AI in Healthcare: Implications for Family Medicine and Primary Care

Artificial Intelligence (AI) has begun to transform industries including healthcare. Unfortunately, Primary Care and the discipline of Family Medicine have tended to lag behind in the implementation of this novel technology. Although the relationship between Family Medicine and AI is in its infancy greater engagement from Primary Care Physician’s (PCP’s) is a must due to the increasing shortage of practitioners. AI has the chance to overturn this problem as well as speed up its development. Considering the vast majority of PCP’s utilize Electronic Medical Records (EMR’s) the field is ripe for innovation. Regrettably, much of the information available remains unused for practice disruption. Primary Care offers a large data platform that can be leveraged with the use of technology to deliver ground-breaking trails forward to provide better comprehensive care for a wide-variety of patients from various backgrounds. The purpose of this chapter is to provide context to AI implementation as it relates to Primary Care and the practice of Family Medicine

Characterization of a far-red analog of ghrelin for imaging GHS-R in P19-derived cardiomyocytes.

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as measured in HEK293 cells overexpressing GHS-R1a was within an order of magnitude of that of fluorescein-ghrelin and native human ghrelin, while the des-acyl Cy5-ghrelin did not bind GHS-R1a. Live cell imaging in HEK293/GHS-R1a cells showed cell surface labeling that was displaced by excess ghrelin. Interestingly, Cy5-ghrelin, but not the des-acyl analog, showed concentration-dependent binding in mouse heart tissue sections. We then used Cy5-ghrelin to track GHS-R expression in P19-derived cardiomyocytes. Live cell imaging at different time points after DMSO-induced differentiation showed that GHS-R expression preceded that of the differentiation marker aMHC and tracked with the contractility marker SERCA 2a. Our far-red analog of ghrelin adds to the tools we are developing to map GHS-R in developing and diseased cardiac tissues

Viral Response to Chemotherapy in Endemic Burkitt Lymphoma

Some Epstein-Barr virus (EBV)-directed therapies are predicted to be effective only when lytic viral replication occurs. We studied whether cyclophosphamide chemotherapy induces EBV to switch from latent to lytic phases of infection in a series of EBV-associated Burkitt lymphomas

The Synaptic Vesicle Glycoprotein 2: Structure, Function, and Disease Relevance.

The synaptic vesicle glycoprotein 2 (SV2) family is comprised of three paralogues: SV2A, SV2B, and SV2C. In vertebrates, SV2s are 12-transmembrane proteins present on every secretory vesicle, including synaptic vesicles, and are critical to neurotransmission. Structural and functional studies suggest that SV2 proteins may play several roles to promote proper vesicular function. Among these roles are their potential to stabilize the transmitter content of vesicles, to maintain and orient the releasable pool of vesicles, and to regulate vesicular calcium sensitivity to ensure efficient, coordinated release of the transmitter. The SV2 family is highly relevant to human health in a number of ways. First, SV2A plays a role in neuronal excitability and as such is the specific target for the antiepileptic drug levetiracetam. SV2 proteins also act as the target by which potent neurotoxins, particularly botulinum, gain access to neurons and exert their toxicity. Both SV2B and SV2C are increasingly implicated in diseases such as Alzheimer\u27s disease and Parkinson\u27s disease. Interestingly, despite decades of intensive research, their exact function remains elusive. Thus, SV2 proteins are intriguing in their potentially diverse roles within the presynaptic terminal, and several recent developments have enhanced our understanding and appreciation of the protein family. Here, we review the structure and function of SV2 proteins as well as their relevance to disease and therapeutic development

Assessing Vesicular Monoamine Transport and Toxicity Using Fluorescent False Neurotransmitters

This manuscript outlines a high-throughput 96-well plate assay to measure the vesicular uptake of the false fluorescent neurotransmitter FFN206 by the vesicular monoamine transporter 2 (VMAT2) in near real-time and following pharmacological and environmental toxicant exposure in HEK293 cells

Image_1.TIF

<p>It has long been recognized that olfaction and emotion are linked. While chemosensory research using both human and rodent models have indicated a change in emotion can contribute to olfactory dysfunction, there are few studies addressing the contribution of olfaction to a modulation in emotion. In mice, olfactory deficits have been linked with heightened anxiety levels, suggesting that there could be an inverse relationship between olfaction and anxiety. Furthermore, increased anxiety is often co-morbid with psychiatric conditions such as attention disorders. Our study aimed to investigate the roles of olfaction in modulating anxiety. Voltage-gated potassium ion channel Kv1.3 knockout mice (Kv1.3−/−), which have heightened olfaction, and wild-type (WT) mice were examined for anxiety-like behaviors using marble burying (MB), light-dark box (LDB) and elevated-plus maze (EPM) tests. Because Kv1.3−/− mice have increased locomotor activity, inattentive and hyperactive behaviors were quantified for both genotypes. Kv1.3−/− mice showed increased anxiety levels compared to their WT counterparts and administration of methylphenidate (MPH) via oral gavage alleviated their increased anxiety. Object-based attention testing indicated young and older Kv1.3−/− mice had attention deficits and treatment with MPH also ameliorated this condition. Locomotor testing through use of a metabolic chamber indicated that Kv1.3−/− mice were not significantly hyperactive and MPH treatment failed to modify this activity. Our data suggest that heightened olfaction does not necessarily lead to decreased anxiety levels, and that Kv1.3−/− mice may have behaviors associated with inattentiveness.</p

A new look at species composition and distribution of invasive Dreissena mussels in the lower St. Louis River and Lake Superior

Presented at the 2024 St. Louis River Summit on 03/06/2024Search for CCTE records in EPA’s Science Inventory by typing in the title at this link.https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25</p

Data from: Vesicular monoamine transporter 2 (VMAT2) level regulates MPTP vulnerability and clearance of excess dopamine in mouse striatal terminals

The vesicular monoamine transporter 2 (VMAT2) packages neurotransmitters for release during neurotransmission and sequesters toxicants into vesicles to prevent neuronal damage. In mice, low VMAT2 levels causes catecholaminergic cell loss and behaviors resembling Parkinson’s disease, while high levels of VMAT2 increase dopamine release and protect against dopaminergic toxicants. However, comparisons across these VMAT2 mouse genotypes were impossible due to the differing genetic background strains of the animals. Following back-crossing to a C57BL/6 line, we confirmed that mice with approximately 95% lower VMAT2 levels compared with wild-type (VMAT2-LO) display significantly reduced vesicular uptake, progressive dopaminergic terminal loss with aging, and exacerbated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. Conversely, VMAT2-overexpressing mice (VMAT2-HI) are protected from the loss of striatal terminals following MPTP treatment. We also provide evidence that enhanced vesicular filling in the VMAT2-HI mice modifies the handling of newly synthesized dopamine, indicated by changes in indirect measures of extracellular dopamine clearance. These results confirm the role of VMAT2 in the protection of vulnerable nigrostriatal dopamine neurons and may also provide new insight into the side effects of L-DOPA treatments in Parkinson’s disease