Benign cutaneous pseudoglandular schwannoma: a case report.
Schwannoma is a common peripheral neural neoplasm that could present as a primary skin lesion. In addition to typical schwannoma with classic Antoni A and Antoni B areas, many variant types have been described, such as plexiform, cellular, epithelioid, and ancient schwannomas. Glandular schwannoma is a rare variant characterized by the presence of glands in an otherwise typical schwannoma. There are also a few reported cases in the literature of pseudoglandular schwannoma from central nervous system, eye, submandible, and shoulder, in which the gland-like structures were lined by Schwann cells. We report here a patient with a benign cutaneous schwannoma composed of predominantly gland-like spaces that contained mucinous material and were lined by Schwann cells confirmed by immunohistochemistry and ultrastructural studies. The tumor was well circumscribed and showed minimal cytologic atypia, indicating benignity. We report this unusual case of benign cutaneous pseudoglandular schwannoma to further awareness of the morphologic diversity of schwannoma.


Functional Biomarkers for Amyotrophic Lateral Sclerosis.
The clinical diagnosis of amyotrophic lateral sclerosis (ALS) relies on determination of progressive dysfunction of both cortical as well as spinal and bulbar motor neurons. However, the variable mix of upper and lower motor neuron signs result in the clinical heterogeneity of patients with ALS, resulting frequently in delay of diagnosis as well as difficulty in monitoring disease progression and treatment outcomes particularly in a clinical trial setting. As such, the present review provides an overview of recently developed novel non-invasive electrophysiological techniques that may serve as biomarkers to assess UMN and LMN dysfunction in ALS patients.


Spatial correlations between MRI-derived wall shear stress and vessel wall thickness in the carotid bifurcation.
To explore the possibility of creating three-dimensional (3D) estimation models for patient-specific wall thickness (WT) maps using patient-specific and cohort-averaged WT, wall shear stress (WSS), and vessel diameter maps in asymptomatic atherosclerotic carotid bifurcations. Twenty subjects (aged 75 ± 6 years [mean ± standard deviation], eight women) underwent a 1.5-T MRI examination. Non-gated 3D phase-contrast gradient-echo images and proton density-weighted echo-planar images were retrospectively assessed for WSS, diameter estimation, and WT measurements. Spearman's ρ and scatter plots were used to determine correlations between individual WT, WSS, and diameter maps. A bootstrapping technique was used to determine correlations between 3D cohort-averaged WT, WSS, and diameter maps. Linear regression between the cohort-averaged WT, WSS, and diameter maps was used to predict individual 3D WT. Spearman's ρ averaged over the subjects was - 0.24 ± 0.18 (p < 0.001) and 0.07 ± 0.28 (p = 0.413) for WT versus WSS and for WT versus diameter relations, respectively. Cohort-averaged ρ, averaged over 1000 bootstraps, was - 0.56 (95% confidence interval [- 0.74,- 0.38]) for WT versus WSS and 0.23 (95% confidence interval [- 0.06, 0.52]) for WT versus diameter. Scatter plots did not reveal relationships between individual WT and WSS or between WT and diameter data. Linear relationships between these parameters became apparent after averaging over the cohort. Spearman's ρ between the original and predicted WT maps was 0.21 ± 0.22 (p < 0.001). With a combination of bootstrapping and cohort-averaging methods, 3D WT maps can be predicted from the individual 3D WSS and diameter maps. The methodology may help to elucidate pathological processes involving WSS in carotid atherosclerosis.


Long-term load duration induces N-cadherin down-regulation and loss of cell phenotype of nucleus pulposus cells in a disc bioreactor culture.
Long-term exposure to a mechanical load causes degenerative changes in the disc nucleus pulposus (NP) tissue. A previous study demonstrated that N-cadherin (N-CDH)-mediated signalling can preserve the NP cell phenotype. However, N-CDH expression and the resulting phenotype alteration in NP cells under mechanical compression remain unclear. The present study investigated the effects of the compressive duration on N-CDH expression and on the phenotype of NP cells in an ex vivo disc organ culture. Porcine discs were organ cultured in a self-developed mechanically active bioreactor for 7 days. The discs were subjected to different dynamic compression durations (1 and 8 h at a magnitude of 0.4 MPa and frequency of 1.0 Hz) once per day. Discs that were not compressed were used as controls. The results showed that long-term compression duration (8 h) significantly down-regulated the expression of N-CDH and NP-specific molecule markers (Brachyury, Laminin, Glypican-3 and Keratin 19), attenuated Alcian Blue staining intensity, decreased glycosaminoglycan (GAG) and hydroxyproline (HYP) contents and decreased matrix macromolecule (aggrecan and collagen II) expression compared with the short-term compression duration (1 h). Taken together, these findings demonstrate that long-term load duration can induce N-CDH down-regulation, loss of normal cell phenotype and result in attenuation of NP-related matrix synthesis in NP cells.


[Automated external defibrillation in children].
Ventricular fibrillation is an infrequent arrhythmia in cardiac arrest occurring in the out-of-hospital setting in infants and small children. However, outcome is good provided early defibrillation is performed; consequently, this procedure is one of the main links in the chain of survival in children with a shockable rhythm. Automated external defibrillators are small devices that can analyze heart rhythm and deliver a dose of electric energy when considered timely by the operator. Automated external defibrillators are easy to use and can be operated, if necessary, by anyone. Therefore, all pediatricians should be aware of how these devices work and be able to use them safely and effectively, following the current defibrillation protocol.


Holographic line field en-face OCT with digital adaptive optics in the retina in vivo.
We demonstrate a high-resolution line field en-face time domain optical coherence tomography (OCT) system using an off-axis holography configuration. Line field en-face OCT produces high speed en-face images at rates of up to 100 Hz. The high frame rate favors good phase stability across the lateral field-of-view which is indispensable for digital adaptive optics (DAO). Human retinal structures are acquired in-vivo with a broadband light source at 840 nm, and line rates of 10 kHz to 100 kHz. Structures of different retinal layers, such as photoreceptors, capillaries, and nerve fibers are visualized with high resolution of 2.8 µm and 5.5 µm in lateral directions. Subaperture based DAO is successfully applied to increase the visibility of cone-photoreceptors and nerve fibers. Furthermore, en-face Doppler OCT maps are generated based on calculating the differential phase shifts between recorded lines.


Use of remote monitoring with continuous glucose monitoring in young children with Type 1 diabetes: the parents' perspective.
Remote monitoring with continuous glucose monitoring (CGM) in children with Type 1 diabetes mellitus has recently become available, but little is known about caregivers' experiences of its use, particularly in younger children. The aim of this study was to explore parents' everyday experiences of using this technology. The parents of children with Type 1 diabetes diagnosed for > 1 year, aged 2-12 years were invited to participate in a semi-structured interview. Interviews were the second phase of a randomized cross-over study using standard insulin therapy with or without CGM and remote monitoring for two 3-month periods. Open-ended questions were used to explore parents' real-life experiences of the remote monitoring and CGM system. Interviews were analysed using thematic analysis. Five themes related to remote monitoring emerged: (i) impact on sleep quality for the parents, (ii) peace of mind, (iii) impact on anxiety, (iv) freedom and confidence for the parents and children, and (v) impact on relationships. Furthermore, parents reported on themes related to CGM in general, such as better understanding of how to manage and control their child's diabetes and experiences related to physical or technical aspects. Overall, parents of primary school children reported that using remote monitoring and CGM was a mostly beneficial experience. However, negative aspects within the themes were also reported. These findings will help to provide a structure to discuss parent and child expectations and provide targeted education at the start of using remote monitoring and CGM.


Dioxin reservoirs in southern Viet Nam--a legacy of Agent Orange.
In the isolated Aluoi Valley of central Viet Nam, very high levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were measured in soil, fish fat, duck fat, pooled human blood and breast milk samples collected from A So village between 1996 and 1999. The village was situated on a former military base occupied by US Special Forces between 1963 and 1966. TCDD was a contaminant of the herbicide "Agent Orange", aerially sprayed in the valley between 1965 and 1970, and stored at the A So base. Measured levels were lower near the sites of two other former US bases in the valley which had been occupied for shorter periods of time. In areas where Agent Orange had been applied by low-flying aircraft, levels of TCDD in soil, food and human samples were elevated, but lower than those near the three former US bases. We confirm the apparent food chain transfer of TCDD from contaminated soil to cultured fish pond sediments to fish and duck tissues, then to humans as measured in whole blood and breast milk. We theorize that the Aluoi Valley is a microcosm of southern Viet Nam, where numerous reservoirs of TCDD exist in the soil of former military installations south of the former demilitarized zone. Large quantities of Agent Orange were stored at many sites, used in ground and aerial applications, and spilled. TCDD, through various forms of soil disturbance, can be mobilized from these reservoirs after decades below the surface, and subsequently, introduced into the human food chain.


Tuning the Origin of Magnetic Relaxation by Substituting the 3d or Rare-Earth Ions into Three Isostructural Cyano-Bridged 3d-4f Heterodinuclear Compounds.
Three isostructural cyano-bridged 3d-4f compounds, [YFe(CN)6(hep)2(H2O)4] (1), [DyFe(CN)6(hep)2(H2O)4] (2), and [DyCo(CN)6(hep)2(H2O)4] (3), were successfully assembled by site-targeted substitution of the 3d or rare-earth ions. All compounds have been structurally characterized to display slightly distorted pentagonal-bipyramidal local coordination geometry around the rare-earth ions. Magnetic analyses revealed negligible magnetic coupling in compound 1, antiferromagnetic intradimer interaction in 2, and weak ferromagnetic coupling through dipolar-dipolar interaction in 3. Under an applied direct-current (dc) field, 1 (Hdc = 2.5 kOe, τ0 = 1.3 × 10(-7) s, and Ueff/kB = 23 K) and 3 (Hdc = 2.0 kOe, τ0 = 7.1 × 10(-11) s, and Ueff/kB = 63 K) respectively indicated magnetic relaxation behavior based on a single [Fe(III)]LS ion and a Dy(III) ion; nevertheless, 2 (Hdc = 2.0 kOe, τ0 = 9.7 × 10(-8) s, and Ueff/kB = 23 K) appeared to be a single-molecule magnet based on a cyano-bridged DyFe dimer. Compound 1, which can be regarded as a single-ion magnet of the [Fe(III)]LS ion linked to a diamagnetic Y(III) ion in a cyano-bridged heterodimer, represents one of the rarely investigated examples based on a single Fe(III) ion explored in magnetic relaxation behavior. It demonstrated that the introduction of intradimer magnetic interaction of 2 through a cyano bridge between Dy(III) and [Fe(III)]LS ions negatively affects the energy barrier and χ″(T) peak temperature compared to 3.


1-Cyclo-hexyl-3-{(E)-[1-(pyridin-2-yl)ethyl-idene]amino}-thio-urea.
In the title thio-urea derivative, C(14)H(20)N(4)S, the non-ring non-H atoms are approximately planar, with an r.m.s. deviation of 0.0720 Å. The pyridine ring is twisted out of this plane and makes a dihedral angle of 16.85 (13)° with it. The mean plane passing through the cyclo-hexyl ring is almost normal to the central plane [dihedral angle = 69.23 (8)°]. An intra-molecular N-H⋯N(imine) hydrogen bond occurs. Centrosymmetric dimers are formed in the crystal structure via pairs of N-H⋯S hydrogen bonds, and these are connected into a supra-molecular chain along the a axis via C-H⋯π(pyrid-yl) inter-actions.


High-Performance and Omnidirectional Thin-Film Amorphous Silicon Solar Cell Modules Achieved by 3D Geometry Design.
High-performance thin-film hydrogenated amorphous silicon solar cells are achieved by combining macroscale 3D tubular substrates and nanoscaled 3D cone-like antireflective films. The tubular geometry delivers a series of advantages for large-scale deployment of photovoltaics, such as omnidirectional performance, easier encapsulation, decreased wind resistance, and easy integration with a second device inside the glass tube.


Nonlinear saturation controller simulation for reducing the high vibrations of a dynamical system.
This paper studies the nonlinear vibrating behaviour of a nonlinear cantilever beam system (primary system) using a nonlinear absorber (the secondary system). The nonlinear vibrating behavior for the present dynamical system is considered with the effect of the external force. The one controller type, nonlinear saturation controller (NSC), is introduced to decrease the vibration of this system. Perturbation method treatment is produced to get the mathematical solution of the equations for the dynamical modeling with NSC. The perturbation technique is used to obtain the approximate solution of the dynamical system. This research focuses on resonance case with primary and 1:2 internal resonance. Time histories of the primary system and the controller are shown to demonstrate the reaction with and without control. The time-history response, as well as the impacts of the parameters on the system and controller, are simulated numerically using the MATLAB program. Routh-Hurwitz criterion is used to examine the stability of the system under primary resonance. A numerical simulation, using the MATLAB program, is obtained to show the time-history response, the effect of the parameters on the system and the controller. The effects of system parameters on the performance of the primary system and the controller are investigated. A comparison between all the obtained solutions made to confirm the results. Validation curves are provided to show how closely the perturbation and numerical solutions are related. A comparison is made with recently released papers.


Production of biosurfactant by Bacillus subtilis LB5a on a pilot scale using cassava wastewater as substrate.
The main characteristic of biosurfactants is their property of reducing the superficial and interfacial tension between two immiscible liquids of different polarities. The main obstacle to the application of biosurfactants is the high production costs, the use of alternative substrates being indicated to solve this problem. This work report the production of biosurfactant by Bacillus subtilis LB5a on a pilot scale using cassava wastewater as the substrate, and the study of the parameters related to its production. The cassava wastewater was heated, centrifuged and poured into a 40-liter batch pilot bioreactor adapted for simultaneous foam collection during the fermentative process. The temperature was maintained at 35 degrees C, agitation at 150 rpm and aeration 0.38 vvm during the first 12 h, and 0.63 vvm for the rest of the process. Samples of liquid fermentate were collected at regular intervals for the analysis of total carbohydrates, reducing sugars, pH, CFU/mL count and superficial tension. The foam was centrifuged and the biosurfactant purified. The kinetic data of the process showed that both the microbial population, which reached a maximum after about 24 h, and the foam production of 10.6 L, peaked between 24 and 36 h, coinciding with the greatest production of biosurfactant. The yield of semi-purified surfactant in the foam was 2.4 g/L. The superficial tension of the medium was reduced from 51 to 27 mN/m and the critical micellar concentration was 11 mg/L, which, in principle, characterizes it as a good tensoactive agent. As a function of its composition and productivity, cassava wastewater was identified as a good substrate for the production of the biosurfactant.


[The structural and functional properties of light and dark mouse hepatocytes].
The morphofunctional analysis of the light and dark hepatocytes of mouse C3HA line has shown that the dark cells have increased electronic density of hyaloplasm in contrast to the light ones. The light hepatocytes predominate among tetra- and octaploid cells. Both cell types are able to incorporate [3H] uridine and [3H] thymidine. Mitosis are met among the light hepatocytes only.


Ethical challenges in advanced heart failure.
Advanced heart failure (AHF) is an increasingly important field. Both the population of AHF patients and the therapeutic and diagnostic interventions available are expanding, creating a host of difficult ethical challenges. This article discusses these important issues and proposes an approach to caring for AHF patients. Recent guidelines and clinical trials describe the benefits of costly and invasive therapies for AHF, such as ventricular assist devices and cardiac resynchronization therapy which prolong life and improve symptoms but may create burdens and conflict over deactivation at the end of life. Prognostication, informed consent, and early involvement of palliative care are central to addressing the decision-making challenges raised by these devices. Societal concerns such as cost-effectiveness and distributive justice will play an increasingly important role in the dissemination of these devices. More research, increased end-of-life education, emphasis on advance directives, a more comprehensive informed consent process, and a true multidisciplinary approach are needed to provide optimal care for patients with AHF.


IL-4 regulates endothelial cell activation by IL-1, tumor necrosis factor, or IFN-gamma.
Alteration in the surface membrane of endothelial cells (EC) is a feature of endothelial activation both at sites of inflammation in vivo and after stimulation with cytokines in vitro. The effects of stimulating EC with IL-1 or TNF include enhanced adhesiveness for polymorphonuclear leukocytes (PMN) and T cells, the induction of EC leukocyte adhesion molecule-1 (ELAM-1) expression, and the increased expression of intercellular adhesion molecule-1 (ICAM-1) and the 1.4C3 Ag. In contrast, IFN-gamma stimulation increases EC binding of T cells but not PMN and enhances ICAM-1 expression but not ELAM-1 or 1.4C3 Ag expression. Recently we have reported that the T cell-derived cytokine IL-4 also increases EC adhesiveness for T cells but not PMN. In this study we have examined the effect of IL-4 on the expression of several cytokine-inducible EC activation Ag, by using a previously described ELISA technique. IL-4 modulation of activation Ag expression was concentration dependent, optimal at around 100 U/ml, and exhibited a unique pattern compared to that seen with the other cytokines. Although, IL-4 stimulation increased 1.4C3 Ag expression (p less than 0.001), it significantly inhibited constitutive ICAM-1 expression (p less than 0.01) and did not induce ELAM-1. Furthermore, IL-4 exhibited significant synergy with IL-1 or TNF in inducing 1.4C3 Ag expression (p less than 0.001) but inhibited the increased expression of ICAM-1 produced by IL-1, TNF, or IFN-gamma (p less than 0.01) and inhibited the induction of ELAM-1 by IL-1 and TNF (p less than 0.001). In contrast, IL-4 had no effect on the expression of EC HLA-class I, -DR, -DP, or -DQ and neither enhanced nor inhibited the effect of IFN-gamma on the expression of these molecules. Finally, although IL-4 alone caused little if any shape change in EC monolayers, it strongly synergized with TNF or IFN-gamma in causing a change in shape to a more fibroblastic morphology. These observations indicate that IL-4 increases EC adhesiveness for T cells by the induction of a different adhesion molecule to ICAM-1. Furthermore, the ability of IL-4 to both enhance and inhibit the expression of activation Ag on EC already activated by IL-1, TNF, or IFN-gamma suggests that it may be important in altering the quality of inflammatory responses such as may occur during the development and maintenance of chronic or immune-mediated inflammation.


Mentoring console improves collaboration and teaching in surgical robotics.
One of the most significant limitations of surgical robots has been their inability to allow multiple surgeons and surgeons-in-training to engage in collaborative control of robotic surgical instruments. We report the initial experience with a novel two-headed da Vinci surgical robot that has two collaborative modes: the "swap" mode allows two surgeons to simultaneously operate and actively swap control of the robot's four arms, and the "nudge" mode allows them to share control of two of the robot's arms. The utility of the mentoring console operating in its two collaborative modes was evaluated through a combination of dry laboratory exercises and animal laboratory surgery. The results from surgeon-resident collaborative performance of complex three-handed surgical tasks were compared to results from single-surgeon and single-resident performance. Statistical significance was determined using Student's t-test. Collaborative surgeon-resident swap control reduced the time to completion of complex three-handed surgical tasks by 25% compared to single-surgeon operation of a four-armed da Vinci (P < 0.01) and by 34% compared to single-resident operation (P < 0.001). While swap mode was found to be most helpful during parts of surgical procedures that require multiple hands (such as isolation and division of vessels), nudge mode was particularly useful for guiding a resident's hands during crucially precise steps of an operation (such as proper placement of stitches). The da Vinci mentoring console greatly facilitates surgeon collaboration during robotic surgery and improves the performance of complex surgical tasks. The mentoring console has the potential to improve resident participation in surgical robotics cases, enhance resident education in surgical training programs engaged in surgical robotics, and improve patient safety during robotic surgery.


Evaluation of a safranin-O-stained antigen microagglutination test for francisella tularensis antibodies.
A microagglutination test for Francisella tularensis, with 0.025-ml amounts of diluted sera and 0.025-ml amounts of safranin-O-stained antigen in U-bottom microtitration plates, was compared with a tube agglutination test by using 137 sera. There was 86.3% agreement (+/- 1 dilution variation) between the microagglutination results and the tube agglutination results for sera with tube agglutination titers of greater than or equal to 20. There was 100% agreement (+/- 1 dilution variation) for sera with titers of less than 20. The advantages of the microagglutination test are: (i) it requires fewer man hours to perform; (ii) it requires only one-twentieth of the amount of antigen; and (iii) it is easier to read.


[NMDAR expression in the cochlear nucleus and hearing damage in neonatal rats with hyperbilirubinemia].
To study the role of N-methyl-D-aspartate-receptor (NMDAR) expression in the development of hearing damage in neonatal rats with hyperbilirubinemia. Sixty seven-day-old Sprague-Dawley rats were randomly injected with bilirubin of 100 microg/g (low-dose treatment group) or 200 microg/g (high-dose treatment group) or normal saline (control group). Auditory brainstem response (ABR) was examined. The concentrations of bilirubin in blood and brain were measured. NMDAR expression in the cochlear nucleus slices was examined by immunohistochemistry assay. ABR reflecting threshold obviously increased, and I, II and III wave latency as well as I-II, II-III and I-III interval were more prolonged in the two bilirubin treatment groups when compared with the control group. The NMDAR expression in the cochlear nucleuse in the two bilirubin treatment groups was obviously lower than that in the control group. The NMDAR expression in the cochlear nucleuse was negatively correlated with the brain bilirubin content and the ABR reflecting threshold in the two bilirubin treatment groups. An increased NMDAR activity may play an important role in hearing damage following hyperbilirubinemia.


GMP-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo.
Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP) conditions. After a single step of magnetic depletion of CD3(+) T cells, the depleted peripheral blood mononuclear cells (PBMCs) were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3(-)CD16(+)CD56(+) NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo.


Neurocognitive functioning in patients with bipolar I disorder recently recovered from a first manic episode.
Although cognitive impairment is an important clinical feature of bipolar disorder, it is unknown whether deficits are present at illness onset. The purpose of this study was to determine whether neuropsychological impairments are present in clinically stable patients with bipolar disorder shortly after resolution of their first manic episode. Within a large university medical center, 45 recently diagnosed (DSM-IV-TR) patients with bipolar disorder type I were evaluated after resolution of their first manic episode, along with 25 matched healthy comparison subjects. Participants were administered a neuropsychological battery evaluating 5 broad cognitive domains, including verbal/premorbid intellectual functioning, learning/memory, spatial/nonverbal reasoning, attention/processing speed, and executive function. Data were collected from July 2004 to August 2007. Relative to controls, patients showed broad impairments in learning/memory, spatial/nonverbal reasoning, executive function, and some aspects of attention (all P < .01). Specifically, deficits were evident on tests assessing sustained attention, attentional and mental set shifting, spatial working memory, nonverbal reasoning, and verbal learning and recall (all P < .01). Cognitive impairments in patients could not be fully attributed to substance abuse, medication status, or residual mood symptoms. Results indicate that core neuropsychological deficits in sustained attention, learning and recall, spatial/nonverbal reasoning, and several aspects of executive function are present at illness onset. Cognitive deficits in bipolar disorder are, thus, most likely not exclusively attributable to progressive decline associated with increased illness burden, cumulative treatment effects, or chronicity of illness. These findings may provide etiologic clues into the illness and identify clinical targets for early treatment.


Parental nicotine replacement therapy and offspring bronchitis/bronchiolitis and asthma - a nationwide population-based cohort study.
Prior evidence shows that environmental tobacco smoke is a risk factor for respiratory tract infections, wheeze, and asthma. Nicotine replacement therapy has been shown to increase smoking cessation. However, no prior studies have explored if parental use decreases the risk of bronchitis/bronchiolitis and asthma in the offspring. To examine whether nicotine replacement therapy varenicline, given to parents, was associated with a reduction in bronchitis/bronchiolitis and/or asthma in their children. This study is a population-based cohort study, linking data from nationwide registers, and using a within-individual design that minimizes selection effects and controls for time-invariant confounding factors. Participants included 37,420 parents with a collected prescription of varenicline with 72,392 offspring <18 years of age. Exposure was defined as collected prescriptions of varenicline among the parents. Primary outcomes were offspring hospital visits for bronchitis/bronchiolitis (ICD10: J20 or J21) and offspring hospital visits for asthma (ICD10: J45). Parental varenicline treatment was associated with a lower rate of visits for bronchitis/bronchiolitis in their children (incidence rate ratio [IRR]=0.67; 95% CI=0.50-0.91), but no association was found for asthma (IRR=1.08; 95% CI=0.97-1.19). The rate reduction of bronchitis/bronchiolitis was similar when we restricted data to children aged 0-3 years (IRR=0.71; 95% CI=0.52-0.97) and to maternal varenicline treatment (IRR=0.64; 95% CI=0.43-0.96). When restricting the outcomes to unplanned visits only (ie, excluding booked appointments, followups, and referrals), no associations were found (IRR=0.72, 95% CI=0.51-1.02). In this cohort study, nicotine replacement treatment in parents was associated with reduced hospital visits for bronchitis/bronchiolitis in their children.


Virtual screening of novel compounds as potential ER-alpha inhibitors.
Majority of breast cancers diagnosed today are estrogen receptor (ER)-positive, however, progesterone receptor-positive (PR-positive) is also responsible for breast cancer. Tumors that are ER/PR-positive are much more likely to respond to hormone therapy than tumors that are ER/PR-negative. Nearly 105 ERa inhibitors from literature when docked resulted in 31 compounds (pyrazolo[1,5-a]pyrimidine analogs and chromen-2-one derivatives) with better binding affinities. The maximum score obtained was -175.282 kcal/mol for compound, [2-(4- Fluoro-phenylamino)-pyridin-3-yl]-{4-[2-phenyl-7- (3, 4, 5-trimethoxy-phenyl)-pyrazolo[1,5-a]pyrimidine-5-carbonyl]-piperazin-1-yl}-methanone. The major H-bond interactions are observed with Thr347. In pursuit to identify novel ERa inhibitory ligands, virtual screening was carried out by docking pyrazole, bipyrazole, thiazole, thiadiazole etc scaffold analogs from literature.34 bipyrazoles from literature revealed Compound 2, ethyl 5-amino-1-(5-amino-3-anilino-4-ethoxycarbonyl-pyrazol-1-yl)-3-anilino-pyrazole-4-carboxylate, with -175.9 kcal/mol binding affinity with the receptor, where a favourable H-bond was formed with Thr347.On the other hand, screening 2035 FDA approved drugs from Drug Bank database resulted in 11 drugs which showed better binding affinities than ERa bound tamoxifen. Consensus scoring using 5 scoring schemes such as Mol Dock score, mcule, SwissDock, Pose&Rank and DSX respectively resulted in better rank-sumsfor Lomitapide, Itraconazole, Cobicistat, Azilsartanmedoxomil, and Zafirlukast.


Y-Balance Test Performance and Leg Muscle Activations of Children with Developmental Coordination Disorder.
This study compared Lower Quarter Y-Balance Test (YBT-LQ) performance and leg muscle kinetics between children with and without developmental coordination disorder (DCD), and investigated the association between YBT-LQ performance and muscle kinetics in children with DCD. Forty-eight children with DCD and 51 children without DCD participated in the study. Leg muscle kinetics were measured using surface electromyography when performing YBT-LQ. Children with DCD exhibited an overall lower YBT-LQ scores than controls. They had a lower peak gastrocnemius medialis activation for YBT-LQ posteromedial direction and shorter duration for the muscle to reach peak torque for YBT-LQ anterior direction. No relationship was found between YBT-LQ performance and leg muscle activations in children with DCD. Children with DCD exhibited a less competent YBT-LQ performance with atypical neuromuscular control.


Synchronizability of directed networks: The power of non-existent ties.
The understanding of how synchronization in directed networks is influenced by structural changes in network topology is far from complete. While the addition of an edge always promotes synchronization in a wide class of undirected networks, this addition may impede synchronization in directed networks. In this paper, we develop the augmented graph stability method, which allows for explicitly connecting the stability of synchronization to changes in network topology. The transformation of a directed network into a symmetrized-and-augmented undirected network is the central component of this new method. This transformation is executed by symmetrizing and weighting the underlying connection graph and adding new undirected edges with consideration made for the mean degree imbalance of each pair of nodes. These new edges represent "non-existent ties" in the original directed network and often control the location of critical nodes whose directed connections can be altered to manipulate the stability of synchronization in a desired way. In particular, we show that the addition of small-world shortcuts to directed networks, which makes "non-existent ties" disappear, can worsen the synchronizability, thereby revealing a destructive role of small-world connections in directed networks. An extension of our method may open the door to studying synchronization in directed multilayer networks, which cannot be effectively handled by the eigenvalue-based methods.


Is primary hyperaldosteronism a risk factor for aortic dissection?
Primary hyperaldosteronism is a rare (<1%) and underdiagnosed cause of secondary hypertension. We present a case of aortic dissection in a patient with primary hyperaldosteronism. To our knowledge, there are six other reported cases of aortic dissection in patients with primary hyperaldosteronism. Our case strengthens the hypothesis that primary hyperaldosteronism is a potential independent risk factor for aortic dissection.


Progesterone receptor: stability studies and correlation between steroid binding assay and enzyme immunoassay.
We evaluated and compared Abbott Laboratories' newly developed enzyme immunoassay (EIA) for measuring progesterone receptors (PgR) with that of DuPont's steroid-binding assay (SBA). We also used both methods to study the stability of PgR under various conditions. THere were excellent correlations for all 59 cytosols compared (r = 0.94) and for the 44 cytosols containing PgR greater than 10 fmol per milligram of protein (r = 0.93), but the correlation for cytosols containing less than 10 fmol of PgR per milligram was poor. We found PgR to be more stable as assayed by EIA than by SBA. The biological half-lives of PgR at 30, 4, and -60 degrees C were approximately 3 h, 6 days, and 19 days, respectively. The effect of molybdate on PgR is complex. Its presence during tissue homogenization leads to analytical recovery of more PgR and may stabilize PgR during storage. Its presence during enzyme immunoassay is less critical. Unlike estrogen receptor, PgR is not protected by its ligand, R5020.


[Activities of the Department of Radiation Diagnosis of the Central Scientific Research Roentgenoradiology Institute].
The main stages in the activities of the scientific units of the Institute since its foundation up to now were represented. The role of Prof. M.I. Nemenov, the founder of the Institute, as a scientist and organizer, and investigations of the staff-members, conducted in different periods, were described. The essence of some researches, carried out at the Institute, was briefly reported.


The Case for TAAR1 as a Modulator of Central Nervous System Function.
TAAR1 is widely expressed across the mammalian brain, particularly in limbic and monoaminergic areas, allegedly involved in mood, attention, memory, fear, and addiction. However, the subcellular distribution of TAAR1 is still unclear, since TAAR1 signal is largely intracellular. In vitro, TAAR1 is activated with nanomolar to micromolar affinity by some endogenous amines, particularly p-tyramine, beta-phenylethylamine, and 3-iodothyronamine (T1AM), the latter representing a novel branch of thyroid hormone signaling. In addition, TAAR1 responds to a number of psychoactive drugs, i.e., amphetamines, ergoline derivatives, bromocriptine and lisuride. Trace amines have been identified as neurotransmitters in invertebrates, and they are considered as potential neuromodulators. In particular, beta-phenylethylamine and p-tyramine have been reported to modify the release and/or the response to dopamine, norepinephrine, acetylcholine and GABA, while evidence of cross-talk between TAAR1 and other aminergic receptors has been provided. Systemic or intracerebroventricular injection of exogenous T1AM produced prolearning and antiamnestic effects, reduced pain threshold, decreased non-REM sleep, and modulated the firing rate of adrenergic neurons in locus coeruleus. However each of these substances may have additional molecular targets, and it is unclear whether their endogenous levels are sufficient to produce significant TAAR1 activation in vivo. TAAR1 knock out mice show a worse performance in anxiety and working memory tests, and they are more prone to develop ethanol addiction. They also show increased locomotor response to amphetamine, and decreased stereotypical responses induced by apomorphine. Notably, human genes for TAARs cluster on chromosome 6 at q23, within a region whose mutations have been reported to confer susceptibility to schizophrenia and bipolar disorder. For human TAAR1, around 200 non-synonymous and 400 synonymous single nucleotide polymorphisms have been identified, but their functional consequences have not been extensively investigated yet. In conclusion, the bulk of evidence points to a significant physiological role of TAAR1 in the modulation of central nervous system function and a potential pharmacological role of TAAR1 agonists in neurology and/or psychiatry. However, the specific effects of TAAR1 stimulation are still controversial, and many crucial issues require further investigation.


Outreach and online training services at the Saccharomyces Genome Database.
The Saccharomyces Genome Database (SGD; www.yeastgenome.org ), the primary genetics and genomics resource for the budding yeast S. cerevisiae , provides free public access to expertly curated information about the yeast genome and its gene products. As the central hub for the yeast research community, SGD engages in a variety of social outreach efforts to inform our users about new developments, promote collaboration, increase public awareness of the importance of yeast to biomedical research, and facilitate scientific discovery. Here we describe these various outreach methods, from networking at scientific conferences to the use of online media such as blog posts and webinars, and include our perspectives on the benefits provided by outreach activities for model organism databases. http://www.yeastgenome.org.


Customized PEG-derived copolymers for tissue-engineering applications.
PEG-containing copolymers play a prominent role as biomaterials for different applications ranging from drug delivery to tissue engineering. These custom-designed materials offer enormous possibilities to change the overall characteristics of biomaterials by improving their biocompatibility and solubility, as well as their ability to crystallize in polymer blends and to resist protein adsorption. This article demonstrates various principles of PEG-based material design that are applied to fine tune the properties of biomaterials for different tissue engineering applications. More specifically, strategies are described to develop PEG copolymers with various block compositions and specific bulk properties, including low melting points and improved surface hydrophilicity. Highly hydrated polymer gel networks for promoting cellular growth or suppressing protein adsorption and cell adhesion are introduced. By incorporating selectively cleavable cross-links, these hydrophilic polymers can also serve as smart hydrogel scaffolds, mimicking the natural extracellular matrix for cell cultivation and tissue growth. Ultimately, these developments lead to the creation of biomimetic materials to immobilize bioactive compounds, allowing precise control of cellular adhesion and tissue growth. [image: see text]


Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report.
High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV0) on rituximab PK and of TMTV0 and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV0 was measured by 18F-fluorodeoxyglucose-positron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m2 rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV0 and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV0 increased (R2 = 0.41, P < .0001). A high AUC in cycle 1 (≥9400 mg × h per liter) was associated with better response (odds ratio, 5.56; P = .0006) and longer PFS (hazard ratio [HR], 0.38; P = .011) and OS (HR, 0.17; P = .001). A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV0 was constructed, and the 375 mg/m2 classical dose would be suitable for patients with TMTV0 <281 cm3 In summary, rituximab exposure is influenced by TMTV0 and correlates with response and outcome of DLBCL patients. Dose individualization according to TMTV0 should be evaluated in prospective studies. These studies were registered at www.clinicaltrials.gov as #NCT00498043 and #NCT00841945.


Internal acidification and cAMP increase are not correlated in Saccharomyces cerevisiae.
Addition of glucose to a yeast suspension can produce both an increase in the level of cAMP and a decrease in the intracellular pH. This observation led to the idea that internal acidification triggers the cAMP increase. We have tested this hypothesis using different approaches. To study the effect of sugar metabolism on internal pH we added to the yeast either glucose or a sugar, like xylose, that cannot be phosphorylated. We also utilized yeast strains lacking hexose kinases or phosphoglucose isomerase. We found that phosphorylation of the sugar added is a requisite for internal acidification but not for the cAMP increase. Internal acidification is due to an imbalance between the rate of the metabolic reactions that generate protons and the rate at which protons can be pumped out of the cell. We have manipulated the excretion of protons by using yeast harvested at different phases of growth and resuspended in a medium with or without added K+. Addition of glucose produced a marked drop in internal pH only when the yeast was harvested in the stationary phase of growth and transferred to a medium without added K+. In contrast an increase in cAMP was observed in all situations. We conclude that in yeast there is no correlation between internal acidification and cAMP increase.


Distribution of caffeine levels in urine in different sports in relation to doping control.
Caffeine concentrations were measured in the urines of 11 361 athletes tested for doping control in the Ghent doping control laboratory during the period 1993 - 2002. Determination of these concentrations was done using an alkaline extraction with a mixture of dichloromethane and methanol (9:1; v/v) followed by high performance liquid chromatography and ultraviolet detection (HPLC-UV). The method was validated according to ISO 17 025 standards (International Organisation for Standardisation). Quantification was done by using a calibration curve in the range from 0 to 20 microg/ml. The limit of quantification (LOQ) was 0.10 microg/ml. Most caffeine concentrations were far below 12 microg/ml. Because the results were not normally distributed, transformation of the data was done to evaluate the difference in detected concentrations in several sports. This resulted in an overall average concentration of 1.22 microg/ml +/- 2.45 microg/ml. Comparison of those sports with more than 200 samples being analysed demonstrated that caffeine concentrations in urine samples from bodybuilders are significantly higher in comparison to urines taken in the other sports. Also, a significant difference between caffeine concentrations found in cycling and concentrations found in other sports, including athletics and some ball sports, was observed.


Exceptional Thermochemical Stability of Graphene on N-Polar GaN for Remote Epitaxy.
In this study, we investigate the thermochemical stability of graphene on the GaN substrate for metal-organic chemical vapor deposition (MOCVD)-based remote epitaxy. Despite excellent physical properties of GaN, making it a compelling choice for high-performance electronic and light-emitting device applications, the challenge of thermochemical decomposition of graphene on a GaN substrate at high temperatures has obstructed the achievement of remote homoepitaxy via MOCVD. Our research uncovers an unexpected stability of graphene on N-polar GaN, thereby enabling the MOCVD-based remote homoepitaxy of N-polar GaN. Our comparative analysis of N- and Ga-polar GaN substrates reveals markedly different outcomes: while a graphene/N-polar GaN substrate produces releasable microcrystals (μCs), a graphene/Ga-polar GaN substrate yields nonreleasable thin films. We attribute this discrepancy to the polarity-dependent thermochemical stability of graphene on the GaN substrate and its subsequent reaction with hydrogen. Evidence obtained from Raman spectroscopy, electron microscopic analyses, and overlayer delamination points to a pronounced thermochemical stability of graphene on N-polar GaN during MOCVD-based remote homoepitaxy. Molecular dynamics simulations, corroborated by experimental data, further substantiate that the thermochemical stability of graphene is reliant on the polarity of GaN, due to different reactions with hydrogen at high temperatures. Based on the N-polar remote homoepitaxy of μCs, the practical application of our findings was demonstrated in fabrication of flexible light-emitting diodes composed of p-n junction μCs with InGaN heterostructures.


Association of IGF-1 Level with Low Bone Mass in Young Patients with Cushing's Disease.
Few related factors of low bone mass in Cushing's disease (CD) have been identified so far, and relevant sufficient powered studies in CD patients are rare. On account of the scarcity of data, we performed a well-powered study to identify related factors associated with low bone mass in young CD patients. This retrospective study included 153 CD patients (33 males and 120 females, under the age of 50 for men and premenopausal women). Bone mineral density (BMD) of the left hip and lumbar spine was measured by dual energy X-ray absorptiometry (DEXA). In this study, low bone mass was defined when the Z score was -2.0 or lower. Among those CD patients, low bone mass occurred in 74 patients (48.37%). Compared to patients with normal BMD, those patients with low bone mass had a higher level of serum cortisol at midnight (22.31 (17.95-29.62) vs. 17.80 (13.75-22.77), p=0.0006), testosterone in women (2.10 (1.33-2.89) vs. 1.54 (0.97-2.05), p=0.0012), higher portion of male (32.43% vs. 11.54%, p=0.0016) as well as hypertension (76.12% vs. 51.67%, p=0.0075), and lower IGF-1 index (0.59 (0.43-0.76) vs. 0.79 (0.60-1.02), p=0.0001). The Z score was positively associated with the IGF-1 index in both the lumbar spine (r = 0.35153, p < 0.0001) and the femoral neck (r = 0.24418, p=0.0057). The Z score in the femoral neck was negatively associated with osteocalcin (r = -0.22744, p=0.0229). Compared to the lowest tertile of the IGF-1 index (<0.5563), the patients with the highest tertile of the IGF-1 index (≥0.7993) had a lower prevalence of low bone mass (95% CI 0.02 (0.001-0.50), p=0.0002), even after adjusting for confounders such as age, gender, duration, BMI, hypertension, serum cortisol at midnight, PTH, and osteocalcin. The higher IGF-1 index was independently associated with lower prevalence of low bone mass in young CD patients, and IGF-1 might play an important role in the pathogenesis of CD-caused low bone mass.


Pathogenesis of the anemia of chronic renal failure: the role of erythropoietin.
In summary, the anemia of CRF results from several interactive processes, chief among these inadequate Ep production relative to the degree of anemia. The anemia of renal failure can be regarded as an endocrine deficiency state, which is corrected by the specific replacement therapy. The advances of molecular biology have provided a biosynthetic Ep, a potent tool for correction and prevention of the anemia of renal failure. However, new problems often arise as new treatments become available. The rapid improvement in hematocrit and the resultant lowering in plasma volume may affect dialysis clearances in hemodialysis patients. Since the well-being and appetite of the patients improves as the hematocrit rises, newer methods to increase the weekly dialysis clearances will be needed to prevent the complication of underdialysis in these patients.


Development of the cortical dysplasia of type II lissencephaly.
A detailed neuropathological study of five immature brains with type II lissencephaly is reported. The cases described include two pairs of siblings. One infant survived for 2 months after birth, the others died at 18, 20, 20 and 32 weeks of gestation. This series of cases demonstrates the sequence in which the malformation develops from mid-gestation to post-natal life and shows that type II lissencephaly is not an intracortical malformation but is the result of massive glial and neuronal ectopia in the leptomeninges. This results from a failure of arrest of neuronal migration due to defects in the integrity of the pial/glial barrier.


Covalently Palladated Oligonucleotides Through Oxidative Addition of Pd0.
An 11-mer oligonucleotide incorporating a central (2-iodobenzoylamino)methyl residue has been synthesized and palladated by oxidative addition of Pd2 (dba)3 . UV melting profiles of the duplexes formed by the palladated oligonucleotide with its natural complements were biphasic and the higher melting temperatures (Tm ) exhibited considerable hysteresis. CD spectra, in turn, resembled those of canonical B-type double helices. Two-step denaturation, with the "low-Tm " melting involving only canonical base pairs and the "high-Tm " melting involving also dissociation of a PdII -mediated base pair, appears the most likely explanation for the observed UV melting profiles. As the latter step in all cases takes place at a higher temperature than denaturation of natural duplexes of the same length, the putative PdII -mediated base pairs are stabilizing.


The correlation between insulin-like growth factor 1 (IGF-1) and novel adipocytokines in postmenopausal women: A population-based study.
The adipocytokines and insulin-like growth factor 1 (IGF-1) are involved in insulin resistance, the cardiometabolic syndrome, and atherosclerosis. Therefore, investigating the relationship between circulating levels of the novel adipocytokines and IGF-1 is worthwhile. The correlation between IGF-1, visfatin, and omentin-1 has not been adequately investigated. In a population-based study, 324 postmenopausal women were randomly selected. Circulating IGF-1, visfatin, omentin-1, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) levels were measured with the highly specific enzyme-linked immunosorbent assay method. In multiple regression analyses adjusted for alkaline phosphatase, osteocalcin, and hs-CRP, circulating IGF-1 was significantly correlated with visfatin levels (standardized β coefficient [β] = 0.13, partial correlation coefficient [r] = 0.12, p = 0.028). The significant positive correlation between serum IGF-1 and visfatin levels remained after additional adjustments for age and BMI (β = 0.12, r = 0.12, p = 0.025), metabolic syndrome (β = 0.13, r = 0.12, p = 0.021), and type 2 diabetes mellitus (β = 0.13, r = 0.12, p = 0.026). No significant correlations were found between IGF-1, adiponectin, and omentin-1. There is a significant correlation between serum IGF-1 and visfatin levels in postmenopausal women beyond metabolic syndrome, type 2 diabetes, bone formation markers, and hs-CRP levels. The observed correlation between higher circulating IGF-1 and the higher visfatin levels might be a physiological compensation and adaptation to protect against visfatin-induced proinflammatory effects.


The effects of chitosan oligosaccharides on OPG and RANKL expression in a rat osteoarthritis model.
To investigate the effect of chitosan oligosaccharides (COS) against osteoarthritis (OA) and preliminarily discuss the osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL) and RANK expression in a rat OA model. Thirty-six 6-week-old Male SD rats were randomly divided into three groups: sham-operated group(CON), OA-induction group(OA), COS intervention group(n=12/group). At 4 weeks after the operation, COS (50 ul) intervention weekily for consecutive 5 weeks. The OA and CON groups received an injection of 50 ul physiological saline. At death, 11 weeks following surgery, cartilage was harvested and total RNA and protein were extracted. Both the morphological changes of the cartilage were observed and harvested the total RNA and protein. Meanwhile, the expression of OPG, RANKL and RANK in cartilage were determined. The expression of OPG and RANKL were both enhanced in the cartilage of the OA model. Compared with the OA group, COS treatment improved the cartilage damage (both extent and grade). Furthermore, the COS group showed highly OPG and lower RANKL. Simultaneously, COS treatment upregulated the ratio of OPG/RANKL and downregulated the RANKL/RANK. Chitosan oligosaccharides may be used as a unique biological agent to prevent and treat osteoarthritis, and this effect is associated with modulation of the expression of osteoprotegerin and receptor activator of NF-κB ligand.


Challenges in exchanging medication information: identifying gaps in clinical document exchange and terminology standards.
The availability of accurate medication history information is invaluable for making sound therapeutic decisions. The Continuity of Care Document (CCD) could serve as a mechanism for exchanging interoperable medication information between EHRs. We evaluate the feasibility of representing a medication and its underlying components in a Healthcare Information Technology Standards Panel (HITSP) compliant CCD. Our evaluation resulted in successfully mapping 94% of medication entries and greater than 92% of medication component mappings to CCD constraints. We identify gaps and provide recommendations for improving the representational adequacy of the Federal Medication Terminology (FMT) to fully represent orderable medication concepts.


Nanoimmiscibility: Selective absorption of liquid methanol-water mixtures in carbon nanotubes.
Despite the continuing research interests in CNT-liquid systems, the microscopic structure and transport behavior of liquid mixtures in carbon nanotubes (CNTs) remain poorly understood. Methanol and water liquids are completely miscible across the entire range of concentration; however, recent research reveals that they are immiscible at a molecular level. In this work, we carried out classical molecular dynamics to study the molecular distribution, structure ordering, clustering and transport behavior of liquid methanol-water mixtures within CNT confinement. We found that CNTs preferentially absorbed methanol over water molecule even though the latter has a smaller molecular size, indicating that chemical effect such as molecular hydrophilicity plays a crucial role in the molecular absorption of CNTs. Due to the selective absorption of CNTs, methanol aqueous solution changes from microscopically immiscible to macroscopically immiscible at nanoscale. This nanoscale immiscibility may be utilized in various applications of CNTs including direct methanol fuel cells, nanosensors, molecular sieves, nanofluidic chips, and capsules for drug delivery.


Bivariate Poisson models with varying offsets: an application to the paired mitochondrial DNA dataset.
To assess the effect of chemotherapy on mitochondrial genome mutations in cancer survivors and their offspring, a study sequenced the full mitochondrial genome and determined the mitochondrial DNA heteroplasmic (mtDNA) mutation rate. To build a model for counts of heteroplasmic mutations in mothers and their offspring, bivariate Poisson regression was used to examine the relationship between mutation count and clinical information while accounting for the paired correlation. However, if the sequencing depth is not adequate, a limited fraction of the mtDNA will be available for variant calling. The classical bivariate Poisson regression model treats the offset term as equal within pairs; thus, it cannot be applied directly. In this research, we propose an extended bivariate Poisson regression model that has a more general offset term to adjust the length of the accessible genome for each observation. We evaluate the performance of the proposed method with comprehensive simulations, and the results show that the regression model provides unbiased parameter estimations. The use of the model is also demonstrated using the paired mtDNA dataset.


Photocyclization by a triplet-triplet annihilation upconversion pair in water - avoiding UV-light and oxygen removal.
We present a formal [2 + 2]-cycloaddition of unsaturated ketones enabled by a green-to-ultraviolet triplet-triplet annihilation upconversion (TTA-UC) pair, using commercially available Ru(bpy)32+ and pyrene as sensitizer and annihilator, respectively. In the developed protocol, visible light irradiation at λmax = 520 nm allows for the reaction to proceed without the need for UV-light and the aqueous medium eliminates the need for oxygen removing protocols. Through this study, the application of the readily available upconversion pair is broadened to include cyclization reactions. We showcase the utility of the system by generating bicyclo[2.1.1]hexanes that are valuable bioisosteres of ortho-substituted benzenes, a promising motif for pharmaceuticals.


Asymmetric Expansion with a Modified Quad Helix for Treatment of Isolated Crossbite.
Unilateral posterior crossbite often involves only one tooth, especially upper first molar; in these cases it is never easy to obtain an asymmetrical movement of a molar and a proper planning of the orthodontic device with its anchorage is necessary to avoid arch overexpansion. Thanks to its simplicity and efficacy, the modified Quad Helix here described represents a valid therapeutic tool in cases of isolated posterior crossbite.


Rap2B promotes angiogenesis via PI3K/AKT/VEGF signaling pathway in human renal cell carcinoma.
Human renal cell carcinoma which is a highly vascular tumor is the leading cause of death from urologic cancers. Angiogenesis has a pivotal role in oncogenesis and in the viability and expansion of renal cell carcinoma. Rap2B, as a small guanosine triphosphate-binding protein of the Ras family, was first discovered in the early 1990s during the screening of a platelet complementary DNA library. Previous studies have shown that Rap2B aberrantly expressed in human carcinogenesis and promoted the development of tumors via multiple signaling pathways. However, the function of Rap2B in tumor angiogenesis that is necessary for tumor growth and metastasis remains unknown. In this study, we examined the role of Rap2B in angiogenesis in renal cell carcinoma by Western blot, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, human umbilical vascular endothelial cells growth assay, and endothelial cell tube formation assay. We found that Rap2B promoted angiogenesis in vitro and in vivo. Moreover, our data illustrated that phosphoinositide 3-kinase/AKT signaling pathway is involved in Rap2B-mediated upregulation of vascular endothelial growth factor and renal cell carcinoma angiogenesis. Taken together, these results revealed that Rap2B promotes renal cell carcinoma angiogenesis via phosphoinositide 3-kinase/AKT/vascular endothelial growth factor signaling pathway, which suggests that Rap2B is a novel therapeutic target for renal cell carcinoma anti-angiogenesis therapy.


Transport of solutes undergoing a Freundlich type nonlinear and nonequilibrium adsorption process.
We investigate the behavior of solutes undergoing nonequilibrium adsorption processes that lead to a Freundlich isotherm in equilibrium. In contrast to a frequently used model we do not assume that the adsorption rate is proportional to the difference between adsorbed and equilibrium concentrations, but inspect two nonlinear laws governing the path to equilibrium. With some asymptotic considerations and numerical simulations we find that depending on the model parameters, the concentration in solution and the mass adsorbed by the matrix do not necessarily reach quasiequilibrium.


Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy.
We applied advanced magnetic resonance imaging and Voxed based Morphometry analysis to assess brain tissue density in patients with cirrhosis. Forty eight patients with cirrhosis without overt hepatic encephalopathy (17 Child A, 13 Child B, and 18 Child C) and 51 healthy subjects were matched for age and sex. Seventeen patients had history of overt hepatic encephalopathy, eight of them had minimal hepatic encephalopathy at inclusion, 10 other patients had minimal hepatic encephalopathy at inclusion but without history of previous overt hepatic encephalopathy, and 21 patients had none of these features. Patients with cirrhosis presented decreased brain density in many areas of the grey and white matter. The extension and size of the affected areas were greater in patients with alcoholic cirrhosis than in those with post-hepatitic cirrhosis and correlated directly with the degree of liver failure and cerebral dysfunction (as estimated by neuropsychological tests and the antecedent of overt hepatic encephalopathy). Twelve additional patients with cirrhosis who underwent liver transplantation were explored after a median time of 11months (7-50months) after liver transplant. At the time of liver transplantation, three patients belonged to class A of the Child-Pugh classification, five to class B and four to class C. Compared to healthy subjects, liver transplant patients showed areas of reduced brain density in both grey and white matter. These results indicate that loss of brain tissue density is common in cirrhosis, progresses during the course of the disease, is greater in patients with history of hepatic encephalopathy, and persists after liver transplantation. The significance, physiopathology, and clinical relevance of this abnormality cannot be ascertained from the current study.


[A case of embryonal carcinoma arising in the basal ganglia of the cerebrum].
The occurrence sites of intracranial primary germ cell tumors are most often the pineal and suprasellar regions. The histological type observed most frequently in these tumors is germinoma. Cases of embryonal carcinoma arising in the basal ganglia are rarely reported. To our knowledge, only 4 such cases have been previously reported in the literature. A case of an embryonal carcinoma arising in the basal ganglia is reported. A 17-year-old boy was admitted to our hospital on July 30, 1988 because of headache and vomiting, and a right hemiparesis. On admission, physical inspection showed no abnormalities and neurological examination revealed obtunded consciousness, a right central facial paresis and a right hemiparesis with Hoffman and Babinski reflexes. Noncontrast CT scan showed a large mass of low-to slightly high-density in the region of the left basal ganglia accompanied with midline shift and ventricular dilatation. Enhancement of the lesion was made by contrast CT scan. It was not homogeneous. Cerebral angiogram displayed a contralateral shift and an unrolling of the anterior cerebral artery, a lateral stretch of middle cerebral artery, a downward stretch of anterior choroidal artery and a tumor stain fed by the Heubner artery. On August 3, left frontotemporal craniotomy was performed. The tumor was totally removed in a piecemeal manner using microsurgical techniques. Histopathological diagnosis was mixed-type of germ cell tumor comprising embryonal carcinoma and teratoma. Postoperative CT scan showed complete disappearance of the tumor. A course of radiation of 4950 rads and two courses of a combination chemotherapy with cis-platinum, vinblastine and bleomycin were given within 3 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)


Recent progress towards the identification of inhibitors of mycobacterial cell wall polysaccharide biosynthesis.
Mycobacterial infections have recently attracted significant attention from international health agencies due to the resurgence of these diseases worldwide. This review summarizes the recent work directed towards the identification of new anti-tuberculosis agents that act by inhibiting mycobacterial cell wall polysaccharide biosynthesis.


A canine ex vivo series shunt for evaluating thrombus deposition on polymer surfaces.
A new acute canine ex vivo femoral A-V series shunt experiment is described. Platelet and fibrinogen deposition on a series of up to ten different polymers may be tested in the same nonanticoagulated animal. The method reduces the time and expense associated with animal testing, and also allows for the simultaneous monitoring of platelet and fibrinogen deposition on a number of polymer surfaces. The series shunt technique was used to examine platelet and fibrinogen deposition on polyethylene, Silastic, polyvinylchloride, and oxidized polyethylene surfaces. Following an initial period of minimal deposition, platelet deposition increased dramatically to a peak by about 15-20 min of blood contact on all surfaces studied. The amount of adsorbed fibrinogen fell from initial levels to a minimum at about 5-10 min of blood contact and then increased to a peak at about the same time as observed for the platelet response. Oxidized polyethylene was the most thrombogenic surface studied, followed by polyethylene, polyvinylchloride, and Silastic. Peak platelet and fibrinogen levels were found to be inversely related to flow rate over the range studied. In this experiment it appears that the interaction of blood components with a foreign surface in vivo or ex vivo is localized to the interface with the flowing blood. Within experimental errors, no effect of segment position or any downstream effects were observed. These results suggest that a series shunt may be used to investigate the short-term interactions of blood with a number of test surfaces.


Crystal and solution structures of human oncoprotein Musashi-2 N-terminal RNA recognition motif 1.
Musashi-2 (MSI2) belongs to Musashi family of RNA binding proteins (RBP). Like Musashi-1 (MSI1), it is overexpressed in a variety of cancers and is a promising therapeutic target. Both MSI proteins contain two N-terminal RNA recognition motifs and play roles in posttranscriptional regulation of target mRNAs. Previously, we have identified several inhibitors of MSI1, all of which bind to MSI2 as well. In order to design MSI2-specific inhibitors and compare the differences of binding mode of the inhibitors, we set out to solve the structure of MSI2-RRM1, the key motif that is responsible for the binding. Here, we report the crystal structure and the first NMR solution structure of MSI2-RRM1, and compare these to the structures of MSI1-RBD1 and other RBPs. A high degree of structural similarity was observed between the crystal and solution NMR structures. MSI2-RRM1 shows a highly similar overall folding topology to MSI1-RBD1 and other RBPs. The structural information of MSI2-RRM1 will be helpful for understanding MSI2-RNA interaction and for guiding rational drug design of MSI2-specific inhibitors.


Comparison of antibody avidity and titre elicited by peptide as a protein conjugate or as expressed in vaccinia.
The immunogenicity of a malaria peptide presented in various forms was tested in terms of the quality and quantity of the antibody response in rabbits. Peptide conjugated to a protein carrier, diphtheria toxoid (DT), required strong adjuvants (e.g. muramyl dipeptide, MDP and Freund's adjuvant, FCA) to elicit high levels of antibody with high avidity. Alum was a poor adjuvant, producing the lowest titre and avidity of antibody compared with all the other groups. Peptide expressed in vaccinia (and without carrier) produced intermediate levels of antibody but the avidity of the antibodies produced were comparable to that produced by peptide conjugates given with muramyl dipeptide.


Peritoneal solute transport predicts survival on CAPD independently of residual renal function.
Loss of residual renal function has a profound effect on the survival of peritoneal dialysis patients. Less is known of the impact of peritoneal function. The purpose of this study was to investigate the influence of solute transport on clinical outcome in CAPD patients. Two hundred and ten consecutive patients commencing CAPD since 1990 were enrolled into a single centre prospective longitudinal observational study of urea, protein, and peritoneal kinetics. On entry, and at 6-monthly intervals, estimations were made of weight, body mass index (BMI), plasma albumin, Kt/V, residual renal function (RRF), NPCR, low-molecular-weight solute transport (D/Pcreat), and peritoneal protein losses. All patients were censored in 1996, regardless of treatment modality. During the 6-year follow up period (median 22 months) there were 51 deaths, and the actuarial survival was 58% at 5 years. Urea, protein and peritoneal kinetics varied with time on dialysis: as anticipated there was a reduction in Kt/V, attributable to loss of RRF, whereas plasma albumin was stable for the first 2 years of treatment, but subsequently started to decline, a trend that became significant at 42 months. Peritoneal kinetics stabilized within the first 6 months of treatment and then showed a trend of increased solute transfer with time on treatment, which became significant by the end of the study. Comparing survivors with non-survivors Kt/V and RRF were similar at the start of treatment, but loss of RRF occurred significantly earlier in non-survivors than survivors (0.37 vs 0.68, P=0.02 at 6 months, 0.19 vs 0.54, P=0.01 at 12 months). D/Pcreat was also identical at commencement of treatment, but subsequently whilst survivors had stable solute transfer, non-survivors had consistently higher solute transfer beyond 6 months that reached increasing significance after 18 months, (0.70 vs 0.67, P=0.05 at 18 months, 0.72 vs 0.66, P=0.03 at 24 months). A Cox proportional hazard model constructed for the variables age, sex, BMI, albumin, Kt/V and D/Pcreat at 6 months of treatment indicated that low Kt/V (P=0.004), high D/Pcreat (P=0.013) and age (P=0.028) were independent predictors of death. There is good reason to believe that high peritoneal solute transport is an independent marker of poor outcome in CAPD patients.


Outcome analysis of laporoscopic D1 and D2 dissection in patients 70 years and older with gastric cancer.
Gastric cancer is a worldwide aggressive tumor with a bad prognosis. The purpose of this study was to retrospectively investigate operative findings of 53 patients aged over 70 with gastric cancer who underwent laporoscopic operations in our clinic. A retrospective review of all patients who underwent laporoscopic surgery for pathologically confirmed gastric cancer at our clinic between March 2008 and October 2010 was conducted. D1 resection (Level1 lymphadenectomy) was compared with D2 resection (Levels 1 and 2 lymphadenectomy). The two groups in which D1 and D2 Lymph node Dissection (LND) were applied were compared with respect to number of patients, sex, age, stage of disease, and score of American Society of Anesthesiologists (ASA). We analyzed surgical methods, the use of staplers, operative time, additional organ resections, hospital stay, postoperative complications and the need for re-operation, operative mortality, and the effects of prognostic factors on survival. The patient group consisted of 31 (58%) males and 22 (42%) females. Of the patients, 28 (52%) underwent D1 and 25 (48%) D2 LND. There was a significant difference between the two groups with regard to length of surgery (p < 0.01). The length of operation, blood loss, and transfusion requirement in the D2 group were significantly more than those in the D1 group. There was no mortality in cases that underwent additional organ resection. The survival times of cases with a ≤ 0.25 ratio of dissected number of lymph nodes to metastatic lymph nodes were significantly longer than those of other cases. The survival time of cases with perineural and vascular invasion was significantly shorter. The survival rates of Stage I patients was significantly higher than those of Stage III (p:0.002) and Stage IV (p:0.003) patients. Although extensive dissection had an increased morbidity, there was no significant statistical difference between the two procedures. Early complications should not be attributed only to the extent of LND. The important prognostic factors related to long-time survival are the stage of the tumor, perineural and perivascular invasion, and metastatic lymph nodes.


Water Environmental Capacity Analysis of Taihu Lake and Parameter Estimation Based on the Integration of the Inverse Method and Bayesian Modeling.
An integrated approach using the inverse method and Bayesian approach, combined with a lake eutrophication water quality model, was developed for parameter estimation and water environmental capacity (WEC) analysis. The model was used to support load reduction and effective water quality management in the Taihu Lake system in eastern China. Water quality was surveyed yearly from 1987 to 2010. Total nitrogen (TN) and total phosphorus (TP) were selected as water quality model variables. Decay rates of TN and TP were estimated using the proposed approach. WECs of TN and TP in 2011 were determined based on the estimated decay rates. Results showed that the historical loading was beyond the WEC, thus, reduction of nitrogen and phosphorus input is necessary to meet water quality goals. Then WEC and allowable discharge capacity (ADC) in 2015 and 2020 were predicted. The reduction ratios of ADC during these years were also provided. All of these enable decision makers to assess the influence of each loading and visualize potential load reductions under different water quality goals, and then to formulate a reasonable water quality management strategy.


Developing a Core Outcome Set for Prognostic Research in Palliative Cancer Care: Protocol for a Mixed Methods Study.
Studies exploring the impact of receiving end-of-life prognoses in patients with advanced cancer use a variety of different measures to evaluate the outcomes, and thus report often conflicting findings. The standardization of outcomes reported in studies of prognostication in palliative cancer care could enable uniform assessment and reporting, as well as intertrial comparisons. A core outcome set promotes consistency in outcome selection and reporting among studies within a particular population. We aim to develop a set of core outcomes to be used to measure the impact of end-of-life prognostication in palliative cancer care. This protocol outlines the proposed methodology to develop a core outcome set for measuring the impact of end-of-life prognostication in palliative cancer care. We will adopt a mixed methods approach consisting of 3 phases using methodology recommended by the Core Outcome Measure in Effectiveness Trials (COMET) initiative. In phase I, we will conduct a systematic review to identify existing outcomes that prognostic studies have previously used, so as to inform the development of items and domains for the proposed core outcome set. Phase II will consist of semistructured interviews with patients with advanced cancer who are receiving palliative care, informal caregivers, and clinicians, to explore their perceptions and experiences of end-of-life prognostication. Outcomes identified in the interviews will be combined with those found in existing literature and taken forward to phase III, a Delphi survey, in which we will ask patients, informal caregivers, clinicians, and relevant researchers to rate these outcomes until consensus is achieved as to which are considered to be the most important for inclusion in the core outcome set. The resulting, prioritized outcomes will be discussed in a consensus meeting to agree and endorse the final core outcome set. Ethical approval was received for this study in September 2022. As of July 2023, we have completed and published the systematic review (phase I) and have started recruitment for phase II. Data analysis for phase II has not yet started. We expect to complete the study by October 2024. This protocol presents the stepwise approach that will be taken to develop a core outcome set for measuring the impact of end-of-life prognostication in palliative cancer care. The final core outcome set has the potential for translation into clinical practice, allowing for consistent evaluation of emerging prognostic algorithms and improving communication of end-of-life prognostication. This study will also potentially facilitate the design of future clinical trials of the impact of end-of-life prognostication in palliative care that are acceptable to key stakeholders. Core Outcome Measures in Effectiveness Trials 2136; https://www.comet-initiative.org/Studies/Details/2136. DERR1-10.2196/49774.


miR-98 acts as an inhibitor in chronic constriction injury-induced neuropathic pain via downregulation of high-mobility group AT-hook 2.
Neuropathic pain, resulting from somatosensory nervous system dysfunction, remains a serious public health problem worldwide. microRNAs are involved in the physiological processes of neuropathic pain. However, the biological roles of miR-98 in neuropathic pain development have not been investigated. Therefore, in our current study, we focused on the effects of miR-98 in neuropathic pain. It was shown that miR-98 was significantly downregulated in chronic sciatic nerve injury (CCI) rat models. In addition, high mobility group A2 (HMGA2) was obviously upregulated in CCI rats. Overexpression of miR-98 inhibited neuropathic pain progression, including mechanical and thermal hyperalgesia. By a bioinformatics analysis, HMGA2 was predicted as a direct target of miR-98. The negative correlation between miR-98 and HMGA2 was validated in our present study. Furthermore, overexpression of miR-98 dramatically repressed HMGA2 protein and messenger RNA (mRNA) expression. Neuroinflammation participates in neural-immune interactions, which can contribute to the neuropathic pain development. Meanwhile, we found that inflammatory cytokine (interleukin [IL]-6, IL-1β, and COX-2) protein expression in rats infected with LV-miR-98 was greatly suppressed. Taking these results together, we concluded that miR-98 might depress neuropathic pain development through modulating HMGA2.


RADON INFILTRATION BUILDING ENVELOPE TEST SYSTEM: EVALUATION OF BARRIER MATERIALS.
The performance of radon barrier materials currently available for housing foundations was evaluated using a unique radon infiltration building envelope test system that was designed to test radon prevention and mitigation systems using real world construction techniques. The reduction in radon concentration measured across the air barrier in the foundations has been used to evaluate five representative barrier materials installed in the radon infiltration building envelope test facility. The reduction in radon concentration in the mock house varied from 68% for 6 mil polyethylene to 98% for the spray polyurethane foam. The five representative barrier materials were selected after determining the radon diffusion coefficient and the corresponding radon resistance from samples of 14 barrier materials in a radon diffusion testing chamber. The Canadian experience evaluating whether radon barrier materials would satisfy building code requirements was described.


Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity.
Triterpenoids are distributed widely in higher plants and are of interest because of their structural diversity and broad range of bioactivities. In particular, there is a very large literature on the propensity of a variety of triterpenoids to act as potential anticancer agents. In the present review, the anticancer potential is summarized for naturally occurring triterpenoids and their semi-synthetic derivatives, including examples of lupane-, oleanane-, ursane-, and cucurbitane-type pentacyclic triterpenoids, along with dammarane-type tetracyclic triterpenes including ginsenosides and their sapogenins and dichapetalins, which have been characterized as antitumor leads from higher plants. Preliminary structure-activity relationships and reported mechanisms of the antineoplastic-related activity are included. Prior studies for triterpenoids of plant origin are supportive of additional work being conducted on the more detailed biological and mechanistic evaluation for the progression of this type of natural products as possible cancer chemotherapeutic agents.


Determining value for money in day hospital care for the elderly.
This paper describes how a prospective evaluation of the costs and effectiveness of day hospital care for the elderly and its alternatives could be undertaken. The number of day hospitals for the elderly has grown from zero to slightly over 300 in just over 20 years. Despite this there is no study in the existing literature which gives an indication of whether day hospitals provide a reasonable return on this substantial investment. The best way of determining whether day hospitals are a better investment than alternative modes of care would be a randomized controlled trial involving comparison of subgroups of day hospital patients against similar subgroups utilizing alternative modes of care, the costing of each patient's consumption of services within the treatment mode in which they commence the study plus any subsequent use of other services over a predetermined time period, the collection of clinical, social and psychological outcome data (including data on dependency) for each subgroup before, during and at the end of the study period, and some measure of patients' and relatives' satisfaction with the treatment received.


Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.
The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.


[Gluten as food additive in The Netherlands: cheese forbidden for celiac patients?].
A new coating for cheese, to be introduced in May, consists entirely of natural degradable components. The coating is based on wheat gluten. This increase in the amount of gluten in the Dutch diet may lead to overt coeliac disease in people with a subclinical form of it, and will limit the dietary choices of patients already suffering from the disease.


Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues.
Diabetic osteoporosis is increasingly recognized as a significant comorbidity of type 1 diabetes mellitus. In contrast, type 2 diabetes mellitus is more commonly associated with modest increases in bone mineral density for age. Despite this dichotomy, clinical, in vivo, and in vitro data uniformly support the concept that new bone formation as well as bone microarchitectural integrity are altered in the diabetic state, leading to an increased risk for fragility fracture and inadequate bone regeneration following injury. In this review, we examine the contribution that insulin, as a potential anabolic agent in bone, may make to the pathophysiology of diabetic bone disease. Specifically, we have assimilated human and animal data examining the effects of endogenous insulin production, exogenous insulin administration, insulin sensitivity, and insulin signaling on bone. In so doing, we present evidence that insulin, acting as an anabolic agent in bone, can preserve and increase bone density and bone strength, presumably through direct and/or indirect effects on bone formation.


Capillaries within compartments: microvascular interpretation of dynamic positron emission tomography data.
Measurement of exchange of substances between blood and tissue has been a long-lasting challenge to physiologists, and considerable theoretical and experimental accomplishments were achieved before the development of the positron emission tomography (PET). Today, when modeling data from modern PET scanners, little use is made of earlier microvascular research in the compartmental models, which have become the standard model by which the vast majority of dynamic PET data are analysed. However, modern PET scanners provide data with a sufficient temporal resolution and good counting statistics to allow estimation of parameters in models with more physiological realism. We explore the standard compartmental model and find that incorporation of blood flow leads to paradoxes, such as kinetic rate constants being time-dependent, and tracers being cleared from a capillary faster than they can be supplied by blood flow. The inability of the standard model to incorporate blood flow consequently raises a need for models that include more physiology, and we develop microvascular models which remove the inconsistencies. The microvascular models can be regarded as a revision of the input function. Whereas the standard model uses the organ inlet concentration as the concentration throughout the vascular compartment, we consider models that make use of spatial averaging of the concentrations in the capillary volume, which is what the PET scanner actually registers. The microvascular models are developed for both single- and multi-capillary systems and include effects of non-exchanging vessels. They are suitable for analysing dynamic PET data from any capillary bed using either intravascular or diffusible tracers, in terms of physiological parameters which include regional blood flow.


Tuning the molecular properties of polybenzimidazole by copolymerization.
In the present work, a series of novel random polybenzimidazole (PBI) copolymers consisting of m- and p-phenylene linkages are synthesized from various stoichiometric mixtures of isophthalic acid (IPA) and terephthalic acid (TPA) with 3,3',4,4'-tetraaminobiphenyl (TAB) by solution copolycondensation in polyphosphoric acid (PPA). The resulting copolymers are characterized by different techniques to obtain their molecular properties parameters. The monomer concentration in the polymerization plays an important role in controlling the molecular weight of the polymer. Surprisingly, a simple change in the dicarboxylic acid architecture from meta (IPA) to para (TPA) increases the molecular weight of the copolymers, which is maximum for the para homopolymer. The low solubility of TPA in PPA is found to be the dominating factor for obtaining the higher molecular weight polymer in the case of the para structure. FT-IR study shows that the introduction of the para structure enhances the conjugation along the polymer chain. The positive deviation of the copolymer composition from the feed ratio is due to the higher reactivity ratio of TPA than IPA, which is obtained from proton NMR studies. The incorporation of the para structure in the chain enhances the thermal stability of the polymers. The para homopolymer shows 59 degrees C lower glass transition temperature compare to the meta homopolymer indicating enhancement of the flexibility of the polymer chain due the introduction of the p-phenylene linkage in the backbone. The T(g) of the copolymers shows both positive and negative deviation from the expected T(g) calculated by the Fox equation. The enhanced conjugation of the polymer chains also influences the photophysical properties of the polymers in solution. All the PBI polymers exhibit strong fluorescence in dimethylacetamide solution. As expected, that all the polymers are amorphous in nature reveals that the copolymerization does not influence the packing characteristics of the PBI chains.


Characteristics of Müller glial cells in MNU-induced retinal degeneration.
Retinal Müller glial cells have been shown to undergo reactive gliosis in a variety of retinal diseases. Upregulation of glial fibrillary acidic protein (GFAP) is a hallmark of Müller cell activation. Reactive gliosis after retinal detachment or ischemia/reperfusion is characterized by hypertrophy and downregulation of inwardly rectifying K+ (Kir) currents. However, this kind of physiological alteration could not be detected in slowly progressing retinal degenerations. The photoreceptor toxin N-methyl-N-nitrosourea (MNU) leads to the rapid loss of cells in the outer nuclear layer and subsequent Müller cell activation. Here, we investigated whether Müller cells from MNU-treated mice exhibit reactive gliosis. We found that Müller cells showed increased GFAP expression and increased membrane capacitance, indicating hypertrophy. Membrane potential and Kir channel-mediated K+ currents were not significantly altered whereas Kir4.1 mRNA expression and Kir-mediated inward current densities were markedly decreased. This suggests that MNU-induced Müller cell gliosis is characterized by plasma membrane increase without alteration in the membrane content of Kir channels. Taken together, our findings show that Müller cells of MNU-treated mice are reactive and respond with a form of gliosis which is characterized by cellular hypertrophy but no changes in Kir current amplitudes.


How one institution overcame the challenges to start an MRI-based brachytherapy program for cervical cancer.
Adaptive magnetic resonance imaging (MRI)-based brachytherapy results in improved local control and decreased high-grade toxicities compared to historical controls. Incorporating MRI into the workflow of a department can be a major challenge when initiating an MRI-based brachytherapy program. This project aims to describe the goals, challenges, and solutions when initiating an MRI-based cervical cancer brachytherapy program at our institution. We describe the 6-month multi-disciplinary planning phase to initiate an MRI-based brachytherapy program. We describe the specific challenges that were encountered prior to treating our first patient. We describe the solutions that were realized and executed to solve the challenges that we faced to establish our MRI-based brachytherapy program. We emphasize detailed coordination of care, planning, and communication to make the workflow feasible. We detail the imaging and radiation physics solutions to safely deliver MRI-based brachytherapy. The focus of these efforts is always on the delivery of optimal, state of the art patient care and treatment delivery within the context of our available institutional resources. Previous publications have supported a transition to MRI-based brachytherapy, and this can be safely and efficiently accomplished as described in this manuscript.


Spiritual care may impact mental health and medication adherence in HIV+ populations.
To explore a potential role for spirituality in medication-related needs assessment for integrated care in chronically ill populations. A systematic literature review was conducted to explore the impact of faith beliefs on health and/or medication adherence in individuals with depression and/or HIV+/AIDS. Retrospective electronic medical record review of adult HIV+ patients of an urban primary care clinic with integrated mental health services was conducted, with Substance Abuse and Mental Illness Symptoms Screener (SAMISS), major depressive disorder (MDD) incidence over the preceding year, and history of contact with a spiritual advisor. A convenience sample was interviewed to qualitatively assess potential medication therapy management needs and medication-related problems. Another sample was examined utilizing the Daily Spiritual Experience Scale. The literature reports positive influence on health behaviors, coping and outcomes; and poor medication adherence and treatment decisions due to patient passivity or resistance. Spiritual advisor contact (not limited to a specific religion) was significantly associated with MDD absence (1.7% vs. 15.3%, P<0.005) and inversely related to SAMISS, depression, and poor health behaviors. Patient interviews reflected significance of faith in terms of insight and acceptance of illness, the role or need for medications, coping, and medication adherence. An illustrative model was designed based on the literature and data collection. Spiritual assessment may help identify positive or negative influence on health. Spiritual interventions could be beneficial in promoting adherence and positive health outcomes. Further research is recommended.


Laparoscopic treatment of biliary atresia and choledochal cyst.
Minimally invasive surgery (MIS) has overcome many technical limitations and has evolved into a safe alternative for the treatment of many complex pediatric surgical procedures. The introduction of this approach for the correction of congenital biliary tract anomalies had to wait until instrumentation and surgeons' skills improved enough. This happened not so long ago: less than 10 years have elapsed since the first reported case of a minimally invasive operation for choledochal cyst and less than 3 years since the first reported case of a laparoscopic Kasai. This article summarizes the experience gained by the authors in laparoscopic treatment of 41 patients with biliary atresia and 15 patients with choledochal cyst with similar surgical techniques, which are described in detail. Based on the encouraging results, the authors believe that MIS will soon become the gold standard for the correction of congenital biliary tract anomalies.


Henoch-Schonlein purpura in pregnancy.
Henoch-Schonlein purpura (HSP) is a hypersensitivity vasculitis. This is a case report of HSP during pregnancy and a review of the literature in this rare pregnant disease. We present a case of a 32-year-old woman with HSP. Treatment with low-dose oral corticosteroids was administered leading to a beneficial outcome for the fetus and the mother. Henoch-Schonlein purpura is the most common connective tissue disorder of children. It is rarely reported in adults. Only 16 cases of HSP during pregnancy have been described in the literature worldwide, and this is the 17th reported case.