Brazilian indigenous nonstarter lactic acid bacteria enhance the diversification of volatile compounds in short-aged cheese.

There is growing interest in using autochthonous lactic acid bacteria (LAB) that provide unique sensory characteristics to dairy products without affecting their safety and quality. This work studied the capacity of three Brazilian indigenous nonstarter LABs (NSLAB) to produce biogenic amines (BAs) and evaluated their effect on the volatile organic compounds (VOCs), microbial LAB communities, and physicochemical profile of short-aged cheese. Initially, the strain's potential for biosynthesis of BAs was assessed by PCR and in vitro assays. Then, a pilot-scale cheese was produced, including the NSLAB, and the microbial and VOC profiles were analyzed after 25 and 45 days of ripening. As a results, the strains did not present genes related to relevant BAs and did not produce them in vitro. During cheese ripening, the Lactococci counts were reduced, probably in the production of alcohols and acid compounds by the NSLAB. Each strain produces a unique VOC profile that changes over the ripening time without the main VOCs related to rancid or old cheese. Particularly, the use of the strain Lacticaseibacillus. paracasei ItalPN16 resulted in production of ester compounds with fruity notes. Thus, indigenous NSLAB could be a valuable tool for the enhancement and diversification of flavor in short-aged cheese.

Clinical Decision Support System for Guidelines-Based Treatment of Gonococcal Infections, Screening for HIV, and Prescription of Pre-Exposure Prophylaxis: Design and Implementation Study.

BACKGROUND: The syndemic nature of gonococcal infections and HIV provides an opportunity to develop a synergistic intervention tool that could address the need for adequate treatment for gonorrhea, screen for HIV infections, and offer pre-exposure prophylaxis (PrEP) for persons who meet the criteria. By leveraging information available on electronic health records, a clinical decision support (CDS) system tool could fulfill this need and improve adherence to Centers for Disease Control and Prevention (CDC) treatment and screening guidelines for gonorrhea, HIV, and PrEP. OBJECTIVE: The goal of this study was to translate portions of CDC treatment guidelines for gonorrhea and relevant portions of HIV screening and prescribing PrEP that stem from a diagnosis of gonorrhea as an electronic health record-based CDS intervention. We also assessed whether this CDS solution worked in real-world clinic. METHODS: We developed 4 tools for this CDS intervention: a form for capturing sexual history information (SmartForm), rule-based alerts (best practice advisory), an enhanced sexually transmitted infection (STI) order set (SmartSet), and a documentation template (SmartText). A mixed methods pre-post design was used to measure the feasibility, use, and usability of the CDS solution. The study period was 12 weeks with a baseline patient sample of 12 weeks immediately prior to the intervention period for comparison. While the entire clinic had access to the CDS solution, we focused on a subset of clinicians who frequently engage in the screening and treatment of STIs within the clinical site under the name "X-Clinic." We measured the use of the CDS solution within the population of patients who had either a confirmed gonococcal infection or an STI-related chief complaint. We conducted 4 midpoint surveys and 3 key informant interviews to quantify perception and impact of the CDS solution and solicit suggestions for potential future enhancements. The findings from qualitative data were determined using a combination of explorative and comparative analysis. Statistical analysis was conducted to compare the differences between patient populations in the baseline and intervention periods. RESULTS: Within the X-Clinic, the CDS alerted clinicians (as a best practice advisory) in one-tenth (348/3451, 10.08%) of clinical encounters. These 348 encounters represented 300 patients; SmartForms were opened for half of these patients (157/300, 52.33%) and was completed for most for them (147/300, 89.81%). STI test orders (SmartSet) were initiated by clinical providers in half of those patients (162/300, 54%). HIV screening was performed during about half of those patient encounters (191/348, 54.89%). CONCLUSIONS: We successfully built and implemented multiple CDC treatment and screening guidelines into a single cohesive CDS solution. The CDS solution was integrated into the clinical workflow and had a high rate of use.

Adults with excess weight or obesity, but not with overweight, report greater pain intensities than individuals with normal weight: a systematic review and meta-analysis.

Context: Over 1.9 billion adult people have overweight or obesity. Considered as a chronic disease itself, obesity is associated with several comorbidities. Chronic pain affects approximately 60 million people and its connection with obesity has been displayed in several studies. However, controversial results showing both lower and higher pain thresholds in subjects with obesity compared to individuals with normal weight and the different parameters used to define such association (e.g., pain severity, frequency or duration) make it hard to draw straight forward conclusions in the matter. The objective of this article is to examine the relationship between overweight and obesity (classified with BMI as recommended by WHO) and self-perceived pain intensity in adults. Methods: A literature search was conducted following PRISMA guidelines using the databases CINAHL, Cochrane Library, EMBASE, PEDro, PubMed, Scopus and Web of Science to identify original studies that provide BMI values and their associated pain intensity assessed by self-report scales. Self-report pain scores were normalized and pooled within meta-analyses. The Cochrane's Q test and I2 index were used to clarify the amount of heterogeneity; meta-regression was performed to explore the relationship between each outcome and the risk of bias. Results: Of 2194 studies, 31 eligible studies were identified and appraised, 22 of which provided data for a quantitative analysis. The results herein suggested that adults with excess weight (BMI ≥ 25.0) or obesity (BMI ≥ 30.0) but not with overweight (pre-obesity) alone (BMI 25.0-29.9), are more likely to report greater intensities of pain than individuals of normal weight (BMI 18.5-24.9). Subgroup analyses regarding the pathology of the patients showed no statistically significant differences between groups. Also, influence of age in the effect size, evaluated by meta-regression, was only observed in one of the four analyses. Furthermore, the robustness of the findings was supported by two different sensitivity analyses. Conclusion: Subjects with obesity and excess weight, but not overweight, reported greater pain intensities than individuals with normal weight. This finding encourages treatment of obesity as a component of pain management. More research is required to better understand the mechanisms of these differences and the clinical utility of the findings. Systematic Review Registration: https://doi.org/10.17605/OSF.IO/RF2G3, identifier OSF.IO/RF2G3.

Higher densities of T-lymphocytes in the subsynovial connective tissue of people with carpal tunnel syndrome.

Symptoms in people with carpal tunnel syndrome (CTS) are traditionally attributed to neural tissue, but recent studies suggest that the subsynovial connective tissue (SSCT) may also play a role in CTS. The SSCT undergoes fibrotic thickening which is generally described as "non-inflammatory" based on basic histology. This study uses immunohistochemistry to determine the presence of macrophages and T-cells within SSCT and their relationship with symptoms in people with CTS. SSCT was collected from twenty people with CTS and eight controls undergoing wrist fracture surgery. Immunohistochemical quantification of CD3+ T-cells and CD68+ macrophage densities as well as CD4+/CD8+ T-cell subpopulations were compared between groups using independent t-tests. Spearman correlations were used to identify associations between immune cell densities and CTS symptom scores. The density of CD3+ T-cells was significantly higher in SSCT of people with CTS compared to controls (CTS mean 26.7 (SD 13.7); controls 6.78 (6.3), p = 0.0005) while the density of CD68+ macrophages was lower (CTS mean 9.5 (SD 6.0); controls 17.7 (8.2), p = 0.0058). Neither CD68+ nor CD3+ cell densities correlated with symptom scores. In contrast to previous assumptions, our data show that the SSCT in the carpal tunnel in both people with CTS and controls is not devoid of immune cells. Whereas the higher density of CD68+ macrophages in control participants may be associated with their early recruitment after acute fracture, CD3+ cells within the SSCT may play a role in chronic CTS.

'The Year of Living Dangerously': Successful Rhodococcus Equi Therapy in an Immunosuppressed Patient with Minimal Toxicity by One Year of Continuous Intravenous Vancomycin Therapy Combined with Oral Levofloxacin And Rifampicin.

Background: Rhodococcus equi is a Gram-positive microorganism that causes infections, particularly in immunocompromised patients. Treatment duration can be prolonged. While vancomycin is an effective drug in this scenario, its use may lead to renal damage. Studies have shown that continuous vancomycin infusion appears to be a safe strategy in terms of adverse effects compared to bolus administration. Case description: We present the case of a 71-year-old female liver transplant recipient. After being diagnosed with a mediastinal infection caused by Rhodococcus equi with poor response to initial therapy, she required 12 months of continuous intravenous domiciliary infusion of vancomycin combined with oral levofloxacin and rifampicin. There was no drug-related complication throughout the follow-up. Conclusions: The use of continuous vancomycin infusion has emerged as a safer, more efficient, and cost-effective alternative to intermittent administration. We want to emphasise the uniqueness of this case, where despite the unprecedented treatment duration, no adverse effects occurred. LEARNING POINTS: Vancomycin therapy based on continuous infusion represents a safer and cheaper strategy than classic intermittent administration.The use of continuous infusion facilitates the management of complex infections with outpatient antimicrobial therapy.

Rational development of topical climbazole formulations.

Dandruff, or pityriasis capitis simplex, is a common scalp condition associated with excessive flaking and scaling of the epidermal tissue. Other features include irregular corneocyte turnover, irritation, itching and an impaired skin barrier function. Previously we reported the characterization of climbazole (CBZ), an antifungal agent used in the management of dandruff. Skin permeation of CBZ from neat solvents was also investigated. In the present work we evaluated CBZ permeation in human skin in vitro from more complex formulations that better represent products used by consumers. The various systems studied were composed of propylene glycol (PG), Transcutol®P (TC), octyl salicylate (OSal) and isopropyl alcohol (IPA). As well as measurement of skin uptake and penetration of CBZ, where possible, the skin retention and permeation of the various solvents was also determined. All vehicles promoted skin permeation of CBZ but no significant differences in amount permeated were evident between the binary vehicles (PG:TC, TC:OSal) and the ternary vehicle studied (PG:IPA:OSal). The binary vehicles generally promoted more skin uptake of CBZ compared with the neat solvents (PG, TC, OSal) studied previously. Permeation and skin extraction of CBZ from the PG:TC vehicles increased with increasing PG content; a similar trend was evident for the PG:IPA:OSal systems. New methods were developed and validated for measurement of PG, TC and OSal. Analysis of the individual solvents indicated that PG permeation was also independent of the amounts of other solvents in the binary or ternary systems. Consistent with previous findings higher proportions of TC permeated compared with PG for the PG:TC binary systems; TC also permeated the skin more rapidly than PG from these vehicles. For OSal, skin extraction was generally higher for TC:OSal compared with the PG:IPA:OSal vehicle. However, increasing the content of OSal did not appear to influence CBZ skin uptake nor permeation. Interestingly, the effects of the various PG:TC vehicles on CBZ skin delivery contrast with results we previous reported for the same systems for a different active. This confirms that with reference to skin permeation, formulation effects and/or skin penetration enhancement should be expected to vary and may not be predicted for specific vehicles.

Bacteriocins against biogenic amine-accumulating lactic acid bacteria in cheese: nisin A shows the broadest antimicrobial spectrum and prevents the formation of biofilms.

Cheese is a food in which toxic concentrations of biogenic amines (BA) may be reached, mainly as a consequence of the decarboxylation of determined amino acids by certain lactic acid bacteria (LAB). To maintain the food safety of cheese, environmentally friendly strategies are needed that specifically prevent the growth of BA-producing LAB and the accumulation of BA. The bacteriocins produced by LAB are natural compounds with great potential as food biopreservatives. This work examines the antimicrobial potential of 7 bacteriocin-containing, cell-free supernatants (CFS: coagulin A-CFS, enterocin A-CFS, enterocin P-CFS, lacticin 481-CFS, nisin A-CFS, nisin Z-CFS and plantaricin A-CFS) produced by LAB against 48 strains of the LAB species largely responsible for the accumulation of the most important BA in cheese, i.e., histamine, tyramine and putrescine. Susceptibility to the different CFS was strain-dependent. The histamine-producing species with the broadest sensitivity spectrum were Lentilactobacillus parabuchneri (the species mainly responsible for the accumulation of histamine in cheese) and Pediococcus parvulus. The tyramine-producing species with the broadest sensitivity spectrum was Enterococcus faecium, while Enterococcus faecalis and Enterococcus hirae were among the most sensitive putrescine producers. Nisin A-CFS was active against 31 of the 48 BA-producing strains (the broadest antimicrobial spectrum recorded). Moreover, commercial nisin A prevented biofilm formation by 67% of the BA-producing, biofilm-forming LAB strains. These findings underscore the potential of bacteriocins in the control of BA-producing LAB, and support the use of nisin A as a food grade biopreservative for keeping BA-producing LAB in check and reducing BA accumulation in cheese.

Largest comparison between onset and relapses of acquired thrombotic thrombocytopenic purpura reveals severe neurological involvement and worse analytic parameters at debut.

It has been proposed that the onset of Acquired Thrombotic Thrombocytopenic Purpura (iTTP) is more severe than subsequent relapses; however, existing studies have limitations. We conducted a retrospective observational study to compare analytical and clinical severity of onset and relapse aTTP cases between 2012 and 2023. A total of 370 episodes of aTTP were analyzed, comprising 272 at initial diagnosis and 98 relapses. At onset, analytical parameters indicative of severity (low hemoglobin, low platelet count, and increased LDH) were significantly worse; patients had severe neurological symptoms (p<0.001) and ≥ 3 points in the TMA mortality score (p<0.001). In conclusion, the onset of aTTP is associated with worse analytical parameters and severe neurological involvement.

HDAC1/2 control mesothelium/ovarian cancer adhesive interactions impacting on Talin-1-α5ß1-integrin-mediated actin cytoskeleton and extracellular matrix protein remodeling.

BACKGROUND: Peritoneal metastasis, which accounts for 85% of all epithelial ovarian carcinoma (EOC) metastases, is a multistep process that requires the establishment of adhesive interactions between cancer cells and the peritoneal membrane. Interrelations between EOC and the mesothelial stroma are critical to facilitate the metastatic process. No data is available so far on the impact of histone acetylation/deacetylation, a potentially relevant mechanism governing EOC metastasis, on mesothelial cells (MCs)-mediated adhesion. METHODS: Static adhesion and peritoneal clearance experiments were performed pretreating mesenchymal-like MCs and platinum-sensitive/resistant EOC cell lines with MS-275-a Histone deacetylase (HDAC)1-3 pharmacological inhibitor currently used in combination trials. Results were acquired by confocal microscopy and were analyzed with an automated Opera software. The role of HDAC1/2 was validated by genetic silencing. The role of α4-, α5-α1 Integrins and Fibronectin-1 was validated using specific monoclonal antibodies. Quantitative proteomic analysis was performed on primary MCs pretreated with MS-275. Decellularized matrices were generated from either MS-275-exposed or untreated cells to study Fibronectin-1 extracellular secretion. The effect of MS-275 on ß1 integrin activity was assessed using specific monoclonal antibodies. The role of Talin-1 in MCs/EOC adhesion was analyzed by genetic silencing. Talin-1 ectopic expression was validated as a rescue tool from MS-275-induced phenotype. The in vivo effect of MS-275-induced MC remodeling was validated in a mouse model of peritoneal EOC dissemination. RESULTS: Treatment of MCs with non-cytotoxic concentrations of MS-275 caused a consistent reduction of EOC adhesion. Proteomic analysis revealed several pathways altered upon MC treatment with MS-275, including ECM deposition/remodeling, adhesion receptors and actin cytoskeleton regulators. HDAC1/2 inhibition hampered actin cytoskeleton polymerization by downregulating actin regulators including Talin-1, impairing ß1 integrin activation, and leading to abnormal extracellular secretion and distribution of Fibronectin-1. Talin-1 ectopic expression rescued EOC adhesion to MS-275-treated MCs. In an experimental mouse model of metastatic EOC, MS-275 limited tumor invasion, Fibronectin-1 secretion and the sub-mesothelial accumulation of MC-derived carcinoma-associated fibroblasts. CONCLUSION: Our study unveils a direct impact of HDAC-1/2 in the regulation of MC/EOC adhesion and highlights the regulation of MC plasticity by epigenetic inhibition as a potential target for therapeutic intervention in EOC peritoneal metastasis.

Regulation and distribution of European sea bass perforins point to their role in the adaptive cytotoxic response against NNV.

Cell-mediated cytotoxicity is a complex immune mechanism that involves the release of several killing molecules, being perforin (PRF) one of the most important effector players. Perforin is synthesized by T lymphocytes and natural killer cells in mammals and responsible for the formation of pores on the target cell membrane during the killing process. Although perforin has been extensively studied in higher vertebrates, this knowledge is very limited in fish. Therefore, in this study we have identified four prf genes in European sea bass (Dicentrarchus labrax) and evaluated their mRNA levels. All sea bass prf genes showed the typical and conserved domains of its human orthologue and were closely clustered by the phylogenetic analysis. In addition, all genes showed constitutive and ubiquitous tissular expression, being prf1.9 gene the most highly expressed in immune tissues. Subsequently, in vitro stimulation of head-kidney (HK) cells with phytohemagglutinin, a T-cell activator, showed an increase of all prf gene levels, except for prf1.3 gene. European sea bass HK cells increased the transcription of prf1.2 and prf1.9 during the innate cell-mediated cytotoxic activity against xenogeneic target cells. In addition, sea bass infected with nodavirus (NNV) showed a similar expression pattern of all prf in HK and brain at 15 days post-infection, except for prf1.3 gene and in the gonad. Finally, the use of a polyclonal antibody against PRF1.9 showed an increase of positive cells in HK, brain and gonad from NNV-infected fish. Taken together, the data seem to indicate that all prf genes, except prf1.3, appear to be involved in the European sea bass immunity, and probably in the cell-mediated cytotoxic response, with PRF1.9 playing the most important role against nodavirus. The involvement of the PRFs and the CMC activity in the vertical transmission success of the virus is also discussed.

Correlation between breast cancer subtypes determined by immunohistochemistry and n-COUNTER PAM50 assay: a real-world study.

PURPOSE: Molecular subtyping based on gene expression profiling (i.e., PAM50 assay) aids in determining the prognosis and treatment of breast cancer (BC), particularly in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, where luminal A and B subtypes have different prognoses and treatments. Several surrogate classifications have been proposed for distinguishing between the luminal A and B subtypes. This study determines the accuracy of local immunohistochemistry (IHC) techniques for classifying HR-positive/HER2-negative (HR+/HER2-) tumors according to intrinsic subtypes using the nCOUNTER PAM50 assay as reference and the HR status definition according the ASCO/CAP recommendations. METHODS: Molecular subtypes resulting from nCOUNTER PAM50 performed in our laboratory between 2014 and 2020 were correlated with three different proxy surrogates proposed in the literature based on ER, PR, HER2, and Ki67 expression with different cut-off values. Concordance was measured using the level of agreement and kappa statistics. RESULTS: From 1049 samples with the nCOUNTER test, 679 and 350 were luminal A and B subtypes, respectively. Only a poor-to-fair correlation was observed between the three proxy surrogates and real genomic subtypes as determined by nCOUNTER PAM50. Moreover, 5-11% and 18-36% of the nCOUNTER PAM50 luminal B and A tumors were classified as luminal A and B, respectively, by these surrogates. CONCLUSION: The concordance between luminal subtypes determined by three different IHC-based classifiers and the nCOUNTER PAM50 assay was suboptimal. Thus, a significant proportion of luminal A and B tumors as determined by the surrogate classifiers could be undertreated or over-treated.

The gene cluster associated with strong biofilm-formation capacity by histamine-producing Lentilactobacillus parabuchneri encodes a sortase-mediated pilus and is located on a plasmid.

Histamine is a biogenic amine synthesized through the enzymatic decarboxylation of the amino acid histidine. It can accumulate at high concentrations in foods through the metabolism of certain bacteria, sometimes leading to adverse reactions in consumers. In cheese, histamine can accumulate at toxic levels; Lentilactobacillus parabuchneri has been identified the major cause of this problem. Previous studies have shown some L. parabuchneri strains to form biofilms on different surfaces, posing a contamination risk during cheese production, particularly for cheeses that are processed post-ripening (e.g., grating or slicing). The food contamination they cause can result in economic losses and even foodborne illness if histamine accumulates in the final product. The aim of the present work was to identify the genes of L. parabuchneri involved in biofilm formation, and to determine their function. The genomes of six strains with different biofilm-production capacities (strong, moderate and weak) were sequenced and analysed. A cluster of four genes, similar to those involved in sortase-mediated pilus formation, was identified in the strong biofilm-producers, suggesting it to have a role in surface adhesion. Cloning and heterologous expression in Lactococcus cremoris NZ9000 confirmed its functionality and involvement in adhesion and, therefore, in biofilm formation. PacBio sequencing showed this cluster to be located on a 33.4 kb plasmid, which might increase its chances of horizontal transmission. These findings provide insight into the genetic factors associated with biofilm formation in histamine-producing L. parabuchneri, and into the risks associated with this bacterium in cheese production.

Cytotoxic activity and gene expression during in vitro adaptive cell-mediated cytotoxicity of head-kidney cells from betanodavirus-infected European sea bass.

Cell-mediated cytotoxicity (CMC) is essential in eradicating virus-infected cells, involving CD8+ T lymphocytes (CTLs) and natural killer (NK) cells, through the activation of different pathways. This immune response is well-studied in mammals but scarcely in teleost fish. Our aim was to investigate the adaptive CMC using head-kidney (HK) cells from European sea bass infected at different times with nodavirus (NNV), as effector cells, and the European sea bass brain cell line (DLB-1) infected with different NNV genotypes, as target cells. Results showed low and unaltered innate cytotoxic activity through the infection time. However, adaptive CMC against RGNNV and SJNNV/RGNNV-infected target cells increased from 7 to 30 days post-infection, peaking at 15 days, demonstrating the specificity of the cytotoxic activity and suggesting the involvement of CTLs. At transcriptomic level, we observed up-regulation of genes related to T cell activation, perforin/granzyme and Fas/FasL effector pathways as well as apoptotic cell death. Further studies are necessary to understand the adaptive role of European sea bass CTLs in the elimination of NNV-infected cells.

Autothreshold algorithm feasibility and safety in left bundle branch pacing.

AIMS: Autothreshold algorithms enable remote monitoring of patients with conventional pacing, but there is limited information on their performance in left bundle branch pacing (LBBP). Our objective was to analyse the behaviour of the autothreshold algorithm in LBBP and compare it with conventional pacing and manual thresholds during initial device programming (acute phase), after 1-7 days (subacute), and 1-3 months later (chronic). METHODS AND RESULTS: A prospective, non-randomized, single-centre comparative study was conducted. Consecutive patients with indication for cardiac pacing were enrolled. Implants were performed in the left bundle branch area or the right ventricle endocardium at the discretion of the operator. Left bundle branch pacing was determined according to published criteria. Autothreshold algorithm was activated in both groups whenever allowed by the device. Seventy-five patients were included, with 50 undergoing LBBP and 25 receiving conventional pacing. Activation of the autothreshold algorithm was more feasible in later phases, showing a favourable trend towards bipolar pacing. Failures in algorithm activation were primarily due to insufficient safety margins (82.8% in LBBP and 90% in conventional pacing). The remainder was attributed to atrial tachyarrhythmias (10.3% and 10%, respectively) and electrical noise (the remaining 6.9% in the LBBP group). In the LBBP group, there were not statistically significant differences between manual and automatic thresholds, and both remained stable during follow-up (mean increase of 0.50 V). CONCLUSION: The autothreshold algorithm is feasible in LBBP, with a favourable trend towards bipolar pacing. Automatic thresholds are similar to manual in patients with LBBP, and they remain stable during follow-up.

PEGylation Strategy for Improving the Pharmacokinetic and Antitumoral Activity of the IL-2 No-alpha Mutein.

BACKGROUND: In a previous work, an IL-2Rßγ biased mutant derived from human IL-2 and called IL-2noα, was designed and developed. Greater antitumor effects and lower toxicity were observed compared to native IL-2. Nevertheless, mutein has some disadvantages, such as a very short half-life of about 9-12 min, propensity for aggregation, and solubility problems. OBJECTIVE: In this study, PEGylation was employed to improve the pharmacokinetic and antitumoral properties of the novel protein. METHODS: Pegylated IL-2noα was characterized by polyacrylamide gel electrophoresis, size exclusion chromatography, in vitro cell proliferation and in vivo cell expansion bioassays, and pharmacokinetic and antitumor studies. RESULTS: IL-2noα-conjugates with polyethylene glycol (PEG) of 1.2 kDa, 20 kDa, and 40 kDa were obtained by classical acylation. No significant changes in the secondary and tertiary structures of the modified protein were detected. A decrease in biological activity in vitro and a significant improvement in half-life were observed, especially for IL-2noα-PEG20K. PEGylation of IL-2noα with PEG20K did not affect the capacity of the mutant to induce preferential expansion of T effector cells over Treg cells. This pegylated IL-2noα exhibited a higher antimetastatic effect compared to unmodified IL-2noα in the B16F0 experimental metastases model, even when administered at lower doses and less frequently. CONCLUSION: PEG20K was selected as the best modification strategy, to improve the blood circulation time of the IL-2noα with a superior antimetastatic effect achieved with lower doses.

DyMnO3: Synthesis, Characterization and Evaluation of Its Photocatalytic Activity in the Visible Spectrum.

DyMnO3 is a p-type semiconductor oxide with two crystal systems, orthorhombic and hexagonal. This material highlights its ferroelectric and ferromagnetic properties, which have been the subject of numerous studies. Nevertheless, its photocatalytic activity has been less explored. In this work, the photocatalytic activity of DyMnO3 is evaluated through the photodegradation of MG dye. For the synthesis of this oxide, a novel and effective method was used: polymer-decomposition. The synthesized powders contain an orthorhombic phase, with a range of absorbances from 300 to 500 nm and a band gap energy of 2.4 eV. It is also highlighted that, when using this synthesis method, some of the main diffraction lines related to the orthorhombic phase appear at 100 °C. Regarding its photocatalytic activity, it was evaluated under visible light (λ = 405 nm), reaching a photodegradation of approximately 88% in a period of 30 min. Photocurrent tests reveal a charge carrier separation (e-,h+) at a 405 nm wavelength. The main reactive oxygen species (ROS) involved in the photodegradation process were radicals, OH•, and photo-holes (h+). These results stand out because it is the first time that the photodegradation capability of this oxide in the visible spectrum has been evaluated.

Survival Outcomes and Health-Related Quality of Life in Older Adults Diagnosed with Acute Myeloid Leukemia Receiving Frontline Therapy in Daily Practice.

Acute myeloid leukemia has a poor prognosis in older adults, and its management is often unclear due to its underrepresentation in clinical trials. Both overall survival (OS) and health-related quality-of-life (HRQoL) are key outcomes in this population, and patient-reported outcomes may contribute to patient stratification and treatment assignment. This prospective study included 138 consecutive patients treated in daily practice with the currently available non-targeted therapies (intensive chemotherapy [IC], attenuated chemotherapy [AC], hypomethylating agents [HMA], or palliative care [PC]). We evaluated patients' condition at diagnosis (Life expectancy [Lee Index for Older Adults], Geriatric Assessment in Hematology [GAH scale], HRQoL [EQ-5D-5L questionnaire], and fatigue [fatigue items of the QLQ-C30 scale]), OS, early death (ED), treatment tolerability (TT) and change in HRQoL over 12 months follow-up. The median OS was 7.1 months (IC not reached, AC 5.9, HMA 8.8, and PC 1.0). Poor risk AML category and receiving just palliative care, as well as a higher Lee index score in the patients receiving active therapy, independently predicted a shorter OS. The Lee Index and GAH scale were not useful for predicting TT. The white blood cell count was a valid predictor for ED. Patients' HRQoL remained stable during follow-up.

Single-Element Dual-Interferometer for Precision Inertial Sensing: Sub-Picometer Structural Stability and Performance as a Reference for Laser Frequency Stabilization.

Future GRACE-like geodesy missions could benefit from adopting accelerometer technology akin to that of the LISA Pathfinder, which employed laser interferometric readout at the sub-picometer level in addition to the conventional capacitive sensing, which is at best at the level of 100 pm. Improving accelerometer performance holds great potential to enhance the scientific output of forthcoming missions, carrying invaluable implications for research in climate, water resource management, and disaster risk reduction. To reach sub-picometer displacement sensing precision in the millihertz range, laser interferometers rely on suppression of laser-frequency noise by several orders of magnitude. Many optical frequency stabilization methods are available with varying levels of complexity, size, and performance. In this paper, we describe the performance of a Mach-Zehnder interferometer based on a compact monolithic optic. The setup consists of a commercial fiber injector, a custom-designed pentaprism used to split and recombine the laser beam, and two photoreceivers placed at the complementary output ports of the interferometer. The structural stability of the prism is transferred to the laser frequency via amplification, integration, and feedback of the balanced-detection signal, achieving a fractional frequency instability better than 6 parts in 1013, corresponding to an interferometer pathlength stability better than 1pm/Hz. The prism was designed to host a second interferometer to interrogate the position of a test mass. This optical scheme has been dubbed "single-element dual-interferometer" or SEDI.

Septal fascicle involvement during a Purkinje-related ventricular tachycardia: Electroanatomic correlation using omnipolar technology.

Idiopathic verapamil-sensitive fascicular ventricular tachycardia (VT) is the most common form of Purkinje-related ventricular tachycardia (PRVT). Left septal fascicle (LSF) involvement and its connections with the other fascicles, have been recently reported as a pathophysiologic mechanism for this form of PRVT. We describe a case of idiopathic PRVT with LSF involvement using omnipolar technology (OT) mapping in relation to a false tendon. Ablation in the area with concealed fusion entrainment did not terminate the tachycardia. However, radiofrequency application in the area of LSF with manifest fusion entrainment, resulted in immediate tachycardia termination. Six months follow-up showed no tachycardia recurrence.