Cooperdalsgaard3229

The oceans harbor a great reservoir of molecules with unknown bioactivities, which could be useful for the treatment of illnesses that nowadays have no cure, such as neurodegenerative diseases. In this work, we evaluated the neuroprotective potential of the marine Fijian compounds tavarua deoxyriboside A and jasplakinolide against oxidative stress and neuroinflammation, crucial mechanisms in neurodegeneration. Both metabolites protected SH-SY5Y human neuroblastoma cells from H2O2 damage, improving mitochondrial function and activating the antioxidant systems of cells. AZD1390 inhibitor These effects were mediated by their ability of inducing Nrf2 translocation. In BV2 microglial cells activated with lipopolysaccharide, Fijian metabolites also displayed promising results, decreasing the release of proinflammatory mediators (ROS, NO, cytokines) through the reduction of gp91 and NFkB-p65 expression. Finally, we performed a coculture among both cell lines, in which treatment with compounds protected SH-SY5Y cells from activated microglia, corroborating their neuroprotective effects. These results suggest that tavarua deoxyriboside A and jasplakinolide could be used as candidate molecules for further studies against neurodegeneration.Semiconductor nanocrystals are promising photocatalysts for a wide range of applications, ranging from alternative fuel generation to biomedical and environmental applications. This stems from their diverse properties, including flexible spectral tunability, stability, and photocatalytic efficiencies. Their functionality depends on the complex influence of multiple parameters, including their composition, dimensions, architecture, surface coating, and environmental conditions. A particularly promising direction for rapid adoption of these nanoparticles as photocatalysts is their ability to act as photoinitiators (PIs) for radical polymerization. Previous studies served to demonstrate the proof of concept for the use of quantum confined semiconductor nanocrystals as photoinitiators, coining the term Quantum PIs, and provided insights for their photocatalytic mechanism of action. However, these early reports suffered from low efficiencies while requiring purging with inert gases, use of additives, and irradiation by high light intensities with very long excitation durations, which limited their potential for real-life applications. The progress in nanocrystal syntheses and surface engineering has opened the way to the introduction of the next generation of Quantum PIs. Herein, we introduce the research area of nanocrystal photocatalysts, review their studies as Quantum PIs for radical polymerization, from suspension polymerization to novel printing, as well as in a new family of polymerization techniques, of reversible deactivation radical polymerization, and provide a forward-looking view for the challenges and prospects of this field.

The treatment of large aneurysms of the posterior circulation is complicated and remains challenging. We here analyzed our institutional clinical outcomes of large unruptured aneurysms of the posterior circulation.

This study included 56 patients who presented with a large (>10 mm) unruptured aneurysm of the posterior circulation between 2002 and 2018.

There were 18 (32.1%) male and 38 (67.9%) female patients, with a mean age of 53.4 years. The most common location was the vertebral artery, followed by the basilar tip and posterior cerebral artery. The median follow-up duration was 29 months. Eighteen patients (32.1%) were treated by transcranial surgery and 38 (67.9%) were treated by endovascular treatment (EVT). Posttreatment complications occurred in 16 patients (28.6%), with there being no significant difference between the transcranial surgery and EVT groups. Complete obliteration was achieved in 30 patients (53.6%), with there being no statistically significant difference between the transcranial surgery and EVT groups. Recurrence occurred in 17 patients (30.4%), and the rate of recurrence was higher in the EVT group than in the transcranial surgery group (39.5% vs. 11.1%, p=0.03). Forty-four (84%) of 56 patients showed a favorable functional outcome. In saccular aneurysm, EVT was negative predictor of worsening of functional status.

Treatment of these aneurysms harbors an inherent high risk of morbidity. No superiority was found between transcranial surgery and EVT in terms of complications and complete obliteration, but transcranial surgery showed a higher treatment durability than EVT.

Treatment of these aneurysms harbors an inherent high risk of morbidity. No superiority was found between transcranial surgery and EVT in terms of complications and complete obliteration, but transcranial surgery showed a higher treatment durability than EVT.

Electrooculography (EOG) records eyeball movements as changes in the potential difference between the negatively charged retina and the positively charged cornea. We aimed to investigate whether reliable EOG waveforms can be evoked by electrical stimulation of the oculomotor and abducens nerves during skull base surgery.

We retrospectively reviewed the records of 18 patients who had undergone a skull base tumor surgery using EOG (11 craniotomies and seven endonasal endoscopic surgeries). Stimulation was performed at 5 Hz with a stimulus duration of 200 μs and an intensity of 0.1-5 mA using a concentric bipolar probe. Recording electrodes were placed on the upper (active) and lower (reference) eyelids, and on the outer corners of both eyes; the active electrode was placed on the contralateral side.

Reproducibly triggered EOG waveforms were observed in all cases. Electrical stimulation of cranial nerves (CNs) III and VI elicited positive waveforms and negative waveforms, respectively, in the horizontal recording. The median latencies were 3.1 and 0.5 ms for craniotomies and endonasal endoscopic surgeries, respectively (p=0.007). Additionally, the median amplitudes were 33.7 and 46.4 μV for craniotomies and endonasal endoscopic surgeries, respectively (p=0.40).

This study showed reliably triggered EOG waveforms with stimulation of CNs III and VI during skull base surgery. The latency was different according to the point of stimulation and thus predictable. As EOG is noninvasive and relatively easy to perform, it can be used to identify the ocular motor nerves during surgeries as an alternative of electromyography.

This study showed reliably triggered EOG waveforms with stimulation of CNs III and VI during skull base surgery. The latency was different according to the point of stimulation and thus predictable. As EOG is noninvasive and relatively easy to perform, it can be used to identify the ocular motor nerves during surgeries as an alternative of electromyography.

Expansion in the spinal canal area (SCA) after laminoplasty is one of the critical factors to relieve the preoperative symptoms. No previous study has compared the increases in SCA achieved by open-door laminoplasty (ODL) and double door laminoplasty (DDL) according to the preoperative lamina angle (LA). This study was designed to clarify the relationship between the laminoplasty opening angle (OA)/laminoplasty opening size (OS) and increases in the SCA following ODL and DDL according to the preoperative LA using a simulation model.

The simulation model was constructed and validated by comparing the clinical data of 64 patients who had undergone C3-C6 laminoplasty (43 patients with ODL and 21 patients with DDL). SCA expansion was predicted with a verified simulation model at various preoperative LAs (from 28° to 32°) with different OAs (40° to 44°) and OSs (10 mm to 14 mm) recruited from patient data.

The constructed simulation model was validated by comparing clinical data and revealed a very high degrle with clinical data. Both laminoplasties achieved enough SCA, and there was no significant difference between them in the usual range.

The treatment of choice for spinal epidural abscess (SEA) generally is urgent surgery in combination with intravenous antibiotic treatment. However, the optimal duration of antibiotic treatment has not been established to date, although 4-8 weeks is generally advised. Moreover, some researchers have reported that bacteremia is a risk factor for failure of antibiotic treatment in SEA. In this study, we investigated the clinical characteristics of SEA accompanied by bacteremia and also determined whether the conventional 4-8 weeks of antibiotic treatment is sufficient.

We retrospectively reviewed the medical records and radiological data of 23 patients with bacterial SEA who underwent open surgery from March 2010 to April 2020. All patients had bacteremia preoperatively and underwent weeks of perioperative antibiotic treatments based on their identified organisms until all symptoms of infection disappeared. All patients underwent microbiological studies of peripheral blood, specimens from SEA and concomitanired a longer duration (>8 weeks) of antibiotic treatment. In addition, the diagnosis was more frequently delayed in patients with concomitant infections. The duration of antibiotic treatment should be extended for SEA with bacteremia, and a high index of suspicion is mandatory for early diagnosis, especially in patients with concomitant infections.

8 weeks) of antibiotic treatment. In addition, the diagnosis was more frequently delayed in patients with concomitant infections. The duration of antibiotic treatment should be extended for SEA with bacteremia, and a high index of suspicion is mandatory for early diagnosis, especially in patients with concomitant infections.Not available.Not available.MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, glycolysis and pentose phosphate pathway and modulates cell adhesion proteins and leukemia-stromal interactions. Inhibition of MCL-1 sensitizes to BCL-2 inhibition in acute myeloid leukemia cells and acute myeloid leukemia stem/progenitor cells, including those with intrinsic and acquired resistance to venetoclax through cooperative release of pro-apoptotic BIM, BAX, and BAK from binding to anti-apoptotic BCL-2 proteins and inhibition of cell metabolism and key stromal microenvironmental mechanisms. The combined inhibition of MCL-1 by MCL-1 inhibitor AZD5991 or CDK9 inhibitor AZD4573 and BCL-2 by venetoclax greatly extended survival of mice bearing patient-derived xenografts established from an acute myeloid leukemia patient who acquired resistance to venetoclax/decitabine. These results demonstrate that co-targeting MCL-1 and BCL-2 improves the efficacy of and overcomes preexisting and acquired resistance to BCL-2 inhibition. Activation of metabolomic pathways and leukemia-stroma interactions are newly discovered functions of MCL-1 in acute myeloid leukemia, which are independent from canonical regulation of apoptosis by MCL-1. Our data provide new mechanisms of synergy and rationale for co-targeting MCL-1 and BCL-2 clinically in patients with acute myeloid leukemia and potentially other cancers.