The under-use of statin in type 2 diabetic patients attending diabetic clinics in Italy.
The greatest decrease in mortality from cardiovascular disease (CAD) that can be achieved with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) is seen in patients with the highest risk for CAD, such as diabetics. Yet, there is evidence for inadequate use of drug therapies to achieve lipid goals. Our aims were to: (1) assess the prevalence of statin use in patients attending diabetic clinics and (2) correlate the use of statins with their risk and clinical status. Of 9921 patients included, only 20.4% of them were receiving statin therapy. Statins were more progressively prescribed in those with risk factors additional to that of diabetes. Patients under statin treatment were older, mostly type 2 diabetics, more hypertensive and hyperlipidemic, had a higher prevalence of both macro- and microvascular disease. Among those with a total cholesterol concentration above 252 mg/dl, statin treatment was given only to 60% of diabetic patients with prior myocardial infarction, 56% of those with angina, 66% of those having had prior revascularization procedure, 54% of those with cerebrovascular disease and 51% of those with peripheral artery disease. At least in Italy, statins are not prescribed to the majority of diabetic patients, and a substantial proportion of patients not treated with statins present significant macro- and microvascular complications.


Laboratory of domesticity: Gender, race, and science at the Bermuda Biological Station for Research, 1903-30.
During the early twentieth century, the Bermuda Biological Station for Research (BBSR) functioned as a multipurpose scientific site. Jointly founded by New York University, Harvard University, and the Bermuda Natural History Society, the BBSR created opportunities for a mostly US-based set of practitioners to study animal biology in the field. I argue that mixed gender field stations like the BBSR supported professional advancement in science, while also operating as important places for women and men to experiment with the social and cultural work of identity formation, courtship and marriage, and social critique. Between 1903 and 1930, the BBSR functioned as a laboratory of domesticity, a temporary scientific household in British Bermuda where women and men interacted with established colonial ideologies about science, sex difference, and racial hierarchy in their public and private accounts of doing biology and socializing in the field. Viewing field stations as generative of multiple forms of labor offers a corrective to narratives within the history of biology, in which scientific practices are considered to be the principal forms of output produced by practitioners in the field. Understanding how women and men at the BBSR engaged with (and at times critiqued) the politics of gender and race from the periphery of U.S. networks of biology suggests that we might view field stations as shaping not only academic science but also domestic life and fields as disparate as fiction and the law.


Extending Wireless Rechargeable Sensor Network Life without Full Knowledge.
When extending the life of Wireless Rechargeable Sensor Networks (WRSN), one challenge is charging networks as they grow larger. Overcoming this limitation will render a WRSN more practical and highly adaptable to growth in the real world. Most charging algorithms require a priori full knowledge of sensor nodes' power levels in order to determine the nodes that require charging. In this work, we present a probabilistic algorithm that extends the life of scalable WRSN without a priori power knowledge and without full network exploration. We develop a probability bound on the power level of the sensor nodes and utilize this bound to make decisions while exploring a WRSN. We verify the algorithm by simulating a wireless power transfer unmanned aerial vehicle, and charging a WRSN to extend its life. Our results show that, without knowledge, our proposed algorithm extends the life of a WRSN on average 90% of what an optimal full knowledge algorithm can achieve. This means that the charging robot does not need to explore the whole network, which enables the scaling of WRSN. We analyze the impact of network parameters on our algorithm and show that it is insensitive to a large range of parameter values.


Time-resolved measurements of the hot-electron population in ignition-scale experiments on the National Ignition Facility (invited).
In laser-driven inertial confinement fusion, hot electrons can preheat the fuel and prevent fusion-pellet compression to ignition conditions. Measuring the hot-electron population is key to designing an optimized ignition platform. The hot electrons in these high-intensity, laser-driven experiments, created via laser-plasma interactions, can be inferred from the bremsstrahlung generated by hot electrons interacting with the target. At the National Ignition Facility (NIF) [G. H. Miller, E. I. Moses, and C. R. Wuest, Opt. Eng. 43, 2841 (2004)], the filter-fluorescer x-ray (FFLEX) diagnostic-a multichannel, hard x-ray spectrometer operating in the 20-500 keV range-has been upgraded to provide fully time-resolved, absolute measurements of the bremsstrahlung spectrum with ∼300 ps resolution. Initial time-resolved data exhibited significant background and low signal-to-noise ratio, leading to a redesign of the FFLEX housing and enhanced shielding around the detector. The FFLEX x-ray sensitivity was characterized with an absolutely calibrated, energy-dispersive high-purity germanium detector using the high-energy x-ray source at NSTec Livermore Operations over a range of K-shell fluorescence energies up to 111 keV (U Kβ). The detectors impulse response function was measured in situ on NIF short-pulse (∼90 ps) experiments, and in off-line tests.


Nitrogen content and morphology dependent field emission properties of nitrogen-doped SiC nanowires and density functional calculations.
Nitrogen-doped SiC nanowires (N-doped SiC NWs) with a nitrogen content from 0.975 wt% to 2.265 wt% have been synthesized via a one-step chemical vapor reaction (CVR), where melamine served as both the carbon and nitrogen source. Interestingly, the morphology of the products changed from slightly curled to very curled with crowding together with the increase of N dopants, which was interpreted reasonably by the proposed N-doping growth model of SiC NWs. In addition, according to the electronic structure calculation results, the band gap is narrowed progressively with the increase of N content, which greatly enhances the field emission (FE) properties. However, the experimental results of the FE measurements substantiate that only when the N content takes an optimal value can the N-doped SiC NWs act as candidates for field emitters with very low turn-on fields (E(to)) of 1.5 V μm(-1) and threshold fields (E(thr)) of 4 V μm(-1). On the basis of the aforementioned phenomenon, a universal cooperativity mechanism was put forward to explain the effect of the N content and morphology on the FE properties of the N-doped SiC NWs.


Pathology of kidney transplant rejection.
In the past year there has been considerable progress in defining the morphologic characteristics of the normally functioning renal allograft in the cyclosporine era. Based on these characteristics and knowledge of clinically validated important changes in rejection, internationally agreed upon standardized terms and criteria have been developed for the histologic diagnosis of acute and chronic rejection and allied conditions. Chronic changes observed in normally functioning grafts at 2 years posttransplantation have been shown to predict the presence of renal functional impairment for 4 years. Important new rejection changes have been identified in the peritubular capillaries. Various alternatives to core biopsy have been explored, but no technique as yet has sufficient sensitivity and specificity for general use in rejection diagnosis. The accurate distinction of chronic rejection from other conditions remains a challenge for the future.


Central stimulation of adrenocortical secretion by 5-hydroxytryptamine1A agonists is mediated by sympathomedullary activation.
The mechanism by which the 5-hydroxytryptamine1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increases adrenocortical secretion was examined using treatments designed to alter the hypothalamo-pituitary-adrenocortical axis and the autonomic nervous system. Adrenocortical responses to peripherally administered 8-OH-DPAT were preserved in animals with radiofrequency lesions of the hypothalamic paraventricular nucleus or with posterior hypothalamic deafferentations. However, adrenocortical responses to 8-OH-DPAT were abolished in hypophysectomized animals, although both acute and chronic treatment with dexamethasone were without effect. The influence of catecholamines in the central and sympathetic nervous systems was investigated using treatments designed to alter central and peripheral catecholaminergic systems. Adrenocortical responses after intracerebroventricular administration of high doses of 8-OH-DPAT were attenuated by i.v. and intra-adrenal treatment with 6-hydroxydopamine (6-OHDA), by adrenal medullectomy, by splanchnicectomy and by combined 6-OHDA-sympathectomy/medullectomy. Responses to i.p. 8-OH-DPAT were only partially attenuated by medullectomy and by 6-OHDA-sympathectomy/medullectomy. The ganglionic blocking agent, chlorisondamine also blocked the adrenocortical response after intracerebroventricular, but not i.p., administration of 8-OH-DPAT. These effects did not appear to be due to surgical damage to the adrenal cortex because the operated animals showed normal adrenocortical responses to challenge with adrenocorticotropic hormone. The data obtained indicate that adrenocortical secretion in response to i.p. and intracerebroventricular administration of the 5-hydroxytryptamine1A receptor agonist 8-OH-DPAT largely involves a sympathomedullary activation, but that additional peripheral mechanisms are also involved after i.p. administration.


Brief History of Opioids in Perioperative and Periprocedural Medicine to Inform the Future.
Background: Opioids and derivatives of opium had been used as analgesics for thousands of years before the introduction of inhalational anesthetic agents. Once these early volatile agents were in widespread use, opioids were used as part of anesthetic care for premedication, as intraoperative adjuncts to general anesthesia, and for the management of postoperative pain. Evidence of growing dependence on opioids in the perioperative and periprocedural patient is supported by the ongoing research to develop synthetic opioids and to customize the pharmacokinetics and pharmacodynamics to achieve specific therapeutic goals. Methods: We explore the history of opioid use in perioperative care as a means of future management in light of new persistent opioid abuse. Results: As the opium chemical structure has been modified, newer nonopioid analgesics have been approved and brought into clinical practice. Opioid-sparing and opioid-free anesthetic techniques are not only a possibility, but a reality. Conclusion: Continuing research in neurobiology and addiction genetics will ultimately lead to a pharmacogenetic approach to patients at risk for new persistent opioid abuse.


Lattice Boltzmann scheme for mixture modeling: analysis of the continuum diffusion regimes recovering Maxwell-Stefan model and incompressible Navier-Stokes equations.
A finite difference lattice Boltzmann scheme for homogeneous mixture modeling, which recovers Maxwell-Stefan diffusion model in the continuum limit, without the restriction of the mixture-averaged diffusion approximation, was recently proposed [P. Asinari, Phys. Rev. E 77, 056706 (2008)]. The theoretical basis is the Bhatnagar-Gross-Krook-type kinetic model for gas mixtures [P. Andries, K. Aoki, and B. Perthame, J. Stat. Phys. 106, 993 (2002)]. In the present paper, the recovered macroscopic equations in the continuum limit are systematically investigated by varying the ratio between the characteristic diffusion speed and the characteristic barycentric speed. It comes out that the diffusion speed must be at least one order of magnitude (in terms of Knudsen number) smaller than the barycentric speed, in order to recover the Navier-Stokes equations for mixtures in the incompressible limit. Some further numerical tests are also reported. In particular, (1) the solvent and dilute test cases are considered, because they are limiting cases in which the Maxwell-Stefan model reduces automatically to Fickian cases. Moreover, (2) some tests based on the Stefan diffusion tube are reported for proving the complete capabilities of the proposed scheme in solving Maxwell-Stefan diffusion problems. The proposed scheme agrees well with the expected theoretical results.


Smartwatch feedback device for high-quality chest compressions by a single rescuer during infant cardiac arrest: a randomized, controlled simulation study.
According to the guidelines, rescuers should provide chest compressions (CC) ~1.5 inches (40 mm) for infants. Feedback devices could help rescuers perform CC with adequate rates (CCR) and depths (CCD). However, there is no CC feedback device for infant cardiopulmonary resuscitation (CPR). We suggest a smartwatch-based CC feedback application for infant CPR. We created a smartwatch-based CC feedback application. This application provides feedback on CCD and CCR by colour and text for infant CPR. To evaluate the application, 30 participants were divided randomly into two groups on the basis of whether CC was performed with or without the assistance of the smartwatch application. Both groups performed continuous CC-only CPR for 2 min on an infant mannequin placed on a firm table. We collected CC parameters from the mannequin, including the proportion of correct depth, CCR, CCD and the proportion of correct decompression depth. Demographics between the two groups were not significantly different. The median (interquartile range) proportion of correct depth was 99 (97-100) with feedback compared with 83 (58-97) without feedback (P = 0.002). The CCR and proportion of correct decompression depth were not significantly different between the two groups (P = 0.482 and 0.089). The CCD of the feedback group was significantly deeper than that of the control group [feedback vs. control: 41.2 (39.8-41.7) mm vs. 38.6 (36.1-39.6) mm; P=0.004]. Rescuers who receive feedback of CC parameters from a smartwatch could perform adequate CC during infant CPR.


Study on luminescent property of Tb(3+)-doped silicate nano-scintillating glass.
By optimizing a Tb(3+)-doped silicate nano-scintillating glass matrix, sensitizer and brightening agent components, the processing conditions such as the melting temperature, holding time, atmosphere, and heat treatment were improved, and the temperature of the heat treatment was changed to generate BaF2 nano-crystal in the glass. The resulting nanocrystals have a better rare earth solubility and a lower phonon energy; therefore the luminescent property of Tb(3+)-doped silicate nano-scintillating glass has been noticeably improved.


Quantitation of nimesulide in human plasma by high-performance liquid chromatography with ultraviolet absorbance detection and its application to a bioequivalence study.
A rapid and simple high-performance liquid chromatography-reversed phase (HPLC-RV) method with ultraviolet detection (258 nm) was developed and validated for the quantitation of nimesulide (CAS 51803-78-2) in human plasma. After the plasma samples were extracted with 6.0 ml of dichloromethane containing the internal standard phenacetin 2 microg/ml in methanol, the analysis of the nimesulide level in the plasma samples was carried out using a reverse phase Supelcosil LC-18 (15 cm x 4.6 mm x 5 pm) column. The chromatographic separation was accomplished with an isocratic mobile phase consisting of a mixture of methanolphosphate buffer (pH 3.5; 0.01 mol/l) (55:45, v/v). The inter-assay accuracy ranged from 103.4 to 113.2%, while intra-day ranged from 105.6 to 117.5%. The inter-assay precision ranged from 11.7 to 14.6%, while intra-assay ranged from 3.2 to 9.5%. The recovery of nimesulide was determined as part of the assay validation process and was excellent. The linearity of the nimesulide curves ranged from 0.20 to 15.0 microg/ml (y = 0.3857-0.0081, r = 0.9975). Short-term stability showed that nimesulide is stable in plasma for at least 24 h at room temperature, while long-term stability studies showed that nimesulide is stable in plasma for at least 180 days when stored at -20 degrees C. This validated method was successfully applied to the bioequivalence study of nimesulide in tablets in healthy volunteers.


Analysis of clinical effects and mechanism of recombinant human interleukin-11 with glucocorticoids for treatment of idiopathic thrombocytopenic purpura.
The aim of the present study was to evaluate the effectiveness and safety of recombinant human interleukin-11 (IL-11) with glucocorticoids for treatment of adult idiopathic thrombocytopenic purpura (ITP) and the regulatory effect on immune mechanisms. A total of 80 patients with initial diagnosis of ITP admitted to our hospital were selected. Patients were randomly divided into the control group and observation group, with 40 cases each. The control group received glucocorticoids treatment, and the observation group received IL-11 and glucocorticoids. The treatment effects were compared. The total effective rate and effective degree of the observation group was higher than in the control group and the difference was statistically significant (P<0.05); comparing the incidence of complications of the two groups, there was no statistical difference (P>0.05). In the observation group, onset time was reduced, platelet recovery level increased and platelet antibody positive rate decreased, and the differences were statistically significant (P<0.05). The total treatment course was shorter and recurrence rate was lower in the observation group compared with the control group, and the differences were statistically significant (P<0.05). The percentage of CD4+CD25+ regulatory T cells decreased in the two groups after treatment, and was more pronounced in the observation group. The difference was statistically significant (P<0.05). In conclusion, IL-11 with glucocorticoids for the treatment of adult ITP is safe and effective, and may be associated with decreased percentage of CD4+CD25+ regulatory T cells.


Study of the OPRM1 A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia.
Genetic polymorphisms of the μ-opioid receptor gene OPRM1 A118G have been shown to influence opioid efficacy. The association of the OPRM1 A118G genetic polymorphism with side effects, such as nausea and vomiting, caused by opioids during analgesia has not been well-represented by the literature . This study aimed to investigate whether the genetic polymorphism of OPRM1 A118G contributed to the variability in nausea and vomiting during fentanyl analgesia in patients undergoing total abdominal hysterectomy or myomectomy. One hundred sixty-five women, of Han nationality, aged 20-50 yrs, of ASA I or II, and scheduled for elective total abdominal hysterectomy or myomectomy under general anesthesia were enrolled. Intravenous fentanyl, patient-controlled analgesia was provided postoperatively for pain control. The presence and scores of postoperative nausea and vomiting for 24 hours were recorded and measured using rating scales. Pain was measured with a visual analog scale, and fentanyl consumption over 24 hours was recorded, as well. Genotyping of the A118G allele was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and patients were divided into three groups according to their genotype. The frequency of the A118G allele was 32.4% for the patients in this study. Patients homozygous for 118G required more fentanyl to achieve adequate pain relief compared with the other two patient groups (patients homozygous for 118A and heterozygous). However, there were no statistically significant differences among the frequencies and scores of nausea and vomiting. OPRM1 A118G has no effect on the individual variation of postoperative nausea and vomiting, the side effects of fentanyl analgesia, in Chinese women undergoing gynecologic surgery.


The X-ray crystallography phase problem solved thanks to AlphaFold and RoseTTAFold models: a case-study report.
The breakthrough recently made in protein structure prediction by deep-learning programs such as AlphaFold and RoseTTAFold will certainly revolutionize biology over the coming decades. The scientific community is only starting to appreciate the various applications, benefits and limitations of these protein models. Yet, after the first thrills due to this revolution, it is important to evaluate the impact of the proposed models and their overall quality to avoid the misinterpretation or overinterpretation of these models by biologists. One of the first applications of these models is in solving the `phase problem' encountered in X-ray crystallography in calculating electron-density maps from diffraction data. Indeed, the most frequently used technique to derive electron-density maps is molecular replacement. As this technique relies on knowledge of the structure of a protein that shares strong structural similarity with the studied protein, the availability of high-accuracy models is then definitely critical for successful structure solution. After the collection of a 2.45 Å resolution data set, we struggled for two years in trying to solve the crystal structure of a protein involved in the nonsense-mediated mRNA decay pathway, an mRNA quality-control pathway dedicated to the elimination of eukaryotic mRNAs harboring premature stop codons. We used different methods (isomorphous replacement, anomalous diffraction and molecular replacement) to determine this structure, but all failed until we straightforwardly succeeded thanks to both AlphaFold and RoseTTAFold models. Here, we describe how these new models helped us to solve this structure and conclude that in our case the AlphaFold model largely outcompetes the other models. We also discuss the importance of search-model generation for successful molecular replacement.


Evolutionary conservation of the product of human c-myc exon 1 and its inducible expression in a murine cell line.
The human c-myc proto-oncogene contains an open reading frame within its first exon which is translated into protein (MYCHEX1). While the murine c-myc exon 1 is obviously non coding, we show that in mouse cells there are polypeptides closely related to human MYCHEX1. These polypeptides share the same immunological reactivities with the human polypeptides. Furthermore, the 32 kDa polypeptide of murine cells has, like its human counterpart, the ability to dimerise in a 58 kDa form in denaturing and reducing SDS-PAGE. The human gene was introduced into a murine cell line by transfection. A cell line was studied, in which the inducible expression of the gene allows a substantial increase in the concentration of the corresponding protein. This inducible protein behaves in any respect like the murine one, either in SDS-PAGE or in a specific immunoassay. These shared properties constitute a further proof that the human and mouse MYCHEX1 proteins are encoded by the sequence overlapping the human myc exon 1 and a related murine sequence. The gene contained in the human c-myc exon 1 is not, therefore, a specific feature of human cells.


Complications and Outcomes of One-Bone Forearm Reconstruction.
Background: The objective of this study was to review the outcomes of patients who underwent one-bone forearm (OBF) reconstruction. Methods: A retrospective review of patients who underwent OBF surgery between 1994 and 2014 was undertaken. Patient demographics, etiology, associated injuries, number of surgeries prior to OBF surgery, surgical details, and postoperative information were collected. A telephone interview was conducted at final follow-up, including a Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, a 10-point scoring system used by Peterson et al, and a series of questions concerning pain and patient satisfaction. Results: There were 6 males and 2 females with a mean age of 44 years (range, 20-66 years). All patients had traumatic etiology, with 6 having open wounds and 2 having closed wounds. All patients had union with a mean follow-up of 83.6 months (range, 16-218 months). The mean pain score was 3 (range, 0-8), of which 3 were painless (score 0). The mean QuickDASH score was 39 (range, 7-75), and 4 patients had good or excellent results according to the 10-point score system used by Peterson et al. All patients were satisfied with the result. Five of 8 had complications related to soft tissues that were residual from their prior injuries and surgeries. One patient had post healing fracture requiring revision fixation and 1 had a postoperative infection requiring parenteral antibiotics. Conclusions: OBF surgery is an effective salvage procedure for complicated forearm instability, particularly after trauma. While union rates are high, complications are typically related to pain and soft tissue secondary to the previous injury and reconstructive procedures.


Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3.
Recent genome- and exome-wide association studies suggest that the human APOE ε4 allele protects against non-alcoholic fatty liver disease (NAFLD), while ε3 promotes hepatic steatosis and steatohepatitis. The present study aimed at examining the APOE genotype-dependent development of fatty liver disease and its underlying mechanisms in a targeted replacement mouse model. Male mice expressing the human APOE3 or APOE4 protein isoforms on a C57BL/6J background and unmodified C57BL/6J mice were chronically fed a high-fat and high-sucrose diet to induce obesity. After 7 months, body weight gain was more pronounced in human APOE than endogenous APOE expressing mice with elevated plasma biomarkers suggesting aggravated metabolic dysfunction. APOE3 mice exhibited the highest liver weights and, compared to APOE4, massive hepatic steatosis. An untargeted quantitative proteome analysis of the liver identified a high number of proteins differentially abundant in APOE3 versus APOE4 mice. The majority of the higher abundant proteins in APOE3 mice could be grouped to inflammation and damage-associated response, and lipid storage, amongst others. Results of the targeted qRT-PCR and Western blot analyses contribute to the overall finding that APOE3 as opposed to APOE4 promotes hepatic steatosis, inflammatory- and damage-associated response signaling and fibrosis in the liver of obese mice. Our experimental data substantiate the observation of an increased NAFLD-risk associated with the human APOEε3 allele, while APOEε4 appears protective. The underlying mechanisms of the protection possibly involve a higher capacity of nonectopic lipid deposition in subcutaneous adipose tissue and lower hepatic pathogen recognition in the APOE4 mice.


Development of SSR Markers Based on Transcriptome Sequencing and Association Analysis with Drought Tolerance in Perennial Grass Miscanthus from China.
Drought has become a critical environmental stress affecting on plant in temperate area. As one of the promising bio-energy crops to sustainable biomass production, the genus Miscanthus has been widely studied around the world. However, the most widely used hybrid cultivar among this genus, Miscanthus × giganteus is proved poor drought tolerance compared to some parental species. Here we mainly focused on Miscanthus sinensis, which is one of the progenitors of M. × giganteus providing a comparable yield and well abiotic stress tolerance in some places. The main objectives were to characterize the physiological and photosynthetic respond to drought stress and to develop simple sequence repeats (SSRs) markers associated with drought tolerance by transcriptome sequencing within an originally collection of 44 Miscanthus genotypes from southwest China. Significant phenotypic differences were observed among genotypes, and the average of leaf relative water content (RWC) were severely affected by drought stress decreasing from 88.27 to 43.21%, which could well contribute to separating the drought resistant and drought sensitive genotype of Miscanthus. Furthermore, a total of 16,566 gene-associated SSRs markers were identified based on Illumina RNA sequencing under drought conditions, and 93 of them were randomly selected to validate. In total, 70 (75.3%) SSRs were successfully amplified and the generated loci from 30 polymorphic SSRs were used to estimate the genetic differentiation and population structure. Finally, two optimum subgroups of the population were determined by structure analysis and based on association analysis, seven significant associations were identified including two markers with leaf RWC and five markers with photosynthetic traits. With the rich sequencing resources annotation, such associations would serve an efficient tool for Miscanthus drought response mechanism study and facilitate genetic improvement of drought resistant for this species.


Ca2+ binding sites of the ryanodine receptor/Ca2+ release channel of sarcoplasmic reticulum. Low affinity binding site(s) as probed by terbium fluorescence.
Fluorescence spectroscopy has been used to study the interaction of Tb3+ (as a Ca2+ analog) with the purified ryanodine receptor (RyR)/Ca2+ release channel of skeletal muscle sarcoplasmic reticulum. Tb3+ replaces Ca2+ in both the high- and the low-affinity sites. Occupation of the low-affinity site (inhibitory), but not of the high-affinity Ca2+ binding site (activating), by Tb3+ results in a strong enhanced green fluorescence (at 543 nm) and in an inhibition of ryanodine binding. The Tb3+ concentrations required for half-maximal enhanced fluorescence and inhibition of ryanodine binding were: 22.5 +/- 2.5 microM (n = 4) and 22.3 +/- 3.1 microM (n = 2), respectively. Tb3+ appears to bind to the protein at two or more cooperative sites (nH = 2.4) and to dissociate from these sites with three different rate constants (K-1,1 = 361 +/- 250 min-1 (n = 6); K-1,2 = 0.45 +/- 0.22 min-1 (n = 11); K-1,3 = 0.011 +/- 0.013 min-1 (n = 7). The enhancement in Tb3+ fluorescence is very fast (K1 >> 5 x 10(5) M-1.min-1), and it is quenched by EGTA, La3+, or Ca2+ addition. About 20% of the bound Tb3+ was not displaced by EGTA or Ca2+; suggesting its "occlusion" in the RyR. This is also reflected in the partially irreversible inhibition of ryanodine binding by Tb3+. Reconstitution of sarcoplasmic reticulum vesicles into a planar bilayer lipid membrane showed that the Ca2+ release channel was activated by submicromolar and inhibited by micromolar concentrations of Tb3+ and La3+. The Tb(3+)-activated channel showed an enhancement of the open dwell time of the channel. The results suggest that RyR/Ca2+ release channel undergoes conformational changes due to Tb3+ binding to the low-affinity Ca2+ binding site, and this binding results in the closing of the Ca2+ release channel.


[On the problems of geriatric carcinomas (author's transl)].
Generally the cancer of the rectum is one besides several other diseases of the patient; clinically it recedes often far into the background of the actual happening. With increasing age the real geriatric diseases come to the foreground of the clinical findings dominated by the arteriosclerosis in all its variations. Therefore the treatment has to take into account the true secondary diseases besides the cancer. Judging the progress of the illness and the therapeutic effect these facts must be considered. Due to the intanglement of geriatric and oncological symptoms it is impossible to separate geriatrics from oncology. Concerning these connections it seems to be justified to characterize the rectum cancer--and also some other cancers--as a particularly geriatric one. The practical consequence of this hypothesis is a change of therapeutic planning, coordinating oncological and geriatric points of view according to the respective requirements. At this psychological and social-medical problems have to be taken into consideration.


Frameless stereotactic placement of foramen ovale electrodes in patients with drug-refractory temporal lobe epilepsy.
Semi-invasive foramen ovale electrodes (FOEs) are used as an alternative to invasive recording techniques in the presurgical evaluation of patients with temporal lobe epilepsy. To maximize patient safety and interventional success, frameless stereotactic FOE placement by use of a variation of an upper jaw fixation device with an external fiducial frame, in combination with an aiming device and standard navigation software, was evaluated by the Innsbruck Epilepsy Surgery Program. Patients were immobilized noninvasively with the Vogele-Bale-Hohner headholder (Medical Intelligence GmbH, Schwabmünchen, Germany) to plan computed tomography and surgery. Frameless stereotactic cannulation of the foramen and intracranial electrode placement were achieved with the help of an aiming device mounted to the base plate of the headholder. Ease of applicability, safety, and results obtained with foramen ovale recording were investigated. Twenty-six FOEs were placed in 13 patients under general anesthesia. The foramen ovale was successfully cannulated in all patients. One patient reported transient painful mastication after the procedure as a complication attributable to use of the Vogele-Bale-Hohner mouthpiece. In one patient, a persistent slight buccal hypesthesia was present 3 months after the procedure. To pass the foramen, slight adjustments in the needle position had to be made in 10 sides (38.4%). To place the intracranial electrodes, adjustments were necessary six times (23.7%). An entirely new path had to be planned once (3.8%). Seizure recording provided conclusive information in all patients (100%). Outcome in operated patients was Engel Class Ia in six patients, Class IId in one patient, Class IIb in one patient, and Class IVa in one patient (minimum follow-up, 6 mo). The Vogele-Bale-Hohner headholder combined with an external registration frame eliminates the need for invasive head clamp fixation. FOE placement can be planned "offline" and performed under general anesthesia later. This can be valuable in patients with distorted anatomy and/or small foramina or in patients not able to undergo the procedure under sedation. Results are satisfactory with regard to patient safety, patient comfort, predictability, and reproducibility. FOEs supported further treatment decisions in all patients.


Collective futures: how projections about the future of society are related to actions and attitudes supporting social change.
We identified the active ingredients in people's visions of society's future ("collective futures") that could drive political behavior in the present. In eight studies (N = 595), people imagined society in 2050 where climate change was mitigated (Study 1), abortion laws relaxed (Study 2), marijuana legalized (Study 3), or the power of different religious groups had increased (Studies 4-8). Participants rated how this future society would differ from today in terms of societal-level dysfunction and development (e.g., crime, inequality, education, technology), people's character (warmth, competence, morality), and their values (e.g., conservation, self-transcendence). These measures were related to present-day attitudes/intentions that would promote/prevent this future (e.g., act on climate change, vote for a Muslim politician). A projection about benevolence in society (i.e., warmth/morality of people's character) was the only dimension consistently and uniquely associated with present-day attitudes and intentions across contexts. Implications for social change theories, political communication, and policy design are discussed.


Reversible switching of the electronic ground state in a pentacoordinated Cu(II) complex.
An easy reversible switching of the electronic ground state in a pentacoordinated copper(II) complex is reported for the first time. The simple protonation of a carboxylic group in a Cu(II) complex with a {dx(2)-y(2)}(1) electronic configuration leads to a flip of the ground electronic configuration from {dx(2)-y(2)}(1) to {dz(2)}(1) in the metal ion.


Analysis of Subway Interior Noise at Peak Commuter Time.
Although mass transit systems are convenient and efficient for urban people, little attention has been paid to the potential hearing hazard from their noise. The purpose of the current study was to measure and analyze levels of subway interior noise at peak commuter times and to provide information about commuters' daily dose of noise exposure. To measure the subway interior noise, nine subway lines inside Seoul (i.e., lines 1-9) and six lines surrounding the capital city area (i.e., Central, Bundang, Sinbundang, Incheon, Gyeongui, and Gyeongchun) were chosen. The noise was measured and recorded by a sound level meter for two-hour periods in the morning and evening. 1) In the LZeq analysis, the average noise level of all 15 lines was 72.78 dB; the maximum and minimum noise levels were 78.34 and 62.46 dB, respectively. The average noise level of the nine lines inside Seoul was 73.45 dB, which was 1.68-dB louder than that of the six lines surrounding the capital city area. 2) Based on the LZeq analysis of 33 measured frequencies, 12.5 Hz was the highest frequency and 20,000 Hz was the lowest. 3) There was no remarkable difference in the level of subway interior noise between morning and evening peak commuter times. We concluded that the level of subway interior noise was not loud enough for commuters to incur noise-induced hearing loss. Regardless, environmental noise control efforts in the subway system might be needed for commuters who take a subway every day.


Taking the tube: Uptake of salpingectomy at the time of hysterectomy for benign indications.
International guidelines recommend the fallopian tubes be removed at the time of hysterectomy, to lower the incidence of ovarian cancer in women. To determine the rate of salpingectomy at the time of hysterectomy at our institution and to discuss a standard rate. Hysterectomies (n = 200) performed for benign indications from 13 January 13, 2015 until 26 April 26, 2016 were reviewed. The overall rate of salpingectomy was 76.0%. Factors associated with non-completion were uterovaginal prolapse indication and vaginal surgical approach. Rates of completing salpingectomy with hysterectomy are high. There may be additional opportunity for ovarian cancer reduction. No standard rate has been published but considering difficulty with removal of fallopian tubes in certain cases, it may not be 100%. Our data allows for comparison by other units performing similar studies. We recommend the formal adoption of local guidelines regarding salpingectomy at the time of hysterectomy for benign indications in order to keep local practice up to date with international recommendations.


Protecting the skin from moisture and associated irritants.
1. Skin that is damp or wet is more permeable to irritating substances and more readily colonized by microorganisms. Less friction is required to abrade or blister skin when it is damp. 2. The goal of nurses who care for patients at risk for skin breakdown secondary to moisture and associated irritants is to keep the skin dry and free of irritants. 3. Although there are many products that claim to protect the skin from the injurious effects of moisture, the research supporting these claims is limited. Nurses, therefore, must be inquisitive and vigilant when selecting products.


Sending CAR T Cells after T-cell Malignancies.
GC027, a new chimeric antigen receptor T-cell therapy manufactured with a proprietary allogeneic platform, TruUCAR, has shown effectiveness in a handful of patients with relapsed/refractory T-cell acute lymphoblastic leukemia, a disease with limited treatment options.


Amplification of the DNA repair gene O6-methylguanine-DNA methyltransferase associated with resistance to alkylating drugs in a mammalian cell line.
The cytotoxic action of such alkylating chemotherapeutic drugs as 2-chloroethyl-N-nitrosourea (CNU) derivatives is countered by the repair protein O6-methylguanine-DNA methyltransferase (MGMT), which removes O6-alkylguanine induced in the DNA by these agents. Resistance to these drugs is often correlated with the MGMT levels in normal and tumor cells of human and rodent origin. Exposure of mouse 3T3 cells to increasing concentrations of CNU, and subsequent selection of resistant cells, led to the isolation of clones with 5-10 times higher levels of MGMT activity than in the control. The increased MGMT expression at both mRNA and protein levels resulted from 5- to 10-fold amplification of the Mgmt gene. Amplification of this gene was not associated with concomitant amplification of another alkylation damage repair gene, N-methylpurine-DNA glycosylase. No amplification of at least three other genes on chromosome 7 (which contains the Mgmt gene) was observed in the drug-resistant cells. Furthermore, the amplified Mgmt sequence was not associated with a homogeneously staining region, or double minute chromosomes, nor present as episomal DNA. In situ hybridization of metaphase chromosomes of the drug-resistant cells indicated both translocation and localized amplification of the Mgmt gene.


Report: economic implications of inflammatory bowel disease and its management.
Crohn's disease and ulcerative colitis, the 2 most common inflammatory bowel diseases (IBDs), are chronic conditions with periods of exacerbation and remission. Patients with IBD experience clinical gastrointestinal (GI) symptoms, as well as the emotional burden that accompanies chronic conditions characterized by reduced quality of life and ability to work. With estimates of direct and indirect costs ranging between $14.6 and $31.6 billion in 2014, there is a significant healthcare burden associated with IBD. Although treatment expenses make up a significant portion of the cost of IBD, studies show that inappropriate treatment, lack of adherence to therapeutic regimens, or suboptimal treatment increase the cost burden. Costs for IBD include hospitalizations, the eventual need for surgery due to disease complications, and physician visits. The staggering economic burden of IBD makes early diagnosis, coupled with effective treatment at onset, imperative. Therefore, management of IBD must evolve beyond symptom control and toward sustained control of GI inflammation as measured by endoscopic, radiologic, and laboratory parameters.Treatment advances have made deep remission a realistic target for some people with IBD. However, achieving deep remission requires a shift in the management paradigm of IBD, encouraging individualized treatment with biologics that focuses less on treating symptoms and more on preventing potential disease progression. Although expensive at onset, this management strategy may ultimately lead to decreased rates of surgeries and hospitalizations, potentially yielding lower long-term costs for treatment.


A study on the vertical transmission of arthropathic and amyloidogenic Enterococcus faecalis.
Ten brown layer parent hens were injected intravenously with arthropathic and amyloidogenic Enterococcus faecalis at 27 weeks of age to assess its vertical transmission during the subsequent 6-week production period. All inoculated hens developed chronic bacteraemia and arthritis, four died due to septicaemia and two of the remaining six showed amyloid arthropathy. The egg production was maintained at a lower level than the controls. Of eggs collected during the first 2 weeks after inoculation, E. faecalis was re-isolated from the yolk sac of 76% (13/17) of infertile eggs and dead embryos detected at the 18-day candling, and 100% (6/6) of non-hatching eggs, and from arthritic joints of 3% (2/66) offspring chicks of the same batch, although the latter did not develop joint amyloidosis by 8 weeks of age. E. faecalis was also re-isolated from ovary and oviduct of parent birds that died due to septicaemia. The E. faecalis organisms re-isolated from blood, ovaries and joints of diseased parent stock, yolk sac of infertile eggs and dead embryos detected at the 18-day candling, and non-hatching eggs, as well as organs and joints of offspring, had the same pulsed-field gel electrophoresis patterns as the E. faecalis isolate used to infect the parent birds. These findings indicate that vertical transmission of arthropathic and amyloidogenic E. faecalis may occur on a small scale.


Characterization of Mycobacterium tuberculosis complex isolates from the cerebrospinal fluid of meningitis patients at six fever hospitals in Egypt.
Mycobacterium tuberculosis complex isolates from cerebrospinal fluid of 67 meningitis patients were obtained from six fever hospitals in Egypt. One M. bovis and 66 M. tuberculosis isolates were identified by PCR-restriction fragment length polymorphism (RFLP) analysis of oxyR. Among the M. tuberculosis isolates, 53 unique strain types (with 3 to 16 copies of IS6110) were found by RFLP analyses. Nine clusters (eight with two isolates each and one with six isolates) were also found. Thirty-six spoligotypes, including at least 10 that have been previously reported from other countries, were also observed. Forty-one (62.1%) of the isolates were in spoligotype clusters, and 22 (33%) of the isolates were in RFLP clusters. Fifty-one of the isolates were susceptible in vitro to all of the antituberculosis drugs tested, 11 were monoresistant to capreomycin, rifampin, isoniazid (INH), pyrazinamide, or streptomycin (STR), 4 were resistant to STR and INH, and 1 was resistant to STR, INH, and ethambutol.


A longitudinal study of serum creatinine levels in patients of rheumatoid arthritis on long term NSAID therapy.
Primary: To study the effect of long term NSAID therapy on serum creatinine in patients of rheumatoid arthritis. Secondary: To study the effect of discontinuation, reduction in the dose or continuation of NSAID and of rechallenge. Case records of RA patients with a minimum two years of follow up were analysed. Age, sex, duration of RA, type, dose and duration of NSAID and DMARD therapy, co-morbid conditions and serial serum creatinine levels were charted. Ninety nine case records were studied. Incidence of abnormal creatinine level (renal insufficiency) defined as rise in creatinine equal to or above the upper limit of normal was 27.7%. This rise was asymptomatic in all patients. No NSAID was particularly associated with an increased risk in renal insufficiency. The rise of serum creatinine was reversible in most patients irrespective of discontinuation or continuation of NSAID but settled at a higher level. Rechallenge resulted in rise of serum creatinine in 50% patients. Hypertension, DM, IHD and diuretics carried a higher but not statistically significant risk of renal insufficiency. NSAID-induced asymptomatic rise of creatinine in patients of RA on long term NSAIDs is common. It is mostly reversible. Regular monitoring of serum creatinine is essential.


Web content accessibility of consumer health information web sites for people with disabilities: a cross sectional evaluation.
The World Wide Web (WWW) has become an increasingly essential resource for health information consumers. The ability to obtain accurate medical information online quickly, conveniently and privately provides health consumers with the opportunity to make informed decisions and participate actively in their personal care. Little is known, however, about whether the content of this online health information is equally accessible to people with disabilities who must rely on special devices or technologies to process online information due to their visual, hearing, mobility, or cognitive limitations. To construct a framework for an automated Web accessibility evaluation; to evaluate the state of accessibility of consumer health information Web sites; and to investigate the possible relationships between accessibility and other features of the Web sites, including function, popularity and importance. We carried out a cross-sectional study of the state of accessibility of health information Web sites to people with disabilities. We selected 108 consumer health information Web sites from the directory service of a Web search engine. A measurement framework was constructed to automatically measure the level of Web Accessibility Barriers (WAB) of Web sites following Web accessibility specifications. We investigated whether there was a difference between WAB scores across various functional categories of the Web sites, and also evaluated the correlation between the WAB and Alexa traffic rank and Google Page Rank of the Web sites. We found that none of the Web sites we looked at are completely accessible to people with disabilities, i.e., there were no sites that had no violation of Web accessibility rules. However, governmental and educational health information Web sites do exhibit better Web accessibility than the other categories of Web sites (P < 0.001). We also found that the correlation between the WAB score and the popularity of a Web site is statistically significant (r = 0.28, P < 0.05), although there is no correlation between the WAB score and the importance of the Web sites (r = 0.15, P = 0.111). Evaluation of health information Web sites shows that no Web site scrupulously abides by Web accessibility specifications, even for entities mandated under relevant laws and regulations. Government and education Web sites show better performance than Web sites among other categories. Accessibility of a Web site may have a positive impact on its popularity in general. However, the Web accessibility of a Web site may not have a significant relationship with its importance on the Web.


A Retrospective Study of Pilonidal Sinus Healing by Secondary Intention Using Negative Pressure Wound Therapy Versus Alginate or Gauze Dressings.
Pilonidal sinus (PS) disease is an inflammatory skin and subcutaneous tissue condition that presents with infection, acute abscess, chronic discharging wounds, and/or pain. Surgery with open healing by secondary intention typically is used to achieve the fastest healing time with minimal recurrence rates. A retrospective analysis was conducted of data extracted from the medical records of 73 consecutive patients who had symptomatic natal cleft PS over a 10-year period to compare use of NPWT to alginate-based/gauze daily dressing (DD) changes in terms of healing time and recurrence. Variables extracted included age, gender, PS wound diameter (small <1 cm, medium 1 cm to 3 cm, large >3 cm), and time in weeks to achieving the endpoint (epithelialization). Risk factors examined that can affect healing or recurrence of previously operated PS disease included initial drainage before excision and risk factors for impaired healing (morbid obesity as determined by body mass index [BMI] ≥35, chronic infective skin conditions, and ongoing therapy with immuno-modulating drugs or chemotherapy), and loss to follow-up. Data were collected and analyzed using the chi-squared statistic, Kaplan-Meier curves, and Cox regression models. The total time of follow-up was 390 weeks for the DD group and 311 weeks for NPWT group. Patient mean age was 26.5 ± 10.7 years, most (53, 72.6%) were male, and 12 (16.4%) had comorbidities potentially affecting healing. Nine (9) were treated with primary closure and 62 patients were treated with open healing by secondary intention (2 additional patients receiving DD were excluded from the analysis because they had small sinuses that made NPWT unfeasible). Among participants, 30 (48%) received DD and 32 had NPWT. The median time to healing was 10 weeks (95% CI: 7-17) in the DD group and 8 weeks (95% CI: 7-9) in the NPWT group (not significantly different). In patients who healed, the average time to healing was 15.0 ± 18.1 and 9.8 ± 6.3 weeks in the DD and NPWT groups, respectively (not significantly different). The PS wound recurred in 5 patients - 4 (12.5%) in the DD group and 1 (3.1%) in the NPWT group (P = .355). In univariate analysis, only the presence of comorbidities was found to significantly affect time to healing (HR 95%, CI: 0.40 [0.17-0.93]; P = .033]. Prospective, randomized controlled clinical studies are warranted.


Dietary dehydrated lemon peel improves the immune but not the antioxidant status of gilthead seabream (Sparus aurata L.).
Lemon (Citrus limon) is the third most important species of citrus in the world, while Spain is the major producer in Europe. Numerous beneficial effects of lemon are known, which explains their use in traditional medicine. The paper describes the effect of dietary dehydrated lemon peel (a sub-product of the lemon industry) on the growth, immune and antioxidant status of gilthead seabream (Sparus aurata L.) over a period of 30 days. Fish fed diets enriched with dehydrated lemon peel (1.5% and 3%) for 15 days showed improved growth and both humoral (seric immunoglobulin M) and cellular (peroxidase activity and phagocytic ability of head kidney leucocytes) immunity, as well as the expression of some immune-related genes (nkefa, il1β, igth and csfr1). However, decreases growth promotion was observed after thirty days of trial. Neither the anti-oxidant enzymes activity nor the expression of several anti-oxidants and anti-stress genes in liver was improved by the diet. The possible inclusion of dehydrated lemon peel in fish diets for its immunostimulant effects is discussed.


Hypoglossal nerve palsy as complication of oral intubation, bronchoscopy and use of the laryngeal mask airway.
Hypoglossal nerve injury is a recognized but rare complication of oropharyngeal manipulation during intubation, bronchoscopy and use of a laryngeal mask airway. We present 2 new cases of temporary hypoglossal nerve palsy after orotracheal intubation for general anesthesia. The relevant literature is reviewed and different hypotheses concerning the pathophysiological mechanisms of nerve damage are discussed.


BeiDou inter-satellite-type bias evaluation and calibration for mixed receiver attitude determination.
The Chinese BeiDou system (BDS), having different types of satellites, is an important addition to the ever growing system of Global Navigation Satellite Systems (GNSS). It consists of Geostationary Earth Orbit (GEO) satellites, Inclined Geosynchronous Satellite Orbit (IGSO) satellites and Medium Earth Orbit (MEO) satellites. This paper investigates the receiver-dependent bias between these satellite types, for which we coined the name "inter-satellite-type bias" (ISTB), and its impact on mixed receiver attitude determination. Assuming different receiver types may have different delays/biases for different satellite types, we model the differential ISTBs among three BeiDou satellite types and investigate their existence and their impact on mixed receiver attitude determination. Our analyses using the real data sets from Curtin's GNSS array consisting of different types of BeiDou enabled receivers and series of zero-baseline experiments with BeiDou-enabled receivers reveal the existence of non-zero ISTBs between different BeiDou satellite types. We then analyse the impact of these biases on BeiDou-only attitude determination using the constrained (C-)LAMBDA method, which exploits the knowledge of baseline length. Results demonstrate that these biases could seriously affect the integer ambiguity resolution for attitude determination using mixed receiver types and that a priori correction of these biases will dramatically improve the success rate.


Unawareness of hepatitis B infection and lack of surveillance are associated with severity of hepatocellular carcinoma.
Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV-related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV-related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety-one (23%) of the HBV-aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.


[Assessment of legal awareness regarding illicit drug use among Kraków university students].
Social survey is a very important source of information concerned with planing the preventive strategy and protecting against problems relevant to the use of psychoactive substances. The survey covered a group of 211 first-year students from five colleges in Kraków. The students showed weak awareness of law. The respondents are of the opinion that the rules dealing with the addiction issue have been too liberal thus far. The emphasis should be put on enforcing the anti-drug law. Otherwise it will not became a powerful weapon to counteract the drug addiction. According to the opinion of respondents the trade and delivery of drugs are highly disapproving and they require inflicting stringent punishments. The results of our analysis are the integral part of Kraków model to help addicted to psychoactive substances and of prevention activities referred to the students of colleges.


Sex-Based Disparities in Leukocyte Migration and Activation in Response to Inhalation Lung Injury: Role of SDF-1/CXCR4 Signaling.
The aim of the study was to determine whether sex-related differences exist in immune response to inhalation lung injury. C57BL/6 mice were exposed to Cl2 gas (500 ppm for 15, 20, or 30 min). Results showed that male mice have higher rates of mortality and lung injury than females. The binding of the chemokine ligand C-X-C motif chemokine 12 (CXCL12), also called stromal-derived-factor-1 (SDF-1), to the C-X-C chemokine receptor type 4 (CXCR4) on lung cells promotes the migration of leukocytes from circulation to lungs. Therefore, the hypothesis was that elevated SDF-1/CXCR4 signaling mediates exaggerated immune response in males. Plasma, blood leukocytes, and lung cells were collected from mice post-Cl2 exposure. Plasma levels of SDF-1 and peripheral levels of CXCR4 in lung cells were higher in male vs. female mice post-Cl2 exposure. Myeloperoxidase (MPO) and elastase activity was significantly increased in leukocytes of male mice exposed to Cl2. Lung cells were then ex vivo treated with SDF-1 (100 ng/mL) in the presence or absence of the CXCR4 inhibitor, AMD3100 (100 nM). SDF-1 significantly increased migration, MPO, and elastase activity in cells obtained from male vs. female mice post-Cl2 exposure. AMD3100 attenuated these effects, suggesting that differential SDF-1/CXCR4 signaling may be responsible for sex-based disparities in the immune response to inhalation lung injury.


Studies of gamma-glutamyltransferase activity in the brain tissue post mortem.
Our experiments showed that the activity of gamma-glutamyltransferase (gamma-GT) did not remarkably change in homogenates of mouse, rat, and bovine brains during the first four days post mortem. In the course of that period, the brain microvessels also retained their gamma-GT activity. gamma-GT of microvessels from bovine brain cortex, solubilized with sodium deoxycholate, was eluted in the void volume Vo when chromatographed on a Sephadex G-200 column with the detergent Triton X-100. In human post mortem brains, the specific activity of gamma-GT in choroid plexi was found to be about five times higher than that in the cerebral cortex, white matter, basal ganglia, pons, and cerebellum but about four times lower than that in the microvessels obtained from the studied brain regions. Our findings suggest that it is possible to study the components of the blood-brain barrier on material from deceased subjects.


Pathophysiological effects of endotoxins in ruminants. 2. Metabolic aspects.
Metabolic disturbances following intravenous and intramammary administration of endotoxins in ruminants are described. In contrast to the similarity in response of blood biochemical parameters after intravenous and intramammary administrations of endotoxins, responses in plasma concentrations of enzyme activities, the thyroid hormones, cortisol, and somatotropin differ markedly. Biochemical changes in blood after endotoxin administration are predominantly dose-dependent; thus some of the biochemical parameters - especially plasma concentrations of Fe and Zn - serve also to evaluate the effects of certain drugs in endotoxin models. Changes in milk composition have been documented only after intramammary infusion of endotoxins and can partly be explained by the increased permeability of the blood/milk barrier. Appearance and production of milk returns to normal within a week after intramammary endotoxin treatment, indicating that the mammary gland is only temporarily damaged by endotoxin-induced mastitis.


The dynamic urethral sphincter function in healthy females assessed by rapid dilatations in the resting state: evaluation of reproducibility.
Recording the pressure response to rapid dilatations enables one to assess urethral sphincter function. The rapid dilatations of the urethra experimentally simulate the ingression of urine. A method that enables standardized dilatations of 2-mm long urethral segments was urine (USED).A method that enables standardized dilatations of 2-mm long urethral segments was used, and the subsequent pressure response was measured. The reproducibility of the urethral pressure response to rapid and standardized dilatations was evaluated by repeating the measurements after 1 week in 10 healthy females. The pressure response showed an acceptable reproducibility. The urethral pressure increase as a response to dilatation is considered to rely on stretching of intra- and periurethral fibers. Calculations of strain (change in length divided by the original length) of circularly arranged fibers when the urethra is dilated indicate that the tension (and pressure) bearing layers must be located outside a circular zone with a radius of 4 mm perpendicular to the longitudinal axis of the urethra.


Successful treatment of renal cell carcinoma with mediastinal lymph node metastasis by interleukin-2: a case report.
A 57-year-old woman presented to our hospital with macrohematuria. Renal cell carcinoma (RCC) of the left kidney with bilateral pulmonary and mediastinal lymph node metastases was diagnosed. Radical nephrectomy was performed. Pathological examination confirmed the diagnosis of RCC (pT2pN0M1), so immunotherapy was performed using interleukin-2 (IL-2). The mediastinal lymph node metastases disappeared completely after 5 months of immunotherapy. Investigation of immunological parameters showed an increase of CD8-positive T cells (CD8) and a decrease of CD14-positive cells (CD14), leading to a marked increase of the CD8/CD14 ratio. Although her pulmonary metastases are unchanged, the mediastinal metastases still show complete remission at 14 months postoperatively. The CD8/CD14 ratio may have potential as a new marker for monitoring the response of RCC to immunotherapy and selecting suitable patients for such therapy.


Family 17 and 28 carbohydrate-binding modules discriminated different cell-wall sites in sweet potato roots.
Endoglucanase Cel5A from Clostridium josui contains a family 17 carbohydrate-binding module (CBM) (CjCBM17) and a family 28 CBM (CjCBM28) in tandem. These two CBMs bound to non-crystalline cellulose and beta-1,3-1,4-glucan. Our results indicate that the CBMs recognized different components on the cell wall of a sweet potato root. The root was cut into longitudinal sections. We used CjCBM17 and CjCBM28 fused to two different fluorescent proteins to visualize differential recognition of the plant cell wall. When they were microscopically observed, CjCBM28-fused cyan fluorescent protein (CFP) differentially bound to the root cap, but CjCBM17-fused blue fluorescent protein (BFP) did not. CjCBM17-BFP bound to the central part or the root apical meristem. These results suggest that CjCBM17 and CjCBM28 recognize different sites of the cell wall and that the cell-wall components and the polysaccharides configuration in the cell wall differ between tissues.


Outcome in shunted hydrocephalic children.
The purpose of the present study was to identify the main risk factors for poor outcome in children with shunted hydrocephalus, including the timing of the operation. The medical records of patients born between 1984 and 1992, who had undergone shunt operation for hydrocephalus before 1994, were analysed retrospectively. The following data were collected: aetiology of hydrocephalus, other pathology in addition to hydrocephalus, timing of drain implantation, number and indication of revisions and several outcome parameters such as school type, seizures and morbidity parameters. Children with a post-haemorrhagic hydrocephalus fared poorly. Children with hydrocephalus due to spina bifida or another congenital malformation had considerably better outcome scores. Pathology in addition to hydrocephalus negatively influenced the prognosis. Regarding the timing of drain implantation, we found a poorer mental and linguistic development in children operated more than 1 month after diagnosis. Patients with more than two revisions seem to have a higher chance of developing seizures. In conclusion, this study confirms earlier reports that peri- and postnatal haemorrhage is an important risk factor for poor outcome. More importantly, we found that delay in surgical treatment might also be a risk factor for poor outcome in hydrocephalic children.


Comparison of intraduodenal and intravenous glucose metabolism under clamp conditions in humans.
To determine whether the uptake and metabolic partition of glucose are influenced by its delivery route, 12 normal volunteers underwent two 3-h euglycemic (approximately 93 mg/dl) hyperinsulinemic (approximately 43 mU/l) clamps at a 3- to 5-wk interval, one with intravenous (i.v.) and the other with intraduodenal (i.d.) glucose labeled with [3-3H]- and [U-14C]glucose. Systemic glucose was traced with [6,6-2H2]glucose in eight subjects. During the last hour of the clamps, the average glucose infusion rate (5.85 +/- 0.37 vs. 5.43 +/- 0.43 mg.kg(-1).min(-1); P = 0.02) and exogenous glucose uptake (5.66 +/- 0.37 vs. 5.26 +/- 0.41 mg.kg(-1).min(-1); P = 0.04) were borderline higher in the i.d. than in the i.v. studies. The increased uptake was entirely accounted for by increased glycolysis (3H2O production), which was attributed to the stimulation of gut metabolism by the absorptive process. No difference was observed in glucose storage whether it was calculated as glucose uptake minus glycolysis (i.d. vs. i.v.: 2.44 +/- 0.28 vs. 2.40 +/- 0.31 mg.kg(-1).min(-1)) or as glucose uptake minus net glucose oxidation (2.86 +/- 0.33 vs. 2.81 +/- 0.35 mg.kg(-1).min(-1)). Because peripheral tissues were exposed to identical glucose, insulin, and free fatty acid levels under the two experimental conditions, we assumed that their glucose uptake and storage were similar during the two tests. We therefore suggest that hepatic glycogen storage (estimated as whole body minus peripheral storage) was also unaffected by the route of glucose delivery. On the other hand, in the i.d. tests, the glucose splanchnic extraction ratio calculated by the dual-isotope technique averaged 4.9 +/- 2.3%, which is close to the figures published for i.v. glucose. Despite the limitations related to whole body measurements, these two sets of data do not support the idea that enteral glucose stimulates hepatic uptake more efficiently than i.v. glucose.


Ultrasound in acute and chronic cholecystitis.
Sonograms of 412 consecutive patients with operatively and histologically proven acute or chronic cholecystitis were reviewed retrospectively. 267 of them had been operated on in an acute phase of gallbladder disease and 145 had undergone an elective operation. 236 patients had an operative and/or histological diagnosis of acute cholecystitis and 176 both operatively and histologically confirmed chronic cholecystitis. A thickened gallbladder wall was seen in 80% of acute cases, wall sonolucency in 39%, dilated gallbladder in 60%, sludge in 26% and stones in 75%, the corresponding proportions of the chronic cases being 18%, 4%, 12%, 13% and 93%. A contracted gallbladder with stones was seen in 15% of the chronic and 1% of the acute cholecystitis cases. 90% of the acute cases had two or more sonographic abnormalities, whereas 70% of the chronic cases had only one abnormality, most frequently gallstones. Only one normal sonographic finding was recorded in each group.


Living Kidney Donor Cancellation at King Hussein Medical Center.
Living-related kidney donation is the main source of renal grafts in Jordan, since kidneys from deceased donors are scarce. Although the Jordanian community accepts the idea of kidney donation to family members, not all potential donors manage to complete the required psychologic and medical evaluations. We review the causes of kidney-donation cancellation and suggest options to increase the number of available organs. We performed a retrospective chart review of all potential living-related kidney donors at King Hussein Medical Center between January 2008 and June 2016. Of 642 potential donors, 366 (57%) were male and 276 (43%) were female, ranging in age from 18 to 66 years with a mean age of 37 years. A total of 384 (59.8%) eventually donated a kidney. A donor issue was the cause of cancellation in 143 (22.3%), whereas 47 (32.9%) had a risk for renal impairment after donation (eg, hematuria, proteinuria, stones, multiple renal cysts, scarred kidney, congenital malformation, recurrent urinary tract infection), and 30 (21%) had blood group or immunologic incompatibilities. Fifteen (10.5%) withdrew during the evaluation process, 13 (9%) had hypertension, 10 (7%) had a high body mass index, 8 (5.6%) were diabetic or prediabetic, 7 (4.9%) were surgically unsuitable, 4 (2.8%) had hepatitis B virus infection, 4 (2.8%) were pregnant, 3 (2.1%) had significant cardiovascular disease, 1 (0.7%) had splenomegaly with lymph node enlargement, and 1 (0.7%) had thyroiditis. Cancellation of kidney donation in Jordan is mainly for medical reasons, the most common being renal issues. Paired donation between blood group and immunologically incompatible duos may increase the number of organs available, as may good psychologic assessment and counseling of those likely to change their mind. Support should be provided for donors who drop out of donation for any cause, especially for renal and vascular issues.


Effect of Resveratrol on Modulation of Endothelial Cells and Macrophages for Rapid Vascular Regeneration from Electrospun Poly(ε-caprolactone) Scaffolds.
Rapid endothelialization is a key factor that determines the success of small-diameter vascular grafts as an artery substitute in the treatment of cardiovascular diseases. Aimed to facilitate vascular regeneration, we developed a vascular scaffold loaded with resveratrol, which is a natural compound extracted from plants and showed multifaceted effects in cardiovascular protection. The tubular poly(ε-caprolactone) (PCL) scaffold was prepared by electrospinning with resveratrol in the PCL solution. In vitro assay demonstrated that resveratrol could be released from the scaffolds in a sustained and controlled manner. Cell culture results indicated that the migration of endothelial cells (ECs), nitric oxide production, and the ability of tube formation increased in the resveratrol-containing PCL scaffold groups compared with the PCL control. Meanwhile, the level of tumor necrosis factor (TNF)-α, the main proinflammatory factor secreted from macrophages, was reduced, and the messenger RNA expressions of the M2 macrophage-related genes were increased in the resveratrol-containing group. Further, in vivo implantation was performed by replacing rat abdominal aorta. We observed fast endothelialization and enhanced vascular regeneration in rats with resveratrol-containing scaffolds. The presence of resveratrol also induced a large number of M2 macrophages to infiltrate into the graft wall. Taken together, the incorporation of resveratrol into the PCL grafts enhanced the vascular regeneration by modulation of ECs and macrophages.


Global health impacts of future aviation emissions under alternative control scenarios.
There is strong evidence of an association between fine particulate matter less than 2.5 μm (PM2.5) in aerodynamic diameter and adverse health outcomes. This study analyzes the global excess mortality attributable to the aviation sector in the present (2006) and in the future (three 2050 scenarios) using the integrated exposure response model that was also used in the 2010 Global Burden of Disease assessment. The PM2.5 concentrations for the present and future scenarios were calculated using aviation emission inventories developed by the Volpe National Transportation Systems Center and a global chemistry-climate model. We found that while excess mortality due to the aviation sector emissions is greater in 2050 compared to 2006, improved fuel policies (technology and operations improvements yielding smaller increases in fuel burn compared to 2006, and conversion to fully sustainable fuels) in 2050 could lead to 72% fewer deaths for adults 25 years and older than a 2050 scenario with no fuel improvements. Among the four health outcomes examined, ischemic heart disease was the greatest cause of death. Our results suggest that implementation of improved fuel policies can have substantial human health benefits.


Dendritic cells in the skin--potential use for melanoma treatment.
Melanoma is an aggressive malignancy with poor prognosis. Eradication of tumor cells requires an effective interaction between melanoma cells and different players of the immune system. As the most potent professional antigen-presenting cells, dendritic cells (DCs) play a pivotal role in mounting a specific immune response where their intratumoral and peritumoral density as well as their functional status are correlated with clinical staging of the disease and with patients' survival. Under steady-state conditions, internalization of apoptotic cells by immature DCs designates a state of tolerance to self-antigens. Nevertheless, pathogens and necrotic cells interacting with pattern recognition receptors trigger downstream signaling pathways that evoke maturation of DCs, leading to the production of pro-inflammatory cytokines. These mature DCs are essential for T-cell priming and subsequent development of a specific immune response. Altered functions of DCs have an impact on the development of various disorders including autoimmune diseases and cancers. Herein, we focus on the checkpoints created throughout DCs antigen capturing and presentation to T cells, with subsequent development of either tolerance or immune response, with an emphasis on the role played by DCs in melanoma tumorigenesis and their therapeutic potential.


Tear Function Alterations and Conjunctival Impression Cytology Findings in Patients With Gout.
The aim of this study was to evaluate the tear functions and conjunctival impression cytology (CIC) findings of patients with gout and compare them with healthy controls. Thirty-four patients with gout (group 1) and 32 age-matched and gender-matched healthy individuals (group 2) were included in this cross-sectional study. Schirmer 1 test, tear breakup time (TBUT), Ocular Surface Disease Index (OSDI) score, and CIC grade were evaluated and compared between the groups. There was no significant difference between the groups in gender and age (P=0.923 and P=0.078, respectively). The mean of Schirmer 1 test result was significantly lower in group 1 (9.74±6.03 mm) than that in group 2 (17.16±9.33 mm) (P<0.001). The TBUT was also significantly lower in group 1 (7.00±2.09 seconds) than that in group 2 (12.75±5.25 seconds) (P<0.001). The OSDI score (20.04±12.92) was significantly higher in group 1 than that in group 2 (6.19±10.07) (P<0.001). Although 10 patients (29.4%) in group 1 had the CIC grade of 2 to 3, none of the controls had CIC grade 2 to 3. The mean CIC grade in group 1 (1.15±0.89) was significantly higher than that in group 2 (0.47±0.51) (P<0.001). The results of this study suggest that ocular surface alterations assessed by CIC and tear function abnormalities are more common in patients with gout.


Interspecific Gene Exchange Introduces High Genetic Variability in Crop Pathogen.
Genome analyses have revealed a profound role of hybridization and introgression in the evolution of many eukaryote lineages, including fungi. The impact of recurrent introgression on fungal evolution however remains elusive. Here, we analyzed signatures of introgression along the genome of the fungal wheat pathogen Zymoseptoria tritici. We applied a comparative population genomics approach, including genome data from five Zymoseptoria species, to characterize the distribution and composition of introgressed regions representing segments with an exceptional haplotype pattern. These regions are found throughout the genome, comprising 5% of the total genome and overlapping with > 1,000 predicted genes. We performed window-based phylogenetic analyses along the genome to distinguish regions which have a monophyletic or nonmonophyletic origin with Z. tritici sequences. A majority of nonmonophyletic windows overlap with the highly variable regions suggesting that these originate from introgression. We verified that incongruent gene genealogies do not result from incomplete lineage sorting by comparing the observed and expected length distribution of haplotype blocks resulting from incomplete lineage sorting. Although protein-coding genes are not enriched in these regions, we identify 18 that encode putative virulence determinants. Moreover, we find an enrichment of transposable elements in these regions implying that hybridization may contribute to the horizontal spread of transposable elements. We detected a similar pattern in the closely related species Zymoseptoria ardabiliae, suggesting that hybridization is widespread among these closely related grass pathogens. Overall, our results demonstrate a significant impact of recurrent hybridization on overall genome evolution of this important wheat pathogen.


Approach bias for erotic stimuli in heterosexual male college students who use pornography.
Addicted individuals often demonstrate relatively automatic action tendencies in response to addiction-related stimuli, whereby they approach rather than avoid addictive stimuli. This study assessed whether an approach bias for erotic stimuli exists among heterosexual college-aged males who report using pornography. We tested 72 male undergraduate students using an approach-avoidance task employing erotic stimuli, during which participants were instructed to push or pull a joystick in response to image orientation. To simulate approach and avoidance movements, pulling the joystick enlarged the image and pushing shrunk the image. Frequency and severity of pornography use was assessed using a Brief Pornography Screener and the Problematic Pornography Use Scale (PPUS). Participants demonstrated a significant approach bias for erotic stimuli as compared to neutral stimuli, and this approach bias significantly correlated with pornography-use measures. Moreover, individuals with problematic pornography use (as classified by the PPUS) showed more than double the approach bias than did non-problematic users. The observation of cognitive biases for erotic stimuli in individuals with problematic pornography use indicate similarities between behavioral and substance addictions.


El Niño Southern Oscillation (ENSO) enhances CO2 exchange rates in freshwater Marsh ecosystems in the Florida everglades.
This research examines the relationships between El Niño Southern Oscillation (ENSO), water level, precipitation patterns and carbon dioxide (CO2) exchange rates in the freshwater wetland ecosystems of the Florida Everglades. Data was obtained over a 5-year study period (2009-2013) from two freshwater marsh sites located in Everglades National Park that differ in hydrology. At the short-hydroperiod site (Taylor Slough; TS) and the long-hydroperiod site (Shark River Slough; SRS) fluctuations in precipitation patterns occurred with changes in ENSO phase, suggesting that extreme ENSO phases alter Everglades hydrology which is known to have a substantial influence on ecosystem carbon dynamics. Variations in both ENSO phase and annual net CO2 exchange rates co-occurred with changes in wet and dry season length and intensity. Combined with site-specific seasonality in CO2 exchanges rates, El Niño and La Niña phases magnified season intensity and CO2 exchange rates at both sites. At TS, net CO2 uptake rates were higher in the dry season, whereas SRS had greater rates of carbon sequestration during the wet season. As La Niña phases were concurrent with drought years and extended dry seasons, TS became a greater sink for CO2 on an annual basis (-11 to -110 g CO2 m-2 yr-1) compared to El Niño and neutral years (-5 to -43.5 g CO2 m-2 yr-1). SRS was a small source for CO2 annually (1.81 to 80 g CO2 m-2 yr-1) except in one exceptionally wet year that was associated with an El Niño phase (-16 g CO2 m-2 yr-1). Considering that future climate predictions suggest a higher frequency and intensity in El Niño and La Niña phases, these results indicate that changes in extreme ENSO phases will significantly alter CO2 dynamics in the Florida Everglades.


Characteristics of Chaotic Weak Reflection in Carbonate Fracture-Cavity Reservoirs: A Case Study of Ordovician Reservoirs in Block 10 of the Tahe Oilfield, Tarim Basin, China.
The identification of carbonate reservoirs is a critical task in oil and gas exploration. Chaotic weak reflection is an important type of reflection characteristic in carbonate reservoirs. Widespread distribution of chaotic weak reflection has been observed in the Ordovician Yijianfang Formation in the Tahe area. However, there is still a lack of systematic research on the distribution, characteristics, reservoir space, and reservoir types of chaotic weak reflection in the Tahe area. To address this issue, this study conducted a comprehensive analysis of multiscale data and found that chaotic weak reflections are distributed within 100 ms below the top interface of the Middle Ordovician. Seismic profiles exhibit a "string of pearls" with a "tail" or "pearl-like" widening feature. On well logs, all three porosity curves exhibit localized peaks, with increases in acoustic (AC) and compensated neutron (CNL) and decreases in density (DEN), while the deep and shallow lateral resistivity (RD, RS) curves show positive amplitude differences. In the FMI, they are represented by dark sinusoidal curves and dark small patches. Based on these response characteristics, two types of reservoir spaces are identified for chaotic weak reflections: high-angle vertical fractures and caves with heights less than 7 m, which can form independent reservoirs or fracture-cavity complexes. Three types of reservoirs are distinguished: fracture, cavity, and cavity-fracture types.


Chronic stress and immunosenescence: a review.
This paper reviews recent work suggesting that human immunosenescence may be closely related to both chronic stress and stress hormones. The age-related immunological changes are also similarly found during chronic stress or glucocorticoid exposure. These data further suggest that endogenous glucocorticoids could be associated with immunosenescence. When compared with young subjects, healthy elders are emotionally distressed in parallel to increased cortisol/dehydroepiandrosterone ratio. Furthermore, chronically stressed elderly subjects may be particularly at risk of stress-related pathology because of further alterations in glucocorticoid-immune signaling. Age-related increase in cortisol/dehydroepiandrosterone ratio could be understood as a major determinant of immunological changes observed during aging. Strictly healthy elders are somewhat protected from chronic stress exposure and show normal cortisol levels and increased T cell function. This information adds a new key dimension to the biology of aging and stress.


Cluster Analysis of Physical Activity Patterns, and Relationship with Sedentary Behavior and Healthy Lifestyles in Prepubertal Children: Genobox Cohort.
Sedentary habits during childhood are associated with adverse health outcomes. The aim of this work was to cluster lifestyle behaviors and metabolic biomarkers to establish different patterns in children. Their physical and sedentary activities were evaluated by accelerometry, and questionnaires that included lifestyle behaviors, such as adherence to a Mediterranean diet, anthropometry and blood biochemical markers. Cluster analysis was performed to establish different groups based on physical activity levels. A total of 489 children were finally selected. Cluster 1 included children with a mostly sedentary state, whereas Cluster 3 included the most active children and Cluster 2 included children that did not fit into either the sedentary or the highly active groups. In Cluster 3, 56% of children were in a sports club, and a lower percentage used electronic devices in their rooms compared to the other groups. Cluster 1 children exhibited higher insulin, HOMA-IR and triacylglycerides with respect to the other groups. No differences were found regarding adherence to a Mediterranean diet. The choice to practice an extracurricular sport could be an influencing factor to increase exercise and ensure an active lifestyle in children. Reducing or limiting screen time mainly in children's rooms could contribute to an active lifestyle.


Polymorphism in Thermoelectric As2Te3.
Metastable β-As2Te3 (R3̅m, a = 4.047 Å and c = 29.492 Å at 300 K) is isostructural to layered Bi2Te3 and is known for similarly displaying good thermoelectric properties around 400 K. Crystallizing glassy-As2Te3 leads to multiphase samples, while β-As2Te3 could indeed be synthesized with good phase purity (97%) by melt quenching. As expected, β-As2Te3 reconstructively transforms into stable α-As2Te3 (C2/m, a = 14.337 Å, b = 4.015 Å, c = 9.887 Å, and β = 95.06°) at 480 K. This β → α transformation can be seen as the displacement of part of the As atoms from their As2Te3 layers into the van der Waals bonding interspace. Upon cooling, β-As2Te3 displacively transforms in two steps below T(S1) = 205-210 K and T(S2) = 193-197 K into a new β'-As2Te3 allotrope. These reversible and first-order phase transitions give rise to anomalies in the resistance and in the calorimetry measurements. The new monoclinic β'-As2Te3 crystal structure (P2(1)/m, a = 6.982 Å, b = 16.187 Å, c = 10.232 Å, β = 103.46° at 20 K) was solved from Rietveld refinements of X-ray and neutron powder patterns collected at low temperatures. These analyses showed that the distortion undergone by β-As2Te3 is accompanied by a 4-fold modulation along its b axis. In agreement with our experimental results, electronic structure calculations indicate that all three structures are semiconducting with the α-phase being the most stable one and the β'-phase being more stable than the β-phase. These calculations also confirm the occurrence of a van der Waals interspace between covalently bonded As2Te3 layers in all three structures.


Application of nonsense-mediated primer exclusion (NOPE) for preparation of unique molecular barcoded libraries.
Recently we proposed efficient method to exclude undesirable primers at any stage of amplification reaction, here termed NOPE (NOnsense-mediated Primer Exclusion). According to this method, added oligonucleotide overlapping with the 3'-end of unwanted amplification primer (NOPE oligo) simultaneously provides a template for its elongation. This elongation disrupts specificity of unwanted primer, preventing its further participation in PCR. The suggested approach allows to rationally manage the course of PCR reactions in order to facilitate analysis of complex DNA mixtures as well as to perform multistage PCR bypassing intermediate purification steps. Here we apply NOPE method to DNA library preparation for the high-throughput sequencing (HTS) with the PCR-based introduction of unique molecular identifiers (UMI). We show that NOPE oligo efficiently neutralizes UMI-containing oligonucleotides after introduction of UMI into sample DNA molecules, thus allowing to proceed with further amplification steps without purification and associated loss of starting material. At the same time, NOPE oligo does not affect the efficiency of target PCR amplification. We describe a simple, robust and cheap modification of UMI-labeled HTS libraries preparation procedure, that allows to bypass purification step and thus to preserve starting material which may be limited, e.g. circulating tumor DNA, circulating fetal DNA, or small amounts of isolated cells of interest. Furthermore, demonstrated simplicity and robustness of NOPE method should make it popular in various PCR protocols.


Twelve-year "cure" of lung cancer with metastasis to the brain.
In managing lung cancer with metastasis to the brain, the clinician must decide whether to treat the primary lesion, the metastasis, neither, or both. A patient enjoying a useful survival of five years or more following treatment may be regarded as apparently cured. This patient was functioning normally twelve years after surgical treatment of the brain and lung lesions. Lung cancer with metastasis to the brain is not always a hopeless situation; occasionally a patient will derive great benefit from treatment.


Destiny and intracellular survival of Leishmania amazonensis in control and dexamethasone-treated glial cultures: protozoa-specific glycoconjugate tagging and TUNEL staining.
Leishmania amazonensis, an obligatory intracellular parasite, survives internalization by macrophages, but no information is available on the involvement of microglia. We have investigated microglia-protozoa interactions in mixed glial cultures infected with promastigote forms of L. amazonensis after lipopolysaccharide (LPS) or dexamethasone (DM) treatment. After 2 hr of exposure to parasites in control cultures, there was a small number of infected microglia (1%). Preincubation with LPS or DM led to 14% or 60% of microglial cells with attached parasites, respectively. DM treatment resulted in 39% of microglial cells with internalized parasites (controls or LPS-treated cells had < or =1%). Scanning electron micrographs showed numerous filopodia in DM-treated cells, whereas these projections were rarely observed in LPS-treated or control cells. DM treatment also affected the intramicroglial survival of Leishmania. In control cultures, internalized parasites, tagged with an anti-lipophosphoglycan (anti-LPG) antibody, showed fragmented DNA [terminal deoxyribonucleotide transferase-mediated dUTP-X nick end labeling (TUNEL+)] after 4 hr of interaction, but changes seemed slightly delayed in DM-treated cultures. After 12 hr, there were no LPG+/TUNEL+ profiles in controls, whereas rare LPG+ profiles still persisted in DM-treated cells. Our results suggest that microglia are highly effective in the elimination of Leishmania and that the process can be effectively studied by LPG/TUNEL double labeling.


Comparing sex steroid levels during the annual cycles of rainbow trout (Oncorhynchus mykiss) diploid female (XX) and triploid female (XXX) genotypic sex.
In this study, the annual cycle of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), 17β-estradiol (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) was determined using radioimmunoassay and then compared for two populations of rainbow trout, XX diploid females (n = 40) and XXX triploid females (n = 15). In females, E2 and DHP levels were found to be significantly related to body weight (r = 0.22513; p < 0.0001 and r = 0.15831; p > 0.001, respectively). In this group, E2 concentrations peaked in November (25.05 ng/ml), while maximum DHP levels, only measurable from October to April, were attained in February (64.14 ng/ml). No significant differences in hormone ranges related to egg output ability were observed. Finally, sex steroid concentrations were low in the triploid female XXX fish compared to the female XX population. Nevertheless, maximum T (33.85 ng/ml) and 11-KT (32.35 ng/ml) levels were recorded in January, for XXX. The levels for these two hormones are relatively high and are also significantly associated (r = 0.8430; p < 0.0001). Diploid females showed significantly higher levels of E2 than triploids over the 12-month study period. The female triploid fish produced the lowest steroid hormone levels, such that these would be the most suitable for human consumption.


Increasing dependency of older people in nursing homes is associated with need for dental treatments.
To determine relationships between the need for dental treatments of institutionalized elderly people and cognitive impairment and the general level of care needed. Two hundred and sixty-eight residents of long-term care facilities in Germany were included in this study. Age, sex, diseases, number of frequently taken drugs, and location of the long-term care facility of the participants were recorded. For each participant, the need for care was assessed by use of the Barthel index (BI). Cognitive impairment was evaluated by use of the mini-mental state examination (MMSE). To assess dental treatment needs, the revised oral assessment guide (ROAG) was applied for different oral health conditions, which were rated "healthy" or "treatment needed". Spearman correlations were performed to evaluate associations between BI and MMSE and dental treatment needs. Statistical analysis revealed significant associations of BI (P<0.001) and MMSE (P=0.015) with the ROAG score. Increasing dependency and decreasing cognitive ability worsen oral health and increase the need for dental treatment.


Lumping evolutionary game dynamics on networks.
We study evolutionary game dynamics on networks (EGN), where players reside in the vertices of a graph, and games are played between neighboring vertices. The model is described by a system of ordinary differential equations which depends on players payoff functions, as well as on the adjacency matrix of the underlying graph. Since the number of differential equations increases with the number of vertices in the graph, the analysis of EGN becomes hard for large graphs. Building on the notion of lumpability for Markov chains, we identify conditions on the network structure allowing to reduce the original graph. In particular, we identify a partition of the vertex set of the graph and show that players in the same block of a lumpable partition have equivalent dynamical behaviors, whenever their payoff functions and initial conditions are equivalent. Therefore, vertices belonging to the same partition block can be merged into a single vertex, giving rise to a reduced graph and consequently to a simplified system of equations. We also introduce a tighter condition, called strong lumpability, which can be used to identify dynamical symmetries in EGN which are related to the interchangeability of players in the system.


Effects of physical activity and exercise on the cognitive function of patients with Alzheimer disease: a meta-analysis.
Alzheimer's disease (AD), as the most common cause of dementia, brings huge economic burden for patients and social health care systems, which motivates researchers to study multiple protective factors, among which physical activity and exercise have been proven to be both effective and economically feasible. A systematic literature search was performed for eligible studies published up to November 1st 2018 on three international databases (PubMed, Cochrane Library, and Embase) and two Chinese databases (Wanfang Data, China National Knowledge Infrastructure). All analyses were conducted using Stata 14.0. Due to heterogeneity between studies, a random-effects model was used for this meta-analysis. Meta-analysis was used to explore if physical activity and exercise can exert positive effects on cognition of elderly with AD and subgroup analyses were conducted to find out if there are dose-response effects. A total of 13 randomized controlled trials were included with a sample size of 673 subjects diagnosed with AD. Intervention groups showed a statistically significant improvement in cognition of included subjects measured by the MMSE score (SMD = 1.12 CI:0.66~1.59) compared to the control groups. Subgroup analyses showed different amounts of physical activity and exercise can generate different effects. As one of few meta-analyses comparing different quantities of physical activity and exercise interventions for AD in details, our study suggests that physical activity and exercise can improve cognition of older adults with AD. While the concomitant effects on cognition functions of high frequency interventions was not greater than that of low frequency interventions, the threshold remains to be settled. However, more RCTs with rigorous study design are needed to support our findings.