Influence of saliva on the sensory properties of US commercial smoke affected wines: Preliminary findings.

Previous research has suggested that the impact of smoke affected wines require human evaluation due to in-mouth changes in perception, perhaps associated with saliva. Smoke affected wines (n = 36) from three major wine growing regions in the US were sourced from commercial wineries. A subset of these wines (n = 7) were evaluated by a consumer panel (n = 57) and electronic tongue (e-tongue) to determine the influence of saliva in the sensory profile. Consumers assessed the wines for aroma and other sensory attributes, before and after individual saliva addition. Pooled saliva from consumers was used to treat all wines obtained (n = 36) and then analyzed using the e-tongue. Results showed that saliva did not significantly alter the overall aroma, other than fruity or woody aroma liking by consumers (p > .05). However, the presence of saliva significantly lowered overall liking in both red and white wines that were affected by smoke (p ≤ .05). Consumers rated the subset of smoke affected wines below the "might purchase" category, indicating these wines were not considered acceptable by consumers. When individual pairs of smoke affected wines (before and after saliva additions) were assessed using the e-tongue, the device was able to differentiate the pairs, validating potential usefulness to discern wine changes, though the discrimination indices were moderate to low (68.8% to 11.9%). Based on these data, in human ratings of the aroma and appearance of smoked affected wines, saliva decreased overall liking, and this was somewhat distinguishable by e-tongue analysis.

Optical power profiles and aberrations of a non-diffractive wavefront-shaping extended depth of focus intraocular lens.

PURPOSE: This study is to evaluate the optical characteristics of a non-diffractive wavefront-shaping intraocular lens which incorporates surface refractive modifications for shaping the wavefront in order to achieve extended depth of focus (EDoF) and to assess whether the nominal power of this IOL influences the attainable add power. METHODS: A commercially available optical bench NIMO TR1504 device (LAMBDA-X, Nivelles, Belgium) was employed to obtain full optical characterization of three non-diffractive EDoF intraocular lenses with + 10 D, + 20 D, and + 30 D powers. After NIMO measurements, data were computed using a custom-made MATLAB program (Mathworks, Inc., Natick, MA, USA) to evaluate the optical quality functions, such as the point spread function (PSF), wavefront profiles, and modulation transfer function (MTF) for two pupil sizes: 3 mm and 4.0 mm. RESULTS: The non-diffractive EDoF intraocular lens showed a central serrated power profile behavior with additions of + 2.00 to + 2.50 D over the nominal power. Higher order aberrations were found to be driven mainly by the spherical aberration, with almost null comatic influence. Optical quality metrics showed good values, better for a 3 mm pupil compared to a 4.5 mm one, as expected. The three IOL powers tested showed a very similar behavior in terms of power and aberrometric profiles, with minimal to null differences related to the nominal power. CONCLUSION: The non-diffractive wavefront-shaping EDoF intraocular lens achieves a near addition up to + 2.50 D aiming for an extended range of vision, almost independently of the base power.

Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth.

Galectin-3 (Gal-3) is a multifunctional protein that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain's immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, play critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.

Second radioiodine treatment in patients with differentiated thyroid carcinoma: Causes and effects.

INTRODUCTION: Patients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies. Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. MATERIAL AND METHODS: Patients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy. Patients were reclassified in the following 6-18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels. The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. RESULTS: Sixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses. A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). CONCLUSIONS: In selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.

Sensory Perception and Food-Evoked Emotions of Older Adults Assessing Microwave-Processed Meals with Different Salt Concentrations.

This study employed a home-use test to explore the sensory perception and evoked emotions of older adults in the assessment of chicken pasta meals with different salt concentrations. Ready-to-eat (RTE) meals with three salt levels (100%, 75%, and 50%) and two treatments-with and without added herbs-were tested. Multiple sensory attributes and overall meal liking were evaluated by participants (n = 54; 60-86 years of age) with hedonic and just-about-right scores. Twenty-five food-evoked emotions were also tested. Sensory results suggested a 50% salt reduction is possible with minimal impact on the overall liking, while a 25% salt reduction did not affect the saltiness and flavor liking of the meals. Herb addition positively impacted the aroma, flavor, and spiciness liking of the meals. The emotions that differed (p < 0.05) among meals were active, aggressive, bored, calm, happy, and wild, with the meals with herbs added eliciting more positive emotions. A questionnaire elicited information about participants' interest in healthy eating, food technology neophobia, and picky behaviors to determine the influence of these factors on participants' salt consumption habits. Sensory acceptance data combined with questionnaires explored what influenced this group of older adults in their acceptance of and interest in RTE meals.

Sensory profiling of pears from the Pacific Northwest: Consumers' perspective and descriptive analysis.

This study used data from consumer testing, descriptive analysis (DA), and preference mapping to determine the sensory characteristics of pear cultivars from two harvest seasons in the Pacific Northwest (PNW). A trained sensory panel (n = 10) used generic DA to evaluate multiple sensory modalities of 22 pear cultivars. Six pears from summer and six from winter season were evaluated by consumers (n = 219) to assess their liking of different attributes. Results of the DA showed the trained panel significantly discriminated the summer and winter pears on most of the sensory modalities. To identify the attributes driving consumer acceptability, external preference mapping was applied. Attributes such as pear aroma, pear flavor, sweet, sour, and juicy were the most contributory attributes to the liking of the summer pears. Conversely, fermented aroma, stemmy-woody aroma, fermented flavor, stemmy-woody flavor, and grainy-gritty attributes were associated with a reduction in consumer liking. Summer cultivars, "Bartlett," coded pear 573, and "Seckel" had the broadest preference, satisfying 60% to 80% of the consumers. Seventy-five percent of the consumers identified winter cultivars "Comice" and "Paragon" as the most appealing. Overall, cluster analysis showed that different pears appeal to different types of consumers; however, summer cultivars like "Bartlett" and "Seckel" and winter cultivars like "Comice" and "Paragon" would appeal to the greatest number of consumers in the PNW market. PRACTICAL APPLICATION: Sensory attributes like pear flavor, sweet, and juicy, were important drivers of liking for pear consumers in the Pacific Northwest. These results should prove useful to pear growers and marketers to increase pear consumption in the United States.

The interaction between wheat and pea protein influences the final chemical and sensory characteristics of extruded high moisture meat analogs.

Plant-based meat analog products, including those produced by extrusion processing, have become increasingly popular. Complete comprehension of the texturization mechanism and the formation of fibrousness would help improve existing products and extend the variety of plant sources used. Therefore, this study aimed to provide improved insight into the mechanism of texturization during the processing of high-moisture meat analog (HMMA) products. Blends with different wheat and pea protein ratios (100:0, 80:20, 60:40, 40:60, 20:80, and 0:100 wheat:pea) were extruded at a screw speed of 400 rpm, two different moisture contents (50% and 55%), and a feed rate of 90 g/min using a co-rotating twin-screw extruder. Extrudates were analyzed for their texture, free sulfhydryl groups, disulfide bonds, and solubility in different extractants relative to the raw ingredient blends. In addition, a sensory analysis was conducted using the rapid and cost-effective "rate-all-that-apply" (RATA) methodology. The interplay between the two protein types had synergistic effects on the system parameters torque, pressure, and specific mechanical energy, as well as on some textural and sensory parameters. Molecular analyses were not influenced by the interplay between wheat and pea protein as the molecular analyses followed linear trends with the pea inclusion level. Analysis of protein solubility suggests that the texturization mechanism differs slightly depending on the protein type. It is suggested that the texturization of wheat protein depends highly on disulfide bonds, whereas the texturization of pea protein relies on the combination of disulfide bonds and non-covalent interactions. Additionally, RATA was found to be a valuable tool for HMMA products.

Revisiting Javal's rule: a fresh and improved power vector approach according to age.

PURPOSE: The scientific community has established Javal's rule as a model linking refractive (RA) and keratometric (KA) astigmatism since its appearance more than 100 years ago. The aim was to improve the accuracy of this relationship according to subject's age by applying the power vector analysis. Posterior corneal curvature has also been studied. METHODS: The IOLMaster 700 optical biometer was used to measure the corneal thickness and the radius of curvature of the anterior and posterior corneal surfaces. Refractive error was determined by a non-cycloplegic subjective refraction process with trial lenses. Linear regression analyses were applied using J0 and J45 power vector components. An evaluation was carried out according to the subject's age resulting into eight regression relationships for each astigmatic vector component for each relationship. RESULTS: A total of 2254 right eyes from 2254 healthy subjects were evaluated. A trend towards against-the-rule astigmatism (ATR) was found with aging, both for refractive astigmatism (RA) and keratometric astigmatism (KA), with 95.2% of subjects under 20 years old having with-the-rule (WTR) KA, and only 22.8% above 79 years old. The following regression equations were found between RA and KA: [Formula: see text] = 0.73 × [Formula: see text] - 0.18 (R = 0.78) and [Formula: see text] = 0.70 × [Formula: see text] + 0.04 (R = 0.69) and between RA and total corneal astigmatism (TCA): [Formula: see text] = 0.73 × [Formula: see text] + 0.13 (R=0.78) and [Formula: see text] = 0.70 × [Formula: see text] - 0.06 (R = 0.68) for the whole sample, but with sensible differences among age groups, both in the slope and in the intercept. CONCLUSION: Ignoring the age of the subject when using Javal's rule could lead to an error in the final cylinder calculation that would increase in high astigmatisms. Applying this new power vector approach based on subject's age could improve the accuracy of the astigmatism prediction.

S-Nitrosylation at the intersection of metabolism and autophagy: Implications for cancer.

Metabolic plasticity, which determines tumour growth and metastasis, is now understood to be a flexible and context-specific process in cancer metabolism. One of the major pathways contributing to metabolic adaptations in eucaryotic cells is autophagy, a cellular degradation and recycling process that is activated during periods of starvation or stress to maintain metabolite and biosynthetic intermediate levels. Consequently, there is a close association between the metabolic adaptive capacity of tumour cells and autophagy-related pathways in cancer. Additionally, nitric oxide regulates protein function and signalling through S-nitrosylation, a post-translational modification that can also impact metabolism and autophagy. The primary objective of this review is to provide an up-to-date overview of the role of S-nitrosylation at the intersection of metabolism and autophagy in cancer. First, we will outline the involvement of S-nitrosylation in the metabolic adaptations that occur in tumours. Then, we will discuss the multifaceted role of autophagy in cancer, the interplay between metabolism and autophagy during tumour progression, and the contribution of S-nitrosylation to autophagic dysregulation in cancer. Finally, we will present insights into relevant therapeutic aspects and discuss prospects for the future.

PET-based radiomics signature can predict durable responses to CAR T-cell therapy in patients with large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). However, only a subset of patients will present long-term benefit. In this study, we explored the potential of PET-based radiomics to predict treatment outcomes with the aim of improving patient selection for CAR T-cell therapy. We conducted a single-center study including 93 consecutive R/R LBCL patients who received a CAR T-cell infusion from 2018 to 2021, split in training set (73 patients) and test set (20 patients). Radiomics features were extracted from baseline PET scans and clinical benefit was defined based on median progression-free survival (PFS). Cox regression models including the radiomics signature, conventional PET biomarkers and clinical variables were performed for most relevant outcomes. A radiomics signature including 4 PET-based parameters achieved an AUC = 0.73 for predicting clinical benefit in the test set, outperforming the predictive value of conventional PET biomarkers (total metabolic tumor volume [TMTV]: AUC = 0.66 and maximum standardized uptake value [SUVmax]: AUC = 0.59). A high radiomics score was also associated with longer PFS and OS in the multivariable analysis. In conclusion, the PET-based radiomics signature predicted efficacy of CAR T-cell therapy and outperformed conventional PET biomarkers in our cohort of LBCL patients.

Optical and Clinical Outcomes of an Isofocal Intraocular Lens vs. a Monofocal Standard Lens.

The aim of this study is to evaluate the results obtained on the optical bench and clinically with an isofocal lens (ISOPure, BVI medical, Belgium) to compare them to a standard monofocal one (MicroPure, BVI medical, Belgium). To do so, we have combined laboratory investigation and a prospective, comparative, and randomized clinical study. First, we have measured the wavefront of the two models studied using a NIMO TR1504 (Lambda-X, Belgium) deflectometer for three nominal powers: +10.00, +20.00 and +30.00 D. In the randomized study with 48 patients, half of them implanted with ISOPure and the other with MicroPure, we have measured visual acuities and contrast sensitivity under photopic and mesopic conditions. The optical bench results show that the isofocal lens presented higher power than the monofocal one, at the lens center, due to the spherical aberration (coefficients Z(4,0), Z(6,0) and Z(8,0)) induced by the greater asphericity of its design. The addition obtained depended on the nominal power, from +1.00 to +1.50 D. The results of the clinical study showed that the ISOPure lens presented better visual outcomes, which were statistically significant, at intermediate distance compared to the MicroPure lens (p-values of 0.014 and 0.022 for 80 and 60 cm, respectively) without decreasing the contrast sensitivity. Clinical outcomes were not affected by pupillary size. In conclusion, due to the increase in power at the lens center due to its highly aspherical design, the isofocal lens evaluated showed better intermediate vision than the monofocal one.

Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells.

The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.

Clinical significance of glycogen synthase kinase 3 (GSK-3) expression and tumor budding grade in colorectal cancer: Implications for targeted therapy.

INTRODUCTION: Glycogen synthase kinase 3 (GSK-3) has been proposed as a novel cancer target due to its regulating role in both tumor and immune cells. However, the connection between GSK-3 and immunoevasive contexture, including tumor budding (TB) has not been previously examined. METHODS: we investigated the expression levels of total GSK-3 as well as its isoforms (GSK-3ß and GSK-3α) and examined their potential correlation with TB grade and the programmed cell death-ligand 1 (PD-L1) in colorectal cancer (CRC) tumor samples. Additionally, we compared the efficacy of GSK-3-inhibition with PD-1/PD-L1 blockade in humanized patient-derived (PDXs) xenografts models of high-grade TB CRC. RESULTS: we show that high-grade (BD3) TB CRC is associated with elevated expression levels of total GSK-3, specifically the GSK-3ß isoform, along with increased expression of PD-L1 in tumor cells. Moreover, we define an improved risk stratification of CRC patients based on the presence of GSK-3+/PD-L1+/BD3 tumors, which are associated with a worse prognosis. Significantly, in contrast to the PD-L1/PD-1 blockade approach, the inhibition GSK-3 demonstrated a remarkable enhancement in the antitumor response. This was achieved through the reduction of tumor buds via necrosis and apoptosis pathways, along with a notable increase of activated tumor-infiltrating CD8+ T cells, NK cells, and CD4- CD8- T cells. CONCLUSIONS: our study provides compelling evidence for the clinical significance of GSK-3 expression and TB grade in risk stratification of CRC patients. Moreover, our findings strongly support GSK-3 inhibition as an effective therapy specifically targeting high-grade TB in CRC.

Real-world experience of therapeutic drug monitoring and PK/PD achievement of ceftaroline administered by different infusion regimens in patients with confirmed infections caused by Gram-positive bacteria.

BACKGROUND: Ceftaroline is a novel cephalosporin active against MDR Gram-positive (GP) bacteria. For ß-lactam antibiotics, such as ceftaroline, prolonged infusions and therapeutic drug monitoring (TDM) are used for dosage optimization based on their pharmacokinetics/pharmacodynamics (PK/PD). OBJECTIVES: To describe our experience with TDM and PK/PD target attainment of ceftaroline administered by intermittent and prolonged infusion in a cohort of patients with MDR-GP bacterial infections. METHODS: Patients treated with ceftaroline administered by continuous (24 h), extended (3 h/6 h) and intermittent infusion (1 h) and undergoing TDM of plasma concentrations were included. A 100%fT>4×MIC was the pre-specified PK/PD target and 100%fT>10×MIC was considered overexposure. Dose recommendations were made based on TDM results and each patient's clinical condition. RESULTS: Twelve patients [83.3% male, median age of 73 (38-83) years] were included. Nine patients (75%) achieved 100%fT>4×MIC, all under prolonged infusions. In one patient, the 100%fT was >10×MIC but no toxicity was observed. Based on TDM results, initial doses were recommended to be maintained in eight patients, decreased in three and increased in one. CONCLUSIONS: The administration of ceftaroline by prolonged infusion together with TDM may be a useful strategy for achieving the desired PK/PD target in these patients. However, more studies evaluating the relationship between PK/PD attainment and clinical outcomes are needed.

Development of a Ready-to-Eat Fish Product Enriched with Fish Oil Entrapped in a κ-Carrageenan Egg White Fish Protein Hydrolysate Dry Powder.

This work describes the development of a ready-to-eat (RTE) product based on an equal mixture of fish mince from three undervalued fish species with different fat contents and protein gelling capacity, which was enriched with fish oil entrapped in a κ-carrageenan egg white fish protein hydrolysate powder, obtained by either spray drying (SD) or heat drying (HD) at 80 °C (HD80). Previously, the spray-dried (SD) powder and heat-dried powders obtained at 45 °C, 60 °C and 80 °C (HD45, HD60 and HD80) were characterised in terms of water solubility, lipid oxidation (TBARS), hygroscopicity and ζ potential. All HD powders showed higher hygroscopicity and lower TBARS than the SD powder. The dry powder was incorporated into a blend composed of salt-ground batter and raw mince to improve binding and textural properties. Changes in water-holding capacity, colour, shear strength and microorganisms were monitored during the processing steps. The RTE product presented a high protein content and a noticeable amount of long-chain ω-3 fatty acids. The use of undervalued fish species together with fish oil and a protein hydrolysate from fish waste contribute to improving the sustainability of fishery resources, being conducive to obtaining a potentially functional RTE product.

Ampicillin-resistant and vancomycin-susceptible Enterococcus faecium bacteremia: a clinical narrative review.

INTRODUCTION: Enterococcus faecium is a commensal microorganism that can cause infections such as bacteremia. Incidence of ampicillin-resistant and vancomycin-susceptible E. faecium (EfARSV) bacteremia is on the rise, and the mortality rate is high. Despite much data, the most appropriate treatment remains a question. AREAS COVERED: This article mostly reviews the relevant aspects of EfARSV bacteremia: microbiology, gastrointestinal tract colonization and invasion, antibiotic resistance, epidemiology, risk factors, mortality, and treatment, including pharmacologic components of employed agents and related clinical evidence. A literature search was conducted on PubMed on 31 July 2022, which was updated on 15 November 2022. EXPERT OPINION: EfARSV bacteremia presents high mortality. However, it is uncertain whether mortality is attributable to or a marker of severity/comorbidities. Considering its antibiotic resistance pattern, EfARSV is considered a difficult-to-treat microorganism. Glycopeptides have been used to treat EfARSV, with linezolid and daptomycin serving as potential alternative agents. Yet, the use of daptomycin is controversial due to a higher risk of treatment failures. Clinical evidence on this issue is scarce, unfortunately, and subject to many limitations. Despite increased incidence and mortality, EfARSV bacteremia presents multiple aspects to be addressed in well-conducted studies.

Metabolic shift underlies tumor progression and immune evasion in S-nitrosoglutathione reductase-deficient cancer.

S-nitrosoglutathione reductase (GSNOR) is a denitrosylase enzyme that has been suggested to play a tumor suppressor role, although the mechanisms responsible are still largely unclear. In this study, we show that GSNOR deficiency in tumors is associated with poor prognostic histopathological features and poor survival in patients with colorectal cancer (CRC). GSNOR-low tumors were characterized by an immunosuppressive microenvironment with exclusion of cytotoxic CD8+ T cells. Notably, GSNOR-low tumors exhibited an immune evasive proteomic signature along with an altered energy metabolism characterized by impaired oxidative phosphorylation (OXPHOS) and energetic dependence on glycolytic activity. CRISPR-Cas9-mediated generation of GSNOR gene knockout (KO) CRC cells confirmed in vitro and in vivo that GSNOR-deficiency conferred higher tumorigenic and tumor-initiating capacities. Moreover, GSNOR-KO cells possessed enhanced immune evasive properties and resistance to immunotherapy, as revealed following xenografting them into humanized mouse models. Importantly, GSNOR-KO cells were characterized by a metabolic shift from OXPHOS to glycolysis to produce energy, as indicated by increased lactate secretion, higher sensitivity to 2-deoxyglucose (2DG), and a fragmented mitochondrial network. Real-time metabolic analysis revealed that GSNOR-KO cells operated close to their maximal glycolytic rate, as a compensation for lower OXPHOS levels, explaining their higher sensitivity to 2DG. Remarkably, this higher susceptibility to glycolysis inhibition with 2DG was validated in patient-derived xenografts and organoids from clinical GSNOR-low tumors. In conclusion, our data support the idea that metabolic reprogramming induced by GSNOR deficiency is an important mechanism for tumor progression and immune evasion in CRC and that the metabolic vulnerabilities associated with the deficiency of this denitrosylase can be exploited therapeutically. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.