Bonding positional accuracy of attachments and marginal adaptation of in-house aligners - A quality improvement laboratory study.

OBJECTIVES: To evaluate the 3D accuracy of attachment positioning and the adaptation of aligners to attachments using in-house templates made with either polyethylene terephthalate glycol (PETG) or ethylene-vinyl acetate (EVA) and either pressure or vacuum thermoforming machines. MATERIALS AND METHODS: Overall, 140 test specimens were resin-printed. Templates for the attachment bonding were made with 1-mm EVA or 0.5-mm PETG laminates. Orthodontic aligners were manufactured with 0.75-mm PETG. The thermoplastification process was carried out using either vacuum or pressure machines. The positional differences between the virtual and bonded attachments were assessed in the X, Y and Z coordinates. The marginal adaptation between the aligners and the attachments was measured. RESULTS: Minor inaccuracies in the positioning of the attachments were observed in all combinations of thermoforming machines and plastic laminates used to fabricate the templates, mainly in the superior-inferior (Z) dimension. PETG performed better than EVA in the anterior region (p < .05). No association was found between thermoplastification machines and the accuracy of the positioning of the attachments (p > .05). While small misadaptations between the aligners and the attachments were observed, the EVA templates performed better than the PETG templates. CONCLUSIONS: The inaccuracy of the attachment positioning and the misadaptation of the aligners to the attachments were slight. The vacuum and pressure thermoplastification machines showed no difference in attachment positioning accuracy. The PETG template was better than the EVA template in the anterior region, but the EVA attachments presented a better adaptation to the aligners than the PETG attachments.

Effects of a pro-resolving drug in COVID-19: preclinical studies to a randomized, placebo-controlled, phase Ib/IIa trial in hospitalized patients.

INTRODUCTION: Pro-resolving molecules may curb disease caused by viruses without altering the capacity of the host to deal with infection. AP1189 is a melanocortin receptor-biased agonist endowed with pro-resolving and anti-inflammatory activity. We evaluated the preclinical and early clinical effects of treatment with AP1189 in the context of COVID-19. METHODS: C57BL/6j mice were infected intranasally with MHV-A59 or hK18-ACE2 mice with SARS-CoV-2. AP1189 (10 mg·kg-1, BID, s.c.) was given to the animals from day 2 and parameters evaluated at day 5. Human PBMCs from health donors were infected with SARS-CoV-2 in presence or absence of AP1189 and production of cytokines quantified. In the clinical study, 6 patients were initially given AP1189 (100 mg daily for 14 days) and this was followed by a randomized (2:1), placebo-controlled, double-blind trial that enrolled 54 hospitalized COVID-19 patients needing oxygen support. The primary outcome was the time in days until respiratory recovery, defined as a SpO2 ≥ 93% in ambient air. RESULTS: Treatment with AP1189 attenuated pulmonary inflammation in mice infected with MHV-A59 or SARS-CoV-2 and decreased the release of CXCL10, TNF-α and IL-1ß by human PBMCs. Hospitalized COVID-19 patients already taking glucocorticoids took a median time of 6 days until respiratory recovery when given placebo versus 4 days when taking AP1189 (P = 0.017). CONCLUSION: Treatment with AP1189 was associated with less disease caused by beta-coronavirus infection both in mice and in humans. This is the first demonstration of the effects of a pro-resolving molecule in the context of severe infection in humans.

Developing a Nomogram for Prioritizing Hysteroscopy in Endometrial Cancer Diagnosis: A Case-Control Study.

(1) Background: The pandemic led to significant healthcare disruptions, resulting in postponed surgeries and extended waiting times for non-urgent treatments, including hysteroscopies essential for diagnosing endometrial cancer. This study aims to formulate a risk stratification model to enhance the prioritization of hysteroscopy procedures in Brazil; (2) Methods: A case-control study was conducted at Vila Santa Catarina Hospital in São Paulo, analyzing the medical records of 2103 women who underwent hysteroscopy between March 2019 and March 2022. We used bivariate analysis and multivariate linear regression to identify risk factors associated with endometrial cancer and formulate a nomogram; (3) Results: The findings revealed a 5.5% incidence of pre-invasive and invasive endometrial disease in the study population, with an average waiting time of 120 days for hysteroscopy procedures. The main risk factors identified were hypertension, diabetes, postmenopausal bleeding, and obesity; (4) Conclusions: This research highlights the urgent need for efficient prioritization of hysteroscopy procedures in the wake of the pandemic. The developed nomogram is an innovative tool for identifying patients at higher risk of endometrial cancer, thus facilitating timely diagnosis and treatment and improving overall patient outcomes in a strained healthcare system.

Birth weight and body fat mass in adults assessed by bioimpedance in the ELSA-Brasil study.

Intrauterine life is a critical period for the development of body fat and metabolic risk. This study investigated associations between birth weight and total and truncal body fat in adults. To do so, we analyzed data on 10,011 adults participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who self-reported birth weight as < 2.5kg, 2.5-4.0kg, or > 4.0kg at baseline (2008-2010) and underwent bioimpedance in the next follow-up visit (2012-2014). Greater mean total and truncal fat mass were seen in those with high birth weight compared with adequate birth weight (p < 0.001) in both sexes (total fat: 25.2 vs. 23.1kg in men and 31.4 vs. 27.7kg in women, and truncal fat: 13.5 vs. 12.4kg in men and 15.9 vs. 14.2kg in women). U-shaped patterns were observed in restricted cubic-spline analyses in the subset of 5,212 individuals reporting exact birth weights, although statistically significant only for those with high birth weight. In the whole sample, in comparing high to adequate birth weight, the latter predicted having a large (> 85 percentile) total and truncal fat mass, respectively: OR = 1.76, 95%CI: 1.37-2.25 (men) and OR = 1.86, 95%CI: 1.42-2.44 (women); OR = 1.68, 95% CI: 1.31-2.16 (men) and OR = 1.73, 95%CI: 1.31-2.28 (women). However, low birth weight predicted having a large (> 85 percentile) % truncal fat only in women (OR = 1.40, 95%CI: 1.03-1.91). In conclusion, in these men and women born in a period in which fetal malnutrition was prevalent, birth weight showed complex, frequently non-linear associations with adult body fat, highlighting the need for interventions to prevent low and high birth weight during pregnancy.

Effect of Physical Training on Exercise-Induced Inflammation and Performance in Mice.

Acute exercise increases the amount of circulating inflammatory cells and cytokines to maintain physiological homeostasis. However, it remains unclear how physical training regulates exercise-induced inflammation and performance. Here, we demonstrate that acute high intensity exercise promotes an inflammatory profile characterized by increased blood IL-6 levels, neutrophil migratory capacity, and leukocyte recruitment to skeletal muscle vessels. Moreover, we found that physical training amplified leukocyte-endothelial cell interaction induced by acute exercise in skeletal muscle vessels and diminished exercise-induced inflammation in skeletal muscle tissue. Furthermore, we verified that disruption of the gp-91 subunit of NADPH-oxidase inhibited exercise-induced leukocyte recruitment on skeletal muscle after training with enhanced exercise time until fatigue. In conclusion, the training was related to physical improvement and immune adaptations. Moreover, reactive oxygen species (ROS) could be related to mechanisms to limit aerobic performance and its absence decreases the inflammatory response elicited by exercise after training.

Birth weight and body fat mass in adults assessed by bioimpedance in the ELSA-Brasil study / Peso ao nascer e adiposidade em adultos avaliados com bioimpedância no estudo ELSA-Brasil / Peso al nacer y masa de grasa corporal en adultos evaluados por bioimpedancia en el estudio ELSA-Brasil

Intrauterine life is a critical period for the development of body fat and metabolic risk. This study investigated associations between birth weight and total and truncal body fat in adults. To do so, we analyzed data on 10,011 adults participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who self-reported birth weight as < 2.5kg, 2.5-4.0kg, or > 4.0kg at baseline (2008-2010) and underwent bioimpedance in the next follow-up visit (2012-2014). Greater mean total and truncal fat mass were seen in those with high birth weight compared with adequate birth weight (p < 0.001) in both sexes (total fat: 25.2 vs. 23.1kg in men and 31.4 vs. 27.7kg in women, and truncal fat: 13.5 vs. 12.4kg in men and 15.9 vs. 14.2kg in women). U-shaped patterns were observed in restricted cubic-spline analyses in the subset of 5,212 individuals reporting exact birth weights, although statistically significant only for those with high birth weight. In the whole sample, in comparing high to adequate birth weight, the latter predicted having a large (> 85 percentile) total and truncal fat mass, respectively: OR = 1.76, 95%CI: 1.37-2.25 (men) and OR = 1.86, 95%CI: 1.42-2.44 (women); OR = 1.68, 95% CI: 1.31-2.16 (men) and OR = 1.73, 95%CI: 1.31-2.28 (women). However, low birth weight predicted having a large (> 85 percentile) % truncal fat only in women (OR = 1.40, 95%CI: 1.03-1.91). In conclusion, in these men and women born in a period in which fetal malnutrition was prevalent, birth weight showed complex, frequently non-linear associations with adult body fat, highlighting the need for interventions to prevent low and high birth weight during pregnancy.

A vida intrauterina é um período crítico para o desenvolvimento da gordura corporal e risco metabólico. O estudo investigou as associações entre peso ao nascer e gordura corporal total e de tronco em adultos. Analisamos os dados de 10.011 participantes do Estudo Longitudinal de Saúde no Adulto (ELSA-Brasil), com peso ao nascer de < 2,5kg, 2,5-4,0kg ou > 4,0kg, autorrelatado na linha de base (2008-2010) e que fizeram exame de bioimpedância na visita seguinte (2012-2014). A gordura corporal total e de tronco mais elevada estava associada com peso ao nascer elevado, quando comparado ao peso adequado (p < 0,001) em ambos os sexos (gordura total: 25,2 vs. 23,1 kg em homens e 31,4 vs. 27,7kg em mulheres, e gordura de tronco: 13,5 vs. 12,4kg em homens e 15,9 vs. 14,2kg em mulheres). Foram observados padrões em "U" nas análises de splines cúbicos restritos, no subconjunto de 5.212 indivíduos que informaram o peso ao nascer com exatidão, embora com significância estatística apenas para aqueles com peso ao nascer alto. Na amostra total, o peso ao nascer alto (comparado com o adequado) predizia (> percentil 85) gordura corporal total e de tronco, respectivamente: OR = 1,76, IC95%: 1,37-2,25 (homens) e OR = 1,86, IC95%: 1,42-2,44 (mulheres); OR = 1,68, IC95%: 1,31-2,16 (homens) e OR = 1,73, IC95%: 1,31-2,28 (mulheres). Entretanto, baixo peso ao nascer predizia gordura de tronco elevada (> percentil 85) apenas nas mulheres (OR = 1,40, IC95%: 1,03-1,91). O estudo conclui que nesse grupo de homens e mulheres que nasceram numa época em que a desnutrição fetal era prevalente, o peso ao nascer mostrou associações complexas, frequentemente não lineares, com a gordura corporal na idade adulta, o que enfatiza a necessidade de intervenções para prevenir, durante a gestação, o baixo e alto peso ao nascer.

La vida intrauterina es un periodo crítico para el desarrollo de la masa de grasa corporal y riesgo metabólico. Investigamos las asociaciones entre peso al nacer y la grasa total y troncal en adultos. Analizamos datos de 10.011 adultos que participaron en el Estudio Longitudinal de Salud en Adultos (ELSA-Brasil) quienes autoinformaron de un peso al nacer < 2,5kg, 2,5-4,0kg, o > 4,0kg en la base de referencia (2008-2010) y experimentaron bioimpedancia en la siguiente visita de seguimiento (2012-2014). La mayor media de masa grasa total y troncal se observó en quienes tuvieron un alto peso al nacer, en comparación con quienes tuvieron un adecuado peso al nacer (p < 0,001) en ambos sexos (grasa total: 25,2 vs. 23,1kg en hombres y 31,4 vs. 27,7kg en mujeres, y grasa troncal: 13,5 vs. 12,4kg en hombres y 15,9 vs. 14,2kg en mujeres). Se observaron patrones en forma de "U" en análisis spline cúbicos restringidos en el subconjunto de 5.212 personas que informaron de sus pesos exactos al nacer, pese a que eran estadísticamente significativos solamente quienes tenían un alto peso al nacer. En toda la muestra con alto peso al nacer, comparada con el adecuado peso al nacer, se pronosticó contar con más masa grasa total y troncal (> percentil 85), respectivamente: OR = 1,76, IC95%: 1,37-2,25 (hombres) y OR = 1,86, IC95%: 1,42-2,44 (mujeres); OR = 1,68, IC95%: 1,31-2,16 (hombres) y OR = 1,73, IC95%: 1,31-2,28 (mujeres). No obstante, contar con un bajo peso al nacer predispuso a contar con más masa grasa troncal solamente en mujeres (> percentil 85) % (OR = 1,40, IC95%: 1,03-1,91). En conclusión, en estos hombres y mujeres nacidos durante un período en el que la malnutrición fetal era prevalente, el peso al nacer mostró frecuentemente asociaciones no lineales complejas, con grasa corporal en la etapa adulta, resaltando la necesidad de intervenciones para prevenir el bajo y el alto peso al nacer durante el embarazo.

Treatment with Apocynin Limits the Development of Acute Graft-versus-Host Disease in Mice.

Graft-versus-host disease (GVHD) is the most serious complication limiting the clinical utility of allogeneic hematopoietic stem cell transplantation (HSCT), in which lymphocytes of donors (graft) are activated in response to the host antigen. This disease is associated with increased inflammatory response through the release of inflammatory mediators such as cytokines, chemokines, and reactive oxygen species (ROS). In this study, we have evaluated the role of ROS in GVHD pathogenesis by treatment of recipient mice with apocynin (apo), an inhibitor of intracellular translocation of cytosolic components of NADPH oxidase complex. The pharmacological blockade of NADPH oxidase resulted in prolonged survival and reduced GVHD clinical score. This reduction in GVHD was associated with reduced levels of ROS and TBARS in target organs of GVHD in apocynin-treated mice at the onset of the mortality phase. These results correlated with reduced intestinal and liver injuries and decreased levels of proinflammatory cytokines and chemokines. Mechanistically, pharmacological blockade of the NADPH oxidase was associated with inhibition of recruitment and accumulation of leukocytes in the target organs. Additionally, the chimerism remained unaffected after treatment with apocynin. Our study demonstrates that ROS plays an important role in mediating GVHD, suggesting that strategies aimed at blocking ROS production may be useful as an adjuvant therapy in patients subjected to bone marrow transplantation.

Avaliação da interleucina 3 como marcador prognóstico na sepse / Role of interleukin-3 as a prognostic marker in septic patients

RESUMO Objetivo: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. Métodos: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. Resultados: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). Conclusão: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.

ABSTRACT Objective: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. Methods: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. Results: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). Conclusion: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

Role of interleukin-3 as a prognostic marker in septic patients. / Avaliação da interleucina 3 como marcador prognóstico na sepse.

OBJECTIVE: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. METHODS: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. RESULTS: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). CONCLUSION: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

OBJETIVO: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. MÉTODOS: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. RESULTADOS: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). CONCLUSÃO: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.

Inhibition of 5-lipoxygenase alleviates graft-versus-host disease.

Leukotriene B4 (LTB4), a proinflammatory mediator produced by the enzyme 5-lipoxygenase (5-LO), is associated with the development of many inflammatory diseases. In this study, we evaluated the participation of the 5-LO/LTB4 axis in graft-versus-host disease (GVHD) pathogenesis by transplanting 5-LO-deficient leukocytes and investigated the effect of pharmacologic 5-LO inhibition by zileuton and LTB4 inhibition by CP-105,696. Mice that received allogeneic transplant showed an increase in nuclear 5-LO expression in splenocytes, indicating enzyme activation after GVHD. Mice receiving 5-LO-deficient cell transplant or zileuton treatment had prolonged survival, reduced GVHD clinical scores, reduced intestinal and liver injury, and decreased levels of serum and hepatic LTB4 These results were associated with inhibition of leukocyte recruitment and decreased production of cytokines and chemokines. Treatment with CP-105,696 achieved similar effects. The chimerism or the beneficial graft-versus-leukemia response remained unaffected. Our data provide evidence that the 5-LO/LTB4 axis orchestrates GVHD development and suggest it could be a target for the development of novel therapeutic strategies for GVHD treatment.

Nanocomposite treatment reduces disease and lethality in a murine model of acute graft-versus-host disease and preserves anti-tumor effects.

Graft versus host disease (GVHD) is an immunological disorder triggered by bone marrow transplantation that affects several organs, including the gastrointestinal tract and liver. Fullerenes and their soluble forms, fullerols, are nanocomposites with a closed symmetrical structure with anti-inflammatory and anti-oxidant properties. The present study evaluated the effects of treatment with the fullerol (C60(OH)18-20) in the development and pathogenesis of GVHD in a murine model. Mice with experimental GVHD that were treated with the fullerol showed reduced clinical signs of disease and mortality compared with untreated mice. Treatment with the fullerol decreased the hepatic damage associated with reduced hepatic levels of reactive oxygen species, pro-inflammatory cytokines and chemokines (IFN-γ TNF-α, CCL2, CCL3 and CCL5) and reduced leukocyte accumulation. The amelioration of GVHD after treatment with the fullerol was also associated with reduced intestinal lesions and consequent bacterial translocation to the blood, liver and peritoneal cavity. Moreover, the fullerol treatment alleviated the GVHD while preserving effects of the graft against a leukemia cell line (GFP+P815). In summary, the fullerol was effective in reducing the GVHD inflammatory response in mice and may suggest novel ways to treat this disease.

Lithothamnion muelleri controls inflammatory responses, target organ injury and lethality associated with graft-versus-host disease in mice.

Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of a group of algae with anti-inflammatory, antitumor, and immunomodulatory properties. The present study evaluated the effects of treatment with Lithothamnion muelleri extract (LM) in a model of acute graft-versus-host disease (GVHD), using a model of adoptive splenocyte transfer from C57BL/6 donors into B6D2F1 recipient mice. Mice treated with LM showed reduced clinical signs of disease and mortality when compared with untreated mice. LM-treated mice had reduced tissue injury, less bacterial translocation, and decreased levels of proinflammatory cytokines and chemokines (interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5)). The polysaccharide-rich fraction derived from LM could inhibit leukocyte rolling and adhesion in intestinal venules, as assessed by intravital microscopy. LM treatment did not impair the beneficial effects of graft-versus-leukaemia (GVL). Altogether, our studies suggest that treatment with Lithothamnion muelleri has a potential therapeutic application in GVHD treatment.

Platelet-activating factor receptor plays a role in the pathogenesis of graft-versus-host disease by regulating leukocyte recruitment, tissue injury, and lethality.

PAF is a potent lipid mediator involved in several manifestations of acute inflammation, including leukocyte influx, leukocyte interaction with endothelium, and production of inflammatory cytokines. The present study evaluated the relevance of PAFR for the pathogenesis of acute GVHD using a model of adoptive transfer of splenocytes from WT or PAFR(-/-) C57BL/6J to B6D2F1 mice. Mice, which received PAFR(-/-) splenocytes or treatment with the PAFR antagonist, showed reduced clinical signs of disease and no mortality. In GVHD mice receiving PAFR(-/-) splenocytes, there was deceased bacterial translocation and tissue injury. Furthermore, production of proinflammatory cytokines and chemokines (TNF-α, IFN-γ, CCL2, CCL3, and CCL5) and accumulation of CD8(+) cells in intestine and liver were reduced in mice transplanted with the PAFR(-/-) splenocyte. Mechanistically, an absence or pharmacological blockade of PAFR was associated with decreased rolling and adhesion of leukocytes to the mesenteric microcirculation, as assessed by intravital microscopy. Despite decreased GVHD, there was maintained GVL activity when PAFR(-/-) leukocytes were transferred into WT mice. In conclusion, PAFR on donor leukocytes plays a critical role in GVHD by mediating leukocyte influx and cytokine production in target tissues. PAFR antagonist may potentially be useful in the treatment of GVHD in bone marrow-transplanted patients.

Silicone elastomer sling for rectal prolapse in cats.

This study reports 2 cases of recurrent rectal prolapse secondary to anal abnormality in cats. In both cases the anus was wide, leading to a rectal mucosal prolapse during defecation. A silicone elastomer sling was introduced around the anus, and the rectal prolapse was definitively resolved.

The CCL3/macrophage inflammatory protein-1alpha-binding protein evasin-1 protects from graft-versus-host disease but does not modify graft-versus-leukemia in mice.

CCL3 is a protein of the CC chemokine family known to be important for T cell recruitment in inflammatory diseases. The aim of the current study was to evaluate the effects and putative mechanism of action of evasin-1, a novel CCL3-binding protein, in the pathogenesis of acute graft-versus-host disease (GVHD). GVHD was induced by the transplantation of splenocytes from C57BL/6J to B6D2F1 mice. Treatment of recipient mice with evasin-1 prevented mortality associated with GVHD. This was correlated with reduced weight loss and clinical disease severity. Analysis of the small intestine showed that evasin-1 treatment reduced the histopathological score and decreased levels of IFN-gamma and CCL5. Mechanistically, evasin-1 treatment reduced the number of CD4(+) and CD8(+) T cells infiltrating the small intestine, as assessed by immunohistochemistry, and the adhesion of leukocytes to intestinal venules of recipient mice, as assessed by intravital microscopy. Evasin-1 was also able to decrease liver damage, as seen by reduction of inflammatory infiltrate and IFN-gamma levels. Treatment with evasin-1 did not interfere with graft-versus-leukemia. Altogether, our studies demonstrate that CCL3 plays a major role in mediating GVHD, but not graft-versus-leukemia in mice and suggest that blockade of CCL3 with evasin-1 has potential therapeutic application in patients undergoing bone marrow transplantation.

Reabilitação vestibular em pacientes idosos portadores de vertigem posicional paroxística benigna / Vestibular rehabilitation in elderly patients with benign paroxysmal positional vertigo

A Vertigem Posicional Paroxística Benigna (VPPB) é um distúrbio vestibular no qual os pacientes relatam breves momentos de vertigem e/ou leve instabilidade postural, ocasionados por uma mudança brusca na movimentaçäo cefálica ou corporal. OBJETIVO: Verificar o benefício da reabilitaçäo vestibular, realizada em grupo, em pacientes idosos portadores de VPPB. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Foram selecionados aleatoriamente 16 pacientes portadores de VPPB, todos medicados com extrato de Gingko-biloba (40mg de 12/12h) durante 30 dias. Oito deles, que formaram o Grupo Experimental, além do medicamento, foram submetidos à reabilitaçäo vestibular e oito compuseram o Grupo Controle que näo realizaram nenhum tipo de exercício. Para avaliaçäo do benefício aplicamos a Escala de Atividades de Vida Diária e Desordens Vestibulares proposta por Cohen e Kimball. Para a análise estatística utilizamos o teste t-student. CONCLUSÄO: Nossos resultados apontaram benefício promovido pela reabilitaçäo vestibular em grupo no tratamento de idosos portadores de VPPB; a avaliaçäo qualitativa mostrou-se instrumento importante para a avaliaçäo de benefício para o tratamento proposto; e a reabilitaçäo vestibular em grupo mostrou ser uma excelente estratégia terapêutica