Evaluation of Abbott ID NOW COVID-19 POC test performance characteristics and integration in the regional health network workflows to improve health care delivery.

With the recent global surge of SARS-CoV-2 Delta variant, there continues to be high demand for COVID-19 diagnostic testing. Abbott ID NOW is a rapid, CLIA-waived, COVID-19 diagnostic test ideally suited for use in urgent care settings or where access to diagnostic testing is limited. In this study we describe the results of rigorous validation of ID NOW and post-implementation study of POC test utilization patterns within community hospitals and clinics. Performance of ID NOW was validated by comparison of the results from 207 consecutive, paired, specimens tested on the ID NOW and on the m2000/Alinity m platforms. Once validated, ID NOW devices were placed for clinical use at four regional hospitals and clinics. We found that the ID NOW and m2000/Alinity m positive and negative percent agreement were 94.5% (95% CI, 85.1% to 98.1%) and 99.3% (95% CI, 96.4% to 99.9%), respectively. As of August 2021, a total of 2,301 tests were performed by ID NOW at individual regional network sites. The population tested consisted of 55.5% White and 42.9% Black patients, with Black patients presenting predominantly in the hospitals, while White patients were more evenly distributed between hospital and clinic sites. Disease prevalence observed among patients tested by ID NOW (12.3%) was aligned with overall prevalence seen at regional sites (11.3%). In summary, the ID NOW test can provide rapid and accurate results in a variety of near-to-patient and POC settings. If used correctly, it could serve as a valuable diagnostic tool to enable equal access to care and improve healthcare delivery within large health network systems.

Molecular profile and response to energy deficit of leptin-receptor neurons in the lateral hypothalamus.

Leptin exerts its effects on energy balance by inhibiting food intake and increasing energy expenditure via leptin receptors in the hypothalamus. While LepR neurons in the arcuate nucleus of the hypothalamus, the primary target of leptin, have been extensively studied, LepR neurons in other hypothalamic nuclei remain understudied. LepR neurons in the lateral hypothalamus contribute to leptin's effects on food intake and reward, but due to the low abundance of this population it has been difficult to study their molecular profile and responses to energy deficit. We here explore the transcriptome of LepR neurons in the LH and their response to energy deficit. Male LepR-Cre mice were injected in the LH with an AAV carrying Cre-dependent L10:GFP. Few weeks later the hypothalami from fed and food-restricted (24-h) mice were dissected and the TRAP protocol was performed, for the isolation of translating mRNAs from LepR cells in the LH, followed by RNA sequencing. After mapping and normalization, differential expression analysis was performed with DESeq2. We confirm that the isolated mRNA is enriched in LepR transcripts and other known neuropeptide markers of LepRLH neurons, of which we investigate the localization patterns in the LH. We identified novel markers of LepRLH neurons with association to energy balance and metabolic disease, such as Acvr1c, Npy1r, Itgb1, and genes that are differentially regulated by food deprivation, such as Fam46a and Rrad. Our dataset provides a reliable and extensive resource of the molecular makeup of LH LepR neurons and their response to food deprivation.

Using the Isolated Rat Placenta to Assess Fetoplacental Hemodynamics.

Placental health is critical to fetal growth and maternal health during gestation. However, investigating placental flow in an ex-vivo isolated system where inflow is independently controlled has yet to be developed in the rat. Here, we describe a novel technique, isolated perfused placenta technique that allows for analysis of placental pressure outflow pressure, placental flow in rats at gestational day 20. Using this method, we successfully perfused placentas from dams and were able to observe increases in outflow pressure and flow as the inflow pressure to the placenta was increased in a step wise fashion. This method will help to advance the functional analysis of placental flow and therefore placental resistance and efficiency.

Incentive value and spatial certainty combine additively to determine visual priorities.

How does the brain combine information predictive of the value of a visually guided task (incentive value) with information predictive of where task-relevant stimuli may occur (spatial certainty)? Human behavioural evidence indicates that these two predictions may be combined additively to bias visual selection (Additive Hypothesis), whereas neuroeconomic studies posit that they may be multiplicatively combined (Expected Value Hypothesis). We sought to adjudicate between these two alternatives. Participants viewed two coloured placeholders that specified the potential value of correctly identifying an imminent letter target if it appeared in that placeholder. Then, prior to the target's presentation, an endogenous spatial cue was presented indicating the target's more likely location. Spatial cues were parametrically manipulated with regard to the information gained (in bits). Across two experiments, performance was better for targets appearing in high versus low value placeholders and better when targets appeared in validly cued locations. Interestingly, as shown with a Bayesian model selection approach, these effects did not interact, clearly supporting the Additive Hypothesis. Even when conditions were adjusted to increase the optimality of a multiplicative operation, support for it remained. These findings refute recent theories that expected value computations are the singular mechanism driving the deployment of endogenous spatial attention. Instead, incentive value and spatial certainty seem to act independently to influence visual selection.

Cognitive Capacity Limits Are Remediated by Practice-Induced Plasticity between the Putamen and Pre-Supplementary Motor Area.

Humans show striking limitations in information processing when multitasking yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 human individuals and the plasticity caused by practice. We observed that multitasking costs, and their practice-induced remediation, are best explained by modulations in information transfer between the striatum and the cortical areas that represent stimulus-response mappings. Specifically, our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). Moreover, we propose that modulations to information transfer between these two regions leads to practice-induced improvements in multitasking.

Olfactory responses of Amblyomma maculatum to rumen fluid and other odourants that attract blood-seeking arthropods.

Amblyomma maculatum Koch (Ixodida: Ixodidae) has emerged as a significant vector of human and companion animal diseases in the U.S.A. When expanding in range, A. maculatum can be difficult to collect in the field and control on livestock. A novel method is needed to improve the field collection of A. maculatum, as well as to control their effects as ectoparasites of livestock and companion animals. The present study aimed to test the effects of known volatiles on the activation and selection choices of A. maculatum in a laboratory-based Y-tube assay and field-based assays. Although the majority of adult A. maculatum were activated to move by five of the seven semiochemicals tested, only rumen fluid significantly attracted ticks to make a selection in the Y-tube apparatus. Rumen fluid attracted the most A. maculatum in the laboratory, with 56% (84/150) making it to the rumen Y-tube arm, although the results were not replicated in semi-field experiments. These studies highlight the need for continued work to identify attractants for tick vectors that will assist field collections. These attractants could also be incorporated into management strategies that lead to prevention technologies to reduce tick burdens on cattle or in risk areas of humans.

Considerations related to the use of short neuropeptide promoters in viral vectors targeting hypothalamic neurons.

Targeting specific neuronal cell types is a major challenge for unraveling their function and utilizing specific cells for gene therapy strategies. Viral vector tools are widely used to target specific cells or circuits for these purposes. Here, we use viral vectors with short promoters of neuropeptide genes to target distinct neuronal populations in the hypothalamus of rats and mice. We show that lowering the amount of genomic copies is effective in increasing specificity of a melanin-concentrating hormone promoter. However, since too low titers reduce transduction efficacy, there is an optimal titer for achieving high specificity and sufficient efficacy. Other previously identified neuropeptide promoters as those for oxytocin and orexin require further sequence optimization to increase target specificity. We conclude that promoter-driven viral vectors should be used with caution in order to target cells specifically.

Single-Arm Resistance Training Study to Determine the Relationship between Training Outcomes and Muscle Growth Factor mRNAs in Older Adults Consuming Numerous Medications and Supplements.

OBJECTIVES: Determine if the muscle mRNA levels of three growth factors (insulin-like growth factor-1 [IGF1], ciliary neurotropic factor [CNTF], and vascular endothelial growth factor-D [VEGFD]) are correlated with muscle size and strength gains from resistance exercise while piloting a training program in older adults taking medications and supplements for age-associated problems. DESIGN: Single-arm prospective study. SETTING: US Veterans Affairs hospital. PARTICIPANTS: Older (70±6 yrs) male Veterans (N=14) of US military service. INTERVENTION: Thirty-five sessions of high-intensity (80% one-rep max) resistance training including leg press, knee curl, and knee extension to target the thigh muscles. MEASUREMENTS: Vastus lateralis biopsies were collected and body composition (DEXA) was determined pre- and post-training. Simple Pearson correlations were used to compare training outcomes to growth factor mRNA levels and other independent variables such as medication and supplement use. RESULTS: Average strength increase for the group was ≥ 25% for each exercise. Subjects averaged taking numerous medications (N=5±3) and supplements (N=2±2). Of the growth factors, a significant correlation (R>0.7, P≤0.003) was only found between pre-training VEGFD and gains in lean thigh mass and extension strength. Mass and strength gains were also correlated with use of α-1 antagonists (R=0.55, P=0.04) and pre-training lean mass (R=0.56, P=0.04), respectively. CONCLUSIONS: Muscle VEGFD, muscle mass, and use of α-1 antagonists may be predisposing factors that influence the response to training in this population of older adults but additional investigation is required to determine if these relationships are due to muscle angiogenesis and blood supply.

Decision-making training reduces the attentional blink.

Practice or training on a particular task often yields gains for the trained task; however, the extent to which these benefits generalize to other stimuli/tasks is contentious. It has been suggested that behavioral decision-making/response selection training may enhance temporal visual attention, as measured using the attentional blink (AB) paradigm. Here, we show that AB can indeed be reduced through response selection training, which requires repeatedly performing a speeded decision-making task. Training gains garnered by this approach transferred to distinct AB measures, but not to unrelated measures of visual search and multitasking ability. Moreover, these changes were still evident 2 weeks after training completion. Crucially, training on 2 active control tasks-visual search and motion discrimination-did not elicit similar gains. Such malleability of temporal visual attention via response selection training offers tantalizing prospects for future cognitive enhancement endeavors. (PsycINFO Database Record

On the relationship between response selection and response inhibition: An individual differences approach.

The abilities to select appropriate responses and suppress unwanted actions are key executive functions that enable flexible and goal-directed behavior. However, to date it has been unclear whether these two cognitive operations tap a common action control resource or reflect two distinct processes. In the present study, we used an individual differences approach to examine the underlying relationships across seven paradigms that varied in their response selection and response inhibition requirements: stop-signal, go-no-go, Stroop, flanker, single-response selection, psychological refractory period, and attentional blink tasks. A confirmatory factor analysis suggested that response inhibition and response selection are separable, with stop-signal and go-no-go task performance being related to response inhibition, and performance in the psychological refractory period, Stroop, single-response selection, and attentional blink tasks being related to response selection. These findings provide evidence in support of the hypothesis that response selection and response inhibition reflect two distinct cognitive operations.

Prefrontal Cortex Structure Predicts Training-Induced Improvements in Multitasking Performance.

The ability to perform multiple, concurrent tasks efficiently is a much-desired cognitive skill, but one that remains elusive due to the brain's inherent information-processing limitations. Multitasking performance can, however, be greatly improved through cognitive training (Van Selst et al., 1999, Dux et al., 2009). Previous studies have examined how patterns of brain activity change following training (for review, see Kelly and Garavan, 2005). Here, in a large-scale human behavioral and imaging study of 100 healthy adults, we tested whether multitasking training benefits, assessed using a standard dual-task paradigm, are associated with variability in brain structure. We found that the volume of the rostral part of the left dorsolateral prefrontal cortex (DLPFC) predicted an individual's response to training. Critically, this association was observed exclusively in a task-specific training group, and not in an active-training control group. Our findings reveal a link between DLPFC structure and an individual's propensity to gain from training on a task that taps the limits of cognitive control. SIGNIFICANCE STATEMENT: Cognitive "brain" training is a rapidly growing, multibillion dollar industry (Hayden, 2012) that has been touted as the panacea for a variety of disorders that result in cognitive decline. A key process targeted by such training is "cognitive control." Here, we combined an established cognitive control measure, multitasking ability, with structural brain imaging in a sample of 100 participants. Our goal was to determine whether individual differences in brain structure predict the extent to which people derive measurable benefits from a cognitive training regime. Ours is the first study to identify a structural brain marker-volume of left hemisphere dorsolateral prefrontal cortex-associated with the magnitude of multitasking performance benefits induced by training at an individual level.

Transfer of training benefits requires rules we cannot see (or hear).

Although humans show a remarkable ability to make rapid and accurate decisions in novel situations, it is surprisingly difficult to observe transferable benefits when training decision-making performance. The current study investigated whether 2 properties of decision-making-amodal processing and encoding of abstract relationships-could be leveraged to produce transferable training gains, compared with the performance of an active-control group. Experiment 1 showed that training responses to visually presented stimuli (letters) did not transfer to benefit performance for the same stimuli presented in the auditory modality. Therefore, training exercises the integration of modality-specific information, not a supramodal category. However, Experiment 2 showed that when stimuli share an abstract rule, training transfers to new materials that conform to the same modality and rule, and to analogous rules in a new modality. Therefore, transfer of training benefits requires an abstract code that can be generalized to new stimulus sets. (PsycINFO Database Record

Training conquers multitasking costs by dividing task representations in the frontoparietal-subcortical system.

Negotiating the information-rich sensory world often requires the concurrent management of multiple tasks. Despite this requirement, humans are thought to be poor at multitasking because of the processing limitations of frontoparietal and subcortical (FP-SC) brain regions. Although training is known to improve multitasking performance, it is unknown how the FP-SC system functionally changes to support improved multitasking. To address this question, we characterized the FP-SC changes that predict training outcomes using an individual differences approach. Participants (n = 100) performed single and multiple tasks in pre- and posttraining magnetic resonance imaging (fMRI) sessions interspersed by either a multitasking or an active-control training regimen. Multivoxel pattern analyses (MVPA) revealed that training induced multitasking improvements were predicted by divergence in the FP-SC blood oxygen level-dependent (BOLD) response patterns to the trained tasks. Importantly, this finding was only observed for participants who completed training on the component (single) tasks and their combination (multitask) and not for the control group. Therefore, the FP-SC system supports multitasking behavior by segregating constituent task representations.

The influence of training on the attentional blink and psychological refractory period.

A growing body of research suggests that dual-task interference in sensory consolidation (e.g., the attentional blink, AB) and response selection (e.g., the psychological refractory period, PRP) stems from a common central bottleneck of information processing. With regard to response selection, it is well known that training reduces dual-task interference. We tested whether training that is known to be effective for response selection can also reduce dual-task interference in sensory consolidation. Over two experiments, performance on a PRP paradigm (Exp. 1) and on AB paradigms (differing in their stimuli and task demands, Exps. 1 and 2) was examined after participants had completed a relevant training regimen (T1 practice for both paradigms), an irrelevant training regimen (comparable sensorimotor training, not related to T1 for both tasks), a visual-search training regimen (Exp. 2 only), or after participants had been allocated to a no-training control group. Training that had shown to be effective for reducing dual-task interference in response selection was also found to be effective for reducing interference in sensory consolidation. In addition, we found some evidence that training benefits transferred to the sensory consolidation of untrained stimuli. Collectively, these findings show that training benefits can transfer across cognitive operations that draw on the central bottleneck in information processing. These findings have implications for theories of the AB and for the design of cognitive-training regimens that aim to produce transferable training benefits.

A novel mutation in the P2Y12 receptor and a function-reducing polymorphism in protease-activated receptor 1 in a patient with chronic bleeding.

BACKGROUND: The study of patients with bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets. We have identified a patient with a chronic bleeding disorder expressing a homozygous P2RY(12) mutation, predicting an arginine to cysteine (R122C) substitution in the G-protein-coupled P2Y(12) receptor. This mutation is found within the DRY motif, which is a highly conserved region in G-protein-coupled receptors (GPCRs) that is speculated to play a critical role in regulating receptor conformational states. OBJECTIVES: To determine the functional consequences of the R122C substitution for P2Y(12) function. PATIENT/METHODS: We performed a detailed phenotypic analysis of an index case and affected family members. An analysis of the variant R122C P2Y(12) stably expressed in cells was also performed. RESULTS: ADP-stimulated platelet aggregation was reduced as a result of a significant impairment of P2Y(12) activity in the patient and family members. Cell surface R122C P2Y(12) expression was reduced both in cell lines and in platelets; in cell lines, this was as a consequence of agonist-independent internalization followed by subsequent receptor trafficking to lysosomes. Strikingly, members of this family also showed reduced thrombin-induced platelet activation, owing to an intronic polymorphism in the F2R gene, which encodes protease-activated receptor 1 (PAR-1), that has been shown to be associated with reduced PAR-1 receptor activity. CONCLUSIONS: Our study is the first to demonstrate a patient with deficits in two stimulatory GPCR pathways that regulate platelet activity, further indicating that bleeding disorders constitute a complex trait.

GHS-R1a signaling in the DMH and VMH contributes to food anticipatory activity.

BACKGROUND: Rats that have restricted access to food at a fixed time point of the circadian phase display high levels of food anticipatory activity (FAA). The orexigenic hormone ghrelin has been implicated in the regulation of FAA. However, it is not known via which brain area ghrelin exerts this effect. Growth hormone secretagogue receptor 1a (GHS-R1a) is highly expressed in the hypothalamus, including the dorsomedial hypothalamus (DMH) and the ventromedial hypothalamus (VMH). These two hypothalamic areas have been reported to play a role in FAA. AIM OF THE STUDY: To examine the role of GHS-R1a signaling in the DMH and VMH in FAA. DESIGN: Adeno-associated virus expressing a shRNA directed against GHS-R1a was used to establish local knockdown of GHS-R1a in the DMH and VMH in rats. Rats were subsequently subjected to a restricted feeding schedule (RFS). RESULTS: Under ad libitum conditions, knockdown of GHS-R1a in the VMH increased food intake and body weight gain. In addition, GHS-R1a knockdown in VMH and DMH reduced body temperature and running wheel activity (RWA). When rats were subjected to a RFS, the main effect of GHS-R1a knockdown in both DMH and VMH was a decrease in RWA and an attenuation of body weight loss. Rats with knockdown of GHS-R1a in DMH and VMH showed a delay in onset of FAA. In addition, GHS-R1a knockdown in DMH resulted in a reduction of FAA amplitude. CONCLUSION: This is the first study to investigate the effect of local hypothalamic knockdown of GHS-R1a on FAA. Our results implicate hypothalamic GHS-R1a signaling in the regulation of FAA. Nevertheless, some FAA remained, suggesting that a distributed network of brain areas and signaling pathways is involved in the development of FAA.

The Interrelationships among albumin, nutrient intake, and inflammation in elderly recuperative care patients.

OBJECTIVES: To examine the interrelationships among low serum albumin, nutritional depletion, and ongoing inflammation in older patients recovering from illness. DESIGN: A prospective cohort study. SETTING: A transitional care unit (TCU) within a Department of Veterans Affairs hospital nursing home care unit. PARTICIPANTS: 275 older veterans (mean age=78.9 ± 7.5y, 99% male) admitted for recuperative care and rehabilitation. MEASUREMENTS: At admission and discharge (median LOS 24d, IQR 16 to 44d), each subject completed a comprehensive standardized evaluation including a nutritional assessment and measurement of serum albumin, C-reactive protein (CRP), interleukin-6 (IL-6) and its soluble receptor, and tumor necrosis factor-alpha (TNF-α) and its soluble receptors (sTNF-RI and II). Complete nutrient intake assessments (calorie counts) were performed daily. RESULTS: Both the discharge albumin and the change in albumin (discharge minus admission) were strongly and inversely correlated with various indicators of inflammation, particularly CRP and IL-6. Change in CRP was the strongest correlate of change in albumin (R2 = 0.21, P<.001) and discharge IL-6 the strongest correlate of discharge albumin (R2 = 0.21, P<.001). Nutrient intake also correlated with albumin and its change, but entered the multivariable models after inflammatory indicators and explained a smaller portion of the variance. Although there were significant interactions between time and both nutrient intake and inflammation, the relative importance of inflammation as a potential determinant of the serum albumin concentration appeared to remain unchanged with longer periods of observation. CONCLUSIONS: Among elderly patients admitted to a TCU, inflammation appears to be a more powerful determinant of albumin and its change during the hospitalization than is nutrient intake. Further study is needed to prove causality and to determine whether the relative importance of inflammation on the albumin concentration diminishes with more prolonged periods of observation.

Melanocortin receptor-mediated effects on obesity are distributed over specific hypothalamic regions.

OBJECTIVE: Reduction of melanocortin signaling in the brain results in obesity. However, where in the brain reduced melanocortin signaling mediates this effect is poorly understood. DESIGN: We determined the effects of long-term inhibition of melanocortin receptor activity in specific brain regions of the rat brain. Melanocortin signaling was inhibited by injection of a recombinant adeno-associated viral (rAAV) vector that overexpressed Agouti-related peptide (AgRP) into the paraventricular nucleus (PVN), the ventromedial hypothalamus (VMH), the lateral hypothalamus (LH) or the accumbens shell (Acc). RESULTS: Overexpression of AgRP in the rat PVN, VMH or LH increased bodyweight, the percentage of white adipose tissue, plasma leptin and insulin concentrations and food intake. Food intake was mainly increased because of an increase in meal size in the light and dark phases, after overexpression of AgRP in the PVN, LH or VMH. Overexpression of AgRP in the PVN or VMH reduced average body core temperature in the dark on day 40 post injection, whereas AgRP overexpression in the LH did not affect temperature. In addition, overexpression of AgRP in the PVN, LH or VMH did not significantly alter mRNA expression of AgRP, neuropeptide Y (NPY), pro-opiomelanocortin (POMC) or suppressor of cytokine signaling 3 (SOCS3) in the arcuate. Overexpression of AgRP in the Acc did not have any effect on the measured parameters. CONCLUSIONS: Reduction of melanocortin signaling in several hypothalamic regions increased meal size. However, there were brain area-specific effects on other parameters such as core temperature and plasma leptin concentrations. In a previous study, where NPY was overexpressed with an rAAV vector in the PVN and LH, meal frequency and meal size were increased respectively, whereas locomotor activity was reduced by NPY overexpression at both nuclei. Taken together, AgRP and NPY have complementary roles in energy balance.

Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus: counterintuitive effects on energy balance.

An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.