Influence of microbiota-driven natural antibodies on dengue transmission.

Dengue has had a significant global health impact, with a dramatic increase in incidence over the past 50 years, affecting more than 100 countries. The absence of a specific treatment or widely applicable vaccine emphasizes the urgent need for innovative strategies. This perspective reevaluates current evidence supporting the concept of dual protection against the dengue virus (DENV) through natural antibodies (NAbs), particularly anti-α-Gal antibodies induced by the host's gut microbiome (GM). These anti-α-Gal antibodies serve a dual purpose. Firstly, they can directly identify DENV, as mosquito-derived viral particles have been observed to carry α-Gal, thereby providing a safeguard against human infections. Secondly, they possess the potential to impede virus development in the vector by interacting with the vector's microbiome and triggering infection-refractory states. The intricate interplay between human GM and NAbs on one side and DENV and vector microbiome on the other suggests a novel approach, using NAbs to directly target DENV and simultaneously disrupt vector microbiome to decrease pathogen transmission and vector competence, thereby blocking DENV transmission cycles.

Hypercapnia Causes Injury of the Cerebral Cortex and Cognitive Deficits in Newborn Piglets.

In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a "safe" range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulted in a delayed onset of synaptosomal membrane lipid peroxidation, suggesting a dissociation between energy failure and the occurrence of synaptosomal lipid peroxidation. Even short durations of HC triggered biochemical responses at the subcellular level of the cortical neurons resulting in altered cortical activity and impaired neurobehavior. The deleterious effects of HC on the developing brain should be carefully considered as crucial elements of clinical decisions in the neonatal intensive care unit.

Clinical and socio-demographic factors associated with dental extractions in a clinical sample.

The objective of the present study was to identify the reasons for dental extractions in patients seeking dental care in a university dental clinic in Mexico. This is a cross-sectional study that assessed 284 consecutive patients at the School of Dentistry, Autonomous University of the State of Mexico between August 2017 and November 2018. In total, 505 extractions were performed. The dependent variable was the reason for extraction: 0) dental caries and ensuing sequels (reference category); 1) periodontal disease and ensuing sequels; and 2) other reasons. Sociodemographic, socioeconomic, and clinical variables were included as independent variables. The analysis was done with multinomial logistic regression (Stata 14.0). Out of all extractions, 63.6% (n=321) were due to dental caries and ensuing sequels; 22.0% (n=111) were due to periodontal disease and ensuing sequels; 5.3% (n=27) endodontic failure; 5.1% (n=26) prosthetic indications; 1.6% (n=8) orthodontic indications; and the rest (2.4%) were due to other reasons. In the multivariate model extractions due to periodontal disease vs dental caries were associated with occasionally smoking tobacco (Odds Ratio, OR=3.90) or daily tobacco use (OR=3.19); the tooth to be extracted having been previously restored (OR=2.35); extracted anterior as opposed to posterior teeth (OR =2.63); and patients with multiple extractions (OR=2.68). In the case of extractions due to "other reasons", no variable was significant. Dental caries and periodontal disease were the main reasons for dental extraction in this sample. Several variables, mostly clinical, were associated with extractions for periodontal reasons.

The Experience of Testing for Coronavirus Disease (COVID-19) at a Single Diagnostic Center in Paraguay before the Introduction of Vaccination.

Soon after the declaration of the COVID-19 pandemic, the Institute for Health Sciences Research (IICS) of the National University of Asunción, Paraguay became a testing laboratory (COVID-Lab) for SARS-CoV-2. The COVID-Lab testing performance was assessed from 1 April 2020 to 12 May 2021. The effect of the pandemic on the IICS and how the COVID-Lab contributed to the academic and research activities of the institute were also assessed. IICS researchers and staff adjusted their work schedules to support the COVID-Lab. Of the 13,082 nasopharyngeal/oropharyngeal swabs processed, 2704 (20.7%) tested positive for SARS-CoV-2 by RT-PCR. Of the individuals testing positive, 55.4% were female and 48.3% were aged 21-40 years. Challenges faced by the COVID-Lab were unstable reagent access and insufficient staff; shifting obligations regarding research, academic instruction, and grantsmanship; and the continuous demands from the public for information on COVID-19. The IICS provided essential testing and reported on the progress of the pandemic. IICS researchers gained better laboratory equipment and expertise in molecular SARS-CoV-2 testing but struggled to manage their conflicting educational and additional research obligations during the pandemic, which affected their productivity. Therefore, policies protecting the time and resources of the faculty and staff engaged in pandemic-related work or research are necessary components of healthcare emergency preparedness.

Use of liquid-based cytology samples reveals genomic instability and cell death in patients undergoing orthodontic treatment.

PURPOSE: To examine the use of liquid-based exfoliative cytology to determine the presence of genomic instability and cell death in the oral mucosa of patients with orthodontic appliances. METHODS: Fifty-four oral mucosa samples were collected from 18 patients and divided into three stages: T0, before fixation of orthodontic appliances; T1, 25 days after appliance fixation; T2, 90 days after appliance fixation. All samples were Papanicolaou-stained and observed by microscopy (1,000 cells/sample) to ascertain the frequency of micronucleated cells (MN) and nuclear abnormalities (nuclear buds (NB), binucleated (BN), condensed chromatin (CC), karyorrhexis (KR), and karyolysis (KL)). Differences were analyzed statistically using the Mann-Whitney, Wilcoxon, Kruskal-Wallis and chi-squared tests. RESULTS: After placement of orthodontic appliances, significant differences were observed for genomic instability biomarkers (MN and NB) and cell death (CC, KR and KL) (P < 0.05). Female patients and older patients exhibited a higher frequency of MN. CONCLUSION: Liquid-based cytology has revealed that orthodontic appliances induce genomic instability and cell death in epithelial tissue of the oral mucosa, facilitating sample preservation and yielding more than one preparation per sample. Future studies should investigate whether such cell damage can be reversed through cell repair or whether cell alterations evolve and lead to disease.

Clinical and socio-demographic factors associated with dental extractions in a clinical sample

Abstract The objective of the present study was to identify the reasons for dental extractions in patients seeking dental care in a university dental clinic in Mexico. This is a cross-sectional study that assessed 284 consecutive patients at the School of Dentistry, Autonomous University of the State of Mexico between August 2017 and November 2018. In total, 505 extractions were performed. The dependent variable was the reason for extraction: 0) dental caries and ensuing sequels (reference category); 1) periodontal disease and ensuing sequels; and 2) other reasons. Sociodemographic, socioeconomic, and clinical variables were included as independent variables. The analysis was done with multinomial logistic regression (Stata 14.0). Out of all extractions, 63.6% (n=321) were due to dental caries and ensuing sequels; 22.0% (n=111) were due to periodontal disease and ensuing sequels; 5.3% (n=27) endodontic failure; 5.1% (n=26) prosthetic indications; 1.6% (n=8) orthodontic indications; and the rest (2.4%) were due to other reasons. In the multivariate model extractions due to periodontal disease vs dental caries were associated with occasionally smoking tobacco (Odds Ratio, OR=3.90) or daily tobacco use (OR=3.19); the tooth to be extracted having been previously restored (OR=2.35); extracted anterior as opposed to posterior teeth (OR =2.63); and patients with multiple extractions (OR=2.68). In the case of extractions due to "other reasons", no variable was significant. Dental caries and periodontal disease were the main reasons for dental extraction in this sample. Several variables, mostly clinical, were associated with extractions for periodontal reasons.

Resumo O objetivo do presente estudo foi identificar os motivos das extrações dentárias em pacientes que procuram atendimento odontológico em uma clínica odontológica universitária no México. Este é um estudo transversal que avaliou 284 pacientes consecutivos na Faculdade de Odontologia da Universidad Autónoma del Estado de México entre agosto de 2017 e novembro de 2018. No total, foram realizadas 505 extrações. A variável dependente foi o motivo da extração: 0) cárie dentária e sequelas subsequentes (categoria de referência); 1) doença periodontal e sequelas subsequentes; e 2) outros motivos. Variáveis sociodemográficas, socioeconômicas e clínicas foram incluídas como variáveis independentes. A análise foi feita com regressão logística multinomial (Stata 14.0). De todas as extrações, 63,6% (n=321) foram devidas a cárie dentária e sequelas subsequentes; 22,0% (n=111) foram devidas a doença periodontal e sequelas subsequentes; 5,3% (n=27) a insucesso endodôntico; 5,1% (n=26) a indicações protéticas; 1,6% (n=8) a indicações ortodônticas; e o restante (2,4%) foi devido a outros motivos. No modelo multivariado, as extrações por doença periodontal vs. cárie dentária foram associadas ao tabagismo ocasional (Odds Ratio, OR=3,90) ou ao uso diário de tabaco (OR=3,19); ao fato de o dente a ser extraído ter sido restaurado anteriormente (OR=2,35); à extração de dentes anteriores em vez de posteriores (OR=2,63); e a pacientes com extrações múltiplas (OR=2,68). No caso de extrações devido a "outros motivos", nenhuma variável foi significativa. A cárie dentária e a doença periodontal foram os principais motivos de extração dentária nessa amostra. Diversas variáveis, principalmente clínicas, foram associadas às extrações por motivos periodontais.

Frequency of F508del Variant in Patients with Cystic Fibrosis from Paraguay

Abstract Cystic fibrosis (CF) is an autosomal recessive disorder and is caused by variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We aimed to study the frequency of the F508del variant, the most common variant worldwide, in patients with CF from Paraguay. The frequency of the F508del variant in Paraguayan patients with a clinical diagnosis of CF was assessed using a polymerase chain reaction followed by the sequencing of the PCR products. 43 of the 86 patients (50%) were homozygous for the F508del variant, 28 were heterozygous (32.56%), and the remaining 15 (17.44%) were non-carriers. In terms of alleles, there were 114 mutated (114/172 or 66.28%) and 58 did not correspond to this variant (58/172 or 33.72%). This is the first study of the frequency of the F508del variant in patients with CF in Paraguay. This information is of utmost relevance when planning and offering treatments from health services.

Enhancement of fluoride release in glass ionomer cements modified with titanium dioxide nanoparticles.

BACKGROUND: Several efforts have been made to improve the glass ionomer cements (GICs) properties with nanotechnology. Fluoride release in once of most beneficial properties of GICs. The purpose of this study was to evaluate the fluoride release, recharge, and cytotoxicity in GICs reinforced with titanium dioxide nanoparticles (TiO2N). OBJECTIVE: Evaluate the fluoride release, recharge, and cytotoxicity in GICs reinforced with TiO2N. METHODS: Four GICs, FUJI IX EXTRA (G1c), KETAC MOLAR (G2c), IONOFILL MOLAR (G3c), and FUJI IX (G4c) were combined with TiO2N (G1e, G2e, G3e, and G4e) and divided into blocks of 5-mm width and 1-mm thickness 10 each. A total of 80 samples were arranged as follows: GICs alone as negative control (n = 40) and GICs + TiO2N as experimental groups (n = 40). The fluoride release was determined for periods of 1, 2, 6, 10, 31, 90, 180, 240, and 300 days. On days 30 and 179, samples were recharged by submerging in 1 mL of 20,000 ppm sodium fluoride gel. Cytotoxic activity was carried out with gingival fibroblasts, using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide cell viability assay. RESULTS: The experimental groups obtained the highest and more constant fluoride released when compared to control groups. After the first recharge, experimental groups (G1e, G3e, and G4e) showed statistically significant results (P = .001, 0.010, and 0.001 respectively) enhancing their recharge ability regarding control groups. The second recharge showed better results in G1e concerning the rest of the groups. No cytotoxic activity was observed in all experimental groups, although significant differences were observed in G3e and G4e regarding control group. CONCLUSION: The incorporation of TiO2N enhance the fluoride release in glass ionomers with a noncytotoxic effect on human gingival fibroblasts.

Mechanical Properties and Antibacterial Effect on Mono-Strain of Streptococcus mutans of Orthodontic Cements Reinforced with Chlorhexidine-Modified Nanotubes.

Recently, several studies have introduced nanotechnology into the area of dental materials with the aim of improving their properties. The objective of this study is to determine the antibacterial and mechanical properties of type I glass ionomers reinforced with halloysite nanotubes modified with 2% chlorhexidine at concentrations of 5% and 10% relative to the total weight of the powder used to construct each sample. Regarding antibacterial effect, 200 samples were established and distributed into four experimental groups and six control groups (4 +ve and 2 -ve), with 20 samples each. The mechanical properties were evaluated in 270 samples, assessing microhardness (30 samples), compressive strength (120 samples), and setting time (120 samples). The groups were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy, and the antibacterial activity of the ionomers was evaluated on Streptococcus mutans for 24 h. The control and positive control groups showed no antibacterial effect, while the experimental group with 5% concentration showed a zone of growth inhibition between 11.35 mm and 11.45 mm, and the group with 10% concentration showed a zone of growth inhibition between 12.50 mm and 13.20 mm. Statistical differences were observed between the experimental groups with 5% and 10% nanotubes. Regarding the mechanical properties, microhardness, and setting time, no statistical difference was found when compared with control groups, while compressive strength showed higher significant values, with ionomers modified with 10% concentration of nanotubes resulting in better compressive strength values. The incorporation of nanotubes at concentrations of 5% and 10% effectively inhibited the presence of S. mutans, particularly when the dose-response relationship was taken into account, with the advantage of maintaining and improving their mechanical properties.

SARS-CoV-2 Variants in Paraguay: Detection and Surveillance with an Economical and Scalable Molecular Protocol.

SARS-CoV-2 variant detection relies on resource-intensive whole-genome sequencing methods. We sought to develop a scalable protocol for variant detection and surveillance in Paraguay, pairing rRT-PCR for spike mutations with Nanopore sequencing. A total of 201 acute-phase nasopharyngeal samples were included. Samples were positive for the SARS-CoV-2 N2 target and tested with the Spike SNP assay to detect mutations associated with the following variants: alpha (501Y), beta/gamma (417variant/484K/501Y), delta (452R/478K), and lambda (452Q/490S). Spike SNP calls were confirmed using amplicon (Sanger) sequencing and whole-genome (Nanopore) sequencing on a subset of samples with confirmed variant lineages. Samples had a mean N2 Ct of 20.8 (SD 5.6); 198/201 samples (98.5%) tested positive in the Spike SNP assay. The most common genotype was 417variant/484K/501Y, detected in 102/198 samples (51.5%), which was consistent with the P.1 lineage (gamma variant) in Paraguay. No mutations (K417 only) were found in 64/198 (32.3%), and K417/484K was identified in 22/198 (11.1%), consistent with P.2 (zeta). Seven samples (3.5%) tested positive for 452R without 478K, and one sample with genotype K417/501Y was confirmed as B.1.1.7 (alpha). The results were confirmed using Sanger sequencing in 181/181 samples, and variant calls were consistent with Nanopore sequencing in 29/29 samples. The Spike SNP assay could improve population-level surveillance for mutations associated with SARS-CoV-2 variants and inform the judicious use of sequencing resources.

Multisite Clinical Validation of Isothermal Amplification-Based SARS-CoV-2 Detection Assays Using Different Sampling Strategies.

Isothermal amplification-based tests have been introduced as rapid, low-cost, and simple alternatives to real-time reverse transcriptase PCR (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. The clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP coronavirus disease of 2019 [COVID-19] detection test and OptiGene COVID-19 direct plus RT-loop-mediated isothermal amplification [LAMP] test) was compared with that of clinical RT-PCR assays using different sampling strategies. A total of 1,378 participants were tested across 4 study sites. Compared with standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic site from which the sample was collected. Sensitivity for nasopharyngeal sampling was 65.4% (range across study sites, 52.8% to 79.8%), for midturbinate was 88.2%, for saliva was 55.1% (range across study sites, 42.9% to 77.8%), and for anterior nares was 66.7% (range across study sites, 63.6% to 76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall, 82.7%) and those with a higher viral load (overall, 92.4% for cycle threshold [CT] of ≤25). Sensitivity and specificity of the OptiGene direct plus RT-LAMP test, which was conducted at a single study site, were 25.5% and 100%, respectively. The Atila iAMP COVID test with midturbinate sampling is a rapid, low-cost assay for detecting SARS-CoV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-CoV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption. IMPORTANCE Numerous SARS-CoV-2 detection assays have been developed and introduced into the market under emergency use authorizations (EUAs). EUAs are granted primarily based on small studies of analytic sensitivity and specificity with limited clinical validations. A thorough clinical performance evaluation of SARS-CoV-2 assays is important to understand the strengths, limitations, and specific applications of these assays. In this first large-scale multicentric study, we evaluated the clinical performance and operational characteristics of two isothermal amplification-based SARS-CoV-2 tests, namely, (i) iAMP COVID-19 detection test (Atila BioSystems, USA) and (ii) COVID-19 direct plus RT-LAMP test (OptiGene Ltd., UK), compared with those of clinical RT-PCR tests using different sampling strategies (i.e., nasopharyngeal, self-sampled anterior nares, self-sampled midturbinate, and saliva). An important specific use for these isothermal amplification-based, rapid, low-cost, and easy-to-perform SARS-CoV-2 assays is to allow for a safer return to preventive clinical encounters, such as cancer screening, particularly in low- and middle-income countries that have low SARS-CoV-2 vaccination rates.

Multi-site clinical validation of Isothermal Amplification based SARS-COV-2 detection assays using different sampling strategies.

BACKGROUND: Isothermal amplification-based tests were developed as rapid, low-cost, and simple alternatives to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-COV-2 detection. METHODS: Clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP COVID-19 detection test and OptiGene COVID-19 Direct Plus RT-LAMP test) was compared to clinical RT-PCR assays using different sampling strategies. A total of 1378 participants were tested across four study sites. RESULTS: Compared to standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic collected site. Sensitivity for nasopharyngeal was 65.4% (range across study sites:52.8%-79.8%), mid-turbinate 88.2%, saliva 55.1% (range across study sites:42.9%-77.8%) and anterior nares 66.7% (range across study sites:63.6%-76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall 82.7%) and those with a higher viral load (overall 92.4% for ct≤25). Sensitivity and specificity of the OptiGene Direct Plus RT-LAMP test, conducted at a single study-site, were 25.5% and 100%, respectively. CONCLUSIONS: The Atila iAMP COVID test with mid-turbinate sampling is a rapid, low-cost assay for detecting SARS-COV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-COV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption.

Consolidation of the Neonatal Screening Program as a Public Health Program in Paraguay

Abstract In Paraguay, neonatal screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) started in October 1999, in 2005 cystic fibrosis (CF) was selectively incorporated. The National Program for Neonatal Screening has a centralized laboratory that encompasses 1.132 Sample Collecting Sites (SCS) distributed in the 18 Health Regions, with over 80% coverage of live births; the incidence of CH being 1:2.060, HPA/PKU 1:6.328 and CF 1:5.671 newborns. The newborn screening program headed by the Ministry of Public Health and Social Welfare in Paraguay has been consolidated itself as a public health program. This publication describes the historic 20-year process, the strategies and activities carried out as well as the results and achievements, among which it is important to point out the achievement of newborns screening laws that make mandatory to detect, diagnose and treat those affected, as well as the human resources committed to newborn screening.

Risk factors and association of body composition components for lumbar disc herniation in Northwest, Mexico.

The goal of this study was to investigate the association of body composition components and to elucidate whether any of these components is a risk factor for Lumbar Disc Herniation (LDH). The group of study consisted of 90 adults involved in a physical activity program due to overweight and obesity. 19 adults with medical diagnostic through Magnetic Resonance Imaging with LDH. Body composition data was obtained with a bioelectrical impedance analyzer. Descriptive statistics and principal components analysis permitted to analyze the information's structure and to visualize information clusters. A logistic regression analysis allowed us to find the association between some of the variables of body composition with LDH. The Degree of Obesity, Body Mass Index, Visceral Fat Area and the Abdominal Circumference resulted associated (P values of 0.0388, 0.0171, 0.0055 and 0.0032, respectively). The application of Odd Ratio allowed us to declare the Visceral Fat Area and Abdominal Circumference as risk factors to develop Lumbar Disk Herniation. Our results provide a new record for future studies, and support for prescription of physical activity and changes in diet, to correct or prevent the development of LDH in the population of Baja California.

Comparison of Fluoride Release in Conventional Glass-Ionomer Cements with a New Mechanical Mixing Cement.

PURPOSE: The aim of this paper was to compare three conventional hand mixing glass-ionomer cements (GICs) and a new mechanical mixing glass-ionomer cement. MATERIALS AND METHODS: Samples were measured on days 1, 2, 6, 10, 31, 90 and 180. After 32 and 181 days of monitoring, the samples were recharged by using 1 ml of 2% sodium fluoride gel. RESULTS: The fluoride release started in high concentration during the first day for all GICs, with a value for GIII of 32.6 ppm. From the 2nd day, a slow, steady decline, with the exception of GII, which showed a marked decline to a value of 3.2 ppm. Analysis of variance (ANOVA) test showed statistically significant differences between the amounts of fluoride of the four materials in the first 24 h. Student t test was used to compare the fluoride release between the first and second recharge in each one of the study groups. Statistically significant differences were found when we compared the fluoride release in groups I (t = -16.95, p = 0.000) and IV (t = -2.644, p = 0.26). CONCLUSIONS: A mechanical mixing was the material with the more constant fluoride release and after recharge showed the highest fluoride release which make it an important benefit for clinicians.

Strategies for Effective Collaboration with Middle School Physical Education Teachers: An Application of School-Engaged Research.

BACKGROUND: Increasing the capacity of teachers to deliver physical education (PE) lessons that are high in moderate to vigorous physical activity (PA) is one strategy to increase the amount of exercise students receive during school. However, traditional research approaches have not directly engaged the school community as equitable partners in the intervention design process. The purpose of this article is to describe the process, outputs, and lessons learned from a school-engaged research study, which incorporates the unique needs of schools-in terms of structure, accountability measures, and array of stakeholders into the research process and design. METHODS: This article describes lessons learned from Project SHAPE, a PA intervention that used principles of school-engaged research to guide program planning, recruitment, implementation, and data dissemination. RESULTS: The study team successfully partnered with 16 schools and enrolled 55 teachers and surveyed 4,773 students. CONCLUSIONS: Efforts to improve PE programs can benefit from a school-engaged research approach that directly involves teachers, fosters mutually beneficial relationships, and integrates the schools' perspective in the research process.

Estrategias implementadas en Paraguay para la detección neonatal, diagnóstico y tratamiento de las personas con fibrosis quística / Strategies implemented in Paraguay for the neonatal detection, diagnosis and treatment of people with cystic fibrosis

Introducción: La fibrosis quística (FQ) es una patología autosómica recesiva, pasible de ser detectada en el periodo neonatal, causada por mutaciones en el gen regulador de conductancia transmembrana de FQ (CFTR, por sus siglas en inglés), la patología es multisistémica y el tratamiento precoz incide en la expectativa y calidad de vida de los afectados. Objetivo: Presentar las principales estrategias y los resultados logrados para la detección, diagnóstico y tratamiento de las personas con FQ, en el Programa Nacional de Detección Neonatal. Metodología: Se realizó una revisión del plan operativo anual, informes, publicaciones y documentos emitidos del 2004 al 2018. Resultado: En 15 años se ejecutaron 16 estrategias que permitieron la detección, el diagnóstico así como el tratamiento de individuos afectados por la FQ. Entre las que se destacan el desarrollo de un proyecto piloto para el tamizaje de la FQ en RN, mediante dosaje de la tripsina inmunoreactiva (TIR), entrega de una canasta básica de medicamentos, insumos y equipos para el tratamiento de los individuos con FQ detectados por el programa así como los diagnosticados con anterioridad, implementación del test del sudor, elaboración de una Guía Clínica multidisciplinaria, automatización del dosaje de la TIR, que permitió la universalización del screening, y por último la identificación de las mutaciones presentes en los individuos afectados. En el 2015 se logró llegar al 100 % de cobertura de los RN atendidos en los servicios del Ministerio de Salud Pública y Bienestar Social. De enero del 2004 a diciembre del 2018, 179 individuos reciben su tratamiento en el programa, 144 de los cuales fueron detectados en el periodo neonatal. Conclusión:Las estrategias ejecutadas han tenido resultados muy auspiciosos que nos permitieron universalizar la detección neonatal y tratamiento, lo que conlleva a una mejor calidad y expectativa de vida de los individuos afectados por la FQ. En la actualidad solo faltaría implementar un Centro de Atención Multidisciplinario para las personas con Fibrosis Quística Palabras claves: Programa, Detección neonatal, Fibrosis Quística

Introduction:Cystic fibrosis (CF) is an autosomal recessive pathology, capable of being detected in the neonatal period, caused by mutations in the CF transmembrane conductance regulator gene (CFTR), the pathology is multisystemic and Early treatment affects the expectation and quality of life of those affected. Objective:Present the main strategies and the results achieved for the detection, diagnosis and treatment of people with CF, in the National Neonatal Screening Program. Methodology:A review of the annual operating plan, reports, publications and documents issued from 2004 to 2018 was made. Result:In 16 years, 16 strategies were implemented that allowed the detection, diagnosis and treatment of individuals affected by CF. Among those that stand out the development of a pilot project for the screening of CF in RN, by means of immunoreactive trypsin (TIR), delivery of a basic basket of medicines, supplies and equipment for the treatment of the individuals with CF detected by the program as well as those previously diagnosed, implementation of the sweat test, elaboration of a multidisciplinary Clinical Guide, automation of the TIR dose, which allowed the universalization of the screening, and finally the identification of the mutations present in the affected individuals . In 2015, it was possible to reach 100% coverage of the RNs assisted in the services of the Ministry of Public Health and Social Welfare. From January 2004 to December 2018, 179 individuals received their treatment in the program, 144 of which were detected in the neonatal period. Conclusion:The strategies implemented have had very auspicious results that allowed us to universalize neonatal detection and treatment, which leads to a better quality and life expectancy of the individuals affected by CF. At present, it would only be necessary to implement a Multidisciplinary Care Center for people with Cystic Fibrosis. Keywords: Program, Neonatal screening, Cystic fibrosis

Inducible Cell Fusion Permits Use of Competitive Fitness Profiling in the Human Pathogenic Fungus Aspergillus fumigatus.

Antifungal agents directed against novel therapeutic targets are required for treating invasive, chronic, and allergic Aspergillus infections. Competitive fitness profiling technologies have been used in a number of bacterial and yeast systems to identify druggable targets; however, the development of similar systems in filamentous fungi is complicated by the fact that they undergo cell fusion and heterokaryosis. Here, we demonstrate that cell fusion in Aspergillus fumigatus under standard culture conditions is not predominately constitutive, as with most ascomycetes, but can be induced by a range of extracellular stressors. Using this knowledge, we have developed a barcode-free genetic profiling system that permits high-throughput parallel determination of strain fitness in a collection of diploid A. fumigatus mutants. We show that heterozygous cyp51A and arf2 null mutants have reduced fitness in the presence of itraconazole and brefeldin A, respectively, and a heterozygous atp17 null mutant is resistant to brefeldin A.

Incidencia de la fibrosis quística en Paraguay / Incidence of cystic fibrosis in Paraguay

Introducción: Fibrosis quística (FQ) patología genética, autosómica recesiva por mutaciones en el gen de la proteína reguladora de la conductancia transmembrana (CFTR cystic fibrosis transmembrane regulator). En una enfermedad multisistémica, afecta el aparato respiratorio, sistema digestivo, glándulas sudoríparas y conducto deferente. En Paraguay la detección, diagnóstico y tratamiento es obligatoria y gratuita para todo recién nacidos (RN). El tamizaje neonatal es realizado a través del dosaje de la tripsinainmuno reactiva (TIR) y la confirmación diagnóstica con el test del sudor. Objetivo: Reportar la incidencia de la FQ en la población de RN de Paraguay. Es un Materiales y Métodos: trabajo descriptivo, retrospectivo de corte trasversal, donde se analizaron los datos del Programa Nacional de Detección Neonatal (PNDN), de enero del 2015 a diciembre del 2017, para el análisis de la base de datos se utilizó una planilla Excel. Resultados: En el 2015 un 91% (79.093/87.181) de las muestras ingresadas al Programa reunieron los criterios (edad y calidad de la muestra) para el estudio de la TIR, arrojando una incidencia de 1 en 6.591 RN. Para el 2016, esto correspondió a un 97% (83.525/86.094) con una incidencia de 1 en 4.176 RN y por último en el 2017, se tuvo un 97% (87.075/90.037) con una incidencia de 1 en 5.112 RN. Conclusión: La incidencia de la FQ en la población de recién nacidos del Paraguay, en los tres años que abarca este estudio, no presentan entre sí diferencias significativas, tampoco con las reportadas para la población hispánica.

Introduction: Cystic fibrosis (CF), is an autosomal recessive genetic pathology that is caused by mutations in the transmembrane conductance regulatory protein (CFTR cystic fibrosis transmembrane regulator) gene. As a multisystem disease, it affects the respiratory system, digestive system, sweat glands and vas deferens. In Paraguay, detection, diagnosis and treatment is mandatory and free for all newborns (NB). Neonatal screening is performed by the immunoreactive trypsinogen assay (IRT) and diagnostic confirmation is performed by the sweat test. Objective: To report the incidence of CF in the NB population of Paraguay. Materials and Methods: This was a descriptive, retrospective, cross-sectional study, where data from the National Neonatal Screening Program (NNSP) were analyzed, from January 2015 to December 2017. To analyze the database, we used an Excel spreadsheet. Results: In 2015, 91% (79,093 / 87,181) of the samples sent to the Program met the criteria (age and sample quality) for the IRT study, with an incidence of 1 in 6,591 NB. In 2016, 97% (83,525 / 86,094) met criteria, with an incidence of 1 in 4,176 NB, while in 2017, 97% (87,075 / 90,037) met criteria, with an incidence of 1 in 5,112 NB. Conclusion: The incidence of CF in the newborn population of Paraguay, during the three years of this study, did not show significant differences between years, nor with those reported for the Hispanic population.