Latent profile analysis reveals the central role of psychological symptoms in driving disease severity in chronic constipation.

BACKGROUND: Chronic constipation (CC) is defined by symptom criteria reflecting heterogenous physiology. However, many patients with CC have significant psychological comorbidities-an alternative definition using a biopsychosocial classification model could be warranted to inform future treatments. We sought to: (1) empirically derive psychological symptom profiles of patients with CC using latent profile analysis and (2) validate these profiles by comparing them on symptom severity, GI-specific anxiety, body mass index (BMI), and anorectal manometry findings. METHODS: Participants included adults presenting for anorectal manometry for CC (N = 468, 82% female, Mage = 47). Depression/anxiety symptoms and eating disorder (ED) symptoms (EAT-26) were used as indicators (i.e., variables used to derive profiles) representing unique psychological constructs. Constipation symptoms, GI-specific anxiety, BMI, and anorectal manometry results were used as validators (i.e., variables used to examine the clinical utility of the resulting profiles). KEY RESULTS: A 5-profile solution provided the best statistical fit, comprising the following latent profiles (LPs): LP1 termed "high dieting, low bulimia;" LP2 termed "high ED symptoms;" LP3 termed "moderate ED symptoms;" LP4 termed "high anxiety and depression, low ED symptoms;" and LP5 termed "low psychological symptoms." The low psychological symptom profile (61% of the sample) had lower abdominal and overall constipation severity and lower GI-specific anxiety compared to the four profiles characterized by higher psychological symptoms (of any type). Profiles did not significantly differ on BMI or anorectal manometry results. CONCLUSIONS AND INFERENCES: Profiles with high psychological symptoms had increased constipation symptom severity and GI-specific anxiety in adults with CC. Future research should test whether these profiles predict differential treatment outcomes.

The preference for sugar over sweetener depends on a gut sensor cell.

Guided by gut sensory cues, humans and animals prefer nutritive sugars over non-caloric sweeteners, but how the gut steers such preferences remains unknown. In the intestine, neuropod cells synapse with vagal neurons to convey sugar stimuli to the brain within seconds. Here, we found that cholecystokinin (CCK)-labeled duodenal neuropod cells differentiate and transduce luminal stimuli from sweeteners and sugars to the vagus nerve using sweet taste receptors and sodium glucose transporters. The two stimulus types elicited distinct neural pathways: while sweetener stimulated purinergic neurotransmission, sugar stimulated glutamatergic neurotransmission. To probe the contribution of these cells to behavior, we developed optogenetics for the gut lumen by engineering a flexible fiberoptic. We showed that preference for sugar over sweetener in mice depends on neuropod cell glutamatergic signaling. By swiftly discerning the precise identity of nutrient stimuli, gut neuropod cells serve as the entry point to guide nutritive choices.

A gut-brain neural circuit for nutrient sensory transduction.

The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell-the enteroendocrine cell. However, these electrically excitable cells contain several features of epithelial transducers. Using a mouse model, we found that enteroendocrine cells synapse with vagal neurons to transduce gut luminal signals in milliseconds by using glutamate as a neurotransmitter. These synaptically connected enteroendocrine cells are referred to henceforth as neuropod cells. The neuroepithelial circuit they form connects the intestinal lumen to the brainstem in one synapse, opening a physical conduit for the brain to sense gut stimuli with the temporal precision and topographical resolution of a synapse.

You Are What You (First) Eat.

As far back as we can remember, we eat. In fact, we eat before we can remember. Our first meal is amniotic fluid. We swallow it during the first trimester of gestation, and with that, we expose our gut to a universe of molecules. These early molecules have a profound influence on gut and brain function. For example, the taste of the amniotic fluid changes based on the mother's diet. Indeed, recent findings suggest that food preferences begin in utero. Likewise, a baby's first exposure to bacteria, previously thought to be during birth, appears to be in utero as well. And just as postnatal food and microbiota are implicated in brain function and dysfunction, prenatal nutrients and microbes may have a long-lasting impact on the development of the gut-brain neural circuits processing food, especially considering their plasticity during this vulnerable period. Here, we use current literature to put forward concepts needed to understand how the gut first meets the brain, and how this encounter may help us remember food.

Influence of resveratrol release on the tissue response to mechanically adaptive cortical implants.

The stability and longevity of recordings obtained from intracortical microelectrodes continues to remain an area of concern for neural interfacing applications. The limited longevity of microelectrode performance has been associated with the integrity of the blood brain barrier (BBB) and the neuroinflammatory response to the microelectrode. Here, we report the investigation of an additive approach that targets both mechanical and chemical factors believed to contribute to chronic BBB instability and the neuroinflammatory response associated with implanted intracortical microelectrodes. The implants investigated were based on a mechanically adaptive, compliant nanocomposite (NC), which reduces the tissue response and tissue strain. This material was doped with various concentrations of the antioxidant resveratrol with the objective of local and rapid delivery. In vitro analysis of resveratrol release, antioxidant activity, and cytotoxicity suggested that a resveratrol content of 0.01% was optimal for in vivo assessment. Thus, probes made from the neat NC reference and probes containing resveratrol (NC Res) were implanted into the cortical tissue of rats for up to sixteen weeks. Histochemical analysis suggested that at three days post-implantation, neither materials nor therapeutic approaches (independently or in combination) could alter the initial wound healing response. However, at two weeks post-implantation, the NC Res implant showed a reduction in activated microglia/macrophages and improvement in neuron density at the tissue-implant interface when compared to the neat NC reference. However, sixteen weeks post-implantation, when the antioxidant was exhausted, NC Res and the neat NC reference exhibited similar tissue responses. The data show that NC Res provides short-term, short-lived benefits due to the antioxidant release, and a long-term reduction in neuroinflammation on account of is mechanical adaptive, compliant nature. Together, these results demonstrate that local delivery of resveratrol can provide an additive advantage by providing a consistent reduction in the tissue response.

Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex.

There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention.

Burning Man 2011: mass gathering medical care in an austere environment.

INTRODUCTION: Burning Man is a large weeklong outdoor arts festival held annually in the rugged and austere Black Rock Desert in northern Nevada. The 2011 event presented several unusual challenges in terms of emergency medical services (EMS) and medical care provision. OBJECTIVE: This paper details the planning and subsequent emergency medical care for Burning Man 2011. METHODS: This was a retrospective, observational review of the preparation, management, and medical care at Burning Man 2011. RESULTS: Attendance at Burning Man 2011 was 53,735. Of these attendees, 2,307 were treated in the field hospital. While most patients had minor injuries, 33 were subsequently transported to a hospital (28 by ambulance and five by helicopter). The most common conditions treated were soft-tissue injuries, dehydration, eye problems, and urinary tract infections. There was one death (subarachnoid hemorrhage) and one patient in cardiac arrest (thoracic aortic dissection) who was successfully resuscitated and transferred. Burning Man 2011 presented numerous challenges in provision of EMS and medical care because of attendance size, the austere environment, and significant distance (150 miles) to definitive medical care. EMS operations included six dedicated ambulances, three quick-response vehicles, two first-aid stations, and a physician-staffed field hospital. The hospital had limited diagnostic capabilities (e.g., x-ray, ultrasound, basic laboratory analysis) and a limited formulary. We found that the use of physicians was necessary because much of the care provided was beyond the scope of paramedics. CONCLUSIONS: We describe the preparation and medical care for a large outdoor mass-gathering event held in a remote and austere environment. We met the stated goals of providing needed medical care while minimizing the need to transport attendees offsite for additional care. Our experience with Burning Man 2011 may aid planners with similar events.

Miracle in the desert. Cardiac case at remote burning man event presents challenges.

This was a miraculous case that illustrates the importance of seamless interaction between field EMS crews and physicians. First, this case occurred in one of the most austere and hostile environments imaginable. Next, it included a patient who was resuscitated from pulseless v tach with a precordial thump performed by a paramedic crew. The patient was subsequently evaluated and diagnosed with a thoracic aorta dissection by medical staff in a tent (with a diagnosis made by plain chest X-ray) and emergently transported 150 miles to a hospital where successful surgery was carried out. It truly was a "perfect storm," or perhaps, it was the general goodwill and spirit of Burning Man. Or maybe those crystals that were everywhere actually worked.

Do echo-enhanced needles improve time to cannulate in a model of short-axis ultrasound-guided vascular access for a group of mostly inexperienced ultrasound users?

BACKGROUND: Vascular access is a critical skill for emergency physicians. However, it can be unpredictably challenging in some patients. While ultrasound-guided vascular access has been encouraged in emergency departments, there have been few studies evaluating echo-enhanced needles and their usefulness in performing vascular access. AIMS: Our purpose was to determine if the use of an echo-enhanced needle tip results in faster vascular access times, with fewer needle sticks, fewer redirections, and improved needle visualization in ultrasound-guided vascular access with the vessel in the short axis. METHODS: This is a prospective, randomized, observational study of ultrasound-guided vascular access on a vascular phantom comparing an echo-enhanced needle with a standard needle. Each participant viewed a teaching video demonstrating typical ultrasound-guided vascular access and then attempted ultrasound-guided vascular access using both a standard and an echo-enhanced needle with the vessel in the short axis. The numbers of needle sticks, redirections, and time to dye flash were measured. RESULTS: The 69 participants attempted 69 short-axis ultrasound-guided vascular cannulations with no difference in time to dye flash between needle types: the median time from needle stick to flash was 17.56 s [interquartile range (IQR): 12.37-33.15] for the standard needle and 19.22 s (IQR: 10.19-31.10) for the echo-enhanced needle. There was no difference between needle types for number of needle sticks or redirects. CONCLUSION: Echo-enhanced needles did not provide objective performance improvement compared to standard needles during ultrasound-guided vascular access with a vascular access model in the short axis.