Analysis of cocaine and cocaine metabolites by high pressure liquid chromatography.
A high pressure liquid chromatography procedure was developed for analysis of cocaine and two metabolites (norcocaine and benzoylecgonine) in biological fluid. Following extraction with chloroform/Isopropanol (3/2), chromatography is performed with a mu-Bondapak C-18 reverse phase column eluted with water/acetonitrile/methanol (8/1/1) containing 1% acetic acid and 0.3 M EDTA. Ultraviolet detection of individual compounds was made at 235 nm and quantitation was based on peak height ratio to internal standard. Detection limit based on 0.5 mL of sample is less than 1 microgram/mL. Confirmation of the individual compounds was made by direct probe mass spectral analysis of the eluted peaks and comparison to known standards.


Reverse transcriptase polymerase chain reaction for detecting Ewing's sarcoma in archival fine needle aspiration biopsies.
Previous studies on pediatric soft tissue sarcomas have demonstrated a chromosomal 11;22 (q24;q12) translocation in Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumors that appears to be a unique oncogenic marker. To investigate the usefulness of reverse transcriptase polymerase chain reaction (RT-PCR) as an ancillary method for cytodiagnosis, we tested archival aspirates derived from ES patients to establish whether any beta-actin RNA expression or tumor-specific EWS/FLI-1 gene translocation had occurred. Sixteen skeletal specimens aspirated 10-15 years earlier from patients with cytologic and histologic diagnoses of ES were prepared for PCR. The amplification products were sequenced. Amplifiable RNA was detected in smears from 12 patients by beta-actin RT-PCR. Seven aspirates from beta-actin-positive patients showed ES-specific genomic translocation (58%). Sequence analysis of the resulting PCR fragments revealed EWS/FLI-1 fusion transcriptions of varying length. When RNA was retrievable, RT-PCR applied to routinely stained aspirate smears was a highly specific method in differential diagnosis of ES.


[Progress in research on etiopathogenesis of schizophrenia in recent decades].
In this paper, a progress in research on etiopathogenesis of schizophrenia made in the recent decade was presented. Two main etiopathogenetic factors in this illness include genetic predisposition and brain damage in early period of life, leading to a disorder of brain development and lateralization, and to an increased susceptibility to stress. The use of new methods of genetic studies brought about a significant progress as to identification of relationship between schizophrenia and various changes within genotype. In the 1990s, many data have been obtained concerning possible brain damaging factors as well as the existence of structural and functional brain abnormalities in this illness. Impaired brain development in schizophrenia results in disturbances of neuronal connection in the cortical structures and in cortical-limbic transmission, what may underlie the appearance of psychopathological symptoms. New neuroleptic drugs introduced in the recent years show more complete therapeutic action against schizophrenic symptoms compared with drugs used so far. This may result from their broader influence on the pathogenetic processes of schizophrenia, which may be due, apart from their effect on dopaminergic system, also to their action on some elements of serotonergic neurotransmission.


N-(2-Bromoethyl)-4-piperidino-1,8-naphthalimide and N-(3-bromopropyl)-4-piperidino-1,8-naphthalimide.
N-(2-Bromoethyl)-4-piperidino-1,8-naphthalimide, C(19)H(19)BrN(2)O(2), (I), and N-(3-bromopropyl)-4-piperidino-1,8-naphthalimide, C(20)H(21)BrN(2)O(2), (II), are an homologous pair of 1,8-naphthalimide derivatives. The naphthalimide units are planar and each piperidine substituent adopts a chair conformation. This study emphasizes the importance of pi-stacking interactions, often augmented by other contacts, in determining the crystal structures of 1,8-naphthalimide derivatives.


Choline and human nutrition.
Choline is crucial for sustaining life. It modulates the basic signaling processes within cells, is a structural element in membranes, and is vital during critical periods in brain development. Choline metabolism is closely interrelated with the metabolism of methionine and folate. We believe that the normal human diet provides sufficient choline to sustain healthy organ function. However, vulnerable populations may become choline deficient, including the growing infant, the pregnant or lactating woman, the cirrhotic, and the patient fed intravenously. Further studies of choline requirements in these groups are required.


[Administration of Electroacupuncture and Da-Cheng-Qi Decoction Has a Synergetic Effect in Relieving Injury of Pancreas, Lung and Large Intestine and Inflammatory Reactions in Rats with Acute Pancreatitis].
To explore the effectiveness of electroacupuncture (EA) stimulation of Shu-and Mu-points of Lung and Large Intestine Meridians combined with administration of Da-Cheng-Qi Decoction (DCQD) in the treatment of inflammatory injury in rats with acute pancreatitis, so as to reveal their synergetic anti-inflammatory effect. Forty male SD rats were randomly divided into five groups: normal control, model, DCQD, EA, EA+DCQD, with 8 rats in each group. All the rats except those in the normal group received a retrograde biliopancreatic duct injection of sodium Taurocholate (3.0%, 0.1 mL/100 g) to induce an acute pancreatitis model. Twenty-four hours after modeling, EA (4 Hz/50 Hz) was applied to bilateral Shu-points "Feishu" (BL 13) and "Dachangshu" (BL 25), and Mu-points "Zhongfu" (LU 1) and "Tianshu" (ST 25) for 20 min, once every 7 h, 3 times in total. Rats of the DCQD and EA+DCQD groups were given intra-gastric gavage of DCQD (1 mL/100 g) 24 h after modeling, and those of the other 3 groups were given intra-gastric gavage of same dosage of normal saline. The histopathological changes of the pancreas, lung and large intestine tissues were observed after H. E. staining and scored according to Schmidt's and colleagues' methods (the severity of edema, inflammation, hemorrhage, necrosis). The concentrations of interleukin-6 (IL-6) and IL-10 in the serum, and those of myeloperoxidase (MPO) and malonaldehyde (MDA) in the lung and large intestine tissues were detected by using double-antibody sandwich ELISA. After modeling, the histopathological scores of pancreas, lung and large intestine tissues, the concentrations of MPO and MDA in lung and large intestine, and the levels of IL-6 and IL-10 in serum were significantly increased in the model group compared with the normal control group (P<0.05). Following the treatment, the histopathological scores of pancreas, lung and large intestine tissues, the contents of MPO and MDA in the lung and large intestine, and serum IL-6 were considerably reduced in the EA, DCQD and EA+DCQD groups relevant to the model group (P<0.05), while serum IL-10 content was notably increased in the three treatment groups (P<0.05). The therapeutic effect of EA+DCQD was significantly superior to that of simple EA and simple DCQD in down-regulating the histopathological scores of lung and large intestine tissues, the contents of MPO and MDA in the lung and large intestine, and serum IL-6 level, and up-regulating serum IL-10 level (P<0.05). No significant differences were found between the EA and DCQD groups in the above-mentioned 9 indexes (P>0.05). EA and DCQD can relieve the inflammatory injury of the pancreas, lung and large intestine tissues in rats with acute pancreatitis, and EA combined with DCQD has a better synergetic effect in reducing oxidative stress level and inflammatory reaction.


Effects of catecholamines on blood pressure in the long bone marrow cavity in rats with bisphosphonate-induced osteopetrosis.
Osteopetrosis is a congenital metabolic bone disease characterized by skeletal sclerosis resulting from defective osteoclast-mediated bone resorption. The disease may, inter alia, be caused by the administration of bisphosphonates (e.g. pamidronate) particularly in young humans. The issue of the effect of pamindronate-induced osteopetrosis on the function of blood circulation and autonomic nervous system remains open. In order to clarify this problem, the present study concentrated on the effect of catecholamines on blood pressure in the marrow cavity in rats with pamindronate-induced osteopetrosis. The experiments consisted in pamidronate administration to young male Wistar rats at doses of 3 mg/kg sc, for 3 or 6 weeks. Norepinephrine, epinephrine, isoprenaline as well as adrenoceptor antagonists (phentolamine and propranolol) were administered to the controls and the rats with pamindronate-induced osteopetrosis. The examinations demonstrated that rats with pamidronate-induced osteopetrosis displayed increased blood pressure in the marrow cavity. In addition, a disorder in the effect of catecholamines on blood pressure in the marrow cavity of osteopetrotic bone was observed.


Beyond single-agent bortezomib: combination regimens in relapsed multiple myeloma.
Bortezomib-based combinations are being investigated in relapsed or refractory multiple myeloma with the aim of improving outcomes. This review presents recent data from clinical trials of these combinations and discusses their implications. Preclinical findings indicating additive or synergistic activity of bortezomib plus conventional and novel agents for multiple myeloma appear to be supported by clinical studies of bortezomib-based combinations. Bortezomib combined with a broad set of active agents results in enhanced response rates, including high complete response rates. Encouraging responses to bortezomib and its combinations are also seen in elderly patients, patients with adverse prognostic factors such as refractory disease and increased beta2-microglobulin, patients with cytogenetic abnormalities such as chromosome 13 deletion, advanced bone disease, extramedullary involvement, and patients with renal impairment, including patients with renal failure requiring dialysis. Toxicities are predictable and manageable and comparable to those seen with bortezomib monotherapy. Bortezomib-based combinations show promising activity in relapsed or refractory multiple myeloma, including reversal of chemoresistance to previously used agents. As high complete and overall response rates translate into longer survival, bortezomib-based combinations appear likely to have a significant impact on the multiple myeloma treatment algorithm and on the course of the disease itself.


Donation after cardiac death in abdominal organ transplantation.
This article reviews the field of donation after cardiac death, focusing on the history, ethicolegal issues, clinical outcomes, best practices, operative techniques, and emerging strategies to optimize utilization of this resource. Donation after cardiac death is one effective way to decrease the organ shortage and has contributed the largest recent increase in abdominal organ allografts. Currently, donation after cardiac death organs confer an increased risk of ischemic cholangiopathy after liver transplant and of delayed graft function after kidney transplant. As this field matures, risk factors for donation after cardiac death organ transplant will be further identified and clinical outcomes will improve as a result of protocol standardization and ongoing research.


Should I stay or should I go? Conceptual underpinnings of goal-directed actions.
All actions, even the simplest like moving an arm to grasp a pen, are associated with energy costs. Thus all mobile organisms possess the ability to evaluate resources and select those behaviors that are most likely to lead to the greatest accrual of valuable items (reward) in the near or, especially in the case of humans, distant future. The evaluation process is performed at all possible stages of the series of decisions that lead to the building of a goal-directed action or to its suppression. This is because all animals have a limited amount of energy and resources; to survive and be able to reproduce they have to minimize the costs and maximize the outcomes of their actions. These computations are at the root of behavioral flexibility. Two executive functions play a major role in generating flexible behaviors: (i) the ability to predict future outcomes of goal-directed actions; and (ii) the ability to cancel them when they are unlikely to accomplish valuable results. These two processes operate continuously during the entire course of a movement: during its genesis, its planning and even its execution, so that the motor output can be modulated or suppressed at any time before its execution. In this review, functional interactions of the extended neural network subserving generation and inhibition of goal-directed movements will be outlined, leading to the intriguing hypothesis that the performance of actions and their suppression are not specified by independent sets of brain regions. Rather, it will be proposed that acting and stopping are functions emerging from specific interactions between largely overlapping brain regions, whose activity is intimately linked (directly or indirectly) to the evaluations of pros and cons of an action. Such mechanism would allow the brain to perform as a highly efficient and flexible system, as different functions could be computed exploiting the same components operating in different configurations.


Filter paper with selective absorption and separation of liquids that differ in surface tension.
Superhydrophobic and superoleophilic filter paper was successfully prepared by treating commercially available filter paper with a mixture of hydrophobic silica nanoparticles and polystyrene solution in toluene. Applications of the filter paper in separating liquids with low surface tensions such as oil and ethanol from water were investigated in detail. The oil uptake ability of the superhydrophobic filter paper was evaluated and the results show that the filter paper can selectively adsorb oil floating on a water surface or in aqueous emulsions. Furthermore, filtration of mixtures of oil and water through the paper can reduce the water content in the oil. Additionally, the filter paper can also extract ethanol from homogeneous aqueous solution.


Amiodarone-induced loculated pleural effusion without pulmonary parenchymal involvement: A case report and literature review.
Amiodarone is an extremely effective antiarrhythmic drug that is known to cause many adverse effects such as pulmonary, thyroid, and liver toxicities. Of these, pulmonary toxicity is most serious. Pulmonary toxicity can present as interstitial pneumonitis, organizing pneumonia, pulmonary nodules and masses, and very rarely pleural effusions. We present a case of a 73-year-old male who presented with progressive exertional dyspnea, nonproductive cough, generalized fatigue, and weakness. He was found to have multiorgan toxicity secondary to long-term treatment with high doses of amiodarone. This case illustrates that amiodarone may cause toxicity involving multiple organs simultaneously in patients receiving long-term therapy and represents the first reported case of amiodarone-induced loculated pleural effusion without associated lung parenchymal involvement.


Development of Monoclonal Antibodies and Characterization of an ELISA Platform Against Kallikrein-Related Peptidase 6 as a Tumor Biomarker.
Kallikrein-related peptidase 6 (KLK6) is a serine protease, and one of fifteen kallikrein members located on chromosome 19. KLK6 is associated with the regulation of axonal growth following spinal injury, tumor cell metastasis, and alpha synuclein aggregate pathologies like Parkinson's, making KLK6 a potentially important biomarker. We generated a KLK6 expression vector for large-scale expression in Escherichia coli. After affinity chromatography purification and SDS-PAGE confirmation, mice were immunized with the purified protein for development of monoclonal B cell populations. Our immunizations generated five hybridomas (1D8, 2E3, 3B7, 5G8, and 5H12) against KLK6. Isotyping analysis revealed that clone 2E3 was IgG2b, while the other four clones were IgG1. Further studies found that clone 5G8 could be used to visualize specific KLK6 bands by Western blot analysis from ovarian cancer patient serum and plasma, and also in mouse liver lysates. Finally, we established a sandwich ELISA pair and determined their sensitivity for KLK6 to be 10 ng/mL. These findings establish an essential tool for the detection and analysis of KLK6.


Molecular and genetic analyses of two patients with Pearson's marrow-pancreas syndrome.
Pearson's syndrome, a rare and fatal disorder characterized by refractory sideroblastic anemia and pancreatic insufficiency in infancy, is classified into mitochondrial cytopathies. To understand the molecular and genetic bases of this disorder, we have investigated the mitochondrial respiratory chain enzymes and the mitochondrial DNA (mtDNA) in two Japanese patients with Pearson's syndrome. Immunoblot analysis from various tissues showed the different grades of defects in the subunits of respiratory enzyme complexes. The analyses of mtDNA showed that the deletion in patient 1 spanned 4977 bp from the ATPase 8 gene to the NADH dehydrogenase 5 gene between 13-bp direct repeats, whereas the deletion in patient 2 spanned 3151 bp from the transfer RNA(His) gene to the cytochrome b gene unrelated to any repeated sequences. The deleted mtDNA was heteroplasmic in all the analyzed tissues, but the proportions of deleted mtDNA were quite different. We observed a tendency for the tissue with low percentages of normal-sized mtDNA to show low contents of complex I subunits. Analysis of the entire sequence of both patient's mtDNA showed several nucleotide substitutions including alteration of the initiation codon of the NADH dehydrogenase 5 gene. Some of these nucleotide substitutions might contribute to the phenotypic expression of Pearson's syndrome synergistically with the deletion.


Adding functional properties to beer with jasmine tea extract.
Hops provide the characteristic bitter taste and attractive aroma to beer; in this study, hops were replaced by jasmine tea extract (JTE) during late-hopping. The addition of JTE improved the beer foam stability 1.52-fold, and increased the polyphenol and organic acid contents. Linalool was the most important aroma compound in hopped (HOPB) and jasmine tea beer (JTB), but other flavor components were markedly different, including dimeric catechins, flavone/flavonol glycosides, and bitter acids and derivatives. Sensory evaluation indicated that addition of JTE increased the floral and fresh-scent aromas, reduced bitterness and improved the organoleptic quality of the beer. The antioxidant capacity of JTB was much higher than that of HOPB. The inhibition of amylase activity by JTB was 30.5% higher than that of HOPB. Functional properties to beer were added by substituting jasmine tea extract for hops during late hopping.


Cellular and genetic control of antibody responses. VIII. MHC restricted recognition of accessory cells, not B cells, by parent-specific subpopulations of normal F1 T helper cells.
Normal F1 helper T cell populations were analyzed under conditions in which the number of T cells was strictly limiting so that anti-hapten PFC responses to TNP-KLH increased linearly with increasing numbers of T cells. The slope of the response line is a measure of the helper activity of the added T cell population and reflects the number of helper T cells activated. In this way, the recognition and activation requirements of normal F1 helper T cell subpopulations were analyzed. It was determined that the F1 helper T cells specific for recognizing antigen in the context of the MHC determinants of only one parent specifically recognized those determinants expressed on accessory cells, but not on B cells. Indeed, each parent-specific F1 T cell subpopulation was only triggered by one parent's accessory cells; but once triggered, each parent-specific F1 T cell subpopulation was capable of activating either parent's B cells.


[Prognostic factors in adult patients hospitalized for pneumonia caused by Legionella pneumophila].
Legionellosis is a multisystem bacterial disease, which causes pneumonia with high mortality in patients with comorbidity and admitted in intensive care units (ICU). Determine predictors of mortality or ICU admission. Retrospective follow-up of patients diagnosed with Legionella pneumophila pneumonia in Complexo Hospitalario Universitario de A Coruña. Period 2000-2013 (n=240). Analysis of multivariate logistic regression was performed. Mean age was 57.2±15.4 years old, 88.3% were male. Average score of comorbidity (Charlson score) was 2.3±2.3. There was a clear seasonal variation. Predominant symptoms were fever (92.5%), dry cough (38.1%) and dyspnea (33.9%). Creatinine clearance was lower than 60 mL/min/1.73 m² in 29.7% and sodium<135 mEq/l in 58.3%. Admission to ICU rate was 16.3% and 10.8% needs mechanical ventilation. Inhospital mortality rate was 4.6%, rising to 23.1% in patients admitted to ICU. Variables associated to predict ICU admission were age (OR=0.96), liver disease (OR=7.13), dyspnea (OR=4.33), delirium (OR=5.86) and high levels of lactatedehydrogenase (OR=1.002). Variables associated with inhospital mortality were Charlson index (OR=1.70), mechanical ventilation (OR=31.44) and high levels of lactatedehydrogenase (OR=1.002). Younger patients with liver disease, dyspnea and confusion are more likely to be admitted to ICU. Comorbidity, mechanical ventilation and elevated LDH levels are associated with higher mortality rate.


The role of the sexual organs in the generation of postembryonic neurons in the leech Hirudo medicinalis.
In adult Hirudo medicinalis, the segmental ganglia (SG) of the fifth and sixth body segments contain a few hundred more cells than the other segmental ganglia of the body (Macagno, 1980). These ganglia innervate the sex organs and are known as the sex SG. As shown here, these cells are stained by neuron-specific antibodies. Cell counts at several developmental stages reveal that the extra cells are added exclusively to the sex SG, and that this addition occurs gradually and almost entirely postembryonically (embryogenesis ends at 30 days of development). Hence, we refer to them as PE cells. Until 16 days of development, deleting the male genitalia or disconnecting them from the sex ganglia results in a complete absence of the PE cells. From 16 days onward, the generation of the PE cells is independent of the male genitalia. No PE cells appear in non-sex SG that innervate male genitalia transplanted to ectopic locations at 10 days or later, indicating that as early as about 10 days of development sex SG are different from other SG in their ability to acquire PE cells. These data suggest that the PE cells are generated within the sex SG, in a process that is triggered by an interaction with the male genitalia and mediated through the innervation of the organs by these ganglia.


Robust Portfolio Optimization Using Pseudodistances.
The presence of outliers in financial asset returns is a frequently occurring phenomenon which may lead to unreliable mean-variance optimized portfolios. This fact is due to the unbounded influence that outliers can have on the mean returns and covariance estimators that are inputs in the optimization procedure. In this paper we present robust estimators of mean and covariance matrix obtained by minimizing an empirical version of a pseudodistance between the assumed model and the true model underlying the data. We prove and discuss theoretical properties of these estimators, such as affine equivariance, B-robustness, asymptotic normality and asymptotic relative efficiency. These estimators can be easily used in place of the classical estimators, thereby providing robust optimized portfolios. A Monte Carlo simulation study and applications to real data show the advantages of the proposed approach. We study both in-sample and out-of-sample performance of the proposed robust portfolios comparing them with some other portfolios known in literature.


Effect of disodium cromoglycate on exercise-induced asthma.
In eight patients with exercise-induced asthma, disodium cromoglycate was found to produce a definite inhibition of the post-exercise fall in forced expiratory volume in one second. This effect may be part of the cause for the subjective improvement experienced with this drug.


A proposed mechanism for the interaction between the Candida albicans Als3 adhesin and streptococcal cell wall proteins.
C. albicans binds various bacteria, including the oral commensal Streptococcus gordonii. Published reports documented the role of C. albicans Als3 and S. gordonii SspB in this interaction, and the importance of the Als N-terminal domain (NT-Als) in C. albicans adhesion. Here, we demonstrate that Als1 also binds S. gordonii. We also describe use of the NT-Als crystal structure to design mutations that precisely disrupt peptide-binding cavity (PBC) or amyloid-forming region (AFR) function in Als3. C. albicans displaying Als3 PBC mutant proteins showed significantly reduced binding to S. gordonii; mutation of the AFR did not affect the interaction. These observations present an enigma: the Als PBC binds free C termini of ligands, but the SspB C terminus is covalently linked to peptidoglycan and thus unavailable as a ligand. These observations and the predicted SspB elongated structure suggest that partial proteolysis of streptococcal cell wall proteins is necessary for recognition by Als adhesins.


Controllable Synthesis of Ultrathin NiCo2 O4 Nanosheets Incorporated onto Composite Nanotubes for Efficient Oxygen Reduction.
Exploring non-precious-metal-based oxygen reduction reaction (ORR) electrocatalysts featuring high efficiency, low cost, and environmental friendliness is of great importance for the broad applications of fuel cells and metal-air batteries. In this work, ultrathin NiCo2 O4 nanosheets deposited on 1D SnO2 nanotubes (SNT) were successfully fabricated through a productive electrospinning technique followed by a sintering and low-temperature coprecipitation strategy. This hierarchically engineered architecture has ultrathin NiCo2 O4 nanosheets uniformly and fully erected on both walls of tubular SNTs, which results in improved electrochemical activity as an ORR catalyst, in terms of positive onset potential and high current density, as well as superior tolerance to crossover effects and long-term durability with respect to the commercial Pt/C catalyst. The excellent performance of SNT@NiCo2 O4 composites may originate from their rationally designed hierarchical tubular nanostructure with completely exposed active sites and interconnected 1D networks for efficient electron and electrolyte transfer; this makes these composite nanotubes promising candidates to replace platinum-based catalysts for practical fuel cell and metal-air battery applications.


HYPERTENSIVE HEART DISEASE AND ENCEPHALOPATHY IN A CENTRAL BEARDED DRAGON (POGONA VITTICEPS) WITH SEVERE ATHEROSCLEROSIS AND FIRST-DEGREE ATRIOVENTRICULAR BLOCK.
A 0.5 kg, 5-yr-old male bearded dragon (Pogona vitticeps) presented with a 2-mo history of lethargy, anorexia, and impaired locomotion. Upon physical examination, bradyarrhythmia (heart rate: 20 beats/min) and balance disorders were noted. Electrocardiography revealed a first-degree atrioventricular block (P-R interval: 360 ms). On echocardiography, all cardiac chambers were slightly above normal ranges. Complete blood count, blood biochemistry, and T4 were unremarkable except for mildly elevated aspartate aminotransferase. Adenovirus testing was negative by polymerase chain reaction. Following euthanasia, necropsy revealed marked thickening of the arterial trunks and histopathology confirmed multifocal atherosclerosis of efferent heart vessels, arteriosclerosis of cerebral arterioles, and multifocal spongiosis of brain tissue, more pronounced in the optic chiasma. Owing to its severity, atherosclerosis may have contributed to chronic arterial hypertension with damages to the heart, brain vessels, and brain tissue-optic chiasma.


Effects of confinement duration and parity on stereotypic behavioral and physiological responses of pregnant sows.
The aim of this study was to evaluate the effects of space restriction stress on the stereotypic behavioral and physiological responses of different parity sows, and it is necessary to understand such effects due to space restriction to improve the welfare of the sows in confined conditions. We selected fifty pregnant sows (Large White) at primiparity and first to fifth parity in a confined farm with the same body condition and due date (3±1.5days). Behavioral observations and physiological analysis were carried out during spatial confinement throughout pregnancy. The results showed that there were no significant changes in vacuum-chewing, bar-biting, trough-biting and the concentrations of serum IL-6 in primiparous sows during the initial confinement (0-8days). With the increase of the confinement duration, the serum cortisol, IgA, IL-6 concentrations and the vacuum-chewing frequency of sows in all groups increased significantly, and the serum concentrations of C-reactive protein and Pig-MAP increased significantly except for the sows in the first and second parity groups. The serum cortisol, IgA, IL-6 concentrations and the vacuum-chewing frequency of older sows were significantly higher than those of the young sows throughout the entire restricted feeding period, but the serum C-reactive protein concentrations of primiparous gilts was significantly higher than those of the other groups. The serum cortisol, IgA, IL-6 concentrations and bar-biting and trough-biting frequencies of all parity sows decreased significantly after entering the delivery bed. In conclusion, long-lasting and recurrent environmental constraints can significantly increase the frequency of stereotypical behavior and serious psychological and physical stress, seriously damaging sow welfare.


Peak running velocity is highly related to distance running performance.
This study examined the relationship between the peak running velocity (PRV) obtained during a horizontal, incremental treadmill test and distance running performance in a group of highly-trained male (N = 14) and female (N = 9) distance runners. Performance (5 km run time) was assessed with a self-paced time trial under laboratory conditions in an attempt to minimize extraneous variables which could affect performance (i.e. environmental conditions, terrain, etc.); relationships with recent best 5 km race time were also determined. PRV was highly related to 5 km performance whether determined from the time trial (r2 = 0.94, p < 0.001) or recent race (r2 = 0.89, p < 0.001). A new finding was that PRV was similarly related to performance in both the male (r2 = 0.83, p < 0.001) and female (r2 = 0.80, p < 0.001) athletes. Peak running velocity is thus highly predictive of distance running performance in highly-trained endurance runners. This finding has important practical implications, as PRV can be measured without extensive metabolic equipment and/or invasive techniques.


The Year in Cardiology 2013: coronary intervention.
The year 2013 was rich of new developments in cardiology, and percutaneous coronary intervention (PCI) in particular. This overview article will focus on contributions in the following areas: training for PCI, appropriateness and indications; access site selection, risk scores, peri-procedural myocardial infarction; trial results and long-term follow-up; PCI for specific patient and lesion subsets, including acute coronary syndrome and ST-segment myocardial infarction; prevention of ischemic and reperfusion injury; stent thrombosis and new coronary stents and scaffolds.


Color Stability of New Esthetic Restorative Materials: A Spectrophotometric Analysis.
The aim of this in vitro study was to evaluate and compare the color stability of different esthetic restorative materials (one microfilled composite, one nanofilled composite, one nanoceramic composite, one microfilled hybrid composite, one microfilled hybrid composite, one nanohybrid Ormocer based composite and one supra-nano spherical hybrid composite) after exposure to different staining solutions (physiological saline, red wine, coffee). All materials were prepared and polymerized into silicon rings (2 mm × 6 mm × 8 mm) to obtain specimens identical in size. Thirty cylindrical specimens of each material were prepared. Specimens were immersed in staining solutions (physiological saline, coffee and red wine) over a 28-day test period. A colorimetric evaluation according to the CIE L*a*b* system was performed by a blind trained operator at 7, 14, 21, 28 days of the staining process. The Shapiro-Wilk test and ANOVA were applied to assess significant differences among restorative materials. A paired t-test was applied to test which CIE L*a*b* parameters significantly changed after immersion in staining solutions. All restorative materials showed significant color differences after immersion in coffee. Coffee caused a significant color change in all types of tested composite resins. Only Filtek Supreme XTE demonstrated a staining susceptibility to red wine; no other significant differences among the materials were demonstrated. Long-term exposure to some food dyes (coffee in particular) can significantly affect the color stability of modern esthetic restorative materials regardless of materials' different compositions.


[Development of tumor selection based on pathological stage in clinically localized prostate carcinoma].
Four hundred and eighty-eight radical retropubic prostatectomies (RRP) were performed on clinically localized prostate cancer at one institution within 5 years (1992-1996). These were then analyzed regarding the migration of pathological tumor stages towards more localized stages. Within the observation period, the annual rate of RRP increased by 81% from 69 to 125 cases. The authors noted a decline in the occurrence of advanced tumor stages (65.0% to 39.2%) and small cancers (< 0.5 cc: 7.2% to 1.6%) and an increase in pathological T2 tumors (30.4% to 55.2%). The rate of positive surgical margins declined from 34.7% to 12.8% (for all pathological stages). These data confirm trends which were observed in the USA with increasing detection and treatment of localized prostate cancer.


The science of consciousness must include its more advanced forms.
Morsella et al. argue that science should not focus on high forms of consciousness. We disagree. An understanding of high forms of consciousness is invaluable to the scientific study of consciousness. Moreover, it poses challenges to the passive frame theory. Specifically, it challenges the notions that conscious thoughts are not connected and that consciousness serves skeletomotor conflict only.


(E,E,E,E)-2,3,5,6-Tetra-kis{2-[4-(dimethyl-amino)-phen-yl]ethen-yl}pyrazine.
In the title compound, C(44)H(48)N(6), the essentially planar mol-ecule [maximum deviation from the mean plane of the π system of 0.271 (3) Å] is located on a crystallographic centre of inversion. The almost planar (angle sums at N atoms = 357.6 and 357.1°) dimethyl-amino groups and short C-N bonds of the aniline groups [both 1.379 (4) Å] indicate strong electronic coupling between these groups and the central pyrazine ring.


E-type prostanoid receptor 4 drives resolution of intestinal inflammation by blocking epithelial necroptosis.
Inflammatory bowel diseases present with elevated levels of intestinal epithelial cell (IEC) death, which compromises the gut barrier, activating immune cells and triggering more IEC death. The endogenous signals that prevent IEC death and break this vicious cycle, allowing resolution of intestinal inflammation, remain largely unknown. Here we show that prostaglandin E2 signalling via the E-type prostanoid receptor 4 (EP4) on IECs represses epithelial necroptosis and induces resolution of colitis. We found that EP4 expression correlates with an improved IBD outcome and that EP4 activation induces a transcriptional signature consistent with resolution of intestinal inflammation. We further show that dysregulated necroptosis prevents resolution, and EP4 agonism suppresses necroptosis in human and mouse IECs. Mechanistically, EP4 signalling on IECs converges on receptor-interacting protein kinase 1 to suppress tumour necrosis factor-induced activation and membrane translocation of the necroptosis effector mixed-lineage kinase domain-like pseudokinase. In summary, our study indicates that EP4 promotes the resolution of colitis by suppressing IEC necroptosis.


Mental stress grading based on fNIRS signals.
In this study, we propose functional near infrared spectroscopy (fNIRS) to objectively grade different levels of mental stress. The levels of stress were set based on the difficulty of arithmetic task, time pressure and negative feedback about peer performance. We examined the proposed approach on twelve human subjects using the Montreal Imaging Stress Task. The experiment results revealed a reduction in cortical activation at prefrontal cortex when stressed, and the differences in hemodynamic response between control condition and under stress were significant for arithmetic difficulty level one, two and three, respectively, (p = 0.0023, 0.0001 and 0.0004). The experiment results thus support the suggestion of fNIRS in grading mental stress.


Sustainable (food) packaging--an overview.
Packaging has an increasingly essential role to play in preserving the value invested in products by ensuring that they can deliver their designed service with minimum wastage. Food contact materials that deliver more units of service with increasingly fewer inputs of energy and materials, and increasingly fewer negative social, economic and environmental impacts, e.g., from emission of wastes, will be more sustainable both in the food processing machines of the industrial system and as packaging for food. Buzz words, whether bio-, nano-, degradable, or whatever comes next, must be critically examined per unit of service delivered to determine if, over the whole life cycle of the products to which they are applied, energy and resource use are minimised, pollution is reduced (not relocated), ecological benefits are created, and social and economic well-being are increased. Only when this caution is applied can a new solution be described as more sustainable.


Histone Deacetylases and Their Regulatory MicroRNAs in Hepatocarcinogenesis.
A growing body of evidence suggests that epigenetic modifications are promising potential mechanisms in cancer research. Among the molecules that mediate epigenetic mechanisms, histone deacetylases (HDACs) are critical regulators of gene expression that promote formation of heterochromatin by deacetylating histone and non-histone proteins. Aberrant regulation of HDACs contributes to malignant transformation and progression in a wide variety of human cancers, including hepatocellular carcinoma (HCC), gastric cancer, lung cancer, and other cancers. Thus, the roles of HDACs have been extensively studied because of their potential as therapeutic targets. However, the underlying mechanism leading to deregulation of individual HDACs remains largely unknown. Some reports have suggested that functional microRNAs (miRNAs) modulate epigenetic effector molecules including HDACs. Here, we describe the oncogenic or tumor suppressive functions of HDAC families and their regulatory miRNAs governing HDAC expression in hepatocarcinogenesis.


Transport of equine ovaries for assisted reproduction.
Use of assisted reproduction to obtain foals from valuable mares post-mortem typically necessitates holding of ovaries during shipment to a laboratory. The present study evaluated whether holding ovaries briefly at a warm ( approximately 30 degrees C) temperature improves meiotic and developmental competence of oocytes, as determined after maturation in vitro and intracytoplasmic sperm injection. Ovaries were packaged in pairs in insulated containers, and held either at 24 or 25-35 degrees C for 4h, followed by cooling. Ovaries in both treatments were held for either a short (mean, 7-7.4h) or long (mean, 20.6-20.7h) duration before oocyte recovery. Control ovaries were collected en masse at the abattoir. The ovary temperature in this treatment slowly decreased to approximately 27 degrees C; oocyte recovery was performed after 3.5-7h total holding. There was no effect of temperature on oocyte meiotic or developmental competence within either treatment time period. Oocytes in the short duration holding group had similar meiotic competence to controls, but had a significantly decreased rate (P<0.05) of blastocyst development. Oocytes in the long duration holding group had decreased (P<0.05) meiotic competence and blastocyst development compared to controls. These findings indicate that storage of equine ovaries for only 7h may decrease blastocyst development, and that longer storage reduces both rate of oocyte maturation and blastocyst development. Further work is needed to determine if there is a critical time before 7h post-mortem by which equine oocytes should be recovered to maximize developmental competence.


Associations between Absolute and Relative Lower Body Strength to Measures of Power and Change of Direction Speed in Division II Female Volleyball Players.
Volleyball is a sport comprised of multiple explosive efforts and multidirectional change of direction speed (CODS) actions. Since strength underpins both of these abilities, it is important to explore the relationship between these variables in order to develop strength and conditioning programs to optimize performance. The purpose of this study is to determine if a relationship exists between absolute and relative strength and measures of power and CODS in collegiate volleyball players. Archived testing data from ten (n = 10, age: 19.1 ± 1.2 yrs, Ht: 173.1 ± 6.64 cm, Wt: 67 ± 7.04 kg) female DII collegiate volleyball players were analyzed. These data included: block vertical jump (Block VJ), approach vertical jump (Approach VJ), a repeat jump test (i.e., four consecutive VJs), modified T-test, 5-0-5 agility test, a single leg triple hop test, and a 1-3RM deadlift. Significant large correlations were observed between relative strength and the repeat jump test, modified T-test, and 5-0-5 agility test. Significant correlations were also observed between absolute strength and the modified T-test. These results indicate that strength and conditioning professionals should emphasize the development of both absolute and relative lower-body strength to improve measures of power and agility in collegiate volleyball players.


Tenomyoplastic procedures to improve shoulder function in the treatment of perinatal brachial plexus palsy.
A contracture of the shoulder joint in the course of perinatal brachial plexus palsy significantly affects the function of the upper limb as a whole. The aim of this paper is to present the authors' experience in surgical procedures carried out to improve shoulder joint function impaired as a result of perinatal brachial plexus palsy and evaluate the treatment outcomes. The study involved 36 patients who underwent 37 tenomyoplastic procedures (subscapular release, teres major transfer, transfer of a portion of the trapezius). Pre- and postoperative shoulder joint function was assessed with the Gilbert scale. Surgical release of the subscapular muscle improved shoulder function in all patients, usually by 1 degree in the Gilbert scale. Teres major transfer improved shoulder function in all 4 patients (grade IV - 3 children, grade V - 1 child). One patient benefited from tenomyoplasty involving the trapezius. 1. Indications for tenomyoplasty procedures in the region of the shoulder joint may be present both in children who had previously undergone microsurgery and in those in whom rehabilitation had led to a good outcome of perinatal brachial plexus palsy. 2. The fact that most patients improved following tenomyoplastic procedures justifies their advisability. A visible functional improvement of the upper limb can be achieved with a relatively low risk of complications.


Isolation and characterization of rufoxin, a novel protein exhibiting neurotoxicity from venom of the psammophiine, Rhamphiophis oxyrhynchus (Rufous beaked snake).
Colubrid snake venoms potentially represent a vast source of novel biological actives and structural motifs owing to their diverse phylogeny. The present study describes the identification of rufoxin, a neurotoxin from the venom of Rhamphiophis oxyrhynchus (Rufous beaked snake) which is a member of the African colubrid lineage, the psammophiines. Rufoxin (1 microM) displayed reversible post-synaptic neurotoxic activity as evidenced by significant inhibition of indirect twitches and responses to exogenous nicotinic agonists in the chick biventer cervicis nerve-muscle preparation. Rufoxin (0.1-1.0 microM) also caused a rightward parallel shift of cumulative concentration-response curves to carbachol (CCh; 0.6-80 microM) without a significant depression of the maximum response, suggestive of classical competitive antagonism at the skeletal muscle nicotinic receptor. Rufoxin lacks NH(2)-terminal sequence homology to previously identified snake venom toxins. This work indicates a wider distribution of neurotoxins across the advanced snake superfamily than previously described.


Intensive care photoplethysmogram datasets and machine-learning for blood pressure estimation: Generalization not guarantied.
The large MIMIC waveform dataset, sourced from intensive care units, has been used extensively for the development of Photoplethysmography (PPG) based blood pressure (BP) estimation algorithms. Yet, because the data comes from patients in severe conditions-often under the effect of drugs-it is regularly noted that the relationship between BP and PPG signal characteristics may be anomalous, a claim that we investigate here. A sample of 12,000 records from the MIMIC waveform dataset was stacked up against the 219 records of the PPG-BP dataset, an alternative public dataset obtained under controlled experimental conditions. The distribution of systolic and diastolic BP data and 31 PPG pulse morphological features was first compared between datasets. Then, the correlation between features and BP, as well as between the features themselves, was analysed. Finally, regression models were trained for each dataset and validated against the other. Statistical analysis showed significant p < 0.001 differences between the datasets in diastolic BP and in 20 out of 31 features when adjusting for heart rate differences. The eight features showing the highest rank correlation ρ > 0.40 to systolic BP in PPG-BP all displayed muted correlation levels ρ < 0.10 in MIMIC. Regression tests showed twice higher baseline predictive power with PPG-BP than with MIMIC. Cross-dataset regression displayed a practically complete loss of predictive power for all models. The differences between the MIMIC and PPG-BP dataset exposed in this study suggest that BP estimation models based on the MIMIC dataset have reduced predictive power on the general population.


Phosphorylation and flexibility of cyclic-AMP-dependent protein kinase (PKA) using (31)P NMR spectroscopy.
Cell signaling pathways rely on phosphotransfer reactions that are catalyzed by protein kinases. The protein kinases themselves are typically regulated by phosphorylation and concurrent structural rearrangements, both near the catalytic site and elsewhere. Thus, physiological function requires posttranslational modification and deformable structures. A prototypical example is provided by cyclic AMP-dependent protein kinase (PKA). It is activated by phosphorylation, is inhomogeneously phosphorylated when expressed in bacteria, and exhibits a wide range of dynamic properties. Here we use (31)P nuclear magnetic resonance (NMR) spectroscopy to characterize the phosphorylation states and to estimate the flexibility of the phosphorylation sites of 2-, 3-, and 4-fold phosphorylated PKA. The phosphorylation sites Ser10, Ser139, Thr197, and Ser338 are assigned to individual NMR resonances, assisted by complexation with AMP-PNP and dephosphorylation with alkaline phosphatase. Rotational diffusion correlation times estimated from resonance line widths show progressively increasing flexibilities for phosphothreonine 197, phosphoserines 139 and 338, and disorder at phosphoserine 10, consistent with crystal structures of PKA. However, because the apparent rotational diffusion correlation time fitted for phosphothreonine 197 of the activation loop is longer than the overall PKA rotational diffusion time, microsecond to millisecond time scale conformational exchange effects involving motions of phosphothreonine 197 are probable. These may represent "open"-"closed" transitions of the uncomplexed protein in solution. These data represent direct measurements of flexibilities also associated with functional properties, such as ATP binding and membrane association, and illustrate the applicability of (31)P NMR for functional and dynamic characterization of protein kinase phosphorylation sites.


Generalized statistical mechanics for superstatistical systems.
Mesoscopic systems in a slowly fluctuating environment are often well described by superstatistical models. We develop a generalized statistical mechanics formalism for superstatistical systems, by mapping the superstatistical complex system onto a system of ordinary statistical mechanics with modified energy levels. We also briefly review recent examples of applications of the superstatistics concept for three very different subject areas, namely train delay statistics, turbulent tracer dynamics and cancer survival statistics.


The power struggle: definition and evaluation of power of muscular performance.
The authors define five different measurements of power of muscular performance. Using an isokinetic dynamometer, the velocity of motion is constant and thus can be controlled. Power, therefore, can be readily assessed. The speed of muscular contraction is of physiological and functional interest. The time it takes for muscles to develop force, the rate at which muscles can contract and sustain a force throughout the range of motion, and the relationship of speed to force are all facets of power. At least five terms which connote power of muscular performances are used today. These terms are power, peak power, average power, instantaneous power, and contractile power. The current misunderstanding of the terms and their misuses are discussed. Suggestions are offered for circumventing confusion in using power to describe motor performance.


MicroRNA-92a promotes epithelial-mesenchymal transition through activation of PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer metastasis.
MicroRNAs (miRNAs) have important roles in various cancers, including non-small cell lung cancer (NSCLC). Although several miRNAs have reported to be involved in the development of NSCLC, understanding the regulatory roles of other miRNAs in NSCLC is essential. Therefore, the aim of the current study was to explore the roles and mechanisms of screened miRNAs in NSCLC. First, the differentially expressed miRNAs that were screened based on GSE29248 microarray data retrieved from Gene Expression Omnibus (GEO). The expression of miR-92a, acted as an oncogene in many cancers, was validated using quantitative real-time PCR (qRT-PCR), and then its association with overall survival was analyzed. The efficacy of miR-92a to promote cell proliferation, invasion and metastasis was evaluated in vitro, and in vivo. Then, the role of miR-92a in epithelial-mesenchymal transition (EMT), a key step of the progression of tumor cell metastasis, was investigated in NSCLC cells. The association of miR-92a and its downstream target was investigated in both cell line and clinical specimens. Furthermore, gain- and loss-of-function studies of the phosphatase and tensin homolog (PTEN) were performed to assess whether the effect of miR-92a promoted growth and metastasis of NSCLC cells were via targeting PTEN. Our results showed that miR-92a was significantly upregulated in NSCLC tissues and NSCLC cell lines, and was positively associated with poor prognosis of NSCLC patients. The overexpression of miR-92a enhanced EMT-relatived protein levels, promoted NSCLC cell migration and invasion in vitro, and increased tumor growth in vivo. Bioinformatic prediction and function assay suggested that PTEN, a negative regulator of PI3K/AKT pathway, was a direct target of miR-92a. It was found that PTEN expression was inversely correlated with miR-92a in NSCLC tissues. In addition, miR-92a could activate the PI3K/AKT pathway by inhibiting PTEN expression. Notably, Transwell and wound healing assays demonstrated that altering PTEN expression abrogated the promotive effects of miR-92a on NSCLC cell migration and invasion. Taken together, these results demonstrated that miR-92a induced EMT and regulated cell migration and invasion in the NSCLC cells through regulating PI3K/AKT signaling pathway by targeting PTEN, indicating that miR-92a may be an attractive target and prognostic marker for NSCLC.


Hydrophobic mismatch in gramicidin A'/lecithin systems.
Gramicidin A' (GA') has been added to three lipid systems of varying hydrophobic thicknesses: dimyristoyllecithin (DML), dipalmitoyllecithin (DPL), and distearoyllecithin (DSL). The similarity in length between the hydrophobic portion of GA' and the hydrocarbon chains of the lipid bilayers has been studied by using 31P and 2H NMR. Hydrophobic mismatch has been found to be most severe in the DML bilayer system and minimal in the case of DSL. In addition, the effects of hydrophobic mismatch on the cooperative properties of the bilayer have been obtained from 2H NMR relaxation measurements. The results indicate that incorporation of the peptide into the bilayer disrupts the cooperative director fluctuations characteristic of pure multilamellar lipid dispersions. Finally, the GA'/lecithin ratio at which the well-known transformation from bilayer to reverse hexagonal (HII) phase occurs (Van Echteld et al., 1982; Chupin et al., 1987) is shown to depend on the acyl chain length of the phospholipid. A rationale is proposed for this chain length dependence.


Social role conflict predicts stimulated cytokine production among men, not women.
To assess whether perceived role conflict is associated with stimulated pro-inflammatory cytokine production and glucocorticoid sensitivity, and whether these associations are moderated by sex. 153 healthy adults (aged 45.8±5.5years, 78% female) listed their 3 main social roles and indicated the amount of role conflict they perceived between each pair of social roles. Subsequently, participants underwent blood draws and leukocyte response to microbial challenge and glucocorticoid sensitivity were assessed by incubating whole blood with lipopolysaccharide (LPS) in the presence or absence of hydrocortisone. Stimulated levels of Interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNFα) were measured. Multiple regression analyses controlling for sociodemographics revealed significant sex×role conflict interactions for LPS-stimulated production of IL-1β, IL-6, and TNFα (all interaction ps<0.05), and a marginal interaction on LPS-stimulated IL-8 production (interaction p<0.10). Greater perceived role conflict was associated with greater pro-inflammatory cytokine production in response to microbial stimulation only among men, not women. There also were significant sex×role conflict interactions with respect to glucocorticoid sensitivity for IL-1β, IL-6, and TNFα production (all interaction ps<0.05) and a marginal interaction for IL-8 (interaction p<0.10). Greater perceived role conflict was unrelated to glucocorticoid sensitivity among women, but associated with less sensitivity to glucocorticoid signaling among men. Perceived social role conflict, indicating greater perceived demand across multiple social roles, may take a greater toll on the regulation of inflammatory processes among men compared to women.


The course of apparent diffusion coefficient values following perinatal arterial ischemic stroke.
Diffusion weighted MR imaging (DWI) plays an important role in the diagnosis of perinatal arterial ischemic stroke (PAIS) during the acute phase. Its derived apparent diffusion coefficient (ADC) can be used to quantify the diffusion restriction. Aim of the current study was to identify the changes in ADC values in the acute phase following PAIS. A cohort of 36 infants with a confirmed PAIS who were examined once during the first ten days of life was studied. ADC values in the core of the ischemic tissue (iADC) were determined and correlated with postnatal age. ADC ratios (rADC) were calculated by dividing the iADC value by the ADC value of the corresponding area in the contralateral 'healthy' hemisphere. Infants were scanned between days two and ten. A non-linear increase in iADC and rADC values was observed over time and large middle cerebral artery strokes resulted in lower iADC and rADC values. Normalisation of rADC values was observed after day seven. rADC values were lower when compared to previously published rADC values of infants with hypoxic ischemic encephalopathy, suggesting more severe injury. Following PAIS, DWI showed decreased ADC values with a non-linear increase during the first week, and pseudonormalization after day 7, which limits the use of DWI to assess PAIS to the first week. Compared to previous studies, ADC values were lower when compared to infants with hypoxic ischemic encephalopathy, most likely due to more severe injury.


Postischemic hypervascularity of infancy: a stage in the evolution of ischemic brain damage with characteristic CT scan.
One to 2 weeks after severe brain ischemia, four infants developed an unusual vascular lesion with a characteristic appearance on computed tomography that has not been reported previously. Restricted areas (most frequently the basal ganglia and thalamus) displayed increased attenuation, which enhanced further upon infusion of contrast medium. Autopsy of one infant revealed that the CT abnormality corresponded to an extremely dense neovascular network which had almost completely replaced the parenchyma in that region. We postulate that this pathological change is a stage in the organization of ischemic brain damage reflecting the infant's vascular plasticity. Thus, hypoxia induces marked capillary proliferation in regions of normally high metabolism and capillary density. The CT pattern may prove useful in predicting the location and extent of sequelae to perinatal asphyxia.


Intensive Care Unit Educators: A Multicenter Evaluation of Behaviors Residents Value in Attending Physicians.
It is important for attending physicians to know which behaviors influence learner perceptions. To date, two studies focusing on general medicine attending physicians have been published addressing internal medicine residents' perceptions of attending physicians; there are no data on intensive care unit (ICU) attending physicians. We sought to expand the evidence regarding this topic through a multicenter study at four geographically diverse academic medical centers. Our study focused on identifying the teaching behaviors of ICU physicians that learners observe in attending physicians who they value as effective educators. The study was conducted at Indiana University (Indianapolis, IN), Johns Hopkins University (Baltimore, MD), University of California-San Francisco (San Francisco, CA), and University of Washington (Seattle, WA). Internal medicine residents completed an anonymous online survey rating the importance of behaviors of ICU attending physician role models. We created a 37-item questionnaire derived from prior studies and from the Clinician Teaching Program from the Stanford Faculty Development Center for Medical Teachers. This questionnaire included behaviors, current and past, that residents observed in their ICU attending physicians. A total of 260 of 605 residents responded to the survey (overall response rate of 43%). The five behaviors of attending physicians most commonly rated as "very important" to residents were: (1) enjoyment of teaching; (2) demonstrating empathy and compassion to patients and families; (3) ability to explain clinical reasoning and differential diagnoses; (4) treating nonphysician staff members respectfully; and (5) enthusiasm on rounds. Behaviors that trainees rated as less important were having numerous research publications, having served as chief resident, sharing personal life with residents, and organizing end-of-rotation social events. Our study provides new information to attending physicians striving to influence resident education. Although prior data demonstrated that learners valued attending physicians having served as chief resident and sharing personal information with learners, our study did not replicate this. We confirmed that learners appreciated teachers who are perceived to enjoy teaching. We discovered that behaviors, such as expression of empathy, explanation of clinical reasoning, and qualities of professionalism, were commonly seen in esteemed teaching attending physicians. Our study was limited by lack of correlation to objective performance metrics and a low response rate. Future work may include assessing the impact of faculty development on identified behaviors.


The influence of censorship laws on Viennese anatomy textbooks from the outgoing 18th century until after the student revolution of 1848 in Austrian absolutism.
Anatomy textbooks´ connection to the rigid censoring laws enacted by Habsburg rulers, was never sufficiently investigated. Using anatomy textbooks written at the University of Vienna, our article aims at investigating the influence of censorship laws on the anatomy textbooks in Vienna between 1786 and 1865. In our case study we compared legal text and archival sources (source material A) with seven prefaces of textbooks written by Viennese anatomists (source material B). The prefaces were comparatively investigated by applying the following questions based on source material A: (1) What motives for writing the textbooks were indicated by the anatomists in the prefaces? (2) What legal or other influences were mentioned as motives that point to a connection to the censorship regulations installed? (3) Referring to changing censorship guidelines is there a change in the mentioned audience? Our results are that we found evidence for censorship regulations (source material A) in the prefaces (source material B). Also, the motives for writing those textbooks changed over time because of changing censorship regulations. Our findings show that Viennese anatomy textbooks were part of the Austrian censorship laws in the investigated period with a timely correlation between the appointment as professor and the publication of the textbooks and prefaces (indirectly) referring to censorship laws. The academic tradition of writing textbooks arose from this system, when freedom of speech stood in opposition to the absolute Habsburg reign. Thus, when working with historical anatomy textbooks it is important to reflect on their censorship heritage.


Predictions of protein secondary structures using factor analysis on Fourier transform infrared spectra: effect of Fourier self-deconvolution of the amide I and amide II bands.
Fourier self-deconvolution (FSD) was performed on protein amide I and II Fourier transform infrared (FTIR) spectra to test if the resultant increased band shape variation would lead to improvements in protein secondary structure prediction with our factor analysis based restricted multiple regression (RMR) methods. FTIR spectra of 23 proteins dissolved in H2O were measured and normalized to a constant amide I peak absorbance. The deconvolved spectra were renormalized by area so that the deconvolved spectra sets had the same area as before. Principal component analysis of the deconvolved spectra sets was carried out, which was followed by a selective multiple linear regression (RMR) analysis of the principal component loadings with regard to the fractional components (FC) of secondary structure. As compared to analyses based on the original spectra set, helix and sheet predictions were not noticeably improved by FSD; but, if a very large number of component spectra (16) were retained in the pool to select which loadings to be used in the RMR optimization, better predictions of turn and "other" resulted. The prediction quality varied depending on the deconvolution parameters used.


Recurrent hepatocellular carcinoma and non-classic adreno-genital syndrome.
Hepatocellular carcinoma (HCC) is one of the most common fatal cancer in the world and androgens are among the possible etiological factors. Congenital adrenal hyperplasia (CAH) is a group of inherited diseases caused by enzyme failure in the steroid biosynthesis of the adrenal cortex, resulting in an augmented 17-hydroxyprogesterone, androstenedione and testosterone production. While the occurrence of testicular adrenal rest tumors and adrenocortical tumors in congenital adrenal hyperplasia is well described in the literature, no data on HCC occurrence are available. A 35-years-old Italian man of Caucasian origin, affected by non-classic CAH due to partial 21-hydroxylase deficiency came to observation for revaluation of his adrenal picture. Besides common hormonal and biochemical analysis, an abdomen Magnetic Resonance Imaging was performed, resulting in an 18 mm large nodular lesion between liver segments VII and VIII. Radiological reports matched with an increased serum α-fetoprotein level. A surgical removal of the lesion was performed. After that, several recurrences of the lesion, which was consequently treated by radiofrequency ablation, occurred. Every recurrence was accompanied by an increase in testosterone and steroid hormone binding globulin serum levels. Our report suggests the need for screening of liver lesions in males affected by this syndrome.


Designing high-performance electrochemical energy-storage nanoarchitectures to balance rate and capacity.
The impressive specific capacitance and high-rate performance reported for many nanometric charge-storing films on planar substrates cannot impact a technology space beyond microdevices unless such performance translates into a macroscale form factor. In this report, we explore how the nanoscale-to-macroscale properties of the electrode architecture (pore size/distribution, void volume, thickness) define energy and power performance when scaled to technologically relevant dimensions. Our test bed is a device-ready electrode architecture in which scalable, manufacturable carbon nanofoam papers with tunable pore sizes (5-200 nm) and thickness (100-300 μm) are painted with ~10 nm coatings of manganese oxide (MnOx). The quantity of capacitance and the rate at which it is delivered for four different MnOx-C variants was assessed by fabricating symmetric electrochemical capacitors using a concentrated aqueous electrolyte. Carbon nanofoam papers containing primarily 10-20 nm mesopores support high MnOx loadings (60 wt%) and device-level capacitance (30 F g(-1)), but the small mesoporous network hinders electrolyte transport and the low void volume restricts the quantity of charge-compensating ions within the electrode, making the full capacitance only accessible at slow rates (5 mV s(-1)). Carbon nanofoam papers with macropores (100-200 nm) facilitate high rate operation (50 mV s(-1)), but deliver significantly lower device capacitance (13 F g(-1)) as a result of lower MnOx loadings (41 wt%). Devices comprising MnOx-carbon nanofoams with interconnecting networks of meso- and macropores balance capacitance and rate performance, delivering 33 F g(-1) at 5 mV s(-1) and 23 F g(-1) at 50 mV s(-1). The use of carbon nanofoam papers with size-tunable pore structures and thickness provides the opportunity to engineer the electrode architecture to deliver scalable quantities of capacitance (F cm(-2)) in tens of seconds with a single device.


Comprehensive Analysis of GDF10 Methylation Site-Associated Genes as Prognostic Markers for Endometrial Cancer.
Growth differentiation factor-10 (GDF10) with its methylation trait has recently been found to play a crucial regulatory and communication role in cancers. This investigation aims to identify GDF10 methylation site-associated genes that are closely associated with endometrial cancer (EC) patients' survival based on normal and UCEC samples from the UCSC Xena database. Our study revealed for the first time that EC exhibited significantly higher levels of GDF10 promoter methylation in comparison with normal tissues. Multiple differentiated methylation sites, which have prognostic value due to their apparent survival differences, were found in the GDF10 promoter region. We performed weighted gene coexpression network analysis (WGCNA) on EC tissues and paraneoplastic tissues while using these differentially methylated sites as phenotypes for selecting the most correlated key modules and their internal genes. To obtain a gene set, the key module genes and differentially expressed genes (DEGs) of EC were intersected. The least absolute shrinkage and selection operator (LASSO) regression along with multivariate Cox regression were performed from the gene set and we screened out the key genes B4GALNT3, DNAJC22, and GREB1. Finally, a prognostic model was validated for effectiveness based on these genes. Additionally, Kaplan-Meier analysis and time-dependent receiver operating characteristics (ROC) were applied to assess and verify the model, and they showed good prognosis prediction. Moreover, the differences in risk scores were statistically significant with age, tumor stage, and grade. They may be related to the immune infiltration of tumors as well. In conclusion, based on the methylation-related genes associated with GDF10, we developed a prognosis model for EC patients. It might provide a fresh view for further research and treatment of EC.


Quality of Life Assessment in Retinoblastoma: A Cross-Sectional Study of 122 Survivors from India.
With current modalities, cure rates of retinoblastoma are high and hence the number of survivors is increasing. However, data on quality of life (QOL) are minimal. We analyzed QOL in 122 retinoblastoma survivors using the PedsQL(TM) 4.0 generic core scale. The self-reported questionnaire was filled by children of more than 5 years of age who had completed treatment for more than 12 months. The questionnaire consists of 23 questions on physical, social, emotional, and school domains on a scale from 0 to 4. This was converted to a scale from 0 to 100, where higher values represented better QOL. The QOL was compared with 50 siblings. Factors predicting the QOL were assessed. The median age of retinoblastoma survivors was 98 months (range 60-247) and 68% were males. Overall QOL was significantly poorer in retinoblastoma survivors as compared with the controls. The emotional health domain of QOL was significantly affected. Difficulties in maintaining friendships and competing were reported in the social health domain. The school health domain showed significantly higher absenteeism. However, the physical health domain, including household work, exercise, and self-care, was similar in both the groups. Lower age at diagnosis (≤ 18 months) predicted better QOL (P = 0.05), whereas age at assessment, sex, IRSS stage, and previous surgery and radiotherapy were not predictive of poor QOL. We found a significantly poorer QOL in retinoblastoma survivors with the psychosocial health domain being more affected than the physical domain. Age less than 18 months at diagnosis predicted better QOL.


Serpin conformational change in ovalbumin. Enhanced reactive center loop insertion through hinge region mutations.
Ovalbumin is a noninhibitory member of the serpin superfamily that does not spontaneously undergo the loop-to-sheet conformational change upon cleavage of its reactive center that is characteristic of inhibitory serpins. We tested the hypothesis that ovalbumin could be turned into a proteinase inhibitor by increasing the rate of loop insertion through hinge region mutations alone. We found that none of the three variants examined showed any detectable proteinase inhibitory properties. However, replacement of the P14 arginine residue of ovalbumin by serine, either alone or in combination with changes of P12-P10 to alanine, resulted in a large increase in the rate of loop insertion into beta-sheet A following cleavage at the P1-P1' bond by porcine pancreatic elastase (PPE), as shown by the spontaneous formation of a loop-inserted form upon cleavage that has increased the thermal stability. From the magnitude of the increase in stability of the cleaved, loop-inserted forms of the P14 ovalbumin variants, as well as the accessibility of the P1-P1'-cleaved reactive center loop to further proteolysis at P8-P7, we concluded that the reactive center loop can only partially insert into beta-sheet A and therefore that ovalbumin is also defective in the ability of beta-sheet A to expand to fully accommodate the whole of the reactive center loop. This defect, through its effect on the extent and/or rate of loop insertion, is likely to be a principal reason for ovalbumin not being a proteinase inhibitor.


Estimation of Profunda Artery Perforator Flap Weight Using Preoperative Computed Tomography Angiography.
Given the relatively small size of thigh-based flaps and the possible necessity for a multiflap reconstruction, it is imperative to arrive at an accurate estimation of flap weight during preoperative planning. It was our objective to develop a novel technique for the preoperative estimation of profunda artery perforator (PAP) flap weight. All patients that underwent transverse PAP flap breast reconstruction at two institutions were retrospectively reviewed. Subcutaneous tissue thicknesses were measured on axial computed tomography angiography scans at several predetermined points. The distance from the inferior gluteal crease to the PAP was also recorded. Linear regression was used to estimate flap weight. A total of 18 patients (32 flaps) were analyzed. The median intraoperative flap weight was 299 g (interquartile range [IQR]: 235-408). The parsimonious model (R 2 = 0.80) estimated flap weight using the Eq. 77.9x + 33.8y + 43.4z - 254.3, where x is subcutaneous tissue thickness (cm) at the lateral border of long head of the biceps femoris at a level 4.5 cm caudal to the inferior gluteal fold, y is distance (cm) from the inferior gluteal fold to the dominant PAP, and z has a value of 1 if the patient was scanned in the supine position or 0 if prone. The aforementioned formula yielded a median estimated flap weight of 305 g (IQR: 234-402) and a median percent error of 10.5% (IQR: 6.1-16.2). The authors demonstrate a simple and accurate formula for the preoperative estimation of transverse PAP flap weight for breast reconstruction.


The impact of TACI mutations: from hypogammaglobulinemia in infancy to autoimmunity in adulthood.
Common variable immunodeficiency (CVID) is considered the most common symptomatic antibody deficiency and, although mainly reported in adults, it may present from childhood. Few data on the impact of TACI defects on the clinical and immunological status of children are available. We screened 42 hypogammaglobulinemic children to investigate the frequency and mutational features of TACI defects. The genetic, clinical and immunological characterization was extended to 31 relatives of 11 children with TACI mutations. Of interest, our analysis showed a considerably higher mutation frequency in hypogammaglobulinemic children (13/42; 31%) than in other cohorts of adult patients. In seven out of nine families with the C104R variant, the prevalence of autoimmunity was significantly higher in C104R heterozygous relatives (8/15; 53%) than in those with no C104R mutation (1/11; 9%). Our data suggest a different impact of TACI mutations, from hypogammaglobulinemia in children to autoimmune disease in adulthood.


A prospective study of the factors influencing entry to alcohol and drug treatment.
Much is known about factors related to entering alcohol and drug treatment, but most research comprises cross-sectional "snapshots" in time. It is not known whether the reasons for entering treatment endure when problem drinkers are studied over time. This study contracts characteristics predicting treatment entry in a cross-sectional analysis at baseline with a longitudinal perspective at 1- and 3-year follow-up interviews. Sociodemographic characteristics were less important in the longitudinal analysis. In contrast to the social consequences important at the baseline interview, physiologic symptoms of alcohol dependence and interventions by medical professionals were prominent at later interview points. The findings have implications for interventions by health professionals, both for the development of early interventions targeting individuals to treatment and for a continuing care service model.


Infectious clones of Chikungunya virus (La Réunion isolate) for vector competence studies.
The recent outbreak of Chikungunya virus (CHIKV) on several islands in the Indian Ocean and in India has focused attention on this reemerging virus and highlighted the need for development of new tools to study vector-virus-host interactions. We have constructed and characterized, in cell culture, Aedes aegypti and Ae. albopictus mosquitoes, infectious cDNA clones of CHIKV using a recent isolate from La Réunion Island. Comparison of the growth kinetics and infection rates of the viral isolate CHIKV strain LR2006 OPY1 (CHIKV-LR) and a full-length infectious clone (CHIKV-LR ic) indicate that the infectious clone has retained the viral phenotypes of the original isolate. Infectious clones that express green fluorescent protein (GFP) were also produced and characterized in cell culture and in Aedes mosquitoes. The CHIKV-LR 5'GFP infected Ae. aegypti and Ae. albopictus mosquitoes at a similar rate to the original virus and to the full length infectious clone. The CHIKV-LR 3'GFP only infected Ae. albopictus mosquitoes at similar rates. The development of these authentic infectious clones will enable targeted studies of the molecular determinants of infection, pathogenesis and transmission competence by Ae. aegypti and Ae. albopictus mosquitoes.


Sympathoadrenal activity facilitates beta-endorphin and alpha-MSH secretion but does not potentiate ACTH secretion during immobilization stress.
The potential involvement of the sympathoadrenal system in stress-induced secretion of peptides from the intermediate lobe of the pituitary gland and the activation of the pituitary-adrenal axis was studied. Male Wistar rats were subjected to control procedures, to sympathectomy by chronic administration (8 weeks) of guanethidine and/or to medullectomy by adrenal enucleation 9 weeks prior to exposure to forced immobilization stress for various periods of time. In intact or sham-operated rats, immobilization caused a prompt increase of circulating norepinephrine, epinephrine (EPI), corticosterone and of immunoreactive adrenocorticotropic hormone (ACTHi), alpha-melanocyte-stimulating hormone (alpha-MSHi) and beta-endorphin (beta-ENDi). Peak levels of pituitary hormones were found after 10 min of stress exposure, but fell to less than 30% of these levels after 2.5 h of immobilization. Adrenal medullectomy, which abolished the stress-induced release of EPI, reduced the acute increase of plasma alpha-MSHi and beta-ENDi, but did not influence the acute increase of plasma ACTHi during immobilization stress. Also in medullectomized plus sympathectomized rats, the initial stress response of circulating ACTHi was not different from that of controls. Adrenal medullectomy with or without additional sympathectomy caused a marked increase in plasma ACTHi concentrations after prolonged stress exposure. We conclude that: catecholamines originating from the adrenalmedulla facilitate the stress-induced secretion of intermediate lobe peptides (alpha-MSHi, beta-ENDi); catecholamines from the sympathoadrenomedullary system do not contribute to the acute release of ACTH during immobilization stress; the sympathoadrenomedullary system is involved in the secondary reduction of circulating ACTHi levels seen during prolonged stress.


A computer-assisted instruction course to teach visual-field interpretation.
A computer-assisted instruction course for visual-field interpretation is described. A multiple-choice, question-and-answer drill was constructed using the VAX/VMS minicomputer and commercially available educational software. Medical and paramedical personnel can use this course to further their knowledge of visual-field description, the location of lesions which lead to visual-field defects, and the underlying processes that cause some of these defects. The advantages of using a particular computer terminal because of its graphic capabilities and screen layout are described. Other uses of computer-assisted instruction in ophthalmology are discussed and encouraged.


The ability of anterior thalamic signals to predict seizures in temporal lobe epilepsy in kainate-treated rats.
To analyze the local field potential (LFP) of the anterior nucleus of the thalamus (ANT) of epileptic rats using the Generic Osorio-Frei algorithm (GOFA), and to determine the ability of the ANT LFP to predict clinical seizures in temporal lobe epilepsy. GOFA is an advanced real-time technique used to detect and predict seizures. In this article, GOFA was utilized to process the electrical signals of ANT and the motor cortex recorded in 12 rat models of temporal lobe epilepsy (TLE) induced via the injection of kainic acid into the unilateral hippocampus. The electroencephalography (EEG) data included (1) 161 clinical seizures (each contained a 10-min segment) involving the ANT and cortical regions and (2) one hundred three 10-min segments of randomly selected interictal (no seizure) data. Minimal false-positives (0.51 ± 0.36/h) and no false-negatives were detected based on the ANT LFP data processed using GOFA. In ANT LFP, the delay from electrographic onset (EO) to automated onset (AO) was 1.24 ± 0.47 s, and the delay from AO to clinical onset (CO) was 7.73 ± 3.23 s. The AO time occurred significantly earlier in the ANT than in the cortex (p = 0.001). In 75.2% of the clinical onsets predicted by ANT LFP, it was 1.37 ± 0.82 s ahead of the prediction of cortical potentials (CPs), and the remainder were 0.84 ± 0.31 s slower than the prediction of CPs. ANT LFP appears to be an optimal option for the prediction of seizures in temporal lobe epilepsy. It was possible to upgrade the responsive neurostimulation system to emit electrical stimulation in response to the prediction of epileptic seizures based on the changes in the ANT LFP.


La Crosse encephalitis in Eastern Tennessee: clinical, environmental, and entomological characteristics from a blinded cohort study.
A blinded cohort study was conducted in 2000 to better understand the emergence of La Crosse virus infection in eastern Tennessee, with special emphasis on the potential mosquito vector(s). Children with suspected central nervous system infection were enrolled at the time of clinical presentation at a large pediatric referral hospital. Clinical, environmental, and entomological data were collected prior to case confirmation. Sixteen of the 40 children included in the final analysis were confirmed to have La Crosse infection by a fourfold increase in antibody titers between collection of acute- and convalescent-phase sera. Factors significantly associated with La Crosse infection included average number of hours per day spent outdoors (5.9 for La Crosse virus cases vs. 4.0 for noncases, p = 0.049); living in a residence with one or more tree holes within 100 m (relative risk = 3.96 vs. no tree holes within 100 m, p = 0.028); and total burden of Aedes albopictus (number of female and male larvae and adults collected at a site), which was more than three times greater around the residences of La Crosse virus cases versus noncases (p = 0.013). Evidence is accumulating that the newly introduced mosquito species Ae. albopictus may be involved in the emergence of La Crosse virus infection in eastern Tennessee.


Rechargeable Zinc-Aqueous Polysulfide Battery with a Mediator-Ion Solid Electrolyte.
Large-scale energy storage for the electric grid will require low-cost and high-energy-density solutions. We demonstrate in this letter a rechargeable zinc-aqueous polysulfide battery in which a metallic zinc anode is separated from a liquid aqueous polysulfide catholyte by an alkali-metal-ion solid-state electrolyte, wherein the alkali metal ion is Na+ or Li+. The solid-state electrolyte effectively separates the anode from the reactive polysulfide catholyte, preventing the crossover of the polysulfide species and maintaining good electrochemical performance with a reversible discharge capacity of 822 mA h g-1 with nearly 100% Coulombic efficiency.


Isolation of Brucella melitensis biotype 3 from epidural empyema in a Bosnian immigrant in Germany.
Brucellosis is a regionally emerging infectious disease in Mediterranean countries with an increasing number of human cases and high morbidity rates. Here, we describe a case of severe B. melitensis biotype 3 infection in an immigrant who had contact with ruminants during a short-term stay in Bosnia before he returned to Germany. The patient developed thoracic spondylodiscitis accompanied by a large epidural empyema and neurological deficits. The isolated strain was characterized and compared to other strains from the Mediterranean region by multiple locus variable number of tandem repeat analysis, showing minor differences between emerging strains from neighbouring geographical areas.


Ruthenium indenylidene "1(st) generation" olefin metathesis catalysts containing triisopropyl phosphite.
The reaction of triisopropyl phosphite with phosphine-based indenylidene pre-catalysts affords "1(st) generation" cis-complexes. These have been used in olefin metathesis reactions. The cis-Ru species exhibit noticeable differences with the trans-Ru parent complexes in terms of structure, thermal stability and reactivity. Experimental data underline the importance of synergistic effects between phosphites and L-type ligands.


Global Metabolomic Profiling of Mice Brains following Experimental Infection with the Cyst-Forming Toxoplasma gondii.
The interplay between the Apicomplexan parasite Toxoplasma gondii and its host has been largely studied. However, molecular changes at the metabolic level in the host central nervous system and pathogenesis-associated metabolites during brain infection are largely unexplored. We used a global metabolomics strategy to identify differentially regulated metabolites and affected metabolic pathways in BALB/c mice during infection with T. gondii Pru strain at 7, 14 and 21 days post-infection (DPI). The non-targeted Liquid Chromatography-Mass Spectrometry (LC-MS) metabolomics analysis detected approximately 2,755 retention time-exact mass pairs, of which more than 60 had significantly differential profiles at different stages of infection. These include amino acids, organic acids, carbohydrates, fatty acids, and vitamins. The biological significance of these metabolites is discussed. Principal Component Analysis and Orthogonal Partial Least Square-Discriminant Analysis showed the metabolites' profile to change over time with the most significant changes occurring at 14 DPI. Correlated metabolic pathway imbalances were observed in carbohydrate metabolism, lipid metabolism, energetic metabolism and fatty acid oxidation. Eight metabolites correlated with the physical recovery from infection-caused illness were identified. These findings indicate that global metabolomics adopted in this study is a sensitive approach for detecting metabolic alterations in T. gondii-infected mice and generated a comparative metabolic profile of brain tissue distinguishing infected from non-infected host.


Expanding the Genetic Code for Site-Directed Spin-Labeling.
Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy enables studies of the structure, dynamics, and interactions of proteins in the noncrystalline state. The scope and analytical value of SDSL⁻EPR experiments crucially depends on the employed labeling strategy, with key aspects being labeling chemoselectivity and biocompatibility, as well as stability and spectroscopic properties of the resulting label. The use of genetically encoded noncanonical amino acids (ncAA) is an emerging strategy for SDSL that holds great promise for providing excellent chemoselectivity and potential for experiments in complex biological environments such as living cells. We here give a focused overview of recent advancements in this field and discuss their potentials and challenges for advancing SDSL⁻EPR studies.


Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN Associated with Invasive Ductal Carcinoma of the Breast.
Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast. A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion. Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.


Effects of a web-based education for community mental health case managers on physical healthcare for clients with severe mental illness.
This study aimed to develop and verify the effects of a web-based physical healthcare education program for community mental health case managers during the time of COVID-19. Six modules of mental health case management physical health education program were developed and provided using the EdWith education platform, which enables real-time streaming, lecture participant management and whether participants have watched the video and watch time. A total of 51 community mental health case managers participated in the study. Collected data were analyzed using SPSS 26.0 software. Participants of the physical healthcare education program testified increased performance in, as well as enhanced attitudes toward physical healthcare. Their confidence in physical healthcare increased significantly from that of the individuals in the control group. The web-based educational program for mental health case managers in physical healthcare may be beneficial to improving the physical health of clients with chronic mental illness.


[Robotic percutaneous coronary intervention: current evidence, practical aspects and future perspectives].
Robotic percutaneous coronary intervention (R-PCI) is an emerging technology designed to improve operator safety and procedural precision. The interventional cardiologist is able to manipulate guidewires, catheters and devices from a specific cockpit. A number of studies evaluating R-PCI have shown high procedural success rates with low complications. R-PCI advantages include the possibility to perform an accurate stent positioning, to reduce the operator radiation exposure and orthopedic injuries. However, there is a limited experience regarding R-PCI in complex anatomies, that may still require manual assistance. Moreover, the technique is limited by current incompatibility with specific materials, the lack of tactile feedback and the possibility to robotically manage only one wire/device at the same time. Globally, R-PCI is a novel approach with future interesting implications, but further investigations are necessary to overcome current limitations.


An unusual promoter controls cell-cycle regulation and dependence on DNA replication of the Caulobacter fliLM early flagellar operon.
Transcription of flagellar genes in Caulobacter crecentus is programmed to occur during the predivisional stage of the cell cycle. The mechanism of activation of Class II flagellar genes, the highest identified genes in the Caulobacter flagellar hierarchy, is unknown. As a step toward understanding this process, we have defined cis-acting sequences necessary for expression of a Class II flagellar operon, fliLM. Deletion analysis indicated that a 55 bp DNA fragment was sufficient for normal, temporally regulated promoter activity. Transcription from this promoter-containing fragment was severely reduced when chromosomal DNA replication was inhibited. Extensive mutational analysis of the promoter region from -42 to -5 identified functionally important nucleotides at -36 and -35, between -29 and -22, and at -12, which correlates well with sequences conserved between fliLM and the analogous regions of two other Class II flagellar operons. The promoter sequence does not resemble that recognized by any known bacterial sigma factor. Models for regulation of Caulobacter early flagellar promoters are discussed in which RNA polymerase containing a novel sigma subunit interacts with an activation factor bound to the central region of the promoter.


Association between single-nucleotide polymorphisms and milk production traits in buffalo.
The aim of this study was to identify single-nucleotide polymorphisms (SNPs) in buffaloes associated with milk yield and content, in addition to somatic cell scores based on the cross-species transferability of SNPs from cattle to buffalo. A total of 15,745 SNPs were analyzed, of which 1562 showed 1% significance and 4742 with 5% significance, which were associated for all traits studied. After application of Bonferroni's correction for multiple tests of the traits analyzed, we found 2 significant SNPs placed on cattle chromosomes BTA15 and BTA20, which are homologous to buffalo chromosomes BBU16 and BBU19, respectively. In this genome association study, we found several significant SNPs affecting buffalo milk production and quality. Furthermore, the use of the high-density bovine BeadChip was suitable for genomic analysis in buffaloes. Although extensive chromosome arm homology was described between cattle and buffalo, the exact chromosomal position of SNP markers associated with these economically important traits in buffalo can be determined only through buffalo genome sequencing.


Haplotype inference in complex pedigrees.
Despite the desirable information contained in complex pedigree data sets, analysis methods struggle to efficiently process these data. The attractiveness of pedigree data is their power for detecting rare variants, particularly in comparison with studies of unrelated individuals. In addition, rather than assuming individuals in a study are unrelated, knowledge of their relationships can avoid spurious results due to confounding population structure effects. However, a major challenge for applying pedigree methods is difficulty in handling complex pedigrees having multiple founding lineages, inbreeding, and half-sibling relationships. A key ingredient in association studies is imputation and inference of haplotypes from genotype data. Existing haplotype inference methods either do not efficiently scale to complex pedigrees or are of limited accuracy. In this article, we present algorithms for efficient haplotype inference and imputation in complex pedigrees. Our method, PhyloPed, leverages the perfect phylogeny model, resulting in an efficient method with high accuracy. PhyloPed effectively combines the founder haplotype information from different lineages and is immune to inaccuracies in prior information about the founders. In addition, we demonstrate that inference of missing data, using PhyloPed, can substantially improve disease association. For Online Supplementary Material, see www.liebertonline.com.


Calcium overload and cardiac myocyte cell damage induced by arachidonate lipoxygenation.
The accumulation of arachidonic acid and lipoxygenase metabolites of arachidonate occurs in ischemic-reperfused myocardium. Although lipoxygenase inhibitors have been shown to attenuate myocardial infarct size after ischemia-reperfusion, the relationship between arachidonate lipoxygenation and myocardial injury remains unclear. To investigate the direct effect of arachidonate lipoxygenation on cardiac myocytes, isolated rat cardiac myocytes loaded with indo 1 were superfused with Tyrode solution containing arachidonic acid mixed with soybean lipoxygenase. Although neither arachidonic acid nor lipoxygenase alone had any effects, arachidonic acid plus lipoxygenase induced an increase in the twitch amplitude associated with an increased intracellular Ca2+ concentration ([Ca2+]i) and irreversible hypercontracture. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, blocked these effects. Linolenic acid, which is also a lipoxygenase substrate, caused the same effects as arachidonic acid in the presence of lipoxygenase, whereas oleic and stearic acid, which do not function as lipoxygenase substrates, did not. Both ascorbic acid and alpha-tocopherol attenuated an increase in [Ca2+]i and the cellular damage, whereas nicardipine and superoxide dismutase had no effects. These results suggest that lipoxygenase metabolites of arachidonic acid cause intracellular Ca2+ overload and cellular damage to cardiomyocytes, probably through augmentation of lipid peroxidation of the cell membranes by free radicals.