CPHEN-013: Comprehensive phenotyping of hematopoietic stem and progenitor cells in the human fetal liver.

Hematopoietic stem cells (HSCs) reside at the top of the hematopoietic hierarchy and can give rise to all the mature blood cell types in our body, while at the same time maintaining a pool of HSCs through self-renewing divisions. This potential is reflected in their functional definition as cells that are capable of long-term multi-lineage engraftment upon transplantation. While all HSCs meet these criteria, subtle differences exist between developmentally different populations of these cells. Here we present a comprehensive overview of traditional and more recently described markers for phenotyping HSCs and their downstream progeny. To address the need to assess the growing number of surface molecules expressed in various HSC-enriched fractions at different developmental stages, we have developed an extensive multi-parameter spectral flow cytometry panel to phenotype hematopoietic stem and multipotent progenitor cells (HSC/MPPs) throughout development. In this study we then employ this panel to comprehensively profile the HSC compartment in the human fetal liver (FL), which is endowed with superior engraftment potential compared to postnatal sources. Spectral cytometry lends an improved resolution of marker expression to our comprehensive approach, allowing to extract combinatorial expression signatures of several relevant HSC/MPP markers to precisely characterize the HSC/MPP fraction in a variety of tissues.

TikTok and Attention-Deficit/Hyperactivity Disorder: A Cross-Sectional Study of Social Media Content Quality.

OBJECTIVES: Social media platforms are increasingly being used to disseminate mental health information online. User-generated content about attention-deficit/hyperactivity disorder (ADHD) is one of the most popular health topics on the video-sharing social media platform TikTok. We sought to investigate the quality of TikTok videos about ADHD. METHOD: The top 100 most popular videos about ADHD uploaded by TikTok video creators were classified as misleading, useful, or personal experience. Descriptive and quantitative characteristics of the videos were obtained. The Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V) and Journal of American Medical Association (JAMA) benchmark criteria were used to assess the overall quality, understandability, and actionability of the videos. RESULTS: Of the 100 videos meeting inclusion criteria, 52% (n = 52) were classified as misleading, 27% (n = 27) as personal experience, and 21% (n = 21) as useful. Classification agreement between clinician ratings was 86% (kappa statistic of 0.7766). Videos on the platform were highly understandable by viewers but had low actionability. Non-healthcare providers uploaded the majority of misleading videos. Healthcare providers uploaded higher quality and more useful videos, compared to non-healthcare providers. CONCLUSIONS: Approximately half of the analyzed TikTok videos about ADHD were misleading. Clinicians should be aware of the widespread dissemination of health misinformation on social media platforms and its potential impact on clinical care.

Intensive control of hypertension and risk of Alzheimer's dementia in older adults with depression.

OBJECTIVES: Intensive control of hypertension has been reported to decrease risk of cognitive decline. However, the effect of this in older adults with hypertension and comorbid depression is not well understood. We aim to identify whether intensive control of systolic blood pressure (BP) is associated with reduced risk of Alzheimer's dementia (AD) in a clinical population. METHODS: Using data from the National Alzheimer's Coordinating Center, we conducted survival analyses in older adults with normal cognition at baseline and treated hypertension. We also examined those with comorbid depression, to determine if intensive control of systolic BP (≤120 mmHg) was associated with reduced risk of AD. RESULTS: In all older adults with treated hypertension (n = 4505), 298 (6.6%) developed AD during a median follow-up duration of 4.2 years. In the comorbid depression subgroup (n = 1327), 152 (11.5%) developed AD. Intensive control of systolic BP was not significantly associated with reduced risk of AD in the overall sample (HR 1.13, 95%, 0.79-1.64). However, in the comorbid depression subgroup, intensive control of systolic BP (≤120 mmHg) was associated with increased risk of AD (HR 1.49, 95%, 1.03-2.15) compared to standard control (121-139 mmHg). CONCLUSIONS: In a clinical population of older adults with hypertension and comorbid depression, we found that an intensive systolic BP target of ≤120 mmHg was associated with increased risk of AD. While these findings are preliminary, they suggest that a more cautious approach to hypertension treatment may be warranted in this vulnerable subgroup.

Worldwide research productivity in the field of full-endoscopic spine surgery: a bibliometric study.

PURPOSE: To investigate the quantity and quality of articles in the field of full-endoscopic spine surgery (FESS) from different countries and assess characteristics of worldwide research productivity. METHODS: Articles published from 1997 to July 23, 2018, were screened using the Web of Science database. All studies were assessed for the following parameters: the number of total publications, h-index, contribution of countries, authors, journals, and institutions. RESULTS: A total of 408 articles were identified between 1997 and 2018. Between 1997 and 2017, the number of published articles tended to increase by 41 times. The largest number of articles was from China (30.15%), followed by South Korea (28.68%), the USA (13.97%), Germany (9.31%), and Japan (4.90%). The highest h-index was found for articles from South Korea (23), followed by the USA (18), Germany (16), China (11), and Japan (7). The highest number of articles was published in World Neurosurgery (12.50%), followed by Pain Physician (10.29%), Spine (6.62%), European Spine Journal (4.66%), and Journal of Neurosurgery: Spine (4.17%). Wooridul Spine Hospital published the largest number of articles (10.29%), followed by Tongji University (5.88%), University of Witten/Herdecke (5.39%), Brown University (5.15%), and Third Military Medical University (3.43%). CONCLUSIONS: The number of articles published in the field of FESS has increased rapidly in the past 20 years. In terms of quantity, China is the most contributive country based on the number of publications. High-quality papers as measured by h-index and the large quantity is from South Korea (second only to China). These slides can be retrieved under Electronic Supplementary Material.

Paradoxical complete and spontaneous resolution of depression, psychosis, and suicidal ideation following a traumatic brain injury.

A 65-year-old male patient with depression and psychosis sustained a traumatic brain injury (TBI) after a suicide attempt involving a motor vehicle. Immediately post-injury, the patient's psychiatric symptoms completely resolved, and cognitive function improved, with minimal neurological deficits. We describe the first case, to our knowledge, of a patient with a paradoxical complete and spontaneous resolution of multiple psychiatric symptoms (depression, psychosis, and suicidal ideation) immediately following a closed-head, left hemispheric TBI.

Spontaneous Displacement of High Viscosity Micrometer Size Oil Droplets from a Curved Solid in Aqueous Solutions.

Spontaneous displacement of high viscosity (∼103 Pa·s) micrometer size oil droplets from a curved solid in aqueous solutions was investigated. For high viscosity oils, the dynamic droplet shape was found to deviate significantly from a spherical cap shape due to the considerable viscous force in the oil phase. The displacement dynamics of high viscosity droplets were analyzed using molecular kinetic and hydrodynamic models. The molecular kinetic model was found to describe the dynamic displacement well for the droplets of small departure from the spherical cap shape, while the hydrodynamic model is more applicable to the droplets of higher three-phase contact line displacement velocities and hence larger deviation of the droplets from the spherical cap shape.

Long-term habituation of the C-start escape response in zebrafish larvae.

The cellular and molecular basis of long-term memory in vertebrates remains poorly understood. Knowledge regarding long-term memory has been impeded by the enormous complexity of the vertebrate brain, particularly the mammalian brain, as well as by the relative complexity of the behavioral alterations examined in most studies of long-term memory in vertebrates. Here, we demonstrate a long-term form of nonassociative learning-specifically, long-term habituation (LTH)-of a simple reflexive escape response, the C-start, in zebrafish larvae. The C-start is triggered by the activation of one of a pair of giant neurons in the zebrafish's hindbrain, the Mauthner cells. We show that LTH of the C-start requires the activity of NMDA receptors and involves macromolecular synthesis. We further show that the long-term habituated reflex can by rapidly dishabituated by a brief tactile stimulus. Our results set the stage for rigorous, mechanistic investigations of the long-term memory for habituation of a reflexive behavioral response, one that is mediated by a relatively simple, neurobiologically tractable, neural circuit. Moreover, the demonstration of NMDAR and transcriptionally dependent LTH in a translucent vertebrate organism should facilitate the use of optical recording, and optogenetic manipulation, of neuronal activity to elucidate the cellular basis of a long-term vertebrate memory.

Treatment of FBSS Low Back Pain with a Novel Percutaneous DRG Wireless Stimulator: Pilot and Feasibility Study.

OBJECTIVES: Test a miniaturized neurostimulator transforaminally placed at the dorsal root ganglion (DRG) and evaluate the device's safety and efficacy in treating failed back surgery syndrome (FBSS) low back pain. DESIGN: Pilot, two-phase study. SUBJECTS: Eleven subjects with chronic intractable neuropathic trunk and/or lower limbs pain were included. METHODS: The system consisted of an implantable, miniaturized stimulator, provided by Stimwave Technologies (Freedom-4) and an external transmitter. Only one stimulator per subject was implanted unilaterally and transforaminally at L1 to L5 levels. During Phase 1 of the study, the stimulators were not anchored. In Phase 2, the stimulators were anchored. Subjects were treated during 45 days after which the stimulator was removed. Pain reduction, implant duration, and stimulator migration were registered. RESULTS: Overall pain reduction was 59.9%, with only one device placed at one location, covering only a portion of the painful areas in the majority of the subjects. In Phase 1, the non-anchored stimulators migrated a mean of 8.80 mm and in Phase 2 a mean of 1.83 mm. Stimulator migration did not correlate with changes in pain relief. Mean time-to-implant duration was 10 minutes and no adverse events were reported during implant, follow-up period, or after explant. CONCLUSIONS: The pain reduction results indicate that the Freedom-4 spinal cord stimulation (SCS) Wireless System is a viable treatment of low back pain through stimulation of the DRG, and better overall pain reduction may be achieved by implanting multiple devices. With short percutaneous implant times and excellent safety profile, this new system may offer health cost savings.

Analysis of the plasma proteome in COPD: Novel low abundance proteins reflect the severity of lung remodeling.

The search for COPD biomarkers has largely employed a targeted approach that focuses on plasma proteins involved in the systemic inflammatory response and in lung injury and repair. This proof of concept study was designed to test the idea that an open, unbiased, in-depth proteomics approach could identify novel, low abundance plasma proteins i.e., ng/mL concentration, which could serve as potential biomarkers. Differentially expressed proteins were identified in a discovery group with severe COPD (FEV1 <45% predicted; n = 10). Subjects with normal lung function matched for age, sex, ethnicity and smoking history served as controls (n = 10). Pooled plasma from each group was exhaustively immunodepleted of abundant proteins, d separated by 1-D gel electrophoresis and extensively fractionated prior to LC-tandem mass spectroscopy (GeLC-MS). Thirty one differentially expressed proteins were identified in the discovery group including markers of lung defense against oxidant stress, alveolar macrophage activation, and lung tissue injury and repair. Four of the 31 proteins (i.e., GRP78, soluble CD163, IL1AP and MSPT9) were measured in a separate verification group of 80 subjects with varying COPD severity by immunoassay. All 4 were significantly altered in COPD and 2 (GRP78 and soluble CD163) correlated with both FEV1 and the extent of emphysema. In-depth, plasma proteomic analysis identified a group of novel, differentially expressed, low abundance proteins that reflect known pathogenic mechanisms and the severity of lung remodeling in COPD. These proteins may also prove useful as COPD biomarkers.

Immunodepletion plasma proteomics by tripleTOF 5600 and Orbitrap elite/LTQ-Orbitrap Velos/Q exactive mass spectrometers.

Plasma proteomic experiments performed rapidly and economically using several of the latest high-resolution mass spectrometers were compared. Four quantitative hyperfractionated plasma proteomics experiments were analyzed in replicates by two AB SCIEX TripleTOF 5600 and three Thermo Scientific Orbitrap (Elite/LTQ-Orbitrap Velos/Q Exactive) instruments. Each experiment compared two iTRAQ isobaric-labeled immunodepleted plasma proteomes, provided as 30 labeled peptide fractions, and 480 LC-MS/MS runs delivered >250 GB of data in 2 months. Several analysis algorithms were compared. At 1% false discovery rate, the relative comparative findings concluded that the Thermo Scientific Q Exactive Mass Spectrometer resulted in the highest number of identified proteins and unique sequences with iTRAQ quantitation. The confidence of iTRAQ fold-change for each protein is dependent on the overall ion statistics (Mascot Protein Score) attainable by each instrument. The benchmarking also suggested how to further improve the mass spectrometry parameters and HPLC conditions. Our findings highlight the special challenges presented by the low abundance peptide ions of iTRAQ plasma proteome because the dynamic range of plasma protein abundance is uniquely high compared with cell lysates, necessitating high instrument sensitivity.

A review of the roles of constituent minerals and residual bitumen in the solid-liquid separation of oil sands tailings.

The efficient dewatering of fluid fine tailings (FFT) generated from warm-water extraction of Canadian oil sands is a major challenge that has limited the timely reclamation of the tailings. It is generally recognized that both chemical amendments and physical/mechanical solid-liquid separation treatments are required to speed up FFT dewatering. Significant efforts have been made to enhance the rate of solid-liquid separation of FFT in the past several decades. The fact that these efforts have met with limited successes calls for a better fundamental understanding of the solid-liquid separation process. In this work, we reviewed and critically analyzed the factors that contribute to the difficult dewatering of FFT, including the role of constituent minerals and residual bitumen. In particular, the effects of mineralogical composition, mineral particle size, and the role of residual bitumen on settling rate, hydraulic conductivity, and filtration rate are reviewed and discussed. This review also points out directions to accelerate the dewatering of FFT, such as reducing the effective volume fraction of swelling clays and releasing bitumen coating from clay surfaces, that may significantly increase the filtration rate of oil sands tailings.

De novo hematopoiesis from the fetal lung.

Hemogenic endothelial cells (HECs) are specialized cells that undergo endothelial-to-hematopoietic transition (EHT) to give rise to the earliest precursors of hematopoietic progenitors that will eventually sustain hematopoiesis throughout the lifetime of an organism. Although HECs are thought to be primarily limited to the aorta-gonad-mesonephros (AGM) during early development, EHT has been described in various other hematopoietic organs and embryonic vessels. Though not defined as a hematopoietic organ, the lung houses many resident hematopoietic cells, aids in platelet biogenesis, and is a reservoir for hematopoietic stem and progenitor cells (HSPCs). However, lung HECs have never been described. Here, we demonstrate that the fetal lung is a potential source of HECs that have the functional capacity to undergo EHT to produce de novo HSPCs and their resultant progeny. Explant cultures of murine and human fetal lungs display adherent endothelial cells transitioning into floating hematopoietic cells, accompanied by the gradual loss of an endothelial signature. Flow cytometric and functional assessment of fetal-lung explants showed the production of multipotent HSPCs that expressed the EHT and pre-HSPC markers EPCR, CD41, CD43, and CD44. scRNA-seq and small molecule modulation demonstrated that fetal lung HECs rely on canonical signaling pathways to undergo EHT, including TGFß/BMP, Notch, and YAP. Collectively, these data support the possibility that post-AGM development, functional HECs are present in the fetal lung, establishing this location as a potential extramedullary site of de novo hematopoiesis.

Durotomy- and Irrigation-Related Serious Adverse Events During Spinal Endoscopy: Illustrative Case Series and International Surgeon Survey.

BACKGROUND: Durotomy during endoscopic spine surgery can cause a patient's neurological or cardiovascular status to deteriorate unexpectedly intra- or postoperatively. There is currently limited literature regarding appropriate fluid management strategies, irrigation-related risk factors, and clinical consequences of incidental durotomy during spinal endoscopy, and no validated irrigation protocol exists for endoscopic spine surgery. Thus, the present article sought to (1) describe 3 cases of durotomy, (2) investigate standard epidural pressure measurements, and (3) survey endoscopic spine surgeons on the incidence of adverse effects believed to result from durotomy. MATERIALS AND METHODS: The authors first reviewed clinical outcomes and analyzed complications in 3 patients with intraoperatively recognized incidental durotomy. Second, the authors conducted a small case series with intraoperative epidural pressure measurements during gravity-assisted irrigated video endoscopy of the lumbar spine. Measurements were conducted on 12 patients with a transducer assembly that was introduced through the endoscopic working channel of the RIWOSpine Panoview Plus and Vertebris endoscope to the decompression site in the spine. Third, the authors conducted a retrospective, multiple-choice survey of endoscopic spine surgeons to better understand the frequency and seriousness of problems they attributed to irrigation fluid escaping from the surgical decompression site into the spinal canal and neural axis. Descriptive and correlative statistical analyses were performed on the surgeons' responses. RESULTS: In the first part of this study, durotomy-related complications during irrigated spinal endoscopy were observed in 3 patients. Postoperative head computed tomographic (CT) images revealed massive blood in the intracranial subarachnoid space, the basal cisterns, the III and IV ventricle, and the lateral ventricles characteristic of an arterial fisher grade IV subarachnoid hemorrhage, and hydrocephalus without evidence of aneurysms or angiomas. Two additional patients developed intraoperative seizures, cardiac arrhythmia, and hypotension. The head CT image in 1 of these 2 patients had intracranial air entrapment.In the second part, epidural pressure measurements in 12 patients who underwent uneventful routine lumbar interlaminar decompression for L4-L5 and L5-S1 disc herniation showed an average epidural pressure of 24.5 mm Hg.In the third part, the online survey was accessed by 766 spine surgeons worldwide and had a response rate of 43.6%. Irrigation-related problems were reported by 38% of responding surgeons. Only 11.8% used irrigation pumps, with 90% running the pump above 40 mm Hg. Headaches (4.5%) and neck pain (4.9%) were observed by nearly a 10th (9.4%) of surgeons. Seizures in combination with headaches, neck and abdominal pain, soft tissue edema, and nerve root injury were reported by another 5 surgeons. One surgeon reported a delirious patient. Another 14 surgeons thought that they had patients with neurological deficits ranging from nerve root injury to cauda equina syndrome related to irrigation fluid. Autonomic dysreflexia associated with hypertension was attributed by 19 of the 244 responding surgeons to the noxious stimulus of escaped irrigation fluid that migrated from the decompression site in the spinal canal. Two of these 19 surgeons reported 1 case associated with a recognized incidental durotomy and another with postoperative paralysis. CONCLUSIONS: Patients should be educated preoperatively about the risk of irrigated spinal endoscopy. Although rare, intracranial blood, hydrocephalus, headaches, neck pain, seizures, and more severe complications, including life-threatening autonomic dysreflexia with hypertension, may arise if irrigation fluid enters the spinal canal or the dural sac and migrates from the endoscopic site along the neural axis rostrally. Experienced endoscopic spine surgeons suspect a correlation between durotomy and irrigation-related extra- and intradural pressure equalization that could be problematic if associated with high volumes of irrigation fluid LEVEL OF EVIDENCE: 3.

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Personalized Interventional Surgery of the Lumbar Spine: A Perspective on Minimally Invasive and Neuroendoscopic Decompression for Spinal Stenosis.

Pain generator-based lumbar spinal decompression surgery is the backbone of modern spine care. In contrast to traditional image-based medical necessity criteria for spinal surgery, assessing the severity of neural element encroachment, instability, and deformity, staged management of common painful degenerative lumbar spine conditions is likely to be more durable and cost-effective. Targeting validated pain generators can be accomplished with simplified decompression procedures associated with lower perioperative complications and long-term revision rates. In this perspective article, the authors summarize the current concepts of successful management of spinal stenosis patients with modern transforaminal endoscopic and translaminar minimally invasive spinal surgery techniques. They represent the consensus statements of 14 international surgeon societies, who have worked in collaborative teams in an open peer-review model based on a systematic review of the existing literature and grading the strength of its clinical evidence. The authors found that personalized clinical care protocols for lumbar spinal stenosis rooted in validated pain generators can successfully treat most patients with sciatica-type back and leg pain including those who fail to meet traditional image-based medical necessity criteria for surgery since nearly half of the surgically treated pain generators are not shown on the preoperative MRI scan. Common pain generators in the lumbar spine include (a) an inflamed disc, (b) an inflamed nerve, (c) a hypervascular scar, (d) a hypertrophied superior articular process (SAP) and ligamentum flavum, (e) a tender capsule, (f) an impacting facet margin, (g) a superior foraminal facet osteophyte and cyst, (h) a superior foraminal ligament impingement, (i) a hidden shoulder osteophyte. The position of the key opinion authors of the perspective article is that further clinical research will continue to validate pain generator-based treatment protocols for lumbar spinal stenosis. The endoscopic technology platform enables spine surgeons to directly visualize pain generators, forming the basis for more simplified targeted surgical pain management therapies. Limitations of this care model are dictated by appropriate patient selection and mastering the learning curve of modern MIS procedures. Decompensated deformity and instability will likely continue to be treated with open corrective surgery. Vertically integrated outpatient spine care programs are the most suitable setting for executing such pain generator-focused programs.

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management: Perspectives from Europe, Latin America, Asia, and The United States.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work-life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur-investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

Assessment of two immunodepletion methods: off-target effects and variations in immunodepletion efficiency may confound plasma proteomics.

Immunodepletion of abundant plasma proteins increases the depth of proteome penetration by mass spectrometry. However, the nature and extent of immunodepletion and the effect of off-target depletion on the quantitative comparison of the residual proteins have not been critically addressed. We performed mass spectrometry label-free quantitation to determine which proteins were immunodepleted and by how much. Two immunodepletion resins were compared: Qproteome (Qiagen) which removes albumin+immunoglobulins and Seppro IgY14+SuperMix (Sigma-Aldrich) which removes 14 target proteins plus a number of unidentified proteins. Plasma collected by P100 proteomic plasma collection tubes (BD) from 20 human subjects was individually immunodepleted to minimize potential variability, prior to pooling. The abundant proteins were quantified better when using only albumin+immunoglobulins removal (Qproteome), while lower abundance proteins were evaluated better using exhaustive immunodepletion (Seppro IgY14+SuperMix). The latter resin removed at least 155 proteins, 38% of the plasma proteome in protein number and 94% of plasma protein in mass. The depth of immunodepletion likely accounts for the effectiveness of this resin in revealing low abundance proteins. However, the more profound immunodepletion achieved with the IgY14+SuperMix may lead to false-positive fold-changes between comparison groups if the reproducibility and efficiency of the depletion of a given protein are not considered.

Stability of emulsified heavy oil: the combined effects of deterministic DLVO forces and random surface charges.

When dispersed in aqueous solution, droplets of bitumen (extra heavy oil) are known to acquire negative surface charges. The resulting electrostatic repulsion, according to traditional DLVO theory, is far too strong for any droplet coalescence to occur. However, from experience it is known that bitumen droplets do coalesce in aqueous suspensions. Furthermore, the process appears to be random, with the probability of coalescence increasing sharply with the drop size. To explain these facts, we modeled the bitumen-water interface as a heterogeneous surface comprising charged "patches"; the zeta potentials of the patches constitute a random variable that is assumed to be Gaussian. The traditional DLVO theory, according to this model, remains sound on the local scale (i.e., for patches interacting across an intervening water layer). Such a theory can predict the probabilities of coalescence in remarkable detail. A parameter central to this theory is the lateral extent of the charged patches, which was estimated to be in the neighborhood of 0.6 µm.

Challenges in Spinal Endoscopy.

The advent of any new technology or technique is fraught with challenges in the early stages of development and adoption. This situation is no different for spinal endoscopy, which has been continuously developing for decades and has only recently gained significant traction in North America. Patient selection can be challenging for even expert endoscopic surgeons, given the limited abilities of current technology for patients with multilevel disease. Anatomic limitations, such as iliac crest location and small foraminal dimensions, can restrict application of the transforaminal approach, considered the "workhorse" of endoscopic techniques. A paucity of dedicated training opportunities has led many to become late adopters or preclude exposure entirely, limiting the next generation of surgeons and expansion of the field. Finally, economic constraints, including capital expenses and issues with insurance reimbursement, have generated difficulties to widespread acquisition. Nonetheless, the future is bright for spinal endoscopy, with potential solutions to these issues already generating progress. In the present report, we have summarized these challenges and discussed some of the current steps underway to help alleviate their impact.

A Differential Clinical Benefit Examination of Full Lumbar Endoscopy vs Interspinous Process Spacers in the Treatment of Spinal Stenosis: An Effect Size Meta-Analysis of Clinical Outcomes.

STUDY DESIGN: A design-agnostic standardized effect meta-analysis of 48 randomized, prospective, and retrospective studies on clinical outcomes with spinal endoscopic and interspinous process spacer (IPS) surgery. OBJECTIVE: The study aimed to provide reference set of Oswestry Disability Index (ODI) and visual analog scale (VAS) effect size data for back and leg pain following endoscopic and IPS decompression for lumbar herniated disc, foraminal, or lateral recess spinal stenosis. BACKGROUND: Mechanical low back pain following endoscopic transforaminal decompression may be more reliably reduced by simultaneous posterior column stabilization with IPS. METHODS: A systematic search of the PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 2 April 2020, identified 880 eligible endoscopy and 362 IPS studies varying in design and metrics. The authors compared calculated standardized effect sizes (Cohen's d) for extracted ODI, VAS-back, and VAS-leg data. RESULTS: The pooled standardized effect size combining the ODI, VAS-back, and VAS-leg data for the total sample of 19862 data sets from the 30 endoscopy and 18 IPS was 0.877 (95% CI = 0.857-0.898). When stratified by surgery, the combined effect sizes were 0.877 (95% CI = 0.849-0.905) for endoscopic decompression and 0.863 (95% CI = 0.796-0.930; P = 0.056) for IPS implantation. The ODI effect sizes calculated on 6462 samples with directly visualized endoscopic decompression were 0.917 (95% CI = 0.891-0.943) versus 0.798 (95% CI = 0.713-0.883; P < 0.001) with indirect IPS decompression (P < 0.001). The VAS-back effect sizes calculated on 3672 samples were 0.661 (95% CI = 0.585-0.738) for endoscopy and 0.784 (95% CI: 0.644-0.923; P = 0.187) for IPS. The VAS-leg effect sizes calculated on 7890 samples were 0.885 (95% CI = 0.852-0.917) for endoscopic decompression and 0.851 (95% CI = 0.767-0.935; P = 0.427). CONCLUSION: Lumbar IPS implantation produces larger reduction in low back pain than spinal endoscopy. On the basis of this meta-analysis, the combination of lumbar transforaminal endoscopy with simultaneous IPS has merits and should be formally investigated in higher grade clinical studies. CLINICAL RELEVANCE: Meta-analysis on the added clinical benefit of combining lumbar endoscopic decompression with an interspinous process spacer.