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CASE SUMMARY: The patient is a 42-year-old female who presented with a de novo missense variant in the PRPS1 gene. Her phenotype includes asymmetric retinal dystrophy with sensory esotropia, congenital sensorineural hearing loss, neuropathy, and severe tremors with recent-onset ataxia. This contributes a new presentation of ophthalmic and neurological findings to the literature.
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Background: The pursuit of selective therapeutic delivery to target tissue types represents a key goal in the treatment of a range of adverse health issues, including diseases afflicting the heart. The development of new cardiac-specific ligands is a crucial step towards effectively targeting therapeutics to the heart. Methods: Utilizing an ex vivo and in vivo SELEX approaches, we enriched a library of 2'-fluoro modified aptamers for ventricular cardiomyocyte specificity. Lead candidates were identified from this library, and their binding and internalization into cardiomyocytes was evaluated in both ex vivo and in vivo mouse studies. Results: The ex vivo and in vivo SELEX processes generated an aptamer library with significant cardiac specificity over non-cardiac tissues such as liver and skeletal muscle. Our lead candidate aptamer from this library, CA1, demonstrates selective in vivo targeting and delivery of a fluorophore cargo to ventricular cardiomyocytes within the murine heart, while minimizing off-target localization to non-cardiac tissues, including the liver. By employing a novel RNase-based assay to evaluate aptamer interactions with cardiomyocytes, we discovered that CA1 predominantly internalizes into ventricular cardiomyocytes; conversely, another candidate CA41 primarily binds to the cardiomyocyte cell surface. Conclusions: These findings suggest that CA1 and CA41 have the potential to be promising candidates for targeted drug delivery and imaging applications in cardiac diseases.
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The intricate molecular environment of the native membrane profoundly influences every aspect of membrane protein (MP) biology. Despite this, the most prevalent method of studying MPs uses detergent-like molecules that disrupt and remove this vital local membrane context. This severely impedes our ability to quantitatively decipher the local molecular context and comprehend its regulatory role in the structure, function, and biogenesis of MPs. Using a library of membrane-active polymers we have developed a platform for the high-throughput analysis of the membrane proteome. The platform enables near-complete spatially resolved extraction of target MPs directly from their endogenous membranes into native nanodiscs that maintain the local membrane context. We accompany this advancement with an open-access database that quantifies the polymer-specific extraction variability for 2065 unique mammalian MPs and provides the most optimized condition for each of them. Our method enables rapid and near-complete extraction and purification of target MPs directly from their endogenous organellar membranes at physiological expression levels while maintaining the nanoscale local membrane environment. Going beyond the plasma membrane proteome, our platform enables extraction from any target organellar membrane including the endoplasmic reticulum, mitochondria, lysosome, Golgi, and even transient organelles such as the autophagosome. To further validate this platform, we took several independent MPs and demonstrated how our resource can enable rapid extraction and purification of target MPs from different organellar membranes with high efficiency and purity. Further, taking two synaptic vesicle MPs, we show how the database can be extended to capture multiprotein complexes between overexpressed MPs. We expect these publicly available resources to empower researchers across disciplines to efficiently capture membrane 'nano-scoops' containing a target MP and interface with structural, functional, and other bioanalytical approaches. We demonstrate an example of this by combining our extraction platform with single-molecule TIRF imaging to demonstrate how it can enable rapid determination of homo-oligomeric states of target MPs in native cell membranes.
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We use the implementation science framework RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) to describe outcomes of In Our DNA SC, a population-wide genomic screening (PWGS) program. In Our DNA SC involves participation through clinical appointments, community events, or at home collection. Participants provide a saliva sample that is sequenced by Helix, and those with a pathogenic variant or likely pathogenic variant for CDC Tier 1 conditions are offered free genetic counseling. We assessed key outcomes among the first cohort of individuals recruited. Over 14 months, 20,478 participants enrolled, and 14,053 samples were collected. The majority selected at-home sample collection followed by clinical sample collection and collection at community events. Participants were predominately female, White (self-identified), non-Hispanic, and between the ages of 40-49. Participants enrolled through community events were the most racially diverse and the youngest. Half of those enrolled completed the program. We identified 137 individuals with pathogenic or likely pathogenic variants for CDC Tier 1 conditions. The majority (77.4%) agreed to genetic counseling, and of those that agreed, 80.2% completed counseling. Twelve clinics participated, and we conducted 108 collection events. Participants enrolled at home were most likely to return their sample for sequencing. Through this evaluation, we identified facilitators and barriers to implementation of our state-wide PWGS program. Standardized reporting using implementation science frameworks can help generalize strategies and improve the impact of PWGS.
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Aconselhamento Genético , Ciência da Implementação , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , GenômicaRESUMO
The oligomeric organization of membrane proteins in native cell membranes is a critical regulator of their function. High-resolution quantitative measurements of oligomeric assemblies and how they change under different conditions are indispensable to understanding membrane protein biology. We report Native-nanoBleach, a total internal reflection fluorescence microscopy-based single-molecule photobleaching step analysis technique to determine the oligomeric distribution of membrane proteins directly from native membranes at an effective spatial resolution of ~10 nm. We achieved this by capturing target membrane proteins in native nanodiscs with their proximal native membrane environment using amphipathic copolymers. We applied Native-nanoBleach to quantify the oligomerization status of structurally and functionally diverse membrane proteins, including a receptor tyrosine kinase (TrkA) and a small GTPase (KRas) under growth-factor binding and oncogenic mutations, respectively. Our data suggest that Native-nanoBleach provides a sensitive, single-molecule platform to quantify membrane protein oligomeric distributions in native membranes under physiologically and clinically relevant conditions.
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Proteínas de Membrana , Proteínas de Membrana/química , Membrana Celular/metabolismoRESUMO
During recent decades, there has been a growing consideration of the role of blue and green spaces on mental health of children, but there is insufficient attention in the literature to the mental health of children with disabilities. This paper presents an overview of the evidence on how blue and green spaces affect the mental health of children with various disabilities. A database search found twenty studies eligible for the review, after several consecutive screening stages. Most studies used a cross-sectional design and were carried out in Europe. The results consistently indicate that blue and green space can reduce emotional, behavioral, and social problems in disabled children. A protective association was found between the level of blue or greenness and depressive and anxiety symptoms. Moreover, in most of the studies there were no significant changes in the result after adjusting for socioeconomic confounders. Generally, there is an identified need for more short-term exposure studies in this area, focusing on the impact of landscape design elements on mental health of disabled children. The findings of this scoping review call on urban planners, health care workers and decision makers to consider appropriate measures and interventions providing more blue and green space exposure to disabled children.
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Crianças com Deficiência , Saúde Mental , Criança , Humanos , Parques Recreativos , Estudos Transversais , Europa (Continente)RESUMO
Freshwater (inland) blue space environments provide a range of public health benefits to visitors. However, health related exposure outcomes are dynamic and can vary depending on several factors, including the environmental characteristics of freshwater environments and their surroundings. Developing and managing inland blue spaces to promote health and wellbeing therefore requires an understanding of whether specific freshwater attributes, and prevailing weather conditions, enhance or devalue landscape aesthetics. The aim of this study was to utilise a mixed-methods research approach to investigate aesthetic preferences of inland blue spaces. A three-phase data collection method was adopted involving (i) analysis of a national-scale landscape image dataset; in combination with (ii) a national-scale online survey; and (iii) a series of in-person focus groups. We found environmental characteristics associated with the waterbody itself, as well as the characteristics of the nearby green space, to have a significant impact on the overall aesthetic appeal of inland blue spaces. Strong preference was demonstrated for inland blue spaces perceived to be of a high environmental quality and which have a natural, rather than human-modified, appearance. The findings highlight the need to conserve the quality of both the waterbody and waterside environment to encourage frequent recreational use and maintain the beneficial public health outcomes associated with inland blue spaces.
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Native mass spectrometry (nMS) has emerged as a key analytical tool to study the organizational states of proteins and their complexes with both endogenous and exogenous ligands. Specifically, for membrane proteins, it provides a key analytical dimension to determine the identity of bound lipids and to decipher their effects on the observed structural assembly. We recently developed an approach to study membrane proteins directly from intact and tunable lipid membranes where both the biophysical properties of the membrane and its lipid compositions can be customized. Extending this, we use our liposome-nMS platform to decipher the lipid specificity of membrane proteins through their multiorganelle trafficking pathways. To demonstrate this, we used VAMP2 and reconstituted it in the endoplasmic reticulum (ER), Golgi, synaptic vesicle (SV), and plasma membrane (PM) mimicking liposomes. By directly studying VAMP2 from these customized liposomes, we show how the same transmembrane protein can bind to different sets of lipids in different organellar-mimicking membranes. Considering that the cellular trafficking pathway of most eukaryotic integral membrane proteins involves residence in multiple organellar membranes, this study highlights how the lipid-specificity of the same integral membrane protein may change depending on the membrane context. Further, leveraging the capability of the platform to study membrane proteins from liposomes with curated biophysical properties, we show how we can disentangle chemical versus biophysical properties, of individual lipids in regulating membrane protein assembly.
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Lipossomos , Lipídeos de Membrana , Lipídeos de Membrana/química , Lipossomos/química , Proteína 2 Associada à Membrana da Vesícula , Espectrometria de MassasRESUMO
Hierarchical organization of integral membrane proteins (IMP) and lipids at the membrane is essential for regulating myriad downstream signaling. A quantitative understanding of these processes requires both detections of oligomeric organization of IMPs and lipids directly from intact membranes and determination of key membrane components and properties that regulate them. Addressing this, we have developed a platform that enables native mass spectrometry (nMS) analysis of IMP-lipid complexes directly from intact and customizable lipid membranes. Both the lipid composition and membrane properties (such as curvature, tension, and fluidity) of these bilayers can be precisely customized to a target membrane. Subsequent direct nMS analysis of these intact proteolipid vesicles can yield the oligomeric states of the embedded IMPs, identify bound lipids, and determine the membrane properties that can regulate the observed IMP-lipid organization. Applying this method, we show how lipid binding regulates neurotransmitter release and how membrane composition regulates the functional oligomeric state of a transporter.
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Lipídeos , Proteínas de Membrana , Espectrometria de Massas/métodos , Transporte Biológico , Lipídeos/química , Proteínas de Membrana/química , Bicamadas Lipídicas/químicaRESUMO
The oligomeric organization of membrane proteins in native cell membranes is a critical regulator of their function. High-resolution quantitative measurements of oligomeric assemblies and how they change under different conditions are indispensable to the understanding of membrane protein biology. We report a single-molecule imaging technique (Native-nanoBleach) to determine the oligomeric distribution of membrane proteins directly from native membranes at an effective spatial resolution of â¼10 nm. We achieved this by capturing target membrane proteins in "native nanodiscs" with their proximal native membrane environment using amphipathic copolymers. We established this method using structurally and functionally diverse membrane proteins with well-established stoichiometries. We then applied Native-nanoBleach to quantify the oligomerization status of a receptor tyrosine kinase (TrkA) and a small GTPase (KRas) under conditions of growth-factor binding or oncogenic mutations, respectively. Native-nanoBleach provides a sensitive, single-molecule platform to quantify membrane protein oligomeric distributions in native membranes at an unprecedented spatial resolution.
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OBJECTIVE: Enhanced Recovery ERP protocols (ERP) have improved surgical outcomes in patients undergoing elective colon cancer (CC) surgery; however, efficacy in different populations may vary. We examined the impact of an ERP in a population with high rates of obesity and multiple comorbidities. METHODS: We performed a retrospective analysis of factors associated with postoperative complications (PoC) and length of stay (LOS) following CC surgery from 2011 to 2019 in a 5-hospital healthcare system which serves a population with higher rates of obesity (body mass index ≥30kg/m2) and multi-comorbidities, as compared to published studies. Univariable and multivariable analyses were performed. RESULTS: A total of 408 elective CC surgery patients with complete oncologic surgical data were identified. Of these, 191 (46.81%) were under ERP. Factors independently associated with PoC included obesity (OR=1.66, P=.029), laparoscopic (OR=.52, P=.020), and hybrid (OR=.38, P=.012) versus open surgery and ASA (American Society of Anesthesiologists) class ≥3 (OR=1.98, P=.006). ERP did not impact PoC but was associated with a reduction in LOS (ß=-1.02 days, 95%CI: -1.75 - -.30, P=.006). ERP had an impact on LOS in both the non-obese and obese groups (P<.001 and P=.034, respectively). PoC significantly increased LOS (ß=6.67 days, 95%CI: 5.41-7.03, P<.001). CONCLUSIONS: Following elective CC surgery, obesity and medical comorbidities were associated with increased PoC and in turn, as expected, increased LOS. ERP was associated with a reduction in LOS in both obese and non-obese patients. In high-risk populations, application of ERP may be particularly important to optimize surgical outcomes following CC surgery.
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Neoplasias do Colo , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/complicações , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Obesidade/complicações , Tempo de InternaçãoRESUMO
BACKGROUND: Despite prophylaxis, deep vein thrombosis (DVT) and pulmonary embolism remain dreaded complications following traumatic injury and are associated with significant morbidity and mortality. Screening ultrasound (US) protocols have been employed in trauma centers for early detection of lower extremity (LE) deep venous thrombosis. We hypothesized that screening lower extremity venous duplex US would not prove cost effective in our trauma population who receives early pharmacologic prophylaxis. METHODS: Data was collected for one year on all adult trauma patients admitted to the trauma service from December 2019 to 2020. DVT screening US was obtained at 3 days after admission for patients with long bone or pelvic fracture, spinal cord injury, immobility, and/or spinal fracture requiring surgery. Screening US was obtained at 7 days for all others and repeated weekly until discharge. Data was retrospectively collected and analyzed. RESULTS: Exactly 1365 patients met inclusion criteria with median ISS 12 (IQR, 9-17), median age 56 (IQR, 36-73 years), and with majority blunt injuries (90.7%). A total of 1369 screening US were performed finding 27 DVTs (2%). The total cost of screening for the year analyzed amounted to over $270,000 with 50.7 screening US needed to detect 1 DVT. This resulted in an average screening cost of over $10,000 for the detection of a single DVT. DISCUSSION: In trauma patients receiving early pharmacologic prophylaxis, routine LE screening US protocols to detect LE DVT are not cost effective.
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Fraturas Ósseas , Trombose Venosa , Adulto , Análise Custo-Benefício , Fraturas Ósseas/complicações , Fraturas Ósseas/diagnóstico por imagem , Humanos , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/complicações , Trombose Venosa/etiologiaRESUMO
BACKGROUND: Platelet dysfunction is known to occur in patients with traumatic brain injury (TBI), and the correction of platelet dysfunction may prevent hemorrhagic progression in TBI. Thromboelastography with platelet mapping (TEG-PM; Haemonetics) evaluates the degree of platelet function inhibition through the adenosine diphosphate (ADP) and arachidonic acid (AA) pathways. We hypothesized that ADP and AA inhibition would improve with the transfusion of platelets in patients with TBI. METHODS: A retrospective review was conducted at a Level I trauma center of all patients presenting with TBI from December 2019 to December 2020. Per a practice management guideline, a platelet mapping assay was obtained on all patients with TBI upon admission. If ADP or AA was found to be inhibited (>60%), the patient was transfused 1 unit of platelets and a repeat platelet mapping assay was ordered. Demographic data, laboratory values, and outcomes were analyzed. RESULTS: Over the 13-month study period, 453 patients with TBI underwent TEG-PM with a protocol adherence rate of 66.5% resulting in a total of 147 patients who received platelets for ADP and/or AA inhibition; of those, 107 underwent repeat TEG-PM after platelets were administered. With the administration of platelets, ADP (p < 0.0001), AA (p < 0.0001), and MA (p = 0.0002) all significantly improved. Of 330 patients with TBI not taking antiplatelet medications, 50.9% showed inhibition in ADP and/or AA. If AA or ADP inhibition was noted on admission, mortality was increased (p = 0.0108). If ADP improved with platelet administration, the need for neurosurgical intervention was noted to decrease (p = 0.0182). CONCLUSION: Patients with TBI and platelet inhibition may benefit from the administration of platelets to correct platelet dysfunction. Thromboelastography with platelet mapping may be implemented in the initial workup of patients presenting with TBI to assess platelet dysfunction and provide prognostic information, which may guide treatment. LEVEL OF EVIDENCE: Therapeutic / Care Management, level III.
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Transtornos Plaquetários , Lesões Encefálicas Traumáticas , Difosfato de Adenosina , Ácido Araquidônico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/cirurgia , Humanos , Transfusão de Plaquetas , Tromboelastografia/métodosRESUMO
BackgroundAcross the World Health Organization European Region, there are few estimates of the proportion of people seeking medical care for influenza-like illness or acute respiratory infections and who have laboratory-confirmed seasonal influenza infection.MethodsWe conducted a meta-analysis of data extracted from studies published between 2004 and 2017 and from sentinel data from the European surveillance system (TESSy) between 2004 and 2018. We pooled within-season estimates by influenza type/subtype, setting (outpatient (OP)/inpatient (IP)) and age group to estimate the proportion of people tested who have laboratory-confirmed and medically-attended seasonal influenza in Europe.ResultsIn the literature review, the pooled proportion for all influenza types was 33% (95% confidence interval (CI): 30-36), higher among OP 36% (95% CI: 33-40) than IP 24% (95% CI: 20-29). Pooled estimates for all influenza types by age group were: 0-17 years, 26% (22-31); 18-64 years, 41% (32-50); ≥ 65 years, 33% (27-40). From TESSy data, 33% (31-34) of OP and 24% (21-27) of IP were positive. The highest proportion of influenza A was in people aged 18-64 years (22%, 16-29). By subtype, A(H1N1)pdm09 was highest in 18-64 year-olds (16%, 11-21%) whereas A(H3N2) was highest in those ≥ 65 years (10%, 2-22). For influenza B, the highest proportion of infections was in those aged 18-64 years (15%, 9-24).ConclusionsLaboratory-confirmed influenza accounted for approximately one third of all acute respiratory infections for which medical care was sought during the influenza season.
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Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Laboratórios , Estações do Ano , Vigilância de Evento Sentinela , Organização Mundial da SaúdeRESUMO
Pericardial rupture is rare after blunt thoracic trauma and is associated with significant mortality. Mesh repair is recommended to prevent cardiac herniation and strangulation.
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Walkable neighbourhood characteristics, such as connectivity and land use mix, have been found to correlate with people walking more and being active. However, the relationship between the built environment and behaviour is highly complex making it difficult to develop generalisable and predictive models. This paper reports qualitative findings from 21 in-depth interviews conducted with urban residents who had relocated between neighbourhoods of high and low walkability. Participants' preferences are reported within key domains (shop access, green space and travel links). These reveal that walkable characteristics were preferred and desired regardless of whether the participant had moved to a high or low walkable area. We contrast surface preferences with an analysis of relocation stories: complex assemblages of biographical narratives, identity work and cultural representations. The findings reveal how neighbourhood types are consistently associated with life stages and that moving to a suburban home was felt to be a definitive type of relocation in which it was acceptable to put neighbourhood preferences aside. Residential self-selection is not yet properly understood and we recommend studies of relocation stories for examining the sociocultural meanings that are likely to inform relocation decisions.
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Planejamento Ambiental , Caminhada , Ambiente Construído , Humanos , Parques Recreativos , Características de ResidênciaRESUMO
Protein prenylation involves the attachment of one or two isoprenoid group(s) onto cysteine residues positioned near the C-terminus. This modification is essential for many signal transduction processes. In this work, the use of the probe C15AlkOPP for metabolic labeling and identification of prenylated proteins in a variety of cell lines and primary cells is explored. Using a single isoprenoid analogue, 78 prenylated protein groups from the three classes of prenylation substrates were identified including three novel prenylation substrates in a single experiment. Applying this method to three brain-related cell lines including neurons, microglia, and astrocytes showed substantial overlap (25%) in the prenylated proteins identified. In addition, some unique prenylated proteins were identified in each type. Eight proteins were observed exclusively in neurons, five were observed exclusively in astrocytes and three were observed exclusively in microglia, suggesting their unique roles in these cells. Furthermore, inhibition of farnesylation in primary astrocytes revealed the differential responses of farnesylated proteins to an FTI. Importantly, these results provide a list of 19 prenylated proteins common to all the cell lines studied here that can be monitored using the C15AlkOPP probe as well as a number of proteins that were observed in only certain cell lines. Taken together, these results suggest that this chemical proteomic approach should be useful in monitoring the levels and exploring the underlying role(s) of prenylated proteins in various diseases.
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Encéfalo/metabolismo , Prenilação de Proteína , Proteoma/metabolismo , Proteômica/métodos , Alcinos/química , Animais , Astrócitos/metabolismo , Encéfalo/citologia , Células COS , Células Cultivadas , Chlorocebus aethiops , Células HeLa , Humanos , Espectrometria de Massas/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismoRESUMO
AIMS: Patients with chronic kidney disease (CKD) are also susceptible to periodontitis. The causal link between periodontitis and CKD may be mediated via systemic inflammation/oxidative stress. Using structural equation modelling (SEM), this cross-sectional study aimed to explore the causal relationship between periodontal inflammation (PI) and renal function. MATERIALS AND METHODS: Baseline data on 770 patients with stage 3-5 (pre-dialysis) CKD from an ongoing cohort study were used. Detailed, bioclinical data on PI and renal function, as well as potential confounders and mediators of the relationship between the two, were collected. SEMs of increasing complexity were created to test the causal assumption that PI affects renal function and vice versa. RESULTS: Structural equation modelling confirmed the assumption that PI and renal function are causally linked, mediated by systemic oxidative stress. The magnitude of this effect was such that a 10% increase in PI resulted in a 3.0% decrease in renal function and a 10% decrease in renal function resulted in a 25% increase in PI. CONCLUSIONS: Periodontal inflammation represents an occult source of oxidative stress in patients with CKD. Further clinical studies are needed to confirm whether periodontal therapy, as a non-pharmacological approach to reducing systemic inflammatory/oxidative stress burden, can improve outcomes in CKD.
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Periodontite , Insuficiência Renal Crônica , Estudos de Coortes , Estudos Transversais , Humanos , Inflamação/complicações , Estresse Oxidativo , Periodontite/complicações , Insuficiência Renal Crônica/complicaçõesRESUMO
Oil spill accidents are a major concern for aquatic organisms. In recent history, the Deepwater Horizon blowout spilled 500 million liters of crude oil into the Gulf of Mexico. Corexit 9500A was used to disperse the oil since it was the method approved at that time, despite safety concerns about its use. A better solution is necessary for dispersing oil from spills that reduces the toxicity to exposed aquatic organisms. To address this challenge, novel engineered nanoparticles were designed using silica cores grafted with hyperbranched poly(glycidol) branches. Because the silica core and polymers are known to be biocompatible, we hypothesized that these particles are nontoxic to fathead minnows (Pimephales promelas) and would decrease their exposure to oil polyaromatic hydrocarbons. Fathead minnow embryos, juveniles and adult stages were exposed to the particles alone or in combination with a water-accommodated fraction of oil. Acute toxicity of nanoparticles to fish was tested by measuring mortality. Sub-lethal effects were also measured including gene expression of cytochrome P450 1a (cyp1a) mRNA and heart rate in embryos. In addition, a mixture of particles plus the water-accommodated fraction was directly introduced to adult female fathead minnows by gavage. Three different nanoparticle concentrations were used (2, 10, and 50 mg/L) in either artificial fresh water or the water-accommodated fraction of the oil. In addition, nanoparticle-free controls were carried out in the two solutions. No significant mortality was observed for any age group or nanoparticle concentration, suggesting the safety of the nanoparticles. In the presence of the water-accommodated fraction alone, juvenile and adult fathead minnows responded by increasing expression of cyp1a. The addition of nanoparticles to the water-accommodated fraction reduced cyp1a gene expression in treatments. Heart rate was also restored to normal parameters in embryos co-exposed to nanoparticles and to the water-accommodated fraction. Measurement of polyaromatic hydrocarbons confirmed their presence in the tested solutions and the reduction of available PAH in WAF treated with the nanoparticles. Our findings suggest the engineered nanoparticles may be protecting the fish by sequestering polyaromatic hydrocarbons from oil, measured indirectly by the induction of cypa1 mRNAs. Furthermore, chemical analysis showed a reduction in PAH content in the water accommodated fraction with the presence of nanoparticles.
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Cyprinidae/metabolismo , Nanopartículas/toxicidade , Poluição por Petróleo/análise , Dióxido de Silício/toxicidade , Testes de Toxicidade , Animais , Cyprinidae/embriologia , Cyprinidae/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Golfo do México , Frequência Cardíaca/efeitos dos fármacos , Micelas , Nanopartículas/química , Petróleo/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Dióxido de Silício/química , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: Influenza virus infections are common and lead to substantial morbidity and mortality worldwide. We characterized the first eight influenza epidemics since the 2009 influenza pandemic by describing the distribution of viruses and epidemics temporally and geographically across the WHO European Region. METHODS: We retrospectively analyzed laboratory-confirmed influenza detections in ambulatory patients from sentinel sites. Data were aggregated by reporting entity and season (weeks 40-20) for 2010-2011 to 2017-2018. We explored geographical spread using correlation coefficients. RESULTS: There was variation in the regional influenza epidemics during the study period. Influenza A virus subtypes alternated in dominance, except for 2013-2014 during which both cocirculated, and only one season (2017-2018) was B virus dominant. The median start week for epidemics in the Region was week 50, the time to the peak ranged between four and 13 weeks, and the duration of the epidemic ranged between 19 and 25 weeks. There was evidence of a west-to-east spread across the Region during epidemics in 2010-2011 (r = .365; P = .019), 2012-2013 (r = .484; P = .001), 2014-2015 (r = .423; P = .006), and 2017-2018 (r = .566; P < .001) seasons. Variation in virus distribution and timing existed within reporting entities across seasons and across reporting entities for a given season. CONCLUSIONS: Aggregated influenza detection data from sentinel surveillance sites by season between 2010 and 2018 have been presented for the European Region for the first time. Substantial diversity exists between influenza epidemics. These data can inform prevention and control efforts at national, sub-national, and international levels. Aggregated, regional surveillance data from early affected reporting entities may provide an early warning function and be helpful for early season forecasting efforts.