Return to Play After Biceps Tenodesis for Isolated SLAP Tears in Overhead Athletes.
Performing open subpectoral biceps tenodesis in overhead athletes with a superior labrum anterior to posterior (SLAP) tear may affect their ability to return to overhead sports. To investigate clinical outcomes in overhead athletes undergoing biceps tenodesis for the treatment of symptomatic, isolated SLAP tears involving the biceps-labral complex. Case series; Level of evidence, 4. A retrospective review of overhead athletes who underwent biceps tenodesis for a SLAP tear was performed. The American Shoulder and Elbow Surgeons (ASES) score, visual analog scale (VAS) score for pain, subjective shoulder value (SSV), patient satisfaction, willingness to undergo surgery again, revision procedures, and return to play were evaluated. Psychological readiness to return to sport was evaluated using the SLAP-Return to Sport after Injury (SLAP-RSI) score. A P value of <.05 was considered to be statistically significant. The current study included 44 overhead athletes. The mean age was 34.9 years (range, 16-46 years), 79.5% were male, and the mean follow-up was 49.0 months (range, 18-107 months). Overall, 81.8% of patients returned to play their overhead sport after biceps tenodesis, and 59.1% of patients returned to the same or higher level of play. It took patients, on average, 8.7 months to return to play after biceps tenodesis. The mean SLAP-RSI score was 69.4, and 70.5% of patients passed the SLAP-RSI threshold of 56. The mean ASES score, VAS score, SSV, and satisfaction were 92.0, 0.8, 80.6, and 87.9%, respectively. No patients in our cohort required revision surgery. This study found that athletes undergoing biceps tenodesis for the treatment of a symptomatic, isolated SLAP tear had a high rate of return to play, good functional outcomes, and a low rate of revision surgery.


Combining the Advantages of Alkene and Azo E-Z Photoisomerizations: Mechanistic Insights into Ketoimine Photoswitches.
We carried out CASPT2//(TD)DFT and CASPT2//CASSCF studies on the working mechanism of imine switches, including a camphorquinone-derived ketoimine (shortened as k-Imine) switch designed by Lehn as well as a model camphorquinone alkene-imine (a-Imine) proposed in this study. Under the experimental conditions (light irradiation with 455 and 365 nm for E and Z, respectively), k-Imine is excited to the S1:(nN,π*) state and then decays toward a perpendicular intermediate following the C═N bond rotation coordinate. During the bond rotation, a mild energy barrier caused by the strong interaction of S1:(nN,π*) and S2:(nO,π*) states will more or less slow down the rotation speed of k-Imine. The large difference in irradiation light wavelength supports k-Imine as a two-way photoswitch. The photoisomerization of a-Imine obeys a similar but fully barrierless pattern while requiring a higher excitation energy to reach the (nN,π*) state. The good directionality of thermal isomerization toward E(a-Imine), plus the barrierless photoisomerization, allows for the design of a thermal and photo-operated switch. For both imines, a minimal-energy crossing point (MECI) located at the perpendicular region, with low relative energy and close to the rotary path, ensures the directionality of C═N bond rotation and confirms imines as optimal candidates for photoswitches and motors.


Anastomotic salvage after rectal cancer resection using the Turnbull-Cutait delayed anastomosis.
Turnbull-Cutait abdominoperineal pull-through followed by delayed coloanal anastomosis (DCA) was first described in 1961. Studies have described its use for challenging colorectal conditions. We reviewed our experience with Turnbull-Cutait DCA as a salvage procedure for complex failure of colorectal anastomosis. We performed a retrospective cohort study from October 2010 to September 2011, with analysis of postoperative morbidity and mortality. Seven DCAs were performed for anastomotic complications (3 chronic leaks, 2 rectovaginal fistulas, 1 colovesical fistula, 1 colonic ischemia) following surgery for rectal cancer. Six patients had a diverting ileostomy constructed as part of previous treatment for anastomotic complications before the salvage procedure. No anastomotic leaks were observed. All procedures but 1 were completed successfully. One patient who underwent DCA subsequently required an abdominoperineal resection and a permanent colostomy for postoperative extensive colonic ischemia. No 30-day mortality occurred. Salvage Turnbull-Cutait DCA appears to be a safe procedure and could be offered to patients with complex anastomotic complications. This procedure could be added to the surgeon's armamentarium as an alternative to the creation of a permanent stoma.


Displacement of fibrinogen from the air/aqueous interface by dilauroylphosphatidylcholine lipid.
Fibrinogen (FB) and other serum proteins leak into the aqueous alveolar lining layer due to lung injuries. The adsorption of these serum proteins at the air/aqueous interface can produce higher surface tensions than the pulmonary lipids, and acute respiratory distress syndrome (ARDS) can ensue. By having a molecular adsorption mechanism, as compared to a particulate adsorption mechanism of other longer chain lipids, dilauroylphosphatidylcholine (DLPC) lipid can expel FB from the air/aqueous interface at 25 degrees C, in water or in phosphate-buffered saline, as proven by tensiometry (also at 37 degrees C), ellipsometry, and infrared reflection-absorption spectroscopy. Moreover, before FB is displaced by DLPC at the interface, there is a substantial initial enhancement in the FB adsorption, consistent with some interaction or binding of DLPC with FB to produce a more hydrophobic protein surface. After the FB molecules have been displaced by DLPC, or when DLPC has already adsorbed at the interface, FB molecules are less favored to adsorb near the DLPC monolayer with the lecithin headgroups facing toward them. The results have implications for possible uses of DLPC lipid in potential lung surfactant formulations in treating patients with ARDS.


A patient with extensive blue rubber bleb nevi associated with multiple congenital anomalies: an overlap or a new syndrome?
We report a case of a 13 year old boy with non-familial, multiple blue rubber bleb nevi (BRBN). He also had additional dysmorphic anomalies including a low hairline, low set ears, narrow nares, ptosis, hypotelorism, a high arched palate and downward slanting of the outer canthi. Skeletal deformities included a short, slightly webbed neck, kyphosis, cubitus valgus, non-traumatic luxation of the head of the right radius and a short left little and index fingers. He had no evidence of gastrointestinal lesions or bleeding, congenital heart or renal disease or enchondromata. The boy was mentally slow compared to his peers. He had normal chromosomes. The absence of gastrointestinal bleeding or iron deficiency anaemia is inconsistent with Bean's syndrome and the lack of enchondromata in this patient militates against the diagnosis of classical Maffucci syndrome. Some of his physical features are obviously similar to those observed in a Noonan's syndrome yet the presence of extensive BRBN would be an extremely unusual finding. Since the overall picture does not fit into any of the classical categories mentioned above, the constellation of his features has yet to find a specific syndrome. It may, however, represent an overlap between them or, possibly, a new syndrome.


Cholesterol 7 alpha-hydroxylase is up-regulated by the competitive inhibitor 7-oxocholesterol in rat liver.
Rats of the Sprague-Dawley strain were infused intravenously with a fat emulsion (Intralipid, trademark of Kabi Pharmacia, Uppsala, Sweden) containing 7-oxocholesterol. This resulted in an increased cholesterol 7 alpha-hydroxylase activity in liver microsomes as compared to controls and was accompanied by increased levels of cholesterol 7 alpha-hydroxylase mRNA and microsomal cholesterol 7 alpha-hydroxylase protein. Rats were also fed a cholestyramine-supplemented diet and infused with 7-oxocholesterol. These animals excreted about half as much bile acids in faeces as cholestyramine-fed controls. Addition of 7-oxocholesterol to liver microsomes from normal rats in amounts corresponding to those present in microsomes from 7-oxocholesterol-treated rats inhibited the cholesterol 7 alpha-hydroxylase activity by about 75%. Cholesterol induced a type-I binding spectrum when added to a purified bacterial-expressed cholesterol 7 alpha-hydroxylase (P-450c7 delta 2-24). 7-Oxocholesterol competitively inhibited the cholesterol binding spectrum, while 7 beta-hydroxycholesterol did not interfere with binding of cholesterol to the enzyme. It is concluded that treatment with the competitive inhibitor 7-oxocholesterol leads to a reduced bile acid biosynthesis and, as a consequence of reduced bile acid inhibition, a compensatory increase in cholesterol 7 alpha-hydroxylase synthesis. The high enzyme activity measured in microsomal preparations from 7-oxocholesterol-treated rats may be due to a continuous conversion of 7-oxocholesterol into less inhibitory metabolites, e.g. 7 beta-hydroxycholesterol. The latter compound was found in high concentrations in liver microsomes from rats treated with 7-oxocholesterol. The physiological importance of these results is discussed in relation to the previous findings that 7-oxocholesterol is accumulated in liver after cholesterol feeding and that 7-oxocholesterol is formed from cholesterol during lipid peroxidation.


Recruitment and retention of pregnant women into clinical research trials: an overview of challenges, facilitators, and best practices.
Pregnant women are a vulnerable group who are needed in clinical research studies to advance prevention and treatment options for this population. Yet, pregnant women remain underrepresented in clinical research. Through the lens of the socioecological model, we highlight reported barriers and facilitators to recruitment and retention of pregnant women in studies that sought their participation. We trace historical, policy-based reasons for the exclusion of pregnant women in clinical studies to present-day rationale for inclusion of this group. The findings highlight why it has been difficult to recruit and retain this population over time. A body of literature suggests that integrative sampling and recruitment methods that leverage the influence and reach of prenatal providers will overcome recruitment challenges. We argue that these strategies, in combination with building strong engagement with existing community-based organizations, will enable teams to more effectively promote and retain pregnant women in future longitudinal cohort studies.


A potent, minimally invasive and simple strategy of enhancing intracellular targeted delivery of Tat peptide-conjugated quantum dots: organic solvent-based permeation enhancer.
Targeted delivery of nanomaterials to specific intracellular locations is essential for the development of many nanomaterials-based biological applications. Thus far the targeting performance has been limited due to various intracellular transport barriers, especially intracellular vesicle trapping. Here we report the application of permeation enhancers based on organic solvents in small percentage to enhance the intracellular targeted delivery of nanomaterials. Previously permeation enhancers based on organic solvents and ionic liquids have been used in overcoming biological transport barriers at tissue, organ, and cellular levels, but this strategy has so far rarely been examined for its potential in facilitating transport of nanometer-scale entities across intracellular barriers, particularly intracellular vesicle trapping. Using the cell nucleus as a model intracellular target and Tat peptide-conjugated quantum dots (QDs-Tat) as a model nanomaterial-based probe, we demonstrate that a small percentage (e.g. 1%) of organic solvent greatly enhances nucleus targeting specificity as well as increasing endocytosis-based cellular uptake of QDs. We combine vesicle colocalization (DiO dye staining), vesicle integrity (calcein dye release), and single-particle studies (pair-correlation function microscopy) to investigate the process of organic solvent-enhanced vesicle escape of QDs-Tat. The organic solvent based vesicle escape-enhancing approach is found to be not only very effective but minimally invasive, resulting in high vesicle escape efficiency with no significant disruption to the membrane integrity of either intracellular vesicles or cells. This approach drastically outperforms the commonly used vesicle escape-enhancing agent (i.e., chloroquine, whose enhancement effect is based on disrupting vesicle integrity) in both potency and minimal invasiveness. Finally, we apply organic solvent-based targeting enhancement to improve the intracellular delivery of the anticancer drug doxorubicin (DOX).


Effects of contrast media on the conducting system of the heart during coronary angiography. A comparison of Renografin-76 to Hypaque-76.
Electrocardiographic changes induced by ionic contrast media can cause complications during coronary angiography. A conduction delay through various parts of the heart is one factor in the genesis of asystole or ventricular fibrillation. Hypaque-76 (H76) and Renografin-76 (R76) are nearly identical ionic contrast media except that R76 binds more calcium than H76 because of the presence of sodium citrate and EDTA in R76. To determine whether the calcium binding additives in ionic contrast media contribute to the cardiac conduction abnormalities, we examined conduction time through the atrioventricular (AV) nodal tissue (via bipolar His bundle electrograms) and through the distal part of the conduction system (recording the QRS complex from the ECG) during coronary angiography. We injected 10 mL of H76 and R76 in 19 closed chest dogs in a blinded, randomized fashion during coronary angiography. The effects of H76 and R76 on heart rate, AH interval, HV interval, V interval and PR interval, and QRS complex duration were recorded. In 14 nonatrial pacing dogs, compared with H76, R76 produced a greater increase in the AV interval (32.9 +/- 6 milliseconds vs 12.4 +/- 2 milliseconds, P less than .01) and the PR interval (29.6 +/- 6 milliseconds vs 11.9 +/- 4 milliseconds, P less than .02). Additionally, the heart rate decreased 13.9 +/- 3.5 beats/minute from control with R76 compared with a decrease of 4.2 +/- 2.6 beats/minute from control with H76 (P less than .05). There was no significant difference between the prolongation of the HV interval and V interval, or QRS complex duration generated by R76 and H76.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of in ovo feeding of carbohydrates on hatchability, body weight, and energy status in domestic pigeons (Columba livia).
The effects of in ovo feeding of carbohydrates on hatchability, BW, yolk sac weights (YSW), pectoral muscle weights (PMW), liver and pectoral muscle glycogen concentration, serum glucose level, and hepatic glucose-6-phosphatase activity of domestic pigeons, hatched from eggs laid by a 40-wk-old breeder flock, were investigated. At 14.5 of incubation, fertile eggs were injected with 200 μL of 1.5% maltose (M) + 1.5% sucrose (S), 2.5% M + 2.5% S, 3.5% M + 3.5% S, or 4.5% M + 4.5% S in 0.75% saline, with controls not injected. Results showed that in ovo injection with 1.5% M + 1.5% S or 2.5% M + 2.5% S increased the hatchability compared with the control, whereas injection of 4.5% M + 4.5% S decreased the hatchability. The BW at hatch was quadratic, and BW was maximized by injecting 2.5% M + 2.5% S. The YSW at hatch decreased linearly by the injection with 3.5% M + 3.5% S compared with the control group. In ovo injection of 2.5% M + 2.5% S increased the PMW at hatch. There were no significant differences between any of the treatment groups for liver glycogen reserves. Serum glucose level at hatch was quadratic, and the glucose level was maximized between supplemental 2.5% M + 2.5% S and supplemental 3.5% M + 3.5% S. The pectoral muscle glycogen reserves increased quadratically as supplemental carbohydrates increased, and the response was maximized by injecting 2.5% M + 2.5% S. In conclusion, the present results demonstrate that the injected carbohydrates are available for use and storage. In ovo feeding of carbohydrates, especially at the level of 2.5% M + 2.5% S, on 14.5 d of incubation can improve the hatchability, BW, and PMW by elevating the pectoral muscle glycogen reserves in domestic pigeons at hatch. Results also suggested that in ovo injection of carbohydrates could increase the yolk sac nutrient utilization and hence might enhance the pigeon enteric development.


Salidroside Ameliorates Alzheimer's Disease by Targeting NLRP3 Inflammasome-Mediated Pyroptosis.
Amyloid β-protein (Aβ) is reported to activate NLRP3 inflammasomes and drive pyroptosis, which is subsequently involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). To date, the pathogenesis of AD is unfortunately insufficiently elucidated. Therefore, this study was conducted to explore whether Salidroside (Sal) treatment could benefit AD by improving pyroptosis. Firstly, two animal models of AD, induced, respectively, by Aβ1-42 and D-galactose (D-gal)/AlCl3, have been created to assist our appreciation of AD pathophysiology. We then confirmed that pyroptosis is related to the pathogenesis of AD, and Sal can slow the progression of AD by inhibiting pyroptosis. Subsequently, we established the D-gal and Nigericin-induced PC12 cells injury model in vitro to verify Sal blocks pyroptosis mainly by targeting the NLRP3 inflammasome. For in vivo studies, we observed that Aβ accumulation, Tau hyperphosphorylation, neurons of hippocampal damage, and cognitive dysfunction in AD mice, caused by bilateral injection of Aβ1-42 into the hippocampus and treatments with D-gal combine AlCl3. Besides, accumulated Aβ promotes NLRP3 inflammasome activation, which leads to the activation and release of a pro-inflammatory cytokine, interleukin-1 beta (IL-1β). Notably, both Aβ accumulation and hyperphosphorylation of Tau decreased and inhibited pyroptosis by downregulating the expression of IL-1β and IL-18, which can be attributed to the treatment of Sal. We further found that Sal can reverse the increased protein expression of TLR4, MyD88, NF-κB, P-NF-κB, NLRP3, ASC, cleaved Caspase-1, cleaved GSDMD, IL-1β, and IL-18 in vitro. The underlying mechanism may be through inhibiting TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway. Our study highlights the importance of NLRP3 inflammasome-mediated pyroptosis in AD, and how the administration of pharmacological doses of Sal can inhibit NLRP3 inflammasome-mediated pyroptosis and ameliorate AD. Thus, we conclude that NLRP3 inflammasome-mediated pyroptosis plays a significant role in AD and Sal could be a therapeutic drug for AD.


Ferroptosis: The Greasy Side of Cell Death.
Ferroptosis is a form of cell death that requires phospholipid peroxidation and has attracted increased attention, both as a means to eradicate tumors resistant to standard chemotherapy and for its potential contribution to tissue damage such as in ischemia/reperfusion. The center stage taken by phospholipid peroxidation in ferroptosis is highlighted by recent discoveries that demonstrate an intricate regulation of both the metabolism of polyunsaturated fatty acids as well as mechanisms leading to their oxidation. These metabolic steps converge at the point of ferroptosis execution through mechanisms that are now only starting to be understood. In this short review, we provide an appraisal of some of the recent advances in the understanding of the ferroptosis process and also provide some perspectives of where this knowledge could take us.


[Three-dimensional computerized tomography of fractures].
In 32 patients with fractures of different localisation the transverse CT layers were compared with three-dimensional reconstructions. Evaluation showed that three-dimensional CT can better visualize complicated anatomical conditions especially if there are dislocated fragments in the facial part of the skull and in the trunk of the body. Hence, 3-D CT is a valuable complement to axial CT which, however, remains the basis of the findings. Misinterpretations are possible of the reconstructions are used alone because of the lack if visualization of the lesions of the soft parts that accompany fractures and because there may be pseudoforamina at thin osseous lamellae.


Effect of soybean ureases on seed germination and plant development.
Urease catalyzes the hydrolysis of urea to ammonia and carbon dioxide. The ammonia (nitrogen (N) product of urease activity) is incorporated into organic compounds. Thus, urease is involved in N remobilization, as well as in primary N assimilation. Two urease isoforms have been described for soybean: the embryo-specific, encoded by the Eu1 gene, and the ubiquitous urease, encoded by Eu4. A third urease-encoding gene was recently identified, designated Eu5, which encodes the putative protein product SBU-III. The present study aimed to evaluate the contribution of soybean ureases to seed germination and plant development. Analyses were performed using Eu1/Eu4/Eu5-co-suppressed transgenic plants and mutants of the Eu1 and Eu4 urease structural genes, as well as a urease-null mutant (eu3-a) that activates neither the ubiquitous nor embryo-specific ureases. The co-suppressed plants presented a developmental delay during the first month after germination; shoots and roots were significantly smaller and lighter. Slower development was observed for the double eu1-a/eu4-a mutant and the eu3-a single mutant. The N content in transgenic plants was significantly lower than in non-transgenic plants. Among the mutants, eu3-a presented the lowest and eu1-a the highest N content. Altogether, these results indicate that increased ureolytic activity plays an important role in plant development.


FUBP/KH domain proteins in transcription: Back to the future.
Drosophila genetic studies demonstrate that cell and tissue growth regulation is a primary developmental function of P-element somatic inhibitor (Psi), the sole ortholog of FUBP family RNA/DNA-binding proteins. Psi achieves growth control through interaction with Mediator, observations that should put to rest controversy surrounding Pol II transcriptional functions for these KH domain proteins.


New chamber stapes prosthesis - A preliminary assessment of the functioning of the prototype.
Piston-stapedotomy is the most common method for hearing restoration in patients with otosclerosis. In this study, we have experimentally examined a prototype of a new chamber stapes prosthesis. The prototype was implanted in a human cadaver temporal bone. The round window vibrations before and after implantation were measured for the acoustic signal (90 dB SPL, 0.8-8 kHz) in the external auditory canal. In comparison with a 0.4-mm piston prosthesis, the chamber prosthesis induced significantly higher vibration of the round window, especially for frequencies above 1.5 kHz. Based on the results, it can be surmised that stapedotomy with a chamber stapes prosthesis could provide better hearing results in comparison with the piston-stapedotomy.


Complement Inhibition Therapy and Dialytic Strategies in Paroxysmal Nocturnal Hemoglobinuria: The Nephrologist's Opinion.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease that presents an estimated incidence of 1.3 cases per million per year, with a prevalence of 15.9 cases per million. It is characterized by hemolysis, bone marrow dysfunction with peripheral blood cytopenia, hypercoagulability, thrombosis, renal impairment and arterial and pulmonary hypertension. Hemolysis and subsequent hemosiderin accumulation in tubular epithelium cells induce tubular atrophy and interstitial fibrosis. The origin of PNH is the somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene located on Xp22: this condition leads to the production of clonal blood cells with a deficiency in those surface proteins that protect against the lytic action of the activated complement system. Despite the increased knowledge of this syndrome, therapies for PNH were still only experimental and symptomatic, until the introduction of the C5 complement blockade agent Eculizumab. A second generation of anti-complement agents is currently under investigation, representing future promising therapeutic strategies for patients affected by PNH. In the case of chronic hemolysis and renal iron deposition, a multidisciplinary approach should be considered to avoid or treat acute tubular injury or acute kidney injury (AKI). New promising perspectives derive from complement inhibitors and iron chelators, as well as more invasive treatments such as immunoadsorption or the use of dedicated hemodialysis filters in the presence of AKI.


Dendritic cells regulate exposure of MHC class II at their plasma membrane by oligoubiquitination.
Dendritic cells (DCs) initiate adaptive immune responses by activating T cells via cognate interactions between MHC-peptide complexes and T cell receptors. In immature DCs, MHC class II is predominantly stored in late endocytic compartments, where it has a short half-life because of degradation. In contrast, mature DCs recruit MHC class II to the plasma membrane. We here demonstrate that in immature DCs, the beta-chain of MHC class II was oligoubiquitinated after proteolytic processing of the associated invariant chain in endosomes and that this modification was required for efficient endocytosis and sorting into luminal vesicles of multivesicular bodies. Ubiquitination of MHC class II was suppressed in lipopolysaccharide-activated DCs. Mutated MHC class II lacking its ubiquitination site was expressed at the plasma membrane, irrespective of DC maturation. Together, these data provide a molecular basis for the regulation of MHC class II-mediated antigen presentation by DCs.


Estimating cell and product yields.
The balance equations for carbon, reduction potential, and energy during cell growth and product formation are rederived in a general form. Cells are treated simply as a very complex product, and the Y(ATP) concept is extended to products. Limitations on the theoretical yield are discussed for different product types. Simple aerobic products cannot be energy limited unless the maintenance requirement is large, while complex products cannot be reduction limited. A maximum yield is defined for products much more oxidized than their substrate (carbon limited) because the theoretical yield conditions may violate the energy balance. For reduced complex products the yield on available electrons is related to Y(ATP), the P/O ratio, and the product composition. Narrow bounds are established on the actual yields in simple anaerobic fermentations, and the significance of the yields in the linear growth equation is discussed.


Effective medium method for sound propagation in a soft medium containing air bubbles.
An effective medium method (EMM) is developed to investigate the nonlinear propagation of acoustic waves for soft media containing air bubbles, which accounts for the effects of weak compressibility, viscosity, surrounding pressure, surface tension, and encapsulating shells. Based on the dynamics model of an individual bubble that has included these effects, the EMM is presented by employing a simple perturbation approach to "homogenize" the bubbly soft media. The equations describing the fundamental and the second harmonic waves are derived that applies to three-dimensional cases, and then solved in a one-dimensional case to obtain the effective acoustical parameters of a longitudinal wave. The EMM is compared with the previous theories in three representative cases regarded as simple models of significant practical applications. The results show that the EMM agrees well with the previous theories and can incorporate the additional effects, which may notably affect the accuracy of the results. The limitations of the EMM are also identified and stated.


Crisis intervention: the nuclear task approach.
Failure to perform certain life tasks adequately contributes to crisis development. Occupational therapists frequently treat individuals in crisis. The state of crisis disrupts normal activity patterns, adding to the individual's sense of helplessness and disequilibrium. Activities may play a crucial role in the process of recovery. "Nuclear tasks" are activities that promote adaptive resolution of crisis elements and spur active problem solving on the part of crisis patients.


Glass transition temperatures of dental porcelains determined by DSC measurement.
The differential scanning calorimetry (DSC) curves for three commercial dentin and incisal porcelains fused-to metal were measured using high-temperature DSC. The glass transition temperatures (Tg) were determined from the DSC curves at heating rates of 7-20 degrees C/min, and the activation energy was derived from an Arrhenius plot of negative reciprocal Tg vs. logarithm of heating rate. The Tg of the dental porcelains depended on the content of aluminum oxide, whereas the activation energy depended on the content of sodium oxide. The ultra-low fusing type porcelains had a low activation energy due to the higher content of sodium oxide than the other porcelains.


Ventilator-derived carbon dioxide production to assess energy expenditure in critically ill patients: proof of concept.
Measurement of energy expenditure (EE) is recommended to guide nutrition in critically ill patients. Availability of a gold standard indirect calorimetry is limited, and continuous measurement is unfeasible. Equations used to predict EE are inaccurate. The purpose of this study was to provide proof of concept that EE can be accurately assessed on the basis of ventilator-derived carbon dioxide production (VCO2) and to determine whether this method is more accurate than frequently used predictive equations. In 84 mechanically ventilated critically ill patients, we performed 24-h indirect calorimetry to obtain a gold standard EE. Simultaneously, we collected 24-h ventilator-derived VCO2, extracted the respiratory quotient of the administered nutrition, and calculated EE with a rewritten Weir formula. Bias, precision, and accuracy and inaccuracy rates were determined and compared with four predictive equations: the Harris-Benedict, Faisy, and Penn State University equations and the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline equation of 25 kcal/kg/day. Mean 24-h indirect calorimetry EE was 1823 ± 408 kcal. EE from ventilator-derived VCO2 was accurate (bias +141 ± 153 kcal/24 h; 7.7 % of gold standard) and more precise than the predictive equations (limits of agreement -166 to +447 kcal/24 h). The 10 % and 15 % accuracy rates were 61 % and 76 %, respectively, which were significantly higher than those of the Harris-Benedict, Faisy, and ESPEN guideline equations. Large errors of more than 30 % inaccuracy did not occur with EE derived from ventilator-derived VCO2. This 30 % inaccuracy rate was significantly lower than that of the predictive equations. In critically ill mechanically ventilated patients, assessment of EE based on ventilator-derived VCO2 is accurate and more precise than frequently used predictive equations. It allows for continuous monitoring and is the best alternative to indirect calorimetry.


Impact of ABO blood groups on tirofiban mediated inhibition of platelet function.
Previous investigations revealed that ABO blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group O as compared to subjects with blood group A, B or AB which might result in a reduced inhibition of platelet aggregation. The aim of the present in-vitro-investigation was to elucidate the impact of ABO blood group dependent vWF concentrations on tirofiban mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100 at baseline and at increasing concentrations of tirofiban and stratified for blood group O vs. A. If measured with the collagen/epinephrine cartridge, blood group O was associated with a prolonged mean baseline closure time in comparison with blood group A (175.8 +/- 64.9 s vs. 121.4 +/- 33.4 s, p = 0.037) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no differences in closure time (227.6 +/- 76.1 s vs. 223.9 +/- 81.9 s, p = 0.96) could be found in the presence of tirofiban (0.1 microg/ml). Thus, tirofiban mediated GP IIb/IIIa receptor antagonism as determined with the PFA-100 seems to be independent on plasma concentration of vWF.


Conversion of retinoid ethers to alcohols by enzymatic activity present in rat liver microsomes.
An enzyme present in rat liver microsomes catalyzes the conversion of retinyl methyl ether (RME) to retinol; NADPH is required for activity. The optimum pH for the reaction is 7.4; the KM and Vmax values are 120 microM RME and 14.3 nmol of retinol/mg protein/hr, respectively. As a substrate, the 2,3,6-trimethyl-4-methoxyphenyl analog of RME is as effective as RME. There is, however, no measurable activity for dealkylation of retinyl ethyl ether or retinyl butyl ether. Hepatic enzyme activity for the metabolism of RME is induced by 3-methylcholanthrene but not by phenobarbital or RME itself. The induced activity also requires NADPH as a cofactor. The optimum pH for the induced enzyme is 8.4; the KM and Vmax values are 50 microM RME and 111 nmol of retinol/mg protein/hr, respectively. For this enzyme, RME is a better substrate than the 2,3,6-trimethyl-4-methoxyphenyl analog of RME; retinyl ethyl ether is less effective; and again, there is no measurable activity with retinyl butyl ether as a substrate. Neither constitutive nor induced activity is detectable in microsomes from lung, spleen, stomach, kidney, small intestine, or large intestine. The enzyme activity that cleaves retinoid ethers appears to be similar to other microsomal NADPH-requiring O-dealkylases and different from a reported tetrahydropteridine-requiring dealkylase.


STUDIES ON THE RELATIONSHIP OF ALLOTYPIC SPECIFICITIES TO ANTIBODY SPECIFICITIES IN THE RABBIT.
Purified antibodies against three different antigens and haptens (ovalbumin, dinitrophenol, and Type II pneumococcal polysaccharide) were prepared from specific precipitates from the antisera of several rabbits. The reactions of these preparations with antisera against the allotypic specificities carried by each of the animals forming the antibodies were used to compare the relative concentrations of molecules bearing each specificity in the different solutions of antibodies from each rabbit. These relative concentrations appeared to vary greatly from one preparation to another, although all the allotypic specificities carried by each animal were found in all the preparations of antibodies from that animal. The interpretation of these results is discussed.


CT characteristics of primary retroperitoneal neoplasms.
Primary retroperitoneal neoplasms account for only 0.1-0.2% of all malignancies. Retroperitoneal neoplasms are most commonly mesodermal, neurogenic or lymphatic in origin, with lymphoma, liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma the vast majority of malignant primary retroperitoneal tumors. Although the radiographic features of retroperitoneal neoplasms often overlap, certain CT characteristics, pattern of spread and specific tumor prevalence among different demographic groups can help suggest the tumor type. CT is used to diagnosis and assess the size and extent of retroperitoneal tumors, as well as assess the involvement of organs and vasculature with resection in mind.


BATF represses BIM to sustain tolerant T cells in the periphery.
T cells that encounter self-antigens after exiting the thymus avert autoimmunity through peripheral tolerance. Pathways for this include an unresponsive state known as anergy, clonal deletion, and T regulatory (Treg) cell induction. The transcription factor cues and kinetics that guide distinct peripheral tolerance outcomes remain unclear. Here, we found that anergic T cells are epigenetically primed for regulation by the non-classical AP-1 family member BATF. Tolerized BATF-deficient CD4+ T cells were resistant to anergy induction and instead underwent clonal deletion due to proapoptotic BIM (Bcl2l11) upregulation. During prolonged antigen exposure, BIM derepression resulted in fewer PD-1+ conventional T cells as well as loss of peripherally induced FOXP3+ Treg cells. Simultaneous Batf and Bcl2l11 knockdown meanwhile restored anergic T cell survival and Treg cell maintenance. The data identify the AP-1 nuclear factor BATF as a dominant driver of sustained T cell anergy and illustrate a mechanism for divergent peripheral tolerance fates.


Carbachol stimulates [35S]guanylyl 5'-(gamma-thio)-triphosphate binding in rapid eye movement sleep-related brainstem nuclei of rat.
Carbachol enhances rapid eye movement (REM) sleep when microinjected into the pontine reticular formation of the cat and rat. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic receptors (mAChRs). The present study used in vitro autoradiography of carbachol-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding to test the hypothesis that carbachol activates mAChRs to induce stimulation of G-proteins in brainstem nuclei contributing to REM sleep generation. The results demonstrate a heterogeneous increase in carbachol-stimulated G-protein activation across rat brainstem. Binding of [35S]GTPgammaS in the presence of carbachol, compared with basal binding, was significantly increased in the laterodorsal tegmental nucleus (75.7%), caudal pontine reticular nucleus (68.9%), oral pontine reticular nucleus (64.5%), pedunculopontine tegmental nucleus (55.7%), and dorsal raphe nucleus (54.0%) but not in the nucleus locus coeruleus. The activation of G-proteins by carbachol was concentration-dependent and antagonized by atropine, demonstrating that G-proteins were activated via mAChR stimulation. The results provide the first direct measures of mAChR-activated G-proteins in brainstem nuclei known to contribute to REM sleep generation.


A simple identification of novel carbonyl reducing enzymes in the metabolism of the tobacco specific carcinogen NNK.
Tobacco smoking is the most widely known cause of human cancer-related death worldwide. NNK is one of the proved human carcinogens contributing to the development of several types of cancer. The carcinogenic effect of NNK depends on the metabolic pathway. Reduction of NNK by carbonyl reducing enzymes leads to the formation of NNAL. This pathway is generally regarded as detoxification pathway although the conditions and circumstances are quite complicated - the process depends on a formed enantiomer of NNAL. In this study a novel method for the determination of the metabolite NNAL was developed. This makes it possible to findand characterize carbonyl reducing enzymes that are involved in NNK metabolism. This simple HPLC method uses conventional HPLC instrumentation and is designed mainly for biochemical laboratories. A new microsomal carbonyl reducing enzyme participating in the metabolism of NNK in vitro has been described. Its activity was compared with other carbonyl reducing enzymes taking part in the biotransformation of NNK.


Bioengineered Temporomandibular Joint Disk Implants: Study Protocol for a Two-Phase Exploratory Randomized Preclinical Pilot Trial in 18 Black Merino Sheep (TEMPOJIMS).
Preclinical trials are essential to test efficacious options to substitute the temporomandibular joint (TMJ) disk. The contemporary absence of an ideal treatment for patients with severe TMJ disorders can be related to difficulties concerning the appropriate study design to conduct preclinical trials in the TMJ field. These difficulties can be associated with the use of heterogeneous animal models, the use of the contralateral TMJ as control, the absence of rigorous randomized controlled preclinical trials with blinded outcomes assessors, and difficulties involving multidisciplinary teams. This study aims to develop a new, reproducible, and effective study design for preclinical research in the TMJ domain, obtaining rigorous data related to (1) identify the impact of bilateral discectomy in black Merino sheep, (2) identify the impact of bilateral discopexy in black Merino sheep, and (3) identify the impact of three different bioengineering TMJ discs in black Merino sheep. A two-phase exploratory randomized controlled preclinical trial with blinded outcomes is proposed. In the first phase, nine sheep are randomized into three different surgical bilateral procedures: bilateral discectomy, bilateral discopexy, and sham surgery. In the second phase, nine sheep are randomized to bilaterally test three different TMJ bioengineering disk implants. The primary outcome is the histological gradation of TMJ. Secondary outcomes are imaging changes, absolute masticatory time, ruminant time per cycle, ruminant kinetics, ruminant area, and sheep weight. Previous preclinical studies in this field have used the contralateral unoperated side as a control, different animal models ranging from mice to a canine model, with nonrandomized, nonblinded and uncontrolled study designs and limited outcomes measures. The main goal of this exploratory preclinical protocol is to set a new standard for future preclinical trials in oromaxillofacial surgery, particularly in the TMJ field, by proposing a rigorous design in black Merino sheep. The authors also intend to test the feasibility of pilot outcomes. The authors expect to increase the quality of further studies in this field and to progress in future treatment options for patients undergoing surgery for TMJ disk replacement. The study has commenced, but it is too early to provide results or conclusions.


Mechanical control of magnetism in oxygen deficient perovskite SrTiO3.
Mechanical control of magnetism in perovskite oxides is an important and promising approach in spintronics. Based on the first-principles calculations, we demonstrate that a negative pressure leads to a great enhancement of magnetic moment in deficient SrTiO3 with oxygen vacancies, whereas a positive pressure results in the gradual disappearance of magnetism. Spin charge density, Bader charge analysis and electronic density of states successfully elucidate the origin and underlying physics of the enhancement and disappearance of magnetism. It is found that the split electronic states of dz(2), dyz and dzx in the 3d orbitals of Ti atoms remarkably contribute to the occupancy of majority spin states under negative pressure, which induces a large magnetic moment. Under positive pressure, however, the equal occupancy of both majority and minority t2g and eg states leads to the disappearance of magnetization. In addition, both negative and positive pressures can largely lower the vacancy formation enthalpy, suggesting that the oxygen vacancy is preferable with pressure. Our findings may provide a mechanism to achieve the pressure control of magnetization in nonmagnetic perovskite oxides.


Cognitive therapy for depression with individuals with intellectual disabilities.
The increase in research into psychopathology in people with intellectual disability has recently spread to include depression. Several reports have appeared on the assessment of depression in the client group and there is a pressing need for research into treatment of depression in people with intellectual disability. The present paper reviews cognitive behaviour therapy for depression and reports on its adaptation for people with intellectual disability. Two case studies of individuals with mild intellectual disability illustrate the clinical applications. All the elements of cognitive behaviour therapy for depression were maintained and simplified. Both subjects were able to monitor their feelings of depression and subject 2 monitored the frequency of suicidal thoughts. Improvements were seen in both cases on the Zung Depression Inventory and daily monitoring of depressive feelings.


Ouabain potentiates the activation of ERK1/2 by carbachol in parotid gland epithelial cells; inhibition of ERK1/2 reduces Na(+)-K(+)-ATPase activity.
The Na(+)-K(+)-ATPase and the ERK1/2 pathway appear to be linked in some fashion in a variety of cells. The Na(+)-K(+)-ATPase inhibitor ouabain can promote ERK1/2 activation. This activation involves Src, intracellular Ca(2+) concentration ([Ca(2+)](i)) elevation, reactive oxygen species (ROS) generation, and EGF receptor (EGFR) transactivation. In contrast, ERK1/2 can mediate changes in Na(+)-K(+)-ATPase activity and/or expression. Thus signaling between ERK1/2 and Na(+)-K(+)-ATPase can occur from either direction. Whether such bidirectionality can occur within the same cell has not been reported. In the present study, we have demonstrated that while ouabain (1 mM) produces only a small ( approximately 50%) increase in ERK1/2 phosphorylation in freshly isolated rat salivary (parotid acinar) epithelial cells, it potentiates the phosphorylation of ERK1/2 by submaximal concentrations of carbachol, a muscarinic receptor ligand that initiates fluid secretion. Although ERK1/2 is only modestly phosphorylated when cells are exposed to 1 mM ouabain or 10(-6) M carbachol, the combination of these agents promotes ERK1/2 phosphorylation to near-maximal levels achieved by a log order carbachol concentration. These effects of ouabain are distinct from Na(+)-K(+)-ATPase inhibition by lowering extracellular K(+), which promotes a rapid and large increase in ERK1/2 phosphorylation. ERK1/2 potentiation by ouabain (EC(50) approximately 100 muM) involves PKC, Src, and alterations in [Ca(2+)](i) but not ROS generation or EGFR transactivation. In addition, inhibition of ERK1/2 reduces Na(+)-K(+)-ATPase activity (measured as stimulation of Qo(2) by carbachol and the cationophore nystatin). These results suggest that ERK1/2 and Na(+)-K(+)-ATPase may signal to each other in each direction under defined conditions in a single cell type.


Complete genome sequencing of newly isolated thermotolerant Corynebacterium glutamicum N24 provides a new insights into its thermotolerant phenotype.
To understand the genetic background of thermotolerance, we determined the complete genome sequence of a thermotolerant Corynebacterium glutamicum N24 strain isolated from soil. The whole genome based phylogenetic analysis between N24 and other related species revealed that N24 diverged from other C. glutamicum strains at earlier stages. Comparisons of thermotolerance between N24 and its related species showed that N24 and Corynebacterium efficiens YS-314 have a higher thermotolerance than Corynebacterium callunae DSM 20147 and C. glutamicum KY9002. In order to understand the link between a particular genetic background and thermotolerance, we compared the genomes of these four strains by mapping their genomes onto the N24 chromosome. We then determined the genes that were conserved in the thermotolerant species. Our results indicated the specific presence of glutathione-dependent aldehyde dehydrogenase, two sortase homologs, and lipid synthesis-related genes in the genomes of thermotolerant strains, YS-314 and N24. Therefore, these genes may be responsible for the differences in their thermotolerant phenotypes.


Changes to transtibial amputee gait with a weighted backpack on multiple surfaces.
Modern prosthetic technology and rehabilitation practices have enabled people with lower extremity amputations to participate in almost all occupations and physical activities. Carrying backpack loads can be an essential component for many of these jobs and activities; however, amputee gait with backpack loads is poorly understood. This knowledge gap must be addressed in order to further improve an individual's quality of living through changes in rehabilitation programs and prosthesis development. Ten male, unilateral, K4-level (ability or potential for prosthetic ambulation that exceeds basic ambulation skills, exhibiting high impact, stress, or energy levels), transtibial amputees completed ten walking trials at a self-selected pace on simulated uneven ground, ramp ascent, and ramp descent. Five trials were with a 24.5 kg backpack load and five trials without. Temporal-spatial parameters and kinematic peak values for the ankle, knee, hip, pelvis, and trunk were collected and analyzed for differences between backpack conditions. Each surface had novel findings not found on the other surfaces. However differences in temporal-spatial parameters were congruent with the literature on able bodied individuals. Pelvis and trunk angular velocities decreased with the backpack. Hip flexion on both limbs increased during weight acceptance while wearing the backpack, a common adaptation seen in able-bodied individuals on level ground. A 24.5 kg backpack load can be accommodated by transtibial amputees at the K4 functional level. Future studies on load carriage and gait training programs should include incline and descent due to the increased difficulty. Rehabilitation programs should verify hip and knee flexor strength and work to reduce intact limb reliance.


Nobiletin promotes the pyroptosis of breast cancer via regulation of miR-200b/JAZF1 axis.
Nobiletin is a polymethoxylated flavone present in citrus fruits, which has been reported to have inhibitory effects on tumorigenesis of cancers. However, the biological function of nobiletin in breast cancer (BC) is largely unknown. To investigate the effect of nobiletin on growth of BC cells, the cell viability of BC was measured by MTT assay. In addition, gene and protein expressions were detected by qRT-PCR and western blot, respectively. The apoptosis and pyroptosis of BC cells were tested by flow cytometry. Finally, the correlation between miR-200b and JAZF1 was detected by dual luciferase report. The data indicated that nobiletin inhibited the proliferation of BC cells in a dose-dependent manner. Moreover, miR-200b mimics-induced pyroptosis of BC cells was further increased by nobiletin. Meanwhile, JAZF1 was found to be the target of miR-200b. Moreover, nobiletin induced apoptosis and pyroptosis of BC cells via miR-200b/JAZF1/NF-κB axis. In conclusion, nobiletin inhibited the tumorigenesis of BC via regulation of miR-200b/JAZF1 axis. Thus, nobiletin might serve as a new agent for the treatment of BC.


Erbium:YAG laser skin resurfacing: preliminary clinical evaluation.
Each of the increasing number of resurfacing lasers uses a unique strategy to produce tissue ablation. Erbium:YAG (Er:YAG) lasers have been used in other applications for precise tissue removal with little thermal effect. Recovery time, duration of erythema, and clinical improvement were evaluated using an Er:YAG resurfacing laser (2.94-microm wavelength, 350-microsec pulse, 2 J, 3-5-mm spot). Twenty-five patients were treated with two passes to the full face and 3 to 5 passes to the most affected aesthetic unit. At each follow-up visit, percent epithelialization, erythema, and swelling were graded, and the presence or absence of complications was noted. Clinical improvement was evaluated at 6 months by optical profilometry on a subset of patients. Er:YAG resurfacing produced a transient whitening of dermis followed by a resumption of pink appearance. The surgical end point was judged by elimination of visible rhytids or presence of punctate bleeding. Bleeding from the dermal surface was encountered less than customarily in dermabrasion, but more than seen with carbon dioxide laser resurfacing. A moderate amount of tissue shrinkage was observable during the treatment. Mean period to full epithelialization was 6.9+/-0.97 days (range, 5-9 days). The mean duration of erythema (4.24+/-1.5 weeks) was relatively short compared with carbon dioxide resurfacing. Clinical improvement was 44+/-30% in the lateral canthal area and 55+/-22% in the upper lip area. There were no infections or hypertrophic scars. Hyperpigmentation and hypopigmentation was seen in 24% and 12% of patients respectively. Er:YAG resurfacing is a reliable means of obtaining rhytid improvement with less recovery time and duration of erythema compared with carbon dioxide resurfacing. The technique is significantly different from carbon dioxide resurfacing in selection of end point, number of passes, and energy settings.


[Ischemic cadiopathy in patients undergoing chronic hemodialysis].
We report a retrospective study of patients on chronic hemodialysis in whom a diagnosis of ischemic heart disease had been established. We compared the findings on coronary cineangiography and the treatment (medical only, surgical revascularisation [CABG] and percutaneous transluminal coronary angioplasty [PTCA]) with the early and late evolution. From a population of 2,287 patients on chronic hemodialysis treatment during the 5 year period 1994-1999, 83 patients who underwent coronary cineangiography after starting dialysis were selected. Their mean age was 63 +/- 9.4 (39-80) and the mean time on hemodialysis was 6 years (6 months-19 years). 65 patients (78%) had severe coronary lesions, 40% of whom had three vessel disease. 14 patients had medical treatment only (group 1), 23 had CABG (group 2) and 28 PTCA (group 3). Mortality within 30 days of intervention was 13% in group 2 and 21.4% in group 3. Global survival at two years was 82% in group 2 and 69% in group 3. Survival without angina at 6 and 24 months were 69% and 46% in group 2 and 55% and 22% in group 3 respectively. Survival without acute myocardial infarction at 6 and 24 months was 95% and 95% in group 2 and 89% and 64% in group 3. Data analysis using Cox proportional risk model showed that PTCA posed a higher risk of angina and death than CABG. Surgery yielded better early and later results than angioplasty even in those patients with severe coronary artery disease.


Management and control of microbiologically influenced corrosion (MIC) in the oil and gas industry-Overview and a North Sea case study.
Microbiologically influenced corrosion (MIC) is the terminology applied where the actions of microorganisms influence the corrosion process. In literature, terms such as microbial corrosion, biocorrosion, microbially influenced/induced corrosion, and biodegradation are often applied. MIC research in the oil and gas industry has seen a revolution over the past decade, with the introduction of molecular microbiological methods: (MMM) as well as new industry standards and procedures of sampling biofilm and corrosion products from the process system. This review aims to capture the most important trends the oil and gas industry has seen regarding MIC research over the past decade. The paper starts out with an overview of where in the process stream MIC occurs - from the oil reservoir to the consumer. Both biotic and abiotic corrosion mechanisms are explained in the context of managing MIC using a structured corrosion management (CM) approach. The corrosion management approach employs the elements of a management system to ensure that essential corrosion control activities are carried out in an effective, sustainable, well-planned and properly executed manner. The 3-phase corrosion management approach covering of both biotic and abiotic internal corrosion mechanisms consists of 1) corrosion assessment, 2) corrosion mitigation and 3) corrosion monitoring. Each of the three phases are described in detail with links to recent field cases, methods, industry standards and sampling protocols. In order to manage the corrosion threat, operators commonly use models to support decision making. The models use qualitative, semi-quantitative or quantitative measures to help assess the rate of degradation caused by MIC. The paper reviews four existing models for MIC Threat Assessment and describe a new model that links the threat of MIC in the oil processing system located on an offshore platform with a Risk Based Inspection (RBI) approach. A recent field case highlights and explains the conflicting historic results obtained through serial dilution of culture media using the most probable number (MPN) method as compared to data obtained from corrosion monitoring and the quantitative polymerase chain reaction (qPCR) method. Results from qPCR application in the field case have changed the way MIC is monitored on the oil production facility in the North Sea. A number of high quality resources have been published as technical conference papers, books, educational videos and peer-reviewed scientific papers, and thus we end the review with an updated list of state-of-the-art resources for anyone desiring to become more familiar with the topic of MIC in the upstream oil and gas sector.


HER2 in situ hybridization in gastric and gastroesophageal adenocarcinoma: comparison of automated dual ISH to FISH.
Patients with gastric and gastroesophageal junction (GEJ) adenocarcinomas that are HER2 positive by immunohistochemistry (IHC) or in situ hybridization show a significant survival benefit with trastuzumab therapy. In situ hybridization is traditionally done by fluorescence in situ hybridization (FISH), despite some limitations. An alternative is the dual in situ hybridization (Dual ISH) technique that is fully automated and uses differentially labeled CEP17 and HER2 probes that can be read by light microscopy on 1 slide. The aim of this study was to assess the utility of Dual ISH in gastric/GEJ cancer and to compare the results with those obtained by IHC and FISH. Cases of gastric/GEJ adenocarcinoma were analyzed by IHC, FISH, and Dual ISH and the correlation between methods calculated. Results for 50 patients were available. There was a 98% (49/50) concordance rate between Dual ISH and FISH. One discrepant case was nonamplified by FISH but showed focal amplification by Dual ISH. Discrepancy was attributed to tumor heterogeneity, which was a frequent finding (78% of HER2-positive cases). There was excellent correlation between Dual ISH and FISH for assessment of HER2 amplification. Dual ISH was rapid, easy to interpret, and maintained cell morphology, which was valuable in identifying tumor heterogeneity.


Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy.
Emerging evidence suggests a potential role of neutrophil extracellular traps (NETs) in linking sterile inflammation and thrombosis. We hypothesized that NETs would be induced during myocardial ischemia-reperfusion (I/R), and NET-mediated microthrombosis may contribute to myocardial "no-reflow". Male Wistar rats were randomly divided into I/R control, DNase (DNase I, 20 μg/rat), recombinant tissue-type plasminogen activator (rt-PA, 420 μg/rat), DNase + rt-PA, and sham control groups after 45-min myocardial ischemia. In situ NET formation, the anatomic "no re-flow" area, and infarct size were evaluated immediately after 3 h of reperfusion. Long-term left ventricular (LV) functional and histological analyses were performed 45 days after operation. Compared with the I/R controls, the DNase + rt-PA group exhibited reduced NET density [8.38 ± 1.98 vs. 26.86 ± 3.07 (per 200 × field), P < 0.001] and "no-flow" area (15.22 ± 0.06 vs. 34.6 ± 0.05%, P < 0.05) in the ischemic region, as well as reduced infarct size (38.39 ± 0.05 vs. 71.00 ± 0.03%, P < 0.001). Additionally, compared with the I/R controls, DNase + rt-PA treatment significantly ameliorated I/R injury-induced LV remodeling (LV ejection fraction: 64.22 ± 3.37 vs. 33.81 ± 2.98%, P < 0.05; LV maximal slope of the LV systolic pressure increment: 3,785 ± 216 vs. 2,596 ± 299 mmHg/s, P < 0.05). The beneficial effect was not observed in rats treated with DNase I or rt-PA alone. Our study provides evidence for the existence of NETs in I/R-challenged myocardium and confirms the long-term benefit of a novel DNase-based reperfusion strategy (DNase I + rt-PA), which might be a promising option for the treatment of myocardial I/R injury and coronary no-reflow.


ABC Transporters and the Alzheimer's Disease Enigma.
Alzheimer's disease (AD) is considered the "disease of the twenty-first century." With a 10-fold increase in global incidence over the past 100 years, AD is now reaching epidemic proportions and by all projections, AD patient numbers will continue to rise. Despite intense research efforts, AD remains a mystery and effective therapies are still unavailable. This represents an unmet need resulting in clinical, social, and economic problems. Over the last decade, a new AD research focus has emerged: ATP-binding cassette (ABC) transporters. In this article, we provide an overview of the ABC transporters ABCA1, ABCA2, P-glycoprotein (ABCB1), MRP1 (ABCC1), and BCRP (ABCG2), all of which are expressed in the brain and have been implicated in AD. We summarize recent findings on the role of these five transporters in AD, and discuss their potential to serve as therapeutic targets.


BCR-ABL Tyrosine Kinase Inhibitors: Which Mechanism(s) May Explain the Risk of Thrombosis?
Imatinib, the first-in-class BCR-ABL tyrosine kinase inhibitor (TKI), had been a revolution for the treatment of chronic myeloid leukemia (CML) and had greatly enhanced patient survival. Second- (dasatinib, nilotinib, and bosutinib) and third-generation (ponatinib) TKIs have been developed to be effective against BCR-ABL mutations making imatinib less effective. However, these treatments have been associated with arterial occlusive events. This review gathers clinical data and experiments about the pathophysiology of these arterial occlusive events with BCR-ABL TKIs. Imatinib is associated with very low rates of thrombosis, suggesting a potentially protecting cardiovascular effect of this treatment in patients with BCR-ABL CML. This protective effect might be mediated by decreased platelet secretion and activation, decreased leukocyte recruitment, and anti-inflammatory or antifibrotic effects. Clinical data have guided mechanistic studies toward alteration of platelet functions and atherosclerosis development, which might be secondary to metabolism impairment. Dasatinib, nilotinib, and ponatinib affect endothelial cells and might induce atherogenesis through increased vascular permeability. Nilotinib also impairs platelet functions and induces hyperglycemia and dyslipidemia that might contribute to atherosclerosis development. Description of the pathophysiology of arterial thrombotic events is necessary to implement risk minimization strategies.


Pterional or Subfrontal Access for Proximal Vascular Control in Anterior Interhemispheric Approach for Ruptured Pericallosal Artery Aneurysms at Risk of Premature Rupture.
Cases of a ruptured pericallosal artery aneurysm with a high risk of intraoperative premature rupture and technical difficulties for proximal vascular control require a technique for the early and safe establishment of proximal vascular control. A combined pterional or subfrontal approach exposes the bilateral A1 segments or the origin of the ipsilateral A2 segment of the anterior cerebral artery (ACA) for proximal vascular control. Proximal control far from the ruptured aneurysm facilitates tentative clipping of the rupture point of the aneurysm without a catastrophic premature rupture. The proximal control is then switched to the pericallosal artery just proximal to the aneurysm and its intermittent clipping facilitates complete aneurysm dissection and neck clipping. Three such cases are reported: a ruptured pericallosal artery aneurysm with a contained leak of the contrast from the proximal side of the aneurysm, a low-lying ruptured pericallosal artery aneurysm with irregularities on its proximal wall, and a multilobulated ruptured pericallosal artery aneurysm with the parasagittal bridging veins hindering surgical access to the proximal parent artery. In each case, the proposed combined pterional-interhemispheric or subfrontal-interhemispheric approach was successfully performed to establish proximal vascular control far from the ruptured aneurysm and facilitated aneurysm clipping via the interhemispheric approach. When using an anterior interhemispheric approach for a ruptured pericallosal artery aneurysm with a high risk of premature rupture, a pterional or subfrontal approach can be combined to establish early proximal vascular control at the bilateral A1 segments or the origin of the A2 segment.


Organisational closure in biological organisms.
The central aim of this paper consists in arguing that biological organisms realize a specific kind of causal regime that we call "organisational closure"; i.e., a distinct level of causation, operating in addition to physical laws, generated by the action of material structures acting as constraints. We argue that organisational closure constitutes a fundamental property of biological systems since even its minimal instances are likely to possess at least some of the typical features of biological organisation as exhibited by more complex organisms. Yet, while being a necessary condition for biological organization, organisational closure underdetermines, as such, the whole set of requirements that a system has to satisfy in order to be taken as a paradigmatic example of organism. As we suggest, additional properties, as modular templates and control mechanisms via dynamical decoupling between constraints, are required to get the complexity typical of full-fledged biological organisms.


The future lies in chiral purity: a perspective.
Racemates are fixed-dose combinations of stereoisomers. Each isomer may have different pharmacokinetic or pharmacodynamic properties. Recent research has allowed appreciation of the need to purify racemates and develop useful unichiral molecules. Some examples are: S-amlodipine besylate, S-atenolol, S-metoprolol succinate, S-pantoprazole sodium and R-ondansetron hydrochloride.


A fourth heavy chain variable region subgroup, w, with 2 variants defined by an induced auto-antiserum in the rabbit.
An antiserum recognizing previously undescribed antigenic determinants (designated subgroup w) of the heavy chain VH region was produced by immunizing a rabbit, homozygous for the VH haplotype a1x-y- with IgG from another a1x-y- rabbit, suppressed for a1. The antiserum gives a single fused precipitin band against sera from homozygous rabbits suppressed for the a1, a2, or a3 allotypes. By gel diffusion analysis, the determinant was found to be distinct from previously described a, x, and y allotypes, and was detectable on IgG, F(ab')2 gamma and the gamma-heavy chain. Radioinhibition analysis revealed 2 patterns of inhibition suggesting 2 variants of w that are closely linked to VH allotypes. Variant w34 was detected at very low levels (0.042 to 5.6 micrograms/mg IgG) in normal rabbits expressing the a1x-y-, a1-y33,30, and a3x32y- VH haplotypes. Variant w35 was detectable in a 2x32y33,- rabbits. Sera from homozygous a allotype-suppressed rabbits representing each of the 4 VH haplotypes similarly exhibited either w34 or w35 patterns of inhibition as described above. The level of w34 in a1- and a3-suppressed rabbits exhibited a dramatic 230-fold median increase. In contrast, w35 levels for a2-suppressed rabbits fell within the normal range. In addition to reacting with essentially all normal and suppressed sera, the antiserum reacted with preimmune serum from the same rabbit. Thus, anti-w represents an induced auto-antibody. These observations are further discussed with regard to rabbit and mouse VH populations.


Therapy with bortezomib plus dexamethasone induces osteoblast activation in responsive patients with multiple myeloma.
Bortezomib is a novel proteasome inhibitor that has shown marked antitumor effects in patients with multiple myeloma (MM). We evaluated the feasibility and efficacy of bortezomib plus dexamethasone (BD) therapy and assessed bone metabolism in relapsed or refractory MM. Fourteen patients received 1.3 mg/m2 bortezomib on days 1, 4, 8, and 11 along with 20 mg/dose of dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 in a 21-day cycle. After 1 to 3 cycles of BD therapy, 9 patients (64%) achieved an objective response (5 very good partial responses and 4 partial responses). Notably, a rapid increase in the serum concentration of alkaline phosphatase (ALP) was observed in 6 of the treatment-responsive patients. Moreover, serum levels of bone-formation markers (bone-specific ALP and osteocalcin) significantly increased in 5 and 2 responsive patients, respectively. Radiographic examination showed improvement in bone lesions, suggesting that BD therapy induces osteoblast activation in responders. Adverse events included thrombocytopenia of grades 1 to 3, peripheral neuropathy of grades 1 to 2, and grade 3 ileus and were transient and manageable. Although severe lung injury has been reported among Japanese patients treated with bortezomib, no pulmonary complications were observed during BD therapy. Our results suggest that BD therapy is a safe and promising therapeutic approach for Japanese patients with MM.


The variants of the protein toxins abrin and ricin. A useful guide to understanding the processing events in the toxin transport.
Kinetic data on inhibition of protein synthesis in thymocyte by three abrins and ricin have been obtained. The intrinsic efficiencies of A chains of four toxins to inactivate ribosomes, as analyzed by ki-versus-concentration plots were abrin II, III > ricin > abrin I. The lag times were 90, 66, 75 and 105 min at a 0.0744 nM concentration of each of abrin I, II, III and ricin, respectively. To account for the observed differences in the dose-dependent lag time, functional and structural variables of toxins such as binding efficiency of B chains to receptors and low-pH-induced structural alterations have been analyzed. The association constants obtained by stopped flow studies showed that abrin-I (4.13 x 10(5) M-1 s-1) association with putative receptor (4-methylumbelliferyl-alpha-D-galactoside) is nearly two times more often than abrin III (2.6 x 10(5) M-1 s-1) at 20 degrees C. Equilibrium binding constants of abrin I and II to thymocyte at 37 degrees C were 2.26 x 10(7) M-1 and 2.8 x 107 M-1 respectively. pH-induced structural alterations as studied by a parallel enhancement in 8-anilino-L-naphthalene sulfonate fluorescence revealed a high degree of qualitative similarity. These results taken with a nearly identical concentration-independent lag time (minimum lag of 41-42 min) indicated that the binding efficiencies and internalization efficiencies of these toxins are the same and that the observed difference in the dose-dependent lag time is causally related to the proposed processing event. The rates of reduction of inter-subunit disulfide bond, an obligatory step in the intoxication process, have been measured and compared under a variety of conditions. Intersubunit disulfide reduction of abrin I is fourfold faster than that of abrin II at pH 7.2. The rate of disulfide reduction in abrin I could be decreased 11-fold by adding lactose, compared to that without lactose. The observed differences in the efficiencies of A chains, the dose-dependent lag period, the modulating effect of lactose on the rates of disulfide reduction and similarity in binding properties make the variants a valuable tool to probe the processing events in toxin transport in detail.


Saffron supplements modulate serum pro-oxidant-antioxidant balance in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial.
We have investigated the effect of a saffron supplement, given at a dose of 100 mg/kg, on prooxidant-antioxidant balance (PAB) in individuals with metabolic syndrome. A randomized, placebo-controlled trial design was used in 75 subjects with metabolic syndrome who were randomly allocated to one of two study groups: (1) the case group received 100mg/kg saffron and (2) the placebo control group received placebo for 12 weeks. The serum PAB assay was applied to all subjects before (week 0) and after (weeks 6 and 12) the intervention. There was a significant (p=0.035) reduction in serum PAB between week 0 to week 6 and also from week 0 to week 12. Saffron supplements can modulate serum PAB in subjects with metabolic syndrome, implying an improvement in some aspects of oxidative stress or antioxidant protection.


An integrated surveillance system of road traffic injuries in the Lazio region of Italy: results of a 5-year study (2001-2005).
Road traffic injuries represent a relevant public-health problem. In the Lazio region of Italy, a surveillance system was activated. The aim of this work is to describe the surveillance system and report the health information in terms of temporal trends for the 5-year period 2001-2005. We identified all emergency department (ED) visits in the emergency database and then linked them with hospital discharges and mortality registry. From the integrated database, we calculated the rates of emergency room visits, of hospital admissions, and of mortality, reporting the temporal trends. Between 2001 and 2005 the rate of ED visits was 3151 per 100,000 inhabitants. Hospitalisation rates showed a significant decreasing trend. The surveillance identified 22% more deaths in the study period than reported by the official statistics. The surveillance revealed a decreasing trend for hospital admissions and a decline in deaths in 2003 concurrent to the introduction of the driver's licence point system.


Medication Consumption Patterns and Polypharmacy among Community-Dwelling Elderly in Lomé (Togo) in 2017.
In the sub-Saharan African, region of the world with a fast growing aging population and where the use of herbal products is very common, there is a paucity of data on medication consumption patterns among elderly people. The objective of this study was to assess the prevalence of polypharmacy and its associated factors among community-dwelling elderly in Lomé, Togo, in 2017. A cross-sectional study was conducted from March to June 2017 in Lomé, Togo among people aged 60 years and older. The Respondent Driven Sampling method was used to recruit participants. Data on socio-demographic characteristics and medication consumption patterns, including the use of medicinal plants and dietary supplements, were collected using a standardized questionnaire during a face-to-face interview at participants' home. Descriptive and binary logistic regression analyses were performed. A total of 370 participants with median age 65 years, (IQR: 62-71) were enrolled in the study. Almost three elderly in five (57.6%) were multimorbid (had two or more chronic diseases). Conventional drugs (78.4%), medicinal plants (14.3%) and other dietary supplements (9.5%) were used by participants. The prevalence of polypharmacy was 22.7% (95% CI: 18.5-27.3%). Concurrent use of conventional drugs and medicinal plants or other dietary supplements was observed among 17.0% of participants and 67.3% reported self-medication. Multimorbidity (aOR = 4.55; 95% CI: [2.42-8.54]) and female sex (aOR = 1.86; 95% CI: [1.00-3.47]) were associated with polypharmacy. One elderly in five uses five or more medications in Togo. Further studies are needed to assess drug-drug interactions and herb-drug interactions among this population.


Tympanometric findings in patients with adenoid hyperplasia, chronic sinusitis and tonsillitis.
Tympanograms were done on 120 patients with adenoid hyperplasia, chronic sinusitis and chronic tonsillitis to measure the middle-ear pressure as a parameter to eustachian tube function. The results were compared with those obtained in 50 normal subjects. The statistical significance of the mean values of middle-ear pressure is very highly significant in patients with adenoid hyperplasia, significant in chronic sinusitis group and insignificant in patients with chronic tonsillitis, as compared to the normal control group. Hence, eustachian tube dysfunction is maximum in patients with obstructing adenoids, less in chronic sinusitis and least in chronic tonsillitis.


Dbp5p/Rat8p is a yeast nuclear pore-associated DEAD-box protein essential for RNA export.
To identify Saccharomyces cerevisiae genes important for nucleocytoplasmic export of messenger RNA, we screened mutant strains to identify those in which poly(A)+ RNA accumulated in nuclei under nonpermissive conditions. We describe the identification of DBP5 as the gene defective in the strain carrying the rat8-1 allele (RAT = ribonucleic acid trafficking). Dbp5p/Rat8p, a previously uncharacterized member of the DEAD-box family of proteins, is closely related to eukaryotic initiation factor 4A(eIF4A) an RNA helicase essential for protein synthesis initiation. Analysis of protein databases suggests most eukaryotic genomes encode a DEAD-box protein that is probably a homolog of yeast Dbp5p/Rat8p. Temperature-sensitive alleles of DBP5/RAT8 were prepared. In rat8 mutant strains, cells displayed rapid, synchronous accumulation of poly(A)+ RNA in nuclei when shifted to the non-permissive temperature. Dbp5p/Rat8p is located within the cytoplasm and concentrated in the perinuclear region. Analysis of the distribution of Dbp5p/Rat8p in yeast strains where nuclear pore complexes are tightly clustered indicated that a fraction of this protein associates with nuclear pore complexes (NPCs). The strong mutant phenotype, association of the protein with NPCs and genetic interaction with factors involved in RNA export provide strong evidence that Dbp5p/Rat8p plays a direct role in RNA export.


Effects of eye-acupuncture combined with rehabilitation training for poststroke dyskinesia: A protocol for systematic review and meta-analysis.
Poststroke dyskinesia is the most common clinical symptom after stroke, which greatly affects the patients' daily life. Eye-acupuncture is an effective method for stroke. And the rehabilitation training has been widely used for patients suffer from stroke. However, whether eye-acupuncture combined with rehabilitation training has greater clinical efficacy for poststroke dyskinesia is still unknown. Our aim in this systematic review was to evaluate the clinical efficacy of eye-acupuncture combined with rehabilitation training (EACRT) as a treatment for dyskinesia after stroke. We will search the following 4 databases of registered trials and 7 electronic databases from inception to March 2021:Cochrane Stroke Group, Cochrane Central Register of Controlled, the World Health Organization International Clinical Trials Registry Platform, the Chinese Clinical Trial Registry; PubMed, MEDLINE, Embase, CNKI, VIP, WanFang, and CBM. All relevant randomized controlled trials focus on EACRT will be included. The primary outcome will be the Fugl-Meyer Assessment. The Secondary outcomes will include Activity of Daily Living, clinical effective rate and the Visual Analogue Score. Two reviewers will independently conduct the Study selection and data extraction. The data synthesis and assessment of risk of bias will be performed by RevMan5.2. The ethical approval is unnecessary that systematic review is based on published articles other than patients. The results of this meta-analysis will be published in an open access (OA) journal according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA). CRD42020168278.


The biomechanical study of the influence to the forefoot plantar pressure of the first tarsometatarsal joint fracture-dislocation fixed by three different implants.
To study the influence of forefoot plantar pressure of the first tarsometatarsal joint fracture-dislocation by three different implants to provide experimental reference in selecting implants. Eight fresh foot specimens were made into the models of the first tarsometatarsal joint fracture-dislocation, which were fixed with 3.5 mm cortical screw, 1/4 tubular plate and compressive staple in turn. After the loading of 600N, the changes of the plantar pressure in forefoot were measured by the method of the F-scan plantar pressure system. After first tarsometatarsal joint fracture-dislocation, the peak pressure under the first metatarsal head would decrease, while the pressure under the second metatarsal head would increase(P<0.05). When the first tarsometatarsal joint was fixed with screw or plate respectively; the peak pressure under the two metatarsal heads would tend to be normal. However, the staple fixation would show the statistical significant difference, although the peak pressure under the first and second metatarsal heads were recovered in some extent(P<0.05). After the first tarsometatarsal joint fracture-dislocation, the plantar pressure might be compensated partly by the adjacent metatarsal heads. While the first tarsometatarsal joint fracture-dislocation was fixed by screw or plate, the plantar pressure of the forefoot would return to the normal state. However, if the joint was fixed by the staple, it would still be difficult to return the plantar pressure to be normal.


Increased cholesterol-ester formation during forced cholesterol synthesis in rat hepatocytes.
By comparing the incorporation of 3H20 and [14C]mevalonate into cholesterol in suspensions of rat hepatocytes, it was calculated that the cholesterol biosynthesis could be stimulated 4--7-fold by addition of mevalonate. The addition of 3.3--6.7 mM mevalonate also caused a 5--6-fold increase in the proportion of newly synthesized cholesterol that was esterifield. The esterification of radioactive cholesterol, entering the cells by exchange with surrounding plasma lipoproteins was also increased, indicating that a true increase in the rate of cholesterol ester formation rather than a more selective utilization of newly synthesized cholesterol for esterification, occurred. The increase in cholesterol esterification was not abolished by cycloheximide, indicating that it did not require an increased synthesis of cholesterol esterifying enzyme. Instead the data suggest that the supply of cholesterol to the esterifiable pool may be an important factor, regulating the rate of cholesterol ester formation in rat liver. The addition of 0.5 mM oleic acid to the medium did not increase the degree of cholesterol esterification significantly, whereas 2 mM oleic acid bound to 1% albumin increased the proportion of newly synthesized cholesterol that was esterified, by about 70%. The cells secreted radioactive cholesterol esters into the medium. Cycloheximide inhibited this secretion to about 80% but did not affect the rate at which newly synthesized cholesterol was transferred to surrounding plasma lipoproteins.


Isolation and characterization of recessive, constitutive mutations for repressible acid phosphatase synthesis in Saccharomyces cerevisiae.
Two new classes of mutants containing recessive constitutive mutations, phoT and phoU, that affect the repressible acid phosphatase (EC 22.214.171.124) in Saccharomyces cerevisiae were isolated along with many previously known phoR mutants. These loci segregated independently from each other, from the phoS gene, and from another regulatory gene, phoD, that exerts positive control for acid phosphatase synthesis. The phoR and phoU mutations showed the same genetic behavior in the double mutants, which also contained the phoS or phoD mutation. In contrast, the phoT mutation could not suppress the phoS mutation, which caused a loss of enzyme activity. Many mutant alleles of phoR and phoU were found to be temperature sensitive (ts), whereas those of phoT were not. These ts mutants were constitutive at 35 C but severely repressible at 25 C. These facts strongly suggest that both the phoR and phoU genes are cooperatively concerned with the production of the repressor, whereas the phoT gene might be involved in another mechanism distinct from that in which phoR and phoU are involved. No single mutation of phoR, phoT, or phoU result in an enzyme level comparable to that of fully derepressed enzyme activities, and the temperature sensitivity of the ts phoR and ts phoU mutations in such combinations almost disappeared. In addition to these observations, since the ts phoR phoS and ts phoU phoS double mutants showed some enzyme synthesis at 25 C under derepressing conditions, a defect in the ts mutant repressors was strongly suggested, even at 25 C.


Comprehensive Analysis to Identify the Encoded Gens of Sodium Channels as a Prognostic Biomarker in Hepatocellular Carcinoma.
The SCN family as the encoded gens of sodium channels has been proven to participate in development of cancers including hepatocellular carcinoma (HCC), but the prognostic value of the SCN family is unclear. The results of the UALCAN database had showed that SCN2A/4A/5A/8A mRNA were highly expressed in tumour tissues, while SCN1A/7A/11A mRNA were expressed at low levels (p < 0.05), furthermore, the expression of SCN4A and SCN7A had the similar levels in microarray analysis result. The pan-tumour analysis showed that SCN7A expression was stably lower in tumours than SCN4A expression by TIMER. Both SCN4A and SCN7A were related to tumour grade, nodal metastatic status, histological subtype, patient race, individual cancer stages and TP53 mutation status to varying degrees. The Kaplan-Meier plotter demonstrated that high SCN4A mRNA expression was correlated with better overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) and that high expression of SCN7A mRNA was associated with better OS; however, in Asians, higher SCN4A was correlated with better OS and DSS, and higher SCN7A was well correlated with better OS, recurrence-free survival (RFS), DSS and PFS. Analysis of data from cBioPortal showed that mutation of SCN7A was related to RFS and PFS. The protein expression of SCN4A and SCN7A had been detected by Immunohistochemistry. Univariate survival analysis revealed that high SCN7A protein expression was significantly linked to better OS (p = 0.001) and RFS (p = 0.003). Moreover, SCN7A displayed as an independent prognostic factor by multivariate analysis. In addition, a lower methylation level indicated a poor outcome. Pathway and functional enrichment analysis predicted a relationship between SCN7A and the PI3K pathway. In conclusion, there are significant and stable changes in SCN4A and SCN7A expression in HCC. SCN7A expression has better prognostic value and might participate in HCC progression.


Polyglycolic acid membrane interpositioning for the prevention of skull deformity following experimental craniosynostosis.
The interpositioning of various materials to complete suturectomy for the treatment of craniosynostosis has been used by many surgeons to prevent early postoperative reunion. Clear scientific proof for this procedure has not yet been obtained with any material, however. A previously described model of experimental craniosynostosis was employed to examine the effects of an interpositioned biodegradable polyglycolic acid (PGA) membrane on the growing skull of 14 newborn rabbits. Additional 11 newborn rabbits served as controls, as on their skulls only unilateral resection of the coronal suture was performed (experimental craniosynostosis). The skulls were examined for shape and histology up to 6 months of age. The 11 rabbits in the control group developed a unilateral deformity on their calvaria as demonstrated by dry-skull osteometry. The 14 rabbit skulls having the interpositioning of a PGA membrane done into the resection site at the time of unilateral suturectomy were found to have grown in a remarkably symmetrical fashion. The interpositioning of a PGA membrane therefore seems to prevent the formation of a skull deformity during growth as compared with early suturectomy alone.


Cost-utility of living donor liver transplantation in a single Japanese center.
Living donor liver transplantation is becoming increasingly important in the Western world, but the economic issues remain controversial. We conducted a cost-utility analysis to evaluate whether living donor liver transplantation is cost-effective. Cost and utility analyses were performed in a longitudinal survey of a single center in Sapporo, Japan. Medical costs were derived from 11 patients who underwent living donor liver transplantation. Health utility was measured in quality-adjusted life year. Data for health utility scores were derived from 19 patients who underwent living donor liver transplantation. Median medical cost was U.S. dollars 154,626 from the first day of preoperative evaluation to 24 months post-transplantation. Cumulative quality-adjusted life years were 1.60 at 24 months after transplantation. Medical cost per quality-adjusted life year decreased progressively, leading to medical cost of U.S. dollars 605,131 per quality-adjusted life year at 3 months to U.S. dollars 94,169 at 24 months after transplantation. The results were sensitive to medical cost. Follow-up survey identified progressive increases in the cost-effectiveness of living donor liver transplantation for patients with end-stage liver disease. Living donor liver transplantation appears to represent a cost-effective medical technology.


An overview of the ongoing insights in selenium research and its role in fish nutrition and fish health.
In the present review, the ongoing researches about selenium research in fish nutrition have been comprehensively discussed. Selenium research is getting popularity in fish nutrition as it is required for the normal growth and proper physiological and biochemical functions in fish. Its deficiency or surplus amounts create severe problems in fish. It is available as inorganic form, organic form, and nano form. In fish, most of the previous research is about the selenium requirements for fish by using only one selenium source mainly the inorganic one. Selenium shows maximum biological activity and bioavailability when it is supplied in proper form. However, to differentiate the more bioavailable and less toxic form of selenium, sufficient information is needed about the comparative bioavailability of different selenium forms in different fish species. In fish, important data about the new forms of selenoproteins is still scarce. Therefore, it is necessary to focus on the determination and elucidation of the new selenoproteins in fish through the utilization of recent approaches of molecular biology and proteomics. The adaptation of these new approaches will replace the old fashioned methodologies regarding the selenium research in fish nutrition. Moreover, the use of molecular biology and proteomics-based new approaches in combination with selenium research will help in optimizing the area of fish nutrition and will improve the feed intake, growth performance, and more importantly the flesh quality which has a promising importance in the consumer market.


Parkinson's disease: initial treatment of motor disorders.
Parkinson's disease is characterised by three main symptoms: slowness and paucity of movements, rigidity, and resting tremor. Rapid improvement in these symptoms after levodopa administration supports the diagnosis of Parkinson's disease. It is important to inform the patient tactfully, allowing him or her to control the pace at which information on the diagnosis, symptoms and prognosis is conveyed. Patients with minimal discomfort or mild disability derive little benefit from drug therapy. Physiotherapy and physical exercises are sometimes useful. Previously untreated patients with marked functional impairment should receive medication. The choice is essentially between levodopa and ropinirole, and mainly depends on the patient's age.


A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy.
Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a unique clinical subset of PM/DM, making them useful in predicting and monitoring certain clinical manifestations. Classic MSAs known for over 30 years include antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP). Anti-Jo-1 is the first autoantibodies to ARS detected in 15-25 % of patients. In addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS) have been reported with prevalence, usually 1-5 % or lower. Patients with any anti-ARS antibodies are associated with anti-synthetase syndrome characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon, and others. Several recent studies suggested heterogeneity in clinical features among different anti-ARS antibody-positive patients and anti-ARS may also be found in idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and associated with good response to steroid treatment and good prognosis. Anti-SRP is specific for PM and associated with treatment-resistant myopathy histologically characterized as necrotizing myopathy. In addition to classic MSAs, several new autoantibodies with strong clinical significance have been described in DM. Antibodies to transcription intermediary factor 1γ/α (TIF1γ/α, p155/140) are frequently found in DM associated with malignancy while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are associated with clinically amyopathic DM (CADM) complicated by rapidly progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new DM-specific autoantibodies. Addition of these new antibodies to clinical practice in the future will help in making earlier and more accurate diagnoses and better management for patients.


[John R Hodges].
John Russell Hodges is an English behavioral neurologist, who is mainly engaged in neuropsychological research for neurocognitive disorders. He contributed to symptomatology of transient global amnesia (TGA), semantic dementia, and behavioral variant frontotemporal dementia (bvFTD). Extensive features of his research work are based on his excellent clinician's approach and his outstanding neuropsychological viewpoint, always keeping that neural basis of the symptoms using neuroimaging and neuropathological techniques, and concerning cure and care for patients. Collaboration with psychiatrists, neuroradiologists, neuropsychologists, neuropathologists, social workers, occupational therapists, research nurses, molecular biologists have supported his broad research work. Karalyn Patterson who is an outstanding clinical and experimental neuropsychologist has been particularly important guiding light for his clinical research. He is an excellent clinician and also looks like a commander of a large and well organized research group.


Electron energy dependence of characteristics of fluorescent plates for ultrahigh-voltage electron microscopes.
The characteristics of fluorescent plates for high energy electron beams (0.5-2.0 MeV) are examined. The thickness and the optical transparency of plates strongly affect the luminous broadening and intensity. The spatial luminous broadening in fluorescent plates is measured and is simply represented by the rise width of a knife edge image. When the thickness is much smaller than the range of incident electrons, the rise width is 1/4-1/5 of the thickness in the case of YAG single crystal plates that are transparent for light, while the rise width is nearly equal to the thickness for the packed P22 powder plates that are opaque for light. To suppress the luminous broadening under 50 microm, the thickness of YAG plates has to be thinner than 250 microm in the energy region around 2 MeV. Under the same condition of the rise width, the luminous intensity of YAG plates is twice as high as that of the P22 plates.


Expression, purification, crystallization and preliminary X-ray analysis of Plasmodium falciparum GTP:AMP phosphotransferase.
Adenylate kinases (AKs) are phosphotransferase enzymes that catalyze the interconversion of adenine nucleotides, thereby playing an important role in energy metabolism. In Plasmodium falciparum, three AK isoforms, namely PfAK1, PfAK2 and GTP:AMP phosphotransferase (PfGAK), have been identified. While PfAK1 and PfAK2 catalyse the conversion of ATP and AMP to two molecules of ADP, PfGAK exhibits a substrate preference for GTP and AMP and does not accept ATP as a substrate. PfGAK was cloned and expressed in Escherichia coli and purified using two-step chromatography. Brown hexagonal crystals of PfGAK were obtained and a preliminary diffraction analysis was performed. X-ray diffraction data for a single PfGAK crystal were processed to 2.9 Å resolution in space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 123.49, c = 180.82 Å, α = β = 90, γ = 120°.


[Expert consensus statement on Hugan Tablets in clinical practice].
Hugan Tablets is a Chinese patent medicine,it has the function of anti-inflammation and reducing transaminase. Based on questionnaire investigation of doctors and a systematic review of research literature on Hugan Tablets,using international clinical practice guidelines' developing methods,with the best available evidence and fully combining expert experience,and following the principle of " evidence-based,consensus-based and experience-based",Expert consensus statement on Hugan Tablets in clinical practice was developed by more than 30 multidisciplinary experts from the nationwide,aimed at guiding and standardizing the rational use of Hugan Tablets by clinicians and to improve clinical efficacy and safety. The expert consensus adopts internationally recognized recommendation criteria for classification of evidence: GRADE. The formation of expert consensus adopts the nominal group technique. Six main considerations are quality of evidence,curative effect,safety,economical efficiency,patient acceptability and other factors. If there is sufficient evidence,a " recommendation" is formed,using GRADE grid voting rule. If there isn' t sufficient evidence,a " consensus opinion" is formed,using majority counting rule. Focus on the indication,usage and dosage,drug use in special population and safety of Hugan Tablets,two recommendations and eight consensus opinions were put forward. Through expert meetings and correspondence,a nationwide consultation and peer review was conducted. This consensus applies to clinicians in hospitals and grass-roots health services,to provide guidance and reference for the rational use of Hugan Tablets.