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Abstract Background Myofascial Pain Syndrome (MPS) is a common pain disorder. Diagnostic criteria include physical findings which are often unreliable or not universally accepted. A precise biosignature may improve diagnosis and treatment effectiveness. The purpose of this study was to assess whether microanalytic assays significantly correlate with characteristic clinical findings in people with MPS. Methods This descriptive, prospective study included 38 participants (25 women) with greater than 3 months of myofascial pain in the upper trapezius. Assessments were performed at a university laboratory. The main outcome measures were the Beighton Index, shoulder range of motion, strength asymmetries and microanalytes: DHEA, Kynurenine, VEGF, interleukins (IL-1b, IL-2, IL-4, IL-5, IL-7, IL-8, IL-13), growth factors (IGF-1, IGF2, G-CSF, GM-CSF), MCP-1, MIP-1b, BDNF, Dopamine, Noradrenaline, NPY, and Acetylcholine. Mann–Whitney test and Spearman’s multivariate correlation were applied for all variables. The Spearman’s analysis results were used to generate a standard correlation matrix and heat map matrix. Results Mean age of participants was 32 years (20–61). Eight (21%) had widespread pain (Widespread Pain Index ≥ 7). Thirteen (34%) had MPS for 1–3 years, 14 (37%) 3–10 years, and 11 (29%) for > 10 years. The following showed strong correlations: IL1b,2,4,5,7,8; GM-CSF and IL 2,4,5,7; between DHEA and BDNF and between BDNF and Kynurenine, NPY and acetylcholine. The heat map analysis demonstrated strong correlations between the Beighton Index and IL 5,7, GM-CSF, DHEA. Asymmetries of shoulder and cervical spine motion and strength associated with select microanalytes. Conclusion Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS.

BackgroundInterest in the effectiveness of mindfulness-based interventions such as yoga in primary schools has grown. Evidence shows promise, as youth who engage in yoga to promote mindfulness show improved coping skills, increased socio-emotional competence and prosocial skills, academic performance, attention span, and ability to deal with stress.ObjectiveThis study reports the results of a program evaluation of a universal health and wellness curriculum, Pure Power, designed to teach youth yoga techniques, mindfulness, and emotion regulation.MethodsA non-randomized comparison design examined outcomes among participants from schools that completed the intervention with highest fidelity of implementation (n = 461) and from students in matched comparison schools (n = 420). Standard measures of coping, emotion regulation and emotion dysregulation, spelling, and math achievement were collected.ResultsAnalyses suggest the youth in the intervention schools demonstrated relative improvement on measures of emotion regulation, spelling, and math.ConclusionsChallenges in implementation in real-life settings are vital to identify. The data provide some real-world evidence for the effectiveness of a universal health and wellness curriculum on emotion regulation and positive academic outcomes. Training school staff to deliver the intervention may foster implementation. Future research should test the effectiveness of who delivers the intervention; for example, teacher-delivered groups vs. other wellness personnel.

Abstract Hypoxia in the neonatal period is associated with early manifestations of adverse cardiovascular health in adulthood including higher risk of hypertension and atherosclerosis. We hypothesize that this occurs due to activation of lysyl oxidases (LOXs) and the remodeling of the large conduit vessels, leading to early arterial stiffening. Newborn C57Bl/6 mice were exposed to hypoxia (FiO2 = 11.5%) from postnatal day 1 (P1) to postnatal day 11 (P11), followed by resumption of normoxia. Controls were maintained in normoxia. Using in vivo (pulse wave velocity; PWV) and ex vivo (tensile testing) arterial stiffness indexes, we determined that mice exposed to neonatal hypoxia had significantly higher arterial stiffness compared with normoxia controls by young adulthood (P60), and it increased further by P120. Echocardiography performed at P60 showed that mice exposed to hypoxia displayed a compensated dilated cardiomyopathy. Western blotting revelated that neonatal hypoxia accelerated age‐related increase in LOXL2 protein expression in the aorta and elevated LOXL2 expression in the PA at P11 with a delayed decay toward normoxic controls. In the heart and lung, gene and protein expression of LOX/LOXL2 were upregulated at P11, with a delayed decay when compared to normoxic controls. Neonatal hypoxia results in a significant increase in arterial stiffness in early adulthood due to aberrant LOX/LOXL2 expression. This suggests an acceleration in the mechanical decline of the cardiovascular system, that contributes to increased risk of hypertension in young adults exposed to neonatal hypoxia that may increase susceptibility to further insults.

Non-cholerae Vibrio species and Shewanella species are organisms that rarely infect humans. Symptoms can range from gastroenteritis to wound infections to septicemia. In addition, these infections can lead to multiple poor outcomes ranging from amputations to death. We present a case of an 11-year-old male with prepatellar bursitis of the right knee due to Vibrio parahaemolyticus and Shewanella algae following an open wound in the Gulf of Mexico complicated by retained oyster shell fragments. He completely recovered after removal of the foreign bodies and organism-directed antimicrobial therapy with ciprofloxacin and doxycycline.

Late childhood is an important period for the development of inhibitory control underlying self-regulation and impulse control behavior. Here, the authors identify brain mechanisms and functional cortical-basal ganglia circuits that predict inhibitory control in children.

PRDM14 is an epigenetic regulator known for maintaining embryonic stem cell identity and resetting potency in primordial germ cells. However, hematopoietic expression of Prdm14 at supraphysiological levels results in fully penetrant and rapid-onset T-cell acute lymphoblastic leukemia (T-ALL) in the mouse. Here, we show that PRDM14-induced T-ALLs are driven by NOTCH1, a frequently mutated driver of human T-ALL. Notch1 is activated in this murine model via RAG-dependent promoter deletions and subsequent production of truncated, ligand-independent protein from downstream regions of the Notch1 locus. These T-ALLs also have focal changes in H3K4me3 deposition at the Notch1 locus and global increases in both H3K4me1 and H3K4me3. Using a PRDM14-FLAG mouse model, we show that PRDM14 binds within an intron of Notch1 prior to leukemia development. Our data support the idea that PRDM14 binding promotes a chromatin state that allows access of the RAG recombinase complex to cryptic RAG signal sequences embedded at the Notch1 locus. Indeed, breeding into a RAG recombination-deficient background abrogates T-ALL development and prevents Notch1 deletions, while allowing for transient hematopoietic stem cell (HSC)-like pre-leukemia cell expansion. Together, our data suggest that PRDM14 expands a progenitor cell population while promoting a permissive epigenetic state for the creation of driver mutations (here, in Notch1), enabling cancer development through the misappropriation of endogenous cellular DNA recombination machinery.

Several theories have been put forth to explain the complex yet symmetrical malformations and the myriad of clinical presentations of caudal duplication syndrome. Hereby, reported case is a 28-year-old female, gravida 2 para 2, with congenital caudal malformation who has undergone partial reconstructive surgeries in infancy to connect her 2 colons. She presented with recurrent left lower abdominal pain associated with nausea, vomiting, and subsequent feculent anal discharge. Imaging reveals duplication of the urinary bladder, urethra, and colon with with cloacal malformations and fistulae from the left-sided cloaca, uterus didelphys with separate cervices and vaginal canals, right-sided aortic arch and descending thoracic aorta, and dysraphic midline sacrococcygeal defect. Hydronephrosis of the left kidney with left hydroureter and inflammation of one of the colons were suspected to be the cause of the patient’s acute complaints. She improved symptomatically over the course of her hospitalization stay with conservative treatments. The management for this syndrome is individualized and may include surgical intervention to fuse or excise the duplicated organs.

The fall and fragmentation of the Caliphate of Cordova in 1009 opened the door to a new apprehension of Islamic political and religious space. Mujāhid al-‘Āmirī, ruler of the taifa of Denia on the Mediterranean coast, created a caliphate ex novo on the Islamic maritime frontier. Similar to the policies of the early Umayyad caliphs, Mujāhid’s state was based on jihād and territorial expansion, and not on the appropriation of an already Islamicized space. This ambition was doubly unique. First of all, the creation of a new caliphate to legitimize this maritime jihād supports the idea of an active struggle against the dār al-ḥarb, and not simple piracy. Secondly, the space sacralized by Mujāhid and the jihād carried out under his authority comprised as much the maritime routes as it did the bordering coasts and islands. The caliphate of Denia ended in failure, but the maritime holy war it had begun continued; the taifa of Denia remained an outpost for Islam on the maritime frontier, while its ships acted as reticular and mobile extensions of Islamic space.

The Taifa kingdoms in the 11th century do not fit into modern notions of a territorial State. Their leaders exercised political power over a given territory, but that territory lacked fixed frontiers, which evolved over time. In the absence of definite boundaries, these territories can be approached on the basis of their capacity to tax, a sign of political power at any given time. The territorial limits of the Taifa of Denia are especially difficult to identify in view of the fact that it was at once a mainland and a maritime power, and also fragmented. The Taifa was conceived as a number of components, an assemblage of networks and points whose territorial sway was marked as much by its ships as by its fortifications. These features then suggest the need for a reassessment of the definition of territory and might even call into question the way that we define a State in a the context of mediaeval Islam.

The overwhelming majority of Congresspersons engage in the acquisition of pork projects, also known as earmarks. In the aggregate, the general public overwhelming opposes pork-barrel spending, yet scholars and Members of Congress both contend that earmarked projects make for grateful constituents. This work attempts to explain this discrepancy. Using experimental data, I show that general discussions of earmarks are not universally beneficial. Recipients are only moved when they are made aware of projects in policy arenas of individual importance. Thus, pork is a nuanced policy tool that must be wielded strategically to gain electoral reward from specific subsets of a constituency.

This article builds on Darling-Hammond, Wilhoit, and Pittenger’s (2014) new paradigm on Accountability for College and Career Readiness by focusing on one of its three pillars—professional accountability. The article begins by offering a conceptual framework for professional accountability for improvement. Next, it highlights slices of four organizations whose improvements efforts serve as a model for professional accountability. Then the article provides an overview of what a complete system of professional accountability would require. The article ends with a narrative of a teacher’s career in an imagined future where school, district, state, and federal contexts are designed and provide resources for a cohesive constellation of policies, programs, and practices that increase learning for children, adults and the entire system.

Organisms are often exposed to environmental pressures that affect homeostasis, so it is important to understand the biological basis of stress-response. Various biological mechanisms have evolved to help cells cope with potentially cytotoxic changes in their environment. miRNAs are small non-coding RNAs which are able to regulate mRNA stability. It has been suggested that miRNAs may tip the balance between continued cytorepair and induction of apoptosis in response to stress. There is a wealth of data in the literature showing the effect of environmental stress on miRNAs, but it is scattered in a large number of disparate publications. Meta-analyses of this data would produce added insight into the molecular mechanisms of stress-response. To facilitate this we created and manually curated the miRStress database, which describes the changes in miRNA levels following an array of stress types in eukaryotic cells. Here we describe this database and validate the miRStress tool for analysing miRNAs that are regulated by stress. To validate the database we performed a cross-species analysis to identify miRNAs that respond to radiation. The analysis tool confirms miR-21 and miR-34a as frequently deregulated in response to radiation, but also identifies novel candidates as potentially important players in this stress response, including miR-15b, miR-19b, and miR-106a. Similarly, we used the miRStress tool to analyse hypoxia-responsive miRNAs. The most frequently deregulated miRNAs were miR-210 and miR-21, as expected. Several other miRNAs were also found to be associated with hypoxia, including miR-181b, miR-26a/b, miR-106a, miR-213 and miR-192. Therefore the miRStress tool has identified miRNAs with hitherto unknown or under-appreciated roles in the response to specific stress types. The miRStress tool, which can be used to uncover new insight into the biological roles of miRNAs, and also has the potential to unearth potential biomarkers for therapeutic response, is freely available at http://mudshark.brookes.ac.uk/MirStress.

The structural principles that govern interactions between l- and d-peptides are not well understood. Among natural proteins, coiled-coil assemblies formed between or among α-helices are the most regular feature of tertiary and quaternary structures. We recently reported the first high-resolution structures for heterochiral coiled-coil dimers, which represent a starting point for understanding associations of l- and d-polypeptides. These structures were an unexpected outcome from crystallization of a racemic peptide corresponding to the transmembrane domain of the influenza A M2 protein (M2-TM). The reported structures raised the possibility that heterochiral coiled-coil dimers prefer an 11-residue (hendecad) sequence repeat, in contrast to the 7-residue (heptad) sequence repeat that is dominant among natural coiled coils. To gain insight on sequence repeat preferences of heterochiral coiled-coils, we have examined three M2-TM variants containing substitutions intended to minimize steric clashes between side chains at the coiled-coil interface. In each of the three new crystal structures, we observed heterochiral coiled-coil associations that closely match a hendecad sequence motif, which strengthens the conclusion that this motif is intrinsic to the pairing of α-helices with opposite handedness. In each case, the presence of a hendecad motif was established by comparing the observed helical frequency to that of an ideal hendecad. This comparison revealed that decreasing the size of the amino acid side chain at positions that project toward the superhelical axis produces tighter packing, as determined by the size of the coiled-coil radius. These results provide a basis for future design of heterochiral coiled-coil pairings.

When implanting a mechanical aortic valve the annulus orientation is important with respect to turbulence. However, the effect on cavitation has not yet been investigated. The aim of this study was to investigate how cavitation is influenced hereof in vivo. Three pigs were included in the study. An Omnicarbon 21mm valve equipped with a rotating mechanism enabling controlled rotation of the valve was implanted in aortic position. Under stable hemodynamic conditions, measurements were performed using a hydrophone positioned at the aortic root. The valve was rotated from 0-360° in increments of 30°. From the pressure fluctuations recorded by the hydrophone the root mean square of the 50 kHz high pass filtered signal as well as the non-deterministic signal energy was calculated as indirect measures of cavitation. Various degrees of cavitation were measured but no relationship was found between either of the two cavitation measures and the valve orientation. Hemodynamics varied during the experiments for all pigs (3.9-5.7 l/min; 5.0-7.2 l/min; 3.1-7.5 l/min). Changes in cavitation quantities seemed to be caused by changes in hemodynamics rather than valve angular position. In conclusion, these results do not favor any position over another in terms of cavitation potential.

Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from d amino acids (d peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious protein-protein interactions. Coiled-coil interactions, between or among α-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled-coil interactions were predicted over 50 years ago by Crick, and limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report two independent crystal structures that elucidate coiled-coil packing between l- and d-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. However, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern.

Hydrogen peroxide was employed as the terminal oxidant in the osmium tetroxide mediated oxidative cleavage of olefins, producing the corresponding aldehyde and ketone products. Aryl olefins are cleaved in good to excellent yield regardless of arene electronics. Alkyl olefins cleave in moderate to good yield for di- and tri-substituted alkenes.

Background and Aim of the Study: Patients with combined aortic valve pathology (stenosis and insufficiency) are often evaluated as if they had only a single pathology, because a means of evaluating the detrimental effects of combined insufficiency and stenosis does not yet exist. The study aim was to test the performance of a new hemodynamic index based on mechanical energy loss to measure the effects of combined valve disease on ventricular workload., Methods: An intact and subsequently perforated and sutured aortic bioprosthesis was tested in an in vitro model of the left heart, varying cardiac output, average diastolic aortic pressure, and the type and combination of valve lesion. The regurgitant fraction (RF), systolic transvalvular pressure gradient (Deltaps), and energy loss indices of forward flow (LPVf), regurgitant flow (LPVr), and the sum of the two (LPVc), were measured for each experimental condition and compared with the increase in work per unit volume net forward flow (DeltaWPV) due to perforation and suturing., Results: Deltaps was found to underestimate LPVf when the valve was perforated. LPVc had an excellent linear relationship with DeltaWPV (slope = 0.98, r2 = 0.97) that was independent of valve lesion or flow and pressure conditions., Conclusion: Deltaps does not describe the increase in ventricular workload, or even the forward flow portion of it, when valve insufficiency is present. LPVc was found to be a very good measure of the decrease in pump effectiveness due to aortic valve insufficiency or combined valve pathology.

Background: The degree of left ventricular overload in patients with aortic valve insufficiency (AI) plays an important role in determining the need and timing of surgical intervention. Because hemodynamic evaluation of AI may potentially predict the effects of an insufficient valve on the ventricle before they occur, it would be useful to guide valve surgery with such a diagnostic tool. The purpose of this study was to test the performance of a new hemodynamic index based on mechanical energy loss for the measurement of the effects of insufficiency on ventricular workload., Methods and Results: An intact and subsequently perforated aortic bioprosthesis was tested within an in vitro model of the left heart, varying cardiac output, diastolic aortic pressure, and the size of perforation. Regurgitant orifice area (ROA), regurgitant volume (RV), regurgitant fraction (RF), and energy loss index (ELI) were measured for each experimental condition and plotted against the increase in workload per unit volume net forward flow (DeltaWPV) due to perforation. ROA, RV, and RF showed good correlations with DeltaWPV, but the relationship between these variables and DeltaWPV became ambiguous as their magnitudes increased. ELI had a near perfect linear relationship with DeltaWPV (slope=1.00, r(2)=0.98) independent of the experimental condition., Conclusions: RV, RF, and ROA do not by themselves fully describe the increase in difficulty the ventricle has in moving the blood across an insufficient valve. ELI, in contrast, was found to be a very good measure of the decrease in pump efficiency due to aortic valve insufficiency.

Background and Aim of the Study: Stresses of leakage flow may contribute to the increased tendency for thromboembolic complications in patients with mechanical valves. In bileaflet valves, leakage occurs primarily in the pivots, and the width of the pivot gap influences viscous stress magnitudes. The present study was conducted to investigate the effects of gap width on viscous stresses within the pivots of a bileaflet mitral valve during the leakage phase., Methods: A computational model of a bileaflet valve was created and inserted between models of the left atrium and ventricle. Three simulations were performed, varying gap width between the leaflet and housing in the pivot region. To validate these calculations, steady leakage across a scaled in-vitro model of a single pivot was initiated, and velocity measurements at specific locations within flow the pivot were obtained using one-component laser Doppler velocimetry., Results: The average viscous stresses on the housing surface of the pivot increased from 198 to 299 Pa, and on the leaflet surface from 242 to 271 Pa, as gap width was increased from 100 to 300 microm. These stresses were similar in magnitude to the maximum turbulent stresses reported within the pivots in previous studies. Velocities measured experimentally were even larger than those estimated computationally., Conclusion: These experiments suggest that viscous stresses in leakage flow across a bileaflet mitral valve increase with gap width, and may contribute more to blood damage and increased risk of thromboembolic complications in patients with such valves than would turbulence.

This study was performed to determine whether annular plane orientation of the Omnicarbon aortic valve influences forward flow turbulence. The Omnicarbon prostheses was modified to allow in situ manual rotation of the valve when implanted in the aortic position of eight 90 kg pigs. Pulsed Doppler ultrasound was used to acquire velocity measurements at 17 locations within the cross-sectional area of the ascending aorta. In each animal, 12 valve rotations were tested in this manner. Reynolds normal stresses were estimated from the velocity measurements. High Reynolds normal stresses were concentrated between left and posterior-right sides of the aortic wall for all orientations studied. No trends in mean or maximum Reynolds normal stresses with respect to valve rotation were consistent in the experiments. Unlike previous experiments with the Medtronic-Hall tilting disc valve, these experiments showed no notable changes in Reynolds normal stress with respect to orientation of the Omnicarbon valve. This suggests that the tendency of turbulent stresses to change with tilting disc valve orientation may be dependent on valve design.

Background and Aim of the Study: Previous studies of leakage jet turbulence have been carried out in vitro, using a Newtonian fluid to simulate blood and large, rigid approximations to the chambers of the heart. The study aim was to apply an in-vivo method of quantifying leakage jet turbulence to a variety of bileaflet mechanical heart valves, and thereafter to determine the effects of exercise and valve design on turbulent shear stresses within leakage flow., Methods: Bileaflet prostheses sewn to a manual traversing device were implanted in the mitral position of 29 pigs of body weight ca. 90 kg. Pulsed Doppler ultrasound was used to acquire velocity measurements within the leakage jets detected 1 mm upstream of the housing. Analytical techniques were used to estimate peak velocities and maximum turbulent shear stresses from these velocity measurements., Results: Maximum turbulent shear stress was found to rise with increasing ventricular pressure. No leakage turbulence was found from a valve with relatively small leakage gap widths. The Medtronic Parallel valve was found to have considerable significant leakage flow disturbance, even under low ventricular pressure conditions. Similar maximum turbulent shear stress magnitudes were estimated in the leakage jets of the St. Jude Medical, CarboMedics and Sorin Bicarbon valves at medium ventricular pressure conditions. The maximum turbulent shear stresses estimated in these experiments were lower than those found in previous in-vitro measurements., Conclusion: Exercise raises the turbulent shear stresses of leakage flow substantially. Hinge design and leakage gap width also affect the magnitudes of these stresses. Leakage flow turbulence may be less damaging to the blood than was previously thought, and is considerably less damaging than forward-flow turbulence.

Presented is a methodology to oxidatively cleave alpha-hydroxyketones and alpha- or beta-diones using the environmentally benign reagent KHSO(5), prepared easily from Oxone, to diesters in one simple transformation. In addition, we undertook a mechanistic study to provide a plausible mechanistic interpretation. These reactions may prove to be valuable alternatives to other related metal-mediated processes.

This work introduces a method for the in vivo measurement and analysis of turbulence within the leakage of a mechanical heart valve. Several analysis techniques were applied to ultrasound measurements acquired within the atrium of a pig, and error associated with these techniques was analyzed. The technique chosen applies cyclic averaging to mean and maximum velocity measurements within small, normalized phase windows to calculate Reynolds normal stresses in the direction of the ultrasound beam. Maximum shear stresses are estimated from these normal stresses using an analytical technique. The stresses observed were smaller than those reported from previous in vitro simulations.

[reaction: see text] A highly efficient, mild, and simple protocol is presented for the tandem OsO(4)-mediated oxidative cleavage/oxidative lactonization of alkenols to lactones. The protocol couples the OsO(4)-catalyzed oxidative cleavage of olefins with Oxone as the co-oxidant with the direct oxidation of aldehydes in alcoholic solvents to their corresponding esters.

Background: Congenital obstructive nephropathy is a condition characterized by hydronephrosis, tubular dilatation, apoptosis, and atrophy, as well as interstitial cellular infiltration and progressive interstitial fibrosis. The renal consequences of chronic unilateral ureteral obstruction (UUO) in the neonatal rat are similar to those of clinical congenital obstructive nephropathy., Methods: To define alterations in renal gene expression induced by chronic neonatal UUO, Sprague-Dawley rats were subjected to UUO or sham operation within the first 2 days of life, and kidneys were harvested after 12 days., Results: Microarray analysis revealed that the mRNA expression of multiple immune modulators, including krox24, interferon-gamma regulating factor-1 (IRF-1), monocyte chemoattractant protein-1 (MCP-1), interleukin-1beta (IL-1beta), CCAAT/enhancer binding protein (C/EBP), p21, c-fos, c-jun, and pJunB, was significantly increased in obstructed compared to sham-operated kidneys (all P < 0.05). Western blot analysis revealed significant changes in immune modulator protein abundance in the obstructed versus sham-operated kidney for krox24 (P = 0.0004), IRF-1 (P = 0.005), MCP-1 (P = 0.01), and JunD (P = 0.0008). Alternatively, the abundance of all of the immune modulator proteins was similar in sham-operated and obstructed kidneys in rats subjected to acute (4 days) neonatal UUO. Microarray analysis studies also reveal that structural genes that comprise the cytoskeleton and cell matrix are significantly up-regulated by chronic neonatal UUO, including calponin, desmin, dynamin, and lumican (all P < 0.05)., Conclusion: Multiple genes are aberrantly expressed in the kidney of rats subjected to chronic neonatal UUO. Elucidation of these genes involved in neonatal UUO may lead to new insight about congenital obstructive nephropathy.

[reaction: see text] A highly efficient, mild, and simple protocol is presented for the oxidation of aldehydes to carboxylic acids utilizing Oxone as the sole oxidant. Direct conversion of aldehydes in alcoholic solvents to their corresponding ester products is also reported. These reactions may prove to be valuable alternatives to traditional metal-mediated oxidations.

Heart valve dysfunction often necessitates surgical implantation of a mechanical heart valve (MHV). Although implantation of a MHV is a life-saving procedure, the patient still faces potentially complications such as thromboembolic events and material failure. These complications may be caused by cavitation, which can occur during valve closure. Cavitation is an erosive phenomenon that can be generated in fluids when the pressure locally drops below the vapor pressure. This paper reviews the literature on cavitation and MHVs and particular features of the valve and closing conditions that potentially increase the intensity of cavitation. Techniques for detecting cavitation will be discussed. Of these, an acoustic approach will be emphasized, since it is currently the only technique able to detect and quantify cavitation in vivo.

Antagonists to the N-methyl-D-aspartate (NMDA) receptor bind to various extraneuronal tissues. We therefore assessed the expression of the main NMDA subunit, NR1, in various tissues. We demonstrate that NR1 appears to be most abundant in the rat kidney and heart. NR1 is present in total rat kidney, cortex, and medulla. Of the NR2 subunits, only the NR2C subunit protein is present in the kidney. The abundance of the NR1 subunit protein increases with kidney development. Both NR1 and NR2C are present in opossum kidney, Madin-Darby canine kidney, and LLC-PK(1) cells. Immunohistochemistry studies show that the NR1 subunit is present in the renal proximal tubule. NR1 is abundant in the atrium and ventricle but is also expressed in the aorta and pulmonary artery. The NR2 subunits are not expressed in the heart. NR1 subunit protein expression is constant throughout heart development. Finally, the NR1 subunit protein is expressed in heart cells (H9c2) grown in culture. These studies reveal the presence of the NMDA receptor in the kidney and the cardiovascular system.

A mild, organometallic alternative to ozonolysis utilizing oxone and OsO(4) is presented. This is a direct oxidation of olefins via the carbon-carbon cleavage of an osmate ester by the action of oxone. Twenty-four different olefins were converted to their corresponding ketones or carboxylic acids in high yields (>80%). Free alcohols, acetate- and benzyl-protected alcohols, and 1,2-diols were stable under these conditions. This method should be applicable for traditional organic synthesis.

In this work, estimates of turbulence were made from pulsatile flow laser Doppler velocimetry measurements using traditional phase averaging and averaging after the removal of cyclic variation. These estimates were compared with estimates obtained from steady leakage flow LDV measurements and an analytical method. The results of these studies indicate that leakage jets which are free and planar in shape may be more unstable than other leakage jets, and that cyclic variation does not cause a gross overestimation of the Reynolds stresses at large distances from the leakage jet orifice.

The clinical histories of the Medtronic Parallel (MP) and St. Jude Medical (SJM) Standard valves suggest pivot geometry influences the thrombogenic characteristics of bileaflet prostheses. This work studied the effects of various pivot geometries on markers of platelet damage in a controlled, in vitro apparatus. The Medtronic Parallel valve, two St. Jude Medical valves, and two demonstration prostheses were used to study the effects of bileaflet pivot design, gap width, and size on platelet secretion and anionic phospholipid expression during leakage flow. A centrifugal pump was used to drive blood through a circuit containing a bileaflet prosthesis. Samples were taken at set time intervals after the start of the pump. These samples were analyzed by cell counting, flow cytometry, and enzyme-linked immunosorbant assay. No significant differences were observed in platelet secretion or anionic phospholipid expression between experiments with the SJM 27 Standard regular leaker, the SJM 20 regular leaker, and the MP 27 valves. Significant differences in platelet secretion and anionic phospholipid expression were observed between a SJM 27 Standard regular leaker and a SJM 27 high leaker valve. These studies suggest that leakage gap width within bileaflet valve pivots has a significant effect on platelet damage initiated by leakage flow.

The quaternizations of dibenzoquinolizines 9 and 14 with 3-halo-1-propanols are highly cis-selective (94-100% cis), results consistent with the N-methylation of O-methylcapaurine (7b), but in contrast to the proposed trans-stereochemistry of dibenzo[a,h]quinolizine methiodide 10 and the analogous quaternizations of 1-benzyl- and 1-phenylisoquinoline congeners 5b and 5c. In this report, we describe stereoselective preparation of the unique cis-dibenzoquinolizinium propanols 15 and 16and their transformation into bis- and mixed-onium chlorofumarates 19, 20ab, and 26. Dibenzo[a,g]quinolizinium propanol 15 was prepared enantioselectively in three steps from dihydroisoquinoline 11. Asymmetric transfer hydrogenation of 11 in the presence of triethylamine/formic acid and Noyori's chiral ruthenium catalyst 12 produced R-(-)-5',8-dimethoxynorlaudanosine (13) in 98% yield and 87% ee. Pictet-Spengler cyclization of 13 in formalin/formic acid afforded the dibenzo[a,g]quinolizine 14 in 65% yield. Quaternization of 14 with 3-chloro-1-propanol under Finkelstein conditions generated cis-dibenzoquinolizinium propanol 15 in 85% yield with >94% cis-selectivity. The cis-dibenzo[a,h]quinolizinium propanol 16 was obtained as a single stereoisomer by reaction of the known tetramethoxyquinolizine 9 with neat 3-iodo-1-propanol. Bis-onium chlorofumarates 18 and 19 and the mixed-onium derivative 20ab were prepared by a pool synthesis procedure from (1R)-trans-6a, 16, and chlorofumaryl chloride (17). Mixed-onium alpha-chlorofumarate 26 was synthesized from (1S)-trans-6d, 15 and (+/-)-trans-2,3-dichlorosuccinic anhydride (22), employing a recently disclosed chlorofumarate mixed-diester synthesis. The title compounds (19, 20ab, and 26) displayed curare-like effects of ultrashort duration in rhesus monkeys.

Background and Aim of the Study: The recent clinical history and experimental studies of the Medtronic Parallel (MP) valve suggest that bileaflet valve leakage flow is a primary initiator of thrombosis. These studies investigated the effects of physiologic leakage flow through a MP valve on various markers of blood damage., Methods: A centrifugal pump was used to drive whole, human blood anticoagulated with PPACK through a circuit containing a MP 27 mm valve in the closed position (experimental runs) or a MP 27 mm valve in the open position (control runs). Samples were taken at set time intervals after the start of the pump. These samples were analyzed by cell counting, flow cytometry, and ELISA., Results: Cell counts remained relatively constant in both the experimental and control runs. Increases in plasma hemoglobin concentration and the percentage of glycophorin A-positive fragments in the cell population were not significant in either the experimental or the control runs. Plasma platelet factor 4 activity and the percentage of the CD41-positive population which was positive for annexin V increased significantly (p <0.05) in the experimental runs compared with the control runs., Conclusion: The results indicate that bileaflet valve leakage flow causes significant platelet disruption, that erythrocytes are more resistant to disruption by leakage flow than platelets and granulocytes, and that annexin V binding to platelets and plasma platelet factor 4 activity are more sensitive markers of leakage induced blood damage than plasma hemoglobin concentration.

The most widely implanted prosthetic valve is the mechanical bileaflet. Recent clinical experiences suggest that some designs are more prone to thromboembolic episodes than others. This study evaluated the hinge flow and near-field forward flow of the new St. Jude Medical Regent bileaflet mechanical heart valve. Laser Doppler velocimetry measurements were conducted within the hinge and near-field forward flow regions of the Regent valve. These pulsatile flow velocity measurements were animated in time to visualize the flow fields throughout the cardiac cycle. During forward flow, a recirculation region developed in the inflow pocket of the Regent hinge but was subsequently abolished by strong backflow during valve closure. Leakage velocities in the hinge region reached 0.72 m/s and Reynolds shear stresses reached 2,600 dyn/cm2. Velocities in the near-field region were highest in the lateral orifice jet, reaching 2.1 m/s. Small regions of separated flow were observed adjacent to the hinge region. Leaflet motion through the Regent hinge creates a washout pattern which restricts the persistence of stagnation zones in its hinge. Based upon the results of these studies, the hematological performance of the Regent series should be at least equivalent to the performance of the Standard series.

Background and Aims of the Study: When choosing a prosthetic replacement for a natural heart valve, one objective should be to minimize the workload placed on the heart. This workload can be raised by fluid mechanical energy losses imposed by the valve. For a patient with left ventricular hypertrophy, certain aortic valve types and orientations could be hemodynamically superior to others., Methods: This study used a control volume analysis to investigate the effects of prosthetic mechanical aortic valve type and orientation on fluid mechanical energy losses in four in vitro models of the left ventricular outflow/aortic inflow tract in various degrees of hypertrophy. Flow visualization studies were performed to qualitatively validate this analysis. The two most commonly used mechanical valve designs were studied: the St. Jude Medical (SJM) bileaflet valve and the Medtronic Hall (MH) tilting disk valve. Experiments were performed in pulsatile flow at a constant heart rate of 60 beats per min for five valve type/orientation combinations. The stroke volume was varied between 40 and 120 ml in five increments for each model and valve/orientation studied., Results: Valve type and orientation was found to have a significant effect on energy losses in these models (p < 0.05). Valve/orientation combinations with leaflets or disks approximately parallel to the proximal flow direction created lower energy losses than others. The MH valve in the 180 degrees orientation caused significantly less energy losses and pressure drops (orifice and recovered) than any of the SJM valve/orientations studied (p < 0.05). The SJM and MH valves in the 0 degree orientation were responsible for significantly more energy loss than other valve/orientations studied (p < 0.05). An aortic inflow tract model with severe (45 degrees) curvature created significantly more energy loss (p < 0.05) than those with less curvature (15 and 30 degrees). However, the insertion of an obstruction simulating a hypertrophic tissue outgrowth caused much more energy loss than increasing the severity of outflow tract curvature from 15 to 45 degrees. Both orifice pressure drop and recovered pressure drop had excellent linear correlations with energy losses found in these models., Conclusions: These results imply that: (i) prosthetic valve type and orientation should be considered when replacing the aortic valve of a hypertropic patient; (ii) removal of obstructions within the aortic inflow tract will decrease ventricular workload; and (iii) the Doppler-estimated pressure gradients commonly use by cardiologists to assess the performance of a prosthetic valve, correlate very well with left ventricular energy loss and work load.