Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells.

Mitochondrial respiration is important for cell proliferation; however, the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here, we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis.

Increased demand for NAD+ relative to ATP drives aerobic glycolysis.

Aerobic glycolysis, or preferential fermentation of glucose-derived pyruvate to lactate despite available oxygen, is associated with proliferation across many organisms and conditions. To better understand that association, we examined the metabolic consequence of activating the pyruvate dehydrogenase complex (PDH) to increase pyruvate oxidation at the expense of fermentation. We find that increasing PDH activity impairs cell proliferation by reducing the NAD+/NADH ratio. This change in NAD+/NADH is caused by increased mitochondrial membrane potential that impairs mitochondrial electron transport and NAD+ regeneration. Uncoupling respiration from ATP synthesis or increasing ATP hydrolysis restores NAD+/NADH homeostasis and proliferation even when glucose oxidation is increased. These data suggest that when demand for NAD+ to support oxidation reactions exceeds the rate of ATP turnover in cells, NAD+ regeneration by mitochondrial respiration becomes constrained, promoting fermentation, despite available oxygen. This argues that cells engage in aerobic glycolysis when the demand for NAD+ is in excess of the demand for ATP.

Redefining hyperviscosity in acute leukemia: Potential implications for red cell transfusions in the microvasculature.

Hyperleukocytosis is an emergency of acute leukemia leading to blood hyperviscosity, potentially resulting in life-threatening microvascular obstruction, or leukostasis. Due to the high number of red cells in the circulation, hematocrit/hemoglobin levels (Hct/Hgb) are major drivers of blood viscosity, but how Hct/Hgb mediates hyperviscosity in acute leukemia remains unknown. In vivo hemorheological studies are difficult to conduct and interpret due to issues related to visualizing and manipulating the microvasculature. To that end, a multi-vessel microfluidic device recapitulating the size-scale and geometry of the microvasculature was designed to investigate how Hct/Hgb interacts with acute leukemia to induce "in vitro" leukostasis. Using patient samples and cell lines, the degree of leukostasis was different among leukemia immunophenotypes with respect to white blood cell (WBC) count and Hct/Hgb. Among lymphoid immunophenotypes, severe anemia is protective against in vitro leukostasis and Hct/Hgb thresholds became apparent above which in vitro leukostasis significantly increased, to a greater extent with B-cell acute lymphoblastic leukemia (ALL) versus T-cell ALL. In vitro leukostasis in acute myeloid leukemia was primarily driven by WBC with little interaction with Hct/Hgb. This sets the stage for prospective clinical studies assessing how red cell transfusion may affect leukostasis risk in immunophenotypically different acute leukemia patients.

The Influence of Body Mass Index on Outcomes in Patients Undergoing Mechanical Thrombectomy for Anterior Circulation Large Vessel Occlusion: Institutional Experience and Meta-analysis.

BACKGROUND: An obesity paradox, whereby patients with higher body mass index (BMI) experience improved outcomes, has been described for ischemic stroke. It is unclear whether this applies to patients undergoing mechanical thrombectomy (MT) for large vessel occlusion (LVO). METHODS: Mechanical thrombectomies for anterior circulation LVO between 2015 and 2021 at a single institution were reviewed. Multivariable logistic regressions were used to determine the association between BMI and favorable functional outcome (90-day modified Rankin Scale 0-2), intracranial hemorrhage, and malignant middle cerebral infarction. A systematic review was performed to identify studies reporting the effect of BMI on outcomes among patients receiving MT for LVO. The data from the systematic review were combined with the institutional data by using a random effects model. RESULTS: The institutional cohort comprised 390 patients with a median BMI of 27 kg/m2. Most patients were obese [36.7% (BMI ≥ 30 kg/m2)], followed by overweight [30.5% (BMI ≥ 25 and < 30 kg/m2)], normal [27.9% (BMI ≥ 18.5 and < 25 kg/m2)], and underweight [4.9% (BMI < 18.5 kg/m2)]. As a continuous variable, BMI was not associated with any of the outcomes. When analyzing BMI ordinally, obesity was associated with lower odds of favorable 90-day modified Rankin Scale (odds ratio 0.42, 95% confidence interval 0.20-0.86). The systematic review identified three eligible studies comprising 1,348 patients for a total of 1,738 patients. In the random effects model, there was no association between obesity and favorable outcome (odds ratio 0.89, 95% confidence interval 0.63-1.24). CONCLUSIONS: Obesity is not associated with favorable outcomes in patients undergoing MT for LVO.

Lack of Evidence for PKM2 Protein Kinase Activity.

The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A unique function of PKM2 proposed to be important for the proliferation of some cancer cells involves the direct activity of this enzyme as a protein kinase; however, a detailed biochemical characterization of this activity is lacking. Using [(32)P]-phosphoenolpyruvate (PEP) we examine the direct substrates of PKM2 using recombinant enzyme and in vitro systems where PKM2 is genetically deleted. Labeling of some protein species from [(32)P]-PEP can be observed; however, most were dependent on the presence of ADP, and none were dependent on the presence of PKM2. In addition, we also failed to observe PKM2-dependent transfer of phosphate from ATP directly to protein. These findings argue against a role for PKM2 as a protein kinase.

Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation.

Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2 deletion affects proliferation and metabolism in nontransformed, nonimmortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis.

Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells.

Eukaryotic cells compartmentalize biochemical processes in different organelles, often relying on metabolic cycles to shuttle reducing equivalents across intracellular membranes. NADPH serves as the electron carrier for the maintenance of redox homeostasis and reductive biosynthesis, with separate cytosolic and mitochondrial pools providing reducing power in each respective location. This cellular organization is critical for numerous functions but complicates analysis of metabolic pathways using available methods. Here we develop an approach to resolve NADP(H)-dependent pathways present within both the cytosol and the mitochondria. By tracing hydrogen in compartmentalized reactions that use NADPH as a cofactor, including the production of 2-hydroxyglutarate by mutant isocitrate dehydrogenase enzymes, we can observe metabolic pathway activity in these distinct cellular compartments. Using this system we determine the direction of serine/glycine interconversion within the mitochondria and cytosol, highlighting the ability of this approach to resolve compartmentalized reactions in intact cells.

SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance.

Cancer cells adapt their metabolic processes to support rapid proliferation, but less is known about how cancer cells alter metabolism to promote cell survival in a poorly vascularized tumour microenvironment. Here we identify a key role for serine and glycine metabolism in the survival of brain cancer cells within the ischaemic zones of gliomas. In human glioblastoma multiforme, mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci. We find that SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumour regions. GLDC inhibition impairs cells with high SHMT2 levels as the excess glycine not metabolized by GLDC can be converted to the toxic molecules aminoacetone and methylglyoxal. Thus, SHMT2 is required for cancer cells to adapt to the tumour environment, but also renders these cells sensitive to glycine cleavage system inhibition.

[Situation analysis of off-label drug use in China].

To introduce current literature reporting situations of the off-label drug use(OLDU) by analyzing relevant literatures published in China, this study comprehensively focused on literatures about OLDU in China in seven Chinese and English databases, then extracted and analyzed the data by different literature types. A total of 667 papers were analyzed. The number of literatures about OLDU data analyzed in hospitals was 325, and the number of clinical studies relating to OLDU was 329, in which case series and case reports were the majority(69.91%). In addition, there were 13 expert consensuses of OLDU and another 56 studies about drug use based on the real-world data characteristics and influencing factors. The number of OLDU data studies has increased year by year. Based on the existing studies, there were more western medicine reports than traditional Chinese medicines, and OLDU types were mainly for over-dosage use. The literatures from OLDU data in hospital were mostly limited to one or several tertiary hospitals in a certain area, and the OLDU types were not uniform. Clinical studies were mainly clinical control trials and case series/reports, but with contradictory reporting results. There were fewer OLDU consensus, and the recommended classification was not uniform. The characteristics and analysis of influencing factors of drug using data in real-world focused on traditional Chinese medicine injections, and the results were not the same. In the future, we shall pay more attention to and strengthen reporting and analysis of OLDU, define study objectives, and unify the content and reporting standards, so as to promote the integrated utilization of OLDU data and reflect real situations in our country.

Effect of air pollution on hospital admissions for systemic lupus erythematosus in Bengbu, China: a time series study.

Recently, exposure to air pollutants has been associated with the development and progression of systemic lupus erythematosus (SLE). The current study aims to evaluate the effects of air pollutants on SLE hospital admissions in Bengbu, China. We performed distributed lag non-linear model combined with quasi-Poisson generalized linear regression to assess the impacts of air pollutants on SLE admissions from 2015 to 2017. Subgroup analyses by admission status (first admission or readmission) were also evaluated. A total of 546 hospital admissions during 2015-2017 were included. For single-day lag structures, the risk effects occurred from lag 2 to lag 9 for the 75th percentile particulate matter (PM)2.5, lag 3 to lag 9 for the 80th percentile PM2.5. For cumulative lag structures, the risk effects occurred from lag 0-5 to lag 0-14 for both 75th PM2.5 and 80th PM2.5, and no significant effect was observed for 90th PM2.5. In addition, the adverse effects on SLE first admissions occurred from lag 0 to lag 1 for NO2, lag 1 to lag 2 for SO2. The maximum effect of PM2.5 on SLE was 4.27 (95% confidence interval: 1.34-13.59) at lag 0-13 day, the minimum effect value was 1.12 (95% confidence interval: 1.03-1.23) at lag 9 day. These findings demonstrate that high PM2.5, NO2 and SO2 are associated with SLE hospital admissions. In addition, this study further revealed that exposure to high concentration of PM2.5 increased the risk of SLE relapse, while high levels of NO2 and SO2 increased the risk of SLE first admissions.

Effects of acarbose and siglitine on blood glucose fluctuation and islet ß-cell function in patients with type 2 diabetes mellitus.

The effects of acarbose and sitagliptin on blood glucose fluctuation and islet ß-cell function in patients with type 2 diabetes mellitus (T2DM) were studied. One hundred and three patients with poorly controlled T2DM with insulin aspart 30 were selected and randomly divided into three groups: group A [continuous subcutaneous insulin infusion (CSII) treatment group], group B (CSII combined with acarbose treatment), group C (CSII combined with sitagliptin treatment). The treatment lasted for two weeks and the clinical indicators in the three groups were measured. The insulin dosage was adjusted according to the blood glucose statuses of the three groups of patients. In the final three days, 72 h of continuous glucose monitoring (CGM) were carried out, and the OGTT test was performed again. The results showed that the MODD (absolute means of daily difference), intra-day blood glucose fluctuation indices [(24 h MBG (mean blood glucose), LAGE (largest amplitude of glycemic excursions) and MAGE (average blood glucose fluctuation)] and postprandial blood glucose fluctuation indices [PGS (postprandial glucose spike), △t, PPGE (postprandial glucose excursion) and T (time) total] in group C and group B were significantly lower than those in group A. Compared with group B, the difference in blood glucose fluctuation indices in group C was not statistically significant (P>0.05). The HOMA-islet (homeostasis model assessment of islet) (CP-DM) index and FC-P (Fasting c-peptide) levels in group C and group B were significantly higher than those in group A (P less than 0.01). The HOMA-IR (CP) index of groups B and C was significantly lower than that of group A (P less than 0.01), and there was no statistically significant difference between groups B and C (P less than 0.05). Sitagliptin combined with intensive insulin pump therapy can reduce blood glucose fluctuation throughout the day, reduce insulin dosage, improve islet B cell function and reduce hypoglycemia better than intensive insulin pump therapy alone.

Impact of ledipasvir/sofosbuvir on the work productivity of genotype 1 chronic hepatitis C patients in Asia.

Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor clinical prognosis and a detrimental impact on patients' lives, including on work productivity. To estimate the value of productivity losses due to genotype 1 (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to estimate the potential productivity gains associated with treating patients with ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a time horizon of 1 year. Hepatitis C virus patients entered the model at 12 weeks post-treatment, having achieved or not achieved sustained virological response (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of data from the ION 1-3 studies. These rates were converted into hours of lost productivity, multiplied by the average wage and applied to the total employed, adult GT1 population in each country. Results were compared assuming no treatment, and assuming all patients were treated with LDV/SOF. Total productivity losses due to untreated HCV were: $11.3 million, $17.1 m, $146.0 m and $349.1 m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment resulted in economic gains of $4.5 m, $6.8 m, $58.7 m and $138 m, respectively. These gains were due to reduced presenteeism. The results were sensitive to changes in the prevalence of HCV and the average wage. In conclusion, productivity losses due to untreated HCV infection represent a substantial economic burden. By instituting universal HCV treatment with LDV/SOF (or other therapies with high SVR rates), productivity gains can be achieved.

Biomechanical study on different lengths of PFNA fixation for unstable intertrochanteric femoral fractures.

OBJECTIVE: The aim of our study was to compare the biomechanical stability of the Proximal Femoral Nail Antirotation (PFNA) (with 200 mm, 240 mm and 280 mm-long main nails) for the management of unstable intertrochanteric femoral fractures. METHODS: Tronzo-Evans Type IV and V fractures were built by applying a three-dimensional finite element model. Further, PFNA-II with 200 mm, 240 mm and 280 mm-long main nails were applied for fixation. The above model is the creation of 3 researchers designed in order to obtain average values of numerical stress. Von Mises stress distribution and medial and lateral stress peak of the femur and PFNA were compared. RESULTS: 240 mm and 280 mm PFNA medial stress peak was reduced significantly in comparison to 200 mm PFNA (p⟨0.05). However, there was no difference between 240 mm and 280 mm PFN. Also, no statistical difference was observed with any of 3 lengths in both medial and lateral stress peak for Evans Type IV and V PFNA. CONCLUSION: 240 mm and 280 mm PFNA could reduce femur fixation medial stress peak. Further, they were more efficient in comparison to the 200 mm PFNA, and their biomechanical stability was similar to that of the 280 mm nail.

Uptake of 2,4-bis(Isopropylamino)-6-methylthio-s-triazine by Vetiver Grass (Chrysopogon zizanioides L.) from Hydroponic Media.

2,4-bis(Isopropylamino)-6-methylthio-s-triazine (prometryn) poses a risk to aquatic environments in several countries, including China, where its use is widespread, particularly due to its chemical stability and biological toxicity. Vetiver grass (Chrysopogon zizanioides L.) was tested for its potential for phytoremediation of prometryn. Vetiver grass was grown in hydroponic media in a greenhouse, in the presence of prometryn, with appropriate controls. Plant uptake and removal of prometryn from the media were monitored for a period of 67 days. The results showed that the removal of the prometryn in the media was expedited by vetiver grass. The removal half-life (t1/2) was shortened by 11.5 days. Prometryn removal followed first-order kinetics (Ct = 1.8070e(-0.0601t)). This study demonstrated the potential of vetiver grass for the phytoremediation for prometryn.

Antibody-mediated neutralization of perfringolysin o for intracellular protein delivery.

Perfringolysin O (PFO) is a member of the cholesterol-dependent cytolysin (CDC) family of bacterial pore-forming proteins, which are highly efficient in delivering exogenous proteins to the cytoplasm. However, the indiscriminate and potent cytotoxicity of PFO limits its practical use as an intracellular delivery system. In this study, we describe the design and engineering of a bispecific, neutralizing antibody against PFO, which targets reversibly attenuated PFO to endocytic compartments via receptor-mediated internalization. This PFO-based system efficiently mediated the endosomal release of a co-targeted gelonin construct with high specificity and minimal toxicity in vitro. Consequently, the therapeutic window of PFO was improved by more than 5 orders of magnitude. Our results demonstrating that the activity of pore-forming proteins can be controlled by antibody-mediated neutralization present a novel strategy for utilizing these potent membrane-lytic agents as a safe and effective intracellular delivery vehicle.

Meta-analysis of the effectiveness of esomeprazole in gastroesophageal reflux disease and Helicobacter pylori infection.

WHAT IS KNOWN AND OBJECTIVE: Proton pump inhibitors (PPIs) are one of the most widely used classes of drugs. However, the quantum clinical benefit of newer and more expensive PPIs over the older generation PPIs remains uncertain. This meta-analysis sought to assess the clinical and safety profiles of esomeprazole versus omeprazole at pharmacologically equivalent doses in healing gastroesophageal reflux disease (GERD), peptic ulcer disease and eradicating Helicobacter pylori (H. pylori) infection. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials comparing esomeprazole with omeprazole at all doses up to February 2015. Trials were assessed by two reviewers for eligibility according to predefined study inclusion criteria. Meta-analysis was conducted using a random effects model, and heterogeneity in the estimated effects was investigated using meta-regression. Sensitivity analysis was performed to test the robustness of the findings. RESULTS AND DISCUSSION: Fifteen trials were included and none of which compared esomeprazole with omeprazole in peptic ulcer disease. The included studies had not evaluated esomeprazole 20 mg versus omeprazole 40 mg. In GERD, esomeprazole 40 mg (relative risk (RR) = 1·07; 95% confidence interval (CI) 1·02 to 1·12) and 20 mg (RR=1·04; 95% CI 1·01 to 1·08) significantly improved esophagitis healing when compared with omeprazole 20 mg at week 8. The corresponding numbers needed to treat were 17 and 30, respectively. No significant difference was observed between esomeprazole 20 mg and omeprazole 20 mg at week 4. In H. pylori eradication, there was no difference in the treatment effects between esomeprazole 20 mg and omeprazole 20 mg (RR = 1·01;95% CI 0·96 to 1·05). Their safety profiles were comparable. WHAT IS NEW AND CONCLUSION: Esomeprazole demonstrated better esophagitis healing rate in patients with GERD than omeprazole at week 8. However, this clinical advantage diminished when both drugs were given at the same doses at week 4. Superiority of esomeprazole was not observed in the H. pylori eradication rates.

Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma.

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63-0.75], p = 1.86×10⁻¹8), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21-1.43], p = 3.87×10⁻¹¹). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50-0.67], p = 1.17×10⁻¹²) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53-0.72], p = 8.88×10⁻¹°). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41-0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54-1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.

A bench-scale assessment for phosphorus release control of sediment by an oxygen-releasing compound (ORC).

The effects of oxygen-releasing compound (ORC) on the control of phosphorus (P) release as well as the spatial and temporal distribution of P fractions in sediment were studied through a bench-scale test. An ORC with an extended oxygen-releasing capacity was prepared. The results of the oxygen-releasing test showed that the ORC provided a prolonged period of oxygen release with a highly effective oxygen content of 60.6% when compared with powdery CaO2. In the bench-scale test, an ORC dose of 180 g·m(-2) provided a higher inhibition efficiency for P release within 50 days. With the application of the ORC, the dissolved oxygen (DO) concentration and redox potential (ORP) of the overlying water were notably improved, and the dissolved total phosphorus (DTP) was maintained below 0.689 mg·L(-1) compared to 2.906 mg·L(-1) without the ORC treatment. According to the P fractions distribution, the summation of all detectable P fractions in each sediment layer exhibited an enhanced accumulation tendency with the application of ORC. Higher phosphorus retention efficiencies were observed in the second and third layers of sediment from days 10 to 20 with the ORC. Phosphorus was trapped mainly in the form of iron bound P (Fe-P) and organically bound P (O-P) in sediment with the ORC, whereas the effects of the ORC on exchangeable P (EX-P), apatite-associated P (A-P) and detrital P (De-P) in the sediment sample were not significant. The microbial activities of the sediment samples demonstrated that both the dehydrogenase activity (DHA) and alkaline phosphatase activity (APA) in the upper sediment layer increased with the ORC treatment, which indicated that the mineralization of P was accelerated and the microbial biomass was increased. As the accumulation of P suppressed the release of P, the sediment exhibited an increased P retention efficiency with the application of the ORC.

Disrupted sleep-wake regulation in the MCI-Park mouse model of Parkinson's disease.

Disrupted sleep has a profound adverse impact on lives of Parkinson's disease (PD) patients and their caregivers. Sleep disturbances are exceedingly common in PD, with substantial heterogeneity in type, timing, and severity. Among the most common sleep-related symptoms reported by PD patients are insomnia, excessive daytime sleepiness, and sleep fragmentation, characterized by interruptions and decreased continuity of sleep. Alterations in brain wave activity, as measured on the electroencephalogram (EEG), also occur in PD, with changes in the pattern and relative contributions of different frequency bands of the EEG spectrum to overall EEG activity in different vigilance states consistently observed. The mechanisms underlying these PD-associated sleep-wake abnormalities are poorly understood, and they are ineffectively treated by conventional PD therapies. To help fill this gap in knowledge, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. These sleep-wake abnormalities resemble those identified in PD patients. Thus, this model may help elucidate the circuit mechanisms underlying sleep disruption in PD and identify targets for novel therapeutic approaches.

Pseudogout mimicking cervical spine osteomyelitis and ventral epidural abscess: A case report and literature review.

Background: Calcium pyrophosphate deposition disease (CPPD), also known as "pseudogout," is a crystal deposition arthropathy involving the synovial and periarticular tissues. Pseudogout rarely presents in the axial spine. Here, we present the case of an 80-year-old female patient admitted after a mechanical fall, initially misdiagnosed on computed tomography (CT)/magnetic resonance studies with cervical osteodiscitis/ventral epidural abscess that proved to be pseudogout. Case Description: An 80-year-old female was admitted after a mechanical fall. The initial cervical CT scan showed multilevel degenerative changes with an acute C6 anterior wedge compression fracture, focal kyphosis, C5-6 disc space collapse, and endplate destruction. The magnetic resonance imaging showed marked contrast enhancement of the C5-6 vertebral bodies and disc space. An interventional radiology-guided biopsy of the C5-6 vertebral bodies and disc space was consistent with calcium pyrophosphate deposits, was diagnostic for pseudogout, and was negative for infection. She was managed conservatively with a rigid collar and seven days of oral prednisone. Conclusion: CPPD involvement in the axial spine is rare. Prompt pathologic diagnosis should be pursued to rule out an infectious process.