Dopamine Signals Learn New Tricks Rothenhoefer, Kathryn M.; Stauffer, William R.
Neuron (Cambridge, Mass.),
04/2020, Letnik:
106, Številka:
1
Journal Article
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In this issue of Neuron, Morrens et al. (2020) show that stimulus-evoked dopamine responses are enhanced by novelty and increase the rate at which animals acquire conditioned responses. These results ...provide a candidate neural mechanism for latent inhibition and illustrate a new role of dopamine signals in learning.
In this issue of Neuron, Morrens et al. (2020) show that stimulus-evoked dopamine responses are enhanced by novelty and increase the rate at which animals acquire conditioned responses. These results provide a candidate neural mechanism for latent inhibition and illustrate a new role of dopamine signals in learning.
In recent years, the price of many older generic drugs, including numerous antibiotics, has increased substantially. We sought to analyze recent price changes and extent of generic competition within ...a cohort of commonly prescribed off-patent oral antibiotics.
We extracted oral antibiotics recommended for common outpatient conditions in the Infectious Diseases Society of America Practice Guidelines. We determined all US Food and Drug Administration-approved manufacturers for each formulation and strength in 2013 and 2016 and the yearly national average drug acquisition cost (NADAC) price between 2013 and 2016. Wilcoxon signed rank test was used to compare changes in drug prices and number of manufacturers from 2013 to 2016. Spearman correlation coefficient was used to assess the association between drug prices and number of manufacturers.
Twenty-two antibiotics (81 formulations and strengths) were analyzed. There was no change in the median NADAC price or the number of manufacturers between 2013 and 2016. However, 11 (14%) formulations increased in price by 90% or more, and 13 (16%) had 2 or fewer manufacturers during all 4 years. Antibiotic prices were negatively associated with the number of available manufacturers.
While prices and the number of manufacturers for common oral antibiotics were overall stable between 2013 and 2016, reduced manufacturer competition was associated with increased prices. A subset of antibiotics exhibited substantial price increases, and most, but not all, had limited manufacturer competition. Policy solutions are needed to ensure availability of low-cost, essential generic antibiotics.
A subset of anti-infective drugs are increasingly unavailable for patients in the United States due to pricing or withdrawal from the market. Timely market solutions are needed. We assert that ...solutions to ensure access to some essential anti-infective agents lie outside capital markets and that public-private partnerships may be the most viable solution.
Language and associated health literacy are powerful social determinants of health. Here, Wilkins et al discuss the study by Steiner et al which identifies language needs as a domain of inequity ...affecting COVID-19 vaccination coverage. They emphasize the relative lack of language resources for the 26.5 million US residents speaking primary languages other than English or Spanish. They found marked disparities in completion of the COVID-19 primary vaccination series by preferred language when comparing 25 of the most common languages represented in their dataset to the control group of Spanish and English speakers. They concluded that standardized accurate collection and documentation of self-identified preferred language is imperative.
The most common causes of eosinophilia globally are helminth parasites. Refugees from high endemic areas are at increased risk of infection compared with the general U.S. population. It is widely ...accepted that eosinophilia is a good marker for helminth infection in this population, yet its absence has little predictive value for excluding infection. During an enhanced premigration health program, the CDC offered voluntary testing and management of intestinal parasites, among other conditions, to U.S.-bound refugees in Thailand. Stool specimens were tested for Ascaris lumbricoides, Strongyloides stercoralis, Trichuris trichiura, hookworms, Giardia lamblia, Cryptosporidium spp., and Entamoeba histolytica using quantitative polymerase chain reaction. Complete blood counts were performed to identify eosinophilia. Predictive values of eosinophilia for parasitic infections were calculated within nematode groups. Between July 9, 2012 and November 29, 2013, 2,004 participants were enrolled. About 73% were infected with at least one parasite. The overall median eosinophil count was 483 cells/μL (interquartile range IQR = 235-876 cells/μL). Compared with participants who did not test positive for any infection, higher eosinophil counts were observed in those infected with A. lumbricoides (RR = 1.3, 95% CI = 1.1-1.4), S. stercoralis (RR = 1.8, 95% CI = 1.4-2.4), Necator americanus (RR = 1.2, 95% CI = 1.1-1.4), and Ancylostoma ceylanicum (RR = 1.8, 95% CI = 1.5-2.2). Eosinophil counts were higher in younger participants (2-4 years versus 65+ years: RR = 4.2, 95% CI = 2.5-6.9), and lower in female participants (RR = 0.9, 95% CI = 0.8-0.9). Sensitivities ranged from 51% to 73%, specificities from 48% to 65%, and predictive values from 4% to 98%. The predictive value of eosinophilia is poor for the most common parasitic infections, and it should not be used alone for screening refugees.
Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and the principal interface between dopamine reward signals and functionally diverse cortico-basal ganglia circuits. ...Information processing in these circuits is dependent on distinct MSN types: cell types that are traditionally defined according to their projection targets or dopamine receptor expression. Single-cell transcriptional studies have revealed greater MSN heterogeneity than predicted by traditional circuit models, but the transcriptional landscape in the primate striatum remains unknown. Here, we set out to establish molecular definitions for MSN subtypes in Rhesus monkeys and to explore the relationships between transcriptionally defined subtypes and anatomical subdivisions of the striatum. Our results suggest at least nine MSN subtypes, including dorsal striatum subtypes associated with striosome and matrix compartments, ventral striatum subtypes associated with the nucleus accumbens shell and olfactory tubercle, and an MSN-like cell type restricted to μ-opioid receptor rich islands in the ventral striatum. Although each subtype was demarcated by discontinuities in gene expression, continuous variation within subtypes defined gradients corresponding to anatomical locations and, potentially, functional specializations. These results lay the foundation for achieving cell-type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific information processing.
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•Archetypal and discontinuity analyses reveal MSN heterogeneity in Rhesus striatum•Distinct molecular signatures for striosome, matrix, and NAc shell D1- and D2-MSNs•Novel TAC3-archetype of D1-MSNs in the NAc medial shell•Unique μ-opioid-receptor-enriched D1-subtype in subset of interface islands
He et al. use single-nucleus RNA-seq and FISH to describe medium spiny neuron (MSN) diversity in the Rhesus macaque striatum; reveal distinct molecular signatures for MSNs in the striosome, matrix, and NAc shell; and identify novel MSN subtypes. The results are a blueprint for studying cell-type-specific striatal contributions to sophisticated behaviors.
To assess appropriate drug treatment of parasitic diseases in the United States, we examined the treatment rates of 11 selected parasitic infections with standard-of-care prescription drugs and ...compared them to the treatment rates of two more common bacterial infections (
Clostridioides difficile
and streptococcal pharyngitis). We used the 2013 to 2019 IBM
®
MarketScan
®
Commercial Claims and Encounters and MarketScan
®
Multi-State Medicaid databases, which included up to 7 years of data for approximately 88 million and 17 million individuals, respectively, to estimate treatment rates of each infection. The number of patients diagnosed with each parasitic infection varied from 57 to 5,266, and from 12 to 2,018, respectively, across the two databases. Treatment rates of 10 of 11 selected parasitic infections (range, 0–56%) were significantly less than those for streptococcal pharyngitis and
Clostridioides difficile
(range, 65–85%); giardiasis treatment (64%) was comparable to
Clostridioides difficile
(65%) in patients using Medicaid. Treatment rates for patients with opisthorchiasis, clonorchiasis, and taeniasis were less than 10%. Although we could not verify that patients had active infections because of limitations inherent to claims data, including coding errors and the inability to review patients’ charts, these data suggest a need for improved treatment of parasitic infections. Further research is needed to verify the results and identify potential clinical and public health consequences.
By using a large, multicenter database, we investigated the characteristics and morbidities of 1591 children returning from 218 global destinations and presenting for care in 19 countries.
Data ...reported to the GeoSentinel Surveillance Network between January 1997 and November 2007 were analyzed, to assess demographic features, travel characteristics, and clinical diagnoses of ill pediatric travelers. Data were compared between children and adults and among 3 pediatric age groups (0-5 years, 6-11 years, and 12-17 years).
Children were predominantly tourist travelers returning from Asia, sub-Saharan Africa, or Latin America. Compared with adults, children disproportionately presented within 7 days after return, required hospitalization, lacked pretravel health advice, and had traveled for the purpose of visiting friends and relatives. Diarrhea (28%), dermatologic conditions (25%), systemic febrile illnesses (23%), and respiratory disorders (11%) accounted for the majority of diagnoses reported for children. No fatalities were reported. Diarrhea occurred disproportionately among children after exposure to the Middle East/North Africa, dermatologic conditions after exposure to Latin America, systemic febrile illnesses after exposure to sub-Saharan Africa or Asia, and respiratory disorders after exposure to Europe or North America. The proportionate morbidity rates of travel-associated diseases differed among the pediatric age groups and between children and adults.
The health care utilization patterns before and after travel and the profiles of travel-associated health problems differed between children and adults. Health professionals providing pretravel advice need to consider destination- and age-specific susceptibility to travel-related morbidities and develop prevention strategies accordingly.
Arthropod-associated diseases are a major cause of morbidity among travelers. Obtaining a detailed travel itinerary and understanding traveler-specific and destination-specific risk factors can help ...mitigate the risk of vector-borne diseases. DEET, picaridin, PMD, and IR3535 are insect repellents that offer sufficient protection against arthropod bites. IR3535 does not provide adequate protection against Anopheles mosquitoes, and should be avoided in malaria-endemic regions. General protective measures, such as bite avoidance, protective clothing, insecticide-treated bed nets, and insecticide-treated clothing, should be recommended, especially in malaria-endemic areas. Spatial repellents may prevent nuisance biting, but have not been shown to prevent against vector-borne disease.
This cross-sectional study examines the association of prices for drugs to treat hookworm and pinworm with prescribing and prescription-filling behaviors and total outpatient treatment costs.
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