Therapeutic hypothermia after out-of-hospital cardiac arrest: evaluation of a regional system to increase access to cooling.
Therapeutic hypothermia (TH) improves survival and confers neuroprotection in out-of-hospital cardiac arrest (OHCA), but TH is underutilized, and regional systems of care for OHCA that include TH are needed. The Cool It protocol has established TH as the standard of care for OHCA across a regional network of hospitals transferring patients to a central TH-capable hospital. Between February 2006 and August 2009, 140 OHCA patients who remained unresponsive after return of spontaneous circulation were cooled and rewarmed with the use of an automated, noninvasive cooling device. Three quarters of the patients (n=107) were transferred to the TH-capable hospital from referring network hospitals. Positive neurological outcome was defined as Cerebral Performance Category 1 or 2 at discharge. Patients with non-ventricular fibrillation arrest or cardiogenic shock were included, and patients with concurrent ST-segment elevation myocardial infarction (n=68) received cardiac intervention and cooling simultaneously. Overall survival to hospital discharge was 56%, and 92% of survivors were discharged with a positive neurological outcome. Survival was similar in transferred and nontransferred patients. Non-ventricular fibrillation arrest and presence of cardiogenic shock were associated strongly with mortality, but survivors with these event characteristics had high rates of positive neurological recovery (100% and 89%, respectively). A 20% increase in the risk of death (95% confidence interval, 4% to 39%) was observed for every hour of delay to initiation of cooling. A comprehensive TH protocol can be integrated into a regional ST-segment elevation myocardial infarction network and achieves broad dispersion of this essential therapy for OHCA.


Association of HTRA1 and ARMS2 gene variation with drusen formation in rhesus macaques.
Age-related macular degeneration (AMD) is a clinically heterogeneous disease and constitutes the major cause of visual impairment in the elderly population worldwide. Rhesus macaques also possess a macula and, like humans, develop drusen-associated, age-related macular pathologies. Susceptibility to AMD in humans and drusen formation in rhesus macaques both have been shown to be associated with variation in the HTRA1 and ARMS2 genes. To corroborate these results we genotyped a cohort of 116 rhesus macaques with and without macular drusen. Like in humans, markers in the two genes showed a significant association with drusen formation at the genotype level. Joint haplotype analysis revealed, however, that the disease association observed in rhesus macaques was entirely attributable to a promoter polymorphism (-558G>T) of the HTRA1 gene.


Comparison of four strategies of ram management in a semen collection centre.
Thirty Merino rams were used to determine the effect of four management systems of rams on semen quality during the anoestrous season. Animals were divided into four groups: Artificial-Photoperiod group (AP; n = 8), which were isolated from females and exposed to artificial long days (16 hr/d) from 1 Feb to 15 Mar; Natural-Photoperiod (NP; n = 8), isolated from females and exposed to the natural photoperiod throughout the experiment; Oestrous-Ewe group (EE; n = 7), housed in a pen adjacent to another pen that housed three ewes in oestrus, and Anestric-Ewe group (AE; n = 7), housed adjacent to another pen that housed three ovariectomized ewes. From 20 Mar to the end of May (10 weeks), semen samples were collected weekly, and blood samples were collected to determine plasma testosterone concentrations. Mean plasma testosterone concentrations, ejaculate volume and reaction time were not affected either by treatment or week. There was a significant effect (p < .01) of ram treatment on sperm concentration, and both TM y PM, and their interaction, were significantly affected by group and week (p < .001). Rams exposed to ewes in oestrus presented the largest sperm concentration (p < .05) compared with the other three groups, although they had the lowest total and progressive motilities (p < .01). In conclusion, management strategy in spring affects semen quality of rams, with the presence of ewes in oestrus being the best plan to increase sperm concentration.


Quantitative Fit Test of a 3D Printed Frame Fitted Over a Surgical Mask: An Alternative Option to N95 Respirator.
COVID-19 has spread worldwide and caused severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to numerous dead cases. However, with the new COVID-19 outbreaks, there is a shortage of personal protective equipment (PPE) especially N95 masks worldwide including Thailand. This issue had placed the health professional in great need of an alternative mask. This study aimed to measure the fit factor of 3D printed frames by quantitative fit testing (QNFT) to find an alternative facemask by using a mask fitter together with 2 different kinds of the American Society for Testing and Materials (ASTM) level 1 surgical mask. Two commonly used surgical masks (Sultan Com-Fit Super Sensitive Ear Loop Mask or "White Mask Group," not water-resistant, and Sultan Blue Com-Fit Super High Filtration Ear Loop Mask or "Blue Mask Group," water-resistant) with and without 3D printed frame covering. The fit performance was measured by a quantitative fit test (QNFT) device (PortaCount, model 8048, TSI Incorporated, Minnesota, USA) accepted by the Occupational Safety and Health Administration (OSHA). The PortaCount device, which is based on a miniature continuous flow condensation nucleus counter (CNC), assesses the respiratory fit by comparing the concentration of ambient dust particles outside the surgical mask to the concentration that has leaked into the surgical mask. The ratio of these two concentrations (Cout/Cin) is called the fit factor. A fit factor of a 3D printed frame of at least 100 is required and considered as a pass level. We found that the mask fitter improves the overall performance of surgical masks significantly. The improved performance is comparable to that of N95. The mask fitter improves the performance of surgical masks. The authors suggested that further study on frame material, shape, and expanded sample size would be beneficial to society.


Simultaneous quantification of APP and tau mRNA by RT-PCR.
We describe here a method for simultaneous relative quantitation of APP and tau expressions in rat muscle using polymerase chain reaction combined with reverse transcription. The target mRNAs were coamplified with an internal control, glyceraldehyde-3-phosphate dehydrogenase (G3PD). The amplified products were measured with a laser image analyzer, and the values were plotted against the cycle number. In the exponential phase of amplification, the linearity and reproducibility of RT-PCR demonstrate identical efficiencies of cDNA synthesis and PCR amplification for APP, tau and G3PD. These results suggest that in the exponential phase of amplification, a relative quantitation of target mRNAs could be accomplished by normalization with internal control. Preliminary experiments indicate that the expressions of both APP and tau in rat muscle were first increased and then decreased by chronic intoxication with chloroquine.


On the Capability of QoE Improvement Based on the Adjustment of RLC Parameters.
The constant evolution in mobile communications networks have led operators to seek new techniques to optimize their mobile networks with the objective of satisfying the expectations of the users. In this way, traditional optimization techniques based on improving radio indicators, have given way to new techniques based on improving the quality of experience (QoE) perceived by users. This paper is focused on analyzing the impact of the adjustment of radio link control (RLC) layer configuration parameters on the QoE perceived by the users of two different types of services. Firstly, an evaluation of the QoE experienced by the user of a real-time video streaming service with respect to the transmission buffer size of the RLC layer in unacknowledged mode (UM) has been carried out. Secondly, the QoE perceived by the user of a file transfer service in relation to the variation of the configuration parameters of the RLC layer in acknowledged mode (AM) has been evaluated. The study, which has been carried out in a simulated cellular environment, has been performed for different system bandwidth values, thus proving the relationship between the QoE perceived by the users, the optimal RLC configuration parameters values and the available bandwidth.


Average 3D Skeletofacial Model as a Template for Maxillomandibular Repositioning During Virtual Orthognathic Surgical Planning.
Virtual planning has revolutionized orthognathic surgery. This study presents a computer-assisted method for constructing average three-dimensional (3D) skeletofacial models that can be applied as a template for surgical planning for maxillomandibular repositioning. We used the images of 60 individuals (30 women and 30 men) who had never undergone orthognathic surgery to construct an average 3D skeletofacial model for male participants and one for female participants. We validated the accuracy of the newly developed skeletofacial models by comparing their images with 30 surgical simulation images (i.e., skulls) that had been created using 3D cephalometric normative data. The comparison was conducted by superimposing surgical simulation images created using our models with the previously created images to analyze their differences, particularly differences in the jawbone position. For all participants, we compared the jaw position in the surgical simulation images created using our average 3D skeletofacial models with that in the images created using 3D cephalometric normative data. The results revealed that the planned maxillary and mandibular positions were similar in both images and that the differences between all facial landmarks were <1 mm, except for one dental position. Most studies have reported <2 mm to be the success criterion for the distance difference between planned and outcome images; thus, our data indicate high consistency between the images in terms of jawbone position. Our average 3D skeletofacial models provide an innovative template-assisted orthognathic surgery planning modality that can enhance the fully digital workflow for virtual orthognathic surgical planning. Therapeutic, II.


Life-long dynamics of the swine gut microbiome and their implications in probiotics development and food safety.
The swine gut microbiome has received remarkable attention in recent years given that pigs serve not only as important sources for animal-derived food but also as excellent biomedical models for human health. However, despite recent advances in the understanding of the swine gut microbiome, many important biological and ecological questions are still largely unanswered. In a recent study, we characterized the life-long dynamics of the swine gut microbiome from birth to market. We showed distinct shifts in gut microbiome structure along different growth stages mainly driven by diet. Here, we summarize these discoveries and provide additional data related to the core swine gut microbiome, probiotics development in the swine industry, and foodborne pathogens in the pork supply chain.


Upper limb joint coordination preserves hand kinematics after a traumatic brachial plexus injury.
Traumatic brachial plexus injury (TBPI) causes a sensorimotor deficit in upper limb (UL) movements. Our aim was to investigate the arm-forearm coordination of both the injured and uninjured UL of TBPI subjects. TBPI participants (n = 13) and controls (n = 10) matched in age, gender, and anthropometric characteristics were recruited. Kinematics from the shoulder, elbow, wrist, and index finger markers were collected, while upstanding participants transported a cup to their mouth and returned the UL to a starting position. The UL coordination was measured through the relative phase (RP) between arm and forearm phase angles and analyzed as a function of the hand kinematics. For all participants, the hand transport had a shorter time to peak velocity (p < 0.01) compared to the return. Also, for the control and the uninjured TBPI UL, the RP showed a coordination pattern that favored forearm movements in the peak velocity of the transport phase (p < 0.001). TBPI participants' injured UL showed a longer movement duration in comparison to controls (p < 0.05), but no differences in peak velocity, time to peak velocity, and trajectory length, indicating preserved hand kinematics. The RP of the injured UL revealed altered coordination in favor of arm movements compared to controls and the uninjured UL (p < 0.001). Finally, TBPI participants' uninjured UL showed altered control of arm and forearm phase angles during the deceleration of hand movements compared to controls (p < 0.05). These results suggest that UL coordination is reorganized after a TBPI so as to preserve hand kinematics.


Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans.
Rifapentine (RPT) is a rifamycin antimycobacterial and, as part of a combination therapy, is indicated for the treatment of pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis Although the results from a number of studies indicate that rifapentine has the potential to shorten treatment duration and enhance completion rates compared to other rifamycin agents utilized in antituberculosis drug regimens (i.e., regimens 1 to 4), its optimal dose and exposure in humans are unknown. To help inform such an optimization, a physiologically based pharmacokinetic (PBPK) model was developed to predict time course, tissue-specific concentrations of RPT and its active metabolite, 25-desacetyl rifapentine (dRPT), in humans after specified administration schedules for RPT. Starting with the development and verification of a PBPK model for rats, the model was extrapolated and then tested using human pharmacokinetic data. Testing and verification of the models included comparisons of predictions to experimental data in several rat tissues and time course RPT and dRPT plasma concentrations in humans from several single- and repeated-dosing studies. Finally, the model was used to predict RPT concentrations in the lung during the intensive and continuation phases of a current recommended TB treatment regimen. Based on these results, it is anticipated that the PBPK model developed in this study will be useful in evaluating dosing regimens for RPT and for characterizing tissue-level doses that could be predictors of problems related to efficacy or safety.


Hemicholinium-3 sensitive choline transport in human T lymphocytes: Evidence for use as a proxy for brain choline transporter (CHT) capacity.
The synaptic uptake of choline via the high-affinity, hemicholinium-3-dependent choline transporter (CHT) strongly influences the capacity of cholinergic neurons to sustain acetylcholine (ACh) synthesis and release. To advance research on the impact of CHT capacity in humans, we established the presence of the neuronal CHT protein in human T lymphocytes. Next, we demonstrated CHT-mediated choline transport in human T cells. To address the validity of T cell-based choline uptake as a proxy for brain CHT capacity, we isolated T cells from the spleen, and synaptosomes from cortex and striatum, of wild type and CHT-overexpressing mice (CHT-OXP). Choline uptake capacity in T cells from CHT-OXP mice was two-fold higher than in wild type mice, mirroring the impact of CHT over-expression on synaptosomal CHT-mediated choline uptake. Monitoring T lymphocyte CHT protein and activity may be useful for estimating human CNS cholinergic capacity and for testing hypotheses concerning the contribution of CHT and, more generally, ACh signaling in cognition, neuroinflammation and disease.


Mixed-Modality Stimulation to Evoke Two Modalities Simultaneously in One Channel for Electrocutaneous Sensory Feedback.
One of the long-standing challenges in upper limb prosthetics is restoring the sensory feedback that is missing due to amputation. Two approaches have previously been presented to provide various types of sensory information to users, namely, multi-modality sensory feedback and using an array of single-modality stimulators. However, the feedback systems used in these approaches were too bulky to be embedded in prosthesis sockets. In this paper, we propose an electrocutaneous sensory feedback method that is capable of conveying two modalities simultaneously with only one electrode. The stimulation method, which we call mixed-modality stimulation, utilizes the phenomenon in which the superposition of two electric pulse trains of different frequencies is able to evoke two different modalities (i.e., pressure and tapping) at the same time. We conducted psychophysical experiments in which healthy subjects were required to recognize the intensity of pressure or the frequency of tapping from mixed-modality or two-channel stimulations. The results demonstrated that the subjects were able to discriminate the features of the two modalities in one electrode during mixed-modality stimulation and that the accuracies of successful recognitions (mean ± standard deviation) for the two feedback variables were 84.3 ± 7% for mixed-modality stimulation and 89.5 ± 6% for two-channel dual-modality stimulation, showing no statistically significant difference. Therefore, mixed-modality stimulation is an attractive method for modulating two modalities independently with only one electrode, and it could be used for implementing a compact sensory feedback system that is able to provide two different types of sensory information from prosthetics.


Dialectical behaviour therapy for posttraumatic stress disorder related to childhood sexual abuse: a pilot study in an outpatient treatment setting.
Background: Dialectical behaviour therapy for posttraumatic stress disorder (DBT-PTSD), which is tailored to treat adults with PTSD and co-occurring emotion regulation difficulties, has already demonstrated its efficacy, acceptance and safety in an inpatient treatment setting. It combines elements of DBT with trauma-focused cognitive behavioural interventions. Objective: To investigate the feasibility, acceptance and safety of DBT-PTSD in an outpatient treatment setting by therapists who were novice to the treatment, we treated 21 female patients suffering from PTSD following childhood sexual abuse (CSA) plus difficulties in emotion regulation in an uncontrolled clinical trial. Method: The Clinician Administered PTSD Symptom Scale (CAPS), the Davidson Trauma Scale (DTS), the Borderline Section of the International Personality Disorder Examination (IPDE) and the Borderline Symptom List (BSL-23) were used as primary outcomes. For secondary outcomes, depression and dissociation were assessed. Assessments were administered at pretreatment, post-treatment and six-week follow-up. Results: Improvement was significant for PTSD as well as for borderline personality symptomatology, with large pretreatment to follow-up effect sizes for completers based on the CAPS (Cohens d = 1.30), DTS (d = 1.50), IPDE (d = 1.60) and BSL-23 (d = 1.20). Conclusion: The outcome suggests that outpatient DBT-PTSD can safely be used to reduce PTSD symptoms and comorbid psychopathology in adults who have experienced CSA.


Instrumental development attachable to high magnification microscopes for obtaining totally focalized images.
A complete system (instrumentation and software) for acquiring micrograph images with an extended depth of focus and with no alteration to the original chromaticity has been developed. The buildup system includes (a) the electromechanical components to be coupled to a commercial microscope in order to improve it, (b) a computer program with which the focusing distance can be micrometrically modified at the same time that a set of digital images can be acquired, and (c) software that permits the in-focus pixels of each image to be extracted and incorporated into a global image with an extended depth of focus greater than that supplied by the optical characteristics of the objective used to visualize the sample. The algorithm used does not have any influence on the sample chromaticity and the generated image can be obtained with full chromaticity.


Atomic Layer Deposition of Alumina-Coated Thin-Film Cathodes for Lithium Microbatteries.
This work shows the electrochemical performance of sputter-deposited, binder-free lithium cobalt oxide thin films with an alumina coating deposited via atomic layer deposition for use in lithium-metal-based microbatteries. The Al2O3 coating can improve the charge-discharge kinetics and suppress the phase transition that occurs at higher potential limits where the crystalline structure of the lithium cobalt oxide is damaged due to the formation of Co4+, causing irreversible capacity loss. The electrochemical performance of the thin film is analysed by imposing 4.2, 4.4 and 4.5 V upper potential limits, which deliver improved performances for 3 nm of Al2O3, while also highlighting evidence of Al doping. Al2O3-coated lithium cobalt oxide of 3 nm is cycled at 147 µA cm-2 (~2.7 C) to an upper potential limit of 4.4 V with an initial capacity of 132 mAh g-1 (65.7 µAh cm-2 µm-1) and a capacity retention of 87% and 70% at cycle 100 and 400, respectively. This shows the high-rate capability and cycling benefits of a 3 nm Al2O3 coating.


Case-control comparison of quality of life in long-term ovarian germ cell tumor survivors: a gynecologic oncology group study.
Ovarian germ cell cancer is a rare tumor. Approximately 1000 to 2000 women in the United States will be diagnosed with ovarian germ cell cancer in 2007. When it occurs, it is usually diagnosed before age 20 and is highly responsive to therapy. Most patients live a full life span. The 5-year relative survival rate is 95%. This article describes differences in quality of life issues between ovarian germ cell cancer survivors and young women who have not experienced cancer and were matched to survivors on age, education, and race (by the acquaintance control method). Survivors and controls completed mail and phone surveys. A multivariable logistic regression model was adjusted for age, education, household income, marital status, and perception of fertility. Compared to controls, germ cell cancer survivors expressed more reproductive concerns and reported worse sexual functioning, but they also experienced greater appreciation of life and more affective (i.e., emotional) social support. Future research is suggested to test interventions to enhance quality of life for ovarian germ cell cancer survivors in the areas of sexual functioning and reproductive concerns, but only for survivors who are in distress or in need of the support. Potential screening questions are offered for clinicians, but further research is needed to assess their validity as screening tools.


Crossover regime of optical vortices generation via electro-optic nonlinearity: the problem of optical vortices with the fractional charge generated by crystals.
In this work, we analyze the behavior of topological defects of optical indicatrix orientation induced by a conically shaped electric field in crystals in a crossover regime that appears at intermediate fields separating the regimes of prevailing Pockels and Kerr electro-optic nonlinearities. We have found that increases in the electric voltage applied to a crystal induce neither topological defects, with the strengths being not multiples of ½, or the optical vortices with fractional charges. Instead, there appear some additional topological defects of the optical indicatrix orientation, the behavior of which we have studied in detail.


Effects of age on complications in adult onset diabetes.
The prevalence of diabetes is greatest among older persons, yet few studies have specifically addressed the impact of age on diabetic complications. The present study examines the prevalence of four diabetic complications: retinopathy, peripheral neuropathy, autonomic neuropathy, and hypertension, as well as depression, in older male patients with noninsulin-dependent diabetes. Participants ranged in age from 53 to 80 years. Multiple risk factors, including age, duration of illness, type of treatment, metabolic control, and obesity were evaluated as predictors of these complications using logistic regression. Results suggest a significant increase in the prevalence of retinopathy with aging, independent of the effects of metabolic control, duration of illness, and other risk variables. Age was also related to prevalence of peripheral neuropathy symptoms, hypertension, and impotence. Current metabolic control was significantly associated with retinopathy, peripheral neuropathy, and hypertension prevalence. Time since diagnosis was only independently related to impotence and hypertension. These findings suggest that the increase in many diabetic complications in older persons cannot be wholly accounted for by simple disease status variables, and may result from an interaction of diabetes variables and general age-related changes.


Comparison of angiographic and postmortem findings in patients with coronary artery disease.
The accuracy of coronary cineangiography in predicting the degree of stenosis in coronary arteries was evaluated by comparing autopsy and premortem cineangiographic findings in 25 patients. Coronary cineangiograms and autopsy specimens were reviewed independently by two cardiologists and two pathologists. Identical diagrams dividing the cononary arteries into 12 segments were used by both groups to record the location and degree of stenosis observed. Cineangiographic findings were in agreement with pathologic findings (less than 25 percent difference in cross-sectional luminal area) in 178 (79 percent) of the 226 segments examined, but overestimated the degree of stenosis in 13 (6 percent) and underestimated it in 34 (15 percent). Thus, cineangiography appears to be a reliable tool in evaluating coronary artery disease. When diagnostic errors are made, they are usually underestimations of the degree of disease; common causes of error are circumferential stenosis, eccentric lesions, obstruction of view by artifical valves and poor opacification due to severe proximal stenosis.


Tryptophan-containing peptide helices: interactions involving the indole side chain.
Two designed peptide sequences containing Trp residues at positions i and i + 5 (Boc-Leu-Trp-Val-Ala-Aib-Leu-Trp-Val-OMe, 1) as well as i and i + 6 (Boc-Leu-Trp-Val-Aib-Ala-Aib-Leu-Trp-Val-OMe, 2) containing one and two centrally positioned Aib residues, respectively, for helix nucleation, have been shown to form stable helices in chloroform solutions. Structures derived from nuclear magnetic resonance (NMR) data reveal six and seven intramolecularly hydrogen-bonded NH groups in peptides 1 and 2, respectively. The helical conformation of octapeptide 1 has also been established in the solid state by X-ray diffraction. The crystal structure reveals an interesting packing motif in which helical columns are stabilized by side chain-backbone hydrogen bonding involving the indole Nepsilon1H of Trp(2) as donor, and an acceptor C=O group from Leu(6) of a neighboring molecule. Helical columns also associate laterally, and strong interactions are observed between the Trp(2) and Trp(7) residues on neighboring molecules. The edge-to-face aromatic interactions between the indoles suggest a potential C-H...pi interaction involving the Czeta3H of Trp(2). Concentration dependence of NMR chemical shifts provides evidence for peptide association in solution involving the Trp(2) Nepsilon1H protons, presumably in a manner similar to that observed in the crystal.


The effect of starvation and re-feeding on mitochondrial potential in the midgut of Neocaridina davidi (Crustacea, Malacostraca).
The midgut in the freshwater shrimp Neocaridina davidi (previously named N. heteropoda) (Crustacea, Malacostraca) is composed of a tube-shaped intestine and a large hepatopancreas that is formed by numerous blind-ended tubules. The precise structure and ultrastructure of these regions were presented in our previous papers, while here we focused on the ultrastructural changes that occurred in the midgut epithelial cells (D-cells in the intestine, B- and F- cells in the hepatopancreas) after long-term starvation and re-feeding. We used transmission electron microscopy, light and confocal microscopes and flow cytometry to describe all of the changes that occurred due to the stressor with special emphasis on mitochondrial alterations. A quantitative assessment of cells with depolarized mitochondria helped us to establish whether there is a relationship between starvation, re-feeding and the inactivation/activation of mitochondria. The results of our studies showed that in the freshwater shrimp N. davidi that were analyzed, long-term starvation activates the degeneration of epithelial cells at the ultrastructural level and causes an increase of cells with depolarized (non-active) mitochondria. The process of re-feeding leads to the gradual regeneration of the cytoplasm of the midgut epithelial cells; however, these changes were observed at the ultrastructural level. Additionally, re-feeding causes the regeneration of mitochondrial ultrastructure. Therefore, we can state that the increase in the number of cells with polarized mitochondria occurs slowly and does not depend on ultrastructural alterations.


c-Met and NF-κB-dependent overexpression of Wnt7a and -7b and Pax2 promotes cystogenesis in polycystic kidney disease.
The mechanisms of cystogenesis in autosomal dominant polycystic kidney disease (ADPKD) are not fully understood. Hyperactivation of the tyrosine kinase c-Met contributes to cyst formation, but we do not know the downstream mediators. Here, we found that hyperactivated c-Met led to increased NF-κB signaling, which in turn, drove de novo expression of Wnt7a and overexpression of Wnt7b in Pkd1(-/-) mouse kidneys. Hyperactivated Wnt signaling increased expression of the transcription factor Pax2 in the cells lining cysts. Furthermore, blocking Wnt signaling with DKK1 decreased cyst formation in an organ culture model of ADPKD. In summary, these results suggest that the c-Met/NF-κB/Wnt/Pax2 signaling transduction axis may provide pharmacological targets for the treatment of ADPKD.


Toward a central-peripheralist model of work decrement.
Payne and others, within a Hullian framework, have analytically defined reactive inhibition in terms of a negative drive occurring within the effector system. In strong support, they have demonstrated that the maintenance of work decrement is dependent upon limb, but not task, specificity. However, equally creditable research by Adams allows interpretations of inhibition based on the processing of information. These contrasting arguments are evaluated, and an initial model integrating the two is proposed.


Propeptin, a new inhibitor of prolyl endopeptidase produced by microbispora II. Determination of chemical structure.
The structure of propeptin, a new inhibitor of prolyl endopeptidase isolated from Microbispora sp. SNA-115, was determined. FAB/MS, Edman degradation and amino acid analysis revealed propeptin to be a cyclic polypeptide consisting of 19 common L-amino acids. By FAB/MS and protein chemical methods, the primary sequence of propeptin was determined to be Gly1-Tyr-Pro-Trp-Trp-Asp-Tyr-Arg-Asp9-Leu-Phe-Gly-Gly-His-Thr-Phe-Ile-Ser-Pro19, which cyclizes between the beta-carboxyl group of Asp9 and the a-amino group of Gly1.


Demographic inference through approximate-Bayesian-computation skyline plots.
The skyline plot is a graphical representation of historical effective population sizes as a function of time. Past population sizes for these plots are estimated from genetic data, without a priori assumptions on the mathematical function defining the shape of the demographic trajectory. Because of this flexibility in shape, skyline plots can, in principle, provide realistic descriptions of the complex demographic scenarios that occur in natural populations. Currently, demographic estimates needed for skyline plots are estimated using coalescent samplers or a composite likelihood approach. Here, we provide a way to estimate historical effective population sizes using an Approximate Bayesian Computation (ABC) framework. We assess its performance using simulated and actual microsatellite datasets. Our method correctly retrieves the signal of contracting, constant and expanding populations, although the graphical shape of the plot is not always an accurate representation of the true demographic trajectory, particularly for recent changes in size and contracting populations. Because of the flexibility of ABC, similar approaches can be extended to other types of data, to multiple populations, or to other parameters that can change through time, such as the migration rate.


Attitudinal Barriers to Analgesic Use among Patients with Substance Use Disorders.
Attitudinal barriers towards analgesic use among primary care patients with chronic pain and substance use disorders (SUDs) are not well understood. We evaluated the prevalence of moderate to significant attitudinal barriers to analgesic use among 597 primary care patients with chronic pain and current analgesic use with 3 subscales from the Barriers Questionaire II: concern about side effects, fear of addiction, and worry about reporting pain to physicians. Concern about side effects was a greater barrier for those with opioid use disorders (OUDs) and non-opioid SUDs than for those with no SUD (OR (95% CI): 2.30 (1.44-3.68), P < 0.001 and 1.64 (1.02-2.65), P = 0.041, resp.). Fear of addiction was a greater barrier for those with OUDs as compared to those with non-opioid SUDs (OR (95% CI): 2.12 (1.04-4.30), P = 0.038) and no SUD (OR (95% CI): 2.69 (1.44-5.03), P = 0.002). Conversely, participants with non-opioid SUDs reported lower levels of worry about reporting pain to physicians than those with no SUD (OR (95% CI): 0.43 (0.24-0.76), P = 0.004). Participants with OUDs reported higher levels of worry about reporting pain than those with non-opioid SUDs (OR (95% CI): 1.91 (1.01-3.60), P = 0.045). Concerns about side effects and fear of addiction can be barriers to analgesic use, moreso for people with SUDs and OUDs.


School-time physical activity among Arab elementary school children in Qatar.
Recent data from a self-administered questionnaire show that approximately 75% of school children in Qatar do not meet the daily recommended levels of physical activity (PA). Since children spend half of their waking hours in school, it is important to understand when and how much PA children accumulate during the school day. This study aimed to objectively assess school-time PA among elementary school children in Qatar and to determine association of PA with age, gender, body mass index (BMI) status, or day of the week. A cross-sectional epidemiological study was conducted in four randomly selected elementary schools in Qatar. Two classes representing grade 1 children (age 5) and grade 4 children (age 9) were randomly selected within each school. A total of 183 elementary school children (86 boys and 97 girls) ages 6-12 years participated in this study. PA was assessed using a three-axial accelerometer (ActiGraph® wGT3X-BT). Participants wore accelerometers on their non-dominant wrist at school (7:00 a.m. to 1:00 p.m.) for five consecutive school days during the week. A cutoff points of 818 counts per 5 s was classified as moderate-to-vigorous physical activity (MVPA). The average duration of MVPA in our study was 28.2 ± 13.5 min per day. Only 39% of participated children reach the recommended school-based MVPA of 30 min or more per day. Students spent on average 58.1 ± 8.4% of school time on sedentary activities. MVPA of boys and girls was similar in age 5 while girls age 9 were less active (23.7 ± 1.5 min/day) than boys of the same age (42.7 ± 1.8 min/day), ES = 0.269, P < 0.001. Neither overweight children nor children at risk for being overweight showed any differences in physical activity parameters when compared to children of normal weight. Our results showed, percentage of MVPA on the first (7.7 ± 5.1%) and last (7.1 ± 4.1%) day of the week was generally lower compared to other weekdays (P < 0.001). This was the first study to objectively assess PA during school hours among elementary school-children in Qatar. This study found that many of school children do not perform sufficient time being physically active at school. All students in two age categories (age 5 and age 9) spend the majority of school time engaged in sedentary activities. The low participation of girls age 9 in MVPA is a cause for concern and need to be addressed.


Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features.
Mendelian susceptibility to mycobacterial diseases confers predisposition to clinical disease caused by weakly virulent mycobacterial species in otherwise healthy individuals. Since 1996, disease-causing mutations have been found in five autosomal genes (IFNGR1, IFNGR2, STAT1, IL12B, IL12BR1) and one X-linked gene (NEMO). These genes display a high degree of allelic heterogeneity, defining at least 13 disorders. Although genetically different, these conditions are immunologically related, as all result in impaired IL-12/23-IFN-gamma-mediated immunity. These disorders were initially thought to be rare, but have now been diagnosed in over 220 patients from over 43 countries worldwide. We review here the molecular, cellular, and clinical features of patients with inborn errors of the IL-12/23-IFN-gamma circuit.


Research on the utilisation of waste chromic materials in the sodium chromate production process.
The results of investigations on the utilisation of waste chromic materials for the production of sodium chromate have been presented. The optimal parameters of the sodium chromate production, which make it possible to select the best technological solutions, have been determined. A mathematical model based on a system of equations describing the process of sodium chromate production as a function of selected process parameters has been devised. This allows the values useful for a practical estimation of the process, such as mass balances, technological indicators and especially the quantity of the produced chromic waste, to be determined.


The supraependymal fibres (SEF) of the mouse brain. as visualized by the Golgi method.
The well-known Golgi method, which impregnates, among other elements, unmyelinated fibres, has been proved suitable to visualize a dense plexus of very winding and smooth axonal processes lying all over the ventricular surface of the mouse brain. Comparisons with other cytochemical studies correlate quite well the pattern of distribution of these supraependymal fibres (SEF), and allow the characterization of most of these axons as serotoninergic. Combining thick sections, selective impregnation and well-defined plane of section, a restricted exit zone of the SEF in the fourth ventricle has been found over the raphe dorsalis region, which is known from previous studies to represent the main site of origin of serotoninergic fibres in the brain. However, this fact does not exclude the possibility of other pathways, yet to be discovered.


Efficacy of parent-child interaction therapy: interim report of a randomized trial with short-term maintenance.
Describes interim results of a study examining the effectiveness of parent-child interaction therapy (PCIT) with families of preschool-age children with oppositional defiant disorder. Following an initial assessment, 64 clinic-referred families were randomly assigned to an immediate treatment (i.t.) or a wait-list control (WL) condition. Results indicated that parents in the IT condition interacted more positively with their child and were more successful in gaining their child's compliance than parents in the WL condition. In addition, parents who received treatment reported decreased parenting stress and a more internal locus of control. Parents in the IT group reported statistically and clinically significant improvements in their child's behavior following PCIT. All families who received treatment reported high levels of satisfaction with both the content and process of PCIT. Preliminary 4-month follow-up data showed that parents maintained gains on all self-report measures.


Role of various pharmacologic agents in alveolar bone regeneration: A review.
Alveolar bone and gingiva are components of the periodontium that house the tooth. It constantly adapts itself to the masticatory forces and position of the tooth. However, localized diseases like chronic periodontitis and certain systemic diseases destroy periodontal tissues, which include the alveolar bone. Various pharmacological agents are being explored for their pleiotropic properties to combat the destruction of alveolar bone. This review focuses on the role of pharmacological agents in alveolar bone regeneration.


Secondary epileptogenesis in humans.
Secondary epileptogenesis as it applies to humans remains a controversial topic despite 40 years of investigation. Part of the controversy stems from disagreement about the definition of secondary epileptogenesis, and part of the controversy stems from the imperfect fit of animal models to the human epileptic syndromes. It may be that models of secondary epileptogenesis can be useful to describe specific epileptic syndromes such as bitemporal epilepsy and secondary bilateral synchrony, but other models may be required for remitting syndromes such as the Landau-Kleffner syndrome. The concept of secondary epileptogenesis may also provide a useful construct for evaluating patients with partial epileptic syndromes, especially those under consideration for epilepsy surgery, and for the evaluation of preventive strategies in epilepsy.


The speed of FtsZ treadmilling is tightly regulated by membrane binding.
As one of the key elements in bacterial cell division, the cytoskeletal protein FtsZ appears to be highly involved in circumferential treadmilling along the inner membrane, yielding circular vortices when transferred to flat membranes. However, it remains unclear how a membrane-targeted protein can produce these dynamics. Here, we dissect the roles of membrane binding, GTPase activity, and the unstructured C-terminal linker on the treadmilling of a chimera FtsZ protein through in vitro reconstitution of different FtsZ-YFP-mts variants on supported membranes. In summary, our results suggest substantial robustness of dynamic vortex formation, where only significant mutations, resulting in abolished membrane binding or compromised lateral interactions, are detrimental for the generation of treadmilling rings. In addition to GTPase activity, which directly affects treadmilling dynamics, we found a striking correlation of membrane binding with treadmilling speed as a result of changing the MTS on our chimera proteins. This discovery leads to the hypothesis that the in vivo existence of two alternative tether proteins for FtsZ could be a mechanism for controlling FtsZ treadmilling.


Protein Kinases as Targets for Opisthorchis viverrini- Associated Cholangiocarcinoma Therapy.
Protein kinases are enzymes that catalyze the transfer of phosphate from ATP to the serine/threonine or tyrosine residues of target molecules. These are key important mediators in a signaling cascade involved in several biological processes. Dysregulation of their activity has been found in various tumors. From the increased understanding of kinase structure and activation mechanisms emerged new strategies for targeting kinase in cancer treatment. Nowadays, kinase specific inhibitors are developed and widely used for clinical cancer treatment. In this review, we focus on protein kinases that are involved in cholangiocarcinoma (CCA). CCA is a slow progression tumor that is recognized as a major public health issue in northeastern Thailand. The standard regimen for CCA treatment is surgical resection. However, the patient's clinical outcome is still problematic. Therefore, the search to identify molecular mechanisms and molecules that are involved in carcinogenesis and the progression of CCA that can be used as therapeutic targets is urgently required. Aberrant expression and activation, as well as the functions of protein kinases in CCA, have been extensively studied in order to apply them as therapeutic targets. This review provides the information on protein kinases and their activity in CCA, as well as the preclinical data on kinase inhibitors that have been evaluated for this cancer.


Congenital cerebrospinal fluid fistula through the inner ear and meningitis.
Congenital deformities of the labyrinth of the inner ear can be associated with a fistulous communication between the intracranial subarachnoid space and the middle ear cavity. We describe seven such cases, six confirmed by high resolution CT and one by postmortem histological section. The seven patients all presented with meningitis although a cerebrospinal fluid fistula was demonstrated at subsequent surgery or postmortem. The lesions were bilateral in three patients, unilateral in three and probably bilateral in the postmortem case although only one temporal bone was obtained. In every case there was a dilated sac instead of the normal two and a half turn cochlea on the affected side and this was confirmed at surgery. The demonstration of the basal cochlear turn is of paramount importance in any deaf child presenting with meningitis. A true Mondini deformity with a normal basal turn and some hearing is not at risk of developing a fistula.


[Evaluation of the appropriateness of hospital use: the case of IRCCS Ospedale Maggiore di Milano, Italy].
To measure the level of not appropriated hospital use for some DRG's a Lombardia Region AEP version was applied to two units in the Ospedale Maggiore in Milano. The aims of the study was to evaluate the level of appropriateness in Neurology and Dermatology wards for some DRG's which are at risk to be applied in not appropriated way, to study the reasons of not appropriated use, to educate medical doctors in neurology and dermatology to apply for the right level of care for they patients and to highlight some limits of the Lombardia Regional protocol.


KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation.
Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity. A cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls. Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate. KIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.


Influence of DNA structure on adjacent site cooperative binding.
Previous NMR studies of Hoechst 33258 with the d(CTTTTGCAAAAG)2 sequence have shown very strong (K2 >> K1) cooperativity between two adjacent binding sites (Searle, M. S.; Embrey, K. J. Nucleic Acids Res. 1990, 18 (13), 3753- 3762). In contrast, surface plasmon resonance (SPR) results with the hairpin analog of the same sequence show significantly reduced cooperativity. In an effort to explain the difference, two-dimensional (2-D) NMR experiments were done on both duplex and hairpin. Hoechst 33258 and an amidine analog, DB183, show very strong cooperativity with the duplex DNA but much weaker cooperativity with the hairpin. The significantly lower thermal melting temperature (Tm) of the duplex (34.8 degrees C) in comparison to its hairpin analog (62.3 degrees C) supports the idea of a dynamic difference between the two DNA structures that can influence cooperativity in binding. These results confirm the role of conformational entropy in positive cooperativity in some DNA interactions.


Activation of CB2 cannabinoid receptors: a novel therapeutic strategy to accelerate osseointegration of dental implants.
Dental implants have been widely inserted in jaw bones as substitutes for teeth to restore oral function over the last few decades, but there still remains a major challenge in difficult clinical situations with poor bone quality and quantity or some diseases like osteoporosis. In the meantime, the bone healing phase and convalescence time after dental implantation should be curtailed to reduce the inconvenience for patients. The osseointegration has been considered the most appropriate bone-implant interface and is crucial for the clinical success of dental implants. The endocannabinoid system is present in some mammalian organs and tissues. Recently, endocannabinoids and their receptors, CB2 cannabinoid receptors, have been discovered in the skeleton. Osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells, synthesize the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) and express CB2 cannabinoid receptors. The activation of CB2 contributes to the maintenance of bone mass by stimulation of osteoblastic bone formation and inhibition of osteoclastic bone resorption. Therefore, we hypothesize that the activation of CB2 with a CB2-specific agonist, such as HU-308, might be a novel therapeutic strategy to accelerate osseointegration of dental implants. HU-308, incorporated into dental implants, might be a desirable agent used in implant dentistry for a higher clinical success rate and a curtailed convalescence time.


Hourly change in cercarial densities of Schistosoma haematobium and S. bovis at different depths in the water and distances from the shore of a dam in Kwale District, Kenya.
Hourly change in cercarial densities was studied at different depths in the water and distances from the shore at a dam in Kwale District (Kenya), where Schistosoma haematobium is highly endemic, by using a filtration apparatus for detecting cercariae. The peak of cercarial density at the surface of water (2-3 cm deep) was at 11:00 hours. Those at the middle point (25 cm deep) and the bottom (50 cm deep) were at 12:00 and 13:00 hours respectively. In the morning, the majority of cercariae (79% of the total detected) was obtained at the surface of water, but none at the bottom. After midday, 40% of the cercariae were obtained at the bottom. Cercariae seemed to sink with time resulting in a wider distribution in the water. The numbers of cercariae obtained at a sampling point 20 cm from the shore, which was inside the wire-screened snail-free area, were 3.4-23 times more than those obtained at a sampling point 340 cm from the shore, indicating that cercariae were accumulating immediately near the shore. Winds might cause the accumulation.


Purification, crystallization and X-ray structures of the two manganese superoxide dismutases from Caenorhabditis elegans.
Caenorhabditis elegans expresses two manganese superoxide dismutase enzymes (MnSOD-2 and MnSOD-3) that are targeted to the mitochondrion. MnSOD-2 is constitutively expressed, while synthesis of MnSOD-3 is inducible. The structures of these two mononuclear metalloenzymes have been determined to 1.8 and 1.7 A resolution, respectively. Pink crystals formed in space group P4(1)2(1)2 for each, with unit-cell parameters a = b = 81.0, c = 137.4 A for MnSOD-2 and a = b = 81.8, c = 136.0 A for MnSOD-3. The final structure of MnSOD-3 was refined to R = 21.6% and R(free) = 26.2% at 293 K, and R = 18.9% and R(free) = 22.6% at 100 K, while that of MnSOD-2 was refined to R = 16.9% and R(free) = 20.1% at 100 K. The asymmetric unit cell is comprised of two subunits. The resulting structures are very similar to that of human MnSOD and form a tetramer corresponding to a dimer of dimers. The subunit interface between dimers is comprised of two four-helix bundles that stabilize the biologically significant homotetramer.


Massive vulval edema secondary to obesity and immobilization: a potential mimic of aggressive angiomyxoma.
We report 2 cases of surgically resected vulval masses in women aged 27 and 40 years. One patient was wheelchair bound and the other was obese, both presented with bilateral vulvar swelling. One specimen measured 45 cm in maximum dimension and the other 5 cm and were described as grossly edematous or gelatinous. Histologically, in both cases, there was edema of the skin overlying the lesion. The lesion itself consisted of markedly edematous connective tissue with widely separated bland spindle-shaped cells and numerous dilated vascular channels, sometimes surrounded by cuffs of lymphocytes and plasma cells. In the larger of the 2 specimens, underlying edematous adipose tissue was present. To some extent, the appearances, especially the morphological features, mimicked aggressive angiomyxoma because of the presence of a mass, the lack of circumscription, the hypocellular, edematous appearance, and the presence of numerous vascular channels. However, a combination of clinical and pathological features, including bilateralism, lack of a true myxoid stroma, the presence of perivascular cuffs of lymphoid cells, and lack of staining with estrogen receptor, is against aggressive angiomyxoma. The appearances were interpreted as those of massive edema. In one case, there was recurrence of the mass after surgery. There has been a single previous report of a similar vulvar case in a quadriplegic female patient and of similar cases involving the upper and lower extremities of obese patients. Clinicians and pathologists should be aware of the existence of this lesion, which is likely due to lymphatic obstruction and lymphedema secondary to immobilization and obesity.


Influence of the implantation profiles of Si(+) on the dielectric function and optical transitions in silicon nanocrystals.
We report optical characterization of silicon nanocrystals embedded in silica thin films by spectroscopic ellipsometry (SE). Silicon nanocrystals (nc-Si) are produced by single energy ion implantation and multienergy Si(+) ion implantation into 250 nm of thermal oxide (SiO(2)) layers on silicon substrate. After thermal annealing, the obtained nc-Si have a Gaussian and uniform profiles for single and multienergy implantation, respectively. SE measurements are performed at room temperature at spectral range from 0.6 to 6.5 eV using the photoelastic modulated spectroscopic ellipsometer. Physical models based on the Maxwell-Garnet approximation combined with Forouhi-Bloomer dispersion formulas and wavelength by wavelength inversion are developed to extract the optical parameters of the layers. The complex dielectric function epsilon(E)=epsilon(r)(E)-iepsilon(i)(E) of nc-Si is determined and analyzed. The obtained epsilon(E) spectra of both uniform and Gaussian profiles are given and compared with those of bulk Si. The nc-Si exhibit a significant reduction of the dielectric function in comparison with bulk Si. We have determined the optical transitions E(1) and E(2) corresponding to Van Hove singularities in the joint density of states. A reduction of the amplitude of E(1) peak with a very weak shift of its energy position is observed. The transition E(2) is characterized by a rather broad peak; the amplitude of this peak is more important than that of E(1). The extended Forouhi-Bloomer model to semiconductor is also used to determine the dielectric functions of nc-Si and optical transitions. In epsilon(i)(E) spectra of nc-Si we have observed that not only the optical transition E(1) peak reduced but it tends to disappear and to form with E(2) only a single broad peak centered at around 4.3 eV. The influence of the distribution profile on the sample's structural and optical characteristics is also investigated. Defects caused by implantation are identified by analyzing the dielectric function behavior. For more reliability, photoluminescence analysis are used to obtain direct optical responses of nc-Si.


Chronic psychological stress seems associated with elements of the metabolic syndrome in patients with ischaemic heart disease.
Chronic psychological stress, the metabolic syndrome (MS) and ischaemic heart disease (IHD) seem closely connected. In this study, we evaluate the association between chronic stress and elements of MS in patients with stable IHD. Cross-sectional cohort study. Three hundred and fifty patients with stable IHD were included. Chronic stress was evaluated by the two questionnaires, Major Depression Inventory (MDI) and the psychological wellbeing index WHO-5, as well as by Pressure Pain Sensitivity (PPS), a physiological measure of hyperalgesia at the sternum known to be associated to elements of the chronic stress syndrome. Elements of MS were evaluated by dual-energy X-ray absorptiometry, body weight, HOMA-IR and blood lipids. Depressive symptoms were associated with a high percentage of body fat (β = 0.179, p = .001), and high level of triglycerides (β = 0.150, p = .007). Low psychological wellbeing was associated with a high percentage of body fat (β = -0.165, p = .002) and low level of HDL cholesterol (β = 0.128, p = .024). Chronic stress measured by PPS was associated with a high percentage body fat (β = 0.327, p < .001), low body weight (β = -0.218, p < .001) and low HDL-cholesterol (β = -0.137, p = .013). Adjusting for several life style factors did not change these results. In patients with stable IHD, different measures of chronic psychological stress seem associated with a high percentage of body fat and adverse blood lipids independent of several lifestyle factors.


Enzyme-dependent responses of stimuli-sensitive systems.
The methods of creating of systems where properties depend both on an outer physical signal and enzyme activity are discussed. The construction of a conjugation chain between responses of stimuli-sensitive materials and urea hydrolysis catalyzed with urease is demonstrated on the basis of light- and thermoreversible polymeric matrices.


Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development.
Premenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone level in luteal phase of the menstrual cycle. In this review, we describe the emotional regulatory effect of allopregnanolone (ALLO), and summarize the relationship between ALLO and γ-aminobutyric acid A (GABAA) receptor subunits based on rodent experiments and clinical observations. A rapid decrease in ALLO reduces the sensitivity of GABAA receptor, and reduces the chloride influx, hindered the inhibitory effect of GABAergic neurons on pyramidal neurons, and then increased the excitability of pyramidal neurons, resulting in PMDD-like behavior. Finally, we discuss in depth the treatment of PMDD with targeted GABAA receptors, hoping to find a precise target for drug development and subsequent clinical application. In conclusion, PMDD pathophysiology is rooted in GABAA receptor sensitivity changes caused by rapid changes in ALLO levels. Targeting GABAA receptors may alleviate the occurrence of PMDD.


A prospective study on the use of intraoperative computed tomography (iCT) for image-guided placement of thoracic pedicle screws.
Placement of thoracic pedicle screws is a technically demanding procedure. The risk of thoracic pedicle breaches range from 6.5 to 41%. Current image guidance systems consist of computer based systems utilizing preoperative CT scans or 2D/3D intraoperative fluoroscopy. The aim of this prospective study was to evaluate the clinical feasibility and accuracy of a new intraoperative CT (iCT) based image guidance system for thoracic pedicle screw instrumentation. We prospectively studied the use of iCT for the first 43 consecutive cases for which thoracic pedicle screws were inserted as part of the instrumentation for spinal fusion between April 2008 and July 2011. In every case, a post-instrumentation intraoperative check CT was done before wound closure to assess accuracy of implant placement. Outcomes were analysed with regards to the incidence of pedicle wall violations detected on intraoperative check CT imaging, and the rate of immediate intraoperative revision of misplaced screws. Pedicle violations were graded according to an established classification system. A total of 261 thoracic pedicle screws (T1-T12) were inserted in 43 patients (age range 13-83). Mean follow-up was 12 months. There were 7 (2.7%) pedicle violations detected on the intraoperative check CT. Out of the seven, three were grade I (< 2 mm), two were grade II (2-4 mm) and rest two were grade III (> 4 mm) violations. Only four of the screws (1.5%) that breached the pedicle wall by more than 2 mm were immediately revised before wound closure. The iCT based spinal neuronavigation system allowed for highly safe and accurate placement (97.3%) of thoracic pedicle screws in our institution with no neurovascular injury reported.


A novel lysosomal acid lipase gene mutation in a patient with cholesteryl ester storage disease.
The molecular defects in the gene encoding the lysosomal acid lipase (LAL) were investigated in an adult male patient affected with cholesteryl ester storage disease (CESD), an autosomal recessive disorder associated with LAL deficient activity. Nucleotide sequencing of amplified LAL genomic DNA or reverse-transcribed mRNA demonstrated that this patient was a compound heterozygote for a previously reported mutation, a G-->A transition at position -1 of the exon 8 splice donor site, resulting in skipping of the complete exon 8, and for a C-->T substitution at position 233 (exon 3), which introduces a premature in-frame termination codon. This yet undescribed mutation, which results in the loss of 89% of LAL amino acids, is very likely to abolish the LAL catalytic activity.


p53 pathway determines the cellular response to alcohol-induced DNA damage in MCF-7 breast cancer cells.
Alcohol consumption is associated with increased breast cancer risk; however, the underlying mechanisms that contribute to mammary tumor initiation and progression are unclear. Alcohol is known to induce oxidative stress and DNA damage; likewise, p53 is a critical modulator of the DNA repair pathway and ensures genomic integrity. p53 mutations are frequently detected in breast and other tumors. The impact of alcohol on p53 is recognized, yet the role of p53 in alcohol-induced mammary carcinogenesis remains poorly defined. In our study, we measured alcohol-mediated oxidative DNA damage in MCF-7 cells using 8-OHdG and p-H2AX foci formation assays. p53 activity and target gene expression after alcohol exposure were determined using p53 luciferase reporter assay, qPCR, and Western blotting. A mechanistic study delineating the role of p53 in DNA damage response and cell cycle arrest was based on isogenic MCF-7 cells stably transfected with control (MCF-7/Con) or p53-targeting siRNA (MCF-7/sip53), and MCF-7 cells that were pretreated with Nutlin-3 (Mdm2 inhibitor) to stabilize p53. Alcohol treatment resulted in significant DNA damage in MCF-7 cells, as indicated by increased levels of 8-OHdG and p-H2AX foci number. A p53-dependent signaling cascade was stimulated by alcohol-induced DNA damage. Moderate to high concentrations of alcohol (0.1-0.8% v/v) induced p53 activation, as indicated by increased p53 phosphorylation, reporter gene activity, and p21/Bax gene expression, which led to G0/G1 cell cycle arrest. Importantly, compared to MCF-7/Con cells, alcohol-induced DNA damage was significantly enhanced, while alcohol-induced p21/Bax expression and cell cycle arrest were attenuated in MCF-7/sip53 cells. In contrast, inhibition of p53 degradation via Nutlin-3 reinforced G0/G1 cell cycle arrest in MCF-7 control cells. Our study suggests that functional p53 plays a critical role in cellular responses to alcohol-induced DNA damage, which protects the cells from DNA damage associated with breast cancer risk.


Medullary cystic disease: a family study.
Medullary cystic disease of the kidney is characterized by progressive tubulointerstitial disease with medullary cyst formation and secondary glomerular sclerosis. We treated a patient with chronic renal failure and investigated the family history of renal disease. The patient, an 18-year-old woman, was admitted due to poor appetite and fatigue for several months. Findings on physical examination were normal except for a pale conjunctiva. Urinalysis revealed only mild proteinuria with clear sediment. The hemogram showed normocytic normochromic anemia with hemoglobin 86 g/L. The patient was azotemic and her creatinine clearance rate was 10.7 mL/min. Renal sonography showed contraction of both kidneys with a marked increase in cortical echogenicity. One small cyst was found in the medullary area. Computed tomography (CT) and magnetic resonance imaging revealed several medullary cysts. Percutaneous renal biopsy showed focal and periglomerular sclerosis, marked tubular atrophy, and interstitial fibrosis. Ten of her family members were examined for renal function, and by sonography and CT. Five had medullary cysts, and three of the five showed abnormal renal function. Medullary cystic disease should be considered in the differential diagnosis of patients with renal disease and a positive family history.


Influence of culture site-specific MIC distributions on the pharmacokinetic and pharmacodynamic properties of piperacillin/tazobactam and piperacillin: a data analysis.
Investigators who perform pharmacokinetic/pharmacodynamic (PK-PD) modeling with Monte Carlo simulation have historically not stratified microbiological data by culture site. This lack of stratification might be problematic if susceptibility patterns differ among sites and might lead to differences in PK-PD. This study compared the PK-PD of 2 antimicrobial regimens against 5 gram-negative bacterial species form 3 culture sites. This data analysis was performed at the Department of Pharmacology, The University of Texas Health Science Center, San Antonio, Texas. Blood, pulmonary (ie, bronchial, endotracheal, lung, respiratory, sputum, and tracheal secretions), and wound distributions of MICs were extracted from the 2002 Intensive Care Unit Surveillance System database. Bacteria included Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The PK properties of piperacillin/tazobactam (3.375 g every 4 hours) and piperacillin (3 g every 4 hours) were obtained from studies in healthy volunteers. Monte Carlo simulation was used in 10,000 patients for each antimicrobial-bacteria-culture site combination. The cumulative fraction of response (CFR) for a free percentage time above the MIC of > or =50% was determined for each combination, and a clinically significant difference was defined a priori as > or =10%. Data from 2408 pulmonary, 490 blood, and 242 wound isolates were included. For piperacillin/tazobactam, the CFR varied <10% by culture site in all 5 bacterial species. Site-specific differences were noted in MIC50 for piperacillin versus E cloacae and E coli and MIC90 for piperacillin/tazobactam versus K pneumoniae and P aeruginosa. Likewise, for piperacillin, the CFR was similar among the 3 culture sites for P aeruginosa. However, the CFR for piperacillin varied by > or =10% for A baumannii (blood > wound), E cloacae (pulmonary > blood), E coli (pulmonary and blood > wound), and K pneumoniae (wound > blood). The PK-PD models based on PK properties found in healthy humans and site-specific MIC distributions in this study suggest that for piperacillin, culture-site differences subsequently resulted in CFR differences that exceeded a predetermined level of clinical significance. Furthermore, these data suggest that traditional reporting strategies for microbiological data (ie, MIC50 and MIC90) might fail to adequately characterize the MIC population.


[Tuberculosis of the CNS--once again a current neurosurgical disease].
Tuberculosis is relative uncommon in developed countries. The incidence is still considerable in India, in the Middle East and South America. Neurosurgically important manifestations of tuberculosis are intracranial tuberculomas, tuberculous meningitis with hydrocephalus and tuberculous spondylitis. Therefore experiences in the management of these three kinds of neurotuberculosis are described and an overview of the literature is given. The diagnosis of intracranial tuberculomas is difficult because the symptoms are similar to those of many other types of intracranial tumor and the CT-findings are unspecific. Clinical recognition of neurotuberculosis rests mainly on the evidence of the general disease. A positive skin test supports the diagnosis. The management of tuberculomas enclosed stereotactic biopsy to confirm the diagnosis, medical treatment and surgery. But surgery is only indicated for larger symptomatic mass lesions producing midline shift and severe intracranial hypertension. With antituberculous drugs treated tuberculomas begin to decrease in size within the first two months of therapy. Hydrocephalus is a common complication of tuberculous meningitis. Due to the low incidence the first diagnosis in industrialized countries is a hydrocephalus of unknown origin. The diagnosis of tuberculous meningitis is suspected in any case of subacute meningitis with a CSF profile demonstrating a predominance of lymphocytes, elevated protein value, hypoglycaemia and negative stains for bacterial or fungal organisms, because positive smears for acid-fast bacilli are seldom. Without treatment, tuberculous meningitis is invariably fatal within 4 to 6 weeks. Therefore, when ever tuberculous meningitis is suspected, antituberculous therapy must be started.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of Smad ubiquitin regulatory factor 2 (Smurf2) in rhesus monkey endometrium and placenta during early pregnancy.
Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that is involved in the Smad-mediated TGF-beta signaling. TGF-beta has been shown to play an important role during normal embryo implantation, but whether Smurf2 is involved in this process has not been reported. This study was first conducted to investigate the expression of Smurf2 transcript and protein in different compartments of the rhesus monkey uteri and placenta during early pregnancy. The results showed that both the cloned partial sequence of Smurf2 gene and the corresponding amino acid residues shared 99% identity with those of human homologs. On day 12 (D12) of pregnancy, strong signals of Smurf2 mRNA were found in basalis glandular epithelium and luminal epithelium, and moderate expressions were detected in functionalis glandular epithelium. During early villi stage and villi placental stage, Smurf2 mRNAs were mainly localized in the placenta villi, trophoblastic column, trophoblastic shell, and basalis glandular epithelium. There appeared strong staining signals in the arterioles on D26 of pregnancy, but faint staining signals on D18 of pregnancy. No specific staining of Smurf2 mRNA was observed in stromal cells and myometrium. The expression pattern of Smurf2 protein was generally similar to that of its mRNA. These results provide the first evidence that Smurf2 may play specific roles in glandular secretion, trophoblastic cell invasion, and placentation through mediating the expression of the related proteins of TGF-beta signaling pathway during early pregnancy.


3D Body shape for regional and appendicular body composition estimation.
Body composition is correlated to bone mineral density, muscle strength, and physical performance. This is important for diagnosing conditions like sarcopenia, which is defined as the age-associated decrease in muscle mass leading to decreased mobile function, increased frailty, and imbalance. Existing methods for body composition measurement either suffer from inaccurate results or require expensive equipment such as Dual-energy x-ray absorptiometry (DXA). Although DXA measures lean mass and not muscle mass, previous studies have considered extremity lean mass as appendicular skeletal muscle mass (ASMM) approximation. In this study, we develop a new shape descriptor to predict regional body composition (in particular, regional lean mass) from 3D body shapes. In addition, we propose a neural network for ASMM assessment which is calculated by lean mass. We evaluate the effectiveness by comparing adjusted R-Squared values and Root Mean Square Error (RMSE). In our experiment, the regression models utilizing level circumference as the training feature outperforms all regional anthropometric measurements and lowers the average RMSE by about 21%. For ASMM, the proposed neural network, which combines shape features and demographic features, surpasses all other traditional regression models and reaches the lowest RMSE at 1.85 kg. Compared to the vanilla linear regression model, our approach improves the RMSE by 17%. The experimental results suggest that the 3D body shape has the potential to be used to predict body composition, and in particular lean mass, for the whole body as well as specific regions of the body.


Closure of large spina bifida cystica defects with bilateral bipedicled musculocutaneous flaps.
A report of 19 cases of large spina bifida cystica defects closed with bilateral bipedicled latissimus dorsi musculocutaneous flaps is presented. This procedure offers a distinct advantage over other procedures used currently: (1) any large defect in the thoracic, lumbar, and sacral area can be repaired without tension; (2) the flaps have good blood supply; (3) they require no delay, and operative time and blood loss are minimized; and (4) excellent results have been obtained using this safe, predictable technique with a minimum of complications.


Frustrated crystallization of a monolayer of magnetized beads under geometrical confinement.
We present a systematic experimental study of the confinement effect on the crystallization of a monolayer of magnetized beads. The particles are millimeter-scale grains interacting through the short range magnetic dipole-dipole potential induced by an external magnetic field. The grains are confined by repulsing walls and are homogeneously distributed inside the cell. A two-dimensional (2d) Brownian motion is induced by horizontal mechanical vibrations. Therefore, the balance between magnetic interaction and agitation allows investigating 2d phases through direct visualization. The effect of both confinement size and shape on the grains' organization in the low-energy state has been investigated. Concerning the confinement shape, triangular, square, pentagonal, hexagonal, heptagonal, and circular geometries have been considered. The grain organization was analyzed after a slow cooling process. Through the measurement of the averaged bond order parameter for the different confinement geometries, it has been shown that cell geometry strongly affects the ordering of the system. Moreover, many kinds of defects, whose observation rate is linked to the geometry, have been observed: disclinations, dislocations, defects chain, and also more exotic defects such as a rosette. Finally, the influence of confinement size has been investigated and we point out that no finite-size effect occurs for a hexagonal cell, but the finite-size effect changes from one geometry to another.


The effect of tacrolimus conversion from immediate- to extended-release formulation on renal function in renal transplant patients: a meta-analysis.
Objective: Tacrolimus formulation affects the outcomes of a renal transplant, while the effect of its immediate- to extended-release conversion remains controversial. This meta-analysis aimed to compare the renal function before and after tacrolimus immediate- to extended-release conversion in renal transplant patients. Methods: PubMed, Cochrane, Embase, CNKI, CQVIP, and Wanfang databases were searched for articles regarding the effect of tacrolimus conversion from immediate- to extended-release formulation on renal function in renal transplant patients. The data on serum creatinine (Scr) or the estimated glomerular filtration rate (eGFR) before and after conversion were extracted and analyzed. Results: Ten studies with 743 renal transplant patients were included. Scr was reduced after conversion versus before conversion [mean difference (MD) (95% confidence interval (CI)): -8.00 (-14.33; -1.66) μmol/L, p = 0.01]. However, eGFR only showed an increased trend after conversion versus before conversion (MD (95% CI): 2.21 (-1.62, 6.03) mL/min/1.73 m2, p = 0.26) but without statistical significance. Furthermore, in patients with a follow-up duration ≥48 weeks, Scr was decreased after conversion versus before conversion (p = 0.005), but eGFR remained unchanged (p = 0.68). However, in patients with a follow-up duration <48 weeks, both Scr (p = 0.36) and eGFR (p = 0.24) were not different before conversion versus after conversion. Moreover, publication bias risk was low, and robustness assessed by sensitivity analysis was generally good. Conclusion: This meta-analysis favors studies indicating that the conversion of tacrolimus from an immediate-release to an extended-release formulation could improve the kidney function to some extent in renal transplant patients, and this advancement may be related to the administration period.


Heat shock proteins, end effectors of myocardium ischemic preconditioning?
The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our "classic" preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called "second protection window."


Long-term consequences of childhood physical abuse.
This article reviews the literature on the long-term consequences of childhood physical abuse. Empirical research is discussed within 7 topic areas: aggressive and violent behavior, nonviolent criminal behavior, substance abuse, self-injurious and suicidal behavior, emotional problems, interpersonal problems, and academic and vocational difficulties. The studies reviewed involve primarily adult populations, although pertinent findings from literature on children and adolescents are briefly summarized. Some variables that affect the relation between physical abuse and long-term consequences are examined. These moderator variables include maltreatment characteristics, individual factors, family factors, and environmental factors. The article ends with suggestions for future research on long-term consequences and variables that may affect these outcomes.


Revising educational requirements: challenging four hours for both basic life support and automated external defibrillators.
The instruction of cardiopulmonary resuscitation (CPR) faces new challenges. With the current poor resuscitation outcomes of victims of sudden death syndrome, the impetus to include early defibrillation as a basic skill for laypersons imposes the need to simplify CPR instruction and reduce the time required to teach this technique. The exploration of an alternative paradigm has gained both public and academic interest. Some of the constraints have evolved around the urgent need to bring both CPR and automated external defibrillation instruction to a much larger population segment and at the same time reduce the time needed to accomplish this task. Additional debate exists with respect to maintaining the current traditional training methods or the use of new media such as video-based instruction, interactive computer-based software, and public service announcements. To answer any one of these questions we are tasked with having to objectively document not only retention and performance of learned skills, but the ultimate impact that any of these elements have on survival and outcome. This has to balance against the ongoing scourge of sudden cardiac death, which claims the lives of 350,000 Americans each year.


The THC-induced suppression of Th1 polarization in response to Legionella pneumophila infection is not mediated by increases in corticosterone and PGE2.
T helper cell type 1 (Th1)-polarizing cytokines are induced by Legionella pneumophila infection and are suppressed by pretreatment with marijuana cannabinoids (CB). Glucocorticoids and prostaglandin E2(PGE2) are also reported to suppress Th1 polarization and are induced by Delta9-tetrahydrocannabinol (THC), so their role in the suppression of polarizing cytokines was examined. Injection of L. pneumophila or THC alone into BALB/c mice induced a rapid and transient rise in serum corticosterone (CS), and the injection of both agents significantly augmented the CS response, demonstrating that THC increased CS in Legionella-infected mice. Pretreatment with the CB receptor 1 (CB1) antagonist SR141716A had no effect on the THC-induced CS response, but CB2 antagonist (SR144528) treatment increased the CS response. To see if increased CS contributed to the down-regulation of Th1 cytokines, mice were pretreated with the steroid antagonist RU486 before THC injection and Legionella infection. The results showed that RU486 did not attenuate the THC-induced suppression of serum interleukin (IL)-12 or interferon-gamma (IFN-gamma). In addition to CS, THC injection increased urinary PGE2 metabolites, and the CB1 antagonist attenuated this increase. Although L. pneumophila infection increased urinary PGE2, THC pretreatment did not enhance this response; in addition, treatment with the cyclooxygenase inhibitor, indomethacin, did not block the THC-induced suppression of IL-12 and IFN-gamma. These results suggest that the elevation of CS and PGE2 does not account for the THC-induced attenuation of the Th1 cytokine response, and it is concluded that other suppressive mediators are induced by THC or that the drug acts directly on immune cells to suppress cytokine production.


Sexual maturation modulates expression of nuclear receptor types in laser-captured single cells of the cichlid (Oreochromis niloticus) pituitary.
The role of steroid/thyroid hormones in the regulation of endocrine cells at the level of the pituitary has remained unclear. Therefore, using single-cell quantitative real-time PCR, we examined absolute amounts of transcripts for nuclear receptors [estrogen receptors (ERs) alpha, beta, and gamma; androgen receptors (ARs) a and b; glucocorticoid receptors (GRs) 1, 2a, and 2b; and thyroid hormone receptors (TRs) alpha1, alpha2, and beta] in pituitary cells of immature (IM) and mature (M) male tilapia, Oreochromis niloticus. In the two reproductive stages, ACTH cells expressed only ERbeta, whereas all other pituitary cell types expressed ERalpha + beta, and a subpopulation coexpressed ARa, ARb, GR1, GR2b, and TRbeta but lacked ERgamma, GR2a, TRalpha1, and TRalpha2. IM males had high percentages of LH cells (IM 46.0% vs. M 10.0%), GH cells (IM 23.3% vs. M 7.9%), and prolactin cells (IM 68.8% vs. M 6.0%) with ERbeta, and TSH cells (IM 19.2% vs. M 0.0%) and MSH cells (IM 25.6% vs. M 0.0%) with ERalpha + TRbeta. A high percentage of FSH cells in IM males expressed ERbeta (IM 46.9% vs. M 18.8%), and FSH cells in M males showed significantly high GR1 transcripts (IM 76.0 +/- 5.0 vs. M 195.0 +/- 10.7 copies per cell; P < 0.05), suggesting that FSH cells are regulated differently in the two reproductive stages. Coexpression of ERalpha + beta in high percentages of cells of the GH family (GH, IM 43.8% vs. M 14.3%; prolactin, IM 8.3% vs. M 59.7%; somatolactin, IM 22.2% vs. M 42.2%) suggests that the expression of both ERs is important for functionality. Thus, differential coexpression of genes for nuclear receptors in subpopulations of pituitary cell types suggests multiple steroid/thyroid hormone regulatory pathways at the level of the pituitary during the two reproductive stages.


ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH HYPOTHYROIDISM AND CONCOMITANT CHRONIC CHOLECYSTITIS.
Activity of endothelial dysfunction markers in patients with hypothyroidism and concomitant chronic cholecystitis was investigated. In patients with hypothyroidism and chronic cholecystitis a increased lactate dehydrogenase and alkaline phosphatase activity was observed, accompanied by the manifestation of cholestasis. In this patients increased vascular endothelium growth factor plasma level and endotheliocytes number was detected, attested the accelerated severity of endothelium dysfunction. Inverse correlation between the vascular endothelium growth factor plasma concentration, desquamated endotheliocytes number in peripheral blood and bilirubin level was detected, that points to the protective role of bilirubin in the prevention of the endothelium dysfunction development.


[Intraoperative Artery Wall Stimulating Electromyography during Microvascular Decompression Surgery to Treat Hemifacial Spasm:A Case Report].
Microvascular decompression(MVD)surgery has been established as a standard treatment for hemifacial spasm. However, because decompression surgery results in unfavorable outcomes in some cases, a more critical monitoring strategy is required. To improve surgical outcome for hemifacial spasms, abnormal muscle response(AMR)has been proposed as a tool for intraoperative electrophysiological monitoring during MVD surgery. Here, we report a single case of surgical MVD monitoring using artery wall stimulating electromyography(AWS-EMG). AWS-EMG was developed as a new monitoring method in addition to AMR. A 60-year-old woman was diagnosed with hemifacial spasm using magnetic resonance imaging and magnetic resonance angiography fusion imaging. We performed MVD surgery using AWS-EMG and AMR. We successfully identified AWS-EMG before decompression and confirmed immediate AWS-EMG loss after decompression. This behavior was consistent with AMR. After surgery, the patient showed no further symptoms of hemifacial spasm. In addition to AMR, AWS-EMG might be a promising candidate for intraoperative monitoring for patients with hemifacial spasm.


Evaluation of the detection limits of PCR for identification of Mycoplasma pneumoniae in clinical samples.
The detection limits of the polymerase chain reaction (PCR) for Mycoplasma pneumoniae were determined using specimens from persons known to have had M. pneumoniae pneumonia. Four primers were selected from the known sequence of the P1 gene. The primer pair (P1-178 and P1-809) which generates a 631 fragment gave the lowest detection limit. Nineteen of 21 throat swabs, which contained between 0.06 and 2 colony-forming units (CFU) per microlitre, from culture positive patients, were positive by PCR. The fact that M. pneumoniae grows in broth culture in spherules causes problems for determining the number of CFU detected in PCR. Filtering broth cultures through a 0.6 micron polycarbonate filter increased the number of CFUs two-to-ten-fold compared to unfiltered cultures. The lysis method needed to assay throat swabs differed from that necessary for broth cultures in that proteinase K treatment for 18 h increased the detection limit 10- to 100-fold when compared to NaOH digestion.


Sliding friction with polymer brushes.
Using high-resolution shear force measurements, we examine in detail the frictional drag between rubbing surfaces bearing end-tethered polymeric surfactants (brushes). The drag attains a maximum on initial motion, attributed to elastic stretching of the chains, which falls by a cascade of relaxations to a value characteristic of kinetic friction. This has a very weak velocity dependence, attributed to chain moieties dragging within a self-regulating, mutual interpenetration zone. When sliding stops, the shear stress across the polymer layers decays logarithmically with time, consistent with the relaxation of a network of dangling ends.


The Influence of Cardiac Risk Factor Burden on Cardiac Stress Test Outcomes.
Chest pain is the most common admission diagnosis for observation unit patients. These patients often undergo cardiac stress testing to further risk stratify for coronary artery disease (CAD). The decision of whom to stress is currently based on clinical judgment. We sought to determine the influence of cardiac risk factor burden on cardiac stress test outcome for patients tested from an observation unit, inpatient or outpatient setting. We performed a retrospective observational cohort study for all patients undergoing stress testing in our institution from June 2006 through July 2007. Cardiac risk factors were collected at the time of stress testing. Risk factors were evaluated in a summative fashion using multivariate regression adjusting for age and known coronary artery disease. The model was tested for goodness of fit and collinearity and the c statistic was calculated using the receiver operating curve. A total of 4026 subjects were included for analysis of which 22% had known CAD. The rates of positive outcome were 89 (12.0%), 95 (12.6%), and 343 (16.9%) for the OU, outpatients, and hospitalized patients respectively. While the odds of a positive test outcome increased for additional cardiac risk factors, ROC curve analysis indicates that simply adding the number of risk factors does not add significant diagnostic value. Hospitalized patients were more likely to have a positive stress test, OR 1.41 (1.10 - 1.81). Our study does not support basing the decision to perform a stress test on the number of cardiac risk factors.


Mapping of 22 expressed sequence tags isolated from a porcine small intestine cDNA library.
Complementary DNA sequences were selected from a resource of tentatively identified clones from a porcine small intestine cDNA library. Forty PCR primer pairs were designed to amplify 101-309 base pairs of the 3' untranslated region of the genes. The PCR conditions were optimized by altering both formamide and magnesium concentrations on samples of pig, mouse, and hamster DNA. Twenty primer pairs that, under stringent conditions, were pig-specific and amplified the expected fragments were chosen for regional assignment in a pig/rodent hybrid cell panel. Furthermore, 22 primer pairs were chosen to amplify DNA from the parental animals of the PiGMaP shared reference families in order to detect possible polymorphisms. Primer pairs that generated polymorphisms were used for genetic mapping. A total of 22 porcine expressed sequence tags (ESTs) were cytogenetically or genetically mapped by this approach. Twelve of the mapped ESTs could be added to the human-porcine comparative map.


Application of platelet/lymphocyte and neutrophil/lymphocyte ratios in early diagnosis and prognostic prediction in patients with resectable gastric cancer.
Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related deaths worldwide. China has a high incidence of gastric cancer. Inflammation is a critical component of tumor progression. It has been widely accepted that gastric cancer is an inflammation-driven cancer. In this study, we investigated the application value of systemic inflammatory response (SIR) markers, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR), in early diagnosis and prognostic prediction in patients with resectable gastric cancer. One hundred and sixty-two patients with resectable gastric cancer were included and separated into groups according to median pre-operative PLR or NLR values (PLR low: < 208 or PLR high: ≥ 208, and NLR low: < 4.02 or NLR high: ≥ 4.02, respectively). To evaluate the changes in PLR or NLR values after operation, we introduced the concept of postpre-operative PLR or NLR ratios (< 1 indicated PLR or NLR values were decreased after operation, while ≥ 1 suggested not decreased PLR or NLR values). Pre-operative PLR and NLR levels were significantly higher in gastric cancer patients compared with the healthy subjects. Low pre-operative PLR and NLR levels correlated with better clinicopathological features, including decreased depth of invasion, less lymph node metastasis and early tumor stage. Kaplan-Meier plots illustrated that higher pre-operative NLR and PLR had decreased overall survival (OS) and disease-free survival (DFS). Surgical tumor resection resulted in a significant PLR and NLR measurements can provide important diagnostic and prognostic results in patients with resectable gastric cancer.


Hepatocellular carcinoma in cirrhotic liver: double-contrast-enhanced, high-resolution 3.0T-MR imaging with pathologic correlation.
To determine the diagnostic performance of double-contrast-enhanced (DCE) magnetic resonance imaging (MRI) at 3.0T in the detection of hepatocellular carcinoma (HCC) in patients with a cirrhotic liver. This study was approved by our Institutional Review Board and did not require informed consent. A total of 61 patients (52 men, 9 women; range 27-83 years) underwent DCE-MRI at 3.0T. DCE-MRI was composed of baseline MR images, superparamagnetic iron oxide-enhanced T2- and T2*-weighted images, and gadobenate-dimeglumine-enhanced dynamic MR images. The diagnosis of HCC was established at transplantation (n = 12) and hepatic resection (n = 49). Three observers independently analyzed each image in random order. The diagnostic performance, sensitivity, positive predictive value, numbers and causes of false positive and negative findings, and interobserver variability were calculated and analyzed on a per-lesion basis. : Sixty-one patients had 95 HCCs. From alternative free-response receiver operating characteristic analysis, averaged diagnostic performance (Az) was 0.90. The mean sensitivity and positive predictive value of DCE-MRI at 3.0T for detection of HCCs were 89% and 97%, respectively. There was a significant difference in the sensitivity for the detection of HCCs between Child-Pugh class A and C patients (97% and 63%, respectively) (P < 0.01). In addition, the sensitivity according to lesion size was significantly different (P < 0.01). There were 7 false-positive lesions [arterio-portal shunt (n = 1), dysplastic nodule (n = 1), hemangioma (n = 2), and partial volume averaging (n = 3)]. Thirteen false-negatives occurred mainly because of small size (n = 4), partial uptake of superparamagnetic iron oxide (n = 6), faint arterial enhancement (n = 7), and location (n = 2). There was good interobserver variability (kappa: 0.622-0.670). DCE 3.0T MR imaging is a highly sensitive modality for diagnosing HCCs in patients with a cirrhotic liver.