Preoperative diagnostic criteria for scleroatrophic gallbladder: A systematic review protocol.

BACKGROUND: Although scleroatrophic gallbladder is a rare condition, it presents significant clinical challenges in diagnosis and management. More agreement is needed on this disorder's diagnostic criteria and optimal management approach. We will conduct a systematic review to summarise the scleroatrophic gallbladder's preoperative diagnostic criteria, including imaging modalities. METHODS: A systematic review will be undertaken using the PRISMA guidelines. The protocol has been registered in PROSPERO (CRD42024503701). We will search in Medline (via PubMed), Embase, SCOPUS, the Cochrane Library, and Web of Science to find original studies reporting about scleroatrophic gallbladder or synonymous. Two reviewers will independently screen the titles and abstracts following the eligibility criteria. We will include all types of studies that describe any diagnostic criteria or tools. After retrieving the full text of the selected studies, we will conduct a standardised data extraction. Finally, a narrative synthesis will be performed. The quality of the identified studies will be assessed using the Quality Assessment of Diagnostic Accuracy Studies- 2 tool. DISCUSSION: This systematic review will provide information on the preoperative diagnostic criteria of the scleroatrophic gallbladder and the value of imaging studies in its diagnosis. In addition, this work will aid doctors in the decision-making process for diagnosing scleroatrophic gallbladder and propose treatment approaches to this condition. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered in PROSPERO (CRD42024503701).

Spinal Cord Stimulation in Refractory Postherpetic Neuralgia in Portugal: A Case Report.

Postherpetic neuralgia is one of the most severe complications after herpes zoster infection. Patients who experience persistent pain despite conservative treatment may benefit from interventional therapies, such as spinal cord stimulation. We present the case of a patient with severe refractory postherpetic neuralgia in the right T8 to L1 distribution who responded effectively to spinal cord stimulation. After its implantation, the patient had improvements in pain intensity, pain-related interference, quality of life, and satisfaction, with a simultaneous reduction of previous medications. This case report highlights the role of spinal cord stimulation in refractory neuropathic pain secondary to herpes zoster.

Can absolute arterial phase hyperenhancement improve sensitivity of detection of hepatocellular carcinoma in indeterminate nodules on CT?

OBJECTIVES: To determine if quantitative assessment of relative (R) and absolute (A) arterial phase hyperenhancement (APHE) and washout (WO) applied to indeterminate nodules on CT would improve the overall sensitivity of detection of hepatocellular carcinoma (HCC). METHODS: One-hundred and fourteen patients (90 male; mean age, 65 years) with 210 treatment-naïve HCC nodules (190 HCCs, 20 benign) who underwent 4-phase CT were included in this retrospective study. Four radiologists independently assigned a qualitative LR (LI-RADS) category per nodule. LR-3/4 nodules were then quantitatively analyzed by the 4 readers, placing ROIs within nodules and adjacent liver parenchyma. A/R-APHE and WO were calculated, and per-reader sensitivity and specificity updated. Interobserver agreement and AUCs were calculated per reader. RESULTS: Qualitative readers 1-4 categorized 57, 69, 57, and 63 nodules as LR-3/4 respectively with moderate to substantial agreement in LR category (kappa 0.56-0.69, p < 0.0001); their diagnostic performances in the detection of HCC were 80%, 73.2%, 77.4%, and 77.4% sensitivity, and 100%, 95%, 70%, and 100% specificity, respectively. A threshold of ≥ 20 HU for A-APHE increased overall sensitivity of HCC detection by 0.5-3.1% without changing specificity for the subset of nodules APHE - /WO + on qualitative read, with 2, 6, 6, and 1 additional HCC detected by readers 1-4. Relative and various A-WO formulae and thresholds all increased sensitivity, but with a drop in specificity for some/all readers. CONCLUSION: Quantitatively assessed A-APHE showed potential to increase sensitivity and maintain specificity of HCC diagnosis when selectively applied to indeterminate nodules demonstrating WO without subjective APHE. Quantitatively assessed R and A-WO increased sensitivity, however reduced specificity. CLINICAL RELEVANCE STATEMENT: A workflow using selective quantification of absolute arterial enhancement is routinely employed in the CT assessment of renal and adrenal nodules. Quantitatively assessed absolute arterial enhancement is a simple tool which may be used as an adjunct to help increase sensitivity and maintain specificity of HCC diagnosis in indeterminate nodules demonstrating WO without subjective APHE. KEY POINTS: • In indeterminate nodules categorized as LI-RADS 3/4 due to absent subjective arterial phase hyperenhancement, a cut-off for absolute arterial phase hyperenhancement of ≥ 20 HU may increase the overall sensitivity of detection of HCC by 0.5-3.1% without affecting specificity. • Relative and various absolute washout formulae and cut-offs increased sensitivity of HCC detection, but with a drop in specificity for some/all readers.

Herlyn-Werner-Wunderlich syndrome: A case report in a young woman, with literature review.

Herlyn-Werner-Wunderlich syndrome is a rare complex congenital disorder, with combined Müllerian and mesonephric duct anomalies, presenting with uterus didelphys, unilateral blind hemivagina and ipsilateral renal agenesis. Hemivaginal obstruction usually leads to impairment of normal menstrual flow, resulting in symptoms after menarche, namely dysmenorrhea, pelvic pain or infertility. Age of presentation depends on the anatomical features of this anomaly. We report a case of a 21-year-old female presenting with few symptoms and incidental findings on transvaginal ultrasound, with typical findings of this disorder on magnetic resonance imaging, which remains the gold standard imaging technique for thorough assessment of Herlyn-Werner-Wunderlich syndrome, allowing for a correct diagnosis and adequate surgical management. Our case also highlights some unusual features, such as the presence of a blind ectopic ureter, with hematic content, and an incomplete septum within the obstructed hemivagina.

COVID-19: What if immunity wanes?

Using a simple economic model in which social distancing reduces contagion, we study the implications of waning immunity for the epidemiological dynamics and social activity. If immunity wanes, we find that COVID-19 likely becomes endemic and that social distancing is here to stay until the discovery of a vaccine or cure. But waning immunity does not necessarily change optimal actions on the onset of the pandemic. Decentralized equilibria are virtually independent of waning immunity until close to peak infections. For centralized equilibria, the relevance of waning immunity decreases in the probability of finding a vaccine or cure, the costs of infection (e.g., infection-fatality rate), the degree of partial immunity and the presence of other NPIs that lower contagion (e.g., quarantining and mask use). In simulations calibrated to July 2020, our model suggests that waning immunity is virtually unimportant for centralized equilibria until at least 2021. This provides vital time for individuals and policy-makers to learn about immunity against SARS-CoV-2 before it becomes critical.

COVID­19 : et si l'immunité diminuait? À l'aide d'un modèle économique simple dans lequel la distanciation sociale permet de réduire la contagion, nous analysons les conséquences d'une baisse de l'immunité sur les dynamiques épidémiologiques et les activités sociales. Nous constatons que si l'immunité décline, c'est que la COVID­19 devient vraisemblablement endémique et que la distanciation sociale est vouée à perdurer jusqu'à la découverte d'un remède ou d'un vaccin. Néanmoins, une diminution de l'immunité ne modifie pas nécessairement les mesures optimales à prendre dès le début de la pandémie. Les équilibres décentralisés sont théoriquement indépendants d'une baisse de l'immunité jusqu'à l'approche du pic d'infection. Pour les équilibres centralisés, l'importance d'une diminution de l'immunité décroît avec la probabilité de trouver un vaccin ou un remède, avec les coûts imputables à l'infection (par exemple le taux de létalité), avec le taux d'immunité partielle et en présence d'autres interventions non pharmaceutiques (INP) permettant de diminuer la contagion (mises en quarantaine et utilisation du masque notamment). Dans les simulations calibrées sur juillet 2020, notre modèle montre qu'une baisse de l'immunité est pratiquement sans importance sur les équilibres centralisés, et ce au moins jusqu'en 2021. Cette période cruciale permettra aux individus et aux législateurs d'en apprendre davantage sur l'immunité contre le SARS­CoV­2 avant que le virus ne devienne critique.

Immobilization of the Tannase From Aspergillus fumigatus CAS21: Screening the Best Derivative for the Treatment of Tannery Effluent Using a Packed Bed Reactor.

Enzyme immobilization is an important alternative to stabilize enzyme properties favoring the efficiency of derivatives (enzyme + support/matrix) for different purposes. According to this, the current study aimed to immobilize the Aspergillus fumigatus CAS21 tannase and the use of the derivatives in the treatment of the effluent produced by the tannery industry. The tannase was immobilized on sodium alginate, DEAE-Sephadex, amberlite, and glass pearls as supports. Calcium alginate was the most adequate support for tannase immobilization with 100% yield and 94.3% for both efficiency and activity. The best tannase activity for the calcium alginate derivative was obtained at 50°C-60°C and pH 5.0. Thermal and pH stabilities evaluated for 24 h at 30°C-60°C and pH 4-7, respectively, were improved if compared to the stability of the free enzyme. Considering the reuse of the calcium alginate derivative, 78% of the initial activity was preserved after 10 catalytic cycles, and after the 9-month storage at 4°C, the activity was maintained in 70%. This derivative was applied in a packed bed reactor (PBR) for the treatment of tannin-rich effluents from the tannery industry. The reduction of the tannin content was effective reaching degradation of 74-78% after 48 h of PBR operation. The concentration of total phenolic compounds was also reduced, and the color and clarity of the effluent improved. In conclusion, the calcium alginate derivative is an attractive alternative as biocatalyst for large-scale treatment of the effluents from the tannery industry.

Proteins from the core genome of Corynebacterium ulcerans respond for pathogenicity and reveal promising vaccine targets for diphtheria.

Corynebacterium ulcerans is an emerging pathogen able to transmit the acute infection diphtheria to humans. Although there is a well-established vaccine based on the toxin produced by Corynebacterium diphtheriae, another species of this genus known to cause the disease, there is still no vaccine formulations described for C. ulcerans; this fact contributes to the increase in cases of infection that has been observed. In this study, we want to provide information at the genomic level of this bacterium in order to suggest proteins as possible vaccine targets. We carried out an in silico prospection of vaccine candidates through reverse vaccinology for targets that exhibit antigenic potential against diphtheria. We found important virulence factors, such as adhesion-related ones, that are responsible for pathogen-host interaction after infection, but we did not find the diphtheria toxin, which is the main component of the currently available vaccine. This study provides detailed information about the exoproteome and hypothetical proteins from the core genome of C. ulcerans, suggesting vaccine targets to be further tested in vitro for the development of a new vaccine against diphtheria.

Expression of F-actin and ß-tubulin genes in free mycelia and robust biofilms of the filamentous fungus Aspergillus niger.

The morphology and growth of the filamentous fungi are influenced by different factors as the culture conditions and the type of fermentative process. The production and secretion of metabolites by these organisms present a direct relationship with their morphology. The organization of the microtubules and actin in the cytoskeleton is determinant for both the fungal growth and morphology. In this context, this study aimed to analyze the expression of the ß-tubulin, F-actin, and glucan synthase in the A. niger mycelia obtained from submerged fermentation and biofilm fermentation through qPCR, as well as the analysis of the nucleus distribution in the hypha. Herein, we showed that ß-tubulin and the F-actin gene were more expressed in the biofilm condition, while the glucan synthase was in the submerged condition. No significant difference was observed in the nucleus distribution between the mycelia obtained from both the fermentative processes. In conclusion, the different morphologies observed for the mycelia from submerged fermentation and biofilm fermentation might be influenced by the differential modulation of genes that codify cytoskeleton proteins, which seems to be potentially regulated by mechanosensing during fungal contact with solid supports.

CT Noise-Reduction Methods for Lower-Dose Scanning: Strengths and Weaknesses of Iterative Reconstruction Algorithms and New Techniques.

Iterative reconstruction (IR) algorithms are the most widely used CT noise-reduction method to improve image quality and have greatly facilitated radiation dose reduction within the radiology community. Various IR methods have different strengths and limitations. Because IR algorithms are typically nonlinear, they can modify spatial resolution and image noise texture in different regions of the CT image; hence traditional image-quality metrics are not appropriate to assess the ability of IR to preserve diagnostic accuracy, especially for low-contrast diagnostic tasks. In this review, the authors highlight emerging IR algorithms and CT noise-reduction techniques and summarize how these techniques can be evaluated to help determine the appropriate radiation dose levels for different diagnostic tasks in CT. In addition to advanced IR techniques, we describe novel CT noise-reduction methods based on convolutional neural networks (CNNs). CNN-based noise-reduction techniques may offer the ability to reduce image noise while maintaining high levels of image detail but may have unique drawbacks. Other novel CT noise-reduction methods are being developed to leverage spatial and/or spectral redundancy in multiphase or multienergy CT. Radiologists and medical physicists should be familiar with these different alternatives to adapt available CT technology for different diagnostic tasks. The scope of this article is (a) to review the clinical applications of IR algorithms as well as their strengths, weaknesses, and methods of assessment and (b) to explore new CT image reconstruction and noise-reduction techniques that promise to facilitate radiation dose reduction. ©RSNA, 2021.

Percepções dos moradores do bairro da Engomadeira sobre UNEB-BA / Perceptions of the Residents of the Engomadeira Neighborhood on the UNEB-BA / Las Percepciones de los Habitantes del barrio de Engomadeira sobre UNEB-BA

Este trabalho tem como objetivo analisar as percepções dos moradores do Bairro Engomadeira sobre a Universidade do Estado da Bahia (UNEB), Campus I, Salvador, para assim propor melhorias nas relações estabelecidas entre a Comunidade e a Universidade. Para a discussão, utilizaram-se autores como Fialho, Midlej e Santos. A pesquisa foi desenvolvida numa abordagem qualitativa, utilizando como instrumento de coleta de dados a entrevista semiestruturada e questionários fechados, aplicados em amostra não probabilística de 20 (vinte) moradores, dividindo-se em três grupos, por escolaridade: nível fundamental, nível médio e nível superior, para identificar e analisar as suas percepções. Recorreu-se à análise de conteúdo de Bardin (2002) e à luz de autores como Midlej e Santos, para tratamento dos dados coletados. Notou-se no referido estudo que as percepções dos moradores da Engomadeira sobre a Uneb diferem pelo nível de escolaridade, em que os moradores de nível fundamental e médio percebem a universidade com relações positivas e os de nível superior com relações negativas.

This work aims to analyze the perceptions of residents of Bairro Engomadeira about the State University of Bahia (UNEB), Campus I, Salvador, to propose improvements in the relations established between the Community and the University. For the discussion, authors such as Fialho (1998), Midlej (2004) and Santos (2014) were consulted. The research was developed in a qualitative approach, using semi-structured interviews and closed questionnaires as a data collection instrument, applied to a non-probabilistic sample of 20 (twenty) residents, dividing into three groups, by level of education: elementary level, medium level and higher level, to identify and analyze their perceptions. Content analysis by Bardin (2002) was used, and in the light of authors such as Midlej (2004) and Santos (2008), for the treatment of the collected data. It was noted in that study, that the perceptions of the residents of the Ironing Company about Uneb differ by the level of education, where the residents of elementary and high school perceive the university with positive relationships and those with higher education, with negative relationships.

Este trabajo tiene como objetivo analizar las percepciones de los habitantes del Barrio Engomadeira sobre la Universidad Estatal de Bahía (UNEB), Campus I, Salvador, con el fin de proponer mejoras en las relaciones establecidas entre la Comunidad y la Universidad. Para la discusión se utilizaron autores como Fialho (1998), Midlej (2004) y Santos (2014). La investigación se desarrolló con un enfoque cualitativo, utilizando entrevistas semi-estructuradas y cuestionarios cerrados como instrumento de recolección de datos, aplicados a una muestra no probabilística de 20 (veinte) residentes, divididos en tres grupos, por nivel de educación: nivel básico, nivel medio y nivel superior, para identificar y analizar sus percepciones. Se utilizó el análisis de contenido de Bardin (2002), ya la luz de autores como Midlej (2004) y Santos (2008), para el tratamiento de los datos recolectados. Se constató en dicho estudio, que las percepciones de los vecinos de la Empresa de Planchado sobre la Uneb difieren por el nivel de educación, donde los residentes de primaria y secundaria perciben la universidad con relaciones positivas y los de educación superior, con relaciones negativas.

Antibody tests: They are more important than we thought.

Antibody testing is a non-pharmaceutical intervention - not recognized so far in the literature - to prevent COVID-19 contagion. I show this in a simple economic model of an epidemic in which agents choose social activity under health state uncertainty. In the model, susceptible and asymptomatic agents are more socially active when they think they might be immune. And this increased activity escalates infections, deaths, and welfare losses. Antibody testing, however, prevents this escalation by revealing that those agents are not immune. Through this mechanism, I find that antibody testing prevents about 12% of COVID-19 related deaths within 12 months.

The added value of contrast-enhanced ultrasound in evaluation of indeterminate small solid renal masses and risk stratification of cystic renal lesions.

OBJECTIVES: To investigate accuracy of contrast-enhanced ultrasound (CEUS) to characterize indeterminate small solid renal masses (sSRMs), excluding lipid-rich AMLs, and cystic renal masses (CRMs) according to the proposed Bosniak Classification 2019 MATERIALS AND METHODS: CEUS of pathology-proven CRMs and sSRMs (without definite enhancement or macroscopic fat on CT/MRI), and CRMs with ≥18 months follow-up were retrospectively reviewed. Two radiologists blindly categorized CRMs according to new Bosniak Classification on CT/MRI. On CEUS, two other radiologists evaluated arterial-phase enhancement of sSRMs relative to renal cortex and categorized CRMs following new Bosniak Classification. Fisher's exact/chi-squared test was used to compare categorical variables, and Cohen κ statistics for inter-observer agreement RESULTS: A total of 237 patients had 241 lesions: 161 pathology-proven sSRMs (122 malignant and 39 benign), 29 pathology-proven CRMs, 51 CRMs with adequate follow-up. Arterial-phase enhancement < renal cortex predicted malignancy with specificity of 97.4% (38/39) (CI 85.6-99.9%), and positive predictive value (PPV) of 98.2% (54/55) (CI 90.4-99.9%). Inter-observer kappa was 0.95. In pathology-proven CRMS, sensitivity of CEUS vs CT/MRI was 100% (15/15) (CI 79.6-100%) vs 60% (9/15) (CI 35.8-80.1%) (p value = .002) and negative predictive value (NPV) 100% (2/2) (CI 17.8-100%) vs 25% (2/8 ) (CI 4.4-59.1%) (p value < 0.0001), with similar specificity (50%) and PPV- 88.2% (15/17) (CI 65.7-97.9%) vs 81.8% (9/11) (CI 52.3-96.8%) ( p value = 0.586). Bosniak Classification inter-observer kappa was 0.92 for CEUS vs 0.68 for CT/MRI (p value = 0.009). CONCLUSION: In our cohort, CEUS had high specificity and PPV to diagnose RCC in sSRMs excluding lipid-rich AML. CEUS had significantly higher sensitivity/NPV to diagnose malignancy in CRMs as compared to CT/MRI. KEY POINTS: • Once lipid-rich AML is excluded by the other modalities, sSRM arterial phase hypo-enhancement relative to renal cortex on CEUS yielded high specificity (97.4%) and PPV (98.2%) to diagnose RCC. • When applying the proposed Bosniak Classification 2019, CEUS showed higher sensitivity compared to CT/MRI (100% vs 60%), p value=.0024, in the stratification of cystic renal masses to diagnose malignancy. • CEUS may reduce the number of CT/MRI Bosniak IIF lesions by assigning them to either II or III/IV categories.

Evaluation of Crohn Disease Activity Using a Potential Abbreviated MRE Protocol Consisting of Balanced Steady-State Free Precession MRI Only Versus Full-Protocol MRE.

OBJECTIVE. The purpose of the present study was to compare the diagnostic performance of an abbreviated MR enterography (MRE) protocol consisting of balanced steady-state free-precession (b-SSFP) imaging only versus standard full-protocol MRE for the evaluation of Crohn disease activity. MATERIALS AND METHODS. This single-center retrospective study included 112 patients with Crohn disease (66 women and 46 men; age range, 18-84 years) who underwent MRE between January 2017 and March 2018. Utilizing binary and 5-point Likert confidence scales, two blinded readers independently interpreted and scored disease activity on b-SSFP sequences only and on full-protocol MRE images. Interreader and intrareader agreement on confidence regarding disease activity were calculated using weighted kappa indexes. Correlation between MRE findings of Crohn disease and the Harvey-Bradshaw index was also performed. RESULTS. Perfect intrareader agreement and strong interreader agreement on disease activity were observed (intrareader agreement: κ = 0.97, 0.96, and 0.96 for reader A, reader B, and both readers combined; interreader agreement: κ = 0.82 for b-SSFP imaging only and κ = 0.81 for MRE). For detecting active Crohn disease, b-SSFP sequences had a sensitivity and specificity of 97% and 100%, respectively, for reader A and 98% and 86%, respectively, for reader B. Strong-to-perfect intrareader agreement was achieved between b-SSFP imaging only and MRE for identification of penetrating disease (κ = 0.80 and 0.97) and stenosing disease (κ = 0.87 and 0.95). Perfect intrareader agreement was also obtained between b-SSFP imaging only and MRE for detecting abnormal bowel segments (κ = 0.91 for reader A; κ = 0.98 for reader B). Weak agreement was noted between both b-SSFP imaging only and MRE versus the Harvey-Bradshaw index (κ = 0.08 of reader A; κ = 0.04 for reader B). CONCLUSION. Robust agreement was observed between b-SSFP imaging only and full-protocol MRE for the assessment of Crohn disease activity and complications. An abbreviated MRE protocol that exclusively uses b-SSFP sequences appears feasible and has significant implications for health care resources.

First Steps in the Analysis of Prokaryotic Pan-Genomes.

Pan-genome is defined as the set of orthologous and unique genes of a specific group of organisms. The pan-genome is composed by the core genome, accessory genome, and species- or strain-specific genes. The pan-genome is considered open or closed based on the alpha value of the Heap law. In an open pan-genome, the number of gene families will continuously increase with the addition of new genomes to the analysis, while in a closed pan-genome, the number of gene families will not increase considerably. The first step of a pan-genome analysis is the homogenization of genome annotation. The same software should be used to annotate genomes, such as GeneMark or RAST. Subsequently, several software are used to calculate the pan-genome such as BPGA, GET_HOMOLOGUES, PGAP, among others. This review presents all these initial steps for those who want to perform a pan-genome analysis, explaining key concepts of the area. Furthermore, we present the pan-genomic analysis of 9 bacterial species. These are the species with the highest number of genomes deposited in GenBank. We also show the influence of the identity and coverage parameters on the prediction of orthologous and paralogous genes. Finally, we cite the perspectives of several research areas where pan-genome analysis can be used to answer important issues.

Dual-energy CT in diffuse liver disease: is there a role?

Dual-energy CT (DECT) can be defined as the use of two different energy levels to identify and quantify material composition. Since its inception, DECT has benefited from remarkable improvements in hardware and clinical applications. DECT enables accurate identification and quantification of multiple materials, including fat, iron, and iodine. As a consequence, multiple studies have investigated the potential role of DECT in the assessment of diffuse liver diseases. While this role is evolving, this article aims to review the most relevant literature on use of DECT for assessment of diffuse liver diseases. Moreover, the basic concepts on DECT techniques, types of image reconstruction, and DECT-dedicated software will be described, focusing on the areas that are most relevant for the evaluation of diffuse liver diseases. Also, we will review the evidence of added value of DECT in detection and assessment of hepatocellular carcinoma which is a known risk in patients with diffuse liver disease.

Stabilization and application of spray-dried tannase from Aspergillus fumigatus CAS21 in the presence of different carriers.

The Aspergillus fumigatus CAS21 tannase was spray dried with ß-cyclodextrin, Capsul® starch, soybean meal, lactose, and maltodextrin as adjuvants. The moisture content and water activity of the products ranged from 5.6 to 11.5% and from 0.249 to 0.448, respectively. The maximal tannase activity was achieved at 40-60 ºC and pH 5.0-6.0 for the powders containing ß-cyclodextrin and Capsul® starch, which was stable at 40 ºC and 40-60 ºC for 120 min, respectively. For all the dried products, tannase retained its activity of over 80% for 120 min at pH 5.0 and 6.0. Salts and solvents influenced the activity of the spray-dried tannase. The activity of the spray-dried tannase was maintained when preserved for 1 year at 4 ºC and 28 ºC. Spray-dried tannase reduced the content of tannins and polyphenolic compounds of leather effluent and sorghum flour and catalyzed the transesterification reaction. The spray drying process stabilized the tannase activity, highlighting the potential of dried products for biotechnological applications.

Assessment of biliary anatomy in potential living liver donors: Added value of gadoxetic acid-enhanced T1 MR Cholangiography (MRC) including utilization of controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) technique in comparison to T2W-MRC.

OBJECTIVES: To assess the added value of gadoxetic-acid-enhanced T1-weighted magnetic resonance Cholangiography (T1W-MRC) including controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-Volumetric Interpolated Breathhold (VIBE) technique compared to T2-weighted MR Cholangiography (T2W-MRC) in depicting biliary anatomy in potential living liver donors. METHODS: Eighty-five potential donors including 34 men with a mean age of 35.6 years (range, 18-55 years) and 51 women with a mean age of 36.7 years (range, 23-57 years), were enrolled in this ethics-approved retrospective study. Image quality for depiction of bile ducts was evaluated by two readers in consensus in 3 separate reading sessions: 1) T2W-MRC alone, 2) T1W-MRC alone (including CAIPI-VIBE and generalized autocalibrating partially parallel acquisitions (GRAPPA)-VIBE techniques, and 3) combined T1W/T2W-MRC. Accuracy of T2W-MRC, T1W-MRC, and combined T1W/T2W-MRC for the identification/classification of the biliary variants was calculated using intraoperative cholangiogram (IOC) as the reference standard. Image quality and reader diagnostic confidence provided by CAIPI-VIBE technique was compared with GRAPPA-VIBE technique. Datasets were compared using the Wilcoxon signed-rank test. RESULTS: Image quality for depiction of the bile ducts was significantly superior in the combined T1W/T2W-MRC group, when compared to each of T2W-MRC and T1W-MRC groups independently (P value = 0.001-0.034). The combination of CAIPI-VIBE and GRAPPA-VIBE was superior compared to each of the sequences individually. The accuracy of T2W-MRC and T1W-MRC was 93% and 91%, respectively. T1W-MRC depicted four biliary variants better than T2W-MRC. Two variants not well seen in T2W-MRC were clearly shown on T1W-MRC. CONCLUSION: Gadoxetic-acid-enhanced T1W-MRC and conventional T2W-MRC techniques are complementary for depiction of biliary variants in potential liver donors and the combination of the two improves the results. The combination of CAIPI-VIBE and GRAPPA-VIBE techniques appear to be complementary for optimal diagnostic yield of T1W-MRC.

The small molecule AZD6244 inhibits dengue virus replication in vitro and protects against lethal challenge in a mouse model.

Dengue virus (DENV) is the most common mosquito-borne viral disease. The World Health Organization estimates that 400 million new cases of dengue fever occur every year. Approximately 500,000 individuals develop severe and life-threatening complications from dengue fever, such as dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF), which cause 22,000 deaths yearly. Currently, there are no specific licensed therapeutics to treat DENV illness. We have previously shown that the MEK/ERK inhibitor U0126 inhibits the replication of the flavivirus yellow fever virus. In this study, we demonstrate that the MEK/ERK inhibitor AZD6244 has potent antiviral efficacy in vitro against DENV-2, DENV-3, and Saint Louis encephalitis virus (SLEV). We also show that it is able to protect AG129 mice from a lethal challenge with DENV-2 (D2S20). The molecule is currently undergoing phase III clinical trials for the treatment of non-small-cell lung cancer. The effect of AZD6244 on the DENV life cycle was attributed to a blockade of morphogenesis. Treatment of AG129 mice twice daily with oral doses of AZD6244 (100 mg/kg/day) prevented the animals from contracting dengue hemorrhagic fever (DHF)-like lethal disease upon intravenous infection with 1 × 105 PFU of D2S20. The effectiveness of AZD6244 was observed even when the treatment of infected animals was initiated 1-2 days postinfection. This was also followed by a reduction in viral copy number in both the serum and the spleen. There was also an increase in IL-1ß and TNF-α levels in mice that were infected with D2S20 and treated with AZD6244 in comparison to infected mice that were treated with the vehicle only. These data demonstrate the potential of AZD6244 as a new therapeutic agent to treat DENV infection and possibly other flavivirus diseases.