Prenatal Ultrasonography and the Incidence of Autism Spectrum Disorder.
JAMA Pediatr. 2018 04 01;172(4):319-320
Authors: Webb SJ, Mourad PD
PMID: 29435566 [PubMed - indexed for MEDLINE]
Impact of aging on the immune response to traumatic brain injury (AIm:TBI) study protocol.
Inj Prev. 2019 Sep 03;:
Authors: Thompson HJ, Rivara F, Becker KJ, Maier R, Temkin N
Abstract
BACKGROUND: Traumatic brain injury (TBI) in older adults leads to considerable morbidity and mortality. Outcomes among older adults with TBI are disparately worse than in younger adults. Differences in immunological response to injury may account for at least some of this disparity. Understanding how ageing differentially affects the immune response to TBI and how older age and these immunological changes affect the natural history of recovery following TBI are the goals of this study.
DESIGN/METHODS: A prospective multiple cohort design is being used to assess the effects of ageing and TBI on immune makers and to test predictors of impairment and disability in older adults following mild TBI. Older adults (>55 years) with mild TBI are enrolled with three comparison groups: younger adults (21-54 years) with mild TBI, non-injured older adults (>55 years) and non-injured young adults (21-54 years). For the primary analysis, we will assess the association between immune markers and Glasgow Outcome Scale-Extended at 6 months, using logistic regression. Predictors of interest will be inflammatory biomarkers. Multivariate linear regression will be used to evaluate associations between biomarkers and other outcomes (symptoms, function and quality of life) at 3 and 6 months. Exploratory analyses will investigate the utility of biomarkers to predict outcome using receiver-operating characteristic curves.
DISCUSSION: A better understanding of the recovery trajectory and biological rationale for disparate outcomes following TBI in older adults could allow for development of specific interventions aimed at reducing or eliminating symptoms. Such interventions could reduce impairment and healthcare costs.
PMID: 31481600 [PubMed - as supplied by publisher]
Targeted Embolization of Aneurysms Associated With Brain Arteriovenous Malformations at High Risk for Surgical Resection: A Case-Control Study.
Neurosurgery. 2018 03 01;82(3):343-349
Authors: Alexander MD, Hippe DS, Cooke DL, Hallam DK, Hetts SW, Kim H, Lawton MT, Sekhar LN, Kim LJ, Ghodke BV
Abstract
BACKGROUND: High-risk components of brain arteriovenous malformations (BAVMs) can be targeted to reduce the risk of lesion rupture.
OBJECTIVE: To evaluate targeted embolization of aneurysms against other means of treatment with a case-control analysis; we previously investigated this approach associated with BAVMs.
METHODS: Retrospective analysis of patients with BAVMs was performed, identifying patients treated with intention to occlude only an aneurysm associated with a BAVM. For each targeted aneurysm embolization (TAE) patient identified, 4 control patients were randomly selected, controlling for rupture status, age, and Spetzler-Martin plus Lawton-Young supplemental score. Analysis was performed to compare rates of adverse events (hemorrhage, new seizure, and death) between the 2 groups.
RESULTS: Thirty-two patients met inclusion criteria, and 128 control patients were identified, out of 1103 patients treated during the study period. Thirty-four adverse events occurred (15 ruptures, 15 new seizures, and 11 deaths) during the follow-up period (mean 1157 d for the TAE cohort and 1036 d for the non-TAE cohort). Statistically lower associations were noted for the TAE group for any adverse event (hazard ratio 0.28, P = .037) and the composite outcome of hemorrhage or new seizure (hazard ratio 0.20, P = .029).
CONCLUSION: For BAVMs at high risk for surgical resection, TAE can be performed safely and effectively. Patients treated with TAE had better outcomes than matched patients undergoing other combinations of treatment. TAE can be considered for BAVMs with high operative risk prior to radiosurgery or when no other treatment options are available.
PMID: 28419337 [PubMed - indexed for MEDLINE]
Functional Status Examination in Patients with Moderate-to-Severe Traumatic Brain Injuries.
J Neurotrauma. 2018 05 15;35(10):1132-1137
Authors: Machamer J, Temkin NR, Manley GT, Dikmen S
Abstract
The assessment of functional status after traumatic brain injury (TBI) is important. The Glasgow Outcome Scale (GOS) and its revised version, the Glasgow Outcome Scale Extended (GOSE), have been used most frequently in TBI research, but there are concerns about the sensitivity of these measures. The current study evaluated the psychometric properties of the Functional Status Examination (FSE) using a sample of 448 moderately to severely injured subjects with TBI. It was shown that the FSE is significantly related to other measures of functional status including the GOSE, Short Form Health Survey, and European Quality of Life Checklist (p < 0.001), is sensitive to TBI severity (p < 0.001), and is responsive to recovery from 3 to 6 months post-injury (p < 0.001). In addition, there was a significant agreement (r = 0.817, p < 0.001) between the patient and significant other's assessment of functional status on the FSE at 6 months post-injury. The FSE may be a valuable measure of functional status after TBI given its strong psychometric properties, including validity, sensitivity to brain injury severity, and recovery over time.
PMID: 29415608 [PubMed - indexed for MEDLINE]
YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis.
Nat Commun. 2019 09 02;10(1):3914
Authors: Pajtler KW, Wei Y, Okonechnikov K, Silva PBG, Vouri M, Zhang L, Brabetz S, Sieber L, Gulley M, Mauermann M, Wedig T, Mack N, Imamura Kawasawa Y, Sharma T, Zuckermann M, Andreiuolo F, Holland E, Maass K, Körkel-Qu H, Liu HK, Sahm F, Capper D, Bunt J, Richards LJ, Jones DTW, Korshunov A, Chavez L, Lichter P, Hoshino M, Pfister SM, Kool M, Li W, Kawauchi D
Abstract
YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses of human YAP1-MAMLD1-positive ependymoma reveal enrichment of NFI and TEAD transcription factor binding site motifs in YAP1-bound regulatory elements, suggesting a role for these transcription factors in YAP1-MAMLD1-driven tumorigenesis. Mutation of the TEAD binding site in the YAP1 fusion or repression of NFI targets prevents tumor induction in mice. Together, these results demonstrate that the YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating a rationale for preclinical studies to block the interaction between YAP1 fusions and NFI and TEAD transcription factors.
PMID: 31477715 [PubMed - indexed for MEDLINE]
Understanding and Remediating Lapses in Professionalism: Lessons From the Island of Last Resort.
Ann Thorac Surg. 2020 02;109(2):317-324
Authors: Williams BW, Williams MV
Abstract
BACKGROUND: The literature on unprofessional behavior is reviewed. It is well accepted that unprofessional behavior, including a lack of civility and respect, can have a negative impact on patient safety and quality of care.
METHODS: We used a focused review in the context of 20 years of experience of assessing, treating, and remediating unprofessional behavior. The review highlights that unprofessional behavior can stem from a variety of sources, including health, psychological/psychiatric issues, social functioning or support, or a combination of these. The review covers the challenges in the work environment and the relationship between outcome, as experienced by the physician, and the likelihood the physician will repeat or modify his or her behavior.
RESULTS: Based on the evidence provided in the review and our clinical and research experience, we offer a new framework for the assessment, treatment, and remediation of physicians with professionalism transgressions: the Environmentally Valid Learning Approach. The approach is related to and expands on Miller's Pyramid by adding bio-psycho-social functioning and professional identity to the Pyramid. It emphasizes the dynamic and environmental characteristics of professional identity.
CONCLUSIONS: Effective intervention is possible. Consideration of contributory factors, addressing/treating those factors, teaching/remediating skill deficiencies, and determining elements that need to be in place to foster implementation and maintenance of the developing skills are necessary components for successful resolution. The behavior is fully remediated when a self-sustaining alternative to the unprofessional behavior is established and the desired behavior becomes a permanent part of the physician's behavioral repertoire.
PMID: 31479640 [PubMed - indexed for MEDLINE]
A Good Practice-Compliant Clinical Trial Imaging Management System for Multicenter Clinical Trials: Development and Validation Study.
JMIR Med Inform. 2019 Aug 30;7(3):e14310
Authors: Shin Y, Kim KW, Lee AJ, Sung YS, Ahn S, Koo JH, Choi CG, Ko Y, Kim HS, Park SH
Abstract
BACKGROUND: With the rapid increase in utilization of imaging endpoints in multicenter clinical trials, the amount of data and workflow complexity have also increased. A Clinical Trial Imaging Management System (CTIMS) is required to comprehensively support imaging processes in clinical trials. The US Food and Drug Administration (FDA) issued a guidance protocol in 2018 for appropriate use of medical imaging in accordance with many regulations including the Good Clinical Practice (GCP) guidelines. Existing research on CTIMS, however, has mainly focused on functions and structures of systems rather than regulation and compliance.
OBJECTIVE: We aimed to develop a comprehensive CTIMS to meet the current regulatory guidelines and various required functions. We also aimed to perform computerized system validation focusing on the regulatory compliance of our CTIMS.
METHODS: Key regulatory requirements of CTIMS were extracted thorough review of many related regulations and guidelines including International Conference on Harmonization-GCP E6, FDA 21 Code of Federal Regulations parts 11 and 820, Good Automated Manufacturing Practice, and Clinical Data Interchange Standards Consortium. The system architecture was designed in accordance with these regulations by a multidisciplinary team including radiologists, engineers, clinical trial specialists, and regulatory medicine professionals. Computerized system validation of the developed CTIMS was performed internally and externally.
RESULTS: Our CTIMS (AiCRO) was developed based on a two-layer design composed of the server system and the client system, which is efficient at meeting the regulatory and functional requirements. The server system manages system security, data archive, backup, and audit trail. The client system provides various functions including deidentification, image transfer, image viewer, image quality control, and electronic record. Computerized system validation was performed internally using a V-model and externally by a global quality assurance company to demonstrate that AiCRO meets all regulatory and functional requirements.
CONCLUSIONS: We developed a Good Practice-compliant CTIMS-AiCRO system-to manage large amounts of image data and complexity of imaging management processes in clinical trials. Our CTIMS adopts and adheres to all regulatory and functional requirements and has been thoroughly validated.
PMID: 31471962 [PubMed]
Use of Dexmedetomidine for Postoperative Pain Management Following Spine Fusion Surgery in a Highly Opioid-Tolerant Patient.
J Pain Palliat Care Pharmacother. 2019 Mar - Jun;33(1-2):49-53
Authors: Wu J, Ku SC, Ko AL
Abstract
A 51-year-old man with metastatic renal cell carcinoma whose fentanyl requirement was 3000-4000 µg/h in inpatient hospice presented for a thoracic (T) vertebral 4-10 posterior spinal fusion for a lytic T7 compression fracture. He underwent total intravenous (IV) anesthesia with propofol, remifentanil, and ketamine; liposome bupivacaine was locally infiltrated at the end of the case. Following extubation on postoperative day (POD) 1, he had severe pain refractory to high-dose IV fentanyl patient control analgesia and ketamine infusion. His pain dramatically improved after a dexmedetomidine infusion was added and titrated to the analgesic effect. He participated in neurological examinations and fulfilled both surgical and pain management goals without side effects. Dexmedetomidine was successfully weaned off on POD 3.
PMID: 31465697 [PubMed - indexed for MEDLINE]
Integration of a Comprehensive Contraception Education Program Into Clinical Practice in a Family Planning Clinic.
Nurs Womens Health. 2019 Oct;23(5):414-423
Authors: Lee ASD, Burke AE
Abstract
OBJECTIVE: To improve rates of contraception adherence by implementing a comprehensive contraception educational program for women receiving care at a family planning clinic.
DESIGN: Quasi-experimental cohort study in which we evaluated women presenting before (control group) and after program implementation (intervention group) and compared the proportion of women returning for contraceptive method change and/or for unintended pregnancy.
SETTING: Family planning clinic of a large academic medical center.
PARTICIPANTS: English-speaking women ages 12 to 50 years who presented to the clinic for pregnancy termination or initiation of a new contraceptive method from May 2012 to May 2014.
INTERVENTION: A provider-facilitated, patient-centered educational intervention was implemented to foster patient knowledge and choice about contraception.
RESULTS: We conducted chart review to identify any clinic visit that occurred in the 12 months after the index visit. Pearson's chi-square test was used to compare results for women in both groups. The intervention group included 201 women, and the control group included 162 women. In the control group, 28% (n = 46/162) returned within the year for unintended pregnancy and/or contraceptive method change, whereas only 17% (n = 35/201) returned in the study group. This difference was statistically significant (p < .05).
CONCLUSION: Initiation of a comprehensive contraception educational program was associated with a decrease in rates of return visits for unintended pregnancy and contraceptive method changes. This implies an improvement in adherence to the initially chosen contraceptive method. Such interventions hold promise for improving contraceptive adherence and decreasing unintended pregnancy. Improving contraceptive adherence is a critical first step to decreasing unintended pregnancies.
PMID: 31465750 [PubMed - indexed for MEDLINE]
Sacroiliac Joint Dysfunction in Patients With Low Back Pain.
Fed Pract. 2019 Aug;36(8):370-375
Authors: Barros G, McGrath L, Gelfenbeyn M
Abstract
Although difficult to distinguish from similarly presenting syndromes, a detailed history, appropriate physical maneuvers, imaging, and adequate response to intra-articular anesthetic can help health care providers treat this painful condition.
PMID: 31456628 [PubMed]
Standard Free Versus Osteoplastic Craniotomy: Assessment of Complication Rates During Intracranial Electroencephalogram Electrode Placement for Seizure Localization.
World Neurosurg. 2019 Dec;132:e599-e603
Authors: Bass DI, Buckley R, Meyer RM, Lawrence B, Paschall C, Ojemann J, Ko AL
Abstract
OBJECTIVE: Patients with medically intractable epilepsy often undergo sequential surgeries and are therefore exposed to an elevated risk for infection, resulting in unanticipated returns to the operating room. The goal of our study was to determine whether use of an osteoplastic bone flap technique would reduce the infection rate in these patients.
METHODS: A single-institution, retrospective chart review of patients with medically intractable epilepsy for grid placement was performed. Univariate analyses and linear regression were used to assess primary outcomes, including infection and hematomas requiring surgical evacuation. Secondary outcomes included duration of treatment and other, unanticipated surgeries.
RESULTS: A total of 199 patients were identified, 56 (28%) with osteoplastic flaps. Standard free flaps were associated with an increased rate of infection at the craniotomy site (n = 24, 17%, vs. 0, 0%, P = 0.003), whereas osteoplastic flaps were associated with more returns to operating room for hematoma evacuation (n = 5, 9% vs. 3.2%, P = 0.024). Overall, the rate of return to operating room for unanticipated surgeries was similar, but infectious complications prolonged the duration of treatment (median: 17 days vs. 2 days, χ2 = 13.97, P < 0.001).
CONCLUSIONS: Osteoplastic bone flaps markedly decreased the risk of craniotomy infections compared with free flaps in patients undergoing sequential surgeries. This decrease is offset, however, by an increase in intracranial hematoma requiring return to the operating room. Infection appeared to be a more significant complication as it was associated with increased duration of treatment. The osteoplastic technique is especially appealing in those patients likely to undergo multiple surgeries in short succession.
PMID: 31442661 [PubMed - indexed for MEDLINE]
Conserved cell types with divergent features in human versus mouse cortex.
Nature. 2019 09;573(7772):61-68
Authors: Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT, Close JL, Long B, Johansen N, Penn O, Yao Z, Eggermont J, Höllt T, Levi BP, Shehata SI, Aevermann B, Beller A, Bertagnolli D, Brouner K, Casper T, Cobbs C, Dalley R, Dee N, Ding SL, Ellenbogen RG, Fong O, Garren E, Goldy J, Gwinn RP, Hirschstein D, Keene CD, Keshk M, Ko AL, Lathia K, Mahfouz A, Maltzer Z, McGraw M, Nguyen TN, Nyhus J, Ojemann JG, Oldre A, Parry S, Reynolds S, Rimorin C, Shapovalova NV, Somasundaram S, Szafer A, Thomsen ER, Tieu M, Quon G, Scheuermann RH, Yuste R, Sunkin SM, Lelieveldt B, Feng D, Ng L, Bernard A, Hawrylycz M, Phillips JW, Tasic B, Zeng H, Jones AR, Koch C, Lein ES
Abstract
Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.
PMID: 31435019 [PubMed - indexed for MEDLINE]
The feasibility and acceptability of using virtual world technology for interprofessional education in palliative care: a mixed methods study.
J Interprof Care. 2019 Aug 21;:1-11
Authors: Lee AL, DeBest M, Koeniger-Donohue R, Strowman SR, Mitchell SE
Abstract
The objective of this mixed methods study was to evaluate the feasibility and acceptability of using a virtual world educational environment for interprofessional health professions students learning about palliative care. Graduate students (n = 35) from five different health professions programs (medicine, nursing, nutrition, physical therapy, and social work) across two educational institutions participated in a small-group immersive educational experience focused on palliative care in the virtual world of Second Life. Collected data included pre and post surveys of interprofessional attitudes using previously-published questionnaires as well as student reflective writing and photographs about their experience. We found it was feasible to create and deliver an interprofessional educational experience in palliative care in a virtual world environment. The educational experience was acceptable to participants, with an improvement in attitudes toward interprofessional education and interprofessional teamwork after a single virtual world educational session, based on both quantitative and qualitative results. Students found the virtual world environment acceptable for interprofessional education focused on palliative care, based on qualitative results. As health professions schools develop interprofessional education curricula, the use of virtual world technology may be an important modality to consider, to effectively and conveniently bring interprofessional learners together.
PMID: 31431115 [PubMed - as supplied by publisher]
Effect of a Care Management Intervention on 12-Month Drinking Outcomes Among Patients With and Without DSM-IV Alcohol Dependence at Baseline.
J Gen Intern Med. 2019 Aug 20;:
Authors: Williams EC, Bobb JF, Lee AK, Ludman EJ, Richards JE, Hawkins EJ, Merrill JO, Saxon AJ, Lapham GT, Matson TE, Chavez LJ, Caldeiro R, Greenberg DM, Kivlahan DR, Bradley KA
Abstract
BACKGROUND: The CHOICE care management intervention did not improve drinking relative to usual care (UC) for patients with frequent heavy drinking at high risk of alcohol use disorders. Patients with alcohol dependence were hypothesized to benefit most. We conducted preplanned secondary analyses to test whether the CHOICE intervention improved drinking relative to UC among patients with and without baseline DSM-IV alcohol dependence.
METHODS: A total of 304 patients reporting frequent heavy drinking from 3 VA primary care clinics were randomized (stratified by DSM-IV alcohol dependence, sex, and site) to UC or the patient-centered, nurse-delivered, 12-month CHOICE care management intervention. Primary outcomes included percent heavy drinking days (%HDD) using 28-day timeline follow-back and a "good drinking outcome" (GDO)-abstaining or drinking below recommended limits and no alcohol-related symptoms on the Short Inventory of Problems at 12 months. Generalized estimating equations binomial regression models (clustered on provider) with interaction terms between dependence and intervention group were fit.
RESULTS: At baseline, 59% of intervention and UC patients had DSM-IV alcohol dependence. Mean drinking outcomes improved for all subgroups. For participants with dependence, 12-month outcomes did not differ for intervention versus UC patients (%HDD 37% versus 38%, p = 0.76 and GDO 16% versus 16%, p = 0.77). For participants without dependence, %HDD did not differ between intervention (41%) and UC (31%) patients (p = 0.12), but the proportion with GDO was significantly higher among UC participants (26% versus 13%, p = 0.046). Neither outcome was significantly modified by dependence (interaction p values 0.19 for %HDD and 0.10 for GDO).
CONCLUSIONS: Among participants with frequent heavy drinking, care management had no benefit relative to UC for patients with dependence, but UC may have had benefits for those without dependence.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01400581 .
PMID: 31432438 [PubMed - as supplied by publisher]
Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men in China: a study protocol for a three-arm cluster randomized controlled trial.
Infect Dis Poverty. 2019 Aug 16;8(1):76
Authors: Zhang TP, Yang F, Tang W, Alexander M, Forastiere L, Kumar N, Li K, Zou F, Yang L, Mi G, Wang Y, Huang W, Lee A, Zhu W, Vickerman P, Wu D, Yang B, Christakis NA, Tucker JD
Abstract
BACKGROUND: Gonorrhea and chlamydia testing rates are poor among Chinese men who have sex with men (MSM). A quasi-experimental study suggested that a pay-it-forward strategy increased dual gonorrhea/chlamydia testing among MSM. Pay-it-forward offers an individual a gift (e.g., a free test) and then asks the same person if they would like to give a gift to another person. This article reports the protocol of a randomized controlled trial to evaluate dual gonorrhea/chlamydia test uptake and other outcomes among MSM in three arms - a pay-it-forward arm, a pay-what-you-want arm, and a standard of care arm.
METHODS: Three hundred MSM will be recruited at three HIV testing sites in Guangzhou and Beijing. Testing sites include two hospital-based MSM sexually transmitted diseases clinics and one MSM community-based organization. Eligible participants will be born biologically male, aged 16 years or older, reporting previous anal sex with another man, having never participated in the pay-it-forward program, without previous gonorrhea and chlamydia testing in the past 12 months, and residing in China. Following a cluster randomized design, every cluster of ten participants will be randomly allocated into one of three arms: (1) a pay-it-forward arm in which men are offered free gonorrhea and chlamydia testing and then asked whether they would like to donate ("pay it forward") toward testing for future testers; (2) a pay-what-you-want arm in which men are offered free testing and told to decide how much to pay after receiving the test; (3) a standard of care arm in which men can pay the full price for dual gonorrhoea and chlamydia testing. The primary outcome is dual gonorrhoea/chlamydia testing as verified by administrative records. Secondary outcomes include incremental cost per test, incremental cost per diagnosis, community connectedness, and social cohesion. Primary outcome will be calculated for each arm using intention-to-treat and compared using one-sided 95% confidence intervals with a margin of 20% increase defined as superiority.
DISCUSSION: This study will examine the pay-it-forward strategy in comparison to the standard of care in improving test uptake for gonorrhea and chlamydia. We will leverage the cluster randomized controlled trial to provide scientific evidence on the potential effect of pay-it-forward. Findings from this study will shed light on novel intervention methods for increasing preventive health service utilization and innovate ways to finance it among communities.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741725 . Registered on 12 November 2018.
PMID: 31426869 [PubMed - indexed for MEDLINE]
Progressive Multifocal Leukoencephalopathy After Carboplatin and Paclitaxel Chemotherapy for Ovarian Carcinoma.
J Oncol Pract. 2019 10;15(10):554-555
Authors: Menon PJ, McKenna MC, Murphy S
PMID: 31425008 [PubMed - indexed for MEDLINE]
GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer.
Life Sci Alliance. 2019 08;2(4):
Authors: Tseng CC, Stanciauskas R, Zhang P, Woo D, Wu K, Kelly K, Gill PS, Yu M, Pinaud F, Lee AS
Abstract
GRP78 conducts protein folding and quality control in the ER and shows elevated expression and cell surface translocation in advanced tumors. However, the underlying mechanisms enabling GRP78 to exert novel signaling functions at cell surface are just emerging. CD44 is a transmembrane protein and an important regulator of cancer metastasis, and isoform switch of CD44 through incorporating additional variable exons to the extracellular juxtamembrane region is frequently observed during cancer progression. Using super-resolution dual-color single-particle tracking, we report that GRP78 interacts with CD44v in plasma membrane nanodomains of breast cancer cells. We further show that targeting cell surface GRP78 by the antibodies can effectively reduce cell surface expression of CD44v and cell spreading of tamoxifen-resistant breast cancer cells. Our results uncover new functions of GRP78 as an interacting partner of CD44v and as a regulator of CD44v membrane homeostasis and cell spreading. This study also provides new insights into anti-CD44 therapy in tamoxifen-resistant breast cancer.
PMID: 31416894 [PubMed - indexed for MEDLINE]
Radiological and clinical predictors of scoliosis in patients with Chiari malformation type I and spinal cord syrinx from the Park-Reeves Syringomyelia Research Consortium.
J Neurosurg Pediatr. 2019 Aug 16;:1-8
Authors: Strahle JM, Taiwo R, Averill C, Torner J, Shannon CN, Bonfield CM, Tuite GF, Bethel-Anderson T, Rutlin J, Brockmeyer DL, Wellons JC, Leonard JR, Mangano FT, Johnston JM, Shah MN, Iskandar BJ, Tyler-Kabara EC, Daniels DJ, Jackson EM, Grant GA, Couture DE, Adelson PD, Alden TD, Aldana PR, Anderson RCE, Selden NR, Baird LC, Bierbrauer K, Chern JJ, Whitehead WE, Ellenbogen RG, Fuchs HE, Guillaume DJ, Hankinson TC, Iantosca MR, Oakes WJ, Keating RF, Khan NR, Muhlbauer MS, McComb JG, Menezes AH, Ragheb J, Smith JL, Maher CO, Greene S, Kelly M, O'Neill BR, Krieger MD, Tamber M, Durham SR, Olavarria G, Stone SSD, Kaufman BA, Heuer GG, Bauer DF, Albert G, Greenfield JP, Wait SD, Van Poppel MD, Eskandari R, Mapstone T, Shimony JS, Dacey RG, Smyth MD, Park TS, Limbrick DD
Abstract
OBJECTIVE: Scoliosis is frequently a presenting sign of Chiari malformation type I (CM-I) with syrinx. The authors' goal was to define scoliosis in this population and describe how radiological characteristics of CM-I and syrinx relate to the presence and severity of scoliosis.
METHODS: A large multicenter retrospective and prospective registry of pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for clinical and radiological characteristics of CM-I, syrinx, and scoliosis (coronal curve ≥ 10°).
RESULTS: Based on available imaging of patients with CM-I and syrinx, 260 of 825 patients (31%) had a clear diagnosis of scoliosis based on radiographs or coronal MRI. Forty-nine patients (5.9%) did not have scoliosis, and in 516 (63%) patients, a clear determination of the presence or absence of scoliosis could not be made. Comparison of patients with and those without a definite scoliosis diagnosis indicated that scoliosis was associated with wider syrinxes (8.7 vs 6.3 mm, OR 1.25, p < 0.001), longer syrinxes (10.3 vs 6.2 levels, OR 1.18, p < 0.001), syrinxes with their rostral extent located in the cervical spine (94% vs 80%, OR 3.91, p = 0.001), and holocord syrinxes (50% vs 16%, OR 5.61, p < 0.001). Multivariable regression analysis revealed syrinx length and the presence of holocord syrinx to be independent predictors of scoliosis in this patient cohort. Scoliosis was not associated with sex, age at CM-I diagnosis, tonsil position, pB-C2 distance (measured perpendicular distance from the ventral dura to a line drawn from the basion to the posterior-inferior aspect of C2), clivoaxial angle, or frontal-occipital horn ratio. Average curve magnitude was 29.9°, and 37.7% of patients had a left thoracic curve. Older age at CM-I or syrinx diagnosis (p < 0.0001) was associated with greater curve magnitude whereas there was no association between syrinx dimensions and curve magnitude.
CONCLUSIONS: Syrinx characteristics, but not tonsil position, were related to the presence of scoliosis in patients with CM-I, and there was an independent association of syrinx length and holocord syrinx with scoliosis. Further study is needed to evaluate the nature of the relationship between syrinx and scoliosis in patients with CM-I.
PMID: 31419800 [PubMed - as supplied by publisher]
Chronic electrocorticography for sensing movement intention and closed-loop deep brain stimulation with wearable sensors in an essential tremor patient.
J Neurosurg. 2017 Sep;127(3):580-587
Authors: Herron JA, Thompson MC, Brown T, Chizeck HJ, Ojemann JG, Ko AL
Abstract
Deep brain stimulation (DBS) has become a widespread and valuable treatment for patients with movement disorders such as essential tremor (ET). However, current DBS treatment constantly delivers stimulation in an open loop, which can be inefficient. Closing the loop with sensors to provide feedback may increase power efficiency and reduce side effects for patients. New implantable neuromodulation platforms, such as the Medtronic Activa PC+S DBS system, offer important data sources by providing chronic neural sensing capabilities and a means of investigating dynamic stimulation based on symptom measurements. The authors implanted in a single patient with ET an Activa PC+S system, a cortical strip of electrodes on the hand sensorimotor cortex, and therapeutic electrodes in the ventral intermediate nucleus of the thalamus. In this paper they describe the effectiveness of the platform when sensing cortical movement intentions while the patient actually performed and imagined performing movements. Additionally, they demonstrate dynamic closed-loop DBS based on several wearable sensor measurements of tremor intensity.
PMID: 27858575 [PubMed - indexed for MEDLINE]
Repression of ferritin light chain translation by human eIF3.
Elife. 2019 08 15;8:
Authors: Pulos-Holmes MC, Srole DN, Juarez MG, Lee AS, McSwiggen DT, Ingolia NT, Cate JH
Abstract
A central problem in human biology remains the discovery of causal molecular links between mutations identified in genome-wide association studies (GWAS) and their corresponding disease traits. This challenge is magnified for variants residing in non-coding regions of the genome. Single-nucleotide polymorphisms (SNPs) in the 5' untranslated region (5'-UTR) of the ferritin light chain (FTL) gene that cause hyperferritinemia are reported to disrupt translation repression by altering iron regulatory protein (IRP) interactions with the FTL mRNA 5'-UTR. Here, we show that human eukaryotic translation initiation factor 3 (eIF3) acts as a distinct repressor of FTL mRNA translation, and eIF3-mediated FTL repression is disrupted by a subset of SNPs in FTL that cause hyperferritinemia. These results identify a direct role for eIF3-mediated translational control in a specific human disease.
PMID: 31414986 [PubMed - indexed for MEDLINE]
