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Decision making is a complex cognitive process that recruits a distributed network of brain regions, including the basolateral amygdala (BLA) and nucleus accumbens shell (NAcSh). Recent work suggests that communication between these structures, as well as activity of cells expressing dopamine (DA) D2 receptors (D2R) in the NAcSh, are necessary for some forms of decision making; however, the contributions of this circuit and cell population during decision making under risk of punishment are unknown. The current experiments addressed this question using circuit-specific and cell type-specific optogenetic approaches in rats during a decision making task involving risk of punishment. In experiment 1, Long-Evans rats received intra-BLA injections of halorhodopsin or mCherry (control) and in experiment 2, D2-Cre transgenic rats received intra-NAcSh injections of Cre-dependent halorhodopsin or mCherry. Optic fibers were implanted in the NAcSh in both experiments. Following training in the decision making task, BLA→NAcSh or D2R-expressing neurons were optogenetically inhibited during different phases of the decision process. Inhibition of the BLA→NAcSh during deliberation (the time between trial initiation and choice) increased preference for the large, risky reward (increased risk taking). Similarly, inhibition during delivery of the large, punished reward increased risk taking, but only in males. Inhibition of D2R-expressing neurons in the NAcSh during deliberation increased risk taking. In contrast, inhibition of these neurons during delivery of the small, safe reward decreased risk taking. These findings extend our knowledge of the neural dynamics of risk taking, revealing sex-dependent circuit recruitment and dissociable activity of selective cell populations during decision making. SIGNIFICANCE STATEMENT Until recently, the ability to dissect the neural substrates of decision making involving risk of punishment (risk taking) in a circuit-specific and cell-specific manner has been limited by the tools available for use in rats. Here, we leveraged the temporal precision of optogenetics, together with transgenic rats, to probe contributions of a specific circuit and cell population to different phases of risk-based decision making. Our findings reveal basolateral amygdala (BLA)→nucleus accumbens shell (NAcSh) is involved in evaluation of punished rewards in a sex-dependent manner. Further, NAcSh D2 receptor (D2R)-expressing neurons make unique contributions to risk taking that vary across the decision making process. These findings advance our understanding of the neural principles of decision making and provide insight into how risk taking may become compromised in neuropsychiatric diseases., (Copyright © 2023 the authors.)

While there is an evolving literature on the benefits of texting and patient-centered technologies, texting initiatives have not focused on family members. We sought to identify patients' family members' perspectives on facilitators and barriers to using 1 digital texting innovation to promote family-centered care during patients' hospitalizations. This qualitative study was conducted at a tertiary care center in Houston, consisting of 7 hospitals (1 academic hospital and 6 community hospitals), involving analyzation of 3137 comments from family members who used the digital texting technology. Thematic analysis methods were used. The data analysis for loved ones' feedback resulted in 4 themes as facilitators: (1) inpatient text messaging keeps loved ones updated and connected (n = 611); (2) inpatient text messaging allows for stronger continuity of communication (n = 69); (3) messaging promotes a sense of staff compassion and service (n = 245); and (4) messaging reduces phone calls (n = 65). The data analysis resulted in 4 themes as barriers to text messaging helpfulness: (1) messages could feel generic (n = 31); (2) inpatient texting was not needed if all loved ones were regularly at bedside (n = 6); (3) messages could have a perceived delay (n = 37); and (4) security features could impact convenience (n = 29). Our findings indicate that family members and loved ones value inpatient text messages, not only for the information the messages provide, but also because the act of writing text messages and preparing loved ones shows inclusiveness, compassion, and family-centered care., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

An important gap in the literature is how clinicians feel about patient-centered technologies and how clinicians experience patient-centered technologies in their workflows. Our goal was to identify clinician users' perspectives on facilitators (pros) and barriers (cons) to using 1 digital texting innovation to promote family centered care during patients' hospitalizations. This qualitative study was conducted at a tertiary care center in Houston, consisting of 7 hospitals (1 academic hospital and 6 community hospitals), involving analyzation of 3 focus groups of 18 physicians, 5 advanced practice providers, and 10 nurse directors and managers, as well as a content analysis of 156 real-time alerts signaling family dissatisfaction on the nursing unit/floor. Thematic analysis methods were used. We selected these participants by attending their regularly scheduled service-line meetings. Clinician feedback from focus groups resulted in 3 themes as facilitators : (a) texting platforms must be integrated within the electronic medical record; (b) texting reduces outgoing phone calls; (c) texting reduces incoming family phone calls. Clinician feedback resulted in 3 themes as barriers : (a) best practice alerts can be disruptive; (b) real-time alerts can create hopelessness; and (c) scale-up is challenging. The analyzation of facilitators (pros) and barriers (cons) pertains only to the clinician's feedback. We also analyzed real-time alerts signaling family dissatisfaction (defined as "service recovery escalation" throughout this manuscript). The most common selection for the source of family dissatisfaction, as reflected through the real-time alerts was, "I haven't heard from physicians enough," appearing in 52 out of 156 alerts (33%). The second most common selection for the source of dissatisfaction was "perceived inconsistent or incomplete information provided by team members," which was selected in 48 cases (31%). Our findings indicate that clinicians value inpatient texting, not only for its ability to quickly relay updates to multiple family members with 1 click, but also because, when used intentionally and meaningfully, texting decreases family phone calls., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Post-traumatic stress disorder (PTSD) develops in a subset of individuals exposed to a trauma with core features being increased anxiety and impaired fear extinction. To model the heterogeneity of PTSD behavioral responses, we exposed male Sprague-Dawley rats to predator scent stress once for 10 min and then assessed anxiety-like behavior 7 days later using the elevated plus maze and acoustic startle response. Rats displaying anxiety-like behavior in both tasks were classified as stress Susceptible, and rats exhibiting behavior no different from un-exposed Controls were classified as stress Resilient. In Resilient rats, we previously found increased mRNA expression of mGlu5 in the amygdala and prefrontal cortex (PFC) and CB1 in the amygdala. Here, we performed fluorescent in situ hybridization (FISH) to determine the subregion and cell-type-specific expression of these genes in Resilient rats 3 weeks after TMT exposure. Resilient rats displayed increased mGlu5 mRNA expression in the basolateral amygdala (BLA) and the infralimbic and prelimbic regions of the PFC and increased BLA CB1 mRNA. These increases were limited to glutamatergic cells. To test the necessity of mGlu5 for attenuating TMT-conditioned contextual fear 3 weeks after TMT conditioning, intra-BLA infusions of the mGlu5 negative allosteric modulator MTEP were administered prior to context re-exposure. In TMT-exposed Resilient rats, but not Controls, MTEP increased freezing on the day of administration, which extinguished over two additional un-drugged sessions. These results suggest that increased mGlu5 expression in BLA glutamate neurons contributes to the behavioral flexibility observed in stress-Resilient animals by facilitating a capacity for extinguishing contextual fear associations., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The diagnosis and prognosis of traumatic brain injury (TBI) is complicated by variability in the type and severity of injuries and the multiple endophenotypes that describe each patient's response and recovery to the injury. It has been challenging to capture the multiple dimensions that describe an injury and its recovery to provide clinically useful information. To address this challenge, we have performed an open-ended search for panels of microRNA (miRNA) biomarkers, packaged inside of brain-derived extracellular vesicles (EVs), that can be combined algorithmically to accurately classify various states of injury. We mapped GluR2+ EV miRNA across a variety of injury types, injury intensities, history of injuries, and time elapsed after injury, and sham controls in a pre-clinical murine model ( n  = 116), as well as in clinical samples ( n  = 36). We combined next-generation sequencing with a technology recently developed by our lab, Track Etched Magnetic Nanopore (TENPO) sorting, to enrich for GluR2+ EVs and profile their miRNA. By mapping and comparing brain-derived EV miRNA between various injuries, we have identified signaling pathways in the packaged miRNA that connect these biomarkers to underlying mechanisms of TBI. Many of these pathways are shared between the pre-clinical model and the clinical samples, and present distinct signatures across different injury models and times elapsed after injury. Using this map of EV miRNA, we applied machine learning to define a panel of biomarkers to successfully classify specific states of injury, paving the way for a prognostic blood test for TBI. We generated a panel of eight miRNAs (miR-150-5p, miR-669c-5p, miR-488-3p, miR-22-5p, miR-9-5p, miR-6236, miR-219a.2-3p, miR-351-3p) for injured mice versus sham mice and four miRNAs (miR-203b-5p, miR-203a-3p, miR-206, miR-185-5p) for TBI patients versus healthy controls.

Background: Despite the growth of and media hype about mobile health (mHealth), there is a paucity of literature supporting the effectiveness of widespread implementation of mHealth technologies., Objective: This study aimed to assess whether an innovative mHealth technology system with several overlapping purposes can impact (1) clinical outcomes (ie, readmission rates, revisit rates, and length of stay) and (2) patient-centered care outcomes (ie, patient engagement, patient experience, and patient satisfaction)., Methods: We compared all patients (2059 patients) of participating orthopedic surgeons using mHealth technology with all patients of nonparticipating orthopedic surgeons (2554 patients). The analyses included Wilcoxon rank-sum tests, Kruskal-Wallis tests for continuous variables, and chi-square tests for categorical variables. Logistic regression models were performed on categorical outcomes and a gamma-distributed model for continuous variables. All models were adjusted for patient demographics and comorbidities., Results: The inpatient readmission rates for the nonparticipating group when compared with the participating group were higher and demonstrated higher odds ratios (ORs) for 30-day inpatient readmissions (nonparticipating group 106/2636, 4.02% and participating group 54/2048, 2.64%; OR 1.48, 95% CI 1.03 to 2.13; P=.04), 60-day inpatient readmissions (nonparticipating group 194/2636, 7.36% and participating group 85/2048, 4.15%; OR 1.79, 95% CI 1.32 to 2.39; P<.001), and 90-day inpatient readmissions (nonparticipating group 261/2636, 9.90% and participating group 115/2048, 5.62%; OR 1.81, 95% CI 1.40 to 2.34; P<.001). The length of stay for the nonparticipating cohort was longer at 1.90 days, whereas the length of stay for the participating cohort was 1.50 days (mean 1.87, SD 2 vs mean 1.50, SD 1.37; P<.001). Patients treated by participating surgeons received and read text messages using mHealth 83% of the time and read emails 84% of the time. Patients responded to 60% of the text messages and 53% of the email surveys. Patients were least responsive to digital monitoring questions when the hospital asked them to do something, and they were most engaged with emails that did not require action, including informational content. A total of 96% (558/580) of patients indicated high satisfaction with using mHealth technology to support their care. Only 0.40% (75/2059) patients opted-out of the mHealth technology program after enrollment., Conclusions: A novel, multicomponent, pathway-driven, patient-facing mHealth technology can positively impact patient outcomes and patient-reported experiences. These technologies can empower patients to play a more active and meaningful role in improving their outcomes. There is a deep need, however, for a better understanding of the interactions between patients, technology, and health care providers. Future research is needed to (1) help identify, address, and improve technology usability and effectiveness; (2) understand patient and provider attributes that support adoption, uptake, and sustainability; and (3) understand the factors that contribute to barriers of technology adoption and how best to overcome them., (©Courtenay R Bruce, Patricia Harrison, Tariq Nisar, Charlie Giammattei, Neema M Tan, Caitlin Bliven, Jamie Shallcross, Aroub Khleif, Nhan Tran, Sayali Kelkar, Noreen Tobias, Ana E Chavez, Dana Rivera, Angela Leong, Angela Romano, S Nicholas Desai, Josh R Sol, Kayla Gutierrez, Christopher Rappel, Eric Haas, Feibi Zheng, Kwan J Park, Stephen Jones, Paul Barach, Roberta Schwartz. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 26.06.2020.)

Post-traumatic stress disorder (PTSD) currently has no FDA-approved treatments that reduce symptoms in the majority of patients. The ability to extinguish fear memory associations is impaired in PTSD individuals. As such, the development of extinction-enhancing pharmacological agents to be used in combination with exposure therapies may benefit the treatment of PTSD. Both mGlu5 and CB1 receptors have been implicated in contextual fear extinction. Thus, here we tested the ability of the mGlu5 positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and cannabidiol (CBD) to reduce both conditioned and unconditioned fear. We used a predator-threat animal model of PTSD which we and others have previously shown to capture the heterogeneity of anxiety responses observed in humans exposed to trauma. Here, 1 week following a 10-min exposure to predator scent stress, rats were classified into stress-Susceptible and stress-Resilient phenotypes using behavioral criteria for elevated plus maze and acoustic startle response performance. Two weeks after classification, rats underwent 3 days of contextual fear extinction and were treated with vehicle, CDPPB or CBD prior to each session. Finally, the light-dark box test was employed to assess phenotypic differences and the effects of CDPPB and CBD on unconditioned anxiety. CDPBB but not CBD, reduced freezing in Susceptible rats relative to vehicle. In the light-dark box test for unconditioned anxiety, CBD, but not CDPPB, reduced anxiety in Susceptible rats. Resilient rats displayed reduced anxiety in the light-dark box relative to Susceptible rats. Taken together, the present data indicate that enhancement of mGlu5 receptor signaling in populations vulnerable to stress may serve to offset a resistance to fear memory extinction without producing anxiogenic effects. Furthermore, in a susceptible population, CBD attenuates unconditioned but not conditioned fear. Taken together, these findings support the use of predator-threat stress exposure in combination with stress-susceptibility phenotype classification as a model for examining the unique drug response profiles and altered neuronal function that emerge as a consequence of the heterogeneity of psychophysiological response to stress.

Cocaine use disorder (CUD) is associated with prefrontal cortex dysfunction and cognitive deficits that may contribute to persistent relapse susceptibility. As the relationship between cognitive deficits, cortical abnormalities and drug seeking is poorly understood, development of relevant animal models is of high clinical importance. Here, we used an animal model to characterize working memory and reversal learning in rats with a history of extended access cocaine self-administration and prolonged abstinence. We also investigated immediate and long-term functional changes within the prelimbic cortex (PrL) in relation to cognitive performance and drug-seeking. Adult male rats underwent 6 days of short-access (1 h/day) followed by 12 days of long-access (6 h/day) cocaine self-administration, or received passive saline infusions. Next, rats were tested in delayed match-to-sample (DMS) and (non)match-to-sample (NMS) tasks, and finally in a single context + cue relapse test on day 90 of abstinence. We found that a history of chronic cocaine self-administration impaired working memory, though sparing reversal learning, and that the components of these cognitive measures correlated with later drug-seeking. Further, we found that dysregulated metabolic activity and mGlu5 receptor signaling in the PrL of cocaine rats correlated with past working memory performance and/or drug-seeking, as indicated by the analysis of cytochrome oxidase reactivity, mGlu5 and Homer 1b/c protein expression, as well as Arc mRNA expression in mGlu5-positive cells. These findings advocate for a persistent post-cocaine PrL dysfunction, rooted in ineffective compensatory changes and manifested as impaired working memory performance and hyperreactivity to cocaine cues. Considering the possible interplay between the neural correlates underlying post-cocaine cognitive deficits and drug-seeking, cognitive function should be evaluated and considered when developing neurobiologically-based treatments of cocaine relapse., (Copyright © 2019 Elsevier Inc. All rights reserved.)

PTSD is highly comorbid with cocaine use disorder (CUD), and cocaine users with PTSD + CUD are more resistant to treatment. Here we sought to develop a rat model of PTSD + CUD in order to identify the neurobiological changes underlying such comorbidity and screen potential medications for reducing cocaine seeking in the PTSD population. We utilized a predator scent stress model of PTSD, wherein rats received a single exposure to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). One week after TMT exposure, stress-susceptible (susceptible), intermediate, and resilient phenotypes were detected and were consistent with behavioral, corticosterone, and gene expression profiles 3 weeks post TMT. We assessed phenotypic differences in cocaine self-administration, extinction, and cue-primed reinstatement. Susceptible rats exhibited deficits in extinction learning and increased cue-primed reinstatement that was not prevented by Ceftriaxone, an antibiotic that consistently attenuates the reinstatement of cocaine seeking. TMT-exposed resilient rats displayed increased mGlu5 gene expression in the amygdala and medial prefrontal cortex and did not display the enhanced cocaine seeking observed in susceptible rats. Combined treatment with the mGlu5 positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1 H-pyrazol-5-yl)benzamide (CDPPB), fear extinction, and ceftriaxone prevented the reinstatement of cocaine seeking in susceptible rats with fear extinction an important mediating condition. These results highlight the need for animal models of PTSD to consider stress-responsivity, as only a subset of trauma-exposed individuals develop PTSD and these individuals likely exhibit distinct neurobiological changes compared with trauma-exposed populations who are resilient to stress. This work further identifies glutamate homeostasis and mGlu5 as a target for treating relapse in comorbid PTSD-cocaine addiction.

Background: Recently, measurement of RNA at single cell resolution has yielded surprising insights. Methods for single-cell RNA sequencing (scRNA-seq) have received considerable attention, but the broad reliability of single cell methods and the factors governing their performance are still poorly known., Results: Here, we conducted a large-scale control experiment to assess the transfer function of three scRNA-seq methods and factors modulating the function. All three methods detected greater than 70% of the expected number of genes and had a 50% probability of detecting genes with abundance greater than 2 to 4 molecules. Despite the small number of molecules, sequencing depth significantly affected gene detection. While biases in detection and quantification were qualitatively similar across methods, the degree of bias differed, consistent with differences in molecular protocol. Measurement reliability increased with expression level for all methods and we conservatively estimate measurements to be quantitative at an expression level greater than ~5-10 molecules., Conclusions: Based on these extensive control studies, we propose that RNA-seq of single cells has come of age, yielding quantitative biological information.

There is now a greater choice of immunosuppressive agents that can be used in the care of kidney transplant patients. Concordance with treatment regimens is of prime importance and nurses working with this patient group have a key role in encouraging adherence to medication and helping patients to achieve a good quality of life.

In this study, we have examined the feasibility of immunisation against measles with plasmid DNA administered by the oral route. After the oral administration, in two 50 microg doses, of poly(DL-lactide-co-glycolide) (PLGA)-encapsulated DNA expressing measles virus nucleoprotein, increasing titres of N-specific serum IgG antibodies were observed in three of ten C3H/He mice over a period of three months. In comparison, oral vaccination of mice with a replication-defective recombinant adenovirus expressing the same transgene induced serum IgG in all animals tested. We also obtained preliminary indication of adjuvant-like activity of PLGA particles when coadministered intraperitoneally (i.p.) with naked plasmid DNA. These experiments demonstrate that oral delivery of either PLGA-encapsulated plasmid DNA or viral vectored DNA is capable of eliciting strong immune responses in mice. We propose that oral administration of biodegradable microparticles offers a novel strategy for future vaccine design for the safe delivery of DNA to mucosal surfaces.

This paper reports a naturally occurring case of meningoencephalitis associated with Listeria innocua in a Polled-Dorset ewe. The ewe was one of a housed group of twenty-five, fed ad lib. on wrapped baled silage. L. innocua was isolated after one week from cold enrichment culture of brain and pituitary tissue. Its identity was confirmed by conventional biochemical tests, API Listeria (BioMerieux UK Ltd), the absence of hly and prfA genes using PCR assay and sequencing two variable regions of 16S rDNA. Histological examination demonstrated lesions of vasculitis and perivascular cuffing in the midbrain which were consistent with listeriosis although limited in distribution and severity.

The fluorogenic redox indicator 5-cyano-2,3-ditolyltetrazolium chloride (CTC) was compared with the chromogenic p-iodonitrotetrazolium violet (INT) and conventional methods to assess cellular viability. Mild heat treatment was used as well-controlled method for producing non-viable and sub-lethally injured cells. CTC gave an underestimation of the viability of Listeria monocytogenes cells when compared with classical plating methods whereas INT gave an overestimation. However, CTC proved to be a sensitive indicator of uninjured cells. The difference between the total count and the CTC count was equivalent to the injured cell population. The fluorescent formazan formed on reduction of CTC was readily detected with a charge coupled device and cells enumerated automatically using image analysis.

The relationship between viability assessed by plate counts and detectability by gene probe-polymerase chain reaction (PCR) techniques was examined with cells of Escherichia coli and Listeria monocytogenes previously exposed to a range of stress treatments. In all cases the organisms were detectable by PCR after plate counts had declined to zero. Treatment with acid or hydrogen peroxide caused loss of PCR soon after viability was lost, but strong PCR signals were obtained from starved or desiccated cells long after cells became non-viable. Exposure to temperatures up to 100 degrees C had little effect on detection by PCR and even autoclaving cells at 121 degrees C for 15 min failed to abolish PCR detection completely. There is thus no simple relationship between viability and detectability by PCR. Detection of pathogens by PCR in environmental monitoring requires additional evidence of viability before risk can be properly assessed.

Phylogenetic studies were performed on some Gram-positive catalase-negative cocci from human clinical sources of uncertain taxonomic position. 16S rRNA sequence analysis demonstrated that the isolates represent a hitherto unknown line of descent within the low G+C Gram-positive bacteria for which the name Globicatella sanguis gen.nov., sp.nov. is proposed.

The impact of corticosteroids on host defense processes has been studied frequently because of its obvious clinical significance in many surgical patients. A technique that quantifies intraleukocyte iodination was used to measure polymorphonuclear leukocyte phagocytosis in heat inactivated and nonheat inactivated sera in the presence of two different corticosteroids: hydrocortisone sodium phosphate (HSP) and methylprednisolone sodium succinate (MSS). HSP produced a significant reduction in phagocytosis in the cells of healthy subjects when both heat inactivated autologous and isologous serum samples were used. MSS showed no such effect. Conversely, MSS produced a significant reduction in phagocytosis in the cells of healthy subjects when nonheat inactivated autologous serum was used but not when isologous serum was used. These data generally tend to confirm previous studies suggesting that MSS is less deleterious to some host defense processes than HSP and may be the steroid of choice when infection threatens the recipient.