Midterm Outcomes of One-Stage Hybrid Aortic Arch Repair for Stanford Type A Aortic Dissection: A Single Center's Experience.
This study sought to identify the midterm outcomes of one-stage hybrid aortic arch repair (HAAR) in patients with Stanford type A aortic dissection (TAAD). Between January 2010 and December 2015, 75 consecutive patients with TAAD involving the aortic arch who underwent one-stage type Ⅱ HAAR at our institution were identified. During this period, 496 consecutive patients with TAAD underwent traditional total aortic arch replacement (TAR) with frozen elephant trunk. The preoperative, perioperative, and postoperative data of all patients were compared. A propensity score-matching analysis was applied to adjust for baseline risk factors. Five hundred and seventy-one patients were included for analysis (428 men; mean age, 48.9 ± 11.1 years). For all patients, the mean follow-up time was 41.1 ± 22.1 months, in-hospital mortality was 4.7%, and the 5-year survival rate was 89.5%. Midterm outcomes between the propensity-matched groups were compared (59 HAAR vs TAR pairs). HAAR group showed shorter cardiopulmonary bypass time (105-159 minutes vs 158-230 minutes, P < 0.001), aortic cross-clamping time, postoperative ventilation time, and intensive care unit stays (33-108 hours vs 45-131 hours, P = 0.010) than the TAR group. There were no significant differences in in-hospital mortality, rate of stroke and rate of paraplegia between the 2 groups, however, better 5-year survival rate was found in HAAR group (94.9% vs 75.8%, Log-rank P = 0.005). As compared to propensity matched cohort of TAR patients, HAAR shows good midterm outcomes for patients with TAAD. Further randomized study was needed to clarify the optimal management strategy of TAAD.


A Refractory Celiac Patient Successfully Treated With Mesenchymal Stem Cell Infusions.
Type II refractory celiac disease (RCD), as defined according to the amount of aberrant intraepithelial lymphocytes, is a condition characterized by severe malabsorption syndrome and poor prognosis, with no effective treatment. Based on the regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs), we investigated the feasibility, safety, and efficacy of serial infusions of autologous bone marrow-derived MSCs in a 51-year-old woman with type II RCD. Mesenchymal stem cells were isolated, expanded, and characterized following standard protocols. Monitoring of the patient's malabsorption indexes, mucosal architecture, and percentage of aberrant intraepithelial lymphocytes was scheduled for the time of enrollment, at each infusion, and after 6 months. Determination of mucosal expression of interleukin (IL)-15 and its receptor was also performed. Expansion of MSCs was feasible, and the patient underwent 4 systemic infusions of 2 × 10(6) MSCs/kg body weight 4 months apart, without adverse effects. During the treatment period, she experienced gradual and durable amelioration of her general condition, with normalization of stool frequency, body mass index, laboratory test results, and mucosal architecture. Remarkably, the expression of IL-15 and its receptor almost completely disappeared. Thus, treatment of RCD with serial MSC infusions seems promising, leading to recovery from the life-threatening condition while blocking the IL-15 pathogenic pathway.


Morphological and functional evaluation of isolated rat hepatocytes in three dimensional culture systems.
Various three-dimensional configurations, such as polyester tissue and woven-nonwoven, hydrophilic polyester fabric, either collagen-coated or uncoated, were investigated as potential scaffold for hepatocyte culture, in view of their use in bioreactors for hybrid liver support systems. Attachment, morphology and ultrastructure of primary adult rat hepatocytes were evaluated, as well as urea production and ammonium detoxification during a 24h incubation period in serum-free tissue culture medium. As control, hepatocytes were also plated onto collagen-coated dextran microcarriers and on plastic petri dishes, either collagen-coated or uncoated. In all the three-dimensional cultures, hepatocytes appeared morphologically intact without any statistically significant difference in metabolic activity. Collagen-coating did not influence cell attachment to polyester substrates, whereas woven-nonwoven hydrophilic polyester fabric may offer some potential advantages as three-dimensional system for hepatocyte culture in hybrid liver support systems.


New method for designing the stigmatically imaging gradient-index lenses of spherical symmetry.
The general solution presented here yields smooth, continuous, and monotonic refractive-index profiles for Luneburg-Morgan lenses with a boundary index of N > 1. The new formula incorporates an original apparent-immersing method as well as the continuous-deflection-function concept recently developed by one of the authors for the description of waveguide lenses.


KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features.
Heterozygous activating mutations in the gene encoding for the ATP-sensitive potassium channel subunit Kir6.2 (KCNJ11) have recently been shown to be a common cause of permanent neonatal diabetes. Kir6.2 is expressed in muscle, neuron and brain as well as the pancreatic beta-cell, so patients with KCNJ11 mutations could have a neurological phenotype in addition to their diabetes. It is proposed that some patients with KCNJ11 mutations have neurological features that are part of a discrete neurological syndrome termed developmental Delay, Epilepsy and Neonatal Diabetes (DEND), but there are also neurological consequences of chronic or acute diabetes. We identified KCNJ11 mutations in four of 10 probands with permanent neonatal diabetes and one affected parent; this included the novel C166F mutation and the previously described V59M and R201H. Four of the five patients with mutations had neurological features: the patient with the C166F mutation had marked developmental delay, severe generalised epilepsy, hypotonia and muscle weakness; mild developmental delay was present in the patient with the V59M mutation; one patient with the R201H mutation had acute and chronic neurological consequences of cerebral oedema and another had diabetic neuropathy from chronic hyperglycaemia. In conclusion, the clinical features in these patients support the existence of a discrete neurological syndrome with KCNJ11 mutations. The severe DEND syndrome was seen with the novel C166F mutation and mild developmental delay with the V59M mutation. These features differ markedly from the neurological consequences of acute or chronic diabetes.


Magnetostimulation limits in magnetic particle imaging.
For magnetic particle imaging (MPI), specific absorption rate (SAR) and more critically magnetostimulation (i.e., dB/dt) safety limits will determine the optimal scan parameters, such as the drive field strength and frequency. These parameters will impact the scanning speed, field-of-view (FOV) and signal-to-noise ratio in MPI. Understanding the potential safety hazards of the drive field is critical for scaling MPI for human use. In this work, we demonstrate that magnetostimulation is the primary magnetic safety consideration in MPI, and we describe the first human-subject magnetostimulation threshold experiments for MPI using homogeneous coils. Our experiments, performed on the arm and leg, indicate that magnetostimulation thresholds monotonically decrease with increasing frequency. Additionally, we show for the first time that a strong inverse correlation exists between the threshold and the body part size. The chronaxie time, on the other hand, did not vary with body part size. We conclude with an estimation of the magnetostimulation thresholds for a full-body MPI scanner: a mean asymptotic threshold of 14.3 mT-pp (peak-to-peak) with a mean chronaxie time of 289 μs, which correspond to a magnetostimulation threshold of about 15 mT-pp for frequencies between 25 and 50 kHz. These findings will have a great impact on the optimization of MPI parameters, especially in determining the number of partial FOVs required to cover a region of interest.


Time-to-reperfusion in patients with acute myocardial infarction and mortality in prehospital emergency care: meta-analysis.
People living in rural areas usually suffer comparatively disadvantaged emergency health care than those living in urban areas, reasons including long transit time due to geographic factors. As for many time critical diseases, it is necessary to obtain treatment as quickly as possible. Screening of eligible studies were conducted based on inclusion an exclusion criteria. A comprehensive search was conducted by using following database: EMBASE, Medline, Cochrane library and Scopus. Quality assessment tool for observational cohort and cross-sectional study is used for assessing the risk of bias. The time group were defined based on the median or mean transit time among patients. In symptom onset-balloon time, we take 120 min transit time as the standard so patients in included studies are divided into two groups:less than 120 min (group A) and more than 120 min (group B). The collected data were used for quantitative analysis, they were inputted into Review Manager Software (v5.3) to produce summary results. Ten studies representing 71,099 patients were included in the meta-analysis. All studies were retrospective and prospective observational studies and RCTs in which patients experienced ST-elevation myocardial infarction (STEMI) and were treated with percutaneous coronary intervention (PCI). Random effects meta-analysis of the point estimate was 0.69 (CI 0.60, 0.79). Heterogeneity between study results was evaluated via examination of the forest plots and quantified by using I2 statistic. Heterogeneity in two stage time was moderate among studies (I2 = 29%, P = 0.23). The meta-analysis for included studies report less mortality in less than 120 min symptom onset-balloon and door-balloon time than that in more than 120 min. It is necessary to optimize the prehospital system for rapid decision making and logical destination and mode of transport with prehospital notification of the cath lab so that the hospital is ready to optimize door to balloon time.


B-type natriuretic peptide 8-32, which is produced from mature BNP 1-32 by the metalloprotease meprin A, has reduced bioactivity.
32-amino acid B-type natriuretic peptide (BNP 1-32) plays an important role in cardiovascular homeostasis. Recently, it was reported that BNP 1-32 is cleaved by the metalloprotease meprin A to BNP 8-32, the bioactivity of which is undefined. We hypothesized that BNP 8-32 has reduced vasodilating and natriuretic bioactivity compared with BNP 1-32 in vivo. Human BNP 8-32 and BNP 1-32 were compared in a crossover study in eight anesthetized normal canines. After a preinfusion clearance, BNP 1-32 was infused at 30 ng.kg(-1) x min(-1) for 45 min followed by a 60-min washout and a second preinfusion clearance. Then, equimolar BNP 8-32 was infused. In half of the studies, the peptide sequence was reversed. Changes with peptides from the respective preinfusion clearance to infusion clearance were compared with paired tests. Mean arterial pressure was reduced by both BNP 8-32 and BNP 1-32 (-8 +/- 3 vs. -6 +/- 2 mmHg, P = 0.48). Changes in right atrial pressure, pulmonary capillary wedge pressure, heart rate, cardiac output, and glomerular filtration rate were similar. However, urinary sodium excretion increased less with BNP 8-32 than with BNP 1-32 (+171 +/- 24 vs. +433 +/- 43 muEq/min; P = 0.008), as did urinary potassium excretion, urine flow, and renal blood flow. While BNP 8-32 has similar vasodilating actions as BNP 1-32, its diuretic and natriuretic actions are reduced, suggesting a role for meprin A in the regulation of BNP 1-32 bioactivity in the kidney. Meprin A inhibition may be a potential strategy to increase the bioactivity of endogenous and exogenous BNP 1-32 in cardiovascular diseases.


Amylase: a disease activity index in multiple myeloma?
This study reports a case of a patient with lambda-light chain multiple myeloma who developed a high hyperamylasaemia of the salivary type during the disease and soon afterwards died. Ectopic production of amylase by myeloma cells has been described in a few cases and demonstrated by tissue culture and immunohistochemical techniques. The common characteristics of these cases were: salivary amylase isoenzyme increase, high tumor mass, extensive extra-medullary spread, extensive bone destruction and poor prognosis. In patients with amylase-producing multiple myeloma, the onset of hyperamylasaemia heralds a rapid disease progression; therefore, in these patients, a simple test such as serum amylase may represent a reliable disease activity index and provide an additional prognostic information.


Pediatric cervical-spine immobilization: achieving neutral position?
This study was designed to evaluate prospectively the ability of current spine-immobilization devices to achieve radiographic-neutral positioning of the cervical spine in pediatric trauma patients. All trauma patients who required spinal immobilization and a lateral cervical spine radiograph were included in the study. A lateral cervical spine radiograph was obtained while the child was immobilized. The Cobb angle (C2-C6) was measured using a handheld goniometer. The method of immobilization, age at injury, and Cobb angle were compared. One hundred and eighteen patients with an average age of 7.9 years were enrolled. The majority were males (71%). The most frequent mechanisms of injury included motor vehicle accidents (35%) and falls (32%). The average Glascow Coma Scale score was 14. Although 31% of the children complained of neck pain, 92% were without neurologic deficits. The Cobb angles ranged from 27 degree kyphosis to 27 degree lordosis, and only 12 of the patients presented in a neutral position (0 degrees). Greater than 5 degrees of kyphosis or lordosis was observed in 60% of the children. Thirty-seven percent of the patients had 10 degrees or greater angulation. The most frequent methods of immobilization included a collar, backboard, and towels (40%), and a collar, backboard, and blocks (20%), but these techniques provided < 5 degrees kyphosis or lordosis in only 45% and 26% of the children respectively. No single method or combination of methods of immobilization consistently placed the children in the neutral position.(ABSTRACT TRUNCATED AT 250 WORDS)


Neonatal stress-induced affective changes in adolescent Wistar rats: early signs of schizophrenia-like behavior.
Psychiatric disorders are multifactorial diseases with etiology that may involve genetic factors, early life environment and stressful life events. The neurodevelopmental hypothesis of schizophrenia is based on a wealth of data on increased vulnerability in individuals exposed to insults during the perinatal period. Maternal deprivation (MD) disinhibits the adrenocortical response to stress in neonatal rats and has been used as an animal model of schizophrenia. To test if long-term affective consequences of early life stress were influenced by maternal presence, we submitted 10-day old rats, either deprived (for 22 h) or not from their dams, to a stress challenge (i.p. saline injection). Corticosterone plasma levels were measured 2 h after the challenge, whereas another subgroup was assessed for behavior in the open field, elevated plus maze (EPM), social investigation and the negative contrast sucrose consumption test in adolescence (postnatal day 45). Maternally deprived rats exhibited increased plasma corticosterone (CORT) levels which were higher in maternally deprived and stress challenged pups. Social investigation was impaired in maternally deprived rats only, while saline injection, independently of MD, was associated with increased anxiety-like behavior in the EPM and an impaired intake decrement in the negative sucrose contrast. In the open field, center exploration was reduced in all maternally-deprived adolescents and in control rats challenged with saline injection. The most striking finding was that exposure to a stressful stimulus per se, regardless of MD, was linked to differential emotional consequences. We therefore propose that besides being a well-known and validated model of schizophrenia in adult rats, the MD paradigm could be extended to model early signs of psychiatric dysfunction, and would particularly be a useful tool to detect early signs that resemble schizophrenia.


Functional Proliferating Human Hepatocytes: In Vitro Hepatocyte Model for Drug Metabolism, Excretion, and Toxicity.
To develop a functional alternative hepatocyte model for primary human hepatocytes (PHHs) with proliferative property, essential drug metabolic, and transporter functions, proliferating human hepatocytes (ProliHHs) expanded from PHHs were fully characterized in vitro. Herein, ProliHHs generated from multiple PHHs donors could be expanded more than 200-fold within four passages and maintained their metabolic or transporter capacities partially. Furthermore, ProliHHs were able to regain the mature hepatic property after three-dimensional (3D) culture. Particularly, the downregulated mRNA expression and function of three major cytochrome P450 (P450) enzymes (CYP1A2, CYP2B6, and CYP3A4) in the proliferating process (ProliHHs-P) could be recovered by 3D culture. The metabolic variabilities across different PHHs donors could be inherited to their matured ProliHHs (ProliHHs-M). The intrinsic clearances of seven major P450 enzymes in ProliHHs-M correlated well (r = 0.87) with those in PHHs. Also, bile canaliculi structures could be observed in sandwich-cultured ProliHHs (SC-ProliHHs), and the biliary excretion index of four probe compounds [cholyl-lys-fluorescein, 5-(and-6)-carboxy-2', 7'-dichlorofluorescein diacetate (CDF), deuterium-labeled sodium taurocholate acid, and rosuvastatin] in SC-ProliHHs (>10%) were close to sandwich-cultured PHHs. More importantly, both ProliHHs-P and ProliHHs-M could be used to evaluate hepatotoxicity. Therefore, these findings demonstrated that the 3D and sandwich culture system could be used to recover the metabolic and transporter functions in ProliHHs for clearance prediction and cholestasis risk assessment, respectively. Together, ProliHHs could be a promising substitute for PHHs in drug metabolism, transport, and hepatotoxicity screening. SIGNIFICANCE STATEMENT: This report describes the study of drug metabolic capacities, efflux transporter functions, and toxicity assessments of proliferating human hepatocytes (ProliHHs). The metabolic variability in different primary human hepatocyte donors could be inherited by their matured ProliHHs derivatives. Also, ProliHHs could form canalicular networks in sandwich culture and display biliary excretion capacities. More importantly, both the proliferative and maturation statuses of ProliHHs could be used to evaluate hepatotoxicity. Together, ProliHHs were feasible to support drug candidate screening in hepatic metabolism, disposition, and toxicity.


"Guide Star" Assisted Noninvasive Photoacoustic Measurement of Glucose.
A novel "guide star" assisted photoacoustic (GSPA) method for noninvasive glucose measurement has been proposed. Instead of receiving PA signals that are directly generated by tissue, a virtual photodiode is employed to amplify the PA signal difference regarding amplitude and peak arrival time caused by glucose concentration variations in an indirect way. Being different from traditional PA spectroscopy, this method can improve sensitivity and accuracy by optimizing optical path lengths (or tissue thickness). On the other hand, being superior to near-infrared (NIR) spectroscopy, it utilizes both optical absorption and acoustic propagation velocity information confered by PA signals. Theoretical analysis and simulation have been done to illustrate how the concentration change affects the PA waveform. In vitro experiments on aqueous glucose solution were conducted with concentrations varying in human physiological range (50-350 mg/dL). Performance of quartz cuvettes with 1 mm and 2 mm optical path lengths were compared in terms of correlation quality ( R2), degree of agreement (Bland-Altman plot), and clinical accuracy (Clarke's Error Grid analysis) to demonstrate the scalability of sensitivity provided by the indirect method. Longer optical length shows better sensitivity and accuracy in this case. Moreover, detection was also done on human blood serum to further prove the potential of the proposed method for clinical application. Our proposed method provides a solution to enhance sensitivity, facilitating development of portable and low-cost PA sensors with low power laser diodes for noninvasive glucose monitoring and other applications.


Indication of Electromagnetic Field Exposure via RBF-SVM Using Time-Series Features of Zebrafish Locomotion.
This paper introduces a novel model based on support vector machine with radial basis function kernel (RBF-SVM) using time-series features of zebrafish (Danio rerio) locomotion exposed to different electromagnetic fields (EMFs) to indicate the corresponding EMF exposure. A group of 14 adult zebrafish was randomly divided into two groups, 7 in each group; the fish of each group have the novel tank test under a sham or real magnetic exposure of 6.78 MHz and about 1 A/m. Their locomotion in the tests was videotaped to convert into the x, y coordinate time-series of the trajectories for reforming time-series matrices according to different time-series lengths. The time-series features of zebrafish locomotion were calculated by the comparative time-series analyzing framework highly comparative time-series analysis (HCTSA), and a limited number of the time-series features that were most relevant to the EMF exposure conditions were selected using the minimum redundancy maximum relevance (mRMR) algorithm for RBF-SVM classification training. Before this, ambient environmental parameters (AEPs) had little effect on the locomotion performance of zebrafish processed by the empirical method, which had been quantitatively verified by regression using another group of 14 adult zebrafish. The results have demonstrated that the purposed model is capable of accurately indicating different EMF exposures. All classification accuracies can be 100%, and the classification precision of several classifiers based on specific parameters and feature sets with specific dimensions can reach higher than 95%. The speculative reason for this result is that the specified EMF has affected the zebrafish neural aspect, which is then reflected in their behaviors. The outcomes of this study have provided a new indication model for EMF exposures and provided a reference for the investigation of the impact of EMF exposure.


Cortical responses of infants with and without a genetic risk for dyslexia: II. Group effects.
Infants born to families with a background of developmental dyslexia have an increased risk of becoming dyslexic. In our previous study no major group or stimulus effects in the event-related potentials (ERPs) of at-risk and control infants were found until the age of 6 months. However, in the current study, when we made the stimulus presentation rate slower, the ERPs to the short deviant /ka/ were different from those to the long standard /kaa/ stimulus already in newborns. In addition, clear group differences in the ERPs were found. The results demonstrate that infants born with a high familial risk for dyslexia process speech/auditory stimulus durations differently from control infants at birth.


The family costs of attending hospital outpatient appointments via videoconference and in person.
We compared the costs incurred by families attending outpatient appointments at the Royal Children's Hospital (RCH) in Brisbane with those incurred by families who had a consultation via videoconference in their regional area. In each category 200 families were interviewed. The median time spent travelling for videoconferences was 30 min compared with 80 min for face-to-face appointments. Families interviewed in the outpatient department had travelled a median distance of 70 km, while those who had a videoconference at the local hospital had travelled only 20 km. It cost these families much more to attend an appointment at the RCH than to attend a videoconference. Ninety-six per cent of families (193) reported at least one of the following types of expense: 150 families had expenses related to parking (median A 10 dollars), 156 had fuel expenses (median A 10 dollars) and 122 reported costs related to meals purchased at the RCH (median A 10 dollars). Only 21 families who had their appointment via local videoconference reported any additional costs. Specialist appointments via videoconference were a more convenient and cheaper option for families living in regional areas of Queensland than the conventional method of attending outpatient appointments at the specialist hospital in Brisbane.


Direct measurement of turgor and osmotic potential in individual epidermal cells : independent confirmation of leaf water potential as determined by in situ psychrometry.
The pressure probe, which is routinely used to measure the turgor potential (Psi(p)) of individual epidermal cells in Tradescantia virginiana (L.), has also been used to sample small volumes of vacuolar fluid from these same cells (as low as 0.02 nl) for measurement of cellular solute (osmotic) potential (Psi(s)) in a micro freezing point osmometer. The water potential components Psi(p) and Psi(o) have been used to calculate the total water potential of individual epidermal cells (Psi(cell)) which has then been directly compared to the total leaf water potential (Psi(leaf)) measured psychrometrically. The relation of Psi(leaf) and Psi(cell) to leaf transpiration indicates that in T. virginiana, a relatively straightforward relation exists between the level of water flow through the leaf tissue, and the DeltaPsi within the leaf, between two points along the water flow pathway. Substantial agreement was found between the two independent, in situ methods of measuring Psi when extrapolated to zero transpiration conditions. These results are discussed with respect to the thermodynamics of water transport in plant tissues.


Molecular photoswitches mediating the strain-driven disassembly of supramolecular tubules.
Chemists have created molecular machines and switches with specific mechanical responses that were typically demonstrated in solution, where mechanically relevant motion is dissipated in the Brownian storm. The next challenge consists of designing specific mechanisms through which the action of individual molecules is transmitted to a supramolecular architecture, with a sense of directionality. Cellular microtubules are capable of meeting such a challenge. While their capacity to generate pushing forces by ratcheting growth is well known, conversely these versatile machines can also pull microscopic objects apart through a burst of their rigid tubular structure. One essential feature of this disassembling mechanism is the accumulation of strain in the tubules, which develops when tubulin dimers change shape, triggered by a hydrolysis event. We envision a strategy toward supramolecular machines generating directional pulling forces by harnessing the mechanically purposeful motion of molecular switches in supramolecular tubules. Here, we report on wholly synthetic, water-soluble, and chiral tubules that incorporate photoswitchable building blocks in their supramolecular architecture. Under illumination, these tubules display a nonlinear operation mode, by which light is transformed into units of strain by the shape changes of individual switches, until a threshold is reached and the tubules unleash the strain energy. The operation of this wholly synthetic and stripped-down system compares to the conformational wave by which cellular microtubules disassemble. Additionally, atomistic simulations provide molecular insight into how strain accumulates to induce destabilization. Our findings pave the way toward supramolecular machines that would photogenerate pulling forces, at the nanoscale and beyond.


Rearing experience differentially affects somatic and cardiac startle responses in rhesus monkeys (Macaca mulatta).
The present study reports, for the first time, somatic and cardiac responses to acoustic startle in 2 groups of rhesus monkeys (Macaca mulatta) with different rearing experiences. Both groups showed a significant direct relationship between startle amplitude and the intensity of the acoustic startle stimulus (80-120 dB) and rapid heart rate acceleration after a 120-dB stimulus. Monkeys reared with a same-age peer (PR) showed higher startle amplitudes than those reared with their mothers (MR), consistent with rearing effects in rodents. The MR monkeys, however, showed faster heart rate acceleration of greater overall magnitude than that of the PR group. The results are discussed with regard to a monkey model for neuropsychiatric disease.


[Therapeutic potential of antisense (AS) Bcl-2 as a chemosensitizer for patients with gastric and breast carcinoma].
Bcl-2 confers resistance to apoptosis resulting in reduction of the effectiveness of chemotherapy. We examined the effect of antisense (AS) Bcl-2 in combination with anticancer drug for targeting therapy against Bcl-2 in gastric and breast cancer cells. One human gastric cancer cell line (MKN-45) and three breast cancer cell lines (BT-474, ZR-75-1 and MDA-MB-231) were examined. The effects of antisense Bcl-2 phosphorothioate oligonucleotides (AS ODNs: 18 mer) on chemosensitivity were tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT assay, and the antitumor effect assessed in vivo by the success of xenograft transplantation into nude mice. Treatment with AS Bcl-2 ODNs resulted in sequence-specific reduction in protein expression, which was compared to controls. Treatment of MKN-45 cells with AS Bcl-2 increased sensitivity to adriamycin (ADM), cisplatin (CDDP), and paclitaxel (PTX) in vitro and in vivo. Similarly, treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased chemosensitivity to ADM, mitomycin C (MMC), PTX, and docetaxel (DOC). This occurred in the setting of increased Bax and cleaved poly (ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs induced splenomegaly in association with increased serum IL-12, expression of CD80, CD83, CD86, and CD27, which was attenuated by methylation of the CpG-motifs of AS Bcl-2, suggesting the involvement of immunomodulatory effect of AS Bcl-2 through pDC and B cell although methylated CpG-failed to negate the increased antitumor effect of AS Bcl-2. Targeted therapy against Bcl-2 protein using AS ODNs might enhance the effects of chemotherapy in patients with gastric and breast cancer.


Sulfasalazine decreases astrogliosis-mediated seizure burden.
Previously, we reported that inhibition of the astrocytic cystine/glutamate antiporter system xc- (SXC), using sulfasalazine (SAS), decreased evoked excitatory signaling in three distinct hyperexcitability models ex vivo. The current study expands on this work by evaluating the in vivo efficacy of SAS in decreasing astrogliosis-mediated seizure burden seen in the beta-1 integrin knockout (B1KO) model. Video-EEG (electroencephalography) monitoring (24/7) was obtained using Biopac EEG acquisition hardware and software. EEG spectral analysis was performed using MATLAB. SAS was used at an equivalence of doses taken by Crohn's disease patients. Whole-cell patch-clamp recordings were made from cortical layer 2/3 pyramidal neurons. We report that 100% of B1KO mice that underwent 24/7 video-EEG monitoring developed spontaneous recurrent seizures and that intraperitoneal administration of SAS significantly reduced seizure frequency in B1KOs compared to B1KOs receiving sham saline. Spectral analysis found an acute reduction in EEG power following SAS treatment in B1KOs; however, this effect was not observed in nonepileptic control mice receiving SAS. Finally, whole-cell recordings from SXC knockout mice had hyperpolarized neurons and SXC-B1 double knockouts fired significantly less action potentials in response to current injection compared to B1KOs with SXC. To devise effective strategies in finding relief for one-in-three patients with epilepsy who experience drug-resistant epilepsy we must continue to explore the mechanisms regulating glutamate homeostasis. This study explored the efficacy of targeting an astrocytic glutamate antiporter, SXC, as a novel antiepileptic drug (AED) target and further characterized a unique mouse model in which chronic astrogliosis is sufficient to induce spontaneous seizures and epilepsy. These findings may serve as a foundation to further assess the potential for SAS or inform the development of more potent and specific compounds that target SXC as a novel treatment for epilepsy.


Attenuation correction using count-limited transmission data in positron emission tomography.
Poisson noise in transmission data can have a significant influence on the statistical uncertainty of PET measurements, particularly at low transmission count rates. In this paper, we investigate the effect of transmission data processing on noise and quantitative accuracy of reconstructed PET images. Differences in spatial resolution between emission and transmission measurements due to transmission data smoothing are shown to have a significant influence on quantitative accuracy and can lead to artifacts in the reconstructed image. In addition, the noise suppression of this technique is insufficient to greatly reduce transmission scan times. Based on these findings, improved strategies for processing count-limited transmission data have been developed, including a method using segmentation of attenuation images. Using this method, accurate attenuation correction can be performed using transmission scan times as low as 2 min without increasing noise in reconstructed PET images.


Five-Year-Old Boy With Behavioral Changes and Papilledema.
A 5-year-old boy had initial symptoms of behavioral changes, nausea, vomiting, headache, weight loss, and progressive vision failure. Brain MRI revealed abnormal signal intensity in both optic nerves, the optic chiasm, the right medial temporal lobe, and tissues surrounding the right supraclinoid internal carotid artery with associated leptomeningeal and spinal cord enhancement. After nondiagnostic dural and spinal arachnoid biopsies, a temporal lobe biopsy was diagnostic for a rare malignant peripheral nerve sheath tumor.


Treatment of midfacial defects using prostheses supported by ITI dental implants.
The purpose of this study was to evaluate retrospectively the use of ITI dental implants used for anchoring facial prostheses in the restorative treatment of midface defects. The authors analyzed the clinical data of 26 patients with orbital defects (n = 11), orbitonasal defects (n = 4), orbitonasomaxillary defects (n = 3), and nasal defects (n = 8). Data included age, sex, primary disease, implant position, implant length, implant failure, prosthetic attachment, radiation therapy, and peri-implant skin reactions. Follow-up was at 1, 3, 6, and 12 months and then on a yearly basis. The authors noted the status of healing and complications, if any. In total, 62 implants were placed as follows: 27 (43.5 percent) for orbital prostheses, 12 (19.4 percent) for orbitonasal prostheses, 14 (22.6 percent) for orbitonasomaxillary prostheses, and nine (14.5 percent) for nasal prostheses. Thirty-eight implants (61.3 percent) were placed in previously irradiated areas in 18 patients (69.2 percent). Mild skin reactions together with mild accumulation of sebaceous crusting around implants were recorded in 14.2 percent of the skin observations. No patient experienced severe inflammation requiring administration of systemic antibiotics or surgical revision. Implant success was 100 percent in both irradiated and nonirradiated patients. In conclusion, ITI dental implants result in a high rate of success in retaining midface prostheses and offer good stability and aesthetic satisfaction.


Two-dimensional spectral line emission reconstruction as a plasma diagnostic.
A technique for reconstructing point-by-point light emission from a plasma using a series of one-dimensional, line-of-sight measurements is described. The method, an adaptation of tomographic x-ray scans, does not assume any symmetry in the plasma, unlike an Abel inversion. Results from the Tormac IV toroidal bicusp device are presented, in which plasma light was collected by a 16-channel polychromator with 0.4-A resolution and a 1-micros time response. Reconstructed plasma light emission with spatial, temporal, and wavelength resolution is then calculated. The profiles of reconstructed spectral lines (Stark broadened H(beta) and Doppler broadened He II 4686-A lines from the 90% H, 10% He plasma) are used to monitor local plasma density and temperature. A spatial resolution of 2 cm in a 14 x 24 cm vessel, which is determined by the number of angles that the plasma is viewed from, is realized. This technique is particularly useful when a high-temperature plasma is surrounded and obscured by a low-temperature, highly emissive plasma near the vessel walls.


Diagnosis of leptomeningeal disease in diffuse large B-cell lymphomas of the central nervous system by flow cytometry and cytopathology.
Reliable detection of leptomeningeal disease has the potential of facilitating the diagnosis of central nervous system (CNS) lymphoma and is important for therapeutic considerations. Currently, the standard diagnostic procedure for the detection of lymphoma in the cerebrospinal fluid is cytopathology. To improve the limited specificity and sensitivity of cytopathology, flow cytometry has been suggested as an alternative. Here, we evaluated multi-parameter flow cytometry in combination with conventional cytopathology in cerebrospinal fluid (CSF) samples from 30 patients with primary CNS lymphoma and seven patients with secondary CNS lymphoma. Overall, in 11 of 37 (29.7%) patients with CNS lymphoma, lymphoma cells were detected in CSF by flow cytometry, while cytopathology was less sensitive displaying unequivocally malignant CSF cells in only seven of all 37 (18.9%) patients. Six (16.2%) patients showed cytopathological results suspicious of lymphoma; however, in only one of these patients, the diagnosis of CSF lymphoma cells could be confirmed by flow cytometry. In primary CNS lymphomas (PCNSL), seven of 30 (23.3%) patients were positive for CSF lymphoma cells in flow cytometry, in contrast to four (13.3%) patients with PCNSL with definitely positive cytopathology. In summary, our results suggest that multi-parameter flow cytometry increases the sensitivity and specificity of leptomeningeal disease detection in CNS lymphomas. Both methods should be applied concurrently for complementary diagnostic assessment in patients with CNS lymphoma.


Multisource feedback in the ambulatory setting.
The Accreditation Council for Graduate Medical Education has mandated multisource feedback (MSF) in the ambulatory setting for internal medicine residents. Few published reports demonstrate actual MSF results for a residency class, and fewer still include clinical quality measures and knowledge-based testing performance in the data set. Residents participating in a year-long group practice experience called the "long-block" received MSF that included self, peer, staff, attending physician, and patient evaluations, as well as concomitant clinical quality data and knowledge-based testing scores. Residents were given a rank for each data point compared with peers in the class, and these data were reviewed with the chief resident and program director over the course of the long-block. Multisource feedback identified residents who performed well on most measures compared with their peers (10%), residents who performed poorly on most measures compared with their peers (10%), and residents who performed well on some measures and poorly on others (80%). Each high-, intermediate-, and low-performing resident had a least one aspect of the MSF that was significantly lower than the other, and this served as the basis of formative feedback during the long-block. Use of multi-source feedback in the ambulatory setting can identify high-, intermediate-, and low-performing residents and suggest specific formative feedback for each. More research needs to be done on the effect of such feedback, as well as the relationships between each of the components in the MSF data set.


Oral bis(tri-n-butyltin) oxide in pregnant mice. II. Alterations in hematological parameters.
The effect of in utero TBTO exposure on blood composition in neonates, pups during weaning, and dams in the same period were investigated in mice. The dams were gavaged at dose levels 0, 5, 10, and 20 mg TBTO/kg body weight on gestational days 6-15. At birth, litters were culled to eight pups, and blood analysis was performed on excess pups. On d 7, 14, and 21 the entire litters were sacrificed and blood (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, and differential leukocyte count) of dams and pups was analyzed. Blood analysis of neonates revealed enhanced WBC count and altered red-cell parameters. Increase in WBC persisted until postnatal day (pnd) 21, while red-cell parameters regained normal values on pnd 7. No significant differences were found in thymus and spleen weights in the treated groups. Dams presented no alteration in blood composition or of spleen or thymus weights. The results of this investigation revealed that in utero exposure to TBTO induces a nonspecific alteration of hematological parameters in mice, but further studies are necessary to understand whether our results are either dependent on maternal status or a direct effect of TBTO on embryonic tissue.


Hemodynamic changes in HH stage 34 chick embryos after treatment with all-trans-retinoic acid.
To obtain insight into the hemodynamics of abnormal cardiac development, a chick embryo model was recently developed in which a spectrum of double outlet right ventricle was induced with all-trans-retinoic acid. In Hamburger and Hamilton (HH) stage 34 white Leghorn chick embryos, we simultaneously measured dorsal aortic flow velocities with a 20 MHz pulsed Doppler velocity meter and vitelline artery blood pressures with a servonull system. These measurements were performed in embryos treated at HH stage 15 with 1 microgram of all-trans-retinoic acid (n = 47), or with the solvent DMSO (n = 15), and in control embryos (n = 21). After the wave form recordings were collected, all embryos were examined histologically. Embryos treated with all-trans-retinoic acid showed in 15 cases hearts with a rightward positioned aorta with an additional subaortic ventricular septal defect and 32 cases without septation abnormalities of the heart. The hemodynamic data were correlated with the morphology. Statistical comparison was performed between control and experimental values. There was no significant discrepancy in hemodynamics of sham-operated and control embryos. Heart rate, peak systolic and mean velocities, peak systolic and mean blood flows, and peak acceleration and stroke volume were reduced in embryos treated with all-trans-retinoic acid (p < 0.01). Furthermore, in the presence of a subaortic ventricular septal defect the diameter of the dorsal aorta was reduced. Pressure readings were not statistically significant. Our findings suggest that the hemodynamic changes are the result of a decrease in cardiac contraction force.


Dietary Fibers: Effects, Underlying Mechanisms and Possible Role in Allergic Asthma Management.
The prevalence of asthma is increasing, but the cause remains under debate. Research currently focuses on environmental and dietary factors that may impact the gut-lung axis. Dietary fibers are considered to play a crucial role in supporting diversity and activity of the microbiome, as well as immune homeostasis in the gut and lung. This review discusses the current state of knowledge on how dietary fibers and their bacterial fermentation products may affect the pathophysiology of allergic asthma. Moreover, the impact of dietary fibers on early type 2 asthma management, as shown in both pre-clinical and clinical studies, is described. Short-chain fatty acids, fiber metabolites, modulate host immunity and might reduce the risk of allergic asthma development. Underlying mechanisms include G protein-coupled receptor activation and histone deacetylase inhibition. These results are supported by studies in mice, children and adults with allergic asthma. Fibers might also exert direct effects on the immune system via yet to be elucidated mechanisms. However, the effects of specific types of fiber, dosages, duration of treatment, and combination with probiotics, need to be explored. There is an urgent need to further valorize the potential of specific dietary fibers in prevention and treatment of allergic asthma by conducting more large-scale dietary intervention trials.


Agar-gelatin hybrid sponge-induced three-dimensional in vitro 'liver-like' HepG2 spheroids for the evaluation of drug cytotoxicity.
Agar-gelatin hybrid sponges were used as scaffolds to induce the formation of three-dimensional (3D) spheroids of HepG2 cells. Agar and gelatin in 2:1 ratio were used to make films and sponges. The cell adhesive properties of the films were evaluated by the attachment kinetics. The growth kinetics of HepG2 cells was studied using MTT assay and morphology of the 3D spheroids was observed through inverted optical microscopy. The liver cell-specific functions of the 3D spheroids were evaluated in terms of albumin secretion and urea synthesis. Paracetamol was used as a model drug to investigate the use of these 3D spheroids in the preliminary cytotoxicity evaluation of drugs. The results showed that the agar-gelatin hybrid sponges induced the formation of 3D HepG2 spheroids with significant liver-specific functions. These spheroids exhibited higher amounts of albumin and urea synthesis than the control monolayer culture. These 3D spheroids were found to be more sensitive to the drug (TCIC(50) value of 4.6 mM) than the control monolayer (TCIC(50) value of 6.2 mM). The study shows that agar-gelatin-induced HepG2 3D spheroids can be used for the preliminary evaluation of the toxicity of drugs and chemicals.


Coping with stress: its influence on periodontal disease.
Various forms of stress behavior were documented and in patients with periodontitis their relationship with periodontal disease was investigated. Eighty-nine patients with different forms of chronic periodontitis were included in this retrospective case-control study. They were all undergoing periodontal treatment at the Department of Dental Prosthetics, University of Graz, or a private dental practice. The control group consisted of 63 persons employed in health care at the Clinic of Graz. All participants completed a stress coping questionnaire of 114 items and 19 actional and intrapsychic stress coping modes. The questionnaire served as a psychodiagnostic survey aimed at collecting data on stress coping strategies. Clinical attachment loss (CAL) served as the clinical parameter. With the help of a factor analysis with a factorization and Varimax rotation, 5 factors were extracted from the 19 subtests. The reliability of the questionnaire was less than 0.70 only for subtests "escape" and "pharmaceutical drugs." Otherwise the internal consistency ranged between 0.74 and 0.92, and the retest reliability between 0.72 and 0.84. Subsequent assessment with the t test for independent random samples at the 5% level showed that patients differ significantly from controls in regard of factor 2 (active coping, P = 0.40) and 3 (distractive coping, P = 0.033), and that they differ very significantly from controls in regard of factor 4 (defensive coping, P = 0.000) and 5 (coping through aggression and pharmaceutical drugs, P = 0.007). In the statistical analysis of factors with regard to the severity of periodontal disease, the patients were divided into 2 groups (mild to moderate and severe). The t test for independent random samples showed significance for factor 4 (defensive coping) in that patients with a defensive coping style had greater attachment loss (pF4 = 0.04). The data corroborate the thesis that periodontitis patients with inadequate stress behavior strategies (defensive coping) are at greater risk for severe periodontal disease. However, further investigations are required to confirm the significance of inappropriate coping styles with respect to the advancement of periodontal disease.


Early biventricular molecular responses to an acute myocardial infarction.
Acute myocardial infarction (AMI) remains as one of the most common lethal diseases in the world and therefore it is necessary to understand its effect on molecular basis. Genome-wide microarray analysis provides us to predict potential biomarkers and signaling pathways for this purpose. The aim of this study is to understand the molecular basis of the immediate right ventricular cellular response to left ventricular AMI. A rat model of left anterior descending coronary artery ligation was used to assess the effect of left ventricular AMI on both the right ventricle as a remote zone and the left ventricle as an ischemic/infarct zone. Microarray technology was applied to detect the gene expression. Gene Ontology and KEGG pathways analysis were done to identify effected pathways and related genes. We found that immune response, cell chemotaxis, inflammation, cytoskeleton organization are significantly deregulated in ischemic zone as early response within 30 min. Unexpectedly, there were several affected signaling pathways such as cell chemotaxis, regulation of endothelial cell proliferation, and regulation of caveolea regulation of anti-apoptosis, regulation of cytoskeleton organization and cell adhesion on the remote zone in the right ventricle. This data demonstrates that there is an immediate molecular response in both ventricles after an AMI. Although the ischemia did not histologically involve the right ventricle; there is a clear molecular response to the infarct in the left ventricle. This provides us new insights to understand molecular mechanisms behind AMI and to find more effective drug targets.


Toward Molecular 4f Single-Ion Magnet Qubits.
Quantum coherence is detected in the 4f single-ion magnet (SIM) Yb(trensal), by isotope selective pulsed EPR spectroscopy on an oriented single crystal. At X-band, the spin-lattice relaxation (T1) and phase memory (Tm) times are found to be independent of the nuclei bearing, or not, a nuclear spin. The observation of Rabi oscillations of the spin echo demonstrates the possibility to coherently manipulate the system for more than 70 rotations. This renders Yb(trensal), a sublimable and chemically modifiable SIM, an excellent candidate for quantum information processing.


Abdominal Aortic Calcification and Cardiovascular Outcomes in Chronic Kidney Disease: Findings from KNOW-CKD Study.
To investigate the association between abdominal aortic calcification score (AACS) assessed by plain radiograph of the lateral abdomen and the risk of cardiovascular (CV) events in patients with pre-dialysis chronic kidney disease (CKD), a total of 2090 pre-dialysis CKD patients from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD) were categorized by AACS into 0, 1-2, 3-4, 5-6, and ≥7. The primary outcome of the study was the composite CV events, defined as a composite of non-fatal CV events and all-cause death. The risk of composite CV events was significantly higher in the subjects with AACS ≥ 7 (adjusted hazard ratio (HR) 1.888, 95% confidence interval (CI) 1.219 to 2.923), compared to that of the subjects with AACS 0. The risks of fatal and non-fatal CV events (adjusted HR 1.052, 95% CI 1.030 to 1.073) and all-cause death (adjusted HR 1.949, 95% CI 1.073 to 3.539) were also significantly higher in the subjects with AACS ≥ 7. In conclusion, AACS assessed by plain radiograph is independently associated with adverse CV outcomes in patients with pre-dialysis CKD. A simple radiographic examination of the lateral abdomen may help CV risk stratification in this population.


Intense deep-blue electroluminescence from ITO/Y₂O₃/Ag structure.
ITO/Y₂O₃/Ag devices were fabricated using Y₂O₃ films as insulator. Four intense and sharp lines with half-peak width of 4 nm were observed for the 293.78 nm InI, 316.10 nm InI, 444.82 nm InII and 403.07 nm InIII transitions. Luminescence mechanism was illustrated by cross-section of the devices based on the analysis of surface morphology. Under the action of strong electric field, the loss of K-shell electrons led to the occurrence of characteristic radiation of indium ions. In addition, the device with turn-on voltage of 10V demonstrates typical I-V diode characteristics. Moreover, Y₂O₃/In₂O₃ multiple films as the insulation layer instead of single Y₂O₃ films was found to improve the device performance with excellent CIE (x, y) coordinates (0.16, 0.03).


Self-Transcendence, Well-Being, and Vulnerability in Healthcare Mission Participants.
The purpose of the study was to investigate the presence and relationship of self-transcendence and spiritual well-being in persons who have participated in short-term, faith-based, foreign, healthcare missions. This was a descriptive correlational study with the addition of open-ended questions. The mean Self-Transcendence Scale score for this sample was higher than mean scores of comparison studies and scores for women were higher than mean scores for men. Qualitative data provided rich accounts of the central concepts of Reed's self-transcendence theory. Reed's theory of self-transcendence was extended to a new and different population.


Application and analysis of the GFPu family of ubiquitin-proteasome system reporters.
The relevance of the ubiquitin proteasome system (UPS) to disease and fundamental cellular processes has generated a demand for methods to monitor the activity of this system in living cells and organisms. Here we describe the GFP(u) family of UPS reporters. These reporters are constitutively degraded, ubiquitin-dependent proteasome substrates that can be used to monitor UPS function in the living cell. The GFP(u) reporter family consists of three variants that can report on global, nuclear, and cytoplasmic UPS function. This article focuses on the properties and design of these reporters and highlights appropriate techniques and applications for their use.


Synthesis and antiplatelet, antiinflammatory and antiallergic activities of 2,3-disubstituted 1,4-naphthoquinones.
Modification of 2-acetamido-3-chloro-1,4-naphthoquinone, which has potent antiplatelet, antiallergic and antiinflammatory activities, led to a series of 2,3-disubstituted 1,4-naphthoquinones. Some of these compounds showed significant antiplatelet, antiallergic and antiinflammatory activities. Among them, 2-methoxy-3-chloro-1,4-naphthoquinone (15) and 2-ethoxy-3-chloro-1,4-naphthoquinone (17) exhibited potent inhibitory effects on neutrophil and mast cell degranulation. 2-Methoxy-1,4-naphthoquinone (20) and 2-ethoxy-1,4-naphthoquinone (21) exhibited potent inhibitory effect on neutrophil superoxide formation. These four compounds were thus selected for further evaluation.


The potential of selected prostanoid receptors as targets in a new therapeutic strategy for allergy and immune diseases.
Allergy and immune diseases including asthma, atopic dermatitis, rhinitis, and autoimmune diseases have been treated mainly with steroid based therapy that has multiple side effects. Even then, these allergic diseases are sometimes still not easy to control. Therefore, new effective treatments with fewer side effects are expected to be developed. Prostanoids consisting of prostaglandins and thromboxane are cyclooxygenase metabolites of arachidonic acid. They exert a range of actions mediated through their respective receptors expressed in target cells. In the skin, a wide variety of prostanoids and their receptors are highly expressed under pathophysiological conditions. However, their roles have not been well clarified. Recent developments in molecular biology have enabled us to investigate the physiological roles for each receptor via the disruption of the respective gene in combination with receptor selective compounds. It has been demonstrated that each prostanoid receptor has multiple functions whose expression is regulated in a context dependent manner, sometimes resulting in opposite, excitatory and inhibitory, outcomes. The balance of prostanoid production and receptor expression is important for homeostasis of the human body. Here, we review new findings on the roles of prostanoids in allergy and immune diseases, focusing on skin disorders as a representative, and discuss the clinical potentials of receptor-selective drugs.


Older rural people's perception of connectedness through a communication application: A qualitative descriptive study.
Connectedness among older people is essential for healthy communities, especially among rural populations where limited social interaction and associated health effects may be cause for concern. In this qualitative descriptive study, we explored older rural people's perception of connectedness through a communication application. The study assessed 10 participants (mean age = 76.2 years) living in rural Japan who regularly participated in a senior citizens' club. From July 2019 to January 2020, the participants used a social media application developed by our research team to meet the needs of older people. Semi-structured interviews were conducted. Six themes representing older rural people's perception of connectedness were identified: (1) thoughtful consideration for members strengthened even without them meeting face-to-face, (2) encouragement received from familiar members, (3) joy in sharing daily routine with neighbors, (4) courage to advance through face-to-face interaction, (5) willingness to continue club membership, and (6) fear of disrupting club's harmony. Participants who used the application felt compensated for the lack of social interaction opportunities in rural settings and strengthened their existing relationships.


Skeletal muscle fiber types and their vascular support.
Different neural and thyroidal influences on mammalian skeletal muscle result in considerable heterogeneity in muscle-fiber characteristics. Muscle fibers can, nonetheless, be grouped into three relatively homogeneous classes, based primarily on their contractile properties. There is a remarkable matching of metabolic support systems to contractile properties and, in turn, appropriate vascular supply for the metabolic systems of each of the three muscle fiber types. The contractile, metabolic, and vascular characteristics of each fiber type are consistent with known patterns of muscle fiber recruitment for the performance of muscular work.


The influence of framed messages and self-affirmation on indoor tanning behavioral intentions in 18- to 30-year-old women.
To investigate the effects of gain- and loss-framed indoor tanning (IT) prevention messages among young adult women, and examine the potential moderating effect of self-affirmation. Young adult women ages 18 to 30 who reported IT at least once in the past year (n = 475) participated in an online experiment. Participants first completed assessments of IT behavior and related constructs and were randomized to either a self-affirmation manipulation or control condition. Then, participants were randomized to either a gain-framed message emphasizing the benefits of avoiding IT or a loss-framed message emphasizing the risks of IT. Participants completed outcome measures of intentions to IT, intentions to quit IT, and emotional and cognitive responses to the framed messages. Compared with gain-framed messages, loss-framed messages led to weaker intentions to IT and stronger intentions to quit IT. Self-affirmation did not moderate message framing effects, but had a main effect increasing intentions to IT. Mediation analyses indicate that loss-framed messages affect IT behavioral intentions by increasing fear, and self-affirmation may have increased intentions to IT by producing defensive reactions to the framed messages. Loss-framed messages were more effective for reducing intentions to IT and promoting intentions to quit IT among young women after a brief exposure, and emotional response appears to be 1 pathway through which loss-framed messages affect behavioral outcomes. Messages emphasizing the risks of IT may be optimal as a public health intervention strategy. Unlike other behavioral domains, self-affirmation did not reduce defensive processing of loss-framed messages.


Determination of aflatoxins B1, B2, G1, G2 and ochratoxin A in animal feed by ultra high-performance liquid chromatography-tandem mass spectrometry.
A rapid and simple method was developed to determine aflatoxins B1, B2, G1, G2 and ochratoxin A in animal feed and pet foods by UHPLC-MS/MS. Because the complexity of the evaluated matrices, the proposed method is based on sonication extraction using an ACN/water mixture (80:20 v/v) followed by a clean-up step utilising C(18) as sorbent. Performance parameters of the method were evaluated, including linearity, trueness, precision and LOQ. Good linearity was found for all mycotoxins, with determination coefficients higher than 0.99 in the range considered, using matrix-matched calibration for quantification purposes. Recoveries ranged from 84 to 113%, with RSD lower than 20%, whereas LOQs were 5 microg/kg for the assayed mycotoxins. Finally, the method was successfully applied to the analysis of 19 real samples, detecting aflatoxin G2 in two samples at 13 and 17 microg/kg respectively, whereas the other mycotoxins were detected at trace levels (<LOQ) in five samples.


Advanced two-stage cascade configurations for energy-efficient -80 °C refrigeration.
In response to the COVID-19 pandemic, some vaccines have been developed requiring ultralow-temperature refrigeration, and the number of these freezers has been increased worldwide. Ultralow-temperature refrigeration operates with a significant temperature lift and, hence, a massive decrease in energy performance. Therefore, cascade cycles based on two vapor compression single-stage cycles are traditionally used for these temperatures. This paper proposes the combination of six different cycles (single-stage with and without internal heat exchanger, vapor injection, liquid injection, and parallel compression with and without economizer) in two-stage cascades to analyze the operational and energy performance in ultralow-temperature freezers. All this leads to 42 different configurations in which the intermediate cascade temperature is optimized to maximize the coefficient of performance. Ultra-low global warming potential natural refrigerants such as R-290 (propane) and R-170 (ethane) for the cascade high- and low-temperature stage have been considered. From the thermodynamic analysis, it can be concluded that liquid and vapor injection cascade configurations are the most energy-efficient. More specifically, those containing a vapor injection in the low-temperature stage (0.89 coefficient of performance, 40 % higher than traditional configurations). Then, using an internal heat exchanger for such low temperatures is unnecessary in terms of energy performance. The optimum intermediate cascade temperature varies significantly among cycles, from -37 °C to 2 °C, substantially impacting energy performance. Parallel compression configuration improves energy performance over single-stage cycles, but not as much as multi-stage (between 20 % and 30 % lower coefficient of performance). For most of low-temperature cycles, the high-temperature stage can be based on a single-stage cycle while keeping the maximum coefficient of performance.


The elite code grey team: a new model for residency preparedness and training in advance of a disaster.
Hurricane Katrina and the resulting levee failures decimated the New Orleans landscape, trapping physicians inside hospital facilities for up to 5 days. With over 2000 people trapped in the 3 primary teaching hospitals, there were only 3 fatalities. Yet despite the lack of adverse events, the experience revealed that graduate medical education is woefully underprepared to deal with disaster. As call schedules obviously did not anticipate the disaster, the assignment of physicians to these shifts was random, without regard to the ability to withstand that stress and the conditions. The group of physicians that was assigned was a heterogeneous mix of personalities, experience levels, and psychological fortitude. None of the physicians had been formally trained in the core principles of disaster management. This article reviews an innovative approach to disaster management, drawing upon the expertise of law enforcement, the airline industry, and on-going physician development programs in disaster medicine.


Tensile Creep Behavior of Quasi-Unidirectional E-Glass Fabric Reinforced Polypropylene Composite.
The present work addressed the creep behavior of quasi-unidirectional E-glass fabric reinforced polypropylene composites under off-axis tensile loading. A series of creep tests were performed on the composite at three different loading stress levels. The creep response of off-axis samples of quasi-unidirectional composites under a constant loading level can be clearly observed. A phenomenological viscoplasticity model was built for describing the creep behavior of the composite. To improve the accuracy of prediction, cyclic loading-unloading tests were adopted to determine the material constants in the model. The predicted results in terms of the strains after a load over a period of time were found to be satisfactory, compared with the experimental results. In addition, same failure mechanism was found in off-axis samples under quasi-static and creep loading cases.


Hypofractionated radical radiotherapy in elderly patients with medically inoperable stage I-II non-small-cell lung cancer.
We described the results of a hypofractionated regimen (HFRT) in a cohort of elderly patients (36 subjects) with stage I-II non-small-cell-lung cancer (NSCLC), tumor size> or =3 cm and ineligible for surgery. HFRT was delivered in 20 daily fractions of 3 Gy per fraction with a total dose of 60 Gy. The median PTV was 145 cm(3). The primary purpose of study was to estimate the local tumor control at 2 years as well as the modifications in the lung function parameters at 6 and 12 months. The local tumor control was 63.9% at 2 years. The incidence of distant recurrence rate at 2 years was 50%. The overall-survival (OS), the cause-specific-survival (CSS) and the disease-free-survival (DSF) at 2 years were 55.6, 57.1, and 38.9%, respectively. The median OS, CSS, and DFS was 25.4 (CI 95% 21.7-32.9), 26.7 (CI 95% 22.5-33.5) and 23.4 months (CI 95% 18.6-30.1), respectively. The two clinical parameters with a positive influence on OS were a KPS> or =90 (HR 1.16; p=0.013) and tumor size< or =4 cm (HR 0.763; p=0.011). No grade 3-4 acute toxicity was reported. No significant change in lung function parameters was measured at 6 and 12 months. For patients with larger or centrally located tumors as well as for subjects with lymph nodes involvement SBRT may be of limited valiance. Although the performances of our regimen were lower than the ones achieved by SBRT, our therapeutic option may offer a lower incidence of complications against a satisfactory local tumor control.


A new bioactive aminophenoxazinone alkaloid from a marine-derived actinomycete.
Chemical investigation of the marine Streptomyces sp. Eg25 led to the isolation of one new natural 2-aminophenoxazin-3-one-8-carboxylic acid methyl ester named maroxazinone (1) as well as the known compounds elloxazinone A (2), exfoliazone (3), carboxyexfoliazone (4), elloxazinone B (5) and venezueline D (6). The chemical structures of the isolated compounds were deduced from extensive studies of NMR ((1)H and (13)C NMR, (1)H-(1)H COSY, HMQC and HMBC) and mass spectra. The cytotoxic activities of the new maroxazinone (1) and venezueline D (6) against breast carcinoma cell line (MCF7), liver carcinoma cell line (HEPG2) and colon carcinoma cell line (HCT116) were investigated.


Dystonia : emerging concepts in pathophysiology.
The essential pathophysiological feature of dystonia is co-contraction of antagonistic muscles. This may be due to derangement of the spinal cord or cortical mechanism. In the cord, there is disruption of the normal reciprocal inhibition of antagonists during agonist contraction. This decreased reciprocal inhibition is due to reduced presynaptic inhibition of muscle afferent input to the inhibitory interneuron. The reduced presynaptic inhibition may in turn be either due to defective suprasegmental control or to changes in the tonic afferent input to the interneuron from cutaneous and muscle afferents. Alternatively, genesis of dystonia may entirely be a cortical mechanism. Overactivity of the premotor cortices, which receive projections from basal ganglia via ventral thalamus, could result in dystonia by abnormal activation of cortical motor neurons. This may again be due to a dopaminergic dysfunction of basal ganglia.


Control beliefs and cognition over a 10-year period: Findings from the ACTIVE trial.
We examined two facets of control beliefs and cognition over 10 years within the Advanced Cognitive Training for Independent and Vital Elderly study. Intellectual Self-Efficacy decreased (β = -0.32 units/year; SE = 0.03) and Concern About Intellectual Aging increased (β = 0.26 units/year; SE = 0.02) over time, with older age being the only predictor of increases in Concern About Intellectual Aging. Although baseline cognitive performance was related to control beliefs over time, the reverse was not supported. Findings were not altered by participation in the ACTIVE training programs, suggesting the need for including intervention components that lead to long-term maintenance or improvements in such beliefs. (PsycINFO Database Record


Emerging role of checkpoint blockade therapy in lymphoma.
Following the successful application of immune checkpoint blockade therapy (CBT) in refractory solid tumors, it has recently gained momentum as a promising modality in the treatment of relapsed lymphoma. This significant therapeutic advance stems from decades of research that elucidated the role of immune regulation pathways and the mechanisms by which tumors can engage these critical pathways to escape immune detection. To date, two main pathways, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), have emerged as key targets of CBT demonstrating unprecedented activity particularly in heavily pretreated relapsed/refractory Hodgkin lymphoma and some forms of non-Hodgkin disease. Herein we provide a brief discussion of checkpoint blockade in the context of lymphoma biology with a specific focus on novel checkpoint inhibitors and their therapeutic activity. We discuss current clinical trials and the landscape of CBT to underscore both the remarkable progress and foreseeable limitations of this novel treatment strategy. In particular, we build upon state-of-the-art knowledge and clinical insights gained from the early trials to review potential approaches to how CBT may be integrated with other treatment modalities, including chemoimmunotherapy to improve patient outcomes in the future. Finally, as the role of CBT evolves to potentially become a cornerstone of therapy in refractory/relapsed lymphoma, we briefly emphasize the importance of predictive biomarkers in an effort to select appropriate patients who are most likely to derive benefit from CBT.


Clinical significance of Fusobacterium nucleatum, epithelial-mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients.
Colorectal cancer (CRC) is a common digestive malignancy and emerging studies have closely linked its initiation and development with gut microbiota changes. Fusobacterium nucleatum (Fn) has been recently identified as a pathogenic bacteria for CRC; however, its prognostic significance for patients is poorly investigated and is less for patients within late stage. Therefore, in this study, we made efforts to analyze its level and prognostic significance in a retrospective cohort of 280 stage III/IV CRC patients. We found that the Fn level was abnormally high in tumor tissues and correlated with tumor invasion, lymph node metastasis status, and distant metastasis. We also identified it as an independent adverse prognostic factor for cancer-specific survival (CSS) and disease-free survival (DFS). The following subgroup analysis indicated that Fn level could stratify CSS and DFS in stage IIIB/C and IV patients but failed in stage IIIA patients. In addition, stage III/IV patients with low Fn level were found to benefit more from adjuvant chemotherapy than those with high Fn level, in terms of DFS. Finally, we analyzed the expression and clinical significance of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) and cancer stem cell (CSC) markers (Nanog, Oct-4, and Sox-2) in CRC tissues. The results indicated that N-cadherin, Nanog, Oct-4, and Sox-2 were adverse prognostic factors in these patients, while the opposite was true for E-cadherin. More importantly, expression of E-cadherin, N-cadherin, and Nanog was significantly correlated with Fn level in tumor tissues, suggesting the potential involvement of Fn in EMT-CSC cross talk during CRC progression. Taken together, these findings indicate that Fn is a novel predictive biomarker for clinical management in stage III/IV patients, and targeting Fn may be an effective adjuvant approach for preventing CRC metastasis and chemotherapy resistance.


Human telomerase contains evolutionarily conserved catalytic and structural subunits.
We have cloned and characterized a human gene encoding TP2 (telomerase-associated protein 2), a protein with similarity to reverse transcriptases and the catalytic telomerase subunits from Saccharomyces cerevisiae and Euplotes aediculatus. Indirect immunofluorescence revealed that TP2 was localized to the nucleus. Using antibodies to endogenous and epitope-tagged TP2, we found that TP2 was associated specifically with human telomerase activity and the recently identified telomerase-associated protein TP1. Mutation of conserved residues within the reverse transcriptase domain of TP2 severely reduced associated telomerase activity. These results suggest that telomerase is an evolutionarily conserved multisubunit complex composed of both structural and catalytic subunits.


Structural studies on the 2.25-MDa homomultimeric phosphoenolpyruvate synthase from Staphylothermus marinus.
The phosphoenolpyruvate synthase of the hyperthermophilic archaeon Staphylothermus marinus forms an unusually large homomultimeric complex of 93 kDa subunits. Electron image analysis of negatively stained and low-dose unstained preparations showed that the complex has a single, stable characteristic view and a well-preserved core with threefold rotational symmetry. The periphery of the assembly is composed of a nebulous, possibly flexible, component. Mass measurements by scanning transmission electron microscopy yielded a molecular weight of 2250 +/- 230 kDa, confirming the well-defined nature of the structure and indicating that it is composed of 24 +/- 2.5 subunits. The stability and symmetry of the characteristic projection views suggest a polyhedral three-dimensional architecture. The novel quaternary arrangement of this enzyme might be a consequence of its adaptation to an extreme environment.


SSCP analysis of long DNA fragments in low pH gel.
Sensitivity of single-strand conformation polymorphism analysis of PCR products (PCR-SSCP analysis) is known to be decreased when the DNA fragments are longer than 300 bp. We examined effects of buffer ions in an attempt to extend the length limit of the analysis. It has been noted that addition of glycerol to the gel containing Tris-borate buffer enhances the sensitivity, but the effects of glycerol have been left unexplained. We found that the effects of glycerol are caused by the reduction of pH of the buffer by the reaction of glycerol and borate ion. We further extended these observations and found that sensitivity of SSCP can be greatly improved by running the electrophoresis in low pH buffer systems. Using a new buffer system and running the electrophoresis at a fixed temperature, we detected 27 of 31 known mutations of factor IX gene in six different sequence contexts ranging in length from 300 to 800 bp.


Challenges in the production of itaconic acid by metabolically engineered Escherichia coli.
Metabolic engineering allows the production of a variety of high-value chemicals in heterologous hosts. For example, itaconic acid (IA) has been produced in several microorganisms, such as Escherichia coli, Aspergillus niger, and Synechocystis sp. through the expression of cis-aconitate decarboxylase gene (cad) from Aspergillus terreus. Recently, we showed that inactivation of the isocitrate dehydrogenase gene and overexpression of the aconitase gene dramatically enhanced the production levels of IA in E. coli expressing cad. Furthermore, we demonstrated that it is possible to produce IA directly from starch by engineered E. coli that additionally expresses the α-amylase gene from Streptococcus bovis. In this study, we sum up our findings regarding the challenges of IA production in E. coli.


The challenge of acute-stroke management: does telemedicine offer a solution?
Several studies have described successful experiences with the use of telemedicine in acute stroke. The objective of this study was to assess the feasibility, acceptability, and treatment delivery reliability, of telemedicine systems for the clinical and radiological assessment, and management of acute-stroke patients. A systematic review of the literature was carried out. Studies were included if they met the following criteria: (1) study population included participants with a diagnosis of suspected acute stroke, (2) intervention included the use of telemedicine systems to aid assessment, diagnosis, or treatment in acute stroke, and (3) outcomes measured related to feasibility in clinical practice, acceptability to patients, carers, and staff, reliability of telemedicine systems, and effectiveness in delivering treatment, especially tissue plasminogen activator (tPA). Overall, 17 relevant non-randomised studies reported that telemedicine systems were feasible and acceptable. Interrater reliability was excellent for global clinical assessments and decisions on radiological exclusion criteria although agreement for individual assessment items was more variable. Telemedicine systems were associated with increased use of tPA. Although there is limited reliable evidence, observational studies have indicated that telemedicine systems can be feasible, acceptable, and reliable in acute-stroke management. In addition, telemedicine consultations were associated with improved delivery of tPA.


Qualitative hemispheric differences for processing trigrams.
The present study investigated qualitative hemispheric differences for processing trigrams by examining the nature of errors made when trigrams were directed to each visual field-hemisphere. Three types of trigrams, pronounceable letter trigrams, unpronounceable letter trigrams, and non-letter symbol trigrams, were presented. Recognition of each trigram type resulted in significant visual field differences in error types. Pronounceable vs. unpronounceable letter trigrams yielded similar visual field differences in error types, whereas letter vs. non-letter symbol trigrams yielded opposite patterns of visual field differences in error types. These results suggest that hemispheric mode of trigram processing changes as a function of letter vs. non-letter type, but not as a function of pronounceability per se. Moreover, the direction of this change is opposite for the two hemispheres.


Semi-Automated, Object-Based Tomography of Dislocation Structures.
The characterization of the three-dimensional arrangement of dislocations is important for many analyses in materials science. Dislocation tomography in transmission electron microscopy is conventionally accomplished through intensity-based reconstruction algorithms. Although such methods work successfully, a disadvantage is that they require many images to be collected over a large tilt range. Here, we present an alternative, semi-automated object-based approach that reduces the data collection requirements by drawing on the prior knowledge that dislocations are line objects. Our approach consists of three steps: (1) initial extraction of dislocation line objects from the individual frames, (2) alignment and matching of these objects across the frames in the tilt series, and (3) tomographic reconstruction to determine the full three-dimensional configuration of the dislocations. Drawing on innovations in graph theory, we employ a node-line segment representation for the dislocation lines and a novel arc-length mapping scheme to relate the dislocations to each other across the images in the tilt series. We demonstrate the method for a dataset collected from a dislocation network imaged by diffraction-contrast scanning transmission electron microscopy. Based on these results and a detailed uncertainty analysis for the algorithm, we discuss opportunities for optimizing data collection and further automating the method.


[Study on the correlation of the effect of entecavir on Th1/Th2 cytokines level in the treatment of chronic hepatitis].
Objective: To explore the expression level of peripheral blood Th1/Th2 type cytokines of chronic hepatitis b (CHB) patients in the entecavir (ETV) antiviral treatment, analyze the relationship between various cytokines, and the correlation among of cytokines and HBV DNA loads. Methods: Luminex Liquid Chip Technology was applied to detect the peripheral blood Th1/Th2 type cytokines expression level of CHB patients; At the same time, liver function was detected by Fully Automatic Biochemical Analyzer; HBV DNA loads were detected by PCR Method; Hepatitis b virology markers were detected by Chemiluminescence Method. F-test and Pearson correlation analysis were used for statistical analysis. Results: Before ETV antiviral treatment, peripheral blood Th1 cytokines IFN gamma expression level in patients with CHB increased significantly (P = 0.010) compared with the healthy control group while TNF alpha expression level having no statistically significant difference (P = 0.095); Th2 type cytokines IL-4, IL-6, IL-10 levels decreased obviously (P = 0.039, P = 0.014, P = 0.026) compared with those in the control group. After 48 weeks of treatment, Th1 cytokines IFN gamma and TNF alpha expression levels were reduced significantly (19.2±5.03 pg/ml vs 24.69±6.51 pg/ml, and 6.09±4.99 pg/ml vs 9.50±7.34 pg/ml, P < 0.001, and P = 0.016) compared with that before treatment; Th2 type cytokines IL-4, IL-6 expression level increased significantly (33.86±22.47 pg/ml vs 21.32±12.84 pg/ml, and 11.65±6.91 pg/ml vs 8.51±4.94 pg/ml, P = 0.004, and P = 0.029) compared with that before treatment while IL-10 expression level having no statistical significance (P = 0.081). There was disorder and irregularity in the correlation between the levels of Th1/Th2 type cytokines. And there was no correlation between the various cytokines and HBV DNA loads in patients with CHB. Conclusion: ETV can not only inhibit HBV DNA replication, reducing HBV DNA loads, but also contribute to regulate Th1/Th2 type cytokines expression level in patients with CHB, but there was no correlation between the levels of various cytokines, various cytokines and HBV DNA loads.


A CMOS-MEMS BEOL 2-axis Lorentz-Force Magnetometer with Device-Level Offset Cancellation.
Lorentz-force Microelectromechanical Systems (MEMS) magnetometers have been proposed as a replacement for magnetometers currently used in consumer electronics market. Being MEMS devices, they can be manufactured in the same die as accelerometers and gyroscopes, greatly reducing current solutions volume and costs. However, they still present low sensitivities and large offsets that hinder their performance. In this article, a 2-axis out-of-plane, lateral field sensing, CMOS-MEMS magnetometer designed using the Back-End-Of-Line (BEOL) metal and oxide layers of a standard CMOS (Complementary Metal-Oxide-Semiconductor) process is proposed. As a result, its integration in the same die area, side-by-side, not only with other MEMS devices, but with the readout electronics is possible. A shielding structure is proposed that cancels out the offset frequently reported in this kind of sensors. Full-wafer device characterization has been performed, which provides valuable information on device yield and performance. The proposed device has a minimum yield of 85.7% with a good uniformity of the resonance frequency fr¯=56.8 kHz, σfr=5.1 kHz and quality factor Q¯=7.3, σQ=1.6 at ambient pressure. Device sensitivity to magnetic field is 37.6fA·μT-1 at P=1130 Pa when driven with I=1mApp.


The Role of Medicinal and Aromatic Plants against Obesity and Arthritis: A Review.
Obesity is a significant health concern, as it causes a massive cascade of chronic inflammations and multiple morbidities. Rheumatoid arthritis and osteoarthritis are chronic inflammatory conditions and often manifest as comorbidities of obesity. Adipose tissues serve as a reservoir of energy as well as releasing several inflammatory cytokines (including IL-6, IFN-γ, and TNF-α) that stimulate low-grade chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, diabetes, hypertension, cardiovascular disorders, fatty liver disease, oxidative stress, and chronic kidney diseases. Dietary intake, low physical activity, unhealthy lifestyle, smoking, alcohol consumption, and genetic and environmental factors can influence obesity and arthritis. Current arthritis management using modern medicines produces various adverse reactions. Medicinal plants have been a significant part of traditional medicine, and various plants and phytochemicals have shown effectiveness against arthritis and obesity; however, scientifically, this traditional plant-based treatment option needs validation through proper clinical trials and toxicity tests. In addition, essential oils obtained from aromatic plants are being widely used as for complementary therapy (e.g., aromatherapy, smelling, spicing, and consumption with food) against arthritis and obesity; scientific evidence is necessary to support their effectiveness. This review is an attempt to understand the pathophysiological connections between obesity and arthritis, and describes treatment options derived from medicinal, spice, and aromatic plants.


Spatial variation in the risk of hospitalization with childhood pneumonia and empyema in the North of England.
The aim of this study was to investigate spatial variation in risk of hospitalization in childhood pneumonia and empyema in the North of England and associated risk factors. Data on childhood (0-14 years) hospital admissions with a diagnosis pneumonia or empyema were linked to postcode districts. Bayesian conditional autoregressive models were used to evaluate spatial variation and the relevance of specific spatial covariates in an area-based study using postcode as the areal unit. There was a sixfold variation in the risk of hospitalization due to pneumonia across the study region. Variation in risk was associated with material deprivation, Child Well-being Index (CWI) health domain score, number of children requiring local authority support, and distance to hospital. No significant spatial variation in risk for empyema was found.


Do the risk factors associated with conduct problems in adolescents vary according to gender?
The present paper examines whether there are gender differences in the associations between conduct problems and risk factors such as family conditions, peer influence, leisure activities, school-related variables and pubertal timing. We analysed self-reported data collected as part of a large general population study of Norwegian adolescents (N=9342). On the basis of earlier studies, conduct problems were decomposed into three dimensions, labelled theft and vandalism, school opposition and covert behaviour. The first dimension includes different kinds of theft and vandalism, whereas the second includes school-related conduct problems of an overt aggressive kind. The last dimension reflects avoidance of arenas under adult control. Whether or not gender differences were detected depended on the aspect of conduct problems considered. The associations between risk factors and "theft and vandalism" and "school opposition" were stronger for boys than for girls. No gender differences were detected in the associations between and risk factors and "covert behaviour". Even though there were gender differences in the strength of these associations, the same risk factors seem to be relevant in explaining conduct problems for both gender groups.


Hepatitis C-A clinical review.
With an estimated prevalence of about 170 million people worldwide, chronic hepatitis C is an important cause of chronic liver disease associated with a substantial risk of cirrhosis and hepatocellular carcinoma. The recent past has borne witness to remarkable advancements in the treatment of chronic hepatitis C with the development of novel, effective, and well tolerated medications that have resulted in paradigm shifts in treatment approaches and may potentially affect the natural history of the disease. We provide a clinical review of current concepts and future developments in the management of chronic hepatitis C to aid in the understanding and individualization of chronic hepatitis C treatment. J. Med. Virol. 88:1844-1855, 2016. © 2016 Wiley Periodicals, Inc.


Copper(I)-catalyzed oxidative coupling between 2-aminobenzothiazole and terminal alkyne: formation of benzothiazine.
An unprecedented formation of benzothiazine during copper(I)-catalyzed oxidative coupling of 2-aminobenzothiazole and terminal alkyne in air has been observed. This unique transformation possibly occurs through the ring opening of 2-aminobenzothiazole and subsequent oxidative coupling with alkyne followed by intramolecular cyclization. A variety of substituted benzo[b][1,4]thiazine-4-carbonitriles are obtained by this protocol.


[Kidney transplant urinary complications. Diagnosis and treatment.]
There are different surgical techniques for reconstruction of the urinary tract in kidney transplant. However, urinary complications are frequent in the postoperative period, being the ureter the frequent location of these complications. This results in high health care costs, increasing patient morbimortality and sometimes graft loss. For this reason, prevention, correct diagnosis and treatment are important. The aim of this review is to describe the surgical techniques most commonly used in kidney transplant for ureteroneocystostomy. To analyze the advantages and disadvantages of each of them and to compare their complications. On the other hand, we summarize the recent literature on the four most frequent urinary complications in the postoperative period after transplantation. The possible causes and treatment of urine leak, ureteri cobstruction, hematuria and vesicoureteral reflux are presented.


EFFECT OF 5-HT3 ANTAGONIST ONDANSETRON ON WRAP-RESTRAINT AND CONDITIONED EMOTIONAL STRESS INDUCED DEFECATION.
The effect of ondansetron was investigated in wrap-restraint and conditioned emotional (footshock) stress induced colonic hypermotility in rat. Ondansetron was administered in doses of 0.1, 0.5 and 1 mg/kg, sc. In wrap-restraint group, ondansetron dose-dependently reduced the fecal output to baseline levels (0.51 ± 0.20 gm/rat, 0.48 ± 0.38 gm/rat, 0.38 ± 0.16 gm/rat with 0.1, 0.5 and 1 mg/kg respectively). Diazepam, 5 mg/kg and atropine, 1 mg/kg also decreased the fecal output in this model. In footshock group, ordansetron did not affect the emotional stress induced increase in fecal pellet output. Diazepam and atropine however, decreased the fecal output in this model also.


[The role of procalcitonin in the patient assessment after surgical procedures].
In the group of 450 patients operated in the Cardiosurgical Department of the Faculty Hospital in Plzen during the period from III/2003 till XI/2003, 1451 samples were collected to examine the following-procalcitonin levels (PCT), white blood cell counts (Leu) and C-reactive protein levels (CRP). The findings were assessed with respect to the respective patient's clinical status, and any correlation between procedures with extracorporeal circulation (MO), signs of inflammation, septic and non-septic serious complications and between the above mentioned markers levels, was searched. It was detected, that the PCT levels correlated well with the clinical signs of inflammation and sepsis, as well as with the non-inflammatory complications. The CRP and Leu changes were not statistically significant and their levels are commonly increased by the surgical procedure itself.


[The neck cysts and infectious mononucleosis due to cytomegalovirus].
Infectious mononucleosis is usually produced as primoinfection by Epstein-Barr virus, but the second most common cause is cytomegalovirus. Clinical presentation of infectious mononucleosis is a pharyngitis and tonsillitis, associated to neck nodes, fever and general malaise, as well as haematological features such as an absolute lymphomonocytosis. Occasionally it is the neck node that is more severe, even without initial lymphomonocytosis. We report a deep neck abscess within a neck node as subacute presentation of infectious mononucleosis by cytomegalovirus. We review the clinical presentation of infectious mononucleosis, specially due to cytomegalovirus, as well as the importance that this disease could have while dealing with diagnosis and management of neck masses.


Successful treatment of disseminated mucormycosis in a neutropenic patient with T-cell acute lymphoblastic leukaemia.
Mucormycosis is a rare angioinvasive fungal infection, more commonly seen in immunosuppressed patients, with reported mortality rates of 95% in disseminated disease. We present a case report of a patient with T-cell acute lymphoblastic leukaemia who developed disseminated infection with mucormycosis (involving the pancreas, left occipital lobe, right lower lobe of lung, appendix and right kidney) after having completed induction and consolidation chemotherapy. Growth of Lichtheimia corymbifera was initially isolated following a right pleural tap with fungal elements identified repeatedly on subsequent pathology specimens. Following radical surgical debridement and concurrent treatment with combination antifungal therapy, the patient survived. This case demonstrates that aggressive multisite surgical de-bulking of disseminated fungal foci, in conjunction with combination antifungal therapy and reversal of immunosuppression, can result in survival despite the grave prognosis associated with disseminated mucormycosis.


Personalized medicine approach for optimizing the dose of tafamidis to potentially ameliorate wild-type transthyretin amyloidosis (cardiomyopathy).
Placebo-controlled clinical trials are useful for identifying the dose of a drug candidate that produces a meaningful clinical response in a patient population. Currently, Pfizer, Inc. is enrolling a 400-person clinical trial to test the efficacy of 20 or 80 mg of tafamidis to ameliorate transthyretin (TTR)-associated cardiomyopathy using clinical endpoints. Herein, we provide guidance for how to optimize the dose of tafamidis for each WT TTR cardiomyopathy patient using its mechanism of action as the key readout, i.e. we identify the dose of tafamidis that maximally kinetically stabilizes TTR in the blood. Tetramer dissociation is rate limiting for TTR aggregation, which appears to drive the pathology of the TTR amyloidoses. Hence, we measure the TTR tetramer dissociation rate (kinetic stability) in the patient's plasma as a function of tafamidis dose to optimize the dose employed to maximize kinetic stability. Historical data tell us that a subset of patients exhibiting higher tafamidis plasma concentrations are maximally kinetically stabilized at the 20-mg tafamidis dose, whereas the patient studied herein required a 60 mg once daily dose to achieve maximum kinetic stabilization. We anticipate that establishing the dose of tafamidis that achieves maximal TTR kinetic stabilization will translate into a maximal clinical effect, but that remains to be demonstrated.


Differential Expression of Long Noncoding RNAs in Normal and Inflamed Human Dental Pulp.
Dental pulp inflammation is an excellent model for the interaction between tissue inflammation and regenerative processes. It is worthwhile to better understand molecular signaling of repair and regeneration in inflammatory processes. Emerging evidence suggests that long noncoding RNA (lncRNA) participates in immune system inflammatory processes. Here we investigate the expression of lncRNAs in pulpitis, the inflammation of dental pulp tissue, and identify lncRNAs that possibly participate in inflammation responses and odontogenesis. Integrated comparative lncRNA microarray was used to examine lncRNA and mRNA expression between inflamed and normal human pulp tissue. The differential expression of lncRNAs and mRNAs was then validated by quantitative real-time polymerase chain reaction. A bioinformatics analysis was performed to predict the function of differentially expressed lncRNAs and mRNAs. Our data indicated 752 lncRNAs were significantly differentially expressed (fold change > 2.0; P < .05) in inflamed pulp tissues compared with normal pulp tissues, including 338 upregulated and 414 downregulated lncRNAs. Among the 646 differentially expressed mRNAs (fold change > 2.0; P < .05), 460 were upregulated, and 186 were downregulated. The differentially downregulated genes are enriched for gene ontology terms related to odontogenesis and cell development in biological processes, whereas the differentially upregulated genes are related to immune and inflammation processes. LncRNAs are differentially expressed in inflamed human pulp tissue compared with normal pulp tissue, indicating that lncRNAs may play key roles in pulpitis pathogenesis and development.