Introduction
The knee in Parkinson’s disease (PD) patients is a problematic joint due to pain, stiffness and gait instability. The aim of this study is to evaluate the functional outcome and degree ...of pain relief achieved after total knee arthroplasty (TKA) in PD patients.
Materials and methods
This is a retrospective review of 26 PD patients (32 knees) with osteoarthritis who underwent a TKA between 1994 and 2013. Comorbidities, anesthetic procedures and complications were recorded. Patient functional status was assessed with the Knee Society Function Score (KFS) and the Knee Society Score (KSS). PD stage was classified with the Hoehn and Yahr Scale.
Results
The mean follow-up was 3.5 years (range 2–9). The mean age was 71 years (range 61–83) with a mean time since PD diagnosis of 11.8 years (range 4–24). PD severity on the Hoehn and Yahr Scale was 1.5 points before surgery and 2 points postoperatively. Pain on the visual analogic scale improved from 8 points preoperatively to 5 points at 1-year follow-up; function improved from 32 (range 20–45) to 71 (range 50–81) and from 34 (range 28–52) to 59 (range 25–76) on the KSS and KFS, respectively. The mean postoperative hospital stay was 9.8 days (range 5–21). Confusion and flexion contracture were the most frequent perioperative complications.
Conclusion
TKA successfully provided pain relief in PD patients. However, the functional outcome is related to disease progression and, therefore, variable. Perioperative complications are difficult to avoid and manage.
Garlic (
) has historically been associated with antioxidant, immunomodulatory, and microbiocidal properties, mainly due to its richness in thiosulfates and sulfur-containing phytoconstituents. ...Sepsis patients could benefit from these properties because it involves both inflammatory and refractory processes. We evaluated the effects of thiosulfinate-enriched
extract (TASE) on the immune response to bacterial lipopolysaccharide (LPS) by monocytes from healthy volunteers (HVs) and patients with sepsis. We also explored the TASE effects in HIF-1α, described as the key transcription factor leading to endotoxin tolerance in sepsis monocytes through
expression. Our results showed TASE reduced the LPS-triggered reactive oxygen species (ROS) production in monocytes from both patients with sepsis and HVs. Moreover, this extract significantly reduced tumor necrosis factor (TNF)-α, interleukin-1β, and interleukin-6 production in LPS-stimulated monocytes from HVs. However, TASE enhanced the inflammatory response in monocytes from patients with sepsis along with increased expression of human leukocyte antigen-DR. Curiously, these dual effects of TASE on immune response were also found when the HV cohort was divided into low- and high-LPS responders. Although TASE enhanced TNFα production in the LPS-low responders, it decreased the inflammatory response in the LPS-high responders. Furthermore, TASE decreased the HIF-1α pathway-associated genes
,
and
in sepsis cells, suggesting HIF-1α inhibition by TASE leads to higher cytokine production in these cells as a consequence of IRAK-M downregulation. The suppression of this pathway by TASE was confirmed in vitro with the prolyl hydroxylase inhibitor dimethyloxalylglycine. Our data revealed TASE's dual effect on monocyte response according to status/phenotype and suggested the HIF-1α suppression as the possible underlying mechanism.
Myocarditis is an inflammation of the myocardium that can progress to a more severe phenotype of dilated cardiomyopathy (DCM). Three main harmful factors determine this progression: inflammation, ...cell death, and oxidative stress. Lipoxins and their derivatives are endogenous proresolving mediators that induce the resolution of the inflammatory process. This study aims to determine whether these mediators play a protective role in a murine model of experimental autoimmune myocarditis (EAM) by treating with the lipoxin A4 analog BML‐111. We observed that EAM mice presented extensive infiltration areas that correlated with higher levels of inflammatory and cardiac damage markers. Both parameters were significantly reduced in BML‐treated EAM mice. Consistently, cardiac dysfunction, hypertrophy, and emerging fibrosis detected in EAM mice was prevented by BML‐111 treatment. At the molecular level, we demonstrated that treatment with BML‐111 hampered apoptosis and oxidative stress induction by EAM. Moreover, both in vivo and in vitro studies revealed that these beneficial effects were mediated by activation of Nrf2 pathway through CaMKK2‐AMPKα kinase pathway. Altogether, our data indicate that treatment with the lipoxin derivative BML‐111 effectively alleviates EAM outcome and prevents cardiac dysfunction, thus, underscoring the therapeutic potential of lipoxins and their derivatives to treat myocarditis and other inflammatory cardiovascular diseases.
Human-adipose-derived mesenchymal stem cells (hADMSCs) are multipotent stem cells which have become of great interest in stem-cell therapy due to their less invasive isolation. However, they have ...limited migration and short lifespans. Therefore, understanding the mechanisms by which these cells could migrate is of critical importance for regenerative medicine. Methods: Looking for novel alternatives, herein, hADMSCs were isolated from adipose tissue and co-cultured with human monocytes ex vivo. Results: A new fused hybrid entity, a foam hybrid cell (FHC), which was CD90+CD14+, resulted from this co-culture and was observed to have enhanced motility, proliferation, immunomodulation properties, and maintained stemness features. Conclusions: Our study demonstrates the generation of a new hybrid cellular population that could provide migration advantages to MSCs, while at the same time maintaining stemness properties.
Background: The cancer cell fusion theory could be one of the best explanations for the metastasis from primary tumours. Methods: Herein, we co-cultured colorectal cancer (CRC) stem cells with human ...monocytes and analysed the properties of the generated tumour hybrid cells (THCs). The presence of THCs in the bloodstream together with samples from primary and metastatic lesions and their clinical correlations were evaluated in CRC patients and were detected by both FACS and immunofluorescence methods. Additionally, the role of SIGLEC5 as an immune evasion molecule in colorectal cancer was evaluated. Results: Our data demonstrated the generation of THCs after the in vitro co-culture of CRC stem cells and monocytes. These cells, defined as CD45+CD14+EpCAM+, showed enhanced migratory and proliferative abilities. The THC-specific cell surface signature allows identification in matched primary tumour tissues and metastases as well as in the bloodstream from patients with CRC, thus functioning as a biomarker. Moreover, SIG-LEC5 expression on in vitro generated THCs has shown to be involved in the mechanism for immune evasion. Additionally, sSIGLEC5 levels correlated with THC numbers in the prospective cohort of patients. Conclusions: Our results indicate the generation of a hybrid entity after the in vitro co-culture between CRC stem cells and human monocytes. Moreover, THC numbers present in patients are related to both prognosis and the later spread of metastases in CRC patients.
Cardiac fibrosis and chronic inflammation are common complications in type 2 diabetes mellitus (T2D). Since nucleotide oligomerization-binding domain 1 (NOD1), an innate immune receptor, is involved ...in the pathogenesis of insulin resistance and diabetes outcomes, we sought to investigate its involvement in cardiac fibrosis. Here, we show that selective staining of cardiac fibroblasts from T2D (db/db;db) mice exhibits up-regulation and activation of the NOD1 pathway, resulting in enhanced NF-κB and TGF-β signalling. Activation of the TGF-β pathway in cardiac fibroblasts from db mice was prevented after inhibition of NF-κB with BAY-11-7082 (BAY). Moreover, fibrosis progression in db mice was also prevented by BAY treatment. Enhanced TGF-β signalling and cardiac fibrosis of db mice was dependent, at least in part, on the sequential activation of NOD1 and NF-κB since treatment of db mice with a selective NOD1 agonist induced activation of the TGF-β pathway, but co-administration of a NOD1 agonist plus BAY, or a NOD1 inhibitor prevented the NOD1-induced fibrosis. Therefore, NOD1 is involved in cardiac fibrosis associated with diabetes, and establishes a new mechanism for the development of heart fibrosis linked to T2D.
The resolution of inflammation is an active process driven by specialized pro-resolving lipid mediators, such as 15-epi-LXA
4
and resolvin D1 (RvD1), that promote tissue regeneration. Macrophages ...regulate the innate immune response being key players during the resolution phase to avoid chronic inflammatory pathologies. Their half-life is tightly regulated to accomplish its phagocytic function, allowing the complete cleaning of the affected area. The balance between apoptosis and autophagy appears to be essential to control the survival of these immune cells within the inflammatory context. In the present work, we demonstrate that 15-epi-LXA
4
and RvD1 at nanomolar concentrations promote autophagy in murine and human macrophages. Both compounds induced the MAP1LC3-I to MAP1LC3-II processing and the degradation of SQSTM1 as well as the formation of MAP1LC3
+
autophagosomes, a typical signature of autophagy. Furthermore, 15-epi-LXA
4
and RvD1 treatment favored the fusion of the autophagosomes with lysosomes, allowing the final processing of the autophagic vesicles. This autophagic response involves the activation of MAPK1 and NFE2L2 pathways, but by an MTOR-independent mechanism. Moreover, these pro-resolving lipids improved the phagocytic activity of macrophages via NFE2L2. Therefore, 15-epi-LXA
4
and RvD1 improved both survival and functionality of macrophages, which likely supports the recovery of tissue homeostasis and avoiding chronic inflammatory diseases.
Introducción: Las técnicas para corregir las deformidades del hallux incluyen osteotomías metatarsianas y falángicas. Las osteotomías sobre la falange proximal corrigen el DASA y el ángulo ...interfalángico. Sin embargo, no se han publicado las indicaciones para la osteotomía de la falange distal. El objetivo de este artículo es comunicar la técnica y las indicaciones de la osteotomía percutánea de la falange distal del hallux, y evaluar los resultados de una serie de casos.
Materiales y Métodos: Se analizaron 14 pies en los que se realizó una osteotomía de la falange distal del hallux para corregir una deformidad. Se midieron el DASA, la oblicuidad interfalángica y el ángulo falange distal-interfalángico en las radiografías. La técnica quirúrgica fue percutánea con control fluoroscópico. Los resultados se evaluaron mediante las escalas analógica visual de dolor y AOFAS. Seguimiento medio: 52 meses.
Resultados: 13 pies de mujeres y un pie de hombre. Edad promedio: 58 años. Los resultados clínico y estético fueron excelentes, con alivio del dolor. Mejoría de la escala AOFAS: promedio 37 puntos. Análisis comparativo de ángulos preoperatorios y posoperatorios: DASA (p = 0,01), excepto cuando se aisló de la muestra a los pacientes con osteotomía tipo Akin (p = 0,33); ángulos F2-IF y F2-MTF (p <0,00001). Se registraron las complicaciones.
Conclusiones: En la deformidad en valgo de la falange distal del hallux sintomática, se debe considerar una osteotomía correctora sola o asociada a osteotomía de la falange proximal. La osteotomía percutánea de la falange distal es un método eficaz, seguro y rápido.
Nivel de Evidencia: IV
We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost ...8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.
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•History of SARS-CoV-2 infection affects longitudinal responses to BNT162b2 vaccine•Lower humoral but enhanced cellular responses early after vaccine in naive subjects•Comparable humoral and cellular responses almost 8 months after vaccination•Similar S-specific B cells late after vaccine in those naive and recovered from COVID-19
Lozano-Rodríguez et al. show that naive subjects have enhanced SARS-CoV-2 spike-specific T reactions but reduced humoral-specific responses compared with individuals recovered from COVID-19. However, almost 8 months after vaccination, comparable specific responses are observed with equivalent levels of SARS-CoV-2-specific B cells and neutralizing antibodies.
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