Protostellar Disk Evolution Over Million-Year Timescales with a Prescription for Magnetized Turbulence

Magnetorotational instability (MRI) is the most promising mechanism behind accretion in low-mass protostellar disks. Here we present the first analysis of the global structure and evolution of non-ideal MRI-driven T-Tauri disks on million-year timescales. We accomplish this in a 1+1D simulation by calculating magnetic diffusivities and utilizing turbulence activity criteria to determine thermal structure and accretion rate without resorting to a 3-D magnetohydrodynamical (MHD) simulation. Our major findings are as follows. First, even for modest surface densities of just a few times the minimum-mass solar nebula, the dead zone encompasses the giant planet-forming region, preserving any compositional gradients. Second, the surface density of the active layer is nearly constant in time at roughly 10 g/cm2, which we use to derive a simple prescription for viscous heating in MRI-active disks for those who wish to avoid detailed MHD computations. Furthermore, unlike a standard disk with constant-alpha viscosity, the disk midplane does not cool off over time, though the surface cools as the star evolves along the Hayashi track. The ice line is firmly in the terrestrial planet-forming region throughout disk evolution and can move either inward or outward with time, depending on whether pileups form near the star. Finally, steady-state mass transport is a poor description of flow through an MRI-active disk. We caution that MRI activity is sensitive to many parameters, including stellar X-ray flux, grain size, gas/small grain mass ratio and magnetic field strength, and we have not performed an exhaustive parameter study here.Comment: Accepted for publication in Astrophysical Journal. 19 pages, including 8 figure

HPV Infection Prevention in Males by Gardasil Vaccination

About 1% of sexually active males in the U.S. have genital warts. Each year 400 males get HPV related cancer of the penis, and 1,500 get HPV related cancer of the anus. 2-3 cases of Genital warts have been reported at Harwood High School (Moretown and Waitsfield), where the school nurse reports 1-3 males students each year seeking information about STIs (including HPV).https://scholarworks.uvm.edu/fmclerk/1019/thumbnail.jp

Mitogen Activated Protein Kinase Phosphatase-1 Prevents the Development of Tactile Sensitivity In a Rodent Model of Neuropathic Pain

Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK) family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs) limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs) as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide). Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38

Evidence for a Role of Endocannabinoids, Astrocytes and p38 Phosphorylation in the Resolution of Postoperative Pain

An alarming portion of patients develop persistent or chronic pain following surgical procedures, but the mechanisms underlying the transition from acute to chronic pain states are not fully understood. In general, endocannabinoids (ECBs) inhibit nociceptive processing by stimulating cannabinoid receptors type 1 (CB(1)) and type 2 (CB(2)). We have previously shown that intrathecal administration of a CB(2) receptor agonist reverses both surgical incision-induced behavioral hypersensitivity and associated over-expression of spinal glial markers. We therefore hypothesized that endocannabinoid signaling promotes the resolution of acute postoperative pain by modulating pro-inflammatory signaling in spinal cord glial cells.To test this hypothesis, rats receiving paw incision surgery were used as a model of acute postoperative pain that spontaneously resolves. We first characterized the concentration of ECBs and localization of CB(1) and CB(2) receptors in the spinal cord following paw incision. We then administered concomitant CB(1) and CB(2) receptor antagonists/inverse agonists (AM281 and AM630, 1 mg x kg(-1) each, i.p.) during the acute phase of paw incision-induced mechanical allodynia and evaluated the expression of glial cell markers and phosphorylated p38 (a MAPK associated with inflammation) in the lumbar dorsal horn. Dual blockade of CB(1) and CB(2) receptor signaling prevented the resolution of postoperative allodynia and resulted in persistent over-expression of spinal Glial Fibrillary Acidic Protein (GFAP, an astrocytic marker) and phospho-p38 in astrocytes. We provide evidence for the functional significance of these astrocytic changes by demonstrating that intrathecal administration of propentofylline (50 microg, i.t.) attenuated both persistent behavioral hypersensitivity and over-expression of GFAP and phospho-p38 in antagonist-treated animals.Our results demonstrate that endocannabinoid signaling via CB(1) and CB(2) receptors is necessary for the resolution of paw incision-induced behavioral hypersensitivity and for the limitation of pro-inflammatory signaling in astrocytes following surgical insult. Our findings suggest that therapeutic strategies designed to enhance endocannabinoid signaling may prevent patients from developing persistent or chronic pain states following surgery

Vasopressin in conjunction with norepinephrine in septic shock: A retrospective cohort study from a low middle-income country

Objectives: Guidelines recommend use of norepinephrine as the first-line treatment for fluid-refractory septic shock and if septic shock persists vasopressin may be initiated. Since there are limited data from low middle-income countries with high disease burden of sepsis, we aimed to compare the outcomes of using vasopressin adjunct to norepinephrine in comparison with norepinephrine alone.Design: Retrospective cohort study.Setting: Aga Khan University Hospital, Karachi, Pakistan.Patients: Six-hundred fifty-three patients diagnosed with septic shock from January 2019 to December 2019, with 498 given norepinephrine only and 155 given norepinephrine-vasopressin combination.Interventions: None.Measurements and main results: Primary outcome was in-hospital mortality. Secondary outcomes were duration of vasopressor used, length of hospital stay, length of ICU stay, and days on ventilatory support. After adjustment by multivariable logistic regression, it was found that mortality was not significantly associated with the norepinephrine-vasopressin combination (adjusted odds ratio, 0.633 [95% CI, 0.370-1.081]). However, Sequential Organ Failure Assessment score at admission (1.100 [1.014-1.193]), lactate at admission (1.167 [1.109-1.227]), duration of vasopressor used (1.481 [1.316-1.666]), and level of care (3.025 [1.682-5.441]) were found to be independently associated with the adjunct usage of norepinephrine and vasopressin.Conclusions: The use of norepinephrine-vasopressin combination has remained debatable in literature. Our study showed that although there was no difference in mortality between the two groups, admission Sequential Organ Failure Assessment scores and admission lactate levels were found to be significantly higher in the norepinephrine-vasopressin group. Hence, physicians from Pakistan used the norepinephrine-vasopressin combination in resistant septic shock patients who were sicker to begin with. Furthermore, duration of vasopressor therapy and ICU admission were also significantly higher in the combination group. Considering the recent hyperinflation of vasopressors costs and that most healthcare expenditure for patients in Pakistan is out-of-pocket, this can consequently lead to unwarranted financial burden for patients and their families

Barriers to and Resources for Asthma Management in Vermont Elementary Schools

Introduction. Asthma is a chronic obstructive lung disease that causes wheezing, coughing, and shortness of breath, and is a cause of school absenteeism. School nurses play an integral role in asthma care for elementary-aged children.https://scholarworks.uvm.edu/comphp_gallery/1189/thumbnail.jp

Cannabinoid receptor type 2 activation induces a microglial anti-inflammatory phenotype and reduces migration via MKP induction and ERK dephosphorylation

<p>Abstract</p> <p>Background</p> <p>Cannabinoid receptor type 2 (CBR2) inhibits microglial reactivity through a molecular mechanism yet to be elucidated. We hypothesized that CBR2 activation induces an anti-inflammatory phenotype in microglia by inhibiting extracellular signal-regulated kinase (ERK) pathway, via mitogen-activated protein kinase-phosphatase (MKP) induction. MKPs regulate mitogen activated protein kinases, but their role in the modulation of microglial phenotype is not fully understood.</p> <p>Results</p> <p>JWH015 (a CBR2 agonist) increased MKP-1 and MKP-3 expression, which in turn reduced p-ERK1/2 in LPS-stimulated primary microglia. These effects resulted in a significant reduction of tumor necrosis factor-α (TNF) expression and microglial migration. We confirmed the causative link of these findings by using MKP inhibitors. We found that the selective inhibition of MKP-1 by Ro-31-8220 and PSI2106, did not affect p-ERK expression in LPS+JWH015-treated microglia. However, the inhibition of both MKP-1 and MKP-3 by triptolide induced an increase in p-ERK expression and in microglial migration using LPS+JWH015-treated microglia.</p> <p>Conclusion</p> <p>Our results uncover a cellular microglial pathway triggered by CBR2 activation. These data suggest that the reduction of pro-inflammatory factors and microglial migration via MKP-3 induction is part of the mechanism of action of CBR2 agonists. These findings may have clinical implications for further drug development.</p

Impaired identification of impoverished animate but not inanimate objects in adults with high-functioning autism spectrum disorder

The ability to identify animate and inanimate objects from impoverished images was investigated in adults with high-functioning autism spectrum disorder (HFA) and in matched typically developed (TD) adults, using a newly developed task. Consecutive frames were presented containing Gabor elements that slightly changed orientation from one frame to the next. For a subset of elements, the changes were such that these elements gradually formed the outline of an object. Elements enclosed within the object's outline gradually adopted one and the same orientation, outside elements adopted random orientations. The subjective experience was that of an object appearing out of a fog. The HFA group required significantly more frames to identify the impoverished objects than the TD group. Crucially, this difference depended on the nature of the objects: the HFA group required significantly more frames to identify animate objects, but with respect to the identification of inanimate objects the groups did not differ. The groups also did not differ with respect to the number and type of incorrect guesses they made. The results suggest a specific impairment in individuals with HFA in identifying animate objects. A number of possible explanations are discussed

Bostonia: The Boston University Alumni Magazine. Volume 10

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs