Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
13
result(s) for
"Kessler, Colleen"
Sort by:
Relationship between In Vivo Receptor Occupancy and Efficacy of Metabotropic Glutamate Receptor Subtype 5 Allosteric Modulators with Different In Vitro Binding Profiles
Allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGlu5) have exciting potential as therapeutic agents for multiple brain disorders. Translational studies with mGlu5 modulators have relied on mGlu5 allosteric site positron emission tomography (PET) radioligands to assess receptor occupancy in the brain. However, recent structural and modeling studies suggest that closely related mGlu5 allosteric modulators can bind to overlapping but not identical sites, which could complicate interpretation of in vivo occupancy data, even when PET ligands and drug leads are developed from the same chemical scaffold. We now report that systemic administration of the novel mGlu5 positive allosteric modulator VU0092273 displaced the structurally related mGlu5 PET ligand, [(18)F]FPEB, with measures of in vivo occupancy that closely aligned with its in vivo efficacy. In contrast, a close analog of VU0092273 and [(18)F]FPEB, VU0360172, provided robust efficacy in rodent models in the absence of detectable occupancy. Furthermore, a structurally unrelated mGlu5 negative allosteric modulator, VU0409106, displayed measures of in vivo occupancy that correlated well with behavioral effects, despite the fact that VU0409106 is structurally unrelated to [(18)F]FPEB. Interestingly, all three compounds inhibit radioligand binding to the prototypical MPEP/FPEB allosteric site in vitro. However, VU0092273 and VU0409106 bind to this site in a fully competitive manner, whereas the interaction of VU0360172 is noncompetitive. Thus, while close structural similarity between PET ligands and drug leads does not circumvent issues associated with differential binding to a given target, detailed molecular pharmacology analysis accurately predicts utility of ligand pairs for in vivo occupancy studies.
Journal Article
A project guide to electricity and magnetism
Looks at the history of the study of electricity and magnetism and presents science experiments and projects that demonstrate these principles.
Book
Drop out from out-patient mental healthcare in the World Health Organization's World Mental Health Survey initiative
Previous community surveys of the drop out from mental health treatment have been carried out only in the USA and Canada.
To explore mental health treatment drop out in the World Health Organization World Mental Health Surveys.
Representative face-to-face household surveys were conducted among adults in 24 countries. People who reported mental health treatment in the 12 months before interview (n = 8482) were asked about drop out, defined as stopping treatment before the provider wanted.
Overall, drop out was 31.7%: 26.3% in high-income countries, 45.1% in upper-middle-income countries, and 37.6% in low/lower-middle-income countries. Drop out from psychiatrists was 21.3% overall and similar across country income groups (high 20.3%, upper-middle 23.6%, low/lower-middle 23.8%) but the pattern of drop out across other sectors differed by country income group. Drop out was more likely early in treatment, particularly after the second visit.
Drop out needs to be reduced to ensure effective treatment.
Journal Article
A project guide to the solar system
An introduction to the solar system, including the moon, eclipses, and space.
Book
Seroprevalence of Old World Hantaviruses and Crimean Congo Hemorrhagic Fever Viruses in Human Populations in Northwestern Ukraine
In Ukraine, a retrospective review of clinical case reports by public health officials suggest that human cases of febrile illnesses associated with hemorrhage may be due to infections of Crimean-Congo hemorrhagic fever virus (CCHFV) and Old World hantaviruses. In a serosurvey of 966 healthy individuals in the Lviv Oblast, Ukraine, bordering Poland, we found that 1.6% showed cross-reactivity to hantaviral antigens by an immunofluorescence assay (IFA) and 1.7% of the study participants had antibodies cross-reactive to CCHFV by enzyme-linked immunosorbent assay (ELISA). Demographic variables and history of exposures obtained through questionnaires were assessed by logistic regression models for association with seroprevalence for both viruses with no significant risk factors found. Analysis of spatial distribution identified two clusters of samples positive for antibodies to both hantaviruses and CCHFV, which, however, were not statistically significant (p > 0.05). In general, the study results suggest that the population of the study area is exposed to hantaviruses and CCHFV. Further surveillance for respective pathogens in Ukraine is warranted and prospective surveillance of febrile patients with unidentified febrile illness.
Journal Article
A project guide to light and optics
Looks at the history of the study of light and optics and presents science experiments and projects that demonstrate these principles.
Book
The impact and efficiency of medical screening exams in forward treatment areas at New York City public hospitals during the initial COVID‐19 surge
New York City (NYC) emergency departments (EDs) experienced a surge of patients because of coronavirus disease 2019 (COVID‐19) in March 2020. NYC Health and Hospitals established rapid medical screening exams (MSE) and each hospital designated areas to perform their MSE. Five of the 11 hospitals created a forward treatment area (FTA) external to the ED to disposition patients before entering who presented with COVID‐like symptoms. Three hospitals used paper‐based, and 2 used an electronic medical record (EMR)‐based MSE. This study evaluated the effectiveness of safely discharging patients home from the FTA while also evaluating the efficiency of using paper‐based versus EMR‐based MSEs.
Charts were reviewed using standardized data extraction templates. Patients discharged from the FTA were contacted by phone, and a structured interview captured additional data regarding subsequent clinical courses. Chi‐square tests were used to compare proportions of patients hospitalized, as well as proportions of patients with vital signs recorded. Mortality rates were compared with Fisher exact test. A logistic regression model with fixed effects to account for clustering at hospitals was used to compare the odds of being sent to the ED for further evaluation based on vital signs and adjusted for age and sex
Across 5 EDs, 3335 patients were evaluated in their FTAs from March 17, 2020, to April 27, 2020. A total of 970 (29.1%) patients were referred for further evaluation into the ED, of which 203 (20.9%) were hospitalized and 19 (2.0%) died. Of 2302 patients discharged from the FTA, 182 (7.9%) returned to the ED within 7 days, resulting in 42 (1.8%) hospitalizations and 7 (0.3%) deaths. Facilities using EMR‐MSE discharged more patients from their FTA (81.9% vs 65.3%, P < 0.001) and had similar 7‐day return (9.3% vs 7.1%, P = 0.055) and mortality rates (0.49% vs 0.20%, P = 0.251).
MSEs in an FTA are an effective process to disposition patients safely in a high‐volume situation. Differences exist in paper‐ versus EMR‐based approaches, suggesting EMR‐MSEs provide better data, efficiency, and effectiveness. This suggests prioritizing an EMR‐based MSE should be considered in future circumstances.
Journal Article
Octopuses
\"Learn more about octopuses, how they use their cleverness to survive, and how they are astonishing scientists with their surprising smarts.\"-- Publisher's website.
Book
Drop out from out-patient mental healthcare in the World Health Organization's World Menta Health Survey initiative
BackgroundPrevious community surveys of the drop out from mental health treatment have been carried out only in the USA and Canada.AimsTo explore mental health treatment drop out in the World Health Organization World Mental Health Surveys.MethodRepresentative face-to-face household surveys were conducted among adults in 24 countries. People who reported mental health treatment in the 12 months before interview (n = 8482) were asked about drop out, defined as stopping treatment before the provider wanted.ResultsOverall, drop out was 31.7%: 26.3% in high-income countries, 45.1% in upper-middle-income countries, and 37.6% in low/ lower/middle-income countries. Drop out from psychiatrists was 21.3% overall and similar across country income groups (high 20.3%, upper-middle 23.6%, low/lower-middle 23.8%) but the pattern of drop out across other sectors differed by country income group. Drop out was more likely early in treatment, particularly after the second visit.ConclusionsDrop out needs to be reduced to ensure effective treatment.
Journal Article