Donor infection with multidrug resistant organisms: Should we change our approach to perioperative prophylaxis?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151251/1/ajt15522_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151251/2/ajt15522.pd

Increased risk donors: A bird in the hand

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142418/1/ajt14643.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142418/2/ajt14643_am.pd

CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca2+ channels upstream of p38 MAPK.

BackgroundThe chemokine receptor CXCR4 (CD184) and its natural ligand CXCL12 contribute to many physiological processes, including decisions about cell death and survival in the central nervous system. In addition, CXCR4 is a co-receptor for human immunodeficiency virus (HIV)-1 and mediates the neurotoxicity of the viral envelope protein gp120. However, we previously observed that CXCL12 also causes toxicity in cerebrocortical neurons but the cellular mechanism remained incompletely defined.MethodsPrimary neuronal-glial cerebrocortical cell cultures from rat were exposed to a neurotoxicity-inducing CXCL12 concentration for different times and the activity of the stress-associated mitogen-activated protein kinase p38 (p38 MAPK) was assessed using an in vitro kinase assay. Neurotoxicity of CXCL12 and cellular localization of p38 MAPK was analyzed by immunofluorescence microscopy. Pharmacological inhibition of NMDA-type glutamate receptor-gated ion channels (NMDAR) of L-type Ca2+ channels was employed during 12- and 24-h exposure to neurotoxic amounts of CXCL12 to study the effects on active p38 MAPK and neuronal survival by Western blotting and microscopy, respectively. Neurotoxicity of CXCL12 was also assessed during pharmacological inhibition of p38 MAPK.ResultsHere, we show that a neurotoxic amount of CXCL12 triggers a significant increase of endogenous p38 MAPK activity in cerebrocortical cells. Immunofluorescence and Western blotting experiments with mixed neuronal-glial and neuron-depleted glial cerebrocortical cells revealed that the majority of active/phosphorylated p38 MAPK was located in neurons. Blockade of NMDAR-gated ion channels or L-type Ca2+ channels both abrogated an increase of active p38 MAPK and toxicity of CXCL12 in cerebrocortical neurons. Inhibition of L-type Ca2+ channels with nimodipine kept the active kinase at levels not significantly different from baseline while blocking NMDAR with MK-801 strongly reduced phosphorylated p38 MAPK below baseline. Finally, we confirmed that directly blocking p38 MAPK also abrogated neurotoxicity of CXCL12.ConclusionsOur findings link CXCL12-induced neuronal death to the regulation of NMDAR-gated ion channels and L-type Ca2+ channels upstream of p38 MAPK activation

HIV Protease Inhibitors: Advances in Therapy and Adverse Reactions, Including Metabolic Complications

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90068/1/phco.19.4.281.30937.pd

Development of Variable Camber Continuous Trailing Edge Flap for Performance Adaptive Aeroelastic Wing

This paper summarizes the recent development of an adaptive aeroelastic wing shaping control technology called variable camber continuous trailing edge flap (VCCTEF). As wing flexibility increases, aeroelastic interactions with aerodynamic forces and moments become an increasingly important consideration in aircraft design and aerodynamic performance. Furthermore, aeroelastic interactions with flight dynamics can result in issues with vehicle stability and control. The initial VCCTEF concept was developed in 2010 by NASA under a NASA Innovation Fund study entitled "Elastically Shaped Future Air Vehicle Concept," which showed that highly flexible wing aerodynamic surfaces can be elastically shaped in-flight by active control of wing twist and bending deflection in order to optimize the spanwise lift distribution for drag reduction. A collaboration between NASA and Boeing Research & Technology was subsequently funded by NASA from 2012 to 2014 to further develop the VCCTEF concept. This paper summarizes some of the key research areas conducted by NASA during the collaboration with Boeing Research and Technology. These research areas include VCCTEF design concepts, aerodynamic analysis of VCCTEF camber shapes, aerodynamic optimization of lift distribution for drag minimization, wind tunnel test results for cruise and high-lift configurations, flutter analysis and suppression control of flexible wing aircraft, and multi-objective flight control for adaptive aeroelastic wing shaping control

Mycobacterium avium complex immune reconstitution inflammatory syndrome: Long term outcomes

Abstract Background To describe long term outcomes of Mycobacterium avium complex (MAC) immune reconstitution inflammatory syndrome (IRIS). Methods Cases of MAC IRIS were retrospectively identified at four HIV clinics (Michigan, Maryland, Rhode Island, and Indiana) from 1996–2004. Patients were included if they were initially diagnosed with AIDS and found to have evidence of focal MAC infection documented by tissue culture or PCR after initiating HAART, and at least 6 months of follow up. Results Among the 20 patients included, the mean age was 40 years, mean CD4 cell count was 24/mm3 at pretreatment baseline and 100/mm3 at time of MAC IRIS diagnosis. Sites of disease included lymph nodes (15 patients [8 peripheral, 8 abdominal and 1 peripheral and abdominal]), gastrointestinal tract (7) and liver (3). Sixteen patients (80%) responded to treatment and were disease free after a mean of 17.4 months of therapy for MAC IRIS; IRIS therapy was withdrawn in 6 without relapse. Four patients (non-responder group) had persistent or relapsing disease despite 27 months of ongoing MAC IRIS treatment. At the time of resolution or last follow-up, the mean CD4 cell count and viral load was 143/mm3 and 7,000 c/mL for responders, and 65/mm3 and 17,000 c/mL for non-responders, respectively. Most patients with peripheral adenopathy were responders (7/8; 88%); many with abdominal adenopathy (4/8; 50%) were nonresponders. Conclusion The majority of patients with MAC IRIS eventually responded to treatment. Our sample size was not adequate to perform statistical analysis, but there was a tendency towards adequate CD4 response to HAART and peripheral rather than intraabdominal adenopathy among responders.http://deepblue.lib.umich.edu/bitstream/2027.42/112767/1/12967_2007_Article_210.pd

Quantum Black Holes: Entropy and Entanglement on the Horizon

We are interested in black holes in Loop Quantum Gravity (LQG). We study the simple model of static black holes: the horizon is made of a given number of identical elementary surfaces and these small surfaces all behaves as a spin-s system accordingly to LQG. The chosen spin-s defines the area unit or area resolution, which the observer uses to probe the space(time) geometry. For s=1/2, we are actually dealing with the qubit model, where the horizon is made of a certain number of qubits. In this context, we compute the black hole entropy and show that the factor in front of the logarithmic correction to the entropy formula is independent of the unit s. We also compute the entanglement between parts of the horizon. We show that these correlations between parts of the horizon are directly responsible for the asymptotic logarithmic corrections. This leads us to speculate on a relation between the evaporation process and the entanglement between a pair of qubits and the rest of the horizon. Finally, we introduce a concept of renormalisation of areas in LQG.Comment: Revtex4, 25 pages, 4 figure

Sarcoma classification by DNA methylation profiling in clinical everyday life: the Charité experience

Background: Sarcomas are a heterogeneous group of rare malignant tumors with more than 100 subtypes. Accurate diagnosis remains challenging due to a lack of characteristic molecular or histomorphological hallmarks. A DNA methylation-based tumor profiling classifier for sarcomas (known as sarcoma classifier) from the German Cancer Research Center (Deutsches Krebsforschungszentrum) is now employed in selected cases to guide tumor classification and treatment decisions at our institution. Data on the usage of the classifier in daily clinical routine are lacking. Methods: In this single-center experience, we describe the clinical course of five sarcoma cases undergoing thorough pathological and reference pathological examination as well as DNA methylation-based profiling and their impact on subsequent treatment decisions. We collected data on the clinical course, DNA methylation analysis, histopathology, radiological imaging, and next-generation sequencing. Results: Five clinical cases involving DNA methylation-based profiling in 2021 at our institution were included. All patients' DNA methylation profiles were successfully matched to a methylation profile cluster of the sarcoma classifier's dataset. In three patients, the classifier reassured diagnosis or aided in finding the correct diagnosis in light of contradictory data and differential diagnoses. In two patients with intracranial tumors, the classifier changed the diagnosis to a novel diagnostic tumor group. Conclusions: The sarcoma classifier is a valuable diagnostic tool that should be used after comprehensive clinical and histopathological evaluation. It may help to reassure the histopathological diagnosis or indicate the need for thorough reassessment in cases where it contradicts previous findings. However, certain limitations (non-classifiable cases, misclassifications, unclear degree of sample purity for analysis and others) currently preclude wide clinical application. The current sarcoma classifier is therefore not yet ready for a broad clinical routine. With further refinements, this promising tool may be implemented in daily clinical practice in selected cases

secondary results of a randomized phase III trial (SAKK 10/94)

Background To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. Methods From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. Results The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 – 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. Conclusions Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival