A Review of Biodegradable Plastics: Chemistry, Applications, Properties, and Future Research Needs.

Environmental concerns over waste plastics' effect on the environment are leading to the creation of biodegradable plastics. Biodegradable plastics may serve as a promising approach to manage the issue of environmental accumulation of plastic waste in the ocean and soil. Biodegradable plastics are the type of polymers that can be degraded by microorganisms into small molecules (e.g., H2O, CO2, and CH4). However, there are misconceptions surrounding biodegradable plastics. For example, the term "biodegradable" on product labeling can be misconstrued by the public to imply that the product will degrade under any environmental conditions. Such misleading information leads to consumer encouragement of excessive consumption of certain goods and increased littering of products labeled as "biodegradable". This review not only provides a comprehensive overview of the state-of-the-art biodegradable plastics but also clarifies the definitions and various terms associated with biodegradable plastics, including oxo-degradable plastics, enzyme-mediated plastics, and biodegradation agents. Analytical techniques and standard test methods to evaluate the biodegradability of polymeric materials in alignment with international standards are summarized. The review summarizes the properties and industrial applications of previously developed biodegradable plastics and then discusses how biomass-derived monomers can create new types of biodegradable polymers by utilizing their unique chemical properties from oxygen-containing functional groups. The terminology and methodologies covered in the paper provide a perspective on directions for the design of new biodegradable polymers that possess not only advanced performance for practical applications but also environmental benefits.

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study.

BACKGROUND & AIMS: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). RESULTS: Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance. CONCLUSION: In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

Efficacy and safety of curcumin in primary sclerosing cholangitis: an open label pilot study.

Goals: To assess if curcumin improves markers of cholestasis among subjects with primary sclerosing cholangitis (PSC). Background: PSC is a chronic cholestatic liver disorder for which there is no established medical therapy. Preclinical data suggest curcumin may have a beneficial effect in PSC. Study: Subjects with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal (ULN) received curcumin 750 mg orally twice daily for 12 weeks in an open-label pilot study. The primary composite endpoint was proportion of subjects who had a reduction of SAP to less than 1.5 times ULN or a 40% reduction in SAP between baseline and week 12. Secondary endpoints included changes in serum aspartate aminotransferase, total bilirubin, Mayo PSC risk score and self-reported health questionnaires. Results: Two-hundred and fifty-eight patients with PSC were screened and 15 subjects were enrolled and all completed 12 weeks of therapy. The most common reason for subject exclusion was SAP less than 1.5 times the ULN (n = 98). Curcumin did not result in a significant median (interquartile range) change in SAP times the ULN [3.43 (2.10-4.32) to 2.46 (1.89-4.41), p = .36], and only 20% (3/15) subjects achieved the primary endpoint. Similarly, there was no significant change in the secondary endpoints. There were no serious adverse events reported. Conclusion: While curcumin was well tolerated, it was not associated with significant improvements in cholestasis or symptoms. Moreover, this study also illustrates that a low SAP is common among those with PSC. Abbreviations PSC: Primary sclerosing cholangitis; IBD: inflammatory bowel disease; CCA: cholangiocarcinoma; SAP: serum alkaline phosphatase; ULN: upper limit of normal; UDCA: ursodeoxycholic acid; CRP: c-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; FIS: fatigue impact scale; AE: adverse events; PREsTo: PSC risk estimate tool; IQR: interquartile range; ELF: enhanced liver fibrosis.

Nicotine dependence as an independent risk factor for atherosclerosis in the National Lung Screening Trial.

BACKGROUND: Atherosclerosis and COPD are systemic inflammatory diseases that share common risk factors including cigarette smoking. A high level of nicotine dependence is emerging as a recently identified risk factor for pulmonary impairment, chronic obstructive pulmonary disease and tobacco-related cancers. We hypothesized that nicotine dependence is associated with the risk of atherosclerosis in long-term cigarette smokers. METHODS: A nested case-control study was conducted within the National Lung Cancer Screening Trial- American College of Radiology Imaging Network. Cases were defined as having a new diagnosis of any type of atherosclerosis. Controls were matched on a 2:1 basis by age, sex, race, study center, smoking status, years of smoking, and frequency of smoking. Dependence was measured by the time to first cigarette after awakening (TTFC). RESULTS: The study included 166 cases and 286 controls. Compared to participants who smoked within 5 min after waking, the risk of atherosclerosis for participants who smoked an hour or more after waking was borderline non-significant (odds ratio = 0.49, 95% confidence intervals [CI] 0.23, 1.00). Findings were similar for men and women. For aortic atherosclerosis, the corresponding odds ratio was 0.24 (95% CI 0.08, 0.69). Hypertension was associated with an increased risk and body mass index was associated with a decreased risk of aortic atherosclerosis. The TTFC was unrelated to coronary atherosclerosis. CONCLUSIONS: Compared to smoking immediately after waking, delaying an hour or more reduces the risk of aortic atherosclerosis even among long-term heavy smokers. Possible mechanisms that explain this association are intensity of smoking, inflammation and oxidative stress, and elevated lipid levels.

The modA10 phasevarion of nontypeable Haemophilus influenzae R2866 regulates multiple virulence-associated traits.

Non-typeable Haemophilus influenzae (NTHi) is a human restricted commensal and pathogen that elicits inflammation by adhering to and invading airway epithelia cells: transcytosis across these cells can result in systemic infection. NTHi strain R2866 was isolated from the blood of a normal 30-month old infant with meningitis, and is unusual for NTHi in that it is able to cause systemic infection. Strain R2866 is able to replicate in normal human serum due to expression of lgtC which mimics human blood group p(k). R2866 contains a phase-variable DNA methyltransferase, modA10 which switches ON and OFF randomly and reversibly due to polymerase slippage over a long tetrameric repeat tract located in its open reading frame. Random gain or loss of repeats during replication can results in expressed (ON), or not expressed (OFF) states, the latter due to a frameshift or transcriptional termination at a premature stop codon. We sought to determine if the unusual virulence of R2866 was modified by modA10 phase-variation. A modA10 knockout mutant was found to have increased adherence to, and invasion of, human ear and airway monolayers in culture, and increased invasion and transcytosis of polarized human bronchial epithelial cells. Intriguingly, the rate of bacteremia was lower in the infant rat model of infection than a wild-type R2866 strain, but the fatality rate was greater. Transcriptional analysis comparing the modA10 knockout to the R2866 wild-type parent strain showed increased expression of genes in the modA10 knockout whose products mediate cellular adherence. We conclude that loss of ModA10 function in strain R2866 enhances colonization and invasion by increasing expression of genes that allow for increased adherence, which can contribute to the increased virulence of this strain.

Using Chemoattractants to Lure Bacteria to Contact-Killing Surfaces.

Antimicrobial surfaces with covalently attached biocidal functionalities only kill microbes that come into direct contact with the surfaces (contact-killing surfaces). Herein, the activity of contact-killing surfaces is shown to be enhanced by using gradients in the concentration of soluble chemoattractants (CAs) to attract bacteria to the surfaces. Two natural and nonbiocidal CAs (aspartate and glucose) were used to attract bacteria to model surfaces decorated with quaternary ammonium groups (known to kill bacteria that come into contact with them). These results demonstrate the killing of Escherichia coli and Salmonella typhimurium, two common pathogens, at levels 10- to 20-times greater than that of the native surfaces alone. This approach is general and provides new strategies for the design of active or dynamic contact-killing surfaces with enhanced antimicrobial activities.

Primary care physician smoking screening and counseling for patients with chronic disease.

BACKGROUND: Evidence-based guidelines recommend smoking cessation treatment, including screening and counseling, for all smokers, including those with chronic diseases exacerbated by smoking. Physician treatment improves smoking cessation. Little data describes smoking treatment guideline uptake for patients with chronic cardiopulmonary smoking-sensitive diseases. OBJECTIVE: Describe U.S. primary care physician (PCP) smoking cessation treatment during patient visits for chronic cardiopulmonary smoking-sensitive diseases. METHODS: The National (Hospital) Ambulatory Medical Care Survey captured PCP visits. We examined smoking screening and counseling time trends for smokers with chronic diseases. Multivariable logistic regression assessed factors associated with smoking counseling for smokers with chronic smoking-sensitive diseases. RESULTS: From 2001-2009 smoking screening and counseling for smokers with chronic smoking-sensitive cardiopulmonary diseases were unchanged. Among smokers with chronic smoking-sensitive diseases, 50%-72% received no counseling. Smokers with chronic obstructive pulmonary disease (COPD) (odds ratio (OR)=6.54, 95% confidence interval (CI) 4.85-8.83) and peripheral vascular disease (OR=4.50, 95% CI 1.72-11.75) were more likely to receive smoking counseling at chronic/preventive care visits, compared with patients without smoking-sensitive diseases. Other factors associated with increased smoking counseling included non-private insurance, preventive and longer visits, and an established PCP. Asthma and cardiovascular disease showed no association with counseling. CONCLUSIONS: Smoking cessation counseling remains infrequent for smokers with chronic smoking-sensitive cardiopulmonary diseases. New strategies are needed to encourage smoking cessation counseling.

From farm accountancy data to environmental indicators: Assessing the environmental performance of Spanish agriculture at a regional level.

Understanding the environmental impacts of current agricultural practices is a starting point for transitioning towards sustainable agriculture, which is a goal to be achieved by the European Union. This study aims to provide a set of environmental impact indicators with which to assess and compare the environmental performance of a broad group of agricultural reference holdings at the Spanish NUTS 2 level. A life cycle assessment approach based on statistical data on farm accountancy is applied. The unit of analysis is a reference holding on which a specific crop is grown in a NUTS 2 and follows a specific management system (open-field irrigated, open-field rainfed, or greenhouse). The system boundaries are set at the farm gate, and the impact results are expressed per 1 € of net value added. For most reference holdings, the EF scores per net value added are similar regardless of their EF scores per kg commodity, suggesting a correspondence between the use of resources and the economic results. The environmental footprint is clustered into four groups. The first one accounts for 78 % of the sample and represents the holdings with the lowest impact (between 9.7·10-5 and 2.88·10-3 EF score·NVAfc-1); the second cluster groups seven reference holdings (3 herbaceous and 4 Mediterranean perennial crops) with an environmental footprint of between 3.04·10-3 and 9.01·10-3 EF score·NVAfc-1; the third group comprises four irrigated herbaceous crops holdings with the highest impact (between 1.37·10-2 and 2.13·10-2 EF score·NVAfc-1); and the last group corresponds to the holdings with economic losses (mostly herbaceous and two Mediterranean perennial crops). This research highlights the challenge of improving the competitiveness and profitability of Spanish farming. In this way, agricultural practices that generate environmental impacts without achieving their economic goals would be avoided.

Dataset to monitor regionalised environmental impacts of the main agricultural products in Spain.

Estimating the average environmental impacts of a representative crop in a specific region is a helpful starting point from which to propose improvements in the agricultural sector. However, data collection from official representative sources is complex, and often they require subsequent treatment to be transformed into meaningful inventory data. This article shows a comprehensive dataset for obtaining inventory data and developing an environmental life cycle impact assessment of representative agricultural production corresponding to reference holdings at a regional level (NUTS 2) in Spain. The dataset comprises Excel files with the data compiled from secondary sources to be used in the assessment and the R code scripts to transform the data into relevant inventory data to estimate the environmental impacts of the reference holdings. This dataset is a reliable tool for researchers and other potential users to be used as a secondary information source for further studies. It can also be used to estimate the environmental impacts of the farming activity of agri-food products in other regions or countries by collecting similar data for the specific region and adjusting the R code.

Simultaneous Fe2+/Fe3+ imaging shows Fe3+ over Fe2+ enrichment in Alzheimer's disease mouse brain.

Visualizing redox-active metal ions, such as Fe2+ and Fe3+ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe2+ and Fe3+ simultaneously in living cells with high selectivity and sensitivity has not been reported. Here, we selected and developed DNAzyme-based fluorescent turn-on sensors that are selective for either Fe2+ or Fe3+, revealing a decreased Fe3+/Fe2+ ratio during ferroptosis and an increased Fe3+/Fe2+ ratio in Alzheimer's disease mouse brain. The elevated Fe3+/Fe2+ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe3+ and/or conversion of Fe2+ to Fe3+. Our sensors can provide deep insights into the biological roles of labile iron redox cycling.

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas.

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients.

The importance of peripheral sequences in determining the metal selectivity of an in vitro-selected Co(2+) -dependent DNAzyme.

DNAzymes are catalytically active DNA molecules that use metal cofactors for their enzymatic functions. While a growing number of DNAzymes with diverse functions and metal selectivities have been reported, the relationships between metal ion selectivity, conserved sequences and structures responsible for selectivity remain to be elucidated. To address this issue, we report biochemical assays of a family of previously reported in vitro selected DNAzymes. This family includes the clone 11 DNAzyme, which was isolated by positive and negative selection, and the clone 18 DNAzyme, which was isolated by positive selection alone. The clone 11 DNAzyme has a higher selectivity for Co(2+) over Pb(2+) compared with clone 18. The reasons for this difference are explored here through phylogenetic comparison, mutational analysis and stepwise truncation. A novel DNAzyme truncation method incorporated a nick in the middle of the DNAzyme to allow for truncation close to the nicked site while preserving peripheral sequences at both ends of the DNAzyme. The results demonstrate that peripheral sequences within the substrate binding arms, most notably the stem loop, loop II, are sufficient to restore its selectivity for Co(2+) over Pb(2+) to levels observed in clone 11. A comparison of these sequences' secondary structures and Co(2+) selectivities suggested that metastable structures affect metal ion selectivity. The Co(2+) selectivity of the clone 11 DNAzyme showed that the metal ion binding and selectivities of small, in vitro selected DNAzymes may be more complex than previously appreciated, and that clone 11 may be more similar to larger ribozymes than to other small DNAzymes in its structural complexity and behavior. These factors should be taken into account when metal-ion selectivity is required in rationally designed DNAzymes and DNAzyme-based biosensors.

Blood pressure regulation in diabetic patients with and without peripheral neuropathy.

Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.

Novel reinforcement of corrugated nanofiber tissue-engineered vascular graft to prevent aneurysm formation for arteriovenous shunts in an ovine model.

Objective: Many patients who require hemodialysis treatment will often require a prosthetic graft after multiple surgeries. However, the patency rate of grafts currently available commercially has not been satisfactory. Tissue engineering vascular grafts (TEVGs) are biodegradable scaffolds created to promote autologous cell proliferation and functional neotissue regeneration and, accordingly, have antithrombogenicity. Therefore, TEVGs can be an alternative prosthesis for small diameter grafts. However, owing to the limitations of the graft materials, most TEVGs are rigid and can easily kink when implanted in limited spaces, precluding future clinical application. Previously, we developed a novel corrugated nanofiber graft to prevent graft kinking. Reinforcement of these grafts to ensure their safety is required in a preclinical study. In the present study, three types of reinforcement were applied, and their effectiveness was examined using large animals. Methods: In the present study, three different reinforcements for the graft composed of corrugated poly-ε-caprolactone (PCL) blended with poly(L-lactide-co-ε-caprolactone) (PLCL) created with electrospinning were evaluated: 1) a polydioxanone suture, 2) a 2-0 polypropylene suture, 3) a polyethylene terephthalate/polyurethane (PET/PU) outer layer, and PCL/PLCL as the control. These different grafts were then implanted in a U-shape between the carotid artery and jugular vein in seven ovine models for a total of 14 grafts during a 3-month period. In evaluating the different reinforcements, the main factors considered were cell proliferation and a lack of graft dilation, which were evaluated using ultrasound examinations and histologic and mechanical analysis. Results: No kinking of the grafts occurred. Overall, re-endothelialization was observed in all the grafts at 3 months after surgery without graft rupture or calcification. The PCL/PLCL grafts and PCL/PLCL grafts with a polydioxanone suture showed high cell infiltration; however, they had become dilated 10 weeks after surgery. In contrast, the PCL/PLCL graft with the 2-0 suture and the PCL/PLCL graft covered with a PET/PU layer did not show any graft expansion. The PCL/PLCL graft covered with a PET/PU layer showed less cell infiltration than that of the PCL/PLCL graft. Conclusions: Reinforcement is required to create grafts that can withstand arterial pressure. Reinforcement with suture materials has the potential to maintain cell infiltration into the graft, which could improve the neotissue formation of the graft.

Location matters: Offset in tissue-engineered vascular graft implantation location affects wall shear stress in porcine models.

Objective: Although surgical simulation using computational fluid dynamics has advanced, little is known about the accuracy of cardiac surgical procedures after patient-specific design. We evaluated the effects of discrepancies in location for patient-specific simulation and actual implantation on hemodynamic performance of patient-specific tissue-engineered vascular grafts (TEVGs) in porcine models. Methods: Magnetic resonance angiography and 4-dimensional (4D) flow data were acquired in porcine models (n = 11) to create individualized TEVGs. Graft shapes were optimized and manufactured by electrospinning bioresorbable material onto a metal mandrel. TEVGs were implanted 1 or 3 months postimaging, and postoperative magnetic resonance angiography and 4D flow data were obtained and segmented. Displacement between intended and observed TEVG position was determined through center of mass analysis. Hemodynamic data were obtained from 4D flow analysis. Displacement and hemodynamic data were compared using linear regression. Results: Patient-specific TEVGs were displaced between 1 and 8 mm during implantation compared with their surgically simulated, intended locations. Greater offset between intended and observed position correlated with greater wall shear stress (WSS) in postoperative vasculature (P < .01). Grafts that were implanted closer to their intended locations showed decreased WSS. Conclusions: Patient-specific TEVGs are designed for precise locations to help optimize hemodynamic performance. However, if TEVGs were implanted far from their intended location, worse WSS was observed. This underscores the importance of not only patient-specific design but also precision-guided implantation to optimize hemodynamics in cardiac surgery and increase reproducibility of surgical simulation.

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors.

BACKGROUND: DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. METHODS: We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET. RESULTS: Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. CONCLUSIONS: Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.

Gliosarcoma stem cells undergo glial and mesenchymal differentiation in vivo.

Cancer stem cells (CSCs) are characterized by their self-renewing potential and by their ability to differentiate and phenocopy the original tumor in orthotopic xenografts. Long-term propagation of glioblastoma (GBM) cells in serum-containing medium results in loss of the CSCs and outgrowth of cells genetically and biologically divergent from the parental tumors. In contrast, the use of a neurosphere assay, a serum-free culture for selection, and propagation of central nervous system-derived stem cells allows the selection of a subpopulation containing CSCs. Gliosarcoma (GS), a morphological variant comprising approximately 2% of GBMs, present a biphasic growth pattern, composed of glial and metaplastic mesenchymal components. To assess whether the neurosphere assay would allow the amplification of a subpopulation of cells with "gliosarcoma stem cell" properties, capable of propagating both components of this malignancy, we have generated neurospheres and serum cultures from primary GS and GBM surgical specimens. Neurosphere cultures from GBM and GS samples expressed neural stem cell markers Sox2, Musashi1, and Nestin. In contrast to the GBM neurosphere lines, the GS neurospheres were negative for the stem cell marker CD133. All neurosphere lines generated high-grade invasive orthotopic tumor xenografts, with histological features strikingly similar to the parental tumors, demonstrating that these cultures indeed are enriched in CSCs. Remarkably, low-passage GS serum cultures retained the expression of stem cell markers, the ability to form neurospheres, and tumorigenicity. The GS experimental tumors phenocopied the parental tumor, exhibiting biphasic glial and mesenchymal components, constituting a clinically relevant model to investigate mesenchymal differentiation in GBMs.

Lower Back Pain as an Occupational Hazard Among Ugandan Health Workers.

Background: Lower back pain is a public health concern affecting 70-85% of the world's population. There is paucity of published data on the prevalence, disability and risk factors for lower back pain among health workers in Uganda. Objective: To determine the frequency rate (note that is it implicit that frequency is a rate like incidence so including rate seems redundant here. This is bounded by zero and infinity. In contrast, prevalence is bounded by 0 and 1 and is thus a proportion not a rate) of lower back pain and its associated risks amongst health professionals in the Arua District of Uganda. Methods: Cross-sectional descriptive study of 245 consecutive participants conducted during February-April 2020. We stratified risks as individual or work related and analyzed the data using IBM SPSS version 25. Chi-square was used to measure the significance of association between categorical variables at 95% confidence interval, regarding a p ≤ 0.05 as significant. Results: The mean age of participants was 40.87 years ± 8.74 (SD), with female predominance (69.8%). Majority were either general nurses or midwives (64.9%) and more than half had practiced for over 6-10 years. The frequency rate of lower back pain was 39.6% (n = 97). Individual factors associated with LBP were; cigarette smoking (X2 = 33.040; P ≤ 0.001), alcohol consumption (X2 = 13.581; P ≤ 0.001), age (X2 = 14.717; P = 0.002), and female gender (X2 = 4.802; P = 0.028). The work related factors significantly associated with lower back pain were: being a nurse/midwife (X2 = 9.829; P = 0.007), working in the outpatient department (X2 = 49.752; P ≤ 0.001), bending (X2 = 43.912; P ≤ 0.001), lifting (X2 = 33.279; P < 0.001), over standing (X2 = 40.096; P ≤ 0.001), being in awkward positions (X2 = 15.607; P= < 0.001), and pushing patients (X2 = 21.999; P ≤ 0.001). Conclusion: The frequency rate of low back pain was high amongst health workers and its main associated individual and work related factors could have been prevented. Health workers should strike a balance between caring for their personal back-health and meeting clients' needs while manually handling patients. Ergonomic structuring, job organization, back health care courses and use of assistive equipment could reduce such occupational hazards in our low resourced settings.

Review of Neurologic Comorbidities in Hospitalized Patients With Opioid Abuse.

PURPOSE OF REVIEW: To determine the prevalence and burden of neurologic comorbidities in hospitalized patients with opioid abuse. RECENT FINDINGS: From 1 year of hospital discharges, 2,182 patients with opioid abuse were identified (prevalence 6.3%), with abuse greater among younger patients (p < 0.0001), women (p < 0.0001), Whites (p < 0.0001), and urban population (p = 0.028). Matching for age, sex, race, and urban-rural residence, 347 patients were reviewed, and 179 (52%) had a neurologic comorbidity. The comorbidities frequently overlapped and included encephalopathy (130), neuromuscular disorders (42), seizures (23), spine disorders (23), strokes (20), CNS infections (3), and movement disorders (2). Abuse patients with neurologic comorbidities experienced substantially greater number of hospital and intensive care unit days and mortality, independent of overdose. SUMMARY: Neurologic comorbidities are a frequent and heretofore underappreciated contributor to the disease burden of hospitalized patients with opioid abuse. The importance of neurologic comorbidities should be included in the public health discussions surrounding the opioid epidemic.