Fever Associated with Gastrointestinal Shigellosis Unmasks Probable Brugada Syndrome

Since it was first described approximately 15 years ago, the Brugada Syndrome has spurred a significant quantity of interest in its underlying mechanism and physiology. The Brugada electrocardiographic pattern is characterized by right bundle branch block morphology and ST segment elevations in the right precordial leads with an absence of identifiable underlying structural heart disease. The syndrome is clinically significant since these patients are at a higher risk of developing malignant ventricular arrhythmias. One of the mechanisms behind the disorder involves mutations in specific myocardial sodium channels. Furthermore, these electrocardiographic changes appear to be temperature dependent. We present the case of a 35-year-old male who presented with intestinal Shigellosis and was also found to have Brugada-type electrocardiographic changes on ECG. The electrocardiographic changes that were present when the patient was admitted and febrile resolved following antibiotic therapy and defervescence

Do health policy advisors know what the public wants? An empirical comparison of how health policy advisors assess public preferences regarding smoke-free air, and what the public actually prefers

Background: Health policy-making, a complex, multi-factorial process, requires balancing conflicting values. A salient issue is public support for policies; however, one reason for limited impact of public opinion may be misperceptions of policy makers regarding public opinion. For example, empirical research is scarce on perceptions of policy makers regarding public opinion on smoke-free public spaces. Methods: Public desire for smoke-free air was compared with health policy advisor (HPA) perception of these desires. Two representative studies were conducted: one with the public (N = 505), and the other with a representative sample of members of Israel’s health-targeting initiative, Healthy Israel 2020 (N = 34), in December 2010. Corresponding questions regarding desire for smoke-free areas were asked. Possible smoke-free areas included: 100% smoke-free bars and pubs; entrances to health facilities; railway platforms; cars with children; college campuses; outdoor areas (e.g., pools and beaches); and common areas of multi-dweller apartment buildings. A 1–7 Likert scale was used for each measure, and responses were averaged into a single primary outcome, DESIRE. Our primary endpoint was the comparison between public preferences and HPA assessment of those preferences. In a secondary analysis, we compared personal preferences of the public with personal preferences of the HPAs for smoke-free air. Results: HPAs underestimated public desire for smoke-free air (Public: Mean: 5.06, 95% CI:[4.94, 5.17]; HPA: Mean: 4.06, 95% CI:[3.61, 4.52]: p < .0001). Differences at the p = .05 level were found between HPA assessment and public preference for the following areas: 100% smoke-free bars and pubs; entrances to healthcare facilities; train platforms; cars carrying children; and common areas of multi-dweller apartment buildings. In our secondary comparison, HPAs more strongly preferred smoke-free areas than did the public (p < .0001). Conclusions: Health policy advisors underestimate public desire for smoke-free air. Better grasp of public opinion by policy makers may lead to stronger legislation. Monitoring policy-maker assessment of public opinion may shed light on incongruities between policy making and public opinion. Further, awareness of policy-maker misperceptions may encourage policy-makers to demand more accurate information before making policy

CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus

Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients.United States. National Institutes of Health (DK085713)National Cancer Institute (U.S.) (P30-CA14051)National Institute of Environmental Health Sciences (P30-ES002109)United States. National Institutes of Health (1K08DK101754

Construct validity of the Dissociative Experiences Scale (DES): I. The relationship between the DES and other self-report measures of DES

p. 185-188The present study attempted to expand the construct validity of the Dissociative Experiences Scale (DES) by comparing it to: (a) other self-report measures of dissociation (e.g., the Tellegen Absorption Scale [TAS] and the Perceptual Alteration Scale [PAS]); (b) the construct of "ambiguity intolerance" (assessed by the Yellen Ambiguity Intolerance Scale [YAIS]); and (c) the Jenkins Activity Schedule (JAS: which measures the degree of Type A behavior). Three hundred and eleven undergraduates participated in an experiment on "Hypnotizability and Personality, " and filled out the DES TAS, PAS, YAIS, and JAS. The DES total score (and three DES factor scores) correlated with the TAS and PAS in the range of .24 - .52 (all correlations were significant at the .001 level, two-tailed). Furthermore, the DES total score (and the three DES factor scores) correlated significantly with the YAIS overall score (r's ranged from .22 - .24, all p's < .001), but did not correlate significantly with the JAS (r's ranged from -.03 - .04, ns). The findings suggest that DES scores (i.e., total scores and each of the three DES factor scores) show good levels of convergent validity as they correlate significantly with other self-report measures of dissociation. However, the intercorrelations were not high enough to consider the different dissociation measures as interchangeable. Furthermore, subjects reporting high levels of dissociative experiences also reported higher levels of ambiguity intolerance. However, no significant association was observed between DES scores and the Type A behavior pattern

Measurements of the Complex Conductivity of NbxSi1-x Alloys on the Insulating Side of the Metal-Insulator Transition

We have conducted temperature and frequency dependent transport measurements in amorphous Nb_x Si_{1-x} samples in the insulating regime. We find a temperature dependent dc conductivity consistent with variable range hopping in a Coulomb glass. The frequency dependent response in the millimeter-wave frequency range can be described by the expression $sigma(omega) \propto (-\imath omega)^alpha$ with the exponent somewhat smaller than one. Our ac results are not consistent with extant theories for the hopping transport.Comment: 4 pages with 3 figures; published version has a different title from original (was: "Electrodynamics in a Coulomb glass"

Presenting signs and patient co-variables in Gaucher disease : outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative

© 2018 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.Background: Gaucher disease (GD) presents with a range of signs and symptoms. Physicians can fail to recognise the early stages of GD owing to a lack of disease awareness, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities. Aim: The Gaucher Earlier Diagnosis Consensus (GED-C) initiative aimed to identify signs and co-variables considered most indicative of early type 1 and type 3 GD, to help non-specialists identify ‘at-risk’ patients who may benefit from diagnostic testing. Methods: An anonymous, three-round Delphi consensus process was deployed among a global panel of 22 specialists in GD (median experience 17.5 years, collectively managing almost 3000 patients). The rounds entailed data gathering, then importance ranking and establishment of consensus, using 5-point Likert scales and scoring thresholds defined a priori. Results: For type 1 disease, seven major signs (splenomegaly, thrombocytopenia, bone-related manifestations, anaemia, hyperferritinaemia, hepatomegaly and gammopathy) and two major co-variables (family history of GD and Ashkenazi-Jewish ancestry) were identified. For type 3 disease, nine major signs (splenomegaly, oculomotor disturbances, thrombocytopenia, epilepsy, anaemia, hepatomegaly, bone pain, motor disturbances and kyphosis) and one major co-variable (family history of GD) were identified. Lack of disease awareness, overlooking mild early signs and failure to consider GD as a diagnostic differential were considered major barriers to early diagnosis. Conclusion: The signs and co-variables identified in the GED-C initiative as potentially indicative of early GD will help to guide non-specialists and raise their index of suspicion in identifying patients potentially suitable for diagnostic testing for GD.Peer reviewedFinal Published versio

Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation.

BackgroundCombat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS.Methods/designWe describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic (EEG) telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale (CAPS) total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked 18FDG PET metabolic changes in limbic circuitry will also be evaluated.DiscussionWhile the rationale for studying DBS for PTSD is ethically and scientifically justified, the importance of the amygdaloid complex and its connections for a myriad of emotional, perceptual, behavioral, and vegetative functions requires a complex trial design in terms of outcome measures. Knowledge generated from this pilot trial can be used to design future studies to determine the potential of DBS to benefit both veterans and nonveterans suffering from treatment-refractory PTSD.Trial registrationPCC121657, 19 March 2014

FGF19 Action in the Brain Induces Insulin-Independent Glucose Lowering

Insulin-independent glucose disposal (referred to as glucose effectiveness [GE]) is crucial for glucose homeostasis and, until recently, was thought to be invariable. However, GE is reduced in type 2 diabetes and markedly decreased in leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore be capable of improving glucose tolerance in these animals. The gut-derived hormone FGF19 has previously been shown to exert potent antidiabetic effects in ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved glucose tolerance through its action in the brain and that a single, low-dose i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2 hours. Minimal model analysis of glucose and insulin data obtained during a frequently sampled i.v. glucose tolerance test showed that the antidiabetic effect of i.c.v. FGF19 was solely due to increased GE and not to changes of either insulin secretion or insulin sensitivity. The mechanism underlying this effect appears to involve increased metabolism of glucose to lactate. Together, these findings implicate the brain in the antidiabetic action of systemic FGF19 and establish the brain’s capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal

Why Effective Medium Theory Fails in Granular Materials

Experimentally it is known that the bulk modulus, K, and shear modulus, \mu, of a granular assembly of elastic spheres increase with pressure, p, faster than the p^1/3 law predicted by effective medium theory (EMT) based on Hertz-Mindlin contact forces. To understand the origin of these discrepancies, we perform numerical simulations of granular aggregates under compression. We show that EMT can describe the moduli pressure dependence if one includes the increasing number of grain-grain contacts with p. Most important, the affine assumption (which underlies EMT), is found to be valid for K(p) but breakdown seriously for \mu(p). This explains why the experimental and numerical values of \mu(p) are much smaller than the EMT predictions.Comment: 4 pages, 5 figures, http://polymer.bu.edu/~hmaks

Deriving measures of intensive care unit antimicrobial use from computerized pharmacy data: Methods, validation, and overcoming barriers

OBJECTIVE: To outline methods for deriving and validating intensive care unit (ICU) antimicrobial utilization (AU) measures from computerized data and to describe programming problems that emerged. DESIGN: Retrospective evaluation of computerized pharmacy and administrative data. SETTING: ICUs from four academic medical centers over 36 months. INTERVENTIONS: Investigators separately developed and validated programming code to report AU measures in selected ICUs. Antibacterial and antifungal drugs for systemic administration were categorized and expressed as antimicrobial days (each day that each antimicrobial drug was given to each patient) and patient-days on antimicrobials (each day that any antimicrobial drug was given to each patient). Monthly rates were compiled and analyzed centrally with ICU patient-days as the denominator. Results were validated against data collected from manual medical record review. Frequent discussion among investigators aided identification and correction of programming problems. RESULTS: AU data were successfully programmed though a reiterative process of computer code revision. After identifying and resolving major programming errors, comparison of computerized patient-level data with data collected by manual medical record review revealed discrepancies in antimicrobial days and patient-days on antimicrobials ranging from <1% to 17.7%. The hospital for which numerator data were derived from electronic medication administration records had the least discrepant results. CONCLUSIONS: Computerized AU measures can be derived feasibly, but threats to validity must be sought and corrected. The magnitude of discrepancies between computerized AU data and a gold standard based on manual chart review varies, with electronic medication administration records providing maximal accuracy