Publications by authors named "David Anderson"

1,342 Publications

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Angina relates to coronary flow in women with ischemia and no obstructive coronary artery disease.

Int J Cardiol 2021 Mar 1. Epub 2021 Mar 1.

Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address:

Background: Women with suspected ischemia and no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) as measured by impaired coronary flow reserve (CFR), which is associated with angina and adverse cardiovascular events. CFR is a ratio of hyperemic to baseline average peak velocity (bAPV), and the relation of baseline flow to angina is not understood.

Methods: We evaluated 259 women enrolled in the WISE-Coronary Vascular Dysfunction (WISE-CVD) project with suspected CMD who underwent invasive coronary functional testing. We analyzed variables stratified by high (e.g. ≥22 cm/s) vs low (<22 cm/s) bAPV, using t-test or Wilcoxon rank; linear and multivariable regression was used with bAPV as a continuous variable.

Results: Women with high bAPV had worse Seattle Angina Questionnaire (SAQ) angina frequency (58 ± 26 vs 67 ± 25, p = 0.005) and SAQ-7 scores (57 ± 22 vs 62 ± 21, p = 0.03), with higher nitrate (p = 0.02) and ranolazine use (p = 0.03). The high bAPV subgroup also had lower CFR (p < 0.001)). Linear regression related higher bAPV with lower SAQ-7 (p = 0.01) and lower angina frequency scores (p = 0.001). These results remained significant in multivariable modelling adjusting for baseline differences (p < 0.04). SAQ-7 was significantly predicted by bAPV.

Conclusions: Among women with suspected INOCA, angina relates to high bAPV, a result supported by the concomitant greater use of anti-anginal drugs. These results suggest that high bAPV contributes to impaired CFR and may represent a specific pathophysiologic contributor to CMD and may be a treatment target in INOCA subjects.
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http://dx.doi.org/10.1016/j.ijcard.2021.02.064DOI Listing
March 2021

Global political responsibility for the conservation of albatrosses and large petrels.

Sci Adv 2021 Mar 3;7(10). Epub 2021 Mar 3.

MARE-Marine and Environmental Sciences Centre, ISPA-Instituto Universitário, Lisboa, Portugal.

Migratory marine species cross political borders and enter the high seas, where the lack of an effective global management framework for biodiversity leaves them vulnerable to threats. Here, we combine 10,108 tracks from 5775 individual birds at 87 sites with data on breeding population sizes to estimate the relative year-round importance of national jurisdictions and high seas areas for 39 species of albatrosses and large petrels. Populations from every country made extensive use of the high seas, indicating the stake each country has in the management of biodiversity in international waters. We quantified the links among national populations of these threatened seabirds and the regional fisheries management organizations (RFMOs) which regulate fishing in the high seas. This work makes explicit the relative responsibilities that each country and RFMO has for the management of shared biodiversity, providing invaluable information for the conservation and management of migratory species in the marine realm.
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http://dx.doi.org/10.1126/sciadv.abd7225DOI Listing
March 2021

Patient Outcomes Following Short-segment Lumbar Fusion Are Not Affected by PI-LL Mismatch.

Clin Spine Surg 2021 Mar;34(2):73-77

Department of Orthopaedic Surgery, Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA.

Study Design: This is a retrospective cohort study.

Objective: The objective of this study was to further elucidate the relationship between pelvic incidence-lumbar lordosis (PI-LL) mismatch and surgical outcomes in patients undergoing short segment lumbar fusions for degenerative lumbar disease.

Summary Of Background Data: There are few studies examining the relationship between spinopelvic parameters and patient reported outcome measurements (PROMs) in short segment lumbar degenerative disease.

Materials And Methods: A retrospective review was conducted at single academic institution. Patients undergoing 1- or 2-level lumbar fusion were retrospectively identified and separated into 2 groups based on postoperative PI-LL mismatch ≤10 degrees (NM) or PI-LL mismatch >10 degrees (M). Outcomes including the Physical Component Score (PCS)-12, Mental Component Score (MCS)-12, Oswestry Disability Index (ODI), Visual Analog Scale (VAS) back and leg scores were analyzed. Absolute PROM scores, the recovery ratio and the percentage of patients achieving minimum clinically important difference between groups were compared and a multiple linear regression analysis was performed.

Results: A total of 306 patients were included, with 59 patients in the NM group and 247 patients in the M group. Patients in the M group started with a higher degree of PI-LL mismatch compared with the NM group (22.2 vs. 7.6 degrees, P<0.001) and this difference increased postoperatively (24.7 vs. 2.5 degrees, P<0.001). There were no differences between the 2 groups in terms of baseline, postoperative, or Δ outcome scores (P>0.05). In addition, having a PI-LL mismatch was not found to be an independent predictor of any PROM on multivariate analysis (P>0.05).

Conclusion: The findings in this study show that even though patients in the M group had a higher degree of mismatch preoperatively and postoperatively, there was no difference in PROMs.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BSD.0000000000001051DOI Listing
March 2021

Physicochemical properties and formulation development of a novel compound inhibiting Staphylococcus aureus biofilm formation.

PLoS One 2021 8;16(2):e0246408. Epub 2021 Feb 8.

Division of Cardiovascular Medicine, Department of Medicine, University of Missouri, Columbia, Missouri, United States of America.

The emergence of antibiotic resistance over the past several decades has given urgency to new antibacterial strategies that apply less selective pressure. A new class of anti-virulence compounds were developed that are active against methicillin-resistant Staphylococcus aureus (MRSA), by inhibiting bacterial virulence without hindering their growth to reduce the selective pressure for resistance development. One of the compounds CCG-211790 has demonstrated potent anti-biofilm activity against MRSA. This new class of anti-virulence compounds inhibited the gene expression of virulence factors involved in biofilm formation and disrupted the biofilm structures. In this study, the physicochemical properties of CCG-211790, including morphology, solubility in pure water or in water containing sodium dodecyl sulfate, solubility in organic solvents, and stability with respect to pH were investigated for the first time. Furthermore, a topical formulation was developed to enhance the therapeutic potential of the compound. The formulation demonstrated acceptable properties for drug release, viscosity, pH, cosmetic elegance and stability of over nine months.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246408PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870075PMC
February 2021

Host cell volume explains differences in the size of DsDNA viruses.

Virus Res 2021 Jan 27;295:198321. Epub 2021 Jan 27.

Dept. of Biology, University of Florida, Gainesville, FL, 32611, USA. Electronic address:

The nearly 3 orders of magnitude variation in size observed among double-stranded DNA viruses (dsDNA) has important ecological consequences, but the factors responsible for this variation remain poorly understood. Here we first evaluate if a relationship exists between the genome size of diverse dsDNA viruses and their hosts in single-celled organisms (prokaryotes and eukaryotes). We find that dsDNA genome size increases systematically, though less than proportionally, with host genome size. We next evaluate possible relationships between virus size, host size and burst size in an analysis that includes both single-celled and multicellular hosts where genome size and cell volume are not as highly correlated. Here we find that virus volume increases sublinearly with host cell volume (but not genome size) across species, and that virus burst volume (burst size * virus volume) increases with host cell volume. These findings suggest that the size and number of dsDNA viruses produced by a particular host may be constrained by the volume of the infected host cell. This may be useful for better understanding virus-host population dynamics, and ultimately, a better understanding of which viruses may infect which hosts (i.e., host specificity) and the likelihood of cross-species transmission events (i.e., host jumping).
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http://dx.doi.org/10.1016/j.virusres.2021.198321DOI Listing
January 2021

The origin of the parrotfish species Scarus compressus in the Tropical Eastern Pacific: region-wide hybridization between ancient species pairs.

BMC Ecol Evol 2021 Jan 21;21(1). Epub 2021 Jan 21.

Departamento de Biología Marina, Universidad Autónoma de Baja California Sur, CP 23081, La Paz, Baja California Sur, México.

Background: In the Tropical Eastern Pacific (TEP), four species of parrotfishes with complex phylogeographic histories co-occur in sympatry on rocky reefs from Baja California to Ecuador: Scarus compressus, S. ghobban, S. perrico, and S. rubroviolaceus. The most divergent, S. perrico, separated from a Central Indo-Pacific ancestor in the late Miocene (6.6 Ma). We tested the hypothesis that S. compressus was the result of ongoing hybridization among the other three species by sequencing four nuclear markers and a mitochondrial locus in samples spanning 2/3 of the latitudinal extent of the TEP.

Results: A Structure model indicated that K = 3 fit the nuclear data and that S. compressus individuals had admixed genomes. Our data could correctly detect and assign pure adults and F1 hybrids with > 0.90 probability, and correct assignment of F2s was also high in some cases. NewHybrids models revealed that 89.8% (n = 59) of the S. compressus samples were F1 hybrids between either S. perrico × S. ghobban or S. perrico × S. rubroviolaceus. Similarly, the most recently diverged S. ghobban and S. rubroviolaceus were hybridizing in small numbers, with half of the admixed individuals assigned to F1 hybrids and the remainder likely > F1 hybrids. We observed strong mito-nuclear discordance in all hybrid pairs. Migrate models favored gene flow between S. perrico and S. ghobban, but not other species pairs.

Conclusions: Mating between divergent species is giving rise to a region-wide, multispecies hybrid complex, characterized by a high frequency of parental and F1 genotypes but a low frequency of > F1 hybrids. Trimodal structure, and evidence for fertility of both male and female F1 hybrids, suggest that fitness declines sharply in later generation hybrids. In contrast, the hybrid population of the two more recently diverged species had similar frequencies of F1 and > F1 hybrids, suggesting accelerating post-mating incompatibility with time. Mitochondrial genotypes in hybrids suggest that indiscriminate mating by male S. perrico is driving pre-zygotic breakdown, which may reflect isolation of this endemic species for millions of years resulting in weak selection for conspecific mate recognition. Despite overlapping habitat use and high rates of hybridization, species boundaries are maintained by a combination of pre- and post-mating processes in this complex.
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http://dx.doi.org/10.1186/s12862-020-01731-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853319PMC
January 2021

Erratum to "Cardiovascular Considerations for the Internist and Hospitalist in the COVID-19 Era" American Journal of Medicine, 133(11); 1254-1261.

Am J Med 2021 Jan 9. Epub 2021 Jan 9.

Division of Cardiovascular Medicine, UF Health, University of Florida, Gainesville.

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http://dx.doi.org/10.1016/j.amjmed.2021.01.001DOI Listing
January 2021

Rapid and high seroprotection rates achieved with a tri-antigenic Hepatitis B vaccine in healthy young adults: Results from a Phase IV study.

Vaccine 2021 Feb 13;39(8):1328-1332. Epub 2021 Jan 13.

VBI Vaccines Inc., Cambridge, MA, United States. Electronic address:

Background: Sci-B-Vac® is a tri-antigenic recombinant Hepatitis B vaccine (TAV) containing the small (s), medium (pre-S2) and large (pre-S1) hepatitis B surface (HBs) antigens. To comply with vaccine licensure, a new reference standard batch was qualified by characterizing the seroprotection rate (SPR) for anti-HBs titers ≥10 mIU/mL, following vaccination.

Methods: Ninety-one healthy adults aged 20-40 years were enrolled in an open label, single-arm phase IV study receiving three IM doses of 10 μg TAV at 0, 1 and 6 months. Immunogenicity was evaluated monthly and at 7, 9 and 12 months. The primary endpoint to qualify the reference standard was an SPR ≥95% by month 7. Secondary endpoints were proportion of high responders (anti-HBs titers ≥100 mIU/mL) and geometric mean concentrations (GMC) of HBs antibodies each month. Participants were followed for safety to month 12.

Results: The primary endpoint was met 2 months after the second dose at month 3 [SPR 98.8%; 95% CI: 93.7%, 99.7%]. Proportion of high responders at months 3 and 7 were 81.4% and 97.6%, respectively. GMC at months 3 and 7 were 413.6 mIU/mL and 6799.9 mIU/mL, respectively. TAV was safe and well-tolerated.

Conclusions: The new reference standard batch of TAV was qualified successfully, demonstrating efficacy, a favorable safety profile and a rapid onset of seroprotection, including after two vaccine doses. Clinical trial registry: NCT04179786.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.050DOI Listing
February 2021

Geographic range estimates and environmental requirements for the harpy eagle derived from spatial models of current and past distribution.

Ecol Evol 2021 Jan 15;11(1):481-497. Epub 2020 Dec 15.

School of Biological and Marine Sciences University of Plymouth Plymouth UK.

Understanding species-environment relationships is key to defining the spatial structure of species distributions and develop effective conservation plans. However, for many species, this baseline information does not exist. With reliable presence data, spatial models that predict geographic ranges and identify environmental processes regulating distribution are a cost-effective and rapid method to achieve this. Yet these spatial models are lacking for many rare and threatened species, particularly in tropical regions. The harpy eagle () is a Neotropical forest raptor of conservation concern with a continental distribution across lowland tropical forests in Central and South America. Currently, the harpy eagle faces threats from habitat loss and persecution and is categorized as Near-Threatened by the International Union for the Conservation of Nature (IUCN). Within a point process modeling (PPM) framework, we use presence-only occurrences with climatic and topographical predictors to estimate current and past distributions and define environmental requirements using Ecological Niche Factor Analysis. The current PPM prediction had high calibration accuracy (Continuous Boyce Index = 0.838) and was robust to null expectations (pROC ratio = 1.407). Three predictors contributed 96% to the PPM prediction, with Climatic Moisture Index the most important (72.1%), followed by minimum temperature of the warmest month (15.6%) and Terrain Roughness Index (8.3%). Assessing distribution in environmental space confirmed the same predictors explaining distribution, along with precipitation in the wettest month. Our reclassified binary model estimated a current range size 11% smaller than the current IUCN range polygon. Paleoclimatic projections combined with the current model predicted stable climatic refugia in the central Amazon, Guyana, eastern Colombia, and Panama. We propose a data-driven geographic range to complement the current IUCN range estimate and that despite its continental distribution, this tropical forest raptor is highly specialized to specific environmental requirements.
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http://dx.doi.org/10.1002/ece3.7068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790654PMC
January 2021

Factors associated with unplanned reinterventions and their relation to early mortality after pediatric cardiac surgery.

J Thorac Cardiovasc Surg 2021 Mar 27;161(3):1155-1166.e9. Epub 2020 Nov 27.

Faculty of Health Sciences, University of Bristol, Bristol, United Kingdom; Department of Paediatric Cardiac Surgery, Bristol Royal Hospital for Children, Bristol, United Kingdom. Electronic address:

Objective: Unplanned reintervention (uRE) is used as an indicator of patient morbidity and quality of care in pediatric cardiac surgery. We investigated associated factors and early mortality after uREs.

Methods: Morbidity data were prospectively collected in 5 UK centers between 2015 and 2017; uRE included surgical cardiac, interventional transcatheter cardiac, permanent pacemaker, and diaphragm plication procedures. Mortality (30-day and 6-month) in uRE/no-uRE patients was reported before and after matching. Predicted 30-day mortality was calculated using the Partial Risk Adjustment in Surgery score.

Results: A total of 3090 procedures (2861 patients) were included (median age, 228 days). There were 146 uREs, resulting in an uRE rate of 4.7%. Partial Risk Adjustment in Surgery score, 30-day mortality and 6-month mortality in uRE and no-uRE groups were 2.4% versus 1.3%, 8.9% versus 1%, and 17.1% versus 2.4%, respectively. After matching, mortality at 6 months remained higher in uRE compared with no-uRE (12.2% vs 1.4%; P = .02; 74 pairs). In the uRE group, 21 out of 25 deaths at 6 months occurred when at least 1 additional postoperative complication was present. In multivariable analysis, neonatal age (P = .002), low weight (P = .009), univentricular heart (P < .001), and arterial shunt (P < .001) were associated with increased risk of uRE, but Partial Risk Adjustment in Surgery score was not (only in univariable analysis).

Conclusions: uREs are a relatively frequent complication after pediatric cardiac surgery and are associated with some patient characteristics, but not the Partial Risk Adjustment in Surgery risk score. Early mortality was higher after uRE, independent of preoperative factors, but linked to other postoperative complications.
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http://dx.doi.org/10.1016/j.jtcvs.2020.10.145DOI Listing
March 2021

Hydrogen atom quantum diffusion in solid parahydrogen: The H + NO → cis-HNNO → trans-HNNO reaction.

J Chem Phys 2021 Jan;154(1):014302

Department of Chemistry, University of Wyoming, Laramie, Wyoming 82071, USA.

The diffusion and reactivity of hydrogen atoms in solid parahydrogen at temperatures between 1.5 K and 4.3 K are investigated by high-resolution infrared spectroscopy. Hydrogen atoms are produced within solid parahydrogen as the by-products of the 193 nm in situ photolysis of NO, which induces a two-step tunneling reaction, H + NO → cis-HNNO → trans-HNNO. The second-order rate constant for the first step to form cis-HNNO is found to be inversely proportional to the NO concentration after photolysis, indicating that the hydrogen atoms move through solid parahydrogen via quantum diffusion. This reaction only readily occurs at temperatures below 2.8 K, not due to an increased rate constant for the first reaction step at low temperatures but rather due to an increased selectivity to the reaction. The rate constant for the second step of the reaction mechanism involving unimolecular isomerization is shown to be independent of the NO concentration as expected. The inverse concentration dependence of the rate constant for the reaction step that involves the hydrogen atom demonstrates clearly that quantum diffusion influences the reactivity of the hydrogen atoms in solid parahydrogen, which does not have an analogy in classical reaction kinetics.
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http://dx.doi.org/10.1063/5.0028853DOI Listing
January 2021

A structural basis for lithium and substrate binding of an inositide phosphatase.

J Biol Chem 2020 Nov 24;296:100059. Epub 2020 Nov 24.

Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, USA. Electronic address:

Inositol polyphosphate 1-phosphatase (INPP1) is a prototype member of metal-dependent/lithium-inhibited phosphomonoesterase protein family defined by a conserved three-dimensional core structure. Enzymes within this family function in distinct pathways including inositide signaling, gluconeogenesis, and sulfur assimilation. Using structural and biochemical studies, we report the effect of substrate and lithium on a network of metal binding sites within the catalytic center of INPP1. We find that lithium preferentially occupies a key site involved in metal-activation only when substrate or product is added. Mutation of a conserved residue that selectively coordinates the putative lithium-binding site results in a dramatic 100-fold reduction in the inhibitory constant as compared with wild-type. Furthermore, we report the INPP1/inositol 1,4-bisphosphate complex which illuminates key features of the enzyme active site. Our results provide insights into a structural basis for uncompetitive lithium inhibition and substrate recognition and define a sequence motif for metal binding within this family of regulatory phosphatases.
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http://dx.doi.org/10.1074/jbc.RA120.014057DOI Listing
November 2020

Bone and Cartilage Interfaces With Orthopedic Implants: A Literature Review.

Front Surg 2020 21;7:601244. Epub 2020 Dec 21.

Large Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN, United States.

The interface between a surgical implant and tissue consists of a complex and dynamic environment characterized by mechanical and biological interactions between the implant and surrounding tissue. The implantation process leads to injury which needs to heal over time and the rapidity of this process as well as the property of restored tissue impact directly the strength of the interface. Bleeding is the first and most relevant step of the healing process because blood provides growth factors and cellular material necessary for tissue repair. Integration of the implants placed in poorly vascularized tissue such as articular cartilage is, therefore, more challenging than compared with the implants placed in well-vascularized tissues such as bone. Bleeding is followed by the establishment of a provisional matrix that is gradually transformed into the native tissue. The ultimate goal of implantation is to obtain a complete integration between the implant and tissue resulting in long-term stability. The stability of the implant has been defined as primary (mechanical) and secondary (biological integration) stability. Successful integration of an implant within the tissue depends on both stabilities and is vital for short- and long-term surgical outcomes. Advances in research aim to improve implant integration resulting in enhanced implant and tissue interface. Numerous methods have been employed to improve the process of modifying both stability types. This review provides a comprehensive discussion of current knowledge regarding implant-tissue interfaces within bone and cartilage as well as novel approaches to strengthen the implant-tissue interface. Furthermore, it gives an insight into the current state-of-art biomechanical testing of the stability of the implants. Current knowledge reveals that the design of the implants closely mimicking the native structure is more likely to become well integrated. The literature provides however several other techniques such as coating with a bioactive compound that will stimulate the integration and successful outcome for the patient.
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http://dx.doi.org/10.3389/fsurg.2020.601244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779634PMC
December 2020

Publisher Correction: Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice.

Nature 2021 Jan;589(7842):E9

Division of Biology and Biological Engineering, TianQiao and Chrissy Chen Institute for Neuroscience, California Institute of Technology, Pasadena, CA, USA.

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http://dx.doi.org/10.1038/s41586-020-03143-1DOI Listing
January 2021

A circuit logic for sexually shared and dimorphic aggressive behaviors in Drosophila.

Cell 2021 Jan 30;184(2):507-520.e16. Epub 2020 Dec 30.

Division of Biology and Biological Engineering 156-29, Tianqiao and Chrissy Chen Institute for Neuroscience, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address:

Aggression involves both sexually monomorphic and dimorphic actions. How the brain implements these two types of actions is poorly understood. We have identified three cell types that regulate aggression in Drosophila: one type is sexually shared, and the other two are sex specific. Shared common aggression-promoting (CAP) neurons mediate aggressive approach in both sexes, whereas functionally downstream dimorphic but homologous cell types, called male-specific aggression-promoting (MAP) neurons in males and fpC1 in females, control dimorphic attack. These symmetric circuits underlie the divergence of male and female aggressive behaviors, from their monomorphic appetitive/motivational to their dimorphic consummatory phases. The strength of the monomorphic → dimorphic functional connection is increased by social isolation in both sexes, suggesting that it may be a locus for isolation-dependent enhancement of aggression. Together, these findings reveal a circuit logic for the neural control of behaviors that include both sexually monomorphic and dimorphic actions, which may generalize to other organisms.
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http://dx.doi.org/10.1016/j.cell.2020.11.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856078PMC
January 2021

Global brain network dynamics predict therapeutic responsiveness to cannabidiol treatment for refractory epilepsy.

Brain Commun 2020 31;2(2):fcaa140. Epub 2020 Aug 31.

Department of Neurological Sciences, University of Nebraska Medical Center, Boys Town, NE 68010, USA.

Refractory epilepsy is a chronic brain network disorder characterized by unresponsiveness to multiple (>2) anti-epileptic drugs. Cannabidiol, a non-psychotropic neuroactive substance, is an emerging anti-epileptic treatment that was recently approved by the US Food and Drug Administration for the treatment of refractory epilepsy, especially Lennox Gastaut syndrome and Dravet syndrome. Here, we evaluated associations between global brain network dynamics and related changes and responsiveness to cannabidiol therapy using a combination of electroencephalography phase coherence and graph theoretical analyses. Refractory epilepsy patients with Lennox Gastaut syndrome or Dravet syndrome underwent serial electroencephalography testing prior to and during cannabidiol treatment. Patients showing greater than 70% seizure frequency reduction were classified as treatment responders for the purposes of this study. We calculated inter-electrode electroencephalography phase coherence in delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (13-30 Hz) frequency bands. Graph theoretical analysis of brain network dynamics was extracted from phase coherence to evaluate measures of network integration (i.e. characteristic path length, global efficiency and degree) and segregation (i.e. modularity and transitivity). We found that responders, relative to non-responders, showed increased network integration-as indexed by relatively higher global efficiency and lower degree-and increased network segregation-as indexed by relatively higher modularity-exclusively in the beta-frequency band. We also found that larger cannabidiol dosages were associated with increased network integration-as indexed by higher global efficiency with increasing dose-and increased network segregation-as indexed by lower transitivity with increasing dose-in the delta, theta and alpha frequency bands. In summary, we demonstrate novel effects of cannabidiol on brain network dynamics with important implications for the treatment of refractory epilepsy and, possibly, across broader research applications in the future.
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http://dx.doi.org/10.1093/braincomms/fcaa140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751013PMC
August 2020

Behavioral Health Care Quality Among Marketplace Insurers in 2019.

Psychiatr Serv 2021 Feb 18;72(2):200-203. Epub 2020 Dec 18.

Division of Health Policy and Management, University of Minnesota, Minneapolis (Abraham); Department of Health Policy and Management, University of Pittsburgh, Pittsburgh (Cai, Drake); Duke University Margolis Center for Health Policy, Durham, North Carolina (Anderson).

Objective: Using 2019 Centers for Medicare and Medicaid Services data, the authors analyzed performance on behavioral health care quality measures among 168 marketplace insurers offering 185 products and investigated whether performance differed by insurer attributes.

Methods: The authors considered four quality measures: antidepressant medication management, follow-up care for children prescribed attention-deficit hyperactivity disorder medication, follow-up care within 7 days after hospitalization for mental illness, and initiation and engagement of alcohol and other drug dependence treatment. Multivariate regression was used to determine whether performance varied by insurers' nonprofit ownership, Blue Cross-Blue Shield affiliation, Medicaid-managed care participation, and preferred provider organization status.

Results: Performance levels were highest for management with antidepressant medication and lowest for initiation and engagement of drug dependence treatment. Systematic differ-ences were observed by ownership status and Medicaid-managed care plan status.

Conclusions: Increasing the transparency of health plan quality information is important for aiding enrollee decision making and encouraging quality improvement among providers and insurers.
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http://dx.doi.org/10.1176/appi.ps.202000115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855409PMC
February 2021

Matrix Drug Screen Identifies Synergistic Drug Combinations to Augment SMAC Mimetic Activity in Ovarian Cancer.

Cancers (Basel) 2020 Dec 15;12(12). Epub 2020 Dec 15.

Women's Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Inhibitor of apoptosis (IAP) proteins are frequently upregulated in ovarian cancer, resulting in the evasion of apoptosis and enhanced cellular survival. Birinapant, a synthetic second mitochondrial activator of caspases (SMAC) mimetic, suppresses the functions of IAP proteins in order to enhance apoptotic pathways and facilitate tumor death. Despite on-target activity, however, pre-clinical trials of single-agent birinapant have exhibited minimal activity in the recurrent ovarian cancer setting. To augment the therapeutic potential of birinapant, we utilized a high-throughput screening matrix to identify synergistic drug combinations. Of those combinations identified, birinapant plus docetaxel was selected for further evaluation, given its remarkable synergy both in vitro and in vivo. We showed that this synergy results from multiple convergent pathways to include increased caspase activation, docetaxel-mediated TNF-α upregulation, alternative NF-kB signaling, and birinapant-induced microtubule stabilization. These findings provide a rationale for the integration of birinapant and docetaxel in a phase 2 clinical trial for recurrent ovarian cancer where treatment options are often limited and minimally effective.
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http://dx.doi.org/10.3390/cancers12123784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765376PMC
December 2020

Are Patient Outcomes Affected by the Presence of a Fellow or Resident in Lumbar Decompression Surgery?

Spine (Phila Pa 1976) 2021 Jan;46(1):35-40

Department of Orthopaedic Surgery, Rothman Institute, Thomas Jefferson University, Philadelphia, PA.

Study Design: Retrospective cohort study.

Objective: The aim of this study was to determine whether the presence of a fellow or resident (F/R) compared to a physician assistant (PA) affected surgical variables or short-term patient outcomes.

Summary Of Background Data: Although orthopedic spine fellows and residents must participate in minimum number of decompression surgeries to gain competency, the impact of trainee presence on patient outcomes has not been assessed.

Methods: One hundred and seventy-one patients that underwent a one- to three-level lumbar spine decompression procedure at a high-volume academic center were retrospectively identified. Operative reports from all cases were examined and patients were placed into one of two groups based on whether the first assist was a F/R or a PA. Univariate analysis was used to compare differences in total surgery duration, 30-day and 90-day readmissions, infection and revision rates, patient-reported outcome measures (Short Form-12 Physical Component Score and Mental Component Score, Oswestry Disability Index, Visual Analog Scale [VAS] Back, VAS Leg) between groups. Multiple linear regression was used to assess change in each patient reported outcome and multiple binary logistic regression was used to determine significant predictors of revision, infection, and 30- or 90-day readmission.

Results: Seventy-eight patients were included in the F/R group compared to 93 patients in the PA group. There were no differences between groups for total surgery time, 30-day or 90-day readmissions, infection, or revision rates. Using univariate analysis, there were no differences between the two groups pre- or postoperatively (P > 0.05). Using multivariate analysis, presence of a surgical trainee did not significantly influence any patient reported outcome and did not affect infection, revision, or 30- and 90-day readmission rates.

Conclusion: This is one of the first studies to show that the presence of an orthopedic spine fellow or resident does not affect patient short-term outcomes in lumbar decompression surgery.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003721DOI Listing
January 2021

Prospective or retrospective ACO attribution matters for seriously ill patients.

Am J Manag Care 2020 12;26(12):534-540

Margolis Center for Health Policy, Duke University, 230 Science Dr, Durham, NC 27705. Email:

Objectives: Since 2019, the Medicare Shared Savings Program (MSSP) has allowed accountable care organizations (ACOs) to choose either retrospectively or prospectively attributed ACO populations. To understand how ACOs' choice of attribution method affects incentives for care among seriously ill Medicare beneficiaries, this study compares beneficiary characteristics and Medicare per capita expenditures between prospective and retrospective ACO populations.

Study Design: This retrospective, cross-sectional analysis describes survival, patient characteristics, and Medicare spending for Medicare fee-for-service beneficiaries identified with serious illness (n = 1,600,629) using 100% Medicare Master Beneficiary Summary and MSSP beneficiary files (2014-2016).

Methods: We used generalized linear models with ACO and year fixed effects to estimate the average within-ACO difference between potential retrospective and prospective ACO populations.

Results: Dying in the first 90 days of the performance year was associated with reduced odds of retrospective ACO attribution (odds ratio [OR], 0.24; 95% CI, 0.24-0.25) relative to beneficiaries surviving 270 days or longer. Similarly, hospice use was associated with reduced odds of retrospective assignment (OR, 0.80; 95% CI, 0.79-0.80). Among ACOs that did not achieve shared savings, average per capita Medicare expenditures (after truncation) were $2459 (95% CI, $2192-$2725) higher for prospective vs retrospective ACO populations. The difference was $834 (95% CI, $402-$1266) greater per capita among ACOs that achieved shared savings.

Conclusions: The difference in survival and spending for ACO populations captured by prospective vs retrospective attribution methods means that ACOs may need to employ different care management strategies to improve performance depending on their attribution method.
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http://dx.doi.org/10.37765/ajmc.2020.88541DOI Listing
December 2020

Melioidosis of the central nervous system; A potentially lethal impersonator.

IDCases 2021 19;23:e01015. Epub 2020 Nov 19.

Department of Medicine, Cairns Hospital, Cairns, Queensland, Australia.

A 57-year-old Australian woman, with a history of hazardous alcohol consumption, presented with a seizure following 2 days of fever and headache. Initial imaging suggested the presence of an isolated brain abscess, however, a thorough physical examination, identified no additional septic focus. Five sets of blood cultures were sterile and serology for was negative. Other investigations including computed tomography of her chest, abdomen and pelvis and a trans-esophageal echocardiogram were normal. Despite the administration of intravenous vancomycin, ceftriaxone, and metronidazole, her condition deteriorated. At emergency craniotomy, the abscess was drained and was cultured, confirming a diagnosis of melioidosis. She received 8 weeks of intravenous meropenem, combined with oral trimethoprim/sulfamethoxazole; the trimethoprim/sulfamethoxazole was continued for a total of 12 months. She recovered completely and was able to return to full-time work. Melioidosis, is endemic to Australia and South East Asia and, globally, is estimated to kill 89,000 every year. It can affect almost any organ, but up to 5% have central nervous system (CNS) involvement, where it may present as an encephalomyelitis, brain abscess or meningitis. is resistant to many commonly used antibiotics and even in well-resourced settings the case-fatality rate of CNS infection may rise to 50 %. This patient lived in a melioid-endemic region, and, with hazardous alcohol consumption, had a classical risk factor for the disease, but the sterile blood cultures and negative serology delayed definitive therapy. Despite the delayed diagnosis, definitive drainage and prolonged anti-bacterial therapy ensured a complete recovery.
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http://dx.doi.org/10.1016/j.idcr.2020.e01015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708931PMC
November 2020

Small Vessel Disease: Perpetrator or Predictor of Stroke in Patients With Atrial Fibrillation?

Stroke 2021 Jan 7;52(1):100-102. Epub 2020 Dec 7.

Department of Neurology, University of Minnesota, Minneapolis (D.C.A.).

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http://dx.doi.org/10.1161/STROKEAHA.120.032536DOI Listing
January 2021

Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice.

Nature 2021 01 2;589(7841):258-263. Epub 2020 Dec 2.

Division of Biology and Biological Engineering, TianQiao and Chrissy Chen Institute for Neuroscience, California Institute of Technology, Pasadena, CA, USA.

Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural circuits is not understood. For example, males of many species can exhibit mounting behaviour towards same- or opposite-sex conspecifics, but it is unclear whether the intent and neural encoding of these behaviours are similar or different. Here we show that female- and male-directed mounting in male laboratory mice are distinguishable by the presence or absence of ultrasonic vocalizations (USVs), respectively. These and additional behavioural data suggest that most male-directed mounting is aggressive, although in rare cases it can be sexual. We investigated whether USV and USV mounting use the same or distinct hypothalamic neural substrates. Micro-endoscopic imaging of neurons positive for oestrogen receptor 1 (ESR1) in either the medial preoptic area (MPOA) or the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) revealed distinct patterns of neuronal activity during USV and USV mounting, and the type of mounting could be decoded from population activity in either region. Intersectional optogenetic stimulation of MPOA neurons that express ESR1 and vesicular GABA transporter (VGAT) (MPOA neurons) robustly promoted USV mounting, and converted male-directed attack to mounting with USVs. By contrast, stimulation of VMHvl neurons that express ESR1 (VMHvl neurons) promoted USV mounting, and inhibited the USVs evoked by female urine. Terminal stimulation experiments suggest that these complementary inhibitory effects are mediated by reciprocal projections between the MPOA and VMHvl. Together, these data identify a hypothalamic subpopulation that is genetically enriched for neurons that causally induce a male reproductive behavioural state, and indicate that reproductive and aggressive states are represented by distinct population codes distributed between MPOA and VMHvl neurons, respectively. Thus, similar behaviours that express different internal states are encoded by distinct hypothalamic neuronal populations.
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http://dx.doi.org/10.1038/s41586-020-2995-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899581PMC
January 2021

Development and Assessment of a Rapidly Collapsible Anastomotic Guide for Use in Anastomosis of the Small Intestine: A Pilot Study Using a Swine Model.

Front Surg 2020 11;7:587951. Epub 2020 Nov 11.

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, United States.

Various conditions in human and veterinary medicine require intestinal resection and anastomosis, and complications from these procedures are frequent. A rapidly collapsible anastomotic guide was developed for small intestinal end-to-end anastomosis and was investigated in order to assess its utility to improve the anastomotic process and to potentially reduce complication rates. A complex manufacturing method for building a polymeric device was established utilizing biocompatible and biodegradable polyvinylpyrrolidone and polyurethane. This combination of polymers would result in rapid collapse of the material. The guide was designed as a hollow cylinder composed of overlaying shingles that separate following exposure to moisture. An study was performed using commercial pigs, with each pig receiving one standard handsewn anastomosis and one guide-facilitated anastomosis. Pigs were sacrificed after 13 days, at which time burst pressure, maximum luminal diameter, and presence of adhesions were assessed. Burst pressures were not statistically different between treatment groups, but anastomoses performed with the guide withstood 10% greater luminal burst pressure and maintained 17% larger luminal diameter than those performed using the standard handsewn technique alone. Surgeons commented that the addition of a guide eased the performance of the anastomosis. Hence, a rapidly collapsible anastomotic guide may be beneficial to the performance of intestinal anastomosis.
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http://dx.doi.org/10.3389/fsurg.2020.587951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686753PMC
November 2020

What do patients with glaucoma see: a novel iPad app to improve glaucoma patient awareness of visual field loss.

Br J Ophthalmol 2020 Nov 20. Epub 2020 Nov 20.

Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA

Purpose: Glaucoma patients with peripheral vision loss have in the past subjectively described their field loss as 'blurred' or 'no vision compromise'. We developed an iPad app for patients to self-characterise perception within areas of glaucomatous visual field loss.

Methods: Twelve glaucoma patients with visual acuity ≥20/40 in each eye, stable and reliable Humphrey Visual Field (HVF) over 2 years were enrolled. An iPad app (held at 33 cm) allowed subjects to modify 'blur' or 'dimness' to match their perception of a 2×2 m wall-mounted poster at 1 m distance. Subjects fixated at the centre of the poster (spanning 45° of field from centre). The output was degree of blur/dim: normal, mild and severe noted on the iPad image at the 54 retinal loci tested by the HVF 24-2 and was compared to threshold sensitivity values at these loci. Monocular (Right eye (OD), left eye (OS)) HVF responses were used to calculate an integrated binocular (OU) visual field index (VFI). All three data sets were analysed separately.

Results: 36 HVF and iPad responses from 12 subjects (mean age 71±8.2y) were analysed. The mean VFI was 77% OD, 76% OS, 83% OU. The most common iPad response reported was normal followed by blur. No subject reported dim response. The mean HVF sensitivity threshold was significantly associated with the iPad response at the corresponding retinal loci (For OD, OS and OU, respectively (dB): normal: 23, 25, 27; mild blur: 18, 16, 22; severe blur: 9, 9, 11). On receiver operative characteristic (ROC) curve analysis, the HVF retinal sensitivity cut-off at which subjects reported blur was 23.4 OD, 23 OS and 23.3 OU (dB).

Conclusions: Glaucoma subjects self-pictorialised their field defects as blur; never dim or black. Our innovation allows translation of HVF data to quantitatively characterise visual perception in patients with glaucomatous field defects.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317034DOI Listing
November 2020

Vitamin D deficiency and COVID-19.

Clin Med (Lond) 2020 11;20(6):e282-e283

East Lancashire Hospitals NHS Trust, UK.

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http://dx.doi.org/10.7861/clinmed.Let.20.6.9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687343PMC
November 2020

How do C2 tilt and C2 slope correlate with patient reported outcomes in patients after anterior cervical discectomy and fusion?

Spine J 2020 Nov 13. Epub 2020 Nov 13.

Department of Orthopaedic Surgery, Rothman Institute, Thomas Jefferson University, 925 Chestnut St, 5th Floor, Philadelphia, PA 19107, USA.

Background/context: C2 tilt and C2 slope are quick and easy measurements to obtain on lateral radiographs and may be used to determine overall cervical sagittal alignment; however, the influence of these measurements on patient outcomes has not been well established in literature.

Purpose: To determine if C2 tilt and/or C2 slope predict patient outcomes better compared with conventional radiographic measures after an anterior cervical discectomy and fusion (ACDF).

Study Design/setting: Retrospective cohort study.

Patient Sample: A total of 249 patients who underwent 1 to 3 level ACDF to address radiculopathy and/or myelopathy at a single academic institution between 2011 and 2015 were identified. Patients with less than 1 year of follow-up were excluded.

Outcome Measures: Patient Reported Outcomes: Neck Disability Index (NDI), Physical Component Score-12 (PCS-12), and Mental Component Score (MCS-12), Visual Analog Score (VAS) Neck and Arm scores Cervical radiographic measurements: C2 tilt, C2 slope, C2-C7 lordosis, cervical SVA, T1 slope, T1 slope minus cervical lordosis (TS-CL), and C2-C7 ROM METHODS: Pearson correlation tests were performed to assess for significant associations between radiographic measurements and patient outcomes. Multiple linear regression models were developed adjusting for demographics and radiographic parameters to determine which factors were predictive of patient outcomes.

Results: C2 tilt and TS-CL correlated with all postoperative physical outcome scores (NDI, PCS-12, VAS Neck and ARM; p<.05), however no association was seen between C2 slope and postoperative outcomes. After accounting for the presence of subaxial deformity, C2 tilt and TS-CL remained strongly correlated to patient outcome scores. With multiple linear regression, C2 tilt was a significant predictor for NDI, whereas TS-CL was a significant predictor for PCS-12, VAS Neck and VAS Arm.

Conclusions: C2 tilt significantly correlated with well-described conventional cervical parameters as well as postoperative physical outcomes measures, especially NDI, on multivariate analysis. C2 tilt may provide an easy and practical tool for predicting physical outcomes after ACDF.
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http://dx.doi.org/10.1016/j.spinee.2020.10.033DOI Listing
November 2020

Lower limb MSK injuries among school-aged rugby and football players: a systematic review.

BMJ Open Sport Exerc Med 2020 28;6(1):e000806. Epub 2020 Oct 28.

Institute of Nursing and Health Research, School of Health Sciences, Ulster University - Jordanstown Campus, Newtownabbey, UK.

Objective: The objective of this systematic review was to explore the incidence of lower limb musculoskeletal (MSK) injuries sustained by rugby union, rugby league, soccer, Australian Rules and Gaelic football players under 18 years. The review sought to identify the mechanisms and types of injury sustained and to compare between sports.

Design: This systematic review focused on the incidence of lower limb injury in adolescent team sports that involved running and kicking a ball. A literature search of studies published prior to January 2020 was conducted using SportDiscus, Medline and PubMed databases. The Standard Quality Assessment Criteria appraisal tool was used to assess the quality of each article included in the review. Two or more authors independently reviewed all papers.

Results: Sixteen papers met the inclusion criteria; prospective cohort (N=14), retrospective (n=1) and longitudinal (n=1). These studies investigated injuries in rugby union and rugby league (n=10), football (soccer) (n=3), Australian Rules (n=2) and Gaelic football (n=1). There were a total of 55 882 participants, aged 7-19 years old, who reported 6525 injuries. The type, site and mechanisms of injury differed across sports.

Summary: Lower limb injuries were common in adolescent rugby, soccer, Gaelic football and Australian Rules football players, however these studies may not fully reflect the true injury burden where recurrent and overuse injuries have not been considered. There were differences between sports in the mechanisms, types and severity of injury.
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http://dx.doi.org/10.1136/bmjsem-2020-000806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642221PMC
October 2020