Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines.

In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4+ and CD8+ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4+ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8+ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8+ T-cell response in previously infected individuals.

Presurgical Use of Hypoxic Mixture for Systemic Perfusion Improvement in Neonates With Complex Congenital Heart Disease: A Systematic Review and Meta-Analysis.

Oxygen therapy is essential for the survival of preterm babies and critically ill newborns; however, it has the potential to cause harm through hypoxemia or hyperoxemia. Newborns with complex congenital heart diseases (CHD) suffer from oxygen fluctuations due to the disease and its treatments, altering pre and postnatal development. The objective of this study is to evaluate the evidence for using a hypoxic mixture to decrease pulmonary over-circulation and improve systemic perfusion before surgical interventions in newborns with complex CHD that course with pulmonary over-circulation and systemic hypoperfusion. A search was conducted in PubMed, EMBASE, LILACS, Scielo, Taylor and Francis, SAGE, and Science Direct databases from 2000 to 2022 by two independent authors, including articles with hypoxic mixture treatment in observational studies or trials, with pre-treatment and post-treatment measurements in the same patient, or two groups or more comparisons. Six articles were selected, with a total of 75 patients. The primary outcome was improved systemic circulation and decreased pulmonary over-circulation measured directly with Qp/Qs and indirectly with oxygen saturation and cerebral near-infrared spectroscopy (NIRS). In addition, we performed a meta-analysis for oxygen saturation and cerebral NIRS. Oxygen saturation was the value uniformly reported; three studies reported a significantly lower oxygen saturation after the hypoxic mixture. The cerebral NIRS was measured in 4 studies, with inconsistent results. After using the hypoxic mixture, the Qp/Qs calculation was lower in the two studies but was not statistically significant. The meta-analysis for oxygen saturation showed a fixed effect post-hypoxic therapy of -0.7 (-1.06; -0.35), p < 0.001. The meta-analysis of two studies that measured cerebral NIRS did not show a statistically significant difference at 12 and 24 hours. In conclusion, this is the first systematic review and meta-analysis regarding the pre-operative use of hypoxic gas mixtures for newborns with complex congenital heart disease. Treatment results in lower oxygen saturations, but there is a lack of evidence of improvement in systemic perfusion. The utilization of this therapy is controversial, and better evidence is necessary.

Impact of congenital heart disease on mortality and other associated outcomes in children hospitalised for acute asthma exacerbation.

BACKGROUND: Acute asthma exacerbation is one of the most common reasons for paediatric emergency room visits and hospital admissions in the United States of America. OBJECTIVE: To assess the impact of CHD on outcomes of children hospitalised for acute asthma exacerbation. METHODS: Children primarily admitted for acute asthma exacerbation were sampled from 2006, 2009, 2012, and 2016 kid inpatient database of the Healthcare Cost and Utilization Project using ICD codes. The disease outcomes were compared between those with and without CHD using multivariate logistic regressions in Stata version 17. RESULTS: There were a total of 639,280 acute asthma exacerbation admissions, of which 5,907 (0.92%) had CHD. The mortality rate was 0.079% for patients without CHD and 0.72% for those with co-existing CHD. Children with CHD had higher odds of mortality (5.51, CI 3.40-8.93, p < 0.001), acute respiratory failure (2.84, CI 2.53-3.20; p < 0.001), need for invasive mechanical ventilation (4.58, CI 3.80-5.52; p < 0.001), acute kidney injury (adjusted odds ratio 3.03, CI 3.03-7.44; p < 0.001), and in-hospital cardiac arrest (adjusted odds ratio 4.52, CI 2.49-8.19; p < 0.001) when compared with those without CHD. The adjusted mean length of hospital stays (CI 2.91-3.91; p < 0.001) and hospital charges (95% CI $31060-$47747) among children with acute asthma exacerbation and CHD were significantly higher than in those without CHD. CONCLUSION AND SIGNIFICANCE: CHD is an independent predictor of mortality, more severe disease course, and higher hospital resource utilisation. Strategies that improve CHD care will likely improve the overall health outcomes of children with CHD hospitalised for acute asthma exacerbation.

Development of a Multispecies Double-Antigen Sandwich ELISA Using N and RBD Proteins to Detect Antibodies against SARS-CoV-2.

SARS-CoV-2 infects humans and a broad spectrum of animal species, such as pets, zoo animals, and nondomestic animals. Monitoring infection in animals is important in terms of the risk of interspecies transmission and the emergence of new viral variants. Economical, fast, efficient, and sensitive diagnostic tests are needed to analyze animal infection. Double-antigen sandwich ELISA has the advantage of being multispecies and can be used for detecting infections caused by pathogens that infect several animal hosts. This study aimed to develop a double-antigen sandwich ELISA using two SARS-CoV-2 proteins, N and RBD. We compared its performance, when using these proteins separately, with an indirect ELISA and with a surrogate virus neutralization test. Positive and negative controls from a cat population (n = 31) were evaluated to compare all of the tests. After confirming that double-antigen sandwich ELISA with both RBD and N proteins had the best performance (AUC= 88%), the cutoff was adjusted using positive and negative samples from cats, humans (n = 32) and guinea pigs (n = 3). The use of samples from tigers (n = 2) and rats (n = 51) showed good agreement with the results previously obtained using the microneutralization test. Additionally, a cohort of samples from dogs with unknown infection status was evaluated. These results show that using two SARS-CoV-2 proteins in the double-antigen sandwich ELISA increases its performance and turns it into a valuable assay with which to monitor previous infection caused by SARS-CoV-2 in different animal species.

A Retrospective Analysis of Porcine Circovirus Type 3 in Samples Collected from 2008 to 2021 in Mexico.

Porcine circovirus type 3 (PCV3) is a nonenveloped virus of the Circoviridae family. This virus has been identified in pigs of different ages and pigs with several clinical manifestations of the disease or even in apparently healthy pigs. While PCV3 was first reported in 2015, several retrospective studies have reported the virus before that year. The earliest report indicates that PCV3 has been circulated in swine farms since 1996. In this study, we evaluated the presence of PCV3 in samples collected in Mexico in 2008, 2015, 2020, and 2021. This study assessed PCV3 DNA by qPCR and antibodies against CAP protein by indirect ELISA. The results showed that PCV3 (DNA and anti-CAP antibodies) was detected in the samples collected from 2008 to 2021. The highest prevalence was in 2008 (100%), and the lowest was in 2015 (negative). Genetic analysis of ORF2 showed that the virus identified belonged to genotype a, as most of the viruses identified thus far. PCV3 was detected in samples from piglets with respiratory signs and growth retardation, sows with reproductive failure, or asymptomatic piglets and sows. Pigs with respiratory signs, growth retardation, or reproductive failure had a higher prevalence of antibodies and qPCR-positive samples. In conclusion, this study showed that PCV3 has been circulating in Mexico since 2008 and that PCV3 DNA and antibodies were more prevalent in samples from pigs with clinical manifestations of diseases.

19n01, a broadly neutralizing antibody against omicron BA.1, BA.2, BA.4/5, and other SARS-CoV-2 variants of concern.

This study reports the isolation and characterization of a human monoclonal antibody (mAb) called 19n01. This mAb was isolated by using single-cell RNAseq of B cells from donors infected with the ancestral strain. This mAb possesses a potent and broad capacity to bind and neutralize all previously circulating variants of concern (VOCs), including Omicron sublineages BA.1, BA.2, and BA.4/5. The pseudovirus neutralization assay revealed robust neutralization capacity against the G614 strain, BA.1, BA.2, and BA.4/5, with inhibitory concentration (IC50) values ranging from 0.0035 to 0.0164 µg/mL. The microneutralization assay using the G614 strain and VOCs demonstrated IC50 values of 0.013-0.267 µg/mL. Biophysical and structural analysis showed that 19n01 cross-competes with ACE2 binding to the receptor-binding domain (RBD) and the kinetic parameters confirmed the high affinity against the Omicron sublineages (KD of 61 and 30 nM for BA.2 and BA.4/5, respectively). These results suggest that the 19n01 is a remarkably potent and broadly reactive mAb.

Downregulation of miR-671-5p promotes IL-10 mRNA increase in porcine moDCs stimulated with the probiotic BB12.

BACKGROUND: Previous work showed that the microRNA (miRNA) miR-671-5p was upregulated in monocyte-derived dendritic cells (moDCs) stimulated with Bifidobacterium animalis subsp. lactis BB12 (BB12) with no increase in IL-10 after six hours of stimulation. In this work, we performed an in silico prediction of genes targeted by miR-671-5p and which are the terms and pathways involved with it. Also, miR-671-5p was transiently downregulated to assess its effect on IL-10 regulation. METHODS AND RESULTS: First, we performed a Gene Ontology enrichment analysis to predict immune response terms and pathways involved with miR-671-5p. Some of the terms and pathways found were related to the immune response promoted by the probiotic, as the terms "negative regulation of the inflammatory response to an antigenic stimulus" and "cancer" were highlighted. Then, to assess the role of miR-671-5p in IL-10 regulation, moDCs were derived from porcine peripheral blood and later transfected with miR-671-5p antisense oligonucleotide (ASO). Flow cytometry was employed to evaluate the transfection efficiency. Then, the moDCs were stimulated with BB12, and the expression of IL-10 was assessed by RT-qPCR and ELISA. An increase in IL-10 transcript in miR-671-5p-ASO-transfected moDCs stimulated with BB12 was observed compared with moDCs stimulated with BB12 but not transfected. These results suggest the participation of miR-671-5p as a negative regulator of IL-10. CONCLUSION: These findings suggest that miR-671-5p participates in the downregulation of IL-10, as previously predicted in silico by our work group. miR-671-5p could play an essential role in the immunomodulation promoted by the probiotic BB12.

Seroprevalence of SARS-CoV-2 in Mexican Health Care Workers after Two Years of the Pandemic: The Picture of an Ophthalmic Medical Centre.

OBJECTIVE: In this study, we investigated the impact of the SARS-CoV-2 vaccination on seroprevalence in a cohort of healthcare workers (HCW) at an ophthalmic medical center. METHODS: IgG antibodies against the N, S1, and S2 antigens of SARS-CoV-2 as well as their serum neutralizing activity were determined. RESULTS: In the present study, we observed that 98.4% of HCW were seropositive for S1/S2 proteins of SARS-CoV-2 due to the national vaccination program. Interestingly, 78.4% of the participants had anti-N protein antibodies, suggesting previous COVID-19 infection. We also evaluated the neutralizing antibodies and found that the mean value was high (90.7%). CONCLUSION: These results indicate that our HCWs cohort presented a robust hybrid humoral response owing to the massive national vaccination program and natural infections.

Antigen Targeting of Porcine Skin DEC205+ Dendritic Cells.

Dendritic cell (DC) targeting by DEC205+ cells effectively promotes the internalization of antigens that may trigger a specific immune response. In this study, we evaluated the ability of a recombinant antibody, anti-DEC205 (rAb ZH9F7), to trigger cellular endocytosis in subpopulations of DCs and targeted cells after intradermal injection and subsequent migration toward lymph nodes. Furthermore, the cellular immune response was evaluated in pigs after intradermal application of the antigenized rAb ZH9F7 combined with porcine circovirus type 2 cap antigen (rAb ZH9F7-Cap). We demonstrated that rAb ZH9F7 recognized conventional type 1 and 2 DCs from the blood and skin and monocytes. It promoted receptor-mediated endocytosis and migration of cDCs and moDCs toward regional lymph nodes. Intradermal application of rAb ZH9F7-Cap induced a higher frequency of IFN-γ-secreting CD4+CD8+ T lymphocytes and antibodies against Cap protein than that in the control group. In conclusion, the rAb ZH9F7-Cap system promoted the target of skin cDC1 and cDC2, provoking migration to the regional lymph nodes and inducing a Th1 response, as evidenced by the proliferation of double-positive CD4+CD8+ T cells, which correlates with an enhanced ability to target the cDC1 subset both in vitro and in vivo.

Analysis of IgG, IgA and IgM antibodies against SARS-CoV-2 spike protein S1 in convalescent and vaccinated patients with the Pfizer-BioNTech and CanSinoBio vaccines.

The SARS-CoV-2 virus was detected for the first time in December 2019 in Wuhan, China. Currently, this virus has spread around the world, and new variants have emerged. This new pandemic virus provoked the rapid development of diagnostic tools, therapies and vaccines to control this new disease called COVID-19. Antibody detection by ELISA has been broadly used to recognize the number of persons infected with this virus or to evaluate the response of vaccinated individuals. As the pandemic spread, new questions arose, such as the prevalence of antibodies after natural infection and the response induced by the different vaccines. In Mexico, as in other countries, mRNA and viral-vectored vaccines have been widely used among the population. In this work, we developed an indirect ELISA test to evaluate S1 antibodies in convalescent and vaccinated individuals. By using this test, we showed that IgG antibodies against the S1 protein of SARS-CoV-2 were detected up to 42 weeks after the onset of the symptoms, in contrast to IgA and IgM, which decreased 14 weeks after the onset of symptoms. The evaluation of the antibody response in individuals vaccinated with Pfizer-BioNTech and CanSinoBio vaccines showed no differences 2 weeks after vaccination. However, after completing the two doses of Pfizer-BioNTech and the one dose of CanSinoBio, a significantly higher response of IgG antibodies was observed in persons vaccinated with Pfizer-BioNTech than in those vaccinated with CanSinoBio. In conclusion, these results confirm that after natural infection with SARS-CoV-2, it is possible to detect antibodies for up to 10 months. Additionally, our results showed that one dose of the CanSinoBio vaccine induces a lower response of IgG antibodies than that induced by the complete scheme of the Pfizer-BioNTech vaccine.

Physician Prescribing and Referral Patterns in Children with Cerebral Visual Impairment.

SIGNIFICANCE: Cerebral visual impairment (CVI) is the leading cause of visual impairment in the developed world. Providing children with CVI with the appropriate treatment ensures the best possible visual outcome and potentially improves quality of life. PURPOSE: The purpose of this study was to determine physician prescribing and visual rehabilitation referral patterns in children with CVI. METHODS: A retrospective chart review was completed on children with CVI examined at Cincinnati Children's Hospital Medical Center from January 1, 2008, to March 1, 2018. Significant refractive error warranting correction was determined using the American Academy of Ophthalmology Preferred Guidelines and the American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee Guidelines. The CVI Range was used as a surrogate to categorize CVI severity. RESULTS: A total of 194 children were included. Sixty-eight (35%) had refractive error warranting correction and were prescribed glasses (group RC), 99 (51%) did not have refractive error warranting correction and were not prescribed glasses (group NRNC), 20 (10%) had refractive error warranting correction but were not prescribed glasses (group RNC), and 7 (4%) did not have refractive error warranting correction but were prescribed glasses (group NRC). There was greater than one-line Snellen equivalent difference between group RC (20/156) and group RNC (20/221). There was greater than six-line Snellen equivalent difference between group NRNC (20/149) and group NRC (20/35). Mean CVI Range score 2 values for each group were 5.9, 4.6, 4.8, and 7.1. CONCLUSIONS: Children with less severe CVI were less likely to have significant refractive error but given glasses. Despite significant refractive error, children with more severe CVI were not prescribed glasses. Children with very low visual function were not prescribed glasses as frequently, possibly limiting their visual rehabilitation. Providers should ensure that all children with CVI are correctly prescribed glasses to provide the best possible visual outcome.

Production of a full chimeric mouse x pig anti-porcine DEC205 receptor recombinant antibody.

Recombinant hybrid antibodies are commonly used in antigen-targeting assays to reduce the immunogenic potential associated with using classic mouse antibodies in other species. The DEC205 receptor has become an attractive target due to its effectiveness in activating the immune response and is considered a promising vaccination target. The aim of this study was to produce a fully chimeric mouse x pig anti-porcine DEC205 recombinant antibody (rAb). Based on a mouse anti-porcine DEC205 monoclonal antibody (mAb), we designed and expressed a chimeric mouse x pig rAb using the Expi293f system. The resulting rAb maintained the recognition capacity of the native mouse mAb toward the porcine DEC205 receptor, as evidenced by western blot analysis. By using flow cytometry, we evaluated the ability of the rAb to recognize DEC205+ dendritic cells. In conclusion, the chimeric mouse x pig anti-DEC205 rAb can be used in antigen-targeting assays as a vaccination strategy in pigs.

Systemic and ocular manifestations of a patient with mosaic ARID1A-associated Coffin-Siris syndrome and review of select mosaic conditions with ophthalmic manifestations.

Mosaic genetic mutations may be somatic, germline, or "gonosomal" and have the potential to cause genetic syndromes, disorders, or malformations. Mutations can occur at any point in embryonic development and the timing determines the extent of distribution of the mutation throughout the body and different tissue types. The eye and visual pathway offer a unique opportunity to study somatic and gonosomal mosaic mutations as the eye consists of tissues derived from all three germ layers allowing disease pathology to be assessed with noninvasive imaging. In this review, we describe systemic and ocular manifestations in a child with mosaic Coffin-Siris syndrome. The patient presented with a significant medical history of accommodative esotropia and hyperopia, macrocephaly, polydactyly, global developmental delay, hypotonia, ureteropelvic junction (UPJ) obstruction, and brain MRI abnormalities. The ophthalmic findings in this patient were nonspecific, however, they are consistent with ocular manifestations reported in other patients with Coffin-Siris syndrome. We also review ophthalmic findings of select mosaic chromosomal and single-gene disorders. Ophthalmic assessment alongside clinical genetic testing may play an important role in diagnosis of genetic syndromes as well as understanding disease pathology, particularly when mosaicism plays a role.

Allergen Immunotherapy in children with respiratory allergic diseases.

Allergen immunotherapy (AIT) is a well-established treatment for allergic respiratory diseases. It represents a cornerstone in the clinical management of allergic children since it is the only curative option to date able to modify the natural history of Ig-E mediated allergic diseases. Through a well-defined immunologic mechanism, AIT promotes regulatory T cells and cuts down the immune response induced by allergens. According to current guidelines based on up-to-date evidence, AIT should be offered to children with moderate-severe allergic rhinitis and/or controlled asthma starting from 5 years of age, further to an adequate risk-benefit assessment which includes patient's adherence to the treatment and a proper selection of the right product. Younger age and mild disease could be considered based on an individual evaluation. Both subcutaneous (SCIT) and sublingual (SLIT) routes of administration have a good efficacy and safety profile with safer outcomes for SLIT compared to SCIT. Only standardized products with documented evidence of clinical efficacy should be used. Although AIT is used worldwide, there are still gaps and limitations, including the lack of reliable biomarkers predictive of the clinical outcome. Novel adjuvants are currently under investigations to boost the strength and efficiency of the immune response, as well as new formulations with better efficacy and better patient's adherence to the treatment. Herein, we aim to provide an overview of current key evidence with major regard to clinical practice as well as knowledge gaps and future research needs in the context of AIT in children with respiratory allergic diseases.

Molecular characterization and expression analysis of the chicken-type and goose-type lysozymes from totoaba (Totoaba macdonaldi).

Lysozymes play a key role in innate immune response to bacterial pathogens, catalyzing the hydrolysis of the peptidoglycan layer of bacterial cell walls. In this study, the genes encoding the c-type (TmLyzc) and g-type (TmLyzg) lysozymes from Totoaba macdonaldi were cloned and characterized. The cDNA sequences of TmLyzg and TmLyzc were 582 and 432 bp, encoding polypeptides of 193 and 143 amino acids, respectively. Amino acid sequences of these lysozymes shared high identity (60-90%) with their counterparts of other teleosts and showed conserved functional-structural signatures of the lysozyme superfamily. Phylogenetic analysis indicated a close relationship with their vertebrate homologues but distinct evolutionary paths for each lysozyme. Expression analysis by qRT-PCR revealed that TmLyzc was expressed in stomach and pyloric caeca, while TmLyzg was highly expressed in stomach and heart. These results suggest that both lysozymes play important roles in defense of totoaba against bacterial infections or as digestive enzyme.

A Pediatric Case of Sirolimus-Associated Pneumonitis After Kidney Transplantation.

Sirolimus is an immunosuppressive medication often used in solid organ transplantation. It has been associated with severe side effects, including pulmonary toxicity. In adult patients, a single center study found that 14% of those treated with sirolimus developed pulmonary pneumonitis; however, the incidence in the pediatric population is not known. Most reports in adult patients indicate that elevated drug concentrations and a prolonged duration of use are associated with pulmonary toxicity. We report a case of a 17-year-old male kidney transplant recipient who developed rapid-onset respiratory failure, necessitating mechanical ventilation and acute renal replacement therapy for ultrafiltration secondary to sirolimus-induced pneumonitis. He had been treated for acute rejection with corticosteroids 17 days prior to the development of pneumonitis. His symptoms developed within 1 week of initiation of sirolimus and with a serum concentration of 1.1 ng/mL. Sirolimus was discontinued, and, following aggressive diuresis and ventilatory support, his respiratory status returned to baseline. Sirolimus-induced pneumonitis is an important diagnosis to be considered in any transplant recipient receiving sirolimus with new onset fever, cough, or dyspnea without an identifiable source, especially if there is a preceding history of treatment with high-dose corticosteroids.

Uso de la medicina no convencional por pacientes diabéticos / Use of non-conventional medicine for patients with diabetes

RESUMEN Fundamento: el interés en las terapias alternativas utilizadas por las personas con diferentes enfermedades ha crecido de manera considerable en los últimos tiempos. Se estima que un gran porcentaje de las personas en regiones menos desarrolladas emplean la medicina tradicional con plantas para el cuidado de la salud. Objetivo: determinar el uso de medicina no convencional en pacientes diabéticos. Métodos: se realizó un estudio observacional descriptivo de corte transversal, dirigido a pacientes que pertenecen al club de diabéticos del Centro Clínico Quirúrgico Hospital del Día Santo Domingo, Ecuador, desde el 5 de junio hasta el 31 de julio de 2018. La población universo estuvo compuesta de 1 300 personas. De acuerdo a los criterios de inclusión y exclusión. Se obtuvo una muestra de 100 personas a las cuales se les aplicó la encuesta como instrumento de investigación. Resultados: se identificó que el sexo femenino fue el que más predominó. De esta población la mayor parte utiliza la medicina no convencional por costumbres familiares. La fitoterapia fue la más conocida y más empleada por los pacientes diabéticos. Las plantas medicinales de mayor uso fueron: Insulina (Costus igneus) y la Zarzgoza (Glycyrrhiza glabra). Conclusiones: se constató que la población diabética hace uso de la medicina no convencional para el tratamiento de su enfermedad, la misma en pocas ocasiones es recomendada por el médico, aunque no se notificaron efectos adversos algunos, la fitoterapia y la acupuntura son las más utilizadas.

ABSTRACT Background: in recent years, the use of alternative medicine as a treatment for different diseases has increased. It is considered that a great percentage of people belonging to less developed communities use alternative medicine for health care. Objective: to determine the use of non-conventional treatment in diabetic patients. Methods: an observational, cross-sectional study was used to a group of patients belonging to a diabetic club at Centro Clínico Quirúrgico Hospital del Día Santo Domingo from June 5th to July 31st, 2018. The population was composed of 1300 persons. Survey was used as research instrument and was applied to the sample of 100 persons. Results: there was predominance of the female gender. The majority used non-conventional medication for family practices. Phytotherapy was identified as the most employed and known alternative therapy used by diabetic patients. The medicinal plants used primarily was Insulina (Costus igneus) and Zarzgoza (Glycyrrhizaglabra). Conclusions: it was found that the diabetic population used non-conventional medicine for the treatment of illness and in some occasions, it was recommended by the physician although no adverse effects were reported. Phytotherapy and acupuncture were the most used procedures.

A class of residuals for outlier identification in zero adjusted regression models.

Zero adjusted regression models are used to fit variables that are discrete at zero and continuous at some interval of the positive real numbers. Diagnostic analysis in these models is usually performed using the randomized quantile residual, which is useful for checking the overall adequacy of a zero adjusted regression model. However, it may fail to identify some outliers. In this work, we introduce a class of residuals for outlier identification in zero adjusted regression models. Monte Carlo simulation studies and two applications suggest that one of the residuals of the class introduced here has good properties and detects outliers that are not identified by the randomized quantile residual.

Evaluation of a Recombinant Mouse X Pig Chimeric Anti-Porcine DEC205 Antibody Fused with Structural and Nonstructural Peptides of PRRS Virus.

Activation of the immune system using antigen targeting to the dendritic cell receptor DEC205 presents great potential in the field of vaccination. The objective of this work was to evaluate the immunogenicity and protectiveness of a recombinant mouse x pig chimeric antibody fused with peptides of structural and nonstructural proteins of porcine respiratory and reproductive syndrome virus (PRRSV) directed to DEC205+ cells. Priming and booster immunizations were performed three weeks apart and administered intradermally in the neck area. All pigs were challenged with PRRSV two weeks after the booster immunization. Immunogenicity was evaluated by assessing the presence of antibodies anti-PRRSV, the response of IFN-γ-producing CD4+ cells, and the proliferation of cells. Protection was determined by assessing the viral load in the blood, lungs, and tonsils using qRT-PCR. The results showed that the vaccine exhibited immunogenicity but conferred limited protection. The vaccine group had a lower viral load in the tonsils and a significantly higher production of antibodies anti-PRRSV than the control group (p < 0.05); the vaccine group also produced more CD4+IFN-γ+ cells in response to peptides from the M and Nsp2 proteins. In conclusion, this antigenized recombinant mouse x pig chimeric antibody had immunogenic properties that could be enhanced to improve the level of protection and vaccine efficiency.