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1.
J Med Screen ; : 9691413241278224, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248023

RESUMO

OBJECTIVE: The psychological consequences of being aware of an increased risk of developing abdominal aortic aneurysm as a first-degree relative of a person with abdominal aortic aneurysm are hitherto unexplored. This study investigates the awareness of heritability and anxiety in male and female adult offspring of abdominal aortic aneurysm patients compared to controls. Health-related quality of life among participants with aortic pathology was compared to participants with normal aortic diameters. METHODS: This was a cross-sectional point prevalence study based on the participants examined in the Detecting Abdominal Aortic Aneurysm in First Degree Relatives Trial (DAAAD; 752 adult offspring, 756 matched controls), 2020-2022. Questionnaires about health-related quality of life and study-specific questions regarding awareness of heritability were collected prior to the aortic ultrasound. RESULTS: Attendance rate was higher among individuals with heredity compared to controls (67% vs. 52%, p < 0.001). Of 1508 adult offspring examined, 65% reported having a close relative with abdominal aortic aneurysm (6% in controls). Female adult offspring reported higher awareness of heritability than controls (38% vs. 12%, p < 0.001), as did males (32% vs. 8%, p < 0.001). A slight majority of participants with awareness reported anxiety (54% of female offspring; 51% of male). There were no measured differences in health-related quality of life between the groups when standard health-related quality of life instruments were used. CONCLUSION: The higher-than-expected proportion of adult offspring with awareness of heritability and anxiety about such risk indicates that we fail to communicate risk to this group appropriately via the current channels of information within the healthcare system. This calls for the development of dedicated strategies for improved communication of abdominal aortic aneurysm risk to patients and their next of kin.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39316070

RESUMO

The interface properties and thermal stability of bismuth (Bi) contacts on molybdenum disulfide (MoS2) shed light on their behavior under various deposition conditions and temperatures. The examination involves extensive techniques including X-ray photoelectron spectroscopy, scanning tunneling microscopy (STM), and scanning tunneling spectroscopy (STS). Bi contacts formed a van der Waals interface on MoS2 regardless of deposition conditions, such as ultrahigh vacuum (UHV, 3 × 10-11 mbar) and high vacuum (HV, 4 × 10-6 mbar), while the oxidation on MoS2 has been observed. However, the semimetallic properties of Bi suppress the impact of defect states, including oxidized-MoS2 and vacancies. Notably, the n-type characteristic of Bi/MoS2 remains unaffected, and no significant changes in the local density of states near the conduction band minimum are observed despite the presence of defects detected by STM and STS. As a result, the Fermi level (EF) resides below the conduction band of MoS2. The study also examines the impact of annealing on the contact interface, revealing no interface reaction between Bi and MoS2 up to 300 °C. These findings enhance our understanding of semimetal (Bi) contacts on MoS2, with implications for improving the performance and reliability of electronic devices.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39251037

RESUMO

OBJECTIVE: Endovascular aneurysm repair (EVAR) has higher long term aneurysm related mortality compared with open surgery, mainly due to aneurysm rupture. Loss of stent graft-vessel apposition at the EVAR sealing zones is a potential cause of post-EVAR rupture. This study aimed to investigate sealing zone failure and its relation to post-EVAR rupture. METHODS: This was a retrospective structured review of pre-operative and post-operative computed tomography (CT) scans of 399 consecutive patients treated with standard bifurcated EVAR. The primary outcome was total loss of seal at last post-operative CT. Secondary outcomes were partial loss of seal, standard follow up detection, post-EVAR rupture, aneurysm sac development, and endoleaks. RESULTS: During a median follow up of 5.3 years, total and partial loss of seal occurred in 85 (21.3%) and 78 (19.5%) patients, respectively. Initial mean sealing zone lengths were within current recommendations but decreased over time, mainly due to vessel dilatation. Mean proximal sealing length at one month CT was 15.5 ± 10.5 mm (95% confidence interval [CI] 12.6 - 18.5 mm) in the group with total loss of seal, 14.3 ± 6.9 mm (95% CI 12.2 - 16.4 mm) with partial loss of seal, and 23.2 ± 7.4 mm (95% CI 22.3 - 24.0 mm) with preserved seal through follow up (p < .001). Mean iliac sealing lengths were 22.4 ± 12.1 mm (95% CI 18.9 - 25.8 mm) if total loss and 21.8 ± 10.0 mm (95% CI 19.6 - 24.0 mm) if partial loss of seal vs. 34.7 ± 12.4 mm (95% CI 33.8 - 35.7 mm) if preserved seal. Larger vessel diameters were associated with loss of seal both in proximal and distal sealing zones. During the study period, 13 post-EVAR ruptures occurred, all preceded by CT findings of total (n = 7) or partial (n = 6) loss of seal. Aneurysm sac expansion was seen in 40% of patients with total loss of seal, 18% with partial loss of seal, and 6.6% with preserved seal. CONCLUSION: Loss of seal after EVAR is frequent and associated with post-EVAR rupture. Increased recommended sealing zones lengths and focus on sealing zones in surveillance may reduce post-EVAR ruptures and aneurysm related mortality.

5.
BMC Plant Biol ; 24(1): 668, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004715

RESUMO

BACKGROUND: Biofortification represents a promising and sustainable strategy for mitigating global nutrient deficiencies. However, its successful implementation poses significant challenges. Among staple crops, wheat emerges as a prime candidate to address these nutritional gaps. Wheat biofortification offers a robust approach to enhance wheat cultivars by elevating the micronutrient levels in grains, addressing one of the most crucial global concerns in the present era. MAIN TEXT: Biofortification is a promising, but complex avenue, with numerous limitations and challenges to face. Notably, micronutrients such as iron (Fe), zinc (Zn), selenium (Se), and copper (Cu) can significantly impact human health. Improving Fe, Zn, Se, and Cu contents in wheat could be therefore relevant to combat malnutrition. In this review, particular emphasis has been placed on understanding the extent of genetic variability of micronutrients in diverse Triticum species, along with their associated mechanisms of uptake, translocation, accumulation and different classical to advanced approaches for wheat biofortification. CONCLUSIONS: By delving into micronutrient variability in Triticum species and their associated mechanisms, this review underscores the potential for targeted wheat biofortification. By integrating various approaches, from conventional breeding to modern biotechnological interventions, the path is paved towards enhancing the nutritional value of this vital crop, promising a brighter and healthier future for global food security and human well-being.


Assuntos
Biofortificação , Desnutrição , Micronutrientes , Triticum , Triticum/metabolismo , Triticum/genética , Micronutrientes/metabolismo , Desnutrição/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Zinco/metabolismo , Valor Nutritivo
6.
medRxiv ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38699341

RESUMO

Children and adolescents with congenital heart disease (CHD) frequently experience neurodevelopmental impairments that can impact academic performance, memory, attention, and behavioral function, ultimately affecting overall quality of life. This study aims to investigate the impact of CHD on functional brain network connectivity and cognitive function. Using resting-state fMRI data, we examined several network metrics across various brain regions utilizing weighted networks and binarized networks with both absolute and proportional thresholds. Regression models were fitted to patient neurocognitive exam scores using various metrics obtained from all three methods. Our results unveil significant differences in network connectivity patterns, particularly in temporal, occipital, and subcortical regions, across both weighted and binarized networks. Furthermore, we identified distinct correlations between network metrics and cognitive performance, suggesting potential compensatory mechanisms within specific brain regions.

7.
Br J Surg ; 111(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38782730

RESUMO

BACKGROUND: Information on the predictive determinants of abdominal aortic aneurysm rupture from CT angiography are scarce. The aim of this study was to investigate biomechanical parameters in abdominal aortic aneurysms and their association with risk of subsequent rupture. METHODS: In this retrospective study, the digital radiological archive was searched for 363 patients with ruptured abdominal aortic aneurysms. All patients who underwent at least one CT angiography examination before aneurysm rupture were included. CT angiography results were analysed to determine maximum aneurysm diameter, aneurysm volume, and biomechanical parameters (peak wall stress and peak wall rupture index). In the primary survival analysis, patients with abdominal aortic aneurysms less than 70 mm were considered. Sensitivity analyses including control patients and abdominal aortic aneurysms of all sizes were performed. RESULTS: A total of 67 patients who underwent 109 CT angiography examinations before aneurysm rupture were identified. The majority were men (47, 70%) and the median age at the time of CTA examination was 77 (71-83) years. The median maximum aneurysm diameter was 56 (interquartile range 46-65) mm and the median time to rupture was 2.13 (interquartile range 0.64-4.72) years. In univariable analysis, maximum aneurysm diameter, aneurysm volume, peak wall stress, and peak wall rupture index were all associated with risk of rupture. Women had an increased HR for rupture when adjusted for maximum aneurysm diameter or aneurysm volume (HR 2.16, 95% c.i. 1.23 to 3.78 (P = 0.007) and HR 1.92, 95% c.i. 1.06 to 3.50 (P = 0.033) respectively). In multivariable analysis, the peak wall rupture index was associated with risk of rupture. The HR for peak wall rupture index was 1.05 (95% c.i. 1.03 to 1.08) per % (P < 0.001) when adjusted for maximum aneurysm diameter and 1.05 (95% c.i. 1.02 to 1.08) per % (P < 0.001) when adjusted for aneurysm volume. CONCLUSION: Biomechanical factors appear to be important in the prediction of abdominal aortic aneurysm rupture. Women are at increased risk of rupture when adjustments are made for maximum aneurysm diameter alone.


Assuntos
Aneurisma da Aorta Abdominal , Ruptura Aórtica , Angiografia por Tomografia Computadorizada , Humanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/patologia , Ruptura Aórtica/etiologia , Ruptura Aórtica/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Feminino , Masculino , Idoso de 80 Anos ou mais , Fatores de Risco , Fatores Sexuais
9.
Plant Physiol Biochem ; 207: 108407, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38340690

RESUMO

Major portion of wheat grain consist of carbohydrate, mainly starch. The proportion of amylose and amylopectin in starch greatly influence the end product quality. Advancement in understanding starch biosynthesis pathway and modulating key genes has enabled the genetic modification of crops resulting in enhanced starch quality. However, the regulation of starch biosynthesis genes still remains unexplored. So, to expand the limited knowledge, here, we characterized a Ser/Thr kinase, SnRK1α in wheat and determined its role in regulating starch biosynthesis. SnRK1 is an evolutionary conserved protein kinase and share homology to yeast SNF1. Yeast complementation assay suggests TaSnRK1α restores growth defect and promotes glycogen accumulation. Domain analysis and complementation assay with truncated domain proteins suggest the importance of ATP-binding and UBA domain in TaSnRK1α activity. Sub-cellular localization identified nuclear and cytoplasmic localization of TaSnRK1α in tobacco leaves. Further, heterologous over-expression (O/E) of TaSnRK1α in Arabidopsis not only led to increase in starch content but also enlarges the starch granules. TaSnRK1α was found to restore starch accumulation in Arabidopsis kin10. Remarkably, TaSnRK1α O/E increases the AGPase activity suggesting the direct regulation of rate limiting enzyme AGPase involved in starch biosynthesis. Furthermore, in vitro and in vivo interaction assay reveal that TaSnRK1α interacts with AGPase large sub-unit. Overall, our findings indicate that TaSnRK1α plays a role in starch biosynthesis by regulating AGPase activity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Triticum/genética , Triticum/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Glucose-1-Fosfato Adenililtransferase/genética , Glucose-1-Fosfato Adenililtransferase/metabolismo , Saccharomyces cerevisiae/metabolismo , Amido/metabolismo , Sacarose/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
10.
Arterioscler Thromb Vasc Biol ; 44(3): 666-689, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38299356

RESUMO

BACKGROUND: Endothelial cells are constantly exposed to mechanical forces in the form of fluid shear stress, extracellular stiffness, and cyclic strain. The mechanoresponsive activity of YAP (Yes-associated protein) and its role in vascular development are well described; however, whether changes to transcription or epigenetic regulation of YAP are involved in these processes remains unanswered. Furthermore, how mechanical forces are transduced to the nucleus to drive transcriptional reprogramming in endothelial cells is poorly understood. The YAP target gene, AmotL2 (angiomotin-like 2), is a junctional mechanotransducer that connects cell-cell junctions to the nuclear membrane via the actin cytoskeleton. METHODS: We applied mechanical manipulations including shear flow, stretching, and substrate stiffness to endothelial cells to investigate the role of mechanical forces in modulating YAP transcription. Using in vitro and in vivo endothelial depletion of AmotL2, we assess nuclear morphology, chromatin organization (using transposase-accessible chromatin sequencing), and whole-mount immunofluorescent staining of the aorta to determine the regulation and functionality of YAP. Finally, we use genetic and chemical inhibition to uncouple the nuclear-cytoskeletal connection to investigate the role of this pathway on YAP transcription. RESULTS: Our results reveal that mechanical forces sensed at cell-cell junctions by the YAP target gene AmotL2 are directly involved in changes in global chromatin accessibility and activity of the histone methyltransferase EZH2, leading to modulation of YAP promotor activity. Functionally, shear stress-induced proliferation of endothelial cells in vivo was reliant on AmotL2 and YAP/TAZ (transcriptional coactivator with PDZ-binding motif) expression. Mechanistically, uncoupling of the nuclear-cytoskeletal connection from junctions and focal adhesions led to altered nuclear morphology, chromatin accessibility, and YAP promotor activity. CONCLUSIONS: Our findings reveal a role for AmotL2 and nuclear-cytoskeletal force transmission in modulating the epigenetic and transcriptional regulation of YAP to maintain a mechano-enforced positive feedback loop of vascular homeostasis. These findings may offer an explanation as to the proinflammatory phenotype that leads to aneurysm formation observed in AmotL2 endothelial deletion models.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Transativadores , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transativadores/metabolismo , Mecanotransdução Celular , Células Endoteliais/metabolismo , Epigênese Genética , Cromatina
11.
Plant Physiol Biochem ; 207: 108336, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38245990

RESUMO

Iron (Fe) is an essential plant nutrient that is indispensable for many physiological activities. This study is an effort to identify the molecular and biochemical basis of wheat genotypes with contrasting tolerance towards Fe deficiency. Our physiological experiments performed at the early growth stage in cv. Kanchan (KAN) showed Fe deficiency tolerance, whereas cv. PBW343 (PBW) was susceptible. Under Fe deficient condition, KAN showed delayed chlorosis, high SPAD values, and low malondialdehyde content compared to PBW, indicative of Fe deficient condition. Comparative shoot transcriptomics revealed increased expression of photosynthetic pathway genes in PBW, further suggesting its sensitivity to Fe fluctuations. Under Fe deficiency, both the cultivars showed distinct molecular re-arrangements such as high expression of genes involved in Fe uptake (including membrane transporters) and its remobilization. Specifically, in KAN these changes lead to high root phytosiderophores (PS) biosynthesis and its release, resulting in enhanced Fe translocation index. Utilizing the non-transgenic TILLING (Targeting Induced Lesions in Genomes) technology, we identified TaZIFL4.2D as a putative PS efflux transporter. Characterization of the wheat TILLING lines indicated that TaZIFL4.2 functions in PS release and Fe acquisition, thereby imparting tolerance to Fe deficiency. Altogether, this work highlights the mechanistic insight into Fe deficiency tolerance of hexaploid wheat, thus enabling breeders to select suitable genotypes to utilize nutrients for maximum yields.


Assuntos
Deficiências de Ferro , Triticum , Triticum/metabolismo , Transcriptoma/genética , Ferro/metabolismo , Transporte Biológico , Proteínas de Membrana Transportadoras/genética , Raízes de Plantas/metabolismo
12.
BJS Open ; 8(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38195162

RESUMO

BACKGROUND: First-degree relatives of patients with abdominal aortic aneurysm (AAA) may have an increased risk of developing the disease. The primary aim was to report the prevalence of AAA in adult male and female offspring of patients with AAA. The secondary aim was to explore the efficiency of a registry-based detection route, and the third aim was to report contemporary prevalence in the population. METHODS: Adult offspring of individuals with AAA and matched controls were identified through national registries. The examination included questionnaires and ultrasound examinations of the infrarenal aorta. Aortic pathology was defined as an aortic diameter ≥25 mm, AAA ≥30 mm. RESULTS: The participation rate among male and female adult offspring was 64% (350/543) and 69% (402/583), respectively. A lower participation rate was found in male and female controls (51% and 52%). No difference in prevalence of AAA was observed between male adult offspring and controls (0.9%, c.i. 0.2 to 2.3%) or in the female population (prevalence of 0.2% in adult offspring and controls). Aortic pathology and previously diagnosed AAA were detected in 5.3% (c.i. 3.3 to 8.0%) of male adult offspring and 2.3% (c.i. 1.1 to 4.2%) in controls. Aortic pathology was more prevalent among adult offspring of females with AAA. CONCLUSION: The prevalence of AAA in the general population is low, but aortic pathology is notably higher among male first-degree relatives. Increased awareness should be directed towards individuals with a possible hereditary predisposition, particularly offspring of females with AAA and older smokers. Risk factor-based targeted screening of adult offspring of patients with AAA after registry-based detection should be further explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT4623268.


Assuntos
Filhos Adultos , Aneurisma da Aorta Abdominal , Adulto , Humanos , Feminino , Masculino , Prevalência , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/epidemiologia , Aorta Abdominal , Predisposição Genética para Doença
13.
Gene ; 896: 148039, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38036075

RESUMO

Wheat (Triticum aestivum L.) is a crucial global staple crop, and is consistently being improved to enhance yield, disease resistance, and quality traits. However, the development of molecular markers is a challenging task due to its hexaploid genome. Molecular marker system such as simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) are helpful for breeding, but SNP has limitations due to its development cost and its conversion to breeder markers. The study proposed an in-silico approach, by utilizing the low-cost transcriptome sequencing of two parental lines, 'TAC 75' and 'WH 1105', to identify polymorphic SSRs for mapping in a recombinant inbred line (RIL) population. This study introduces a new approach to bridge wheat genetics intricacies and next-generation sequencing potential. It presents a comprehensive genome-wide SSR distribution using IWGSC CS RefSeq v2.1 genome assembly and to identify 189 polymorphic loci through in-silico strategy. Of these, 54.76% showed polymorphism between parents, surpassing the traditional low polymorphic success rate. A RIL population screening validated these markers, demonstrating the fitness of identified markers through chi-square tests. The designed SSRs were also validated for genetic diversity analysis in a subset of 37 Indian wheat genotypes and cross-transferability in the wild/relative wheat species. In diversity analysis, a subset of 38 markers revealed 95 alleles (2.5 allele/locus), indicating substantial genetic variation. Population structure analysis unveiled three distinct groups, supported by phylogenetic and PCoA analyses. Further the polymorphic SSRs were also analyzed for SSR-gene association using gene ontology analysis. By utilizing the developing seed transcriptome data within parental lines, the study has enhanced the polymorphic SSR identification precision and facilitated in the RIL population. The undertaken study pioneers the use of transcriptome sequencing and genetic mapping to overcome challenges posed by the intricate wheat genome. This approach offers a cost-effective, less labour-intensive alternative to conventional methods, providing a platform for advancing wheat breeding research.


Assuntos
Melhoramento Vegetal , Triticum , Triticum/genética , Marcadores Genéticos , Filogenia , Repetições de Microssatélites/genética , Polimorfismo de Nucleotídeo Único , Genoma de Planta
14.
Br J Surg ; 111(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37963191

RESUMO

BACKGROUND: It is unclear whether women derive mortality benefit from early repair of abdominal aortic aneurysms (AAA). The aim of this study was to compare short- and mid-term mortality for women treated at small versus large diameters. METHOD: Women receiving elective repair of AAA at small (49-54 mm) and large (≥55 mm) diameters from 2008 to 2022 were extracted from the Swedish National Registry for Vascular Surgery (n = 1642 women). The effect of diameter on 90-day, 1- and 3-year mortality was studied in logistic regression and propensity score models. Age, co-morbidities, smoking and repair modality were considered as confounders. Men (n = 9047) were analysed in parallel. RESULTS: Some 1642 women were analysed, of whom 34% underwent repair at small diameters (versus 52% of men). Women with small (versus large) AAAs were younger (73 versus 75 years, P < 0.001), and 63% of women in both size groups had endovascular repairs (P = 0.120). Mortality was 3.5% (90 days), 7.1% (1 year) and 15.8% (3 years), with no differences between the size strata. There was no consistent association between AAA size and mortality in multivariable models. Sex differences in mortality were almost entirely due to mortality in younger-than-average women versus men (3-year mortality: small AAAs 11.1% versus 7.3%, P < 0.030, or large 14.4% versus 10.7%, P < 0.038). CONCLUSION: Mortality in women is high and unaffected by AAA size at repair. The optimal threshold for women remains undefined. The higher rupture risk in women should not automatically translate into a lower, women-specific threshold.


Assuntos
Aneurisma da Aorta Abdominal , Procedimentos Endovasculares , Procedimentos de Cirurgia Plástica , Humanos , Masculino , Feminino , Estudos Retrospectivos , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos , Fatores de Risco , Resultado do Tratamento
15.
BJS Open ; 7(5)2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37882629

RESUMO

BACKGROUND: Current recommendations regarding the number of open groin hernia repairs that surgical trainees are required to perform during their residency are arbitrarily defined and vary between different curricula. This register-based study sought to investigate the learning curve of surgeons performing open anterior mesh repair for groin hernia by assessing hernia recurrence rates, surgical complications and operating times in relation to the number of procedures performed. METHOD: Nationwide data on open anterior mesh repair for groin hernia performed by surgical residents were collected from the Swedish Hernia Register between 2005 and 2020. The data were analysed in a cohort undergoing procedures carried out by surgeons performing their first registered repair as resident general surgeons. Repairs by surgeons with fewer than 30 repairs were excluded. RESULTS: A total of 38 845 repairs carried out by 663 surgeons were included. Operation time decreased with increasing number of performed procedures, mean (s.d.) operation time was 79 (26) min for the first 15 procedures and 60 (23) min after 241 procedures (P <0.001). A turning point where complication rates began to decrease was seen after 60 procedures. Complication rates were 3.6 per cent (396 of 10 978) for procedures 31-60 and 2.7 per cent (157 of 5 798) for procedures 61-120 (P = 0.002). There was no significant relationship between the number of procedures performed and the rate of operation on for recurrence (P = 0.894). CONCLUSION: Sixty performed procedures during surgical residency is a reasonable target for achieving competency to perform open anterior mesh repair for groin hernia safely without supervision.


Assuntos
Hérnia Inguinal , Cirurgiões , Humanos , Curva de Aprendizado , Virilha/cirurgia , Hérnia Inguinal/cirurgia , Currículo
16.
Strahlenther Onkol ; 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37676483

RESUMO

PURPOSE: Co-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency. METHODS: A retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort. RESULTS: Between 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association. CONCLUSION: In this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

17.
Mol Ther Nucleic Acids ; 33: 848-865, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37680984

RESUMO

An abdominal aortic aneurysm (AAA) is a pathological widening of the aortic wall characterized by loss of smooth muscle cells (SMCs), extracellular matrix degradation, and local inflammation. This condition is often asymptomatic until rupture occurs, leading to high morbidity and mortality rates. Diagnosis is mostly accidental and the only currently available treatment option remains surgical intervention. Circular RNAs (circRNAs) represent a novel class of regulatory non-coding RNAs that originate from backsplicing. Their highly stable loop structure, combined with a remarkable enrichment in body fluids, make circRNAs promising disease biomarkers. We investigated the contribution of circRNAs to AAA pathogenesis and their potential application to improve AAA diagnostics. Gene expression analysis revealed the presence of deregulated circular transcripts stemming from AAA-relevant gene loci. Among these, the circRNA to the Ataxia Telangiectasia Mutated gene (cATM) was upregulated in human AAA specimens, in AAA-derived SMCs, and serum samples collected from aneurysm patients. In primary aortic SMCs, cATM increased upon angiotensin II and doxorubicin stimulation, while its silencing triggered apoptosis. Higher cATM levels made AAA-derived SMCs less vulnerable to oxidative stress, compared with control SMCs. These data suggest that cATM contributes to elicit an adaptive oxidative-stress response in SMCs and provides a reliable AAA disease signature.

18.
Planta ; 258(5): 91, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37777666

RESUMO

MAIN CONCLUSION: Due to harsh lifestyle changes, in the present era, nutritional security is needed along with food security so it is necessary to include underutilized cereal crops (UCCs) in our daily diet to counteract the rising danger of human metabolic illness. We can attain both the goal of zero hunger and nutritional security by developing improved UCCs using advanced pan-omics (genomics, transcriptomics, proteomics, metabolomics, nutrigenomics, phenomics and ionomics) practices. Plant sciences research progressed profoundly since the last few decades with the introduction of advanced technologies and approaches, addressing issues of food demand of the growing population, nutritional security challenges and climate change. However, throughout the expansion and popularization of commonly consumed major cereal crops such as wheat and rice, other cereal crops such as millet, rye, sorghum, and others were impeded, despite their potential medicinal and nutraceutical qualities. Undoubtedly neglected underutilized cereal crops (UCCs) also have the capability to withstand diverse climate change. To relieve the burden of major crops, it is necessary to introduce the new crops in our diet in the way of UCCs. Introgression of agronomically and nutritionally important traits by pan-omics approaches in UCCs could be a defining moment for the population's well-being on the globe. This review discusses the importance of underutilized cereal crops, as well as the application of contemporary omics techniques and advanced bioinformatics tools that could open up new avenues for future study and be valuable assets in the development and usage of UCCs in the perspective of green system biology. The increased and improved use of UCCs is dependent on number of factors that necessitate a concerted research effort in agricultural sciences. The emergence of functional genomics with molecular genetics might gear toward the reawakening of interest in underutilized cereals crops. The need of this era is to focus on potential UCCs in advanced agriculture and breeding programmes. Hence, targeting the UCCs, might provide a bright future for better health and scientific rationale for its use.


Assuntos
Grão Comestível , Melhoramento Vegetal , Humanos , Grão Comestível/genética , Grão Comestível/metabolismo , Melhoramento Vegetal/métodos , Produtos Agrícolas/genética , Proteômica/métodos , Genômica/métodos
19.
Opt Express ; 31(18): 29536-29557, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710752

RESUMO

Spoof-surface-plasmon-polariton (SSPP) interconnects are potential candidates for next-generation interconnects to satisfy the growing demand for high-speed, large-volume data transfer in chip-to-chip and inter-chip communication networks. As in any interconnect, the viability and efficiency of the modulation technique employed will play a crucial role in the effective utilization of SSPP interconnects. In light of the lack of a comprehensive platform for the performance analysis of SSPP signal modulation, this work presents a theoretical framework that contributes to the following: 1) predictions of the maximum attainable modulation speed, limited by geometric dispersion in SSPP waveguide, 2) quantification of the fundamental trade-off relation between modulation speed and energy-efficiency for an arbitrary design of SSPP structure, 3) extension of the analysis over a broad category of SSPP modulation technique. In conjunction, a novel SSPP signal modulation technique is introduced, involving controlled alteration of the resonant condition of the SSPP interconnect using a variable resistor. Analyzing a sample SSPP waveguide with a 7 GHz cut-off frequency, the study identifies a potential ∼28% change in its transmission-band by varying the implanted resistor from 5kΩ to 5Ω, a range of values practically attainable with gate-controlled, state-of-the-art submicron scale field-effect transistors. The assertions of the theoretical model have been independently validated by finite-element method based numerical simulations, which show that the underlying concept can be utilized to realize the digital modulation scheme of the amplitude shift keying. For a millimeter-scale SSPP channel having 2.75 GHz transmission bandwidth, up to 300 Mbps modulation speed with nominal power loss is achieved in a standard, thermal-noise limited communication system. By scaling the interconnect to micrometer dimensions, the speed can be augmented up to 10 Gbps for data transfer over 100 mm distance with ≥80% energy efficiency. Essentially, the presented theory is the first of its kind that provides the foundational design guideline for designing and optimizing diverse range of SSPP modulators.

20.
Plant Physiol Biochem ; 203: 108040, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37738867

RESUMO

Amylose, a starch subcomponent, can bind lipids within its helical groove and form an amylose-lipid complex, known as resistant starch type 5 (RS-5). RS contributes to lower glycaemic index of grain with health benefits. Unfortunately, genes involved in lipid biosynthesis in wheat grain remain elusive. Our study aims to characterize the lipid biosynthesis gene and its post-transcriptional regulation using the parent bread wheat variety 'C 306' and its EMS-induced mutant line 'TAC 75' varying in amylose content. Quantitative analyses of starch-bound lipids showed that 'TAC 75' has significantly higher lipid content in grains than 'C 306' variety. Furthermore, expression analyses revealed the higher expression of wheat phospholipid: diacylglycerol acyltransferase-like (PDAT-like) in the 'TAC 75' compared to the 'C 306'. Overexpression and ectopic expression of TaPDAT in yeast and tobacco leaf confirmed its ability to accumulate lipids in vivo. Enzyme activity assay showed that TaPDAT catalyzes the triacylglycerol synthesis by acylating 1,2-diacylglycerol. Interestingly, the long non-coding RNA, lnc663, was upregulated with the TaPDAT gene, while the miRNA, miR1128, downregulated in the 'TAC 75', indicating a regulatory relationship. The GFP reporter assay confirmed that the lnc663 acts as a positive regulator, and the miR1128 as a negative regulator of the TaPDAT gene, which controls lipid accumulation in wheat grain. Our findings outline TaPDAT-mediated biosynthesis of lipid accumulation and reveal the molecular mechanism of the lnc663 and miR1128 mediated regulation of the TaPDAT gene in wheat grain.

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