Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 331
Filtrar
1.
Sci Transl Med ; 16(747): eadl4497, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748771

RESUMO

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography (nOCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The nOCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using nOCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. nOCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.


Assuntos
Artérias Cerebrais , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Artérias Cerebrais/diagnóstico por imagem , Microscopia/métodos , Miniaturização , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos
2.
Pediatr Neurol ; 155: 55-61, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38608551

RESUMO

BACKGROUND: To examine the association between race, ethnicity, and parental educational attainment on tic-related outcomes among Tourette Syndrome (TS) participants in the Tourette Association of America International Consortium for Genetics (TAAICG) database. METHODS: 723 participants in the TAAICG dataset aged ≤21 years were included. The relationships between tic-related outcomes and race and ethnicity were examined using linear and logistic regressions. Parametric and nonparametric tests were performed to examine the association between parental educational attainment and tic-related outcomes. RESULTS: Race and ethnicity were collapsed as non-Hispanic white (N=566, 88.0%) versus Other (N=77, 12.0%). Tic symptom onset was earlier by 1.1 years (P < 0.0001) and TS diagnosis age was earlier by 0.9 years (P = 0.0045) in the Other group (versus non-Hispanic white). Sex and parental education as covariates did not contribute to the differences observed in TS diagnosis age. There were no significant group differences observed across the tic-related outcomes in parental education variable. CONCLUSIONS: Our study was limited by the low number of nonwhite or Hispanic individuals in the cohort. Racial and ethnic minoritized groups experienced an earlier age of TS diagnosis than non-Hispanic white individuals. Tic severity did not differ between the two groups, and parental educational attainment did not affect tic-related outcomes. There remain significant disparities and gaps in knowledge regarding TS and associated comorbid conditions. Our study suggests the need for more proactive steps to engage individuals with tic disorders from all racial and ethnic minoritized groups to participate in research studies.


Assuntos
Determinantes Sociais da Saúde , Síndrome de Tourette , Humanos , Masculino , Feminino , Adolescente , Criança , Adulto Jovem , Pré-Escolar , Escolaridade , Adulto , Pais , Estados Unidos , Etnicidade
3.
medRxiv ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38260551

RESUMO

Background and Objective: Tourette Syndrome (TS) and Persistent Motor or Vocal Tic Disorders (PMVT) are more prevalent in males (vs. females). Females with TS may have a delay in diagnosis, and more complex tic features (vs. males). With respect to comorbidities, obsessive-compulsive disorder (OCD) is more prevalent in females; attention-deficit hyperactivity disorder (ADHD) is more prevalent in males. Less is known about sex differences in PMVT. This study analyzes sex differences in outcomes among individuals with TS and PMVT in the Tourette Association of America International Consortium for Genetics dataset (TAAICG). Design/Methods: Data from 2403 individuals (N=2109 TS; N=294 PMVT) from the TAAICG were analyzed to explore the relationship between sex and TS or PMVT outcomes: age at tic onset; age at diagnosis; time-to-diagnosis; tic severity; and comorbidity rates. Regression models were adjusted for age and family relationships to examine the impact of sex on outcomes. Results: Females with TS (25.5% of the sample) had a later age of symptom onset (6.5±2.8 vs. 6.0±2.7; p=0.001), later age at diagnosis (13.3±11.2 vs. 10.7±8.1; p=0.0001), and a longer time-to-diagnosis [3 (1,7) vs. 2 (1,5), p=0.01] than males. The total Yale-Global Tic Severity Scale (YGTSS) was lower in females with TS (28.4±9.1 vs. 30.7±8.7); p<0.0001); OCD was slightly more prevalent in females (55% vs. 48.7%; p=0.01) although OCD severity did not differ by sex; ADHD was more prevalent in males (55.7% vs 38.9%; p<0.001). Females with TS had 0.46 lower odds of being diagnosed with TS (p<0.00001). Females with PMVT (42.9% of the sample) had an earlier age of symptom onset (7.9±3.3 vs. 8.9±3.7; p=0.05). Motor or vocal tic severity (YGTSS) was not significantly different. OCD, but not ADHD, was more prevalent in females (OCD: 41.9% vs. 22.2%; p<0.001: ADHD:16.5% vs 21.0%; p=0.4). Conclusion: Females with TS are less likely to be formally diagnosed and have a later age of symptom onset, later age at diagnosis, longer time-to-diagnosis, higher prevalence of OCD, and lower prevalence of ADHD (vs. males). Females with PMVT have an earlier age of symptom onset, higher prevalence of OCD, but similar ADHD prevalence rates (vs. males). Females with TS and PMVT may be clinically different than males with TS. Future research is needed to understand differences longitudinally in TS and PMVT.

4.
Obes Surg ; 34(3): 866-873, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38114775

RESUMO

PURPOSE: The first assistant (FA) plays an important role in the operating room for bariatric surgery. The aim of this study was to examine the relationship between the type of FA and operative time (OT) and postoperative outcomes comparing robotic and laparoscopic approaches in bariatric surgery. METHODS AND MATERIALS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) data for 2016-2019 was queried. Log-normal regression was performed to evaluate the association of FAs and OT variations within and between groups. We used logistic regression to examine the relationship between the type of FA and 30-day outcomes across all procedures and approaches. RESULTS: A total of 691,789 patients who underwent robotic (R), and laparoscopic (L) sleeve gastrectomy (SG), Roux-en-Y gastric-bypass (RYGB), and duodenal switch (DS) were included. The percentage variation of OT was higher in the laparoscopic group (L-SG: 8.18%, L-RYGB: 9.88%, and L-DS: 15.00%) compared to the robotic group (R-SG: 2.43%, R-RYGB: 5.76%, and R-DS: 0.80%). There was not a significant difference in 30-day outcomes between laparoscopic and robotic approaches for the same procedures. CONCLUSIONS: The FA was associated with a decreased variability in OT in the robotic cohort compared to the laparoscopic group with no significant difference in complication rates. These results suggest that the robotic approach may decrease the need for skilled FAs in bariatric procedures.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Procedimentos Cirúrgicos Robóticos , Humanos , Obesidade Mórbida/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Melhoria de Qualidade , Resultado do Tratamento , Estudos Retrospectivos , Cirurgia Bariátrica/métodos , Derivação Gástrica/métodos , Laparoscopia/métodos , Gastrectomia/métodos , Acreditação
5.
Chest ; 164(5): e135-e138, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37945195

RESUMO

CASE PRESENTATION: A 28-year-old woman with a history of congenital hip dysplasia was referred for evaluation of recurrent bronchitis. She had undergone left hip replacement with titanium implants 11 years prior to presentation. The patient reported frequent bouts of bronchitis, sinusitis, and left-sided nontender facial swelling that started after the hip replacement surgery. She also reported nail discoloration of her left first toenail 1 year after this procedure, and nail discoloration of her right first toenail 3 years after the procedure. She was treated for onychomycosis without improvement. Review of symptoms was positive for chronic dry cough and facial tenderness but was negative for dyspnea, wheezing, or chest tightness. She previously had been diagnosed with common variable immunodeficiency based on low immunoglobulin levels, and the condition was maintained with monthly IV immunoglobulins but without any improvement or change in the frequency of sinusitis, bronchitis, or facial swelling. She did not use tobacco, and her family history was unremarkable.


Assuntos
Bronquite , Sinusite , Humanos , Feminino , Adulto , Dispneia/diagnóstico , Dispneia/etiologia
6.
Mol Ther Methods Clin Dev ; 31: 101122, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37920238

RESUMO

Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies.

8.
Omega (Westport) ; : 302228231203357, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726936

RESUMO

The typical near-death experience (NDE) is generally understood as an altered state of consciousness in which the experient has the impression of existing as an extrapersonal self out of and/or away from their physical body during real or presumed life-threatening and/or near-death circumstances. This presumed extrapersonal self can sometimes have a perception of being located within the proximity of the physical body whereas at other times it is under the assumption of having ventured to a transcendental location such as an otherworldly realm. The ego, while in this presumed disembodied state, often has the impression of encountering NDE personages such as deceased people, otherworldly spirits, and/or divine beings, especially during transcendental NDEs. However, this paper suggests that all of these noted features are part of a broader recognizable death motif in NDE reports, and provides qualitative examples of different types of this death symbolism for examination and exploration. It then discusses how the death motif in NDE reports possibly indicates a purposeful psychological function to heighten awareness of a threat to life though death symbolism that is meant to boost the desire and resilience to live and survive.

9.
J Neurointerv Surg ; 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37527927

RESUMO

BACKGROUND: Intrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a new intrasaccular device, and compare the findings with the well-established Woven EndoBridge (WEB) device in an animal model of saccular aneurysms. METHODS: In a rabbit model, elastase-induced aneurysms were treated with SEAL Arc (n=11) devices. HF-OCT and DSA were performed after implant and repeated after 12 weeks. Device protrusion and malapposition were assessed at implant time and scored on a binary system. Aneurysm occlusion was assessed at 12 weeks with the WEB Occlusion Scale and dichotomized to complete (A and B) or incomplete (C and D) occlusion. The percentage of neointimal coverage after 12 weeks was quantified using HF-OCT. We compared these data to previously published historical controls treated with the gold-standard WEB device (n=24) in the same model. RESULTS: Aneurysm size and device placement were not significantly different between the two groups. Complete occlusion was demonstrated in 80% of the SEAL Arc devices, which compared favorably to the 21% of the aneurysms treated with WEB devices (P=0.002). Neointimal coverage across SEAL Arc devices was 86±15% compared with 49±27% for WEB (P=0.001). Protruding devices had significantly less neointimal coverage (P<0.001) as did incompletely occluded aneurysms (P<0.001). Histologically, all aneurysms treated with SEAL Arc devices were completely healed. CONCLUSION: Complete early aneurysm occlusion was frequently observed in the SEAL Arc treated aneurysms, with significant neointimal coverage after 12 weeks.

10.
J Neurointerv Surg ; 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37399337

RESUMO

BACKGROUND: Flow diverters carry the risk of thromboembolic complications (TEC). We tested a coating with covalently bound heparin that activates antithrombin to address TEC by locally downregulating the coagulation cascade. We hypothesized that the neuroimaging evidence of TEC would be reduced by the coating. METHODS: 16 dogs were implanted with overlapping flow diverters in the basilar artery, separated into two groups: heparin-coated (n=9) and uncoated (n=7). Following implantation, high-frequency optical coherence tomography (HF-OCT) was acquired to quantify acute thrombus (AT) formation on the flow diverters. MRI was performed postoperatively and repeated at 1, 2, 3, 4, and 8 weeks, consisting of T1-weighted imaging, time-0f-flight (ToF), diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and fluid attenuated inversion recovery (FLAIR) sequences. Neurological examinations were performed throughout the 8-week duration of the study. RESULTS: The mean AT volume on coated devices was lower than uncoated (0.014 vs 0.018 mm3); however, this was not significant (P=0.3). The mean number of foci of magnetic susceptibility artifacts (MSAs) on SWI was significantly different between the uncoated and coated groups at the 1-week follow-up (P<0.02), and remained statistically different throughout the duration of the study. The AT volume showed a direct linear correlation with the MSA count and 80% of the variance in the MSA could be explained by the AT volume (P<0.001). Pathological analysis showed evidence of ischemic injury at locations of MSA. CONCLUSIONS: Heparin-coated flow diverters significantly reduced the number of new MSAs after 1 week follow-up, showing the potential to reduce TEC.

11.
J Neurointerv Surg ; 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37402572

RESUMO

BACKGROUND: Flow diversion has become a standard treatment for cerebral aneurysms. However, major drawbacks include the need for dual antiplatelet therapy after implant and delayed complete occlusion of the aneurysm, which occurs when new tissue growth excludes the aneurysm from the parent artery. Biomimetic surface modifications such as the phosphorylcholine polymer (Shield surface modification) represent major advances in reducing thrombogenicity of these devices. However, in vitro studies have raised concerns that this modification may also delay endothelialization of flow diverters. METHODS: Bare metal Pipeline, Pipeline Shield, and Vantage with Shield devices were implanted in the common carotid arteries (CCAs) of 10 rabbits (two in the left CCA, one in the right CCA). Following implant and at 5, 10, 15, and 30 days, the devices were imaged with high-frequency optical coherence tomography and conventional angiography to evaluate tissue growth. At 30 days the devices were explanted and their endothelial growth was assessed with scanning electron microscopy (SEM) at five locations along their length using a semi-quantitative score. RESULTS: The average tissue growth thickness (ATGT) was not different between the three devices. Neointima was apparent at 5 days and all devices demonstrated similar ATGT at each time point. On SEM, no difference was found in the endothelium scores between the device types. CONCLUSION: In vivo, neither the Shield surface modification nor the device design (Vantage) altered the longitudinal healing of the flow diverter.

12.
J Health Econ Outcomes Res ; 10(2): 1-9, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37485470

RESUMO

Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than localized (ward closure) scenarios, across perspectives. Components of this insurance value match previously published estimates of operational costs and mortality impacts. Conclusions: Insurance value of novel antimicrobials can be systematically modeled and substantially augments their traditional health economic value in normal circumstances. These approaches are generalizable to similar health interventions and form a framework for health systems and governments to capture broader value in health technology assessments, improve healthcare access, and increase resilience by planning for adverse scenarios.

13.
Ann Vasc Surg ; 97: 139-146, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37495093

RESUMO

BACKGROUND: Inefficient clinical workflows can have downstream effects of increased costs, poor resource utilization, and worse patient outcomes. The surgical consultation process can be complex with unclear communication, potentially delaying care for patients requiring time-sensitive intervention in an acute setting. A novel electronic health records (EHR)-based workflow was implemented to improve the consultation process. After implementation, we assessed the impact of this initiative in patients requiring vascular surgery consultation. METHODS: An EHR-driven consultation workflow was implemented at a single institution, standardizing the process across all consulting services. This order-initiated workflow automated notification to clinicians of consult requests, communication of patient data, patient addition to consultants' lists, and tracking consult completion. Preimplementation (1/1/2020-1/31/2022) and postimplementation (2/1/2022-12/4/2022) vascular surgery consultation cohorts were compared to evaluate the impact of this initiative on timeliness of care. RESULTS: There were 554 inpatient vascular surgery consultations (255 preimplementation and 299 postimplementation); 45 and 76 consults required surgery before and after implementation, respectively. The novel workflow resulted in placement of a consult note 32 min faster than preimplementation (preimplementation: 462 min, postimplementation: 430 min, P = 0.001) for all vascular surgery consults. Furthermore, vascular surgery patients with ASA class III or IV status requiring an urgent or emergent operation were transported to the operating room 63.3% faster after implementation of the workflow (preimplementation: 284 min, postimplementation: 180 min, P = 0.02). There were no differences in procedure duration, postoperative disposition, or intraoperative complication rates. CONCLUSIONS: We implemented a novel workflow utilizing the EHR to standardize and automate the consultation process in the acute inpatient setting. This institutional initiative significantly improved timeliness of care for vascular surgery patients, including decreased time to operation. Innovations such as this can be further disseminated across shared EHR platforms across institutions, representing a powerful tool to increase the value of care in vascular surgery and healthcare overall.


Assuntos
Registros Eletrônicos de Saúde , Salas Cirúrgicas , Humanos , Fluxo de Trabalho , Resultado do Tratamento , Encaminhamento e Consulta , Procedimentos Cirúrgicos Vasculares/efeitos adversos
14.
J Clin Neurosci ; 113: 121-125, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37262981

RESUMO

BACKGROUND: Diagnosing and treating acute ischemic stroke patients within a narrow timeframe is challenging. Time needed to access the occluded vessel and initiate thrombectomy is dictated by the availability of information regarding vascular anatomy and trajectory. Absence of such information potentially impacts device selection, procedure success, and stroke outcomes. While the cervical vessels allow neurointerventionalists to navigate devices to the occlusion site, procedures are often encumbered due to tortuous pathways. The purpose of this retrospective study was to determine how neurointerventionalists consider the physical nature of carotid segments when evaluating a procedure's difficulty. METHODS: Seven neurointerventionalists reviewed 3D reconstructions of CT angiograms of left and right carotid arteries from 49 subjects and rated the perceived procedural difficulty on a three-point scale (easy, medium, difficult) to reach the targeted M1. Twenty-two vessel metrics were quantified by dividing the carotids into 5 segments and measuring the radius of curvature, tortuosity, vessel radius, and vessel length of each segment. RESULTS: The tortuosity and length of the arch-cervical and cervical regions significantly impacted difficulty ratings. Additionally, two-way interaction between the radius of curvature and tortuosity on the arch-cervical region was significant (p < 0.0001) wherein, for example, at a given arch-cervical tortuosity, an increased radius of curvature reduced the perceived case difficulty. CONCLUSIONS: Examining the vessel metrics and providing detailed vascular data tailored to patient characteristics may result in better procedure preparation, facilitate faster vessel access time, and improve thrombectomy outcomes. Additionally, documenting these correlations can enhance device design to ensure they suitably function under various vessel conditions.


Assuntos
Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Estudos Retrospectivos , Imageamento Tridimensional , Trombectomia/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/métodos
15.
ASAIO J ; 69(7): e333-e341, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37191472

RESUMO

Lung transplantation survival estimates are traditionally reported as fixed 1-, 5-, and 10-year mortality rates. Alternatively, this study aims to demonstrate how conditional survival models can provide useful prognostic information tailored to the time a recipient has already survived from the date of transplantation. Recipient data was obtained from the Organ Procurement and Transplantation Network database. Data from 24,820 adult recipients over age 18 who received a lung transplant between 2002 and 2017 were included in the study. Five-year observed conditional survival estimates were calculated by recipient age, sex, race, transplant indication, transplant type ( i.e. , single or double), and renal function at the time of transplantation. Significant variability exists in conditional survival following lung transplantation. Each specific recipient characteristic significantly impacted conditional survival during at least one time point in the first 5 years. Younger age and double lung transplantation were the two most positive predictors of improved conditional survival consistently throughout the 5-year study period. Conditional survival in lung transplantation recipients changes over time and across recipient characteristics. Hazards of mortality are not fixed and need to be dynamically evaluated as a function of time. Conditional survival calculations can provide more accurate prognostic predictions than unconditional survival estimates.


Assuntos
Transplante de Coração , Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Adolescente , Sobrevivência de Enxerto , Transplante de Pulmão/efeitos adversos , Transplantados , Taxa de Sobrevida , Estudos Retrospectivos , Doadores de Tecidos
16.
Plant Genome ; 16(4): e20335, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37138544

RESUMO

Wheat (Triticum aestivum L.) is a major source of nutrients for populations across the globe, but the amino acid composition of wheat grain does not provide optimal nutrition. The nutritional value of wheat grain is limited by low concentrations of lysine (the most limiting essential amino acid) and high concentrations of free asparagine (precursor to the processing contaminant acrylamide). There are currently few available solutions for asparagine reduction and lysine biofortification through breeding. In this study, we investigated the genetic architecture controlling grain free amino acid composition and its relationship to other traits in a Robigus × Claire doubled haploid population. Multivariate analysis of amino acids and other traits showed that the two groups are largely independent of one another, with the largest effect on amino acids being from the environment. Linkage analysis of the population allowed identification of quantitative trait loci (QTL) controlling free amino acids and other traits, and this was compared against genomic prediction methods. Following identification of a QTL controlling free lysine content, wheat pangenome resources facilitated analysis of candidate genes in this region of the genome. These findings can be used to select appropriate strategies for lysine biofortification and free asparagine reduction in wheat breeding programs.


Assuntos
Aminoácidos , Triticum , Aminoácidos/genética , Mapeamento Cromossômico , Triticum/genética , Triticum/química , Asparagina/análise , Asparagina/genética , Lisina/genética , Melhoramento Vegetal , Grão Comestível/genética , Reino Unido
17.
Front Plant Sci ; 14: 1140824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37206970

RESUMO

"Mutagenomics" is the combination of random mutagenesis, phenotypic screening, and whole-genome re-sequencing to uncover all tagged and untagged mutations linked with phenotypic changes in an organism. In this study, we performed a mutagenomics screen on the wheat pathogenic fungus Zymoseptoria tritici for altered morphogenetic switching and stress sensitivity phenotypes using Agrobacterium-mediated "random" T-DNA mutagenesis (ATMT). Biological screening identified four mutants which were strongly reduced in virulence on wheat. Whole genome re-sequencing defined the positions of the T-DNA insertion events and revealed several unlinked mutations potentially affecting gene functions. Remarkably, two independent reduced virulence mutant strains, with similarly altered stress sensitivities and aberrant hyphal growth phenotypes, were found to have a distinct loss of function mutations in the ZtSSK2 MAPKKK gene. One mutant strain had a direct T-DNA insertion affecting the predicted protein's N-terminus, while the other possessed an unlinked frameshift mutation towards the C-terminus. We used genetic complementation to restore both strains' wild-type (WT) function (virulence, morphogenesis, and stress response). We demonstrated that ZtSSK2 has a non-redundant function with ZtSTE11 in virulence through the biochemical activation of the stress-activated HOG1 MAPK pathway. Moreover, we present data suggesting that SSK2 has a unique role in activating this pathway in response to specific stresses. Finally, dual RNAseq-based transcriptome profiling of WT and SSK2 mutant strains revealed many HOG1-dependent transcriptional changes in the fungus during early infection and suggested that the host response does not discriminate between WT and mutant strains during this early phase. Together these data define new genes implicated in the virulence of the pathogen and emphasise the importance of a whole genome sequencing step in mutagenomic discovery pipelines.

19.
Molecules ; 28(7)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37049751

RESUMO

The geometries and energetics of the n-vertex polyhedral dicobaltadithiaboranes and dicobaltadiselenaboranes Cp2Co2E2Bn-4Hn-4 (E = S, Se; n = 8 to 12) have been investigated via the density functional theory. Most of the lowest-energy structures in these systems are generated from the (n + 1)-vertex most spherical closo deltahedra by removal of a single vertex, leading to a tetragonal, pentagonal, or hexagonal face depending on the degree of the vertex removed. In all of these low-energy structures, the chalcogen atoms are located at the vertices of the non-triangular face. Alternatively, the central polyhedron in most of the 12-vertex structures can be derived from a Co2E2B8 icosahedron with adjacent chalcogen (E) vertices by breaking the E-E edge and 1 or more E-B edges to create a hexagonal face. Examples of the arachno polyhedra with two tetragonal and/or pentagonal faces derived from the removal of two vertices from isocloso deltahedra were found among the set of lowest-energy Cp2Co2E2Bn-4Hn-4 (E = S, Se; n = 8 and 12) structures.

20.
Heliyon ; 9(4): e14837, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37025889

RESUMO

Background: Infarct volume measured from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices is critical to in vivo stroke models. In this study, we developed an interactive, tunable, software that automatically computes whole-brain infarct metrics from serial TTC-stained brain sections. Methods: Three rat ischemic stroke cohorts were used in this study (Total n = 91 rats; Cohort 1 n = 21, Cohort 2 n = 40, Cohort 3 n = 30). For each, brains were serially-sliced, stained with TTC and scanned on both anterior and posterior sides. Ground truth annotation and infarct morphometric analysis (e.g., brain-Vbrain, infarct-Vinfarct, and non-infarct-Vnon-infarct volumes) were completed by domain experts. We used Cohort 1 for brain and infarct segmentation model development (n = 3 training cases with 36 slices [18 anterior and posterior faces], n = 18 testing cases with 218 slices [109 anterior and posterior faces]), as well as infarct morphometrics automation. The infarct quantification pipeline and pre-trained model were packaged as a standalone software and applied to Cohort 2, an internal validation dataset. Finally, software and model trainability were tested as a use-case with Cohort 3, a dataset from a separate institute. Results: Both high segmentation and statistically significant quantification performance (correlation between manual and software) were observed across all datasets. Segmentation performance: Cohort 1 brain accuracy = 0.95/f1-score = 0.90, infarct accuracy = 0.96/f1-score = 0.89; Cohort 2 brain accuracy = 0.97/f1-score = 0.90, infarct accuracy = 0.97/f1-score = 0.80; Cohort 3 brain accuracy = 0.96/f1-score = 0.92, infarct accuracy = 0.95/f1-score = 0.82. Infarct quantification (cohort average): Vbrain (ρ = 0.87, p < 0.001), Vinfarct (0.92, p < 0.001), Vnon-infarct (0.80, p < 0.001), %infarct (0.87, p = 0.001), and infarct:non-infact ratio (ρ = 0.92, p < 0.001). Conclusion: Tectonic Infarct Analysis software offers a robust and adaptable approach for rapid TTC-based stroke assessment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...