Clinical Manifestations of Kawasaki Disease at Different Age Spectrum: A Ten-Year Study.

Background and objectives: The present study is the first known in Latin America to enroll a substantial number of Kawasaki disease (KD) patients with an extended follow-up. This study aimed to: (1) to expose the difficulties and delays in the diagnosis of KD in a developing country, (2) to describe and correlate the clinical features of this disorder with the children's age at the time of disease onset, (3) to correlate the frequent lack of early diagnosis with a delayed application of appropriate treatment, and (4) to describe the outcome and eventual recurrences of KD in our region. Materials and Methods: Three hundred and one participants (183 males and 118 females) included in the study were diagnosed and, subsequently, clinically followed for ten years (January 2007 to December 2016) at the Pediatric Rheumatology Walk-in Clinic of the Children's Hospital of Brasilia. Results: Episodes ranged from four months to two years. This rate of recurrence was well-above that disclosed by previous reports. Delay in diagnosis, in all age groups, caused an undesirable delay between the disease onset, the final diagnosis, and the administration of intravenous immunoglobulin (IVIG). KD recurred in 25 (8.3%) of the children during the first three years of follow-up. In seven patients, KD recurred twice, with an interval between episodes ranging from four months to two years. Conclusions: This rate of recurrence was well-above that disclosed by previous reports. In Latin America, aside from a handful of physicians and researchers, KD is being ignored. There is a pressing need to educate primary health care physicians and bring awareness to the fact that KD is not an exotic condition that affects only the Asian populations but a disorder that already exists among us and that frequently results in severe consequences.

Molecular evaluation of anti-inflammatory activity of phenolic lipid extracted from cashew nut shell liquid (CNSL).

BACKGROUND: Anacardium occidentale L phenolic lipid (LDT11) is used in traditional medicine as anti-inflammatory, astringent, antidiarrheal, anti-asthmatic and depurative. Phenolic derivatives, such as anacardic acid, extracted from cashew nut shell liquid (CNSL) have demonstrated biological and pharmacological properties, and its profile makes it a candidate for the development of new anti-inflammatory agents. The objective of the present study was to evaluate the anti-inflammatory profile of a derivative, synthesized from LDT11, on an in vitro cellular model. METHODS: Organic synthesis of the phenolic derivative of CNSL that results in the hemi-synthetic compound LDT11. The cytotoxicity of the planned compound, LDT11, was analyzed in murine macrophages cell line, RAW264.7. The cells were previously treated with LDT11, and then, the inflammation was stimulated with lipopolysaccharide (LPS), in intervals of 6 h and 24 h. The analysis of the gene expression of inflammatory markers (TNFα, iNOS, COX-2, NF-κB, IL-1ß and IL-6), nitric oxide (NO) dosage, and cytokine IL-6 were realized. RESULTS: The results showed that the phenolic derivative, LDT11, influenced the modulatory gene expression. The relative gene transcripts quantification demonstrated that the LDT11 disclosed an immunoprotective effect against inflammation by decreasing genes expression when compared with cells stimulated with LPS in the control group. The NO and IL-6 dosages confirmed the results found in gene expression. DISCUSSION: The present study evaluated the immunoprotective effect of LDT11. In addition to a significant reduction in the expression of inflammatory genes, LDT11 also had a faster and superior anti-inflammatory action than the commercial products, and its response was already evident in the test carried out six hours after the treatment of the cells. CONCLUSION: This study demonstrated LDT11 is potentially valuable as a rapid immunoprotective anti-inflammatory agent. Treatment with LDT11 decreased the gene expression of inflammatory markers, and the NO, and IL-6 production. When compared to commercial drugs, LDT11 showed a superior anti-inflammatory action.

Gluten contamination in gluten-free bakery products: a risk for coeliac disease patients.

OBJECTIVE: The present study aimed to assess the safety of gluten-free bakery products for consumption by coeliac patients. Design/setting In the current exploratory cross-sectional quantitative study, a total of 130 samples were collected from twenty-five bakeries in Brasilia (Brazil). For the quantification of gluten, an ELISA was used. The threshold of 20 ppm gluten was considered as the safe upper limit for gluten-free food, as proposed in the Codex Alimentarius. RESULTS: The results revealed a total of 21·5 % of contamination among the bakery products sampled. Sixty-four per cent of the bakeries sold at least one contaminated product in our sample. CONCLUSIONS: These findings represent a risk for coeliac patients since the ingestion of gluten traces may be sufficient to adversely impact on their health.

Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant.

Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25 169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P = 1.79 × 10(-49)), without any novel associations. The conditional analysis on this top SNP-indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P < 0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 × 10(-44)). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P = 3.12 × 10(-49)), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD.

Activity of crude extracts from Brazilian cerrado plants against clinically relevant Candida species.

BACKGROUND: Medicinal plants have traditionally been used in many parts of the world as alternative medicine. Many extracts and essential oils isolated from plants have disclosed biological activity, justifying the investigation of their potential antimicrobial activity. In this study, the in vitro antifungal activity of six Brazilian Cerrado medicinal plant species were evaluated against clinically relevant Candida species. METHODS: The crude extract plants were evaluated against American Type Culture Collection (ATCC) standard strains of Candida spp. using disk diffusion method and determining the minimum inhibitory concentration (MIC). The chemical study results were confirmed by HPLC method. RESULTS: All six plant species showed antifungal activity. Among the species studied, Eugenia dysenterica and Pouteria ramiflora showed significant inhibitory activity against C. tropicalis at lowest MIC value of 125 and 500 µg/disc, respectively. The Eugenia dysenterica also disclosed MIC value of 125 µg/disc against C. famata, 250 µg/disc against C. krusei and 500 µg/disc against C. guilliermondii and C. parapsilosis. Pouteria torta, Bauhinia rufa, Erythroxylum daphnites and Erythroxylum subrotundum showed activity against the yeast strains with MIC value of 1000 µg/disc. The chemical study of the most bioactive extracts of Eugenia dysenterica and Pouteria ramiflora revealed catechin derivatives and flavonoids as main components. CONCLUSIONS: All six evaluated plant species showed good antifungal potential against several Candida strains. However, E .dysenterica and P. ramiflora showed the higher inhibitory effect against the non-albicans Candida species. Our results may contribute to the continuing search of new natural occurring products with antifungal activity.

Hyper-responsiveness to acute stress, emotional problems and poorer memory in former preterm children.

The prevalence of preterm birth (PTB) is high worldwide, especially in developing countries like Brazil. PTB is marked by a stressful environment in intra- as well as extrauterine life, which can affect neurodevelopment and hormonal and physiological systems and lead to long-term negative outcomes. Nevertheless, little is known about PTB and related outcomes later on in childhood. Thus, the goals of the current study were threefold: (1) comparing cortisol and alpha-amylase (sAA) profiles, including cortisol awakening response (CAR), between preterm and full-term children; (2) evaluating whether preterm children are more responsive to acute stress and (3) assessing their memory skills and emotional and behavioral profiles. Basal cortisol and sAA profiles, including CAR of 30 preterm children, aged 6 to 10 years, were evaluated. Further, we assessed memory functions using the Wide Range Assessment of Memory and Learning, and we screened behavior/emotion using the Strengths and Difficulties Questionnaire. The results of preterm children were compared to an age- and sex-matched control group. One week later, participants were exposed to a standardized laboratory stressor [Trier Social Stress Test for Children (TSST-C)], in which cortisol and sAA were measured at baseline, 1, 10 and 25 min after stressor exposure. Preterm children had higher cortisol concentrations at awakening, a flattened CAR and an exaggerated response to TSST-C compared to full-term children. These alterations were more pronounced in girls. In addition, preterm children were characterized by more emotional problems and poorer memory performance. Our findings illustrate the long-lasting and in part sex-dependent effects of PTB on the hypothalamic-pituitary-adrenal (HPA) axis, internalizing behavior and memory. The findings are in line with the idea that early adversity alters the set-point of the HPA axis, thereby creating a more vulnerable phenotype.

Screening for celiac disease in 1st degree relatives: a 10-year follow-up study.

BACKGROUND: Although it is known that first degree relatives of celiac patients have an increased risk for celiac disease few studies are available on its incidence. We investigated the incidence of serologic conversion and of new cases of celiac disease among first degree relatives with negative results at a first screening. METHODS: From a total of 634 first degree relatives of 186 biopsy-proven celiac disease patients diagnosed between October 2000 and October 2010, 450 subjects agreed to participate in the study (Group I), and underwent serologic screening. Between January 2010 and October 2012, out of the initial group of 450, 205 previously sero-negative subjects consented to participate in a second stage of the study and undergo new serologic testing (Group II). All serologically positive individuals of both groups (I and II) were genotyped for celiac disease-predisposing alleles (HLA-DQ2/DQ8). RESULTS: 19 subjects (4.2%) out of the 450 subjects of Group I disclosed positive serologic results, presence of DQ2 and/or DQ8 alleles and celiac disease-compatible mucosal abnormalities. The 205 previously negative first degree relatives from Group II that underwent new serologic testing disclosed eight sero-converted subjects. Mucosal abnormalities in five of these patients confirmed the diagnosis of celiac disease. During the 10-year period of the study the incidence of sero-conversion was 8/205 and the incidence of biopsy-proven celiac disease cases was 5/205. CONCLUSIONS: Our data are coincident with other works on this subject and confirm once again that relatives of celiac patients, especially first degree relatives are at high risk of developing celiac disease. In view of the relatively low incidence further studies are needed to try to establish a useful and cost-effective algorithm for follow-up of relatives of celiac patients.

Evaluation of 25-hydroxy-vitamin D and parathyroid hormone in Callithrix penicillata primates living in their natural habitat in Brazil.

BACKGROUND: Vitamin D is a secosteroid hormone with important roles in the control of bone and mineral metabolism of vertebrates and in the maintenance of systemic homeostasis. This study aimed (i) to evaluate the serum concentrations of 25-hydroxy-vitamin D levels [25(OH)D], parathyroid hormone (PTH) and ionized calcium (iCa) of wild Callithrix penicillata (black-tufted marmosets) and (ii) to propose reference ranges for those analytes for free-living marmosets. METHODS: Blood samples were collected from 15 wild animals and analyzed for 25(OH)D, PTH and iCa. Reference values were calculated following standard analytical criteria. RESULTS: The observed mean serum levels (±standard deviation) were 25(OH)D, 61.7 (±20.8) ng/ml; PTH, 275.2 (±34.1) pg/ml; iCai 4.0 (±0.6) mg/dl. CONCLUSIONS: For free-living marmosets, the proposed physiological range for 25(OH)D is 20.1-103.3 ng/ml and for PTH is 207.0-343.3 pg/dl, with a confidence interval of 95%.

Does celiac disease occur in Afro-derived Brazilian populations?

BACKGROUND: Celiac disease is an autoimmune disorder that occurs in genetically susceptible individuals in whom the ingestion of dietary gluten induces intestinal mucosa inflammation. Previous studies suggest that celiac disease may either be very rare or underdiagnosed in African and/or African-derived population. AIM: Determine the prevalence of celiac disease in Sub-Saharan African-derived Brazilian communities using serological screening. SUBJECTS AND METHODS: Inhabitants from 10 African-derived communities from Northeastern of Brazil were screened for celiac disease. All sera were tested for endomysial class IgA antibody using indirect immunofluorescence. RESULTS: No positive test for IgA-endomysial was observed in the 860 individuals tested. CONCLUSION: Our data suggests a low prevalence of celiac disease in African-derived Brazilian populations.

Health-Related Quality of Life and Experiences of Brazilian Celiac Individuals over the Course of the Sars-Cov-2 Pandemic.

Since the end of 2019, the world has been facing an unpredicted COVID-19 pandemic with consequences for the economy, environment, society, and health. The COVID-19 pandemic has increased the risk of death, bringing unbearable psychological pressure upon people worldwide. For celiac patients, the pandemic may represent an additional burden concerning the inherent aspects of celiac disease (CD) that compromise these individuals' quality of life (QoL). Therefore, the objective of this study was to evaluate Brazilian celiac patients' QoL during the course of the COVID-19 pandemic caused by its outbreak and rapid spread and subsequent restrictive measures in addition to the dietary restrictions and other burdens caused by CD. This country-wide cross-sectional study was conducted using a self-administered instrument previously validated in Brazilian-Portuguese to investigate the QoL of individuals with CD. Data collected through the online self-administration of the Brazilian version of the celiac disease quality of life questionnaire (CDQ) comprised 674 CD individuals' responses. Although pandemics have historically posed a challenge for Brazilian population, this period was not associated with a negative impact on Brazilian CD individuals' QoL. During the pandemic, the QoL of Brazilian's with CD was more affected by gastrointestinal aspects than emotions and social aspects and worries. Gender, age, marital status, having (or not) children, occupation, and a positive test for COVID-19 did not affect CD individuals' QoL. However, the study revealed a larger burden and diminished QoL for individuals not following a gluten-free diet and those using antidepressants. Additional research is necessary to verify how the length of the pandemic will affect celiac individuals and then compare those outcomes compare to the COVID-19 period and after.

Quality of Life in Caregivers of Children and Adolescents with Autistic Spectrum Disorder: Development and Validation of the Questionnaire.

Studies have shown that children and adolescents with autism and their relatives present a high level of stress and more family problems, impacting parents' and caregivers' quality of life (QoL). Despite studies on this subject, there is no specific questionnaire to evaluate QoL in parents or caregivers of children and adolescents with an autistic spectrum disorder (ASD) in Brazil. Therefore, this study's primary purpose was to develop and validate a specific questionnaire to evaluate QoL in these individuals. The study was performed using the following steps: development of the ASD Parent/caregiver QoL questionnaire (autistic spectrum disorder parent/caregiver quality of life-ASDPC-QoL), subjective evaluation, validation of the questionnaire by the Delphi method, assessment of internal consistency, responsiveness, and reliability of the ASLPC-QoL, and administration of the questionnaire to 881 Brazilian ASD caregivers or parents. ASDPC-QoL comprises 28 questions divided into four domains (social, concerns, physical and mental health) with good psychometric properties (reproducibility, reliability, internal consistency, responsiveness, and validity). Our data showed that worries and physical health were the domains with the lowest scores in ASDPCA-QoL. ASDPCA-QoL did not differ among gender and age of child considering the total and all domains. Older participants (≥41 y/o) presented the best scores for social and worries domains but did not differ in other domains and the total. Parents or caregivers of ASD children diagnosed for more than three years have better mental and physical health domains than those recently diagnosed (up to 1 year) but did not differ in the total and other domains. Individuals with a partner and with the highest educational level present the best score for the social domain. Employed individuals showed better scores than unemployed ones for all domains and the total, except for worries, which did not differ. It also occurred comparing the individuals that do not use antidepressants and the ones that use them. Assessing and better understanding the QoL of caregivers is highly relevant. By understanding the social, worries, physical, and emotional health domains of caregivers, it is possible to track harmful aspects, prevent and treat pathologies, in addition to assisting in the implementation of effective public policies.

Host DNA repair response to oxidative damage is modulated by Trypanosoma cruzi in a strain-dependent manner.

The conservation of genomic integrity and stability is essential for cell survival. DNA Damage Responses (DDRs) are considered of paramount importance for all living beings and involve mechanisms of cell cycle regulation and damage-specific DNA repair pathways. Hydrogen peroxide (H2O2) is a compound that, in supraphysiological concentrations, damages biomolecules including the DNA, causing base modifications and strand breaks. There is evidence that Trypanosoma cruzi, the protozoan that causes Chagas disease, interferes in the host cell's DNA metabolism. In order to investigate the influence of T. cruzi infection over the host cell capacity to withstand and repair DNA damage, we analyzed L6 cells infected with Berenice, and Colombiana T. cruzi strains according to their viability, proliferation, morphology, DNA degradation, expression of DNA repair, and cell cycle genes following H2O2 treatment. It was noted that T. cruzi infection might act as either a stressor or a protective element of host DNA, depending on the strain and H2O2 concentration. Cells infected with Berenice strain and treated with 0.8 mM H2O2 presented a reduced DNA damage response intensity (e.g., BER and HR). Infection with T. cruzi Colombiana prevented the activation of DNA repair pathways in response to 0.8mM and 1.6mM H2O2 (NER and MMR). Nevertheless, since cellular viability was not significantly compromised in Colombiana-infected cells following the oxidative insult, it is possible that the parasite directly influenced the host DNA repair machinery. Our results support the notion that T. cruzi is able to modulate the host cell DNA metabolism in a strain-dependent manner, an event which can be explored in future drug development strategies.

Isolation, Identification, and Screening of Lactic Acid Bacteria with Probiotic Potential in Silage of Different Species of Forage Plants, Cocoa Beans, and Artisanal Salami.

The objective of this study was to isolate and characterize lactic acid bacteria with probiotic potential in silages of different species of forage plants, cocoa beans, and artisanal salami. The obtained isolates were submitted to the following evaluations: (i) screening for tolerance to pH 2 and bile salts, (ii) genotypic identification of isolates, (iii) survival in simulated gastric and pancreatic conditions, (iv) antimicrobial activity, (v) antibiotic susceptibility and safety, and (vi) properties associated with adhesion capacity. A total of 82 isolates were obtained and were screened for pH 2.0 tolerance and capacity to growth in the presence of bile salts (1.0 and 2.0%). Only 19 strains simultaneously presented tolerance to pH 2.0 and bile salts. These 19 strains were evaluated for genetic profile by Box-PCR. Subsequently, the selected strains were subjected to partial sequencing of the 16S rRNA gene. The species Lactobacillus plantarum was prevalent. The identified strains were evaluated for survival under simulated gastric and pancreatic conditions. Some strains have shown tolerance in both conditions. Different strains showed variations in antimicrobial activity, susceptibility to antibiotics, and properties associated with adhesion (hydrophobicity, autoaggregation, coaggregation, and adhesion to CaCo2 cells). All strains were negative for hemolysis, DNase, gelatinase, and biogenic amine synthesis activity. The L. plantarum SBR64.7 strain can be considered the most promising for it presented the lowest viability reduction when exposed to gastric and pancreatic juices.

25-hydroxy-vitamin D levels among Callithrix penicillata primate species raised in captivity.

BACKGROUND: Animals in captivity should receive adequate sunlight exposure for sufficient generation of vitamin D [25(OH)D]. In the present study, 25(OH)D serum levels of 84 Callithrix penicillata primates were evaluated. OBJECTIVES: To determine 25(OH)D levels of those animals; to evaluate the influence of gender and period of sunlight exposure on their 25(OH)D levels. METHODS: Three groups were evaluated: group 1 (n = 29) on free sunlight exposure; group 2 (n = 34) on partial sunlight exposure; group 3 (n = 21) without sunlight exposure. RESULTS: The obtained 25(OH)D values were: group 1, 121.2 +/- 33.3 ng/ml; group 2, 115.2 +/- 32.2 ng/ml; group 3, 53.3 +/- 10.4 ng/ml. Significant statistical differences were obtained between groups 1 and 3 (p < 0.001) and groups 2 and 3 (p < 0.001); no statistical difference was found between genders. CONCLUSION: Direct sunlight exposure is essential for 25(OH)D sufficiency and it is proposed that the 25(OH)D normal range for captive Callithrix penicillata would be from 104.8 to 137.1 ng/ml (CI = 95%).

Auditory-evoked response analysis in Brazilian patients with sickle cell disease.

The objective of the present study was to evaluate the integrity of the peripheral and central auditory systems of sickle cell disease (SCD) patients, through electrophysiological evaluation utilizing auditory evoked potentials, and comparing the results obtained in SCD patients with individuals without SCD. A total of 80 individuals were evaluated: 40 SCD patients; and 40 healthy age- and sex-matched controls. Brainstem auditory evoked response (BAER) was used to check neural integrity and electrophysiological thresholds, and cognitive potential (P300) to analyse the auditory selective attention. Despite the exclusion of individuals with comorbidities typical of SCD, the predominance of hearing loss among the patients was detected in 16 ears (20%). The absolute latencies of the BAER were within the expected range but the SCD group showed a small but statistically significant reduction of the interpeaks I-V, indicative of cochlear alteration. P300 latency and amplitude were adequate for both groups suggesting the absence of central auditory system abnormalities. The present findings suggest that SCD causes variable degree of cochlear abnormalities without evidence of neural problems.

Sensorineural hearing loss: an underdiagnosed complication of Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology in which the main complication is coronary arteritis. Sensorineural hearing loss (SNHL) has also been described as a complication of this disorder. The objective of this study was to evaluate the prevalence of SNHL in patients with KD and to determine the possible causative abnormality, correlating the findings with the prevalence of cardiac complications, with the use of gammaglobulin, and with the results of laboratory tests. METHODS: A clinical cohort of 40 patients with KD seen between 2005 and 2007 was evaluated by acoustic immittance measurement and brainstem-evoked response audiometry that were performed within the first 30 days of disease and 6 months after the first evaluation. Patients with hearing disability after this period underwent further testing through otoacoustic emissions analysis. All patients were treated with intravenous administration of immunoglobulin. RESULTS: Ten (25%) of the 40 patients developed coronary aneurysm, and 22 (55%) disclosed hearing loss within the first 30 days, although this problem was noticed by the parents in only 3 children. In 12 (30%), the hearing loss persisted after 6 months. Ten (83.3%) of these 12 patients also showed thrombocytosis (platelets, >500,000), 8 (66%) had anemia (hemoglobin, <10 mg/dL), and all had high erythrocyte sedimentation rate (>50 mm/hr) persisting more than 30 days. CONCLUSION: SNHL was more prevalent than coronary complications. A significant association was found between persistent SNHL, although often not initially noted, with a prolonged presence of thrombocytosis, anemia, and high erythrocyte sedimentation rate and the delayed use of intravenous administration of immunoglobulin after the first 10 days of illness.

Repercussion of COVID-19 Pandemic on Brazilians' Quality of Life: A Nationwide Cross-Sectional Study.

The COVID-19 outbreak, caused by Sars-Cov-2, was officially declared a global pandemic in February 2020, after an unexpected increase in hospitalization and mortality. When faced with this new disease, social and physical distancing and quarantine emerged as solutions to reduce virus transmission. This article examines the quality of life (QoL) of the Brazilian population's during this period of isolation, due to the COVID-19 pandemic by analyzing; physical, psychological, social, and economic aspects. An online survey was distributed from 27 May to 14 August of 2020. A total of 1859 surveys were completed. Our results indicate that Brazilians were more affected by economic and social aspects than psychological and physical. Unemployed participants and individuals who tested positive for COVID-19 presented the lowest QoL. Females showed worst QoL scores than males, but having children did not influence the score. Higher educational level was associated with a better perception of QoL. Not following social distancing guidelines presented better scores in the psychological domain than the ones following restrict or partial social distancing rules. This study is the first to evaluate adults' QoL related to the Sars-Cov-2 pandemic in Brazil at a national level. Our data may help health authorities identify the main factors affecting the QoL of the Brazilian population, thereby orientating them to recover after the pandemic.

Current trends in the pharmacological management of Chagas disease.

Chagas disease (CD) is a tropical neglected illness, affecting mainly populations of low socioeconomic status in Latin America. An estimated 6 to 8 million people worldwide are infected with Trypanosoma cruzi, the etiological agent of CD. Despite being one of the main global health problems, this disease continues without effective treatment during the chronic phase of the infection. The limitation of therapeutic strategies has been one of the biggest challenges on the fight against CD. Nifurtimox and benznidazole, developed in the 1970s, are still the only commercial options with established efficacy on CD. However, the efficacy of these drugs have a proven efficacy only during early infection and the benefits in the chronic phase are questionable. Consequently, there is a growing need for new pharmacological alternatives, either by optimization of existing drugs or by the formulation of new compounds. In the present study, a literature review of the currently adopted therapy, its concomitant combination with other drugs, and potential future treatments for CD was performed, considering articles published from 2012. The revised articles were selected according to the protocol of treatment: evaluation of drug association, drug repositioning and research of new drugs. As a result of the present revision, it was possible to conclude that the use of benznidazole in combination with other compounds showed better results when compared with its use as a single therapy. The search of new drugs has been the strategy most used in pursuing more effective forms of treatment for CD. However, studies have still focused on basic research, that is, they are still in a pre-clinical stage, using methodologies based on in vitro or in animal studies.

Evaluation of Quality of Life of Adult Patients with Celiac Disease in Argentina: From Questionnaire Validation to Assessment.

This cross-sectional study aimed to translate, culturally adapt, validate, and apply a Celiac Disease Quality of Life (CD-QoL) questionnaire to a representative sample of Argentina's celiac population. A previously developed and validated questionnaire (Celiac Disease Questionnaire: CDQ) was chosen as a tool for assessing the health-related quality of Life (HRQoL) of adult celiac patients in Argentina. Therefore, the study was performed in four stages: (a) translation and re-translation of the CDQ to Argentinian-Spanish language; (b) cultural adaptation and semantic evaluation; based on the Delphi method (c) validation of the CDQ by applying it to a representative sample of Argentinian celiac patients; (d) statistical analysis of the data. The result of stages (a) and (b) was a translated and culturally adapted an Argentinian-Spanish version of the CDQ, which was generated after reaching consensus between the corresponding four (phase a) and 10 (phase b) professionals involved in the different phases of this process. Among them, we can cite bilingual healthcare professionals with extensive experience in research and celiac disease, celiac patients, gastroenterologists, general practitioners, dieticians, and psychologists. The resulting CDQ proved to be an appropriate measuring tool to assess the HRQoL of Argentinian celiac patients confirmed by a good fit in the confirmatory factor validity analysis (RMSEA < 0.001 and χ2 = 267.325, df = 313, p = 0.971) and high values of internal consistency (Cronbach's alpha > 0.7). A total of 191 participants accessed the questionnaire, and 171 individuals from 20 out of 23 Argentinian states completed the questionnaire. There was no correlation between higher educational level nor marital status with QoL. Individuals on a strict gluten-free diet (GFD) and those who do not take antidepressants showed higher QoL. Male gender also presented better HRQoL. There was no correlation between differences in HRQoL and age of the respondent, age at diagnosis, symptoms at diagnosis, or having other chronic diseases. However, a significantly higher score of HRQoL was reported among those individuals who disclosed having knowledge of CD related national regulations and benefits. This study highlights the importance of maintaining current public health regulations that support chronic disease patients, such as celiac patients.

Assessment of BDNF serum levels as a diagnostic marker in children with autism spectrum disorder.

There has been a significant increase in autism spectrum disorder (ASD) in the last decades that cannot be exclusively attributed to better diagnosis and an increase in the communication of new cases. Patients with ASD often show dysregulation of proteins associated with synaptic plasticity, notably brain-derived neurotrophic factor (BDNF). The objective of the present study was to analyze BDNF serum concentration levels in children with classic forms autism and a healthy control group to determine if there is a correlation between ASD and BDNF serum levels. Forty-nine children with severe classic form of autism, and 37 healthy children were enrolled in the study. Blood samples, from both patients and controls, were collected and BNDF levels from both groups were analyzed. The average BDNF serum concentration level was statistically higher for children with ASD (P < 0.000) compared to the control group. There is little doubt that BDNF plays a role in the pathophysiology of ASD development and evolution, but its brain levels may fluctuate depending on several known and unknown factors. The critical question is not if BDNF levels can be considered a prognostic or diagnostic marker of ASD, but to determine its role in the onset and progression of this disorder.