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The complement system plays an important role in the innate and acquired immune response against pathogens. It consists of more than 30 proteins found in soluble form or attached to cell membranes. Most complement proteins circulate in inactive forms and can be sequentially activated by the classical, alternative, or lectin pathways. Biological functions, such as opsonization, removal of apoptotic cells, adjuvant function, activation of B lymphocytes, degranulation of mast cells and basophils, and solubilization and clearance of immune complex and cell lysis, are dependent on complement activation. Although the activation of the complement system is important to avoid infections, it also can contribute to the inflammatory response triggered by immune complex deposition in tissues in autoimmune diseases. Paradoxically, the deficiency of early complement proteins from the classical pathway (CP) is strongly associated with development of systemic lupus erythematous (SLE) - mainly C1q deficiency (93%) and C4 deficiency (75%). The aim of this review is to focus on the deficiencies of early components of the CP (C1q, C1r, C1s, C4, and C2) proteins in SLE patients.

Episignatures are popular tools for the diagnosis of rare neurodevelopmental disorders. They are commonly based on a set of differentially methylated CpGs used in combination with a support vector machine model. DNA methylation (DNAm) data often include missing values due to changes in data generation technology and batch effects. While many normalization methods exist for DNAm data, their impact on episignature performance have never been assessed. In addition, technologies to quantify DNAm evolve quickly and this may lead to poor transposition of existing episignatures generated on deprecated array versions to new ones. Indeed, probe removal between array versions, technologies or during preprocessing leads to missing values. Thus, the effect of missing data on episignature performance must also be carefully evaluated and addressed through imputation or an innovative approach to episignatures design. In this paper, we used data from patients suffering from Kabuki and Sotos syndrome to evaluate the influence of normalization methods, classification models and missing data on the prediction performances of two existing episignatures. We compare how six popular normalization methods for methylarray data affect episignature classification performances in Kabuki and Sotos syndromes and provide best practice suggestions when building new episignatures. In this setting, we show that Illumina, Noob or Funnorm normalization methods achieved higher classification performances on the testing sets compared to Quantile, Raw and Swan normalization methods. We further show that penalized logistic regression and support vector machines perform best in the classification of Kabuki and Sotos syndrome patients. Then, we describe a new paradigm to build episignatures based on the detection of differentially methylated regions (DMRs) and evaluate their performance compared to classical differentially methylated cytosines (DMCs)-based episignatures in the presence of missing data. We show that the performance of classical DMC-based episignatures suffers from the presence of missing data more than the DMR-based approach. We present a comprehensive evaluation of how the normalization of DNA methylation data affects episignature performance, using three popular classification models. We further evaluate how missing data affect those models’ predictions. Finally, we propose a novel methodology to develop episignatures based on differentially methylated regions identification and show how this method slightly outperforms classical episignatures in the presence of missing data.

Cancer, a major world public health problem, is associated with chemotherapy treatments whose administration leads to secondary concerns, such as oral mucositis (OM). The OM disorder is characterized by the presence of ulcers in the oral mucosa that cause pain, bleeding, and difficulty in ingesting fluids and solids, or speaking. Bioactive compounds from natural sources have arisen as an effective approach for OM. This review aims to summarize the new potential application of different natural products in the prevention and treatment of OM in comparison to conventional ones, also providing a deep insight into the most recent clinical studies. Natural products, such as Aloe vera, Glycyrrhiza glabra, Camellia sinensis, Calendula officinalis, or honeybee crops, constitute examples of sources of bioactive compounds with pharmacological interest due to their well-reported activities (e.g., antimicrobial, antiviral, anti-inflammatory, analgesic, or wound healing). These activities are associated with the bioactive compounds present in their matrix (such as flavonoids), which are associated with in vivo biological activities and minimal or absent toxicity. Finally, encapsulation has arisen as a future opportunity to preserve the chemical stability and the drug bioa vailability of bioactive compounds and, most importantly, to improve the buccal retention period and the therapeutic effects.

An outbreak of Chagas disease, possibly involving its vector Triatoma brasiliensis brasiliensis , was identified in the state of Rio Grande do Norte (RN). Given the historical significance of this vector in public health, the study aimed to evaluate its role in the transmission dynamics of the protozoan Trypanosoma cruzi in an area undergoing desertification in the Seridó region, RN, Brazil. We captured triatomines in sylvatic and anthropic ecotopes. Natural vector infection was determined using parasitological and molecular methods and we identified discrete typing units (DTUs) of T . cruzi by analyzing the COII gene of mtDNA, 24Sα rDNA, and mini-exon gene. Their blood meals sources were identified by amplification and sequencing of the mtDNA cytochrome b gene. A total of 952 T . b . brasiliensis were captured in peridomestic (69.9%) and sylvatic ecotopes (30.4%). A wide range of natural infection rates were observed in peridomestic (36.0% - 71.1%) and sylvatic populations (28.6% - 100.0%). We observed the circulation of TcI and TcII DTUs with a predominance of Tcl in sylvatic and peridomestic environments. Kerodon rupestris , rocky cavy (13/39), Homo sapiens , human (8/39), and Bos taurus , ox (6/39) were the most frequently detected blood meals sources. Thus, Triatoma b . brasiliensis is invading and colonizing the human dwellings. Furthermore, high levels of natural infection, coupled with the detection of TcI and TcII DTUs, and also the detection of K . rupestris and H . sapiens as blood meals sources of infected T . b . brasiliensis indicate a risk of T . cruzi transmission to human populations in areas undergoing desertification.

β-Lactam antibiotics are safe and cost-effective antibiotics, being amoxicillin the most common antibiotic used among the paediatric population.Many patients report allergic reactions to this antibiotic, but amoxicillin allergy range between 1-10%. However, clinicians hesitate to prescribe it when a suspected, but unproven, allergy exists. Our aim is to confirm amoxicillin allergy in children with clinical suspicion.This study was done between January 2018 and December 2020, in children younger than 18 years, admitted to the emergency room with suspicion of clinical allergic reaction to amoxicillin. According to the protocol of our hospital, they were referred for pediatric allergology appointment to perform prick tests and afterwards oral provocation test.A total of 57 cases were referred for evaluation. The average age was 8.4(1-17) years old, and 53% were female. The suspicion was based on late rash reaction presented in 68,.4%, urticarial exanthema in 19.3%, edema in 8.8%, vomit in 8.8%, cutaneous rash in 7% and dyspnea in 2,1%. In 18 patients, specific IgE screening for amoxicillin was performed, but all results were negative. All children did a prick test for amoxicillin and oral provocation test. There were no positive results for prick tests, but two positive results in the oral provocation test (3.5%).Confirmation of amoxicillin allergy, before deciding to use it is or not, is an important tool for antimicrobial stewardship and, consequently, to decrease the rate of antibiotic resistance. So far, in our hospital, there were only two positive results.

IntroductionAbdominal pain is one of the most frequent causes of pediatric Hospital admission, and therefore is frequently overlooked; its cause is usually attributed to cramps or constipation.Nevertheless, a thorough investigation should always be performed.Case Study14 year-old girl, institutionalized, admitted to the Emergency Department due to abdominal pain, in the context of constipation, which was already known.The patient has a history of Psychiatric disease, and is taking Risperidone 0.5mg once daily.The patient did an abdominal radiography that showed abdominal distension and presence of a large amount of feces.After bowel enema, the pain persisted, and due to the recurrent symptoms, she was hospitalized.Her blood tests demonstrated only Anemia (Hb: 10g/dL; MCV: 74.7 fL; MCH:20.9 pg; CHCM: 27.9 g/dL), low total proteins: 5.18 g/dL; and low Albumin: 3.17 g/dL.Her abdominal pain was progressively increasing, and she then performed an abdominal CT scan, which showed a large mass in the stomach extending up to the pylorus, with extra-abdominal gas adjacent to the gastric antrum. The hypothesis of trichobezoar with gastric perforation was primarily considered. A small pleural effusion on the left side was also described.Surgical approach was performed and a large trichobezoar, of about 20cm, was successfully removed. Anterior stomach perforation and chemical peritonitis was also found.After surgery, the patient then admitted to suffer from Tricophagy, as a part o f her Psychiatric condition.During recovery, the pleural effusion increased in size, despite intravenous albumin therapy and drainage was performed. She was then discharged to her institution after a week.Currently, her bowel movement is completely restored, and she is taking iron oral supplements.She maintains follow-up at our outpatient clinic, maintaining slight chest pain of pleuritic character.ConclusionAmong adolescents, the frequency of psychosomatic symptoms is common. Nevertheless, and as we can see in this case, sometimes the etiology of abdominal pain can be quite serious, and even fatal if left untreated.We should always value the overall clinical state of the patient in order to guide our medical approach. The collaboration between Pediatrics, Radiology and General Surgery was vital for a successful diagnosis and treatment.

β-Lactam antibiotics are safe and cost-effective antibiotics, being amoxicillin the most common antibiotic used among the paediatric population.Many patients report allergic reactions to this antibiotic, but amoxicillin allergy range between 1-10%. However, clinicians hesitate to prescribe it when a suspected, but unproven, allergy exists. Our aim is to confirm amoxicillin allergy in children with clinical suspicion.This retrospective study was done between January 2018 and December 2019, in children younger than 18 years, admitted to the emergency room with suspicion of clinical allergic reaction to amoxicillin. According to the protocol of our hospital, they were referred for pediatric allergology appointment to perform prick tests and afterwards oral provocation test.A total of 48 cases were referred for evaluation. The average age was 8.5(1-17) years old, and 54% were female. The suspicion was based on late rash reaction presented in 75%, urticarial exanthema in 18.8%, edema in 8.3%, vomit in 8.3%, and dyspnea in 2,1%. In 18 patients, specific IgE screening for amoxicillin was performed, but all results were negative. All children did a prick test for amoxicillin and oral provocation test. There were no positive results for prick tests, but two positive results in the oral provocation test (4.2%).Confirmation of amoxicillin allergy, before deciding to use it is or not, is an important tool for antimicrobial stewardship and, consequently, to decrease the rate of antibiotic resistance. So far, in our hospital, there were only two positive results.

Aneuploidy, an abnormal chromosome number, has been linked to aging and age-associated diseases, but the underlying molecular mechanisms remain unknown. Here we show, through direct live-cell imaging of young, middle-aged, and old-aged primary human dermal fibroblasts, that aneuploidy increases with aging due to general dysfunction of the mitotic machinery. Increased chromosome mis-segregation in elderly mitotic cells correlates with an early senescence-associated secretory phenotype (SASP) and repression of Forkhead box M1 (FoxM1), the transcription factor that drives G2/M gene expression. FoxM1 induction in elderly and Hutchison–Gilford progeria syndrome fibroblasts prevents aneuploidy and, importantly, ameliorates cellular aging phenotypes. Moreover, we show that senescent fibroblasts isolated from elderly donors’ cultures are often aneuploid, and that aneuploidy is a key trigger into full senescence phenotypes. Based on this feedback loop between cellular aging and aneuploidy, we propose modulation of mitotic efficiency through FoxM1 as a potential strategy against aging and progeria syndromes. Evidence for mitotic decline in aged cells and for aneuploidy-driven progression into full senescence is limited. Here, the authors find that in aged cells, mitotic gene repression leads to increased chromosome mis-segregation and aneuploidy that triggers permanent cell cycle arrest and full senescence.

Triatoma costalimai and Triatoma jatai are related species, which occur in sympatry in Paranã,Tocantins, Brazil, in rocky outcrops and in peridomicile and intradomicile environments. This study compared morphologic and morphometric aspects of the eggs of these species using optical microscopy (OM) and scanning electron microscopy (SEM). Operculum cells (OP) and egg body (EB) were drawn and photographed, their surfaces were measured, and spots were quantified. Statistical analyses were performed using ANOVA and t-tests. OM showed an egg exochorium with spots in T. costalimai and a predominance of short lines in T. jatai. We found significant differences in egg length and width, which were larger in T. costalimai. SEM analysis showed that the operculum of both species had cells with straight and/or rounded rims, with a smooth aspect, random spots, and predominantly pentagonal shape. In the EB, hexagonal cells were predominant, with indices exceeding 60% in both species. Triatoma costalimai cells were flat, with a discrete definition of the rims, whereas T. jatai cells were smooth with well-defined rims. Statistical tests showed significant differences for EB, where T. costalimai cells were larger and have more spots than T. jatai. The eggs can thus be differentiated, thereby contributing to integrative taxonomy.

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.