Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 443
Filtrar
1.
Sci Adv ; 10(23): eadn6603, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38838146

RESUMO

Standard zebrafish transgenesis involves random transgene integration with resource-intensive screening. While phiC31 integrase-based attP/attB recombination has streamlined transgenesis in mice and Drosophila, validated attP-based landing sites for universal applications are lacking in zebrafish. Here, we developed phiC31 Integrase Genomic Loci Engineered for Transgenesis (pIGLET) as transgenesis approach, with two attP landing sites pIGLET14a and pIGLET24b from well-validated Tol2 transgenes. Both sites facilitate diverse transgenesis applications including reporters and Cre/loxP transgenes. The pIGLET14a and pIGLET24b landing sites consistently yield 25 to 50% germline transmission, substantially reducing the resources needed for transgenic line generation. Transgenesis into these sites enables reproducible expression patterns in F0 zebrafish embryos for enhancer discovery and testing of gene regulatory variants. Together, our new landing sites streamline targeted, reproducible zebrafish transgenesis as a robust platform for various applications while minimizing the workload for generating transgenic lines.


Assuntos
Animais Geneticamente Modificados , Técnicas de Transferência de Genes , Transgenes , Peixe-Zebra , Animais , Peixe-Zebra/genética , Integrases/genética , Integrases/metabolismo , Sítios de Ligação Microbiológicos/genética
2.
Mol Pharmacol ; 105(5): 348-358, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38423750

RESUMO

Metabotropic glutamate receptor 7 (mGlu7) is the most highly conserved and abundantly expressed mGlu receptor in the human brain. The presynaptic localization of mGlu7, coupled with its low affinity for its endogenous agonist, glutamate, are features that contribute to the receptor's role in modulating neuronal excitation and inhibition patterns, including long-term potentiation, in various brain regions. These characteristics suggest that mGlu7 modulation may serve as a novel therapeutic strategy in disorders of cognitive dysfunction, including neurodevelopmental disorders that cause impairments in learning, memory, and attention. Primary mutations in the GRM7 gene have recently been identified as novel causes of neurodevelopmental disorders, and these patients exhibit profound intellectual and cognitive disability. Pharmacological tools, such as agonists, antagonists, and allosteric modulators, have been the mainstay for targeting mGlu7 in its endogenous homodimeric form to probe effects of its function and modulation in disease models. However, recent research has identified diversity in dimerization, as well as trans-synaptic interacting proteins, that also play a role in mGlu7 signaling and pharmacological properties. These novel findings represent exciting opportunities in the field of mGlu receptor drug discovery and highlight the importance of further understanding the functions of mGlu7 in complex neurologic conditions at both the molecular and physiologic levels. SIGNIFICANCE STATEMENT: Proper expression and function of mGlu7 is essential for learning, attention, and memory formation at the molecular level within neural circuits. The pharmacological targeting of mGlu7 is undergoing a paradigm shift by incorporating an understanding of receptor interaction with other cis- and trans- acting synaptic proteins, as well as various intracellular signaling pathways. Based upon these new findings, mGlu7's potential as a drug target in the treatment of cognitive disorders and learning impairments is primed for exploration.


Assuntos
Disfunção Cognitiva , Receptores de Glutamato Metabotrópico , Humanos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Potenciação de Longa Duração , Receptores de Glutamato Metabotrópico/metabolismo , Transdução de Sinais
3.
bioRxiv ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37090609

RESUMO

Defects in blood development frequently occur among syndromic congenital anomalies. Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets (hypomegakaryocytic thrombocytopenia) and forelimb anomalies, concurrent with more variable heart and kidney defects. TAR syndrome associates with hypomorphic gene function for RBM8A/Y14 that encodes a component of the exon junction complex involved in mRNA splicing, transport, and nonsense-mediated decay. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish rbm8a perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling that controls developmental cell re-arrangements. In hypomorphic rbm8a zebrafish, we observe a significant reduction of cd41-positive thrombocytes. rbm8a-mutant zebrafish embryos accumulate mRNAs with individual retained introns, a hallmark of defective nonsense-mediated decay; affected mRNAs include transcripts for non-canonical Wnt/PCP pathway components. We establish that rbm8a-mutant embryos show convergent extension defects and that reduced rbm8a function interacts with perturbations in non-canonical Wnt/PCP pathway genes wnt5b, wnt11f2, fzd7a, and vangl2. Using live-imaging, we found reduced rbm8a function impairs the architecture of the lateral plate mesoderm (LPM) that forms hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors as affected in TAR Syndrome. Both mutants for rbm8a and for the PCP gene vangl2 feature impaired expression of early hematopoietic/endothelial genes including runx1 and the megakaryocyte regulator gfi1aa. Together, our data propose aberrant LPM patterning and hematopoietic defects as consequence of attenuated non-canonical Wnt/PCP signaling upon reduced rbm8a function. These results also link TAR Syndrome to a potential LPM origin and a developmental mechanism.

4.
bioRxiv ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38106217

RESUMO

Standard methods for transgenesis in zebrafish depend on random transgene integration into the genome followed by resource-intensive screening and validation. Targeted vector integration into validated genomic loci using phiC31 integrase-based attP/attB recombination has transformed mouse and Drosophila transgenesis. However, while the phiC31 system functions in zebrafish, validated loci carrying attP-based landing or safe harbor sites suitable for universal transgenesis applications in zebrafish have not been established. Here, using CRISPR-Cas9, we converted two well-validated single insertion Tol2-based zebrafish transgenes with long-standing genetic stability into two attP landing sites, called phiC31 Integrase Genomic Loci Engineered for Transgenesis (pIGLET). Generating fluorescent reporters, loxP-based Switch lines, CreERT2 drivers, and gene-regulatory variant reporters in the pIGLET14a and pIGLET24b landing site alleles, we document their suitability for transgenesis applications across cell types and developmental stages. For both landing sites, we routinely achieve 25-50% germline transmission of targeted transgene integrations, drastically reducing the number of required animals and necessary resources to generate individual transgenic lines. We document that phiC31 integrase-based transgenesis into pIGLET14a and pIGLET24b reproducibly results in representative reporter expression patterns in injected F0 zebrafish embryos suitable for enhancer discovery and qualitative and quantitative comparison of gene-regulatory element variants. Taken together, our new phiC31 integrase-based transgene landing sites establish reproducible, targeted zebrafish transgenesis for numerous applications while greatly reducing the workload of generating new transgenic zebrafish lines.

5.
Front Cell Dev Biol ; 11: 1204160, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497478

RESUMO

Chronic inflammation is a common feature of aging and numerous diseases such as diabetes, obesity, and autoimmune syndromes and has been linked to the development of hematological malignancy. Blood-forming hematopoietic stem cells (HSC) can contribute to these diseases via the production of tissue-damaging myeloid cells and/or the acquisition of mutations in epigenetic and transcriptional regulators that initiate evolution toward leukemogenesis. We previously showed that the myeloid "master regulator" transcription factor PU.1 is robustly induced in HSC by pro-inflammatory cytokines such as interleukin (IL)-1ß and limits their proliferative activity. Here, we used a PU.1-deficient mouse model to investigate the broader role of PU.1 in regulating hematopoietic activity in response to chronic inflammatory challenges. We found that PU.1 is critical in restraining inflammatory myelopoiesis via suppression of cell cycle and self-renewal gene programs in myeloid-biased multipotent progenitor (MPP) cells. Our data show that while PU.1 functions as a key driver of myeloid differentiation, it plays an equally critical role in tailoring hematopoietic responses to inflammatory stimuli while limiting expansion and self-renewal gene expression in MPPs. These data identify PU.1 as a key regulator of "emergency" myelopoiesis relevant to inflammatory disease and leukemogenesis.

6.
Nat Biomed Eng ; 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37500749

RESUMO

Multimodal sensory feedback from upper-limb prostheses can increase their function and usability. Here we show that intuitive thermal perceptions during cold-object grasping with a prosthesis can be restored in a phantom hand through targeted nerve stimulation via a wearable thin-film thermoelectric device with high cooling power density and speed. We found that specific regions of the residual limb, when thermally stimulated, elicited thermal sensations in the phantom hand that remained stable beyond 48 weeks. We also found stimulation sites that selectively elicited sensations of temperature, touch or both, depending on whether the stimulation was thermal or mechanical. In closed-loop functional tasks involving the identification of cold objects by amputees and by non-amputee participants, and compared with traditional bulk thermoelectric devices, the wearable thin-film device reliably elicited cooling sensations that were up to 8 times faster and up to 3 times greater in intensity while using half the energy and 1/600th the mass of active thermoelectric material. Wearable thin-film thermoelectric devices may allow for the non-invasive restoration of thermal perceptions during touch.

7.
Proc Biol Sci ; 290(2001): 20230584, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37339745

RESUMO

Temporal patterns in spawning and juvenile recruitment can have major effects on population size and the demographic structure of coral reef fishes. For harvested species, these patterns are crucial in determining stock size and optimizing management strategies such as seasonal closures. For the commercially important coral grouper (Plectropomus spp.) on the Great Barrier Reef, histological studies indicate peak spawning around the summer new moons. Here we examine the timing of spawning activity for P. maculatus in the southern Great Barrier Reef by deriving age in days for 761 juvenile fish collected between 2007 and 2022, and back-calculating settlement and spawning dates. Age-length relationships were used to estimate spawning and settlement times for a further 1002 juveniles collected over this period. Unexpectedly, our findings indicate year-round spawning activity generates distinct recruitment cohorts that span several weeks to months. Peak spawning varied between years with no clear association with environmental cues, and little to no alignment with existing seasonal fisheries closures around the new moon. Given the variability and uncertainty in peak spawning times, this fishery may benefit from additional and longer seasonal closures, or alternative fisheries management strategies, to maximize the recruitment contribution from periods of greatest reproductive success.


Assuntos
Antozoários , Bass , Animais , Estações do Ano , Peixes , Recifes de Corais , Pesqueiros , Envelhecimento
8.
Educ Technol Res Dev ; : 1-18, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37359483

RESUMO

The outbreak of the coronavirus disease 2019 (COVID-19) promoted online teaching on an unprecedented scale, raising researchers' attention to the importance of faculty's acceptance of this urgent teaching shift. This study aimed to explore the influence of organizational factors on faculty's acceptance of online teaching in terms of behavioral intention and perceived usefulness. A multilevel structural equation model was employed to analyze data on 209,058 faculty in 858 higher education institutions based on a nationwide survey conducted in mainland China. The results showed that three key organizational factors, namely strategic planning, leadership, and teaching quality monitoring, impacted faculty's acceptance of online teaching, although in different ways. Strategic planning had a direct impact on perceived usefulness, while leadership had a direct impact on behavioral intentions, and teaching quality monitoring had a direct impact on both perceived usefulness and behavioral intentions. In addition, an indirect effect was found between strategic planning and faculty's behavioral intentions through the mediation of the perceived usefulness of online teaching. The findings of this study have practical implications for college administrators and policymakers, which should effectively implement and promote online teaching and learning, and consider key organizational factors to increase faculty acceptance.

9.
Perspect Public Health ; 143(3): 156-172, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37178030

RESUMO

AIM: Socio-economic deprivation encompasses the relative disadvantage experienced by individuals or communities in relation to financial, material or social resources. Nature-based interventions (NBIs) are a public health approach that promote sustainable, healthy communities through engagement with nature and show potential to address inequalities experienced by socio-economically deprived communities. This narrative review aims to identify and evaluate the benefits of NBIs in socio-economically deprived communities. METHOD: A systematic literature search of six electronic publication databases (APA PsycInfo, CENTRAL, CDSR, CINAHL, Medline and Web of Science) was conducted on 5 February 2021 and repeated on 30 August 2022. In total, 3852 records were identified and 18 experimental studies (published between 2015 and 2022) were included in this review. RESULTS: Interventions including therapeutic horticulture, care farming, green exercise and wilderness arts and craft were evaluated in the literature. Key benefits were observed for cost savings, diet diversity, food security, anthropometric outcomes, mental health outcomes, nature visits, physical activity and physical health. Age, gender, ethnicity, level of engagement and perception of environment safety influenced the effectiveness of the interventions. CONCLUSION: Results demonstrate there are clear benefits of NBIs on economic, environmental, health and social outcomes. Further research including qualitative analyses, more stringent experimental designs and use of standardised outcome measures is recommended.


Assuntos
Dieta , Exercício Físico , Humanos , Nível de Saúde , Pobreza
10.
Philos Trans R Soc Lond B Biol Sci ; 378(1878): 20220099, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37066643

RESUMO

Birds in mixed-species flocks benefit from greater foraging efficiency and reduced predation, but also face costs related to competition and activity matching. Because this cost-benefit trade-off is context-dependent (e.g. abiotic conditions and habitat quality), the structure of flocks is expected to vary along elevational, latitudinal and disturbance gradients. Specifically, we predicted that the connectivity and cohesion of flocking networks would (i) decline towards tropical latitudes and lower elevations, where competition and activity matching costs are higher, and (ii) increase with lower forest cover and greater human disturbance. We analysed the structure of 84 flock networks across the Andes and assessed the effect of elevation, latitude, forest cover and human disturbance on network characteristics. We found that Andean flocks are overall open-membership systems (unstructured), though the extent of network structure varied across gradients. Elevation was the main predictor of structure, with more connected and less modular flocks upslope. As expected, flocks in areas with higher forest cover were less cohesive, with better defined flock subtypes. Flocks also varied across latitude and disturbance gradients as predicted, but effect sizes were small. Our findings indicate that the unstructured nature of Andean flocks might arise as a strategy to cope with harsh environmental conditions. This article is part of the theme issue 'Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes'.


Assuntos
Aves , Ecossistema , Animais , Florestas
11.
Mar Pollut Bull ; 191: 114907, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37080018

RESUMO

Climate-induced coral bleaching represents the foremost threat to coral assemblages globally, however bleaching susceptibility varies among and within coral taxa. We compared bleaching susceptibility among 10 coral morpho-taxa and two colony size classes relative to reef-scale bleaching severity at 33 reefs across the Great Barrier Reef and Coral Sea Marine Parks in February-March 2020. Colony size and bleaching severity caused the hierarchy of bleaching susceptibility among taxa to change considerably. Notably, massive Porites shifted from being among the least likely taxa to exhibit bleaching, to among the most susceptible as overall bleaching severity increased. Juvenile corals (≤5 cm diameter) were generally more resistant to bleaching, except for Montipora and Pocillopora colonies, which were more likely to bleach than adults (>5 cm). These findings suggest that colony size and reef-scale bleaching severity are important determinants of bleaching susceptibility among taxa and provide insights into possible shifts in the structure of coral assemblages caused by bleaching events.


Assuntos
Antozoários , Animais , Recifes de Corais , Clima , Austrália
12.
Eur J Public Health ; 33(1): 49-55, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36453890

RESUMO

BACKGROUND: Within the current context of continued austerity and post-pandemic recovery, it remains important that Local Government services address the increasing needs of residents as cost-effectively as possible. Alliancing, whereby services work collaboratively focusing on the 'whole-system', has gained popularity as a tool with the potential to support collaborative whole systems approaches. This synthesis aims to identify how alliancing can be successfully operationalised in the commissioning of public health, wider National Health Service (NHS) and social care-related services. METHODS: A realist literature synthesis was undertaken in order to identify underlying generative mechanisms associated with alliancing, the contextual conditions surrounding the implementation and operationalisation of the alliancing approach mechanisms, and the outcomes produced as a result. An iterative approach was taken, using a recent systematic review of the effectiveness of Alliancing, online database searches, and grey literature searches. RESULTS: Three mechanistic components were identified within the data as being core to the successful implementation of alliances in public health and social care-related services within Local Government: (i) Achieving a system-level approach; (ii) placing local populations at the heart of the system; and (iii) creating a cultural shift. Programme theories were postulated within these components. CONCLUSIONS: The alliancing approach offers an opportunity to achieve system-level change with the potential to benefit local populations. The realist synthesis approach taken within this study has provided insights into the necessary contextual and mechanistic factors of the Alliancing approach, above and beyond effectiveness outcomes typically collected through more conventional evaluation methodologies.


Assuntos
Saúde Pública , Medicina Estatal , Humanos , Governo Local , Projetos de Pesquisa , Grupos Populacionais
13.
Sci Rep ; 12(1): 16831, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207307

RESUMO

Understanding the distribution and abundance of heat tolerant corals across seascapes is imperative for predicting responses to climate change and to support novel management actions. Thermal tolerance is variable in corals and intrinsic and extrinsic drivers of tolerance are not well understood. Traditional experimental evaluations of coral heat and bleaching tolerance typically involve ramp-and-hold experiments run across days to weeks within aquarium facilities with limits to colony replication. Field-based acute heat stress assays have emerged as an alternative experimental approach to rapidly quantify heat tolerance in many samples yet the role of key methodological considerations on the stress response measured remains unresolved. Here, we quantify the effects of coral fragment size, sampling time point, and physiological measures on the acute heat stress response in adult corals. The effect of fragment size differed between species (Acropora tenuis and Pocillopora damicornis). Most physiological parameters measured here declined over time (tissue colour, chlorophyll-a and protein content) from the onset of heating, with the exception of maximum photosynthetic efficiency (Fv/Fm) which was surprisingly stable over this time scale. Based on our experiments, we identified photosynthetic efficiency, tissue colour change, and host-specific assays such as catalase activity as key physiological measures for rapid quantification of thermal tolerance. We recommend that future applications of acute heat stress assays include larger fragments (> 9 cm2) where possible and sample between 10 and 24 h after the end of heat stress. A validated high-throughput experimental approach combined with cost-effective genomic and physiological measurements underpins the development of markers and maps of heat tolerance across seascapes and ocean warming scenarios.


Assuntos
Antozoários , Animais , Antozoários/fisiologia , Catalase , Clorofila , Recifes de Corais , Resposta ao Choque Térmico , Simbiose
14.
Otolaryngol Clin North Am ; 55(4): 859-870, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35752492

RESUMO

Facial feminization surgery (FFS) combines a series of facial bone and soft tissue surgeries to feminize the masculine appearance of the face in a transgender female patient. Jaw reduction surgery is an extremely critical component of FFS and is generally performed in combination with genioplasty. Our technique of jaw reduction involves sagittal resection of the mandible from the angle of the jaw to the mental nerve region. This creates a smooth transition from the ramus to the chin and also retains the integrity of the inner portion of the mandible. We discuss our techniques of jaw reduction surgery in this article.


Assuntos
Procedimentos Cirúrgicos Ortognáticos , Procedimentos de Cirurgia Plástica , Queixo/cirurgia , Feminino , Mentoplastia/métodos , Humanos , Mandíbula/cirurgia , Procedimentos de Cirurgia Plástica/métodos
15.
Br J Neurosci Nurs ; 18(3): 142-145, 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38807712

RESUMO

Stroke remains one of the leading causes of death worldwide. In order to tackle the negative impacts of stroke, a high standard of clinical practice and a commitment to continuous quality improvement is needed across the stroke care pathway. One approach to quality improvement is the formation and implementation of quality improvement collaboratives (QIC's). However, there are several barriers to the implementation of a QIC for stroke care which may impact on their success. This article critically appraises a systematic review which assessed the effectiveness of QIC's for driving improvements in stroke care and explored the barriers to implementing a QIC's to improve care.

16.
Infect Prev Pract ; 3(4): 100186, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34812417

RESUMO

BACKGROUND: Point-of-care (POC) SARS-CoV-2 lateral-flow antigen detection (LFD) testing in the emergency department (ED) could inform rapid infection control decisions but requirements for safe deployment have not been fully defined. METHODS: Review of LFD test results, laboratory and POC-RT-PCR results and ED-performance metrics during a two-week high SARS-CoV-2 prevalence period followed by several months of falling prevalence. AIM: Determine whether LFD testing can be safely deployed in ED to provide an effective universal SARS-CoV-2 testing capability. FINDINGS: 93% (345/371) of COVID-19 patients left ED with a virological diagnosis during the 2-week universal LFD evaluation period compared to 77% with targeted POC-RT-PCR deployment alone, on background of approximately one-third having an NHS Track and Trace RT-PCR test-result at presentation. LFD sensitivity and specificity was 70.7% and 99.1% respectively providing a PPV of 97.7% and NPV of 86.4% with disease prevalence of 34.7%. ED discharge-delays (breaches) attributable to COVID-19 fell to 33/3532 (0.94%) compared with the preceding POC-RT-PCR period (107/4114 (2.6%); p=<0.0001). Importantly, LFD testing identified 1 or 2 clinically-unsuspected COVID-19 patients/day. Three clinically-confirmed LFD false positive patients were appropriately triaged based on LFD action-card flowchart, and only 5 of 95 false-negative LFD results were inappropriately admitted to non-COVID-19 areas where no onward-transmission was identified. LFD testing was restricted to asymptomatic patients when disease prevalence fell below 5% and detected 1-3 cases/week. CONCLUSION: Universal SARS-CoV-2 LFD testing can be safely and effectively deployed in ED alongside POC-RT-PCR testing during periods of high and low disease prevalence.

17.
Sci Rep ; 11(1): 16342, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381102

RESUMO

The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others' policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country's first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.


Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Política de Saúde , Modelos Teóricos , COVID-19/terapia , Dinamarca/epidemiologia , Humanos , Suécia/epidemiologia , Reino Unido/epidemiologia
18.
J Burn Care Res ; 42(5): 1026-1029, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33769492

RESUMO

Paraquat is used throughout the world as an herbicide due to its efficacy and relative safety with proper handling. Accidents and misuse still occur, leading to countries banning its use or employing extra safeguards and special handling certifications. Severe toxicity is primarily associated with ingestion, but skin exposure leads to corrosive injury to the dermis, occurs rapidly, and progresses for up to 24 h. Prolonged skin exposure or the presence of open wounds can lead to systemic absorption. This is the first known report of burn injury and treatment due to secondary exposure to the urine of a patient who had accidental ingestion of paraquat. A 50-year-old Caucasian male presented to the emergency room after accidental ingestion of eight ounces of Gramoxone extra (Paraquat 30% concentration). During the initial care of the patient, the bedside registered nurse was placing an indwelling foley catheter when her forearms were contaminated with urine while wearing basic personal protective equipment (gloves). The registered nurse noticed bullae to bilateral forearms a short time after exposure to the urine. She presented to the burn center for evaluation and treatment. Poison Control was contacted but was unable to offer advise due to a lack of supportive literature. The risk and effects of primary exposure to Paraquat is described throughout the literature and documented in Material Safety Data Sheets (MSDS), but data regarding risk and treatment of secondary exposure is lacking. This case will aid outreach efforts for the prevention and treatment of burn injuries from secondary exposure to paraquat.


Assuntos
Acidentes de Trabalho , Queimaduras Químicas/terapia , Exposição Ocupacional/efeitos adversos , Paraquat/efeitos adversos , Queimaduras Químicas/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Local de Trabalho
19.
Kidney Int ; 99(6): 1392-1407, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33705824

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD), primarily due to PKD1 or PKD2 mutations, causes progressive kidney cyst development and kidney failure. There is significant intrafamilial variability likely due to the genetic background and environmental/lifestyle factors; variability that can be modeled in PKD mice. Here, we characterized mice homozygous for the PKD1 hypomorphic allele, p.Arg3277Cys (Pkd1RC/RC), inbred into the BALB/cJ (BC) or the 129S6/SvEvTac (129) strains, plus F1 progeny bred with the previously characterized C57BL/6J (B6) model; F1(BC/B6) or F1(129/B6). By one-month cystic disease in both the BC and 129 Pkd1RC/RC mice was more severe than in B6 and continued with more rapid progression to six to nine months. Thereafter, the expansive disease stage plateaued/declined, coinciding with increased fibrosis and a clear decline in kidney function. Greater severity correlated with more inter-animal and inter-kidney disease variability, especially in the 129-line. Both F1 combinations had intermediate disease severity, more similar to B6 but progressive from one-month of age. Mild biliary dysgenesis, and an early switch from proximal tubule to collecting duct cysts, was seen in all backgrounds. Preclinical testing with a positive control, tolvaptan, employed the F1(129/B6)-Pkd1RC/RC line, which has moderately progressive disease and limited isogenic variability. Magnetic resonance imaging was utilized to randomize animals and provide total kidney volume endpoints; complementing more traditional data. Thus, we show how genetic background can tailor the Pkd1RC/RC model to address different aspects of pathogenesis and disease modification, and describe a possible standardized protocol for preclinical testing.


Assuntos
Rim Policístico Autossômico Dominante , Animais , Patrimônio Genético , Rim , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética
20.
J Perinatol ; 41(4): 803-813, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33649432

RESUMO

OBJECTIVE: Describe inpatient pulmonary hypertension (PH) treatment and factors associated with therapy at discharge in a multicenter cohort of infants with CDH. METHODS: Six years linked records from Children's Hospitals Neonatal Database and Pediatric Health Information System were used to describe associations between prenatal/perinatal factors, clinical outcomes, echocardiographic findings and PH medications (PHM), during hospitalization and at discharge. RESULTS: Of 1106 CDH infants from 23 centers, 62.8% of infants received PHM, and 11.6% of survivors were discharged on PHM. Survivors discharged on PHM more frequently had intrathoracic liver, small for gestational age, and low 5 min APGARs compared with those discharged without PHM (p < 0.0001). Nearly one-third of infants discharged without PHM had PH on last inpatient echo. CONCLUSIONS: PH medication use is common in CDH. Identification of infants at risk for persistent PH may impact ongoing management. Post-discharge follow-up of all CDH infants with echocardiographic evidence of PH is warranted.


Assuntos
Hérnias Diafragmáticas Congênitas , Hipertensão Pulmonar , Assistência ao Convalescente , Criança , Feminino , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/terapia , Hospitalização , Humanos , Hipertensão Pulmonar/terapia , Lactente , Recém-Nascido , Alta do Paciente , Gravidez , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA