It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here, we show evidence that Aβ more potently blocks the potentiation of excitatory ...postsynaptic potential (EPSP)-spike coupling (E-S potentiation). This occurs, not by direct effect on excitatory synapses or postsynaptic neurons, but rather through an indirect mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition. During high-frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation. This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer’s disease.
•Aβ blocks E-S potentiation•Aβ suppresses endocannabinoid-mediated GABAergic disinhibition•Aβ is acting to block the activity of the CB1 cannabinoid receptor•Aβ block of synaptic plasticity is via loss of cannabinoid-mediated disinhibition
Orr et al. show that the peptide Aβ, which accumulates in the brains of Alzheimer’s patients, interrupts the actions of the brain’s endogenous cannabinoid system, preventing cannabinoid-mediated blockade of synaptic inhibition, thus indirectly preventing the induction of neuroplasticity and learning.
Older adults with cancer use the emergency department (ED) for acute concerns.
Characterize the palliative care needs and clinical outcomes of advanced cancer patients in the ED.
A planned secondary ...data analysis of the Comprehensive Oncologic Emergencies Research Network (CONCERN) data.
Cancer patients who presented to the 18 CONCERN affiliated EDs in the United States.
Survey included demographics, cancer type, functional status, symptom burden, palliative and hospice care enrollment, and advance directive code status.
Of the total (674/1075, 62.3%) patients had advanced cancer and most were White (78.6%) and female (50.3%); median age was 64 (interquartile range 54-71) years. A small proportion of them were receiving palliative (6.5% 95% confidence interval; CI 3.0-7.6;
= 0.005) and hospice (1.3% 95% CI 1.0-3.2;
= 0.52) care and had a higher 30-day mortality rate (8.3%, 95% CI 6.2-10.4).
Patients with advanced cancer continue to present to the ED despite recommendations for early delivery of palliative care.
Patients with active cancer account for a growing percentage of all emergency department (ED) visits and have a unique set of risks related to their disease and its treatments. Effective triage for ...this population is fundamental to facilitating their emergency care.
We evaluated the validity of the Emergency Severity Index (ESI; version 4) triage tool to predict ED-relevant outcomes among adult patients with active cancer.
We conducted a prespecified analysis of the observational cohort established by the National Cancer Institute–supported Comprehensive Oncologic Emergencies Research Network’s multicenter (18 sites) study of ED visits by patients with active cancer (N = 1075). We used a series of χ2 tests for independence to relate ESI scores with 1) disposition, 2) ED resource use, 3) hospital length of stay, and 4) 30-day mortality.
Among the 1008 subjects included in this analysis, the ESI distribution skewed heavily toward high acuity (>95% of subjects had an ESI level of 1, 2, or 3). ESI was significantly associated with patient disposition and ED resource use (p values < 0.05). No significant associations were observed between ESI and the non-ED based outcomes of hospital length of stay or 30-day mortality.
ESI scores among ED patients with active cancer indicate higher acuity than the general ED population and are predictive of disposition and ED resource use. These findings show that the ESI is a valid triage tool for use in this population for outcomes directly relevant to ED care.
It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here, we show evidence that Aβ more potently blocks the potentiation of excitatory ...postsynaptic potential (EPSP)-spike coupling (E-S potentiation). This occurs, not by direct effect on excitatory synapses or postsynaptic neurons, but rather through an indirect mechanism: reduction of endocannabinoid-mediated peritetanic disinhibition. During high-frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation. This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.
It has been widely reported that β-amyloid peptide (Aβ) blocks long-term potentiation (LTP) of hippocampal synapses. Here we show evidence that Aβ more potently blocks the potentiation of excitatory ...post-synaptic potential (EPSP) -spike coupling (E-S potentiation). This occurs not by direct effect on excitatory synapses or postsynaptic neurons, but rather through a novel indirect mechanism: reduction of endocannabinoid-mediated peri-tetanic disinhibition. During high frequency (tetanic) stimulation, somatic synaptic inhibition is suppressed by endocannabinoids. We find that Aβ prevents this endocannabinoid-mediated disinhibition, thus leaving synaptic inhibition more intact during tetanic stimulation. This intact inhibition opposes the normal depolarization of hippocampal pyramidal neurons that occurs during tetanus, thus opposing the induction of synaptic plasticity. Thus, a novel pathway through which Aβ can act to modulate neural activity is identified, relevant to learning and memory and how it may mediate aspects of the cognitive decline seen in Alzheimer's disease.
Disparities in care of older adults in cancer treatment trials and emergency department (ED) use exist. This report provides a baseline description of older adults ≥65 years old who present to the ED ...with active cancer.
Planned secondary analysis of the Comprehensive Oncologic Emergencies Research Network observational ED cohort study sponsored by the National Cancer Institute. Of 1564 eligible adults with active cancer, 1075 patients were prospectively enrolled, of which 505 were ≥ 65 years old. We recruited this convenience sample from eighteen participating sites across the United States between February 1, 2016 and January 30, 2017.
Compared to cancer patients younger than 65 years of age, older adults were more likely to be transported to the ED by emergency medical services, have a higher Charlson Comorbidity Index score, and be admitted despite no significant difference in acuity as measured by the Emergency Severity Index. Despite the higher admission rate, no significant difference was noted in hospitalization length of stay, 30-day mortality, ED revisit or hospital admission within 30 days after the index visit. Three of the top five ED diagnoses for older adults were symptom-related (fever of other and unknown origin, abdominal and pelvic pain, and pain in throat and chest). Despite this, older adults were less likely to report symptoms and less likely to receive symptomatic treatment for pain and nausea than the younger comparison group. Both younger and older adults reported a higher symptom burden on the patient reported Condensed Memorial Symptom Assessment Scale than to ED providers. When treating suspected infection, no differences were noted in regard to administration of antibiotics in the ED, admissions, or length of stay ≤2 days for those receiving ED antibiotics.
We identified several differences between older (≥65 years old) and younger adults with active cancer seeking emergency care. Older adults frequently presented for symptom-related diagnoses but received fewer symptomatic interventions in the ED suggesting that important opportunities to improve the care of older adults with cancer in the ED exist.
For patients with cancer, the impact of observation status on hospital and patient outcomes is not well understood. Our objective was to assess the impact that an observation unit had on hospital use ...for patients with cancer who presented to the Urgent Care Center at a comprehensive cancer center.
We assessed the proportion of Urgent Care Center visits that resulted in an admission to the hospital at a comprehensive cancer center, before (July 9, 2012-December 31, 2012) versus after (July 9, 2013-December 31, 2013) implementation of the observation unit. We also assessed differences in length of stay and stratified the data by presenting complaint.
During each 6-month study interval, there were more than 10,000 patient visits to the Urgent Care Center, representing approximately 6,000 unique patients. Fewer visits resulted in an inpatient admission postimplementation (47%) compared with preimplementation (50%). The duration of hospital stay for admitted patients was higher in the post period (median 108 hours) than in the pre period (median 96 hours). Alternatively, the proportion of hospital admissions with a length of stay less than 24 hours was lower in the post period (pre: 7%; post: 5%). Lower admission rates postimplementation were observed for patients who presented with fluid and electrolyte disorders, nausea and vomiting, syncope, and chest pain.
We observed reductions in hospital use for patients with cancer related to an observation unit in a comprehensive cancer center. Adoption of this approach for this patient population has the potential to reduce hospital use, which is of interest to hospitals, payers, and patients.
The emergence and popularity of mobile and social media have transformed the nature of
the parasocial relationship between weathercaster and audience. Two experts and nine television
viewers were ...selected for qualitative interviewing via non-probability sampling to gain an
understanding of how respondents’ growing use of social media and other emerging media has
impacted the relationship with the local television weathercaster. Additionally, these interviews
explored the ways in which these relationships have ultimately changed how viewers receive
weather warnings. Storms producing strong straight-line winds and multiple tornadoes in the Fort
Wayne, Indiana television market provided a case study that illuminated the role of trust in the
complex relationships between weather forecasting and new social media. Mobile and social
media have increased the weather forecasters’ influence over the audience, while quickly
allowing them to provide severe weather warnings.
This study demonstrates the popularity of social media among diverse age groups and
that user demographics do not indicate any level of social media literacy. Second, as the literature
suggests, this study confirms users’ trust in their weather forecasters as well as the informationseeking
behavior displayed during severe weather. Third, this research finds that social media has
transformed parasocial relationships. Finally, this study suggests that stations have not recognized
nor taken advantage of these new parasocial relationships, and that they can do so by promoting
TV personalities’ online social profiles.
Introduction -- Literature review -- Methods -- Trust, weather forecasting and social media -- Online presence -- Conclusion.
Department of Geography
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