Investigation of Molecular Mechanism of Chronic Pain in the Anterior Cingulate Cortex Using Genetically Engineered Mice

Recent advances into the understanding of molecular mechanism of chronic pain have been largely developed through the use of genetic manipulations. This is in part due to the scarcity of selective pharmacological tools, which can be readily solved by creating knockout or transgenic mice. By identifying new genes that are of import, our efforts can then be aimed at studying relevant signaling pathways, and combination of pharmacological manipulations with genetic models can be used to further examine the specific mechanisms involved in chronic pain. In this review, we will examine the genetic models that are currently in use to study chronic pain in the anterior cingulate cortex: knockout mice; transgenic mice; and the strength of combining pharmacology with these genetic models

The Potential Trajectory of Carbapenem-Resistant Enterobacteriaceae, an Emerging Threat to Health-Care Facilities, and the Impact of the Centers for Disease Control and Prevention Toolkit.

Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County health-care facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half

Role of Dendritic Cells in Differential Susceptibility to Viral Demyelinating Disease

Although persistent viral diseases are a global health concern, the mechanisms of differential susceptibility to such infections among individuals are unknown. Here, we report that differential interactions between dendritic cells (DCs) and virus are critical in determining resistance versus susceptibility in the Theiler murine encephalomyelitis virus–induced demyelinating disease model of multiple sclerosis. This virus induces a chronic demyelinating disease in susceptible mice, whereas the virus is completely cleared in resistant strains of mice. DCs from susceptible mice are more permissive to viral infection, resulting in severe deficiencies in development, expansion, and function, in contrast to DCs from resistant mice. Although protective prior to viral infection, higher levels of type I interferons (IFNs) and IFN-γ produced by virus-infected DCs from susceptible mice further contribute to the differential inhibition of DC development and function. An increased DC number and/or acquired resistance of DCs to viral infection render susceptible mice resistant to viral persistence and disease progression. Thus, the differential permissiveness of DCs to infectious agents and its subsequent functional and developmental deficiencies determine the outcome of infection- associated diseases. Therefore, arming DCs against viral infection–induced functional decline may provide a useful intervention for chronic infection-associated diseases

Comparison of opioid prescribing by dentists in the United States and England

Importance: The United States consumes most of the opioids worldwide despite representing a small portion of the world\u27s population. Dentists are one of the most frequent US prescribers of opioids despite data suggesting that nonopioid analgesics are similarly effective for oral pain. While oral health and dentist use are generally similar between the United States and England, it is unclear how opioid prescribing by dentists varies between the 2 countries. Objective: To compare opioid prescribing by dentists in the United States and England. Design, Setting, and Participants: Cross-sectional study of prescriptions for opioids dispensed from outpatient pharmacies and health care settings between January 1 and December 31, 2016, by dentists in the United States and England. Data were analyzed from October 2018 to January 2019. Exposures: Opioids prescribed by dentists. Main Outcomes and Measures: Proportion and prescribing rates of opioid prescriptions. Results: In 2016, the proportion of prescriptions written by US dentists that were for opioids was 37 times greater than the proportion written by English dentists. In all, 22.3% of US dental prescriptions were opioids (11.4 million prescriptions) compared with 0.6% of English dental prescriptions (28 082 prescriptions) (difference, 21.7%; 95% CI, 13.8%-32.1%; P \u3c .001). Dentists in the United States also had a higher number of opioid prescriptions per 1000 population (35.4 per 1000 US population [95% CI, 25.2-48.7 per 1000 population] vs 0.5 per 1000 England population [95% CI, 0.03-3.7 per 1000 population]) and number of opioid prescriptions per dentist (58.2 prescriptions per dentist [95% CI, 44.9-75.0 prescriptions per dentist] vs 1.2 prescriptions per dentist [95% CI, 0.2-5.6 prescriptions per dentist]). While the codeine derivative dihydrocodeine was the sole opioid prescribed by English dentists, US dentists prescribed a range of opioids containing hydrocodone (62.3%), codeine (23.2%), oxycodone (9.1%), and tramadol (4.8%). Dentists in the United States also prescribed long-acting opioids (0.06% of opioids prescribed by US dentists [6425 prescriptions]). Long-acting opioids were not prescribed by English dentists. Conclusions and Relevance: This study found that in 2016, dentists in the United States prescribed opioids with significantly greater frequency than their English counterparts. Opioids with a high potential for abuse, such as oxycodone, were frequently prescribed by US dentists but not prescribed in England. These results illustrate how 1 source of opioids differs substantially in the United States vs England. To reduce dental opioid prescribing in the United States, dentists could adopt measures similar to those used in England, including national guidelines for treating dental pain that emphasize prescribing opioids conservatively

Behavioral Deficits and Axonal Injury Persistence after Rotational Head Injury Are Direction Dependent

Pigs continue to grow in importance as a tool in neuroscience. However, behavioral tests that have been validated in the rodent model do not translate well to pigs because of their very different responses to behavioral stimuli. We refined metrics for assessing porcine open field behavior to detect a wide spectrum of clinically relevant behaviors in the piglet post-traumatic brain injury (TBI). Female neonatal piglets underwent a rapid non-impact head rotation in the sagittal plane (n=8 evaluable) or were instrumented shams (n=7 evaluable). Open field testing was conducted 1 day prior to injury (day −1) in order to establish an individual baseline for analysis, and at days +1 and +4 after injury. Animals were then killed on day +6 after injury for neuropathological assessment of axonal injury. Injured piglets were less interested in interacting with environmental stimuli and had a lower activity level than did shams. These data were compared with previously published data for axial rotational injuries in neonatal piglets. Acute behavioral outcomes post-TBI showed a dependence on the rotational plane of the brain injury, with animals with sagittal injuries demonstrating a greater level of inactivity and less random usage of the open field space than those with axial injuries. The persistence of axonal injury is also dependent on the rotational plane, with sagittal rotations causing more prolonged injuries than axial rotations. These results are consistent with animal studies, finite element models, and studies of concussions in football, which have all demonstrated differences in injury severity depending upon the direction of head impact rotation

Slow Pathway Ablation for Atrioventricular Nodal Reentry Using a Right Internal Jugular Vein Approach: A Case Series

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74747/1/j.1540-8159.2006.00292.x.pd

Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex

Functional human brain imaging studies have indicated the essential role of cortical regions, such as the anterior cingulate cortex (ACC), in romantic love and sex. However, the neurobiological basis of how the ACC neurons are activated and engaged in sexual attraction remains unknown. Using transgenic mice in which the expression of green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos, we found that ACC pyramidal neurons are activated by sexual attraction. The presynaptic glutamate release to the activated neurons is increased and pharmacological inhibition of neuronal activities in the ACC reduced the interest of male mice to female mice. Our results present direct evidence of the critical role of the ACC in sexual attraction, and long-term increases in glutamate mediated excitatory transmission may contribute to sexual attraction between male and female mice