Relativistic, QED, and nuclear mass effects in the magnetic shielding of 3^3He

The magnetic shielding $\sigma$ of $^3$He is studied. The complete relativistic corrections of order $O(\alpha^2)$, leading QED corrections of order $O(\alpha^3 \ln\alpha)$, and finite nuclear mass effects of order $O(m/m_{\rm N})$ are calculated with high numerical precision. The resulting theoretical predictions for $\sigma = 59.967~43(10)\cdot 10^{-6}$ are the most accurate to date among all elements and support the use of $^3$He as a NMR standard.Comment: 10 pages, corrected minor errors in Eqs.(6,7

Cysteinyl leukotrienes as novel host factors facilitating Cryptococcus neoformans penetration into the brain

Cryptococcus neoformas infection of the central nervous system (CNS) continues to be an important cause of mortality and morbidity, and a major contributing factor is our incomplete knowledge of the pathogenesis of this disease. Here, we provide the first direct evidence that C. neoformans exploits host cysteinyl leukotrienes (LTs), formed via LT biosynthetic pathways involving cytosolic phospholipase A2α (cPLA2α) and 5â lipoxygenase (5â LO) and acting via cysteinyl leukotriene type 1 receptor (CysLT1), for penetration of the bloodâ brain barrier. Gene deletion of cPLA2α and 5â LO and pharmacological inhibition of cPLA2α, 5â LO and CysLT1 were effective in preventing C. neoformans penetration of the bloodâ brain barrier in vitro and in vivo. A CysLT1 antagonist enhanced the efficacy of an antiâ fungal agent in therapy of C. neoformans CNS infection in mice. These findings demonstrate that host cysteinyl LTs, dependent on the actions of cPLA2α and 5â LO, promote C. neoformans penetration of the bloodâ brain barrier and represent novel targets for elucidating the pathogenesis and therapeutic development of C. neoformans CNS infection.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136343/1/cmi12661_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136343/2/cmi12661.pd

Astrocyte inositol triphosphate receptor type 2 and cytosolic phospholipase A2 alpha regulate arteriole responses in mouse neocortical brain slices.

Functional hyperemia of the cerebral vascular system matches regional blood flow to the metabolic demands of the brain. One current model of neurovascular control holds that glutamate released by neurons activates group I metabotropic glutamate receptors (mGluRs) on astrocytes, resulting in the production of diffusible messengers that act to regulate smooth muscle cells surrounding cerebral arterioles. The acute mouse brain slice is an experimental system in which changes in arteriole diameter can precisely measured with light microscopy. Stimulation of the brain slice triggers specific cellular responses that can be correlated to changes in arteriole diameter. Here we used inositol trisphosphate receptor type 2 (IP(3)R2) and cytosolic phospholipase A(2) alpha (cPLA(2)α) deficient mice to determine if astrocyte mGluR activation coupled to IP(3)R2-mediated Ca(2+) release and subsequent cPLA(2)α activation is required for arteriole regulation. We measured changes in astrocyte cytosolic free Ca(2+) and arteriole diameters in response to mGluR agonist or electrical field stimulation in acute neocortical mouse brain slices maintained in 95% or 20% O(2). Astrocyte Ca(2+) and arteriole responses to mGluR activation were absent in IP(3)R2(-/-) slices. Astrocyte Ca(2+) responses to mGluR activation were unchanged by deletion of cPLA(2)α but arteriole responses to either mGluR agonist or electrical stimulation were ablated. The valence of changes in arteriole diameter (dilation/constriction) was dependent upon both stimulus and O(2) concentration. Neuron-derived NO and activation of the group I mGluRs are required for responses to electrical stimulation. These findings indicate that an mGluR/IP(3)R2/cPLA(2)α signaling cascade in astrocytes is required to transduce neuronal glutamate release into arteriole responses

A consultative telemedicine service improves compliance with best practice guidelines in a highly staffed intensive care unit

Introduction: Telemedicine in the intensive care unit (ICU) is in the nascent stages of its development and usage. Little is known about its potential to improve quality of care in the ICU environment.Hypothesis: A consultative ICU telemedicine service improves compliance with best care practices in a highly staffed ICU of an academic medical center.Methods: We conducted a prospective study over a 10 week period. Best practice measures were defined relating to mechanical and pharmacological deep venous thrombosis (DVT) prophylaxis, gastric and decubitus ulcer prophylaxis, and prophylaxis against ventilator associated pneumonias (VAP). Baseline rates were collected during the first 2 weeks of the study period. A remote, consultative ICU telemedicine service was then implemented using two-way audio-visual communication, existing electronic documentation and real-time physiologic monitoring. Staffing was by an intensivist and nurse between 7p-7a daily. Compliance with the best practice measures was checked and recommendations to improve observed deficiencies were made for the 8 week intervention period. Pre and post-intervention data was analyzed using the Chisquare test.|Results: Baseline metrics were gathered for 125 patients pre- and 605 patients post-intervention. Compliance was defined as either adherence to best practice or presence of a therapeutic contraindication. Compliance improved for both mechanical (93.6% vs 98.2%; p24 hours were assessed for VAP prophylaxis. Compliance to sedation holidays (69.7% vs 85.5%; p0.05). There were no differences in compliance for stress ulcer prophylaxis (86.4% vs 81.5%; p\u3e0.05), regular repositioning for decubitus ulcer prophylaxis (85.6% vs 90.9%; p\u3e0.05) or elevation of the head of the bed 30 degrees (75.2% vs 73.6%; p\u3e0.05).Conclusions: A consultative ICU telemedicine service made clinically significant improvements in adherence with and documentation of best care practices in a highly staffed academic ICU

Centralized triage for multiple intensive care units: The central intensivist physician

Subspecialization of critical care units and overall increasing demand for critical care services has led to inefficiencies in allocation of critical care resources with potential impacts on hospital economics and patient outcomes. Centralized management of critical care resource allocation within an institution may improve use while simultaneously ensuring quality of patient care. The authors\u27 institution has implemented a Central Intensivist Physician (CIP) program to oversee resource allocation within the adult surgical intensive care units (ICUs). The result has been an improvement in patient flow throughout the surgical ICUs manifested by steady case cancellation rates despite increasing acuity and length of stay. Additionally, triage duties have been shifted from the individual unit physician to the CIP, resulting in improved provider satisfaction from improved continuity of rounds. The authors conclude that the CIP program may improve overall critical care resource use while maintaining unit specialization within a large tertiary care hospital setting

132 Impact of hospital census and ICU throughput on hospital length of stay

Introduction: High acuity hospitals often experience delays in transferring patients from one care unit to another within the facility. One strategy to increase inpatient ward capacity and improve throughput is to delay transfer of appropriate patients from intensive care units (ICU’s) to inpatient wards. The practice of boarding “floor” patients in the ICU when there is a lack of inpatient floor beds assumes that patients will receive the appropriate care necessary to progress toward hospital discharge.Hypothesis: We hypothesized that the care provided in an inpatient ward and an ICU boarding a “floor” patient were not equivalent in terms of ancillary services and appropriate resources to prepare patients for eventual discharge from the hospital. This difference has the potential to impact length of stay and further degrade hospital throughput.Methods: We conducted a retrospective analysis of patients admitted to the Weinberg Intensive Care Unit (WICU) between July 1, 2011 and June 30, 2012. Patients were divided into two group based on whether patients remained in the ICU after critical care services were no longer deemed necessary. Suitability for ICU discharge was reached by consensus between the patients’ primary surgeon and an intensive care physician. Our control group consisted of patients that left the ICU within 24 hours of being deemed appropriate for transfer. The floor group consisted of patients that remained in the ICU for greater than 24 hours after meeting clinical discharge criteria. Our primary outcome measure was length of hospital stay.Results: During the study period there were 1518 patients qualified for our control group and 129 patients met criteria for our boarding group. Using a linear regression model we determined that there were no significant differences between the groups in terms of age, sex, APR severity, admitting service, and mortality. Patients in the floor group had a statistically significant increase in the mean length of stay when compared to the standard group (13.0 days vs. 10.6 days p \u3c 0.05).Conclusions: These results suggest that boarding patients in an ICU when critical care services are no longer needed is associated with increased hospital length of stay in otherwise similar patients. It is possible that this increase is due to bias in selection of patients, exposure to pathogens in the ICU environment, or delays in progression of care along normal pathways of recovery. Further study will need to prospectively address the finding that delayed discharge of patients from the ICU increases hospital LOS

Tele ICU: Paradox or panacea?

Telemedicine has been studied in the intensive care unit for several decades, but many questions remain unanswered regarding the costs and the benefits of its application. Telemedicine ICU (Tele-ICU) is an electronic means to link physical ICUs to another location which assists in medical decision making. Given the shortage of intensive care physicians in the US, Tele-ICU systems could be an efficient mechanism for physicians to manage a larger number of critical care patients. This chapter will examine the current state of telemedicine in an age of rapidly expanding medical information technology and increasing demand for intensive care services. While we believe that the future of Tele-ICU is promising, there are multiple issues that must be addressed to increase the benefit of Tele-ICU. Tele-ICU is expensive to deploy and use, it may add burdens to existing intensivists, and it requires organizational and culture changes that can be difficult to accomplish

Astrocyte Ca²⁺ responses in neocortical slices to mGluR agonist application are not altered by absence of cPLA₂α expression.

<p>Cortical brain slices from S100β-EGFP/cPLA₂α^+/+ (upper panel) and S100β-EGFP/cPLA₂α<b>⁻</b>^/− (lower panel) mice were loaded with the Ca²⁺-sensitive fluorophore Rhod-2/AM. Regions of interest representing astrocyte soma (white circles) and vascular foot processes (white box) were identified by EGFP expression and histologic location. Regions of interest representing background fluorescence for soma and endfeet are depicted by blue outlines. Ca²⁺ fluorescence measured for the soma and endfeet are displayed at 3 times in relation to 1S,3R-ACPD treatment: (a) before, (b) at peak response and (c) after. Representative Ca²⁺ measurements for soma and endfeet for each genotype are depicted in the right panel. The time of the 1S, 3R ACPD application is indicated by the black bar. The Ca²⁺ responses of astrocyte populations are shown in <b>B.</b> Soma (+/+, n = 169; <b>⁻</b>^/−, n = 166) and <b>C.</b> endfeet (+/+, n = 36; <b>⁻</b>^/−, n = 33) and were measured as Ca²⁺ peak amplitude, area under curve, half width, rise time, decay time or decay tau (as defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042194#s4" target="_blank">Methods</a>). The graphs show cumulative probability histograms analysis of the astrocyte populations by parameters compared between cPLA₂α^+/+ (open circles and bars) and <b>⁻</b>^/− (closed circles and bars) while inset bar graph shows the mean ± S.E.M. for each parameter. There were no significant differences between the genotypes.</p

Arteriole responses to mGluR agonist application are eliminated in IP₃R2^−/− neocortical slices.

<p><b>A.</b> Gradient contrast imaging was used to measure arteriole responses to treatment. Responses to 1S,3R-ACPD were quantified by defining 6 points (2 of the points are shown in this figure) at which to measure changes in arteriole diameter over time (described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042194#s4" target="_blank">Methods</a>). The arteriole diameter is expressed as the average diameter of the points. Scale bar: 5 µm. <b>B.</b> Cortical slices from IP₃R2^+/+ (open circle, n = 18) and IP₃R2<b>⁻</b>^/− (filled circle, n = 24) were treated with 1S,3R-ACPD followed by PGE₂ and arteriole responses were measured. <b>C.</b> During continuous application of U-46619 the IP₃R2^+/+ and IP₃R2<b>⁻</b>^/− were treated with 1S,3R-ACPD while another group of IP₃R2^+/+ slices were treated with vehicle instead of 1S,3R-ACPD (red inverted triangle, n = 7). Inset shows the complete experiment from the time of application of U-46619. The dashed white box indicates the expanded graph. Treatment with U-46619 (100 nM) constricted arterioles of both IP₃R2^+/+ (n = 16) and IP₃R2<b>⁻</b>^/− slices (n = 17) to a similar extent. **, <i>P</i><0.01 comparing IP₃R2^+/+ to IP₃R2<b>⁻</b>^/−10 min following 1S, 3R-ACPD application.</p

Neocortical arterioles of IP₃R2⁻^/− slices do not respond to electrical field stimulation.

<p><b>A.</b> Responses of arterioles in 95% O₂ following electrical field stimulation. Cortical slices from IP₃R2^+/+ (open circle) and IP₃R2<b>⁻</b>^/− mice (closed circle) were treated with electrical field stimulation (EFS) of 100 Hz trains of 200 ms at 0.2 Hz for 4 minutes as indicated by the dark bar. Arteriole diameter was measured every 5 min during the experiment. IP₃R2^+/+, n = 15; IP₃R2<b>⁻</b>^/− n = 15. **, <i>P</i><0.01, IP₃R2^+/+ compared to IP₃R2<b>⁻</b>^/−. <b>B.</b> Pretreatment with U-46619 for 30 min was followed by electrical stimulation and arteriole diameters of IP₃R2<b>⁻</b>^/− were compared to IP₃R2^+/+. IP₃R2^+/+, n = 15; IP₃R2<b>⁻</b>^/− n = 14. **, <i>P</i><0.01; ***, <i>P</i><0.001. <b>C.</b> Blockade of Group I mGluR with MPEP and JNJ prevents arteriole responses to electrical stimulation in IP₃R2^+/+ slices (inverted triangles) while a 20% O2 environment does not alter responses of naïve IP₃R2^+/+ or IP₃R2<b>⁻</b>^/− arterioles. IP₃R2^+/+, n = 14; IP₃R2<b>⁻</b>^/− n = 12, IP₃R2^+/+ with MPEP/JNJ, n = 9. **, <i>P</i><0.01; ***, <i>P</i><0.001.</p