Accessible Eco-Friendly Method for Wastewater Removal of the Azo Dye Reactive Black 5 by Reusable Protonated Chitosan-Deep Eutectic Solvent Beads.

A novel approach to enhance the utilization of low-cost and sustainable chitosan for wastewater remediation is presented in this investigation. The study centers around the modification of chitosan beads using a deep eutectic solvent composed of choline chloride and urea at a molar ratio of 1:2, followed by treatment with sulfuric acid using an impregnation accessible methodology. The effectiveness of the modified chitosan beads as an adsorbent was evaluated by studying the removal of the azo dye Reactive Black 5 (RB5) from aqueous solutions. Remarkably, the modified chitosan beads demonstrated a substantial increase in adsorption efficiency, achieving excellent removal of RB5 within the concentration range of 25-250 mg/L, ultimately leading to complete elimination. Several key parameters influencing the adsorption process were investigated, including initial RB5 concentration, adsorbent dosage, contact time, temperature, and pH. Quantitative analysis revealed that the pseudo-second-order kinetic model provided the best fit for the experimental data at lower dye concentrations, while the intraparticle diffusion model showed superior performance at higher RB5 concentration ranges (150-250 mg/L). The experimental data were successfully explained by the Langmuir isotherm model, and the maximum adsorption capacities were found to be 116.78 mg/g at 298 K and 379.90 mg/g at 318 K. Desorption studies demonstrated that approximately 41.7% of the dye could be successfully desorbed in a single cycle. Moreover, the regenerated adsorbent exhibited highly efficient RB5 removal (80.0-87.6%) for at least five consecutive uses. The outstanding adsorption properties of the modified chitosan beads can be attributed to the increased porosity, surface area, and swelling behavior resulting from the acidic treatment in combination with the DES modification. These findings establish the modified chitosan beads as a stable, versatile, and reusable eco-friendly adsorbent with high potential for industrial implementation.

Relevant SARS-CoV-2 viremia is associated with COVID-19 severity: Prospective cohort study and validation cohort.

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.

miR-181a-2* expression is different amongst carcinomas from the colorectal serrated route.

Serrated adenocarcinoma (SAC) and colorectal carcinomas showing histological and molecular features of high-level of microsatellite instability (hmMSI-H) are both end points of the serrated pathway of colorectal carcinogenesis. Despite common features (right-sided location, CpG island methylation phenotype and BRAF mutation) there are no studies comparing the microRNA (miRNA) expression profiles in SACs and hmMSI-H. The microtranscriptome from 12 SACs and 8 hmMSI-H were analysed using Affymetrix GeneChip miRNA 3.0 arrays and differentially enriched functions involving immune response were observed from this comparison. miR-181a-2* was found significantly more expressed in hmMSI-H than in SAC and higher expression of this miRNA in microsatellite unstable colorectal cancer were corroborated by Real-Time PCR in an extended series (61 SAC, 21 hmMSI-H). An analysis of genes possibly regulated by miR-181a-2* was carried out and, amongst these, an inverse correlation of NAMPT with miR-181a-2* expression was observed, whereas, for TRAF1 and SALL1, additional regulation mechanisms involving CpG island methylation were observed. miR-181a-2* is associated with particular histological and molecular features of colorectal carcinomas within the serrated pathological pathway and might play a role in the immune responses of microsatellite instability carcinomas.

Correction to: Efficacy and safety of endoscopic balloon dilation in inflammatory bowel disease: results of the large multicenter study of the ENEIDA registry.

Javier P. Gisbert was listed incorrectly as Javier Pérez-Gisbert.

Efficacy and safety of endoscopic balloon dilation in inflammatory bowel disease: results of the large multicenter study of the ENEIDA registry.

BACKGROUND: There is no information regarding the outcome of Crohn's disease (CD) patients treated with endoscopic balloon dilation (EBD) in non-referral hospitals, nor on the efficacy of EBD in ulcerative colitis (UC). We report herein the results of the largest series published to date. AIM: To assess the efficacy and safety of EBD for inflammatory bowel disease (IBD) stenosis performed in 19 hospitals with different levels of complexity and to determine factors related to therapeutic success. METHODS: We identified IBD patients undergoing EBD in the ENEIDA database. Efficacy of EBD was compared between CD and UC and between secondary and tertiary hospitals. Predictive factors of therapeutic success were assessed with multivariate analysis. RESULTS: Four-hundred dilations (41.2% anastomotic) were performed in 187 IBD patients (13 UC/Indeterminate colitis). Technical and therapeutic success per dilation was achieved in 79.5% and 55.3%, respectively. Therapeutic success per patient was achieved in 78.1% of cases (median follow-up: 40 months) with 49.7% requiring more than one dilation. No differences related to either diagnosis or hospital complexity was found. Technical success [OR 4.12 (95%CI 2.4-7.1)] and not receiving anti-TNF at the time of dilation [OR 1.7 (95% CI 1.1-2.6)] were independently related to therapeutic success per dilation. A stricture length ≤ 2 cm [HR 2.43 (95% CI 1.11-5.31)] was a predictive factor of long-term success per patient. The rate of major complications was 1.3%. CONCLUSIONS: EBD can be performed with similar efficacy and safety in hospitals with differing levels of complexity and it might be a suitable treatment for UC with short stenosis. To achieve a technical success and the short length of the stenosis seem to be critical for long-term therapeutic success.

Biology and Therapeutic Targets of Colorectal Serrated Adenocarcinoma; Clues for a Histologically Based Treatment against an Aggressive Tumor.

Serrated adenocarcinoma (SAC) is a tumor recognized by the WHO as a histological subtype accounting for around 9% of colorectal carcinomas. Compared to conventional carcinomas, SACs are characterized by a worse prognosis, weak development of the immune response, an active invasive front and a frequent resistance to targeted therapy due to a high occurrence of KRAS or BRAF mutation. Nonetheless, several high-throughput studies have recently been carried out unveiling the biology of this cancer and identifying potential molecular targets, favoring a future histologically based treatment. This review revises the current evidence, aiming to propose potential molecular targets and specific treatments for this aggressive tumor.

Liquid-liquid extraction of phenolic compounds from water using ionic liquids: Literature review and new experimental data using [C2mim]FSI.

In this work, the capability of the ionic liquid, 1-ethyl-3-methylimidazolium bis(fluorosulfonyl)imide, [C2mim]FSI, to extract o-cresol, 2-chlorophenol, resorcinol and phenol from water, reaching the legal limit of 1 mg L-1 was analyzed. The extraction process was carried out for each one of these phenolic compounds varying the initial concentration in water from 3 mg L-1 to 1000 mg L-1, and for aqueous mixtures of the four phenolic compounds in the same concentration range. Because of the scarcity of physical properties of the [C2mim]FSI, density, speed of sound, dynamic viscosity and refractive index were measured from 293.15 to 343.15 K at atmospheric pressure. From the experimental data, the thermal expansion coefficient and the isentropic compressibility for the pure ionic liquid were calculated. Even though [C2mim]FSI is hydrophobic, it can solve small quantities of water that can hinder the recovery of the ionic liquid, consequently the solubility of water in the ionic liquid was determined at several temperatures and atmospheric pressure. In addition to experimental data, a literature review on the use of ionic liquids to extract phenolic compounds from water was performed.

Three-dimensional balance of cortical tension and axial contractility enables fast amoeboid migration.

Fast amoeboid migration requires cells to apply mechanical forces on their surroundings via transient adhesions. However, the role these forces play in controlling cell migration speed remains largely unknown. We used three-dimensional force microscopy to measure the three-dimensional forces exerted by chemotaxing Dictyostelium cells, and examined wild-type cells as well as mutants with defects in contractility, internal F-actin crosslinking, and cortical integrity. We showed that cells pull on their substrate adhesions using two distinct, yet interconnected mechanisms: axial actomyosin contractility and cortical tension. We found that the migration speed increases when axial contractility overcomes cortical tension to produce the cell shape changes needed for locomotion. We demonstrated that the three-dimensional pulling forces generated by both mechanisms are internally balanced by an increase in cytoplasmic pressure that allows cells to push on their substrate without adhering to it, and which may be relevant for amoeboid migration in complex three-dimensional environments.

Incidence, clinical outcomes, and therapeutic approaches of capsule endoscopy-related adverse events in a large study population.

INTRODUCTION: Capsule endoscopy (CE) has become a first-line tool for small bowel (SB) examination. However, adverse events (AEs), such as CE retention or aspiration, may occur. The aims of this study were to evaluate incidence, clinical outcomes and therapeutic approaches of CE-related AEs in the largest series published to date. METHODS: Data from 5428 procedures performed at 12 institutions between August 2001 and January 2012 were retrospectively analyzed. Baseline patient characteristics; procedure; type, localization and symptoms before/after AEs; previous patency tests performed; therapeutic management and patient's outcome were recorded. RESULTS: The overall incidence of CE-related AEs was 1.9%: 2.0% for SB, 0.9% for esophageal and 0.5% for colon CE. The incidence of capsule retention was significantly higher than capsule aspiration (1.87% vs. 0.003%; p < 0.05), in patients suffering from inflammatory bowel disease (IBD) than in obscure GI bleeding (OGIB) (3.3% vs. 1.5%; p < 0.05) and in patients with the combination of nausea/vomiting, abdominal pain and distension. The SB was the most frequent localization of retention (88.2%). The use of patency tests -except for Patency© capsule- before CE was not a good predictor for AEs. Most of the patients with AEs developed no or mild symptoms (97%) and were managed by non-surgical methods (64.4%). CONCLUSIONS: CE-related AEs are uncommon and difficult to predict by imagiological examinations. SB retention, that is usually asymptomatic, is the most frequent AE. In absence of symptoms, non-surgical management of CE-related AEs is recommended.

A universal protocol to generate consensus level genome sequences for foot-and-mouth disease virus and other positive-sense polyadenylated RNA viruses using the Illumina MiSeq.

BACKGROUND: Next-Generation Sequencing (NGS) is revolutionizing molecular epidemiology by providing new approaches to undertake whole genome sequencing (WGS) in diagnostic settings for a variety of human and veterinary pathogens. Previous sequencing protocols have been subject to biases such as those encountered during PCR amplification and cell culture, or are restricted by the need for large quantities of starting material. We describe here a simple and robust methodology for the generation of whole genome sequences on the Illumina MiSeq. This protocol is specific for foot-and-mouth disease virus (FMDV) or other polyadenylated RNA viruses and circumvents both the use of PCR and the requirement for large amounts of initial template. RESULTS: The protocol was successfully validated using five FMDV positive clinical samples from the 2001 epidemic in the United Kingdom, as well as a panel of representative viruses from all seven serotypes. In addition, this protocol was successfully used to recover 94% of an FMDV genome that had previously been identified as cell culture negative. Genome sequences from three other non-FMDV polyadenylated RNA viruses (EMCV, ERAV, VESV) were also obtained with minor protocol amendments. We calculated that a minimum coverage depth of 22 reads was required to produce an accurate consensus sequence for FMDV O. This was achieved in 5 FMDV/O/UKG isolates and the type O FMDV from the serotype panel with the exception of the 5' genomic termini and area immediately flanking the poly(C) region. CONCLUSIONS: We have developed a universal WGS method for FMDV and other polyadenylated RNA viruses. This method works successfully from a limited quantity of starting material and eliminates the requirement for genome-specific PCR amplification. This protocol has the potential to generate consensus-level sequences within a routine high-throughput diagnostic environment.

A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus.

The stamping-out policy for the control of foot-and-mouth disease virus (FMDV) in countries that are free from FMD without vaccination has a dramatic socio-economic impact, huge animal welfare issues and may result in the loss of farm animal genetic resources. As an alternative to pre-emptive culling or emergency vaccination we further explore the possibility to use antiviral drugs in the event of an FMD outbreak. In the present study, we tested the in vitro cytotoxicity and anti-FMDV activity of 1,2,4,5-tetrahydro-[1,4]thiazepino[4,5-a]benzimidazole. The molecule was shown to inhibit the replication of reference strains of the Eurasian FMDV serotypes O, A, C and Asia but not the FMDV serotypes from the South African Territories (SAT) neither a related picornavirus, i.e. swine vesicular disease virus. The molecule can be added until 2h post inoculation in a 'single replication cycle experiment' without losing its antiviral activity. The genetic characterization of progressively selected resistant FMD viruses shows that the molecule presumably interacts with the non-structural 2C protein of FMDV. Further studies are required on the use of this molecule in vivo.

Changes in breast cancer reports after pathology second opinion.

Breast cancer pathology reports contain valuable information about the histologic diagnosis, prognostic factors and predictive indicators of therapeutic response. A second opinion may be requested by medical oncologists and surgeons, when a patient is referred from another institution for treatment. We report the experience with pathology second opinion in selected patients referred to the Breast Oncology Unit. 205 cases referred to the Breast Oncology Unit were selected for second opinion after clinical evaluation, between 2002 and 2012. The cases reviewed included 102 core needle biopsies, 88 surgical specimens from the breast and 18 lymphadenopathies, 14 from the axillary region. Pathology second opinion was based on a review of hematoxylin-eosin preparations, recuts of submitted paraffin blocks and written external pathology reports. Immunohistochemical studies for hormone receptors, HER2, myoepithelial cells, and other markers were performed in selected cases. A case was reclassified as showing major change when second opinion showed a potential for significant change in prognosis or treatment. Otherwise, it was considered to represent minor change or to be concordant. In 52 cases (25.4%), the pathology review showed changes. Thirty-three (16%) patients were reclassified for major changes and 19 (9.2%) as minor changes. In six patients, more than one major change was identified. The major discrepancies identified were related to the histologic classification (12 cases), the presence or absence of invasion in ductal carcinoma (15 cases), the results of hormone receptors (5 cases), and HER2 (7 cases). Major changes in histologic classification included two cases diagnosed as invasive ductal carcinoma and reclassified as benign, four cases with diagnosis of breast cancer reclassified as metastatic lung cancer, one case diagnosed as small cell carcinoma of lung metastatic in the breast, reclassified as primary carcinoma of the breast, and three cases with diagnosis of breast cancer in the axilla reclassified as primary cutaneous adnexal carcinomas (2) and metastatic melanoma (1), respectively. In two cases, the histologic type of the primary breast tumor was changed. Second opinion in breast pathology may uncover significant discrepancies that impact on patient management and prognosis. Major discrepancies are most frequently related to the assessment of the presence or absence of invasion in ductal carcinoma, the results of predictive makers of therapeutic response, and the differential diagnosis of breast cancer and nonmammary tumors in the breast, the axilla, and at distant sites.

Venturi Injector Optimization for Precise Powder Transport for Directed Energy Deposition Manufacturing Using the Discrete Element Method and Genetic Algorithms.

Additive manufacturing technologies such as directed energy deposition use powder as their raw material, and it must be deposited in a precise and controlled manner. Venturi injectors could be a solution for the highly precise transport of particulate material. They have been studied from different perspectives, but they are always under high-pressure conditions and mostly fed by gravity. In the present study, an optimization of the different dimensional parameters needed for the manufacturing of a Venturi injector in relation to a particle has been carried out to maximize the amount of powder capable of being sucked and transported for a specific flow in a low-pressure system with high precision in transport. For this optimization, simulations of Venturi usage were performed using the discrete element method, generating different variations proposed by a genetic algorithm based on a preliminary design of experiments. Statistical analysis was also performed to determine the most influential design variables on the objective, with these being the suction diameter (D3), the throat diameter (d2), and the nozzle diameter (d1). The optimal dimensional relationships were as follows: a D3 34 times the particle diameter, a d2 26.5 times the particle diameter, a d1 40% the d2, a contraction angle alpha of 18.73°, and an expansion angle beta of 8.28°. With these proportions, an 85% improvement in powder suction compared to the initial attempts was achieved, with a maximum 2% loss of load.

Monastrol suppresses invasion and metastasis in human colorectal cancer cells by targeting fascin independent of kinesin-Eg5 pathway.

Rearrangement of the actin cytoskeleton is a prerequisite for carcinoma cells to develop cellular protrusions, which are required for migration, invasion, and metastasis. Fascin is a key protein involved in actin bundling and is expressed in aggressive and invasive carcinomas. Additionally, fascin appears to be involved in tubulin-binding and microtubule rearrangement. Pharmacophoric-based in silico screening was performed to identify compounds with better fascin inhibitory properties than migrastatin, a gold-standard fascin inhibitor. We hypothesized that monastrol displays anti-migratory and anti-invasive properties via fascin blocking in colorectal cancer cell lines. Biophysical (thermofluor and ligand titration followed by fluorescence spectroscopy), biochemical (NMR), and cellular assays (MTT, invasion of human tissue), as well as animal model studies (zebrafish invasion) were performed to characterize the inhibitory effect of monastrol on fascin activity. In silico analysis revealed that monastrol is a potential fascin-binding compound. Biophysical and biochemical assays demonstrated that monastrol binds to fascin and interferes with its actin-bundling activity. Cell culture studies, including a 3D human myoma disc model, showed that monastrol inhibited fascin-driven cytoplasmic protrusions as well as invasion. In silico, confocal microscopy, and immunoprecipitation assays demonstrated that monastrol disrupted fascin-tubulin interactions. These anti-invasive effects were confirmed in vivo. In silico confocal microscopy and immunoprecipitation assays were carried out to test whether monastrol disrupted the fascin-tubulin interaction. This study reports, for the first time, the in vitro and in vivo anti-invasive properties of monastrol in colorectal tumor cells. The number and types of interactions suggest potential binding of monastrol across actin and tubulin sites on fascin, which could be valuable for the development of antitumor therapies.

Accumulation of nucleotide substitutions occurring during experimental transmission of foot-and-mouth disease virus.

Analysis of full-genome sequences was previously used to trace the origin and transmission pathways of foot-and-mouth disease virus (FMDV) outbreaks in the UK in 2001 and 2007. Interpretation of these data was sometimes at variance with conventional epidemiological tracing, and was also used to predict the presence of undisclosed infected premises that were later discovered during serological surveillance. Here we report the genome changes associated with sequential passage of a highly BHK-21-cell-adapted (heparan sulphate-binding) strain of FMDV arising from two independent transmission chains in cattle. In vivo virus replication rapidly selected for a wild-type variant with an amino acid substitution at VP3(56). Full-genome sequence analysis clearly demonstrated sequence divergence during parallel passage. The genetic diversity generated over the course of infection and the rate at which these changes became fixed and were transmitted between cattle occurred at a rate sufficient to enable reliable tracing of transmission pathways at the level of the individual animal. However, tracing of transmission pathways was only clear when sequences from epithelial lesions were compared. Sequences derived from oesophageal-pharyngeal scrapings were problematic to interpret, with a varying number of ambiguities suggestive of a more diverse virus population. These findings will help to correctly interpret full-genome sequence analyses to resolve transmission pathways within future FMDV epidemics.

Genome sequences of SAT 2 foot-and-mouth disease viruses from Egypt and Palestinian Autonomous Territories (Gaza Strip).

Two foot-and-mouth disease virus (FMDV) genome sequences have been determined for isolates collected from recent field outbreaks in North Africa (Egypt) and the Middle East (Palestinian Autonomous Territories). These data represent the first examples of complete genomic sequences for the FMDV SAT 2 topotype VII, which is thought to be endemic in countries immediately to the south of the Sahara desert. Further studies are now urgently required to provide insights into the epidemiological links between these outbreaks and to define the pathogenicity of this emerging lineage.

Multiple introductions of serotype O foot-and-mouth disease viruses into East Asia in 2010-2011.

Foot-and-mouth disease virus (FMDV) is a highly contagious and genetically variable virus. Sporadic introductions of this virus into FMD-free countries may cause outbreaks with devastating consequences. In 2010 and 2011, incursions of the FMDV O/SEA/Mya-98 strain, normally restricted to countries in mainland Southeast Asia, caused extensive outbreaks across East Asia. In this study, 12 full genome FMDV sequences for representative samples collected from the People's Republic of China (PR China) including the Hong Kong Special Administrative Region (SAR), the Republic of Korea, the Democratic People's Republic of Korea, Japan, Mongolia and The Russian Federation were generated and compared with additional contemporary sequences from viruses within this lineage. These complete genomes were 8119 to 8193 nucleotides in length and differed at 1181 sites, sharing a nucleotide identity ≥ 91.0% and an amino acid identity ≥ 96.6%. An unexpected deletion of 70 nucleotides within the 5'-untranslated region which resulted in a shorter predicted RNA stem-loop for the S-fragment was revealed in two sequences from PR China and Hong Kong SAR and five additional related samples from the region. Statistical parsimony and Bayesian phylogenetic analysis provide evidence that these outbreaks in East Asia were generated by two independent introductions of the O/SEA/Mya-98 lineage sometime between August 2008 and March 2010. The rapid emergence of these viruses from Southeast Asia highlights the importance of adopting approaches to closely monitor the spread of this lineage that now poses a threat to livestock industries in other regions.

Metastatic renal cell carcinoma: radiologic findings and assessment of response to targeted antiangiogenic therapy by using multidetector CT.

Recent advances in treatment of metastatic renal cell carcinoma (RCC), such as new molecular therapies that use novel antiangiogenic agents, have led to revision of the most frequently used guideline to evaluate tumor response to therapy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Assessment of the response of metastatic RCC to therapy has traditionally been based on changes in target lesion size. However, the mechanism of action of newer antiangiogenic therapies is more cytostatic than cytotoxic, which leads to disease stabilization rather than to tumor regression. This change in tumor response makes RECIST 1.1--a system whose criteria are based exclusively on tumor size--inadequate to discriminate patients with early tumor progression from those with more progression-free disease and prolonged survival. New criteria such as changes in attenuation, morphology, and structure, as seen at contrast-enhanced multidetector computed tomography (CT), are being incorporated into new classifications used to assess response of metastatic RCC to antiangiogenic therapies. The new classifications provide better assessments of tumor response to the new therapies, but they have some limitations. The authors provide a practical review of these systems--the Choi, modified Choi, and Morphology, Attenuation, Size, and Structure (MASS) criteria--by explaining their differences and limitations that may influence the feasibility and reproducibility of these classifications. The authors review the use of multidetector CT in the detection of metastatic RCC and the different appearances and locations of these lesions. They also provide an overview of the new antiangiogenic therapies and their mechanisms of action and a brief introduction to functional imaging techniques. Functional imaging techniques, especially dynamic contrast-enhanced CT, seem promising for assessing response of metastatic RCC to treatment. Nonetheless, further studies are needed before functional imaging can be used in routine clinical practice.