developed and evaluated. This systematic review identifies DHIs for postoperative monitoring and evaluates their readiness for implementation into routine health care. Studies were defined according to idea, development, exploration, assessment, and long-term follow-up (IDEAL) stages of innovation. A novel clinical innovation network analysis used coauthorship and citations to examine collaboration and progression within the field. 126 DHIs were identified, with 101 (80%) being early stage innovations (IDEAL stage 1 and 2a). None of the DHIs identified had large-scale routine implementation. There is little evidence of collaboration, and there are clear omissions in the evaluation of feasibility, accessibility, and the health-care impact. Use of DHIs for postoperative monitoring remains at an early stage of innovation, with promising but generally low-quality supporting evidence. Comprehensive evaluation within high-quality, large-scale trials and real-world data are required to definitively establish readiness for routine implementation.


Subject(s)
Postoperative Care , Telemedicine , Humans
6.
ChemSusChem ; 15(22): e202201250, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36107441

ABSTRACT

Catalytic conversion of CO2 and hydrogen to methanol was achieved in a self-separating multiphasic system comprising the tailor-made complex [Ru(CO)ClH(MACHO-C12 )] (MACHO-C12 =bis{2-[bis(4-dodecylphenyl)phosphino]ethyl}amine) in n-decane as the catalyst phase. Effective catalyst recycling was demonstrated for the carbonate and the amine-assisted pathway from CO2 to methanol. The polar products MeOH or MeOH/H2 O generated from the catalytic reactions spontaneously formed a separate phase, allowing product isolation and catalyst separation without the need for any additional solvent. In the amine-assisted hydrogenation of CO2 , the catalyst phase was recycled over ten subsequent runs, reaching a total turnover number to MeOH of 19200 with an average selectivity of 96 %.

7.
Clin Colon Rectal Surg ; 35(5): 362-370, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36111078

ABSTRACT

Surgical care is now recognized as a fundamental component of universal health coverage. Unfortunately, most of the world is still without access to safe and timely surgical care, including 9 out of 10 people living in low- and middle-income countries (LMICs). Additionally, even in LMICs with sustainable surgical programs, surgical outcomes continue to lag behind those in high-income countries. In this article, we will provide a brief history and introduction to global surgery, an overview of the existing literature on global surgical outcomes, and a discussion surrounding the challenges to building surgical capacity and improving surgical outcomes in LMICs. In addition, we will discuss the existing frameworks for building surgical care into national universal healthcare plans and initiatives striving improve surgical outcomes in LMICs.

8.
Int J Cancer ; 151(10): 1696-1702, 2022 11 15.
Article in English | MEDLINE | ID: mdl-35748343

ABSTRACT

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.


Subject(s)
Kidney Neoplasms , Pleural Effusion, Malignant , Pleural Effusion , Surgical Oncology , Wilms Tumor , Child , Humans , Incidence , Kidney Neoplasms/epidemiology , Kidney Neoplasms/surgery , Pleural Effusion/epidemiology , Pleural Effusion/etiology , Pleural Effusion, Malignant/epidemiology , Pleural Effusion, Malignant/etiology , Pleural Effusion, Malignant/surgery , Retrospective Studies , Wilms Tumor/epidemiology , Wilms Tumor/surgery
9.
BMJ Surg Interv Health Technol ; 4(1): e000104, 2022.
Article in English | MEDLINE | ID: mdl-35321073

ABSTRACT

Introduction: The postoperative period represents a time where patients are at a high-risk of morbidity, which warrants effective surveillance. While digital health interventions (DHIs) for postoperative monitoring are promising, a coordinated, standardized and evidence-based approach regarding their implementation and evaluation is currently lacking. This study aimed to identify DHIs implemented and evaluated in postoperative care to highlight research gaps and assess the readiness for routine implementation. Methods: A systematic review will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies describing the implementation and evaluation of DHIs for postoperative monitoring published since 2000 (PROSPERO ID: CRD42021264289). This will encompass the Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and ClinicalTrials.gov databases, and manual search of bibliographies for relevant studies and gray literature. Methodological reporting quality will be evaluated using the Idea, Development, Exploration, Assessment and Long-term Follow-up (IDEAL) reporting guideline relevant to the IDEAL stage of the study, and risk of bias will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Data will be extracted according to the WHO framework for monitoring and evaluating DHIs, and a narrative synthesis will be performed. Discussion: This review will assess the readiness for implementation of DHIs for routine postoperative monitoring and will include studies describing best practice from service changes already being piloted out of necessity during the COVID-19 pandemic. This will identify interventions with sufficient evidence to progress to the next IDEAL stage, and promote standardized and comprehensive evaluation of future implementational studies.

10.
Surgery ; 172(1): 219-225, 2022 07.
Article in English | MEDLINE | ID: mdl-35086727

ABSTRACT

BACKGROUND: Poorly coordinated transitions of care in complex abdominal surgery patients contribute to frequent hospital readmissions and inflated healthcare spending. Mobile health (mHealth) transitional care technologies may reduce surgical readmissions yet remain understudied in high-risk surgical populations. METHODS: We conducted a single-group, prepost study of a mHealth transitional care app in 50 complex surgical patients. Eligible patients were adults undergoing complex abdominal surgery in the divisions of Surgical Oncology and Colorectal Surgery. The main outcome was app engagement, calculated by notification response rate (number of participant-entered datapoints divided by the total number of app-requested datapoints) over the 30-day postoperative period. Secondary outcomes included changes in engagement over time and by individual app feature. RESULTS: A total of 85% (50/59) of eligible patients enrolled. Most participants were male (58%, n = 29), and mean age was 50 years (range 24-80 years). Overall notification response rate was 28%. Among the 58% of participants (29/50) who engaged with the app at least once after discharge (app users), the average notification response rate was 45%. The mean notification response rate among app users decreased over time from 50% to 32% between weeks 1 and 4 after hospital discharge. Engagement with individual app features ranged from 48-81%, with highest engagement for symptom reports and lowest engagement for wound care instructions. CONCLUSION: mHealth transitional care is feasible in complex surgical patients using only patients' existing smart devices. Randomized controlled trials are required to determine the impact on hospital readmissions, surgical outcomes, patient satisfaction, and overall resource utilization.


Subject(s)
Mobile Applications , Telemedicine , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Patient Participation , Patient Transfer , Pilot Projects , Young Adult
11.
Contemp Clin Trials ; 113: 106658, 2022 02.
Article in English | MEDLINE | ID: mdl-34954099

ABSTRACT

BACKGROUND: Hospital readmissions are estimated to cost $17.4 billion per year in the Medicare population alone, with readmission rates as high as 30% for patients undergoing complex abdominal surgery. Improved transitional care and self-monitoring may reduce preventable readmissions for such high-risk populations. In this study, we will conduct a single-institution randomized controlled trial (RCT) to assess the effect of a novel transitional care mobile app, MobiMD, on hospital readmission in complex abdominal surgery patients. METHODS: Three hundred patients will be randomized 1:1 to standard of care (SOC) versus SOC plus MobiMD app in a parallel, single-blinded, two-arm RCT. Eligible patients are those who undergo complex abdominal surgery in the division of Surgical Oncology, Colorectal Surgery or Transplant Surgery. The MobiMD app provides push notification reminders directly to the patient's smart device, prompting them to enter clinical data and patient-reported outcomes. Clinical data collected via the MobiMD app include vital signs, red flag symptoms, daily wound and surgical drain images, ostomy output, drain output, medication compliance, and wound care compliance. These data are reviewed daily by a physician. The primary outcome is the proportion of participants readmitted to the hospital within 30 days of surgery. Secondary outcomes are 90-day hospital readmission, emergency department and urgent care visits, complication severity, and total readmission cost. DISCUSSION: If effective, mobile health apps such as MobiMD could be routinely integrated into surgical transitional care programs to minimize unnecessary hospital readmissions, emergency department visits and healthcare resource utilization. Clinical trials identifier: NCT04540315.


Subject(s)
Mobile Applications , Telemedicine , Transitional Care , Emergency Service, Hospital , Humans , Patient Readmission , Randomized Controlled Trials as Topic
12.
Curr Treat Options Oncol ; 22(9): 82, 2021 07 05.
Article in English | MEDLINE | ID: mdl-34224023

ABSTRACT

OPINION STATEMENT: Treatment for metastatic colorectal cancer (CRC) has changed significantly over the last few decades as cytotoxic and targeted chemotherapies have evolved and resection of (technically feasible) colorectal liver metastases (CRLM) has become standard of care for eligible patients. Overall, survival for metastatic CRC has considerably improved, but recurrences are common. Numerous clinical risk scores have been suggested to guide patient selection for CRLM resection, but none perfectly predict outcomes; therefore, a personalized approach to metastatic CRC treatment using genetic profiles for risk stratification and prognostication is a critically important advancement. All patients with suspected metastatic CRC should undergo genetic testing for common oncogene mutations (e.g., KRAS, BRAF, and NRAS) in addition to a triphasic CT scan of the chest, abdomen, and pelvis; if hepatectomy may be entertained and there is concern about the future liver remnant (FLR), liver volumetrics should also be performed. MRI and PET are useful adjuncts for cases in which diagnosis or extent of disease is unclear. The decision to operate should be individualized and based on each patient's condition, tumor biology, and technical resectability. Genetic profiles should be used to inform multidisciplinary meetings surrounding topics of chemotherapy and surgical resection, as well as patient discussions concerning the risks and benefits of surgery. In the end, most patients with technically resectable colorectal cancers and adequate cardiopulmonary fitness benefit from surgical resection, as it remains the only chance of long-term survival.


Subject(s)
Colorectal Neoplasms/pathology , Hepatectomy , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Patient Selection , Biomarkers, Tumor , Clinical Decision-Making , Colorectal Neoplasms/etiology , Colorectal Neoplasms/metabolism , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Disease Management , Disease Susceptibility , Hepatectomy/adverse effects , Hepatectomy/methods , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Microsatellite Instability , Molecular Diagnostic Techniques , Mutation , Treatment Outcome
14.
JAMA Neurol ; 76(11): 1340-1351, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31305918

ABSTRACT

IMPORTANCE: Blood biomarkers able to diagnose Alzheimer disease (AD) at the preclinical stage would enable trial enrollment when the disease is potentially reversible. Plasma neuronal-enriched extracellular vesicles (nEVs) of patients with AD were reported to exhibit elevated levels of phosphorylated (p) tau, Aß42, and phosphorylated insulin receptor substrate 1 (IRS-1). OBJECTIVE: To validate nEV biomarkers as AD predictors. DESIGN, SETTING, PARTICIPANTS: This case-control study included longitudinal plasma samples from cognitively normal participants in the Baltimore Longitudinal Study of Aging (BLSA) cohort who developed AD up to January 2015 and age- and sex-matched controls who remained cognitively normal over a similar length of follow-up. Repeated samples were blindly analyzed over 1 year from participants with clinical AD and controls from the Johns Hopkins Alzheimer Disease Research Center (JHADRC). Data were collected from September 2016 to January 2018. Analyses were conducted in March 2019. MAIN OUTCOMES AND MEASURES: Neuronal-enriched extracellular vesicles were immunoprecipitated; tau, Aß42, and IRS-1 biomarkers were quantified by immunoassays; and nEV concentration and diameter were determined by nanoparticle tracking analysis. Levels and longitudinal trajectories of nEV biomarkers between participants with future AD and control participants were compared. RESULTS: Overall, 887 longitudinal plasma samples from 128 BLSA participants who eventually developed AD and 222 age and sex-matched controls who remained cognitively normal were analyzed. Participants were followed up (from earliest sample to AD symptom onset) for a mean (SD) of 3.5 (2.31) years (range, 0-9.73 years). Overall, 161 participants were included in the training set, and 80 were in the test set. Participants in the BLSA cohort with future AD (mean [SD] age, 79.09 [7.02] years; 68 women [53.13%]) had longitudinally higher p-tau181, p-tau231, pSer312-IRS-1, pY-IRS-1, and nEV diameter than controls (mean [SD] age, 76.2 [7.36] years; 110 women [50.45%]) but had similar Aß42, total tau, TSG101, and nEV concentration. In the training BLSA set, a model combining preclinical longitudinal data achieved 89.6% area under curve (AUC), 81.8% sensitivity, and 85.8% specificity for predicting AD. The model was validated in the test BLSA set (80% AUC, 55.6% sensitivity, 88.7% specificity). Preclinical levels of nEV biomarkers were associated with cognitive performance. In addition, 128 repeated samples over 1 year from 64 JHADRC participants with clinical AD and controls were analyzed. In the JHADRC cohort (35 participants with AD: mean [SD] age, 74.03 [8.73] years; 18 women [51.43%] and 29 controls: mean [SD] age, 72.14 [7.86] years; 23 women [79.31%]), nEV biomarkers achieved discrimination with 98.9% AUC, 100% sensitivity, and 94.7% specificity in the training set and 76.7% AUC, 91.7% sensitivity, and 60% specificity in the test set. CONCLUSIONS AND RELEVANCE: We validated nEV biomarker candidates and further demonstrated that their preclinical longitudinal trajectories can predict AD diagnosis. These findings motivate further development of nEV biomarkers toward a clinical blood test for AD.

15.
Gastroenterol Res Pract ; 2018: 7980413, 2018.
Article in English | MEDLINE | ID: mdl-30116267

ABSTRACT

BACKGROUND: Hepatitis E virus (HEV) is a major cause of hepatitis in developing and industrialized countries worldwide. The modes of HEV transmission in industrialized countries, including the United States, remain largely unknown. This study is aimed at evaluating the association between HEV seropositivity and consumption of self-grown foods in the United States. METHODS: Cross-sectional data was extracted from the 2009-2012 National Health and Nutrition Examination Survey (NHANES). Data from the dietary interview and the serum HEV IgG and IgM enzyme immunoassay test results were linked and examined. Univariate and multivariable logistic regression models were used to evaluate the significance and effect size of an association between self-grown food consumption and hepatitis E seropositivity. RESULTS: The estimated HEV seroprevalence in the civilian, noninstitutionalized US population was 6.6% in 2009-2012, which corresponds to an estimated hepatitis E national seroprevalence of 17,196,457 people. Overall, 10.9% of participants who ingested self-grown foods had positive HEV antibodies versus 6.1% of participants who did not consume self-grown foods (P < 0.001; odds ratio (OR) 1.87; 95% CI 1.41-2.48). In the age-stratified multivariable analysis, the correlation between ingesting self-grown foods and HEV seropositivity was significant for participants 40-59 years old, but not overall, or for those < 40 years or ≥60 years. CONCLUSIONS: Ingesting self-grown food, or simply the process of gardening/farming, may be a source of zoonotic HEV transmission.

16.
Front Aging Neurosci ; 9: 118, 2017.
Article in English | MEDLINE | ID: mdl-28515688

ABSTRACT

Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments. We present two promising biomarkers for brain IR in AD: insulin cascade mediators probed in extracellular vesicles (EVs) enriched for neuronal origin, and two-dimensional magnetic resonance spectroscopy (MRS) measures of brain glucose. As further evidence for a fundamental link between brain IR and AD, we provide a novel analysis demonstrating the close spatial correlation between brain expression of genes implicated in IR (using Allen Human Brain Atlas data) and tau and beta-amyloid pathologies. We proceed to propose the bold hypotheses that baseline differences in the metabolic reliance on glycolysis, and the expression of glucose transporters (GLUT) and insulin signaling genes determine the vulnerability of different brain regions to Tau and/or Amyloid beta (Aß) pathology, and that IR is a critical link between these two pathologies that define AD. Lastly, we provide an overview of ongoing clinical trials that target IR as an angle to treat AD, and suggest how biomarkers may be used to evaluate treatment efficacy and target engagement.

17.
Transl Res ; 183: 26-40, 2017 05.
Article in English | MEDLINE | ID: mdl-28034760

ABSTRACT

The links between systemic insulin resistance (IR), brain-specific IR, and Alzheimer's disease (AD) have been an extremely productive area of current research. This review will cover the fundamentals and pathways leading to IR, its connection to AD via cellular mechanisms, the most prominent methods and models used to examine it, an introduction to the role of extracellular vesicles (EVs) as a source of biomarkers for IR and AD, and an overview of modern clinical studies on the subject. To provide additional context, we also present a novel analysis of the spatial correlation of gene expression in the brain with the aid of Allen Human Brain Atlas data. Ultimately, examining the relation between IR and AD can be seen as a means of advancing the understanding of both disease states, with IR being a promising target for therapeutic strategies in AD treatment. In conclusion, we highlight the therapeutic potential of targeting brain IR in AD and the main strategies to pursue this goal.


Subject(s)
Alzheimer Disease/complications , Insulin Resistance/physiology , Diabetes Mellitus, Type 2/metabolism , Gene Expression Regulation/physiology , Humans , Signal Transduction
18.
J Geophys Res Atmos ; 121(12): 7254-7283, 2016 Jun 27.
Article in English | MEDLINE | ID: mdl-32818126

ABSTRACT

The ability of 11 models in simulating the aerosol vertical distribution from regional to global scales, as part of the second phase of the AeroCom model intercomparison initiative (AeroCom II), is assessed and compared to results of the first phase. The evaluation is performed using a global monthly gridded data set of aerosol extinction profiles built for this purpose from the CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) Layer Product 3.01. Results over 12 subcontinental regions show that five models improved, whereas three degraded in reproducing the interregional variability in Z α0-6 km, the mean extinction height diagnostic, as computed from the CALIOP aerosol profiles over the 0-6 km altitude range for each studied region and season. While the models' performance remains highly variable, the simulation of the timing of the Z α0-6 km peak season has also improved for all but two models from AeroCom Phase I to Phase II. The biases in Z α0-6 km are smaller in all regions except Central Atlantic, East Asia, and North and South Africa. Most of the models now underestimate Z α0-6 km over land, notably in the dust and biomass burning regions in Asia and Africa. At global scale, the AeroCom II models better reproduce the Z α0-6 km latitudinal variability over ocean than over land. Hypotheses for the performance and evolution of the individual models and for the intermodel diversity are discussed. We also provide an analysis of the CALIOP limitations and uncertainties contributing to the differences between the simulations and observations.

19.
J Ultrasound Med ; 24(4): 501-16, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15784769

ABSTRACT

OBJECTIVE: Current determinations of diagnostic ultrasound exposure parameters (eg, peak rarefactional pressure and pulse intensity integral) are intended to correspond to propagation through soft tissue with a propagation speed of 1540 m/s and attenuation of 0.3 dB x cm(-1) x MHz(-1). These current measurements are made in water, which has very little attenuation, and a linear derating factor is applied to approximate 0.3 dB x cm(-1) x MHz(-1) attenuation. The fact that propagation through water as well as through soft tissue involves nonlinear propagation is not directly addressed. A better way to determine exposure parameters would be to use a liquid that has the desired tissue-mimicking properties, including a value of the nonlinearity parameter B/A representative of soft tissue. To be of practical use in the laboratory, the ultrasonic properties of this liquid must remain stable and spatially uniform for many months or years without need for periodic mixing by the user. METHODS: Fifty-two samples of fat-free milk that was concentrated to one third of its original volume by ultrafiltration were created. Each sample was preserved by a different method. The speed of sound, attenuation, and nonlinearity parameter B/A of each sample were periodically monitored by narrowband through-transmission techniques. RESULTS: Six of the 52 samples remained liquid and retained acceptably stable acoustic properties over 22 months of storage at room temperature. CONCLUSIONS: Fat-free milk, concentrated via ultrafiltration and preserved in 1 of 6 different methods, has been found to be a stable tissue-mimicking liquid with acoustic properties appropriate for use in exposimetry.


Subject(s)
Acoustics , Milk , Ultrasonography/instrumentation , Animals , Preservatives, Pharmaceutical
20.
Science ; 302(5645): 624-7, 2003 Oct 24.
Article in English | MEDLINE | ID: mdl-14576429

ABSTRACT

If today's surface traffic fleet were powered entirely by hydrogen fuel cell technology, anthropogenic emissions of the ozone precursors nitrogen oxide (NOx) and carbon monoxide could be reduced by up to 50%, leading to significant improvements in air quality throughout the Northern Hemisphere. Model simulations of such a scenario predict a decrease in global OH and an increased lifetime of methane, caused primarily by the reduction of the NOx emissions. The sign of the change in climate forcing caused by carbon dioxide and methane depends on the technology used to generate the molecular hydrogen. A possible rise in atmospheric hydrogen concentrations is unlikely to cause significant perturbations of the climate system.

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