Investigating the correlation between genotype and phenotype in Prader-Willi syndrome: a study of 45 cases from Brazil.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in PWS is crucial for improved genetic counseling and prognosis. In this study, we aimed to investigate the correlation between genotype and phenotype in 45 PWS patients who previously underwent methylation-sensitive high-resolution melting (MS-HRM) for diagnosis. RESULTS: We employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and Sanger sequencing, along with collecting phenotypic data from the patients for comparison. Among the 45 patients, 29 (64%) exhibited a deletion of 15q11-q13, while the remaining 16 (36%) had uniparental disomy. No statistically significant differences were found in the main signs and symptoms of PWS. However, three clinical features showed significant differences between the groups. Deletion patients had a higher prevalence of myopia than those with uniparental disomy, as well as obstructive sleep apnea and an unusual skill with puzzles. CONCLUSIONS: The diagnostic tests (MS-HRM, MS-MLPA, and Sanger sequencing) yielded positive results, supporting their applicability in PWS diagnosis. The study's findings indicate a general similarity in the genotype-phenotype correlation across genetic subtypes of PWS.

The cost of genetic diagnosis of suspected hereditary pediatric cataracts with whole-exome sequencing from a middle-income country perspective: a mixed costing analysis.

Up to 25% of pediatric cataract cases are inherited. There is sparse information in the literature regarding the cost of whole-exome sequencing (WES) for suspected hereditary pediatric cataracts. Molecular diagnosis of suspected hereditary pediatric cataracts is important for comprehensive genetic counseling. We performed a partial economic evaluation with a mixed costing analysis, using reimbursement data and microcosting approach with a bottom-up technique to estimate the cost of using WES for genetic diagnosis of suspected hereditary pediatric cataracts from the perspective of the Brazilian governmental health care system. One hundred and ten participants from twenty-nine families in Rio de Janeiro (RJ) were included. Costs of consumables, staff and equipment were calculated. Two scenarios were created: (1) The reference scenario included patients from RJ with suspected hereditary pediatric cataracts plus two family members. (2) The alternative scenario considered other genetic diseases, resulting in 5,280 exams per month. Sensitivity analysis was also performed. In the reference scenario, the total cost per exam was 700.09 United States dollars (USD), and in the alternative scenario, the total cost was 559.23 USD. The cost of WES alone was 527.85 USD in the reference scenario and 386.98 USD in the alternative scenario. Sensitivity analysis revealed that the largest costs were associated with consumables in both scenarios. Economic evaluations can help inform policy decisions, especially in middle-income countries such as Brazil.

Establishing a Standardized DNA Extraction Method Using NaCl from Oral Mucosa Cells for Its Application in Imprinting Diseases Such as Prader-Willi and Angelman Syndromes: A Preliminary Investigation.

BACKGROUND: Diagnosing imprinting defects in neonates and young children presents challenges, often necessitating molecular analysis for a conclusive diagnosis. The isolation of genetic material from oral swabs becomes crucial, especially in settings where blood sample collection is impractical or for vulnerable populations like newborns, who possess limited blood volumes and are often too fragile for invasive procedures. Oral swab samples emerge as an excellent source of DNA, effectively overcoming obstacles associated with rare diseases. METHODS: In our study, we specifically addressed the determination of the quality and quantity of DNA extracted from oral swab samples using NaCl procedures. RESULTS: We compared these results with extractions performed using a commercial kit. Subsequently, the obtained material underwent MS-HRM analysis for loci associated with imprinting diseases such as Prader-Willi and Angelman syndromes. CONCLUSIONS: Our study emphasizes the significance of oral swab samples as a reliable source for obtaining DNA for MS-HRM analysis. NaCl extraction stands out as a practical and cost-effective method for genetic studies, contributing to a molecular diagnosis that proves particularly beneficial for patients facing delays in characterization, ultimately influencing their treatment.

Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling.

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

Magnetic Mesoporous Silica for Targeted Drug Delivery of Chloroquine: Synthesis, Characterization, and In Vitro Evaluation.

Malaria is a dangerous tropical disease, with high morbidity in developing countries. The responsible parasite has developed resistance to the existing drugs; therefore, new drug delivery systems are being studied to increase efficacy by targeting hemozoin, a parasite paramagnetic metabolite. Herein, magnetic mesoporous silica (magMCM) was synthesized using iron oxide particles dispersed in the silica structure for magnetically driven behavior. The X-ray diffractogram (XRD) and Mössbauer spectra show patterns corresponding to magnetite and maghemite. Furthermore, Mössbauer spectroscopy revealed superparamagnetic behavior, attributed to single magnetic domains in particles smaller than 10 nm. Even in the presence of iron oxide particles, the hexagonal structure of MCM is clearly identified in XRD (low-angle region) and the channels are visible in TEM images. The drug chloroquine (CQ) was encapsulated by incipient wetness impregnation (magMCM-CQ). The N2 adsorption-desorption isotherms show that CQ molecules were encapsulated in the pores, without completely filling the mesopores. BET surface area values were 630 m2 g-1 (magMCM) and 467 m2 g-1 (magMCM-CQ). Encapsulated CQ exhibited rapid delivery (99% in 3 h) in buffer medium and improved solubility compared to the non-encapsulated drug, attributed to CQ encapsulation in amorphous form. The biocompatibility assessment of magMCM, magMCM-CQ, and CQ against MRC5 non-tumoral lung fibroblasts using the MTT assay after 24 h revealed no toxicity associated with magMCM. On the other hand, the non-encapsulated CQ and magMCM-CQ exhibited comparable dose-response activity, indicating a similar cytotoxic effect.

Exploring uterine inflammation in postpartum primiparous precocious and conventional and multiparous Bos indicus beef cows.

This study aimed to compare the postpartum uterine dynamics of primiparous precocious (PP), primiparous conventional (PC) and multiparous conventional (MC) Bos indicus beef cows. For this purpose, PP (n = 8), PC (n = 18) and MC (n = 12) cows were enrolled in this study. These cows were evaluated at 20 and 10 days prepartum and weekly from parturition to 42 days postpartum (DPP). During this period, body weight (BW), subcutaneous fat thickness (SFT) and serum concentrations of glucose, ß-hydroxybutyrate, albumin and haptoglobin were measured. Proportion of polymorphonuclear (PMN) cells, and abundance of mRNA transcripts of genes involved in uterine inflammation and uterine health were evaluated. The PP cows had lower (p < .05) BW and SFT than that for PC and MC cows during the study period. The serum concentration of albumin after 35 DPP was lower (p < .05) in PP cows. The PP cows had the highest proportion of PMN on 28 and 35 DPP compared to PC and MC cows. The relative mRNA abundance of IL-1ß and IL-8 increased after 21 DPP in PP cows compared to the other groups. The PC had the highest, MC had an intermediate, and PP cows had the lowest relative abundance of IL10 mRNA. Overall, these findings indicated that uterine inflammation was more pronounced in PP cows. Moreover, based on the proportion of PMN and abundance of transcripts associated with inflammation in the uterus, PP cows may require a longer period to recover their uterine health after calving.

Real-time PCR in the diagnosis of congenital toxoplasmosis.

The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of newborns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.

Impact of Genomic Deletion RD16 on the Expression of the Mycobacterium bovis BCG Moreau VapBC47 Toxin-Antitoxin System.

Mycobacterium bovis BCG is the only vaccine against tuberculosis. The variable forms of cultivation throughout the years, before seed-lots were developed, allowed in vitro evolution of the original strain, generating a family of vaccines with different phenotypic and genotypic characteristics. Molecular studies revealed regions of difference (RDs) in the genomes of the various BCG strains. This work aims to characterize the gene pair rv3407-rv3408 (vapB47-vapC47), coding for a toxin-antitoxin system of the VapBC family, and to evaluate possible transcriptional effects due to the adjacent BCG Moreau-specific genomic deletion RD16. We show that these genes are co-transcribed in BCG strains Moreau and Pasteur, and that the inactivation of an upstream transcriptional repressor (Rv3405c) due to RD16 has a polar effect, leading to increased vapBC47 expression. Furthermore, we detect VapB47 DNA binding in vitro, dependent on a 5' vapB47 sequence that contributes to a palindrome, spanning the promoter and coding region. Our data shed light on the regulation of VapBC systems and on the impact of the BCG Moreau RD16 deletion in the expression of adjacent genes, contributing to a better understanding of BCG Moreau physiology.

GnRH34 with or without estradiol cypionate in timed AI in Bos indicus beef cows.

Two experiments were performed to evaluate the effects of GnRH treatment on the fertility of suckled Nelore beef cows treated with an estradiol/progesterone (E2/P4)-based protocol for timed artificial insemination (TAI). Experiment 1 focused on determining the effects of estradiol cypionate (EC) on ovulation in TAI cows treated with GnRH 34 h after removal of the intravaginal P4 device (IPD). Suckled cows (n = 26) were treated with 2 mg estradiol benzoate (EB) and IPD containing 1 g P4. After 8 days, IPDs were removed, and all cows were treated with 150 µg of d-cloprostenol (prostaglandin F2 alpha analog) and 300 IU of equine chorionic gonadotropin (eCG), then separated into two treatment groups consisting of cows who received 1) saline 0.9% i.m. (GnRH34 group) or 2) 0.6 mg i.m. of EC (EC-GnRH34 group). On day 9 (05:00 p.m.), all cows were given GnRH (10.5 µg of buserelin acetate) i.m. No differences were observed between the groups (P > 0.05) in the time of ovulation after IPD removal or in the proportion of cows ovulating. Experiment 2 focused on determining the effects of GnRH34 along with or in the absence of EC on day 8 on pregnancy per AI (P/AI) in postpartum beef cows. Cows (n = 981) were treated similarly to those in Experiment 1, but an additional group, the EC-GnRH48 group, was included, in which cows received EC on day 8 whereas those that did not show estrus received GnRH at TAI. Thus, in this experiment, groups consisted of GnRH34 (n = 322), EC-GnRH34 (n = 335), and EC-GnRH48 (n = 324). A higher rate of estrus expression was observed in cows treated with EC following IPD removal (EC-GnRH34: 69%, EC-GnRH48: 64.8%) than in cows in the GnRH34 group (45.6%). No difference in P/AI was observed between the treatment groups (P = 0.45), but P/AI in cows in the EC-GnRH34 group (64.2%) tended to be greater (P = 0.1) than in cows in the GnRH34 group (58%). In summary, although ovulation synchrony did not differ among the groups, P/AI in cows treated with EC and GnRH 34 h after IPD removal tended to be greater than in cows treated solely with GnRH; this was most likely due to a shorter proestrus/estrus period, considering the lower proportion of cows that displayed estrus in the GnRH34 group. Finally, given that P/AI did not differ between the EC-GnRH34 and EC-GnRH48 groups, our results suggest that, for cows not displaying estrus, administration of EC at the time of IPD removal followed by treatment with GnRH 48 h afterward represents the most cost-efficient TAI strategy for South American Zebu-based beef operations.

Barriers to employing digital technologies for a circular economy: A multi-level perspective.

Industry 4.0 and digital technologies might significantly impact resource optimization in a smart circular economy. However, adopting digital technologies is not easy due to barriers that may arise during this process. While prior literature offers initial insights into barriers at the firm level, these studies pay less attention to these barriers' multi-level nature. Focusing only on one particular level while ignoring others may not unleash the full potential of DTs in a circular economy. To overcome barriers, it's necessary to have a systemic understanding of the phenomenon, which is missing in previous literature. By combining a systematic literature review and multiple case studies of nine firms, this study aims to unpack the multi-level nature of barriers to a smart circular economy. The primary contribution of this study is a new theoretical framework composed of eight dimensions of barriers. Each dimension provides unique insights related to the multi-level nature of the smart circular economy transition. In total, 45 barriers were identified and categorized into the following dimensions: 1. Knowledge management (five barriers), 2. Financial (three barriers), 3. Process management & Governance (eight barriers), 4. Technological (ten barriers), 5. Product & Material (three barriers), 6. Reverse logistic infrastructure (four barriers), 7. Social behaviour (seven barriers), and 8. Policy & Regulatory (five barriers). This study examines how each dimension and multi-level barrier affects the transitions toward a smart circular economy. An effective transition copes with complex, multidimensional, multi-level barriers, which might require mobilization beyond a single firm. Government actions need to be more effective and correlated with sustainable initiatives. Policies also should focus on mitigating barriers. Overall, the study contributes to smart circular economy literature by increasing theoretical and empirical understanding of digital transformation barriers towards circularity.

Real-time PCR in the diagnosis of congenital toxoplasmosis

ABSTRACT The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of new-borns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.

Internal load in male professional volleyball: a systematic review.

INTRODUCTION: The aims of this systematic review were to synthesize the volleyball internal load values presents in the literature, verify the applicability of the different tools for quantification and monitoring these variables, and analyze the similarity with the matches and training loads. EVIDENCE ACQUISITION: This review followed the PRISMA statement recommendations, and the search was carried out in the databases: PubMed/NCBI, SportDiscus via EBSCOhost, SciELO and in the Brazilian Library of Theses. Twenty-six studies meet the criteria and were included. EVIDENCE SYNTHESIS: The most used and indicate tools for quantification, monitoring and evaluation of volleyball internal load are the rating of perceived exertion (RPE), session rating of perceived exertion (sRPE) and other metrics derived from these data. Volleyball training sessions range from 4 to 7 in Brog Scale and sessions with more jumps present a higher load. The sRPE values found ranged from 51.92 (AU) to 627 (AU) and presents an undulating kinetic intra and inter weeks. Higher total week training load values are observed in the preparatory period than in competitive periods and wellbeing and recovery questionnaires are sensible to increased loads. CONCLUSIONS: In professional male volleyball, training load seem to be planned with variation according to the period of the season and days of week. The intraweek variation in load dynamics is necessary to allow the correct athlete's recovery and adaptation to volleyball efforts and the interweek load increase can be monitored by the ACWR.

Leisure-time exercise is associated with lower depressive symptoms in community dwelling adults.

Physical activity has been associated with enhanced mental health among adults. However, it is not clear in the literature which domains (occupational, transport and leisure-time exercise) and intensities (moderate, vigorous and moderate-to-vigorous) of activity provide the greatest benefits. The aim of the present study was to describe the association of different domains and intensities of physical activity with depressive symptoms in adults. This was a cross-sectional observational study conducted among 209 adults (≥18 years) in Brazil. Depressive symptoms were assessed using the HADS questionnaire (Hospital Anxiety and Depression Scale). Physical activity intensities (moderate, vigorous and moderate-to-vigorous) were device-measured by accelerometry. Physical activity in different domains (occupational, transport, and leisure-time exercise) was self-reported using a questionnaire. Chronological age, ethnicity, body mass index, highest academic achievement, employment status, alcohol consumption, tobacco smoking, chronic morbidity and soft-drink ingestion were adopted as adjustment confounding factors. Linear regression analysis revealed that total self-reported physical activity [ß = -0.100 (95%CI: -0.180 to -0.019)] and leisure-time exercise [ß = -0.311 (95%CI: -0.468 to -0.155)] were negatively associated with depressive symptoms, but only leisure-time exercise remained significant after adjustment for confounding factors [ß = -0.243 (95%CI: -0.409 to -0.076)]. Thus, leisure-time exercise was cross-sectionally associated with lower depressive symptoms in community-dwelling adults.HighlightsLeisure-time physical activity was the only physical activity domain associated with lower depressive symptoms.This association appears to be independent of potential confounders.Potential interventions should focus on leisure-time domain.

Análise de sobrevivência de coroas unitárias sobre pilares para CAD/CAM com diferentes alturas de cimentação / Comparative analysis between two different abutment heights in single crowns

Objetivo: Avaliar o comportamento biomecânico do pilar protético Link Universal (TiBase) com diferentes alturas em restaurações implanto-suportadas. Materiais e Métodos: foram utilizados 40 implantes cone morse Titaniumfix Profile (4 x 10 mm) em titânio, divididos em dois grupos (n=20): Link Universal curto (Short) e Link Universal longo (Long). Vinte implantes receberam o pilar protético Link Universal de 4,5 x 4 mm (Short) e vinte implantes receberam o pilar protético Link Universal de 4,5 x 5,5 mm (Long). Por meio da tecnologia CAD/CAM foram usinadas as coroas em zircônia, cimentadas sobre os pilares protéticos. No ensaio de carga máxima para fratura, o grupo Longo apresentou média de 41,1 ± 6,96 kgf, enquanto a média do grupo curto foi de 49,5 ± 7,68, sem diferença estatística entre eles. Os espécimes passaram pelo teste de sobrevivência em fadiga (2.000.000 ciclos na frequência de 2 Hz com aplicador de aço inoxidável de 1,6 mm de diâmetro), conforme parâmetros descritos na ISO 14801:2007 e não apresentaram falhas. Na sequência, foram submetidos ao teste de sobrevivência stepwise, os espécimes não apresentaram diferenças em relação ao número de ciclos para falha, porém, em relação à carga aplicada, o pilar Link Universal Longo mostrou-se mais resistente que o pilar Link Universal Curto. A análise por elementos finitos foi realizada com os parâmetros obtidos no teste stepwise, com aplicação de carga de 450 N em 30º, simulando a condição do teste de fadiga. Os desenhos foram montados com o software Rhinoceros (version 5.4.2 SR8, McNeel Noth America, Seattle, WA, EUA) e processados no software Ansys (version 19.2, ANSYS Inc., Houston, TX, USA). O comportamento biomecânico do conjunto composto por implante, pilar protético, parafuso passante e coroa monolítica foi semelhante entre os grupos. Concluiu-se que ambas alturas da área de cimentação do pilar Link Universal apresentaram comportamento à fadiga favorável à sobrevivência clínica. (AU)

Objective: Evaluate the biomechanical behavior of the Universal Link (Ti-Base) prosthetic abutment with different heights in implant-supported restorations. Materials and Methods: 40 Titaniumfix Profile implants (4 x 10 mm) in titanium were used, divided into two groups (n=20): Short Universal Link (Short) and Long Universal Link (Long). Twenty implants received the 4.5 x 4 mm Link Universal Prosthetic Abutment (Short) and twenty implants received the 4.5 x 5.5 mm Link Universal Prosthetic Abutment (Long). Using CAD/CAM technology, the zirconia crowns were machined and cemented on the prosthetic abutments. In the maximum fracture load test, the Long group presented an average of 41.1 ± 6.96 kgf, while the average of the short group was 49.5 ± 7.68, with no statistical difference between them. The specimens passed the fatigue survival test (2,000,000 cycles at a frequency of 2 Hz with a stainless steel applicator with a diameter of 1.6 mm), according to the parameters described in ISO 14801:2007 and showed no failures. Subsequently, they were submitted to the stepwise survival test, the specimens did not show differences in relation to the number of cycles to failure, however, in relation to the applied load, the Long Universal Link abutment was more resistant than the Short Universal Link abutment. The finite element analysis was performed with the parameters obtained in the stepwise test, with a load of 450 N at 30º, simulating the condition of the fatigue test. The drawings were assembled with Rhinoceros software (version 5.4.2 SR8, McNeel Noth America, Seattle, WA, USA) and processed in Ansys software (version 19.2, ANSYS Inc., Houston, TX, USA). The biomechanical behavior of the set consisting of implant, prosthetic abutment, through screw and monolithic crown was similar between the groups. It was concluded that the Link Universal abutment presented fatigue behavior favorable to clinical survival independently of it's height (AU)

Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

Host factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. Here, we accessed samples from 153 pregnant women (77 without and 76 with CZS) and 143 newborns (77 without and 66 with CZS) exposed to ZIKV conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS outcome, and characterized placenta gene expression profile at term. Newborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.41; IC=1.35-8.60; Pcorrected=0.032). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. We found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. Despite of the low sample size se findings shed light on the host-pathogen interaction focusing on the genetically regulated type I/type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections.

­ Todos ao Colyseu ­educação e modernidade num parque de diversão em Curitiba (1905-1913) / ­Todos ao Colyseu ­education and modernity in an amusement park in Curitiba (1905-1913)

O presente estudo tem por objetivo discutir as experiências em torno de um pioneiro parque diversões de Curitiba, o ColyseuCuritybano, entre os anos de 1905 (momento de sua implementação) e 1913 (quando a estrutura fecha as portas). O propósito foi investigar as repercussões das atrações ofertadas no local na formulação de possíveis processos de instrução para a experiência moderna. Para tanto foram utilizados como fontes as publicações de jornais da época. A título de conclusão, o artigo aponta que o Colyseu durante seus anos de existência foi um lócus de circulação de ideias de modernidade na capital paranaense e que, através dos divertimentos ali ofertados, frequentadores (as) puderam sintonizar-se e instruir-se de e para diversas experiências do mundo moderno.

The present study aims to discuss the experiences around a pioneer amusement park in Curitiba, the ColyseuCuritybano, between the years 1905 (when it was implemented) and 1913 (when the structure closed its doors). The purpose was to investigate the repercussions of the attractions offered on the site in the formulation of possible instructional processes for the modern experience. For this purpose, newspapers of the time were used as sources. In conclusion, the article points out that Colyseu during its years of existence was a locus for the circulation of ideas of modernity in the capital of Paraná and that, through the amusements offered there, regulars were able to tune in and learn and for different experiences in the modern world.

Novel Mutation in CRYBB3 Causing Pediatric Cataract and Microphthalmia.

Up to 25% of pediatric cataract cases are inherited, with half of the known mutant genes belonging to the crystallin family. Within these, crystallin beta B3 (CRYBB3) has the smallest number of reported variants. Clinical ophthalmological and genetic-dysmorphological evaluation were performed in three autosomal dominant family members with pediatric cataract and microphthalmia, as well as one unaffected family member. Peripheral blood was collected from all participating family members and next-generation sequencing was performed. Bioinformatics analysis revealed a novel missense variant c.467G>A/p.Gly156Glu in CRYBB3 in all family members with childhood cataract. This variant is classified as likely pathogenic by ACMG, and no previous descriptions of it were found in ClinVar, HGMD or Cat-Map. The only other mutation previously described in the fifth exon of CRYBB3 is a missense variant that causes a change in amino acid from the same 156th amino acid to arginine and has been associated with pediatric cataract and microphthalmia. To the best of our knowledge, this is the first time the c.467G>A/p.Gly156Glu variant is reported and the second time a mutation in CRYBB3 has been associated with microphthalmia.

Whole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn's genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10-5). The IL12RB2 gene (p-value: 2.18x10-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.

PCR-based diagnosis is not always useful in the acute acquired toxoplasmosis in immunocompetent individuals.

Toxoplasmosis is the most prevalent zoonosis in the world and is associated with a large spectrum of diseases. Acute acquired toxoplasmosis (AAT) is considered a benign and self-limiting disease but severe postnatal infections have been reported, particularly in South America. Laboratory diagnosis is based on the detection of anti-Toxoplasma gondii IgM, IgG, and presence of low IgG avidity. However, these assays present limitations, and therefore, PCR has been suggested as an alternative diagnostic tool. In this study, we performed real-time and nested PCR in DNA blood samples from 59 individuals with AAT lasting less than 80 days. None of the patients had parasitic DNA detected by PCR, even in the more severe cases or when blood was collected early after disease onset. These negative results indicate that the parasitemia kinetics needs investigation to determine the best time for blood sampling, especially in immunocompetent individuals. Thus, we emphasize that a negative PCR result does not exclude recent T. gondii infection, and serological criteria are still decisive for the laboratory diagnosis of AAT.