Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-ß Antibodies.

Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-ß Abs from PBMCs of individuals treated with IFN-α or IFN-ß, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-ß1a-specific signaling and able to block lipopolysaccharide or S100 calcium-binding protein A14-induced IFN-ß signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-ß suggests potential for diverse research and clinical applications.

Epidemiological and Financial Aspects of Hospitalizations for Bacterial Meningitis in Brazil.

Introduction: Understanding the epidemiology and cost implications of acute bacterial meningitis is crucial for effective health planning, timely treatment implementation, and comprehensive patient support measures, as well as for determining appropriate hospital expenses. Therefore, we conducted an analysis of hospitalization cases for bacterial meningitis in Brazil from January 2008 to December 2019. Methods: This is a descriptive ecological study that utilized the Hospital Information System of Brazil's National Unified Health System (SIH/SUS) database. The variables included sex, region, age group, hospitalizations, deaths, lethality rate, and hospital service expenses. The data were tabulated to focus specifically on the epidemiological aspect of bacterial meningitis. Results: During the study period, there were 20,207 hospitalizations for bacterial meningitis in Brazil. Men accounted for a higher number of cases, with 11,690 (57.67%), while women had a higher lethality rate of 10.64%. The Southeast region had the highest percentage of both hospitalizations (45.78%) and deaths (46.42%). Bacterial meningitis remains an important cause of morbidity and mortality, particularly in children under 5 years of age. Notably, the elderly and the Northeast region showed higher rates of lethality. The total expenditure on hospital services exceeded 43 million in Brazilian real, with the highest expenditure observed in 2019 and the lowest in 2011. Conclusion: A higher prevalence of the disease was observed in males, in children under 1-year-old and in the southeast region. Hospital expenditures were found to be substantial and increasing over time, underscoring the significance of early diagnosis and the promotion of vaccination campaigns.

Effects of Physical Exercise on Cerebral Blood Velocity in Older Adults: A Systematic Review and Meta-Analysis.

As the older population grows, there is an increasing interest in understanding how physical exercise can counteract the changes seen with aging. The benefits of exercise to general health, and especially to the cardiovascular system, have been a topic of discussion for decades. However, there is still a need to elucidate the effects of training programs on the cerebrovascular blood velocity in older people. This systematic review and meta-analysis aimed to investigate the effect of physical exercise on the cerebral blood velocity in older people (PROSPERO CRD42019136305). A search was performed on PubMed, Web of Science, EBSCO, ScienceDirect, and Scopus from the inception of this study to October 2023, retrieving 493 results, of which 26 were included, analyzing more than 1000 participants. An overall moderate risk of bias was found for the studies using the Cochrane risk-of-bias tools for randomized and non-randomized clinical trials. The pooled results of randomized trials showed that older people who underwent physical exercise presented a statistically significant increase in cerebral blood velocity (3.58; 95%CI = 0.51, 6.65; p = 0.02). This result indicates that physical exercise is important to help maintain cerebral health in older adults.

Assessment of the non-surgical treatment of patients with rectal cancer who underwent neoadjuvant treatment with chemotherapy and radiotherapy at the oncology department / Avaliação do tratamento não cirúrgico de pacientes com câncer de reto submetido ao tratamento neoadjuvante com quimioterapia e radioterapia no serviço de oncologia

ABSTRACT Objective: To describe the partial results of a study in patients with rectal cancer who underwent neoadjuvant treatment with chemotherapy and radiotherapy regarding the rate of complete clinical response, disease-free survival, anorectal function, and quality of life. Material and methods: This was a prospective study from June 2015 to June 2018, in patients with low- or mid-rectum adenocarcinoma and clinical stage II or III, treated with radiotherapy and chemotherapy (IMRT 54 Gy for six weeks) concomitant with 5-fluorouracil (5-FU) 380 mg/m2 and folinic acid (LV) 20 mg/m2 for five days in the first and fifth weeks and two cycles after radiotherapy (5-FU 400 mg/m2 and LV 20 mg/m2) every 28 days. After the treatment, clinical examination, rectosigmoidoscopy, pelvic magnetic resonance imaging, chest and upper abdomen computed tomography, and CEA testing were performed. Resection surgery was performed in those with incomplete clinical response (iCR). Those with complete clinical response (cCR) are under observation (wait-and-see policy). Manometry and scintigraphic function and quality of life scales were collected before treatment and at 30 and 90 days after the end of treatment. Results: As of June 2018, 11 patients were recruited. One was excluded from the analysis for presenting severe toxicity, suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency, after the first chemotherapy cycle. All others completed the treatment. Two patients presented toxicity grade 3/4 related to chemotherapy and had their doses reduced. Seven patients (70%) presented iRC; three underwent rectosigmoidectomy, and the anatomopathological evaluation indicated complete pathological response in two cases (28.5%). Three (30%) presented cCR and did not present evidence of disease after a mean follow-up of 19 months. Patients presented improvement of anorectal function and quality of life. Conclusions: Advances in the neoadjuvant treatment of rectal tumors contributed to better rates of complete pathological responses. New paradigms promote an increase in the complete clinical response rates, which would allow organ preservation and consequent reduction of surgical morbidity.

RESUMO Objetivo: Descrever os resultados parciais de estudo em pacientes com câncer de reto submetidos a tratamento neoadjuvante com quimioterapia e radioterapia quanto à taxa resposta clínica completa, sobrevida livre de doença, função anorretal e qualidade de vida. Material e métodos: Estudo prospectivo desde junho 2015 até junho de 2018, em paciente com adenocarcinoma de reto baixo ou médio e estadio clínico II ou III tratados com RT/QT (IMRT 54 Gy em 6 semanas) concomitante a 5-Fuorouracil (5-FU) 380 mg/m2 e ácido folínico (LV) 20 mg/m2 por 5 dias nas primeira e quinta semanas e dois ciclos após RT (5-FU 400 mg/m2 e LV 20 mg/m2) a cada 28 dias. Após o tratamento, realizou-se exame clínico, retossigmoidoscopia, RNM de pelve, TC de tórax e abdômen superior e dosagem de CEA. Naqueles com Resposta Clínica Incompleta (iRC) procedeu-se à cirurgia de ressecção. Aqueles com Resposta Completa (cRC) estão em observação (wait and see policy). Manometria e escalas de função esfincteriana e qualidade de vida foram obtidas antes e após 30 e 90 dias do término do tratamento. Resultados: Até junho de 2018, recrutaram-se 11 pacientes. Um foi excluído da análise, pois apresentou toxicidade severa sugestiva de deficiência de DPD após o primeiro ciclo de QT. Todos os demais concluíram o tratamento. Toxicidades graus 3/4 relacionadas à QT ocorreram dois pacientes, reduzindo-se sua dose. Sete (70%) apresentaram iRC, submetendo três à retossigmoidectomia cuja avaliação anatomopatológica evidenciou Resposta Completa (pRC) em dois casos (28,5%). Três (30%) apresentaram cRC e estão sem evidência de doença com seguimento médio de 19 meses. Houve melhora da função anorretal e da qualidade de vida. Conclusões: Avanços no tratamento neoadjuvante dos tumores de reto contribuíram para melhores taxas de pRC. Novos paradigmas promovem crescentes índices de cRC, o que possibilitaria a preservação do órgão e consequente redução da morbidade cirúrgica.

Effect of RGD-disintegrins on melanoma cell growth and metastasis: involvement of the actin cytoskeleton, FAK and c-Fos.

The effects and molecular mechanisms of RGD-disintegrins isolated from snake venoms on the growth and metastatic potential of B16F10-melanoma cells were investigated. Jarastatin (JT) from Bothrops jararaca is a ligand of alpha(5)beta(1), alpha(v)beta(3) and alpha(m)beta(2) integrins, flavoridin (FL) from Trimeresurus flavoridis binds preferentially to alpha(5)beta(1) and kistrin (KR) from Calloselasma rhodostoma is a selective ligand of alpha(v)beta(3). When injected simultaneously with melanoma cells in mice, the three disintegrins significantly reduced tumor lung colonization. On the other hand, JT and FL, but not KR, inhibited B16F10 cell growth in vitro. Interaction of JT or FL with melanoma cells induced actin cytoskeleton rearrangement, increasing actin polymerization and FAK phosphorylation. The effect of FL correlates with the decrease in the constitutively high nuclear content of c-Fos, whereas JT interfered with NF-kappaB translocation in melanoma cells. None of the disintegrins produced alterations in the nuclear Erk-2. The results provide further evidence to suggest RGD-disintegrins as potent anti-metastatic agents in vivo, and indicate that their interaction with alpha(5)beta(1) integrin interfere with integrin-couple signaling, down-regulating transcription factors and negatively modulating cell proliferation. These effects may contribute to inhibition of melanoma cell invasion in vivo.