Correction: STAT3 balances myocyte hypertrophy vis-à-vis autophagy in response to Angiotensin II by modulating the AMPKα/mTOR axis.

[This corrects the article DOI: 10.1371/journal.pone.0179835.].

Primary thoracic intramedullary spinal cord tumor with likely metastases of glial origin to the lumbosacral vertebrae: Illustrative case.

Background: Metastasis of systemic neoplasms to the spine is common; however, the metastasis of primary spinal cord tumors to other regions in the body is an infrequent occurrence. A few case reports have described the metastasis of primary spinal cord tumors, and in most cases, patients were younger than 30 years of age. Case Description: We present an illustrative case of a 47-year-old female with metastatic lesions to the lumbosacral vertebrae years after the initial diagnosis of an intradural, intramedullary spinal cord tumor (IMSCT). Although the surgical biopsy of the IMSCT was nondiagnostic, the patient was not found to have a separate primary neoplastic source, and the specimens of the metastatic lesions from the lumbar vertebral body were of glial origin. Conclusion: Metastasis from primary IMSCTs is extremely rare. Distant vertebral body and intracranial metastasis are even rarer yet possible. The clinical course is highly aggressive and responds poorly to current standard treatment.

Willingness to receive COVID-19 booster dose and its associated factors in Ghana: A cross-sectional study.

Background and Aim: The COVID-19 booster dose has been cited as an important supplement for the control of the COVID-19 pandemic due to reports of waning immunity among fully vaccinated persons. Determining factors that would affect its acceptability is necessary for initiating successful vaccination programs. In this study, we aimed to evaluate the factors associated with the acceptability of the COVID-19 booster dose in Ghana. Methods: We conducted an online cross-sectional survey among the public. A self-administered questionnaire was used to collect information on demographic characteristics, willingness to vaccinate, perceptions toward COVID-19 vaccines, and trust in the government. Participants provided reasons and sources of advice that may affect their willingness to accept a booster dose. Using IBM SPSS and R Statistic; descriptive, univariate, and multivariate analyses were performed. Results: Out of 812 respondents, 375 (46.2%) intended to accept the booster dose. Individuals who were males (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.07-2.48), had previously received other forms of vaccination twice (aOR 1.96, 95% CI 1.07-3.57) or in most years (aOR 2.51, 95% CI 1.38-4.57), tested positive for COVID-19 (aOR 3.46, 95% CI 1.23-10.52), have high trust in government (aOR=1.77, 95% CI: 1.15-2.74) and had positive perceptions regarding COVID-19 vaccines (OR = 14.24, 95% CI: 9.28-22.44) were more likely to accept a booster dose. Experiencing side effects from the primer dose (aOR 0.12, 95% CI 0.08-0.18) was associated with reduced acceptance. Concerns about vaccine safety and efficacy were the common reasons impeding willingness, while advice from health professionals would be the most considered. Conclusion: Low intention to accept the booster dose which is associated with a range of factors including the perception of vaccines and trust in the government, is a cause for concern. Thus, more effort would have to be taken through education and policy interventions to increase booster vaccine acceptability.

Ventriculoperitoneal shunt complications in an adult population: A comparison of various shunt designs to prevent overdrainage.

BACKGROUND: Overdrainage after cerebrospinal fluid diversion remains a significant morbidity. The hydrostatic, gravitational force in the upright position can aggravate this. Siphon control (SC) mechanisms, as well as programmable and flow regulating devices, were developed to counteract this. However, limited studies have evaluated their safety and efficacy. In this study, direct comparisons of the complication rates between siphon control (SC) and non-SC (NSC), fixed versus programmable, and flow- versus pressure regulating valves are undertaken. METHODS: A retrospective chart review was performed over all shunt implantations from January 2011 to December 2016 within the Houston Methodist Hospital system. Complication rates within 6 months of the operative date, including infection, subdural hematoma, malfunction, and any other shunt-related complication, were analyzed via Fisher's exact test, with P < 0.05 regarded as significant. Subgroup analyses based on diagnoses - normal pressure hydrocephalus (HCP), pseudotumor cerebri, or other HCP - were also performed. RESULTS: The overall shunt-related complication rate in this study was 19%. Overall rates of infection, shunt failure, and readmission within 180 days were 3%, 11%, and 34%, respectively. No difference was seen between SC and NSC groups in any complication rate overall or on subgroup analyses. When comparing fixed versus programmable and flow- versus pressure-regulating valves, the latter in each analysis had significantly lower malfunction and total complication rates. CONCLUSIONS: Programmable and pressure regulating devices may lead to lower shunt malfunction and total complication rates. Proper patient selection should guide valve choice. Future prospective studies may further elucidate the difference in complication rates between these various shunt designs.

STAT3 balances myocyte hypertrophy vis-à-vis autophagy in response to Angiotensin II by modulating the AMPKα/mTOR axis.

Signal transducers and activators of transcription 3 (STAT3) is known to participate in various cardiovascular signal transduction pathways, including those responsible for cardiac hypertrophy and cytoprotection. However, the role of STAT3 signaling in cardiomyocyte autophagy remains unclear. We tested the hypothesis that Angiotensin II (Ang II)-induced cardiomyocyte hypertrophy is effected, at least in part, through STAT3-mediated inhibition of cellular autophagy. In H9c2 cells, Ang II treatment resulted in STAT3 activation and cellular hypertrophy in a dose-dependent manner. Ang II enhanced autophagy, albeit without impacting AMPKα/mTOR signaling or cellular ADP/ATP ratio. Pharmacologic inhibition of STAT3 with WP1066 suppressed Ang II-induced myocyte hypertrophy and mRNA expression of hypertrophy-related genes ANP and ß-MHC. These molecular events were recapitulated in cells with STAT3 knockdown. Genetic or pharmacologic inhibition of STAT3 significantly increased myocyte ADP/ATP ratio and enhanced autophagy through AMPKα/mTOR signaling. Pharmacologic activation and inhibition of AMPKα attenuated and exaggerated, respectively, the effects of Ang II on ANP and ß-MHC gene expression, while concomitant inhibition of STAT3 accentuated the inhibition of hypertrophy. Together, these data indicate that novel nongenomic effects of STAT3 influence myocyte energy status and modulate AMPKα/mTOR signaling and autophagy to balance the transcriptional hypertrophic response to Ang II stimulation. These findings may have significant relevance for various cardiovascular pathological processes mediated by Ang II signaling.

Intradural-extramedullary isolated compressive sarcoid lesion.

BACKGROUND: Sarcoid involvement of the central nervous system is a rare occurrence, with involvement in approximately 5-10% of all cases. Isolated spinal involvement is an even rarer encounter, only 0.3-1% of all cases. These lesions can form compressive nodules leading to myelopathy. In the presented case of cervical sarcoid, the patient required a decompressive procedure to address cord compression. CASE DESCRIPTION: This is the case of a 39-year-old male presenting with cervical myelopathy caused by a compressive sarcoid nodule who underwent a successful posterior decompressive procedure. The pathology demonstrated a non-caseating granuloma, consistent with sarcoid. Postoperatively, the patient's myelopathic symptoms improved. CONCLUSIONS: Sarcoid is rarely associated with an isolated compressive cervical lesion. Although sarcoid management typically involves immune suppression, in cases of active cord compression surgical intervention is warranted.

Improved membrane fluidity of ionic polysaccharide bead-supported phospholipid bilayer membrane systems.

Supported phospholipid bilayer membranes on polysaccharide-based cationic polymer beads (cationic group: -[OCH2CH(OH)CH2]2N(+)(CH3)3·X(-), 45-165 µm in diameter) were prepared using small unilamellar vesicles from mixtures of phosphatidylserine (PS) and phosphatidylcholine (PC). Confocal fluorescence microscopic observations with a fluorescent membrane probe (N-4-nitrobenzo-2-oxa-1,3-diazole-phosphatidylethanolamine) revealed that the phospholipid molecules in the phospholipid-bead complexes were along the outer surface of the beads. The fluidity of the phospholipid bilayer membranes in the PS/PC-bead complexes was investigated by the fluorescence recovery after photobleaching (FRAP) technique. The lateral diffusion coefficients (D) for the PS/PC-bead complexes were lower than that for the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine giant unilamellar vesicles without solid supports. Such less fluid membranes in the complexes appeared to be due to the immobilization of the phospholipid bilayer membranes by electrostatic attractive forces between PS and the bead. The D values for the PS/PC-bead complexes were dependent on the phospholipid composition; the PS(100 mol%)/PC(0 mol%)-bead complex had the least fluid membranes among the PS/PC-bead complexes tested in this study. The phospholipid bilayer membranes formed on the polysaccharide-based cationic polymer beads were much more fluid than those on a polystyrene-based one. Furthermore, such fluid phospholipid bilayer membranes formed on the polysaccharide-based cationic polymer bead were maintained for 10 days, even though the complex sample was stood in plain buffer (pH 8.5) at ambient temperature.

Fluorescence microscopic characterization of ionic polymer bead-supported phospholipid bilayer membrane systems.

Supported phospholipid membrane structures on cationic organic polymer beads were prepared using mixtures of dioleoylphosphatidylserine (PS) and egg yolk phosphatidylcholine (PC). Confocal fluorescence microscopic observations using a fluorescent membrane probe (N-4-nitrobenzo-2-oxa-1,3-diazole-phosphatidylethanolamine) revealed that the phospholipid molecules in the PS/PC-bead complexes were along the outer surface of the beads, but not inside the beads. The anionic PS on the most outer surface of the PS/PC-bead complexes was responsible for the binding of a positively charged macromolecule, rhodamine isothiocyanate dextran (M(w) 70,000) by electrostatic attractive forces. The fluidity of the membranes in the PS/PC-bead complexes was investigated by the fluorescence recovery after a photobleaching technique. The lateral diffusion coefficients (D) for the PS/PC-bead complexes were one-half or less than that for 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine giant unilamellar vesicles without solid supporting materials. Such a constrain of the phospholipid bilayer membrane in the complexes appeared to be due to its immobilization on the cationic polymer bead by electrostatic attractive forces between the PS and ammonium group on the surface of the bead. The D values for the complexes were dependent on the phospholipid composition; the PS(25 mol%)/PC(75 mol%)-bead complex produced a more fluid membrane than the PS(50 mol%)/PC(50 mol%)-bead one. Thus, the fluidity of the phospholipid bilayer membranes formed on the cationic polymer beads was significantly affected by the anionic phospholipid fraction used for the preparation of the complexes.

One-step direct reconstitution of biomembranes onto cationic organic polymer bead supports.

In this study, we addressed the straightforward reconstitution of red blood cell (RBC) membranes on the surface of cationic organic polymer beads. The RBC membrane-bead complex was obtained by the incubation of white, unsealed rat RBC ghost membranes with a nonporous quaternary ammonium-type anion-exchange polymer bead with a 350-550 microm diameter. Confocal microscopic observations using a fluorescence membrane probe revealed that the RBC membranes were reconstituted on the outer surface of the bead without any remarkable structural gaps in the membrane. The absence of activity of two peripheral enzymes that latently reside on the cytoplasmic face of the RBC membranes demonstrated that the orientation of the RBC membranes immobilized on the beads was asymmetric as well as that in the native state. The RBC membrane-polymer bead complex was incubated with a primary antibody that is directed against the amino-terminal extracellular domain of the integral protein glycophorin A (GPA). The resulting complex was further incubated with a fluorescent secondary antibody and then subjected to confocal microscopic observations. Fluorescence resulting in the binding of the secondary antibody was found on the surface of the complex, which indicates that the amino-terminal extracellular domain of GPA is exposed to the surface of the complex. In addition, the anion uptake function of the most abundant integral protein anion-exchanger 1 (AE1) immobilized on the polymer beads was inhibited by pretreatment with its specific inhibitor 4,4'-diisothiocyano-2,2'-stilbene disulfonate, as is observed for the intact RBCs. Based on all these results, the RBC membranes were thought to be reconstituted on the ionic polymer beads by our one-pot procedure while maintaining the orientation and functions of the membrane proteins to some extent.