Notes

Mechanogenomic coupling regarding bronchi tissues firmness, EMT and also coronavirus pathogenicity.
Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of coronavirus disease 2019, which has been termed multisystem inflammatory syndrome in children (MIS-C).

This study aimed to analyze echocardiographic manifestations in MIS-C.

A total of 28 MIS-C, 20 healthy control subjects and 20 classic Kawasaki disease (KD) patients were retrospectively reviewed. The study reviewed echocardiographic parameters in the acute phase of the MIS-C and KD groups, and during the subacute period in the MIS-C group (interval 5.2 ± 3days).

Only 1 case in the MIS-C group (4%) manifested coronary artery dilatation (z score=3.15) in the acute phase, showing resolution during early follow-up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters were worse in patients with MIS-C compared with KD. Moreover, MIS-C patients with myocardial injury were more affected than those without myocardial injury with rteries may be spared in early MIS-C; however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms.Our aim was to identify the longitudinal changes in gray matter volume (GMV) and secondary alterations of structural covariance after pontine stroke (PS). Structural MRI and behavioral scores were obtained at 1 week, 1 month, 3 months, 6 months in 11 patients with PS. Twenty healthy subjects underwent the same examination only once. We used voxel-based morphometry and seed-based structural covariance to investigate the altered GMV and structural covariance patterns. Furthermore, the associations between the GMV changes and behavioral scores were assessed. With the progression of the disease, GMV decreased significantly in the bilateral cerebellar posterior lobe (ipsilateral Crus II (CBE Crus II_IL) and contralateral Crus I (CBE Crus I_CL)), which were initially detected at the first month and then continued to decrease during the following 6 months. Based on the CBE Crus II_IL and CBE Crus I_CL as seed regions, structural covariance analysis revealed that there were more positively and negatively correlated brain regions in PS group, mainly distributed in the bilateral prefrontal lobe, parietal lobe, temporal lobe, paralimbic system and cerebellum. In addition, PS group showed more additional correlations between these covariant brain regions, and the changes of GMV in these regions were correlated with behavioral scores related to motor and cognitive functions. These findings indicate that PS could lead to significant GMV atrophy in the bilateral cerebellar posterior lobe at the early stage, accompanied by anomalous structural covariance patterns with more covariant brain regions and additional structural connectivity, which may provide useful information for understanding the neurobiological mechanisms of behavioral recovery after PS.Both rare, high risk, loss-of-function mutations and common, low risk, genetic variants in the CUL3 gene are strongly associated with neuropsychiatric disorders. Network analyses of neuropsychiatric risk genes have shown high CUL3 expression in the prenatal human brain and an enrichment in neural precursor cells (NPCs) and cortical neurons. The role of CUL3 in human neurodevelopment however, is poorly understood. In the present study, we used CRISPR/Cas9 nickase to knockout CUL3 in human induced pluripotent stem cells (iPSCs). iPSCs were subsequently differentiated into cortical glutamatergic neurons using two different protocols and tested for structural/functional alterations. Immunocytochemical analysis and transcriptomic profiling revealed that pluripotency of heterozygous CUL3 knockout (KO) iPSCs remained unchanged compared to isogenic control iPSCs. Following small molecule-mediated differentiation into cortical glutamatergic neurons however, we detected a significant delay in transition from proliferating radial glia cells/NPCs to postmitotic neurons in CUL3 KO cultures. Notably, direct neural conversion of CUL3 KO iPSCs by lentiviral expression of Neurogenin-2 massively attenuated the neurodevelopmental delay. However, both optogenetic and electrical stimulation of induced neurons revealed decreased excitability in Cullin-3 deficient cultures, while basal synaptic transmission remained unchanged. Analysis of target gene expression pointed to alterations in FGF signaling in CUL3 KO NPCs, which is required for NPC proliferation and self-renewal, while RhoA and Notch signaling appeared unaffected. Our data provide first evidence for a major role of Cullin-3 in neuronal differentiation, and for neurodevelopmental deficits underlying neuropsychiatric disorders associated with CUL3 mutations.Chemokine receptors are key regulators of cell migration in terms of immunity and inflammation. Among these, CCR5 and CXCR4 play pivotal roles in cancer metastasis and HIV-1 transmission and infection. They act as essential co-receptors for HIV and furnish a route to the cell entry. In particular, inhibition of either CCR5 or CXCR4 leads very often the virus to shift to a more virulent dual-tropic strain. Therefore, dual receptor inhibition might improve the therapeutic strategies against HIV. In this study, we aimed to discover selective CCR5, CXCR4, and dual CCR5/CXCR4 antagonists using both receptor- and ligand-based computational methods. We employed this approach to fully incorporate the interaction attributes of the binding pocket together with molecular dynamics (MD) simulations and binding free energy calculations. The best hits were evaluated for their anti-HIV-1 activity against CXCR4- and CCR5-specific NL4.3 and BaL strains. Moreover, the Ca2+ mobilization assay was used to evaluate their antagonistic activity. From the 27 tested compounds, three were identified as inhibitors compounds 27 (CCR5), 6 (CXCR4) and 3 (dual) with IC50 values ranging from 10.64 to 64.56 μM. The binding mode analysis suggests that the active compounds form a salt bridge with the glutamates and π-stacking interactions with the aromatic side chains binding site residues of the respective co-receptor. The presented hierarchical virtual screening approach provides essential aspects in identifying potential antagonists in terms of selectivity against a specific co-receptor. The compounds having multiple heterocyclic nitrogen atoms proved to be relatively more specific towards CXCR4 inhibition as compared to CCR5. The identified compounds serve as a starting point for further development of HIV entry inhibitors through synthesis and quantitative structure-activity relationship studies.The involvement of brainstem noradrenergic system in thermoregulation during exercise was evaluated by assessing the neuronal activation of A1, A2, locus coeruleus (LC) during exercise. Male Wistar rats weighing 280-330 g were used in the present study. Ninety minutes after exercise bout until fatigue, animals were anaesthesiated and brain removed and processed immunohistochemically for Fos protein and tyrosine hydroxylase in A1, A2 and LC and for Fos in POA subregions. Core and tail temperature were recorded during all running period by telemetry system. Heat storage rate (HSR, cal.min-1), maximum tail vasoconstriction (°C) and vasodilatation threshold (°C) were calculated and correlated with Fos expression in all nuclei studied. Fos expression in LC correlated inversely with maximum tail skin vasoconstriction (r = -0.787, p less then 0.03) and HSR (r = -0.834, p less then 0.02) and positively to time to fatigue (r = 0.862, p less then 0.01). A1 nucleus showed an inverse correlation with tail skin vasodilatation threshold (r = -0.861, p less then 0.01). Fos expression in LC correlated inversely with Fos expression in the median (MnPO, r = -0.909, p less then 0.01) and medial preoptic nucleus (MPOM, r = -0.942, p less then 0.05). Our results bring further evidences that noradrenergic neurons from LC and A1 nuclei are involved in cutaneous heat loss mechanisms during exercise. LC nucleus probably modulates the sympathetic tonus of tail artery and integrates the central network LC / POA that could represent an important circuitry of temperature regulation during exercise. Also, noradrenergic neurons from A1 nucleus could be involved in cutaneous heat loss during exercise by modulating of vasodilatation threshold.
Although level 1 evidence supports the use of single-fraction radiation therapy (SFRT) compared with multiple-fraction radiation therapy (MFRT) for the palliative management of bone metastases, SFRT is underused. In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation campaign in Manitoba, Canada featuring educational outreach visits, local consensus meetings, and audit and feedback interventions to encourage greater use of SFRT. This study assessed the impact of this campaign on SFRT use and identified variables associated with MFRT usage.

This retrospective, population-based cohort study identified all patients treated with palliative radiation therapy for bone metastases in Manitoba, Canada, from January 1, 2017, to December 31, 2017, using the provincial radiation therapy database. Baseline characteristics were extracted and tabulated by fractionation schedule. The proportion of patients treated with SFRT in 2017 (postintervention)back strategies are recommended to further reinforce knowledge translation efforts supporting SFRT use in the future.The research aims were to find out further intraosseous mandible organization indications and to structure it systematically.
in our research 400 mandibles were used for the intraosseous examinations in total 300 mandibles of persons aged 20-65 were used. For all corpses cephalic index was measured. Segmentation of the mandibles were made by Jigley saw between medial root of the first molar at one side and central and second incisor of the opposite one. After that segments were stained with Schiff's reagent with following preparation. Dry preparations (n = 100) were used in exploration of mental foramen macroanatomy.

mental foramen cavity depth was divided into three types low, n = 33 (depth 269 ± 081 mm), medium, n = 36 (depth 358 ± 092 mm) and deep, n = 31 (depth 417 ± 036 mm); transverse size of the cavity is 3109 ± 041 mm and longitudinal size is 397 ± 055 mm. According to the mandible anterior intraosseous organization research it is possible to make a mental nerve intraosseous canal types systematizane and to the incisors.Cocrystallization of Active Pharmaceutical Ingredients (API) with formers can induce positive or negative synergistic effects on activity; however, the underlying mechanism is unclear. In this study, we screened two cocrystals of gallic acid (GA) GA-p-aminobenzoic acid (cocrystal A) and GA-amino acetic acid (cocrystal B). Solubility, dissolution rate, and oral bioavailability and hypoglycemic effect of the two cocrystals were evaluated. Additionally, we examined the effect induced by cocrystallization of GA with each former on inhibition activity on α-glucosidase, a protein target involved in hypoglycemic effects. Cocrystals A and B were constructed in a 11 API/former molar ratio by CO⋯HN and OH⋯OC hydrogen bonds, respectively. As predicted, cocrystallization improved oral bioavailability; AUC0-∞s of cocrystal A and B were 2.24-fold and 1.70-fold higher than that of GA. Interestingly, the α-glucosidase inhibition rate increased with cocrystal A (i.e., positive synergism) and decreased with cocrystal B (i.e., ch former induced variation not only on physiochemical properties and bioavailability but also on biological profiles involving inhibition rate on target proteins, which likely contributed to the observed positive and negative synergistic effects on API activity.One of the most difficult challenges for risk assessment is evaluation of chemicals that predominately co-occur in mixtures like polycyclic aromatic hydrocarbons (PAHs). We previously developed a classification model in which systems biology data collected from mice short-term after chemical exposure accurately predict tumor outcome. The present study demonstrates translation of this approach into a human in vitro model in which chemical-specific bioactivity profiles from 3D human bronchial epithelial cells (HBEC) classify PAHs by carcinogenic potency. Gene expression profiles were analyzed from HBEC exposed to carcinogenic and non-carcinogenic PAHs and classification accuracies were identified for individual pathway-based gene sets. Posterior probabilities of best performing gene sets were combined via Bayesian integration resulting in a classifier with four gene sets, including aryl hydrocarbon receptor signaling, regulation of epithelial mesenchymal transition, regulation of angiogenesis, and cell cycle G2-M. In addition, transcriptional benchmark dose modeling of benzo[a]pyrene (BAP) showed that the most sensitive gene sets to BAP regulation were largely dissimilar from those that best classified PAH carcinogenicity challenging current assumptions that BAP carcinogenicity (and subsequent mode of action) is reflective of overall PAH carcinogenicity. These results illustrate utility of using systems toxicology approaches to analyze global gene expression towards carcinogenic hazard assessment.Buclizine (BCZ) is a chiral synthetic piperazine derivative which has antihistaminic, anti-muscarinic and antiemetic properties, and has been reintroduced as an appetite stimulant, especially for pediatric patients. Structural information about this drug, as well as other buclizine crystalline forms (solvates, salts and co-crystals) including the BCZ free-base (BCZ-FB), is non-existent. Here, we present for the first time the crystal structure of the monohydrochloride monohydrate salt of BCZ (BCZHCl·H2O), and of its anhydrous form, BCZHCl. Interestingly, BCZHCl·H2O was obtained by recrystallization from the raw material (BCZH2Cl2) in ethanolwater solution showing that BCZ anhydrous dihydrochloride salt changes easily to a monohydrochloride monohydrate salt modification, which raise concerns about formulation quality control. BCZHCl·H2O and BCZHCl crystallize in the orthorhombic space groups (Pna21 and Pca21) belonging to the mm2 point group and are thus classified as non-centrosymmetric achiral structures (NA). Intuitively, we expect these salts to crystallize in a space group with a center of symmetry, since less than 5% of the known racemic compounds crystallize in the NA type. The crystal structures of BCZH2Cl2 and BCZ-FB were not determined, but their existence was verified by other techniques (chloride ion analysis, PXRD, HPLC, FT-IR, DSC, TGA) and by comparison of the obtained results with those found for BCZHCl. Additionally, we have also performed an evaluation of the equilibrium solubility (at six different aqueous media) and the dissolution profile of the BCZHCl salt compared to the raw material and BCZ-FB. Different equilibrium solubility values were found comparing the three forms in acidic and neutral pH ranges and all of them were insoluble at pH > 7.0. Moreover, tablets prepared with BCZH2Cl2, BCZHCl or BCZ-FB show significant differences in terms of dissolution profile.The study presented was conducted to determine whether a percolation threshold value, previously determined for ibuprofen/microcrystalline cellulose (MCC) blends using percolation theory and compression data (Queiroz et al., 2019), could translate to tablet disintegration and dissolution data. The influence of MCC grade (air stream dried versus spray dried) on tablet disintegration and dissolution was also investigated. Complementary to conventional disintegration and dissolution testing, Raman imaging determined drug distribution within tablets, and in-line particle video microscopy (PVM) and focused-beam reflectance measurement (FBRM) monitored tablet disintegration. Tablets were prepared containing 0-30% w/w ibuprofen. Raman imaging confirmed the percolation threshold by quantifying the number and equivalent circular diameters of ibuprofen domains on tablet surfaces. Across the percolation threshold, a step change in dissolution behaviour occurred, and tablets containing air stream dried MCC showed slower disintegration rates compared to tablets containing spray dried MCC. Dissolution measurements confirmed experimentally a percolation threshold in agreement with that determined using percolation theory and compression data. An increase in drug domains, due to cluster formation, and less efficient tablet disintegration contributed to slower ibuprofen dissolution above the percolation threshold. Slower dissolution was measured for tablets containing air stream dried compared to spray dried MCC.This study aimed to exert the synergistic action of ketoconazole (KCZ) and ionic liquids (ILs) for improving antifungal effect. Various ILs were engineered and demonstrated different solubilization capacity for KCZ. Among them, the IL formed by choline and geranic acid ([Ch][Ger]) was the optimal one and able to imporve the solubility of KCZ by around 100-fold. The in vitro antifungal test revealed the [Ch][Ger] significantly inhibited the activity of T. Interdigitale and exerted the synergistic action with KCZ. Compared to Daktarin®, the [Ch][Ger] not only promoted KCZ to penetrate into deep skin layer but also improved in vivo anti-T. Interdigitale activity significantly. Besides, the [Ch][Ger] was able to strip the skin of the lesion site in a flaky manner to remove fungi more thoroughly. However, the skin can recover to be normal state after treatment and there was no evident skin irritation found in [Ch][Ger] group. The ILs may offer promising opportunities to deliver anti-fungal drugs to treat inner skin fungal infections by synergistic action.Ocular inflammation is a natural defensive phenomenon, but, it results in discomfort in the eye; as well as makes the eye vulnerable to other diseases. The aim of this work is to investigate that Curcumin (CUR) could be an effective safer biofreindly alternative for treatment of ocular inflammation. Complete in-vitro characterization of proniosomal gel loading-CUR using different surfactants was studied. A comparative in-vivo evaluation of selected formulation to a marketed corticosteroid drops in induced-eye inflammation model in rabbits was assessed. The selected formulation (FCr 300) composed of Cremophore RH surfactant, lecithin and cholesterol (991) loading CUR (1.2% w/w). The formulation showed mean PS(212.0 ± 0.1)nm, PDI (0.3 ± 0.1) , ZP(-5.1 ± 0.2)mV and % EE (96.0 ± 0.1). TEM showed multilamellar circular shaped niosomes with smooth surface. SEM showed ruptured vesicles for the lyophilized formula. Selected proniosomal gel showed enhanced permeability 3.22-fold and 1.76-fold higher than CUR dispersion and its lyophilized form respectively. Both proniosomal gel (FCr300) and corticosteroid drops reduced the induced inflammatory signs effectively by 40% on day-one and complete recovery on day-four. This anti-inflammatory result was confirmed by histopathological analysis after treatment. Assessment of cumulative IOP as a predicted side effect verified the goal of this work. In conclusion, the use of CUR as a natural biofreindly alternative to the current chemical conventional ocular anti-inflammatory treatment protocols is comparable as an anti-inflammatory drug with much less side effects.Thermostability and decreased component costs are desirable features for adjuvanted, recombinant vaccines. We previously showed that a model malaria transmission-blocking vaccine candidate antigen, Pfs25, can be rendered more immunogenic when mixed with liposomes containing cobalt porphyrin-phospholipid (CoPoP) and a synthetic monophosphoryl lipid A (MPLA) variant. CoPoP can induce stable particle formation of recombinant antigens based on interaction with their polyhistidine tag. In the present work, different synthetic MPLA variants and concentrations were assessed in CoPoP liposomes. Long-term biophysical stability and immunogenicity were not adversely impacted by a 60% reduction in MPLA content. When admixed with Pfs25, the adjuvant formulations effectively induced functional antibodies in immunized mice and rabbits. Lyophilized, antigen-bound liposomes were formed using sucrose and trehalose cryoprotectants, which improved vaccine reconstitution for a variety of model antigens. Compared to liquid storage, the lyophilized Pfs25 and CoPoP liposomes exhibited thermostability with respect to size, biochemical integrity, binding capacity, protein folding and immunogenicity. Following 6 weeks of storage at 60 °C, the most extended storage period assessed, the lyophilized formulation induced functional antibodies in mice with immunization.
Carotid revascularization for asymptomatic carotid artery stenosis (ACAS) has become increasingly controversial in the past few decades as the best medical therapy has improved. The aim of this study was to assess and define contemporary trends in the rate of carotid revascularization procedures for ACAS in the United States and to characterize outlier physicians performing a higher rate of asymptomatic revascularization compared to their peers.

We used 100% Medicare fee-for-service claims to identify all patients who were newly diagnosed with ACAS between 01/2011-06/2018. Patients with symptomatic carotid artery stenosis, those with prior carotid revascularization, and surgeons who performed ≤10 CEAs during the study period were excluded. We used a hierarchical multivariable logistic regression model to evaluate patient and physician characteristics associated with undergoing a carotid endarterectomy or carotid artery stent procedure within 3months after the initial diagnosis of ACAS. We also assessed testics that are associated with higher rates of carotid revascularization that cannot be fully contextualized without high-level contemporary outcomes data to guide decision making in ACAS.
Delayed open conversion (OpC) after endovascular aortic aneurysm repair (EVAR) is becoming increasingly common worldwide. We reviewed our experience to characterize the perioperative spectrum of OpC repairs.

A retrospective analysis of a prospectively maintained institutional database to identify patients who underwent late OpC after failed EVAR was performed. Patient and aneurysm baseline characteristics, mechanism of failure, perioperative details, including type of repair/complications/survival, and late outcomes were examined.

From January 2003 to January 2020, 38 male patients (mean age, 75±7years; range, 60-90) required late OpC. Interval time from initial EVAR to OpC was 63.6±33.8months (range, 17-120). Mean diameter of the aneurysms was 82.2±22.1mm before OpC compared with 62.9±13mm before endograft implantation. Mechanisms of failure were type Ia, Ib, II, and III endoleaks in 14 (36.8%), 9 (23.7%), 4 (10.5%), and 1 (2.6%) patient(s), respectively; infection in 3 (7.9%), leg ischemia in 2 (5.3%) recorded 11 deaths (2 were aneurysm related).

Despite high technical success, OpC has a significant mortality in patients presenting with hemorrhagic shock and had active fixation endografts or experiencing high complication rate. Many other confounding factors may play a role.
Despite high technical success, OpC has a significant mortality in patients presenting with hemorrhagic shock and had active fixation endografts or experiencing high complication rate. Many other confounding factors may play a role.
To evaluate if features of occlusion analyzable on preoperative computed tomography scan could predict risks of technical failure or iliac rupture of endovascular treatment of TransAtlantic InterSociety Consensus C-D aortoiliac chronic total occlusion.

All patients treated by endovascular techniques for a TransAtlantic InterSociety Consensus C-D aortoiliac chronic total occlusion between 2009 and 2016 were included (107 patients, 148 iliac arteries). We evaluated the location of the occlusion and the importance of the arterial calcifications. For this factor, patients were divided into 3 groups the Black occlusion group with mild or no calcifications, the white occlusion group with moderate no protrusive calcifications, and the white protrusive occlusion group with heavy endoluminal calcifications. Technical failure occurred in 11 iliac arteries and peroperative iliac rupture in 6. The location in the external iliac artery is the most significate risk factor of technical failure in univariate (OR=9.93; P=0.0012) and multivariate analysis (OR=15.26; P=0.0006). The presence of heavy endoluminal calcifications is a further significate risk factor (OR=13.88; P=0.0365). Rupture rate was comparable between the 3 groups.

Preoperative computed tomography scan can predict risk of technical failure but not of iliac rupture.
Preoperative computed tomography scan can predict risk of technical failure but not of iliac rupture.
Fusion imaging makes it possible to improve endovascular procedures and is mainly used in hybrid rooms for aortic procedures. The objective of this study was to evaluate the feasibility of fusion imaging for femoropopliteal endovascular procedures with a mobile flat plane sensor and dedicated software to assist endovascular navigation.

Between May and December 2017, 41 patients requiring femoropopliteal endovascular revascularization were included. Interventions were carried out in a conventional surgical room equipped with a mobile plane sensor (Cios Alpha, Siemens). The numerical video stream was transmitted to an angionavigation station (EndoNaut (EN), Therenva). The software created an osseous and arterial panorama of the treated limb from the angiographies carried out at the beginning of procedure. After each displacement of the table, the software relocated the current image on the osseous panorama, with 2D-2D resetting, and amalgamated the mask of the arterial panorama. The success rates of creatio injected VC. The clinical benefit must be evaluated in more patients in a randomized comparative study with a rigorous methodology.
This preliminary study showed that fusion imaging is possible in a nonhybrid room for peripheral procedures. Imagery of mobile C-arms can be improved for femoropopliteal endovascular procedures without heavy equipment. These imagery tools bring an operative comfort and could probably reduce irradiation and the injected VC. The clinical benefit must be evaluated in more patients in a randomized comparative study with a rigorous methodology.
Combat-related extremity vascular injuries (EVI) have long-lasting impact on Iraq/Afghanistan veterans. The purpose of this study is to describe long-term functional outcomes in veterans with EVI using survey measures and identify modifiable factors that may be improved to reduce chronic pain and injury-related dysfunction.

Veterans with upper and lower EVI undergoing an initial limb salvage attempt were identified using the Department of Defense Trauma Registry and validated with chart abstraction. Surveys measured pain; Short Musculoskeletal Function Assessment (SMFA) for self-reported bother and dysfunction; and Veterans RAND 12-Item Health Survey (VR-12) physical and mental component scores (PCS; MCS) for quality of life, depression, post-traumatic stress disorder, and the potentially modifiable factors of reintegration into civilian life, resilient coping, resilience, and family functioning.

Eighty-one patients responded with an average time since injury of 129months (SD 31; range 67-180months). Mem disability with lasting deficits in physical function, frequent depressive symptoms, and below average self-reported quality of life. Strengthening modifiable factors including resiliency and resilient coping, and providing ongoing assistance to improve reintegration into civilian life, may ameliorate the functional disabilities and chronic pain experienced by veterans with EVI.
EVI results in significant long-term disability with lasting deficits in physical function, frequent depressive symptoms, and below average self-reported quality of life. Strengthening modifiable factors including resiliency and resilient coping, and providing ongoing assistance to improve reintegration into civilian life, may ameliorate the functional disabilities and chronic pain experienced by veterans with EVI.
Peripheral arterial occlusive disease (PAOD) continues to be a vexing problem despite the advent of endovascular techniques augmenting traditional open repair. At our institution, we have found there is a growing number of patients with PAOD who are vein-challenged and have undergone prosthetic bypass previously for infrainguinal arterial reconstruction. When occluded, these grafts have been abandoned for a new bypass strategy or amputation. We present a novel technique of reestablishing flow through chronically occluded prosthetic bypass grafts.

A retrospective review of a prospectively maintained database compiled at 2 institutions between 2016 and 2019 was performed. Six patients had previous prosthetic bypass grafts with 4 patients having femoral to popliteal grafts, 1 patient with a femoral to femoral graft, and 1 with a femoral to posterior tibial bypass graft. All patients had an attempted single-stage intervention to clear chronically occluded grafts.

A total of 6 patients were included in the snd as use increases, requires further interrogation.
Often, the timing of bypass graft occlusion is unknown, and the risk of embolism with lysis for chronically occluded bypass grafts is concerning with traditional peripheral intervention techniques. We report a new and unique minimally invasive approach to resurrect chronically occluded prosthetic bypass grafts often successful in just one stage. This tool offers an alternative technique for limb salvage in complex patients and as use increases, requires further interrogation.
Aneurysmal degeneration of medically managed type B aortic dissection (TBAD) can be a life-threatening condition. Preventive thoracic endovascular aorta repair (TEVAR) in patients at risk could potentially be beneficial. The aim of this study was to examine the predictors for late aneurysmal dilatation after TBAD.

A retrospective study was conducted on 82 patients with medically managed acute TBAD for a minimum of 14days. Relevant demographic, biochemical, and radiographic variables at presentation were studied. The aortic dissection risk calculator tool developed by Sailer etal., predicting the risk of adverse events after aortic dissection based on demographic and radiographic variables at presentation, was tested retrospectively.

With a median follow-up of 36months (range 13-68), 25 (30.5%) patients underwent surgery (92% TEVAR). A larger initial aortic and false lumen diameter as well as a greater distal extension of the dissection was associated with higher need for surgery (respectively, P=0.003, P=0.004, and P=0.001). We observed higher growth rates of maximum aortic diameter in patients with a greater distal extension of the dissection, larger false lumen diameters and false lumen outflow, and entry tears located at the inner aortic arch (respectively, P=0.001, P=0.005, P=0.001 and P=0.014). No significant correlations could be found for the risks provided by the calculator tool.

The initial maximum aortic diameter of TBAD is a key predictor for aortic growth. Furthermore, the distal extension of the dissection also seems to play an important role in late aneurysmal degeneration. However, we were not able to confirm the added value of the risk calculator tool in our study group.
The initial maximum aortic diameter of TBAD is a key predictor for aortic growth. Furthermore, the distal extension of the dissection also seems to play an important role in late aneurysmal degeneration. However, we were not able to confirm the added value of the risk calculator tool in our study group.
Traditional practice suggests the abandonment of veins smaller than 3mm in diameter for arteriovenous fistula (AVF) creation because of a low rate of maturation. This study aims to show that with balloon-assisted maturation (BAM), undersized veins can be used to create functional AVFs with a high rate of success.

All patients who underwent AVF creation between 2014 and 2018 at a tertiary academic medical center were retrospectively reviewed. The patients without preoperative vein mapping, those who failed to follow-up, and the patients who were not on dialysis were excluded. A fistula was considered to be mature if it was successfully cannulated for dialysis. A total of 596 patients were identified for analysis. The cohort was divided into the small-vein group (SVG, <2.5mm) and large-vein group (LVG, ≥2.5mm) based on preoperative vein size. Categorical variables were analyzed with the chi-squared test for their association with maturation status. Continuous variables were analyzed with the Wilcoxon ran fistula maturation between the groups (1.5±0.8 for the SVG vs. 1.4±0.7 for the LVG). In multivariable logistic regression analysis, vein size ≥2.5mm (odds ratio (OR)=2.11, confidence interval (CI) 1.36-3.27, P=0.0009) and male sex (OR=2.30, CI 1.49-3.57, P=0.0002) were independent predictors of maturation.

Small veins can be used for AVF creation with lower but still favorable maturation rates using BAM interventions, especially in male patients. This practice can increase the creation of autogenous dialysis access and potentially reduce complications related to prosthetic dialysis access.
Small veins can be used for AVF creation with lower but still favorable maturation rates using BAM interventions, especially in male patients. This practice can increase the creation of autogenous dialysis access and potentially reduce complications related to prosthetic dialysis access.
Central venous occlusive disease (CVOD) is a prevalent problem in patients with end-stage renal disease (ESRD) and can lead to access malfunction or ligation for symptomatic relief. The purpose of this study is to evaluate the efficacy of the TriForce® Peripheral Crossing Set (Cook Medical), a novel reinforced telescoping catheter set designed to provide additional support for crossing difficult central venous occlusions.

This is a single-center retrospective study from a quaternary referral center. We identified 37 patients over a 17-month period who underwent 56 attempts at endovascular recanalization for the treatment of central venous occlusion. Technical success rates, procedural data, and outcomes were compared between those undergoing recanalization using traditional wire/catheter sets versus the TriForce catheter set.

Average age was 48±2years. Comorbidities were similar between the two cohorts and included ESRD (61%), deep venous thrombosis (30%), and May-Thurner syndrome (7%). Forty attempts w a useful adjunct that may improve recanalization rates of CVOD compared with traditional wire/catheter sets.
Renal dysfunction, requiring renal replacement therapy (RRT) is commonly encountered in patients with left ventricular assist devices (LVADs). Continuous flow LVAD (CFLVAD) is the most widely used device. Nonpulsatile blood flow begets special hemodynamic changes. This poses a unique challenge in choosing a long-term dialysis access for patients with CFLVAD where life expectancy is limited.

A 61-year-old man with an implanted CFLVAD and renal dysfunction receiving intermittent RRT through a nontunneled dialysis catheter had progressed to dialysis-dependent renal failure. He was referred to us for a permanent hemodialysis access.

The patient underwent a right brachio-brachial arterio-venous graft (AVG) placement. The graft was successfully cannulated for hemodialysis on postoperative day 15. On regular follow-up at 18months, the graft was still functional.

Dialysis access for patients on LVAD is an exceptional management problem owing to both altered physiology and guarded overall prognosis. We recommend the use of AVG as a convenient and durable option-facilitating early cannulation and expediting freedom from indwelling catheters that may lead to catastrophic consequences. This should limit the need for secondary interventions, hospitalization, and cost, thus improving quality of life.
Dialysis access for patients on LVAD is an exceptional management problem owing to both altered physiology and guarded overall prognosis. We recommend the use of AVG as a convenient and durable option-facilitating early cannulation and expediting freedom from indwelling catheters that may lead to catastrophic consequences. This should limit the need for secondary interventions, hospitalization, and cost, thus improving quality of life.
The research aims to study the effect of circumferential compliance of synthetic vascular prostheses on their healing during implantation in the infrarenal abdominal aorta of pigs.

In an experiment, 12 pigs were implanted with blood vessel prostheses in the infrarenal abdominal aorta. The prostheses possessed elastic characteristics obtained by a tensile testing machine, and differed in circumferential compliance rigid (polycaprolactone [PCL]); less compliant than the native aorta (polyurethane [PU]); comparable in compliance to the native aorta (copolymer of vinylidene fluoride with hexafluoropropylene) before (FKM) and after radiation treatment (FKM-γ). The implanted prostheses compliance was measured by aortography during the first 3days and 1month after implantation, the condition of the prosthesis capsule was evaluated by macroscopic preparations and histologic examination.

Pulsation on PCL prostheses was nonexistent immediately after implantation. On PU prostheses, slight pulsation was noted durinre of the capsule is characterized by a greater degree of differentiation and approaches the structure of the native arterial wall.
The healing and degree of inflammation in a capsule of blood vessel prostheses implanted in the infrarenal abdominal aorta of pigs depend on the degree of their circumferential compliance. Although maintaining pulsations, the cellular structure of the capsule is characterized by a greater degree of differentiation and approaches the structure of the native arterial wall.
The aim of this study is to identify preoperative and intraoperative factors associated with in-hospital mortality of intact abdominal aortoiliac aneurysm repair.

In this observational study, prospectively collected information included demographics, risk factors, comorbidities, aneurysm characteristics (including special aneurysm presentation, i.e., inflammatory, mycotic/infected, aortocaval fistula), investigations, and operative variables. Receiver operating characteristic) curve analysis of the Glasgow aneurysm score (GAS) and the Vascular Study Group of New England (VSGNE) score was performed in the subgroup of bland aneurysms undergoing isolated elective repair.

A total of 928 cases with intact aortoiliac aneurysms had an elective (n=882) or urgent (n=46) repair, associated with an in-hospital mortality of 1.7% and 8.7%, respectively (P=0.01). Open repair (n=514) was a predictor of higher mortality (3.3% vs. 0.5% for endovascular aneurysm repair [EVAR], n=414, odds ratio [OR] 7.1, P=0.003), and solated elective repair.

Our study has demonstrated independent risk factors for mortality, which should be considered when contemplating aortoiliac aneurysm repair. We failed to externally validate the GAS and VSGNE score.
Our study has demonstrated independent risk factors for mortality, which should be considered when contemplating aortoiliac aneurysm repair. We failed to externally validate the GAS and VSGNE score.Patent foramen ovale (PFO) usually represents a benign incidental finding. Occasionally, a PFO can open widely, resulting in paradoxical embolism, with potentially devastating consequence. Floating intracardiac thrombi and thrombus straddling a PFO are 2 extremely rare conditions associated with a dismal prognosis and encountered almost exclusively in the setting of pulmonary embolism (PE). We report the unusual case of a 47-year-old man with an unremarkable medical history who presented with a bilateral PE and multiple paradoxical and intracardiac floating thrombi in the setting of a thrombus entrapped in a PFO.
To observe the morphology of the transverse geniculate ligament of the knee (TGL) by magnetic resonance imaging (MRI) and to analyze the cause of the pseudotear sign of the anterior horn of the meniscus caused by the TGL.

Patients who underwent MRI examination of the knee joint in the orthopaedics department of our hospital from July 2016 to August 2019 were identified. The occurrence rate, length, width, thickness, cross-sectional shape, pattern, appearance, and position relative to the anterior horn of the lateral and medial meniscus and anatomical variations were observed by multiplane and multisequence MRI. The frequency and cause of the pseudotear sign also were observed.

The data of 101 patients were analyzed. Among them, 60 were male, and 41 were female. The average age was 42.01 (18-75) years. The occurrence rate of the TGL was 67.3% (68/101), the average length was 38.75 ± 3.56 mm, the median coronal diameter was 1.79 ± 0.60 mm, the median sagittal diameter was 1.88 ± 0.35 mm, and the cross-seceniscus, true and false tears of the anterior horn of the meniscus can be identified.

Level III, diagnostic study (retrospective, noncomparative, observational case series without a consistently applied reference "gold" standard).
Level III, diagnostic study (retrospective, noncomparative, observational case series without a consistently applied reference "gold" standard).
The objective of the study was to determine the change in quality of evidence in updates of Cochrane reviews that were initially published between January 1, 2013 and June 30,2014. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to document evidence quality.

We searched the Cochrane Database of Systematic Reviews on March 20, 2020 to identify which of the reviews from the initial (2013/14) sample had been updated. Using the same methods to determine the quality of evidence in the previous analysis, we assessed the quality of evidence for the first-listed primary outcomes in the updated reviews.

Of the 608 reviews in the original sample, 154 had been updated with and 151 contained available data for both original and updated systematic reviews (24.8%). The updated reviews included 15 (9.9%) with high-quality evidence, 56 (37.1%) with moderate-quality evidence, 47 (31.1%) with low-quality evidence, and 33 (21.9%) with very low-quality evidence. No change in the GRADE quality of evidence was found for most (103, 68.2%) of the updated reviews. The quality of evidence rating was downgraded in 28 reviews (58.3%) and upgraded in 20 (41.7%), although only six reviews were promoted to high quality.

Updated systematic reviews continued to suggest that only a minority of outcomes for health care interventions are supported by high-quality evidence. The quality of the evidence did not consistently improve or worsen in updated reviews.
Updated systematic reviews continued to suggest that only a minority of outcomes for health care interventions are supported by high-quality evidence. The quality of the evidence did not consistently improve or worsen in updated reviews.Present investigation is aimed to analyze the role of an uncharacterized ORF of Candida glabrata (CBS138), CAGL0M02233g (an ortholog of RAD53, a key DNA checkpoint effector in Saccharomyces cerevisiae) in tolerance of various stresses and in biofilm formation. The CAGL0M02233g was cloned in p416TEF shuttle vector for constitutive expression under TEF1 promoter in BG14 strain (ura3 auxotrophic C. glabrata), and upregulated expression of the cloned ORF was confirmed by immunoblotting. The constitutive expression of CAGL0M02233g rendered cells resistant to the DNA damage stressor (MMS), replication stressor (HU) and hypoxia mimetic (CoCl2) in plate spot and growth curve assays. Hypoxia (a low oxygen condition) is an imperative host factor that influences Candida pathogenesis. Biofilm formation by the BG14 cells transformed with p416TEF-CAGL0M02233g (REX cell) was reduced to approximately 50% under hypoxia. It is notable that biofilm formation by the REX cells was significantly lower than that of BG14 cells transformed with p416TEF vector (VC cell) under hypoxia. The biofilm of the REX cells has shown higher susceptibility to fluconazole than that of VC cells under hypoxia and REX cells at normoxia. This is the first report on the function of CAGL0M02233g in tolerance of various stressors and in modulation of the biofilm under hypoxia.Category-based induction task was combined with ERP to unravel whether prior knowledge and property interact when inferring on genes or diseases. Larger P2 amplitudes for near taxonomic/causal distances relative to far ones, as well as larger LPC for taxonomic relation relative to thematic relation, are found in both gene and disease tasks. However, smaller N400 is found for taxonomic relation in gene task and thematic relation in disease task, respectively, and larger LPC at 700-850 ms for near taxonomic distance in the gene task and near causal distance in the disease task. These results suggested that the category-based inductive reasoning is context-sensitive, and there may be four stages of category-based inductive reasoning the early automatic comparison of features/relations (P2), features/relations generalization process (N400), the extraction of common relationship/rule (LPC at 550-700 ms), the inference generation (LPC at 700-850 ms).Pyrite-bearing coal wastes are responsible of the formation of acid mine drainage (AMD), and their management to mitigate environmental impacts is a challenge to the coal mine industry in Europe and worldwide. The European CEReS project sought to develop a generic co-processing strategy to reuse and recycle coal wastes, based on removal of AMD generating potential through bioleaching. Chemolitoautotrophic iron- and sulfur-oxidizing microbial consortia were enriched from a Polish coal waste at 30 °C and 48 °C, but not 42 °C. Pyrite leaching yield, determined from bioleaching tests in 2-L stirred bioreactors, was best with the 48 °C endogenous consortium (80%), then the 42 °C exogenous BRGM-KCC consortium (71%), and finally the 30 °C endogenous consortium (50%). 16S rRNA gene-targeted metagenomics from five surface locations on the dump waste revealed a microbial community adapted to the site context, composed of iron- and/or sulfur-oxidizing genera thriving in low pH and metal rich environments and involved in AMD generation. All together, the results confirmed the predisposition of the pyritic coal waste to bioleaching and the potential of endogenous microorganisms for efficient bioleaching at 48 °C. The good leaching yields open the perspective to optimize further and scale-up the bioleaching process.Skin integrity and function depends to a large extent on the composition of the extracellular matrix, which regulates tissue organization. Collagen XII is a homotrimer with short collagenous domains that confer binding to the surface of collagen I-containing fibrils and extended flexible arms, which bind to non-collagenous matrix components. Thereby, collagen XII helps to maintain collagen suprastructure and to absorb stress. Mutant or absent collagen XII leads to reduced muscle and bone strength and lax skin, whereas increased collagen XII amounts are observed in tumor stroma, scarring and fibrosis. This study aimed at uncovering in vivo mechanisms by which collagen XII may achieve these contrasting outcomes. We analyzed skin as a model tissue that contains abundant fibrils, composed of collagen I, III and V with collagen XII decorating their surface, and which is subject to mechanical stress. The impact of different collagen XII levels was investigated in collagen XII-deficient (Col12-KO) mice and in mice wnction. Together, these functions are pivotal for re-establishing homeostasis after injury.Acquired BRAF/MAPK/extracellular signal‒regulated kinase inhibitor resistance in melanoma results in a new transcriptional state associated with an increased risk of metastasis. In this study, we identified noncanonical ephrin receptor (Eph) EphA2 signaling as a driver of the resistance-associated metastatic state. We used mass spectrometry‒based proteomic and phenotypic assays to demonstrate that the expression of active noncanonical EphA2-S897E in melanoma cells led to a mesenchymal-to-amoeboid transition driven by Cdc42 activation. The induction of mesenchymal-to-amoeboid transition promoted melanoma cell invasion, survival under shear stress, adhesion to endothelial cells under continuous-flow conditions, increased permeability of endothelial cell monolayers, and stimulated melanoma transendothelial cell migration. In vivo, melanoma cells expressing EphA2-S897E or active Cdc42 showed superior lung retention after tail-vain injection. Analysis of BRAF inhibitor‒sensitive and ‒resistant melanoma cells demonstrated resistance to be associated with a mesenchymal-to-amoeboid transition switch, upregulation of Cdc42 activity, increased invasion, and transendothelial migration. The drug-resistant metastatic state was dependent on histone deacetylase 8 activity. Silencing of histone deacetylase 8 led to the inhibition of EphA2 and protein kinase B phosphorylation, reduced invasion, and impaired melanoma cell-endothelial cell interactions. In summary, we have demonstrated that the metastatic state associated with acquired BRAF inhibitor resistance is dependent on noncanonical EphA2 signaling, leading to increased melanoma-endothelial cell interactions and enhanced tumor dissemination.The coronavirus disease 2019 (COVID-19) pandemic is a grave public health crisis, causing massive disruption to daily life. Dermatology clinical trials in psoriasis, atopic dermatitis, and hidradenitis have been suspended, terminated, or otherwise disrupted. Clinical investigators need to embrace a COVID-19 new normal and adjust research procedures to mitigate the risk of transmitting severe acute respiratory syndrome coronavirus 2 and depleting personal protective equipment while maintaining scientific rigor.Slac2-b, also known as exophilin-5, is a Rab27b effector protein with a role in exosome transport and is encoded by the EXPH5 gene. We previously described biallelic loss-of-function mutations in EXPH5 in an autosomal recessive form of epidermolysis bullosa simplex. However, how the loss of Slac2-b expression leads to skin fragility and erosions is unknown. In this study, we demonstrate that keratinocytes (KCs) isolated from two different individuals with mutations in EXPH5 have significant defects in cell‒matrix adhesion. EXPH5-mutant KCs also showed increased perinuclear accumulation and significantly reduced trafficking of CD63+ vesicles. These phenotypes were also seen in Slac2-b‒deficient KCs. This was coincident with a reduction in Rab27a protein expression in Slac2-b‒mutant KCs as well as reduced secretion of extracellular vesicles containing extracellular matrix proteins. Live imaging analysis revealed a strong correlation between CD63+ vesicle trafficking to the plasma membrane and focal adhesion dynamics.
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