Comparison of antibody response to SARS-CoV-2 after two doses of inactivated virus and BNT162b2 mRNA vaccines in kidney transplant.

BACKGROUND: Antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA or adenoviral vector-based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (CoronaVac®) and BNT162b2 mRNA. METHODS: A national multicentre cross-sectional study was conducted. The study group was composed of patients from all KT centres in Uruguay, vaccinated between 1 and 31 May 2021 (CoronaVac®, n = 245 and BNT162b2, n = 39). The control group was constituted of 82 healthy individuals. Participants had no prior confirmed coronavirus disease 2019 (COVID-19) test. Blood samples were collected between 30 and 40 days after the second dose. Serum-specific immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein were determined using the COVID-19 IgG QUANT ELISA Kit. RESULTS: Only 29% of KT recipients showed seroconversion (36.5% BNT162b2, 27.8% inactivated virus, P = 0.248) in comparison with 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [median (interquartile range) 173 (73-554) and 29 (11-70) binding antibody units (BAU)/mL, P < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209-335) and BNT162b2: 2638 (2608-3808) BAU/mL, P < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, estimated glomerular filtration rate and time post-KT. CONCLUSION: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need for strategies to improve immunogenicity in KT recipients after two doses of either vaccine.

Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy.

Simlukafusp alfa (FAP-IL2v, RO6874281/RG7461) is an immunocytokine comprising an antibody against fibroblast activation protein α (FAP) and an IL-2 variant with a retained affinity for IL-2Rßγ > IL-2 Rßγ and abolished binding to IL-2 Rα. Here, we investigated the immunostimulatory properties of FAP-IL2v and its combination with programmed cell death protein 1 (PD-1) checkpoint inhibition, CD40 agonism, T cell bispecific and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. The binding and immunostimulatory properties of FAP-IL2v were investigated in vitro and compared with FAP-IL2wt. Tumor targeting was investigated in tumor-bearing mice and in a rhesus monkey. The ability of FAP-IL2v to potentiate the efficacy of different immunotherapies was investigated in different xenograft and syngeneic murine tumor models. FAP-IL2v bound IL-2 Rßγ and FAP with high affinity in vitro, inducing dose-dependent proliferation of natural killer (NK) cells and CD4+/CD8+ T cells while being significantly less potent than FAP-IL2wt in activating immunosuppressive regulatory T cells (Tregs). T cells activated by FAP-IL2v were less sensitive to Fas-mediated apoptosis than those activated by FAP-IL2wt. Imaging studies demonstrated improved tumor targeting of FAP-IL2v compared to FAP-IL2wt. Furthermore, FAP-IL2v significantly enhanced the in vitro and in vivo activity of therapeutic antibodies that mediate antibody-dependent or T cell-dependent cellular cytotoxicity (TDCC) and of programmed death-ligand 1 (PD-L1) checkpoint inhibition. The triple combination of FAP-IL2v with an anti-PD-L1 antibody and an agonistic CD40 antibody was most efficacious. These data indicate that FAP-IL2v is a potent immunocytokine that potentiates the efficacy of different T- and NK-cell-based cancer immunotherapies.

Software sensors for biomass concentration in a SSC process using artificial neural networks and support vector machine.

The lack of sensors for some relevant state variables in fermentation processes can be coped by developing appropriate software sensors. In this work, NARX-ANN, NARMAX-ANN, NARX-SVM and NARMAX-SVM models are compared when acting as software sensors of biomass concentration for a solid substrate cultivation (SSC) process. Results show that NARMAX-SVM outperforms the other models with an SMAPE index under 9 for a 20 % amplitude noise. In addition, NARMAX models perform better than NARX models under the same noise conditions because of their better predictive capabilities as they include prediction errors as inputs. In the case of perturbation of initial conditions of the autoregressive variable, NARX models exhibited better convergence capabilities. This work also confirms that a difficult to measure variable, like biomass concentration, can be estimated on-line from easy to measure variables like CO2 and O2 using an adequate software sensor based on computational intelligence techniques.

Comparison of artificial neural networks an support vector machines for feature selection in electrogastrography signal processing.

The paper describes a feature selection process applied to electrogastrogram (EGG) processing. The data set is formed by 42 EGG records from functional dyspeptic (FD) patients and 22 from healthy controls. A wrapper configuration classifier was implemented to discriminate between both classes. The aim of this work is to compare artificial neural networks (ANN) and support vector machines (SVM) when acting as fitness functions of a genetic algorithm (GA) that performs a feature selection process over some features extracted from the EGG signals. These features correspond to those that literature shows to be the most used in EGG analysis. The results show that the SVM classifier is faster, requires less memory and reached the same performance (86% of exactitude) than the ANN classifier when acting as the fitness function for the GA.

Validez y confiabilidad de la versión chilena del Alcohol Use Disorders Identification Test (AUDIT) / Assessment of the alcohol use disorders identification test (AUDIT) to detect problem drinkers

Background: AUDIT is a self-reported questionnaire used to detect problem drinkers. It must be translated into Spanish and validated in order to be used in Chile. Aim: To assess the validity of a Chilean version of the AUDIT questionnaire. Material and methods: The English version of the questionnaire was translated into Spanish and adapted to the Chilean cultural environment. Using the Delphi method, an expert group examined the text and then decided on which would be the definitive version. This test was translated to English again and was approved by one of the original authors. It was then applied to 93 subjects aged 37 ± 12 years (60 percent males) consulting at a primary health care center These subjects also answered the Composite International Diagnostic Interview (CIDI), version 2.1 that was used as the gold standard for the diagnosis of hazardous drinking and alcohol dependence. Cronbach alpha and test-retest validity were analyzed. Sensitivity and specificity were determined using receiver operating (ROC) curves. Results: The internal consistency of AUDIT was 0.93, its test re-tests reliability was 0.97 (95 percent confidence intervals 0.96-0.98). Using a cutoff point of 6 for hazardous consumption, its sensitivity and specificity were 83 percent and 88 percent, respectively. The figures for dependence and harmful consumption, using a cutoff point of 9, were 87 percent and 85 percent, respectively. Conclusions: AUDIT is a valid questionnaire to detect problem drinkers.

The Alcohol Use Disorders Identification Test (AUDIT) as a screening instrument for adolescents.

BACKGROUND: The Alcohol Use Disorders Identification Test (AUDIT) is an international screening instrument extensively employed in adult target groups. However, there is scarce information on screening with the AUDIT in adolescent populations. The purpose of this study was to determine the cut-off point for hazardous, harmful, and dependent alcohol use through the validation of the AUDIT in a Chilean adolescent sample. METHODS: The original English version of the AUDIT was translated into Spanish, using the procedure recommended by the World Health Organization. The text was then back-translated and sent to one of the original authors (Thomas Babor), who approved the translation. Students attending public schools in Santiago, Chile, self-administered the AUDIT, and those older than 15 years completed the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), which served as a gold standard. Between 1 and 4 weeks after the CIDI-SAM, participants answered a second AUDIT. RESULTS: A total of 42 female and 53 male adolescents (mean age: 15.9 [SD=1.2]) completed the AUDIT, with a mean score of 4.3. Reliability according to Cronbach's alpha was 0.83. Test-retest correlation was also satisfactory (intra-class correlation 0.81 [95% CI 0.73-0.87]). Analysis of the receiver operating characteristic (ROC) curve yielded cut-off points for hazardous, harmful, and dependent alcohol use of 3, 5, and 7 points, respectively. CONCLUSIONS: The Chilean version of the AUDIT is a valid and reliable tool for identifying adolescents with hazardous, harmful, and dependent alcohol use. The suggested cut-off points make screening with the AUDIT more accurate for adolescent populations.

[Assessment of the alcohol use disorders identification test (AUDIT) to detect problem drinkers]. / Validez y confiabilidad de la versión chilena del Alcohol Use Disorders Identification Test (AUDIT).

BACKGROUND: AUDIT is a self-reported questionnaire used to detect problem drinkers. It must be translated into Spanish and validated in order to be used in Chile. AIM: To assess the validity of a Chilean version of the AUDIT questionnaire. MATERIAL AND METHODS: The English version of the questionnaire was translated into Spanish and adapted to the Chilean cultural environment. Using the Delphi method, an expert group examined the text and then decided on which would be the definitive version. This test was translated to English again and was approved by one of the original authors. It was then applied to 93 subjects aged 37 +/- 12 years (60% males) consulting at a primary health care center These subjects also answered the Composite International Diagnostic Interview (CIDI), version 2.1 that was used as the gold standard for the diagnosis of hazardous drinking and alcohol dependence. Cronbach alpha and test-retest validity were analyzed. Sensitivity and specificity were determined using receiver operating (ROC) curves. RESULTS: The internal consistency of AUDIT was 0.93, its test re-tests reliability was 0.97 (95% confidence intervals 0.96-0.98). Using a cutoff point of 6 for hazardous consumption, its sensitivity and specificity were 83% and 88%, respectively. The figures for dependence and harmful consumption, using a cutoff point of 9, were 87% and 85%, respectively. CONCLUSIONS: AUDIT is a valid questionnaire to detect problem drinkers.

Alterations in fetal kidney development and elevations in arterial blood pressure in young adult sheep after clinical doses of antenatal glucocorticoids.

Epidemiologic studies have yielded controversial information regarding an association between antenatal steroid administration and elevations in arterial blood pressure (BP). The aim of the study was to determine whether antenatal administration of a clinically relevant dose of steroids at a time when fetal nephrogenesis is at its highest results in abnormal kidney development and adult hypertension. Pregnant sheep were treated with either vehicle or betamethasone. Maternal injections were given 24 h apart at 80 d of gestational age (dGA; 0.55 of gestation). Animals were studied either as fetuses or as immature adults. Fetuses were delivered by cesarean section at 135 dGA. Adults were studied at 6 mo of age. Betamethasone administration did not induce premature labor or intrauterine growth restriction. In the betamethasone-exposed group, we found at 135 dGA a 25.5% decrease in the number of glomeruli with no differences in fetal kidney weight. In adults, mean, systolic, and diastolic arterial BPs were significantly higher, whereas there were no significant differences in heart rate over the same study period. The major finding of this study is that a single course of antenatal steroids alters renal development and is associated with elevations in arterial BP in lambs at 6 mo of age. We conclude that antenatal glucocorticoid administration under the National Institutes of Health consensus guidelines may alter human fetal renal development.

A specific bacterial aminoacylase cleaves odorant precursors secreted in the human axilla.

Human axillary odor is known to be formed upon the action of Corynebacteria sp. on odorless axilla secretions. The known axilla odor determinant 3-methyl-2-hexenoic acid was identified in hydrolyzed axilla secretions along with a chemically related compound, 3-hydroxy-3-methylhexanoic acid. The natural precursors of both these acids were purified from non-hydrolyzed axilla secretions. From liquid chromatography/mass spectrometry analysis, it appeared that the acids are covalently linked to a glutamine residue in fresh axilla secretions, and the corresponding conjugates were synthesized for confirmation. Bacterial isolates obtained from the human axilla and belonging to the Corynebacteria were found to release the acids from these odorless precursors in vitro. A Zn(2+)-dependent aminoacylase mediating this cleavage was purified from Corynebacterium striatum Ax20, and the corresponding gene agaA was cloned and heterologously expressed in Escherichia coli. The enzyme is highly specific for the glutamine residue but has a low specificity for the acyl part of the substrate. agaA is closely related to many genes coding for enzymes involved in the cleavage of N-terminal acyl and aryl substituents from amino acids. This is the first report of the structure elucidation of precursors for human body odorants and the isolation of the bacterial enzyme involved in their cleavage.

Pharmacogenetic analysis of adverse drug effect reveals genetic variant for susceptibility to liver toxicity.

A retrospective pharmacogenetic study was conducted to identify possible genetic susceptibility factors in patients in whom the administration of the anti-Parkinson drug, tolcapone (TASMAR), was associated with hepatic toxicity. We studied 135 cases of patients with elevated liver transaminase levels (ELT) of >/=1.5 times above the upper limit of normal, in comparison with matched controls that had also received the drug but had not experienced ELT. DNA samples were genotyped for 30 previously described or newly characterized bi-allelic single nucleotide polymorphisms (SNPs), representing 12 candidate genes selected based on the known metabolic pathways involved in the tolcapone elimination. SNPs located within the UDP-glucuronosyl transferase 1A gene complex, which codes for the enzymes involved in the main elimination pathway of the drug, were found to be significantly associated with the occurrence of tolcapone-associated ELTs.