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1.
PLoS One ; 19(7): e0304779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980887

RESUMO

OBJECTIVE: This study examines the association between changes in mental health before and during the COVID-19 pandemic and COVID-19 mortality across geographic areas and by race/ethnicity. METHODS: A cross-sectional survey was conducted in Los Angeles County between April and May 2021. The study used the Patient Health Questionnaire-2 to assess major depression risk. Participants' home ZIP codes were classified into low, middle, and high COVID-19 mortality impacted areas (CMIA). RESULTS: While there were existing mental health disparities due to differences in demographics and social determinants of health across CMIA in 2018, the pandemic exacerbated the disparities, especially for residents living in high CMIA. Non-White residents in high CMIA reported the largest deterioration in mental health. Differences in mental health by CMIA persisted after controlling for resident characteristics. CONCLUSIONS: Living in an area with higher COVID-19 mortality rates may have been associated with worse mental health, with Non-White residents reporting worse mental health outcomes in the high mortality area. POLICY IMPLICATIONS: It is crucial to advocate for greater mental health resources in high COVID-19 mortality areas especially for racial/ethnic minorities.


Assuntos
COVID-19 , Saúde Mental , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/psicologia , Los Angeles/epidemiologia , Saúde Mental/estatística & dados numéricos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Idoso , Pandemias , SARS-CoV-2/isolamento & purificação , Estudos de Coortes
2.
DNA Repair (Amst) ; 141: 103715, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39029375

RESUMO

Glioblastoma (GBM) is a highly aggressive brain tumor associated with poor patient survival. The current standard treatment involves invasive surgery, radiotherapy, and chemotherapy employing temozolomide (TMZ). Resistance to TMZ is, however, a major challenge. Previous work from our group has identified candidate genes linked to TMZ resistance, including genes encoding translesion synthesis (TLS) DNA polymerases iota (PolÉ©) and kappa (Polκ). These specialized enzymes are known for bypassing lesions and tolerating DNA damage. Here, we investigated the roles of PolÉ© and Polκ in TMZ resistance, employing MGMT-deficient U251-MG glioblastoma cells, with knockout of either POLI or POLK genes encoding PolÉ© and Polκ, respectively, and assess their viability and genotoxic stress responses upon subsequent TMZ treatment. Cells lacking either of these polymerases exhibited a significant decrease in viability following TMZ treatment compared to parental counterparts. The restoration of the missing polymerase led to a recovery of cell viability. Furthermore, knockout cells displayed increased cell cycle arrest, mainly in late S-phase, and lower levels of genotoxic stress after TMZ treatment, as assessed by a reduction of γH2AX foci and flow cytometry data. This implies that TMZ treatment does not trigger a significant H2AX phosphorylation response in the absence of these proteins. Interestingly, combining TMZ with Mirin (double-strand break repair pathway inhibitor) further reduced the cell viability and increased DNA damage and γH2AX positive cells in TLS KO cells, but not in parental cells. These findings underscore the crucial roles of PolÉ© and Polκ in conferring TMZ resistance and the potential backup role of homologous recombination in the absence of these TLS polymerases. Targeting these TLS enzymes, along with double-strand break DNA repair inhibition, could, therefore, provide a promising strategy to enhance TMZ's effectiveness in treating GBM.

3.
JMIR AI ; 3: e49784, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38875594

RESUMO

BACKGROUND: Despite its high lethality, sepsis can be difficult to detect on initial presentation to the emergency department (ED). Machine learning-based tools may provide avenues for earlier detection and lifesaving intervention. OBJECTIVE: The study aimed to predict sepsis at the time of ED triage using natural language processing of nursing triage notes and available clinical data. METHODS: We constructed a retrospective cohort of all 1,234,434 consecutive ED encounters in 2015-2021 from 4 separate clinically heterogeneous academically affiliated EDs. After exclusion criteria were applied, the final cohort included 1,059,386 adult ED encounters. The primary outcome criteria for sepsis were presumed severe infection and acute organ dysfunction. After vectorization and dimensional reduction of triage notes and clinical data available at triage, a decision tree-based ensemble (time-of-triage) model was trained to predict sepsis using the training subset (n=950,921). A separate (comprehensive) model was trained using these data and laboratory data, as it became available at 1-hour intervals, after triage. Model performances were evaluated using the test (n=108,465) subset. RESULTS: Sepsis occurred in 35,318 encounters (incidence 3.45%). For sepsis prediction at the time of patient triage, using the primary definition, the area under the receiver operating characteristic curve (AUC) and macro F1-score for sepsis were 0.94 and 0.61, respectively. Sensitivity, specificity, and false positive rate were 0.87, 0.85, and 0.15, respectively. The time-of-triage model accurately predicted sepsis in 76% (1635/2150) of sepsis cases where sepsis screening was not initiated at triage and 97.5% (1630/1671) of cases where sepsis screening was initiated at triage. Positive and negative predictive values were 0.18 and 0.99, respectively. For sepsis prediction using laboratory data available each hour after ED arrival, the AUC peaked to 0.97 at 12 hours. Similar results were obtained when stratifying by hospital and when Centers for Disease Control and Prevention hospital toolkit for adult sepsis surveillance criteria were used to define sepsis. Among septic cases, sepsis was predicted in 36.1% (1375/3814), 49.9% (1902/3814), and 68.3% (2604/3814) of encounters, respectively, at 3, 2, and 1 hours prior to the first intravenous antibiotic order or where antibiotics where not ordered within the first 12 hours. CONCLUSIONS: Sepsis can accurately be predicted at ED presentation using nursing triage notes and clinical information available at the time of triage. This indicates that machine learning can facilitate timely and reliable alerting for intervention. Free-text data can improve the performance of predictive modeling at the time of triage and throughout the ED course.

4.
Neoreviews ; 25(7): e443-e446, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38945964
5.
PLoS One ; 18(8): e0289805, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37585439

RESUMO

Key ecological features (KEFs) are elements of Australia's Commonwealth marine environment considered to be important for biodiversity or ecosystem function, yet many KEFs are poorly researched, which can impede effective decision-making about future development and conservation. This study investigates a KEF positioned over the Last Glacial Maximum (LGM) shoreline on the northwest shelf of Australia (known as the 'Ancient Coastline at ~125m depth contour'; AC125). Seafloor bathymetry, sedimentology and benthic habitats were characterised within five study areas using multibeam sonar, sediment samples and towed video imagery. Direct evidence for the existence of a palaeoshoreline formed during the LGM was not found, however candidate areas to find palaeoshoreline material at or just below the modern seabed were discovered. Approximately 98% of the seabed surveyed was comprised of unconsolidated soft sediment habitat (mud/sand/silt) supporting negligible epibenthic biota. The prevalence of soft sediment suggests that post-glacial sediments have infilled parts of the palaeoshoreline, with cross-shelf, probably tidal currents in the northern section of the study area responsible for some of the sediment mobilisation and southern study areas more influenced by oceanic conditions. Within study areas, total biotic cover ranged from 0.02% to 1.07%. Of the biota encountered, most comprised filter feeder organisms (including gorgonians, sponges, and whip corals) whose distribution was associated with pockets of consolidated hard substrate. Benthic community composition varied with both study area and position in relation to the predicted AC125. In general, consolidated substrate was proportionally higher in water shallower than the AC125 compared to on the AC125 or deeper than the AC125. Spatially continuous maps of predicted benthic habitat classes (pre-determined benthic communities) in each study area were developed to characterise biodiversity. Spatial modelling corroborated depth and large-scale structural complexity of the seafloor as surrogates for predicting likely habitat class. This study provides an important assessment of the AC125 and shows that if a distinct coastline exists in the areas we surveyed, it is now largely buried and as such does not provide a unique hard substrate habitat. However, much work remains to fully locate and map the ancient coastline within the vast region of the AC125 and additional surveys in shallow waters adjacent to the AC125 may identify whether some sections lie outside the currently defined KEF.


Assuntos
Antozoários , Ecossistema , Animais , Austrália Ocidental , Biodiversidade , Biota
6.
Front Public Health ; 11: 1106740, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397779

RESUMO

Introduction: Traditional perinatal care alone cannot address the social and structural determinants that drive disparities in adverse birth outcomes. Despite the wide acceptance of partnerships between healthcare systems and social service agencies to address this challenge, there needs to be more research on the implementation factors that facilitate (or hinder) cross-sector partnerships, particularly from the perspective of community-based organizations. This study aimed to integrate the views of healthcare staff and community-based partner organizations to describe the implementation of a cross-sector partnership designed to address social and structural determinants in pregnancy. Methods: We used a mixed methods design (in-depth interviews and social network analysis) to integrate the perspectives of healthcare clinicians and staff with those of community-based partner organizations to identify implementation factors related to cross-sector partnerships. Results: We identified seven implementation factors related to three overarching themes: relationship-centered care, barriers and facilitators of cross-sector partnerships, and strengths of a network approach to cross-sector collaboration. Findings emphasized establishing relationships between healthcare staff, patients, and community-based partner organizations. Conclusion: This study provides practical insights for healthcare organizations, policymakers, and community organizations that aim to improve access to social services among historically marginalized perinatal populations.


Assuntos
Complicações na Gravidez , Determinantes Sociais da Saúde , Humanos , Feminino , Organizações , Atenção à Saúde
7.
ACS Nano ; 17(12): 11362-11373, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37154668

RESUMO

Metal nanocavities can generate plasmon-enhanced light upconversion signals under ultrashort pulse excitations through anti-Stokes photoluminescence (ASPL) or nonlinear harmonic generation processes, offering various applications in bioimaging, sensing, interfacial science, nanothermometry, and integrated photonics. However, achieving broadband multiresonant enhancement of both ASPL and harmonic generation processes within the same metal nanocavities remains challenging, impeding applications based on dual-modal or wavelength-multiplexed operations. Here, we report a combined experimental and theoretical study on dual-modal plasmon-enhanced light upconversion through both ASPL and second-harmonic generation (SHG) from broadband multiresonant metal nanocavities in two-tier Ag/SiO2/Ag nanolaminate plasmonic crystals (NLPCs) that can support multiple hybridized plasmons with high spatial mode overlaps. Our measurements reveal the distinctions and correlations between the plasmon-enhanced ASPL and SHG processes under different modal and ultrashort pulsed laser excitation conditions, including incident fluence, wavelength, and polarization. To analyze the observed effects of the excitation and modal conditions on the ASPL and SHG emissions, we developed a time-domain modeling framework that simultaneously captures the mode coupling-enhancement characteristics, quantum excitation-emission transitions, and hot carrier population statistical mechanics. Notably, ASPL and SHG from the same metal nanocavities exhibit distinct plasmon-enhanced emission behaviors due to the intrinsic differences between the incoherent hot carrier-mediated ASPL sources with temporally evolving energy and spatial distributions and instantaneous SHG emitters. Mechanistic understanding of ASPL and SHG emissions from broadband multiresonant plasmonic nanocavities marks a milestone toward creating multimodal or wavelength-multiplexed upconversion nanoplasmonic devices for bioimaging, sensing, interfacial monitoring, and integrated photonics applications.

8.
J Endovasc Ther ; 30(6): 976-979, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-35735200

RESUMO

PURPOSE: Takayasu arteritis is a large-vessel vasculitis in women of childbearing age that affects large vessels including the aorta and its main branches. Inflammation of arteries can produce lesions that lead to occlusion, stenosis, or aneurysms which can lead to complications. If signs of organ dysfunction are present, vascular intervention may be necessary. CASE REPORT: In this article, we present a case of Takayasu arteritis with high-grade stenosis of all the great vessels of the thoracic aorta treated with drug-coated balloon (DCB) angioplasty and stenting requiring multiple follow-up interventions over a 1-year follow-up. CONCLUSION: The DCB angioplasty is a potential endovascular treatment for thoracic great artery stenosis in Takayasu arteritis that could be further explored.


Assuntos
Angioplastia com Balão , Arterite de Takayasu , Humanos , Feminino , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/terapia , Seguimentos , Constrição Patológica , Resultado do Tratamento
9.
AIMS Public Health ; 9(3): 482-489, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330284

RESUMO

Background: Children age 5-11 became eligible for COVID-19 vaccination in November 2021 in the United States, but vaccine uptake in this age group remains low. Understanding reasons why parents are hesitant to vaccinate their children may provide critical insights to help protect children from COVID-19 infection. This study examines factors associated with parents' willingness to vaccinate their children. Methods: We conducted a cross-sectional survey focusing on the Los Angeles County adult residents between March and June 2021. Our analytic sample focused on a subgroup of participants who self-report having a child. Predictors included parents' vaccination status and beliefs about COVID-19. We used multivariable logistic regression analysis and calculated the predicted probabilities of parents' willingness to vaccinate their children. Results: Parents (n = 401) who worried about catching the virus, had trust in vaccine development and the COVID-19 vaccine approval process, and vaccinated against COVID-19 were more likely to be willing to vaccinate their children. Socio-economic, racial and ethnic differences were no longer statistically significant in the adjusted model. Predicted probabilities of parents who were willing to vaccine their children were 55% among the vaccinated and 36% among the unvaccinated. Conclusions: Parents' intent to vaccinate their children is influenced by their perceived severity of the pandemic, trust in the vaccine development process, and their vaccination status, which can be the potential drivers of hesitancy to vaccinate their children.

10.
PLoS One ; 16(6): e0253549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166416

RESUMO

The objective of this study was to use available data on the prevalence of COVID-19 risk factors in subpopulations and epidemic dynamics at the population level to estimate probabilities of severe illness and the case and infection fatality rates (CFR and IFR) stratified across subgroups representing all combinations of the risk factors age, comorbidities, obesity, and smoking status. We focus on the first year of the epidemic in Los Angeles County (LAC) (March 1, 2020-March 1, 2021), spanning three epidemic waves. A relative risk modeling approach was developed to estimate conditional effects from available marginal data. A dynamic stochastic epidemic model was developed to produce time-varying population estimates of epidemic parameters including the transmission and infection observation rate. The epidemic and risk models were integrated to produce estimates of subpopulation-stratified probabilities of disease progression and CFR and IFR for LAC. The probabilities of disease progression and CFR and IFR were found to vary as extensively between age groups as within age categories combined with the presence of absence of other risk factors, suggesting that it is inappropriate to summarize epidemiological parameters for age categories alone, let alone the entire population. The fine-grained subpopulation-stratified estimates of COVID-19 outcomes produced in this study are useful in understanding disparities in the effect of the epidemic on different groups in LAC, and can inform analyses of targeted subpopulation-level policy interventions.


Assuntos
COVID-19/mortalidade , COVID-19/transmissão , Modelos Biológicos , SARS-CoV-2 , California/epidemiologia , Feminino , Humanos , Masculino , Medição de Risco
11.
Transfusion ; 61(6): 1780-1788, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33665853

RESUMO

BACKGROUND: Severe blood donor adverse events are rare, but due to their rarity studying them can be difficult. To get an accurate estimate of their frequency and rate in the donor population it may be necessary to combine donation data across countries. STUDY DESIGN AND METHODS: International blood collection organizations (BCOs) provided data on rare/severe donor reactions as well as denominator information for their donor populations from 2015 to 2017. Donor reactions were classified using standardized definitions. RESULTS: BCOs from six countries provided reaction data for more than 22 million donations. A total of 480 rare reactions were reported of which 76.7% were imputed as definite and 11% probable. Rates of rare reactions were higher in females and first-time donors. Systemic rare reactions were the most common reaction type, accounting for over three quarters of reactions reported. Of systemic reactions, vasovagal reactions with loss of consciousness and injury or off-site (n = 350) made up the majority and occurred 1.53 per 100,000 donations. For the 22.3% that were localized reactions, the majority of these were cellulitis (n = 71, 0.31 per 100,000 donations) followed by deep venous thrombosis (n = 21, 0.09 per 100,000 donations). CONCLUSION: Pulling together data from multiple BCOs across countries allows for a better understanding of rare reactions, such as vasovagal reaction with injury or cellulitis, and for generating a reliable incidence rate for air embolism or compartment syndrome. However, gaps remain due to missing elements such as unknown donor status or location of reaction.


Assuntos
Doadores de Sangue , Celulite (Flegmão)/etiologia , Síncope Vasovagal/etiologia , Trombose Venosa/etiologia , Adolescente , Adulto , Idoso , Remoção de Componentes Sanguíneos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
13.
medRxiv ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33367291

RESUMO

Background: Health disparities have emerged with the COVID-19 epidemic because the risk of exposure to infection and the prevalence of risk factors for severe outcomes given infection vary within and between populations. However, estimated epidemic quantities such as rates of severe illness and death, the case fatality rate (CFR), and infection fatality rate (IFR), are often expressed in terms of aggregated population-level estimates due to the lack of epidemiological data at the refined subpopulation level. For public health policy makers to better address the pandemic, stratified estimates are necessary to investigate the potential outcomes of policy scenarios targeting specific subpopulations. Methods: We develop a framework for using available data on the prevalence of COVID-19 risk factors (age, comorbidities, BMI, smoking status) in subpopulations, and epidemic dynamics at the population level and stratified by age, to estimate subpopulation-stratified probabilities of severe illness and the CFR (as deaths over observed infections) and IFR (as deaths over estimated total infections) across risk profiles representing all combinations of risk factors including age, comorbidities, obesity class, and smoking status. A dynamic epidemic model is integrated with a relative risk model to produce time-varying subpopulation-stratified estimates. The integrated model is used to analyze dynamic outcomes and parameters by population and subpopulation, and to simulate alternate policy scenarios that protect specific at-risk subpopulations or modify the population-wide transmission rate. The model is calibrated to data from the Los Angeles County population during the period March 1 - October 15 2020. Findings: We estimate a rate of 0.23 (95% CI: 0.13,0.33) of infections observed before April 15, which increased over the epidemic course to 0.41 (0.11,0.69). Overall population-average IFR( t ) estimates for LAC peaked at 0.77% (0.38%,1.15%) on May 15 and decreased to 0.55% (0.24%,0.90%) by October 15. The population-average IFR( t ) stratified by age group varied extensively across subprofiles representing each combination of the additional risk factors considered (comorbidities, BMI, smoking). We found median IFRs ranging from 0.009%-0.04% in the youngest age group (0-19), from 0.1%-1.8% for those aged 20-44, 0.36%-4.3% for those aged 45-64, and 1.02%-5.42% for those aged 65+. In the group aged 65+ for which the rate of unobserved infections is likely much lower, we find median CFRs in the range 4.4%-23.45%. The initial societal lockdown period avoided overwhelming healthcare capacity and greatly reduced the observed death count. In comparative scenario analysis, alternative policies in which the population-wide transmission rate is reduced to a moderate and sustainable level of non-pharmaceutical interventions (NPIs) would not have been sufficient to avoid overwhelming healthcare capacity, and additionally would have exceeded the observed death count. Combining the moderate NPI policy with stringent protection of the at-risk subpopulation of individuals 65+ would have resulted in a death count similar to observed levels, but hospital counts would have approached capacity limits. Interpretation: The risk of severe illness and death of COVID-19 varies tremendously across subpopulations and over time, suggesting that it is inappropriate to summarize epidemiological parameters for the entire population and epidemic time period. This includes variation not only across age groups, but also within age categories combined with other risk factors analyzed in this study (comorbidities, obesity status, smoking). In the policy analysis accounting for differences in IFR across risk groups in comparing the control of infections and protection of higher risk groups, we find that the strict initial lockdown period in LAC was effective because it both reduced overall transmission and protected individuals at greater risk, resulting in preventing both healthcare overload and deaths. While similar numbers of deaths as observed in LAC could have been achieved with a more moderate NPI policy combined with greater protection of individuals 65+, this would have come at the expense of overwhelming the healthcare system. In anticipation of a continued rise in cases in LAC this winter, policy makers need to consider the trade offs of various policy options on the numbers of the overall population that may become infected, severely ill, and that die when considering policies targeted at subpopulations at greatest risk of transmitting infection and at greatest risk for developing severe outcomes.

14.
Oncol Lett ; 20(3): 2191-2198, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782536

RESUMO

N6-methyladenosine (m6A) RNA modification regulates multiple biological functions. Methyltransferase like 3 (METTL3), one of the major N6-methyltransferases, is highly expressed in gastric cancer, but its potential role in disease is unclear. The current study knocked out METTL3 (METTL3-KO) in human gastric cancer AGS cells using CRISPR/Cas9. METTL3-KO AGS cells exhibited decreased m6A methylation levels. A significant inhibition of cell proliferation was observed in METTL3-KO AGS cells. Silencing METTL3 in AGS cells altered the expression profile of many effector molecules that were previously demonstrated to serve key roles in AGS cell proliferation, including the suppressor of cytokine signaling (SOCS) family of proteins. The results further demonstrated that SOCS2 upregulation in METTL3-KO AGS cells was associated with a decreased RNA decay rate. Furthermore, SOCS2 KO or SOCS2 overexpression caused a significant increase and decrease in AGS cell proliferation, respectively. The current data suggested that METTL3-KO in gastric cancer cells resulted in the suppression of cell proliferation by inducing SOCS2, suggesting a potential role of elevated METTL3 expression in gastric cancer progression.

15.
Front Neurosci ; 14: 285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32327969

RESUMO

Neuroinflammatory processes play an integral role in the exacerbation and progression of pathology in tauopathies, a class of neurodegenerative disease characterized by aggregation of hyperphosphorylated tau protein. The RNA binding protein (RBP) T-cell Intracellular Antigen 1 (TIA1) is an important regulator of the innate immune response in the periphery, dampening cytotoxic inflammation and apoptosis during cellular stress, however, its role in neuroinflammation is unknown. We have recently shown that TIA1 regulates tau pathophysiology and toxicity in part through the binding of phospho-tau oligomers into pathological stress granules, and that haploinsufficiency of TIA1 in the P301S mouse model of tauopathy results in reduced accumulation of toxic tau oligomers, pathologic stress granules, and the development of downstream pathological features of tauopathy. The putative role of TIA1 as a regulator of the peripheral immune response led us to investigate the effects of TIA1 on neuroinflammation in the context of tauopathy, a chronic stressor in the neural environment. Here, we evaluated indicators of neuroinflammation including; reactive microgliosis and phagocytosis, pro-inflammatory cytokine release, and oxidative stress in hippocampal neurons and glia of wildtype and P301S transgenic mice expressing TIA1+/+, TIA1+/-, and TIA1-/- in both early (5 month) and advanced (9 month) disease states through biochemical, ultrastructural, and histological analyses. Our data show that both TIA1 haploinsufficiency and TIA1 knockout exacerbate neuroinflammatory processes in advanced stages of tauopathy, suggesting that TIA1 dampens the immune response in the central nervous system during chronic stress.

16.
Proc (Bayl Univ Med Cent) ; 34(1): 156-158, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33456184

RESUMO

In rare instances, pediatric Langerhans cell histiocytosis (LCH) may manifest as lung disease. While the imaging features at presentation have been reported, we present sequential computed tomography (CT) scans of a 3-year-old boy with pulmonary LCH, revealing the evolution and regression of the disease. Sequential CT scans during treatment demonstrated variable evolution of pulmonary cysts, including changes in size, thinning of walls, and a pattern of collapse into irregular nodules and involution. Our case represents a rare opportunity to examine sequential CT findings of pediatric pulmonary LCH regression.

17.
Opt Express ; 27(10): 13681-13693, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31163828

RESUMO

Many insects use the pattern of polarized light in the sky as a navigational cue. In this study, we use this sensory ability as a source of inspiration to create a computational orientation model based on an artificial neural network (POL-ANN). After a training phase using numerically generated sky polarization patterns, stable and convergent networks are obtained. We undertook a series of verification tests using four typical but different sky conditions and showed that the post-trained networks were able to make an accurate prediction of the direction of the sun. Comparisons between the proposed models and models based on the convolutional neural network (CNN) structure revealed the merits of the bio-inspired architecture. We further investigated the accuracy of the models based on two different (locust-like, broader; Drosophila-like, narrower) visual fields of the sky. We find that the accuracy of the computations depends on the overhead visual scene, specifically that wider fields of view perform better when information about the overhead polarization pattern is missing.

18.
JAAPA ; 32(4): 51-53, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30913151

RESUMO

Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure in adults and a major cause of acute liver failure in children. Prompt treatment with N-acetylcysteine can mitigate hepatotoxicity and progression to liver failure. This article describes a 16-year-old girl who ingested a large dose of extra-strength acetaminophen, and how the 150 rule was used in her management.


Assuntos
Acetaminofen/efeitos adversos , Acetaminofen/toxicidade , Overdose de Drogas/diagnóstico , Overdose de Drogas/etiologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/prevenção & controle , Acetaminofen/farmacocinética , Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Adolescente , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Falência Hepática Aguda/tratamento farmacológico
19.
J Med Chem ; 61(17): 7589-7613, 2018 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-30141927

RESUMO

Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.


Assuntos
Vesícula Biliar/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Tiazolidinas/química , Animais , Cães , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/química , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Células HEK293 , Humanos , Células Madin Darby de Rim Canino , Masculino , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-Atividade
20.
J Med Imaging (Bellingham) ; 5(1): 013504, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29430474

RESUMO

This work concerns the validation of the Kyoto-Kagaku thorax anthropomorphic phantom Lungman for use in chest radiography optimization. The equivalence in terms of polymethyl methacrylate (PMMA) was established for the lung and mediastinum regions of the phantom. Patient chest examination data acquired under automatic exposure control were collated over a 2-year period for a standard x-ray room. Parameters surveyed included exposure index, air kerma area product, and exposure time, which were compared with Lungman values. Finally, a voxel model was developed by segmenting computed tomography images of the phantom and implemented in PENELOPE/penEasy Monte Carlo code to compare phantom tissue-equivalent materials with materials from ICRP Publication 89 in terms of organ dose. PMMA equivalence varied depending on tube voltage, from 9.5 to 10.0 cm and from 13.5 to 13.7 cm, for the lungs and mediastinum regions, respectively. For the survey, close agreement was found between the phantom and the patients' median values (deviations lay between 8% and 14%). Differences in lung doses, an important organ for optimization in chest radiography, were below 13% when comparing the use of phantom tissue-equivalent materials versus ICRP materials. The study confirms the value of the Lungman for chest optimization studies.

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