Amniotic fluid metabolomics identifies impairment of glycerophospholipid and amino acid metabolism during congenital Zika syndrome development.

PURPOSE: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression. EXPERIMENTAL DESIGN: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses. RESULTS: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE: This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.

Frequency of breakfast consumption and its associations with food consumption by degree of industrial processing and with indicators of overweight in Brazilian adolescents (EVA-JF Study).

OBJECTIVE: The aim of this study was to investigate the frequency of breakfast consumption and estimate its associations with the consumption of food at different degrees of industrial processing and with overweight indicators in Brazilian adolescents. METHODS: This cross-sectional study involved a probabilistic sample of 14- to 19-y-old adolescents enrolled in 29 public schools in the municipality of Juiz de Fora, MG, Southeast Brazil (n = 805). The frequency of breakfast consumption was evaluated via a questionnaire (classified into "do not consume", "sometimes consume", and "regularly consume"). The evaluation of food consumption involved two 24-h dietary recalls, the items of which were analyzed according to the NOVA classification system. Overweight indicators (waist circumference, body mass index for age (BMI-for-age), and body fat percentage) were evaluated according to a standard protocol. Linear regression models were performed, first without and then with adjustments for sociodemographic characteristics. RESULTS: We found that 20% of adolescents skipped breakfast, and ∼46% of the caloric intake came from ultra-processed foods. Breakfast omission was associated with a mean increase of 3.02% (95% confidence interval [CI], 0.52-5.53) in energy intake from ultra-processed foods, in addition to a mean increase of 0.28 z-score (95% CI, 0.05- 0.52) of BMI-for-age and of 1.64% (95% CI, 0.21-3.08) in body fat. CONCLUSIONS: We verified that the omission of breakfast was associated with higher consumption of ultra-processed foods, as well as a higher BMI-for-age and higher percentage of body fat, reinforcing the importance of actions to encourage the consumption of this meal and the adoption of healthy eating practices in adolescents.

Prevalence of urologic sequelae and bladder and bowel dysfunctions in patients with congenital Zika syndrome: A multicenter evaluation of the Zika virus bladder and bowel sequelae assistance network.

INTRODUCTION: Neurogenic bladder was first confirmed as a urological sequela of Congenital Zika Syndrome (CZS) in 2018. Further clinical-epidemiological evidence also confirmed neurogenic bowel dysfunction and cryptorchidism. To strengthen the care for these children, the Congenital Zika Virus Bladder and Bowel Sequelae Network (RASZ in Brazilian) was created, including six integrated centers in Brazil. This article represents the initial outcome of the efforts by RASZ. OBJECTIVE: To evaluate the prevalence of bladder and bowel dysfunction, cryptorchidism and other urological sequelae related to CZS in cohorts attended in six Brazilian states. STUDY DESIGN: Observational, prospective, multicenter study including children with CZS assisted in one of six RASZ collaborative centers between June 2016 and February 2023. Data were collected from patient's first assessment using the same protocols for urological and bowel evaluation. Categorical variables were analyzed by frequency of occurrence and numerical variables by mean, median, and standard deviation. The study was approved by the Research Ethics Committees of each center, all parents/caregivers provided written informed consent. RESULTS: The study included 414 children aged 2 months to 7 years (mean 2.77 years, SD 1.73), 227 (54.8 %) were male and 140 (33,8 %) referred urological and bowel symptoms on arrival. Prevalence of both urological and bowel sequelae was 66.7 %, 51 % of children aged 4 years and older had urinary incontinence (UI). UTI was confirmed in 23.4 % (two presented toxemia) and among males, 18.1 % had cryptorchidism. Renal ultrasonography, performed in 186 children, was abnormal in 25 (13.4 %), 7 had hydronephrosis. Among the 287 children who performed urodynamics, 283 (98.6 %) were altered: 232 had a lower bladder capacity, 144 a maximum bladder pressure of ≥40 cm H2O, and 127 did not satisfactorily empty their bladder. DISCUSSION: A higher prevalence of NLUTD, neurogenic bowel and cryptorchidism was confirmed in children with CZS. Early diagnosis and appropriate treatment, including a multidisciplinary approach, may reduce the risk of UTIs, UI and kidney damage. A limitation of the study was the inability of children to complete the protocol, specifically urodynamic evaluation, and ultrasonography. In both exams, the percentage of abnormal cases was higher than that expected in the normal population. CONCLUSION: A 66,7 % prevalence of combined urological sequelae and bladder-bowel dysfunction related to CZS was confirmed in patients evaluated in six Brazilian cohorts. The most frequent changes were related to NLUTD, neurogenic bowel, and cryptorchidism. Prevalence may be underestimated due to access restrictions to diagnostic tests.

Encoding of speech sounds with frequency-following response in infants with Congenital Zika Syndrome: A case-controlled study

ABSTRACT Purpose: to investigate the frequency-following response (FFR) for sustained neural activity. Methods: 39 individuals, aged between 20 to 47 months old were divided into 2 groups: (i) 20 individuals without prenatal exposure to the congenital Zika syndrome (CZS) or hydrocephaly, normal development, no risk factors for hearing loss or syndromic hearing impairment and (ii) 19 individuals diagnosed with CZS and microcephaly - based on imaging studies linked to the clinical presentation of the condition. All participants exhibited normal click-ABR tests. FFR waveforms were documented using the /da/ syllable employing the Navigator Pro. The statistical analysis used was ANOVA (p-value <0.05). Results: no distinctions were observed concerning the variables of group, age, or gender with respect to FFR latency values, except for an interaction between gender and group for latency values associated with waves V and F. Children with CZS and microcephaly showed a difference for latency values in wave V for both males and females, when compared to the control group. Conclusion: children presented with CZS and microcephaly showed higher average latencies for waves V, A, C, D and F (male) compared to the control group, whereas, in waves E, F (female) and O they showed higher values in the control group.

Morphological and functional cardiac alterations in children with congenital Zika syndrome and severe neurological deficits.

INTRODUCTION: Zika virus infection during pregnancy causes fetal microcephaly and brain damage. Congenital Zika syndrome (CZS) is characterized by systemic involvement with diffuse muscle impairment, a high frequency of arthrogryposis, and microphthalmia. Cardiac impairment in CZS has rarely been evaluated. Our study assessed morphology and biventricular cardiac function in children with CZS and advanced neurological dysfunction. METHODS: This cross-sectional study was conducted on 52 children with CZS (Zika group; ZG) and 25 healthy children (control group; CG) in Paraiba, Brazil. Clinical evaluation, electrocardiogram (EKG), and transthoracic echocardiogram (TTE) were performed on all children. Additionally, troponin I and natriuretic peptide type B (BNP) levels, the degree of cerebral palsy, and neuroimaging findings were assessed in the ZG group. RESULTS: The median age of the study population was 5 years in both groups, and 40.4% (ZG) and 60% (CG) were female. The most prevalent electrocardiographic alteration was sinus arrhythmia in both the ZG (n = 9, 17.3%) and CG (n = 4, 16%). The morphological parameters adjusted for Z score were as follows: left ventricular (LV) end-diastolic diameter in ZG: -2.36 [-5.10, 2.63] vs. CG: -1.07 [-3.43, 0.61], p<0.001); ascending aorta (ZG: -0.09 [-2.08, 1.60] vs. CG: 0.43 [-1.47, 2.2], p = 0.021); basal diameter of the right ventricle (RV) (ZG: -2.34 [-4.90, 0.97] vs. CG: -0.96 [-2.21, 0.40], p<0.01); and pulmonary artery dimension (ZG: -2.13 [-5.99, 0.98] vs. CG: -0.24 [-2.53, 0.59], p<0.01). The ejection fractions (%) were 65.7 and 65.6 in the ZG and CG, respectively (p = 0.968). The left atrium volume indices (mL/m2) in the ZG and CG were 13.15 [6.80, 18.00] and 18.80 [5.90, 25.30] (p<0.01), respectively, and the right atrium volume indices (mL/m2) were 10.10 [4.90, 15.30] and 15.80 [4.10, 24.80] (p<0.01). The functional findings adjusted for Z score were as follows: lateral systolic excursion of the mitral annular plane (MAPSE) (ZG: 0.36 [-2.79, 4.71] vs. CG: 1.79 [-0.93, 4.5], p = 0.001); tricuspid annular plane systolic excursion (TAPSE) (ZG: -2.43 [-5.47, 5.09] vs. CG: 0.07 [-1.98, 3.64], p<0.001); and the S' of the RV (ZG: 1.20 [3.35, 2.90] vs. CG: -0.20 [-2.15, 1.50], p = 0.0121). No differences in biventricular strain measurements were observed between the groups. Troponin I and BNP levels were normal in in the ZG. Grade V cerebral palsy and subcortical calcification were found in 88.6% and 97.22% of children in the ZG group, respectively. CONCLUSION: A reduction in cardiac dimensions and functional changes were found in CZS patients, based on the TAPSE, S' of the RV, and MAPSE, suggesting the importance of cardiac evaluation and follow-up in this group of patients.

Sleep in children from northeastern Brazil with congenital Zika syndrome: assessment using polysomnography.

STUDY OBJECTIVES: We performed this study to describe the characteristics of sleep in children with congenital Zika syndrome through polysomnographic assessment. METHODS: Polysomnography with neurological setup and capnography was performed. Respiratory events were scored according to American Academy of Sleep Medicine criteria. Children were classified based on neuroclinical examination as having corticospinal plus neuromuscular abnormalities or exclusively corticospinal abnormalities. Neuroradiological classification was based on imaging exams, with children classed as having supratentorial plus infratentorial abnormalities or exclusively supratentorial abnormalities. RESULTS: Of 65 children diagnosed with congenital Zika syndrome, sleep apnea was present in 23 children (35.4%), desaturation in 26 (40%), and snoring in 13 (20%). The most prevalent apnea type was central in 15 children (65.2%), followed by obstructive apnea in 5 (21.7%) and mixed type in 3 (13%). The average of the lowest saturation recorded was slightly below normal (89.1 ± 4.9%) and the mean partial pressure of end-tidal carbon dioxide value was normal. Periodic leg movements were present in 48 of 65 children. Lower ferritin levels were observed in 84.6% of children. Palatine and pharyngeal tonsils (adenoids) were small in most children and not associated with the presence of obstructive apnea. Ventriculomegaly and subcortical and nucleus calcification were the most frequent neuroimaging findings. Supratentorial and infratentorial anomalies were present in 26.7% (16 of 60) and exclusively supratentorial changes in 73.3% (44 of 60). In the neuroclinical classification, isolated corticospinal changes were more frequent and the mean peak in capnography was lower in this group. There was no difference regarding the presence of apnea for children in the neuroclinical and neuroradiological classification groups. CONCLUSIONS: Sleep disorders were frequent in children with congenital Zika syndrome, with central sleep apnea being the main finding. CITATION: Brandão Marquis V, de Oliveira Melo A, Pradella-Hallinan M, et al. Sleep in children from northeastern Brazil with congenital Zika syndrome: assessment using polysomnography. J Clin Sleep Med. 2023;19(10):1759-1767.

Follow-up of infants with congenital syphilis during the penicillin shortage period

Abstract Objective To analyze the follow-up, in specialized outpatient clinics, of infants reported with congenital syphilis during the penicillin shortage. Method A cross-sectional study was carried out in ten public maternity hospitals affiliated with the Brazilian Unified Health System in the city of Fortaleza, state of Ceará. Clinical records of infants reported with congenital syphilis who were born alive in 2015 were used to describe correlates of attendance at recommended clinical follow-up appointments. Results A total of 469 infants reported with CS from January 1/2015 to December 31/2015 were included in the analysis. The results show that most infants did not attend the follow-up visits (368/469, 78.5%) and the main associated factors are that the follow-up clinic is located in a different hospital from that where the infant was born (OR: 3.7; CI: 2.20-6.22; p< 0.001) and the use of illicit drugs by the mother (OR: 3.2; CI: 1.57-6.87; p= 0.002). Only 33.7% (34/101) were followed until discharge. Conclusion The majority of infants with reported congenital syphilis during this period did not attend the follow-up visits. Public health efforts aimed at reaching the parents of infants with CS should be a priority to ensure appropriate clinical identification and management of the associated outcomes of this vertically transmitted infection.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2).

INTRODUCTION: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. PATIENTS AND METHODS: This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. RESULTS: Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. CONCLUSION: The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.

Acute and chronic lung injuries are among the leading causes of mortality worldwide. Lung injury can affect several components of the respiratory system, including the airways, parenchyma, and pulmonary vasculature. Although acute and chronic lung injuries represent an enormous economic and clinical burden, currently available therapies primarily focus on alleviating disease symptoms rather than reversing and/or preventing lung pathology. Moreover, some supportive interventions, such as oxygen and mechanical ventilation, can lead to (further) deterioration of lung function and even the development of permanent injuries. Lastly, sepsis, which can originate extrapulmonary or in the respiratory system itself, contributes to many cases of lung-associated deaths. Considering these challenges, we aim to summarize molecular and cellular mechanisms, with a particular focus on airway inflammation and oxidative stress that lead to the characteristic pathophysiology of acute and chronic lung injuries. In addition, we will highlight the limitations of current therapeutic strategies and explore new antioxidant-based drug options that could potentially be effective in managing acute and chronic lung injuries.

Motor and cognitive response to intensive multidisciplinary therapy: the first reported case of congenital Zika virus syndrome.

PURPOSE: To provide a detailed description of the development of the first case of congenital Zika syndrome (CZS) to be reported in the literature worldwide. CASE DESCRIPTION: This report describes the case of a child with CZS monitored from pregnancy until four years of age, with periodic evaluations of head circumference, weight, height, motor function according to the Gross Motor Function Measure (GMFM-88), and the occurrence of comorbidities. OUTCOMES: The child's birth weight and length were normal (z-score = 1.1 and -1.95, respectively), while head circumference was below the expected value (z-score = -3.15). At 48 months, head circumference reached 43 cm (z-score = -4.48). During daily home physiotherapy sessions, the child achieved developmental milestones, standing unsupported at 17 months, with a GMFM-88x score of 137. With specialist therapy, the child walked independently at 36 months and a total GMFM-66 score of 214 was achieved by 42 months. In the four years of follow-up, the child was hospitalized four times for different reasons. No convulsive seizures occurred. CONCLUSIONS: Despite severe neurological impairment, the child's weight and height are adequate for age, with motor and cognitive function improving over the first four years of life.

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Follow-up of infants with congenital syphilis during the penicillin shortage period.

OBJECTIVE: To analyze the follow-up, in specialized outpatient clinics, of infants reported with congenital syphilis during the penicillin shortage. METHOD: A cross-sectional study was carried out in ten public maternity hospitals affiliated with the Brazilian Unified Health System in the city of Fortaleza, state of Ceará. Clinical records of infants reported with congenital syphilis who were born alive in 2015 were used to describe correlates of attendance at recommended clinical follow-up appointments. RESULTS: A total of 469 infants reported with CS from January 1/2015 to December 31/2015 were included in the analysis. The results show that most infants did not attend the follow-up visits (368/469, 78.5%) and the main associated factors are that the follow-up clinic is located in a different hospital from that where the infant was born (OR: 3.7; CI: 2.20-6.22; p < 0.001) and the use of illicit drugs by the mother (OR: 3.2; CI: 1.57-6.87; p = 0.002). Only 33.7% (34/101) were followed until discharge. CONCLUSION: The majority of infants with reported congenital syphilis during this period did not attend the follow-up visits. Public health efforts aimed at reaching the parents of infants with CS should be a priority to ensure appropriate clinical identification and management of the associated outcomes of this vertically transmitted infection.

The Impact of COVID-19 Pandemic and Social Distancing on Motor Function and Growth of Children with Congenital Zika Syndrome: A Prospective Cohort Study.

This article describes the impact of social distancing during the COVID-19 pandemic on the motor function and growth of children with congenital Zika syndrome (CZS). Children's motor function, weight, height and joint range of movement (ROM) were evaluated before the onset of the pandemic and soon after their return to face-to-face activities at a rehabilitation center. Fifty-two children (Mean 46.07 months, SD 3.76 months) were assessed. Results showed a reduction in proportion of children with adequate body mass index (p = .04), an increase in proportion with adequate height (p < 0.001), deterioration in gross motor function in children with severe motor impairment (p < .01), and a reduction in the maximum ROM for shoulder (p < .01) and wrist flexion (p = .046), elbow (p = .01), knee (p = .03) and ankle extension (p < .01), and an increase in hip flexion (p = .04). The social distancing period appears to have contributed to important losses in motor function and joint mobility of children with CZS; however, this period of time appeared to have less impact on their growth.

A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)

Abstract Introduction The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary (t).

My child is growing and now? Exploring the environmental needs of children with congenital Zika syndrome according to their caregivers' perceptions.

INTRODUCTION: Promoting social inclusion of children with congenital Zika virus syndrome (CZS) is challenging, mostly, when there is a transport problem, low access to information and a long distance between the house and health services. Participation can be understood as involvement in a life situation and is strongly influenced by physical, social and attitudinal environmental factors; however, was still little explored in the case of children with CZS. In this sense, this study aimed to explore the perception of caregivers about the environmental needs of children with CZS, differentiating barriers and facilitators. METHODS: This is qualitative research. Thematic analysis was used to identify the environmental needs perceived by caregivers of children with CZS. The patient public involvement (PPI) approach was incorporated with the purpose of validating the data analysis performed by the researchers. After this step, the data were categorized in terms of barriers and facilitators and validated by the group of researchers. RESULTS: A relevant environmental need reported by caregivers as a barrier was social support for children with CZS. Ableism was also evidenced as an important attitudinal barrier. Health services were essential for the lives of children with CZS and the availability of auxiliary devices as facilitators of participation. Environmental factors related to medication and food routines were, for the most part, facilitators. CONCLUSION: This study contributes to critical approaches to the impacts linked to environmental factors of children with CZS, recognition of these children is an evolving process and fundamental to basic rights for adequate living in society. The data point to the need to implement public policies aimed at children with CZS, as well as the availability of qualified professionals to apply family-centred care and skills-focused management. Building friendly environments that promote broad social participation will contribute to the healthy growth of children with CZS. PATIENT OR PUBLIC CONTRIBUTION: Six caregivers (20% of the caregivers) as part of the PPI approach were contacted and participated in individual virtual meetings to discuss the results of the thematic analysis regarding the environmental needs of children with CZS.

Effect of neurodevelopmental treatment in children with congenital Zika syndrome: A pilot study.

AIM: To evaluate the effects of neurodevelopmental treatment (NDT) in children with congenital Zika syndrome (CZS). METHODS: This prospective, interventional cohort study involved children with CZS undergoing follow-up at a specialist centre in northeastern Brazil. The duration of the proposed NDT protocol was 1 year, with 45-min sessions delivered one to five times weekly. Motor function, weight, height, head circumference and the incidence of comorbidities were evaluated in children before protocol initiation and then at 3, 6 and 12 months of treatment. RESULTS: Thirty children were evaluated (age mean 30.1 ± 3 months). Motor function improved from baseline to 6 months (P = 0.001). No difference in weight and head circumference z-score (P = 0.51 and P = 0.29, respectively), but an increase in height z-score (P < 0.001) was observed over the evaluation period. There was a reduction in the incidence of upper respiratory tract infections, pneumonia and urinary tract infections over the follow-up period. CONCLUSIONS: NDT proved to be a viable treatment approach that can improve motor function and reduce the incidence of comorbidities in children with CZS, while having no harmful effects on their growth.

Microbial inoculation and fertilizer application on growth of cowpea and spore-based assemblages of arbuscular mycorrhizal fungi in its rhizophere.

In this study, the effect of microbial inoculants and fertilizer application on cowpea (BRS Pujante) growth and on the structure and composition of arbuscular mycorrhizal fungi (AMF) assemblages were evaluated. A completely randomized experiment was set up involving 17 treatments: four with AMF, three with nodulating bacteria, six with AMF + nodulating bacteria, two with phosphorus, one with nitrogen and one control (reference) in five replicates. Plant growth and nutritional content, mycorrhizal colonization, glomerospores number, spore-based AMF assemblages and ecological indices were evaluated. Mycorrhizal inoculants associated with Bradyrhizobium BR3267 strain were more effective than the Microvirga BR3296 strain. Multidimensional scaling analysis showed that Acaulospora longula treatments were more similar among themselves, and distinct from the other treatments. A difference was observed in the structure of AMF community assemblage between treatments with G. albida + Bradyrhizobium BR 3267 and A. longula, with greater Shannon diversity and Pielou equitability indices in the first treatment and greater dominance in the treatment with A. longula only. Long-term studies are required to determine if the successful establishment of A. longula among indigenous species persists over time and if its dominant behavior is not deleterious to the AMF native community.

Urological outcomes in children with congenital Zika syndrome: The experience of a cohort in Campina Grande, Brazil.

OBJECTIVE: To describe the urological outcomes in children with congenital Zika syndrome (CZS) and investigate the relationship between clinical and urological findings in this population. METHODS: This cross-sectional study involved children with CZS followed up by a referral centre for children with microcephaly in the state of Paraiba in northeast Brazil. The urological evaluation included clinical history, urine culture results, ultrasonography of the urinary tract, and urodynamic evaluation, following the protocol proposed by Costa Monteiro et al. (2017). Descriptive statistical analysis was performed in addition to association and correlation tests, considering clinical and urodynamic variables. RESULTS: Among the 88 children with CZS (35.5 ± 5.5 months), 97.7% had microcephaly, and 51% presented urinary tract infection (UTI) confirmed with clinical history and lab tests. The number of confirmed UTI episodes varied from one to 14 per child. The urodynamic evaluation confirmed the presence of an overactive bladder in 78 children and incomplete voiding in 50. Urodynamic findings were associated with the number of confirmed UTI episodes, child's sex, and actual weight, in addition to the use of anticonvulsant and myorelaxant drugs. CONCLUSIONS: UTIs were confirmed in most children. Other urological outcomes observed were overactive bladder and low bladder capacity, which were associated with the number of confirmed UTI episodes, use of anticonvulsants and myorelaxants, and the child's sex and weight. These are treatable conditions, and it is paramount that paediatricians, neonatologists, and infectious disease specialists are aware of them to make clinical decisions and help reduce the risk of renal damage and other morbidities.

Organização do processo de trabalho através de conhecimento, atitudes e práticas para administração segura de vacinas em crianças: uma revisão de escopo / Organización del proceso de trabajo a través de conocimientos, actitudes y prácticas para la administración segura de vacunas en niños: una revisión de alcance / Organization of the work process through knowledge, attitudes, and practices for safe administration of vaccines in children: a scoping review

RESUMO Objetivo: mapear a organização do processo de trabalho através de conhecimento, atitudes e práticas para administração segura de vacinas em crianças. Método: realizou-se uma revisão de literatura com o método Scoping Review, de acordo com as recomendações do guia internacional PRISMA-ScR, e o método do Joanna Briggs Institute Reviewers Manual. A busca eletrônica dos estudos foi realizada nas bases de dados PubMed, CINAHL, Web of Science, Scopus, COCHRANE, LILACS e PsycINFO e na literatura cinzenta, entre os anos 2000 e 2021. Foram incluídos artigos, revisões, teses, dissertações e manuais disponibilizados na íntegra que estivessem em consonância com o objetivo deste estudo, tendo sido contemplando os idiomas inglês, português, italiano, espanhol e francês. Foram excluídos da revisão estudos não gratuitos pela plataforma CAFe, duplicados, que não tivessem relação com a temática pesquisada e não tivessem sua metodologia bem definida. Resultados: a revisão englobou 19 estudos publicados. O Brasil foi o país com maior número de estudos. Os principais achados propiciaram a construção das categorias conceituais. As sete primeiras se referem às principais características dos estudos incluídos nesta revisão de escopo; as outras três categorias objetivaram responder à questão norteadora e foram compostas por indicadores presentes na organização do processo de trabalho antes, durante e após a administração segura de uma vacina na criança. Conclusão: conclui-se que os objetivos desta pesquisa foram alcançados mediante mapeamento da organização do processo de trabalho através de conhecimento, atitudes e práticas para administração segura de vacinas em crianças. Como limitação deste estudo, evidencia-se a escassez de pesquisas que norteiam os cuidados pós-vacinação e sugere-se que novas pesquisas sejam realizadas.

RESUMEN Objetivo: mapear la organización del proceso de trabajo a través de los conocimientos, actitudes y prácticas para la administración segura de vacunas en niños. Método: se realizó una revisión de la literatura mediante el método Scoping Review, según las recomendaciones de la guía internacional PRISMA-ScR y el método Joanna Briggs Institute Reviewers Manual. La búsqueda electrónica de estudios se realizó en las bases de datos PubMed, CINAHL, Web of Science, Scopus, COCHRANE, LILACS y PsycINFO y en la literatura gris entre los años 2000 y 2021. Se incluyeron artículos, revisiones, tesis, disertaciones y manuales disponibles en su totalidad que estuvieran en línea con el objetivo de este estudio, en inglés, portugués, italiano, español y francés. Se excluyeron de la revisión los estudios no gratuitos a través de la plataforma CAFe, los duplicados, los que no estaban relacionados con el tema investigado y los que no tenían bien definida su metodología. Resultados: la revisión incluyó 19 estudios publicados. Brasil fue el país con el mayor número de estudios. Los principales resultados propiciaron la construcción de las categorías concebidas, las siete primeras se refieren a las principales características de los estudios incluidos en esta revisión de alcance, las otras tres categorías tienen como objetivo responder a la pregunta orientadora y se componen de indicadores presentes en la organización del proceso de trabajo antes, durante y después de la administración segura de una vacuna en el niño. Conclusión: se concluye que se lograron los objetivos de esta investigación al mapear la organización del proceso de trabajo a través de los conocimientos, actitudes y prácticas para la administración segura de las vacunas en los niños, se evidencia como limitación de este estudio la escasez de investigaciones que orienten la atención post-vacunación y se sugiere la realización de nuevas investigaciones.

ABSTRACT Objective to map the organization of the work process through knowledge, attitudes, and practices for the safe administration of vaccines in children. Method: a literature review was carried out using the Scoping Review method, in accordance with the recommendations of the international PRISMA-ScR guide, and the method of the Joanna Briggs Institute Reviewers Manual. The electronic search of the studies was carried out in the databases PubMed, CINAHL, Web of Science, Scopus, COCHRANE, LILACS and PsycINFO and in the gray literature, between the years 2000 and 2021. Articles, reviews, theses, dissertations, and manuals available were included. in full that were in line with the objective of this study, having been contemplating the English, Portuguese, Italian, Spanish and French languages. Studies that were not free of charge through the CAFe platform, duplicated, unrelated to the researched theme and that did not have a well-defined methodology were excluded from the review. Results: the review included 19 published studies. Brazil was the country with the highest number of studies. The main findings led to the construction of conceptual categories. The first seven refer to the main characteristics of the studies included in this scope review; the other three categories aimed to answer the guiding question and were composed of indicators present in the organization of the work process before, during and after the safe administration of a vaccine to the child. Conclusion: it is concluded that the objectives of this research were achieved by mapping the organization of the work process through knowledge, attitudes, and practices for the safe administration of vaccines in children. As a limitation of this study, there is a lack of research that guides post-vaccination care, and it is suggested that further research be carried out.

Identification and characterisation of SARS-CoV-2 and Human alphaherpesvirus 1 from a productive coinfection in a fatal COVID-19 case.

BACKGROUND: During routine Coronavirus disease 2019 (COVID-19) diagnosis, an unusually high viral load was detected by reverse transcription real-time polymerase chain reaction (RT-qPCR) in a nasopharyngeal swab sample collected from a patient with respiratory and neurological symptoms who rapidly succumbed to the disease. Therefore we sought to characterise the infection. OBJECTIVES: We aimed to determine and characterise the etiological agent responsible for the poor outcome. METHODS: Classical virological methods, such as plaque assay and plaque reduction neutralisation test combined with amplicon-based sequencing, as well as a viral metagenomic approach, were performed to characterise the etiological agents of the infection. FINDINGS: Plaque assay revealed two distinct plaque phenotypes, suggesting either the presence of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains or a productive coinfection of two different species of virus. Amplicon-based sequencing did not support the presence of any SARS-CoV-2 genetic variants that would explain the high viral load and suggested the presence of a single SARS-CoV-2 strain. Nonetheless, the viral metagenomic analysis revealed that Coronaviridae and Herpesviridae were the predominant virus families within the sample. This finding was confirmed by a plaque reduction neutralisation test and PCR. MAIN CONCLUSIONS: We characterised a productive coinfection of SARS-CoV-2 and Herpes simplex virus 1 (HSV-1) in a patient with severe symptoms that succumbed to the disease. Although we cannot establish the causal relationship between the coinfection and the severity of the clinical case, this work serves as a warning for future studies focused on the interplay between SARS-CoV-2 and HSV-1 coinfection and COVID-19 severity.