Dissingsherman2675
Despite any possible advantages of one technique over the other, which approach is best for each patient must be decided on a case-by-case basis and more long-term follow-up data are warranted.Renal tubulointerstitial fibrosis (RIF), characterized by epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs), is the main cause of diabetic renal fibrosis. Oxidative stress plays a pivotal role in the development of diabetic RIF. Connexin32 (Cx32), prominently expressed in renal TECs, has emerged as an important player in the regulation of oxidative stress. However, the role of Cx32 in diabetic RIF has not been explored yet. Here, we showed that adenovirus-mediated Cx32 overexpression suppressed EMT to ameliorate RIF and renal function in STZ-induced diabetic mice, while knockout (KO) of Cx32 exacerbated RIF in diabetic mice. Moreover, overexpression of Cx32 inhibited EMT and the production of extra cellular matrix (ECM) in high glucose (HG) induced NRK-52E cells, whereas knockdown of Cx32 showed the opposite effects. Furthermore, we showed that NOX4, the main source of ROS in renal tubular, was down-regulated by Cx32. Mechanistically, Cx32 down-regulated the expression of PKC alpha in a carboxyl-terminal-dependent manner, thereby inhibiting the phosphorylation at Thr147 of p22phox triggered by PKC alpha, which ultimately repressed the formation of the p22phox-NOX4 complex to reduce the protein level of NOX4. Thus, we establish Cx32 as a novel target and confirm the protection mechanism in RIF.Herpesviruses can either cause primary infection or may get reactivated after both hematopoietic cell and solid organ transplantations. In general, viral infections increase post-transplant morbidity and mortality. Prophylactic, preemptive, or therapeutically administered antiviral drugs may be associated with serious side effects and may induce viral resistance. Virus-specific T cells represent a valuable addition to antiviral treatment, with high rates of response and minimal side effects. Even low numbers of virus-specific T cells manufactured by direct selection methods can reconstitute virus-specific immunity after transplantation and control viral replication. Virus-specific T cells belong to the advanced therapy medicinal products, and their production is regulated by appropriate legislation; also, strict safety regulations are required to minimize their side effects.Chimeric antigen receptor (CAR) T-cell immunotherapies targeting CD19 can achieve impressive clinical remission rates in the treatment of B-cell non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia. Canagliflozin However, relapse after CD19-CAR T treatment remains a major issue, with CD19 antigen-negative relapse being one of the main reasons. CD22, another antigen expressed in a B-cell lineage-specific pattern, is retained following CD19 loss. Accordingly, we hypothesized that CD22 could represent an alternative target to alleviate or compensate for the ineffectiveness of CD19-CAR T therapy. To this end, we generated camelid-derived CD22 nanobodies, whose smaller size, greater stability, and lower immunogenicity offer better quality than classical antibodies, and we used them to construct third-generation CD22-CARs containing 4-1BB and ICOS co-stimulatory domains. The novel CD22-CAR T cells exhibited impressive cytotoxicity both in vitro and in vivo and significantly prolonged the overall survival of tumor-bearing NSG mice. These findings provide the basis for further translational studies employing CD22-CARs.
This systematic review investigated the incidence of stent migration in patients with acute and chronic deep venous iliofemoral disease who were treated with dedicated venous stents. Procedural approaches, clinical and stent patency outcomes, and other complications are described.
MEDLINE and Embase were searched for literature published from January, 2012 to December, 2021. Evidence on the study population and procedural characteristics, and outcomes related to symptomatic changes, health-related quality of life, stent patency and complications was presented.
Fourty-two studies were identified from 857 articles found through the database searches. Five-hundred seventy acute deep vein thrombosis patients and 2,859 chronic disease patients were included. Ten dedicated venous stent brands were employed. There were six episodes of stent migration (0.17% of patients) of which three involved a closed-cell stent and one involved a hybrid-design stent. The 12-month primary patency rate in patients with acute deep vein thrombosis ranged from 86 to 88%, whilst secondary patency was 96%. Amongst the chronic-disease cohort the primary and secondary patency were noted to range from 59 to 94%, and 87 to 100%, respectively. The pooled 12-month primary and secondary stent patency rates were 73.8% and 91.5%, respectively.
Iliofemoral stenting using dedicated venous stents is associated with a low rate of stent migration although this may be due to a lack of reporting. Further research with specific surveillance protocols is necessary to reliably determine the true incidence of stent migration.
Iliofemoral stenting using dedicated venous stents is associated with a low rate of stent migration although this may be due to a lack of reporting. Further research with specific surveillance protocols is necessary to reliably determine the true incidence of stent migration.
There is a paucity of data regarding the conversion rate from dry gangrene to wet gangrene after lower extremity revascularization. This study aimed to determine the rate of conversion from dry to wet gangrene within 30 days post-procedure in patients who underwent endovascular or open revascularization for critical limb ischemia. Secondary aims included determining the time to conversion and associated risk factors with conversion.
A multicenter, retrospective review was performed utilizing the MGH/Brigham Healthcare System's Research Patient Data Registry (RPDR). All adult patients who had lower extremity dry gangrene that underwent a revascularization procedure (endo, open, hybrid) from April 2002 to March 2020 were included. Patients who had no lower extremity gangrene, a concurrent amputation with the revascularization procedure, or wet gangrene on initial presentation were excluded. Univariate analysis was performed using the Fisher's exact test and Wilcoxon rank-sum test.
There were 1,518 patients identified who underwent revascularization; 194 (12.8%) patients met inclusion criteria and served as our study cohort. There were 15 (7.7%) conversions from dry to wet gangrene within 30 days post-procedure. The mean time to conversion was 13.5 ± 8.6 days. Univariate analysis did not identify any associated risk factors for conversion.
The rate of dry to wet gangrene conversion post revascularization is 7.7% within 30 days. The mean time of conversion is 13.5 ± 8.6 days.
The rate of dry to wet gangrene conversion post revascularization is 7.7% within 30 days. The mean time of conversion is 13.5 ± 8.6 days.
Failure of maturation of arteriovenous fistulae (AVF) remains an ongoing concern for dialysis access. One etiology is the presence of side branches that divert flow from the main AVF channel. This study aims to evaluate the outcomes of endovascular and open surgical interventions for AVF side branches in the setting of maturation failure.
A retrospective review of all patients within a 10-year period with primary radio cephalic and brachiocephalic AVF was undertaken, and 380 cases of maturation failure related to branch diversion were selected for the study. Fifty-four percent and 48% of the AVF in the ENDO and OPEN groups respectively have concomitant stenosis further along in the flow path that required intervention by balloon angioplasty at the same time as a side branch intervention. All patients underwent duplex imaging or a fistulogram before intervention. Indications were low flow (<600 mL/min) or failure to increase in size (<6 mm diameter) in all cases. Interventions were divided into endovthe cases with no difference between ENDO and OPEN. Recannulation of the ENDO branches occurred in 10% of the cases requiring repeat intervention. Sixty one percent of isolated endovascular (n=49) and 64% of isolated open (n=68) matured to successful cannulation (P=0.84). Median functional dialysis durations remained equivalent between ENDO (2.6 years) and OPEN (2.8 years) groups (P=0.12).
There is an improved maturation rate following the ENDO group compared to OPEN interventions while both ENDO and OPEN modalities demonstrated similar long-term functionality.
There is an improved maturation rate following the ENDO group compared to OPEN interventions while both ENDO and OPEN modalities demonstrated similar long-term functionality.Mathematical modeling of the relationship between the functional activity and the structural wiring of the brain has largely been undertaken using non-linear and biophysically detailed mathematical models with regionally varying parameters. While this approach provides us a rich repertoire of multistable dynamics that can be displayed by the brain, it is computationally demanding. Moreover, although neuronal dynamics at the microscopic level are nonlinear and chaotic, it is unclear if such detailed nonlinear models are required to capture the emergent meso-(regional population ensemble) and macro-scale (whole brain) behavior, which is largely deterministic and reproducible across individuals. Indeed, recent modeling effort based on spectral graph theory has shown that an analytical model without regionally varying parameters and without multistable dynamics can capture the empirical magnetoencephalography frequency spectra and the spatial patterns of the alpha and beta frequency bands accurately. In this work, we demonstrate an improved hierarchical, linearized, and analytic spectral graph theory-based model that can capture the frequency spectra obtained from magnetoencephalography recordings of resting healthy subjects. We reformulated the spectral graph theory model in line with classical neural mass models, therefore providing more biologically interpretable parameters, especially at the local scale. We demonstrated that this model performs better than the original model when comparing the spectral correlation of modeled frequency spectra and that obtained from the magnetoencephalography recordings. This model also performs equally well in predicting the spatial patterns of the empirical alpha and beta frequency bands.Relating individual differences in cognitive traits to brain functional organization is a long-lasting challenge for the neuroscience community. Individual intelligence scores were previously predicted from whole-brain connectivity patterns, extracted from functional magnetic resonance imaging (fMRI) data acquired at rest. Recently, it was shown that task-induced brain activation maps outperform these resting-state connectivity patterns in predicting individual intelligence, suggesting that a cognitively demanding environment improves prediction of cognitive abilities. Here, we use data from the Human Connectome Project to predict task-induced brain activation maps from resting-state fMRI, and proceed to use these predicted activity maps to further predict individual differences in a variety of traits. While models based on original task activation maps remain the most accurate, models based on predicted maps significantly outperformed those based on the resting-state connectome. Thus, we provide a promising approach for the evaluation of measures of human behavior from brain activation maps, that could be used without having participants actually perform the tasks.