Living arrangements and socioeconomic-based health disparities in Mexico.

OBJECTIVE: To investigate the role living arrangements play in the co-dynamics of socioeconomic position and health in the latter part of life. MATERIALS AND METHODS: Based on longitudinal data from the Mexican Health and Aging Study (MHAS), latent class analysis (LCA) and locally weighted regressions, in this article we estimate age trajectories to examine the degree to which wealth and health-related outcomes correlate with typical living arrangement dynamics. RESULTS: Main results suggest a complex dynamic relationship between living arrangements and social inequalities in health, with important differences by sex, unlike mortality trends as they appear to diverge with differences in wealth regardless of household structure. CONCLUSIONS: Our methodological approach provides new insights regarding the likely effect household structure plays when analyzing the dynamics of social inequality. To date, this is the first longitudinal analysis to offer this kind of empirical evidence for the region.

Real-time PCR in the diagnosis of congenital toxoplasmosis.

The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of newborns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.

Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. DR has non-proliferative stages, characterized in part by retinal neuroinflammation and ischemia, and proliferative stages, characterized by retinal angiogenesis. Several systemic factors, including poor glycemic control, hypertension, and hyperlipidemia, increase the risk of DR progression to vision-threatening stages. Identification of cellular or molecular targets in early DR events could allow more prompt interventions pre-empting DR progression to vision-threatening stages. Glia mediate homeostasis and repair. They contribute to immune surveillance and defense, cytokine and growth factor production and secretion, ion and neurotransmitter balance, neuroprotection, and, potentially, regeneration. Therefore, it is likely that glia orchestrate events throughout the development and progression of retinopathy. Understanding glial responses to products of diabetes-associated systemic dyshomeostasis may reveal novel insights into the pathophysiology of DR and guide the development of novel therapies for this potentially blinding condition. In this article, first, we review normal glial functions and their putative roles in the development of DR. We then describe glial transcriptome alterations in response to systemic circulating factors that are upregulated in patients with diabetes and diabetes-related comorbidities; namely glucose in hyperglycemia, angiotensin II in hypertension, and the free fatty acid palmitic acid in hyperlipidemia. Finally, we discuss potential benefits and challenges associated with studying glia as targets of DR therapeutic interventions. In vitro stimulation of glia with glucose, angiotensin II and palmitic acid suggests that: 1) astrocytes may be more responsive than other glia to these products of systemic dyshomeostasis; 2) the effects of hyperglycemia on glia are likely to be largely osmotic; 3) fatty acid accumulation may compound DR pathophysiology by promoting predominantly proinflammatory and proangiogenic transcriptional alterations of macro and microglia; and 4) cell-targeted therapies may offer safer and more effective avenues for DR treatment as they may circumvent the complication of pleiotropism in retinal cell responses. Although several molecules previously implicated in DR pathophysiology are validated in this review, some less explored molecules emerge as potential therapeutic targets. Whereas much is known regarding glial cell activation, future studies characterizing the role of glia in DR and how their activation is regulated and sustained (independently or as part of retinal cell networks) may help elucidate mechanisms of DR pathogenesis and identify novel drug targets for this blinding disease.

Single Dose of Tranexamic Acid Effectively Reduces Blood Loss in Patients Undergoing Spine Surgery: A Prospective Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of oral administration of tranexamic acid (TXA) in spine surgery to achieve blood loss reduction. METHODS: Sixty patients undergoing major surgery of the spine were randomly assigned into 2 groups. Group 1 was assigned as the control group and the other group comprised patients who received oral administration of TXA 2 hours before surgery. Outcome measures included intraoperative blood loss, postoperative blood loss, hematologic parameters, blood transfusion needed, and surgical complications. RESULTS: Sixty patients linked up with the inclusion criteria. Intraoperative blood loss was significantly lower in the TXA oral group than in the control group; total blood loss in the TXA group was 930.66 ± 614 mL, which was lower than in the control group, with 1075.66 ± 956.11 mL. The mean reduction of hemoglobin was almost the same in both groups. Similarly, the total transfusion package received was lower, and the number of complications and length of stay were akin in both groups. A logistic regression model was performed with patients who had blood loss >1000 mL and surgery time >230 minutes. This result was related to the risk of bleeding, with an odds ratio of 1.31, 95% confidence interval, 1.004-1.023, P = 0.004, independent of the group. CONCLUSIONS: Oral TXA is as an effective measure for reducing total blood loss among patients undergoing elective spine surgery.

Real-time PCR in the diagnosis of congenital toxoplasmosis

ABSTRACT The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of new-borns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid.

Virulence Potential and Antibiotic Susceptibility of S. aureus Strains Isolated from Food Handlers.

Staphylococcus spp. are common members of the normal human flora. However, some Staphylococcus species are recognised as human pathogens due to the production of several virulence factors and enterotoxins that are particularly worrisome in food poisoning. Since many of Staphylococcal food poisoning outbreaks are typically associated with cross-contamination, the detection of S. aureus on food handlers was performed. Hand swabs from 167 food handlers were analysed for the presence of S. aureus. More than 11% of the samples were positive for S. aureus. All S. aureus strains were isolated and analysed for the presence of virulence and enterotoxin genes, namely, sea, seb, sec, sed, seg, sei, tsst-1 and pvl. The same strains were phenotypically characterised in terms of antibiotic susceptibility using the disc diffusion method and antimicrobial agents from 12 different classes. A low prevalence of antibiotic-resistant strains was found, with 55.6% of the strains being sensitive to all of the antimicrobial agents tested. However, a high prevalence of resistance to macrolides was found, with 44.4% of the strains showing resistance to erythromycin. At least one of the virulence or toxin genes was detected in 61.1% of the strains, and seg was the most prevalent toxin gene, being detected in 44.4% of the strains.

Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma.

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin's functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin's cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.

Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones.

In this paper we describe the synthesis of new N-heterocyclic carbene (NHC) gold(I) derivatives with flavone-derived ligands with a propargyl ether group. The compounds were screened for their antimicrobial and anticancer activities, showing greater activity against bacteria than against colon cancer cells (Caco-2). Complexes [Au(L2b)(IMe)] (1b) and [Au(L2b)(IPr)] (2b) were found to be active against both Gram-positive and Gram-negative strains. The mechanism of action of 1b was evaluated by measurement of thioredoxin reductase (TrxR) and dihydrofolate reductase (DHFR) activity, besides scanning electron microscopy (SEM). Inhibition of the enzyme thioredoxin reductase is not observed in either Escherichia Coli or Caco-2 cells; however, DHFR activity is compromised after incubation of E. coli cells with complex 1b. Moreover, loss of structural integrity and change in bacterial shape is observed in the images obtained from scanning electron microscopy (SEM) after treatment E. coli cells with complex 1b.

Scientometric Analysis of Publications from 2004-2021 in the Spine Surgery Field: A Latin American Perspective.

OBJECTIVE: To determine characteristics of Latin American (LA) productivity in spine surgery published worldwide between 2004 and 2021 compared between periods and global literature. METHODS: A comprehensive search about LA productivity in the field of spine surgery using the Scopus and PubMed databases was performed in February 2022. The results were limited to articles published in indexed journals from 2004 to 2021. RESULTS: A total of 1447 publications were identified in the study period. The number of publications has increased across evaluated decades, with 583 between 2004 and 2013 (58.3/year) and 864 between 2014 and 2021 (108/year), and a yearly increase was demonstrated (P = 0.0001). Comparing the most productive year in the first (2012) and last decade (2020), a 1.79-fold increase was demonstrated. Brazil ranked first in productivity (51.14%), followed by Mexico (26.40%) and Argentina (8.64%). Coluna/Columna published the largest number, with 309 articles (21.35%). The top 10 institutions published at least 475 (32.82%) and the most productive was the University of Campinas (Brazil, 74). CONCLUSIONS: This scientometric study is one of the first regional evaluations worldwide. The number of publications in the spine surgery field in Latin America has continued to increase over evaluated decades from 58.3 per year to 108, and a 1.79-fold increase between the most productive years for each decade. Brazil is still the greatest contributor (51.14%), with Mexico (26.40%) and Argentina (8.64%) as growing contributor countries. Most publications were classified as Level of Evidence 4, and this result reflects the importance of continuous research development in the quality of research for our region.

The Matrix Effect in the RT-PCR Detection of SARS-CoV-2 Using Saliva without RNA Extraction.

The present work focuses on the detection of SARS-CoV-2 in saliva, contributing to understanding the inhibition effect of the matrix and its influence on the results. Detection of viral genes ORF1ab, N, and E was performed by RT-PCR using saliva directly in the reaction without RNA extraction. Different amounts of saliva were spiked with increasing amounts of viral RNA from COVID-19 patients and subjected to RT-PCR detection. In parallel, 64 saliva samples from confirmed COVID-19 patients were used in two different amounts directly in the RT-PCR reaction and their results compared. The presence of saliva in the RT-PCR always causes a positive shift of the Ct values, but a very high between-person variability of its magnitude was obtained, with increases ranging from 0.93 to 11.36. Viral targets are also affected differently depending on the initial number of viral particles. Due to inhibitors present in saliva, the duplication of sample volume causes only 48 to 61% of the expected Ct value decrease depending on the viral target gene. The use of saliva has advantages, but also limitations, due to potential inhibitors present in the matrix. However, the choice of the target and the right amount of sample may significantly influence the results.

Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone.

Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs. We present a novel rodent model to analyze the bidirectional signaling between GBM tumors and cells contained within the SVZ. Patient-derived GBM cells expressing GFP and luciferase were engrafted at locations proximal, intermediate, and distal to the LVs in immunosuppressed mice. Mice were either sacrificed after 4 weeks for immunohistochemical analysis of the tumor and SVZ or maintained for survival analysis. Analysis of the GFP+ tumor bulk revealed that GBM tumors proximal to the LV show increased levels of proliferation and tumor growth than LV-distal counterparts and is accompanied by decreased median survival. Conversely, numbers of innate proliferative cells, neural stem cells (NSCs), migratory cells and progenitors contained within the SVZ are decreased as a result of GBM proximity to the LV. These results indicate that our rodent model is able to accurately recapitulate several of the clinical aspects of LV-associated GBM, including increased tumor growth and decreased median survival. Additionally, we have found the neurogenic and cell division process of the SVZ in these adult mice is negatively influenced according to the presence and proximity of the tumor mass. This model will be invaluable for further investigation into the bidirectional signaling between GBM and the neurogenic cell populations of the SVZ.

Performance of saliva as a specimen to detect SARS-CoV-2.

Massive testing to detect SARS-CoV-2 is an imperious need in times of epidemic but also presents challenges in terms of its concretization. The use of saliva as an alternative to nasopharyngeal swabs (NPS) has advantages, being more friendly to the patient and not requiring trained health workers, so much needed in other functions. This study used a total of 452 dual samples (saliva and NPS) of patients suspected of having COVID-19 to compare results obtained for the different specimens when using RT-PCR of RNA extracted from NPS and saliva, as well as saliva directly without RNA extraction. SARS-CoV-2 was not detected in 13 saliva (direct) of the 80 positive NPS samples and in 16 saliva (RNA) of a total of 76 NPS positive samples. Sensitivity of detection of viral genes ORF1ab, E and N in saliva is affected differently and detection of these genes in saliva samples presents great variability when NPS samples present Ct-values above approximately 20, with sensitivities ranging from 76.3% to 86.3%. On average an increase in 7.3 Ct-values (average standard deviation of 4.78) is observed in saliva samples when compared to NPS. The use of this specimen should be carefully considered due to the false negative rate and the system used for detection may be also very relevant since the different viral genes are affected differently in terms of detection sensitivity using saliva.

Anti-inflammatory mechanisms of fruits and by-products from Mauritia flexuosa, an exotic plant with functional benefits.

Mauritia flexuosa L., traditionally known as "buriti", exhibits chemoprotective properties including antioxidant, antithrombotic, and nutritional actions. The aim of this study was to examine the oral anti-inflammatory activity of epicarp, mesocarp and endocarp obtained from M. flexuosa fruits using in vivo models to verify physiological benefits. The anti-edematogenic action was determined using phlogistic agents to induce paw edema and peritonitis. Pro-inflammatory cytokines, cell migration of peritoneal cells, histological changes, and abdominal swelling induced by acetic acid were also investigated. Carrageenan-induced edema was found to be decreased in mice pre-treated with epicarp by 50.8%, 53.7% and 39.2% and mesocarp by 41.8%, 65.3% and 71.9% after 2, 3, and 4 hr stimuli, respectively. Edema initiated by specific agents such as compound 48/80, histamine, serotonin, and prostaglandin E2 were also reduced, and better outcomes were found against histamine-induced edema, as evidenced by the decline at all times analyzed (30-120 min) with both doses of water extract of mesocarp (500 or 1000 mg/kg). Mesocarp-pre-treatment reduced inflammatory tissue parameters such as number of peritoneal leukocytes and TNF-α levels, but only epicarp diminished abdominal pain. In summary, M. flexuosa fruits, especially mesocarp, exhibited oral physiological benefits and capacity to modify biochemical and cellular steps in the inflammatory cascade, indicating that dietary supplements containing these fruits may be combined with pharmacological tools to ameliorate or prevent diseases of inflammatory origin.

The use of proprioceptive neuromuscular facilitation for increasing throwing performance / Uso da facilitação neuromuscular proprioceptiva para aumentar o desempenho do arremesso / Uso de facilitación neuromuscular propioceptiva para mejorar el rendimiento del lanzamiento

ABSTRACT Introduction Throwing is considered the most important technical skill in Handball. However, it requires the athlete to perform this movement with maximum speed and accuracy, as it can define the final score of the game. Objective The aim of this study was to evaluate the effect of Proprioceptive Neuromuscular Facilitation, known as the Kabat method, on the throwing performance of handball athletes. Methods An experimental study of 18 male handball athletes with a mean age of 14 ± 1.13 years. The athletes were divided into two groups: control group (CG) and Kabat method group (KG). The athletes performed 16 training sessions, with analyses at the beginning and end of each session. Range of motion (ROM) of internal and external shoulder rotation, strength, muscle imbalance, throwing speed and accuracy were measured. The results were compared by the Student t-test of repeated measures. Results KG significantly increased external shoulder rotation and muscle strength in all the analyzed shoulder complex muscles. CG also increased strength, but not in all muscles. KG significantly increased the speed and accuracy of the pitch. Conclusion The Kabat method, through proprioceptive neuromuscular facilitation, significantly increased throwing performance, speed and accuracy in handball athletes when compared to the control group. Level of evidence III; Randomized Experimental Study.

RESUMO Introdução O arremesso é considerado a habilidade técnica mais importante do handebol. Porém, exige que o atleta realize esse movimento com máxima velocidade e precisão, visto que ele pode definir a pontuação final do jogo. Objetivo O objetivo deste estudo foi avaliar o efeito da facilitação neuromuscular proprioceptiva, conhecida como método Kabat, no desempenho de arremesso em atletas de handebol. Métodos Estudo experimental com 18 atletas de handebol masculino, com média de idade de 14 ± 1,13 anos. Os atletas foram divididos em dois grupos: grupo controle (GC) e grupo método Kabat (GK). Os atletas realizaram 16 sessões de treinamento com análise inicial e final. A amplitude de movimento (ADM) da rotação interna e externa do ombro, a força, o desequilíbrio muscular, a velocidade e precisão do arremesso foram medidos. Os resultados foram comparados com o teste t de Student de medidas repetidas. Resultados O GK teve aumento significativo da rotação externa do ombro e da força muscular em todos os músculos do complexo do ombro analisados. O GC também teve aumento da força, mas não em todos os músculos. O GK teve elevação significativa da velocidade e da precisão do arremesso. Conclusão O método Kabat, com a técnica de facilitação neuromuscular proprioceptiva, aumentou significativamente o desempenho, a velocidade e a precisão do arremesso nos atletas de handebol quando comparado com o grupo controle. Nível de evidência III; Estudo Experimental Randomizado.

RESUMEN Introducción El lanzamiento se considera la habilidad técnica más importante del balonmano. Sin embargo, requiere que el atleta realice este movimiento con la máxima velocidad y precisión, ya que puede establecer el puntaje final del juego. Objetivo El objetivo de este estudio fue evaluar el efecto de la facilitación neuromuscular propioceptiva, conocida como el método Kabat, en el rendimiento del lanzamiento de atletas de balonmano. Métodos Estudio experimental de 18 atletas de balonmano masculino con edad promedio de 14 ± 1,13 años. Los atletas se dividieron en dos grupos: grupo control (CG) y grupo método Kabat (GK). Los atletas realizaron 16 sesiones de entrenamiento con análisis inicial y final. Se midió el rango de movimiento (RDM) de la rotación interna y externa del hombro, la fuerza, el desequilibrio muscular, la velocidad y la precisión de lanzamiento. Los resultados se compararon con la prueba t de Student de medidas repetidas. Resultados El GK tuvo un aumento significativo en la rotación externa del hombro y la fuerza muscular en todos los músculos del complejo del hombro analizados. El CG también tuvo aumento en la fuerza, pero no en todos los músculos. El GK tuvo un aumento significativo en la velocidad y precisión del lanzamiento. Conclusión El método Kabat, con la facilitación neuromuscular propioceptiva, aumentó significativamente el rendimiento, la velocidad y la precisión del lanzamiento en los atletas de balonmano en comparación con el grupo control. Nivel de evidencia III; Estudio experimental aleatorizado.

Posterior Grade 4 Osteotomy With Vertebral Shortening Is Effective for the Treatment of Kyphosis Associated With Vertebral Discitis/Osteomyelitis.

BACKGROUND: In the retrospective study of a prospectively maintained database, we present a case series of patients with kyphotic deformity secondary to spinal infection treated using a posterior-only approach with 3-column shortening and posterior instrumentation. METHODS: This is a case series of patients presenting with postural deformity and sagittal imbalance treated consecutively by 1 surgeon between 2012 and 2014. Clinical assessments and radiographic evaluations were made preoperatively and at 12- and 24-month postoperative follow-ups. All patients underwent computed tomography 24 months after surgery to evaluate spinal fusion. RESULTS: The study included 5 patients with a mean age of 50 years (range, 32-60 years). Three patients had comorbidities. Three patients were classified as American Spinal Injury Association (ASIA) grade C and were not ambulatory; 2 were ASIA grade D. At follow-up, all patients were ambulatory and classified as ASIA grade E. Kyphosis was corrected from a preoperative mean of 32° (range, 15°-58°) to 10° (range, 1°-42°) at the 2-year follow-up. A mean improvement of 22° and 75% reduction in kyphosis was obtained with fixation 2 levels above and below the lesion. Interbody fusion was observed in all patients. No major complications occurred during surgery. CONCLUSIONS: Posterior grade 4 osteotomy with vertebral shortening can be performed safely in patients with kyphosis associated with vertebral discitis/osteomyelitis in the thoracolumbar region. The single approach allowed the surgeon to debride the infection, correct the kyphosis, decompress the spinal canal, and stabilize the spine. LEVEL OF EVIDENCE: 4.

Unravelling the Biological Potential of Pinus pinaster Bark Extracts.

Natural compounds from agro-food by-products have fostered interest in food industries. The aim of this study was to unravel potential uses for Pinus pinaster bark extracts (PBE). As functional features of this type of extracts are usually attributed to phenolic compounds, the extraction process was studied. Different PBEs were achieved, with high content in phenolic compounds, using different water/ethanol combinations as a solvent. These PBEs were chemically characterized, and their bioactivity and in vitro cell viability were evaluated. Extracts obtained with hydroethanolic solvents had higher content in phenolic and flavonoid compounds. All the PBEs presented high antioxidant, antibacterial and antihyperglycemic activities. Moreover, PBEs have low cytotoxicity and a selective activity against cancer cells as these were negatively affected. These features may allow the extracts to be used in food formulation and processing (as preservatives, antioxidants or bioactive ingredients), but they showed also potential for the pharmaceutical or nutraceutical sectors.

Impact of severe acute kidney injury and chronic kidney disease on allogeneic hematopoietic cell transplant recipients: a retrospective single center analysis.

Acute kidney injury (AKI) increases early mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients and may accelerate chronic kidney disease (CKD) development. We analyzed prospective variables related to AKI and CKD in 422 allo-HCT recipients to establish risk factors of severe acute renal failure and CKD. Renal function and creatinine were periodically assessed from baseline till the last follow-up. Sixty-three patients (14%) developed severe AKI (AKI-3) at 100 days post transplant and 15% at 12 months. Variables associated with AKI-3 were age above 55 years [hazard ratio (HR): 2.4; p = 0.019], total body irradiation (TBI) (HR: 1.8; p = 0.044), high-risk cytomegalovirus reactivation (HR: 1.8; p = 0.041), and methotrexate as GVHD prophylaxis (HR: 2.1; p = 0.024). AKI-3 increased the mortality risk (HR: 2.5, 95% confidence interval: 1.9-3.4). The CKD prevalence in 161 living patients was 10.2% at the last follow-up and in most, CKD developed 1 year post HCT, independent of AKI. The CKD at 1 year post HCT was associated with increased mortality (HR: 3.54; p < 0.001). Interestingly, pretransplant CKD was associated with early mortality (HR: 5.6; p < 0.001). In fact, pre- and posttransplant CKD had independent unfavorable long-term outcomes. These pretransplant factors can potentially be targeted to improve allo-HCT outcomes.

A reproducible and safe at-home allogeneic haematopoietic cell transplant program: first experience in Central and Southern Europe.

In 2015, we implemented an at-home allogeneic haematopoietic cell transplant (allo-HCT) program. Between 2015 and 2018, 252 patients underwent allo-HCT; 41 patients underwent allo-HCT in the at-home program (46% myeloablative; 63% unrelated donor; 32% posttransplant cyclophosphamide), and these patients were compared with 39 in-patients; safety, capacity to release beds for other programs, and economic efficiency cost were evaluated. We observed a lower incidence of febrile neutropenia in the at-home group compared with that in the in-patient group (32% versus 90%; p < 0.0001), whereas the incidence of aspergillosis was similar among groups (at-home 1% versus in-patient 3%; p = 0.5). The at-home patients showed a lower incidence of 1-year severe graft-versus-host disease (GVHD; 10% versus 29%; p = 0.03). There were no differences in 1-year transplant-related mortality, relapse, or overall survival among groups. The re-admission rate in the at-home group was 7%. The at-home setting was less expensive (9087 €/transplant), and its implementation increased capacity by 10.5 allo-HCTs/year. Moreover, a chimeric antigen receptor T-cell program could be established without increasing beds. Thus, our at-home allo-HCT program may be a safe modality to reduce febrile neutropenia and acute GVHD, resulting in lower re-admission rates.

The peroxisome proliferator-activated receptor-ß/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.

Diabetic retinopathy (DR) is triggered by retinal cell damage stimulated by the diabetic milieu, including increased levels of intraocular free fatty acids. Free fatty acids may serve as an initiator of inflammatory cytokine release from Müller cells, and the resulting cytokines are potent stimulators of retinal endothelial pathology, such as leukostasis, vascular permeability, and basement membrane thickening. Our previous studies have elucidated a role for peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) in promoting several steps in the pathologic cascade in DR, including angiogenesis and expression of inflammatory mediators. Furthermore, PPARß/δ is a known target of lipid signaling, suggesting a potential role for this transcription factor in fatty acid-induced retinal inflammation. Therefore, we hypothesized that PPARß/δ stimulates both the induction of inflammatory mediators by Müller cells as well the paracrine induction of leukostasis in endothelial cells (EC) by Müller cell inflammatory products. To test this, we used the PPARß/δ inhibitor, GSK0660, in primary human Müller cells (HMC), human retinal microvascular endothelial cells (HRMEC) and mouse retina. We found that palmitic acid (PA) activation of PPARß/δ in HMC leads to the production of pro-angiogenic and/or inflammatory cytokines that may constitute DR-relevant upstream paracrine inflammatory signals to EC and other retinal cells. Downstream, EC transduce these signals and increase their synthesis and release of chemokines such as CCL8 and CXCL10 that regulate leukostasis and other cellular events related to vascular inflammation in DR. Our results indicate that PPARß/δ inhibition mitigates these upstream (MC) as well as downstream (EC) inflammatory signaling events elicited by metabolic stimuli and inflammatory cytokines. Therefore, our data suggest that PPARß/δ inhibition is a potential therapeutic strategy against early DR pathology.

Toxicological findings about an anticancer fraction with casearins described by traditional and alternative techniques as support to the Brazilian Unified Health System (SUS).

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts, essential oils and molecules from Casearia sylvestris have popularly shown pharmacological actions against chronic diseases, as anxiety, inflammation, cancer and dyslipidemia. In the context of antitumoral therapy, we investigated in vitro, ex vivo and in vivo toxicological changes induced by a Fraction with Casearins (FC) and its component Casearin X isolated from C. sylvestris on animal and vegetal cells, and upon invertebrates and mammals. MATERIAL AND METHODS: Cytotoxicity was carried out using normal lines and absorbance and flow cytometry techniques, Artemia salina nauplii, Danio rerio embryos and meristematic cells from Allium cepa roots. Acute and 30 days-mice analysis were done by behavioral, hematological and histological investigations and DNA/chromosomal damages detected by alkaline Cometa and micronucleus assays. RESULTS: FC was cytotoxic against lung and fibroblasts cells and caused DNA breaks, loss of integrity and mitochondrial depolarization on ex vivo human leukocytes. It revealed 24 h-LC50 values of 48.8 and 36.7 µg/mL on A. salina nauplii and D. rerio embryos, reduced mitotic index of A. cepa roots, leading to cell cycle arrest at metaphase and anaphase and micronuclei. FC showed i.p. and oral LD50 values of 80.9 and 267.1 mg/kg body weight. Subacute i.p. injections induced loss of weight, swelling of hepatocytes and tubules, tubular and glomerular hemorrhage, microvesicular steatosis, lung inflammatory infiltration, augment of GPT, decrease of albumin, alkaline phosphatase, glucose, erythrocytes, and lymphocytes, and neutrophilia (p > 0.05). FC-treated animals at 10 mg/kg/day i.p. caused micronuclei in bone marrow and DNA strand breaks in peripheral leukocytes. CONCLUSIONS: This research postulated suggestive side effects after use of FC-related drugs, demonstrating FC as antiproliferative and genotoxic on mammal and meristematic cells, including human leukocytes, teratogenicity upon zebrafish embryos, myelosuppression, clastogenicity, and morphological and biochemical markers indicating liver as main target for FC-induced systemic toxicity.