Onset of Irritable Bowel Syndrome, Dyspepsia, Diarrhea, Bloating, and Constipation in Deployed Gulf War Veterans.

An estimated 694,550 United States service members were actively deployed to the Persian Gulf from 1990-1991. Many veterans who were deployed developed Persian Gulf War Syndrome along with chronic gastrointestinal symptoms after returning from the Persian Gulf. Our objective in this study was to determine the phenotypic expression of gastrointestinal symptom complexes in previously healthy veterans who had been stationed in the Persian Gulf. One hundred and four consecutive veterans (88 males, 16 females) who had previously been deployed in 1990-91 were evaluated for their bowel habits and gastrointestinal symptoms. A workup was completed to find identifiable causes of their symptoms and all veterans were asked to do a modified version of the Bowel Disease Questionnaire symptom survey. None of the veterans reported gastrointestinal symptoms before deployment. During deployment to the Persian Gulf: 22 veterans (21%) developed irritable bowel syndrome; 17 (16%) developed dyspepsia; 50 (48%) developed diarrhea; 11 (11%) developed bloating; and 4 (4%) developed constipation. The results of the current study suggest that the development of irritable bowel syndrome, dyspepsia, diarrhea, bloating, and constipation is frequently seen in deployed Gulf War Veterans and the gastrointestinal symptoms commonly persist upon returning home. These novel findings are very important for currently deployed veterans who are serving in the Middle East and are at a high risk of developing gastrointestinal disorders.

Antioxidant activities, phenolic compounds, and mineral composition of seed from Acacia retinodes, A. Provincialis and A. Tenuissima.

Seeds of the species Acacia retinodes, A. provincialis, and A. tenuissima) from different growing locations were analysed for their mineral composition, free and bound polyphenols, and flavonoids. Previous research has studied these compounds in only a limited number of Acacia species, and only one study reports significant differences between three species. All species were rich in potassium (353 - 427 mg/100 g), sodium (14 - 240 mg/100 g) and iron (7 - 8 mg/100 g). The free polyphenol extracts of all species had higher total phenolic content, total flavonoid content and antioxidant activities than their bound counterparts, indicating the possibility of higher bioavailability than the bound polyphenol extracts. The predominant phenolic compounds found in the Acacia polyphenol seed extracts were 6-Hydroxy-2-methylindole and 2,2'-Methylenebis(6-tert-butyl-methylphenol), though no phenolic compounds were identified in the bound extracts of A. retinodes Grampians and A. provincialis Tarrington. Other compounds identified in the seed extracts include sucrose, d-fructofuranose and d-pinitol.

Two Commercially Available Blood-Stabilization Reagents Serve as Potent Inactivators of Coronaviruses.

The continued circulation of SARS-CoV-2 and the increasing frequency of coronavirus (CoV) outbreaks over the decades demonstrates the enduring threat that the CoV family poses. There remains a significant need to develop tools to monitor and prevent the spread of these viruses. We tested blood-stabilization reagents from two commercially available blood collection tubes (BCTs) for their ability to inactivate three different coronaviruses (MHV, OC-43, and SARS-CoV-2) and stabilize their RNA. Both Cell-Free DNA BCT® (cfDNA) and Cyto-Chex® BCT (CytoChex) reagents reduced infectious virus in the buffer to below the limit of detection within 18 h of treatment, with some conditions showing this effect in as little as 3 h. CytoChex had more potent activity than cfDNA as in all cases it more rapidly reduced the actively replicating virus to the limit of detection. Despite the rapid inactivation of the virus, both reagents effectively preserved viral RNA for 7 days. Finally, both reagents accelerated viral inactivation in blood compared to the control samples. These results indicate that cfDNA and CytoChex could be used to inactivate and preserve CoV RNA for detection and further testing.

Two-photon microendoscope for label-free imaging in stereotactic neurosurgery.

We demonstrate a gradient refractive index (GRIN) microendoscope with an outer diameter of ∼1.2 mm and a length of ∼186 mm that can fit into a stereotactic surgical cannula. Two photon imaging at an excitation wavelength of 900 nm showed a field of view of ∼180 microns and a lateral and axial resolution of 0.86 microns and 9.6 microns respectively. The microendoscope was tested by imaging autofluorescence and second harmonic generation (SHG) in label-free human brain tissue. Furthermore, preliminary image analysis indicates that image classification models can predict if an image is from the subthalamic nucleus or the surrounding tissue using conventional, bench-top two-photon autofluorescence.

Pericardial Tamponade in a Patient With a History of Pneumonectomy.

Shock is the clinical presentation of circulatory failure with impaired perfusion that results in inadequate cellular oxygen utilization. Treatment requires properly identifying the type of shock that is impacting the patient (obstructive, distributive, cardiogenic, and/or hypovolemic). Complex cases may involve numerous contributors to each type of shock and/or multiple types of shock which can present interesting diagnostic and management challenges to the clinician. In this case report, we present a 54-year-old male with a remote history of a right lung pneumonectomy presenting with multifactorial shock including cardiac tamponade, with initial compression of the expanding pericardial effusion by the postoperative fluid accumulation within the right hemithorax. While in the emergency department, the patient gradually became hypotensive with worsening tachycardia and dyspnea. A bedside echocardiogram revealed an increase in size of the pericardial effusion. An emergent ultrasound-guided pericardial drain was inserted with gradual improvement of his hemodynamics followed by placement of thoracostomy tube. This unique case highlights the importance of utilizing point-of-care ultrasound along with emergent intervention in critical resuscitation.

Catechol-O-Methyltransferase Loss Drives Cell-Specific Nociceptive Signaling via the Enteric Catechol-O-Methyltransferase/microRNA-155/Tumor Necrosis Factor α Axis.

BACKGROUND & AIMS: The etiology of abdominal pain in postinfectious, diarrhea-predominant irritable bowel syndrome (PI-IBS-D) is unknown, and few treatment options exist. Catechol-O-methyltransferase (COMT), an enzyme that inactivates and degrades biologically active catecholamines, plays an important role in numerous physiologic processes, including modulation of pain perception. Our objective was to determine the mechanism(s) of how decreased colonic COMT in PI-IBS-D patients contributes to the chronic abdominal pain phenotype after enteric infections. METHODS: Colon neurons, epithelial cells, and macrophages were procured with laser capture microdissection from PI-IBS-D patients to evaluate cell-specific colonic COMT, microRNA-155 (miR-155), and tumor necrosis factor (TNF) α expression levels compared to recovered patients (infection cleared: did not develop PI-IBS-D) and control individuals. COMT-/-, colon-specific COMT-/-, and miR-155-/- mice and human colonoids were used to model phenotypic expression of COMT in PI-IBS-D patients and to investigate signaling pathways linking abdominal pain. Citrobacter rodentium and trinitrobenzene sulfonic acid animal models were used to model postinflammatory changes seen in PI-IBS-D patients. RESULTS: Colonic COMT levels were significantly decreased and correlated with increased visual analog scale abdominal pain ratings in PI-IBS-D patients compared to recovered patients and control individuals. Colonic miR-155 and TNF-α were increased in PI-IBS-D patients with diminished colonic COMT. COMT-/- mice had significantly increased expression of miR-155 and TNF-α in both colon tissues and dorsal root ganglia. Introduction of cV1q antibody (anti-TNF-α) into mice reversed visceral hypersensitivity after C rodentium and trinitrobenzene sulfonic acid. CONCLUSIONS: Decreased colonic COMT in PI-IBS-D patients drives abdominal pain phenotypes via the COMT/miR-155/TNF-α axis. These important findings will allow new treatment paradigms and more targeted and personalized medicine approaches for gastrointestinal disorders after enteric infections.

Evaluation of subjective anterior disc space widening on trauma cervical spine CT as a potential sign of ligamentous injury.

INTRODUCTION: MRI is commonly accepted as the gold standard imaging technique for identification of isolated discoligamentous injury to the cervical spine. Widening of the anterior disc space (ADW) has been suggested as signs of injury to the anterior longitudinal ligament (ALL). The purpose of this study aimed to assess the accuracy of ADW reported on CT as a sign of ligamentous injury compared. METHODS: The study was performed at a level 1 trauma centre. All patients over a 5-year period from 1 January 2015 to 31 January 2019 who underwent a cervical CT scan for the indication of trauma and who subsequently received a cervical spine MRI during the same admission were included if no fracture was found on the initial CT. Demographic data were collected along with mechanism of injury and time period between CT and MRI. Presence or absence of subjective CT-ADW along with presence or absence of ALL injury on MRI was recorded by retrospective review of the radiology reports. Sensitivity, specificity and positive and negative predictive values were then calculated. RESULTS: Over a 5-year period, 1,305 patients fulfilled the study criteria. CT-ADW had a sensitivity, specificity and positive predictive value of 8.2% (95% CI: 2.7-18.1%), 96.2% (95% CI: 95.3-97.4%) and 10.2% (95% CI: 3.4-22.2%) respectively. CONCLUSION: Subjective CT-ADW is a poor predictor of ALL injury as assessed by MRI and should not be relied upon in isolation to diagnose ligamentous injury of the cervical spine in the setting of trauma.

Epigenetic modulation of visceral nociception.

Epigenetics is a process that alters gene activity or phenotype without any changes in the underlying DNA sequence or genotype. These biological changes may have deleterious effects and can lead to various human diseases. Ongoing research is continuing to illuminate the role of epigenetics in a variety of pathophysiologic processes. Several categories of epigenetic mechanisms have been studied including chromatin remodeling, DNA methylation, histone modification, and non-coding RNA mechanisms. These epigenetic changes can have a long-term effect on gene expression without any underlying changes in the DNA sequences. The underlying pathophysiology of disorders of brain-gut interaction and stress-induced visceral pain are not fully understood and the role of epigenetic mechanisms in these disorders are starting to be better understood. Current work is underway to determine how epigenetics plays a role in the neurobiology of patients with chronic visceral pain and heightened visceral nociception. More recently, both animal models and human studies have shown how epigenetic regulation modulates stress-induced visceral pain. While much more work is needed to fully delineate the mechanistic role of epigenetics in the neurobiology of chronic visceral nociception, the current study by Louwies et al., in Neurogastroenterology and Motility provides additional evidence supporting the involvement of epigenetic alterations in the central nucleus of the amygdala in stress-induced visceral hypersensitivity in rodents.

A Rare Cause of Chest Pain Identified on Point-of-care Echocardiography: A Case Report.

INTRODUCTION: Cardiac masses are a rare cause of chest pain. They can often be missed on a chest radiograph performed to evaluate non-specific chest pain and are not readily evaluated with traditional laboratory testing. However, these masses can be visualized with point-of-care ultrasound. CASE REPORT: We present a case of a 19-year-old female presenting with intermittent chest pain, palpitations, and weakness present for two months. The patient had previously been evaluated at our emergency department one week earlier and was diagnosed with anxiety before being discharged. Besides a tachycardic and labile heart rate, physical examination and laboratory testing were unremarkable. Point-of-care cardiac echocardiography subsequently demonstrated findings concerning for a cardiac mass. CONCLUSION: Cardiac masses are a rare cause of chest pain and palpitations that are easily missed. The advent of point-of-care ultrasonography has afforded us the ability to rapidly assess for structural and functional cardiac abnormalities at bedside, and incorporation of this tool into the evaluation of patients with chest pain offers the ability to detect these rare pathologies.

Comparison of emergency airway management techniques in the performance of emergent Cricothyrotomy.

INTRODUCTION: Emergent cricothyrotomy (EC) is a rare and lifesaving procedure to secure a difficult airway when other methods have failed. Many techniques have been discussed in the literature. This study aimed to identify major techniques used to perform EC in a regional trauma center and evaluate outcomes associated with the techniques. METHODS: Patients who underwent EC at Arrowhead Regional Medical Center between 1-1-2009 and 1-1-2019 were reviewed for eligibility for this study. Patients' data were extracted from the trauma database. Chi-square tests were conducted to assess the difference on variables between the techniques. RESULTS: A total of 51 (0.17%) of these patients required EC and were included in the database. The two most prevalent techniques were the scalpel-bougie-tube (SBT) and the surgical cricothyrotomy technique (SCT). More than half (n = 27, 52.9%) of the cohort received the SBT. There was no statistically significant difference between the two techniques with regards to demographic variables, including age (p = 0.7528), injury severity score (ISS, p = 0.896), gender (p = 0.3709), and race (p = 0.8935). However, the SCT group had a statistically higher Glasgow Coma Scale (GCS) than the SBT group (p = 0.0036). There was no statistically significant difference in mortality or complications between these two groups (p = 0.2172 for mortality). DISCUSSION: Two techniques of EC were identified as preferred techniques. Both procedures were successful in securing an emergency airway, noting a difference in the time to completion of the two techniques. Given the rarity of the procedure, practitioners may choose the method based on their training and the availability of appropriate instruments.

Excitable Axonal Domains Adapt to Sensory Deprivation in the Olfactory System.

The axon initial segment (AIS), nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the faithful, coordinated transmission of action potentials (APs) to downstream brain regions. In the olfactory bulb (OB), olfactory discrimination tasks lead to adaptive changes in cell firing patterns, and the output signals must reliably travel large distances to other brain regions along highly myelinated tracts. Whether myelinated axons adapt to facilitate olfactory sensory processing is unknown. Here, we investigate the morphology and physiology of mitral cell (MC) axons in the olfactory system of adult male and female mice and show that unilateral sensory deprivation causes system-wide adaptations in axonal morphology and myelin thickness. MC spiking patterns and APs also adapted to sensory deprivation. Strikingly, myelination and MC physiology were altered on both the deprived and nondeprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system.SIGNIFICANCE STATEMENT Successful transmission of information from the olfactory bulb (OB) to piriform cortex through the lateral olfactory tract (LOT) relies on synchronized arrival of action potentials (APs). The coincident arrival of APs is dependent on reliable generation of APs in the axon initial segment (AIS) and fast conduction mediated by axon myelination. Here, we studied changes in mitral cell (MC) firing and AIS structure as well as changes in myelination of the LOT on unilateral olfactory deprivation in the adult mouse. Strikingly, myelination and MC physiology were altered on both the deprived and nondeprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system.

Beyond Extracorporeal Cardiopulmonary Resuscitation: Systems of Care Supporting Cardiac Arrest Patients.

Introduction: Out-of-hospital cardiac arrest (OHCA) is a major cause of death and disability in the United States. Cardiac arrest centers (CAC) are necessary for the management of these critically ill and complex post arrest patients due to their specialized services and provider expertise. We report the case of a patient with OHCA and the systems of care involved in his resuscitation and recovery. Case Report: Emergency medical services attended a 39-year-old male with ongoing bystander cardiopulmonary resuscitation (CPR) after a witnessed collapse. Despite receiving appropriate advanced cardiac life support, including three defibrillations, he remained in refractory ventricular fibrillation. A prehospital physician identified him as an extracorporeal cardiopulmonary resuscitation (ECPR) candidate due to his age, witnessed arrest, refractory rhythm, and functional status. He was expedited to a CAC but no longer qualified for ECPR due to the time limit. He was resuscitated by the multiple teams activated prior to his arrival. He eventually had sustained return of circulation, was taken to the catheterization lab for emergent percutaneous coronary intervention, and recovered with a good neurologic outcome. Conclusion: Cardiac arrest centers may be capable of advanced interventions including ECPR. However, the systems of care offered by these centers is itself a lifesaving intervention. As this case highlights, despite not receiving the specified intervention (ECPR) the systems of care required to offer such a resource led to this favorable outcome.

Acute Inhalant-Induced Atrial Fibrillation With Severe Hypocalcemia: A Case Report and Review of the Pathophysiology.

The recreational use of inhalants is associated with various detrimental health effects ranging from inebriation to cardiac arrest. It also presents a challenging clinical problem as the diagnosis is made by the presentation and patient's history, which is often difficult to obtain in an intoxicated or obtunded individual. The incidence of inhalant use is relatively high. National surveys have reported that nearly 21.7 million Americans aged 12 and older have used inhaled substances at least once in their lives. There is no reversal agent or antidote for inhalants and supportive care is generally recommended. We present a case of a young patient presenting with acute inhalant toxicity accompanied by atrial fibrillation with a rapid ventricular response and severe hypocalcemia.

Cytoplasmic tail truncation of SARS-CoV-2 Spike protein enhances titer of pseudotyped vectors but masks the effect of the D614G mutation

The high pathogenicity of SARS-CoV-2 requires it to be handled under biosafety level 3 conditions. Consequently, Spike protein pseudotyped vectors are a useful tool to study viral entry and its inhibition, with retroviral, lentiviral (LV) and vesicular stomatitis virus (VSV) vectors the most commonly used systems. Methods to increase the titer of such vectors commonly include concentration by ultracentrifugation and truncation of the Spike protein cytoplasmic tail. However, limited studies have examined whether such a modification also impacts the proteins function. Here, we optimized concentration methods for SARS-CoV-2 Spike pseudotyped VSV vectors, finding that tangential flow filtration produced vectors with more consistent titers than ultracentrifugation. We also examined the impact of Spike tail truncation on transduction of various cell types and sensitivity to convalescent serum neutralization. We found that tail truncation increased Spike incorporation into both LV and VSV vectors and resulted in enhanced titers, but had no impact on sensitivity to convalescent serum inhibition. In addition, we analyzed the effect of the D614G mutation, which became a dominant SARS-CoV-2 variant early in the pandemic. Our studies revealed that, similar to the tail truncation, D614G independently increases Spike incorporation and vector titers, but that this effect is masked by also including the cytoplasmic tail truncation. Therefore, the use of full-length Spike protein, combined with tangential flow filtration, is recommended as a method to generate high titer pseudotyped vectors that retain native Spike protein functions. IMPORTANCEPseudotyped viral vectors are useful tools to study the properties of viral fusion proteins, especially those from highly pathogenic viruses. The Spike protein of SARS-CoV-2 has been investigated using pseudotyped lentiviral and VSV vector systems, where truncation of its cytoplasmic tail is commonly used to enhance Spike incorporation into vectors and to increase the titers of the resulting vectors. However, our studies have shown that such effects can also mask the phenotype of the D614G mutation in the ectodomain of the protein, which was a dominant variant early in the COVID-19 pandemic. To better ensure the authenticity of Spike protein phenotypes when using pseudotyped vectors, we therefore recommend using full-length Spike proteins, combined with tangential flow filtration methods of concentration, if higher titer vectors are required.

Bilateral peripheral facial paralysis during pregnancy: a presentation of acute HIV seroconversion.

A G7P5A1 woman in her 40s presented to the emergency department at 37 weeks 3 days' estimated gestational age (EGA) with headache, lip tingling and several days of difficulty speaking. Physical examination demonstrated bilateral facial weakness in a peripheral distribution, as well as decreased corneal reflexes and cervical lymphadenopathy. Routine fourth generation HIV screening had previously been negative at 14 and 28 weeks' EGA. Brain MRI was unremarkable, and lumbar puncture disclosed a low-grade, mononuclear cerebrospinal fluid pleocytosis; the patient was treated supportively. She returned for induction of labour at 39 weeks, at which time HIV infection was unexpectedly diagnosed. While unilateral idiopathic peripheral facial paralysis is associated with the third trimester of pregnancy and the early postpartum period, bilateral facial paralysis is rare and should prompt work-up for an underlying systemic cause, such as HIV infection.

Endoplasmic reticulum stress in biological processing and disease.

The ability of translated cellular proteins to perform their functions requires their proper folding after synthesis. The endoplasmic reticulum (ER) is responsible for coordinating protein folding and maturation. Infections, genetic mutations, environmental factors and many other conditions can lead to challenges to the ER known as ER stress. Altering ER homeostasis results in accumulation of misfolded or unfolded proteins. To eliminate this problem, a response is initiated by the cell called the unfolded protein response (UPR), which involves multiple signaling pathways. Prolonged ER stress or a dysregulated UPR can lead to premature apoptosis and an exaggerated inflammatory response. Following these discoveries, ER stress was shown to be related to several chronic diseases, such as diabetes mellitus, neurodegenerative disorders, fatty liver disease and inflammatory bowel disease that have not yet been clearly demonstrated pathophysiologically. Here, we review the field and present up-to-date information on the relationship between biological processing, ER stress, UPR, and several chronic diseases.

The Use of B-Cell Polysome Profiling to Validate Novel RPL5 (uL18) and RPL26 (uL24) Variants in Diamond-Blackfan Anemia.

Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome usually caused by heterozygous variants in ribosomal proteins (RP) and which leads to severe anemia. Genetic studies in DBA rely primarily on multigene panels that often result in variants of unknown significance. Our objective was to optimize polysome profiling to functionally validate new large subunit RP variants. We determined the optimal experimental conditions for B-cell polysome profiles then performed this analysis on 2 children with DBA and novel missense RPL5 (uL18) and RPL26 (uL24) variants of unknown significance. Both patients had reduced 60S and 80S fractions when compared with an unaffected parent consistent with a large ribosomal subunit defect. Polysome profiling using primary B-cells is an adjunctive tool that can assist in validation of large subunit RP variants of uncertain significance. Further studies are necessary to validate this method in patients with known DBA mutations, small RP subunit variants, and silent carriers.

The Olfactory Bulb Facilitates Use of Category Bounds for Classification of Odorants in Different Intensity Groups.

Signal processing of odor inputs to the olfactory bulb (OB) changes through top-down modulation whose shaping of neural rhythms in response to changes in stimulus intensity is not understood. Here we asked whether the representation of a high vs. low intensity odorant in the OB by oscillatory neural activity changed as the animal learned to discriminate odorant concentration ranges in a go-no go task. We trained mice to discriminate between high vs. low concentration odorants by learning to lick to the rewarded group (low or high). We recorded the local field potential (LFP) in the OB of these mice and calculated the theta-referenced beta or gamma oscillation power (theta phase-referenced power, or tPRP). We found that as the mouse learned to differentiate odorant concentrations, tPRP diverged between trials for the rewarded vs. the unrewarded concentration range. For the proficient animal, linear discriminant analysis was able to predict the rewarded odorant group and the performance of this classifier correlated with the percent correct behavior in the odor concentration discrimination task. Interestingly, the behavioral response and decoding accuracy were asymmetric as a function of concentration when the rewarded stimulus was shifted between the high and low odorant concentration ranges. A model for decision making motivated by the statistics of OB activity that uses a single threshold in a logarithmic concentration scale displays this asymmetry. Taken together with previous studies on the intensity criteria for decisions on odorant concentrations, our finding suggests that OB oscillatory events facilitate decision making to classify concentrations using a single intensity criterion.