Direct neuronal reprogramming by temporal identity factors.

Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that coexpression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial (MG) cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside. We name these "induced ONL (iONL)" cells. Using genetic lineage tracing, histological, immunohistochemical, and single-cell transcriptome and multiome analyses, we show that expression of Ikzf1/4 in MG in vivo, without retinal injury, mostly generates iONL cells that share molecular characteristics with bipolar cells, although a fraction of them stain for Rxrg, a cone photoreceptor marker. Furthermore, we show that coexpression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons in culture by rapidly remodeling chromatin and activating a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in terminally differentiated cells.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Elevated extracellular inorganic phosphate inhibits ecto-phosphatase activity in breast cancer cells: Regulation by hydrogen peroxide.

For cells to obtain inorganic phosphate, ectoenzymes in the plasma membrane, which contain a catalytic site facing the extracellular environment, hydrolyze phosphorylated molecules. In this study, we show that increased Pi levels in the extracellular environment promote a decrease in ecto-phosphatase activity, which is associated with Pi-induced oxidative stress. High levels of Pi inhibit ecto-phosphatase because Pi generates H2 O2 . Ecto-phosphatase activity is inhibited by H2 O2 , and this inhibition is selective for phospho-tyrosine hydrolysis. Additionally, it is shown that the mechanism of inhibition of ecto-phosphatase activity involves lipid peroxidation. In addition, the inhibition of ecto-phosphatase activity by H2 O2 is irreversible. These findings have new implications for understanding ecto-phosphatase regulation in the tumor microenvironment. H2 O2 stimulated by high Pi inhibits ecto-phosphatase activity to prevent excessive accumulation of extracellular Pi, functioning as a regulatory mechanism of Pi variations in the tumor microenvironment.

Comparative characterisation of an ecto-5'-nucleotidase (CD73) in non-tumoral MCF10-A breast cells and triple-negative MDA-MB-231 breast cancer cells.

Ecto-5'-nucleotidase (CD73) hydrolyses 5'AMP to adenosine and inorganic phosphate. Breast cancer cells (MDA-MB-231) express high CD73 levels, and this enzyme has been found to play a tumour-promoting role in breast cancer. However, no studies have sought to investigate whether CD73 has differential affinity or substrate preferences between noncancerous and cancerous breast cells. In the present study, we aimed to biochemically characterise ecto-5'-nucleotidase in breast cancer cell lines and assess whether its catalytic function and tumour progression are correlated in breast cancer cells. The results showed that compared to nontumoral breast MCF-10A cells, triple-negative breast cancer MDA-MB-231 cells had a higher ecto-5'-nucleotidase expression level and enzymatic activity. Although ecto-5'-nucleotidase activity in the MDA-MB-231 cell line showed no selectivity among monophosphorylated substrates, 5'AMP was preferred by the MCF-10A cell line. Compared to the MCF-10A cell line, the MDA-MB-231 cell line has better hydrolytic ability, lower substrate affinity, and high inhibitory potential after treatment with a specific CD73 inhibitor α,ß­methylene ADP (APCP). Therefore, we demonstrated that a specific inhibitor of the ecto-5-nucleotidase significantly reduced the migratory and invasive capacity of MDA-MB-231 cells, suggesting that ecto-5-nucleotidase activity might play an important role in metastatic progression.

Pyricularia Are Mostly Host-Specialized with Limited Reciprocal Cross-Infection Between Wheat and Endemic Grasses in Minas Gerais, Brazil.

Wheat blast, caused by Pyricularia oryzae Triticum (PoT), is an emerging threat to global wheat production. The current understanding of the population biology of the pathogen and epidemiology of the disease has been based on phylogenomic studies that compared the wheat blast pathogen with isolates collected from grasses that were invasive to Brazilian wheat fields. In this study, we performed a comprehensive sampling of blast lesions in wheat crops and endemic grasses found in and away from wheat fields in Minas Gerais. A total of 1,368 diseased samples were collected (976 leaves of wheat and grasses and 392 wheat heads), which yielded a working collection of 564 Pyricularia isolates. We show that, contrary to earlier implications, PoT was rarely found on endemic grasses, and, conversely, members of grass-adapted lineages were rarely found on wheat. Instead, most lineages were host-specialized, with constituent isolates usually grouping according to their host of origin. With regard to the dominant role proposed for signalgrass in wheat blast epidemiology, we found only one PoT member in 67 isolates collected from signalgrass grown away from wheat fields and only three members of Urochloa-adapted lineages among hundreds of isolates from wheat. Cross-inoculation assays on wheat and a signalgrass used in pastures (U. brizantha) suggested that the limited cross-infection observed in the field may be due to innate compatibility differences. Whether or not the observed level of cross-infection would be sufficient to provide an inoculum reservoir, or serve as a bridge between wheat growing regions, is questionable and, therefore, deserves further investigation.

A Reevaluation of Phylogenomic Data Reveals that Current Understanding in Wheat Blast Population Biology and Epidemiology Is Obfuscated by Oversights in Population Sampling.

Wheat blast, caused by the Pyricularia oryzae Triticum lineage (PoT), first emerged in Brazil and quickly spread to neighboring countries. Its recent appearance in Bangladesh and Zambia highlights a need to understand the disease's population biology and epidemiology so as to mitigate pandemic outbreaks. Current knowledge is mostly based on characterizations of Brazilian wheat blast isolates and comparison with isolates from non-wheat, endemic grasses. These foregoing studies concluded that the wheat blast population lacks host specificity and, as a result, undergoes extensive gene flow with populations infecting non-wheat hosts. Additionally, based on genetic similarity between wheat blast and isolates infecting Urochloa species, it was proposed that the disease originally emerged via a host jump from this grass and that Urochloa likely plays a central role in wheat blast epidemiology owing to its widespread use as a pasture grass. However, due to inconsistencies with broader phylogenetic studies, we suspected that these seminal studies had not actually sampled the populations normally found on endemic grasses and, instead, had repeatedly isolated members of PoT and the related Lolium pathogen lineage (PoL1). Re-analysis of the Brazilian data as part of a comprehensive, global, phylogenomic dataset that included a small number of South American isolates sampled away from wheat confirmed our suspicion and identified four new P. oryzae lineages on grass hosts. As a result, the conclusions underpinning current understanding in wheat blast's evolution, population biology, and epidemiology are unsubstantiated and could be equivocal.

Bilateral same-day myringoplasty: a feasible option?

PURPOSE: Retrospective evaluation of bilateral same-day myringoplasty outcomes. METHODS: Patients who underwent bilateral same-day myringoplasty from 2005 to 2019. RESULTS: Thirty-eight patients underwent bilateral myringoplasty. Mean age was 44.5 years and 55.3% patients were male. Tragal perichondrium-cartilage composite graft was the most frequently used graft material (82.9%). Perforation closure was achieved in 78.9%. Postoperative Pure Tone Average and Air-Bone Gap decreased significantly (p < 0.05), except for the Air-Bone Gap of the right ear (p = 0.058). The complications were cholesteatoma (1.3%), otorrhea (6.6%) and tympanic membrane retraction (1.3%). CONCLUSIONS: Bilateral same-day myringoplasty is a feasible procedure in selected patients. Good anatomic and functional outcomes, as well as a low rate of complications, are achieved with this procedure, improving patient comfort and allowing for a reduction in operation time and costs.

Effect of drying temperature and storage time on the crispiness of homemade apple snacks.

BACKGROUND: The apple (Malus domestica Borkh.) plays an important role in the trendy market of dried snacks because of its exceptional flavor and texture. In addition to the health benefits, there is also a general disposition to consume organic and do-it-yourself products. RESULTS: Three different drying temperatures, 65, 75, and 85 °C, were tested using a commercial ventilated drying oven in 'Royal Gala' and 'Golden Delicious' cultivars. Physical changes, including texture, color, shrinkage ratio, and microstructure, were evaluated for the temperatures and cultivars considered. Based on the results, particularly in terms of shrinkage, hardness, and crispiness, a drying temperature of 75 °C was selected to perform texture profile analyses throughout the drying period. Storability conditions were evaluated to determine the best moment to maintain the physical properties of the dried snacks during storage. Considered the more important property related to consumer preferences, crispiness was followed with puncture tests. CONCLUSION: The storage of apple chips, dried at the various temperatures, that must be performed in 5-10 min after removing from the drying oven, was assessed over the course of a month. Both the drying process and the subsequent storage proved effective in preserving the desired texture of the apple snacks, regardless of the specific cultivar or drying temperature used. Through this study, with a refined understanding of the changes occurring during the drying process and the optimization of storage conditions, we can confidently offer consumers the best combination of crispy and healthy snacks that meet their expectations. © 2023 Society of Chemical Industry.

Behavior of diclofenac from contaminated fish after cooking and in vitro digestion.

BACKGROUND: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4'-hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g-1) and submitted to three culinary treatments (roasting, steaming and grilling). RESULTS: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1-98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4'-hydroxydiclofenac was not detected after cooking or digestion. CONCLUSION: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Innate immune response in patients with acute Chikungunya disease.

Chikungunya disease (CHIKD) is an arbovirose that presents with high morbidity, mainly due to arthralgia. Inflammatory mediators including IL-6, IL-1ß, GM-CSF and others have been implicated in the pathogenesis of CHIKD, whilst type I interferons can be associated with better outcomes. The role of pattern recognition receptors has been studied incompletely. Here, we evaluated the expression of RNA-specific PRRs, their adaptor molecules and downstream cytokines in acute CHIKD patients. Twenty-eight patients were recruited during the 3rd-5th day after the symptoms onset for clinical examination, peripheral blood collection and qRT-PCR analysis of PBMC to compare to the healthy control group (n = 20). We observed common symptoms of acute CHIKD, with fever, arthralgia, headache and myalgia being the most frequent. Compared with uninfected controls, acute CHIKV infection upregulates the expression of the receptors TLR3, RIG-I and MDA5, and also the adaptor molecule TRIF. Regarding cytokine expression, we found an upregulation of IL-6, IL-12, IFN-α, IFN-ß and IFN-γ, which are related directly to the inflammatory or antiviral response. The TLR3-TRIF axis correlated with high expression of IL-6 and IFN-α. Interestingly, greater expression of MDA5, IL-12 and IFN-α was related to lower viral loads in CHIKD acute patients. Together, these findings help to complete the picture of innate immune activation during acute CHIKD, while confirming the induction of strong antiviral responses. Drawing the next steps in the understanding of the immunopathology and virus clearance mechanisms of CHIKD should be of utter importance in the aid of the development of effective treatment to reduce the severity of this debilitating disease.

Emerging mycotoxins in infant and children foods: A review.

A proper nutrition is crucial for children's healthy development. Regardless of the usual recommendations to follow a varied diet, some foods can be a source of toxic natural contaminants such as mycotoxins, potent secondary metabolites produced by filamentous fungi. In addition to the most well-known mycotoxins, many of which are subject to tight regulation regarding the maximum levels allowed in different types of food, there is a large group of mycotoxins, the so-called emerging mycotoxins, about which less knowledge has already been acquired, which have gradually been the target of interest from the scientific community due to their prevalence in most foodstuffs, particularly in cereals and cereal-based products. Alternariol and his metabolite alternariol mono-methyl ether, beauvericin, citrinin, culmorin, enniatins, ergot alkaloids, fusaproliferin, kojic acid, moniliformin, sterigmatocystin, tentoxin and tenuazonic acid are the most representative of them. The current review gathered the information of the last ten years that have been published on the levels of emerging mycotoxins in food products dedicated for infants and children. European Union countries are responsible for most of the reported studies, which showed levels that can reach hundreds of mg/kg.

Synthesis of new non-natural L-glycosidic flavonoid derivatives and their evaluation as inhibitors of Trypanosoma cruzi ecto-nucleoside triphosphate diphosphohydrolase 1 (TcNTPDase1).

Trypanosoma cruzi is the pathogen of Chagas disease, a neglected tropical disease that affects more than 6 million people worldwide. There are no vaccines to prevent infection, and the therapeutic arsenal is very minimal and toxic. The unique E-NTPDase of T. cruzi (TcNTPDase1) plays essential roles in adhesion and infection and is a virulence factor. Quercetin is a flavonoid with antimicrobial, antiviral, and antitumor activities. Its potential as a partial inhibitor of NTPDases has also been demonstrated. In this work, we synthesized the non-natural L-glycoside derivatives of quercetin and evaluated them as inhibitors of recombinant TcNTPDase1 (rTcNTPDase1). These compounds, and quercetin and miquelianin, a natural quercetin derivative, were also tested. Compound 16 showed the most significant inhibitory effect (94%). Quercetin, miquelianin, and compound 14 showed inhibition close to 50%. We thoroughly investigated the inhibitory effect of 16. Our data suggested a competitive inhibition with a Ki of 8.39 µM (± 0.90). To better understand the interaction of compound 16 and rTcNTPDase1, we performed molecular dynamics simulations of the enzyme and docking analyses with the compounds. Our predictions show that compound 16 binds to the enzyme's catalytic site and interacts with important residues for NTPDase activity. As an inhibitor of a critical T. cruzi enzyme, (16) could be helpful as a starting point in the developing of a future treatment for Chagas disease. Furthermore, the discovery of (16) as an inhibitor of TcNTPDase1 may open new avenues in the study and development of new inhibitors of E-NTPDases.

HHV-6 infections in hospitalized young children of Gabon.

PURPOSE: Fever is a common cause for hospitalization among the pediatric population. The spectrum of causative agents is diverse. Human herpesvirus 6 (HHV-6) is a ubiquitous virus that often causes hospitalization of children in western countries. Previously, we investigated the cause of fever of 600 febrile hospitalized children in Gabon, and in 91 cases the causative pathogen was not determined. In this study, we assessed HHV-6 infection as potential cause of hospitalization in this group. METHODS: Blood samples were assessed for HHV-6 using real-time quantitative PCR. Three groups were investigated: (1) group of interest: 91 hospitalized children with febrile illness without a diagnosed causing pathogen; (2) hospitalized control: 91 age-matched children hospitalized with febrile illness with a potentially disease-causing pathogen identified; both groups were recruited at the Albert Schweitzer Hospital in Lambaréné, Gabon and (3) healthy control: 91 healthy children from the same area. RESULTS: Samples from 273 children were assessed. Age range was two months to 14 years, median (IQR) age was 36 (12-71) months; 52% were female. HHV-6 was detected in 64% (58/91), 41% (37/91), and 26% (24/91) of the samples from groups 1, 2, and 3, respectively; with statistically significant odds of being infected with HHV-6 in group 1 (OR = 4.62, 95% CI [2.46, 8.90]). Only HHV-6B was detected. CONCLUSIONS: Although tropical diseases account for a large proportion of children's hospitalizations, considering common childhood diseases such as HHV-6 when diagnosing febrile illnesses in pediatric populations in tropical countries is of importance.

Pesticide residues in herbs and their transfer for infusions.

In this work, a cost-effective gas chromatography-mass spectrometry method was validated for the analysis of twenty-five pesticide residues in herbs and infusions using a quick, easy, cheap, effective, rugged, and safe procedure or a dispersive liquid-liquid microextraction method, respectively. Figures of merit of the method showed good accordance with current guidelines. From the 58 herb samples studied (pertaining to 20 different species), 80% presented at least one detectable pesticide, with 62% of them above the maximum residual level. Results showed that pesticide residues from naturally contaminated herbs were not transferred at a significant rate to the herbal infusions. When a control assay was conducted by spiking a blank herb sample with a large amount of each pesticide (7 mg/L) 15 analytes were detected below the limit of quantification in the infusion.

Anaerobic energy metabolism in human microaerophile parasites.

Mucosal-associated parasites, such as Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis, have significant clinical relevance. The pathologies associated with infection by these parasites are among those with the highest incidence of gastroenteritis (giardiasis and amoebiasis) and sexually transmitted infections (trichomoniasis). The treatment of these diseases is based on drugs that act on the anaerobic metabolism of these parasites, such as nitroimidazole and benzimidazole derivatives. One interesting feature of parasites is their ability to produce ATP under anaerobic conditions. Due to the absence of enzymes capable of producing ATP under anaerobic conditions in the vertebrate host, they have become interesting therapeutic targets. This review discusses anaerobic energy metabolism in mucosal-associated parasites, focusing on the anaerobic metabolism of pyruvate, the importance of these enzymes as therapeutic targets, and the importance of treating their infections.

Polygenic Risk Score for Cardiovascular Diseases in Artificial Intelligence Paradigm: A Review.

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established. It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction. Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans.

The Impact of the Proctor Assistance for a Safe Learning Curve in the Development of a Complex Aortic Endovascular Program.

INTRODUCTION: Initiating an endovascular aortic program for treatment of complex aortic aneurysms with fenestrated and branched grafts (FB-EVAR) is challenging. Using a Proctor is one option for training and development of the team. However, this approach has not been formally analyzed. The aim of this study was to analyze the learning curve and the effect of the Proctor regarding safety and effectiveness in FB-EVAR. METHODS: A single-center retrospective cohort study was performed, including all consecutive elective patients submitted to FB-EVAR (including both thoraco-abdominal-TAAA and complex abdominal aortic aneurysms-C-AAA) from 2013 to 2021. Patients were divided into 2 groups, the first operated with the Proctor present and the second without. Primary outcomes were 30-day mortality (safety) and technical and procedure success (efficacy). Secondary outcomes included treatment performance (procedure time, blood loss, contrast, and radiation use), re-interventions, aneurysm shrinking, target vessel patency, 30-day mortality, aneurysm-related mortality, and overall mortality. RESULTS: Overall, 105 patients were included in the study, 35 operated with Proctor and 70 operated without. The first 20 patients were operated always with the Proctor, and the remaining were operated with the Proctor selectively. Mean age was 71.8 (±7.3) years and 95 patients were male (90.5%). Overall, 62 (65%) patients had C-AAA or extent IV TAAAs and 43 (35%) had extensive TAAAs. There were no significant differences regarding 30-day mortality (Log Rank=0.99), technical success (p=0.4), or procedure success (p=0.8). Mean surgical time was longer in the non-Proctor group (p=0.005), as well as significant intra-operative blood loss (p=0.042). Contrast use (p=0.5) and radiation (p=0.53) were non-significantly different between groups. There were no significant differences regarding length of stay (p=0.4), major adverse events (p=0.6), target vessel patency (Log Rank=0.97), early (p=0.7) and late endoleaks (0.7), aneurysm shrinking (p=0.6), re-interventions (p=0.2), and overall mortality (Log Rank=0.87). CONCLUSION: In our experience, the use of a Proctor to start and accompany our complex endovascular aortic program for FB-EVAR was both safe and effective and may serve as a template by other countries and centers that aim to developing their programs.

Anaerobic ATP synthesis pathways and inorganic phosphate transport and their possible roles in encystment in Acanthamoeba castellanii.

Acanthamoeba castellanii is the etiological agent of amoebic keratitis and is present in the environment in trophozoite or cyst forms. Both forms can infect the vertebrate host and colonize different tissues. The high resistance of cysts to standard drugs used in clinics contributes to the lack of effective treatments. Therefore, in this context, studies have emerged to understand cyst physiology and metabolism. Phosphate transporters are proteins responsible for the uptake of extracellular inorganic phosphate and transport to the cytosol. This work aims to verify the relationship between Pi transport and energetic metabolism in cysts of A. castellanii. The phosphate uptake ratio was higher in cysts compared with trophozoites. Recently, three sequences related to phosphate transporters have been identified in the A. castellanii genome (AcPHS1, AcPHS2, and AcPHS3); the messenger RNA expression levels of which differ depending on the amoeba life form. Pi uptake in cysts displayed peak activity at alkaline pH, whereas Pi transport in trophozoites was not affected in the same pH ranges. Cysts harbor a low-affinity Pi transport system (K0,5 and Vmax values of 1.76 ± 0.26 mM and 104.6 ± 6.3 nmol Pi × h-1 × 106 cells) compared to the trophozoite phosphate transport system. Pi transport seems important for anaerobic adenosine triphosphate synthesis in cysts, which initially occurs through the glycolytic pathway and subsequently through the pyruvate ferredoxin oxidoreductase pathway. Altogether, these results suggest that contrary to that previously postulated, cysts are active metabolic forms, and, as noted in trophozoites, phosphate uptake is important for energetic metabolism.

MRI of Penile Prostheses: The Challenge of Diagnosing Postsurgical Complications.

Penile implants are surgically inserted devices used for the treatment of erectile disfunction. Improvements in surgical techniques and in the manufacturing of these implants have reduced the risk of intra- and postoperative complications and increased the popularity and use of this therapeutic option. Routine imaging is not recommended before penile prosthesis surgery. Malleable penile prostheses use noninflatable shafts inserted into each corpus cavernosum, which appear hypointense on T1- and T2-weighted MR images. Inflatable penile prostheses (IPPs) may consist of two or three parts and are composed of two cylinders inserted into the corpora cavernosa that are filled with a saline solution to produce rigidity. These appear homogeneously T2 hyperintense and the silicone-based covering of the cylinders appears T2 hypointense, thereby clearly delineating the cylinders. In the case of three-piece IPPs, a reservoir containing the fluid may be placed in the pelvis. The most frequent complications are related to infection and mechanical failure, the latter being more common in IPPs because more components are involved. Less common complications include malpositioning. Detection and management of postoperative complications are challenging, and MRI plays a crucial role as it permits evaluation of the positioning and configuration of the prosthesis components, as well as assists in functional evaluation of IPPs when images are obtained of both the flaccid and inflated states. ©RSNA, 2021.