Do stand-alone interbody spacers with integrated screws provide adequate segmental stability for multilevel cervical arthrodesis?

Background contextSome postoperative complications after anterior cervical fusions have been attributed to anterior cervical plate (ACP) profiles and the necessary wide operative exposure for their insertion. Consequently, low-profile stand-alone interbody spacers with integrated screws (SIS) have been developed. Although SIS constructs have demonstrated similar biomechanical stability to the ACP in single-level fusions, their role as a stand-alone device in multilevel reconstructions has not been thoroughly evaluated.PurposeTo evaluate the acute segmental stability afforded by an SIS device compared with the traditional ACP in the setting of a multilevel cervical arthrodesis.Study designIn vitro human cadaveric biomechanical analysis.MethodsThirteen human cadaveric cervical spines (C2–T1) were nondestructively tested with a custom 6 df spine simulator under axial rotation, flexion-extension, and lateral bending loading. After intact analysis, eight single-levels (C4–C5/C6–C7) from four specimens were instrumented and tested with ACP and SIS. Nine specimens were tested with C5–C7 SIS, C5–C7 ACP, C4–C7 ACP, C4–C7 ACP+posterior fixation, C4–C7 SIS, and C4–C7 SIS+posterior fixation. Testing order was randomized with each additional level instrumented. Full range of motion (ROM) data were obtained and analyzed by each loading modality, using mean comparisons with repeated measures analysis of variance. Paired t tests were used for post hoc analysis with Sidak correction for multiple comparisons.ResultsNo significant difference in ROM was noted between the ACP and SIS for single-level fixation (p>.05). For multisegment reconstructions (two and three levels), the ACP proved superior to SIS and intact condition, with significantly lower ROM in all planes (p<.05). When either the three-level SIS or ACP constructs were supplemented with posterior lateral mass fixation, there was a greater than 80% reduction in ROM under all testing modalities (p<.05), with no significant difference between the ACP and SIS constructs (p>.05).ConclusionsThe SIS device may be a reasonable option as a stand-alone device for single-level fixation. However, SIS devices should be used with careful consideration in the setting of multilevel cervical fusion. However, when supplemented with posterior fixation, SIS devices are a sound biomechanical alternative to ACP for multilevel fusion constructs.     

Assessment of a proposed “three-criteria” cocaine addiction model for use in reinstatement studies with rats

Rationale

Relapse is a primary obstacle in the treatment of addiction disorders, and as such, understanding this phenomenon is a major effort of clinical and preclinical studies of cocaine addiction.

Objective

A recently developed protocol uses laboratory rats to model cocaine addiction by examining three criteria of addiction-like behaviors (persistent seeking in the absence of drug, high motivation for drug, and resistance to punishment during drug seeking) to detect subjects that possess an addiction phenotype. We closely followed this protocol in order to detect rats possessing this addiction phenotype, with the goal of utilizing this model in future studies investigating potential therapies for relapse in human cocaine addicts.

Results

The majority of the rats used in this study exhibited multiple characteristics thought to be associated with addiction-like behavior in rats, including robust reinstatement to multiple stimuli and high motivation to obtain cocaine. However, no rats displayed the complete addiction phenotype as previously described, due to a complete lack of addiction-like behavior in all subjects on two of the three addiction criteria (drug seeking in the absence of drug and resistance to punishment).

Conclusions

Our data highlight the independence of behavioral aspects of a rat addiction-like phenotype and suggest that some of these behavioral criteria may be altogether absent in some rat populations. Furthermore, our results suggest a closer review and analysis of some parameters used in this protocol and its global utility.     

CYP3A4 activity reduces the cytotoxic effects of okadaic acid in HepaRG cells

The biotoxin okadaic acid (OA), produced by dinoflagellates in marine environment, can accumulate in sponges and shellfish. Consumption of contaminated shellfish induces acute toxic effects such as diarrhea, nausea, vomiting, and abdominal pain. CYP3A4, one of the most important human xenobiotic metabolizing enzymes, is supposed to be involved in the metabolism of OA. Aim of our study was to evaluate the role of CYP3A4 in OA in vitro metabolism as well as in cell cytotoxicity in parallel. Therefore, a metabolic competent HepaRG cell line was exposed to OA with and without addition of the CYP3A4 inhibitor ketoconazole. Without the inhibitor, two mono-hydroxylated metabolites could be identified, whereas in its presence, no metabolites could be detected. Confirmation of the formed metabolites was accomplished by measuring the exact masses and investigating the fragmentation pattern. Data obtained from cytotoxicity assays showed that OA cytotoxicity is reduced when CYP3A4 is active. Thus, hydroxylation appears to be a crucial step for metabolic OA detoxification.     

Convenient synthesis of 18F‐radiolabeled R‐(−)‐N‐n‐propyl‐2‐(3‐fluoropropanoxy‐11‐hydroxynoraporphine

Aporphines are attractive candidates for imaging D₂ receptor function because, as agonists rather than antagonists, they are selective for the receptor in the high affinity state. In contrast, D₂ antagonists do not distinguish between the high and low affinity states, and in vitro data suggests that this distinction may be important in studying diseases characterized by D₂ dysregulation, such as schizophrenia and Parkinson's disease. Accordingly, MCL‐536 (R‐(?)‐N‐n‐propyl‐2‐(3‐[¹⁸F]fluoropropanoxy‐11‐hydroxynoraporphine) was selected for labeling with ¹⁸F based on in vitro data obtained for the non‐radioactive (¹⁹F) compound. Fluorine‐18‐labeled MCL‐536 was synthesized in 70% radiochemical yield, >99% radiochemical purity, and specific activity of 167 GBq/µmol (4.5 Ci/µmol) using p‐toluenesulfonyl (tosyl) both as a novel protecting group for the phenol and a leaving group for the radiofluorination.     

Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.     

Optimizing Peritoneal Dialysis–Associated Peritonitis Prevention in the United States: From Standardized Peritoneal Dialysis–Associated Peritonitis Reporting and Beyond

Peritoneal dialysis (PD)–associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.     

Uncommon malignant renal tumors and atypical presentation of common ones: a guide for radiologists

Abdominal Radiology - While the typical imaging features of the more common RCC subtypes have previously been described, they can at times have unusual, but distinguishing features. Rarer renal...