Miracle-dz/UniFAR-FTUs huggingface dataset:
Perceived decisional responsibility for mechanical ventilation and weaning: a Norwegian survey.

AIM To explore variability in perceptions of nurse managers and physician directors regarding roles, responsibilities and clinical-decision making related to mechanical ventilator weaning in Norwegian intensive care units (ICUs). BACKGROUND Effective teamwork is crucial for providing optimal patient care in ICU. More knowledge on nurses' and physicians' perceptions of responsibility in clinical decision-making for mechanical ventilation is needed. METHODS Self-administered survey of mechanical ventilation and weaning responsibilities was sent to nurse managers and physician directors of Norwegian adult ICUs. Nurses' decisional influence and autonomy were estimated on a numeric rating scale (NRS) from 0 to 10 (least to most). RESULTS Response rate was 38/60 (63%) nurses and 38/52 (73%) physicians. On the NRS nurse managers perceived the autonomy and influence of nurses' ventilator decisions higher than physician directors: median of 7 (IQR 5-8) (nurses) versus 5 (3-6) (physicians), (p < 0·01), and 8 (7-9) (nurses) versus 7 (5-8) (physicians), (p < 0·01) respectively. Respondents agreed that nurses collaborated in assessment of patient response to ventilator changes and titrating ventilator settings: 92% of nurses and 87% of physicians, (p = 0·46), and recognizing weaning failure 84% of nurses and 84% of physicians, (p = 0·96). Physician directors perceived significantly less collaborative decision-making on weaning method (p = 0·01), weaning readiness (p = 0·04) and readiness to extubate (p < 0·01) than nurse managers. Both groups acknowledged the importance of 'knowing the patient' for weaning success, and agreed that the assessment of work of breathing, well-being, and clinical deterioration were important for determining weaning tolerance. CONCLUSIONS Nurse managers perceived nurses to have greater autonomy, influence and collaborative interaction regarding decisions on mechanical ventilation than physician directors. Greater awareness and acknowledgment of nurses' role may promote interprofessional collaboration and improve patient care.
A Review of Pathogenic Vibrio Infections for Clinicians

Vibrio infections are becoming increasingly common in the United States. Pathogenic vibrios cause 3 major syndromes of clinical illness: gastroenteritis, wound infections, and septicemia. Many cases of Vibrio-associated gastroenteritis are substantially underrecognized because vibrios are not readily identified in routine stool cultures. Epidemiologic data suggest that the majority of these infections are foodborne and associated with consumption of raw or undercooked shellfish. In persons who develop acute gastroenteritis after eating raw or undercooked shellfish, clinicians should order testing of a stool specimen using a selective medium for vibrios. Clinicians should obtain a travel history when evaluating a patient with acute watery diarrhea, and should consider cholera in the differential diagnosis when a patient has returned from a trip to a country where cholera is known or suspected to be present.
Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality.

BACKGROUND In cross-sectional studies, low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease. This study aimed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality. METHODS Prospective cohort study of 3258 consecutive male and female patients (mean [SD] age, 62 [10] years) scheduled for coronary angiography at a single tertiary center. We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings. The main outcome measures were all-cause and cardiovascular deaths. RESULTS During a median follow-up period of 7.7 years, 737 patients (22.6%) died, including 463 deaths from cardiovascular causes. Multivariate-adjusted hazard ratios (HRs) for patients in the lower two 25-hydroxyvitamin D quartiles (median, 7.6 and 13.3 ng/mL [to convert 25-hydroxyvitamin D levels to nanomoles per liter, multiply by 2.496]) were higher for all-cause mortality (HR, 2.08; 95% confidence interval [CI], 1.60-2.70; and HR, 1.53; 95% CI, 1.17-2.01; respectively) and for cardiovascular mortality (HR, 2.22; 95% CI, 1.57-3.13; and HR, 1.82; 95% CI, 1.29-2.58; respectively) compared with patients in the highest 25-hydroxyvitamin D quartile (median, 28.4 ng/mL). Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile. These effects were independent of coronary artery disease, physical activity level, Charlson Comorbidity Index, variables of mineral metabolism, and New York Heart Association functional class. Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation (C-reactive protein and interleukin 6 levels), oxidative burden (serum phospholipid and glutathione levels), and cell adhesion (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels). CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality. A causal relationship has yet to be proved by intervention trials using vitamin D.
Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease

Environmental toxins have been implicated in the etiology of Parkinson's disease. Recent findings of defects in the ubiquitin‐proteasome system in hereditary and sporadic forms of the illness suggest that environmental proteasome inhibitors are candidate PD‐inducing toxins. Here, we systemically injected six doses of naturally occurring (epoxomicin) or synthetic (Z‐lle‐Glu(OtBu)‐Ala‐Leu‐al [PSI]) proteasome inhibitors into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developed progressive parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture, which improved with apomorphine treatment. Positron emission tomography demonstrated reduced carbon‐11‐labeled 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane (CFT) binding to dopaminergic nerve terminals in the striatum, indicative of degeneration of the nigrostriatal pathway. Postmortem analyses showed striatal dopamine depletion and dopaminergic cell death with apoptosis and inflammation in the substantia nigra pars compacta. In addition, neurodegeneration occurred in the locus coeruleus, dorsal motor nucleus of the vagus, and the nucleus basalis of Meynert. At neurodegenerative sites, intracytoplasmic, eosinophilic, α‐synuclein/ubiquitin–containing, inclusions resembling Lewy bodies were present in some of the remaining neurons. This animal model induced by proteasome inhibitors closely recapitulates key features of PD and may be valuable in studying etiopathogenic mechanisms and putative neuroprotective therapies for the illness. Ann Neurol 2004
Multiple Types of Ca2+ Channels in Mouse Motor Nerve Terminals

We measured neurotransmitter release and motor nerve terminal currents in mouse phrenic nerve‐diaphragm and triangularis sterni preparations, to evaluate the role of Ca2+‐channel subtypes in regulating transmitter release. Saturated concentrations of either ωagatoxin IVA [ω‐Aga‐IVA (0.3 μM), a blocker of P‐type Ca2+channels] or ω‐conotoxin MVIIC [ω‐CTx‐MVIIC (2 μM), a P‐and Q‐type Ca2+‐channel blocker], inhibited nerve‐evoked muscle contractions and the amplitude of endplate potentials respectively. In contrast, combined treatment with nifedipine (50 μM, a blocker of L‐type Ca2+ channels) plus ω‐conotoxin GVIA [ω‐CTx‐GVIA (2 μM), a blocker of N‐type Ca2+ channels] did not elicit inhibitory effects on nerve‐evoked muscle contractions, endplate potentials or nerve terminal waveforms. Because of the non‐linear relationship between endplate potentials and Ca2+ signals, a small decrease in presynaptic Ca2+ entry can significantly reduce the amplitude of the endplate potential. Thus, we applied 3, 4‐diaminopyridine (3, 4‐DAP, a k+‐channel blocker) or high Ca2+(10 mM) to accelerate and amplify the endplate potentials and Ca2+ currents. The endplate potentials amplified by 3, 4‐DAP or by high Ca2+ correspondingly proved to be quite resistant to both ω‐Aga‐IVA and ω‐CTx‐MVIIC; ωAga‐IVA exerted only a partial inhibitory effect on endplate potentials, and the ω‐Aga‐IVA‐resistant component was further inhibited by ω‐CTx‐MVIIC. The component that was resistant to the two toxins could be completely blocked by the non‐selective Ca2+ channel blocker Cd2+ (300 μM). A combination of the two toxins had no significant effects on either spontaneous transmitter release or postsynaptic resting membrane potentials of the diaphragm preparation and the Na+ and K+ waveforms of the triangularis sterni preparations. This finding suggests a preferential inhibitory effect at a presynaptic site. Measuring the Ca2+ currents in the triangularis sterni also revealed partial inhibition by ω‐CTx‐MVIIC with further incomplete inhibition by ω‐Aga‐IVA. Cd2+ (300 μM) abolished the toxin‐resistant component of the Ca2+ current. In contrast, a combination of nifedipine (50 μM) with ω‐CTx‐GVIA (2 μM) was without inhibitory effect. We conclude that multiple types of Ca2+channels, i.e. ω‐Aga‐IVA‐sensitive, ω‐CTx‐MVIIC‐sensitive and toxin‐resistant Ca2+ channels, coexist in mouse motor nerve terminals.
Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice.

BACKGROUND Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in the progression of atherosclerosis is unknown. In this report, we first demonstrate that intimal vessels occur in advanced lesions of apolipoprotein E-deficient (apoE -/-) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE -/- mice. METHODS AND RESULTS ApoE -/- mice were fed a 0.15% cholesterol diet. At age 20 weeks, mice were divided into 3 groups and treated for 16 weeks as follows: group 1, recombinant mouse endostatin, 20 mg. kg-1. d-1; group 2, fumagillin analogue TNP-470, 30 mg/kg every other day; and group 3, control animals that received a similar volume of buffer. Average cholesterol levels were similar in all groups. Plaque areas were quantified at the aortic origin. Median plaque area before treatment was 0.250 mm2 (range, 0.170 to 0.348; n=10). Median plaque areas were 0.321 (0.238 to 0.412; n=10), 0.402 (0.248 to 0.533; n=15), and 0.751 mm2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (P</=0.0001). Therefore, endostatin and TNP-470 inhibited plaque growth during the treatment period by 85% and 70%. Intimal smooth muscle cell contents of plaques from control and treated mice were similar. CONCLUSIONS Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE -/- mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.
Acquisition of multiple drug resistance by CCRF-CEM cells selected for different degrees of resistance to vincristine.

We studied the acquisition of multiple drug resistance to several "natural product" drugs by cultured human leukemic lymphoblasts selected for increasing resistance to vincristine (VCR). Three apparent types of cross-resistance patterns could be distinguished: specific, pleiotropic, and mixed. Cross-resistance to vindesine developed in parallel with VCR resistance, appearing at the lowest levels of VCR resistance (approximately fivefold). Vinblastine resistance did not become noticeable until VCR resistance was higher (approximately equal to 50-100-fold). Cross-resistance resistance to three other tubulin-binding agents developed in a different pattern, however. While cross-resistance to maytansine was seen in cells of intermediate (approximately equal to 50-fold) resistance to VCR, colchicine cross-resistance occurred only in cells that were highly resistant to VCR (approximately equal to 500-fold). Even at the highest level of VCR resistance (approximately equal to 600-fold), complete sensitivity to podophyllotoxin was retained. Conversely, cross-resistance to the epipodophyllotoxins , teniposide and etoposide, semisynthetic derivatives of podophyllotoxin, was seen in cells that were greater than 50-fold resistant to VCR. The same pattern obtained for the anthracyclines, doxorubicin and daunorubicin. We conclude that resistance to low concentrations of VCR does not uniformly confer cross-resistance to other classes of natural product drugs.
A Flow-Based Hybrid Mechanism to Improve Performance in NOX and Wireless OpenFlow Switch Networks

With the advantage of practical way to experiment with new network protocols in realistic settings, NOX and OpenFlow switch networks are becoming extremely popular. However, because of basic characteristics of NOX and OpenFlow switch based on the separation between control and data plane, every OpenFlow switch faces a long transmission and retransmission delay when it fails to transmit its data. Until now, the virtualized programmable networks only consider how to achieve the throughput for the direct link between OpenFlow switches. Since wireless channel experiences different conditions and NOX and OpenFlow switch networks supports the maximum flow size threshold, the aggregated flow size of a neighbor OpenFlow switch may be delivered faster than through the direct link if the neighbor link has higher RSS (Received Signal Strength). In this paper, we propose a flow-based hybrid mechanism to improve performance in NOX and wireless OpenFlow switch networks. The main idea of this scheme is that when the transmission of a OpenFlow switch fails, one of neighbor OpenFlow switches with better channel condition transmits the lost frame as well as the own data using flow aggregation scheme. To do so, every OpenFlow switch should manage overhear table to buffer the transmitted packets that is not yet acknowledged. We also present algorithms to retransmit lost packets, to maintain the overhear table and to compensate for the retransmission of packets of other OpenFlow switches. Simulation results show that the proposed flow-based hybrid mechanism can significantly improve the system throughput and the throughput gain.
Eradication of a Large Outbreak of a Single Strain of vanB Vancomycin-Resistant Enterococcus faecium at a Major Australian Teaching Hospital

Abstract Objective: To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital. Interventions: Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistant Enterococcus faecium despite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group; (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection of vanA and vanB resistance genes; (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts; (4) environmental screening and increased cleaning; (5) electronic flagging of medical records of contacts; and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin). Results: A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistant E. faecium. Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregat-ed patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of $2.7 million (Australian dollars). Conclusion: Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.
A Low-Order Harmonic Elimination Scheme for Induction Motor Drives Using a Multilevel Octadecagonal Space Vector Structure With a Single DC Source

Conventional voltage-source inverters used for induction motor drives generate a hexagonal space vector structure. In the overmodulation range, the hexagonal space vector structure generates low-order harmonics in the phase voltage resulting in low-order torque ripple in the motor. Inverter topologies with an octadecagonal (18 sided) space vector structure eliminate fifth-, seventh-, eleventh-, and thirteenth-order harmonics from the phase voltage, and hence, the dominant sixth- and twelfth-order torque ripple generation is eliminated. Octadecagonal space vector structures proposed in the past require multiple dc sources, which makes four-quadrant operation of the drive system difficult and costly. In this paper, the formation of a multilevel nine-concentric octadecagonal space vector structure using a single dc source is proposed. Detailed experimental results, using open-loop $V/f$ control and rotor field-oriented control, are presented to validate the effectiveness of the proposed drive scheme.
The Crystal Structure of the Inhibitor-complexed Carboxypeptidase D Domain II and the Modeling of Regulatory Carboxypeptidases*

The three-dimensional crystal structure of duck carboxypeptidase D domain II has been solved in a complex with the peptidomimetic inhibitor, guanidinoethylmercaptosuccinic acid, occupying the specificity pocket. This structure allows a clear definition of the substrate binding sites and the substrate funnel-like access. The structure of domain II is the only one available from the regulatory carboxypeptidase family and can be used as a general template for its members. Here, it has been used to model the structures of domains I and III from the former protein and of human carboxypeptidase E. The models obtained show that the overall topology is similar in all cases, the main differences being local and because of insertions in non-regular loops. In both carboxypeptidase D domain I and carboxypeptidase E slightly different shapes of the access to the active site are predicted, implying some kind of structural selection of protein or peptide substrates. Furthermore, emplacement of the inhibitor structure in the active site of the constructed models showed that the inhibitor fits very well in all of them and that the relevant interactions observed with domain II are conserved in domain I and carboxypeptidase E but not in the non-active domain III because of the absence of catalytically indispensable residues in the latter protein. However, in domain III some of the residues potentially involved in substrate binding are well preserved, together with others of unknown roles, which also are highly conserved among all carboxypeptidases. These observations, taken together with others, suggest that domain III might play a role in the binding and presentation of proteins or peptide substrates, such as the pre-S domain of the large envelope protein of duck hepatitis B virus.
Ranking the Influence of Tissue Conductivities on Forward-Calculated ECGs

This paper examined the effects that different tissue conductivities had on forward-calculated ECGs. To this end, we ranked the influence of tissues by performing repetitive forward calculations while varying the respective tissue conductivity. The torso model included all major anatomical structures like blood, lungs, fat, anisotropic skeletal muscle, intestine, liver, kidneys, bone, cartilage, and spleen. Cardiac electrical sources were derived from realistic atrial and ventricular simulations. The conductivity rankings were based on one of two methods: First, we considered fixed percental conductivity changes to probe the sensitivity of the ECG regarding conductivity alterations. Second, we set conductivities to the reported minimum and maximum values to evaluate the effects of the existing conductivity uncertainties. The amplitudes of both atrial and ventricular ECGs were most sensitive for blood, skeletal muscle conductivity and anisotropy as well as for heart, fat, and lungs. If signal morphology was considered, fat was more important whereas skeletal muscle was less important. When comparing atria and ventricles, the lungs had a larger effect on the atria yet the heart conductivity had a stronger impact on the ventricles. The effects of conductivity uncertainties were significant. Future studies dealing with electrocardiographic simulations should consider these effects.
Relational victimization and proactive versus reactive relational aggression: The moderating effects of respiratory sinus arrhythmia and skin conductance.

This research examined the moderating effect of the autonomic nervous system (ANS) on the associations between relational victimization and reactive and proactive relational aggression. Both branches of the ANS, the parasympathetic nervous system (indexed by respiratory sinus arrhythmia reactivity; RSA-Reactivity) and the sympathetic nervous system (indexed by skin conductance level reactivity; SCL-Reactivity), were examined. Emerging adults (N = 168) self-reported on relational victimization and proactive and reactive relational aggression; RSA-Reactivity and SCL-Reactivity were assessed in response to a laboratory stressor. Relational victimization predicted heightened reactive relational aggression given RSA augmentation/high SCL-Reactivity (i.e., coactivation) and RSA withdrawal/low SCL-Reactivity (i.e., coinhibition). In addition, relational victimization predicted heightened reactive relational aggression given RSA augmentation/low SCL-Reactivity (i.e., reciprocal parasympathetic activation). This study extends previous research on relational victimization and provides novel evidence that (a) exposure to relational victimization is associated with reactive relational aggression, but not proactive relational aggression, and (b) parasympathetic and sympathetic nervous system reactivity jointly moderate the link between relational victimization and reactive relational aggression.
Disruption of cellular cholesterol transport and homeostasis as a novel mechanism of action of membrane‐targeted alkylphospholipid analogues

Background and purpose: Alkylphospholipid (APL) analogues constitute a new class of synthetic anti‐tumour agents that act directly on cell membranes. We have previously demonstrated that hexadecylphosphocholine (HePC) alters intracellular cholesterol traffic and metabolism in HepG2 cells. We now extended our studies to analyse the effects of other clinically relevant APLs, such as edelfosine, erucylphosphocholine and perifosine on intracellular cholesterol homeostasis.