BETA CELL DYSFUNCTION OCCURS INDEPENDENTLY OF INSULITIS IN TYPE 1 DIABETES PATHOGENESIS.

During type 1 diabetes (T1D) progression, beta cells become dysfunctional and exhibit reduced first-phase insulin release. While this period of beta cell dysfunction is well established, its cause and underlying mechanism remain unknown. To address this knowledge gap, live human pancreas tissue slices were prepared from autoantibody-negative organ donors without diabetes (ND), donors positive for one or more islet autoantibodies (AAb+), and donors with T1D within 0-4 years of diagnosis (T1D+).

Feedback lock-in: A versatile multi-terminal measurement system for electrical transport devices.

We present the design and implementation of a measurement system that enables parallel drive and detection of small currents and voltages at numerous electrical contacts to a multi-terminal electrical device. This system, which we term a feedback lock-in, combines digital control-loop feedback with software-defined lock-in measurements to dynamically source currents and measure small, pre-amplified potentials. The effective input impedance of each current/voltage probe can be set via software, permitting any given contact to behave as an open-circuit voltage lead or as a virtually grounded current source/sink.

Helicopter Crashes in the Deployed Combat Setting: The Department of Defense Trauma Registry Experience.

Background: Military helicopter mishaps frequently lead to multiple casualty events with complex injury patterns. Data specific to this mechanism of injury in the deployed setting are limited. We describe injury patterns associated with helicopter crashes.

Generating Competent Special Operations Clinicians From Military Graduate Medical Education.

Units within the Special Operations Forces (SOF) community require medically competent and operationally proficient medical providers (physicians, physician assistants, and nurse practitioners, among others) to support complex mission sets. The expectations placed on providers who successfully assess for and are selected into these units are high. These providers are not only expected to be experts in their respective subspecialities, but also to serve as staff officers, provide medical direction for SOF medics, serve as medical advisors to the command team, and provide direct medical support for kinetic operations.

Preparing Emergency Physicians for the Next War: Residency Capstone Training in Prolonged Casualty Care.

As the landscape and resources of combat operations change and become more unpredictable, the ability to provide prolonged combat casualty care in austere environments will become increasingly important. Prolonged casualty care (PCC) (until recently, prolonged field care [PFC]) is an emerging niche of military medicine that requires specific and dedicated training within our military medical education curricula for providers at all levels. That training should incorporate both didactic classroom instruction and high-fidelity, hands-on, full-scale training in order to prepare providers for delivering care beyond the standard doctrinal timelines employed in recent combat operations.

The Myths of Uncontrolled Emergence Reactions and Consideration to Stop Mandatory, Protocolled Midazolam Coadministration With Ketamine.

Ketamine continues to demonstrate its utility and safety in the austere and prehospital environment, but myths persist regarding the frequency of behavioral disturbances and unpleasant reactions. These myths have led to protocolled midazolam co-administration. Properties of midazolam and other benzodiazepines have the potential to cause significant morbidity and potential mortality.

Prehospital Intervention Analysis of Helicopter Crashes in Afghanistan.

Background: Based on isolated case reports, military helicopter mishaps often result in multiple critical casualties leading to complicated stabilization and evacuation by healthcare providers. The aim of this retrospective descriptive analysis is to describe the incidence of common prehospital injuries associated with rotary wing crashes in order to improve mission planning and casualty survivability.

Methods: This is a secondary analysis of data from the Prehospital Trauma Registry and the Department of Defense Trauma Registry (DoDTR) from April 2003 through May 2019.

Toxicity From Blue Lotus (Nymphaea caerulea) After Ingestion or Inhalation: A Case Series.

Plant extracts and other novel psychoactives can be ingested, vaped, injected, or insufflated. This includes products such as extracts from the blue lotus flower (Nypmhaea caerulea), which is known to produce euphoria and hallucinations at high doses. Blue lotus is sold in several forms, including dried plant material, teas, and extracts for use in electronic cigarettes.

Altered cellular localisation and expression, together with unconventional protein trafficking, of prion protein, PrP, in type 1 diabetes.

Aims/hypothesis: Normal cellular prion protein (PrP) is a conserved mammalian glycoprotein found on the outer plasma membrane leaflet through a glycophosphatidylinositol anchor. Although PrP is expressed by a wide range of tissues throughout the body, the complete repertoire of its functions has not been fully determined. The misfolded pathogenic isoform PrP (the scrapie form of PrP) is a causative agent of neurodegenerative prion diseases.

Nicotine Toxicity Secondary to Aftermarket Modifications to a Vaping Device.

Electronic cigarettes continue to rise in popularity as a reportedly safe alternative to standard cigarette smoking. Their use has become common in our society and specifically in our young active duty population. This cigarette smoking alternative has come under recent scrutiny with the discovery of e-cigarette or vaping product use-associated lung injury.

Monogenic Diabetes and Integrated Stress Response Genes Display Altered Gene Expression in Type 1 Diabetes.

Type 1 diabetes (T1D) has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with and at risk for T1D would exhibit dysregulated expression of genes associated with monogenic forms of diabetes caused by nonredundant single-gene mutations. Using a "monogenetic transcriptomic strategy," we measured the expression of these genes in human T1D, autoantibody-positive (autoantibody+), and control pancreas tissues with real-time quantitative PCR in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines.

Observing Islet Function and Islet-Immune Cell Interactions in Live Pancreatic Tissue Slices.

Live pancreatic tissue slices allow for the study of islet physiology and function in the context of an intact islet microenvironment. Slices are prepared from live human and mouse pancreatic tissue embedded in agarose and cut using a vibratome. This method allows for the tissue to maintain viability and function in addition to preserving underlying pathologies such as type 1 (T1D) and type 2 diabetes (T2D).

Anterior Mediastinal Mass Causing Intermittent Atrial Fibrillation.

Mediastinal masses are a rare finding in the emergency department and typically present with vague chest complaints such as chest discomfort, chest pain, or dyspnea. Rarely do these tumors present with dysrhythmias, and when dysrhythmias are present, they typically arise secondary to endocrine or metabolic effects exerted by the tumor. Here we report a case of a patient who presented to the emergency department with atrial fibrillation with rapid ventricular response, concomitant with a history of recurrent palpitations that were previously aborted with self-induced vagal maneuvers.

Community hospital experience in the emergency management of COVID-19: Preventing morbidity and preserving resources.

An incredible amount of information has been published regarding inpatient management of patients with COVID-19. Although this is vitally important, critical interventions that occur in the emergency department (ED) can have a profound impact on the individual patient and the healthcare system as a whole.  Much has been written regarding care in large centers, but there has been little discussion regarding similar patients in community settings.

Melon with a Twist: A Case of Nicotine Overdose After Ingestion and Aspiration of Vape Liquid.

We present the case of an active duty 21-year-old male with severe hypoxic respiratory failure after accidentally ingesting, and subsequently aspirating, vaping liquid while intoxicated. Because of the increasing prevalence of vaping devices, this case highlights a unique risk of vape liquids with concentrated nicotine levels and appetizing labels and aromas. Vaping-associated pulmonary injury has been previously described in multiple publications, but unlike those patients with pathology after inhaling vaping products, our patient ingested and subsequently aspirated the highly nicotinic substance.

Publisher Correction: Long-term culture of human pancreatic slices as a model to study real-time islet regeneration.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Long-term culture of human pancreatic slices as a model to study real-time islet regeneration.

The culture of live pancreatic tissue slices is a powerful tool for the interrogation of physiology and pathology in an in vitro setting that retains near-intact cytoarchitecture. However, current culture conditions for human pancreatic slices (HPSs) have only been tested for short-term applications, which are not permissive for the long-term, longitudinal study of pancreatic endocrine regeneration. Using a culture system designed to mimic the physiological oxygenation of the pancreas, we demonstrate high viability and preserved endocrine and exocrine function in HPS for at least 10 days after sectioning.

Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis.

In type 1 diabetes (T1D), autoimmune destruction of pancreatic β cells leads to insulin deficiency and loss of glycemic control. However, knowledge about human pancreas pathophysiology in T1D remains incomplete. To address this limitation, we established a pancreas tissue slice platform of donor organs with and without diabetes, facilitating the first live cell studies of human pancreas in T1D pathogenesis to our knowledge.

Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues.

Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g.

Direct assessment of adherence and drug interactions in patients with hypertensive crisis-A cross-sectional study in the Emergency Department.

Though drug adherence is supposed to be low in hypertensive crisis (HTN-C), there are no data available from direct adherence assessments. The aim of the present study was to evaluate adherence to prescribed antihypertensives and potential interactions of concomitant drugs and foods with prescribed antihypertensives in patients with HTN-C by a direct evaluation via biochemical urine analysis. In the present cross-sectional study, 100 patients with HTN-C, admitted to the emergency department (ED), were included.

A novel rat model of comorbid PTSD and addiction reveals intersections between stress susceptibility and enhanced cocaine seeking with a role for mGlu5 receptors.

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).

Coupling corticotropin-releasing-hormone and angiotensin converting enzyme 2 dampens stress responsiveness in male mice.

This study used mice to evaluate whether coupling expression of corticotropin-releasing hormone (CRH) and angiotensin converting enzyme 2 (ACE2) creates central interactions that blunt endocrine and behavioral responses to psychogenic stress. Central administration of diminazene aceturate, an ACE2 activator, had no effect on restraint-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis; however, mice that ubiquitously overexpress ACE2 had reduced plasma corticosterone (CORT) and pituitary expression of POMC mRNA. The Cre-LoxP system was used to restrict ACE2 overexpression to CRH synthesizing cells and probe whether HPA axis suppression was the result of central ACE2 and CRH interactions.

A Single Angiotensin II Hypertensive Stimulus Is Associated with Prolonged Neuronal and Immune System Activation in Wistar-Kyoto Rats.

Activation of autonomic neural pathways by chronic hypertensive stimuli plays a significant role in pathogenesis of hypertension. Here, we proposed that even a single acute hypertensive stimulus will activate neural and immune pathways that may be important in initiation of memory imprinting seen in chronic hypertension. We investigated the effects of acute angiotensin II (Ang II) administration on blood pressure, neural activation in cardioregulatory brain regions, and central and systemic immune responses, at 1 and 24 h post-injection.

A Unique "Angiotensin-Sensitive" Neuronal Population Coordinates Neuroendocrine, Cardiovascular, and Behavioral Responses to Stress.

Stress elicits neuroendocrine, autonomic, and behavioral responses that mitigate homeostatic imbalance and ensure survival. However, chronic engagement of such responses promotes psychological, cardiovascular, and metabolic impairments. In recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known.

Angiotensin type 1a receptors in the paraventricular nucleus of the hypothalamus control cardiovascular reactivity and anxiety-like behavior in male mice.

This study tested the hypothesis that deletion of angiotensin type 1a receptors (AT1a) from the paraventricular nucleus of hypothalamus (PVN) attenuates anxiety-like behavior, hypothalamic-pituitary-adrenal (HPA) axis activity, and cardiovascular reactivity. We used the Cre/LoxP system to generate male mice with AT1a specifically deleted from the PVN. Deletion of the AT1a from the PVN reduced anxiety-like behavior as indicated by increased time spent in the open arms of the elevated plus maze.