Innate and adaptive immune response of Rainbow trout (Oncorhynchus mykiss) naturally infected with Yersinia ruckeri.

Rainbow trout is an important fish species for Peruvian artisanal aquaculture, comprising over 60 % of the total aquaculture production. However, their industry has been highly affected by several bacterial agents such as Yersinia ruckeri. This pathogen is the causative agent of Enteric Redmouth Disease, and causes high mortality in fingerlings and chronic infection in adult rainbow trout. To date, the immune response of rainbow trout against Y. ruckeri has been well studied in laboratory-controlled infection studies (i.e. intraperitoneal infection, bath immersion), however, the immune response during natural infection has not been explored. To address this, in this study, 35 clinically healthy O. mykiss without evidence of lesions or changes in behavior and 32 rainbow trout naturally infected by Y. ruckeri, were collected from semi-intensive fish farms located in the Central Highlands of Peru. To evaluate the effect on the immune response, RT-qPCR, western blotting, and ELISA were conducted using head kidney, spleen, and skin tissues to evaluate the relative gene expression and protein levels. Our results show a significant increase in the expression of the pro-inflammatory cytokines il1b, tnfa, and il6, as well as ifng in all three tissues, as well as increases in IL-1ß and IFN-γ protein levels. The endogenous pathway of antigen presentation showed to play a key role in defense against Y. ruckeri, due to the upregulation of mhc-I, tapasin, and b2m transcripts, and the significant increase of Tapasin protein levels in infected rainbow trout. None of the genes associated with the exogenous pathway of antigen presentation showed a significant increase in infected fish, suggesting that this pathway is not involved in the response against this intracellular pathogen. Finally, the transcripts of immunoglobulins IgM and IgT did not show a modulation, nor were the protein levels evaluated in this study.

BioHabana 2022: Preventive and Immunotherapeutic Strategies Against COVID-19 and Cancer in Cuba.

The convergence of life sciences with neurosciences, nanotechnology, data management, and engineering has caused a technological diversification of the biotechnology, pharmaceutical, and medical technology industries, including the phenomenon of digital transformation, which has given rise to the so-called Fourth Industrial Revolution (Industry 4.0). Confronting the COVID-19 pandemic revealed the outstanding response capacity of the scientific community and the biopharmaceutical industry, based on a multidisciplinary and interinstitutional approach that has achieved an unprecedented integration in the history of biomedical science. Cuba, a small country, with scarce material resources, has had remarkable success in controlling the disease, which also highlights the impact of social factors. This report presents a summary of the most relevant presentations of selected topics during the scientific meeting, "BioHabana 2022: Cancer Immunotherapy and the COVID-19 Pandemic," which was held in Havana Cuba in April 2022.

New Evidence for the Role of Pituitary Adenylate Cyclase-Activating Polypeptide as an Antimicrobial Peptide in Teleost Fish.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is a multifunctional neuropeptide that is widely distributed and conserved across species. We have previously shown that in teleost fish, PACAP not only possesses direct antimicrobial properties but also immunomodulatory effects against the bacterial pathogens Flavobacterium psychrophilum and Pseudomonas aeruginosa using in vitro and in vivo experiments. These previous results suggest PACAP can be used as an alternative to antibiotics to prevent and/or treat bacterial infections in the aquaculture industry. To accomplish this goal, more studies are needed to better understand the effect of PACAP on pathogens affecting fish in live infections. In the present study, the transcripts PACAP, PRP/PACAP, and VPAC2 receptor were examined in rainbow trout (Oncorhynchus mykiss) naturally infected with Yersinia ruckeri, which exhibited an increase in their expression in the spleen when compared to healthy fish. Synthetic Clarias gariepinus PACAP-38 has direct antimicrobial activity on Y. ruckeri and inhibits up to 60% of the bacterial growth when the peptide is at concentrations between 50 and 100 µM in TSB. The growth inhibition increased up to 90% in the presence of 12.5 µM of PACAP-38 when salt-free LB broth was used instead of TSB. It was also found to inhibit Y. ruckeri growth in a dose-dependent manner when the rainbow trout monocyte/macrophage-like cell line (RTS11) was pre-treated with lower concentrations of the peptide (0.02 and 0.1 µM) before going through infection. Differential gene expression was analyzed in this in vitro model. Overall, the results revealed new evidence to support the role of PACAP as an antimicrobial and immunomodulatory peptide treatment in teleosts.

Eficacia del nimotuzumab según índices inflamatorios en pacientes con cáncer de pulmón no microcítico avanzado / Efficacy of nimotuzumab according to inflammatory indices in patients with advanced non-small cell lung cancer

Introducción: La respuesta a las terapias en el cáncer de pulmón avanzado pudiera estar relacionada con determinados factores pronósticos como los índices inflamatorios. Objetivo: Evaluar la eficacia del anticuerpo monoclonal humanizado nimotuzumab en pacientes portadores de cáncer de pulmón no microcítico avanzado según índices inflamatorios. Método: Se realizó un estudio de evaluación longitudinal retrospectivo, en un universo de 498 pacientes mayores de 18 años, con diagnóstico citohistológico de cáncer de pulmón de células no pequeñas, en estadios avanzados, después de la primera línea de terapia oncológica, incluidos en ensayos clínicos multicéntricos promovidos por el Centro de Inmunología Molecular desde 2002 a 2018. Se aplicó la estadística descriptiva, se utilizó el software x-tile 3.6.1 para el test de Kaplan Meier; se consideraron diferencias significativas cuando p< 0,05. Resultados: En los pacientes analizados el nimotuzumab mostró beneficio terapéutico en el grupo de pacientes no progresores a la primera línea de tratamiento con quimioterapia o quimiorradioterapia, cuando tenían menor índice de neutrófilos/linfocitos (p= 0,017 y p= 0,027) y menor índice de plaquetas/linfocitos (p= 0,030 y p= 0,009). Conclusión: La selección de un paciente con menor índice inflamatorio beneficia la eficacia del tratamiento con el AcM humanizado nimotuzumab en el cáncer de pulmón avanzado no microcítico, la que se convierte en una herramienta predictiva de la respuesta al tratamiento(AU)

Introduction: The response to therapies in advanced lung cancer could be related to certain prognostic factors such as inflammatory indices. Objective: To evaluate the efficacy of the humanized monoclonal antibody nimotuzumab in patients with advanced non-small cell lung cancer according to inflammatory indices. Method: A retrospective longitudinal evaluation study was carried out in a universe of 498 patients older than 18 years, with a cytohistological diagnosis of non-small cell lung cancer, in advanced stages, after the first line of oncological therapy, including in multicenter clinical trials promoted by the Center for Molecular Immunology from 2002 to 2018. Descriptive statistics were applied, the x-tile 3.6.1 software was used for the Kaplan Meier test, significant differences were considered when p< 0,05. Results: In the patients analyzed, nimotuzumab showed therapeutic benefit in the group of patients who did not progress to the first line of treatment with chemotherapy or chemoradiotherapy, when they had a lower neutrophil-lymphocyte index (p= 0,017 and p= 0,027) and a lower platelet-lymphocyte index (p= 0,030 and p= 0,009). Conclusion: Selecting a patient with a lower inflammatory index benefits the efficacy of treatment with the humanized mAb nimotuzumab in advanced non-small cell lung cancer, which becomes a predictive tool for response to treatment(AU)

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss the preclinical evidence that suggests that EP300 inhibition can attenuate fibrosis-related molecular processes, including extracellular matrix deposition, inflammation, and epithelial-to-mesenchymal transition. We also highlight the contributions of small molecule inhibitors and gene therapy approaches targeting EP300 as novel therapies against fibrosis.

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics.

In spite of the advances in immunotherapy and targeted therapies, lung cancer continues to be the leading cause of cancer-related death. The epidermal growth factor receptor is an established target for non-small cell lung cancer (NSCLC), and its overactivation by the ligands can induce accelerated proliferation, angiogenesis, and metastasis as well as proinflammatory or immunosuppressive signals. CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy that is approved for the treatment of NSCLC patients in Cuba. The study was designed as a phase IV trial to characterize the safety and effectiveness of CIMAvax-EGF in advanced NSCLC patients treated in 119 community polyclinics and 24 hospitals. CIMAvax-EGF treatment consisted of four bi-weekly doses followed by monthly boosters. Overall, 741 NSCLC patients ineligible for further cancer-specific treatment were enrolled. CIMAvax-EGF was safe, and the most common adverse events consisted of mild-to-moderate injection site reactions, fever, chills, tremors, and headache. For patients completing the loading doses, the median survival was 9.9 months. For individuals achieving at least stable disease to the frontline and completing vaccination induction, the median survival was 12 months. Most of the functional activities and symptoms evaluated through the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire improved over time. In conclusion, this real-world trial demonstrated that CIMAvax-EGF was safe and effective in patients who were vaccinated in the maintenance scenario. A larger effect was seen in subjects with poor prognosis like those with squamous tumors and high EGF levels. Remarkably, this community-based intervention was very important because it demonstrated the feasibility of treating advanced lung cancer patients with active immunotherapy in primary care institutions. In addition to CIMAvax-EGF, patients received supportive care at the community clinic. Vaccine administration by the family doctors at the polyclinics reduced the patients' burden on the medical oncology services that continued providing chemotherapy and other complex therapies. We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition. Clinical trial registration: https://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205.

Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.

Blocking EGFR with nimotuzumab: a novel strategy for COVID-19 treatment.

Background: Lung injury and STAT1 deficit induce EGFR overexpression in SARS-CoV-2 infection. Patients & methods: A phase I/II trial was done to evaluate the safety and preliminary effect of nimotuzumab, an anti-EGFR antibody, in COVID-19 patients. Patients received from one to three infusions together with other drugs included in the national guideline. Results: 41 patients (31 severe and 10 moderate) received nimotuzumab. The median age was 62 years and the main comorbidities were hypertension, diabetes and cardiovascular disease. The antibody was very safe and the 14-day recovery rate was 82.9%. Inflammatory markers decreased over time. Patients did not show signs of fibrosis. Conclusion: Nimotuzumab is a safe antibody that might reduce inflammation and prevent fibrosis in severe and moderate COVID-19 patients. Clinical Trial Registration: RPCEC00000369 (rpcec.sld.cu).

Background: After SARS-CoV-2 infection, many cells in the lung express a new receptor called EGFR. Overexpression of EGFR can worsen the pulmonary disease and provoke fibrosis. Patients & methods: The initial impact of using a drug that blocks EGFR, nimotuzumab, was evaluated in COVID-19 patients. Results: 41 patients received nimotuzumab by the intravenous route together with other medications. The median age was 62 years, and patients had many chronic conditions including hypertension, diabetes and cardiac problems. Treatment was well tolerated and 82.9% of the patients were discharged by day 14. Serial laboratory tests, x-rays and CT scan evaluations showed the improvement of the patients. Conclusion: Nimotuzumab is a safe drug that can be useful to treat COVID-19 patients.

Nimotuzumab for COVID-19: case series.

Background: In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis. Methods: Nimotuzumab, a humanized anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was well tolerated. IL-6 decreased from the first antibody infusion. Clinical symptoms significantly improved after nimotuzumab administration, and the CT scans at discharge showed major resolution of the lung lesions and no signs of fibrosis. Conclusion: Safe anti-EGFR antibodies like nimotuzumab may modulate COVID-19-associated hyperinflammation and prevent fibrosis. Clinical Trial Registration: RPCEC00000369 (RPCEC rpcec.sld.cu).

Lay abstract Background: In COVID-19, the protein EGFR is overactive in the infected lung cells. Methods: Nimotuzumab, an anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was safe. The most important inflammatory markers decreased from the first administration. The patients' clinical symptoms and imaging results improved significantly. Conclusion: Anti-EGFR antibodies like nimotuzumab may contribute to the recovery of COVID-19 patients without long-term consequences.

Evaluación de la calidad de vida de pacientes con cáncer de pulmón de células no pequeñas tratados con la vacuna CIMAvaxEGF® / Evaluation of quality of life in patients with non-small cell lung cancer treated with CIMAvaxEGF® vaccine

Este reporte corresponde al análisis de la calidad de vida de los pacientes que se incluyeron en el ensayo clínico fase III de evaluación de la vacuna CIMAvaxEGF® en cáncer de pulmón de células no pequeñas. La calidad de vida se evaluó empleando los cuestionarios EORTC QLQ-C30 y QLQ-C13, al inicio y cada 3 meses hasta el fallecimiento del paciente a criterio del investigador. Para comparar las medianas entre los dos grupos se utilizó la prueba no paramétrica de Mann-Whitney. Las comparaciones entre el nivel basal y los diferentes tiempos de seguimiento se realizaron a través de la prueba no paramétrica de Wilcoxon. El cuestionario QLQ-C30 evidenció un beneficio en cuanto a calidad de vida para el grupo vacunado con la vacuna CIMAvaxEGF® en las escalas funcionales (global, rol y social), en las escalas de síntomas de la enfermedad y del tratamiento (dolor) se observó que mejora la calidad de los mismos a favor de los pacientes tratados con la vacuna CIMAvaxEGF®. El cuestionario QLQ-C13, también evidenció ventajas para el grupo vacunado desde el punto de vista de beneficio clínico en los síntomas (disnea, disfagia, alopecia y dolor en el pecho). Se señala como significativo que disminuye la hemoptisis y la tos en el grupo vacunado, observándose un empeoramiento en el grupo control(AU)

This report corresponds to quality of life analysis of patient with non-small cell lung cancer included in the phase III clinical trials Evaluation of CIMAvaxEGF® vaccine in lung cancer. The quality of life was evaluate using the EORTC questionnaires QLQ-C30 y QLQ-C13, at the beginning and every 3 months. To compare the median between two groups the Mann-Whitney non-parametric test was used. To compare the baseline and different follows times the Wilcoxon non-parametric test was used. The QLQ-C30 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the functional scores (global, role and social) and symptoms of the disease (pain). The QLQ-LC13 questionnaire showed a benefit in terms of the quality of life for the CIMAvaxEGF® vaccine group on the symptoms scores (dyspnea, dysphagia, alopecia and chest pain). It is noted as significant that the hemoptysis decreases in the group vaccinated as well as the dysphagia, the cough and the dyspnea observing a worsening in the control group(AU)

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer.

Advanced non-small cell lung cancer (NSCLC) has faced a therapeutic revolution with the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoints inhibitors (ICIs) approved for first and subsequent therapies. CIMAvax-EGF is a chemical conjugate between human-recombinant EGF and P64, a recombinant protein from Neisseria meningitides, which induces neutralizing antibodies against EGF. In the last 15 years, it has been extensively evaluated in advanced NSCLC patients. CIMAvax-EGF is safe, even after extended use, and able to keep EGF serum concentration below detectable levels. In a randomized phase III study, CIMAvax-EGF increased median overall survival of advanced NSCLC patients with at least stable disease after front-line chemotherapy. Patients bearing squamous-cell or adenocarcinomas and serum EGF concentration above 870 pg/ml had better survival compared to control patients treated with best supportive care as maintenance, confirming tumors' sensitivity to the EGF depletion. This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.

PACAP modulates the transcription of TLR-1/TLR-5/MyD88 pathway genes and boosts antimicrobial defenses in Clarias gariepinus.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide that belongs to the secretin/glucagon/GHRH/VIP superfamily. Some of these molecules have antimicrobial activity and they are capable of stimulating the immune system. The present work studied the antibacterial and immunostimulatory activity of PACAP-38 from African catfish Clarias gariepinus against the Gram-negative bacterium Pseudomonas aeruginosa in an in vivo test. PACAP-38 improved antimicrobial activity of skin mucus molecules against P. aeruginosa. The peptide modulates the gene expression profile of TLR-1, TLR-5, MyD88, IL-1ß, TNF-ɑ, IL-8, pardaxin, hepcidin and G/C-type lysozymes in skin, spleen and head kidney. The influenced exerted depended on the time after infection and tissue analyzed. This study provides the first evidence of a link between PACAP and antimicrobial peptides hepcidin and pardaxin. Our results suggest further use of PACAP as antimicrobial agent that could potentially be used to control disease in aquaculture.

Risk factors for anterior open bite: A case-control study.

BACKGROUND: Anterior open bite (AOB) is noteworthy because it is a complex dysplasia, and clinical studies on this malocclusion are usually epidemiological studies or experimental models with small samples and no control group, which renders the data on AOB incomplete and therefore inconclusive. The objective this study was to assess the risk factors involved in developing AOB. MATERIALS AND METHODS: A case-control study was provided with a total of 96 lateral cephalometric radiographs of male and female patients aged between 8 and 14 years were used, regardless of facial type. The dependent variable was the presence or absence of AOB, which divided the participants into case and control groups, respectively; these groups were matched for gender and age. The case and control groups data were analyzed by descriptive and inferential analysis by binary logistic regression using at the 5% significance level. RESULTS: The occurrence of AOB was associated with the presence of deleterious oral habits (P = 0.014; Chi-square test) and was approximately three times (odds ratio = 3.04) more likely to occur in participants with AOB. No significant association between the presence of mouth breathing and the occurrence of AOB was found (P = 0.151; Chi-square test). The odds associated with tongue interposition were 10.51 times higher than those of participants with no such deglutition. The odds associated with the dolichofacial pattern were 5.74 times those of participants with a nondolichofacial pattern. CONCLUSION: Tongue interposition and dolichocephalic facial pattern were risk factors for developing AOB.

Nimotuzumab for Patients With Inoperable Cancer of the Head and Neck.

EGFR activation induces cell proliferation, neoformation of blood vessels, survival, and metastasis of the cancer cells. Nimotuzumab is an engineered, intermediate affinity anti-EGFR antibody, that apart from other drugs in its class, is very safe and does not cause hypomagnesemia or grade 3-4 cutaneous rash. The antibody inhibits cell proliferation and angiogenesis, activates natural killer cells, stimulates dendritic cell maturation, and induces cytotoxic T cells. Nimotuzumab restores MHC-I expression on tumor cells, hindering one of the EGFR immune-escape ways. The antibody has been extensively studied in 7 clinical trials, concurrently with irradiation or irradiation plus chemotherapy in subjects with inoperable head and neck tumors. Nimotuzumab was safe and efficacious in unfit patients receiving irradiation alone and in subjects treated with cisplatin and radiotherapy. In patients with locally advanced squamous cell carcinomas of the head and neck, nimotuzumab in combination with low dose cisplatin and radiotherapy was superior to cisplatin and radiotherapy in progression free survival, disease free survival, and locoregional tumor control.

First in vivo evidence of pituitary adenylate cyclase-activating polypeptide antiviral activity in teleost.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide belonging to the glucagon/secretin superfamily. In teleost fish, PACAP has been demonstrated to have an immunomodulatory role. Although previous studies have shown that viral/bacterial infections can influence the transcription of PACAP splicing variants and associated receptors in salmonids, the antiviral activity of PACAP has never been studied in teleost. Thus, in the present work, we investigated in vitro the influence of synthetic Clarias gariepinus PACAP-38 on the transcription of genes related to viral immunity using the rainbow trout monocyte/macrophage-like cell line RTS11 as a model. Positive transcriptional modulation of interferon gamma (IFNγ), interferon alpha (FNα1,2), interleukin 8 (IL-8), Mx and Toll-like receptor 3 (TLR3) genes was found in a dose and time dependent manner. We also explored how a pre-treatment with PACAP could enhance antiviral immune response using poly (I:C) as viral mimic. Interferons and IL-8 transcription levels were enhanced when PACAP was added 24 h previous to poly (I:C) exposure. With these evidences, we tested in vivo how PACAP administration by immersion bath affected the survival of rainbow trout fry to a challenge with viral hemorrhagic septicemia virus (VHSV). After challenge, PACAP-treated fish had increased survival compared to non-treated/challenge fish. Furthermore, PACAP was able to decrease the viral load in spleen/kidney and stimulate the transcription of IFNs and Mx when compared to untreated infected fish. Altogether, the results of this work provide valuable insights regarding the role of teleost PACAP in antiviral immunity and point to a potential application of this peptide to reduce the impact of viral infections in aquaculture.

Associação entre padrão de crescimento facial e dimensão de orofaringe / Association between facial growth pattern and oropharynx dimension

Este estudo objetivou investigar a associação entre estenose de naso e orofaringe com o padrão de desenvolvimento facial. Selecionou-se 96 telerradiografias laterais digitais, pré-tratamento ortodôntico, faixa etária de 8 a 14 anos. Para a determinação do padrão facial foram utilizados o índice Vert de Riketts e o quociente de Jarabak. Os dados foram analisados através do Statistical Package for Social Sciences 20 (SPSS). O teste qui-quadrado foi utilizado nos cruzamentos das variáveis naso e orofaringe com tipo facial. Para analisar a concordância intraexaminador, foi realizado o teste Kappa. Segundo a classificação de Ricketts, a maioria da amostra consiste em pacientes com padrão dolicofacial, enquanto que, segundo análise Jarabak, na mesma amostra, a predominância foi do padrão braquifacial. Ao analisar as condições das vias aéreas, observou-se uma relação significativa entre estenose de nasofaringe e o perfil dolicofacial, quando classificado por Jarabak. Usando a classificação de Ricketts, essa mesma associação não foi observada. Considerando-se a orofaringe, não foram encontradas associações estatisticamente significantes com o padrão facial. Houve divergência na classificação do padrão facial de crescimento quando comparadas as análises de Ricketts e Jarabak; ao analisar as dimensões das vias aéreas, associada ao padrão facial, observou-se uma relação significativa entre o estreitamento da nasofaringe e o perfil dolicocefálico, quando classificado por Jarabak. O mesmo não foi evidenciado ao utilizar-se a classificação de Ricketts. Considerando-se a orofaringe, não houve associação desta com nenhuma das classificações de padrão facial utilizadas neste trabalho de pesquisa. (AU)

This study aimed to investigate the association between naso stenosis and oropharynx with facial development pattern. We selected 96 lateral digital teleradiographs, pre-orthodontic treatment, age range from 8 to 14 years old. The Riketts Vert index and the Jarabak quotient were used to determine the facial pattern. Data were analyzed through the Statistical Package for Social Sciences 20 (SPSS). The chi-square test was used in the naso and oropharyngeal variables crossing with facial type. To analyze the intra-examiner agreement, the Kappa test was performed. According to Ricketts classification, the majority of the sample consists of patients with a dolichofacial pattern, whereas according to Jarabak, in the same sample, the predominance was brachyfacial. When analyzing the airway conditions, there was a significant relationship between nasopharyngeal stenosis and the dolichofacial profile, when classified by Jarabak. Using the Ricketts classification, the same association was not observed. Considering the oropharynx, no statistically significant associations were found with the facial pattern. There was divergence in the classification of facial growth pattern when comparing the Ricketts and Jarabak analyzes; when analyzing the airways dimensions, associated with facial pattern, a significant relationship was observed between nasopharyngeal narrowing and the dolichocephalic profile, when classified by Jarabak. The same was not evidenced using the Ricketts classification. Considering the oropharynx, there was no association of this with any of the facial pattern classifications used in this research study.(AU)

Facial Growth Changes Induced by Orthodontic Treatment in Patients With Unilateral Cleft Lip and Palate.

The aim of this study was to investigate the effect of orthodontic treatment on the maxillofacial growth of patients with unilateral cleft lip and palate. The Great Ormond Street, London and Oslo (GOSLON) yardstick was used for a longitudinal evaluation of 24 patients with cleft lip and palate treated at the Cleft Center of the Lauro Wanderley University Hospital, Paraiba State, northeastern Brazil. Dental casts were evaluated by 3 orthodontists and classified according to the GOSLON yardstick. The evaluation was performed at 2 different stages: T1 (before orthodontic treatment) and T2 (follow-up evaluation) after a 6-year mean follow-up interval. The Kappa test was used to evaluate intra- and interexaminer agreement, and paired t-test was used to compare the differences between T1 and T2, with a 99% confidence interval. The average intraexaminer Kappa was 0.979, ranging from 0.971 to 0.990. The interexaminer Kappa value was 0.926 at T1, ranging from 0.885 to 0.964, and 0.896 at T2, ranging from 0.696 to 1.0. The mean GOSLON yardstick found at T1 was 2.5 ±â€Š1.18 with 50% in G1 + G2, 29.18% in G3, and 20.82% in G4 + G5. At T2, the GOSLON average was 1.71 ±â€Š1.12, with 79.18% in G1 + G2, 12.5% in G3, and 8.32% in G4 + G5. A statistically significant difference was found between T1 and T2. The results suggest that orthodontic treatment improves facial growth in patients with unilateral cleft lip and palate.

Investigação de surto de doença meningocócica do grupo C no município de Cachoeirinha/Rio Grande do Sul, 2015 / Investigation of meningococcal disease outbreak of group c in the municipality of Cachoeirinha/Rio Grande do Sul, 2015

Confirmar a ocorrência do surto, descrever suas características epidemiológicas e desencadear medidas de controle. (AU)

Nitric oxide synthase-dependent immune response against gram negative bacteria in a crustacean, Litopenaeus vannamei.

Nitric oxide (NO) is a short-lived radical generated by nitric oxide synthases (NOS). NO is involved in a variety of functions in invertebrates, including host defense. In previous studies, we isolated and sequenced for the first time the NOS gene from hemocytes of Panulirus argus, demonstrating the inducibility of this enzyme by lipopolysaccharide in vitro e in vivo. Hyperimmune serum was obtained from rabbits immunized with a P. argus -NOS fragment of 31 kDa produced in Escherichia coli, which specifically detected the recombinant polypeptide and the endogenous NOS from lobster hemocytes by western blotting and immunofluorescence. In the present work, we demonstrate that the hyperimmune serum obtained against P. argus NOS also recognizes Litopenaeus vannamei NOS in hemocytes by western blotting and immunofluorescence. Our data also show that while the hemolymph of L. vannamei has a strong antibacterial activity against the Gram negative bacteria Aeromonas hydrophila, the administration of the anti NOS serum reduce the natural bacterial clearance. These results strongly suggest that NOS is required for the shrimp immune defense toward Gram negative bacteria. Therefore, the monitoring of induction of NOS could be an important tool for testing immunity in shrimp farming.