County-level surveillance for the lone star tick, Amblyomma americanum, and its associated pathogen, Ehrlichia chaffeensis, in Kentucky.

Kentucky experiences some of the highest incidence rates for ehrlichiosis nationwide. Ehrlichiosis is a bacterial infection caused primarily by the pathogen Ehrlichia chaffeensis and can be transmitted to humans through the bite of an infected tick, notably Amblyomma americanum. Amblyomma americanum, the lone star tick, is common to Kentucky and much of the southeast, but has expanded farther north in recent years. As an abundant and aggressive nondiscriminatory biter, this species is of major public health concern for transmission of pathogens to humans. As this vector's range expands, surveillance remains a necessary tool providing data that allows researchers to track this expansion over time. The historical information on tick distribution in Kentucky is variable with very little data on a statewide scale. From January 2019 to December 2020, we conducted surveillance for A. americanum in Kentucky through field collections and the establishment of a statewide tick submission program with the help of the Kentucky Department for Public Health and screened for E. chaffeensis on a county-level throughout the state. We collected 5,726 A. americanum ticks in 77 counties and detected E. chaffeensis in 32 counties. The minimum infection rate was 1.8%. With the expansion of A. americanum and increasing cases of tick-borne diseases, future surveillance is needed to monitor this important tick vector over time.

Mapping distributions of the Lyme disease vector, Ixodes scapularis, and spirochete, Borrelia burgdorferi, in Kentucky using passive and active surveillance.

Lyme disease is the most common tick-borne illness in the United States and is becoming more prevalent each year. It is transmitted to humans and animals through the bites of Ixodes scapularis ticks infected with Borrelia burgdorferi in the eastern United States, I. pacificus in the western U.S, and I. ricinus in Europe and Asia. In Kentucky, where Lyme disease is non-endemic, the number of reported human cases in 2010 totaled five. In 2019, that number had increased by over 300%. Identifying the distribution of I. scapularis populations infected with B. burgdorferi is important data for effective prevention strategies and an important first step in monitoring disease spread. In collaboration with the Kentucky Department for Public Health, we performed surveillance for I. scapularis throughout the state of Kentucky using both active and passive surveillance methods. Diagnostic testing for the identification of B. burgdorferi (sensu stricto) was also conducted. We identified 457 I. scapularis ticks from March 2019 to December 2020 from 32 counties in Kentucky. B. burgdorferi was detected in I. scapularis populations collected from 14 different counties. These results add to the little data that exists in Kentucky on I. scapularis and B. burgdorferi distribution.

Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning.

An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning.

Preliminary study of themes of meaning and psychosocial service use among informal cancer caregivers.

OBJECTIVE: The burden experienced by informal caregivers (ICs) of patients with advanced cancer is well documented. ICs are at risk for anxiety and depression, as well as existential concerns that arise when a loved one is facing a terminal illness. Few psychosocial interventions focus on existential concerns of ICs. However, a growing body of literature indicates that finding meaning in the experience of being an IC for a person with cancer has the potential to buffer against burden. The purpose of this study was to collect preliminary descriptive data regarding caregiver burden, meaning, and psychosocial service use to inform the adaptation of a meaning-centered intervention for ICs. METHOD: Twenty-five caregivers and 32 patients completed brief, anonymous questionnaires that asked about their role as a caregiver or their perception of their loved one as a caregiver, caregiver burden, and psychosocial service use. RESULTS: Caregivers and patients identified anxiety and depression as top correlates of burden experienced by caregivers, whereas guilt, issues with role/sense of identity, and self-care were additional areas of concern. The majority of caregivers were not receiving psychosocial services, although they almost unanimously reported desiring services. A greater proportion of patients than caregivers believed that an intervention designed to enhance meaning would ameliorate burden, but, nevertheless, close to three quarters of caregivers reported interest in participating in such an intervention. SIGNIFICANCE OF RESULTS: These study findings provide further support for, at a minimum, engaging ICs of persons with advanced cancer in interventions that address existential issues, mental health, self-care, and service use. Such interventions are likely to improve the quality of life of both patients with cancer and their ICs.

Sandmeyer reaction repurposed for the site-selective, non-oxidizing radioiodination of fully-deprotected peptides: studies on the endogenous opioid peptide α-neoendorphin.

Standard radioiodination methods lack site-selectivity and either mask charges (Bolton-Hunter) or involve oxidative reaction conditions (chloramine-T). Opioid peptides are very sensitive to certain structural modifications, making these labeling methods untenable. In our model opioid peptide, α-neoendorphin, we replaced a tyrosyl hydroxyl with an iodine, and in cell lines stably expressing mu, delta, or kappa opioid receptors, we saw no negative effects on binding. We then optimized a repurposed Sandmeyer reaction using copper(I) catalysts with non-redoxing/non-nucleophilic ligands, bringing the radiochemical yield up to around 30%, and site-selectively incorporated radioactive iodine into this position under non-oxidizing reaction conditions, which should be broadly compatible with most peptides. The (125)I- and (131)I-labeled versions of the compound bound with high affinity to opioid receptors in mouse brain homogenates, thus demonstrating the general utility of the labeling strategy and of the peptide for exploring opioid binding sites.

Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated µ opioid receptor (MOR-1) splice variants.

3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogues were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3'or 4' position of the phenyl ring, and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower δ opioid receptor affinity than its naltrexamine analogue, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence, and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity.