Spinal and far-field components of human somatosensory evoked potentials to posterior tibial nerve stimulation analysed with oesophageal derivations and non-cephalic reference recording.
Somatosensory evoked potentials (SEPs) were elicited by stimulation of the right posterior tibial nerve at the ankle in 20 experiments on 18 normal adults. A non-cephalic reference on the left knee was used throughout (with triggering of averaging cycles from the ECG), except for recording the peripheral nerve potentials. The responses were recorded along the spine, from oesophageal probes and from the scalp. The peripheral nerve volley propagated at a mean maximum conduction velocity (CV) of 59.2 m/sec served to identify the spinal entry time (mean 19.7 msec) at spinal segments S1-S3, under the D12 spine. This entry time coincided with the onset of the N21 component which was interpreted as the dorsal column volley and considered equivalent to the neck N11 of the median nerve SEP. The large voltage of the spinal response at the D12 spine probably results from summation of N21 with a fixed latency N24 potential that phase reverses at oesophageal recording sites into a P24. The N24-P24 reflects a horizontal dipole in the dorsal horn and is equivalent to the N13-P13 of the neck SEP to median nerve stimulation. Spinal conduction between D12-C7 spines was spuriously overestimated because the true length of the dorsal spinal cord is shorter by about 13% than the distance measured on the skin over the dorsal convexity. This correction should be applied routinely and it leads to a mean maximum spinal CV of 57 m/sec. Several positive far fields with widespread scalp distribution and stationary latencies have been identified. The P17 (over spine and head) reflects the peripheral nerve volley at the upper buttock. The P21 is synchronous with the N21 at the D12 spine and reflects the initial volley in the dorsal column. No far-field equivalent has been found for the N24-P24, due to the horizontal axis of the corresponding dipole. The P26 far field reflects the ascending volley at spinal levels D10-D4. The P31 reflects the initial volley in the medial lemniscus. The P40 at Cz represents the cortical response of the foot projection. Average central CVs were calculated and discussed.


Augmentation of pressure in a vessel indenting the surface of the lung.
The lungs and intrathoracic cardiovascular structures compete for space within the thorax, interacting through their adjacent surfaces via the pleural space. Theoretical analysis and in vitro model studies (detailed here) established that when a vessel indents the lung surface, the increase in intravascular pressure with positive pressure lung inflation can be greater than the change in the pleural surface pressure measured outside of the interaction area. We define this phenomenon as intravessel pressure augmentation. We determined the average intravessel pressure gain as the slope of the linear regression of the pressure in a vascular structure or balloon indenting the lung on the pleural surface pressure measured by a flat disk-shaped device (disk). The analysis showed that the disk pressure overestimates the pleural pressure. Therefore, the derived pressure gain underestimated the pressure augmentation. In five dogs, the disk and a 2-ml balloon were placed in the lateral pleural space, and a segment of IVC was ligated at both ends and filled with saline. The dogs were ventilated with fixed tidal volumes, while the positive end-expiratory pressure was changed. The pressures were compared at the end of expiration. For the IVC segment, the pressure gains under four different tidal volumes were significantly greater than one [95% confidence interval of mean value (CIM) = 1.57 +/- 0.16, P less than 10(-4)], and for the small balloon, this was the case for three of four tidal volumes (95% CIM for all four volumes 1.13 +/- 0.04, P less than 10(-4)). We conclude that the surface interaction of the lungs with adjacent cardiovascular structures causes appreciable pressure augmentation in those structures during ventilation with the positive end-expiratory pressure.


Delayed Access to Involuntary Mental Health Examinations.
Delayed access to involuntary mental health examination for people who receive care in emergency departments (EDs) was examined, and factors that influenced delayed access were explored. A retrospective review of records for the 12 months prior to data collection was conducted to address the study questions. The health services utilization model served as the conceptual framework for this study. Societal, system, and individual factors were considered in examining access to involuntary emergency mental health examination by adult ED patients. Records of 170 people who sought care in EDs and who required involuntary mental health examinations at two hospitals in Florida served as the sources for study data. The mean duration of delay was 14.9 h. The determinants that were significantly associated with longer delays were being male, increased age, and intoxication. The findings can inform the allocation of resources to increase opportunities for positive long-term outcomes following involuntary care.


Coarse woody debris as a refuge from predation in aquatic communities : An experimental test.
This study demonstrates experimentally that coarse woody debris (CWD) can provide refuge from predation in aquatic habitats. In the Rhode River subestuary of Chesapeake Bay, Maryland, (USA), we (1) measured the abundance of CWD, (2) examined the utilization of CWD by mobile epibenthic fish and crustaceans, and (3) tested experimentally the value of CWD as a refuge from predation. CWD was the dominant above-bottom physical structure in shallow water, ranging in size from small branches (<2 cm diameter) to fallen trees (>50 cm diameter). In response to experimental additions of CWD, densities of common epibenthic cpecies (Callinectes sapidus, Fundulus heteroclitus, Fundulus majalis, Gobiosoma bosc, Gobiesox strumosus, Palaemonetes pugio, and Rithropanopeus harrisii) increased significantly compared to control sites without CWD. In laboratory experiments, grass shrimp (P. pugio) responded to predatory fish (F. heteroclitus and Micropogonias undulatus) by utilizing shelter at CWD more frequently than in absence of fish. Access to CWD increased survivorship of grass shrimp in laboratory and field experiments. These experimental results (1) support the hypothesis, commonly proposed but untested for freshwater habitats, that CWD can provide a refuge from predation for epibenthic fish and invertebrates and (2) extend the recognized functional importance of CWD in freshwater to estuarine and marine communities. We hypothesize that CWD is an especially important refuge habitat in the many estuarine and freshwater systems for which alternative physical structure (e.g., vegetation or oyster reefs) are absent or in low abundance.


exma: an X-linked insertional mutation that disrupts forebrain and eye development.
Formation of the neural tube plays a primary role in establishing the body plan of the vertebrate embryo. Here we describe the phenotype and physical mapping of a highly penetrant X-linked male-lethal murine mutation, exma (exencephaly, microphthalmia/anophthalmia), that specifically disrupts development of the rostral neural tube and eye. The mutation arose from the random insertion of a transgene into the mouse X Chromosome (Chr). Eighty-three percent of transgenic male embryos display an open, disorganized forebrain and lack optic vesicles. No transgenic males survive beyond birth. Hemizygous females show a variable phenotype, including reduced viability and occasional exencephaly and/or microphthalmia. Altered or reduced expression patterns of Otx2, Pax6, Six3, and Mrx, known markers of early forebrain and eye development, confirmed the highly disorganized structure of the forebrain and lack of eye development in affected exma male embryos. Physical mapping of the transgene by FISH localized a single insertion site to the interval between Dmd and Zfx on the X Chr. A 1-Mb contig of BAC clones was assembled by using sequences flanking the transgene and revealed that the insertion lies close to Pola1 and Arx, a gene encoding a highly conserved homeobox protein known to be expressed in the developing forebrain of the mouse. Data from Southern blots of normal and transgenic DNA demonstrated that a large segment of DNA encompassing Arx and including part of Pola1 was duplicated as a result of the transgene insertion. From the physical mapping results, we propose a model of the gross rearrangements that accompanied transgene integration and discuss its implications for evaluating candidate genes for exma.


Stimulus-secretion coupling by high-affinity IgE receptor: new developments.
Stimulation of mast cells through their high affinity IgE receptor (FcεRI) leads to the secretion of pre- and neoformed soluble mediators through vesicular carriers. This process is highly regulated in order to adapt the secretion of these potentially dangerous factors to the physiological needs. This regulation requires numerous essential effectors that are necessary to transmit the initial signal of FcεRI aggregation and couple it to the sophisticated secretory machinery of membrane fusion. Studies in recent years have led to the discovery of a series of new effector molecules that link FcεRI to secretion. We describe here some of the new developments that have allowed to obtain a clearer picture of stimulus/secretion coupling in mast cells.


Laser engravings as reason for mechanical failure of titanium-alloyed total hip stems.
Two revisions of broken β-titanium total hip stems had to be performed in our hospital after 2 and 4 years in situ. Since both fractures were located at the level of a laser engraving, a failure analysis was conducted. Both retrieved hip stems were disinfected and collected in our retrieval database after patient's signed agreement. Each fragment was macroscopically photographed. Fracture surfaces were analyzed using scanning electron microscopy (SEM). Quantification of element content was conducted using energy dispersive X-ray (EDX) analysis. Both stems show fatigue fracture, as displayed by the lines of rest on the fracture surface. The origin of fracture was identified directly at the laser engraving of the company logo at both stems by means of SEM. The EDX analysis showed an oxygen level beneath the laser engraving about twice as high as in the substrate, causing material embrittlement. Laser engravings need to be reduced to a minimum of necessary information, and should be placed at locations with minimum mechanical load. Biomechanical analyses are recommended to identify less loaded areas in implant components to avoid such implant failures.


Copper sulfide anchored MXene improving photo-responsive self-healing polyurethane with enhanced mechanical and antibacterial properties.
Diseases caused by bacterial infection are becoming a major threat to human health. Therefore, developing efficient antibacterial materials is of great significance in improving medical care and protecting people's health. In this work, an accordion-like structural Ti3C2@CuS was synthesized by copper sulfide (CuS) nanospheres anchored firmly on the surface of Ti3C2Tx via the hydrothermal method. The multilayer Ti3C2@CuS becomes few-layered nanosheets after ultrasonic treatment, which have an enjoyable dispersion in the polyurethane (PU) matrix. PU and the released Cu2+ from Ti3C2@CuS are firmly linked by a coordination bond, which improves the mechanical properties and thermal stability of Ti3C2@CuS-PU and reduces the heavy metal ion pollution by blocking the Cu2+ released by forming coordination bonds. Moreover, Ti3C2@CuS-PU exhibits an excellent self-healing performance after 30 tensile cycles. Additionally, Ti3C2Tx and CuS could improve the separation efficiency of the electron-hole pairs of CuS to produce more reactive oxygen species (ROS) to kill bacteria. Ti3C2@CuS-PU maintains a highly long-term sterilization ability of more than 90 % in 30 days because of the synergistic effect of the sustained release of copper ions, the elevated ROS production ability, and the excellent dispersion of Ti3C2@CuS in PU. This work demonstrates a simple and promising route for designing multifunctional antibacterial self-healing materials.


Effects of gait training with auditory biofeedback on biomechanics and talar cartilage characteristics in individuals with chronic ankle instability: A randomized controlled trial.
Altered walking gait is a typical impairment following ankle sprains which may increase susceptibility to recurring injuries and development of posttraumatic osteoarthritis at the ankle. There is a lack of targeted gait training interventions focusing on specific modifications in individuals with chronic ankle instability (CAI). Additionally, there is a need to focus on cartilage health changes following gait training to mitigate osteoarthritis progression. To determine the immediate and retention effects of gait training using auditory biofeedback (AudFB) in patients with chronic ankle instability (CAI) on biomechanics and talar cartilage characteristics. Eighteen participants with CAI were randomly assigned into Control (n = 7) or AudFB (n = 11) groups. Each group completed 8-sessions of 30-minute treadmill walking. The AudFB group received biofeedback through a pressure sensor fashioned to the lateral foot and instructions to walk while avoiding noise from the sensor. The Control group did not receive instructions during sessions. An in-shoe insole system measured peak pressure, maximum force, and center of the pressure gait line (COP) during walking. Ultrasonography captured talar cartilage thickness and echo intensity before and after walking. Biomechanics and ultrasound were measured at baseline, immediately, and 1-week after the intervention. Repeated measures mixed-methods analysis of variance assessed changes within groups across time. The AudFB group significantly reduced pressure and force in the lateral foot and medially shifted their COP at Immediate and 1-week Post. There were no observed changes in the Control group. In addition, neither group demonstrated changes in ultrasound measures at follow-up. Implementation of auditory biofeedback during gait training can be a valuable tool for clinicians treating patients with CAI.


The CPP Tat enhances eGFP cell internalization and transepithelial transport by the larval midgut of Bombyx mori (Lepidoptera, Bombycidae).
Cell-Penetrating Peptides (CPPs) are short peptides that are able to translocate across the cell membrane a wide range of cargoes. In the past decade, different mammalian cell lines have been used to clarify the mechanism of CPPs penetration and to characterize the internalization process, which has been described either as an energy-independent direct penetration through the plasma membrane, or as endocytic uptake. Whatever the mechanism involved, the cell penetration properties of these peptides make their use very attractive as vector for promoting the cellular uptake of coupled bioactive macromolecules, such as peptides, proteins and oligonucleotides. Here we demonstrate, for the first time in insect, that cultured columnar cells from the larval midgut of Bombyx mori more readily internalize eGFP (enhanced Green Fluorescent Protein) when fused to CPP Tat. Tat-eGFP translocates across the plasma membrane of absorptive cells in an energy-independent and non-endocytic manner, since no inhibition of the fusion protein uptake is exerted by metabolic inhibitors and by drugs that interfere with the endocytic uptake. Moreover, the CPP Tat enhances the internalization of eGFP in the columnar cells of intact midgut tissue, mounted in a suitable perfusion apparatus, and the transepithelial flux of the protein. These results open new perspectives for effective delivery of insecticidal macromolecules targeting receptors located both within the insect gut epithelium and behind the gut barrier, in the hemocoel compartment.


Characterization of DeltaN-Zfp36l2 mutant associated with arrest of early embryonic development and female infertility.
The zinc finger protein 36-like 2, Zfp36l2, has been implicated in female mouse infertility, because an amino-terminal truncation mutation (ΔN-Zfp36l2) leads to two-cell stage arrest of embryos derived from the homozygous mutant female gamete. Zfp36l2 is a member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins that can bind to transcripts containing AU-rich elements (ARE), resulting in deadenylation and destabilization of these transcripts. I show here that the mouse Zfp36l2 is composed of two exons and a single intron, encoding a polypeptide of 484 amino acids. I observed that ΔN-Zfp36l2 protein is similar to both wild-type Zfp36l2 and TTP (Zfp36) in that it shuttles between the cytoplasm and nucleus, binds to RNAs containing AREs, and promotes deadenylation of a model ARE transcript in a cell-based co-transfection assay. Surprisingly, in contrast to TTP, Zfp36l2 mRNA and protein were rapidly down-regulated upon LPS exposure in bone marrow-derived macrophages. The ΔN-Zfp36l2 protein was substantially more resistant to stimulus-induced down-regulation than the WT. I postulate that the embryonic arrest linked to the ΔN-Zfp36l2 truncation might be related to its resistance to stimulus-induced down-regulation.


Chest compression during sustained inflation versus 3:1 chest compression:ventilation ratio during neonatal cardiopulmonary resuscitation: a randomised feasibility trial.
Current neonatal resuscitation guidelines recommend 3:1 compression:ventilation (C:V) ratio. Recently, animal studies reported that continuous chest compressions (CC) during a sustained inflation (SI) significantly improved return of spontaneous circulation (ROSC). The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation. It is a feasibility study to compare CC+SI versus 3:1 C:V ratio during neonatal resuscitation in the delivery room. We hypothesised that during neonatal resuscitation, CC+SI will reduce the time to ROSC. Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C:V CPR in preterm infants <33 weeks of gestation. Randomised feasibility trial. Once CC was indicated all eligible infants were immediately and randomly allocated to either CC+SI group or 3:1 C:V group. A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team at the start of CC. Infants in the CC+SI group received CC at a rate of 90/min during an SI with a duration of 20 s (CC+SI). After 20 s, the SI was interrupted for 1 s and the next SI was started for another 20 s until ROSC. Infants in the '3:1 group' received CC using 3:1 C:V ratio until ROSC. Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) s compared with 138 (72) s in the 3:1 C:V group (p=0.011). CC+SI is feasible in the delivery room. Clinicaltrials.gov NCT02083705, pre-results.


Minimal climate change impacts on the geographic distribution of Nepeta glomerulosa, medicinal species endemic to southwestern and central Asia.
Medicinal plants are valuable species, but their geographic distributions may be limited or exposed to extinction by climate change. Therefore, research on medicinal plants in the face of climate change is fundamental for developing conservation strategies. Distributional patterns for a semi-endemic medicinal plant species, Nepeta glomerulosa, distributed in southwestern and central Asia was determined based on a maximum-entropy algorithm. We evaluated potential geographic shifts in suitability patterns for this species under two Shared Socioeconomic Pathways scenarios (SSP2-4.5 and SSP5-8.5) of climate change for 2060. Our models based on climatic features indicate that the species occupies montane areas under current conditions; transfer of the model to future climate scenarios indicated that suitable areas for the species will increase in general, and the species will likely track its favored set of climate conditions. But the types and degrees of these changes differ among areas. Our findings can be used to inform conservation management programs for medicinal, endemic, and endangered species that probably respond similarly to climate change in southwestern and central Asia.


Methemoglobinemia in Patient with G6PD Deficiency and SARS-CoV-2 Infection.
We report a case of intravascular hemolysis and methemoglobinemia, precipitated by severe acute respiratory syndrome coronavirus 2 infection, in a patient with undiagnosed glucose-6-phosphate dehydrogenase deficiency. Clinicians should be aware of this complication of coronavirus disease as a cause of error in pulse oximetry and a potential risk for drug-induced hemolysis.


Vanadium exposure-induced neurobehavioral alterations among Chinese workers.
Vanadium-containing products are manufactured and widely used in the modern industry. Yet the neurobehavioral toxicity due to occupational exposure to vanadium remained elusive. This cross-sectional study was designed to examine the neurotoxic effects of occupational vanadium exposure. A total of 463 vanadium-exposed workers (exposed group) and 251 non-exposed workers (control group) were recruited from a Steel and Iron Group in Sichuan, China. A WHO-recommended neurobehavioral core test battery (NCTB) and event-related auditory evoked potentials test (P300) were used to assess the neurobehavioral functions of all study subjects. A general linear model was used to compare outcome scores between the two groups while controlling for possible confounders. The exposed group showed a statistically significant neurobehavioral alteration more than the control group in the NCTB tests. The exposed workers also exhibited an increased anger-hostility, depression-dejection and fatigue-inertia on the profile of mood states (p<0.05). Performances in the simple reaction time, digit span, benton visual retention and pursuit aiming were also poorer among exposed workers as compared to unexposed control workers (p<0.05). Some of these poor performances in tests were also significantly related to workers' exposure duration. P300 latencies were longer in the exposed group than in the control (p<0.05). Longer mean reaction times and more counting errors were also found in the exposed workers (p<0.05). Given the findings of our study and the limitations of neurobehavioral workplace testing, we found evidence of altered neurobehavioral outcomes by occupational exposure to vanadium.


Heterotrophic growth of Thiobacillus A2 on sugars and organic acids.
Thiobacillus A2 grew on a number of organic acids, pentoses, hexoses and alpha-linked disaccharides, but not on beta-linked disaccharides or galactosides. Growth was slow on glucose, although fast-growing strains were selectively isolated. Additive growth rates occured on glucose and galactose; growth on glucose with fructose, pyruvate or gluconate was biphasic rather than diauxic; fructose was used preferentially over glucose; slow growth on glucose was accelerated by some disaccharides; growth on acetate, fumarate or succinate with glucose gave diauxic growth with preferential use of the acid and repression of glucose incorporation. Acetate and succinate tended to be used preferentially even with cultures grown on them in mixture with fructose or sucrose.


[Hip luxation caused by fibrous dysplasia of the acetabulum].
A case of monostotic acetabular fibrous dysplasia in 12 month old twin-girl is described. The location of the disease caused dislocation of the left hip. Open reduction, synovectomy and curettage of the tumor was performed. A stable reduction and no sign of recurrence was found at follow-up.


The temporal distribution of stimulus information in the visual evoked potential.
Research in psychophysics (Bloch's law) and perceptual experiments concerned with the integration of successively presented stimuli suggest that the perception of form is a process that occurs over a period of as much as 200-300 msec. Such results prompted the question of whether the visual evoked potential (VEP) might contain information about the distribution over time of perceptual processing. Subjects viewed lines formed from combinations of three lengths and four angles while the EEG was recorded. Analysis of the VEPs indicated that the length and angle of the lines produced temporal distributions of information in the VEP and that the distributions for length and angle were somewhat different. The major difference was that the processing of angle begins earlier and is completed sooner than the processing of length. A conclusion of the experiment was that an alternative or supplement to analyzing VEPs for specific waveform features is to consider the encoding of stimulus information in the VEP as a density or concentration over time.


Partial stabilization-based guidance.
A novel nonlinear missile guidance law against maneuvering targets is designed based on the principles of partial stability. It is demonstrated that in a real approach which is adopted with actual situations, each state of the guidance system must have a special behavior and asymptotic stability or exponential stability of all states is not realistic. Thus, a new guidance law is developed based on the partial stability theorem in such a way that the behaviors of states in the closed-loop system are in conformity with a real guidance scenario that leads to collision. The performance of the proposed guidance law in terms of interception time and control effort is compared with the sliding mode guidance law by means of numerical simulations.


Copper-catalyzed asymmetric allylic substitution with aryl and ethyl Grignard reagents.
Phenyl- and ethyl-magnesium bromides undergo regioselective asymmetric allylic substitution with high enantioselectivity under the catalysis of chiral amidophosphane-copper(I) complexes.


Renal denervation: Not as easy as it looks.
Renal sympathetic denervation with intravascular radiofrequency catheters in hypertensive patients is less effective than anticipated, owing to radio frequency energy being applied to a part of the renal artery where the nerves are at the greatest distance from the aortic lumen and to distortion of energy distribution and temperature gradients by regional tissue anatomical variations (Tzafriri et al., this issue).


Pulmonary chronic thromboembolic disease.
Persistent thrombotic lesions are common in patients with pulmonary embolism. These lesions occur on a clinical spectrum, ranging from an asymptomatic course with complete functional recovery to chronic thromboembolic pulmonary hypertension. The concept of chronic thromboembolic disease has emerged in recent years to describe a subgroup of patients with persistent thrombotic lesions who have symptoms on exertion and pulmonary vascular dysfunction, but no pulmonary hypertension at rest. The prevalence of this entity is unknown and the criteria for diagnosing it are not defined. The aim of this article is to analyze post-pulmonary embolism sequelae and review existing evidence on chronic thromboembolic disease, with special emphasis on its diagnosis and therapeutic approach.


Different photorespiratory mechanisms in conifer leaves, where peroxisomes have intrinsically low catalase activity.
Photorespiration is an essential metabolic mechanism associated with photosynthesis; however, little is known about the photorespiratory pathway of conifer gymnosperms. Metabolite analyses of the leaves of 27 tree species showed that the mean glycerate content in conifer leaves was lower than that in angiosperm leaves. We performed experiments where [13 C]-serine was fed to detached shoots of a conifer (Cryptomeria japonica), via the transpiration stream, and compared the labeling patterns of photorespiratory metabolites with those of an angiosperm tree (Populus nigra), because glycerate is produced from serine via hydroxypyruvate in peroxisomes. In P. nigra, hydroxypyruvate, glycerate and glycine were labeled with 13 C, whereas in C. japonica, glycolate and a non-canonical photorespiratory metabolite, formate, were also labeled, suggesting that an H2 O2 -mediated non-enzymatic decarboxylation (NED) reaction occurs in C. japonica. We analyzed changes in the metabolite contents of leaves kept in the dark and leaves exposed to illuminated photorespiration-promoting conditions: a positive relationship between formate and serine levels in C. japonica implied that the active C1 -metabolism pathway synthesizes serine from formate. Leaf gas exchange analyses revealed that CO2 produced through NED was recaptured by chloroplasts. Database analysis of the peroxisomal targeting signal motifs of an H2 O2 -scavenging enzyme, catalase, derived from various species, including nine coniferous species, as well as analyses of peroxisomal fractions isolated from C. japonica and P. nigra leaves indicated that conifer peroxisomes had less catalase activity. These results suggest that NED and the subsequent C1 metabolism are involved in the photorespiratory pathway of conifer leaves, where peroxisomes have intrinsically low catalase activity.


Electrospun cellulose acetate/activated carbon composite modified by EDTA (rC/AC-EDTA) for efficient methylene blue dye removal.
The present study fabricated regenerated cellulose nanofiber incorporated with activated carbon and functionalized rC/AC3.7 with EDTA reagent for methylene blue (MB) dye removal. The rC/AC3.7 was fabricated by electrospinning cellulose acetate (CA) with activated carbon (AC) solution followed by deacetylation. FT-IR spectroscopy was applied to prove the chemical structures. In contrast, BET, SEM, TGA and DSC analyses were applied to study the fiber diameter and structure morphology, the thermal properties and the surface properties of rC/AC3.7-EDTA. The CA was successfully deacetylated to give regenerated cellulose nanofiber/activated carbon, and then ethylenediaminetetraacetic acid dianhydride was used to functionalize the fabricated nanofiber composite. The rC/AC3.7-EDTA, rC/AC5.5-EDTA and rC/AC6.7-EDTA were tested for adsorption of MB dye with maximum removal percentages reaching 97.48, 90.44 and 94.17%, respectively. The best circumstances for batch absorption experiments of MB dye on rC/AC3.7-EDTA were pH 7, an adsorbent dose of 2 g/L, and a starting MB dye concentration of 20 mg/L for 180 min of contact time, with a maximum removal percentage of 99.14%. The best-fit isotherm models are Temkin and Hasely. The outcome of isotherm models illustrates the applicability of the Langmuir isotherm model (LIM). The maximal monolayer capacity Qm determined from the linear LIM is 60.61 for 0.5 g/L of rC/AC3.7-EDTA. However, based on the results from error function studies, the generalized isotherm model has the lowest accuracy. The data obtained by the kinetic models' studies exposed that the absorption system follows the pseudo-second-order kinetic model (PSOM) throughout the absorption period.


Multilevel modelling of factors associated with caesarean section in Ethiopia: community based cross sectional study.
The aim of this study was to identify socio-demographic and health related factors associated with caesarean section in Ethiopia. A total of 256 mothers undergoing to CS among 7193 delivery. Average maternal age of a participant was 29.26 years and 80% of mothers having two and more children. A woman delivered in private institution was 30% (AOR = 1.29; 95% CI 1.25, 1.32) more likely undergoing CS as compared to home delivery. Factors associated with CS were higher education level (AOR = 1.09, 95% CI 1.07, 1.12), preceding birth interval (AOR = 1.01; 95% CI 1.00. 1.03), multiple pregnancy (AOR = 1.11; 95% CI 1.08, 1.15), multiple parity (AOR = 0.98; 95% CI 0.97, 0.99), large size the child (AOR = 1.01; 95% CI 1.001, 1.02), richest households (AOR = 0.98; 95% CI 0.97, 0.99), rural residence (AOR = 0.98 95% CI 0.96, 0.99) and Addis Ababa (AOR = 1.06; 95% CI 1.04,1.09). As a conclusion and recommendation, the prevalence of CS higher in private institutions and Addis Ababa, so professionals should apply CS alone medical indication.


Integration of in silico methods and computational systems biology to explore endocrine-disrupting chemical binding with nuclear hormone receptors.
Thousands of potential endocrine-disrupting chemicals present difficult regulatory challenges. Endocrine-disrupting chemicals can interfere with several nuclear hormone receptors associated with a variety of adverse health effects. The U.S. Environmental Protection Agency (U.S. EPA) has released its reviews of Tier 1 screening assay results for a set of pesticides in the Endocrine Disruptor Screening Program (EDSP), and recently, the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) data. In this study, the predictive ability of QSAR and docking approaches is evaluated using these data sets. This study also presents a computational systems biology approach using carbaryl (1-naphthyl methylcarbamate) as a case study. For estrogen receptor and androgen receptor binding predictions, two commercial and two open source QSAR tools were used, as was the publicly available docking tool Endocrine Disruptome. For estrogen receptor binding predictions, the ADMET Predictor, VEGA, and OCHEM models (specificity: 0.88, 0.88, and 0.86, and accuracy: 0.81, 0.84, and 0.88, respectively) were each more reliable than the MetaDrug™ model (specificity 0.81 and accuracy 0.77). For androgen receptor binding predictions, the Endocrine Disruptome and ADMET Predictor models (specificity: 0.94 and 0.8, and accuracy: 0.78 and 0.71, respectively) were more reliable than the MetaDrug™ model (specificity 0.33 and accuracy 0.4). A consensus approach is proposed that reaches general agreement among the models (specificity 0.94 and accuracy 0.89). This study integrates QSAR, docking, and systems biology approaches as a virtual screening tool for use in risk assessment. As such, this systems biology pathways and network analysis approach provides a means to more critically assess the potential effects of endocrine-disrupting chemicals.


Orchiectomy reduces hepatotumorigenesis of H-ras12V transgenic mice via the MAPK pathway.
A common characteristic of hepatocellular carcinoma in humans and animals is a striking male prevalence. However, the underlying mechanisms remain largely unknown. We have reported that hepatotumorigenesis is prevalent in male H-ras12V transgenic mice (Wang et al., 2005). Orchiectomy and ovariectomy were performed to determine if the presence of sex organ-related factors contributes to hepatotumorigenesis. After orchiectomy and ovariectomy, the mice were sampled at 6 months of age. The pathological diagnosis, sex hormone levels, expression of the H-ras12V transgene, and ras related signal pathways were determined. Orchiectomy significantly reduced the incidence of hepatotumorigenesis in males. However, no significant difference was detected in the incidence of tumorigenesis between ovariectomized and non-ovariectomized females. Molecular biochemical experiments showed that the sex organ-related factors significantly influenced transgene expression, which contributed to activation of the MAPK signaling pathway. The present study demonstrates that testis-related factors play important roles in hepatotumorigenesis in H-ras12V transgenic mice.


Lung Fibroblasts Support Metastasis through Immune Microenvironment Remodeling.
COX-2+ lung fibroblasts reprogram myeloid cells to be immunosuppressive and support lung metastasis.


A novel osmosis membrane bioreactor-membrane distillation hybrid system for wastewater treatment and reuse.
A novel approach was designed to simultaneously enhance nutrient removal and reduce membrane fouling for wastewater treatment using an attached growth biofilm (AGB) integrated with an osmosis membrane bioreactor (OsMBR) system for the first time. In this study, a highly charged organic compound (HEDTA(3-)) was employed as a novel draw solution in the AGB-OsMBR system to obtain a low reverse salt flux, maintain a healthy environment for the microorganisms. The AGB-OsMBR system achieved a stable water flux of 3.62L/m(2)h, high nutrient removal of 99% and less fouling during a 60-day operation. Furthermore, the high salinity of diluted draw solution could be effectively recovered by membrane distillation (MD) process with salt rejection of 99.7%. The diluted draw solution was re-concentrated to its initial status (56.1mS/cm) at recovery of 9.8% after 6h. The work demonstrated that novel multi-barrier systems could produce high quality potable water from impaired streams.


Serotonin 5-HT2A receptor expression and functionality in postmortem frontal cortex of subjects with schizophrenia: Selective biased agonism via Gαi1-proteins.
Serotonin 5-HT2A receptors (5-HT2ARs) have been implicated in schizophrenia. However, postmortem studies on 5-HT2ARs expression and functionality in schizophrenia are scarce. The 5-HT2AR mRNA and immunoreactive protein expression were evaluated in postmortem tissue from dorsolateral prefrontal cortex (DLPFC) of antipsychotic-free (n = 18) and antipsychotic-treated (n = 9) subjects with schizophrenia, and matched controls (n = 27). Functional coupling of 5-HT2AR to G-proteins was tested by measuring the activation induced by the agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride ((±)DOI) in antibody-capture [35S]GTPγS scintillation proximity assays (SPA). In antipsychotic-free schizophrenia subjects, 5-HT2AR mRNA expression and protein immunoreactivity in total homogenates was similar to controls. In contrast, in antipsychotic-treated schizophrenia subjects, lower mRNA expression (60±9% vs controls) and a trend to reduced protein immunoreactivity (86±5% vs antipsychotic-free subjects) just in membrane-enriched fractions was observed. [35S]GTPγS SPA revealed a significant ~6% higher stimulation of Gαi1-protein by (±)DOI in schizophrenia, whereas activation of the canonical Gαq/11-protein pathway by (±)DOI remained unchanged. Expression of Gαi1- and Gαq/11-proteins did not differ between groups. Accordingly, in rats chronically treated with clozapine, but not with haloperidol, a 30-40% reduction was observed in 5-HT2AR mRNA expression, 5-HT2AR protein immunoreactivity and [3H]ketanserin binding in brain cortical membranes. Overall, the data suggest a supersensitive 5-HT2AR signaling through inhibitory Gαi1-proteins in schizophrenia. Together with previous results, a dysfunctional pro-hallucinogenic agonist-sensitive 5-HT2AR conformation in postmortem DLPFC of subjects with schizophrenia is proposed. Atypical antipsychotic treatment would contribute to counterbalance this 5-HT2AR supersensitivity by reducing receptor expression.


Detection of in vitro macrophage colony-forming cells (M-CFC) in mouse bone marrow, spleen, and peripheral blood.
In vitro macrophage colony-forming cells (M-CFC) have been detected in bone marrow (BM) (317/10(5) cells), spleen (SPL) (81/10(5)), and peripheral blood leukocytes (PBL) (242/10(5)) of the mouse. These M-CFCs were similar to those previously detected in thymus (T) (30/10(6)) and lymph node (LN) (22/10(6)) tissue in several respects. BM- and SPL-derived M-CFC required PMUE to consistently initiate colony formation, whereas PBL-derived M-CFC formed colonies with stimulation by either PMUE or L-cell-conditioned medium. All colonies formed showed a singular macrophage line of differentiation, a lag of 13 to 18 days prior to initiating colony formation, a marked ability to survive in culture in the absence of PMUE, and markedly slow rates of appearance in culture once colony formation was initiated. The macrophage progeny were identified on the basis of morphology, glass adherence, the phagocytosis of agar, bacteria and SRBC, and the presence of receptors for IgG. These characteristics are also shared by those macrophage CFCs observed within stimulated peritoneal exudate, pleural effusion, and alveolar space. These M-CFCs are most likely members of a large, heterogeneous population of macrophage progenitor cells distributed throughout the hemato-lymphopoietic organs, serosal cavities and surfaces, and inflammatory and alveolar tissue sites. The degree of heterogeneity may be determined in part by the influence of tissue-specific microenvironment.


Verminoside from Pseudolysimachion rotundum var. subintegrum sensitizes cisplatin-resistant cancer cells and suppresses metastatic growth of human breast cancer.
Breast cancer is one of the most common cancers in women and is associated with a high mortality rate. The majority of deaths resulting from breast cancer are attributable to metastatic growth; in addition, chemoresistance is a major concern in the treatment of patients with breast cancer. However, limited drugs are available for the treatment of metastatic breast cancer. In this study, the chemoadjuvant effects of a methanolic extract from the leaves of Pseudolysimachion rotundum var. subintegrum (NC13) and an active component isolated from the plant, verminoside (Vms), were evaluated. Furthermore, their potent anti-metastatic activities were validated in vitro and in vivo in animal models. The anti-metastatic and chemosensitizing activities of NC13 and Vms on cisplatin treatment were found to be partly mediated by suppression of the epithelial-mesenchymal transition of cancer cells. Collectively, our results implied that NC13 and its bioactive component Vms could be developed as effective chemoadjuvants in combination with conventional therapeutics.


Diagnosis and initial management of laryngotracheal injuries associated with facial fractures.
Laryngotracheal injuries are uncommon with an estimated incidence of 1 per thousand (1-6 patients per 15000-42500 trauma victims). They may be associated with fractures of the facial skeleton. Their symptoms are variable ranging from obvious airway obstruction to minor or almost missing symptoms. Early diagnosis and proper initial management may sometimes be difficult or delayed. Three patients with maxillofacial fractures and concomitant laryngotracheal injuries are presented. The diagnostic procedures used and the management of these injuries are reported. Due to their low incidence and their hidden nature laryngotracheal injuries may pose diagnostic problems, especially in polytraumatized or intubated patients. Subcutaneous emphysema is the chief clinical sign. Fibreoptic endoscopy is the most important and informative diagnostic examination. Radiographic evaluation by CT scan provides additional information about the extent of the injury and the indication for surgery. A coordinated team approach is necessary for proper management of these injuries.


Effect of Brahmyadi Churna (Brahmi, Shankhapushpi, Jatamansi, Jyotishmati, Vacha, Ashwagandha) and tablet Shilajatu in essential hypertension: An observational study.
Hypertension (HTN) is one among the fiery health problems of the present era. Since it does not cause symptoms usually for many years until a vital organ is damaged. The present study was carried out on 40 patients of essential HTN with Brahmyadi Churna and tablet Shilajatu for a period of 1 month with milk as Anupana. Observation was done before the treatment, 3 mid test assessments on 7(th), 14(th), and 21(st) day, posttest assessment was done on 30(th) day. Intervention revealed that 19 had marked improvement, 14 had moderate improvement, 5 had mild improvement, and no improvement was noticed in 2 individuals. Reduction in blood pressure was observed markedly with P < 0.000.


Human genetics after the bomb: Archives, clinics, proving grounds and board rooms.
In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention.


Intra-atrial course of right coronary artery - case report.
Intra-atrial course of the right coronary artery is a rare anomaly. The recognition of this entity is crucial to avoid potential hazards related to vessel injury during interventional procedures such as right heart catheterization, pacemaker implantation, invasive electrophysiology testing or atrial flutter ablation. We present a case of a 62-year old female with paroxysmal atrial flutter and atrial fibrillation, whose cardiac computed tomography revealed an anomalous course of the right coronary artery through the right atrium. Cardiac computed tomography examination enables an accurate assessment of morphology and location of the anomalous vessel course.


Identification of a natural cycle involving Rickettsia typhi infection of Monopsyllus sciurorum sciurorum fleas from the nests of the fat dormouse (Glis glis).
In a mountainous area in the Dinaric Beech-Fir Forest of southern Slovenia, summer nests of the European fat dormouse (Glis glis) were collected. From these dormouse nests, 180 Monopsyllus sciurorum sciurorum fleas were examined by polymerase chain reaction with primers for the Rickettsia citrate synthase gene. Samples from one nest yielded the expected 381 base pair DNA product. The origin of the DNA product was identified as Rickettsia typhi by AluI restriction fragment length polymorphism analysis. Inoculation of the triturated positive fleas into Vero cell culture resulted in the cultivation of a rickettsia which reacted with polyclonal and species-specific monoclonal antibodies for R. typhi. The widespread distribution of this sylvatic flea species in nearly all of Europe as well as in the Middle East and its presence on other mammalian and avian hosts suggests that R. typhi might exist in unrecognised enzootic cycles. Further investigations are needed to determine the extent of these cycles in Europe and the potential occurrence of human infections.


Cytogenetic monitoring of industrial populations potentially exposed to genotoxic chemicals and of control populations.
Currently the most applied technique for monitoring biological effects of exposure to genotoxic chemicals in industrial workers is the measurement of chromosome aberrations in peripheral blood lymphocytes. In the Shell petrochemical complex in The Netherlands cytogenetic monitoring studies have been carried out from 1976 till 1981 inclusive, in workers potentially exposed to a variety of genotoxic chemicals, i.e. vinyl chloride, ethylene oxide, benzene, epichlorohydrin, epoxy resins. Average exposure levels to these chemicals were well below the occupational exposure limits. Results of these studies indicate that no biologically significant increase in the frequencies of chromosome aberrations in the exposed populations occurred compared with control populations. Our experience with this methodology has shown that the results of chromosome analyses are difficult to interpret, due to the variable and high background levels of chromosome aberrations in control populations and in individuals. It is concluded that the method is not sufficiently sensitive for routine monitoring of cytogenetic effects in workers exposed to the low levels of genotoxic compounds.


The effects of single versus combined cue presentations on picture naming by aphasic adults.
Research has demonstrated that the presentation of auditory and visual cues is an effective clinical procedure for improving picture naming of nonfluent aphasic speakers. The effect of combined cue presentation, however, has not been clearly demonstrated. The present study investigated the effect of single and multiple cueing techniques used with nonfluent (Broca's) aphasic patients. The subjects were divided into a minimum or maximum error group based on their performance on a picture-naming task. Printed words (in either cursive or manuscript style), initial syllables, and sentence completion cues were presented independently and in combination. Discussion is directed toward the potential clinical application of multiple cueing techniques.


Chemoreceptor stimulation interferes with regional hypoxic pulmonary vasoconstriction.
Hypoxemia interferes with the diversion of blood flow away from hypoxic regions of the lung, possibly through activation of the arterial chemoreceptor reflex. The purpose of this study was to determine if selective stimulation of carotid chemoreceptors reduces the diversion of flow (hypoxic vasoconstriction) when normal systemic oxygen levels are present. Chloralose anesthetized dogs were paralyzed and each lung was separately ventilated via a dual-lumen endobronchial tube. Left pulmonary artery (QL) and main pulmonary artery (QT) blood flows were measured with electromagnetic flow probes. Chemoreceptors were stimulated by perfusion of the carotid sinuses with hypoxic, hypercapnic blood. QL/QT averaged 46 +/- 4, 29 +/- 2, and 36 +/- 4% during bilateral O2 ventilation (control), left lung N2 ventilation, and left lung N2 plus chemoreceptor stimulation in dogs treated with the cyclo-oxygenase inhibitor meclofenamate. After vagotomy, QL/QT averaged 45 +/- 4, 27 +/- 3, and 28 +/- 2% during the same conditions. QL/QT decreased significantly from control (P less than 0.05) during left lung N2 alone but did not decrease during left lung N2 plus chemoreceptor stimulation in dogs with intact vagi. In contrast, QL/QT decreased significantly both before and during chemoreceptor stimulation in vagotomized dogs. The same responses were observed in dogs not treated with meclofenamate. These results indicate that selective stimulation of arterial chemoreceptors can interfere with regional hypoxic vasoconstriction and suggest that the vagus nerves may mediate this effect.


Lewis base catalyzed ring opening of aziridines with silylated nucleophiles.
The ring opening of N-tosylaziridines with trimethylsilylated nucleophiles, catalyzed by N,N,N',N'-tetramethylethylenediamine, led to the production of beta-functionalized sulfonamides in good to excellent yields with high regioselectivity. [reaction: see text]


Influence of absorbable dusting powders on wound infection.
Surgical glove dusting powders are commonly used as mold-release agents and to facilitate donning. Cornstarch and CaCO3 are commonly used absorbable dusting powders. This experimental study demonstrates that these absorbable dusting powders significantly potentiate bacterial growth and enhance a wound's inflammatory response. The infection-potentiating effects of CaCO3 are significantly greater than those of cornstarch.


Interface analysis of titanium and zirconium bone implants.
A thin layer of titanium or zirconium was evaporated onto the surface of a plastic implant which was then inserted in the rabbit tibial metaphysis for six months. The implants and surrounding bone were cut out en bloc and sectioned for phase contrast microscopy, scanning- and transmission-electron microscopy. The intact bone-to-metal interface in the case of titanium revealed a fibrous tissue-free boundary zone with a 200-400 A thick proteoglycan coat immediately adjacent to the titanium oxide. Thereafter collagen filaments were seen and, at approximately 1000 A from the interface, collagen bundles. The tissues surrounding the zirconium-coated implant consisted of a 300-500 A thick proteoglycan layer, followed by a zone with collagen filaments and collagen bundles, not closer to the zirconium oxide than a few thousand A.


Quantification of cytosolic steroid receptors in secretory and non-secretory epithelial cells of the canine prostate.
Radiolabelled methyltrienolone, dihydrotestosterone and estradiol were used as ligands to identify and quantify androgen and estrogen receptors in freshly dispersed cells from the canine prostate. Soluble extracts (cytosols) were obtained from secretory and non-secretory epithelial cells separated on the basis of their density in Percoll gradients. For both cell types, as well as for the whole prostate, Scatchard plot analyses were linear and showed a single class of high affinity binding sites: Kd values of 3.6 +/- 2.2 X 10(-9) M and 3.0 +/- 1.2 X 10(-10) M were measured for the androgen and estrogen receptors, respectively. The number of binding sites for the cytosolic androgen receptor, expressed per mg of protein or per mg of DNA, was 2.4- to 6.7-fold higher in the non-secretory cells compared to the secretory cells. However, these two cell types contained a similar number of specific sites for the estrogens. The specificities of the androgen and estrogen receptors were shown to be identical for the two cell types: the binding of [3H]R1881 was strongly inhibited by unlabelled R1881, 5 alpha-androstane-3 alpha, 17 beta-diol and dihydrotestosterone, while 5 alpha-androstane-3 beta, 17 beta-diol, estradiol and estrone did not displace bound R1881. The addition of triamcinolone acetonide did not alter the binding of R1881 in extracts of either cell type or in the whole prostate. The binding of [3H]estradiol to the estrogen receptor was highly specific since a strong displacement was only observed with estradiol (83%).


Crossover comparison of captopril and propranolol as step 2 agents in hypertension.
The efficacy of captopril treatment was compared with that of propranolol in a single-blind crossover study in 14 patients with essential hypertension uncontrolled on diuretic alone. Both captopril (37.5 to 75 mg daily) and propranolol (60 to 120 mg daily), in combination with hydrochlorothiazide (50 mg daily), caused a significant fall in sitting systolic and diastolic blood pressure. Heart rate, plasma renin activity, and plasma aldosterone data were consistent with the effects of converting enzyme inhibition or beta blockade. Both drugs were well tolerated. Captopril appeared to be equivalent in efficacy and safety to propranolol when added to hydrochlorothiazide. It may be considered as an alternative step 2 antihypertensive agent, especially in patients experiencing unwanted effects on beta blockers.


Sensitivity of bone histomorphometry in the diagnosis of metabolic bone diseases.
Diagnostic sensitivity of bone histomorphometry was assessed in different metabolic bone diseases, after fixing the specificity at 75%, 90% and 95% reference levels. Sensitivity was particularly high in cases with greatly increased osteoid and/or resorption features, as in renal osteodystrophy (ROD). All the remodeling indicators were highly sensitive toward advanced or severe forms of mixed ROD (mROD). Osteoid indicators were the most sensitive parameters in ROD with predominant osteomalacia (oROD). Osteoclastic and several osteoid indicators were very sensitive in all grades of ROD with predominant hyperparathyroidism (hROD). Sensitivity was generally low in uremic patients without bone changes (wROD) and also in patients with idiopathic osteoporosis (OP). It is our recommendation, however, that for each individual patient the definite diagnosis should be based on both morphological, clinical and metabolic parameters.


Effects of dividing amlodipine daily doses on trough drug concentrations and blood pressure control over a 24-hour period.
In the treatment of hypertension, once-daily administration of long-acting antihypertensive drugs has been recommended for the improvement of treatment adherence; however, it is unclear whether dividing daily doses has the additional benefit of more ideal blood pressure (BP) control over a 24-hour period. The aim of the study was to investigate whether dividing a 10-mg daily dose of amlodipine, a long-acting calcium channel blocker, is associated with increased trough plasma amlodipine concentrations, reduced arterial stiffness, and improved BP control over a 24-hour period. Outpatients with essential hypertension were included this open-label, 2-period crossover study. The patients were administered amlodipine 10 mg/d in 2 divided doses for 8 weeks. At week 4, blood was collected just before amlodipine administration for the evaluation of trough plasma amlodipine concentrations. At week 8, 24-hour, daytime, nighttime, and early morning BP, as well as arterial stiffness, were measured using ambulatory BP monitoring (ABPM) and cardio-ankle vascular index (CAVI), respectively. In the subsequent study period, amlodipine 10 mg/d was administered once daily, and the same tests were performed at the same timings as in period 1. Ten patients were enrolled (7 men, 3 women; mean age, 61.0 [15.3] years). Mean 24-hour BP with twice-daily administration was not significantly lower than that with once-daily administration (129.7 [7.3]/80.1 [7.9] mm Hg vs 130.5 [11.8]/80.1 [7.9] mm Hg, respectively). Similarly, there were no significant differences in daytime, nighttime, or early morning BP between twice- and once-daily administration. In addition, the differences in trough plasma amlodipine concentrations (22.37 [7.66] ng/mL vs 20.57 [8.22] ng/mL) and CAVI values (8.2 [1.8] vs 8.5 [1.0]) were not significantly different between twice- and once-daily administration. Administering amlodipine in 2 divided doses was not associated with increased trough plasma amlodipine concentrations, reduced arterial stiffness, or improved BP control over a 24-hour period in patients with essential hypertension.


Synthesis and biological evaluation of novel ferrocenyl curcuminoid derivatives.
With the purpose to improve the biological activities of curcumin, eight novel ferrocenyl curcuminoids were synthesized by covalent anchorage of three different ferrocenyl ligands. We evaluated their cytotoxicity on B16 melanoma cells and normal NIH 3T3 cells, their inhibition of tubulin polymerization and their effect on the morphology of endothelial cells. The presence of a ferrocenyl side chain was clearly shown to improve the biological activity of most of their corresponding organic curcuminoid analogues.


Best variable identification by means of data-mining and cooperative game theory.
To develop and evaluate methods to assess single and grouped variables impact on measuring intervention severities and support a search for most expressive variables. Datasets of cohort studies are analyzed automatically based on algorithms. For this, a metric is developed to compare measured variables in different cohorts in a data-mining process. Variables are measured in all possible combinations to detect possible synergies of certain variable constellations and allow for a ranking of the combinations' expressiveness. Such ranking serves as a basis for a wide range of algorithmic data analysis. In an exemplary application, every group member's impact on the total result is determined based on the principle of the cooperative game theory besides to the total expressiveness of the variable groups. For different types of interventions, the method is applied to experimental data containing multiple recorded medical lab values. The expressiveness of variable combinations to indicate severity is ranked by means of a metric. Within each combination, any variable's contribution to the total effect is determined and accumulated over whole datasets to yield local and global variable importance measures. The computed results have been successfully matched with clinical expectations to prove their plausibility. Algorithmic evaluation shows to be a promising approach in automatized quantification of variable expressiveness. It can assess descriptive power of measurements, help to improve future study designs and expose worthwhile research issues.


Laryngotracheal reconstruction with resorbable microplate buttressing.
In patients undergoing laryngotracheal reconstruction (LTR), malacic segments of trachea can pose challenges to successful reconstruction. Malacic segments may inadequately support cartilage grafts used in augmentation surgery, sometimes requiring cricotracheal or tracheal resections. We describe a novel technique of LTR with resorbable microplate buttressing of malacic lateral tracheal segments. Retrospective case series. Review of technique, treatment outcomes, and complications of seven children with subglottic stenosis and tracheomalacia requiring a microplate-augmented LTR technique. Seven infants ranging from 26 months to 9 years of age successfully underwent LTR for subglottic stenosis. Six children had a grade III subglottic stenosis. The seventh child had grade II subglottic stenosis, bilateral vocal fold paralysis, an elliptical cricoid, and an obstructing giant suprastomal fibroma. Five children underwent a double-stage LTR with resorbable microplates sutured bilaterally to support severely malacic lateral tracheal segments. A cricotracheal resection would not have been feasible in one child due to the resection length and inadequate tracheal mobilization. Two children underwent a single-stage LTR with unilateral application of a microplate. Six children were decannulated within 3 months and continue without airway symptoms or complications. One child, who is just over 2 months from reconstructive surgery, is being setup for decannulation. No complications were encountered. LTR with resorbable microplate buttressing of malacic lateral tracheal segments is technically feasible, safe, and can avoid more extensive surgery requiring tracheal resection. Further experience may support the use of this technique in challenging airway reconstructions.


Relationship between metabolic syndrome and acylated/desacylated ghrelin ratio in patients with schizophrenia under olanzapine medication.
Ghrelin is a peptide hormone that mediates glucose homeostasis and lipid metabolism. Acylated ghrelin (AG) and desacylated ghrelin (DAG) are the two main forms of ghrelin, which have opposing roles in energy homeostasis. The AG/DAG ratio has been proposed to be associated with metabolic syndrome (MetS) in the general population. This study compared the relationships between MetS and ghrelin parameters in patients with schizophrenia. Patients diagnosed with schizophrenia and under olanzapine monotherapy were recruited. Fasting blood samples were collected for the analyses of metabolic and ghrelin parameters. The serum levels of total ghrelin and AG were measured by enzyme-linked immunosorbent assay kits. DAG level was calculated by subtracting the AG level from the total ghrelin level. We recruited 151 subjects with schizophrenia, and classified them into those with MetS (n = 41) and those without MetS (n = 110). Subjects with MetS had a significantly higher AG/DAG ratio, as well as lower total ghrelin and DAG levels. There were no sex differences in ghrelin parameters. The AG/DAG ratio was significantly and positively correlated with weight, body mass index, waist circumference, insulin level, homeostasis model assessment of insulin resistance and number of MetS components. Multiple linear regression analysis indicated that the number of MetS components remained significantly associated with the AG/DAG ratio. Our results revealed that lower AG/DAG ratios were associated with better metabolic profiles in olanzapine-treated patients with schizophrenia. These observations suggest that the balance between AG and DAG plays a crucial role in the metabolic homeostasis among patients with schizophrenia.


Heart rate pattern during sleep in an infant with congenital prolongation of the Q-T interval (Romano-Ward syndrome).
Heart rate and the variability of the heart rate, indices of autonomic control, were studied during sleep in an infant with prolonged Q-T interval (Romano-Ward syndrome) and were compared to the heart rate and variability of heart rate in 18 normal infants studied at monthly intervals during the first four months of life. The overall variability and beat-to-beat variability in the infant with Romano-Ward syndrome were significantly below the median in the normal infants at each age and sleep state. This decrease in overall and beat-to-beat variability persisted after normalization by the absolute heart rate; however, the heart rate in the infant with Romano-Ward syndrome was not different from those in normal infants. These data suggest that the presence of a normal heart rate does not exclude abnormal autonomic activity; and in certain clinical situations, the variability of heart rate may be a more sensitive index of abnormal autonomic function than the heart rate itself.


Adverse events following live-attenuated intranasal influenza vaccination of children with cystic fibrosis: Results from two influenza seasons.
Despite the approved use of live-attenuated intranasal influenza vaccine (LAIV) for seasonal immunization of patients with cystic fibrosis (CF), many questions remain unanswered regarding the timing, duration, and types of adverse events that occur following administration of this vaccine. In 2012 and 2013, 264 LAIV doses were administered to 198 patients aged 2-19 with CF. Vaccinees were followed prospectively for 55 days after vaccination (day 0) and information on adverse events was collected. Bayesian change-point analysis was used to identify the risk period following LAIV during which participants had a higher risk of reporting adverse events. Multivariable zero-inflated Poisson regression models were then used to estimate the adjusted incidence rate ratio (aIRR) and 95% credible interval (CrI) of reporting each adverse event in the risk period versus the control period. There was a higher risk of reporting serious adverse events (SAEs) (aIRR 1.45, 95% CrI (0.29, 5.17)) and solicited symptoms during days 0-6 of follow-up compared to control period days 7-55. However, most SAEs were not causally related to LAIV and the solicited symptom episodes were brief, usually lasting 1-2 days. There was no increased risk of antibiotic prescriptions for respiratory conditions in the risk vs. control periods (aIRR 0.48, 95% CrI (0.23, 0.91)). Adverse events were most common 0-6 days after LAIV administration but were generally benign and self-limiting. Pulmonary exacerbations did not increase in frequency.


Elevated lactate impairs the efficacy of antiviral treatment on post-hepatectomy survival for advanced stage hepatitis B virus - related hepatocellular carcinoma.
Nucleoside and nucleotide analogues (NAs) have a risk of mitochondrial toxicity and then inducing the increase of lactate. We aim to evaluate the impact of lactate on the effects of NAs therapy in hepatitis B virus-related hepatocellular carcinoma (HCC) patients after curative liver resection. Five hundred and fifty-seven HBV-related HCC patients were divided into the treatment and control group according to whether they received NAs therapy or not. Perioperative and prognosis data were retrospectively reviewed. The treatment group had a better overall survival rate (OS) than the control group (P = 0.017). The recurrence-free survival rate (RFS) did not significantly differ between the two groups (P = 0.174). NAs could improve the OS of early stage HCC patients (P = 0.028), as well as the OS of advanced stage HCC patients with low level of lactate in subgroup analysis stratified against the level of lactate (P = 0.037). Advanced stage HCC patients in the treatment group had a higher value of lactate than those in the control group (P = 0.024). Besides, advanced stage HCC patients had a higher value of lactate than early stage HCC patients in the treatment group (P < 0.001), as well as in the control group (P < 0.001). NAs could improve the long-term outcomes of HBV-related HCC patients after curative liver resection. However, the improvement effect of NAs therapy is counteracted by the adverse effect of elevated lactate in advanced stage HBV-related HCC patients.


Comparing retinal changes measured by optical coherence tomography in patients with schizophrenia and their siblings with healthy controls: Are retinal findings potential endophenotype candidates?
The aim of our study is to examine whether differences in retinal structure may reflect endophenotypes for schizophrenia by comparing thicknesses of retinal layers between patients with schizophrenia, their unaffected siblings, and healthy control groups and investigating the relationship between OCT findings and disease parameters. 46 patients with schizophrenia, their 46 healthy siblings, and 46 age and gender-matched healthy controls were enrolled in the study and underwent spectral domain OCT (examinations to assess differences in peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL)+ inner plexiform layer (IPL) thicknesses and macular volumes (MV) in both eyes). Clinical variables were also recorded in the patient group. There was no difference between the groups in terms of RNFL thicknesses. The GCL+IPL thicknesses of the siblings are between the patients and controls but according to post hoc comparisons the GCL+IPLs of the patients were only thinner than controls. Additionally, MVs were significantly lower in the patient group compared to the sibling group. There was no correlation between any clinical parameters and the GCL+IPLs of all groups, however there were some correlations between RNFL and clinical features especially in the patients group. GCL+IPL values do not seem to be affected by the disease parameters or the factors like body mass index or nicotine use. On the other hand, further studies are needed to determine whether GCL+IPL could be an endophenotype candidate.


Improving medical approaches to primary CNS malignancies--retinoid therapy and more.
Successfully inducing differentiation in ectodermal diseases, retinoids harbour considerable therapeutic potential in the treatment of neuroectodermal-neuroepithelial malignancies. The principal tissue retinoid, retinoic acid, can be potently upregulated in vivo by a relatively specific catabolic inhibitor, R75251 (liarozole). Both substances have been given orally over 2 years in addition to standard treatment, and have been well tolerated. Corresponding closely to plasma retinoid levels, cutaneous side effects facilitate individual dosing. We evaluate this adjuvant retinoid approach and additional efforts to improve therapy of primary CNS malignancies, including the topical administration of retinoids in gamma linolenic acid.


DNA interstrand cross-linking efficiency and cytotoxic activity of novel cadmium(II)-thiocarbodiazone complexes.
We have prepared mono- and binuclear complexes of Zn(II) and Cd(II) with bis(2-pyridyl aldehyde) thiocarbodiazone (H(2)L(1)) and bis(methyl 3-pyridyl ketone) thiocarbodiazone (H(2)L(2)). Cytotoxicity data against the ovarian tumor cell line A2780cisR (acquired resistance to cisplatin) indicate that the mononuclear complex Cd/H(2)L(2) (1) and the binuclear complex Cd(2)/H(2)L(1) (4) are able to circumvent cisplatin resistance and that their cytotoxic activity does not substantially vary after depletion of intracellular levels of glutathione. Moreover, DNA binding studies show that complexes 1 and 4 have higher efficiency than cisplatin at forming DNA interstrand cross-links in both naked pBR322 plasmid and A2780cisR cellular DNA. Interestingly, the thiocarbodiazone ligands alone do not show the biological properties of complexes 1 and 4. Altogether these results suggest that DNA interstrand cross-link formation by compounds 1 and 4 might be related with their cytotoxic activity in cisplatin-resistant cells. We think that compounds 1 and 4 may represent a novel structural lead for the development of cadmium cytotoxic agents capable of improving antitumor activity in cisplatin-resistant tumors.


Massive Pulmonary Embolism Mimicking Acute Myocardial Infarction: Successful use of extracorporeal membrane oxygenation support as bridge to diagnosis.
Prolonged cardiac arrest with pulseless electrical activity (PEA) results in death if its aetiology cannot be corrected immediately. We describe the case of a 75-year-old man with chest pain and his electrocardiogram (ECG) revealing ST-segment elevation in leads II, III, and aVf. Inferior wall myocardial infarction was subsequently diagnosed. Before performing emergency coronary angiography, however, a sudden cardiac arrest with PEA developed and the patient was placed on advanced cardiac life support. Oxygenation support for the extracorporeal membrane was initiated approximately 65min after prolonged cardiopulmonary resuscitation. Emergency coronary arteriogram showed no obstructive lesions in the right coronary artery. This result, however, was not consistent with the ECG findings, and thus, a massive pulmonary embolism was suspected. Subsequent pulmonary artery angiography showed severe emboli in bilateral branches of the pulmonary arteries. Catheter-directed thrombolysis with urokinase was administered, which ultimately failed, and surgical embolectomy was performed with extracorporeal membrane oxygenation support. After the above intervention, the patient was discharged on hospital day 60 without any sequelae or neurological deficits.


Long-standing insulinoma: two case reports and review of the literature.
Insulinomas are rare pancreatic endocrine tumors. Most are benign and solitary. However, the nonspecific symptoms and small size of these tumors led to difficulties of diagnosis and localization. We present two Arab patients with pancreatic long-standing insulinoma. Both patients presented episodic hypoglycemic symptoms respectively during 10 and 2 years. Biochemical and morphological workup detected localized pancreatic insulinoma. Open procedure surgery was done for the two patients and insulinomas were successfully removed by enucleation. Insulinoma remains a diagnostic challenge to practitioners. Diagnosis of suspected cases is easily confirmed by standard endocrine tests, especially the supervised fasting test. Accurate preoperative localization is essential for more effective and safest surgery.


Tricuspid and pulmonary atresia with coarctation of the aorta: a rare combination possibly explained by persistence of the fifth aortic arch with a systemic-to-pulmonary arterial connection.
A ten-day old baby was found to have tricuspid and pulmonary atresia, and a "ductal-dependent" pulmonary circulation that was prostaglandin-sensitive. An unusual coarctation of the aorta was not recognised until an autopsy was performed, some 11 days after construction of an aortopulmonary shunt. A previously undefined anomaly in this neonate was persistence of the fifth aortic arch with a systemic-to-pulmonary artery connection on the same side as the definitive aorta. The histology of the fifth aortic arch is consistent with the pattern of an arterial duct.


Characterization of sulfate transport in the hepatic endoplasmic reticulum.
The transport of sulfate ion across the endoplasmic reticulum membrane was investigated using rapid filtration and light scattering assays. We found a protein-mediated, bi-directional, low-affinity, and high-capacity, facilitative sulfate transport in rat liver microsomes, which could be inhibited by the prototypical anion transport inhibitor, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. It was resistant to various phosphate transport inhibitors and was not influenced by high concentration of phosphate or pyrophosphate, which is contradictory to involvement of phosphate transporters. It was sensitive to S3483 that has been reported to inhibit the glucose 6-phosphate transporter (G6PT), but the weak competition between sulfate and glucose 6-phosphate did not confirm the participation of this transporter. Moreover, the comparison of the activity and S3483 sensitivity of sulfate transport in microsomes prepared from G6PT-overexpressing or wild type COS-7 cells did not show any significant difference. Our results indicate that sulfate fluxes in the endoplasmic reticulum are mediated by a novel, S3483-sensitive transport pathway(s).


Increased level of IL-32 during human immunodeficiency virus infection suppresses HIV replication.
Interleukin-32 was recently identified as a pro-inflammatory cytokine produced by T-lymphocytes, natural killer cells, epithelial cells, and blood monocytes. IL-32 is induced by IFN-gamma in a time-dependent manner suggesting a role for IL-32 in innate and adaptive immune responses. In this study we present evidence that Human immunodeficiency virus promotes interleukin-32 production at both mRNA and protein levels. Our results showed that there is a 74% increase in the serum levels of IL-32 among HIV patients as compared to healthy individuals. There was a three-fold increase in the promoter activity of the IL-32 in the present infections HIV clone. This increase in IL-32 promoter activity was substantiated by increased IL-32 mRNA and protein levels. We have also demonstrated that IL-32 suppresses HIV replication. Our results show that HIV LTR activity was increased by more than six-folds when endogenous IL-32 was knocked down by IL-32-specific siRNA whereas it decreased by one-fold when IL-32 was over expressed in the cells. Similarly a more than two-fold increase and a 50% decrease in HIV p24 values were noted when IL-32 was knocked down and when IL-32 was over expressed in the cells, respectively. Our present work shows that raised IL-32 levels in HIV infection may in turn hamper HIV replication; one of the protective mechanisms of nature.


Bcl-6 is the nexus transcription factor of T follicular helper cells via repressor-of-repressor circuits.
T follicular helper (TFH) cells are a distinct type of CD4+ T cells that are essential for most antibody and B lymphocyte responses. TFH cell regulation and dysregulation is involved in a range of diseases. Bcl-6 is the lineage-defining transcription factor of TFH cells and its activity is essential for TFH cell differentiation and function. However, how Bcl-6 controls TFH biology has largely remained unclear, at least in part due to the intrinsic challenges of connecting repressors to gene upregulation in complex cell types with multiple possible differentiation fates. Multiple competing models were tested here by a series of experimental approaches to determine that Bcl-6 exhibits negative autoregulation and controls pleiotropic attributes of TFH differentiation and function, including migration, costimulation, inhibitory receptors and cytokines, via multiple repressor-of-repressor gene circuits.


Simulation and investigation into the pluvial effect on peri-urban unsewered drainage basin of Kolkata due to rapid urbanization.
A pluvial effect is a geologic event caused by the action of water during excessive precipitation in a particular region, resulting in water logging, which affects the drainage system of that area, or it may be caused by the spill of a large amount of water beyond the normal limit from the water bodies. The pluvial effect is also referred to as a flood having highly devastating consequences when it affects a region's urban or peri-urban areas. It affects the day-to-day activities of people staying in those areas and causes various social and economic losses. This effect would even grow further if proper planning and management of land were not done in a given time. Therefore, through this paper, the authors try to address the issue of urban flooding along with its consequences and impacts. For this study, the peri-urban region of the Tollygunge-Panchannagram Basin in Kolkata, India, is considered. The zero inertia model, Triangular Irregular Network Flood (TINFLOOD), is employed for surface flow simulation, whereas the storm water management model (SWMM) is used to determine the lateral flow. The output of this study provides various hyetographic presentations, considering infiltration during advanced, intermediate, and delayed rainfall conditions. Here, the time of concentration is also examined for different rainfall intensities to observe the time for peak flow. The simulated data obtained from this model has been validated with the real-time data of a pumping station situated at Chowbhaga. Nevertheless, this study helps assess flood risk management upstream of a region's basin and peri-urban areas.


The Effect of Ventilation Strategy on Arterial and Cerebral Oxygenation During Laparoscopic Bariatric Surgery.
We investigated the effect of prolonged inspiratory to expiratory (I/E) ratio ventilation on respiratory mechanics, gas exchange, and regional cerebral oxygen saturation (rSO2) in obese patients undergoing laparoscopic bariatric surgery in the reverse Trendelenburg position. Twenty-eight adult patients scheduled for laparoscopic sleeve gastrectomy were enrolled in this prospective observational study. After anesthesia induction, pressure-controlled ventilation was conducted initially at a conventional I/E ratio of 1:2 and a positive end-expiratory pressure of 5 cmH2O. Twenty minutes after pneumoperitoneum, the I/E ratio was changed to 1:1 for 20 min and then to 2:1 for 20 min. Hemodynamic variables, end-tidal carbon dioxide tension, rSO2, arterial blood gas analysis results, and respiratory variables were recorded. No significant changes in hemodynamic values and rSO2 were observed during the study. Peak airway pressure was significantly lower, but mean airway pressure and dynamic compliance were significantly higher at I/E ratios of 1:1 and 2:1 than during conventional I/E ratio ventilation. Arterial oxygen tension (PaO2) value was significantly higher (p = 0.009), and alveolar-arterial oxygen tension gradient was lower (p = 0.015) at an I/E ratio of 2:1 than during conventional ratio ventilation. The use of prolonged I/E ratio of 2:1 significantly improved respiratory mechanics and arterial oxygenation without causing hemodynamic derangements or cerebral desaturation during laparoscopic bariatric surgery in the reverse Trendelenburg position.


Germ-cell degeneration in experimental unilateral cryptorchidism: role of apoptosis.
We investigated the possible involvement of apoptosis in the increased germ-cell degeneration in undescended testes (UDT). Experimental unilateral cryptorchidism was induced in 21-day-old rats, and both testes were removed for in-situ TUNEL staining of apoptotic cells at 1, 3, 7, 10, and 14 days postoperation. A gradual increase in the incidence of apoptosis was seen at 21-28 days of age in the control testes, followed by a decrease thereafter. After 10 days postoperation, the weight of the UDT was significantly lower than that of the contralateral descended testis (CDT) and the controls. However, the weight of scrotal testes in each group was similar. UDTs demonstrated a markedly increased incidence of apoptosis. By 7 days postoperation, the percentage of seminiferous tubules containing apoptotic germ cells significantly increased in UDTs compared with that in CDTs and controls (P < 0.001). Moreover, there was a significant difference in the percentage of seminiferous tubules containing apoptotic germ cells between CDTs and controls (P < 0.01). In addition, an increased incidence of seminiferous tubules containing 8-10 and >10 apoptotic germ cells from 7, 10, and 14 days postoperation in UDTs was detected. In-situ TUNEL analysis demonstrated spermatocytes to be the main type of germ cells affected in all groups. These findings suggest that spermatogenesis decreases not only in the UDT, but also in the CDT, and that the germ-cell degeneration in cryptorchidism took the form of apoptosis.


Ecophysiological investigations on wild and cultivated plants in the Negev Desert : I. Methods: A mobile laboratory for measuring carbon dioxide and water vapour exchange.
Carbon dioxide exchange and transpiration measurements of various wild and cultivated plants were carried out during the dry summer period in 1967 in the Central Negev Desert (Israel). A mobile laboratory used for these investigations is described. Measurements were carried out with conditioned plant chambers which followed either the ambient temperature and humidity or else allowed the experiments to be carried out under constant conditions. The accuracy of the measurements was estimated. The mean error of the determination of the CO2 exchange rate amounts to ±0.07 mg CO2·g-1·h-1. Transpiration rate is measured with an error of ±0.15 g H2O·g-1·h-1. The response time of the instrumentation to reach 90% equilibrium after a change in photosynthesis or transpiration is 7 to 9 minutes. Errors which are caused by changes of quality of incident radiant energy and altered turbulence conditions for the leaves enclosed in the chamber, are discussed.


Speciation in Cloudless Sulphurs Gleaned from Complete Genomes.
For 200 years, zoologists have relied on phenotypes to learn about the evolution of animals. A glance at the genotype, even through several gene markers, revolutionized our understanding of animal phylogeny. Recent advances in sequencing techniques allow researchers to study speciation mechanisms and the link between genotype and phenotype using complete genomes. We sequenced and assembled a complete genome of the Cloudless Sulphur (Phoebis sennae) from a single wild-caught specimen. This genome was used as reference to compare genomes of six specimens, three from the eastern populations (Oklahoma and north Texas), referred to as a subspeciesPhoebis sennae eubule, and three from the southwestern populations (south Texas) known as a subspeciesPhoebis sennae marcellina While the two subspecies differ only subtly in phenotype and mitochondrial DNA, comparison of their complete genomes revealed consistent and significant differences, which are more prominent than those between tiger swallowtailsPterourus canadensisandPterourus glaucus The two sulphur taxa differed in histone methylation regulators, chromatin-associated proteins, circadian clock, and early development proteins. Despite being well separated on the whole-genome level, the two taxa show introgression, with gene flow mainly fromP. s. marcellinatoP. s. eubule Functional analysis of introgressed genes reveals enrichment in transmembrane transporters. Many transporters are responsible for nutrient uptake, and their introgression may be of selective advantage for caterpillars to feed on more diverse food resources. Phylogenetically, complete genomes place family Pieridae away from Papilionidae, which is consistent with previous analyses based on several gene markers.


Comparing cytotoxicity and genotoxicity in HaCaT cells caused by 6-aminochrysene and 5,6-chrysenequinone under ultraviolet A irradiation.
Chrysene is one of the basic polycyclic aromatic hydrocarbons that are toxic environmental pollutants. The photoproducts of 6-aminochrysene (6AC) include 5,6-chrysenequinone (5,6-CQ) along with some minor products. In this study, cytotoxicity and genotoxicity of 6AC and 5,6-CQ to a human skin cell line, HaCaT, were measured with the fluorescein diacetate uptake (FDA) test and comet assay, respectively, in the presence or absence of ultraviolet A (UVA) irradiation. The FDA test result showed that HaCaT cell viability decreased dose dependently after exposure to UVA irradiation in both 6AC (0, 0.1, 0.5, 1, 5, 10, 50 microM) and 5,6-CQ (0, 0.05, 0.25, 0.5, 2.5, 5, 25 microM) groups, with the 6AC group having lower cell viability at the same substrate concentrations; therefore, 6AC was more cytotoxic. Results of the comet assay showed that the extent of DNA damage was also dose dependent after the combined UVA and 6AC treatment (0, 0.05, 0.1, 0.5, 1 microM), although no DNA damage was detectable in the 6AC group without UVA irradiation. In addition, no DNA damage was found in the 5,6-CQ group with or without UVA irradiation. Our study indicated that 5,6-CQ, the major photoproduct of 6AC, was less photocytotoxic than the parent compound and was not photogenotoxic to HaCaT cells under the experimental conditions.


Analysis of the GAD65-GAD65 autoantibody interaction.
GAD(65)Ab are important markers of risk of development of type 1 DM. With the need to improve the disease specificity of GAD(65)Ab measurement in mind, we have analysed the interaction between recombinant human GAD(65) and GAD(65)Ab from different groups of subjects in terms of association and dissociation rate constants and equilibrium constants. In addition, binding of GAD(65)Ab from various groups of subjects to wild-type GAD(65) versus GAD(65) containing a mutation E517P was studied. Affinity constants for serum GAD(65)Ab in 12 type 1 DM patients ranged from 0.9 x 10(10) L/mol to 11.2 x 10(10) L/mol and from 0.8 x 10(10) L/mol to 14.0 x 10(10) L/mol in sera from 11 individuals without type 1 DM. Serum GAD(65)Ab concentrations assessed by Scatchard analysis ranged from 0.04 to 24.8 microg/mL in type 1 DM patients (n=12) and from 0.04 to 141.8 microg/mL in individuals without type 1 DM (n=11). Overall, our study indicated that GAD(65)Ab in different patients studied showed similar association and dissociation rate constants and similar affinity constants. However, GAD(65)Ab concentrations vary widely between different sera. There was a modest reduction of the median binding of GAD(65)Ab to GAD(65) E517P in the group of patients with type 1 DM compared to patients without type 1 DM.


Prior regular exercise improves clinical outcome and reduces demyelination and axonal injury in experimental autoimmune encephalomyelitis.
Although previous studies have shown that forced exercise modulates inflammation and is therapeutic acutely for experimental autoimmune encephalomyelitis (EAE), the long-term benefits have not been evaluated. In this study, we investigated the effects of preconditioning exercise on the clinical and pathological progression of EAE. Female C57BL/6 mice were randomly assigned to either an exercised (Ex) or unexercised (UEx) group and all of them were induced for EAE. Mice in the Ex group had an attenuated clinical score relative to UEx mice throughout the study. At 42 dpi, flow cytometry analysis showed a significant reduction in B cells, CD4(+) T cells, and CD8(+) T cells infiltrating into the spinal cord in the Ex group compared to UEx. Ex mice also had a significant reduction in myelin damage with a corresponding increase in proteolipid protein expression. Finally, Ex mice had a significant reduction in axonal damage. Collectively, our study demonstrates for the first time that a prolonged and forced preconditioning protocol of exercise improves clinical outcome and attenuates pathological hallmarks of EAE at chronic disease. In this study, we show that a program of 6 weeks of preconditioning exercise promoted a significant reduction of cells infiltrating into the spinal cord, a significant reduction in myelin damage and a significant reduction in axonal damage in experimental autoimmune encephalomyelitis (EAE) mice at 42 dpi. Collectively, our study demonstrates for the first time that a preconditioning protocol of exercise improves clinical outcome and attenuates pathological hallmarks of EAE at chronic disease.


Near-infrared light-triggered nano-prodrug for cancer gas therapy.
Gas therapy (GT) has attracted increasing attention in recent years as a new cancer treatment method with favorable therapeutic efficacy and reduced side effects. Several gas molecules, such as nitric oxide (NO), carbon monoxide (CO), hydrogen (H2), hydrogen sulfide (H2S) and sulfur dioxide (SO2), have been employed to treat cancers by directly killing tumor cells, enhancing drug accumulation in tumors or sensitizing tumor cells to chemotherapy, photodynamic therapy or radiotherapy. Despite the great progress of gas therapy, most gas molecules are prone to nonspecific distribution when administered systemically, resulting in strong toxicity to normal tissues. Therefore, how to deliver and release gas molecules to targeted tissues on demand is the main issue to be considered before clinical applications of gas therapy. As a specific and noninvasive stimulus with deep penetration, near-infrared (NIR) light has been widely used to trigger the cleavage and release of gas from nano-prodrugs via photothermal or photodynamic effects, achieving the on-demand release of gas molecules with high controllability. In this review, we will summarize the recent progress in cancer gas therapy triggered by NIR light. Furthermore, the prospects and challenges in this field are presented, with the hope for ongoing development.


Canavanine-resistant variants of human lymphoblasts.
Variants resistant to canavanine, an arginine analogue, have been isolated from two long-term human lymphoblastoid cell lines. They are 20-fold more resistant to canavanine than the parental lines and this phenotype is stable in the absence of canavanine for more than 100 generations. The specific activity of argininosuccinate synthetase, the first of two enzymes necessary for the conversion of citrulline to arginine, is elevated in variants from both cell lines. Furthermore, this enzyme activity is refractory to the repression caused by arginine in normal lymphoblasts. The specific activity of argininosuccinate lyase, the second enzyme in the pathway from citrulline to arginine, is not appreciably changed. Arginine uptake appears normal in the variants since they grow as well as the parental lines in media containing a wide range of arginine concentrations. Arginyl-tRNA synthetase activity is also unchanged. Thus the canavanine-resistant variants have altered control of at least one urea cycle enzyme and appear to be regulatory mutants of human cells.


Group-level differences in visual search asymmetry.
East Asians and Westerners differ in various aspects of perception and cognition. For example, visual memory for East Asians is believed to be more influenced by the contextual aspects of a scene than is the case for Westerners (Masuda & Nisbett in Journal of Personality and Social Psychology, 81, 922-934, 2001). There are also differences in visual search: For Westerners, search is faster for a long line among short ones than for a short line among long ones, whereas this difference does not appear to hold for East Asians (Ueda et al., 2016). However, it is unclear how these group-level differences originate. To investigate the extent to which they depend upon environment, we tested visual search and visual memory in East Asian immigrants who had lived in Canada for different amounts of time. Recent immigrants were found to exhibit no search asymmetry, unlike Westerners who had spent their lives in Canada. However, immigrants who had lived in Canada for more than 2 years showed performance comparable to that of Westerners. These differences could not be explained by the general analytic/holistic processing distinction believed to differentiate Westerners and East Asians, since all observers showed a strong holistic tendency for visual recognition. The results instead support the suggestion that exposure to a new environment can significantly affect the particular processes used to perceive a given stimulus.


Emerging role of ER quality control in plant cell signal perception.
The endoplasmic reticulum quality control (ER-QC) is a conserved mechanism in surveillance of secreted signaling factors during cell-to-cell communication in eukaryotes. Recent data show that the ER-QC plays important roles in diverse cell-to-cell signaling processes during immune response, vegetative and reproductive development in plants. Pollen tube guidance is a precisely guided cell-cell communication process between the male and female gametophytes during plant reproduction. Recently, the female signal has been identified as small secreted peptides, but how the pollen tube responds to this signal is still unclear. In this review, we intend to summarize the role of ER-QC in plants and discuss the recent advances regarding our understanding of the mechanism of pollen tube response to the female signals.


Tibial motor and sural electrophysiological relationship in subjects without and patients with mild axonal peripheral neuropathy.
The distal motor fibers of the tibial and sural nerves are predominantly derived from the S1 root. We aimed to describe the electrophysiological relationship of these two nerves. Clinical, radiological and neurophysiological data of patients with mild, length-dependent, peripheral neuropathy (PN) and subjects without PN were retrospectively collected and analyzed. Eighty-eight individuals without PN and 24 patients with mild axonal PN who had no evidence of lumbosacral radiculopathy were included for analysis. Significant positive correlations were observed for the tibial CMAP and the sural SNAP for both controls and patients. Multivariate linear regression analyses showed that the predicted tibial CMAP can be calculated using the following equations: for male subjects without PN, tibial CMAP = 20.7 - 0.21 × age; for female subjects without PN, tibial CMAP = 23.3 - 0.21 × age and for patients with mild PN, tibial CMAP = 2.7 + sural SNAP. This study demonstrates the high correlation between the tibial CMAP and the sural SNAP in subjects without PN and patients with mild axonal peripheral neuropathy, and provides mathematical equations for the calculation of the predicted tibial CMAP for such individuals.


Lack of generalization of nisoxetine with amphetamine in the rat.
Rats were trained to discriminate between the stimulus properties of intraperitoneally administered d-amphetamine (0.8 mg/kg) and its vehicle in a two-lever, food-motivated operant task. Once trained, doses of the norepinephrine reuptake inhibiting agent nisoxetine, ranging from 10 to 20 mg/kg, were administered to investigate if the amphetamine-trained rats would generalize to this agent. This did not, however, occur. Thus, it would seem that noradrenergic mechanisms have a negligible role in the production of the amphetamine-induced discriminative stimulus cue in the rat. Previous evidence that indicated a noradrenergic mediation of amphetamine discrimination in the mouse contrasted with the present results in rats and this discrepancy should warrant caution in comparing results of discriminative studies in these two species.