A Large Retinal Capillary Hemangioma in the Anterior Retina Treated with Photodynamic Therapy

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Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection. The alteplase dose assessment for Pleural infection Therapy project

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. Results: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22–58] to 16% [8–31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247–2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. Conclusions: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pl

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

INTRODUCTION: Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP

Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (–)-epigallocatechin-3-gallate

Excessive production of Aβ (amyloid β-peptide) has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease). Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species) in neurons through an NMDA (N-methyl-d-aspartate)-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid) release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III)-tetrakis(4-benzoic acid)-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pre-treatment of neurons with EGCG [(−)-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD

Uncoupling Caveolae from Intracellular Signaling in Vivo

© 2016 Nature America, Inc. Rationale: Caveolin-1 (Cav-1) negatively regulates endothelial nitric oxide (NO) synthase-derived NO production, and this has been mapped to several residues on Cav-1, including F92. Herein, we reasoned that endothelial expression of an F92ACav-1 transgene would let us decipher the mechanisms and relationships between caveolae structure and intracellular signaling. Objective: This study was designed to separate caveolae formation from its downstream signaling effects. Methods and Results: An endothelial-specific doxycycline-regulated mouse model for the expression of Cav-1-F92A was developed. Blood pressure by telemetry and nitric oxide bioavailability by electron paramagnetic resonance and phosphorylation of vasodilator-stimulated phosphoprotein were determined. Caveolae integrity in the presence of Cav-1-F92A was measured by stabilization of caveolin-2, sucrose gradient, and electron microscopy. Histological analysis of heart and lung, echocardiography, and signaling were performed. Conclusions: This study shows that mutant Cav-1-F92A forms caveolae structures similar to WT but leads to increases in NO bioavailability in vivo, thereby demonstrating that caveolae formation and downstream signaling events occur through independent mechanisms

Effect of Early Preventive Dental Visits on Subsequent Dental Treatment and Expenditures

Professional organizations recommend a preventive dental visit by one year of age. This study compared dental treatment and expenditures for Medicaid children who have a preventive visit before age 18-months to those who have a visit at age 18-42 months

Barriers to Pediatricians’ Adherence to American Academy of Pediatrics Oral Health Referral Guidelines: North Carolina General Dentists’ Opinions

Purpose—The purposes of this study were to: (1) assess knowledge, attitudes, and behaviors of North Carolina general dentists (GDs) regarding American Academy of Pediatrics (AAP) dental referral guidelines; and (2) determine factors that influence pediatricians’ ability to comply with AAP guidelines. Methods—One thousand GDs were surveyed to determine barriers toward acceptance of physician referrals of infants and toddlers. The primary outcome using ordered logistic regression was GDs’ acceptance of children described in five case scenarios, with different levels of risk and oral health status. Results—GDs believed pediatricians should refer patients at risk for caries to a dentist. While 61 to 75 percent of GDs were willing to accept low caries risk referrals of infants and toddlers, only 35 percent would accept referrals when caries was present. Predictors of referral acceptance were correct knowledge about AAP guidelines (OR=2.0, 95%CI=1.2-3.3), confidence in pro- viding preventive care to infants and toddlers (OR=2.6, 95%CI=1.3-4.9), and agreement that parents see importance in dental referrals (OR=2.1, 95% CI=1.2-3.6). Conclusions—This study identified factors influencing acceptance of pediatrician referrals for the age one dental visit among North Carolina GDs and highlighted challenges pediatricians face in referring young children for dental care

Endothelial Cell Autonomous Role of Akt1

© 2018 American Heart Association, Inc. Objective - The importance of PI3K/Akt signaling in the vasculature has been demonstrated in several models, as global loss of Akt1 results in impaired postnatal ischemia- and VEGF-induced angiogenesis. The ubiquitous expression of Akt1, however, raises the possibility of cell-type-dependent Akt1-driven actions, thereby necessitating tissue-specific characterization. Approach and Results - Herein, we used an inducible, endothelial-specific Akt1-deleted adult mouse model (Akt1iECKO) to characterize the endothelial cell autonomous functions of Akt1 in the vascular system. Endothelial-targeted ablation of Akt1 reduces eNOS (endothelial nitric oxide synthase) phosphorylation and promotes both increased vascular contractility in isolated vessels and elevated diastolic blood pressures throughout the diurnal cycle in vivo. Furthermore, Akt1iECKO mice subject to the hindlimb ischemia model display impaired blood flow and decreased arteriogenesis. Conclusions - Endothelial Akt1 signaling is necessary for ischemic resolution post-injury and likely reflects the consequence of NO insufficiency critical for vascular repair

(Re)constructing Dimensions

Compactifying a higher-dimensional theory defined in R^{1,3+n} on an n-dimensional manifold {\cal M} results in a spectrum of four-dimensional (bosonic) fields with masses m^2_i = \lambda_i, where - \lambda_i are the eigenvalues of the Laplacian on the compact manifold. The question we address in this paper is the inverse: given the masses of the Kaluza-Klein fields in four dimensions, what can we say about the size and shape (i.e. the topology and the metric) of the compact manifold? We present some examples of isospectral manifolds (i.e., different manifolds which give rise to the same Kaluza-Klein mass spectrum). Some of these examples are Ricci-flat, complex and K\"{a}hler and so they are isospectral backgrounds for string theory. Utilizing results from finite spectral geometry, we also discuss the accuracy of reconstructing the properties of the compact manifold (e.g., its dimension, volume, and curvature etc) from measuring the masses of only a finite number of Kaluza-Klein modes.Comment: 23 pages, 3 figures, 2 references adde

Comparing Medical and Dental Providers of Oral Health Services on Early Dental Caries Experience

Objectives. Most state Medicaid programs reimburse nondental primary care providers (PCPs) for providing preventive oral health services to young children. We examined the association between who (PCP, dentist, or both) provides these services to Medicaid enrollees before age 3 years and oral health at age 5 years