The treatment of peripheral nerve injuries remains a major problem worldwide despite the availability of a number of Food and Drug Administration (FDA) approved devices which fail to match the ...efficacy of autografts. Different strategies are used to improve regeneration and functional recovery using biomaterial nerve conduits. However, there is little investigation of the transcriptomic and proteomic changes which occur as a result of these interventions, particularly regarding transection injuries. This study explores differences between autograft‐mediated repair and conduit‐material‐mediated repair of peripheral nerve injuries to understand fundamental differences in their repair mechanisms at the proteomics level at the proximal, middle, and distal components in the early stages of repair. Pathway analysis demonstrates that each material selectively activates different regenerative pathways and alters different biological functions spatially throughout the biomaterial conduits. The analysis highlights some of the deficiencies in conduit‐mediated repair in comparison to autograft (e.g., recycling of myelin and cholesterol, reduction in reactive oxygen species, and higher expression of regenerative proteins). These findings thus suggest that by supplementing the expression of these proteins on the biomaterial of choice, this study can potentially attain regeneration equivalent to autograft. This approach paves the way for incorporating future biomaterial‐specific functionalities in nerve guidance conduits.
The proteomic changes that occur spatially throughout a natural or synthetic nerve guidance conduit or within an autograft during the treatment of peripheral nerve injuries are investigated in this study. Using pathway analysis tools, this study explores how different materials in conduit‐mediated nerve repair, and how autografts, activate different biological functions during the early stages of regeneration.
Medicaid expansion under the Patient Protection and Affordable Care Act occurred almost concurrently with 2012 U.S. Preventive Services Task Force recommendations against prostate specific antigen ...screening. Here the relative influence on prostate specific antigen screening rates by 2 concurrent and opposing system-level policy initiatives is investigated: improved access to care and change in clinical practice guidelines.
Behavioral Risk Factor Surveillance System data from years 2012 to 2018 were analyzed for trends in self-reported prostate specific antigen screening and insurance coverage. Subanalyses included state Medicaid expansion status and respondent federal poverty level. Multivariable logistic regression was performed to evaluate factors associated with prostate specific antigen screening.
From 2012 to 2018 prostate specific antigen screening predominantly declined with a notable exception of an increase of 7.3% for men at <138% federal poverty level between 2011 and 2013 in early expansion states. Initial increases did not continue, and screening trends mirrored those of nonexpansion states by 2018. Notably, 2014 planned expansions states did not follow this trend with minimal change between 2015 and 2017 compared to declines in early expansion states and nonexpansion states (-0.4% vs -6.7% and -8.6%, respectively).
Medicaid expansion was associated with increased rates of insured men at <138% federal poverty level from 2012 to 2018 in early expansion states. In this group, initial increases in prostate specific antigen screening were not durable and followed the trend of reduced screening seen across the United States. In planned expansions states the global drop in prostate specific antigen screening from 2016 to 2018 was offset in men at <138% federal poverty level by expanding access to care. Nonexpansion states showed a steady decline in prostate specific antigen screening rates. This suggests that policy such as U.S. Preventive Services Task Force recommendations against screening competes with and often outmatches access to care.
Abstract The current microsurgical gold standard for repairing long gap nerve injuries is the autograft. Autograft provides a protective environment for repair and a natural internal architecture, ...which is essential for regeneration. Current clinically approved hollow nerve guidance conduits allow provision of this protective environment; however they fail to provide an essential internal architecture to the regenerating nerve. In the present study both structured and unstructured intraluminal collagen fibres are investigated to assess their ability to enhance conduit mediated nerve repair. This study presents a direct comparison of both structured and unstructured fibres in vivo . The addition of intraluminal guidance structures was shown to significantly decrease axonal dispersion within the conduit and reduced axonal mismatch of distal nerve targets ( p < 0.05). The intraluminal fibres were shown to be successfully incorporated into the host regenerative process, acting as a platform for Schwann cell migration and axonal regeneration. Ultimately the fibres were able to provide a platform for nerve regeneration in a long term regeneration study (16 weeks) and facilitated increased guidance of regenerating axons towards their distal nerve targets.
Objectives To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days ...after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. Design Retrospective, observational, cohort study design. Setting Single-center, university hospital. Participants The study included 708 adult liver transplantations performed from 2008 to 2013. Interventions None. Measurements and Main Results EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. Conclusions The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation.
N-Arylated chitosans were synthesized via Schiff bases formed by the reaction between the primary amino group of chitosan with aromatic aldehydes followed by reduction of the Schiff base ...intermediates with sodium cyanoborohydride. Treatment of chitosan containing
N,N-dimethylaminobenzyl and
N-pyridylmethyl substituents with iodomethane under basic conditions led to quaternized
N-(4-
N,N-dimethylaminobenzyl) chitosan and quaternized
N-(4-pyridylmethyl) chitosan. Methylation occurred at either
N,N-dimethylaminobenzyl and
N-pyridylmethyl groups before the residual primary amino groups of chitosan GlcN units were substituted. The total degree of quaternization of each chitosan varied depending on the extent of
N-substitution (ES) and the sodium hydroxide concentration used in methylation. Increasing ES increased the total degree of quaternization but reduced attack at the GlcN units.
N,N-dimethylation and
N-methylation at the primary amino group of chitosan decreased at higher ES’s. Higher total degrees of quaternization and degrees of
O-methylation resulted when higher concentrations of sodium hydroxide were used. The molecular weight of chitosan before and after methylation was determined by gel permeation chromatography under mild acidic condition. The methylation of the
N,N-dimethylaminobenzyl derivative with iodomethane was accompanied by numerous backbone cleavages and a concomitant reduction in the molecular weight of the methylated product was observed. The antibacterial activity of water-soluble methylated chitosan derivatives was determined using
Escherichia coli (Gram-negative) and
Staphylococcus aureus (Gram-positive) bacteria; minimum inhibitory concentrations (MIC) of these derivatives ranged from 32 to 128
μg/mL. The presence of the
N,N-dimethylaminobenzyl and
N-pyridylmethyl substituents on chitosan backbone after methylation did not enhance the antibacterial activity against
S. aureus. However,
N-(4-
N,N-dimethylaminobenzyl) chitosan with degree of quaternization at the aromatic substituent and the primary amino group of chitosan of 17% and 16–30%, respectively, exhibited a slightly increased antibacterial activity against
E. coli.
Giant multiloculated cystadenoma of the prostate (GMPC) is a rare, massive and benign tumor. Recurrence rates after resection are low but have been recorded. An open approach is most common, with few ...laparoscopic and no robotic cases reported. We report on a case of a 65-year-old man with a new presentation of a 400 cc cystic prostatic mass thought to be GMPC. This patient underwent what is, to our knowledge, the first reported case of RARP in the treatment of GMPC. A robotic approach to massive GMPC was safe and efficacious in our initial experience.
•Clinical nodal staging is associated with a substantial false positive rate.•Patients with discordant staging had better overall survival.•Clinical nodal staging may lead to underutilization of ...curative treatment in some.
A prostate cancer (CaP) patient with nonmetastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compare overall survival (OS) between cN+ men that underwent radical prostatectomy (RP) and were found to have negative node status (pN) with those found to have positive nodal status (pN+), and assess predictors of discordant nodal status. We queried the National Cancer Data Base between 2004 and 2015 for patients that were cT1-3 cN+ cM0 CaP treated with RP. Patients with 0 nodes, cT4, or cM1 disease were excluded. We compared groups based on pathologic nodal status: Discordant (cN+ -> pN) & Concordant (cN+ -> pN+). Kaplan Meier estimations were used to compare OS. Logistic regression was used to determine possible predictors of nodal status. We find that of 6470 cN+ patients, 1,367 (21.1%) underwent RP, 866 (13.4%) had confirmed nodal status. Discordant status was found in 159 (18.4%) and concordant staging in 707 (81.6%). Differences exist in PSA at diagnosis (7.3 vs. 11.2), biopsy group, # of nodes examined (7 vs. 10), race, and Charlson index. Discordant staging had longer OS compared to Concordant staging (P = 0.007) and similar OS to a 3:1 matched cohort of high risk localized CaP patients used as reference (P = 0.46). Lower Gleason Score (GG1-3) was associated with an increased likelihood of discordant staging. Clinical nodal staging is associated with a substantial false positive rate. Discordant status had better OS than Concordant status and similar OS to matched patients with localized CaP. Clinical nodal staging may inappropriately lead to noncurative therapy in a substantial number of men with potentially curable disease.
Selective
N-arylation of chitosan was performed via a Schiff bases formed by the reaction between the 2-amino group of glucosamine residue of chitosan with an aromatic aldehyde under acidic condition ...followed by reduction of the Schiff base intermediate with sodium cyanoborohydride (Borch reduction). Aromatic aldehydes bearing either an electron donating or electron withdrawing substituent were used. The chemical structures and thermal properties of the
N-aryl chitosans were characterized by FT-IR,
1H NMR,
13C NMR, TGA, and DSC. The extent of
N-substitution (ES) was influenced by the molar ratio of the aldehyde to the glucosamine residue of chitosan, the reaction time and the substituent on the aromatic ring. Lower ESs resulted from
N-arylation using an aldehyde with an electron donating substituent. A linear relationship between the targeted ES and the ES obtained was observed when aldehydes bearing electron withdrawing substituents were employed.
Retained and subsequently encrusted stents can lead to a number of complications, the most dire being deterioration of renal function. Limited literature exists concerning endourologic management of ...stents retained for extreme durations and few that concerns patients with abnormal renal anatomy.
A 70-year-old man with history of Crohn's disease and partially duplicated collecting system presented with rising creatinine and was found to have bilateral retained Double-J stents, originally placed before small bowel resection 22 years prior. The patient underwent staged bilateral percutaneous nephrolithotomy with ultimate effective removal of both stents. The patient has had subsequent improvement in renal function and has not required dialysis.
Removal of ureteral stents in a timely manner is paramount to prevent long-term retention and complication, but when required retained stents can be safely managed with a well-planned endourologic approach, even if significant deterioration in renal function has occurred.
There is a vital need to develop in vitro models of the developing human brain to recapitulate the biological effects that toxic compounds have on the brain. To model perineural vascular plexus ...(PNVP) in vitro, which is a key stage in embryonic development, human embryonic stem cells (hESC)‐derived endothelial cells (ECs), neural progenitor cells, and microglia (MG) with primary pericytes (PCs) in synthetic hydrogels in a custom‐designed microfluidics device are cocultured. The formation of a vascular plexus that includes networks of ECs (CD31+, VE‐cadherin+), MG (IBA1+), and PCs (PDGFRβ+), and an overlying neuronal layer that includes differentiated neuronal cells (βIII Tubulin+, GFAP+) and radial glia (Nestin+, Notch2NL+), are characterized. Increased brain‐derived neurotrophic factor secretion and differential metabolite secretion by the vascular plexus and the neuronal cells over time are consistent with PNVP functionality. Multiple concentrations of developmental toxicants (teratogens, microglial disruptor, and vascular network disruptors) significantly reduce the migration of ECs and MG toward the neuronal layer, inhibit formation of the vascular network, and decrease vascular endothelial growth factor A (VEGFA) secretion. By quantifying 3D cell migration, metabolic activity, vascular network disruption, and cytotoxicity, the PNVP model may be a useful tool to make physiologically relevant predictions of developmental toxicity.
Current models of in vitro brain development fail to mimic mechanisms in vivo, partly as they use animal‐derived matrices. The current study incorporates differentiated cell lines in a fabricated synthetic hydrogel in a microfluidics plate to recapitulate perineural vascular plexus in vivo. By analyzing endpoints such as growth factors, metabolites and 3D cell migration, this model predicts acute toxicity mechanisms.
PDF
