A randomized comparative-effectiveness study of two enhanced prenatal care models for low-income pregnant people: Engaging Mothers & Babies; Reimagining Antenatal Care for Everyone (EMBRACE).

BACKGROUND: Improving perinatal mental health and care experiences and preventing adverse maternal and infant outcomes are essential prenatal care components, yet existing services often miss the mark, particularly for low-income populations. An enhanced group prenatal care program, "Glow! Group Prenatal Care and Support," was developed in California's Central Valley in response to poor perinatal mental health, disrespectful care experiences, and high rates of adverse birth outcomes among families with low incomes. METHODS: Engaging Mothers & Babies; Reimagining Antenatal Care for Everyone (EMBRACE) is a pragmatic, two-arm, randomized, comparative-effectiveness study designed to assess depression (primary outcome), the experience of care (secondary outcome), and preterm birth (exploratory outcome) among Medi-Cal (California's Medicaid program)-eligible pregnant and birthing people, comparing those assigned to Glow! Group Prenatal Care and Support (Glow/GC) with those assigned to enhanced, individual prenatal care through the California Department of Public Health's Comprehensive Perinatal Services Program (CPSP/IC). Participating clinical practices offer the two comparators, alternating between comparators every 6 weeks, with the starting comparator randomized at the practice level. Participant-reported outcomes are assessed through interviewer-administered surveys at study entry, during the participant's third trimester, and at 3 months postpartum; preterm birth and other clinical outcomes are abstracted from labor and delivery records. Patient care experiences are further assessed in qualitative interviews. The protocol complies with the Standard Protocol Items for Randomized Trials. CONCLUSIONS: This comparative-effectiveness study will be used to determine which of two forms of enhanced prenatal care is more effective, informing future decisions regarding their use. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04154423.

Nutritional Support System (NSS) as a New Therapeutic Strategy for Cerebral Palsy.

Cerebral palsy (CP) is part of a group of nonprogressive motor disorders. The disease affects movement and posture and constitutes the most frequent cause of motor disability in childhood. CP is characterized by spasticity, reflecting lesions in the pyramidal pathway. Treatment is currently focused on physical rehabilitation, and the annual progression of the disease is 2-3%. About 60% of these patients present severe degrees of malnutrition associated with dysphagia, gastrointestinal abnormalities, malabsorption, increased metabolism, and depression. These alterations promote sarcopenia functional dependence and affect the quality of life and delay the evolution of motor skills. Currently, there is evidence that the supplementation of several nutrients, dietary correction, and probiotics can improve neurological response by stimulating neuroplasticity, neuroregeneration, neurogenesis, and myelination. This therapeutic strategy could shorten the response period to treatment and increase both gross and fine motor skills. The interaction of nutrients and functional foods integrating a Nutritional Support System (NSS) has shown greater efficiency in neurological stimulation than when nutrients are supplied separately. The most studied elements in the neurological response are glutamine, arginine, zinc, selenium, cholecalciferol, nicotinic acid, thiamine, pyridoxine, folate, cobalamin, Spirulina, omega-3 fatty acids, ascorbic acid, glycine, tryptophan, and probiotics. The NSS represents a therapeutic alternative that will restore neurological function in patients with spasticity and pyramidal pathway lesions, both characteristics of patients with CP.

The Impact of the COVID-19 Pandemic in Postoperative Neurosurgical Infections at a Reference Center in México.

The COVID-19 pandemic has had a major global impact on the treatment of hospitalized surgical patients. Our study retrospectively evaluates the impact of the COVID-19 pandemic at a neurosurgical reference center in Mexico City. We compared the number of neurosurgeries, the rate and type of postoperative infections, the causative microorganisms and in-hospital mortality rates in a 4-year period, from the pre-pandemic year 2019 until 2022. A total of 4150 neurosurgical procedures were registered. In 2020 the total number of surgeries was reduced by 36% compared to 2019 OR = 0.689 (95% CI 0.566-0.834) p ≤ 0.001, transnasal/trans sphenoidal pituitary resections decreased by 53%, and spinal surgeries by 52%. The rate of neurosurgical infections increased from 3.5% in 2019 to 5.6% in 2020 (p = 0.002). Regarding the microorganisms that caused infections, gram positive cocci accounted for 43.5% of isolates, Klebsiella spp. and Pseudomonas spp. caused one third of the infections. No significant differences were found for in-hospital mortality nor patterns of resistance to antibiotics. The number of surgeries increased in the last two years, although the infection rate has returned to pre-pandemic levels. We observed a lower impact from subsequent waves of COVID-19 and despite an increase in the number of surgeries, the surgeries have not amounted to the full pre-pandemic levels.

Integration of Multiple Interferometers in Highly Multiplexed Diagnostic KITs to Evaluate Several Biomarkers of COVID-19 in Serum.

In the present work, highly multiplexed diagnostic KITs based on an Interferometric Optical Detection Method (IODM) were developed to evaluate six Coronavirus Disease 2019 (COVID-19)-related biomarkers. These biomarkers of COVID-19 were evaluated in 74 serum samples from severe, moderate, and mild patients with positive polymerase chain reaction (PCR), collected at the end of March 2020 in the Hospital Clínico San Carlos, in Madrid (Spain). The developed multiplexed diagnostic KITs were biofunctionalized to simultaneously measure different types of specific biomarkers involved in COVID-19. Thus, the serum samples were investigated by measuring the total specific Immunoglobulins (sIgT), specific Immunoglobulins G (sIgG), specific Immunoglobulins M (sIgM), specific Immunoglobulins A (sIgA), all of them against SARS-CoV-2, together with two biomarkers involved in inflammatory disorders, Ferritin (FER) and C Reactive Protein (CRP). To assess the results, a Multiple Linear Regression Model (MLRM) was carried out to study the influence of IgGs, IgMs, IgAs, FER, and CRP against the total sIgTs in these serum samples with a goodness of fit of 73.01% (Adjusted R-Squared).

Alt a 1 Promotes Allergic Asthma In Vivo Through TLR4-Alveolar Macrophages.

The mold Alternaria alternata is one of the main sources of asthma exacerbation, being its major allergen, Alt a 1, indispensable for its development. The main objective of this work was to answer two main questions: 1) can Alt a 1 by itself (without any other context) induce an asthmatic profile in vivo?; and 2) Which molecular mechanisms take place during this phenomenon? To answer both questions, we have developed a mouse model of allergic asthma using only Alt a 1 for mice sensitization. We also made use of in-vitro cellular models and computational studies to support some aspects of our hypothesis. Our results showed that Alt a 1 can induce an asthmatic phenotype, promoting tissue remodeling and infiltration of CD45+ cells, especially eosinophils and macrophages (Siglec F+ and F4/80+). Also, we have found that Alt a 1 sensitization is mediated by the TLR4-macrophage axis.

Lipid Ligands and Allergenic LTPs: Redefining the Paradigm of the Protein-Centered Vision in Allergy.

Lipid Transfer Proteins (LTPs) have been described as one of the most prevalent and cross-reactive allergen families in the general population. They are widely distributed among the plant kingdom, as well as in different plant organs ranging from pollen to fruits. Thus, they can initiate allergic reactions with very different outcomes, such as asthma and food allergy. Several mouse models have been developed to unravel the mechanisms that lead LTPs to promote such strong sensitization patterns. Interestingly, the union of certain ligands can strengthen the allergenic capacity of LTPs, suggesting that not only is the protein relevant in the sensitization process, but also the ligands that LTPs carry in their cavity. In fact, different LTPs with pro-allergenic capacity have been shown to transport similar ligands, thus positioning lipids in a central role during the first stages of the allergic response. Here, we offer the latest advances in the use of experimental animals to study the topic, remarking differences among them and providing future researchers a tool to choose the most suitable model to achieve their goals. Also, recent results derived from metabolomic studies in humans are included, highlighting how allergic diseases alter the lipidic metabolism toward a pathogenic state in the individual. Altogether, this review offers a comprehensive body of work that sums up the background evidence supporting the role of lipids as modulators of allergic diseases. Studying the role of lipids during allergic sensitization might broaden our understanding of the molecular events leading to tolerance breakdown in the epithelium, thus helping us to understand how allergy is initiated and established in the individuals.

NLRP3 priming due to skin damage precedes LTP allergic sensitization in a mouse model.

Allergic sensitization is initiated by protein and epithelia interaction, although the molecular mechanisms leading this encounter toward an allergic phenotype remain unknown. Here, we apply the two-hit hypothesis of inflammatory diseases to the study of food allergy sensitization. First, we studied the effects of long-term depilation in mice by analyzing samples at different time points. Several weeks of depilation were needed until clear immunological changes were evidenced, starting with upregulation of NLRP3 protein levels, which was followed by overexpression of Il1b and Il18 transcripts. Secondly, we assessed the effects of allergen addition (in this case, Pru p 3 in complex with its natural lipid ligand) over depilated skin. Systemic sensitization was evaluated by intraperitoneal provocation with Pru p 3 and measure of body temperature. Anaphylaxis was achieved, but only in mice sensitized with Prup3_complex and not treated with the NLRP3 inhibitor MCC950, thus demonstrating the importance of both hits (depilation + allergen addition) in the consecution of the allergic phenotype. In addition, allergen encounter (but not depilation) promoted skin remodeling, as well as CD45+ infiltration not only in the sensitized area (the skin), but across several mucosal tissues (skin, lungs, and gut), furtherly validating the systemization of the response. Finally, a low-scale study with human ILC2s is reported, where we demonstrate that Prup3_complex can induce their phenotype switch (↑CD86, ↑S1P1) when cultured in vitro, although more data is needed to understand the implications of these changes in food allergy development.

Plant non-specific lipid transfer proteins: An overview.

Plant non-specific lipid transfer proteins (nsLTPs) are usually defined as small, basic proteins, with a wide distribution in all orders of higher plants. Structurally, nsLTPs contain a conserved motif of eight cysteines, linked by four disulphide bonds, and a hydrophobic cavity in which the ligand is housed. This structure confers stability and enhances the ability to bind and transport a variety of hydrophobic molecules. Their highly conserved structural resemblance but low sequence identity reflects the wide variety of ligands they can carry, as well as the broad biological functions to which they are linked to, such as membrane stabilization, cell wall organization and signal transduction. In addition, they have also been described as essential in resistance to biotic and abiotic stresses, plant growth and development, seed development, and germination. Hence, there is growing interest in this family of proteins for their critical roles in plant development and for the many unresolved questions that need to be clarified, regarding their subcellular localization, transfer capacity, expression profile, biological function, and evolution.

Alternaria as an Inducer of Allergic Sensitization.

Alternaria alternata is a saprophytic mold whose spores are disseminated in warm dry air, the typical weather of the Mediterranean climate region (from 30° to 45°), with a peak during the late summer and early autumn. Alternaria spores are known to be biological contaminants and a potent source of aeroallergens. One consequence of human exposure to Alternaria is an increased risk of developing asthma, with Alt a 1 as its main elicitor and a marker of primary sensitization. Although the action mechanism needs further investigation, a key role of the epithelium in cytokine production, TLR-activated alveolar macrophages and innate lymphoid cells in the adaptive response was demonstrated. Furthermore, sensitization to A. alternata seems to be a trigger for the development of co-sensitization to other allergen sources and may act as an exacerbator of symptoms and an elicitor of food allergies. The prevalence of A. alternata allergy is increasing and has led to expanding research on the role of this fungal species in the induction of IgE-mediated respiratory diseases. Indeed, recent research has allowed new perspectives to be considered in the assessment of exposure and diagnosis of fungi-induced allergies, although more studies are needed for the standardization of immunotherapy formulations.

The key to the allergenicity of lipid transfer protein (LTP) ligands: A structural characterization.

Plant lipid transfer proteins are a large family that can be found in all land plants. They have a hydrophobic cavity that allows them to harbor lipids and facilitates their traffic between membranes. However, in humans, this plant protein family is responsible for the main food allergies in the Mediterranean area. Nevertheless, not only the protein itself but also its ligand is relevant for allergic sensitization. The main aim of the present work is to analyse the natural ligands carried by four allergenic LTPs (Tri a 14, Art v 3, Par j 2, and Ole e 7), compared with the previously identified ligand of Pru p 3 (CPT-PHS ligand), and clarify their role within the immunological reactions. Results showed that the ligands of the LTPs studied shared a chemical identity, in which the presence of a polar head was essential to the protein-ligand binding. This ligand was transported through a skin cellular model, and phosphorylated phytosphingosine could be detected as result of cell metabolism. Since sphingosine kinase 1 was overexpressed in keratinocytes incubated with the LTP-ligand complex, this enzyme might be responsible for the phosphorylation of the phytosphingosine fraction of the CPT-PHS ligand. This way, phytosphingosine-1-phosphate could be mimicking the role of the human inflammatory mediator sphingosine-1-phosphate, explaining why LTPs are associated with more severe allergic responses. In conclusion, this work contributes to the understanding of the chemical nature and behavior of lipid ligands carried by allergens, which would help to gain insight into their role during allergic sensitization.

Synthesis and Antimycobacterial Activity of 2,5-Disubstituted and 1,2,5-Trisubstituted Benzimidazoles.

The appearance of drug-resistant strains of Mycobacterium tuberculosis and the dramatic increase in infection rates worldwide evidences the urgency of developing new and effective compounds for treating tuberculosis. Benzimidazoles represent one possible source of new compounds given that antimycobacterial activity has already been documented for some derivatives, such as those bearing electron-withdrawing groups. The aim of this study was to synthesize two series of benzimidazoles, di- and trisubstituted derivatives, and evaluate their antimycobacterial activity. Accordingly, 5a and 5b were synthesized from hydroxymoyl halides 3a and 3b, and nitro-substituted o-phenylenediamine 4. Compound 11 was synthesized from an aromatic nitro compound, 4-chloro-1,2-phenylenediamine 9, mixed with 3-nitrobenzaldehyde 10, and bentonite clay. Although the synthesis of 11 has already been reported, its antimycobacterial activity is herein examined for the first time. 1,2,5-trisubstituted benzimidazoles 7a, 7b, and 12 were obtained from N-alkylation of 5a, 5b, and 11. All benzimidazole derivatives were characterized by FT-IR, NMR, and HR-MS, and then screened for their in vitro antimycobacterial effect against the M. tuberculosis H37Rv strain. The N-alkylated molecules (7a, 7b, and 12) generated very limited in vitro inhibition of mycobacterial growth. The benzimidazoles (5a, 5b, and 11) showed in vitro potency against mycobacteria, reflected in minimal inhibitory concentration (MIC) values in the range of 6.25-25 µg/mL. Consequently, only the 2,5-disubstituted benzimidazoles were assessed for biological activity on mouse macrophages infected with M. tuberculosis. A good effect was found for the three compounds. The cytotoxicity assay revealed very low toxicity for all the test compounds against the macrophage cell line. According to the docking study, 2,5-disubstituted benzimidazoles exhibit high affinity for an interdomain cleft that plays a key role in the GTP-dependent polymerization of the filamentous temperature-sensitive Z (FtsZ) protein. The ability of different benzimidazoles to impede FtsZ polymerization is reportedly related to their antimycobacterial activity. On the other hand, the 1,2,5-trisubstituted benzimidazoles docked to the N-terminal of the protein, close to the GTP binding domain, and did not show strong binding energies. Overall, 5a, 5b, and 11 proved to be good candidates for in vivo testing to determine their potential for treating tuberculosis.

Structural and functional characterization of three Type B and C chloramphenicol acetyltransferases from Vibrio species.

Chloramphenicol acetyltransferases (CATs) were among the first antibiotic resistance enzymes identified and have long been studied as model enzymes for examining plasmid-mediated antibiotic resistance. These enzymes acetylate the antibiotic chloramphenicol, which renders it incapable of inhibiting bacterial protein synthesis. CATs can be classified into different types: Type A CATs are known to be important for antibiotic resistance to chloramphenicol and fusidic acid. Type B CATs are often called xenobiotic acetyltransferases and adopt a similar structural fold to streptogramin acetyltransferases, which are known to be critical for streptogramin antibiotic resistance. Type C CATs have recently been identified and can also acetylate chloramphenicol, but their roles in antibiotic resistance are largely unknown. Here, we structurally and kinetically characterized three Vibrio CAT proteins from a nonpathogenic species (Aliivibrio fisheri) and two important human pathogens (Vibrio cholerae and Vibrio vulnificus). We found all three proteins, including one in a superintegron (V. cholerae), acetylated chloramphenicol, but did not acetylate aminoglycosides or dalfopristin. We also determined the 3D crystal structures of these CATs alone and in complex with crystal violet and taurocholate. These compounds are known inhibitors of Type A CATs, but have not been explored in Type B and Type C CATs. Based on sequence, structure, and kinetic analysis, we concluded that the V. cholerae and V. vulnificus CATs belong to the Type B class and the A. fisheri CAT belongs to the Type C class. Ultimately, our results provide a framework for studying the evolution of antibiotic resistance gene acquisition and chloramphenicol acetylation in Vibrio and other species.

Interaction of Alt a 1 with SLC22A17 in the airway mucosa.

BACKGROUND: Despite all the efforts made up to now, the reasons that facilitate a protein becoming an allergen have not been elucidated yet. Alt a 1 protein is the major fungal allergen responsible for chronic asthma, but little is known about its immunological activity. Our main purpose was to investigate the ligand-dependent interactions of Alt a 1 in the human airway epithelium. METHODS: Alt a 1 with and without its ligand (holo- and apo- forms) was incubated with the pulmonary epithelial monolayer model, Calu-3 cells. Allergen transport and cytokine production were measured. Pull-down and immunofluorescence assays were employed to identify the receptor of Alt a 1 using the epithelial cell model and mouse tissues. Receptor-allergen-ligand interactions were analyzed by computational modeling. RESULTS: The holo-form could activate human monocytes, PBMCs, and polarized airway epithelial (Calu-3) cell lines. The allergen was also transported through the monolayer, without any alteration of the epithelial integrity (TEER). Alt a 1 also induced the production of proinflammatory IL8 and specific epithelial cytokines (IL33 and IL25) by Calu-3 cells. The interaction between epithelial cells and holo-Alt a 1 was found to be mediated by the SLC22A17 receptor, and its recognition of Alt a 1 was explained in structural terms. CONCLUSIONS: Our findings identified the Alt a 1 ligand as a central player in the interaction of the allergen with airway mucosa, shedding light into its potential role in the immunological response, while unveiling its potential as a new target for therapy intervention.

Determinación de la frecuencia de PNUs en una población heterogénea cerrada y su utilidad como marcadores para estudios de asociación genética en casos de labio y paladar hendido no sindrómico / Determination of frequency of SNP's in a population of mixed genetic origin and its use as genetic markers for association studies in cases of not syndromic cleft lip and palate

RESUMEN El labio y paladar hendido es una de las patologías congénitas con mayor prevalencia en el mundo. En el presente trabajo se hace un análisis de 12 PNU localizados en las secuencias genómicas de ABCA4, BMP4, MSX1, SUMO1, VAX1 y IRF6, bajo una perspectiva epidemiológica, de genética molecular, genómica y de genética de poblaciones; todo lo anterior aplicado a una población de Querétaro, México, de origen genético mixto. Material y métodos: Se realizó un estudio observacional, analítico y descriptivo a partir de muestras de 93 tríadas (sujetos de estudio y sus padres). Al seleccionar PNU que puedan ser diferenciados por medio de RFLP esperamos distinguir entre marcadores genéticos que: 1) cumplan con la ecuación de equilibrio de Hardy-Weinberg y 2) validarlos como potenciales marcadores genéticos para ser empleados en estudios de asociación en poblaciones cerradas de origen genético mixto con labio y paladar hendido (Amealco, Querétaro, México). De ser así, posteriormente se plantea probar las frecuencias obtenidas con una población seleccionada genéticamente cerrada de Amealco, Querétaro. Resultados: Después de realizar el análisis RFLP de 12 PNU localizados en la secuencia de genes ABCA4, BMP4, MSX1, SUMO1, VAX1 y IRF6, hallamos el mismo alelo para PNU analizado, el cual se encuentra en el 100% de la población. Conclusión: De los 12 PNU analizados, en este reporte, por primera vez se menciona la frecuencia de cinco de ellos. Los restantes siete presentaron la misma frecuencia reportada en la literatura. Aunque los PNU seleccionados no fueron de utilidad como marcadores genéticos debido a que el mismo alelo está presente en el 100% de la población general. El hecho de haberlos encontrado en el mismo genotipo de todas las muestras indica que la población de la ciudad de Querétaro es genéticamente cerrada y con base en esto extremadamente útil para futuras validaciones de otros PNU como posibles marcadores genéticos.

ABSTRACT The cleft lip and palate is one of the congenital pathologies with greater prevalence in the world. In the present work, there is an analysis of 12 SNP's located in genomic sequences of ABCA4, BMP4, MSX1, SUMO1, VAX1 andIRF6, under an epidemiological perspective, molecular genetics, genomics and population genetics. All of the above applied to a population of Queretaro, Mexico, of mixed genetic origin. Material and methods: A study was conducted of observation, analytic and descriptive study with samples from 93 triads (study subjects and their parents). When you select SNP's that can be differentiated by RFLP (Restriction Fragment Length Polymorphism)we hope to distinguish between genetic markers that: 1)comply with the equation of balance of Hardy-Weiner and 2) Validate them as potential genetic markers to be used in studies of association in closed populations of genetic origin mixed with cleft lip and palate in Amealco, Queretaro, Mexico. If so subsequently raises test the frequencies obtained with a selected population genetically closed in Amealco, Queretaro. Results: After performing the RFLP analysis of 12 SNP's located in the sequence of genes ABCA4, BMP4, MSX1, SUMO1, VAX1 and IRF6, we find the same allele for SNP analyzed which is located in the 100% of the population. Conclusion: Of the 12 SNP's analyzed in this report, for the fi rst time 5 of them are mentioned their frequency. The rest of them had the same frequency reported in the literature. Although the SNP's selected were not useful as a genetic markers due to the same allele is present in 100% of the general population. The fact of having found in the same genotype of all samples indicates that the population of the city of Queretaro is genetically closed and on the basis of this extremely useful for future validations of other SNP's as potential genetic markers.

Hepatitis C seroprevalence in an at-risk population in the southwest Madrid region of Spain. / Seroprevalencia de hepatitis C en población con factores de riesgo del suroeste de la Comunidad de Madrid.

INTRODUCTION: The estimated seroprevalence of hepatitis C virus (HCV) in Spain is 1.7%, but is much higher in the at-risk population. The most efficient national screening strategy is unclear. AIMS: To estimate the prevalence of HCV among the at-risk population seen in primary care (PC), and to determine their epidemiological profile. MATERIALS AND METHODS: Cross-sectional descriptive prevalence study that included adult patients with risk factors for HCV infection seen in PC in the southwest Madrid region between 2010 and 2012. RESULTS: A total of 158 patients (men=51.3%), mean age 46 years (SD=16.6), were included. The most common risk factors were hypertransaminasaemia (44.3%) and major surgery (13.3%). Immigration, unsafe sexual practices, and tattoos or body piercing were more prevalent in patients younger than 45 years of age. Fifteen patients (9.5%) were positive for anti-HCV; 9 of these (5.7%) were HCV-ARN positive. Of the positive patients, 4 (44.4%) had significant fibrosis at diagnosis (F3-F4). Male patients had a higher rate of positive anti-HCV results (13.8 vs. 5.3%; P=.072), as did patients older than 45 years of age (12.8 vs. 6.3%; P=.167). Intravenous and intranasal drug use were associated with a higher rate of positive anti-HCV results (50 vs. 8.5%; P=.005 and 66.7 vs. 8.4%; P=.001, respectively). CONCLUSIONS: Patients with risk factors for HCV infection have high seroprevalence. Screening programmes must therefore be implemented to detect HCV infection in this population in PC.

[Discriminant analysis to predict the clinical diagnosis of primary immunodeficiencies: a preliminary report]. / Análisis discriminante para predecir el diagnóstico clínico de inmunodeficiencias primarias: reporte preliminar.

BACKGROUND: The features in a clinical history from a patient with suspected primary immunodeficiency (PID) direct the differential diagnosis through pattern recognition. PIDs are a heterogeneous group of more than 250 congenital diseases with increased susceptibility to infection, inflammation, autoimmunity, allergy and malignancy. Linear discriminant analysis (LDA) is a multivariate supervised classification method to sort objects of study into groups by finding linear combinations of a number of variables. OBJECTIVE: To identify the features that best explain membership of pediatric PID patients to a group of defect or disease. MATERIAL AND METHOD: An analytic cross-sectional study was done with a pre-existing database with clinical and laboratory records from 168 patients with PID, followed at the National Institute of Pediatrics during 1991-2012, it was used to build linear discriminant models that would explain membership of each patient to the different group defects and to the most prevalent PIDs in our registry. After a preliminary run only 30 features were included (4 demographic, 10 clinical, 10 laboratory, 6 germs), with which the training models were developed through a stepwise regression algorithm. We compared the automatic feature selection with a selection made by a human expert, and then assessed the diagnostic usefulness of the resulting models (sensitivity, specificity, prediction accuracy and kappa coefficient), with 95% confidence intervals. RESULTS: The models incorporated 6 to 14 features to explain membership of PID patients to the five most abundant defect groups (combined, antibody, well-defined, dysregulation and phagocytosis), and to the four most prevalent PID diseases (X-linked agammaglobulinemia, chronic granulomatous disease, common variable immunodeficiency and ataxiatelangiectasia). In practically all cases of feature selection the machine outperformed the human expert. Diagnosis prediction using the equations created had a global accuracy of 83 to 94%, with sensitivity of 60 to 100%, specificity of 83 to 95% and kappa coefficient of 0.37 to 0.76. CONCLUSIONS: In general, the selection of features has clinical plausibility, and the practical advantage of utilizing only clinical attributes, infecting germs and routine lab results (blood cell counts and serum immunoglobulins). The performance of the model as a diagnostic tool was acceptable. The study's main limitations are a limited sample size and a lack of cross validation. This is only the first step in the construction of a machine learning system, with a wider approach that includes a larger database and different methodologies, to assist the clinical diagnosis of primary immunodeficiencies.

Antecedentes: las características clínicas de un paciente con sospecha de inmunodeficiencia primaria orientan el diagnóstico diferencial por medio del reconocimiento de patrones. Las inmunodeficiencias primarias son un grupo heterogéneo de más de 250 enfermedades congénitas con mayor susceptibilidad a padecer infecciones, autoinflamación, autoinmunidad, alergia y cáncer. El análisis discriminante lineal es un método multivariante de clasificación supervisada para agrupar a los sujetos a partir de encontrar combinaciones lineales de un número de variables. Objetivo: identificar las características que mejor explican la pertenencia de pacientes pediátricos con inmunodeficiencias primarias a un grupo de defectos o a una enfermedad. Material y método: estudio analítico transversal en el que a partir de una base de datos preexistente, con registros clínicos y de laboratorio de 168 pacientes con inmunodeficiencia primaria, seguidos en el Instituto Nacional de Pediatría de 1991 a 2012, construimos modelos discriminantes lineales para explicar la pertenencia de cada paciente a los diferentes grupos de defectos y a las inmunodeficiencias primarias más prevalentes en nuestro registro. Luego de una corrida preliminar se incluyeron únicamente las 30 variables (4 demográficas, 10 clínicas, 10 de laboratorio y 6 gérmenes) de mayor peso, a partir de las que se construyeron los modelos de entrenamiento con el algoritmo paso-a-paso (stepwise) hacia atrás, utilizando selección automatizada de variables e incorporación manual "teórica" por un experto humano. Se evaluó la utilidad clínica de los modelos resultantes (sensibilidad, especificidad, exactitud y coeficiente kappa), con intervalos de confianza de 95%. Resultados: los modelos incluyeron 6 a 14 variables para explicar la pertenencia de 168 pacientes con inmunodeficiencias primarias a los cinco grupos más numerosos (combinados, anticuerpos, bien definidos, desregulación y fagocitosis) y las cuatro enfermedades más prevalentes (agammaglobulinemia ligada al cromosoma X, enfermedad granulomatosa crónica, inmunodeficiencia común variable y ataxia-telangiectasia). Prácticamente en todos los casos el desempeño de la máquina fue superior al del experto humano en lo que respecta a la selección de los atributos más pertinentes para incorporar en los modelos. La predicción del diagnóstico con base en las ecuaciones construidas tuvo exactitud global de 83 a 94%, con sensibilidad de 60 a 100%, especificidad de 83 a 95% y coeficiente kappa de 0.37 a 0.76. Conclusiones: la selección de variables, en general, tiene plausibilidad clínica y tiene la ventaja práctica de utilizar solamente atributos clínicos, gérmenes encontrados y estudios de laboratorio de rutina (biometría hemática e inmunoglobulinas séricas). El desempeño del modelo como herramienta de predicción fue aceptable. Las principales limitaciones del estudio incluyen un tamaño de muestra limitado, lo que no permitió que realizáramos validación cruzada en la evaluación. Éste es solamente un primer paso en la construcción de un sistema de aprendizaje automático, con un abordaje más amplio que incluya una base de datos más grande y diferentes metodologías, para asistir el diagnóstico clínico de las inmunodeficiencias primarias.

Haematological and histological findings in birds experimentally infected with highly pathogenic H5N2 avian influenza virus.

Experimental infection of specific-pathogen-free (SPF) Leghorn chickens with a highly pathogenic H5N2 avian influenza virus produced cellular hyperplasia in the bone marrow at 36 hours post infection (hpi) and haematological evidence of monocytosis, thrombocytopenia and heterophilia was also detected. An early, significant and progressive haematological change was thrombocytopenia starting at 24 hpi without an increase of prothrombin time. The findings suggest that highly pathogenic avian influenza virus interferes only with the primary haemostatic mechanisms by consumption of thrombocytes, while the secondary haemostatic mechanisms remain intact.

Exploring nursing roles across North American borders.

Professional nurses are challenged by the increasing complexity of their own healthcare delivery systems and by the growing interconnectivity of healthcare systems worldwide. There are increasing calls for practice across boundaries; however, the role and scope of nursing practice within individual countries are often unclear, ill-defined, and misunderstood by nurses from other countries. In this collaborative educational project among six schools of nursing located in Canada, México, and the United States, nursing students and faculty are exploring the role of the nurse within each country's healthcare system while striving to develop their multicultural awareness. Participating faculty describe the process, challenges, and keys to success found in creating and living this international project. They share strategies for addressing challenges, which included meeting deadlines, time differences, differing academic schedules, writing joint documents in two languages, designing and presenting a shared course, and creating an exchange process between the six partner schools. They describe the evolution of their working relationships, the language challenges, and the joy of coming together as newfound colleagues and friends.