Opiophobia in Emergency Department Healthcare Providers: A Survey in Western Switzerland.

Opiophobia contributes to oligoanalgesia in the emergency department (ED), but its definition varies, and its association to healthcare providers' personality traits has been scantly explored. Our purpose was to study the different definitions of opiophobia and their association with two personality traits of doctors and nurses working in EDs, namely the stress from uncertainty and risk-taking. We used three online questionnaires: the 'Attitude Towards Morphine Use' Score (ATMS), the Stress From Uncertainty Scale (SUS) and the Risk-Taking Scale (RTS). Doctors and nurses from nine hospital EDs in francophone Switzerland were invited to participate. The ATMS score was analyzed according to demographic characteristics, SUS, and RTS. The response rate was 56%, with 57% of respondents being nurses and 63% women. Doctors, less experienced and non-indigenous participants had a significantly higher ATMS (all p ≤ 0.01). The main contributors of the ATMS were the fear of side effects and of addiction. In multivariate analysis, being a doctor, less experience and non-indigenous status were predictive of the ATMS; each point of the SUS increased the ATMS by 0.24 point. The fear of side effects and of addiction were the major contributors of opiophobia among ED healthcare providers; opiophobia was also associated with their personality traits.

Clinical Approach to Personality Change Due to Another Medical Condition.

BACKGROUND: Medical personality change (MPC) is a codable diagnosis (i.e., F07.0) that deserves consideration when a patient is inexplicably no longer "acting like him/herself." Its presentation ranges from subtle to severe and is often characterized by bafflingly poor judgment and impairment in several aspects of a person's life. Despite the global impact that MPC can have on a patient's functioning, occupation, and relationships, this condition receives far less clinical consideration than better known syndromes such as depression or anxiety and is often likely incorrectly formulated as such. OBJECTIVE/METHODS: This article provides a clinically focused review of MPC. We review its clinical assessment followed by a review of its subtypes, which we have categorized to reflect the behavioral correlates of known frontotemporal-subcortical circuits. These include the apathetic type (ventromedial prefrontal cortex), the labile and disinhibited types (orbitofrontal cortex), and the aggressive and paranoid types (medial temporal lobes). RESULTS: For each of these 3 categories, we describe the clinical presentation and review management strategies. For each category, we focus on 3 common causes for MPC-traumatic brain injury, Huntington disease, and brain tumors-which we have selected because clinical features of MPC due to these conditions generalize to many other etiologies of MPC. CONCLUSIONS: MPC warrants clinical attention for the range of dysfunction and distress it can cause. It also deserves further scientific study to better characterize its phenotypes, to tailor instruments for its clinical assessment, and to identify effective treatments.

Klotho rewires cellular metabolism of breast cancer cells through alteration of calcium shuttling and mitochondrial activity.

Klotho is a transmembrane protein, which can be shed and act as a circulating hormone and is involved in regulating cellular calcium levels and inhibition of the PI3K/AKT pathway. As a longevity hormone, it protects normal cells from oxidative stress, and as a tumor suppressor it inhibits growth of cancer cells. Mechanisms governing these differential activities have not been addressed. Altered cellular metabolism is a hallmark of cancer and dysregulation of mitochondrial activity is a hallmark of aging. We hypothesized that klotho exerts its differential effects through regulation of these two hallmarks. Treatment with klotho inhibited glycolysis, reduced mitochondrial activity and membrane potential only in cancer cells. Accordingly, global metabolic screen revealed that klotho altered pivotal metabolic pathways, amongst them glycolysis and tricarboxylic acid cycle in breast cancer cells. Alteration of metabolic activity and increased AMP/ATP ratio lead to LKB1-dependent AMPK activation. Indeed, klotho induced AMPK phosphorylation; furthermore, inhibition of LKB1 partially abolished klotho's tumor suppressor activity. By diminishing deltapsi (Δψ) klotho also inhibited mitochondria Ca2+ shuttling thereby impairing mitochondria communication with SOCE leading to reduced Ca2+ influx by SOCE channels. The reduced SOCE was followed by ER Ca2+ depletion and stress. These data delineate mechanisms mediating the differential effects of klotho toward cancer versus normal cells, and indicate klotho as a potent regulator of metabolic activity.

Clinical Approach to Personality Change Due to Another Medical Condition.

BACKGROUND: Medical personality change (MPC) is a codable diagnosis (i.e., F07.0) that deserves consideration when a patient is inexplicably no longer "acting like him/herself." Its presentation ranges from subtle to severe and is often characterized by bafflingly poor judgment and impairment in several aspects of a person's life. Despite the global impact that MPC can have on a patient's functioning, occupation, and relationships, this condition receives far less clinical consideration than better known syndromes such as depression or anxiety and is often likely incorrectly formulated as such. OBJECTIVE/METHODS: This article provides a clinically focused review of MPC. We review its clinical assessment followed by a review of its subtypes, which we have categorized to reflect the behavioral correlates of known frontotemporal-subcortical circuits. These include the apathetic type (ventromedial prefrontal cortex), the labile and disinhibited types (orbitofrontal cortex), and the aggressive and paranoid types (medial temporal lobes). RESULTS: For each of these 3 categories, we describe the clinical presentation and review management strategies. For each category, we focus on 3 common causes for MPC-traumatic brain injury, Huntington disease, and brain tumors-which we have selected because clinical features of MPC due to these conditions generalize to many other etiologies of MPC. CONCLUSIONS: MPC warrants clinical attention for the range of dysfunction and distress it can cause. It also deserves further scientific study to better characterize its phenotypes, to tailor instruments for its clinical assessment, and to identify effective treatments.

Case report of an unusual combination of purulent pericarditis and false aneurysm of the ascending aorta.

BACKGROUND: Purulent pericarditis is an uncommon entity, which is, in very rare cases, associated to infection of the aorta. CASE PRESENTATION: We present the case of a 42-year-old male patient, who was admitted to hospital complaining of tiredness, diarrhea and leg edema. Clinical examination revealed a hypotensive and obviously shocked patient. He was ultimately diagnosed with a rare combination of purulent pericarditis followed by false aneurysm of the ascending aorta. He was successfully treated by surgical pericardial drainage, replacement of the ascending aorta and antibiotics. CONCLUSION: Mycotic aneurysms can rarely be associated with purulent pericarditis. Our literature review shows that there are two mechanisms explaining this association and that in most of the published cases infective endocarditis could not be demonstrated.

Prevalence and Prognostic Significance of Nonsustained Ventricular Tachycardia in Patients With a Left Ventricular Ejection Fraction from 35% to 50.

The risk of life-threatening ventricular arrhythmias in patients with mild-to-moderately reduced left ventricular ejection fraction (LVEF) is unknown. This retrospective case-control study aims to identify the prevalence, risk factors, and outcomes associated with the development of nonsustained ventricular tachycardia (NSVT) as documented on permanent pacemakers or implantable loop recorders in tertiary care center patients with an LVEF of 35% to 50%. Data pertaining to patient demographics, previous medical history, heart failure functional class, echocardiographic parameters, and survival were compared between the groups. Of the 326 patients with an LVEF within the target range, 90 patients (27.6%) had NSVT recorded on their device and 236 patients (72.4%) did not. Compared with patients without NSVT, patients with NSVT had a higher body mass index (28.4 kg/m2 vs 26.8 kg/m2, p = 0.02), more ischemic heart disease (57.8% vs 32.8%, p < 0.0001), higher left atrial volume index (45.8 ml/m2 vs 42.0 ml/m2, p = 0.04), and lower use of antiarrhythmic medications (4.4% vs 11.9%, p = 0.04). The presence of NSVT and the duration of NSVT had no relation to survival, supporting the notion that NSVT is a benign finding in patients with an LVEF of 35% to 50%.

Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

Key mitochondrial functions such as ATP production, Ca2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔµH+) across the inner membrane. Although several drugs can modulate ΔµH+, their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψm) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca2+ dynamics, and respiratory metabolism. By directly modulating Δψm, the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic ß-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.

Anti-Metastatic Effect of Semi-Purified Nuphar Lutea Leaf Extracts.

Nuphar lutea L. SM., leaf and rhizome extracts (NUP), contain nupharidines as active components. Nupharidines belong to the sesquiterpene lactones class of a naturally occurring plant terpenoids. This family of compounds has gained considerable interest for treating infection, inflammation and cancer. NF-κB is a central, downstream regulator of inflammation, cell proliferation and apoptosis. In our previous work we demonstrated strong inhibition of NF-κB activity and induction of apoptosis by NUP. In addition, NUP exhibited anti-inflammatory properties and partial protection from LPS-induced septic shock by modulating ERK pathway and cytokine secretion in macrophages. In the present study, we examined the effect of NUP in a B16 melanoma experimental murine lung metastasis model and its ability to affect the ERK and NF-κB pathways in variety of cell lines. We showed that NUP and cisplatin combined treatment was synergistic and reduced the lung metastatic load. In addition NUP treatment inhibited TNFα-induced IκBα degradation and NF- κB nuclear translocation. We also observed that NUP induced ERK activation. Furthermore, ERK inhibition prevented NF-κB inactivation by NUP. Overall, our work implies that co-administration of NF-κB inhibitors such as NUP, with standard anti-cancer drugs, may act as "sensitizers" for more effective chemotherapy.

Definition and management of varicella zoster virus-associated meningoradiculitis: a case report.

BACKGROUND: The varicella zoster virus affects the central or peripheral nervous systems upon reactivation, especially when cell-mediated immunity is impaired. Among varicella zoster virus-related neurological syndromes, meningoradiculitis is an ill-defined condition for which clear management guidelines are still lacking. Zoster paresis is usually considered to be a varicella zoster virus-peripheral nervous system complication and treated with oral antiviral therapy. Yet in the literature, the few reported cases of herpes zoster with mild cerebral spinal fluid inflammation were all considered meningoradiculitis and treated using intravenous antiviral drugs, despite absence of systemic signs of meningitis. Nevertheless, these two clinical pictures are very similar. CASE PRESENTATION: We report the case of an alcohol-dependent elderly Caucasian man presenting with left lower limb zoster paresis and mild cerebral spinal fluid inflammation, with favorable outcome upon IV antiviral treatment. We discuss interpretation of liquor inflammation in the absence of clinical meningitis and implications for the antiviral treatment route. CONCLUSION: From this case report we suggest that varicella zoster virus-associated meningoradiculitis should necessarily include meningitis symptoms with the peripheral neurological deficits and cerebral spinal fluid inflammation, requiring intravenous antiviral treatment. In the absence of (cell-mediated) immunosuppression, isolated zoster paresis does not necessitate spinal tap or intravenous antiviral therapy.

Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by extremely heterogeneous molecular and biologic abnormalities that hamper the development of effective targeted treatment modalities. While AML cells are highly sensitive to cytotoxic Ca2+ overload, the feasibility of Ca2+- targeted therapy of this disease remains unclear. Here, we show that apoptotic response of AML cells to the synergistically acting polyphenols curcumin (CUR) and carnosic acid (CA), combined at low, non-cytotoxic doses of each compound was mediated solely by disruption of cellular Ca2+ homeostasis. Specifically, activation of caspase cascade in CUR+CA-treated AML cells resulted from sustained elevation of cytosolic Ca2+ (Ca2+cyt) and was not preceded by endoplasmic reticulum stress or mitochondrial damage. The CUR+CA-induced Ca2+cyt rise did not involve excessive influx of extracellular Ca2+ but, rather, occurred due to massive Ca2+ release from intracellular stores concomitant with inhibition of Ca2+cyt extrusion through the plasma membrane. Notably, the CUR+CA combination did not alter Ca2+ homeostasis and viability in non-neoplastic hematopoietic cells, suggesting its cancer-selective action. Most importantly, co-administration of CUR and CA to AML-bearing mice markedly attenuated disease progression in two animal models. Collectively, our results provide the mechanistic and translational basis for further characterization of this combination as a prototype of novel Ca2+-targeted pharmacological tools for the treatment of AML.

Juvenile fibromyalgia in an adolescent patient with sickle cell disease presenting with chronic pain.

Juvenile fibromyalgia in children with sickle cell disease has not been reported in the literature. We report an adolescent patient with sickle cell whose pain symptoms progressed from having recurrent acute sickle cell pain crisis episodes to a chronic pain syndrome over several years. He was eventually diagnosed with juvenile fibromyalgia based on the clinical history and myofascial tender points and his pain symptoms responded better to multidisciplinary strategies for chronic fibromyalgia pain. Chronic pain in sickle cell disease is an area of poor research, and in addition there is inconsistency in the definition of chronic pain in sickle cell disease. Central sensitisation to pain is shown to occur after recurrent painful stimuli in a genetically vulnerable individual. In a chronic pain condition such as fibromyalgia central sensitisation is thought to play a key role. Fibromyalgia should be considered as one of the main differential diagnosis in any sickle cell patient with chronic pain.

[Benefit of ultrasound in the early management of patients in shock]. / Apport de l'echographie dans la prise en charge initiate des patients en etat de choc.

Shock is a hemodynamic situation that aggravates the vital prognostic of every patient regardless of the underlying pathology. It has been well documented that the speed at which hemodynamics is restored to standard values significantly decreases the mortality and morbidity in these patients. Initially described in traumatology, then in every type of shock, the contribution of ultrasonography performed at the bedside by the physician in charge allows for a significant shortening of the diagnostic procedure and thus an earlier start for a goal-directed treatment.

Amplified lipid rafts of malignant cells constitute a target for inhibition of aberrantly active NFAT and melanoma tumor growth by the aminobisphosphonate zoledronic acid.

Nuclear factors of activated T cells (NFAT) are critical modulators of cancer cell growth and survival. However, the mechanisms of their oncogenic dysregulation and strategies for targeting in tumors remain elusive. Here, we report coupling of anti- apoptotic NFAT (NFAT2) activation to cholesterol-enriched lipid raft microdomains of malignant melanoma cells and interruption of this pathway by the aminobisphosphonate zoledronic acid (Zol). The pathway was indicated by capability of Zol to promote apoptosis and to retard in vivo outgrowth of tumorigenic melanoma cell variants through inhibition of permanently active NFAT2. NFAT2 inhibition resulted from disintegration of cholesterol-enriched rafts due to reduction of cellular cholesterol by Zol. Mechanistically, raft disruption abolished raft-localized robust store-operated Ca(2+) (SOC) entry, blocking constitutive activation of protein kinase B/Akt (PKB) and thereby reactivating the NFAT repressor glycogen synthase kinase 3ß (GSK3ß). Pro-apoptotic inactivation of NFAT2 also followed reactivation of GSK3ß by direct inhibition of PKB or SOC, whereas GSK3ß blockade prevented Zol-induced NFAT2 inhibition and cell death. The rescuing effect of GSK3ß blockade was reproduced by recovery of entire SOC/PKB/GSK3ß cascade after reconstitution of rafts by cholesterol replenishment of Zol-treated tumorigenic cells. Remarkably, these malignant cells displayed higher cholesterol and lipid raft content than non-tumorigenic cells, which expressed weak SOC, PKB and NFAT2 activities and resisted raft-ablating action of Zol. Together, the results underscore the functional relevance of amplified melanoma rafts for tumor-promoting NFAT2 signaling and reveal these distinctive microdomains as a target for in vitro and in vivo demise of tumorigenic cells through NFAT2 inhibition by the clinical agent Zol.

Integrated evaluation of cost, emissions, and resource potential for algal biofuels at the national scale.

Costs, emissions, and resource availability were modeled for the production of 5 billion gallons yr(-1) (5 BGY) of renewable diesel in the United States from Chlorella biomass by hydrothermal liquefaction (HTL). The HTL model utilized data from a continuous 1-L reactor including catalytic hydrothermal gasification of the aqueous phase, and catalytic hydrotreatment of the HTL oil. A biophysical algae growth model coupled with weather and pond simulations predicted biomass productivity from experimental growth parameters, allowing site-by-site and temporal prediction of biomass production. The 5 BGY scale required geographically and climatically distributed sites. Even though screening down to 5 BGY significantly reduced spatial and temporal variability, site-to-site, season-to-season, and interannual variations in productivity affected economic and environmental performance. Performance metrics based on annual average or peak productivity were inadequate; temporally and spatially explicit computations allowed more rigorous analysis of these dynamic systems. For example, 3-season operation with a winter shutdown was favored to avoid high greenhouse gas emissions, but economic performance was harmed by underutilized equipment during slow-growth periods. Thus, analysis of algal biofuel pathways must combine spatiotemporal resource assessment, economic analysis, and environmental analysis integrated over many sites when assessing national scale performance.

Toward a firmer foundation for DSM-5.1: domains of impairment in DSM-IV/DSM-5 personality disorders.

In recent editions of the Diagnostic and Statistical Manual of Mental Disorders, personality disorders (PDs) have been conceptualized as reflecting impairments in four areas: cognition, affectivity, interpersonal functioning, and impulse control. However, there have been no systematic surveys of PD symptoms to assess the degree to which these four domains of impairment are actually represented in the DSM-IV/DSM-5 PD symptom criteria. Results of such a survey indicated that the most common domain of impairment for DSM-IV/DSM-5 PDs is interpersonal functioning (41% of all PD symptoms), followed by cognition (30%), and affectivity (18%), with relatively few PD symptoms reflecting difficulties in impulse control (6%). Comparison of the proportions of symptoms in different impairment domains in DSM-III, DSM-III-R, and DSM-IV/DSM-5 confirmed that these symptom distributions have been stable across revisions of the diagnostic manual. Implications of these results for the conceptualization of PDs in DSM-5.1 and beyond are discussed.

Non-redundant properties of IL-1α and IL-1ß during acute colon inflammation in mice.

OBJECTIVE: The differential role of the IL-1 agonists, IL-1α, which is mainly cell-associated versus IL-1ß, which is mostly secreted, was studied in colon inflammation. DESIGN: Dextran sodium sulfate (DSS) colitis was induced in mice globally deficient in either IL-1α or IL-1ß, and in wild-type mice, or in mice with conditional deletion of IL-1α in intestinal epithelial cells (IECs). Bone marrow transplantation experiments were performed to assess the role of IL-1α or IL-1ß of myeloid versus colon non-hematopoietic cells in inflammation and repair in acute colitis. RESULTS: IL-1α released from damaged IECs acts as an alarmin by initiating and propagating colon inflammation, as IL-1α deficient mice exhibited mild disease symptoms with improved recovery. IL-1ß is involved in repair of IECs and reconstitution of the epithelial barrier during the resolution of colitis; its deficiency correlates with disease exacerbation. Neutralisation of IL-1α in control mice during acute colitis led to alleviation of clinical and histological manifestations, whereas treatment with rIL-1Ra or anti-IL-1ß antibodies was not effective. Repair after colitis correlated with accumulation of CD8 and regulatory T cells in damaged crypts. CONCLUSIONS: The role of IL-1α and IL-1ß differs in DSS-induced colitis in that IL-1α, mainly of colon epithelial cells is inflammatory, whereas IL-1ß, mainly of myeloid cell origin, promotes healing and repair. Given the dissimilar functions of each IL-1 agonistic molecule, an IL-1 receptor blockade would not be as therapeutically effective as specific neutralising of IL-1α, which leaves IL-1ß function intact.

Awareness of HIV testing guidelines is low among Swiss emergency doctors: a survey of five teaching hospitals in French-speaking Switzerland.

BACKGROUND: In Switzerland, 30% of HIV-infected individuals are diagnosed late. To optimize HIV testing, the Swiss Federal Office of Public Health (FOPH) updated 'Provider Induced Counseling and Testing' (PICT) recommendations in 2010. These permit doctors to test patients if HIV infection is suspected, without explicit consent or pre-test counseling; patients should nonetheless be informed that testing will be performed. We examined awareness of these updated recommendations among emergency department (ED) doctors. METHODS: We conducted a questionnaire-based survey among 167 ED doctors at five teaching hospitals in French-Speaking Switzerland between 1(st) May and 31(st) July 2011. For 25 clinical scenarios, participants had to state whether HIV testing was indicated or whether patient consent or pre-test counseling was required. We asked how many HIV tests participants had requested in the previous month, and whether they were aware of the FOPH testing recommendations. RESULTS: 144/167 doctors (88%) returned the questionnaire. Median postgraduate experience was 6.5 years (interquartile range [IQR] 3; 12). Mean percentage of correct answers was 59 ± 11%, senior doctors scoring higher (P=0.001). Lowest-scoring questions pertained to acute HIV infection and scenarios where patient consent was not required. Median number of test requests was 1 (IQR 0-2, range 0-10). Only 26/144 (18%) of participants were aware of the updated FOPH recommendations. Those aware had higher scores (P=0.001) but did not perform more HIV tests. CONCLUSIONS: Swiss ED doctors are not aware of the national HIV testing recommendations and rarely perform HIV tests. Improved recommendation dissemination and adherence is required if ED doctors are to contribute to earlier HIV diagnoses.

Unnoticed intrusions: dissociations of meta-consciousness in thought suppression.

The current research investigates the interaction between thought suppression and individuals' explicit awareness of their thoughts. Participants in three experiments attempted to suppress thoughts of a prior romantic relationship and their success at doing so was measured using a combination of self-catching and experience-sampling. In addition to thoughts that individuals spontaneously noticed, individuals were frequently caught engaging in thoughts of their previous partner at experience-sampling probes. Furthermore, probe-caught thoughts were: (i) associated with stronger decoupling of attention from the environment, (ii) more likely to occur under cognitive load, (iii) more frequent for individuals with a desire to reconcile, and (iv) associated with individual differences in the tendency to suppress thoughts. Together, these data suggest that individuals can lack meta-awareness that they have begun to think about a topic they are attempting to suppress, providing novel insight into the cognitive processes that are involved in attempting to control undesired mental states.