Influence of Interoceptive Fear Learning on Visceral Perception.

Objectives: Interoceptive fear learning and generalization have been hypothesized to play a key role in unexplained abdominal and esophageal pain in patients with functional gastrointestinal disorders. However, there is no experimental evidence demonstrating that fear learning and generalization to visceral sensations can be established in humans and alter visceral perception.

Methods: In a novel fear learning-generalization paradigm, an innocuous esophageal balloon distension served as conditioned stimulus (CS), and distensions at three different pressure levels around the pain detection threshold were used as generalization stimuli.

Efficacy of Mirtazapine in Patients With Functional Dyspepsia and Weight Loss.

Background & Aims: A subset of patients with functional dyspepsia (FD) present with early satiation and weight loss, for which there are no established therapeutic options. We investigated the efficacy of mirtazapine (an antidepressant and antagonist of the histamine receptor H1, the α2 adrenergic receptor, and the serotonin receptors 5-HT2C and 5-HT-3) in patients with FD and weight loss.

Methods: We conducted a randomized, placebo-controlled pilot trial that studied 34 patients with FD (29 women; mean age, 35.

Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes.

Type II diabetes increases the risk for cognitive decline via multiple traits. Amylin is a pancreatic hormone that has amyloidogenic and cytotoxic properties similar to the amyloid-β peptide. The amylin hormone is overexpressed in individuals with pre-diabetic insulin resistance or obesity leading to amylin oligomerization and deposition in pancreatic islets.

Differential Inhibition of Macrophage Activation by Lymphocytic Choriomeningitis Virus and Pichinde Virus Is Mediated by the Z Protein N-Terminal Domain.

Several arenavirus pathogens, such as Lassa and Junin viruses, inhibit macrophage activation, the molecular mechanism of which is unclear. We show that lymphocytic choriomeningitis virus (LCMV) can also inhibit macrophage activation, in contrast to Pichinde and Tacaribe viruses, which are not known to naturally cause human diseases. Using a recombinant Pichinde virus system, we show that the LCMV Z N-terminal domain (NTD) mediates the inhibition of macrophage activation and immune functions.

Contrast-Induced Nephropathy: From Pathophysiology to Preventive Strategies.

Contrast-induced nephropathy (CIN) is a frequent cause of acute kidney injury in hospitalized patients. CIN is most commonly defined as either an absolute (≥ 0.5 mg/dL; ≥ 44 μmol/L) or relative (≥ 25%) increase in serum creatinine levels at 48-72 hours after exposure to iodinated contrast media (CM).

Startle responding in the context of visceral pain.

This study aimed to investigate affective modulation of eye blink startle by aversive visceral stimulation. Startle blink EMG responses were measured in 31 healthy participants receiving painful, intermittent balloon distentions in the distal esophagus during 4 blocks (positive, negative, neutral or no pictures), and compared with startles during 3 'safe' blocks without esophageal stimulations (positive, negative or neutral emotional pictures). Women showed enhanced startle during blocks with distentions (as compared with 'safe' blocks), both when the balloon was in inflated and deflated states, suggesting that fear and/or expectations may have played a role.

Nature of the Surface-Exposed Cytochrome-Electrode Interactions in Electroactive Biofilms of Desulfuromonas acetoxidans.

Metal-respiring bacteria are microorganisms capable of oxidizing organic pollutants present in wastewater and transferring the liberated electrons to an electrode. This ability has led to their application as catalysts in bioelectrochemical systems (BESs), a sustainable technology coupling bioremediation to electricity production. Crucial for the functioning of these BESs is a complex protein architecture consisting of several surface-exposed multiheme proteins, called outer membrane cytochromes, wiring the cell metabolism to the electrode.

Human hemorrhagic Fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis.

Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases.

Highly Amino Acid Selective Hydrolysis of Myoglobin at Aspartate Residues as Promoted by Zirconium(IV)-Substituted Polyoxometalates.

SDS-PAGE/Edman degradation and HPLC MS/MS showed that zirconium(IV)-substituted Lindqvist-, Keggin-, and Wells-Dawson-type polyoxometalates (POMs) selectively hydrolyze the protein myoglobin at Asp-X peptide bonds under mildly acidic and neutral conditions. This transformation is the first example of highly sequence selective protein hydrolysis by POMs, a novel class of protein-hydrolyzing agents. The selectivity is directed by Asp residues located on the surface of the protein and is further assisted by electrostatic interactions between the negatively charged POMs and positively charged surface patches in the vicinity of the cleavage site.

Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments.

Unlabelled: Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV.

Direct stenting versus pre-dilation in ST-elevation myocardial infarction: a systematic review and meta-analysis.

Objectives: This study aimed at comparing direct stenting (DS) versus stenting with pre-dilation (SP) in patients with ST-elevation myocardial infarction (STEMI), using a systematic review and meta-analysis of published evidence.

Background: There is conflicting evidence whether stenting strategy impacts clinical outcomes in patients with STEMI.

Methods: We searched EMBASE, MEDLINE, and CENTRAL, from inception to December 2014.

In vitro and in vivo characterizations of pichinde viral nucleoprotein exoribonuclease functions.

Unlabelled: Arenaviruses cause severe hemorrhagic fever diseases in humans, and there are limited preventative and therapeutic measures against these diseases. Previous structural and functional analyses of arenavirus nucleoproteins (NPs) revealed a conserved DEDDH exoribonuclease (RNase) domain that is important for type I interferon (IFN) suppression, but the biological roles of the NP RNase in viral replication and host immune suppression have not been well characterized. Infection of guinea pigs with Pichinde virus (PICV), a prototype arenavirus, can serve as a surrogate small animal model for arenavirus hemorrhagic fevers.

Acute Anxiety and Anxiety Disorders Are Associated With Impaired Gastric Accommodation in Patients With Functional Dyspepsia.

Background & Aims: Functional dyspepsia (FD) is associated with impaired gastric accommodation, as well as gastric hypersensitivity, delayed emptying, and psychosocial comorbidities. In healthy people, acute anxiety impairs gastric accommodation, which is traditionally quantified as the average increase in gastric volume after a meal over 1 hour. However, this quantification approach does not address the complex time course of the gastric accommodation response to a meal.

Increased cerebral cannabinoid-1 receptor availability is a stable feature of functional dyspepsia: a [F]MK-9470 PET study.

Background: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder (FGID) defined by chronic epigastric symptoms in the absence of organic abnormalities likely to explain them. Comorbidity with mood and anxiety disorders as well as with other FGIDs and functional somatic syndrome (FSS) is high. FD is characterized by abnormal regional cerebral activity in cognitive/affective pain modulatory circuits, but it is unknown which neurotransmitter systems are involved.

Characterization of immunological responses in patients with severe fever with thrombocytopenia syndrome: a cohort study in China.

Background: The immunological responses of patients with severe fever with thrombocytopenia syndrome (SFTS) remain largely unknown. We aim to study the magnitude and sustainability of host immune responses and their correlation with clinical, virological and hematological parameters.

Methods: A longitudinal cohort study was performed in a SFTS reference hospital.

The Z proteins of pathogenic but not nonpathogenic arenaviruses inhibit RIG-I-like receptor-dependent interferon production.

Unlabelled: Arenavirus pathogens cause a wide spectrum of diseases in humans ranging from central nervous system disease to lethal hemorrhagic fevers with few treatment options. The reason why some arenaviruses can cause severe human diseases while others cannot is unknown. We find that the Z proteins of all known pathogenic arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Lassa, Junin, Machupo, Sabia, Guanarito, Chapare, Dandenong, and Lujo viruses, can inhibit retinoic acid-inducible gene 1 (RIG-i) and Melanoma Differentiation-Associated protein 5 (MDA5), in sharp contrast to those of 14 other nonpathogenic arenaviruses.

Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteers.

The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing.

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology/Canadian Society of Cardiac Surgery position statement on revascularization--multivessel coronary artery disease.

This position statement addresses issues in revascularization for multivessel coronary artery disease (CAD) from the perspective of both cardiologists and cardiac surgeons. Recommendations are made based on evidence from clinical trials and observational studies, with an emphasis on the increasing number of individuals with significant comorbid disease burden and functional debilitation who are being referred for definitive management of their multivessel CAD in the context of routine clinical practice. These types of individuals have traditionally not been included in the many clinical trials that have been the basis for guidelines and recommendations, and the objective of the proposed medical intervention or revascularization (or both) would not necessarily be to improve prognosis but to improve quality of life.

An adult male with progressive spastic paraparesis and gait instability.

This is a case of an adult male with history of motor difficulties, speech, and behavioral problems since early childhood found to have progressive spastic paraparesis, impaired vibration and proprioception, and gait instability. His medical history included bilateral cataracts status post surgical removal at the age of 30, cholelithiasis status post cholecystectomy at age 45, and high cholesterol levels.

Normal values and reproducibility of the real-time index of vagal tone in healthy humans: a multi-center study.

Background: The parasympathetic nervous system has been implicated in the pathogenesis of a number of gastrointestinal disorders including irritable bowel syndrome. Within the field, cardiometric parameters of parasympathetic/vagal tone are most commonly derived from time, or frequency, domain analysis of heart rate variability (HRV), yet it has limited temporal resolution. Cardiac vagal tone (CVT) is a non-invasive beat-to-beat measure of brainstem efferent vagal activity that overcomes many of the temporal limitations of HRV parameters.

Laser atherectomy for balloon failure in chronic total occlusion. When the going gets tough.

Excimer laser coronary atherectomy (ELCA) is based on ultraviolet energy and is capable of disintegrating atheroma, without burning or grossly fragmenting it. ELCA has proven effective in the percutaneous treatment of a variety of complex lesions, including chronic total occlusions (CTO) and severely calcified lesions, in case of balloon failure-tocross or failure-to-expand. Here we present a case of a successful CTO recanalization with ELCA after balloon failure, review the literature on this topic, and present an algorithm outlining the management of this challenging clinical scenario.