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1.
Proc Natl Acad Sci U S A ; 116(50): 25278-25286, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767763

RESUMO

Surface protein layers (S-layers) often form the only structural component of the archaeal cell wall and are therefore important for cell survival. S-layers have a plethora of cellular functions including maintenance of cell shape, osmotic, and mechanical stability, the formation of a semipermeable protective barrier around the cell, and cell-cell interaction, as well as surface adhesion. Despite the central importance of S-layers for archaeal life, their 3-dimensional (3D) architecture is still poorly understood. Here we present detailed 3D electron cryomicroscopy maps of archaeal S-layers from 3 different Sulfolobus strains. We were able to pinpoint the positions and determine the structure of the 2 subunits SlaA and SlaB. We also present a model describing the assembly of the mature S-layer.


Assuntos
Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/ultraestrutura , Sulfolobus/metabolismo , Microscopia Crioeletrônica , Dimerização , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Sulfolobus/química , Sulfolobus/genética , Sulfolobus/ultraestrutura
2.
Environ Sci Policy ; 128: 347-358, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34867081

RESUMO

Extreme heat events are the deadliest weather-related event in the United States. Cities throughout the United States have worked to develop heat adaptation strategies to limit the impact of extreme heat on vulnerable populations. However, the COVID-19 pandemic presented unprecedented challenges to local governments. This paper provides a preliminary review of strategies and interventions used to manage compound COVID-19-extreme heat events in the 25 most populous cities of the United States. Heat adaptation strategies employed prior to the COVID-19 pandemic were not adequate to meet during the co-occurring compound hazard of COVID-19-EHE. Long-term climate-adaptation strategies will require leveraging physical, financial, and community resources across multiple city departments to meet the needs of compound hazards, such as COVID-19 and extreme heat.

3.
Nucleic Acids Res ; 45(7): 3875-3887, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28160601

RESUMO

The PcrA/UvrD helicase functions in multiple pathways that promote bacterial genome stability including the suppression of conflicts between replication and transcription and facilitating the repair of transcribed DNA. The reported ability of PcrA/UvrD to bind and backtrack RNA polymerase (1,2) might be relevant to these functions, but the structural basis for this activity is poorly understood. In this work, we define a minimal RNA polymerase interaction domain in PcrA, and report its crystal structure at 1.5 Å resolution. The domain adopts a Tudor-like fold that is similar to other RNA polymerase interaction domains, including that of the prototype transcription-repair coupling factor Mfd. Removal or mutation of the interaction domain reduces the ability of PcrA/UvrD to interact with and to remodel RNA polymerase complexes in vitro. The implications of this work for our understanding of the role of PcrA/UvrD at the interface of DNA replication, transcription and repair are discussed.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , DNA Helicases/química , DNA Helicases/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Aminoácidos/química , Geobacillus stearothermophilus/enzimologia , Modelos Moleculares , Ligação Proteica , Elongação da Transcrição Genética , Domínio Tudor
4.
Malar J ; 17(1): 220, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29859081

RESUMO

BACKGROUND: Reactive case detection (RACD) is an active case finding strategy where households and neighbours of a passively identified case (index case) are screened to identify and treat additional malaria infections with the goal of gathering surveillance information and potentially reducing further transmission. Although it is widely considered a key strategy in low burden settings, little is known about the costs and the cost-effectiveness of different diagnostic methods used for RACD. The aims of this study were to measure the cost of conducting RACD and compare the cost-effectiveness of microscopy to the more sensitive diagnostic method loop-mediated isothermal amplification (LAMP). METHODS: The study was conducted in RACD surveillance sites in five sub-districts in Aceh Besar, Indonesia. The cost inputs and yield of implementing RACD with microscopy and/or LAMP were collected prospectively over a 20 months study period between May 2014 and December 2015. Costs and cost-effectiveness (USD) of the different strategies were examined. The main cost measures were cost per RACD event, per person screened, per population at risk (PAR); defined as total population in each sub-district, and per infection found. The main cost-effectiveness measure was incremental cost-effectiveness ratio (ICER), expressed as cost per malaria infection detected by LAMP versus microscopy. The effects of varying test positivity rate or diagnostic yield on cost per infection identified and ICER were also assessed. RESULTS: Among 1495 household members and neighbours screened in 36 RACD events, two infections were detected by microscopy and confirmed by LAMP, and four infections were missed by microscopy but detected by LAMP. The average total cost of conducting RACD using microscopy and LAMP was $1178 per event with LAMP-specific consumables and personnel being the main cost drivers. The average cost of screening one individual during RACD was $11, with an additional cost of diagnostics at $0.62 and $16 per person for microscopy and LAMP, respectively. As a public health intervention, RACD using both diagnostics cost an average of $0.42 per PAR per year. Comparing RACD using microscopy only versus RACD using LAMP only, the cost per infection found was $8930 and $6915, respectively. To add LAMP as an additional intervention accompanying RACD would cost $9 per individual screened annually in this setting. The ICER was estimated to be $5907 per additional malaria infection detected by LAMP versus microscopy. Cost per infection identified and ICER declined with increasing test positivity rate and increasing diagnostic yield. CONCLUSIONS: This study provides the first estimates on the cost and cost-effectiveness of RACD from a low transmission setting. Costs per individual screened were high, though costs per PAR were low. Compared to microscopy, the use of LAMP in RACD was more costly but more cost-effective for the detection of infections, with diminishing returns observed when findings were extrapolated to scenarios with higher prevalence of infection using more sensitive diagnostics. As malaria programmes consider active case detection and the integration of more sensitive diagnostics, these findings may inform strategic and budgetary planning.


Assuntos
Testes Diagnósticos de Rotina/economia , Testes Diagnósticos de Rotina/métodos , Malária/diagnóstico , Plasmodium/isolamento & purificação , Análise Custo-Benefício , Humanos , Indonésia , Malária/transmissão , Microscopia/economia , Microscopia/métodos , Técnicas de Amplificação de Ácido Nucleico/economia , Técnicas de Amplificação de Ácido Nucleico/métodos , Plasmodium/classificação
5.
Environ Sci Technol ; 52(11): 6695-6703, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29738237

RESUMO

The United States (US) energy system is a large water user, but the nature of that use is poorly understood. To support resource comanagement and fill this noted gap in the literature, this work presents detailed estimates for US-based water consumption and withdrawals for the US energy system as of 2014, including both intensity values and the first known estimate of total water consumption and withdrawal by the US energy system. We address 126 unit processes, many of which are new additions to the literature, differentiated among 17 fuel cycles, five life cycle stages, three water source categories, and four levels of water quality. Overall coverage is about 99% of commercially traded US primary energy consumption with detailed energy flows by unit process. Energy-related water consumption, or water removed from its source and not directly returned, accounts for about 10% of both total and freshwater US water consumption. Major consumers include biofuels (via irrigation), oil (via deep well injection, usually of nonfreshwater), and hydropower (via evaporation and seepage). The US energy system also accounts for about 40% of both total and freshwater US water withdrawals, i.e., water removed from its source regardless of fate. About 70% of withdrawals are associated with the once-through cooling systems of approximately 300 steam cycle power plants that produce about 25% of US electricity.


Assuntos
Abastecimento de Água , Água , Ingestão de Líquidos , Água Doce , Centrais Elétricas , Estados Unidos
6.
Environ Sci Technol ; 50(8): 4537-45, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-26967826

RESUMO

The US power sector is a leading contributor of emissions that affect air quality and climate. It also requires a lot of water for cooling thermoelectric power plants. Although these impacts affect ecosystems and human health unevenly in space and time, there has been very little quantification of these environmental trade-offs on decision-relevant scales. This work quantifies hourly water consumption, emissions (i.e., carbon dioxide, nitrogen oxides, and sulfur oxides), and marginal heat rates for 252 electricity generating units (EGUs) in the Electric Reliability Council of Texas (ERCOT) region in 2011 using a unit commitment and dispatch model (UC&D). Annual, seasonal, and daily variations, as well as spatial variability are assessed. When normalized over the grid, hourly average emissions and water consumption intensities (i.e., output per MWh) are found to be highest when electricity demand is the lowest, as baseload EGUs tend to be the most water and emissions intensive. Results suggest that a large fraction of emissions and water consumption are caused by a small number of power plants, mainly baseload coal-fired generators. Replacing 8-10 existing power plants with modern natural gas combined cycle units would result in reductions of 19-29%, 51-55%, 60-62%, and 13-27% in CO2 emissions, NOx emissions, SOx emissions, and water consumption, respectively, across the ERCOT region for two different conversion scenarios.


Assuntos
Poluição do Ar/prevenção & controle , Conservação dos Recursos Naturais , Eletricidade , Modelos Teóricos , Centrais Elétricas , Poluição do Ar/estatística & dados numéricos , Dióxido de Carbono/análise , Carvão Mineral/análise , Conservação dos Recursos Naturais/estatística & dados numéricos , Gás Natural/análise , Óxidos de Nitrogênio/análise , Reprodutibilidade dos Testes , Estações do Ano , Análise Espaço-Temporal , Dióxido de Enxofre/análise , Texas
7.
Stem Cells ; 32(10): 2605-15, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24898611

RESUMO

The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). In EBs, expression of mesodermal and endodermal markers is also delayed. However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation.


Assuntos
Acetilglucosamina/metabolismo , Diferenciação Celular/genética , Células-Tronco Embrionárias/citologia , Epigênese Genética , Animais , Diferenciação Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Epigênese Genética/efeitos dos fármacos , Glicosilação/efeitos dos fármacos , Camundongos , N-Acetilglucosaminiltransferases/antagonistas & inibidores , N-Acetilglucosaminiltransferases/metabolismo , Fosforilação/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos
8.
Environ Sci Technol ; 49(1): 51-66, 2015 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-25486256

RESUMO

Electricity generation often requires large amounts of water, most notably for cooling thermoelectric power generators and moving hydroelectric turbines. This so-called "electricity-water nexus" has received increasing attention in recent years by governments, nongovernmental organizations, industry, and academics, especially in light of increasing water stress in many regions around the world. Although many analyses have attempted to project the future water requirements of electricity generation, projections vary considerably due to differences in temporal and spatial boundaries, modeling frameworks, and scenario definitions. This manuscript is intended to provide a critical review of recent publications that address the future water requirements of electricity production and define the factors that will moderate the water requirements of the electric grid moving forward to inform future research. The five variables identified include changes in (1) fuel consumption patterns, (2) cooling technology preferences, (3) environmental regulations, (4) ambient climate conditions, and (5) electric grid characteristics. These five factors are analyzed to provide guidance for future research related to the electricity-water nexus.


Assuntos
Eletricidade , Fontes Geradoras de Energia , Tecnologia/métodos , Abastecimento de Água , Meio Ambiente , Água Doce , Centrais Elétricas
9.
Malar J ; 13: 24, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24443824

RESUMO

BACKGROUND: Countries in the Asia Pacific region have made great progress in the fight against malaria; several are rapidly approaching elimination. However, malaria control programmes operating in elimination settings face substantial challenges, particularly around mobile migrant populations, access to remote areas and the diversity of vectors with varying biting and breeding behaviours. These challenges can be addressed through subnational collaborations with commercial partners, such as mining or plantation companies, that can conduct or support malaria control activities to cover employees. Such partnerships can be a useful tool for accessing high-risk populations and supporting malaria elimination goals. METHODS: This observational qualitative case study employed semi-structured key informant interviews to describe partnerships between the Malaysian Malaria Control Programme (MCP), and private palm oil, rubber and acacia plantations in the state of Sabah. Semi-structured interview guides were used to examine resource commitments, incentives, challenges, and successes of the collaborations. RESULTS: Interviews with workers from private plantations and the state of Sabah MCP indicated that partnerships with the commercial sector had contributed to decreases in incidence at plantation sites since 1991. Several plantations contribute financial and human resources toward malaria control efforts and all plantations frequently communicate with the MCP to help monitor the malaria situation on-site. Management of partnerships between private corporations and government entities can be challenging, as prioritization of malaria control may change with annual profits or arrival of new management. CONCLUSIONS: Partnering with the commercial sector has been an essential operational strategy to support malaria elimination in Sabah. The successes of these partnerships rely on a common understanding that elimination will be a mutually beneficial outcome for employers and the general public. Best practices included consistent communication, developing government-staffed subsector offices for malaria control on-site, engaging commercial plantations to provide financial and human resources for malaria control activities, and the development of new worker screening programmes. The successes and challenges associated with partnerships between the public and commercial sector can serve as an example for other malaria-eliminating countries with large plantation sectors, and may also be applied to other sectors that employ migrant workers or have commercial enterprises in hard to reach areas.


Assuntos
Malária/prevenção & controle , Saúde Pública/métodos , Parcerias Público-Privadas , Agricultura Florestal , Governo , Humanos , Malásia , Saúde Pública/economia , Inquéritos e Questionários
10.
Environ Sci Technol ; 48(12): 7128-34, 2014 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-24832169

RESUMO

We utilize a unit commitment and dispatch model to estimate how water use fees on power generators would affect dispatching and water requirements by the power sector in the Electric Reliability Council of Texas' (ERCOT) electric grid. Fees ranging from 10 to 1000 USD per acre-foot were separately applied to water withdrawals and consumption. Fees were chosen to be comparable in cost to a range of water supply projects proposed in the Texas Water Development Board's State Water Plan to meet demand through 2050. We found that these fees can reduce water withdrawals and consumption for cooling thermoelectric power plants in ERCOT by as much as 75% and 23%, respectively. To achieve these water savings, wholesale electricity generation costs might increase as much as 120% based on 2011 fuel costs and generation characteristics. We estimate that water saved through these fees is not as cost-effective as conventional long-term water supply projects. However, the electric grid offers short-term flexibility that conventional water supply projects do not. Furthermore, this manuscript discusses conditions under which the grid could be effective at "supplying" water, particularly during emergency drought conditions, by changing its operational conditions.


Assuntos
Temperatura Baixa , Centrais Elétricas/economia , Abastecimento de Água/economia , Água , Análise Custo-Benefício , Eletricidade , Fontes Geradoras de Energia/economia , Texas
11.
Phys Ther ; 104(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38513257

RESUMO

A clinical practice guideline on telerehabilitation was developed by an American Physical Therapy Association volunteer guideline development group consisting of international physical therapists and physiotherapists, a physician, and a consumer. The guideline was based on systematic reviews of current scientific literature, clinical information, and accepted approaches to telerehabilitation in physical therapist practice. Seven recommendations address the impact of, preparation for, and implementation of telerehabilitation in physical therapist practice. Research recommendations identify current gaps in knowledge. Overall, with shared decision-making between clinicians and patients to inform patients of service delivery options, direct and indirect costs, barriers, and facilitators of telerehabilitation, the evidence supports the use of telerehabilitation by physical therapists for both examination and intervention. The Spanish and Chinese versions of this clinical practice guideline, as well as the French version of the recommendations, are available as supplementary material (Suppl. Materials).


Assuntos
Telerreabilitação , Humanos , Estados Unidos , Especialidade de Fisioterapia/normas , Modalidades de Fisioterapia/normas , Fisioterapeutas
12.
Elife ; 132024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251732

RESUMO

Surface layers (S-layers) are resilient two-dimensional protein lattices that encapsulate many bacteria and most archaea. In archaea, S-layers usually form the only structural component of the cell wall and thus act as the final frontier between the cell and its environment. Therefore, S-layers are crucial for supporting microbial life. Notwithstanding their importance, little is known about archaeal S-layers at the atomic level. Here, we combined single-particle cryo electron microscopy, cryo electron tomography, and Alphafold2 predictions to generate an atomic model of the two-component S-layer of Sulfolobus acidocaldarius. The outer component of this S-layer (SlaA) is a flexible, highly glycosylated, and stable protein. Together with the inner and membrane-bound component (SlaB), they assemble into a porous and interwoven lattice. We hypothesise that jackknife-like conformational changes in SlaA play important roles in S-layer assembly.


Assuntos
Sulfolobus acidocaldarius , Sulfolobus acidocaldarius/metabolismo , Archaea , Bactérias , Parede Celular
13.
Artigo em Inglês | MEDLINE | ID: mdl-38523132

RESUMO

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE. METHODS: We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted January 2018 - June 2022 were included. Patients on prehospital anticoagulants, history of inherited bleeding disorder, and who died within the first 24 hours were excluded. Statin users were matched to non-users by statin use indications including age, current heart and cardiovascular conditions and history, hyperlipidemia, injury severity, and body mass index. Time to in-hospital statin initiation and occurrence of VTE and other complications within 60 days were collected. Differences between groups were determined by univariate, multivariable logistic regression, and Cox proportional hazard analyses. RESULTS: Of 3,062 eligible patients, 79 were statin users that were matched to 79 non-users. There were no differences in admissions demographics, vital signs, injury pattern, transfusion volumes, lengths of stay, or mortality between groups. The overall VTE incidence was 10.8% (17/158). Incidence of VTE in statin users was significantly lower (3%) than non-users (19%; P = 0.003). Differences between statin users and non-users were observed for rates of DVT (0% vs 9%), PE (3% vs 15%), and sepsis (0% vs 5%). Exposure to statins was associated with an 82% decreased risk of developing VTE (hazard ratio = 0.18, 95% CI 0.04 - 0.86; P = 0.033). CONCLUSIONS: Statin exposure was associated with decline in VTE and lower individual rates of DVT, PE, and sepsis. Our findings indicate that statins should be evaluated further as a possible adjunctive therapy for VTE chemoprophylaxis after traumatic injury. LEVEL OF EVIDENCE AND STUDY TYPE: Level III, Retrospective Cohort Study.

14.
Malar J ; 12: 358, 2013 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-24103345

RESUMO

BACKGROUND: Moving from malaria control to elimination requires national malaria control programmes to implement strategies to detect both symptomatic and asymptomatic cases in the community. In order to do this, malaria elimination programmes follow up malaria cases reported by health facilities to carry out case investigations that will determine the origin of the infection, whether it has been imported or is due to local malaria transmission. If necessary, the malaria programme will also carry out active surveillance to find additional malaria cases in the locality to prevent further transmission. To understand current practices and share information on malaria elimination strategies, a survey specifically addressing country policies on case investigation and reactive case detection was carried out among fourteen countries of the Asia Pacific Malaria Elimination Network (APMEN). METHODS: A questionnaire was distributed to the malaria control programme managers amongst 14 countries in the Asia Pacific who have national or sub-national malaria elimination goals. RESULTS: Results indicate that there are a wide variety of case investigation and active case detection activities employed by the 13 countries that responded to the survey. All respondents report conducting case investigation as part of surveillance activities. More than half of these countries conduct investigations for each case. Over half aim to accomplish the investigation within one to two days of a case report. Programmes collect a broad array of demographic data during investigation procedures and definitions for imported cases are varied across respondents. Some countries report intra-national (from a different province or district) importation while others report only international importation (from a different country). Reactive case detection in respondent countries is defined as screening households within a pre-determined radius in order to identify other locally acquired infections, whether symptomatic or asymptomatic. Respondents report that reactive case detection can be triggered in different ways, in some cases with only a single case report and in others if a defined threshold of multiple cases occurs. The spatial range of screening conducted varies from a certain number of households to an entire administrative unit (e g, village). Some countries target symptomatic people whereas others target all people in order to detect asymptomatic infections. The majority of respondent programmes collect a range of information from those screened for malaria, similar to the range of information collected during case investigation. CONCLUSION: Case investigation and reactive case detection are implemented in the malaria elimination programmes in the Asia Pacific, however practices vary widely from country to country. There is little evidence available to support countries in deciding which methods to maintain, change or adopt for improved effectiveness and efficiency. The development and use of common evaluation metrics for these activities will allow malaria programmes to assess performance and results of resource-intensive surveillance measures and may benefit other countries that are considering implementing these activities.


Assuntos
Erradicação de Doenças , Métodos Epidemiológicos , Malária/diagnóstico , Malária/prevenção & controle , Sudeste Asiático , Política de Saúde , Humanos , Ilhas do Pacífico , Inquéritos e Questionários
15.
Shock ; 60(5): 637-645, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37647085

RESUMO

ABSTRACT: Background: Tissue trauma and hemorrhage result in pronounced activation of the innate immune system. Given known crosstalk between inflammation and coagulation, soluble inflammatory mediators could be associated with venous thromboembolisms (VTEs) after major trauma. Objectives : This study aimed to identify plasma inflammatory mediators that are independent predictors of VTE risk in trauma patients. Methods: We performed a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios (PROPPR) study. Plasma levels of 27 cytokines/chemokines were measured by Bio-Plex at admission and 2, 4, 6, 12, 24, 48, and 72 h later. Patients who died from exsanguination or within 24 h were excluded. Mann-Whitney tests were performed to assess no-VTE and VTE groups at each time point. Multivariable logistic regression was used to determine the adjusted effects of inflammatory mediators on VTE risk. Results: Eighty-six of the 575 patients (15%) included developed VTE. Interleukin (IL)-1ra, IL-6, IL-8, IL-10, eotaxin, granulocyte colony-stimulating factor, interferon-γ-inducible protein, monocyte chemoattractant protein 1 (MCP-1), and chemokine ligand 5 (regulated on activation, normal T cell expressed and secreted) were all significantly increased among VTE patients. Multivariable analyses demonstrated that IL-6, IL-8, interferon-γ-inducible protein, and MCP-1 were independently associated with VTE. Cox proportional hazards modeling identified IL-6, IL-8, and MCP-1 as independent predictors of accelerated VTE development. We identified significant correlations between inflammation and markers of coagulation and endothelial activation. Conclusion: Sustained systemic inflammation is a key driver of VTE risk after major trauma. Therapeutics targeting innate immune activation should be considered for development of future multimodal strategies to augment current VTE prophylaxis.


Assuntos
Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Interferon gama , Interleucina-6 , Interleucina-8 , Quimiocinas/metabolismo , Inflamação , Mediadores da Inflamação
16.
Surgery ; 174(2): 376-381, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37270299

RESUMO

BACKGROUND: Venous thromboembolism is a leading cause of morbidity after trauma. Endothelial cells are essential regulators of coagulation. Although endothelial cell dysregulation is widely reported after trauma, the link between endothelial injury and venous thromboembolism has not been reported. METHODS: We conducted a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios study. Deaths from hemorrhage or within 24 hours were excluded. Venous thromboembolism was diagnosed by duplex ultrasound or chest computed tomography. Endothelial markers soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 were measured in plasma by enzyme-linked immunosorbent assay and compared over the first 72 hours from admission using the Mann-Whitney test. Multivariable logistic regression assessed the adjusted effects of endothelial markers on venous thromboembolism risk. RESULTS: Of 575 patients enrolled, 86 developed venous thromboembolism (15%). The median time to venous thromboembolism was 6 days ([Q1, Q3], [4, 13]). No differences were identified in demographics or injury severity. Soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 showed significant increases over time among patients who developed venous thromboembolism compared to those who did not. Using the last available values, patients were stratified into high and low-soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 groups. Multivariable analyses revealed an independent association between elevated soluble endothelial protein c receptor and venous thromboembolism risk (odds ratio 1.63; 95% confidence interval 1.01, 2.63; P = .04). Cox proportional hazards modeling demonstrated a strong yet nonsignificant trend between elevated soluble endothelial protein c receptor and time to venous thromboembolism. CONCLUSION: Plasma markers of endothelial injury, particularly soluble endothelial protein c receptor, are strongly associated with trauma-related venous thromboembolism. Therapeutics targeting endothelial function could mitigate the incidence of venous thromboembolism after trauma.


Assuntos
Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Trombomodulina , Sindecana-1 , Estudos Prospectivos , Receptor de Proteína C Endotelial , Células Endoteliais
17.
BMJ Open ; 13(1): e067210, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707110

RESUMO

INTRODUCTION: As of July 2022, a little over one-third of Guatemalans were fully vaccinated. While COVID-19 vaccination rates are not officially reported nationally by racial/ethnic groups, non-governmental organisations and reporters have observed that COVID-19 vaccination rates are especially low among high-risk Indigenous populations. We conducted one of the first studies on COVID-19 vaccine acceptance in Indigenous populations in the Central Highlands of Guatemala, which aimed to better understand the barriers to COVID-19 vaccine uptake and how to improve vaccine promotional campaigns. METHODS: In November 2021, we conducted eight focus group discussions (FGDs) with 42 Indigenous men and women and 16 in-depth interviews (IDIs) with community health workers, nurses and physicians in Chimaltenango and Sololá. Using a participatory design approach, our qualitative analysis used constant comparative methods to understand the inductive and deductive themes from the FGD and IDI transcripts. RESULTS: We found three major overarching barriers to vaccination within the sampled population: (1) a lack of available easily understandable, linguistically appropriate and culturally sensitive COVID-19 vaccine information; (2) vaccine access and supply issues that prevented people from being vaccinated efficiently and quickly; and (3) widespread misinformation and disinformation that prey on people's fears of the unknown and mistrust of the medical establishment and government. CONCLUSION: When developing COVID-19 vaccine messages, content should be culturally relevant, appropriate for low-literacy populations and in the languages that people prefer to speak. Promotional materials should be in multiple modalities (print, radio and social media) and also have specific Maya cultural references (dress, food and concepts of disease) to ensure messaging connects with intended targets. This study supports the need for more robust research into best practices for communicating about COVID-19 vaccines to marginalised communities globally and suggests that policy makers should invest in targeted local solutions to increase vaccine uptake.


Assuntos
COVID-19 , Vacinas , Masculino , Feminino , Humanos , Vacinas contra COVID-19 , Guatemala , COVID-19/prevenção & controle , Vacinação , Povos Indígenas
18.
Environ Int ; 173: 107824, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36809710

RESUMO

BACKGROUND: Significant mortality and morbidity in pregnant women and their offspring are linked to premature rupture of membranes (PROM). Epidemiological evidence for heat-related PROM risk is extremely limited. We investigated associations between acute heatwave exposure and spontaneous PROM. METHODS: We conducted this retrospective cohort study among mothers in Kaiser Permanente Southern California who experienced membrane ruptures during the warm season (May-September) from 2008 to 2018. Twelve definitions of heatwaves with different cut-off percentiles (75th, 90th, 95th, and 98th) and durations (≥ 2, 3, and 4 consecutive days) were developed using the daily maximum heat index, which incorporates both daily maximum temperature and minimum relative humidity in the last gestational week. Cox proportional hazards models were fitted separately for spontaneous PROM, term PROM (TPROM), and preterm PROM (PPROM) with zip codes as the random effect and gestational week as the temporal unit. Effect modification by air pollution (i.e., PM2.5 and NO2), climate adaptation measures (i.e., green space and air conditioning [AC] penetration), sociodemographic factors, and smoking behavior was examined. RESULTS: In total, we included 190,767 subjects with 16,490 (8.6%) spontaneous PROMs. We identified a 9-14% increase in PROM risks associated with less intense heatwaves. Similar patterns as PROM were found for TPROM and PPROM. The heat-related PROM risks were greater among mothers exposed to a higher level of PM2.5 during pregnancy, under 25 years old, with lower education and household income level, and who smoked. Even though climate adaptation factors were not statistically significant effect modifiers, mothers living with lower green space or lower AC penetration were at consistently higher heat-related PROM risks compared to their counterparts. CONCLUSION: Using a rich and high-quality clinical database, we detected harmful heat exposure for spontaneous PROM in preterm and term deliveries. Some subgroups with specific characteristics were more susceptible to heat-related PROM risk.


Assuntos
Calor Extremo , Ruptura Prematura de Membranas Fetais , Recém-Nascido , Humanos , Gravidez , Feminino , Adulto , Estudos Retrospectivos , Ruptura Prematura de Membranas Fetais/epidemiologia , California/epidemiologia , Material Particulado
20.
BMJ Open ; 12(12): e066365, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36523220

RESUMO

OBJECTIVES: To evaluate the impact of culturally and linguistically tailored informational videos delivered via social media campaigns on COVID-19 vaccine uptake in Indigenous Maya communities in Guatemala. METHODS: Our team designed a series of videos utilising community input and evaluated the impact using a pre-post intervention design. In-person preintervention surveys were collected from a sample of respondents in four rural municipalities in Guatemala in March 2022. Facebook, Instagram and browser ads were flooded with COVID-19 vaccine informational videos in Spanish, Kaqchikel and Kiche for 3 weeks. Postintervention surveys were conducted by telephone among the same participants in April 2022. Logistic regression models were used to estimate the OR of COVID-19 vaccine uptake following exposure to the intervention videos. RESULTS: Preintervention and postintervention surveys were collected from 1572 participants. The median age was 28 years; 63% (N=998) identified as women, and 36% spoke an Indigenous Mayan language. Twenty-one per cent of participants (N=327) reported watching the intervention content on social media. At baseline, 89% (N=1402) of participants reported having at least one COVID-19 vaccine, compared with 97% (N=1507) in the follow-up. Those who reported watching the videos had 1.78 times the odds (95% CI 1.14 to 2.77) of getting vaccinated after watching the videos compared with those who did not see the videos when adjusted by age, community, sex and language. CONCLUSION: Our findings suggest that culturally and linguistically tailored videos addressing COVID-19 vaccine misinformation deployed over social media can increase vaccinations in a rural, indigenous population in Guatemala, implying that social media content can influence vaccination uptake. Providing accurate, culturally sensitive information in local languages from trusted sources may help increase vaccine uptake in historically marginalised populations.


Assuntos
COVID-19 , Mídias Sociais , Feminino , Humanos , Adulto , Vacinas contra COVID-19 , Guatemala , COVID-19/prevenção & controle , Povos Indígenas
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