The Prominence of Action Sequences and Behavioral Similarity in the Morris Water Task.

The question of What is learned when navigating to a place is reinforced has been the subject of considerable debate. Prevailing views emphasize cognitive structures (e.g., maps) or associative learning, which has shaped measurement in spatial navigation tasks (e.g., the Morris water task [MWT]) toward selection of coarse measures that do not capture precise behaviors of individual animals. We analyzed the navigation paths of 15 rats (60 trials each) in the MWT at high temporal resolution (30Hz) and utilized dynamic time warping to quantify the similarity of paths within and between animals. Paths were largely direct, yet suboptimal, and included changes in speed and trajectory that were established early in training and unique to each animal. Individual rats executed similar paths from the same release point from trial to trial, which were distinct from paths executed by other rats as well as paths performed by the same rat from other release points. These observations suggest that rats learn to execute similar path sequences from trial to trial for each release point in the MWT. Occasional spontaneous deviations from the established, unique behavioral sequence, resulted in profound disruption in navigation accuracy. We discuss the potential implications of sequence navigation behaviors for understanding relations between behavior and spatial neural signals such as place cells, grid cells, and head direction cells. Supplementary Information: The online version contains supplementary material available at 10.1007/s40614-024-00402-8.

Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease.

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi.Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

[Box: see text].

Epidemiology of ANCA vasculitis in Northern Spain.

OBJECTIVES: The incidence of anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) shows disparate results due to variable classification criteria and heterogeneous-population series. We aimed to estimate the incidence of AAV in a well-defined population with standardized classification criteria. METHODS: Population-based study of AAV patients diagnosed from January 2000 to December 2023 in Cantabria, Northern Spain. Patients were classified according to ACR/EULAR 2022 into granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or unclassified vasculitis if the criteria were not met. Eosinophilic granulomatosis with polyangiitis (EGPA) patients were not included. The annual incidence rates were estimated by cases over 1,000 000 (106) (95% CI) including overall AVV, type of AAV, sex, and year of diagnosis. A literature review was also performed. RESULTS: We included 152 (80/72 men; mean age; 70.6 ± 13.18 years) patients. They were classified as MPA (67; 44%), GPA (64; 42.2%), and unclassified vasculitis (21; 13.8%). Annual incidence was 13.4 (10-16.8)/106 [male 14.5 (10.5-18.5); female 12.1 (8.7-15.6)]. The Annual incidence of MPA was 5.9 (4-7.8)/106 and GPA 5.6 (3.9-7.3)/106. The mean Annual incidence increased from 6.1 (4.5-7.7)/106-16.5 (5.6-27.4)/106 in the last three years, particularly, in GPA from 2.3 (0.3-4.9)/106-8.2 (2-14.5)/106. The prevalence of AAV was 184.7 (181-188)/106. CONCLUSION: During a 20-year period we found that the incidence of AAV (GPA and MPA) in Northern Spain is higher than Southern Spain, but lower than Northern European countries. An increase in the incidence was observed in the last years.

Carcinoma Cuniculatum, a Rare Variant of Oral Squamous Cell Carcinoma: Presentation of Five Clinical Cases and Review of the Literature.

Background: Oral carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma. It exhibits a locally aggressive behaviour, and its histopathology poses a diagnostic challenge, as it can be mistaken for other conditions. We present five cases of oral CC treated at our institution and conduct a comprehensive review of the current literature. Case Series: Five patients (two women and three men) were treated in our institution with a final diagnosis of oral CC. Ages ranged from 9 to 85 years at the time of diagnosis. Four patients had mandibular involvement requiring mandibulectomy and reconstruction using an osseous free flap. The diagnosis of oral CC was straightforward in the most recent cases. However, for the first two cases, the diagnosis of oral CC was established after thorough discussions between the surgeons and the pathologist regarding the similarities with recent cases. Consequently, the pathological specimens had to be retrospectively re-evaluated to confirm these diagnoses. Conclusions: Oral CC is a locally aggressive tumour that can present a challenge for pathologists, often leading to misdiagnosis. According to the existing literature, surgical resection with clear margins is the preferred treatment approach.

Synthesis of Silver Nanoparticles Using Extracts from Different Parts of the Paullinia cupana Kunth Plant: Characterization and In Vitro Antimicrobial Activity.

The green synthesis of silver nanoparticles (AgNPs) can be developed using safe and environmentally friendly routes, can replace potentially toxic chemical methods, and can increase the scale of production. This study aimed to synthesize AgNPs from aqueous extracts of guarana (Paullinia cupana) leaves and flowers, collected in different seasons of the year, as a source of active biomolecules capable of reducing silver ions (Ag+) and promoting the stabilization of colloidal silver (Ag0). The plant aqueous extracts were characterized regarding their metabolic composition by liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS/MS), phenolic compound content, and antioxidant potential against free radicals. The synthesized AgNPs were characterized by UV/Vis spectrophotometry, dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and scanning electron microscopy coupled to energy-dispersive X-ray spectrometry (EDX). The results demonstrated that the chemical characterization indicated the presence of secondary metabolites of many classes of compounds in the studied aqueous extracts studied, but alkaloids and flavonoids were predominant, which are widely recognized for their antioxidant capabilities. It was possible to notice subtle changes in the properties of the nanostructures depending on parameters such as seasonality and the part of the plant used, with the AgNPs showing surface plasmon resonance bands between 410 and 420 nm using the leaf extract and between 440 and 460 nm when prepared using the flower extract. Overall, the average hydrodynamic diameters of the AgNPs were similar among the samples (61.98 to 101.6 nm). Polydispersity index remained in the range of 0.2 to 0.4, indicating that colloidal stability did not change with storage time. Zeta potential was above -30 mV after one month of analysis, which is adequate for biological applications. TEM images showed AgNPs with diameters between 40.72 to 48.85 nm and particles of different morphologies. EDX indicated silver content by weight between 24.06 and 28.81%. The synthesized AgNPs exhibited antimicrobial efficacy against various pathogenic microorganisms of clinical and environmental interest, with MIC values between 2.12 and 21.25 µg/mL, which is close to those described for MBC values. Therefore, our results revealed the potential use of a native species of plant from Brazilian biodiversity combined with nanotechnology to produce antimicrobial agents.

The histamine H3 receptor inverse agonist SAR-152954 reverses deficits in long-term potentiation associated with moderate prenatal alcohol exposure.

Prenatal alcohol exposure can have persistent effects on learning, memory, and synaptic plasticity. Previous work from our group demonstrated deficits in long-term potentiation (LTP) of excitatory synapses on dentate gyrus granule cells in adult offspring of rat dams that consumed moderate levels of alcohol during pregnancy. At present, there are no pharmacotherapeutic agents approved for these deficits. Prior work established that systemic administration of the histaminergic H3R inverse agonist ABT-239 reversed deficits in LTP observed following moderate PAE. The present study examines the effect of a second H3R inverse agonist, SAR-152954, on LTP deficits following moderate PAE. We demonstrate that systemic administration of 1 mg/kg of SAR-152954 reverses deficits in potentiation of field excitatory post-synaptic potentials (fEPSPs) in adult male rats exposed to moderate PAE. Time-frequency analyses of evoked responses revealed PAE-related reductions in power during the fEPSP, and increased power during later components of evoked responses which are associated with feedback circuitry that are typically not assessed with traditional amplitude-based measures. Both effects were reversed by SAR-152954. These findings provide further evidence that H3R inverse agonism is a potential therapeutic strategy to address deficits in synaptic plasticity associated with PAE.

Low-risk delisting strategy in highly sensitized patients without donor offers included in exchange donation programs. One single-center experience.

Donor exchange programs were designed to allocate organs for highly sensitized (HS) patients. The allocation algorithm differs slightly among countries and includes different strategies to improve access to transplants in HS patients. However, many HS patients with a calculated panel reactive of antibodies (cPRA) of 100 % remain on the waiting list for a long time. Some allocation algorithms assume immunological risk, including Imlifidase treatment, to increase the chance of transplantation in very HS patients. Here, we describe our unicenter experience of low-risk delisting strategy in 15 HS patients included in the Spanish donor exchange program without donor offers. After delisting, 7 out of 15 HS patients reduced the cPRA below 99.95 % and impacted the reduction of time on the waiting list (p = 0.01), where 5 out of 7 achieved transplantation. Within those HS that remained above 99.95 %, 1 out of 8 was transplanted. All the HS were transplanted with delisted DSA, and only one with DSA level rebounded early after transplantation. All HS transplanted after delisting maintain graft function. The transplant immunology laboratories are challenged to search intermediate risk assessment methods for delisting high HS patients.

Tuberculosis among children visiting friends & relatives.

BACKGROUND: Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR. METHODS: We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8-12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus. RESULTS: Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8-28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3-9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9-20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1-13.3). CONCLUSIONS: The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions.

Doubling the life of Cu/ZnO methanol synthesis catalysts via use of Si as a structural promoter to inhibit sintering.

Cu/ZnO/Al2O3 catalysts used to synthesize methanol undergo extensive deactivation during use, mainly due to sintering. Here, we report on formulations wherein deactivation has been substantially reduced by the targeted use of a small quantity of a Si-based promoter, resulting in accrued activity benefits that can exceed a factor of 1.8 versus unpromoted catalysts. This enhanced stability also provides longer lifetimes, up to double that of prior generation catalysts. Detailed characterization of a library of aged catalysts has allowed the most important deactivation mechanisms to be established and the chemical state of the silicon promoter to be identified. We show that silicon is incorporated within the ZnO lattice, providing a pronounced improvement in the hydrothermal stability of this component. These findings have important implications for sustainable methanol production from H2 and CO2.

ANCA detection with solid phase chemiluminescence assay: diagnostic and severity association in vasculitis.

ANCA-associated vasculitis (AAV) comprises a group of necrotizing vasculitis that mainly affects small- and medium-sized vessels. Serum anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (anti-MPO) and anti-proteinase 3 (anti-PR3), levels may correlate to severity, prognosis, and recurrence of the disease. A retrospective analysis of 101 patients with MPO-positive and 54 PR3-positive vasculitis was performed, using laboratory established cut-off value, measured by chemiluminescence. Furthermore, data of renal disease and pulmonary involvement were collected at vasculitis diagnosis, as well as the progress, requiring dialysis, transplant, or mortality. For anti-MPO antibodies with a diagnosis of vasculitis (n = 77), an area under the curve (AUC) was calculated (AUC = 0.8084), and a cut-off point of 41.5 IU/ml was determined. There were significant differences in anti-MPO levels between patients with renal or pulmonary dysfunction (n = 65) versus those without them (n = 36) (p = 0.0003), and a cut-off threshold of 60 IU/ml was established. For anti-PR3 antibodies with a diagnosis of vasculitis (n = 44), an area under the curve (AUC) was calculated (AUC = 0.7318), and a cut-off point of 20.5 IU/ml was determined. Significant differences in anti-PR3 levels were observed between those patients with renal or pulmonary dysfunction (n = 30) and those without them (n = 24) (p = 0.0048), and a cut-off threshold of 41.5 IU/ml was established. No significant differences between those patients who had a worse disease progression and those who did not were found for anti-MPO and anti-PR3. Anti-MPO and anti-PR3 levels at the moment of vasculitis diagnosis are related with disease severity but not with disease outcome or vasculitis recurrence.

Effect of the ketogenic diet as a treatment for refractory epilepsy in children and adolescents: a systematic review of reviews.

CONTEXT: Epilepsy is one of the most prevalent neurological disorders in childhood. Antiepileptic drugs are the preferred treatment. However, 30% of children continue suffering seizures. A ketogenic diet (KD) is one of the emerging alternative treatments. OBJECTIVE: This review aims to analyze the current evidence regarding the use of a KD for the treatment of refractory epilepsy (RE) in childhood. DATA SOURCES: A systematic review of reviews was performed, based on MEDLINE (PubMed) as at January 2021. DATA EXTRACTION: The data extracted included the first author's last name; the year of publication; the country; the study design; the population; the diagnosis, concept, and description of KD types; and major outcome. RESULTS: Twenty-one reviews were included, 8 with systematic methodology (2 of them included a meta-analysis) and 13 with unsystematic methodology. The main difference between the 2 types of reviews is the reproducibility of their methodology. Therefore, the results of each type of review were analyzed separately. Each type of review described 4 categories of KD: classic KD, modified Atkins diet (MAD), use of medium-chain triglycerides (MCTs), and low glycemic index treatment (LGIT). In terms of effectiveness, the considered systematic reviews reported reductions in the frequency of seizures greater than 50% in about half of the patients. Reviews without systematic methodology reported that 30%-60% of the children showed a 50% or greater reduction in seizures. The most frequently described adverse effects in the 8 systematic reviews were: vomiting (6/8), constipation (6/8), and diarrhea (6/8); and in the unsystematic reviews: vomiting and nausea (10/13), constipation (10/13), and acidosis (9/13). CONCLUSION: KD can be an effective treatment for RE, with a more than 50% reduction in the frequency of seizures and cognitive improvement being achieved in half of the pediatric patients. The effectiveness of the various types of KD is comparable, and the KD can be adapted to the needs of the patient. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021244142.

[Challenges and strategies to recover and dynamize primary care: SWOT-CAME analysis in a Health Department]. / Retos y estrategias para recuperar y dinamizar la atención primaria. Metodología DAFO (Debilidades, Amenazas, Fortalezas y Oportunidades)-CAME (Corregir, Afrontar, Mantener y Explotar) en un departamento de salud.

OBJECTIVE: To identify strengths, obstacles, changes in the environment, and capabilities of primary care teams and support units, with the aim of providing high-quality care in an integrated healthcare area. DESIGN: Mixed methods study based on the SWOT matrix and CAME analysis. LOCATION: Primary care, Valencian community. PARTICIPANTS: A total of 271 professionals from different collectives and patient association representatives participated. 99 in the idea generation phase, 154 in the SWOT matrix development phase, and 18 in the CAME analysis development phase. INTERVENTIONS: A SWOT-CAME analysis was conducted, from which action lines were established. Information capture was carried out through nominal groups, and the consensus phase involved integrating all professionals through Delphi and consensus conference techniques. MAIN MEASUREMENTS: Prioritization of proposals to maintain strengths, address threats, exploit opportunities, and correct weaknesses within the framework of an integrated healthcare area action plan. RESULTS: A total of 82 different ideas were proposed (20 strengths; 40 weaknesses; 4 threats; 12 opportunities; 6 threats-opportunities), which, once prioritized, were translated into 7 lines and 33 prioritized actions/interventions (CAME analysis). CONCLUSIONS: Integrated care, seeking collaborative approaches between care levels, redefining roles, digital solutions, staff training, and improvements in equipment and support processes, along with measures to address the aging population and the needs of socio-sanitary centers, constitute the challenges to be addressed.

Case report: Self-administration of alpha-1 antitrypsin therapy: a report of two cases.

Intravenous augmentation therapy with human alpha-1 proteinase inhibitor for the management of respiratory disease is recommended for people with alpha-1 antitrypsin deficiency (AATD) who are nonsmokers or former smokers. Augmentation therapy usually requires weekly administration at the hospital or clinic and poses an additional burden for patients due to interference with daily life, including work and social activities. Self-administration is a useful alternative to overcome this limitation, but there is a lack of published information on clinical outcomes. We report two cases of individuals with AATD at different stages of the disease who were successfully managed with self-administered augmentation therapy, with increased satisfaction because of the independence gained, lack of interference with clinical stability, and no relevant safety issues.

Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience.

In the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability-as measured by Oswestry Head and Neck Pain Scale and social isolation-as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length was negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line length, anterior CSF space) and symptom severity (disability and loneliness) on estrogen and intereukin-6 levels. These results are consistent with allostatic load. That is, when the combination of CSF crowding and self-report symptom (disability and loneliness) severity exceed the capacity of biological resilience factors, then biomarkers such as neuroprotective estrogen levels drop, rather than rise, with increasing symptom severity.

[Dietary patterns and factors and their association with the anxiety in adult population: proposed recommendations based on a scoping review of systematic reviews and meta-analyses]. / Patrones y factores dietéticos y su asociación con la ansiedad en población adulta: propuesta de recomendaciones basada en una revisión de alcance de revisiones sistemáticas y metaanálisis.

Introduction: A high percentage of the population suffers from anxiety, a disorder that can be influenced by dietary habits. The aim of this review was to compile the existing evidence on dietary patterns and factors, and their association with anxiety to propose clinically applicable recommendations. A scoping review of systematic reviews and meta-analyses was conducted in the MEDLINE database (PubMed) until January 2021, reporting the main findings based on PRISMA (2020). To construct the search strategy, MeSH language, keywords ("diet", "nutrients", "healthy lifestyle", "anxiety") and filters were used, combined using Boolean operators. Twelve articles, seven systematic reviews with meta-analysis and five systematic reviews were selected. Several results were obtained evaluating the relationship between anxiety and different aspects of diet. The main associations found were between increased consumption of raw vegetables and fruits, substitution of refined cereals by whole grains, intake of omega-3 and omega-6 fats, and increased intake of minerals and vitamins, tryptophan and antioxidants. Based on the systematic reviews and meta-analyses included as findings, ten recommendations on food consumption that should be considered as a priority for these patients were proposed. Based on the literature reviewed, it is concluded that there are dietary patterns and factors that could have a stronger positive influence on anxiety. This proposal of evidence-based dietary recommendations may allow healthcare professionals to have updated recommendations to provide a first orientation.

Introducción: Un alto porcentaje de la población sufre ansiedad, trastorno que puede verse influenciado por los hábitos dietéticos. El objetivo de esta revisión fue recopilar la evidencia existente sobre los patrones y factores dietéticos, y su asociación con la ansiedad para proponer unas recomendaciones clínicamente aplicables. Se realizó una revisión de alcance (Scoping Review) de revisiones sistemáticas y metaanálisis en la base de datos MEDLINE (PubMed) hasta enero de 2021, informando de los principales hallazgos según PRISMA (2020). Para construir la estrategia de búsqueda, se emplearon el lenguaje MeSH, palabras clave ("dieta", "nutrientes", "estilo de vida saludable", "ansiedad") y filtros, combinándose mediante operadores booleanos. Se seleccionaron 12 artículos, siete revisiones sistemáticas con metaanálisis y cinco revisiones sistemáticas. Se obtuvieron diversos resultados en los que se evaluaba la relación entre la ansiedad y diferentes aspectos de la dieta. Las principales asociaciones encontradas se observaron entre un mayor consumo de verduras crudas y frutas, la sustitución de cereales refinados por integrales, la ingesta de AGP omega-3 y omega-6 y el incremento del consumo de minerales y vitaminas, triptófano y antioxidantes. De acuerdo con las revisiones sistemáticas y metaanálisis incluidos como resultados, se propusieron diez recomendaciones sobre el consumo de alimentos y la ingesta de nutrientes que deberían priorizarse en estos pacientes. Según la literatura revisada, se concluye que existen patrones y factores dietéticos que podrían ejercer una mayor influencia protectora sobre la ansiedad. Esta propuesta de recomendaciones dietéticas basadas en la evidenciapermitirá a los profesionales sanitarios disponer de unas pautas actualizadas que sirvan como una primera guía.

House dust mite subcutaneous immunotherapy has sustained long-term effectiveness on allergic rhinitis and asthma: A 10-year follow-up.

BACKGROUND: Maintenance doses for allergen immunotherapy (AIT) have been recommended for at least 3 years but little data on long-term efficacy is available depending on AIT duration. To show sustained efficacy 10 years after completion of treatment with depigmented-polymerized house dust mite (dpg-pol HDM) allergen extract in adults with asthma and/or rhinoconjunctivitis. METHODS: Patients included in a double-blind placebo-controlled AIT study with dpg-pol HDM allergen extract were reviewed at completion of the perennial treatment and 10-year follow-up (10y-FU). Change in symptom and rescue medication score was the primary objective. Visual analog scale (VAS), asthma control test (ACT), and degree of disease control were the secondary objectives. A comparative analysis between patients who underwent AIT treatment for <3 years and ≥3 years was performed. RESULTS: Data from 31 patients (mean age 38 years) were available at 10y-FU. All had asthma and 29 had rhinoconjunctivitis at baseline. Twenty-three patients were treated ≥3 years and 8 for <3 years. Seventeen (55%) patients were asymptomatic at completion of AIT, with significant differences for nasal, conjunctival, and bronchial symptoms (p < .0001) compared with baseline only in those patients treated ≥3 years. Nine (52.9%) patients remained completely asymptomatic at 10y-FU, all were treated for ≥3 years. Moreover, significant reduction in the number of patients with rhinitis (p = .0117), conjunctivitis (p < .0001), and bronchial (p = .0005) symptoms was observed at 10y-FU compared with baseline only in the ≥3 years treated. Ten (32.3%) patients did not require any rescue medication at 10y-FU, all had been treated for ≥3 years. ACT at 10y-FU showed a good control of asthma (median 23.5; 95% IC[22.0, 25.0]). No significant differences were observed between VAS at end of treatment compared with VAS at 10y-FU. CONCLUSIONS: Sustained clinical efficacy is achieved 10 years after completion of depigmented-polymerized HDM, however, these findings were observed only if patients are treated for at least 3 years.

Donor-Derived Cell-Free DNA at 1 Month after Kidney Transplantation Relates to HLA Class II Eplet Mismatch Load.

Kidney transplantation is the preferred therapeutic option for end-stage renal disease; however, the alloimmune response is still the leading cause of renal allograft failure. To better identify immunologic disparities in order to evaluate HLA compatibility between the donor and the recipient, the concept of eplet load has arisen. Regular kidney function monitoring is essential for the accurate and timely diagnosis of allograft rejection and the appropriate treatment. Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a potential biomarker of acute rejection and graft failure in kidney transplantation. The proportion of plasma dd-cfDNA was determined in forty-two kidney patients at 1 month after transplantation. A total of eleven (26.2%) patients had a dd-cfDNA proportion of ≥1.0%. The only pretransplant variable related to dd-cfDNA > 1.0% was the HLA class II eplet mismatch load, mainly the HLA-DQB1 eplet mismatch load. Furthermore, dd-cfDNA was able to discriminate the patients with antibody-mediated rejection (AbMR) (AUC 87.3%), acute rejection (AUC 78.2%), and troubled graft (AUC 81.4%). Increased dd-cfDNA levels were associated with kidney allograft deterioration, particularly rejection, as well as a greater HLA class II eplet mismatch load. Consequently, combining dd-cfDNA determination and HLA eplet mismatch load calculation should improve the assessment of the risk of short- and long-term allograft damage.

The Effect of Third Dose of Pfizer/BioNTech and Moderna COVID-19 mRNA Vaccines on IgG Antibody Titers.

With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the Centers for Disease Control and Prevention (CDC) authorized the third dose of the Pfizer-BioNTech (BNT162b2) vaccine with the rationale for prolonged elevation of anti-SARS-CoV-2 antibody titers and protection against the SARS-CoV-2 virus. To better understand how administration of the third dose of the Pfizer/BioNTech coronavirus disease 2019 (COVID-19) vaccine affects the incidence and severity of SARS-CoV-2 infections, we administered the third dose of the Pfizer-BioNTech (BNT162b2) to 189 participants. Blood samples were collected from participants during each of their scheduled visits (baseline, week two, week 12, and week 24) and tested for semi-quantitative anti-SARS-CoV-2 immunoglobulin G (IgG) titers. Our results showed that administration of the third dose of the Pfizer-BioNTech (BNT162b2) vaccine elicited elevated anti-SARS-CoV-2 IgG antibodies for the 24-week duration of the study. IgG antibody titers were greatest in week two, and progressively decreased by week 12 and week 24, with statistically significant differences between the IgG antibody titers for each collection date.

Pharmacokinetics of Curcumin Delivered by Nanoparticles and the Relationship with Antitumor Efficacy: A Systematic Review.

Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor. Although it is a pleiotropic molecule, curcumin's free form, which is lipophilic, has low bioavailability and is rapidly metabolized, limiting its clinical use. With the advances in techniques for loading curcumin into nanostructures, it is possible to improve its bioavailability and extend its applications. In this review, we gather evidence about the comparison of the pharmacokinetics (biodistribution and bioavailability) between free curcumin (Cur) and nanostructured curcumin (Cur-NPs) and their respective relationships with antitumor efficacy. The search was performed in the following databases: Cochrane, LILACS, Embase, MEDLINE/Pubmed, Clinical Trials, BSV regional portal, ScienceDirect, Scopus, and Web of Science. The selected studies were based on studies that used High-Performance Liquid Chromatography (HPLC) as the pharmacokinetics evaluation method. Of the 345 studies initially pooled, 11 met the inclusion criteria and all included studies classified as high quality. In this search, a variety of nanoparticles used to deliver curcumin (polymeric, copolymeric, nanocrystals, nanovesicles, and nanosuspension) were found. Most Cur-NPs presented negative Zeta potential ranging from -25 mV to 12.7 mV, polydispersion index (PDI) ranging from 0.06 to 0.283, and hydrodynamic diameter ranging from 30.47 to 550.1 nm. Selected studies adopted mainly oral and intravenous administrations. In the pharmacokinetics analysis, samples of plasma, liver, tumor, lung, brain, kidney, and spleen were evaluated. The administration of curcumin, in nanoparticle systems, resulted in a higher level of curcumin in tumors compared to free curcumin, leading to an improved antitumor effect. Thus, the use of nanoparticles can be a promising alternative for curcumin delivery since this improves its bioavailability.

CD64 expression on neutrophils as a potential biomarker for bacterial infection in ascitic fluid of cirrhotic patients.

BACKGROUND: CD64 expression on neutrophils surface (CD64N) by flow cytometry has been validated as a rapid biomarker for bacterial infections in both peripheral blood and other biological fluids. Ascites is a common complication in cirrhotic patients that a variety of factors can cause, including bacterial infections. Manual counting of polymorphonuclear (PMN) cells in ascitic fluid and microbiologic culture are essential for its diagnosis. We aimed to validate the determination of CD64N by flow cytometry in ascitic fluid and assess its potential usefulness in the rapid identification of bacterial infections. MATERIALS AND METHODS: A prospective unicentre study was conducted. Flow cytometry was used to analyse the expression of CD64N in 77 ascitic fluid samples from the initial paracentesis of 60 cirrhotic patients in different admission episodes from November 2021 to December 2022. RESULTS: Seventeen samples were diagnosed with bacterial infection based on a positive microbiologic culture or by PMN count (>250 PMN/mm3 in ascitic fluid). The median of CD64N MFI was significantly increased in the bacterial infection group (3690.5 MFI [1635.23-6521.18] vs. 1105.9 MFI [737.3-2048.2], p < 0.001). The CD64 MFI ratio of granulocytes to lymphocytes was elevated in the bacterial infection group (13.06 [6.38-24.58] vs. 5.01 [3.38-7.36], p < 0.001). A CD64N ratio higher than 9.9 identified those patients with bacterial infection with 70.6 and 86.7% sensitivity and specificity, with an area under the curve (AUC) of 79.4%. CONCLUSION: The CD64N determined by flow cytometry on ascitic fluid could help quickly identify bacterial infections in ascites patients, allowing early antibiotic treatment.