Design and investigation of interactions of novel peptide conjugates of purine and pyrimidine derivatives with EGFR and its mutant T790M/L858R: an in silico and laboratory study.

Peptide-based therapeutics have been gaining attention due to their ability to actively target tumor cells. Additionally, several varieties of nucleotide derivatives have been developed to reduce cell proliferation and induce apoptosis of tumor cells. In this work, we have developed novel peptide conjugates with newly designed purine analogs and pyrimidine derivatives and explored the binding interactions with the kinase domain of wild-type EGFR and its mutant EGFR [L858R/ T790M] which are known to be over-expressed in tumor cells. The peptides explored included WNWKV (derived from sea cucumber) and LARFFS, which in previous work was predicted to bind to Domain I of EGFR. Computational studies conducted to explore binding interactions include molecular docking studies, molecular dynamics simulations and MMGBSA to investigate the binding abilities and stability of the complexes. The results indicate that conjugation enhanced binding capabilities, particularly for the WNWKV conjugates. MMGBSA analysis revealed nearly twofold higher binding toward the T790M/L858R double mutant receptor. Several conjugates were shown to have strong and stable binding with both wild-type and mutant EGFR. As a proof of concept, we synthesized pyrimidine conjugates with both peptides and determined the KD values using SPR analysis. The results corroborated with the computational analyses. Additionally, cell viability and apoptosis studies with lung cancer cells expressing the wild-type and double mutant proteins revealed that the WNWKV conjugate showed greater potency than the LARFFS conjugate, while LARFFS peptide alone showed poor binding to the kinase domain. Thus, we have designed peptide conjugates that show potential for further laboratory studies for developing therapeutics for targeting the EGFR receptor and its mutant T790M/L858R.

Dissecting the pathways coordinating patterning and growth by plant boundary domains.

Boundary domains play important roles during morphogenesis in plants and animals, but how they contribute to patterning and growth coordination in plants is not understood. The CUC genes determine the boundary domains in the aerial part of the plants and, in particular, they have a conserved role in regulating leaf complexity across Angiosperms. Here, we used tooth formation at the Arabidopsis leaf margin controlled by the CUC2 transcription factor to untangle intertwined events during boundary-controlled morphogenesis in plants. Combining conditional restoration of CUC2 function with morphometrics as well as quantification of gene expression and hormone signaling, we first established that tooth morphogenesis involves a patterning phase and a growth phase. These phases can be separated, as patterning requires CUC2 while growth can occur independently of CUC2. Next, we show that CUC2 acts as a trigger to promote growth through the activation of three functional relays. In particular, we show that KLUH acts downstream of CUC2 to modulate auxin response and that expressing KLUH can compensate for deficient CUC2 expression during tooth growth. Together, we reveal a genetic and molecular network that allows coordination of patterning and growth by CUC2-defined boundaries during morphogenesis at the leaf margin.

IL6 genetic variants haplotype is associated with susceptibility and disease activity but not with therapy response in patients with inflammatory bowel disease.

PURPOSE: The aim of the present study was to evaluate the IL6 -174 G>C (rs1800795) and -572 G>C (rs1800796) genetic variants and their association with inflammatory bowel diseases (IBDs), disease activity, and response to TNF-α inhibitors. METHODS: The study included 178 patients with IBD and 224 healthy controls. Among the IBD patients, 66 of them were in use of TNF-α inhibitors therapy and were followed during 48 weeks and categorized as responders and non-responders. RESULTS: In total, 89 (50.0%) had ulcerative colitis (UC) and 89 (50.0%) had Crohn's disease (CD). The IL6 -572 CC genotype presented a protective effect in CD patients in codominant and recessive models, while the IL6 -174 CC genotype was associated with susceptibility to UC and CD. The presence of G/C haplotype in the recessive model (GCGC) was associated with UC. The Crohn's disease endoscopic index of severity was low in those patients carrying the GCGC haplotype. It was observed that there was no association between the IL6 genetic variants and TNF-α inhibitor therapy response. CONCLUSION: The G/C haplotype (recessive model) was associated with susceptibility to UC but not to CD. However, the G/C haplotype (dominant model) was associated with the endoscopic activity of CD. Moreover, these IL6 variants did not predict the TNF-α inhibitor therapy response.

Multiscale quantification of morphodynamics: MorphoLeaf software for 2D shape analysis.

A major challenge in morphometrics is to analyse complex biological shapes formed by structures at different scales. Leaves exemplify this challenge as they combine differences in their overall shape with smaller shape variations at their margin, leading to lobes or teeth. Current methods based on contour or on landmark analysis are successful in quantifying either overall leaf shape or leaf margin dissection, but fail in combining the two. Here, we present a comprehensive strategy and its associated freely available platform for the quantitative, multiscale analysis of the morphology of leaves with different architectures. For this, biologically relevant landmarks are automatically extracted and hierarchised, and used to guide the reconstruction of accurate average contours that properly represent both global and local features. Using this method, we establish a quantitative framework of the developmental trajectory of Arabidopsis leaves of different ranks and retrace the origin of leaf heteroblasty. When applied to different mutant forms, our method can contribute to a better understanding of gene function, as we show here for the role of CUC2 during Arabidopsis leaf serration. Finally, we illustrate the wider applicability of our tool by analysing hand morphometrics.

The effects of galectin-3 depletion apheresis on induced skin inflammation in a porcine model.

Galectin-3 (Gal-3), a ß-galactoside-binding lectin that is expressed in mammalian cells, is known to modulate several biological functions such as cell-cell adhesion, macrophage activation, angiogenesis, metastasis, and fibrosis. The goal of this study was to evaluate the ability of Gal-3 depletion apheresis using an adsorption column with immobilized anti-Gal-3-antibody to reduce inflammation induced by Complete Freund's Adjuvant injection in a skin inflammation porcine model. Here, we report that plasma perfusion by apheresis through a Gal-3 binding immuno-affinity column reduces plasma Gal-3 levels to below limits of quantitative detection, and results in significant decrease in skin inflammation, including degree and duration of inflammatory lesions. Human plasma was tested ex vivo and found to be efficiently depleted using the anti-Gal-3 affinity column. This study demonstrates the potential of Gal-3 depletion apheresis as a therapeutic method for inflammation-mediated disease, supporting continued research in this area for clinical application.

GDP-L-fucose is required for boundary definition in plants.

The CUP-SHAPED COTYLEDON (CUC) transcription factors control plant boundary formation, thus allowing the emergence of novel growth axes. While the developmental roles of the CUC genes in different organs and across species are well characterized, upstream and downstream events that contribute to their function are still poorly understood. To identify new players in this network, we performed a suppressor screen of CUC2g-m4, a line overexpressing CUC2 that has highly serrated leaves. We identified a mutation that simplifies leaf shape and affects MURUS1 (MUR1), which is responsible for GDP-L-fucose production. Using detailed morphometric analysis, we show that GDP-L-fucose has an essential role in leaf shape acquisition by sustaining differential growth at the leaf margins. Accordingly, reduced CUC2 expression levels are observed in mur1 leaves. Furthermore, genetic analyses reveal a conserved role for GDP-L-fucose in different developmental contexts where it contributes to organ separation in the same pathway as CUC2. Taken together, our results reveal that GDP-L-fucose is necessary for proper establishment of boundary domains in various developmental contexts.

A conserved role for CUP-SHAPED COTYLEDON genes during ovule development.

The evolution of plant reproductive strategies has led to a remarkable diversity of structures, especially within the flower, a structure characteristic of the angiosperms. In flowering plants, sexual reproduction depends notably on the development of the gynoecium that produces and protects the ovules. In Arabidopsis thaliana, ovule initiation is promoted by the concerted action of auxin with CUC1 (CUP-SHAPED COTYLEDON1) and CUC2, two genes that encode transcription factors of the NAC family (NAM/ATAF1,2/CUC). Here we highlight an additional role for CUC2 and CUC3 in Arabidopsis thaliana ovule separation. While CUC1 and CUC2 are broadly expressed in the medial tissue of the gynoecium, CUC2 and CUC3 are expressed in the placental tissue between developing ovules. Consistent with the partial overlap between CUC1, CUC2 and CUC3 expression patterns, we show that CUC proteins can physically interact, both in yeast cells and in planta. We found that the cuc2;cuc3 double mutant specifically harbours defects in ovule separation, producing fused seeds that share the seed coat, and suggesting that CUC2 and CUC3 promote ovule separation in a partially redundant manner. Functional analyses show that CUC transcription factors are also involved in ovule development in Cardamine hirsuta. Additionally we show a conserved expression pattern of CUC orthologues between ovule primordia in other phylogenetically distant species with different gynoecium architectures. Taken together these results suggest an ancient role for CUC transcription factors in ovule separation, and shed light on the conservation of mechanisms involved in the development of innovative structures.

Low Ankle-Brachial Index is a Simple Physical Exam Sign Predicting Intracranial Atherosclerotic Stenosis in Ischemic Stroke Patients.

BACKGROUND: The investigation of ischemic stroke etiology is commonly limited to the heart and extracranial vessels. Nevertheless, the diagnosis of intracranial stenosis may carry important therapeutic implications. The aims of this study were to determine the prevalence and clinical predictors of intracranial atherosclerotic stenosis (ICAS) in a sample of patients with ischemic stroke. METHODS: Consecutive patients admitted to a university-based outpatient stroke clinic underwent CT angiography of the intracranial and extracranial brain vessels. Clinical, demographic, and laboratory characteristics were compared between patients with increasing levels of stenosis. Ankle-brachial index (ABI) was measured to quantify peripheral arterial disease, defined as an ABI less than or equal to .9. Multivariable ordinal logistic regression was constructed to predict increasing stenosis grades (none, 1%-49%-mild, 50%-69%-moderate, 70%-100%-severe). RESULTS: We studied 106 subjects, mean age 62 ± 15 years, 54% female. ICAS was present in 38 (36%) patients: 19 (50%) mild, 7 (18%) moderate, and 12 (32%) severe. Of 74 patients where ABI was measured, low ABI was found more frequently with increasing ICAS severity (26%, 42%, 67%, and 89% of patients with none, mild, moderate, and severe ICAS, respectively). In univariable analysis, higher age, presence of diabetes, abdominal obesity, and low ABI correlated with increasing stenosis grades. In multivariable analysis, only low ABI remained independently associated with increasing stenosis grades. CONCLUSIONS: The ABI is independently associated with increasing severity of ICAS, making it a potentially useful triaging tool for more invasive test selection.

An APETALA3 homolog controls both petal identity and floral meristem patterning in Nigella damascena L. (Ranunculaceae).

Flower architecture mutants provide a unique opportunity to address the genetic origin of flower diversity. Here we study a naturally occurring floral dimorphism in Nigella damascena (Ranunculaceae), involving replacement of the petals by numerous sepal-like and chimeric sepal/stamen organs. We performed a comparative study of floral morphology and floral development, and characterized the expression of APETALA3 and PISTILLATA homologs in both morphs. Segregation analyses and gene silencing were used to determine the involvement of an APETALA3 paralog (NdAP3-3) in the floral dimorphism. We demonstrate that the complex floral dimorphism is controlled by a single locus, which perfectly co-segregates with the NdAP3-3 gene. This gene is not expressed in the apetalous morph and exhibits a particular expression dynamic during early floral development in the petalous morph. NdAP3-3 silencing in petalous plants perfectly phenocopies the apetalous morph. Our results show that NdAP3-3 is fully responsible for the complex N. damascena floral dimorphism, suggesting that it plays a role not only in petal identity but also in meristem patterning, possibly through regulation of perianth organ number and the perianth/stamen boundary.

Time to Start a New Enhanced Recovery After Surgery (ERAS): A Retrospective Cohort Study.

BACKGROUND: The enhanced recovery after surgery (ERAS®) is a multimodal perioperative care pathway designed to reduce surgical stress and ultimately improve patient recovery and outcome. It can require significant resources but with proven benefits. The main goal of this study was to perform a diagnostic assessment of perioperative practice in a local colorectal surgical center. METHODS: 93 patients who underwent elective colorectal surgery from January to December 2022 were analyzed. Preadmission, preoperative, and postoperative data of all patients were collected in a database developed by the researchers, according to ERAS® guidelines. Descriptive statistics were employed to summarize demographic and clinical characteristics. Chi-square and T-test were performed to identify possible associations between categorical variables and postoperative complications. RESULTS: Overall analysis showed deficient preoperative patient optimization, especially regarding nutritional counseling and supplementation, smoking and alcohol cessation, anemia treatment (9%), and pre-anesthetic medication (42%). Removal of invasive devices was significantly delayed (removal of urinary catheter average on the fourthday and surgical drain average on the fifth day) in the postoperatively period and oral intake (average onset on the sixth day). Both contribute to hospital length of stay (mean of 13 days) and a significant number of complications. CONCLUSION: The results lead us to an individual and multidisciplinary reflection on current practices and outcomes. ERAS® program, already adopted by many centers, could have a positive impact on the immediate postoperative recovery of colorectal patients in Funchal Central Hospital and implementation seems necessary.

The impact of anastomotic leakage after curative colon cancer resection on long-term survival: A retrospective cohort study.

INTRODUCTION: Anastomotic leakage (AL) is one of the most feared postoperative complications in colon cancer surgery due to an association with increased morbidity and mortality, although its impact on long-term survival is not consensual. The aim of this study was to investigate the influence of AL on long-term survival of patients undergoing curative colon cancer resection. METHODS: A single-centre retrospective cohort study was designed. Clinical records of all consecutive patients undergoing surgery at our institution between 01/01/2010 and 12/31/2019 were reviewed. Survival analysis was performed by Kaplan-Meier method to estimate overall and conditional survival and Cox regression to search for risk factors impacting survival. RESULTS: A total of 2351 patients submitted to colorectal surgery were screened for eligibility, of which 686 with colon cancer were included. AL occurred in 57 patients (8,3%) and was associated with higher postoperative morbidity and mortality, length of stay and early readmissions (P < 0,05). Overall survival was inferior in the leakage group (Hazard Ratio 2,08 [1,02-4,24]). Conditional overall survival at 30, 90 days and 6 months was also inferior in the leakage group (P < 0,05), but not at 1 year. Risk factors independently associated with reduced overall survival included AL occurrence, higher ASA classification and delayed/missed adjuvant chemotherapy. AL did not impact local and distant recurrence (P > 0,05). CONCLUSION: AL has a negative impact on survival. Its effect is more pronounced on short-term mortality. AL does not appear to be associated with disease progression.

IL-8 but not other biomarkers of endothelial damage is associated with disease activity in patients with ankylosing spondylitis without treatment with anti-TNF agents.

The objective of the study was to investigate the association between IL-8 and other biomarkers of endothelial dysfunction (MCP-1, V-CAM, I-CAM) and the disease activity scores in a sample of 54 patients with ankylosing spondylitis (AS) without use of biological agents. Fifty-four AS patients without treatment with anti-TNFs agents between 18 and 80 years old, who met modified New York criteria and at the same time the axial ASAS criteria, were evaluated using an epidemiological questionnaire that included among others clinical data, BASDAI, BASFI, ASQoL, ASDAS and plasma levels of CRP, ESR, MCP-1, IL-8, ICAM-1 and VCAM-1. IL-8 varied in proportion to disease activity rates (BASDAI and ASDAS) p < 0.05, being strongly correlated with the disease activity. The levels of adhesion molecules I-CAM and VCAM, as described in other studies, were positively correlated with predisposing factors for cardiovascular disease. IL-8 has shown to be strongly correlated with clinical markers of disease activity and inflammatory activity and may be an additional variable to the overall assessment of the activity of the AS.

Sputum induction and its diagnostic applications in inflammatory airway disorders: a review.

Sputum induction is a technique that covers the induction and the subsequent processing of the expectorate primarily for the analysis of cells and different inflammatory biomarkers present in the airways to further understand the pathophysiology of different inflammatory respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) as well as the diagnosis of lung diseases such as lung cancer, tuberculosis, and Pneumocystis jirovecii pneumonia. It is a non-invasive, safe, cost-effective, and reliable technique reported to exhibit a high success rate. However, due to being technically demanding and time-consuming and having the need of employing trained staff, this technique is only used in restricted research centres and in limited centres of clinical use. When the sputum is collected after induction, the primary goal is to obtain a differential cell count and evaluate the molecular biomarkers of airway inflammation such as eosinophil cationic protein, eosinophil-derived neurotoxin, major basic protein, tryptase, cytokine production [e.g., interleukin (IL)-5], albumin, and fibrinogen. In addition, cytospins from the processed sputum are used for immunocytochemical staining of cellular products such as EG-2 reactive protein, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor alpha, and IL-8 that play significant roles in understanding the pathophysiology of inflammatory airway diseases. Nowadays, this technique can be further used by performing an additional analysis such as flow cytometry and in situ hybridisation on the sputum supernatant to investigate more the immune response and pathophysiological process of such various respiratory diseases. In addition, the application of sputum fluid phase to assess the biomarkers could be used more routinely in pathological laboratories for diagnosing lung cancer, COPD, and asthma as well as for monitoring lung cancer progression and asthma and COPD treatment, allowing for early detection and a better treatment provided by the clinicians.

A computational and laboratory approach for the investigation of interactions of peptide conjugated natural terpenes with EpHA2 receptor.

CONTEXT: Ephrin type A receptor 2 (EphA2) is a well-known drug target for cancer treatment due to its overexpression in numerous types of cancers. Thus, it is crucial to determine the binding interactions of this receptor with both the ligand-binding domain (LBD) and the kinase-binding domain (KBD) through a targeted approach in order to modulate its activity. In this work, natural terpenes with inherent anticancer properties were conjugated with short peptides YSAYP and SWLAY that are known to bind to the LBD of EphA2 receptor. We examined the binding interactions of six terpenes (maslinic acid, levopimaric acid, quinopimaric acid, oleanolic, polyalthic, and hydroxybetulinic acid) conjugated to the above peptides with the ligand-binding domain (LBD) of EphA2 receptor computationally. Additionally, following the "target-hopping approach," we also examined the interactions of the conjugates with the KBD. Our results indicated that most of the conjugates showed higher binding interactions with the EphA2 kinase domain compared to LBD. Furthermore, the binding affinities of the terpenes increased upon conjugating the peptides with the terpenes. In order to further investigate the specificity toward EphA2 kinase domain, we also examined the binding interactions of the terpenes conjugated to VPWXE (x = norleucine), as VPWXE has been shown to bind to other RTKs. Our results indicated that the terpenes conjugated to SWLAY in particular showed high efficacy toward binding to the KBD. We also designed conjugates where in the peptide portion and the terpenes were separated by a butyl (C4) group linker to examine if the binding interactions could be enhanced. Docking studies showed that the conjugates with linkers had enhanced binding with the LBD compared to those without linkers, though binding remained slightly higher without linkers toward the KBD. As a proof of concept, maslinate and oleanolate conjugates of each of the peptides were then tested with F98 tumor cells which are known to overexpress EphA2 receptor. Results indicated that the oleanolate-amido-SWLAY conjugates were efficacious in reducing the cell proliferation of the tumor cells and may be potentially developed and further studied for targeting tumor cells overexpressing the EphA2 receptor. To test if these conjugates could bind to the receptor and potentially function as kinase inhibitors, we conducted SPR analysis and ADP-Glo assay. Our results indicated that OA conjugate with SWLAY showed the highest inhibition. METHODS: Docking studies were carried out using AutoDock Vina, v.1.2.0; Molecular Dynamics and MMGBSA calculations were carried out through Schrodinger Software DESMOND.

Development of Self-Assembled Biomimetic Nanoscale Collagen-like Peptide-Based Scaffolds for Tissue Engineering: An In Silico and Laboratory Study.

Development of biocomposite scaffolds has gained tremendous attention due to their potential for tissue regeneration. However, most scaffolds often contain animal-derived collagen that may elicit an immunological response, necessitating the development of new biomaterials. Herein, we developed a new collagen-like peptide,(Pro-Ala-His)10 (PAH)10, and explored its ability to be utilized as a functional biomaterial by incorporating it with a newly synthesized peptide-based self-assembled gel. The gel was prepared by conjugating a pectin derivative, galataric acid, with a pro-angiogenic peptide (LHYQDLLQLQY) and further functionalized with a cortistatin-derived peptide, (Phe-Trp-Lys-Thr)4 (FWKT)4, and the bio-ionic liquid choline acetate. The self-assembly of (PAH)10 and its interactions with the galactarate-peptide conjugates were examined using replica exchange molecular dynamics (REMD) simulations. Results revealed the formation of a multi-layered scaffold, with enhanced stability at higher temperatures. We then synthesized the scaffold and examined its physicochemical properties and its ability to integrate with aortic smooth muscle cells. The scaffold was further utilized as a bioink for bioprinting to form three-dimensional cell-scaffold matrices. Furthermore, the formation of actin filaments and elongated cell morphology was observed. These results indicate that the (PAH)10 hybrid scaffold provides a suitable environment for cell adhesion, proliferation and growth, making it a potentially valuable biomaterial for tissue engineering.

Correction: Maternal mortality associated with COVID-19 in Brazil in 2020 and 2021: Comparison with non-pregnant women and men.

[This corrects the article DOI: 10.1371/journal.pone.0261492.].

Interactions of Nanoscale Self-Assembled Peptide-Based Assemblies with Glioblastoma Cell Models and Spheroids.

Peptide nanoassemblies have garnered remarkable importance in the development of novel nanoscale biomaterials for drug delivery into tumor cells. Taking advantage of receptor mediated recognition of two known peptides, angiopep-2 (TFFYGGSRGKRNNFKTEEY) and A-COOP-K (ACGLSGLC10 VAK) that bind to the over-expressed receptors low density lipoprotein (LRP-1) and fatty acid binding protein (FABP3) respectively, we have developed new peptide conjugates by combining the anti-inflammatory, antitumor compound azelaic acid with angiopep-2, which efficiently self-assembled into nanofibers. Those nanofibers were then functionalized with the A-COOP-K sequence and formed supramolecular hierarchical structures that were found to entrap the chemotherapeutic drug doxorubicin efficaciously. Furthermore, the nanoassemblies were found to release the drug in a dose-dependent manner and showed a stepwise increase over a period of 2 weeks under acidic conditions. Two cell lines (U-87-MG and U-138-MG) were utilized as models for glioblastoma cells grown in the presence of serum and under serum-free conditions to mimic the growth conditions of natural tumors. The drug entrapped assemblies were found to inhibit the cell proliferation of both U-87 and U-138MG glioblastoma cells. Three dimensional spheroids of different sizes were grown to mimic the tumors and evaluate the efficacy of drug release and internalization. Our results indicated that the nanoassemblies were found to have higher internalization of DOX and were well-spread throughout the spheroids grown, particularly under serum-free conditions. The nanoassemblies also displayed blood-brain barrier penetration when tested with a multicellular in vitro model. Such self-assembled nanostructures with targeting ability may provide a suitable platform for the development of new peptide-based biomaterials that can provide more insights about the mechanistic approach for drug delivery for not only 2D cell cultures but also 3D tumoroids that mimic the tumor microenvironments.

High and low-fidelity simulation for respiratory diseases pediatric training: a prospective and randomized study.

OBJECTIVE: To compare high and low-fidelity simulations for the recognition of respiratory distress and failure in urgency and emergency pediatric scenarios. METHODS: 70 fourth-year medical students were randomly distributed in high and low-fidelity groups and simulated different types of respiratory problems. Theory tests, performance checklists, and satisfaction and self-confidence questionnaires were used in the assessment. Face-to-face simulation and memory retention was applied. The statistics were evaluated by averages and quartiles, Kappa, and generalized estimating equations. The p-value was considered 0.05. RESULTS: In the theory test there was an increase in scores in both methodologies (p < 0.001); in memory retention (p = 0.043) and at the end of the process the high-fidelity group had better results. The performance in the practical checklists was better after the second simulation (p > 0,05). The high-fidelity group felt more challenged in both phases (p = 0.042; p = 0.018) and showed greater self-confidence to recognize changes in clinical conditions and in memory retention (p = 0.050). The same group, in relation to the hypothetical real patient to be treated in the future, felt better confident to recognize respiratory distress and failure (p = 0.008; p = 0.004), and better prepared to make a systematic clinical evaluation of the patient in memory retention (p = 0.016). CONCLUSION: The two levels of simulations enhance diagnostic skills. High fidelity improves knowledge, leads the student to feel more challenged and more self-confident in recognizing the severity of the clinical case, including memory retention, and showed benefits regarding self-confidence in recognizing respiratory distress and failure in pediatric cases.

Serum Anti-Spike Antibodies Are Not Affected by Immunosuppressants in SARS-CoV-2 Vaccinations Given to Brazilian Patients with Inflammatory Bowel Disease.

This study aimed to evaluate humoral responses after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of patients with inflammatory bowel disease (IBD). Patients with IBD enrolled in a tertiary outpatient unit were followed up between September 2021 and September 2022 via serial blood collection. Immunoglobulin G antibody titers against SARS-CoV-2 were measured before administration and 1 and 6 months after the administration of two doses of different vaccination regimens. The results were compared with those of a healthy control group obtained during the same period. The mean pre-vaccination antibody titers were 452.0 and 93.3 AU/mL in the IBD (n = 42) and control (n = 89) groups, respectively. After two doses of the vaccine, the titers significantly increased in both groups (IBD, 8568.0 AU/mL; control, 7471.0 AU/mL; p < 0.001). One month after the second dose, no significant differences were observed between the two groups (p = 0.955). Significant differences between vaccination schemes in the IBD group were observed, with higher titers in those who received Pfizer, younger patients (p < 0.005), and those with a previous coronavirus disease 2019 (COVID-19) infection (p < 0.012). The use of immunosuppressants and immunobiologicals did not affect the overall humoral response to COVID-19 vaccine in patients with IBD, but specific vaccine regimens, age, and previous coronavirus infection significantly did. This study reinforces the positive impact of booster doses and the safety of SARS-CoV-2 vaccination.

Figure-based speech perception test: applicability in children with Down syndrome. / Teste de percepção de fala com figuras: aplicabilidade em crianças com síndrome de Down.

PURPOSE: To verify the applicability of the picture-based speech perception test in children with Down syndrome. METHODS: Observational, descriptive, prospective study, carried out at two speech therapy centers, approved by their Research Ethics Committees under numbers 82522217.5.0000.5440 and 79510317.8.0000.5257. A total of 41 children with Down syndrome, of both sexes, aged 2 years to 10 years and 11 months participated. They were divided into three groups: GI (2 years to 4 years and 11 months); GII (5 years to 7 years and 11 months); GIII (8 years to 10 years and 11 months). We verified their medical history and carried out meatoscopy, pure-tone threshold audiometry, speech recognition threshold test with pictures, and immittance tests. For statistical analysis, we used Fisher's Exact Test with the 5% significance level. Results: The analysis of hits and misses in relation to chronological age revealed significance in seven words: "ice", "knife", "cow", "key", "mouse", "dog", and "sun". We then analyzed this study participants' performance in the speech test with pictures and those in the study that developed and validated this test. Comparing the percentage of correct answers in the two groups, we found that the words with the most correct answers were "hand", "house", and "frog". Conclusion: The test applied in this study provides a clear and objective interpretation of the results, regardless of the child's verbal production.

OBJETIVO: Verificar a aplicabilidade do teste de percepção de fala com figuras em crianças com síndrome de Down. MÉTODO: Estudo observacional, descritivo e prospectivo, realizado em dois centros fonoaudiológicos, aprovado pelos Comitês de Ética em Pesquisa sob número 82522217.5.0000.5440 e 79510317.8.0000.5257. Participaram 41 crianças com síndrome de Down, de ambos os sexos, com idade entre dois anos e dez anos e 11 meses, as quais foram divididas em três grupos: GI (dois a quatro anos e 11 meses); GII (cinco a sete anos e 11 meses) e GIII (oito a dez anos e 11 meses). Foram realizados os procedimentos de anamnese, meatoscopia, audiometria tonal liminar, teste de limiar de recepção de fala com figuras e imitanciometria. Para a análise estatística, Teste Exato de Fisher com nível de significância de 5%. RESULTADOS: Ao ser analisado o número de acertos e erros, em relação à idade cronológica, foi encontrada significância para sete palavras: gelo, faca, vaca, chave, rato, cão e sol. Foi analisado, posteriormente, o desempenho no teste de fala com figuras, dos participantes desse estudo e o desempenho dos participantes do estudo que elaborou e validou este teste. Foi observado que, quando se equiparou a porcentagem de acertos nos dois grupos, as palavras com maior ocorrência de acertos foram: mão, casa e sapo. Conclusão: O teste aplicado nesse estudo proporciona a interpretação do resultado de forma clara e objetiva e independe da produção verbal da criança.