Silver Nanowire-Based Transparent Electrodes for V2O5 Thin Films with Electrochromic Properties.

The development of electrochromic systems, known for the modulation of their optical properties under an applied voltage, depends on the replacement of the state-of-the-art ITO (In2O3:Sn) transparent electrode (TE) as well as the improvement of electrochromic films. This study presents an innovative ITO-free electrochromic film architecture utilizing oxide-coated silver nanowire (AgNW) networks as a TE and V2O5 as an electrochromic oxide layer. The TE was prepared by simple spray deposition of AgNWs that allowed for tuning different densities of the network and hence the resistance and transparency of the film. The conformal oxide coating (SnO2 or ZnO) on AgNWs was deposited by atmospheric-pressure spatial atomic layer deposition, an open-air fast and scalable process yielding a highly stable electrode. V2O5 thin films were then deposited by radio frequency magnetron sputtering on the AgNW-based TE. Independent of the oxide's nature, a 20 nm protective layer thickness was insufficient to prevent the deterioration of the AgNW network during V2O5 deposition. On the contrary, crystalline V2O5 films were grown on 30 nm thick ZnO or SnO2-coated AgNWs, exhibiting a typical orange color. Electrochromic characterization demonstrated that only V2O5 films deposited on 30 nm thick SnO2-coated AgNW showed characteristic oxidation-reduction peaks in the Li+-based liquid electrolyte associated with a reversible orange-to-blue color switch for at least 500 cycles. The electrochromic key properties of AgNW/SnO2 (30 nm)/V2O5 films are discussed in terms of structural and morphological changes due to the AgNW network and the nature and thickness of the two protective oxide coatings.

Preoperative Levosimendan in Patients With Severe Left Ventricular Dysfunction Undergoing Isolated Coronary Artery Bypass Grafting: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To verify the impact of preoperative levosimendan on patients with severe left ventricular dysfunction (ejection fraction <35%) undergoing isolated coronary artery bypass grafting. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: The authors included 1,225 patients from 6 randomized controlled trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors performed a meta-analysis of trials that compared preoperative levosimendan with placebo or no therapy, reporting efficacy and safety endpoints. Statistical analyses used mean differences and risk ratios (RR), with a random effects model. Six studies were included, comprising 1,225 patients, of whom 615 (50.2%) received preoperative levosimendan, and 610 (49.8%) received placebo/no therapy. Preoperative levosimendan showed a lower risk of all-cause mortality (RR 0.31; 95% CI 0.16-0.60; p < 0.01; I2 = 0%), postoperative acute kidney injury (RR 0.44; 95% CI 0.25-0.77; p < 0.01; I2 = 0%), low-cardiac-output syndrome (RR 0.45; 95% CI 0.30-0.66; p < 0.001; I2 = 0%), and postoperative atrial fibrillation (RR 0.49; 95% CI 0.25-0.98; p = 0.04; I2 = 85%) compared to control. Moreover, levosimendan significantly reduced the need for postoperative inotropes and increased the cardiac index at 24 hours postoperatively. There were no differences between groups for perioperative myocardial infarction, hypotension, or any adverse events. CONCLUSION: Preoperative levosimendan in patients with severe left ventricular dysfunction undergoing isolated coronary artery bypass grafting was associated with reduced all-cause mortality, low-cardiac-output syndrome, acute kidney injury, postoperative atrial fibrillation, and the need for circulatory support without compromising safety.

Efectos de la mastectomía en los parámetros baropodométricos de pacientes con cáncer de seno / The effect of mastectomy on baropodometric parameters for breast cancer patients / Efeitos da mastectomia nos parâmetros baropodometricos de pacientes com câncer de mama

Objetivo: la mastectomía posterior al cáncer de seno produce diversas alteraciones posturales y biomecánicas en el plano frontal y sagital. Dichos cambios conducen a una cinemática alterada de la columna vertebral, desequilibrio muscular y alteración del soporte del peso del pie. Este estudio pretende describir las alteraciones de la baropodometría después de la mastectomía, con base en análisis baropodométricos de la presión media y la carga estática. Metodología: se realizó un estudio descriptivo correlacional. Las propiedades de carga del pie se identificaron en 17 mujeres mastectomizadas. Se utilizó una placa de presión Ecosanit Foot para medir la carga del pie en posición anatómica y con los pies juntos. Resultados: en el estudio participaron 17 mujeres mastectomizadas con una edad media de 54.16 años. Las pacientes reportaron una presión media significativamente mayor en la posición anatómica del lado dominante mastectomizado en comparación con el lado no dominante mastectomizado (227.2 ± 22.16 vs. 175.6 ± 14.95, p =0.05). No hubo diferencia significativa para la carga estática entre el lado dominante mastectomizado y el lado no dominante mastectomizado en la posición anatómica (52.43±4.069 vs. 49.69 ± 4.094, de forma respectiva). Conclusión: los resultados actuales de nuestro estudio evidenciaron la distribución desequilibrada del peso (vector carga en el pie) en pacientes después de la mastectomía. Por tanto, en este texto se describen las alteraciones posturales, musculares, y el desequilibrio estático y dinámico en pacientes con cáncer de seno.

Objective: mastectomy after breast cancer produces several postural and biomechanical alterations in the frontal and sagittal plane. Such changes lead to disturbed kinematics of the spine, muscle imbalance and altered foot weight bearing. This study aims to describe body balance alterations after mastectomy based on the baropodometric analysis of their mean pressure and static load. Methodology: a descriptive correlational research was carried out. Foot weight-bearing properties were identified in 17 patients who have undergone a mastectomy. An Ecosanit Foot pressure plate was used to measure foot load at anatomical position and keeping the feet together. Results: 17 female patients who had undergo mastectomy with a mean age of 54.16 years took part on the research. Patients who have had a dominant-side mastectomy demonstrated significant greater mean pressure at anatomical position when compared to those patients who have had a non-dominant side mastectomy (227.2 ± 22.16 versus 175.6 ± 14.95, p =0.05). There was no significant difference for static load between the patients who have had a dominant side mastectomy and patients who have had a non dominant side mastectomy at anatomical position (52.43 ± 4.069 versus 49.69 ± 4.094, respectively). Conclusion: the current results of our research showed the unbalanced weight distribution in patients after mastectomy. Consequently, it describes the postural and muscular alterations, and the static and dynamic imbalance in breast cancer patients.

Objetivo: A mastectomia após câncer de mama produz diversas alterações posturais e biomecânicas nos planos frontal e sagital. Tais mudanças levam a alteração da cinemática da coluna, desequilíbrio muscular e alteração do suporte de peso do pé. Este estudo tem como objetivo descrever as alterações baropodométricas após mastectomia, com base em análises baropodométricas de pressão média e carga estática. Metodologia: foi realizado estudo correlacional descritivo. Propriedades de carga nos pés foram identificadas em 17 mulheres mastectomizadas. Uma placa de pressão Ecosanit Foot foi usada para medir a carga do pé em posição anatômica e com os pés juntos. Resultados: participaram do estudo 17 mulheres mastectomizadas com idade média de 54,16 anos. Os pacientes relataram uma pressão média significativamente maior na posição anatômica do lado mastectomizado dominante em comparação ao lado mastectomizado não dominante (227,2 ± 22,16 vs. 175,6 ± 14,95, p =0,05). Não houve diferença significativa para a carga estática entre o lado mastectomizado dominante e o lado mastectomizado não dominante na posição anatômica (52,43 ± 4,069 vs. 49,69 ± 4,094, respectivamente). Conclusão: Os resultados atuais do nosso estudo mostraram distribuição de peso desequilibrada (carga vetorial no pé) em pacientes após mastectomia. Portanto, este texto descreve alterações posturais, musculares e desequilíbrio estático e dinâmico em pacientes com câncer de mama.

NGSEP 4: Efficient and accurate identification of orthogroups and whole-genome alignment.

Whole-genome alignment allows researchers to understand the genomic structure and variation among genomes. Approaches based on direct pairwise comparisons of DNA sequences require large computational capacities. As a consequence, pipelines combining tools for orthologous gene identification and synteny have been developed. In this manuscript, we present the latest functionalities implemented in NGSEP 4, to identify orthogroups and perform whole genome alignments. NGSEP implements functionalities for identification of clusters of homologus genes, synteny analysis and whole genome alignment. Our results showed that the NGSEP algorithm for orthogroups identification has competitive accuracy and efficiency in comparison to commonly used tools. The implementation also includes a visualization of the whole genome alignment based on synteny of the orthogroups that were identified, and a reconstruction of the pangenome based on frequencies of the orthogroups among the genomes. NGSEP 4 also includes a new graphical user interface based on the JavaFX technology. We expect that these new developments will be very useful for several studies in evolutionary biology and population genomics.

Emergence of CWD strains.

Chronic wasting disease (CWD) strains present a novel challenge to defining and mitigating this contagious prion disease of deer, elk, moose, and reindeer. Similar to strains of other prion diseases (bovine spongiform encephalopathy, sheep scrapie), CWD strains can affect biochemical and neuropathological properties of the infectious agent, and importantly interspecies transmission. To date, ten CWD strains have been characterized. The expanding range of CWD in North America and its presence in South Korea as well as Scandinavian countries will potentially result in millions of cervids infected with CWD; thus, novel strains will continue to emerge. In this review, we will summarize the characteristics of known CWD strains and describe the impact of prion protein gene polymorphisms on the generation of strains. We will also discuss the evidence that individual cervids can harbor more than one CWD strain, complicating strain analysis, and affecting selection and adaptation of strains in new hosts.

Silver Nanowire Networks: Ways to Enhance Their Physical Properties and Stability.

Silver nanowire (AgNW) networks have been intensively investigated in recent years. Thanks to their attractive physical properties in terms of optical transparency and electrical conductivity, as well as their mechanical performance, AgNW networks are promising transparent electrodes (TE) for several devices, such as solar cells, transparent heaters, touch screens or light-emitting devices. However, morphological instabilities, low adhesion to the substrate, surface roughness and ageing issues may limit their broader use and need to be tackled for a successful performance and long working lifetime. The aim of the present work is to highlight efficient strategies to optimize the physical properties of AgNW networks. In order to situate our work in relation to existing literature, we briefly reported recent studies which investigated physical properties of AgNW networks. First, we investigated the optimization of optical transparency and electrical conductivity by comparing two types of AgNWs with different morphologies, including PVP layer and AgNW dimensions. In addition, their response to thermal treatment was deeply investigated. Then, zinc oxide (ZnO) and tin oxide (SnO2) protective films deposited by Atmospheric Pressure Spatial Atomic Layer Deposition (AP-SALD) were compared for one type of AgNW. We clearly demonstrated that coating AgNW networks with these thin oxide layers is an efficient approach to enhance the morphological stability of AgNWs when subjected to thermal stress. Finally, we discussed the main future challenges linked with AgNW networks optimization processes.

Chronic wasting disease: a cervid prion infection looming to spillover.

The spread of chronic wasting disease (CWD) during the last six decades has resulted in cervid populations of North America where CWD has become enzootic. This insidious disease has also been reported in wild and captive cervids from other continents, threatening ecosystems, livestock and public health. These CWD "hot zones" are particularly complex given the interplay between cervid PRNP genetics, the infection biology, the strain diversity of infectious prions and the long-term environmental persistence of infectivity, which hinder eradication efforts. Here, we review different aspects of CWD including transmission mechanisms, pathogenesis, epidemiology and assessment of interspecies infection. Further understanding of these aspects could help identify "control points" that could help reduce exposure for humans and livestock and decrease CWD spread between cervids.

A Cyber-Physical Data Collection System Integrating Remote Sensing and Wireless Sensor Networks for Coffee Leaf Rust Diagnosis.

Coffee Leaf Rust (CLR) is a fungal epidemic disease that has been affecting coffee trees around the world since the 1980s. The early diagnosis of CLR would contribute strategically to minimize the impact on the crops and, therefore, protect the farmers' profitability. In this research, a cyber-physical data-collection system was developed, by integrating Remote Sensing and Wireless Sensor Networks, to gather data, during the development of the CLR, on a test bench coffee-crop. The system is capable of automatically collecting, structuring, and locally and remotely storing reliable multi-type data from different field sensors, Red-Green-Blue (RGB) and multi-spectral cameras (RE and RGN). In addition, a data-visualization dashboard was implemented to monitor the data-collection routines in real-time. The operation of the data collection system allowed to create a three-month size dataset that can be used to train CLR diagnosis machine learning models. This result validates that the designed system can collect, store, and transfer reliable data of a test bench coffee-crop towards CLR diagnosis.

New and distinct chronic wasting disease strains associated with cervid polymorphism at codon 116 of the Prnp gene.

Chronic wasting disease (CWD) is a prion disease affecting cervids. Polymorphisms in the prion protein gene can result in extended survival of CWD-infected animals. However, the impact of polymorphisms on cellular prion protein (PrPC) and prion properties is less understood. Previously, we characterized the effects of a polymorphism at codon 116 (A>G) of the white-tailed deer (WTD) prion protein and determined that it destabilizes PrPC structure. Comparing CWD isolates from WTD expressing homozygous wild-type (116AA) or heterozygous (116AG) PrP, we found that 116AG-prions were conformationally less stable, more sensitive to proteases, with lower seeding activity in cell-free conversion and reduced infectivity. Here, we aimed to understand CWD strain emergence and adaptation. We show that the WTD-116AG isolate contains two different prion strains, distinguished by their host range, biochemical properties, and pathogenesis from WTD-116AA prions (Wisc-1). Serial passages of WTD-116AG prions in tg(CerPrP)1536+/+ mice overexpressing wild-type deer-PrPC revealed two populations of mice with short and long incubation periods, respectively, and remarkably prolonged clinical phase upon inoculation with WTD-116AG prions. Inoculation of serially diluted brain homogenates confirmed the presence of two strains in the 116AG isolate with distinct pathology in the brain. Interestingly, deglycosylation revealed proteinase K-resistant fragments with different electrophoretic mobility in both tg(CerPrP)1536+/+ mice and Syrian golden hamsters infected with WTD-116AG. Infection of tg60 mice expressing deer S96-PrP with 116AG, but not Wisc-1 prions induced clinical disease. On the contrary, bank voles resisted 116AG prions, but not Wisc-1 infection. Our data indicate that two strains co-existed in the WTD-116AG isolate, expanding the variety of CWD prion strains. We argue that the 116AG isolate does not contain Wisc-1 prions, indicating that the presence of 116G-PrPC diverted 116A-PrPC from adopting a Wisc-1 structure. This can have important implications for their possible distinct capacities to cross species barriers into both cervids and non-cervids.

Amino Acid Metabolomic Profiles in Bovine Mammary Epithelial Cells under Essential Amino Acid Restriction.

Mammary epithelial cells (MECs) in culture are a useful model for elucidating mammary gland metabolism and changes that occur under different nutrient disponibility. MECs were exposed to different treatments: 100% EAA for 8 h and 24 h restriction (R); 2% EAA for 8 h and 24 h R; 2% EAA for 8 h and 24 h + 100% EAA for 8 h and 24 h restriction + re-feeding (R + RF). Western blotting and protein quantification was performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) software identified the amino acids (AAs) and signaling pathways. The chi-squared test, multiple classification analysis, and analysis of variance were used for the purification and identification of data. Intracellular casein levels were not affected. The KEGG analysis revealed that the important pathways of metabolism of AAs, which were involved in processes related to metabolism and biosynthesis of phenylalanine, tyrosine, and tryptophan (fumarate, acetyl-CoA, and tricarboxylic acid (TCA) cycle), were affected by both R and R + RF treatments, mainly through the glutamic-oxaloacetic transaminase-2 enzyme. Additionally, metabolic processes mediated by the mitochondrial malate dehydrogenase, S-adenosylmethionine synthetase, and asparagine synthase proteins positively regulated the carbohydrate pathway, pyruvate, and TCA cycles, as well as the metabolism of alanine, aspartate, and glutamate metabolism (carbohydrate and TCA cycle). We hypothesized that MECs have the capacity to utilize alternative pathways that ensure the availability of substrates for composing milk proteins.

Asymmetric-flow field-flow fractionation of prions reveals a strain-specific continuum of quaternary structures with protease resistance developing at a hydrodynamic radius of 15 nm.

Prion diseases are transmissible neurodegenerative disorders that affect mammals, including humans. The central molecular event is the conversion of cellular prion glycoprotein, PrPC, into a plethora of assemblies, PrPSc, associated with disease. Distinct phenotypes of disease led to the concept of prion strains, which are associated with distinct PrPSc structures. However, the degree to which intra- and inter-strain PrPSc heterogeneity contributes to disease pathogenesis remains unclear. Addressing this question requires the precise isolation and characterization of all PrPSc subpopulations from the prion-infected brains. Until now, this has been challenging. We used asymmetric-flow field-flow fractionation (AF4) to isolate all PrPSc subpopulations from brains of hamsters infected with three prion strains: Hyper (HY) and 263K, which produce almost identical phenotypes, and Drowsy (DY), a strain with a distinct presentation. In-line dynamic and multi-angle light scattering (DLS/MALS) data provided accurate measurements of particle sizes and estimation of the shape and number of PrPSc particles. We found that each strain had a continuum of PrPSc assemblies, with strong correlation between PrPSc quaternary structure and phenotype. HY and 263K were enriched with large, protease-resistant PrPSc aggregates, whereas DY consisted primarily of smaller, more protease-sensitive aggregates. For all strains, a transition from protease-sensitive to protease-resistant PrPSc took place at a hydrodynamic radius (Rh) of 15 nm and was accompanied by a change in glycosylation and seeding activity. Our results show that the combination of AF4 with in-line MALS/DLS is a powerful tool for analyzing PrPSc subpopulations and demonstrate that while PrPSc quaternary structure is a major contributor to PrPSc structural heterogeneity, a fundamental change, likely in secondary/tertiary structure, prevents PrPSc particles from maintaining proteinase K resistance below an Rh of 15 nm, regardless of strain. This results in two biochemically distinctive subpopulations, the proportion, seeding activity, and stability of which correlate with prion strain phenotype.

White-tailed deer S96 prion protein does not support stable in vitro propagation of most common CWD strains.

PrPC variation at residue 96 (G/S) plays an important role in the epidemiology of chronic wasting disease (CWD) in exposed white-tailed deer populations. In vivo studies have demonstrated the protective effect of serine at codon 96, which hinders the propagation of common CWD strains when expressed in homozygosis and increases the survival period of S96/wt heterozygous deer after challenge with CWD. Previous in vitro studies of the transmission barrier suggested that following a single amplification step, wt and S96 PrPC were equally susceptible to misfolding when seeded with various CWD prions. When we performed serial prion amplification in vitro using S96-PrPC, we observed a reduction in the efficiency of propagation with the Wisc-1 or CWD2 strains, suggesting these strains cannot stably template their conformations on this PrPC once the primary sequence has changed after the first round of replication. Our data shows the S96-PrPC polymorphism is detrimental to prion conversion of some CWD strains. These data suggests that deer homozygous for S96-PrPC may not sustain prion transmission as compared to a deer expressing G96-PrPC.

Chronic wasting disease (CWD) prion strains evolve via adaptive diversification of conformers in hosts expressing prion protein polymorphisms.

Chronic wasting disease (CWD) is caused by an unknown spectrum of prions and has become enzootic in populations of cervid species that express cellular prion protein (PrPC) molecules varying in amino acid composition. These PrPC polymorphisms can affect prion transmission, disease progression, neuropathology, and emergence of new prion strains, but the mechanistic steps in prion evolution are not understood. Here, using conformation-dependent immunoassay, conformation stability assay, and protein-misfolding cyclic amplification, we monitored the conformational and phenotypic characteristics of CWD prions passaged through deer and transgenic mice expressing different cervid PrPC polymorphisms. We observed that transmission through hosts with distinct PrPC sequences diversifies the PrPCWD conformations and causes a shift toward oligomers with defined structural organization, replication rate, and host range. When passaged in host environments that restrict prion replication, distinct co-existing PrPCWD conformers underwent competitive selection, stabilizing a new prion strain. Nonadaptive conformers exhibited unstable replication and accumulated only to low levels. These results suggest a continuously evolving diversity of CWD conformers and imply a critical interplay between CWD prion plasticity and PrPC polymorphisms during prion strain evolution.

A General Mass Spectrometry-Based Method of Quantitating Prion Polymorphisms from Heterozygous Chronic Wasting Disease-Infected Cervids.

Chronic wasting disease (CWD) is the only prion disease naturally transmitted among farmed and free-ranging cervids (deer, elk, moose, etc.). These diseases are always fatal and have long asymptomatic incubation periods. By 2019, CWD-infected cervids had been detected in 26 states, three Canadian provinces, South Korea, Norway, Finland, and Sweden. Prions (PrPSc) replicate by inducing a normal cellular prion protein (PrPC) to adopt the prion conformation. This prion templated conformational conversion is influenced by PrPC polymorphisms. Cervid PrPC contains at least 20 different polymorphic sites. By using chymotrypsin, trypsin, or trypsin followed by chymotrypsin to digest denatured cervid PrP, 19 peptides suitable for multiple reaction monitoring (MRM)-based analysis and spanning positions 30-51, 61-112, and 114-231 of cervid PrP were identified. Ten of these peptides span polymorphism-containing regions of cervid PrP. The other nine contain no polymorphisms, so they can be used as internal standards. Calibration curves relating the area ratios of MRM signals from polymorphism-containing peptides to appropriate internal standard peptides were linear and had excellent correlation coefficients. Samples from heterozygous (G96/S96) white-tailed deer orally dosed with CWD from homozygous (G96/G96) deer were analyzed. The G96 polymorphism comprised 75 ± 5% of the total PrP from the G96/S96 heterozygotes. Heterozygous animals facilitate conversion of different PrPC polymorphisms into PrPSc. This approach can be used to quantitate the relative amounts of the polymorphisms present in other animal species and even humans.

Natural history and management of Kommerell's diverticulum in a single tertiary referral center.

OBJECTIVE: The Kommerell diverticulum (KD) is an extremely rare developmental abnormality of the aorta related to an aberrant subclavian artery (ASCA). The objective of our study was to review the natural history of KD and ASCA using our single-center experience in diagnosing and managing KD and ASCA. METHODS: A retrospective review of the Yale radiological database from January 1999 to December 2016 was performed. Only patients with KD/ASCA and a computed tomography (CT) scan of the chest were selected for review. The primary goal was to examine the natural history of KD and ASCA and the secondary goals were to review the management and outcomes of those patients treated for KD and ASCA. RESULTS: There were 75 patients with KD/ASCA identified, with a mean age of 63 ± 19 years; 49 were female (65%). On CT scans, left- and right-sided aortas were present in 47 (63%) and 28 (37%) patients. A right ASCA or a left ASCA were present in 47 (63%) and 28 (37%) patients. Six patients were symptomatic on presentation. Symptoms included dysphagia, chest or back pain, and emboli to the fingers. The mean KD diameter was 21.8 ± 6.0 mm and the distance to the opposite aortic wall (DAW) was 48.3 ± 10.8 mm. Sixty-six patients were followed for a mean of 31.7 ± 32.5 months. One patient ruptured without repair. Nine patients underwent operative intervention, including eight open and one endovascular repair. Complications from operative intervention included ischemic stroke with hemorrhagic transformation, deep vein thrombosis and pneumonia. The mean growth rate for KD and DAW was 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year, respectively. On multivariable regression analysis, hypertension was a predictor of growth of DAW (P = .03). CONCLUSIONS: KD is uncommon and shows a female predominance. The diverticulum grows, albeit slowly (KD and DAW growth rates of 1.45 ± 0.39 mm/year and 2.29 ± 0.47 mm/year). Most patients are asymptomatic, but dysphagia, chest/back pain, and distal emboli may occur. Rupture is rare. Symptomatic patients should be operated. Asymptomatic patients can be followed with serial CT scans.

Complex two-stage open surgical repair of an aortoesophageal fistula after thoracic endovascular aortic repair.

Aortoesophageal fistula after thoracic endovascular aortic repair is a rare but fatal complication, and no clear guidelines exist in the literature for optimal management. Herein, we report a complex case of a patient with an infected thoracic endograft that led to an aortoesophageal fistula. The treatment comprised a two-stage open surgical approach-an extra-anatomic aortic bypass in the first stage, followed by explantation of the infected endograft with ligation of the descending thoracic aorta in the second. This approach controls the focus of infection while allowing flow to the aorta distal to the infected endograft, minimizing visceral ischemia time.

Prion protein polymorphisms associated with reduced CWD susceptibility limit peripheral PrPCWD deposition in orally infected white-tailed deer.

BACKGROUND: Chronic wasting disease (CWD) is a prion disease affecting members of the Cervidae family. PrPC primary structures play a key role in CWD susceptibility resulting in extended incubation periods and regulating the propagation of CWD strains. We analyzed the distribution of abnormal prion protein (PrPCWD) aggregates in brain and peripheral organs from orally inoculated white-tailed deer expressing four different PRNP genotypes: Q95G96/Q95G96 (wt/wt), S96/wt, H95/wt and H95/S96 to determine if there are substantial differences in the deposition pattern of PrPCWD between different PRNP genotypes. RESULTS: Although we detected differences in certain brain areas, globally, the different genotypes showed similar PrPCWD deposition patterns in the brain. However, we found that clinically affected deer expressing H95 PrPC, despite having the longest survival periods, presented less PrPCWD immunoreactivity in particular peripheral organs. In addition, no PrPCWD was detected in skeletal muscle of any of the deer. CONCLUSIONS: Our data suggest that expression of H95-PrPC limits peripheral accumulation of PrPCWD as detected by immunohistochemistry. Conversely, infected S96/wt and wt/wt deer presented with similar PrPCWD peripheral distribution at terminal stage of disease, suggesting that the S96-PrPC allele, although delaying CWD progression, does not completely limit the peripheral accumulation of the infectious agent.

Thoracic aortic aneurysm: unlocking the "silent killer" secrets.

Thoracic aortic aneurysm (TAA) is an increasingly recognized condition that is often diagnosed incidentally. This review discusses ten of the most relevant epidemiological and clinical secrets of this disease; (1) the difference in pathogenesis between ascending and descending TAAs. TAAs at these two sites act as different diseases, which is related to the different embryologic origins of the ascending and descending aorta. (2) The familial pattern and genetics of thoracic aneurysms. Syndromic TAAs only explain 5% of the pattern of inheritance. (3) The effect of female sex on TAA growth and outcome. Females have been found to have worse outcomes compared to males. (4) Guilt by Association. TAAs are associated with abdominal aortic aneurysms, intracranial aneurysms, bicuspid aortic valve, and inflammatory disorders. (5) Natural history of TAAs. Important findings have been made regarding the expansion rate (in relation to familial pattern, location and size), and also regarding the risk of rupture or dissection. (6) The aortic size paradox. Size only is not a sufficient predictor of risk of dissection. (7) Biomarker void. Although many serum biomarkers have been studied, imaging remains the only reliable method for diagnosis and follow-up. (8) Indications for repair. Decisions are made depending on symptoms, location, size, and familial patterns. (9) Types of repair. Both open and endovascular repair options are available for certain TAAs. (10) Medical treatment. The efficacy of prescribing beta blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers remains dubious.

Decision-making algorithm for ascending aortic aneurysm: Effectiveness in clinical application?

OBJECTIVE: The risk of rupture and dissection in ascending thoracic aortic aneurysms increases as the aortic diameter exceeds 5 cm. This study evaluates the clinical effectiveness of a specific algorithm based on size and symptoms for preemptive surgery to prevent complications. METHODS: A total of 781 patients with nondissecting ascending thoracic aortic aneurysms who presented electively for evaluation to our institution from 2011 to 2017 were triaged to surgery (n = 607, 77%) or medical observation (n = 181, 24%) based on a specific algorithm: surgery for large (>5 cm) or symptomatic aneurysms. A total of 309 of 781 patients did not undergo surgery. Of these, 128 (16%) had been triaged to prompt repair but did not undergo surgery for a variety of reasons ("surgery noncompliant and overwhelming comorbidities" group). Another 181 patients (24%) were triaged to medical management ("medical" group). RESULTS: In the "surgery noncompliant and overwhelming comorbidities" versus the "medical" group, mean aortic diameters were 5 ± 0.5 cm versus 4.45 ± 0.4 cm and aortic events (rupture/dissection) occurred in 17 patients (13.3%) versus 3 patients (1.7%), respectively (P < .001). Later elective surgeries (representing late compliance in the "surgery noncompliant and overwhelming comorbidities group" or onset of growth or symptoms in the "medical" group) were conducted in 21 patients (16.4%) versus 15 patients (8.3%) (P = .04), respectively. Death ensued in 20 patients (15.6%) versus 6 patients (3.3%) (P < .001), respectively. In the "surgery noncompliant and overwhelming comorbidities" group, 7 of 20 patients died of definite aortic causes compared with none in the "medical" group. CONCLUSIONS: Patients with ascending thoracic aortic aneurysms who did not follow surgical recommendations experienced substantially worse outcomes compared with medically triaged candidates. The specific algorithm based on size and symptoms functioned effectively in the clinical setting, correctly identifying both at-risk and safe patients.