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1.
Article in English | MEDLINE | ID: mdl-38453631

ABSTRACT

OBJECTIVE: The study aimed to assess the accuracy of the Yale Swallow Protocol (YSP) in screening aspiration in adults with acute moderate-to-severe traumatic brain injury (TBI) by comparing the YSP with a videofluoroscopic swallow study (VFSS). SETTING: Level 1 academic trauma center. PARTICIPANTS: The study involved a cohort of 50 consecutive adults with a history of acute moderate-to-severe TBI. DESIGN: The prospective cohort study was conducted between July 2020 and June 2021. Participants underwent the YSP to assess aspiration risk, followed by a VFSS within 5 to 10 minutes after the YSP, to assess the accuracy of the YSP compared with the VFSS. MAIN MEASURE: The accuracy of the YSP in identifying aspiration in adults with acute moderate-to-severe TBI. RESULTS: The interrater agreement for identifying aspiration on the VFSS and the YSP was excellent, as well as 100% agreement between the speech-language pathologists and the radiologist and between the 2 speech-language pathologists, respectively. Of the 50 participants, 16 passed the YSP, while 34 failed. Among those who failed, 30 were confirmed to have aspirated on the VFSS (true-positives) and 4 did not show aspiration on the VFSS (false-positives). The YSP demonstrated a high sensitivity of 96.8%, a specificity of 78.9%, a positive predictive value of 88.2%, and a negative predictive value of 93.8% in identification of aspiration in this cohort. CONCLUSIONS: To date, no dedicated prospective studies have been conducted to assess the utility of the YSP as a screening tool for identifying aspiration risk in persons with moderate-to-severe TBI. The results of this study conclude that the YSP is an effective screening tool for prediction of aspiration in acute care patients with moderate-to-severe TBI due to its high sensitivity and negative predictive value. These factors aid in identification of individuals at risk for aspiration and facilitate timely interventions to prevent complications.

3.
J Vitreoretin Dis ; 7(5): 429-434, 2023.
Article in English | MEDLINE | ID: mdl-37706079

ABSTRACT

Purpose: To expand the current knowledge of tubulointerstitial nephritis and uveitis syndrome (TINU), which might assist other ophthalmologists in recognizing and treating patients with this rare disease. Methods: A patient with atypical demographics and features was compared with previously described TINU cases. The case was analyzed in terms of how it compares with more "classic" cases, and the differences were identified. Results: The diagnosis of TINU is ultimately clinical, although aided by previous studies. Thus, it might present challenges when patients do not have the typical demographics or presenting features of TINU. Conclusions: Our patient showed features that deviated from classic TINU. Knowledge of the disease and a comprehensive view of the patient's medical state might help lead to accurate diagnosis and treatment.

5.
Clin Case Rep ; 10(8): e6201, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35949413

ABSTRACT

Since the introduction of universal gonococcal and chlamydia prophylaxis, other etiologies for neonatal conjunctivitis such as Escherichia coli have become more common. Early eye culturing as part of the management plan could provide swifter treatment and preservation of vision potential in affected neonates.

6.
J Pediatr Ophthalmol Strabismus ; 58(6): e44-e48, 2021.
Article in English | MEDLINE | ID: mdl-34851787

ABSTRACT

Tetrasomy 18p is often the result of an additional isochromosome for the short arm of chromosome 18. Although many organ systems are affected phenotypically, the ocular manifestations associated with tetrasomy 18p have not been well characterized in the literature. This case report presents the ocular and facial features associated with tetrasomy 18p in a 4-year-old Black girl, along with a review of clinical presentations previously reported in the literature. A systematic review of the literature in PubMed was conducted to summarize the reported eye, ocular adnexa, and distinctive facial features in individuals with confirmed tetrasomy 18p. Searching "Tetrasomy 18p" generated 65 article results, of which 28 articles had sufficient eye and facial descriptions. Including the patient in this report, 90 patients had confirmed tetrasomy 18p. The most common features noted in these 90 patients, with a roughly equal male-to-female ratio of impact (7:8), were as follows: microcephaly (57%), triangular facies (18%), anomalous palpebral fissures (31%), strabismus (48%), low-set ears (52%), hearing loss to some extent (16%), depressed or flat nasal bridge (18%), smooth philtrum (41%), thin upper lip (27%), and highly arched palate (21%). Additionally, many were noted to have feeding difficulties (28%), developmental delay (58%), and abnormal brain findings on imaging (20%). Muscle tone was abnormal in 23% of the patients. This report elucidates the reoccurring eye, ocular adnexa, and distinctive facial features associated with tetrasomy 18p. This knowledge may assist in timely diagnosis and encourage providers to use a multidisciplinary approach for the treatment of affected individuals. [J Pediatr Ophthalmol Strabismus. 2021;58(6):e44-e48.].


Subject(s)
Aneuploidy , Chromosomes, Human, Pair 18 , Child, Preschool , Chromosomes, Human, Pair 18/genetics , Eye , Female , Humans , Male
7.
Clin J Oncol Nurs ; 25(3): 329-332, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-34019032

ABSTRACT

Patients in the hematology-oncology and stem cell transplantation (SCT) setting are at high risk for functional decline and falls related to prolonged hospitalizations and inactivity during inpatient treatment. After underperforming on the Press Ganey National Database of Nursing Quality Indicators benchmark for falls in 2018, staff on a hematology-oncology and SCT unit implemented a practical and evidence-based fall prevention program. Fall rates from 2018 to 2019 ranged from 3.4 to 4.8 falls per 1,000 patient days. After the introduction of the unit-based gym program, early mobility increased and falls decreased to 2.57 per 1,000 patient days.


Subject(s)
Hematology , Inpatients , Humans , Stem Cell Transplantation
8.
Semin Oncol Nurs ; 37(2): 151134, 2021 04.
Article in English | MEDLINE | ID: mdl-33795179

ABSTRACT

OBJECTIVE: Chimeric antigen receptor (CAR) T-cell therapy is a genetically modified cellular therapy approved for the treatment of acute lymphocytic leukemia and B-cell lymphoma. This therapy requires patients to remain hospitalized for at least 7 days to monitor for two black-box warnings: cytokine release syndrome and neurotoxicity. Both toxicities require astute monitoring and early treatment to prevent complication. DATA SOURCE: We use a case study to illustrate the assessment and toxicity management of a patient receiving CAR T-cell therapy for diffuse large B-cell lymphoma at an academic medical center. CONCLUSION: Cytokine release syndrome and neurotoxicity are two common, potentially life-threatening toxicities that can be reversed with early nursing identification and treatment using evidence-based interventions. IMPLICATIONS FOR NURSING PRACTICE: Objective assessment and consensus grading is essential for identification and management of CAR T-cell toxicities.


Subject(s)
Receptors, Chimeric Antigen , Emergencies , Humans , Immunotherapy, Adoptive , Inpatients , T-Lymphocytes
9.
Infect Control Hosp Epidemiol ; 42(2): 127-130, 2021 02.
Article in English | MEDLINE | ID: mdl-32741425

ABSTRACT

OBJECTIVES: Prolonged survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces and personal protective equipment may lead to these surfaces transmitting this pathogen to others. We sought to determine the effectiveness of a pulsed-xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators. METHODS: Chamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and were exposed to different durations of PX-UV. RESULTS: For hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 log10, >4.54 log10, and >4.12 log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in >4.79 log10 reduction in viral load. PX-UV significantly reduced SARS-CoV-2 on hard surfaces and N95 respirators. CONCLUSION: With the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology to reduce environmental and personal protective equipment bioburden and to enhance both healthcare worker and patient safety by reducing the risk of exposure to SARS-CoV-2.


Subject(s)
COVID-19/prevention & control , Disinfection/methods , SARS-CoV-2/radiation effects , Ultraviolet Rays , Animals , COVID-19/transmission , COVID-19/virology , Chlorocebus aethiops , Disinfection/instrumentation , Equipment Reuse/standards , Humans , N95 Respirators , Personal Protective Equipment , SARS-CoV-2/physiology , Time Factors , Vero Cells , Xenon
10.
Am J Case Rep ; 21: e925221, 2020 Dec 21.
Article in English | MEDLINE | ID: mdl-33347427

ABSTRACT

BACKGROUND Strongyloidiasis, caused by infection with Strongyloides stercoralis parasitic nematodes, is most prevalent in tropical regions of the world, such as South America, Southeast Asia, and sub-Saharan Africa, but its incidence has increased in nonendemic areas of the United States due to immigration. The majority of patients remain asymptomatic or have only mild gastrointestinal, respiratory, or dermatologic symptoms. Unrecognized strongyloidiasis can progress to Strongyloides hyperinfection syndrome, a highly fatal complication that can occur in response to immunosuppressive therapy. This rare complication is easily misdiagnosed because of its similar presentation to asthma or exacerbation of chronic obstructive pulmonary disease. CASE REPORT We report a case of worsening therapeutic response to systemic corticosteroids in an elderly Colombian man who presented with symptoms of acute exacerbation of asthma. His history was positive for residence in a region endemic to S. stercoralis, and he had undergone multiple hospitalizations over the past few years for pulmonary, gastrointestinal, and dermatologic complaints. Laboratory results were significant for increased eosinophilia, and chest radiography showed blunting of the left costophrenic angle. The patient was found to have S. stercoralis hyperinfection after parasitic larvae were detected in a bronchoalveolar lavage sample. Symptoms improved after a course of ivermectin, and the patient was subsequently discharged. CONCLUSIONS This unusual presentation of Strongyloides hyperinfection syndrome showcases the dangers of corticosteroid therapy in individuals with undiagnosed Strongyloides infection who present with a presumed diagnosis of asthma exacerbation. Clinicians should maintain a high level of suspicion when treating patients from S. stercoralis endemic regions presenting with pulmonary, gastrointestinal, and/or dermatologic symptoms. Ivermectin is the current standard of care for both asymptomatic and complicated strongyloidiasis.


Subject(s)
Asthma , Strongyloides stercoralis , Strongyloidiasis , Adrenal Cortex Hormones , Aged , Animals , Humans , Ivermectin/therapeutic use , Male , Strongyloidiasis/complications , Strongyloidiasis/diagnosis , Strongyloidiasis/drug therapy
11.
Insects ; 11(2)2020 Feb 18.
Article in English | MEDLINE | ID: mdl-32085627

ABSTRACT

Pollinator nutritional ecology provides insights into plant-pollinator interactions, coevolution, and the restoration of declining pollinator populations. Bees obtain their protein and lipid nutrient intake from pollen, which is essential for larval growth and development as well as adult health and reproduction. Our previous research revealed that pollen protein to lipid ratios (P:L) shape bumble bee foraging preferences among pollen host-plant species, and these preferred ratios link to bumble bee colony health and fitness. Yet, we are still in the early stages of integrating data on P:L ratios across plant and bee species. Here, using a standard laboratory protocol, we present over 80 plant species' protein and lipid concentrations and P:L values, and we evaluate the P:L ratios of pollen collected by three bee species. We discuss the general phylogenetic, phenotypic, behavioral, and ecological trends observed in these P:L ratios that may drive plant-pollinator interactions; we also present future research questions to further strengthen the field of pollination nutritional ecology. This dataset provides a foundation for researchers studying the nutritional drivers of plant-pollinator interactions as well as for stakeholders developing planting schemes to best support pollinators.

12.
J Learn Disabil ; 51(6): 589-599, 2018.
Article in English | MEDLINE | ID: mdl-28748729

ABSTRACT

This investigation employs categorical content analysis processes as a mechanism to examine trends and issues in a sampling of highly cited (100+) literature in special education journals. The authors had two goals: (a) broadly identifying trends across publication type, content area, and methodology and (b) specifically identifying articles with disaggregated outcomes for students with learning disabilities (LD). Content analyses were conducted across highly cited (100+) articles published during a 20-year period (1992-2013) in a sample ( n = 3) of journals focused primarily on LD, and in one broad, cross-categorical journal recognized for its impact in the field. Results indicated trends in the article type (i.e., commentary and position papers), content (i.e., reading and behavior), and methodology (i.e., small proportions of experimental and quasi-experimental designs). Results also revealed stability in the proportion of intervention research studies when compared to previous analyses and a decline in the proportion of those that disaggregated data specifically for students with LD.


Subject(s)
Bibliographies as Topic , Education, Special/trends , Humans , Qualitative Research
13.
Eur J Neurosci ; 45(7): 912-921, 2017 04.
Article in English | MEDLINE | ID: mdl-28186680

ABSTRACT

Group II metabotropic glutamate receptor agonists have been suggested as potential anti-psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome-wide association studies. We found that LY354740 failed to rescue the spatial working memory deficit in Gria1-/- mice during rewarded alternation performance in the T-maze. In contrast, LY354740 did reduce the locomotor hyperactivity in these animals to a level that was similar to controls. A similar pattern was found with the dopamine receptor antagonist haloperidol, with no amelioration of the spatial working memory deficit in Gria1-/- mice, even though the same dose of haloperidol reduced their locomotor hyperactivity. These results with LY354740 contrast with the rescue of spatial working memory in models of glutamatergic hypofunction using non-competitive NMDAR antagonists. Future studies should determine whether group II mGluR agonists can rescue spatial working memory deficits with other NMDAR manipulations, including genetic models and other pharmacological manipulations of NMDAR function.


Subject(s)
Bridged Bicyclo Compounds/pharmacology , Dopamine Antagonists/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Haloperidol/pharmacology , Hyperkinesis/metabolism , Memory, Short-Term/drug effects , Receptors, AMPA/genetics , Animals , Bridged Bicyclo Compounds/therapeutic use , Dopamine Antagonists/therapeutic use , Excitatory Amino Acid Agonists/therapeutic use , Female , Haloperidol/therapeutic use , Hyperkinesis/drug therapy , Hyperkinesis/physiopathology , Locomotion/drug effects , Male , Mice , Mice, Inbred C57BL , Receptors, AMPA/antagonists & inhibitors , Receptors, AMPA/metabolism
14.
Clin Nutr ; 36(3): 686-696, 2017 06.
Article in English | MEDLINE | ID: mdl-27302208

ABSTRACT

BACKGROUND: Adults with diabetes (DM) and chronic kidney disease (CKD) are at risk for vitamin D (vitD) insufficiency, suboptimal bone health and reduced quality of life (QoL) due to limited sunlight exposure, poor vitD intake and CKD. AIMS: This open-labeled, randomized clinical trial, compared the impact of daily (2000 IU/D) verses monthly (40,000 IU/month) vitD3 supplementation over six months on markers of vitD status, bone health and QoL in adults with DM and CKD (stages: 1-4). METHODS: Participants (18-80 years) were randomized to daily (n = 60) or monthly (n = 60) vitD3 for six months. Primary outcomes included: vitD status (25-hydroxyvitD [25(OH)D], 1, 25-dihydroxyvitD [1,25(OH)2D], bone health (bone mineral density [BMD] and serum concentrations of bone-specific alkaline phosphatase [BSAP], osteocalcin [OC], N-telopeptide-type 1-collagen [NTx]) and Fibroblast Growth Factor-23 (FGF-23). Secondary outcomes included QoL (Short Form-36 questionnaire). RESULTS: Adherence by dose allocation over six months was 95.0 ± 5.7% (daily) and 94.1 ± 4.1% (monthly), respectively (p = 0.44); resulting in an overall median [95% CI] increase in serum 25(OH)D of 19 (12-26) nmol/L (p < 0.001). Serum 25(OH)D increased at three (p < 0.001) and six months (p < 0.001) in the daily and monthly groups, respectively. No significant differences over six months between groups were observed in serum concentrations of 1,25(OH)2D, FGF-23, OC and NTx, BMD and QoL measures (p > 0.05). Serum 25(OH)D ≥ 75 nmol/L was associated with significant reductions in BSAP (p = 0.01) and improved physical functioning vs those with concentrations < 75 nmol/L (62.5 ± 26.8 vs 52.7 ± 26.3; p = 0.03) in the monthly and daily groups, respectively. CONCLUSIONS: Daily (2000 IU/D) and monthly (40,000 IU/month) vitD3 supplementation for six months in adults with DM and CKD was safe, and resulted in equivalent adherence and improvements in overall vitD status, but only modest changes in markers of bone health and QoL.


Subject(s)
Bone Density/drug effects , Bone and Bones/drug effects , Cholecalciferol/administration & dosage , Diabetes Mellitus/physiopathology , Renal Insufficiency, Chronic/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Alkaline Phosphatase/blood , Body Mass Index , Bone and Bones/physiology , Cholecalciferol/blood , Collagen Type I/blood , Dietary Supplements , Dose-Response Relationship, Drug , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/blood , Humans , Male , Middle Aged , Osteocalcin/blood , Patient Compliance , Peptides/blood , Quality of Life , Vitamin D Deficiency/prevention & control , Young Adult
15.
Can J Diet Pract Res ; 78(1): 11-19, 2017 03.
Article in English | MEDLINE | ID: mdl-27779902

ABSTRACT

PURPOSE: Patients with diabetes (DM) and chronic kidney disease (CKD) are at increased risk for suboptimal bone health. The study objective was to investigate the relationships between vitamin D (vitD), vitamin K1 (vitK1), and calcium intake with bone mineral density (BMD) and vitamin D status in an ambulatory population with DM and CKD. METHODS: Adults (age 18-80 years; n = 62) with DM and CKD (stages 1-4) were recruited from the Northern Alberta Renal Program. Primary outcome variables included vitD, vitK1, and calcium intake; serum 25(OH)D, 1,25(OH)2D; and BMD as measured by dual X-ray absorptiometry. Statistical significance was determined at P < 0.05. RESULTS: Participants met the estimated average requirement or adequate intake for vitD, vitK1, and calcium intake in 73% (n = 45), 66% (n = 39), and 52% (n = 31), respectively, with a combined intake of micronutrient supplementation and diet. Participants had serum 25(OH)D concentrations ≥75 nmol/L (n = 41), normal BMDs (n = 48), and 66% (n = 41/62) were taking vitD supplements (>1000 IU/D). BMD was positively influenced by serum 25(OH)D. However, serum 25(OH) ≥100 nmol/L was associated with lower BMD (absolute and T-scores) for whole-body and spine (P ≤ 0.05). VitK1 intake (≥200 µg/day) was associated with higher whole-body and femoral-neck BMDs (absoluteand T-scores; P ≤ 0.05). CONCLUSION: VitD status and BMD in adults with DM and CKD was influenced by vitD supplementation and vitK1 intake.


Subject(s)
Bone Density/drug effects , Diabetes Mellitus/drug therapy , Renal Insufficiency, Chronic/drug therapy , Vitamin D/administration & dosage , Vitamin D/blood , Vitamin K 1/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Alberta , Blood Glucose/metabolism , Calcium, Dietary/administration & dosage , Calcium, Dietary/blood , Diabetes Mellitus/blood , Diet , Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Dietary Supplements , Female , Humans , Male , Micronutrients/administration & dosage , Micronutrients/blood , Middle Aged , Nutrition Assessment , Nutritional Status , Renal Insufficiency, Chronic/blood , Vitamin K 1/blood , Young Adult
16.
Food Funct ; 7(4): 1839-48, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26988895

ABSTRACT

Identification of dietary strategies to increase large intestinal production and absorption of short-chain fatty acids (SCFAs), especially butyrate, is of great interest due to the possible health promoting effects. We explored the effect of an enzymatically modified arabinoxylan-rich diet (EAXD) versus a Western-style control diet (WSD) low in dietary fiber with or without orally administrated Butyrivibrio fibrisolvens, a butyrate producer, on the SCFA pool in the cecal content and feces and the SCFA concentration in the blood of rats. The pool of acetate, butyrate and total SCFA was more than double in the cecal content from EAXD-fed rats compared with WSD-fed rats, and this was also reflected as an increase in portal plasma SCFA concentrations. Acetate, propionate and total SCFA concentrations were higher in mixed venous plasma following the EAXD. The number of B. fibrisolvens did not increase significantly in cecal content following administration of the bacteria. Furthermore, there was no interaction between the EAXD and B. fibrisolvens on the measured parameters.


Subject(s)
Butyrivibrio fibrisolvens/metabolism , Cecum/metabolism , Fatty Acids, Volatile/metabolism , Synbiotics/analysis , Xylans/chemistry , Xylans/metabolism , Animals , Butyrates/metabolism , Cecum/microbiology , Cellulases/chemistry , Diet , Dietary Fiber/metabolism , Endo-1,4-beta Xylanases/chemistry , Fatty Acids, Volatile/blood , Fatty Acids, Volatile/chemistry , Gastrointestinal Microbiome , Male , Rats , Rats, Wistar , Synbiotics/administration & dosage
17.
J Contin Educ Nurs ; 47(2): 75-81, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26840239

ABSTRACT

A continued education needs assessment and associated education plan are required for organizations on the journey for American Nurses Credentialing Center Magnet® designation. Leveraging technology to support the assessment and analysis of continuing education needs was a new venture for a 12-hospital regional health system. The purpose of this performance improvement project was to design and conduct an enhanced process to increase the efficiency and effectiveness of gathering data on nurses' preferences and increase nurse satisfaction with the learner assessment portion of the process. Educators trialed the use of a standardized approach via an electronic survey tool to replace the highly variable processes previously used. Educators were able to view graphical summary of responses by category and setting, which substantially decreased analysis and action planning time for education implementation plans at the system, site, or setting level. Based on these findings, specific continuing education action plans were drafted for each category and classification of nurses.


Subject(s)
Attitude of Health Personnel , Clinical Competence/standards , Education, Nursing, Continuing/standards , Needs Assessment , Nursing Staff/education , Nursing Staff/psychology , Adult , Female , Humans , Male , Middle Aged , Nursing Education Research , Surveys and Questionnaires , United States
18.
J Neurosci ; 35(46): 15466-76, 2015 Nov 18.
Article in English | MEDLINE | ID: mdl-26586832

ABSTRACT

Humans shape their hands to grasp, manipulate objects, and to communicate. From nonhuman primate studies, we know that visual and motor properties for grasps can be derived from cells in the posterior parietal cortex (PPC). Are non-grasp-related hand shapes in humans represented similarly? Here we show for the first time how single neurons in the PPC of humans are selective for particular imagined hand shapes independent of graspable objects. We find that motor imagery to shape the hand can be successfully decoded from the PPC by implementing a version of the popular Rock-Paper-Scissors game and its extension Rock-Paper-Scissors-Lizard-Spock. By simultaneous presentation of visual and auditory cues, we can discriminate motor imagery from visual information and show differences in auditory and visual information processing in the PPC. These results also demonstrate that neural signals from human PPC can be used to drive a dexterous cortical neuroprosthesis. SIGNIFICANCE STATEMENT: This study shows for the first time hand-shape decoding from human PPC. Unlike nonhuman primate studies in which the visual stimuli are the objects to be grasped, the visually cued hand shapes that we use are independent of the stimuli. Furthermore, we can show that distinct neuronal populations are activated for the visual cue and the imagined hand shape. Additionally we found that auditory and visual stimuli that cue the same hand shape are processed differently in PPC. Early on in a trial, only the visual stimuli and not the auditory stimuli can be decoded. During the later stages of a trial, the motor imagery for a particular hand shape can be decoded for both modalities.


Subject(s)
Brain Mapping , Hand Strength/physiology , Imagination/physiology , Parietal Lobe/physiology , Acoustic Stimulation , Cues , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Models, Neurological , Movement , Neurons/physiology , Oxygen/blood , Parietal Lobe/blood supply , Parietal Lobe/cytology , Photic Stimulation
19.
Science ; 348(6237): 906-10, 2015 May 22.
Article in English | MEDLINE | ID: mdl-25999506

ABSTRACT

Nonhuman primate and human studies have suggested that populations of neurons in the posterior parietal cortex (PPC) may represent high-level aspects of action planning that can be used to control external devices as part of a brain-machine interface. However, there is no direct neuron-recording evidence that human PPC is involved in action planning, and the suitability of these signals for neuroprosthetic control has not been tested. We recorded neural population activity with arrays of microelectrodes implanted in the PPC of a tetraplegic subject. Motor imagery could be decoded from these neural populations, including imagined goals, trajectories, and types of movement. These findings indicate that the PPC of humans represents high-level, cognitive aspects of action and that the PPC can be a rich source for cognitive control signals for neural prosthetics that assist paralyzed patients.


Subject(s)
Functional Neuroimaging/methods , Neural Prostheses , Neurons/physiology , Parietal Lobe/physiopathology , Quadriplegia/physiopathology , Quadriplegia/therapy , Brain-Computer Interfaces , Cognition , Electrodes, Implanted , Humans , Microelectrodes , Motor Activity , Movement
20.
Cancer Immunol Res ; 3(2): 116-24, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25516478

ABSTRACT

Coinhibitory receptor blockade is a promising strategy to boost T-cell immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for advanced mechanistic understanding to improve patient outcomes and uncover clinically relevant biomarkers of treatment efficacy. However, the T-cell-intrinsic signaling pathways engaged during checkpoint blockade treatment are not well defined, particularly for combination approaches. Using a murine model to study how effector CD8(+) T-cell responses to tumors may be enhanced in a tolerizing environment, we identified a critical role for the T-box transcription factor T-bet. Combination blockade of CTLA-4, PD-1, and LAG-3 induced T-bet expression in responding tumor/self-reactive CD8(+) T cells. Eradication of established leukemia using this immunotherapy regimen depended on T-bet induction, which was required for IFNγ production and cytotoxicity by tumor-infiltrating T cells, and for efficient trafficking to disseminated tumor sites. These data provide new insight into the success of checkpoint blockade for cancer immunotherapy, revealing T-bet as a key transcriptional regulator of tumor-reactive CD8(+) T-cell effector differentiation under otherwise tolerizing conditions.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immunotherapy/methods , Lymphocytes, Tumor-Infiltrating/immunology , T-Box Domain Proteins/immunology , Animals , Cell Line, Tumor , Cytotoxicity, Immunologic/immunology , Gene Expression Regulation, Neoplastic/immunology , Immune Tolerance/immunology , Leukemia, Experimental/genetics , Leukemia, Experimental/immunology , Leukemia, Experimental/therapy , Mice, Transgenic , Neoplasm Transplantation
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