Interaction and dimerization energies in methyl-blocked alpha,gamma-peptide nanotube segments.
The building blocks of a promising class of peptide nanotubes composed of alternating D-alpha-amino acids and (1R,3S)-3-aminocyclohexane (or cyclopentane) carboxylic acid (D-gamma-Ach or D-gamma-Acp) were explored by computational methods. Specifically, density functional theory (DFT) calculations on monomers and dimers of gamma-Ach-based and gamma-Acp-based alpha,gamma-cyclo-hexapeptides and cyclo-octapeptides were carried out to investigate the experimentally observed preference for alpha-alpha over gamma-gamma dimerization, associated with the two types of stacking patterns present in these peptide nanotubes, as well as the preference for heterodimerization versus homodimerization. Full geometry optimizations were performed at the B3LYP/6-31G(d) level, and single point calculations were subsequently carried out with the B3LYP and M05-2X functionals and the 6-31+G(d,p) basis set. The calculations predict that the interaction energies in the alpha-alpha species are quite similar to those in the gamma-gamma dimers. However, a comparison of dimerization energies (i.e., interaction energies plus deformation energies of monomers) shows that alpha-alpha dimerization is energetically favored over gamma-gamma dimerization. The calculations strongly suggest that the preference for alpha-alpha binding is governed by differences between the deformation energies in the alpha and gamma monomers, rather than by differences between the relative strengths of the alpha-alpha and gamma-gamma hydrogen-bonding patterns. Calculations based on local properties of the electron density support the previous suggestion that the H-N bonds of the alpha-amino acids are more polarized than those of the gamma-amino acids.


Phosphorylation of P0 glycoprotein in peripheral nerve myelin.
The P0 protein in mammalian PNS myelin is known to undergo several posttranslational modifications, such as glycosylation, acylation, sulfation, and phosphorylation. Phosphorylation of purified P0 protein in vitro was studied comparatively using three enzymes, i.e., calcium/phospholipid-dependent protein kinase (protein kinase C), calcium/calmodulin-dependent protein kinase II (CaM kinase II), and the catalytic subunit of cyclic AMP-dependent protein kinase (A kinase). The phosphorylation of P0 protein by CaM kinase II was the greatest, followed by that by protein kinase C; phosphorylation by A kinase, however, was much lower. In order to identify phosphorylation sites, P0 protein was phosphorylated with [32P]ATP and each kinase and then digested with lysylendopeptidase. The resulting phosphopeptides were isolated by HPLC. Subsequent amino acid sequence analysis and comparison with the known sequence of P0 protein revealed that Ser181 and Ser204 were strongly phosphorylated by both protein kinase C and CaM kinase II. In addition, Ser214 was also phosphorylated by protein kinase C, but not by CaM kinase II. Because all of these sites are located in the cytoplasmic domain of P0 protein, phosphorylation may be important for maintenance of the major dense line of PNS myelin.


The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour.
1. The jugular lymphatic trunks were cannulated in anaesthetized rabbits and cats. Over 6-8 hr, the mean lymph flow was 2.3 microliters min-1 in the rabbit (one side only) and 5.0 microliters min-1 in the cat (sum of both sides). 2. After a single injection of radio-iodinated albumin into a lateral cerebral ventricle without significant rise in pressure, a mean of 14.4% of the radioactivity was recovered in deep cervical lymph of one side in the rabbit and of 12.9% in that of both sides in the cat. 3. During slow infusion of [125I]albumin and fluorescent dextran of 150,000 mol. wt. into a lateral ventricle of the cat at 20 microliters min-1, radioactivity and fluorescence reached plateaus in deep cervical lymph at 47.4 and 50.0% of their concentrations in cisternal c.s.f. respectively. 4. No significant radioactivity, other than from blood, was detected in superficial cervical lymph after intraventricular injection of radio-iodinated albumin in the cat. 5. No significant radioactivity, other than from blood, was detected in deep cervical lymph of the rabbit or in deep and superficial cervical lymph of the cat within 6 hr after injection of radio-iodinated albumin into the aqueous humour or orbital fat. 6. Gradients of radioactivity in tissues within the orbit suggested that there is a small flow of c.s.f., 0.05-0.15 microliters min-1 in the rabbit, passing centrifugally along the subarachnoid space of the optic nerve, through the posterior part of the globe and into the orbital tissue. Also a small proportion of aqueous humour, 1-2% or more, drains through the anterior sclera into the surrounding tissue. 7. A substantial quantity of cerebrospinal fluid drains into the deep cervical lymphatic system of the rabbit, 30% or more, and of the cat, 10-15% or more. The small component of aqueous humour drainage passing through the wall of the glove does not enter cervical lymph within 6 hr, if at all.


Acceptability and perceived effectiveness of a district co-ordinating service for terminal care: implications for quality assurance.
As part of a randomized controlled trial of a new district co-ordinating service for the care of terminally ill cancer patients, the activities of the nurse co-ordinators and the acceptability and perceived effectiveness of the service were assessed. Co-ordinators' activities were self-recorded; professional caregivers completed a postal questionnaire; and family carers were interviewed at home. Thirty-eight per cent of patients allocated to the co-ordinators were not visited at home. Overall, 41% of professionals had heard of the co-ordinating service and 20% had been contacted. A third of relatives, whether allocated or not to the co-ordinating service, felt that terminal care of their patient was not well co-ordinated and that they did not know how to get the help they needed for their dying relative. It may be that the nurse co-ordinators were unwilling or unable to relinquish their skills in order to provide a 'broker' style of co-ordination. Perhaps less skilled co-ordinators would have been more successful. Moreover, the co-ordinating service had no budgetary responsibility. Those concerned with quality assurance in co-ordination of terminal care might consider the skill mix and professional training of the co-ordinators as well as their budgetary responsibilities and authority.


Expression of P53 and bcl-2 proteins in T-cell lymphoblastic lymphoma: prognostic implications.
In patients (pts) with non-Hodgkin's lymphoma (NHL) under 25 years, treatment with MCP-842 protocol, a short duration intense protocol, yields worse survival in pts with lymphoblastic lymphoma (LL) compared to other high grade lymphomas. In order to identify both favourable and unfavourable subgroups in pts with T-cell LL (T-LL) with respect to relapse free survival following treatment with MCP-842 protocol, we analysed the expression of p53 and bcl-2 proteins in 22 pts with T-LL treated at the Tata Memorial Hospital, Mumbai by immunohistochemistry. p53 protein overexpression was noted in 59% cases and bcl-2 overexpression was noted in 29.4% cases. p53 expression correlated with a higher rate of relapse (p = 0.03; RR 7.9). The 5-year relapse free survival (RFS) was better in p53 negative patients compared to positive patients (70 vs 38%) (log-rank sigma = 0.04). In conclusion, in this study, overexpression of p53 protein was common in patients with T-LL. T-LL pts negative for p53 are likely to benefit from the short intense protocol--MCL-842. Bcl-2 protein overexpression was not a prognostic factor in these patients.


Serum cholesterol reduction by chromium in hypercholesterolemic rats.
The addition of chromium (III) to the drinking water of rats in a normal laboratory environment on a hypercholesterolemic diet resulted in lower serum cholesterol concentrations whether the dietary carbohydrate was either sucrose or starch. However, rats fed the sucrose diet with chromium in drinking water had serum cholesterol concentrations similar to those of rats fed the starch diet without chromium in drinking water.


Microgobius meeki as a potential bio-indicator of habitat disturbance in shallow estuarine areas: a useful tool for the assessment of estuarine quality.
The relationships between changes in habitat quality (disturbed and undisturbed sites) and the population parameters (density, size distribution, reproductive activity and diet) of a goby Microgobius meeki were investigated in a tropical estuary to assess its value as an indicator of anthropogenic changes, predominantly the effects of sedimentation and mangrove removal in shallow estuarine areas. Fish sampling surveys were conducted bimonthly between June 2009 and May 2010 over the entire estuarine gradient of the Paraguaçu River estuary, located on the central Brazilian coast. A predictive model was developed to assess the population changes of this species in 10 other tropical estuaries with different dimensions, basin features and distinct levels of anthropogenic disturbance. General linear models were used to relate the population structure of M. meeki to sediment type, habitat type resulting from mangrove conservation status, anthropogenic pressure and environmental characteristics such as salinity, dissolved oxygen concentrations and temperature. Sediment type and the presence of mangrove forests were the most effective predictors of local variability in the population structure of M. meeki. Individuals with mature gonads and high rates of feeding activity were associated predominantly with undisturbed habitats. Estuaries and estuarine sectors with high levels of sedimentation in shallow marginal areas, anthropogenic pressure from domestic and industrial effluents, and evidence of mangrove deforestation yielded the lowest capture rates of both juvenile and adult M. meeki. Based on these findings, M. meeki is identified as a potential indicator of the consequences of anthropogenic disturbance in transitional waters. A simple, but efficient collection protocol, in which overt signs of distress can be promptly observed is proposed. Testing the generality of this approach across different systems might prove useful in a broader conservation biology context.


Combined theoretical and time-resolved photoluminescence investigations of [Mo₆Brⁱ₈Br(a)₆]²⁻ metal cluster units: evidence of dual emission.
The combined time-resolved photoluminescence (PL) and theoretical study performed on luminescent [Mo6Br(i)8Br(a)6](2-)-based systems unambiguously shows that their NIR-luminescence is due to at least two emissive states. By quantum chemical studies, we show for the first time that important geometrical relaxations occur at the triplet states either by the outstretching of an apex away from the square plane of the Mo6 octahedron or by the elongation of one Mo-Mo bond. Experimental PL measurements demonstrate that the external environment (counter-ions, crystal packing) of the cluster has a noticeable impact on its relaxation processes. Temperature and excitation wavelength dependence of the two components of the luminescence spectra is representative of multiple competitive de-excitation processes in contradiction with Kasha's rule. Our results also demonstrate that the relaxation processes before and after emission can be tracked via fast time-resolved spectroscopy. They also show that the surroundings of the luminescent cluster unit and the excitation wavelength could be modulated for target applications.


Investigation of Lysozyme Diffusion in Agarose Hydrogels Employing a Microfluidics-Based UV Imaging Approach.
Hydrogels are polymer-based materials with a high water content. Due to their biocompatible and cell-friendly nature, they play a major role in a variety of biotechnological applications. For many of these applications, diffusibility is an essential property influencing the choice of material. We present an approach to estimate diffusion coefficients in hydrogels based on absorbance measurements of a UV area imaging system. A microfluidic chip with a y-junction was employed to generate a fluid-hydrogel interface and the diffusion of lysozyme from the fluid into the hydrogel phase was monitored. Employing automated image and data processing, analyte concentration profiles were generated from the absorbance measurements and fits with an analytical solution of Fick's second law of diffusion were applied to estimate diffusion coefficients. As a case study, the diffusion of lysozyme in hydrogels made from different concentrations (0.5-1.5% (w/w)) of an unmodified and a low-melt agarose was investigated. The estimated diffusion coefficients for lysozyme were between 0.80 ± 0.04×10-10 m2 s-1 for 1.5% (w/w) low-melt agarose and 1.14 ± 0.02×10-10 m2 s-1 for 0.5% (w/w) unmodified agarose. The method proved sensitive enough to resolve significant differences between the diffusion coefficients in different concentrations and types of agarose. The microfluidic approach offers low consumption of analyte and hydrogel and requires only relatively simple instrumentation.


Early-Stage Development of an Anti-Evaporative Liposomal Formulation for the Potential Treatment of Dry Eyes.
Dry eye disease (DED), the most common ocular disorder, reduces the quality of life for hundreds of millions of people annually. In healthy eyes, the tear film lipid layer (TFLL) stabilizes the tear film and moderates the evaporation rate of tear fluid. In >80% of DED cases, these central features are compromised leading to tear film instability and excessive evaporation of tear fluid. Herein we assess the potential of liposomal formulations featuring phosphatidylcholines and tailored lipid species from the wax ester and O-acyl-ω-hydroxy fatty acid categories in targeting this defect. The developed lead formulation displays good evaporation-resistant properties and respreadability over compression-expansion cycles in our Langmuir model system and a promising safety and efficacy profile in vitro. Preclinical in vivo studies will in the future be required to further assess and validate the potential of this concept in the treatment of DED.


The Morphology of TiO2 (B) Nanoparticles.
The morphology of a nanomaterial (geometric shape and dimension) has a significant impact on its physical and chemical properties. It is, therefore, essential to determine the morphology of nanomaterials so as to link shape with performance in specific applications. In practice, structural features with different length scales are encoded in a specific angular range of the X-ray or neutron total scattering pattern of the material. By combining small- and wide-angle scattering (typically X-ray) experiments, the full angular range can be covered, allowing structure to be determined accurately at both the meso- and the nanoscale. In this Article, a comprehensive morphology analysis of lithium-ion battery anode material, TiO2 (B) nanoparticles (described in Ren, Y.; Liu, Z.; Pourpoint, F.; Armstrong, A. R.; Grey, C. P.; Bruce, P. G. Angew. Chem. Int. Ed. 2012, 51, 2164), incorporating structure modeling with small-angle X-ray scattering (SAXS), pair distribution function (PDF), and X-ray powder diffraction (XRPD) techniques, is presented. The particles are oblate-shaped, contracted along the [010] direction, this particular morphology providing a plausible rationale for the excellent electrochemical behavior of these TiO2(B) nanoparticles, while also provides a structural foundation to model the strain-driven distortion induced by lithiation. The work demonstrates the importance of analyzing various structure features at multiple length scales to determine the morphologies of nanomaterials.


Chronic inguinal pain in children.
To present our experience in the management of chronic groin pain in children. We report 4 patients (age range 0-18 years old) who presented with history of chronic groin pain (April 2010 January 2017). After failure of all conservative treatments they underwent surgical management as ultima ratio. Currently, there is no consensus on treatment of 'Sportsman's Hernia' and literature on paediatric population is still poor. There are no appropriate randomised controlled trials supporting a standardized management of chronic groin pain. Initial approach should be conservative [Physical Medicine and Rehabilitation (PM&R) follow-up for 3-6 months] and surgical treatment proposed after failure of conservative therapies. It is advisable to consider surgery at least months after clinical onset. More recently, some studies suggested surgery as a first line treatment. Most of surgical cases manage to recover to full activity without pain, as reported in our experience. Surgical approach to the groin can be anterior (open) or posterior (laparoscopic), both these procedures have shown good results. Surgeons having different opinions on the aetiology of 'Sportsman's Hernia' may sustain the suitability of different surgical techniques. In our experience, pain was localized at the pubic tubercle therefore we preferred the 'open' approach ensuring a successful release of ilioinguinal and genitofemoral nerves. Children with chronic groin pain can benefit of surgical treatment. In our experience, surgery always proved to be successful for treating chronic groin pain in paediatric age. Further multicentric studies are needed to support these results. Bernhardt-Roth syndrome, Children, Chronic groin pain, Chronic inguinal pain, Meralgia Paraesthetic, Sportsman's Hernia.


Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial.
Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old, and testosterone therapy (TTh) can improve the quality of life in these patients. To evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively. This was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75 mg) and E100 (8 pellets of 100 mg). We evaluated adverse events after implantation and followed men at 2, 4, and 6 months for morning laboratory levels (prior to 10 am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen. After randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6 months, with most men (82%) dropping to <300 ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone <300 ng/dL, with similar rates between the groups in the study. Men treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD. Strengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort. E100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD.


Accurate Power Sharing and Voltage Regulation for AC Microgrids: An Event-Triggered Coordinated Control Approach.
The microgrid with the high proportion of renewable sources has become the trend of the future. However, the negative features, such as renewable energy perturbation, nonlinear counterpart, and so on, are prone to causing the low-power quality of the ac microgrid. To deal with these problems, this article proposes an event-triggered consensus control approach. First, the nonlinear state-space function regarding the ac microgrid is built, which is further transformed into the standard linear multiagent model by using the singular perturbation method. It provides indispensable preprocessing for the direct application of advanced linear control approaches. Then, based on this standard linear multiagent model, the secondary consensus approach with the leader is designed to compensate for the output voltage deviation and achieve accurate power sharing. In order to decrease the communication among various distributed generators, the event-triggered communication method is further proposed. Meanwhile, the Zeno behavior is avoided through the theoretical proof. Finally, simulation results are presented to demonstrate the effectiveness of the proposed approach.


Incoherent broadband cavity-enhanced total internal reflection spectroscopy of surface-adsorbed metallo-porphyrins.
An improvement of conventional attenuated total reflection (ATR) spectroscopy is demonstrated by applying an incoherent broadband light source (short-arc Xe-lamp) in a cavity-enhanced evanescent-wave absorption method. With this novel approach the absorption spectra of several metallo-octaethyl porphyrins (palladium (PdOEP), platinum (PtOEP) and zinc (ZnOEP)) in thin acetone solution layers and on a fused silica (FS) surface are studied between approximately 390 and 625 nm. The time dependence of the evaporation process of the solution on the FS surface is described. The maximum sensitivity of the setup is estimated at approximately 2 x 10(-5) per pass, which translates into a minimal detectable surface density of less than 2 x 10(-3) monolayers for the porphyrins studied (based on the strong absorption in the Soret bands). Changes of surface and solution spectra are characterised and discussed on the basis of observed band broadenings and spectral shifts. For Pd- and PtOEP the changes of spectral feature can be interpreted with respect to J-aggregate formation supported by polarization dependent measurements. The reason for an observed blue-shift of ca. 10 nm for the Soret band in ZnOEP in combination with a large red-shift of the Q-bands (11 nm for Q1 and 18 nm for Q2) is discussed.


Testosterone and dihydrotestosterone inhibit gallbladder motility through multiple signalling pathways.
Testosterone (T) has been shown to cause vasodilation in rabbit coronary arteries through a nongenomic pathway. Part of this T-induced relaxation was shown to be mediated by opening voltage dependent K(+) channels. T infusion also reduces peripheral resistance in human males with heart failure. The effects of T or its active metabolite 5-alpha dihydrotestosterone (DHT) are not well studied. This study investigates the effect of T and DHT on contraction in guinea pig gallbladder strips. T or DHT induced a concentration-dependent relaxation of cholecystokinin octapeptide (CCK)-induced tension. Pretreatment of the strips with PKA inhibitor 14-22 amide myristolated had no significant effect on the relaxation induced by either T or DHT. Pretreatment of strips with 2-APB, an inhibitor of IP(3) induced Ca(2+) release, produced a significant (p<0.001) reduction in the T- or DHT-induced relaxation. Bisindolymaleimide IV and chelerythrine Cl(-) when used in combination had no significant effect on the amount of CCK-induced tension, but significantly (p<0.01) decreased the amount of T- or DHT-induced relaxation. The flavone chrysin, an aromatase inhibitor, and genistein, an isoflavone, each produced a significant (p<0.01) reduction in CCK-induced tension. Chrysin significantly (p<0.05) increased T-induced relaxation; however, genistein had no effect on T-induced relaxation. It is concluded that T and DHT inhibits gallbladder motility rapidly by nongenomic actions of the hormones. Multiple pathways that include inhibition of intracellular Ca(2+) release, inhibition of extracellular Ca(2+) entry, and the actions of PKC may mediate this effect.


Mechanisms of depressant action of muscle relaxants on spinal reflexes: participation of membrane stabilizing action.
The participation of local anesthetic action in spinal reflex inhibition produced by mephenesin-type muscle relaxants was examined by comparing the local anesthetic effects (in vitro), the depressant effects on muscle afferent discharges (in situ) and the depressant effects on spinal reflexes (in situ) of the drugs in rats. At doses producing depression of spinal reflexes, mephenesin, tolperisone (mephenesin-type) and lidocaine (local anesthetic) reduced the frequency of afferent discharges from the muscle. The order of reducing afferent discharges by these drugs corresponded to that of their conduction blocking activities in the isolated sciatic nerve of rats. These results suggest the participation of a membrane stabilizing action in spinal reflex inhibition produced by mephenesin-type muscle relaxants. Baclofen (non-mephenesin-type) did not show any local anesthetic action.


Scanning ion conductance microscope with a capacitance-compensated current source amplifier.
A high-speed imaging method for a scanning ion conductance microscope (SICM) based on a current source amplifier that compensates for unavoidable capacitance is proposed. The capacitance is generated on a side wall of a nanopipette in the principle of the SICM. The electrical response time is deteriorated due to the capacitance, and the probe overshoots the setpoint of the detection of the sample surface. A capacitance compensation circuit was installed in a feedback circuit of the current source amplifier. The proposed capacitance compensation method is useful because it can shorten the imaging time by only installing the compensation circuit in the ion current detection circuit of an existing SICM. The maximum approaching speeds with and without capacitance compensation were found to be 1050 and 450 µm/s, respectively. The approaching speed with capacitance compensation was 2.3 times faster than that without capacitance compensation. A topographic image of the test sample was successfully obtained at an approaching speed of 1050 µm/s. The images of microvillus dynamics of COS-7 cells were obtained at ∼23.4 s/frame as an application of the developed technology.


Machine-Learning Approach for Modeling Myelosuppression Attributed to Nimustine Hydrochloride.
A major adverse effect arising from nimustine hydrochloride (ACNU) therapy for brain tumors is myelosuppression. Because its timing and severity vary among individual patients, the ACNU dose level has been adjusted in an empiric manner at individual medical facilities. To our knowledge, ours is the first study to develop a machine-learning approach to estimate myelosuppression through analysis of patient factors before treatment and attempts to clarify the relationship between myelosuppression and hematopoietic stem cells from daily clinical data. Adverse effect prediction will allow ACNU dose adjustment for patients predicted to have decreases in blood cell counts and will enable focused follow-up of patients undergoing chemoradiotherapy. Patients were newly pathologically diagnosed with WHO grade 2 or 3 tumors and were treated with ACNU-based chemoradiotherapy. For detailed analysis of the timing and intensity of adverse effects in patients, we developed a data-weighted support vector machine (SVM) based on adverse event criteria (nadir-weighted SVM [NwSVM]). To evaluate the estimation accuracy of blood cell count dynamics, the determination coefficient ( r2) between real and estimated data was calculated by three regression methods: polynomial, SVM, and NwSVM. Only the NwSVM-based regression enabled estimation of the dynamics of all blood cell types with high accuracy (mean r2 = 0.81). The mean timing of nadir arrival estimated using this regression was 35 days for platelets, 41 days for RBCs, 52 days for lymphocytes, 57 days for WBCs, and 62 days for neutrophils. The NwSVM can be used to predict myelosuppression and clearly depicts nadir timing differences between platelets and other blood cells.


Glutamate Deregulation in Ketamine-Induced Psychosis-A Potential Role of PSD95, NMDA Receptor and PMCA Interaction.
Ketamine causes psychotic episodes and is often used as pharmacological model of psychotic-like behavior in animals. There is increasing evidence that molecular mechanism of its action is more complicated than just N-methyl-D-aspartic acid (NMDA) receptor antagonism and involves interaction with the components of calcium homeostatic machinery, in particular plasma membrane calcium pump (PMCA). Therefore, in this study we aimed to characterize brain region-specific effects of ketamine on PMCA activity, interaction with NMDA receptor through postsynaptic density protein 95 (PSD95) scaffolding proteins and glutamate release from nerve endings. In our study, ketamine induced behavioral changes in healthy male rats consistent with psychotic effects. In the same animals, we were able to demonstrate significant inhibition of plasma membrane calcium ATPase (PMCA) activity in cerebellum, hippocampus and striatum. The expression level and isoform composition of PMCAs were also affected in some of these brain compartments, with possible compensatory effects of PMCA1 substituting for decreased expression of PMCA3. Expression of the PDZ domain-containing scaffold protein PSD95 was induced and its association with PMCA4 was higher in most brain compartments upon ketamine treatment. Moreover, increased PSD95/NMDA receptor direct interaction was also reported, strongly suggesting the formation of multiprotein complexes potentially mediating the effect of ketamine on calcium signaling. We further support this molecular mechanism by showing brain region-specific changes in PSD95/PMCA4 spatial colocalization. We also show that ketamine significantly increases synaptic glutamate release in cortex and striatum (without affecting total tissue glutamate content), inducing the expression of vesicular glutamate transporters and decreasing the expression of membrane glutamate reuptake pump excitatory amino acid transporters 2 (EAAT2). Thus, ketamine-mediated PMCA inhibition, by decreasing total Ca2+ clearing potency, may locally raise cytosolic Ca2+ promoting excessive glutamate release. Regional alterations in glutamate secretion can be further driven by PSD95-mediated spatial recruitment of signaling complexes including glutamate receptors and calcium pumps, representing a novel mechanism of psychogenic action of ketamine.


Characterization of dissipation factors in terms of piezoelectric equivalent circuit parameters.
The equivalent circuit of a piezoelectric ceramic is established composed of the equivalent circuit parameters derived from the complex materials coefficients. The equivalent circuit parameters are connected to real and imaginary parts of the complex materials coefficients of the piezoelectric ceramics. With respect to the definition of dissipation factors, the dielectric, elastic, and piezoelectric dissipation factors which represent the losses in the materials are thus expressed through the equivalent circuit parameters. In temperature and stress experiments, by measuring the equivalent circuit parameters during the process of the temperature and stress changes, three dissipation factors are computed. Compared with the results of other previous research, a similar increase of the elastic dissipation factor with stress is observed. Moreover, it is also found that the elastic dissipation factor reaches its saturation over a stress level of about 10 MPa. The responses of dissipation factors in lower temperature (-30 degrees C to 20 degrees C) are studied.


The ossified interclinoid ligament.
The paper presents an anatomical description of the ossified interclinoid ligament which was found in a male human skull. In the case studied the ossified ligament exists as a bony bridge between the anterior and posterior clinoid processes on the left side of the skull. The length of this connection was measured as 5.0 mm, while its thickness was 3.2 mm. We conjecture that the presence of a considerably thick bony trabecula within the sella region might have had an impact on the course of the internal carotid artery or the oculomotor nerve, causing compression of these structures.


Involvement of the local immune response in a case of advanced cervical cancer in a patient with systemic lupus erythematosus.
Although patients with systemic lupus erythematosus (SLE) have frequently accompanying malignancies, there are few documented cases in the literature of advanced cervical cancer patients with SLE. This report describes a case of advanced cervical cancer in a 39-year-old patient with a 20-year history of SLE (FIGO stage IIIb) and evaluates the immunological response of the tumor. The clinical course of this patient with SLE, with rapid growth of cervical cancer and a poor prognosis, may suggest that T cells play a key role in the growth of cancer.


Effects of hyperbaric oxygen therapy on circulating interleukin-8, nitric oxide, and insulin-like growth factors in patients with type 2 diabetes mellitus.
The potential benefits of hyperbaric oxygen therapy (HBOT) have been reported in diabetic patients with foot ulcers. However, the roles of HBOT on wound healing-associated growth factors and inflammatory mediators are not completely understood in diabetes mellitus (DM). The aim of this study was to investigate the effects of HBOT on circulating cytokines, NO, and insulin-like growth factors (IGF) in patients with type 2 DM. Serum samples were collected from patients with type 2 DM (n=31) and healthy subjects (n=29) before (baseline) and after the first and third exposure. Before HBOT, body mass index (BMI) and serum HbA1c were significantly greater, whereas serum IGF-I was significantly lower in diabetic patients compared to healthy subjects (one-way ANOVA, p<0.05). After adjusting for age, gender, and BMI, serum insulin, growth hormone (GH), IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3, leptin, interleukin (IL)-8, and NO were not significantly altered by HBOT in diabetic patients and healthy subjects (repeated-measures ANOVA). Change in serum insulin (baseline to the third exposure) was a positive predictor of changes in leptin and NO in healthy subjects and diabetic patients, respectively. Our results suggest that short-term HBOT may not alter the circulating insulin, IGF, leptin, IL-8, and NO levels. In addition, healthy subjects and diabetic patients showed differential responses to HBOT in the relationships of leptin, insulin, and NO. Further studies are needed to clarify the mechanism of HBOT-improved wound healing in diabetic patients with foot ulcers.


Time-intensity profiles of cutaneous pain in normal and hyperalgesic skin: a comparison with C-fiber nociceptor activities in monkey and human.
Contributions of evoked discharge in nociceptors with C-fibers to the temporal profiles of magnitude judgments of pain by humans were determined for heat stimulations of the skin before and after the development of hyperalgesia (increased sensitivity to pain) produced by a mild heat injury. Human subjects continuously rated the magnitude of pain evoked by short-duration heat stimuli of 39-51 degrees C delivered to the hairy skin of the arm or leg (calf or foot) before and after the development of hyperalgesia produced by a conditioning stimulus (CS) of either 50 degrees C for 100 s or 48 degrees C for 360 s. During heat stimulations of the leg in humans, magnitude judgments of pain were obtained simultaneously with recordings of evoked discharges in single C-fiber mechanoheat (CMH) nociceptive afferent fibers. Seven fibers were studied before and after the CS. In other experiments, magnitude ratings of pain evoked by heat stimulations of the arm were compared with heat-evoked discharges in 21 CMH nociceptive afferent fibers innervating the hairy skin of the wrist or hand in anesthetized monkeys. From CMH responses obtained in each species, median response latencies were calculated as well as poststimulus time (PST) histograms--the latter plotting mean frequency of discharge versus time during each stimulus. In these analyses, the times of action potentials in CMHs were calculated as they would occur at entry to the lumbar or cervical spinal cord in humans, taking into account the temporal dispersion that should occur because of differing conduction velocities. These results were then compared with response latencies for pain and the temporal profiles of pain ratings made by individual subjects. Comparisons were made for data obtained before the CS (normal skin) and those obtained 10 min after the CS in heat-sensitized (hyperalgesic) skin. For normal skin, PST histograms of mean frequencies of discharge were similar for CMHs with similar heat thresholds (41-43 degrees) in the anesthetized monkey and the awake human. Despite minor discrepancies, there were similarities in the changes in these histograms for monkey and human CMHs following heat sensitization after the CS. It was concluded that CMHs in monkeys and humans have similar response magnitudes and temporal profiles of response to heat. The major differences in the temporal profiles of CMH responses and human pain ratings were the latencies at which CMH responses and pain ratings began, reached maximum, and ended.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of acidosis on alpha 1- and alpha 2-adrenoceptor-mediated vasoconstrictor responses in isolated arteries.
We have investigated the effect of reducing the pH (from 7.5 to 7.0 by addition of HCl) on vasoconstrictor responses to noradrenaline in cat middle cerebral artery (in which responses are mediated almost entirely by alpha 2-adrenoceptors) and in rabbit pulmonary artery (in which responses are mediated by alpha 1-adrenoceptors). In the cerebral artery, a reduction in pH caused a pronounced inhibition of the responses to noradrenaline, and the antagonistic effect of idazoxan (100 nM) was increased 10-fold. In contrast, in the pulmonary artery, a reduction in pH had no effect on the responses to noradrenaline and the antagonistic effect of prazosin (100 nM) was not altered. We conclude that acidosis selectively reduces the vasoconstriction mediated by alpha 2-adrenoceptors in vitro.


Do hip OA patients referred to orthopedic surgeons by general practitioners and rheumatologists differ?
There is no consensus regarding indications for total hip arthroplasty (THA) in hip osteoarthritis (OA). Patients can be referred to surgeons either by a general practitioner (GP) or a rheumatologist. The aim of this study was to determine whether patients referred to orthopedic surgeons by GP and rheumatologists differed. GPs and rheumatologists were asked to include one patient suffering from hip OA for whom a consultation with a surgeon was planned to determine if THA was indicated. Surgeons' decisions were obtained by follow-up questionnaires. Univariate and then multivariate statistical analysis evaluated differences between patients referred by GPs and those referred by rheumatologists. A total of 558 patients were included. THA was prescribed in 71.6 % of patients referred by rheumatologists vs. 57.6 % of patients referred by GPs (p = 0.008). Patients referred by rheumatologists were younger (66.3 vs. 69.3 years; p = 0.006), less frequently retired (72.9 vs. 84.2 %; p = 0.007), and presented with a higher New Zealand score (54.3 vs. 48.1; p = 0.0009). On multivariate analysis, the variables related to patients referred by rheumatologists were the SF-12 mental score, the New Zealand score, and the surgeon's decision. Patients consulting a surgeon to discuss THA were more likely to be operated on when referred by a rheumatologist, which might be due to differences in the rheumatologists' and GPs' opinions on the right time to perform surgery or due to differences in the populations followed by rheumatologists and GPs, those followed by rheumatologists being younger, more active, more urban, with a greater willingness to undergo surgery.


Translocation of surface-inoculated Escherichia coli O157:H7 into beef subprimals following blade tenderization.
In phase I, beef subprimals were inoculated on the lean side with ca. 0.5 to 3.5 log CFU/g of a rifampin-resistant (rifr) cocktail of Escherichia coli O157:H7 and passed once, lean side up, through a mechanical blade tenderizer. Inoculated subprimals that were not tenderized served as controls. Ten core samples were removed from each subprimal and cut into six consecutive segments: segments 1 to 4 comprised the top 4 cm and segments 5 and 6 the deepest 4 cm. Levels of E. coli O157:H7 recovered from segment 1 of control subprimals when inoculated with ca. 0.5, 1.5, 2.5, or 3.5 log CFU/g were 0.6, 1.46, 2.5, and 3.19 log CFU/g, respectively. Following tenderization, pathogen levels recovered from segment 1 inoculated with 0.5 to 3.5 log CFU/g were 0.22, 1.06, 2.04, and 2.7 log CFU/g, respectively. Levels recovered in segment 2 were 7- to 34-fold lower than levels recovered from segment 1. Next, in phase II, the translocation of ca. 4 log CFU of the pathogen per g was assessed for lean-side-inoculated subprimals passed either once (LS) or twice (LD) through the tenderizer and for fat-side-inoculated subprimals passed either once (FS) or twice (FD) through the tenderizer. Levels in segment 1 for LS, LD, FS, and FD tenderized subprimals were 3.63, 3.52, 2.85, and 3.55 log CFU/g, respectively. The levels recovered in segment 2 were 14- to 50-fold lower than levels recovered in segment 1 for LS, LD, FS, and FD subprimals. Thus, blade tenderization transfers E. coli O157:H7 primarily into the topmost 1 cm, but also into the deeper tissues of beef subprimals.


Unabsorbed light beamlets for diagnosing coronal density profiles and absorption nonuniformity in direct-drive implosions on OMEGA.
Laser light scattered from a target is the most-direct measurement for diagnosing laser absorption in a direct-drive implosion. The 3ω gated optical imager beamlets diagnostic images unabsorbed light from all 60 OMEGA beams as distinct "beamlet" spots for each beam. The implosion can be diagnosed using the position and intensity of these beamlets. The position of each beamlet in the image is determined by refraction and can be used to fit the coronal plasma density profile of the implosion. The inferred plasma density profiles are comparable to the profiles predicted by the 1D hydrodynamics code LILAC but suggest that the predictions underestimate the density farther out in the corona. The intensity of light in each spot depends on the cumulative effects of absorption and cross-beam energy transfer along the beamlet's path through the corona. The measured variation in intensity and polarization between similar spots indicates that absorption during OMEGA implosions is less uniform than previously known.


Does the Type of Maxillomandibular Deformity Influence Complication Rate in Orthognathic Surgery?
Patients may encounter various complications during and after orthognathic surgery. The aim of this study was to compare the prevalence of complications in various skeletal deformities to see if an association exists. This retrospective cohort study assessed patients in 2 groups. Group 1 had class III skeletal deformity and group 2 had class II skeletal deformity with vertical maxillary excess (VME). Complications were studied in 2 stages: Stage 1 included perioperative and immediate (first 24 hours) postoperative complications namely difficult intubation, blood transfusion, bad splits, pain, and postoperative airway problems. Stage 2 included postoperative complications (from 24 hours up to 6 months after surgery namely bad splits and relapse). Age, sex, operation time, and the amount of jaw movements were considered as variables. Types of skeletal deformity were predictive factor of the study. The authors studied 248 patients in 2 groups. In group 1, 13 (8.2%) patients needed blood transfusion during surgery up to 24 hours after operation and 27 (30%) patients in group 2. Analysis of data demonstrated a significant difference for blood transfusion between 2 groups (P = 0.001). In group 1, 8 (5.1%) patients had a difficult intubation compared with 13 (14.4%) patients in group 2.Comparison of mandibular movement and maximum mouth opening (MMO) did not show significant differences between 2 groups (P > 0.05). The amount of maxillary movement and horizontal discrepancy were different statistically in 2 groups (P < 0.05). Analysis of the data showed a significant difference in intubation between the 2 groups (P < 0.05). There were no differences between the 2 groups for bad splits, postoperative airway problems, or paresthesia (P > 0.05). Results did not demonstrate a significant difference for pain between the 2 groups (P > 0.05). Patients with class II skeletal deformity and VME may have higher risk of perioperative blood loss and difficult intubation compared with patients with class III skeletal deformity.


Role of vagus in the antagonism of ouabain induced arrhythmias in dogs by beta-adrenoceptor antagonists and related drugs.
The effects of propranolol and related drugs were investigated on ouabain-induced ventricular tachycardia (VT) in dogs with intact and ablated vagi. Propranolol and UM-272 completely antagonized the ouabain VT in dogs with intact vagi, whereas timolol was ineffective. Bilateral vagotomy completely abolished the effect of UM-272 and reduced the effect of propranolol. Diphenylhydantoin, however, reversed ouabain VT in dogs with both intact and ablated vagi. It is inferred that the vagus plays a significant role in the arrhythmolytic effect of propranolol and UM-272.


Spatially tuned normalization explains attention modulation variance within neurons.
Spatial attention improves perception of attended parts of a scene, a behavioral enhancement accompanied by modulations of neuronal firing rates. These modulations vary in size across neurons in the same brain area. Models of normalization explain much of this variance in attention modulation with differences in tuned normalization across neurons (Lee J, Maunsell JHR. PLoS One 4: e4651, 2009; Ni AM, Ray S, Maunsell JHR. Neuron 73: 803-813, 2012). However, recent studies suggest that normalization tuning varies with spatial location both across and within neurons (Ruff DA, Alberts JJ, Cohen MR. J Neurophysiol 116: 1375-1386, 2016; Verhoef BE, Maunsell JHR. eLife 5: e17256, 2016). Here we show directly that attention modulation and normalization tuning do in fact covary within individual neurons, in addition to across neurons as previously demonstrated. We recorded the activity of isolated neurons in the middle temporal area of two rhesus monkeys as they performed a change-detection task that controlled the focus of spatial attention. Using the same two drifting Gabor stimuli and the same two receptive field locations for each neuron, we found that switching which stimulus was presented at which location affected both attention modulation and normalization in a correlated way within neurons. We present an equal-maximum-suppression spatially tuned normalization model that explains this covariance both across and within neurons: each stimulus generates equally strong suppression of its own excitatory drive, but its suppression of distant stimuli is typically less. This new model specifies how the tuned normalization associated with each stimulus location varies across space both within and across neurons, changing our understanding of the normalization mechanism and how attention modulations depend on this mechanism.NEW & NOTEWORTHY Tuned normalization studies have demonstrated that the variance in attention modulation size seen across neurons from the same cortical area can be largely explained by between-neuron differences in normalization strength. Here we demonstrate that attention modulation size varies within neurons as well and that this variance is largely explained by within-neuron differences in normalization strength. We provide a new spatially tuned normalization model that explains this broad range of observed normalization and attention effects.


Evaluation of gene xpert for routine diagnosis of HIV-associated tuberculosis in Nigeria: A prospective cohort study.
Xpert MTB/Rif (Xpert) is described as a game changer in tuberculosis (TB) control. We evaluated the impact of Xpert on diagnosis, time to treatment, and treatment outcome among patients with HIV associated TB in Nigeria. Adults with HIV being evaluated for pulmonary TB (PTB) were consecutively enrolled into the study cohort. At baseline, expectorated sputa were examined using Xpert and smear microscopy for Mycobacterium tuberculosis (MTB) and acid fast bacilli, respectively. Patients diagnosed with TB were followed-up until 6 months post TB diagnosis. TB was defined as sputum positive by smear microscopy, Xpert detection of MTB (bacteriologically confirmed case), or clinician diagnosed TB with initiation of full TB treatment (clinical diagnosis). Time to treatment was time from first clinic presentation for TB evaluation to initiation of TB treatment. We examined the proportion PTB patients with a positive Xpert result and compared time to TB treatment and outcome of TB treatment in patients based on sputum test results. A total of 310 adults with HIV were enrolled. The median CD4 cell count was 242 (interquartile range (IQR) 120-425) cells/mm3 and 88.1% were receiving antiretroviral therapy (ART). PTB was diagnosed in 76 (24.5%) patients, with 71 (93.4%) being bacteriologically confirmed. Among patients with PTB, 56 (73.7%) were Xpert positive. Median time to treatment was 5 (IQR 2-8) days and 12 (IQR 5-35) days in patient with and without Xpert positive results, respectively; p = 0.005. Overall 73.1% had symptom free survival at 6 months post PTB treatment initiation with no significant differences observed based on TB test method. 10 (14.9%) died within 6 months of TB treatment initiation. In analysis adjusted for age, sex, and mode of diagnosis (Xpert positive or negative), only ART use independently predicted mortality (AOR 0.10; 95% CI 0.01-0.93). The use of Xpert for routine care reduced time to PTB treatment, but did not improve survival in patients with HIV treated for susceptible PTB.


Randomized controlled trial comparing a conventional needle and a novel needle for endoscopic ultrasound (EUS)-guided histology of peripancreatic masses.
Cytological study of samples obtained by Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) allows for recognition of clear signs of malignant transformation. However, certain neoplasms can be difficult to diagnose without histological analysis. Recently, a novel EUS-guided fine needle biopsy (EUS-FNB) needle was developed to increase tissue acquisition. This study set out to investigate the usefulness of this novel EUS-FNB needle (NEFN) in terms of obtaining a proper histology compared with a conventional EUS-FNA needle (CEFN). This investigation was a prospective, single-blind, randomized study in a single academic hospital. Primary outcome was the acquisition rate of an appropriate and sufficient specimen for histologic assessment. Secondary outcomes were diagnostic yield of peripancreatic masses using a CEFN and a NEFN. Furthermore, we assessed the feasibility of determining K-ras mutation status according to needle type. The study enrolled 56 consecutive patients. Technical success rates were 96.6% (28/29) for the CEFN and 100% (27/27) for the NEFN (P = 1.000). No complications occurred during or after the procedure in either needle group. An adequate sample for cytologic diagnosis was obtained in 89.7% (26/29) of patients in the CEFN group vs 96.3% (26/27) of patients in the NEFN group (P = .612). For histologic diagnosis, a sample with a biopsy adequacy score of 2 or more was obtained in 41.4% (12/29) of CEFN-acquired samples vs 88.9% (24/27) of NEFN-acquired samples (P < .001). K-ras mutation analysis using histologic specimens was possible in 13 (44.8%) CEFN-acquired samples and 25 (92.6%) of NEFN-acquired samples. This difference was significant (P < .001). The present study suggests that the NEFN is an effective and reliable alternative compared to a CEFN in terms of tissue acquisition rate and quality of histologic sampling.


Supramolecular helical columns from the self-assembly of chiral rods.
Chiral-bridged rod molecules (CBRs) that consisted of bis(penta-p-phenylene) conjugated to an opened or closed chiral bridging group as a rigid segment and oligoether dendrons as flexible segments were synthesized and characterized. In the bulk state, both molecules self-assemble into a hexagonal columnar structure, as confirmed by X-ray scatterings and transmission electron microscopy (TEM) observations. Interestingly, these structures display opposite Cotton effects in the chromophore of the aromatic unit in spite of the same chirality (R,R) of the chiral bridging groups. The molecules were observed to self-assemble into cylindrical micellar aggregates in aqueous solution, as confirmed by light scattering and TEM investigations, and exhibit intense signals in the circular dichroism (CD) spectra, which are indicative of one-handed helical conformations. The CD spectra of each molecule showed opposite signals to each other, which were similar to those in the bulk. Notably, when the opened CBR was added to a solution of closed CBRs up to a certain concentration, the CD signal of the closed CBR was amplified. This implies that both molecules co-assemble into a one-handed helical structure because the opened chiral bridge is conformationally flexible, which is inverted to co-assemble with the closed CBR. These results demonstrate that small structural modifications of the chiral moiety can transfer the chiral information to a supramolecular assembly in the opposite way.


Microsponges: A Pioneering Tool for Biomedical Applications.
Microparticulate drug delivery systems have been explored across the globe due to their various advantages. In 1987, Won developed microsponge systems (Micsys), also known as solid-phase porous microspheres, having numerous interconnected voids, which serve as non-collapsible residence for bioactive compounds. A Micsys particle ranges from 5 to 300 μm in size and shows a wide range of entrapment efficiency with desired release rates. This topical drug delivery system bestows a controlled release of bioactive compounds into the skin with reduced systemic side effects. Currently, the application fields of this promising system include oral, ocular, pulmonary, and parenteral delivery of bioactive compounds. In the present review, we summarize the updated biomedical application potential of Micsys as an effective drug-delivery vector, including an in-depth explanation of the drug-release kinetic models and drug-release mechanisms. We also discuss different techniques used to prepare a Micsys, along with their advantages and disadvantages. Moreover, in this review, we report a plethora of Micsys details, such as drug candidates and polymers, exploited in this field, along with marketed formulations, characterization methods, clinical perspectives, and patents received. This assembly of detailed literature summaries will contribute to future advances in the development of porous carriers.


Near-infrared light controlled fluorogenic labeling of glycoengineered sialic acids in vivo with upconverting photoclick nanoprobe.
Sialic acid serves as an important determinant for profiling cell activities in diverse biological and pathological processes. The precise control of sialic acid labeling to visualize its biological pathways under endogenous conditions is significant but still challenging due to the lack of reliable methods. Herein, we developed an effective strategy to spatiotemporally label thesialic acids with a near-infrared (NIR) light activated upconverting nanoprobe (Tz-UCNP). With this photoclickable nanoprobe and a stable N-alkene-d-mannosamine (Ac4ManNIPFA), metabolically synthesized alkene sialic acids on the cell surface were labeled and imaged in real time through fluorogenic cycloaddition. More importantly, we achieved spatially selective visualization of sialic acids in specific tumor tissues of the mice under NIR light activation in a spatially controlled manner. This in situ controllable labeling strategy thus enables the metabolic labeling of specific sialic acids in complex biological systems.


A Biologically-validated HCV E1E2 Heterodimer Structural Model.
The design of vaccine strategies and the development of drugs targeting the early stages of Hepatitis C virus (HCV) infection are hampered by the lack of structural information about its surface glycoproteins E1 and E2, the two constituents of HCV entry machinery. Despite the recent crystal resolution of limited versions of both proteins in truncated form, a complete picture of the E1E2 complex is still missing. Here we combined deep computational analysis of E1E2 secondary, tertiary and quaternary structure with functional and immunological mutational analysis across E1E2 in order to propose an in silico model for the ectodomain of the E1E2 heterodimer. Our model describes E1-E2 ectodomain dimerization interfaces, provides a structural explanation of E1 and E2 immunogenicity and sheds light on the molecular processes and disulfide bridges isomerization underlying the conformational changes required for fusion. Comprehensive alanine mutational analysis across 553 residues of E1E2 also resulted in identifying the epitope maps of diverse mAbs and the disulfide connectivity underlying E1E2 native conformation. The predicted structure unveils E1 and E2 structures in complex, thus representing a step towards the rational design of immunogens and drugs inhibiting HCV entry.


Autonomic function in cholinergic urticaria and atopic eczema.
Autonomic function in patients with cholinergic urticaria and atopic eczema was compared with that in patients with chronic idiopathic urticaria and non-atopic allergic contact dermatitis, respectively. Forty-nine patients were studied. The following specific tests of sympathetic and parasympathetic function were used to assess the integrity of autonomic control: pupillary reflex amplitude in response to pulsed light stimulation and response to topical arecoline hydrobromide (parasympathetic); the speed of pupillary dilatation following a large light reflex (sympathetic); pupillary resting diameter (sympathetic and parasympathetic); sweat gland response to forearm intradermal injection of acetylcholine chloride; and the effect of postural change and deep breathing on blood pressure and heart rate (sinus arrhythmia indicating parasympathetic function). No significant difference in autonomic function was found between the four groups of patients.


On the Finite Element Implementation of Functionally Graded Materials.
We investigate the numerical implementation of functionally graded properties in the context of the finite element method. The macroscopic variation of elastic properties inherent to functionally graded materials (FGMs) is introduced at the element level by means of the two most commonly used schemes: (i) nodal based gradation, often via an auxiliary (non-physical) temperature-dependence, and (ii) Gauss integration point based gradation. These formulations are extensively compared by solving a number of paradigmatic boundary value problems for which analytical solutions can be obtained. The nature of the notable differences revealed by the results is investigated in detail. We provide a user subroutine for the finite element package ABAQUS to overcome the limitations of the most popular approach for implementing FGMs in commercial software. The use of reliable, element-based formulations to define the material property variation could be key in fracture assessment of FGMs and other non-homogeneous materials.


Role of Peroral Cholangioscopy in the Diagnosis of Primary Sclerosing Cholangitis.
Primary sclerosing cholangitis (PSC) is characterized by idiopathic biliary stricture followed by progressive cholestasis and fibrosis. When diagnosing PSC, its differentiation from other types of sclerosing cholangitis and cholangiocarcinoma is necessary. The cholangioscopic findings of PSC have not been investigated sufficiently. PSC and IgG4-related sclerosing cholangitis are difficult to distinguish by peroral cholangioscopy (POCS), but POCS is useful for excluding cholangiocarcinoma. POCS findings vary according to the condition and stage of disease. In the active phase, findings such as mucosal erythema, ulceration, fibrinous white exudate, and an irregular surface are observed and may reflect strong inflammation in the biliary epithelium. On the other hand, findings such as scarring, pseudodiverticula, and bile duct stenosis appear in the chronic phase and may reflect fibrosis and stenosis resulting from repeated inflammation. Observation of inside the bile duct by POCS might confirm the current PSC activity. Because POCS offers not only information regarding the diagnosis of PSC and PSC-associated cholangiocarcinoma but also the current statuses of biliary inflammation and stenosis, POCS could significantly contribute to the diagnosis and treatment of PSC once the characteristic findings of PSC are confirmed by future studies.


Water accessibility to the binding cleft as a major switching factor from entropy-driven to enthalpy-driven binding of an alkyl group by synthetic receptors.
Free energy, enthalpy, and entropy changes in the binding of alkyl pyridines to water-soluble zinc porphyrin receptors with varying accessibility of water to the binding cleft were determined to explain why the driving force of hydrophobic effects is enthalpic in some occasions and entropic in others. Zinc porphyrins bearing four alkyl pillars with terminal solubilizing poly(oxyethylene) (POE) chains of molecular weight of 750 (1), with eight alkyl pillars with terminal solubilizing POE chains of molecular weight of 350 (3), and with eight alkyl pillars with POE of molecular weight of 750 (4) had a binding cleft with decreasing water accessibility in this order as revealed by binding selectivity of imidazole/pyridine. Although all these porphyrins showed that the free energy of binding (-DeltaG(o)) increases linearly as the alkyl group of the guest is lengthened (-DeltaG(o) per CH(2) was 2.6, 2.8, and 2.6 kJ mol(-1) for 1, 3, and 4, respectively), the origin of the free energy gain was much different. Receptor 1 with the most hydrophilic binding site bound the alkyl group by an enthalpic driving force (4-pentylpyridine favored over 4-methylpyridine by DeltaDeltaH(o)=-16.4 kJ mol(-1)), while receptor 4 with the most hydrophobic binding site by an entropic driving force (4-pentylpyridine favored over 4-methylpyridine by DeltaDeltaS(o)=39.6 J K(-1) mol(-1)). Receptor 3 showed intermediate behavior: both enthalpic and entropic terms drove the binding of the alkyl group with the enthalpic driving force being dominant. The binding site of the four-pillared receptor (1) is open and accessible to water molecules, and is more hydrophilic than that of the eight-pillared receptor (4). We propose that the alkyl chains of 1 are exposed to water to produce a room to accommodate the guest to result in enthalpy-driven hydrophobic binding, whereas 4 can accommodate the guest without such structural changes to lead to entropy-driven hydrophobic binding. Therefore, accessibility of water or exposure of the binding site to the water phase switches the driving force of hydrophobic effects from an entropic force to an enthalpic force.


Evaluation of CD8+ T cell subpopulations in paracoccidioidomycosis.
Aim: We aimed to verify the frequency of CD8+ T cell subsets in patients with acute form and chronic form of paracoccidioidomycosis. Material & Methods: Mononuclear cells from paracoccidioidomycosis patients and healthy donors were isolated and phenotyped by flow cytometry. Dendritic cells were pulsed with Paracoccidioides brasiliensis yeast and co-cultures with lymphocytes. Cytokine production was measured by ELISA. Results: Acute form patients present a higher frequency of Tc1 and Tc10 cells, while chronic form patients have more Tc1 and Tc21 cells, compared with healthy controls. In vitro assays showed that P. brasiliensis induced polarization to the Tc17/Tc22 subsets. Conclusion: Our results suggest that CD8+ T cells can respond in a similar way to P. brasiliensis infection, regardless of the clinical presentation of the disease.


Radioresistant derivatives of an X-ray-sensitive CHO cell line exhibit distinct patterns of sensitivity to DNA-damaging agents.
X-ray-resistant clones of the xrs-5 radiosensitive derivative of the CHO-K1 cell line were generated by transfecting cosmid library DNAs into the X-ray-sensitive cells. Transfectants were selected for both a dominant drug resistance marker present in the vector sequences and return to wild-type survival. Three cell lines were isolated which show X-ray survival characteristics similar to parental K1 cells. These revertant lines were examined for their cross-sensitivity to cis-diamminedichloroplatinum(II) (cisplatin) and bleomycin. Although these cell lines reverted with regard to X-ray sensitivity, they retained their sensitivity to cisplatin. Furthermore, changes in bleomycin and X-ray sensitivity did not correlate. There was a positive correlation between return to wild-type radiosensitivity and an increase in the rate of DNA double-strand break rejoining.


Inhaled nicotine in humans: effect on the respiratory and cardiovascular systems.
Inhalation of nicotine (0-64 mg/ml) and capsaicin (2 x 10(-6)-2.5 x 10(-4) M) in 24 healthy nonsmoking subjects produced a concentration-dependent cough response. Two subjects coughed to capsaicin but not to nicotine. The mean (95% confidence interval) nicotine concentrations causing two and five coughs were 5.5 (3.5-8.7) and 15.8 (10.0-25.1) mg/ml, respectively, and were reproducible over 3 different days. Capsaicin inhalation did not alter the response to nicotine and vice versa. Both agents increased respiratory resistance, but the response was more rapid to capsaicin. Inhalation of nicotine (0-8 mg/ml) over 5 min caused increases in heart rate and blood pressure and a decrease in skin temperature. Inhaled ipratropium bromide (0.50 mg) had an antitussive effect and also inhibited the nicotine-induced bronchoconstriction, indicating a vagally mediated effect. Sodium cromoglycate (0.20 mg) did not affect cough or airway resistance changes caused by nicotine. This study shows that inhaled nicotine produces a concentration-dependent cough and airway obstruction in healthy subjects, probably because of stimulation of afferent nerve endings in the bronchial mucosa and mediated through parasympathetic cholinergic pathways. Respiratory reflexes evoked by nicotine are similar to those produced by capsaicin, but it is unclear whether these reflexes are mediated by the same type of sensory nerves.


Diastereoselective Construction of the 6-Oxa-2-azabicyclo[3.2.1]octane Scaffold from Chiral α-Hydroxyaldehyde Derivatives by the Aza-Prins Reaction.
(R)-2,3-Di-O-benzylglyceraldehyde and N-tosyl homoallylamine undergo aza-Prins cyclization to afford (1R,5S,7S)-7-[(benzyloxy)methyl]-2-tosyl-6-oxa-2-azabicyclo[3.2.1]octane in a highly diastereoselective manner through an unexpected intramolecular nucleophilic attack. Our work has opened a new route toward the asymmetric synthesis of 7-(alkyl or aryl)-6-oxa-2-azabicyclo[3.2.1]octane derivatives from chiral α-hydroxyaldehyde derivatives in one step.


Stable aromatic dianion in water.
Perylene diimide (PDI) bearing polyethylene glycol substituents at the imide positions was reduced in water with sodium dithionite to produce an aromatic dianion. The latter is stable for months in deoxygenated aqueous solutions, in contrast to all known aromatic dianions which readily react with water. Such stability is due to extensive electron delocalization and the aromatic character of the dianion, as evidenced by spectroscopic and theoretical studies. The dianion reacts with oxygen to restore the parent neutral compound, which can be reduced again in an inert atmosphere with sodium dithionite to give the dianion. Such reversible charging renders PDIs useful for controlled electron storage and release in aqueous media. Simple preparation of the dianion, reversible charging, high photoredox power, and stability in water can lead to development of new photofunctional and electron transfer systems in the aqueous phase.


Antibacterial properties of peptides from chia (Salvia hispanica L.) applied to pork meat preservation.
Chia-derived peptides might represent a novel alternative to conventional preservatives in food. Despite the antibacterial potential of these molecules, their food application is still limited. This study aimed to evaluate chia-derived peptides' antibacterial and antibiofilm potential in food preservation. The peptides YACLKVK, KLKKNL, KLLKKYL, and KKLLKI were synthesized, and their antibacterial activity against Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Salmonella Enteritidis was evaluated through microdilution tests. A bacterial killing kinetic assay determined bacterial growth over time. The ability to prevent and eradicate S. aureus biofilm was assessed by crystal violet staining. The hemolytic and cytotoxic activities were determined in human red blood cells and fibroblasts using free hemoglobin detection and (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays, respectively. Finally, a microbial challenge was performed on meat samples inoculated with L. monocytogenes and S. Enteritidis to determine their inhibitory effects on pork meat. Results showed the potential antibacterial activity of these peptides, with minimum inhibitory concentrations ranging from 0.23 to 5.58 mg/mL. Biofilm inhibition percentages were above 40%, and eradication percentages were lower than 20%. In vitro assays in human red blood cells and fibroblasts demonstrated that peptides are not hemolytic or cytotoxic agents. In microbiological challenge testing, KKLLKI showed the most promising antibacterial effects against S. Enteritidis on refrigerated pork meat samples. These findings suggest that chia-derived peptides have the potential as natural food preservatives due to their antibacterial and antibiofilm properties. Notably, KKLLKI demonstrated promising antibacterial effects against Salmonella spp. on a complex food matrix, such as pork meat. PRACTICAL APPLICATION: Chia-derived peptides can be a safer alternative to synthetic preservatives in the food industry because the latter may be detrimental to human health. Salmonella spp. growth on chilled pork meat was shown to be inhibited by the peptide KKLLKI, indicating that the use of these peptides may offer a more secure and natural alternative to synthetic preservatives.


Avoidable Hospitalization Trends From Ambulatory Care-Sensitive Conditions in the Public Health System in México.
To estimate and identify the variations in rates of Avoidable Hospitalization for Ambulatory Care Sensitive Conditions (AH-ACSC) in public institutions of the Mexican health system during the period 2010-2017. Secondary analysis of the hospital discharge database of the Ministry of Health (MoH) from 2010 to 2017. AH for ACSC was calculated by age group and sex per 100,000. Variations per year between institutions were calculated with the extreme quotient (EQ), coefficient of variation (CV) and systematic component of variance (SCV). Adjusted AH rates were calculated by group of causes (acute, chronic and preventable by vaccination). Adjusted AH trend rates were analyzed by Join Point Regression. For the period 2010-2017, the number of AH for ACSC decreased from 676,705 to 612,897, going from almost 13% to 10.7% of hospital discharges. There is consistency in terms of relative variance magnitude. But, with regards to SCV, the change remained constant, and in a second period of 2015-2017, high variation was observed by SCV ≥ 3. All-cause AH is diminishing in all institutions. AH rates for diabetes are the highest, but like other chronic diseases, there was a decline in the period from 2010 to 2017. The relative reduction varied from 15% for heart failure to 38% for complications from diabetes or hypertension, to 75% for angina. AH for ACSC is an indirect indicator of quality and access to first-level care. Variations by institutions are observed. This variation in CV and SCV across subsystems and states may be due to inequities in the provision of services. The factors that contribute to the burden of AH for ACSC in the Mexican Health System require detailed analysis.


The genome of the generalist plant pathogen Fusarium avenaceum is enriched with genes involved in redox, signaling and secondary metabolism.
Fusarium avenaceum is a fungus commonly isolated from soil and associated with a wide range of host plants. We present here three genome sequences of F. avenaceum, one isolated from barley in Finland and two from spring and winter wheat in Canada. The sizes of the three genomes range from 41.6-43.1 MB, with 13217-13445 predicted protein-coding genes. Whole-genome analysis showed that the three genomes are highly syntenic, and share>95% gene orthologs. Comparative analysis to other sequenced Fusaria shows that F. avenaceum has a very large potential for producing secondary metabolites, with between 75 and 80 key enzymes belonging to the polyketide, non-ribosomal peptide, terpene, alkaloid and indole-diterpene synthase classes. In addition to known metabolites from F. avenaceum, fuscofusarin and JM-47 were detected for the first time in this species. Many protein families are expanded in F. avenaceum, such as transcription factors, and proteins involved in redox reactions and signal transduction, suggesting evolutionary adaptation to a diverse and cosmopolitan ecology. We found that 20% of all predicted proteins were considered to be secreted, supporting a life in the extracellular space during interaction with plant hosts.


Analysis of multilevel spiral phase plates using a Dammann vortex sensing grating.
Optical vortices can be easily generated using a multilevel spiral phase plate (SPP). However the quality of the generated vortex beam depends on the number of phase segments. We review the theory for this multilevel SPP using a Fourier expansion of integer topological charged vortices. We then experimentally examine the validity of this expansion using a fabricated Dammann vortex diffraction grating spectrum analyzer. The Dammann vortex diffraction grating is fabricated using SU-8 photoresist on glass substrate and yields uniform diffraction efficiency across a desired number of diffracted orders. Experimental results show the extra angular harmonics of a multilevel SPP and agree with the theory.


Acoustic performance of boundaries having constant phase gradient.
In this paper, inhomogeneous boundaries having constant phase gradient are investigated. In principle, such a theoretically proposed boundary is dispersionless. In practice, however, when the boundary is realized by a subwavelength-structured tubes array, the impedance discretization brings about sub-reflections at high frequencies. Moreover, determined by the longest duct in the array, a realized boundary is impractically thick. Therefore, a finite-thickness boundary is further proposed by truncating and periodizing the tubes in the array. In this paper, the theoretical analysis agrees well with the numerical simulations. By appropriately choosing its phase gradient and target frequency, the finite-thickness boundaries have potential applications in noise control.


Online detection of concerned HIV-related messages in web forums.
Web forums become the means of online communication and information sharing sources for the learning about health care and related treatment knowledge. By adopting web crawlers and natural language processing techniques, the automatic identification approach of the concerned HIV-related messages is proposed to facilitate the health authorities and social support groups in instant counseling. The proposed supervised GA/k-means for classification approach can help construct an effective identification and classification model with acceptable classification performance accompanied with its full flexibility to develop different fitness functions in accordance with the need of different requirements. Furthermore, with the aid of correspondence analysis, the most frequently used terms in concerned HIV-related messages are identified and focus on risky sexual behavior whereas unconcerned messages are those who of worried well.


Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception.
The purpose of this study was to determine the rate of early postmenopausal bone loss in women who had used depot medroxyprogesterone acetate contraception through to menopause. Bone mineral density at the lumbar spine and femoral neck was assessed prospectively over 3 years in 15 women who reached a natural menopause and who did not undergo hormone replacement therapy and in 16 long-term users of depot medroxyprogesterone acetate who discontinued depot medroxyprogesterone acetate only on reaching menopause. Of the latter, 5 women subsequently underwent hormone replacement therapy. Early menopausal bone loss was rapid in the control group (6% from both sites over 3 years), but the users of depot medroxyprogesterone acetate (who did not take hormone replacement therapy) showed little change in bone mineral density. Between-group differences were statistically significant at years 2 and 3 at both sites (P <.03-<.002). In the users of depot medroxyprogesterone acetate who underwent hormone replacement therapy, bone mineral density increased significantly (P <.03) at the lumbar spine and was stable at the femoral neck. Women who use depot medroxyprogesterone acetate through to menopause have attenuated rates of bone loss from the lumbar spine and femoral neck, presumably because they have already lost the estrogen-sensitive component of bone.


Lipid-protein nanodiscs as reference medium in detergent screening for high-resolution NMR studies of integral membrane proteins.
The choice of a suitable detergent-based membrane mimetic is of crucial importance for high-resolution NMR studies of membrane proteins. The present report describes a new approach of detergent screening. It is based on the comparison of 2D (1)H,(15)N-correlation spectra of a protein in a membrane-bilayer "reference" medium and in "trial" detergent-based environments. The proposed "reference" medium is the lipid-protein nanodisc (LPN) representing nanoscale phospholipid bilayers wrapped around by apolipoprotein A-1. The set of zwitterionic (DPC, DMPC/DHPC), anionic (SDS, LMPG, LPPG), and weakly cationic (LDAO) detergent-based media was screened for their ability to represent the native structure of the isolated voltage-sensing domain (VSD) of the archaeal potassium channel KvAP. The VSD/LPN complexes composed of saturated zwitterionic (DMPC), anionic (DMPG), or a mixture of unsaturated differently charged (POPC/DOPG, 3:1) lipids were used as reference. All assayed detergent media demonstrate similar CD spectra of the domain with a high level (approximately 60%) of overall helicity but different 2D NMR spectra. Using the reference spectrum of the VSD in LPN, we were able to choose the detergent composition in which the membrane-like structure of the VSD is preserved.


Fish consumption and risk of non-Hodgkin lymphoma: A meta-analysis of observational studies.
Objectives: Whether a relationship between fish consumption and non-Hodgkin lymphoma (NHL) risk exists is an open issue. We carried out a meta-analysis to explore this association according to the published observational studies.Methods: We performed a search of databases in MEDLINE and EMBASE to identify relevant studies. We derived meta-analytic estimates using random-effects models, and assessed between-study heterogeneity using the Cochran's Q and I2 statistics.Results: We identified a total of seven case-control and two prospective cohort studies, including 7696 subjects with NHL. The summary relative risks (SRRs) estimated for NHL were 0.80 (95% confidence intervals (CIs): 0.68-0.94) for those in the highest fish consumption category compared with those in the lowest consumption category. There was evidence of significant heterogeneity across studies (Q = 26.72, Pheterogeneity = 0.002, I2 = 66.3%). Stratified analysis by study design indicated that a significant risk association between fish consumption and NHL was observed in case-control studies, but not in cohort studies. Based on the dose-response meta-analysis, the SRRs of NHL were 0.85 (95% CIs: 0.71-1.01) for three servings increased per week of fish consumed with evidence of significant heterogeneity (Pheterogeneity = 0.007, I2 = 63.9%).Conclusions: Findings from our meta-analysis indicate that consumption of fish may be not related to NHL risk.


Antioxidative mechanism in the course of varicose veins.
Objective Our objective was to evaluate the state of oxidative stress in the great saphenous varicose vein wall and blood of varicose vein patients taken from the antecubital vein. Methods The superoxide dismutase, reduced glutathione (GSH) and total antioxidant status were measured with commercially available colorimetric kits in erythrocytes, plasma and varicose vein wall of 65 patients (second degree of clinical state classification, etiology, anatomy and pathophysiology) aged 22-70 (49 women, 16 men) in comparison to normal great saphenous vein walls collected from 10 patients who underwent coronary artery bypass graft and blood collected from 20 healthy individuals. Results A statistically significant decrease (p < 0.001) in superoxide dismutase activity in erythrocytes and the increase (p < 0.05) in superoxide dismutase activity in varicose vein has been observed. There have been no significant changes in the concentration of GSH in plasma and in varicose vein. The decreased concentration of total antioxidant status in plasma (p < 0.001) and in varicose vein wall (p < 0.05) in comparison to the control has been noticed. Conclusion The varicose vein patients are affected by oxidative stress. Our results indicate impaired antioxidant defense mechanism in the blood of varicose vein patients. In contrast to the blood, an increased process of antioxidant defense in the varicose vein wall was noticed.


Efficacy of ankle foot orthoses types on walking in children with cerebral palsy: A systematic review.
Ankle foot orthoses (AFOs) are orthotic devices that can be used to normalize the walking pattern of children with cerebral palsy (CP). One of the aims of orthotic management is to produce a more normal gait pattern by positioning joints in the proper position to reduce pathological reflex or spasticity. To conduct a systematic review of the literature and establish the effect of treatment with various types of AFOs on gait patterns of children with CP. PubMed, Scopus, ISI Web of knowledge, Cochrane Library, EMBASE and Google Scholar were searched for articles published between 2007 and 2015 of studies of children with CP wearing the following AFOs: hinged (HAFO), solid (SAFO), floor reaction (FRO), posterior leaf spring (PLS) and dynamic (DAFO). Studies that combined treatment options were excluded. Outcomes investigated were a change in gait pattern and subsequent walking ability. The PEDro scale used to assess the methodological quality of relevant studies. We included 17 studies investigating a total of 1139 children with CP. The PEDro score was poor for most studies (3/10). Only 4 studies, of 209 children in total, were randomized controlled trials, for a good PEDro score (5, 7, 9/10) and an appropriate level of evidence. One study used a case-based series and the remainder a cross-sectional design. In general, the use of AFOs improved speed and stride length. The HAFO was effective for improving gait parameters and decreasing energy expenditure with hemiplegic CP as compared with the barefoot condition. It also improved stride length, speed of walking, single limb support and gait symmetry with hemiplegic CP. The plastic SAFO and FRO were effective in reducing energy expenditure with diplegic CP. With diplegic CP, the HAFO and SAFO improved gross motor function. For children with CP, use of specific types of AFOs improved gait parameters, including ankle and knee range of motion, walking speed and stride length. AFOs reduced energy expenditure in children with spastic CP. However, further studies with good PEDro scores are required for more conclusive evidence regarding the effectiveness of AFOs in children with CP.


Marine biofilms on artificial surfaces: structure and dynamics.
The search for new antifouling (AF) coatings that are environmentally benign has led to renewed interest in the ways that micro-organisms colonize substrates in the marine environment. This review covers recently published research on the global species composition and dynamics of marine biofilms, consisting mainly of bacteria and diatoms found on man-made surfaces including AF coatings. Marine biofilms directly interact with larger organisms (macrofoulers) during colonization processes; hence, recent literature on understanding the basis of the biofilm/macrofouling interactions is essential and will also be reviewed here. Overall, differences have been identified in species composition between biofilm and planktonic forms for both diatoms and bacteria at various exposure sites. In most studies, the underlying biofilm was found to induce larval and spore settlement of macrofoulers; however, issues such as reproducibility, differences in exposure sites and biofilm composition (natural multispecies vs. monospecific species) may influence the outcomes.


[Computer-aided diagnosis of fatty liver based on ultrasonic images].
This study aims to provide a computer-aided method for the diagnosis of fatty liver by B-scan ultrasonic imaging. Fatty liver is referred to the infiltration of triglycerides and other fats of the liver cells, which affected the texture of liver tissue. In this paper, some features including mean intensity ratio, as well as angular second moment, entropy and inverse differential moment of gray level co-occurrence matrix were extracted from B-scan ultrasonic liver images. Feature vectors which indicated two classes of images were created with the four features. Then we used kappa-means clustering algorithm, self-organized feature mapping (SOFM) artificial neural network and back-propagation (BP) artificial neural network to classify these vectors. The accuracy rate of kappa-means clustering algorithm was 100% for normal liver and 63.6% for fatty liver. The results of SOFM neural network showed that the accuracy rate was 84.8% for normal liver and 90.9% for fatty liver. The accuracy rate of neural network was 100% both for normal liver and fatty liver. This technology could detect the characteristics of B-scan images of normal liver and fatty liver more accurately. It could greatly improve the accuracy of the diagnosis of fatty liver.


Impact of posterior occlusal support on the condylar position.
The purpose of this study was to investigate condylar displacement related to the loss of posterior occlusal support. Each of 23 subjects received one occlusal adjusted splint that covered all teeth from the right to the left second mandibular molar. None of the subjects had a third molar and none of them had a missing tooth or showed tooth mobility. The splint was inserted and vertical and horizontal condylar position was measured by an ultrasonic motion analyser. The splint was then unilateraly shortened tooth-by-tooth up to the canine tooth and the measurement was repeated after each shortening. Cutting off the splint's second molar on one side lead to a slight ipsilateral cranial motion of the condyle if subjects clenched with maximum voluntary force. If the second and first molar were cut off, a noticeable cranial condylar movement of about 0.3 mm was observed even when teeth occluded with low force. These results suggest that loss of posterior occlusal support as it happens in routine oral rehabilitation leads to a noticeable cranial condyle movement during registration, even if the clenching force is low.


Compressive radial nerve palsy induced by military shooting training: clinical and electrophysiological study.
Ten recruited soldiers developed acute left wrist drop and numbness on the back of the thumb after a three hour military shooting training. Neurological examination disclosed decreased muscle power (0-2/5) of left wrist dorsiflexion, hypalgesia and hypaesthesia on the radial side of the left hand, and diminished brachioradialis reflex. Electrophysiological studies showed prolonged distal latency, reduced amplitude and slowness of left radial nerve motor conduction velocity between the axilla and elbow. Electromyography (EMG) revealed fibrillation potentials at rest, polyphasic motor unit and an incomplete interference pattern at volition over the extensor digitorum communis and brachioradialis. Nine patients recovered completely clinically and electrophysiologically between nine and 12 weeks after the onset of the palsy. Sensation recovered faster than the weakness. One patient failed to recover after three months, possibly because of the longer duration of nerve compression. Longer nerve compression time and sustained, decreased muscle power with signs of active denervation in EMG are indicators of poor prognosis.


Prognostic factors in patients with hepatocellular carcinoma. Attempts for the selection of patients with prolonged survival.
A prognostic study based on 127 untreated patients with hepatocellular carcinoma was undertaken to evaluate their survival time and to find clinical and biologic criteria which allow the selection of patients with a survival time longer than 60 days who could enter a therapeutic trial. Twenty-eight clinical and biologic variables were assessed using univariate and multivariate semiparametric regression (Cox's) models. Ten variables were isolated by univariate analysis. Multivariate analysis found a negative relationship between a survival time longer than 60 days and five of these variables; these variables were in decreasing order: encephalopathy, alcohol consumption, aspartate amino transferase (AST), blood urea nitrogen, and total bilirubin. Prevalence, positive, and negative predictive values of encephalopathy were 20%, 27.5%, and 97% respectively. When three other criteria: ASAT greater than four times the upper limit of the normal (N), blood urea nitrogen greater than N, and total bilirubin greater than 2N were added, their prevalence, positive, and negative predictive values were 72%, 89.7%, and 57.1% respectively. These results suggest that in countries where incidence of hepatocellular carcinoma is low and recruitment of patients difficult, absence of encephalopathy must be the only criterion for selection of patients with hepatocellular carcinoma in therapeutic trials; whereas, in countries with a high incidence of hepatocellular carcinoma the other criteria may be added.


Coral aquaculture to support drug discovery.
Marine natural products (NP) are unanimously acknowledged as the 'blue gold' in the urgent quest for new pharmaceuticals. Although corals are among the marine organisms with the greatest diversity of secondary metabolites, growing evidence suggest that their symbiotic bacteria produce most of these bioactive metabolites. The ex hospite culture of coral symbiotic microbiota is extremely challenging and only limited examples of successful culture exist today. By contrast, in toto aquaculture of corals is a commonly applied technology to produce corals for aquaria. Here, we suggest that coral aquaculture could as well be a viable and economically feasible option to produce the biomass required to execute the first steps of the NP-based drug discovery pipeline.


MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5.
Retinoblastoma is a common intraocular malignancy that occurs during childhood. MicroRNAs play critical roles in the regulation of retinoblastoma initiation and progression, and aberrant expression of miR-613 had been reported in various types of cancer. However, the role and mechanism of its function in retinoblastoma are still unclear. In this study, we found that miR-613 was downregulated in retinoblastoma tissues and cell lines. Overexpression of miR-613 suppressed retinoblastoma cell proliferation, migration, and invasion and induced cell cycle arrest in vitro. Additionally, overexpressed miR-613 also inhibited tumor formation of retinoblastoma cells in vivo. We further identified E2F5 as a direct target of miR-613. Reintroduction of E2F5 without 3'-untranslated region reversed the inhibitory effects of miR-613 on cell proliferation and invasion. Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma.


Cross-Scale Seepage Characteristics of Fractured Horizontal Wells in Tight Gas Reservoirs.
Tight gas reservoirs are rich in microscale pores and fractures. The effect of microscale gas seepage in tight sandstone matrix on gas well productivity cannot be ignored. At present, the effect of microscale gas flow on the well testing model of fractured horizontal wells has not been systematically studied. In this paper, first, the coupling influence mechanism of "multicomponent gas effect-fracture geometry characteristics" is expounded, second, a seepage model coupling the flow in the fracture and the flow in the gas reservoir is established on the fracture wall surface, and third, an unsteady pressure analysis model for fractured horizontal wells in tight gas reservoirs is established. Results show that (a) when the microscale fracture is at a quite small level, the Knudsen diffusion plays a dominant role at a wide range of pressures; (b) the mass transfer rate of multicomponent shale gas through macrofractures increases with increasing CO2 fraction; (c) the unsteady flow process is divided into six stages in turn: microscale diffusion stage, linear flow stage in fractures, linear flow stage between fractures, early radial flow stage in gas reservoirs, linear flow stage in gas reservoirs, and late radial flow stage in gas reservoirs; and (d) with an increase of dimensionless bottom-hole storage coefficient, the second and third stages of flow are gradually covered up.


In vitro approaches to investigation of the early steps of colicin-OmpF interaction.
The OmpF porin plays a central role during the colicin uptake by sensitive Escherichia coli cells. Lipopolysaccharide-OmpF complexes (-1bLPS-OmpF), which contain one tightly bound and no loosely bound LPS molecules for each porin trimer, is able to recognize and bind to immobilized colicins. This association is specific to colicins A and N, which both use the OmpF porin as receptor, and depends on the presence of the porin-receptor domain on the bacteriocin molecule. The -1bLPS-OmpF complex protects sensitive cells against colicin A and N activity. The protection level depends on the native conformation, as demonstrated by heat denaturation of the trimeric porin which abolishes the protection. This indicates that the purified OmpF trimer presents an affinity site for the colicin which efficiently mimics the native cellular receptor site. These results are discussed with regard to the conformation of the receptor site and to the early steps of colicin uptake.


Estimating ICU Benefit: A Randomized Study of Physicians.
The distinction between overuse and appropriate use of the ICU hinges on whether a patient would benefit from ICU care. We sought to test 1) whether physicians agree about which types of patients benefit from ICU care and 2) whether estimates of ICU benefit are influenced by factors unrelated to severity of illness. Randomized study. Online vignettes. U.S. critical care physicians. Physicians were provided with eight vignettes of hypothetical patients. Each vignette had a single patient or hospital factor randomized across participants (four factors related and four unrelated to severity of illness). The primary outcome was the estimate of ICU benefit, assessed with a 4-point Likert-type scale. In total, 1,223 of 8,792 physicians volunteered to participate (14% recruitment rate). Physician agreement of ICU benefit was poor (mean intraclass correlation coefficient for each vignette: 0.06; range: 0-0.18). There were no vignettes in which more than two thirds of physicians agreed about the extent to which a patient would benefit from ICU care. Increasing severity of illness resulted in greater estimated benefit of ICU care. Among factors unrelated to severity of illness, physicians felt ICU care was more beneficial when told one ICU bed was available than if ICU bed availability was unmentioned. Physicians felt ICU care was less beneficial when family was present than when family presence was unmentioned. The patient's age, but not race/ethnicity, also impacted estimates of ICU benefit. Estimates of ICU benefit are widely dissimilar and influenced by factors unrelated to severity of illness, potentially resulting in inconsistent allocation of ICU care.


Lobular capillary haemangioma of the nasal cavity during pregnancy.
We report a pregnant patient with a rapidly growing mass within the nasal cavity, which required pre-operative super-selective embolisation and subsequent removal under general anaesthesia after childbirth. We also discuss the clinical, radiological and histological characteristics of lobular capillary haemangioma, and its treatment. Case report and literature review. Lobular capillary haemangioma is a benign lesion originating in the vascular tissue of skin, mucosa, muscles, glands and bone. These lesions grow rapidly. Nasal localisation is rare. Microtrauma and pregnancy are the most commonly proposed aetiological factors. Reported incidence during pregnancy ranges from less than 2 per cent to approximately 5 per cent. The management of a pregnant woman with such a lesion may be complex, and depends on the severity of symptoms and the status of the pregnancy. Complete surgical excision, with or without pre-operative embolisation, is the treatment of choice. This uncommon lesion should be considered in any pregnant patient with a mass in the mouth or nasal cavity.