• The Impact of COVID-19 on Radiation Oncology Clinics and Patients With Cancer in the United States

      Rivera, A.; Ohri, N.; Miller, R. (Elsevier Inc, 2020)
      Patients with cancer are known to be at an increased risk for community-acquired respiratory viruses, such as influenza, because of their frequently observed immunocompromised state.5 The spread of SARS-CoV-2 is of particular concern in this vulnerable population, given the higher case fatality rate seen in Wuhan and the potentially increased severity of the disease course with COVID-19.
    • Challenges in the diagnosis of tuberculous meningitis

      Foppiano Palacios, C.; Saleeb, P.G. (Elsevier Ltd, 2020)
      Tuberculosis (TB) continues to pose a significant public health problem. Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary TB. TBM carries a high mortality rate, including for those receiving treatment for TB. Diagnosis of TBM is difficult for clinicians as it can clinically present similarly to other forms of meningitis. The difficulty in diagnosis often leads to a delay in treatment and subsequent mortality. Those who survive are left with long-term sequelae leading to lifelong disability. The microbiologic diagnosis of TBM requires the isolation of Mycobacterium tuberculosis from the cerebrospinal fluid (CSF) of an infected patient. The diagnosis of tuberculous meningitis continues to be challenging for clinicians. Unfortunately, many cases of TBM cannot be confirmed based on clinical and imaging findings as the clinical findings are nonspecific, while laboratory techniques are largely insensitive or slow. Until recently, the lack of accessible and timely tests has contributed to a delay in diagnosis and subsequent morbidity and mortality for many patients, particularly those in resourcelimited settings. The availability of Xpert Ultra and point-of-care lipoarabinomannan (LAM) testing could represent a new era of prompt diagnosis and early treatment of tuberculous meningitis. However, clinicians must be cautious when ruling out TBM with Xpert Ultra due to its low negative predictive value. Due to the limitations of current diagnostics, clinicians should utilize a combination of diagnostic modalities in order to prevent morbidity in patients with TBM. Copyright 2020 The Author(s)
    • A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer

      Wagner, A.H.; Schriml, L.M.; Variant Interpretation for Cancer Consortium (Springer Nature, 2020)
      Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.
    • Projecting the demand for ventilators at the peak of the COVID-19 outbreak in the USA

      Wells, C.R.; Fitzpatrick, M.C.; Sah, P. (Lancet Publishing Group, 2020)
      The coronavirus disease 2019 (COVID-19) pandemic has been straining health-care systems worldwide. For countries still in the early phase of an outbreak, there is concern regarding insufficient supply of intensive care unit (ICU) beds and ventilators to handle the impending surge in critically ill patients. To inform pandemic preparations, we projected the number of ventilators that will be required in the USA at the peak of the COVID-19 outbreak.
    • Viral status, immune microenvironment and immunological response to checkpoint inhibitors in hepatocellular carcinoma

      Ho, W.J.; Danilova, L.; Sztein, M.B. (BMJ Publishing Group, 2020)
      Background and aims Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have clinical activity in hepatocellular carcinoma (HCC), but only a subset of patients respond to these therapies, highlighting a need for novel biomarkers to improve clinical benefit. HCC usually occurs in the setting of liver cirrhosis from chronic hepatitis B or C viral infection, but the effects of viral status on the tumor immune microenvironment and clinical responses to ICIs in HCC remains unclear. Methods We conducted a meta-analysis to estimate the objective response rates for PD-1/PD-L1 inhibitors in virally-infected and uninfected patients, and examined the effects of viral etiology on the tumor microenvironment using data from The Cancer Genome Atlas, as well as peripheral blood responses using an independent cohort of patients studied by mass cytometry (cytometry by time-of-flight (CyTOF)). Results Meta-analysis comparing objective response rates (ORR) between virally-infected and uninfected patients showed no clinically meaningful difference (absolute difference of ORR in virally-infected vs uninfected=-1.4%, 95% CI: -13.5% to 10.6%). There was no relationship between viral etiology on features of the tumor immune microenvironment that are known to modulate responses to PD-1/PD-L1 inhibitors, and the tumor mutational burden was similar between virally-infected and uninfected HCC. RNA sequencing of tissue-resident T cell and B cell repertoires similarly showed no effect of viral status on their diversity. CyTOF analysis of peripheral blood specimens further demonstrated similar expression of immune-related markers in response to PD-1 inhibitor therapy in virally-infected and uninfected HCC. Conclusion There is no significant effect of viral etiology on the tumor immune microenvironment in HCC, and viral status should not be used as a criterion to select patients for PD-1/PD-L1 therapy. Copyright Author(s)
    • Return of Individual Research Results: A Guide for Biomedical Researchers Utilizing Human Biospecimens

      Sobel, M.E.; Dreyfus, J.C.; O'Leary, T.J. (Elsevier Inc., 2020)
      The recent movement toward returning individual research results to study subjects/participants generates ethical and legal challenges for laboratories performing research on human biospecimens. The concept of an individual's interest in knowing the results of testing on their tissue is pitted against individual and systemic risks and an established legal framework regulating the performance of laboratory testing for medical care purposes. This article discusses the rationale for returning individual research results to subjects, the potential risks associated with returning these results, and the legal framework in the United States that governs testing of identifiable human biospecimens. On the basis of these considerations, this article provides recommendations for investigators to consider when planning and executing human biospecimen research, with the objective of appropriately balancing the interests of research subjects, the need for ensuring integrity of the research process, and compliance with US laws and regulations. Copyright 2020 American Society for Investigative Pathology
    • Oxidized Phospholipids in Healthy and Diseased Lung Endothelium

      Karki, P.; Birukov, K.G. (MDPI AG, 2020)
      Circulating and cell membrane phospholipids undergo oxidation caused by enzymatic and non-enzymatic mechanisms. As a result, a diverse group of bioactive oxidized phospholipids generated in these conditions have both beneficial and harmful effects on the human body. Increased production of oxidized phospholipid products with deleterious effects is linked to the pathogenesis of various cardiopulmonary disorders such as atherosclerosis, thrombosis, acute lung injury (ALI), and inflammation. It has been determined that the contrasting biological effects of lipid oxidation products are governed by their structural variations. For example, full-length products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine oxidation (OxPAPC) have prominent endothelial barrier protective and anti-inflammatory activities while most of the truncated oxidized phospholipids induce vascular leak and exacerbate inflammation. The extensive studies from our group and other groups have demonstrated a strong potential of OxPAPC in mitigating a wide range of agonist-induced lung injuries and inflammation in pulmonary endothelial cell culture and rodent models of ALI. Concurrently, elevated levels of truncated oxidized phospholipids are present in aged mice lungs that potentiate the inflammatory agents-induced lung injury. On the other hand, increased levels of full length OxPAPC products accelerate ALI recovery by facilitating production of anti-inflammatory lipid mediator, lipoxin A4, and other molecules with anti-inflammatory properties. These findings suggest that OxPAPC-assisted lipid program switch may be a promising therapeutic strategy for treatment of acute inflammatory syndromes. In this review, we will summarize the vascular-protective and deleterious aspects of oxidized phospholipids and discuss their therapeutic potential including engineering of stable analogs of oxidized phospholipids with improved anti-inflammatory and barrier-protective properties.
    • Cognitive Training for Very High Risk Incarcerated Adolescent Males

      Rowlands, A.; Fisher, M.; Mishra, J. (Frontiers Media S.A., 2020)
      Objective: Persistent violent and antisocial behavior, as manifested in conduct disorder (CD) traits, are associated with a range of cognitive deficits. Individuals with more severe cognitive deficits are more likely to commit violent crimes. Currently, no treatments target improving cognition in high-risk CD youth. This pilot study tests the feasibility and efficacy of delivering intensive tablet-based cognitive training (CT) to adolescent males incarcerated in a youth maximum-security prison. Methods: Participants were fourteen adolescent males, diagnosed with CD. All participants completed up to 30 h of unsupervised, intensive, adaptive CT exercises that targeted multiple neurocognitive domains, as well as a battery of standardized neurocognitive measures and computerized assessments at baseline and post-training. Conclusions and Implications for Practice: At baseline, participants exhibited significant impairments on neurocognitive measures, relative to age-matched healthy controls. Twelve participants completed training and showed evidence of target engagement, as indexed by improvement in cognitive processing speed. Significant gains were observed in measures of global cognition, with additional gains in cognitive flexibility at trend level significance. Improvements in these measures were positively related to total training time. In summary, both assessments and intervention appear to be feasible, tolerable, and acceptable in incarcerated youth. Intensive CT shows preliminary efficacy in improving neurocognitive performance in key domains, with large effect sizes, and significant performance improvement associations with the time in training. Copyright 2020 The Authors
    • A cross-sectional pilot study of birth mode and vaginal microbiota in reproductive-age women

      Stennett, C.A.; Robinson, C.K.; Ravel, J.; Brotman, R.M. (Public Library of Science, 2020)
      Recent studies suggest that birth mode (Cesarean section [C-section] or vaginal delivery) is an important event in the initial colonization of the human microbiome and may be associated with long-term health outcomes. We sought to determine the association between a woman’s birth mode and her vaginal microbiota in adulthood. We re-contacted 144 adult women from two U.S. studies and administered a brief survey. Vaginal microbiota was characterized on a single sample by amplicon sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene and clustered into community state types (CSTs). We evaluated the association between birth mode and a CST with low relative abundance of Lactobacillus spp. (“molecular bacterial vaginosis” [Molecular-BV]) compared to Lactobacillus-dominated CSTs in logistic regression modeling which adjusted for body mass index, a confounder in this analysis. Twenty-seven women (19%) reported C-section. Overall, C-section showed a non-significant trend towards increased odds of Molecular-BV (aOR = 1.22, 95% CI: 0.45, 3.32), and Prevotella bivia was the strongest single taxa associated with C-section. However, because the two archived studies had different inclusion criteria (interaction p = 0.048), we stratified the analysis by study site. In the study with a larger sample size (n = 88), women born by C-section had 3-fold higher odds of Molecular-BV compared to vaginally-delivered women (aOR = 3.55, p = 0.06, 95% CI: 0.97–13.02). No association was found in the smaller study (n = 56, aOR = 0.19, p = 0.14, 95% CI: 0.02–1.71). This pilot cross-sectional study suggests a possible association between C-section and Molecular-BV in adulthood. However, the analysis is limited by small sample size and lack of comparability in participant age and other characteristics between the study sites. Future longitudinal studies could recruit larger samples of women, address the temporal dynamics of vaginal microbiota, and explore other confounders, including maternal factors, breastfeeding history, and socioeconomic status, which may affect the relationship between birth mode and vaginal microbiota. Copyright 2020 Stennett et al.
    • A literature review of painful Hashimoto thyroiditis: 70 published cases in the past 70 years

      Peng, C.C.-H.; Pennant, M.; Munir, K.M. (Endocrine Society, 2020)
      Painful Hashimoto thyroiditis (pHT) is a rare diagnosis, and optimal treatment remains unclear. To better characterize pHT, PubMed, Embase, Scopus, and Web of Science indexes were searched for case reports or case series reporting pHT, published between 1951 and February 2019. Seventy cases reported in 24 publications were identified. Female predominance (91.4%) and a median age of 39.00 years (interquartile range, 32.50-49.75 years) were observed. Among reported cases, 50.8% had known thyroid disease (including Hashimoto thyroiditis, Graves disease, and seronegative goiters), 83.3% had positive antithyroid peroxidase antibodies, and 71.2% had antithyroglobulin antibodies. Most cases did not have preceding upper respiratory tract symptoms or leukocytosis. Ultrasound features were consistent with Hashimoto thyroiditis. Thyroid function at initial presentation was hypothyroid (35.9%), euthyroid (28.1%), or thyrotoxic (35.9%). Cases evolved into hypothyroidism (55.3%) and euthyroidism (44.7%), whereas none became hyperthyroid after medical treatment. Thyroid size usually decreased after medical treatment. Most cases were empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no therapy provided sustained pain resolution. In subgroup analysis, low-dose oral prednisone (<25 mg/d) and intrathyroidal corticosteroid injection showed more favorable outcomes. Total thyroidectomy yielded 100% sustained pain resolution. Diagnosis of pHT is based on clinical evidence of Hashimoto thyroiditis and recurrent thyroid pain after medical treatment. The reference standard of diagnosis is pathology. Total thyroidectomy or intrathyroidal glucocorticoid injection should be considered if low-dose oral prednisone fails to achieve pain control.
    • Antibiotic prescribing in New York State medicare part B beneficiaries diagnosed with cystitis between 2016 and 2017

      Yu, J.Y.; McKenna, V.A.; Dumyati, G.K. (Oxford University Press, 2020)
      Background. Statewide tracking and reporting is an outpatient antimicrobial stewardship tool that may be useful for many stakeholders. However, to date, these evaluations have been limited. This study aimed to track and report outpatient antibiotic prescribing in Medicare Part B enrollees diagnosed with cystitis in the outpatient setting. Methods. This was a retrospective, cohort study of Medicare Part B enrollees in New York State. Inclusion criteria include outpatient visit in 2016 or 2017, cystitis diagnosis code, and oral antibiotic prescription ?3 days after diagnosis of cystitis. Antibiotics were categorized as first-line, oral ?-lactams, fluoroquinolones, or other per Infectious Diseases Society of America acute uncomplicated cystitis guidelines. Data were stratified by sex. Annual prescriptions proportions were compared using ?2 test or Fisher's exact test as appropriate. Results. A total of 50 658 prescriptions were included. For females' prescriptions, first line increased (41.5% vs 43.8%, P &lt; .0001), oral ?-lactams increased (17.8% vs 20.5%, P &lt; .0001), fluoroquinolones decreased (34.1% vs 29.1%, P &lt; .0001), and other increased (6.5% vs 6.6%, P = .76) in 2017. For males' prescriptions, first line increased (25.2% vs 26.7%, P = .11), oral ?-lactams increased (23.1% vs 26.2%, P = .0003), fluoroquinolones decreased (44.0% vs 39.3%, P &lt; .0001), and other remained unchanged (7.8% vs 7.8%, P = .92) in 2017. Conclusions. Guideline concordant therapy prescribing for cystitis increased among Medicare Part B beneficiaries in New York State between 2016 and 2017. However, there was still a high prevalence of fluoroquinolone prescribing. These data highlight the need for additional outpatient antimicrobial stewardship efforts in New York State. Copyright The Author(s) 2020.
    • Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report

      Mazzone, P.J.; Gould, M.K.; White, C.S. (Elsevier Inc, 2020)
      Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small cell lung cancer. Conclusions: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.
    • Mothers' satisfaction with health extension services and the associated factors in Gamo Goffa zone, Southern Ethiopia

      Mergia, M.; Shegaze, M.; Memiah, P. (Public Library of Science, 2020)
      Background Providing compassionate and respectful maternity services in order to bring satisfaction to service users is one of the health extension services packages in Ethiopia. Though the service utilization and its associated factors have been well documented so far, yet there is a dearth of information on client satisfaction; particularly among rural women who are mostly the target groups of health extension services within the Ethiopia. Thus, this study aimed to assess mothers' satisfaction with health extension services and the associated factors in the Gamo Goffa Zone, of Southern Ethiopia. Methods A community based cross sectional study was conducted among 478 women from February 1st to February 28th of 2018. A pre-tested and interviewer administered questionnaire was used to collect the data. The study participants were selected using a systematic random sampling technique by allocating a proportion to each rural kebeles. Both bivariate and multivariate logistic regression analysis were performed to identify associated factors. Odds ratio with its 95% confidence interval was used to determine the degree of association. Level of statistical significance was set at a p-value of less than 0.05. Result The overall proportion of mothers who were satisfied with health extension services was 37.4% with 95% CI (33-44%). Mothers who had good family monthly income [AOR = 4.66 (95% CI: 1.1, 20.6)], whose husbands participated in the health extension program [AOR = 4.02 (95% CI: 2.0, 8.1)], who had recent participation in planning of health extension programs [AOR = 5.75 (95% CI: 2.0, 16.5)], who were recognized as a model family [AOR = 2.23 (95% CI: 1.1, 4.6)] had higher odds of satisfaction with health extension services. Conclusion Satisfaction with the health extension services was low among women in the study area. A better household monthly income, women's and their husbands' participation in health extension services and being a member of a model family were positively associated with their satisfaction. Interventions to enhance women's satisfaction in the health extension service need to focus on household-based involvement of them and their husbands in planning and implementing the services. Likewise, expansion of experiences of model families in the community would raise satisfaction levels. Copyright 2020 Mergia et al.
    • Mechanical Ventilation Lessons Learned From Alveolar Micromechanics

      Kollisch-Singule, M.; Satalin, J.; Andrews, P.L. (Frontiers Media S.A., 2020)
      Morbidity and mortality associated with lung injury remains disappointingly unchanged over the last two decades, in part due to the current reliance on lung macro-parameters set on the ventilator instead of considering the micro-environment and the response of the alveoli and alveolar ducts to ventilator adjustments. The response of alveoli and alveolar ducts to mechanical ventilation modes cannot be predicted with current bedside methods of assessment including lung compliance, oxygenation, and pressure-volume curves. Alveolar tidal volumes (Vt) are less determined by the Vt set on the mechanical ventilator and more dependent on the number of recruited alveoli available to accommodate that Vt and their heterogeneous mechanical properties, such that high lung Vt can lead to a low alveolar Vt and low Vt can lead to high alveolar Vt. The degree of alveolar heterogeneity that exists cannot be predicted based on lung calculations that average the individual alveolar Vt and compliance. Finally, the importance of time in promoting alveolar stability, specifically the inspiratory and expiratory times set on the ventilator, are currently under-appreciated. In order to improve outcomes related to lung injury, the respiratory physiology of the individual patient, specifically at the level of the alveolus, must be targeted. With experimental data, this review highlights some of the known mechanical ventilation adjustments that are helpful or harmful at the level of the alveolus. Copyright 2020 The Authors.
    • A distinct class of plant and animal viral proteins that disrupt mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1

      Jin, H.; Li, G.; Zhao, R.Y. (American Association for the Advancement of Science, 2020)
      Many animal viral proteins, e.g., Vpr of HIV-1, disrupt host mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1. However, it is unknown whether plant viruses may use this mechanism in their pathogenesis. Here, we report that the 17K protein, encoded by barley yellow dwarf viruses and related poleroviruses, delays G2/M transition and disrupts mitosis in both host (barley) and nonhost (fission yeast, Arabidopsis thaliana, and tobacco) cells through interrupting the function of Wee1-Cdc25-CDKA/Cdc2 via direct protein-protein interactions and alteration of CDKA/Cdc2 phosphorylation. When ectopically expressed, 17K disrupts the mitosis of cultured human cells, and HIV-1 Vpr inhibits plant cell growth. Furthermore, 17K and Vpr share similar secondary structural feature and common amino acid residues required for interacting with plant CDKA. Thus, our work reveals a distinct class of mitosis regulators that are conserved between plant and animal viruses and play active roles in viral pathogenesis. Copyright 2020 The Authors.
    • Dietary Supplementation With Magnolia Bark Extract Alters Chicken Intestinal Metabolite Levels

      Park, I.; Oh, S.; Lillehoj, E.P. (Frontiers Media S.A., 2020)
      Magnolia bark extract administered as a dietary supplement to poultry confers a performance and health benefit, but the mechanisms are unknown. Here, a metabolomics approach was used to identify changes in intestinal metabolite levels in chickens fed an unsupplemented diet or a diet supplemented with magnolia bark extract. Total body weight gains of chickens fed magnolia bark-supplemented diets were increased 2% (from 861 to 878 g/chicken), compared with chickens fed an unsupplemented diet. Compared with unsupplemented controls, the levels of 278 intestinal biochemicals (metabolites) were altered (165 increased, 113 decreased) in chickens given the magnolia-supplemented diet. Data for biochemicals of intestinal contents of chickens fed the unsupplemented diet clustered on the left side of the PCA score plot, while those of the magnolia-supplemented diet were separated and clustered on the right side. The biochemicals included changes in the levels of amino acids, fatty acids, peptides, and nucleosides, which provided a distinctive biochemical signature unique to the magnolia-supplemented group, compared with the unsupplemented group. These results provide the foundation for future studies to identify naturally-produced biochemicals that might be used to improve poultry growth performance. Copyright Authors.
    • Nonalcoholic fatty liver disease experiences accumulation of hepatic liquid crystal associated with increasing lipophagy

      Wang, L.; Xu, M.; Bryant, J.L. (BioMed Central Ltd., 2020)
      Background: In the past 30 years, incidences of non-alcoholic fatty liver disease (NAFLD) has risen by 30%. However, there is still no clear mechanism or accurate method of anticipating liver failure. Here we reveal the phase transitions of liquid crystalline qualities in hepatic lipid droplets (HLDs) as a novel method of anticipating prognosis. Methods: NAFLD was induced by feeding C57BL/6J mice on a high-fat (HiF) diet. These NAFLD livers were then evaluated under polarized microscopy, X-ray diffraction and small-angle scattering, lipid component chromatography analysis and protein expression analysis. Optically active HLDs from mouse model and patient samples were both then confirmed to have liquid crystal characteristics. Liver MAP1LC3A expression was then evaluated to determine the role of autophagy in liquid crystal HLD (LC-HLD) formation. Results: Unlike the normal diet cohort, HiF diet mice developed NAFLD livers containing HLDs exhibiting Maltese cross birefringence, phase transition, and fluidity signature to liquid crystals. These LC-HLDs transitioned to anisotropic crystal at 0 °C and remain crystalline. Temperature increase to 42 °C causes both liquid crystal and crystal HLDs to convert to isotropic droplet form. These isotropic HLDs successfully transition to anisotropic LC with fast temperature decrease and anisotropic crystal with slow temperature decrease. These findings were duplicated in patient liver. Patient LC-HLDs with no inner optical activity were discovered, hinting at lipid saturation as the mechanism through which HLD acquire LC characteristics. Downregulation of MAP1LC3A in conjunction with increased LC-HLD also implicated autophagy in NAFLD LC-HLD formation. Conclusions: Increasing concentrations of amphiphilic lipids in HLDs favors organization into alternating hydrophilic and hydrophobic layers, which present as LC-HLDs. Thus, evaluating the extent of liquid crystallization with phase transition in HLDs of NAFLD patients may reveal disease severity and predict impending liver damage. Copyright 2020 The Author(s).
    • Effects of larval exposure to sublethal doses of Bacillus thuringiensis var. israelensis on body size, oviposition and survival of adult Anopheles coluzzii mosquitoes

      Gowelo, S.; Chirombo, J.; McCann, R. (Springer Nature, 2020)
      BACKGROUND: Application of the larvicide Bacillus thuringiensis var. israelensis (Bti) is a viable complementary strategy for malaria control. Efficacy of Bti is dose-dependent. There is a knowledge gap on the effects of larval exposure to sublethal Bti doses on emerging adult mosquitoes. The present study examined the effect of larval exposure to sublethal doses of Bti on the survival, body size and oviposition rate in adult Anopheles coluzzii. METHODS: Third-instar An. coluzzii larvae were exposed to control and sublethal Bti concentrations at LC20, LC50 and LC70 for 48 h. Surviving larvae were reared to adults under standard colony conditions. Thirty randomly selected females from each treatment were placed in separate cages and allowed to blood feed. Twenty-five gravid females from the blood-feeding cages were randomly selected and transferred into new cages where they were provided with oviposition cups. Numbers of eggs laid in each cage and mortality of all adult mosquitoes were recorded daily. Wing lengths were measured of 570 mosquitoes as a proxy for body size. RESULTS: Exposure to LC70Bti doses for 48 h as third-instar larvae reduced longevity of adult An. coluzzii mosquitoes. Time to death was 2.58 times shorter in females exposed to LC70Bti when compared to the control females. Estimated mortality hazard rates were also higher in females exposed to the LC50 and LC20 treatments, but these differences were not statistically significant. The females exposed to LC70 concentrations had 12% longer wings than the control group (P < 0.01). No differences in oviposition rate of the gravid females were observed between the treatments. CONCLUSIONS: Exposure of An. coluzzii larvae to sublethal Bti doses reduces longevity of resultant adults and is associated with larger adult size and unclear effect on oviposition. These findings suggest that anopheline larval exposure to sublethal Bti doses, though not recommended, could reduce vectorial capacity for malaria vector populations by increasing mortality of resultant adults.
    • Long-term exposure to particulate air pollution and brachial artery flow-mediated dilation in the Old Order Amish

      Salimi, S.; Vogel, R.; Mitchell, B.D. (BioMed Central Ltd., 2020)
      Background: Atmospheric particulate matter (PM) has been associated with endothelial dysfunction, an early marker of cardiovascular risk. Our aim was to extend this research to a genetically homogenous, geographically stable rural population using location-specific moving-average air pollution exposure estimates indexed to the date of endothelial function measurement. Methods: We measured endothelial function using brachial artery flow-mediated dilation (FMD) in 615 community-dwelling healthy Amish participants. Exposures to PM &lt; 2.5 ?m (PM2.5) and PM &lt; 10 ?m (PM10) were estimated at participants' residential addresses using previously developed geographic information system-based spatio-temporal models and normalized. Associations between PM exposures and FMD were evaluated using linear mixed-effects regression models, and polynomial distributed lag (PDL) models followed by Bayesian model averaging (BMA) were used to assess response to delayed effects occurring across multiple months. Results: Exposure to PM10 was consistently inversely associated with FMD, with the strongest (most negative) association for a 12-month moving average (- 0.09; 95% CI: - 0.15, - 0.03). Associations with PM2.5 were also strongest for a 12-month moving average but were weaker than for PM10 (- 0.07; 95% CI: - 0.13, - 0.09). Associations of PM2.5 and PM10 with FMD were somewhat stronger in men than in women, particularly for PM10. Conclusions: Using location-specific moving-average air pollution exposure estimates, we have shown that 12-month moving-average estimates of PM2.5 and PM10 exposure are associated with impaired endothelial function in a rural population. Copyright 2020 The Author(s).