Sex differences in spontaneous locomotor activity and rotational behavior in meadow voles.
Sex differences in rotational behavior have been most clearly established in laboratory rats with females exhibiting a turning bias. Here, using an automated open-field apparatus, locomotor activity and spontaneous rotational behavior were examined in diurnally crepuscularly active reproductive male and female meadow voles (Microtus pennsylvanicus). Meadow voles, being induced ovulators, permitted analysis of females in constant behavioral estrous. Males displayed significantly greater levels of activity and also significantly greater levels of clockwise but not counterclockwise rotational behavior relative to the females. Rotational behavior was less strongly related to activity levels in female as compared to male voles. In addition, females displayed an overall turning bias. These results contrast with findings from laboratory rats in which females are reported to display greater levels of both locomotor activity and rotational behavior. They are, however, consistent with the rotational bias evident in female rats. The present findings confirm the presence of sex differences in rotational behavior and indicate that factors other than activity levels are involved in the generation and/or expression of these sex differences. Sex differences in anxiety and routine-like behavior (i.e., asymmetry in movement) are discussed as possible factors contributing to these male-female differences in rotational behavior.


Novel two-chain structure utilizing KIRS2/DAP12 domain improves the safety and efficacy of CAR-T cells in adults with r/r B-ALL.
Engineered T cells that express chimeric antigen receptors (CARs) have been a promising therapy for hematologic malignancies. The optimization of CAR structure using different signaling domains can alter a wide range of CAR-T cell properties, including anti-tumor activity, long-term persistence, and safety. In this study, we developed a novel CAR structure based on KIRS2/Dap12 for B cell acute lymphoblastic leukemia (B-ALL) antigen CD19 and compared the anti-tumor efficacy and safety of this construct in transduced T cells with standard second-generation CAR-T cells targeting CD19 for B-ALL in vitro and in vivo and in adult relapsed/refractory (r/r) B-ALL patients. We discovered that KIRS2/Dap12 receptor infused with 4-1BB co-stimulation domain could enhance anti-tumor efficacy by remarkably increasing the production of pro-inflammatory interleukin-2 (IL-2), especially when co-cultured with antigen-positive tumor cells. In addition, CD19-KIRS2/Dap12-BB CAR-T cells showed the inspiring outcome that complete responses were seen in 4 of 4 (100%) patients without neurotoxicity and a high rate of severe cytokine release syndrome (CRS) after CAR-T infusion in a phase I clinical trial. Given these encouraging findings, CD19-KIRS2/Dap12-BB CAR-T cells are safe and can lead to clinical responses in adult patients with r/r B-ALL, indicating that further assessment of this therapy is warranted.


Enhancement of operational stability of an enzyme biosensor for glucose and sucrose using protein based stabilizing agents.
With the incorporation of lysozyme during the immobilization step, considerable enhancement of the operational stability of a biosensor has been demonstrated in the case of an immobilized single enzyme (glucose oxidase) system for glucose and multienzyme (invertase, mutarotase and glucose oxidase) system for sucrose. Thus an increased number of repeated analyses of 750 samples during 230 days for glucose and 400 samples during 40 days of operation for sucrose have been achieved. The increased operational stability of immobilized single and multienzyme system, will improve the operating cost effectiveness of the biosensor.


Comparison of two sedation protocols for long electroretinography in horses using the Koijman electrode.
In modern times, horses are utilized not only for labour and transportation purposes but also for recreational activities such as competition and pleasure riding. In these various pursuits, the role of vision plays a crucial role. Electroretinography is the most used test to diagnose diseases of the retinal outer segment. There is a wide variety of devices to perform the electroretinography differing one from each other in the corneal electrode and the light stimulation. The Koijman electrode has been tested in dogs but not in horses. The main purpose of this study was to compare electroretinography parameters from horses sedated with detomidine alone or in combination with butorphanol, during a standardized protocol using the Koijman electrode and RETI-port® system. Seven mares were allocated to the detomidine and detomidine plus butorphanol group in a randomised, controlled, crossover study. Friedman and Willcoxon-signed ranked tests were used to compare the electroretinogram parameters. A Student's t-test was used to compare differences in the number of artefacts to valid values ratio obtained under both sedation protocols. Dark adaptation peaked after 16 min under scotopic conditions in both groups. No significant differences in electroretinogram parameters between groups were observed. During the mixed rod and cone response evaluation under scotopic conditions, all mares made a movement of the head resulting in a high number of artefacts. The detomidine plus butorphanol group showed a non-significant tendency to have fewer artefacts and a longer duration of sedation compared to the detomidine group. Detomidine alone or combined with butorphanol may be suitable to use Koijman electrode and the RETI-port® to perform a standardized long protocol in horses with some adaptations.


External fixation of complex carpal dislocations: a preliminary report.
In ten cases of complex carpal fracture dislocations an external fixator between the radius and the second or third metacarpals was used as an adjunct to open reduction and internal fixation. The external fixator facilitates reduction, ligamentous repair, and internal fixation of the carpal bones. Furthermore, continuous postoperative distraction of the wrist maintains a stable reduction of the carpus permitting cast free after treatment and early active motion of the neighboring joints. This method is particularly useful for carpal stabilization when combined injuries of the same extremity coexist.


Single molecule recognition of protein binding epitopes in brush border membranes by force microscopy.
Sidedness and accessibility of protein epitopes in intact brush border membrane vesicles were analyzed by detecting single molecule interaction forces using molecular recognition force microscopy in aqueous physiological solutions. Frequent antibody-antigen recognition events were observed with a force microscopy tip carrying an antibody directed against the periplasmically located gamma-glutamyltrans- peptidase, suggesting a right side out orientation of the vesicles. Phlorizin attached to the tips bound to NA+/D-glucose cotransporter molecules present in the vesicles. The recognition was sodium dependent and inhibited by free phlorizin and D-glucose, and revealed an apparent K(D) of 0.2 microM. Binding events were also observed with an antibody directed against the epitope aa603-aa630 close to the C terminus of the transporter. In the presence of phlorizin the probability of antibody binding was reduced but the most probable unbinding force f(u) = 100 pN remained unchanged. In the presence of D-glucose and sodium, however, both the binding probability and the most probable binding force (f(u) = 50 pN) were lower than in its absence. These studies demonstrate that molecular recognition force microscopy is a versatile tool to probe orientation and conformational changes of epitopes of membrane components during binding and trans-membrane transport.


Effects of dietary fats on red blood cell membrane insulin receptor in normo- and hypercholesterolemic miniature swine.
It has been demonstrated that the type of dietary fat affects insulin receptors in various tissues in normal humans and animals by altering membrane fluidity. This study compares the effects of n-3 fatty acids from fish oil and n-6 fatty acids from corn oil on red blood cell membrane insulin receptors in normal and hypercholesterolemic minipigs. A group of minipigs were made hypercholesterolemic by feeding cholesterol and lard for 2 months; the other group served as controls and was fed stock diet. Both groups were then fed experimental diets containing either corn oil or menhaden oil or a mixture of the two for 23 additional weeks. Blood was collected at 0, 2, 12 and 23 weeks after the start of the experimental diets and membranes were prepared from the red blood cells. Insulin binding to red blood cell membranes was measured by radioreceptor assay. Plasma insulin was measured by radioimmunoassay. Insulin binding to red blood cell membrane was compared with the fluidity of the membrane measured and reported earlier. There was no significant effect of cholesterol feeding on plasma insulin concentrations. After 23 weeks on experimental diet plasma insulin was significantly higher in minipigs fed menhaden oil compared to those fed corn oil. No such effect was observed in hypercholesterolemic minipigs. No significant effect of either hypercholesterolemia or fish oil was observed on red blood cell insulin binding. A significant negative relationship was observed between insulin binding and anisotropy at 4°C for all probes but at 37°C significant negative relationship was observed only with polar probes. The data suggest that n-3 fatty acids from fish oil significantly increases plasma insulin in minipigs compared to n-6 fatty acids from corn oil. However, the unsaturation has no significant effect on insulin receptors on erythrocytes. Similarly, prior hypercholesterolemic state also has no effect on plasma insulin levels or the insulin binding to red blood cell membranes.


Association between genetic variants in DICER1 and cancer risk: An updated meta-analysis.
Dysfunctions in mechanisms of gene regulation based on RNA interference are recognized as a common feature of the molecular basis of cancer pathogenesis. Therefore, as one of the crucial components of the machinery involved in the biogenesis of both siRNAs and microRNA molecules, DICER was recognized as one of the candidates for the research in the field of carcinogenesis. Due to their potential functional properties, several genetic variants located within DICER1 gene were analyzed for their possible association with the susceptibility to cancer through case-control studies. In order to elucidate their effect on the overall cancer risk, we conducted an updated meta-analysis of all eligible association studies. The publications were selected based on PubMed database search, while OpenMeta-analyst and MetaGenyo software were used for quantitative data synthesis. Statistically significant results were found for the association of rs1057035 with the overall cancer risk under multiple genetic models (PCT vs. TT < 0.001, ORCT vs. TT = 0.870, 95% CI = 0.812-0.933; Pallelic = 0.009, ORallelic = 0.896, 95% CI = 0.825-0.973; Pdom < 0.001, ORdom = 0.874, 95% CI = 0.817-0.934; Poverdom = 0.004, ORoverdom = 0.858, 95% CI = 0.773-0.953). Other selected genetic variants within DICER1, rs13078, rs1209904 and rs3742330, did not show the association with the overall susceptibility to malignant diseases. We conclude that rs1057035 may represent a potential biomarker associated with the risk of developing cancer, which requires a confirmation in a larger set of studies.


Sub-fractionation and characterization of lysine-rich histones from Oberling Guerin-Guerin's myeloma.
The H1 fraction in Oberling Guerin-Guerin's myeloma was isolated, and an electrophoretic study was carried out in order to establish its composition. The results obtained show that the H1 fraction is heterogeneous and is formed of 2 sub-fractions. These were separated by preparative gel electrophoresis. They differ in molecular weight, electrophoretic mobility, and primary structure. Each sub-fraction exists in 2 different electric states.


Multifunctional PNIPAM/Fe3O4-ZnS hybrid hollow spheres: synthesis, characterization, and properties.
Multifunctional PNIPAM/Fe3O4-ZnS hybrid hollow spheres integrating magnetism, luminescence, and temperature responses into one single entity have been successfully fabricated via a facile method. First, the cross-linked Poly (N-isopropylacrylamide) (PNIPAM) hollow spheres were synthesized via a classical method, named one-pot "self-removing" process. Then, Fe3O4 and ZnS nanoparticles were in situ precipitated on the surface of the PNIPAM hollow spheres. The PNIPAM/Fe3O4-ZnS hybrid hollow spheres exhibit magnetic property, which indicates the potential application in drug targeting. In addition, ZnS nanoparticles in the shell play an important role as a luminescent label for tracking the drug delivery. Meanwhile, the existence of PNIPAM provides a thermosensitive property. All these results indicate that the obtained composite can be expected to be used as a smart drug delivery material.


Tea catechins improve left ventricular dysfunction, suppress myocardial inflammation and fibrosis, and alter cytokine expression in rat autoimmune myocarditis.
Myocarditis is a clinically serious disease. Tea catechins have been shown to reduce inflammation; however the effects of catechins on the development of myocarditis have not been well studied. To clarify the role of catechins, using an experimental autoimmune myocarditis (EAM) model. Lewis rats were immunized with porcine cardiac myosin to establish EAM. Tea catechins were administered orally from day 0 to day 21 (Group A, n=12), from day 14 to day 21 (Group B, n=8), or saline (Group C, n=9) daily. Rats were killed on day 21. Echocardiograms indicated that Group A showed significantly improved cardiac function compared to Group C. Pathologically, non-treated EAM hearts showed severe myocardial cell infiltration and fibrosis; however Group A showed significantly less area. Immunohistochemistry revealed enhanced expression of NF-kappaB and ICAM-1 in non-treated EAM hearts, which was suppressed by catechin administration in Group A. mRNA levels of TNF-alpha were decreased and Th2 cytokines were markedly enhanced in Group A compared with the control group. Late catechin administration (Group B) showed limited effects on EAM. The catechins suppressed ventricular remodelling in EAM; thus catechin treatment might be a promising option for the prevention of EAM myocarditis.


Boosting variant-calling performance with multi-platform sequencing data using Clair3-MP.
With the continuous advances in third-generation sequencing technology and the increasing affordability of next-generation sequencing technology, sequencing data from different sequencing technology platforms is becoming more common. While numerous benchmarking studies have been conducted to compare variant-calling performance across different platforms and approaches, little attention has been paid to the potential of leveraging the strengths of different platforms to optimize overall performance, especially integrating Oxford Nanopore and Illumina sequencing data. We investigated the impact of multi-platform data on the performance of variant calling through carefully designed experiments with a deep learning-based variant caller named Clair3-MP (Multi-Platform). Through our research, we not only demonstrated the capability of ONT-Illumina data for improved variant calling, but also identified the optimal scenarios for utilizing ONT-Illumina data. In addition, we revealed that the improvement in variant calling using ONT-Illumina data comes from an improvement in difficult genomic regions, such as the large low-complexity regions and segmental and collapse duplication regions. Moreover, Clair3-MP can incorporate reference genome stratification information to achieve a small but measurable improvement in variant calling. Clair3-MP is accessible as an open-source project at: https://github.com/HKU-BAL/Clair3-MP . These insights have important implications for researchers and practitioners alike, providing valuable guidance for improving the reliability and efficiency of genomic analysis in diverse applications.


Capillary blood pressure.
Human capillary blood pressure may be measured directly in nailfold capillaries of the fingers and toes. By applying servonulling pressure measuring techniques rapid fluctuations in capillary pressure may be recorded, opening the way to a greater understanding of capillary pressure control in health and disease. The estimation of mean pressure which may be accomplished manometrically is of value in determining the mechanism of oedema, identifying the site of raised peripheral resistance in disease states, evaluating the effects of vasoactive drugs on peripheral resistance, and investigating haemodynamic abnormalities associated with microangiopathies. Capillary pulse waveform analysis, made possible by servonulling techniques and computer analysis has already revealed important changes in hypertension.


Pharmaceutical companies abandon case against South Africa: victory for people with HIV/AIDS.
On 19 April 2001, 39 pharmaceutical companies bowed to worldwide condemnation and pressure, and completely abandoned their court action against the South African government over legislation that could be used to make essential drugs affordable for millions of South Africans.


N-doped direction-dependent electronic and mechanical properties of single-walled carbon nanotube (SWCNT) from a first-principles density functional theory (DFT) and MD-simulation.
In this paper, the electronic and mechanical properties of Nitrogen (N) doped (6,1) single walled carbon nanotube (SWCNT) is analysed based on the first principles density functional theory (DFT) and Molecular dynamic (MD) calculation. A systematic N-doping on SWCNT was performed along zigzag (zz) and armchair (ac) direction, where the armchair doping is parallel to tube axis while zigzag is along the cross-section perpendicular to tube axis. The zz and ac doping resulted in variations in the electronic properties of the even and odd number of N-dopant atoms. To evaluate the mechanical properties, ab - initio MD-simulations was carried out. We found a dependence of the tensile response of the tube on the dopant concentration and doping pattern. Single N-doped system show enhanced tensile stress by 55% as compared to the pristine SWCNT with marginal changes in the young's modulus for all N-doped systems.


Characterization of Drosophila palmitoyl-protein thioesterase 1.
Batten disease or neuronal ceroid lipofuscinoses (NCL) are a group of genetic neurodegenerative diseases that primarily afflict infants and children and are characterized by progressive loss of brain functions caused by the death of central nervous system (CNS) neurons. The most severe form of the disease is infantile NCL (INCL). INCL is caused by mutations in the palmitoyl-protein thioesterase 1 (PPT1) gene, which encodes a palmitoyl-protein thioesterase 1 enzyme that cleaves long-chain fatty acids from S-acylated proteins within the lysosome. How the loss of this activity causes the death of CNS neurons is not known. A PPT1 homolog and palmitoyl-protein thioesterase 1 enzyme activity were characterized in Drosophila melanogaster as an initial step in developing Drosophila as a model system for studying the etiology of INCL. Predicted gene CG12108 in region 8A2 of the X chromosome is 55% identical and 72% similar to human PPT1 and contains conserved catalytic residues and sites of glycosylation. Northern-blot hybridizations revealed a major 1.5 kb CG12108 transcript in unfertilized eggs, embryos, larvae, pupae, adult head and thorax, ovary, testis, and S2 tissue culture cells, as well as several minor mRNA species in some tissues. Levels of the 1.5 kb transcript were fairly uniform among tissues except in testis, where the transcript was enriched 5-fold. The same tissues also contained palmitoyl-protein thioesterase 1 enzyme activity measured using the fluorometric substrate 4-methylumbelliferyl-6-thiopalmitoyl-beta-D-glucoside. Enzyme activity was highest in testis and varied among the other tissues to a greater extent than did CG12108 message, suggesting that CG12108 is subjected to post-transcriptional regulation. Finally, flies homozygous for a deletion that removes CG12108 and three unrelated neighboring genes had less than 3% of wildtype levels of enzyme activity, consistent with CG12108 encoding functional palmitoyl-protein thioesterase 1 activity and being the fly ortholog of human PPT1. CG12108 has been appropriately renamed Ppt1.


Sweat and odor in sportswear - A review.
Sportswear worn next to the skin is easily soaked by sweat and may become a breeding ground for the microbiome, thus a source of malodor. Malodor can cause social embarrassment and discomfort to both wearer and others. Given the risks current deodorant products pose to nature and human life, the development of sustainable textiles for odor control comes to the forefront. This review introduces the odor-generating mechanism in clothing from the perspectives of perspiration composition and cutaneous microbiome. With the knowledge of the significant role of sweat in odor formation, the sweat distribution of the human body, measurement techniques, and advanced technologies developed for quick-dry function are presented in the second part. Lastly, odor management in sportswear is evaluated, covering the odor-assessing techniques, the effects of various textile materials, and emerging solutions in terms of antibacterial treatment, adsorbent materials, and photocatalytic degradations of odorous compounds. Overall, it is of both personal and social value to develop novel textile materials with odor-control functions by making use of natural materials and fabric designs.


The influence of "C-factor" and light activation technique on polymerization contraction forces of resin composite.
This study evaluated the influence of the cavity configuration factor ("C-Factor") and light activation technique on polymerization contraction forces of a Bis-GMA-based composite resin (Charisma, Heraeus Kulzer). Three different pairs of steel moving bases were connected to a universal testing machine (emic DL 500): groups A and B - 2x2 mm (CF=0.33), groups C and D - 3x2 mm (CF=0.66), groups e and F - 6x2 mm (CF=1.5). After adjustment of the height between the pair of bases so that the resin had a volume of 12 mm³ in all groups, the material was inserted and polymerized by two different methods: pulse delay (100 mW/cm² for 5 s, 40 s interval, 600 mW/cm² for 20 s) and continuous pulse (600 mW/cm² for 20 s). Each configuration was light cured with both techniques. Tensions generated during polymerization were recorded by 120 s. The values were expressed in curves (Force(N) x Time(s)) and averages compared by statistical analysis (ANOVA and Tukey's test, p<0.05). For the 2x2 and 3x2 bases, with a reduced C-Factor, significant differences were found between the light curing methods. For 6x2 base, with high C-Factor, the light curing method did not influence the contraction forces of the composite resin. Pulse delay technique can determine less stress on tooth/restoration interface of adhesive restorations only when a reduced C-Factor is present.


Systematic evaluation of nitrate and perchlorate bioreduction kinetics in groundwater using a hydrogen-based membrane biofilm reactor.
To evaluate the simultaneous reduction kinetics of the oxidized compounds, we treated nitrate-contaminated groundwater (approximately 9.4 mg-N/L) containing low concentrations of perchlorate (approximately 12.5 microg/L) and saturated with dissolved oxygen (approximately 8 mg/L) in a hydrogen-based membrane biofilm reactor (MBfR). We systematically increased the hydrogen availability and simultaneously varied the surface loading of the oxidized compounds on the biofilm in order to provide a comprehensive, quantitative data set with which to evaluate the relationship between electron donor (H(2)) availability, surface loading of the electron acceptors (oxidized compounds), and simultaneous bioreduction of the electron acceptors. Increasing the H(2) pressure delivered more H(2) gas, and the total H(2) flux increased linearly from approximately 0.04 mg/cm(2)-d for 0.5 psig (0.034 atm) to 0.13 mg/cm(2)-d for 9.5 psig (0.65 atm). This increased rate of H(2) delivery allowed for continued reduction of the acceptors as their surface loading increased. The electron acceptors had a clear hydrogen-utilization order when the availability of hydrogen was limited: oxygen, nitrate, nitrite, and then perchlorate. Spiking the influent with perchlorate or nitrate allowed us to identify the maximum surface loadings that still achieved more than 99.5% reduction of both oxidized contaminants: 0.21 mg NO(3)-N/cm(2)-d and 3.4 microg ClO(4)/cm(2)-d. Both maximum values appear to be controlled by factors other than hydrogen availability.


Understanding local population genetics of tsetse: the case of an isolated population of Glossina palpalis gambiensis in Burkina Faso.
Tsetse flies are the vectors of human and animal trypanosomiases. For tsetse eradication programs, it is crucial to be able to identify and target isolated populations, because they can be targeted for eradication without risk of reinvasion. However, most data that are available on non-isolated populations fail to find how these populations are locally structured, because Wahlund effect (admixture of individuals from genetically different units) always interfere with interpretations. In this paper, we investigated the genetic population structure of a possibly isolated population of Glossina palpalis gambiensis in a sacred wood in South Burkina Faso, using microsatellite DNA markers. We found that genotypic proportions in this population were in agreement with random mating model and that these tsetse were genetically highly differentiated from other populations of the same Mouhoun river basin only a few kilometers away, confirming its genetic isolation. The population also displayed substantial temporal differentiation in a two years period that lead to an estimate of effective population size of ∼100 individuals. The fact that no Wahlund effect was identified allowed us to accurately measure the basic genetic parameters of this isolated population. Identifying such isolated and small populations is crucial for eradication programs and should be implemented more often.


Correction: Mudie et al. In Vitro-In Silico Tools for Streamlined Development of Acalabrutinib Amorphous Solid Dispersion Tablets. Pharmaceutics 2021, 13, 1257.
The authors wish to make the following corrections to this paper [...].


Cervical screening in England: the past, present, and future.
Cervical screening in England commenced in a disorganized fashion in 1964. The flaws of this approach became apparent in the mid-1980s and led to the inception of the National Health Service Cervical Screening Programme (NHSCSP). The main features of this program are its population-based registry, accessibility to all women within the screening age range, its systematic process of call and recall, national coordination, and quality assurance. Its success is in part based on its ability to evolve as evidence necessitates, and throughout the period of 2000-2010, it embarked upon a series of developments involving liquid-based cytology, which also provided the means to conduct reflex high-risk human papillomavirus (HR-HPV) testing and the potential to automate the screening process. As a result of evidence acquired since 2000, the NHSCSP is currently based on a system of primary cytology with HPV triage for low-grade abnormalities combined with cytology plus a HR-HPV "test of cure" for women who have received treatment for cervical intraepithelial neoplasia. Future challenges for the program will involve finding solutions to increasing screening uptake among women <30 years of age-a problem that may be exacerbated when vaccinated women reach the screening age, while making plans to accommodate HPV primary screening.


Anaplastic large cell lymphoma in a human immunodeficiency virus-positive patient with cytologic findings in bladder wash: a case report.
Anaplastic large cell lymphoma (ALCL) (Ki-1/CD-30 positive) is an uncommon lymphoproliferative disorder that may be of T cell or null cell type. ALCL has been reported in fine needle aspirations of lymph nodes and pleural or peritoneal fluid cytology. In human immunodeficiency virus (HIV)-positive patients, ALCL appears to be more common and run a more aggressive course. A 39-year-old black man, seropositive for HIV, presented with acute renal failure secondary to bilateral ureteral obstruction by a pelvic mass involving the urinary bladder. Bladder wash cytology and subsequent biopsy of the mass were diagnostic of ALCL. The ALCL was CD30+ and null cell type, with negative CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD45, CD79a, ALK-1, granzyme B, cytokeratin (AE1/AE3), placental alkaline phosphatase (PLAP) and S-100. The patient expired 9 months after the diagnosis, despite aggressive therapy. This is a rare occurrence of ALCL (CD 30 positive, null cell type) in the urinary bladder in an HIV+ patient. Presumptive diagnosis was made by bladder wash cytology and subsequently confirmed by biopsy. Urinary cytologic examination is a useful diagnostic tool. In HIV+/immunosuppressed patients with urinary symptoms and an obstructive mass, ALCL should be considered in the differential diagnosis.


Designing chemical bonds between active materials and current collectors for packaging a high-performance supercapacitor.
Clarifying the interaction between active materials and current collectors of the same electrode is crucial for understanding the electrochemical energy storage mechanism and designing high-performance supercapacitors. The interaction mechanism is mainly due to the evolution of chemical bonding. Here, we explore the chemical bonding evolution between cobalt-nickel layered double hydroxide and carbon fiber paper by using ex situ x-ray photoelectron spectroscopy during redox reaction. The results reveal that chemical bonding corresponds to more ionic states at the lowest potential and more covalent states at the highest potential. Attributed to the formation of C-O-Metal (Co, Ni) chemical bonds, high capacitance with enhanced stability and rate capability is obtained. The Co-Ni layered double hydroxide electrode exhibits a high areal and mass specific capacitance of 0.55 and 952 F g-1 at a low mass loading of 0.58 mg cm-2. At a high mass loading of 3.59 mg cm-2, high areal and mass specific capacitance of 3.24 F cm-2 and 811 F g-1 are obtained. Based on this, a hybrid supercapacitor is fabricated with high-mass-loading Co-Ni layered double hydroxide and active carbon as positive and negative electrodes, respectively. As a result, this device delivers a prominent energy density of 20.9 Wh cm-3 at a power density of 0.12 W cm-3.


Odontogenic epithelium induces similar molecular responses in chick and mouse mandibular mesenchyme.
Previous observations have shown that, during the initiation phase of odontogenesis, signals from mouse odontogenic epithelium can elicit teeth in non-odontogenic but neural crest-derived mesenchyme isolated from ectopic sites including chick mandibular mesenchyme. In the present study the formation of ectopic tooth buds and dental mesenchyme in chick mandibular mesenchyme was examined using heterospecific recombinations between E11 mouse odontogenic epithelium and stage 23 chick lateral mandibular mesenchyme. Both morphological criteria and chick-specific probes for Msx-1, Msx-2, and Bmp-4 mRNAs were used as markers for early dental mesenchyme. Our results demonstrated that interactions of mouse odontogenic epithelium with chick mandibular mesenchyme induce early changes in the chick mandibular mesenchyme including the appearance of a translucent zone, cell proliferation, and induction of expression of Msx-1, Msx-2, and Bmp-4, which have been shown to be associated with the formation of dental mesenchyme. In addition, tooth bud-like structures that resemble E13 tooth buds in vivo both morphologically and in their patterns of gene expression formed after 6 days in the heterospecific recombinations. The tooth bud-like structures consist of invaginated mouse mandibular epithelium and condensed chick mandibular mesenchyme expressing high levels of Msx-1 and Bmp-4, but undetectable levels of Msx-2. Unlike the induction of Msx-1, Msx-2, and Bmp-4 in the underlying mesenchyme, which is specific for signals derived from odontogenic epithelium, the induction of a translucent zone and cellular proliferation in the underlying mesenchyme may be related to the growth-promoting potential of embryonic epithelia and not be specific to signals derived from the odontogenic epithelium. Similar to mouse odontogenic epithelium, agarose beads soaked in recombinant BMP-4 induced a translucent zone, cellular proliferation, and expression of Msx-1, Msx-2, and Bmp-4 in chick mandibular mesenchyme after 24 hours. These observations together showed that avian mandibular mesenchyme has odontogenic potential that is expressed upon interactions with inductive signals from mouse odontogenic epithelium. Similar to odontogenesis in vivo, formation of dental mesenchyme in chick mandibular mesenchyme is mediated by the activation of Msx-1, Msx-2, and Bmp-4.


2-Deoxy-D-glucose increases the sensitivity of glioblastoma cells to BCNU through the regulation of glycolysis, ROS and ERS pathways: In vitro and in vivo validation.
Chloroethylnitrosoureas (CENUs) exert antitumor activity via producing dG-dC interstrand crosslinks (ICLs). However, tumor resistance make it necessary to find novel strategies to improve the therapeutic effect of CENUs. 2-Deoxy-D-glucose (2-DG) is a well-known glycolytic inhibitor, which can reprogram tumor energy metabolism closely related to tumor resistance. Here, we investigated the chemosensitization effect of 2-DG on l,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against glioblastoma cells and the underlying mechanisms. We found that 2-DG significantly increased the inhibitory effects of BCNU on tumor cells compared with BCNU alone, while 2-DG showed no obvious enhancing effect on the BCNU-induced cytotoxicity for normal HaCaT and HA1800 cells. Proliferation, migration and invasion determinations presented the same trend as survival on tumor cells. 2-DG plus BCNU increased the energy deficiency through a more effective inhibition of glycolytic pathway. Notably, the combination of 2-DG and BCNU aggravated oxidative stress in glioblastoma cells, along with a significant decrease in glutathione (GSH) levels, and an increase in intracellular reactive oxygen species (ROS). Subsequently, we demonstrated that the combination treatment led to increased apoptosis via activating mitochondria and endoplasmic reticulum stress (ERS) related apoptosis pathways. Finally, we found that the dG-dC level was significantly increased after 2-DG pretreatment compared to BCNU alone by HPLC-ESI-MS/MS analysis. Finally, in vivo, 2-DG plus BCNU significantly suppressed tumor growth with lower side effects compared with BCNU alone in tumor-bearing mice. In summary, we proposed that 2-DG may have potential to increase the sensitivity of glioblastoma cells to BCNU by regulating glycolysis, ROS and ERS pathways in clinical setting.


Analysis of protein-based binding media found in paintings using laser induced fluorescence spectroscopy.
Laser induced fluorescence (LIF) spectroscopy of intrinsic fluorophores from organic media found in paintings (casein, animal glue and egg proteins) provides novel non-invasive means of characterisation of general classes of media on the basis of fluorescence emission arising from the presence of certain amino acids and their degradation byproducts. Proteins from traditionally employed binding media include collagen, casein, albumin and other egg proteins, of animal sources (skins, milk and egg respectively). Wavelength dependence of the spectra is presented for analyses of thin films of protein-based binding media.


A multidimensional approach to inform family planning needs, preferences and behaviours amongst women in South Africa through body mapping.
In recent decades there have been great improvements in the reproductive health of women in low- and middle-income countries and increases in the use of modern contraceptive methods. Nonetheless, many women are not able to access information, contraceptive technologies and services that could facilitate preventing unintended pregnancies and planning the number and timing of desired pregnancies. In South Africa, the contraceptive prevalence rate is 64.6%. However, this relatively high contraceptive prevalence rate masks problems with quality contraceptive service delivery, equitable access, and women's ability to correctly and consistently, use contraceptive methods of their choice. This study set out to understand the specific family planning and contraceptive needs and behaviours of women of reproductive age in South Africa, through a lived experience, multisensory approach. Participatory qualitative research methods were used including body mapping workshops amongst reproductive aged women recruited from urban and peri urban areas in the Western Cape South Africa. Data including body map images were analysed using a thematic analysis approach. Women had limited biomedical knowledge of the female reproductive anatomy, conception, fertility and how contraceptives worked, compounded by a lack of contraceptive counseling and support from health care providers. Women's preferences for different contraceptive methods were not based on a single, sensory or experiential factor. Rather, they were made up of a composite of sensory, physical, social and emotional experiences underscored by potential for threats to bodily harm. This study highlighted the need to address communication and knowledge gaps around the female reproductive anatomy, different contraceptive methods and how contraception works to prevent a pregnancy. Women, including younger women, identified sexual and reproductive health knowledge gaps themselves and identified these gaps as important factors that influenced uptake and effective contraceptive use. These knowledge gaps were overwhelmingly linked to poor or absent communication and counseling provided by health care providers. Body mapping techniques could be used in education and communication strategies around sexual and reproductive health programmes in diverse settings.


50-Hz magnetic field induces EGF-receptor clustering and activates RAS.
In a previous study, we found that exposure to a 50 Hz magnetic field (MF) could activate stress-activated protein kinase (SAPK) and P38 mitogen-activated protein (MAP) kinase (P38 MAPK) in Chinese hamster lung (CHL) fibroblast cells, and simultaneous exposure to a 'noise' MF of the same intensity inhibited these effects. In order to explore the possible target sites and upstream signal transduction molecules of SAPK and P38 MAPK, and further validate the interference effects of 'noise' MF on 50 Hz MF, the effects of MF exposure on clustering of epidermal growth factor (EGF) receptors and Ras protein activation were investigated. CHL cells were exposed to a 50 Hz sinusoidal MF at 0.4 mT for different durations, and clustering of EGF receptors on cellular membrane and Ras protein activation were analyzed using immunofluorescence confocal microscopy and co-precipitation technology. EGF treatment served as the positive control. The results showed that, compared with sham-exposed cells, exposure to a 50 Hz MF at 0.4 mT for 5 min slightly induced EGF receptor clustering, whereas exposure for 15 min enhanced receptor clustering significantly. Corresponding to receptor clustering, Ras protein was also activated after exposure to the 50 Hz MF. Exposure to a 'noise' MF (with frequency ranges from 30 - 90 Hz) at the same intensity and durations, did not significantly affect EGF receptor clustering and Ras protein. However, by superimposing the 'noise' MF, receptor clustering and Ras activation induced by 50 Hz MF were inhibited. The results suggested that membrane receptors could be one of the most important targets where extremely low frequency (ELF) MF interacts with cells, and Ras may participate in the signal transduction process of 50 Hz MF. Furthermore, a 'noise' MF could inhibit these effects caused by ELF-MF.


Triggered and controlled release of bioactives in food applications.
Bioactive compounds (e.g., nutraceuticals, micronutrients, antimicrobial, antioxidant) are added to food products and formulations to enhance sensorial/nutritional attributes and/or shelf-life. Many of these bioactives are susceptible to degradation when exposed to environmental and processing factors. Others involve in undesirable interactions with food constituents. Encapsulation is a useful tool for addressing these issues through various stabilization mechanisms. Besides protection, another important requirement of encapsulation is to design a carrier that predictably releases the encapsulated bioactive at the target site to elicit its intended functionality. To this end, controlled release carrier systems derived from interactive materials have been developed and commercially exploited to meet the requirements of various applications. This chapter provides an overview on basic controlled and triggered release concepts relevant to food and active packaging applications. Different approaches to encapsulate bioactive compounds and their mode of release are presented, from simple blending with a compatible matrix to complex multiphase carrier systems. To further elucidate the mass transport processes, selected diffusion and empirical release kinetic models are presented, along with their brief historical significance. Finally, interactive carriers that are responsive to moisture, pH, thermal and chemical stimuli are presented to illustrate how these triggered release mechanisms can be useful for food applications.


Distribution and morphological characteristics of dopamine-immunoreactive neurons in the midbrain of the squirrel monkey (Saimiri sciureus).
The distribution and morphological characteristics of dopamine (DA) neurons in the midbrain of the squirrel monkey (Saimiri sciureus) were investigated by peroxidase-antiperoxidase (PAP) immunohistochemistry with a highly specific antiserum raised against DA-glutaraldehyde-lysyl-protein conjugate (donated by M. Geffard). Four contiguous areas contained DA-immunostained nerve cell bodies: (1) the substantia nigra, pars compacta (SNc), (2) the ventral tegmental area (VTA), (3) the retrorubral area (RRA), and (4) the periaqueductal gray (PAG). The SNc composed the vast majority of DA-immunostained neurons. Most of these neurons were relatively large (mean diameters: 35 x 15 micron) and varied in shape from fusiform to polygonal, but a few smaller (16 x 10.5 micron) globular cells were dispersed among them. The caudal two-thirds of the SNc was particularly rich in DA somata. Rostrally, these DA cells formed several distinct columns impinging deeply upon the underlying pars reticulata. Large oval sectors mostly devoid of immunoreactivity were delineated by these trabeculae. The long dendritic processes of DA neurons in the SNc were generally oriented in prominent dorsoventral bundles the ventralmost portion of which arborized diffusely along the dorsal surface of the cerebral peduncle. In the VTA, the DA neurons were regrouped in a triangular zone located dorsal to the interpeduncular nucleus, medial to the substantia nigra and ventral to the oculomotor nucleus. These DA cells were of medium size (19 x 10.5 micron), globular or fusiform, and usually showed one or two thick primary dendrites oriented dorsoventrally. The DA cells in the RRA lay in continuity with the most caudal DA-containing elements of the substantia nigra but could be distinguished by their smaller size (26 x 12 micron), shorter and more profusely branched dendrites, and darker immunostaining. These DA neurons were characteristically scattered among and medial to the fibers of the medial lemniscus, and a few could be observed as far caudally as the pedunculopontine nucleus. In the PAG, DA-immunostained neurons were seen in the rostral half of the mesencephalic central gray and predominated in its ventral half. These cells were of medium size (22.5 x 10 micron) and some of them were found in proximity to the ventricular lining. At caudal levels, the DA-positive cells in the PAG did not intermingle with dorsal raphe neurons.(ABSTRACT TRUNCATED AT 400 WORDS)


[Results' analysis of estradiol and progesterone supplementation in luteal phase vs progesterone alone in an assisted reproduction program].
To correlate estradiol and progesterone concentrations in luteal phase with pregnancy rates, and to determine the real value of estradiol administration during luteal phase support. In a prospective and comparative study, 69 patients who underwent IVF-ET program were divided in two groups: group 1 (n = 32) received luteal phase support only with progesterone and group 2, (n = 37) luteal phase support with estradiol and progesterone. Ovarian stimulation was made with recombinant FSH and GnRH analogues (agonists or antagonists) and 24 hours after oocyte retrieval we began luteal phase support: group 1 progesterone (in oily solution) 100 mg/day IM, and group 2 same progesterone doses plus 2 mg of estradiol valerianate. Statistical analysis was performed using students' t- test and ROC curves. No statistical differences were observed in age, preovulatory estradiol levels, oocytes retrieved, fertilization rates, number of embryos transferred, or difficulty of embryo transfer among groups. The overall pregnancy rate was of 34.78% per cycle, no significant differences were observed among groups (37.5 vs 32.43%). We observed greater incidence of miscarriage in group 2 (4.35 vs 0%), without statistical significance. When comparing estradiol levels and pregnancy outcomes, higher levels were observed in the pregnancy group (403.3 vs 221.85 pg/mL) on day 7 post-transfer. Same results were reported for progesterone levels (107.04 vs 240.76). We determined that estradiol levels on day 7, higher than 244 pg/mL, could predict pregnancy with sensitivity of 58% and specificity of 70%, whereas progesterone levels greater than 108.6 ng/mL had specificity and sensitivity of 50 and 70%, respectively. We couldn't determine any advantage with estradiol supplementation during luteal phase support; however, measurement on day 7 of estradiol and progesterone allowed a greater predictive accuracy of pregnancy outcome.


Drug findings in 'Driving Under the Influence of Drugs' cases: a problem of illicit drug use.
Drug findings in 137 drug positive cases of Driving Under the Influence of Drugs (DUID) occurring in St. Louis, Missouri, U.S.A. from June 1983 through May 1986 are presented. Thirty-two different drugs were detected. A single agent was detected in only 34% (47/137) of cases. The most frequently encountered drugs, expressed as percent of positive cases, were: phencyclidine, 47%; marijuana, 47%; benzodiazepines, 22%; barbiturates, 15%; opiates, 11%; and cocaine, 9%. Most multiple drug cases involved popular illicit drug mixtures, such as cocaine and morphine (speedballs) or phencyclidine on marijuana (whack). All the drivers in this survey had displayed inappropriate or impaired operation of a motor vehicle to the extent that a law enforcement officer had stopped and charged them for DUID. In at least 81% of the drug positive cases, persons impaired in the operation of a motor vehicle from a drug or drugs other than alcohol, were impaired not as the result of side effects of therapeutic drug use, but as the result of deliberate self intoxication with illicit or controlled substances.


A clinical evaluation of the accuracy of the Nellcor N-100 and Ohmeda 3700 pulse oximeters.
Two pulse oximeters, the Nellcor N-100 and the Ohmeda 3700, were compared with arterial blood values and with each other in a clinical evaluation of performance. Three hundred twenty-nine simultaneously sampled blood/oximeter data pairs from use of both makes of pulse oximeters on each of 152 test subjects were included in the comparison analysis for each oximeter. Among the patients, disease type and severity and hospital location varied widely. Basic descriptive statistics and linear regression analysis were employed to facilitate comparison. Both oximeters displayed a statistically significant but clinically insignificant bias when compared with arterial blood oxyhemoglobin: -0.31 (P = 0.023) and 0.59 (P = 0.001) for the Ohmeda 3700 pulse oximeter and the Nellcor N-100 pulse oximeter, respectively. Relative to arterial blood oxyhemoglobin, the 95% tolerance intervals were +4.84 to -5.45 (10.3) for the Ohmeda 3700 and +6.94 to -5.76 (12.7) for the Nellcor N-100. Regressed against [oxyhemoglobin + carboxyhemoglobin + methemoglobin] as x, the Nellcor N-100 read y = 0.85(x) + 12.5, r = 0.83, P less than 0.0001, and the Ohmeda 3700 read y = 1.02(x) - 5.3, r = 0.86, P less than 0.0001.


Attentional correlates of illness anxiety in a non-clinical sample.
Attentional processes are assumed to play an important role in the maintenance of illness anxiety, although empirical support is relatively scarce. The present study explores the relationship between selective attention (i.e. private body consciousness and symptom reporting), intensive concentration (i.e. attentional control and sustained attention), and illness anxiety in 57 non-clinical subjects. Zero-order and multiple correlations suggest that illness anxiety is significantly related to cognitive failures in everyday life and private body consciousness and to a lesser extent to symptom reporting. It is concluded that illness anxiety can be partly predicted from specific attentional variables. However, specific operationalizations of attentional parameters seems to determine the existence and magnitude of these relations.


Autologous platelet lysates local injections for treatment of tibia non-union with breakage of the nickelclad: a case report.
Nonunions of the tibia represent challenging orthopedic problems, which require the surgeon to analyze numerous factors and choose an appropriate treatment. This article presents a case report of tibia and fibula fracture patient who failed the internal fixation surgery and successfully recovered after one course of percutaneous autologous platelet lysates injection. The patient received an internal nickelclad breakage at 9 months post-surgery but reluctant to accept a second surgery, then autologous platelet lysates (APL) injection which is a less invasive method was recommended. The injections were carried once a week for three times. Radiologic evaluation was conducted every month until recovery. To the best of our knowledge, this is the first reported case of tibia delayed union with breakage of the plate resolved with APL injection. Improved clinical evidence was observed at 4 and 6 months after injection. The patient got good bony union at 8 months post-injection. The patient didn't feel any discomfort postinjection, no complications such as infection, refracture etc. were observed. APL percutaneous injection could be a new therapeutic option for the treatment of nonunion or delayed healing fractures.


Best evidence topic report. Intravenous magnesium in chronic obstructive pulmonary disease.
A short cut review was carried out to establish whether the addition of intravenous magnesium to standard treatments improved outcome in patients with exacerbations of COPD. Altogether 465 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.


Personalized pulmonary rehabilitation and occupational therapy based on cardiopulmonary exercise testing for patients with advanced chronic obstructive pulmonary disease.
Personalized pulmonary rehabilitation including occupational therapy improves the prognosis of patients with advanced COPD. We previously reported that patients with chronic obstructive pulmonary disease (COPD) exhibit three exercise-induced life-threatening conditions: hypoxemia, sympathetic overactivity, and respiratory acidosis. We aimed to verify whether mortality in patients with advanced COPD could be reduced by a personalized pulmonary rehabilitation (PPR) program in hospital, which determines individual safe ranges and includes occupational therapy (PPR-OT), to prevent desaturation and sympathetic nerve activation during daily activities. The novel PPR-OT program was evaluated in a retrospective study of patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Grade D) who underwent cardiopulmonary exercise testing (CPET) between April 1990 and December 1999. They received regular treatment without the proposed therapy (control group: n=61; male-to-female ratio [M:F] =57:4; mean age: 68.5±6.7 years) or with the proposed therapy (PPR-OT group: n=46; M:F =44:2; mean age: 68.7±7.1 years). A prospective observational study included patients with COPD receiving home oxygen therapy (HOT) between April 1995 and March 2007 to compare the survival rates of the control group (n=47; M:F ratio =34:13; mean age: 71.3±10.0 years) and the PPR-OT group (n=85; M:F =78:7; mean age: 70.7±6.1 years) who completed the proposed therapy. Survival after CPET or HOT was analyzed using Cox proportional-hazards regression and Kaplan-Meier analyses. In both studies, the program significantly improved all-cause mortality (retrospective study: risk ratio =0.389 [range: 0.172-0.800]; P=0.0094; log-rank test, P=0.0094; observational study: risk ratio =0.515 [range: 0.296-0.933]; P=0.0291; log-rank test, P=0.0232]. At 5 years and 7 years, all-cause mortality was extremely low in patients in the PPR-OT group receiving HOT (18.8% and 28.2%, respectively), compared to that in the control group (34.0% and 44.7%, respectively). Survival of patients with life-threatening pathophysiological conditions also greatly improved. The PPR-OT program improved the survival of patients with advanced COPD probably because it modified life-threatening conditions.


Inhibition of angiotensin II and platelet-derived growth factor-induced vascular smooth muscle cell proliferation by calcium entry blockers.
Structural changes within the blood vessel wall such as hyperplasia and hypertrophy of vascular smooth muscle cells are important factors in the pathogenesis of hypertension. Humoral growth factors such as angiotensin II (AII) and platelet-derived growth factor BB (PDGF-BB) may participate in the remodelling of the blood vessel wall. Whether and by which mechanisms antihypertensive treatment is capable of influencing the structural blood vessel alterations to date remains unclear. In the present study, the effect of nifedipine and diltiazem on AII- and PDGF-BB-induced vascular smooth muscle cell proliferation was examined. Nifedipine and diltiazem at a concentration of 10 microM did not affect baseline DNA synthesis in isolated vascular smooth muscle cells in culture. AII (final concentration 100 nM) and PDGF-BB (50 ng/ml) stimulated DNA synthesis by approximately 9.0- and 4.6-fold, respectively. Both AII- and PDGF-BB-induced DNA synthesis was significantly blunted by diltiazem and nifedipine in a concentration of 10 microM, while no significant influence was seen with concentrations from 10 nM up to 1 microM. In contrast, no significant influence of these drugs could be observed on fetal calf serum 5%-induced DNA synthesis. The findings indicate that calcium antagonists possess antimitogenic potential and that they may thus contribute to the regression of structural changes of the blood vessels associated with hypertension.


LC-MS/MS determination of tideglusib, a novel GSK-3β inhibitor in mice plasma and its application to a pharmacokinetic study in mice.
A sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of tideglusib in mice plasma using warfarin as an internal standard (I.S.) as per regulatory guidelines. Sample preparation was accomplished through liquid-liquid extraction process. Chromatographic separation was performed on Atlantis dC18 column using mobile phase A (acetonitrile) and B (5mM ammonium acetate in water) in a flow-gradient mode. Elution of tideglusib and the I.S. occurred at ∼2.06 and 1.29min, respectively. The total chromatographic run time was 3.2min. A linear response function was established in the concentration range of 20.2-1008ng/mL. The intra- and inter-day accuracy and precision were in the range of 4.61-12.6 and 6.04-11.8%, respectively. This novel method has been applied to a pharmacokinetic study in mice.


Interdisciplinary treatment with implant-supported prostheses for an adolescent with ectodermal dysplasia: A clinical report.
This clinical report describes interdisciplinary treatments for a 17-year-old girl with ectodermal dysplasia. The treatment was initiated with orthodontic therapy. After the remaining primary teeth had been extracted, 6 implants were placed in the maxilla with bilateral sinus floor elevations, and 6 implants were placed in the mandible. Immediate restorations were provided. Definitive restorations included screw-retained partial dental prostheses and ceramic crowns.


Association between sexual function in women and sleep quality.
To determine the relationship between sexual dysfunction and sleep disorders. Observational study was conducted in 2021 and 2022 including 975 Spanish women over 18 years of age. The Women's Sexual Function Questionnaire (FSM-12) was used as a source of information, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. A bivariate and multivariate analysis was performed using binary logistic regression, adjusting for confounding variables. Crude (OR) and adjusted (aOR) odds ratios were estimated with their respective 95% confidence intervals (CI). Around 29.2% (285) of the women presented some type of sexual dysfunction, and 73.4% (716) showed sleep disturbance with scores ≥5 on the PSQI scale. The mean score on the PSQI was 8.23 points (SD = 3.93). All the dimensions of the sexual function scale were statistically related to sleep disturbance (p ≤ 0.05), except for sexual activity and the reasons for sexual activity not having penetration. In the multivariable analysis, women with sexual dysfunction presented an aOR of sleep disturbance of 1.88 (95% CI: 1.29-2.76) compared to women without dysfunction. Global sexual dysfunction and almost all the dimensions that make up sexual function are related to changes in sleep quality.


Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014.
In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.


Early-onset stroke with moyamoya-like syndrome and extraneurological signs: a first reported paediatric series.
Moyamoya syndrome is characterised by an occlusion of the carotid terminations with the development of collateral vessels. Our objective is to describe a series of infants presenting early-onset moyamoya-like syndrome, which may constitute a distinct entity. From a cohort of children with rare cerebral vascular pathologies, we studied eight infants (28 days-1 year) with early-onset moyamoya-like syndrome demonstrated by angiography. We retrospectively analysed the patterns on MRI and MRA, as well as all other available data. Median age at diagnosis was 7 months (IQR: 6-8) with arterial ischaemic stroke in the middle cerebral artery territory. All of the children experienced severe stroke recurrence within a median time of 11 months (IQR: 10-12), and all showed extraneurological symptoms. The anterior cerebral circulation was involved in all cases and the posterior circulation was involved in six. Two children died and all of the other children suffered permanent neurological deficits. The presence of extraneurological signs in cases of early-onset moyamoya syndrome is suggestive of a newly described systemic vasculopathy with predominantly cerebrovascular expression. Given its rapid progression marked by severe recurrent strokes and poor clinical outcome, early diagnosis could help in the decision to institute aggressive therapy.


Analyzing the roles of multi-functional proteins in cells: The case of arrestins and GRKs.
Most proteins have multiple functions. Obviously, conventional methods of manipulating the level of the protein of interest in the cell, such as over-expression, knockout or knockdown, affect all of its functions simultaneously. The key advantage of these methods is that over-expression, knockout or knockdown does not require any knowledge of the molecular mechanisms of the function(s) of the protein of interest. The disadvantage is that these approaches are inadequate to elucidate the role of an individual function of the protein in a particular cellular process. An alternative is the use of re-engineered proteins, in which a single function is eliminated or enhanced. The use of mono-functional elements of a multi-functional protein can also yield cleaner answers. This approach requires detailed knowledge of the structural basis of each function of the protein in question. Thus, a lot of preliminary structure-function work is necessary to make it possible. However, when this information is available, replacing the protein of interest with a mutant in which individual functions are modified can shed light on the biological role of those particular functions. Here, we illustrate this point using the example of protein kinases, most of which have additional non-enzymatic functions, as well as arrestins, known multi-functional signaling regulators in the cell.


Analysis of radiographic classifications for rotational ankle fractures.
The acute ankle fracture has been often cited as one of the most commonly treated orthopedic injuries. As such, significant research has been conducted, along with many clinical studies, aiming to evaluate conservative versus surgical management, as well as radiographic classification and long-term outcomes. Because these clinical outcomes are pertinent to practicing physicians, this article aims to examine studies that assess the reliability and reproducibility of familiar classification systems for rotational ankle fractures.


Inhibition of RANK/RANKL signal transduction pathway: a promising approach for osteoporosis treatment.
Osteoporosis is a bone disease causing impaired bone strength. It is characterized by increased osteoclast formation or enhanced bone resorption, leading to an increased risk of fragility fractures. Its prevalence increases with age. The advent of an aging population suggests that progressively more individuals will develop this disease in the aging population. A number of drugs for the prevention and treatment of osteoporosis act by inhibiting bone resorption. However, the effectiveness of osteoporosis treatment in clinical practice is limited. Since the osteoclast is the only cell in the body that is capable of resorbing bone, understanding its biology will be necessary for developing a new therapeutic approach for osteoporosis. Recently, it was discovered that the receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system is an important signal transduction pathway that regulates osteoclast formation. The binding of OPG to RANKL inhibits the binding between RANKL and RANK; this, in turn, prevents osteoclast precursors from differentiating and fusing to form mature osteoclasts. Therefore, the inhibition of the RANK/RANKL pathway inhibits osteoclast formation, differentiation, activation, and bone resorption. A potential clinical antiresorptive therapy can be developed by using an anti-RANKL monoclonal antibody, such as denosumab, that binds to RANKL with high affinity and specificity and blocks RANKL-RANK interactions.


Observations were carried out at the Biological Station Lunz in Lower Austria.If chemical and temperature conditions are kept constant, the subimagines of B. alpinus emerge under natural illumination only in light, mainly between 12.00 and sunset. In permanent light the rhythmicity of emergence seems to be disturbed, in permanent darkness emergence is suppressed.Under natural conditions the duration of the subimago stage depends only on temperature and is not fixed to a particular time of day.


Mindfulness interventions for psychosis: a meta-analysis.
An increasing number of mindfulness interventions are being used with individuals with psychosis or schizophrenia, but no known meta-analysis has investigated their effectiveness. To evaluate the efficacy of mindfulness interventions for psychosis or schizophrenia, we conducted an effect-size analysis of initial studies. A systematic review of studies published in journals or in dissertations in PubMED, PsycINFO or MedLine from the first available date until July 25, 2013. A total of 13 studies (n=468) were included. Effect-size estimates suggested that mindfulness interventions are moderately effective in pre-post analyses (n=12; Hedge's g=.52). When compared with a control group, we found a smaller effect size (n=7; Hedge's g=.41). The obtained results were maintained at follow-up when data were available (n=6; Hedge's g=.62 for pre-post analyses; results only approached significance for controlled analyses, n=3; Hedge's g=.55, p=.08). Results suggested higher effects on negative symptoms compared with positive ones. When combined together, mindfulness, acceptance, and compassion strongly moderated the clinical effect size. However, heterogeneity was significant among the trials, probably due to the diversity of interventions included and outcomes assessed. Mindfulness interventions are moderately effective in treating negative symptoms and can be useful adjunct to pharmacotherapy; however, more research is warranted to identify the most effective elements of mindfulness interventions.


A simulated heat wave-but not herbicide exposure-alters resource investment strategy in an insect.
Animals are increasingly exposed to potential stressors related to environmental change, and multiple stressors may alter the dynamics by which animals acquire resources and invest those resources into important life-history traits. Stress may lead to the prioritization of current reproduction to maximize lifetime reproduction (i.e., terminal investment [TI]) or, in contrast, prioritize somatic investment over current reproduction to facilitate future reproductive opportunities (i.e., reproductive restraint [RR]). Tests of the TI and RR hypotheses typically use immune challenges as stressors, and have not been explicitly tested in the context of environmental change even though warming influences resource allocation patterns across taxa. Further, the multiple-stressor framework has been a useful construct to clarify the costs of complex environmental shifts to animals, but it has not been leveraged to understand such effects on investment strategy. Thus, we tested the TI and RR hypotheses by manipulating widespread features of environmental change-glyphosate-based herbicide (GBH; Roundup®) exposure and a simulated heat wave-in the variable field cricket (Gryllus lineaticeps). A simulated heat wave affected the life-history tradeoff between investment into reproduction and soma. Specifically, heat wave prioritized investment into ovary mass over non-reproductive tissue, even after accounting for food consumption, in support of the TI hypothesis. In contrast, GBH exposure did not affect any measured trait, and crickets did not discriminate between tap water and GBH solution during drinking. Therefore, some-but not all-aspects of environmental change may alter resource investment strategies in animals. We encourage continued integration of the multiple-stressor framework and life-history theory to better understand how animals respond to their rapidly changing environments.


Effect of fluorophore linkage position of n-(9-anthroyloxy) fatty acids on probe distribution between coexisting gel and fluid phospholipid phases.
The quenching of probe fluorescence by spin-labeled phospholipid has been used to determine the distribution of a series of n-(9-anthroyloxy) fatty acids between coexisting gel and fluid liquid-crystal phases in multilamellar phospholipid vesicles. The phase distribution ratio in every case is found to favor the fluid lipid phase, but is much greater between fluid and Ca2+-induced gel than between fluid and thermal gel. For a given gel type, n-(9-anthroyloxy)stearic acids with n = 3, 6, 9 or 12 as well as 11-(9-anthroyloxy)undecanoic acid all exhibit similar behavior, favoring the fluid phase by about a factor of 4 over thermally-induced lipid gel phase and by 18 over Ca2+-induced gel phase. 16-(9-Anthroyloxy)palmitic acid, with the bulky probe at the terminus of the 16-carbon chain, favors the fluid phase less strongly, by a factor of 1.5 or 11 over thermally-induced or Ca2+-induced gel phase, respectively, indicating better packing of this probe in phospholipid gel phases.


Pause-dependent mitral isthmus conduction block during ablation of the mitral isthmus: What is the mechanism?
Mitral isthmus (MI) ablation is commonly performed as an adjunct therapy to pulmonary isolation during the treatment for persistent atrial fibrillation. Confirmation of complete MI block is essential because an incomplete MI block may result in iatrogenic atrial tachycardia. However, there are several pitfalls in the diagnosis of an MI line block. We herein report a case of transient pause-dependent MI block during MI ablation.


Nitroblue tetrazolium (NBT) activity in human leucocytes after freezing.
Human peripheral blood leucocytes (neutrophil-rich) were collected either with heparin or acid citrate dextrose, frozen with dimethyl sulphoxide at a controlled rate, stored in liquid nitrogen at--196 degrees C and reconstituted with a solution containing dextran. After reconstitution, 20.2% of cells (in absolute numbers 1 in 5 fresh cells) showed a strongly positive nitroblue tetrazolium (NBT) reaction. The quantitative NBT test confirmed the synthesis of formazan/10(6) reconstituted neutrophilsa s15% of the fresh capacity. A slow titration reconstitution method for cells did not improve the functional capacity of thawed leucocytes as judged by the NBT test. When comparing anticoagulants, heparin increased the post-reconstitution cell yields after freezing and increased the absolute number of reconstituted cells capable of developing a positive NBT reaction.


Urodynamic use of fiberoptic microtipped catheter.
Solid state microtransducers are used widely in urodynamics to record bladder and intraluminal urethral pressures. They are sensitive and capable of giving high quality, reproducible pressure recordings. They do not require the determination of a reference point but they are expensive and fragile, and calibration may be difficult to perform. We describe our experience with a new catheter for pressure recording based on fiberoptic technology. In addition to the advantages of the conventional microtipped catheters, the new catheter is thinner (4F), easier to calibrate and less expensive. Controlled testing of the new catheter was performed in an experimental setting and in clinical trials during urodynamic evaluation. The catheter provides reliable pressure recordings compared to standard microtipped catheters.


Basic principles of immunotherapy for neurologic diseases.
Immunosuppressive drugs and immunomodulating procedures can improve the quality of life in patients with immune-related neurologic diseases and can even be lifesaving if properly used to avoid deleterious or irreversible adverse effects. For the successful use of these drugs or procedures, the treating physician must be familiar and comfortable with the drugs' mode of action, the accuracy of the diagnosis, the goals and expectations of therapy, and the risk-benefit ratio of the therapy. Improvement must be based on a beneficial change in activities of daily living and not solely on a change in the laboratory test values.


Intelligence, alcohol consumption, and adverse consequences. A study of young Norwegian men.
Research suggests that intelligence is positively related to alcohol consumption. However, some studies of people born around 1950, particularly from Sweden, have reported that higher intelligence is associated with lower consumption and fewer alcohol-related problems. We investigated the relationships between intelligence, alcohol consumption, and adverse consequences of drinking in young men from Norway (a neighboring Scandinavian country) born in the late 1970s. This analysis was based on the population-based Young in Norway Longitudinal Study. Our sample included young men who had been followed from their mid-teens until their late 20s (n = 1126). Measures included self-reported alcohol consumption/intoxication, alcohol use disorders (AUDIT), and a scale measuring adverse consequences of drinking. Controls included family background, parental bonding, and parents' and peers' drinking. Intelligence test scores-scaled in 9 "stanines" (population mean of 5 and standard deviation of 2)-were taken from conscription assessment. Men with higher intelligence scores reported average drinking frequency and slightly fewer adverse consequences in their early 20s. In their late 20s, they reported more frequent drinking than men with lower intelligence scores (0.30 more occasions per week, per stanine, age adjusted; 95% CI: 0.12 to 0. 49). Intelligence was not associated with intoxication frequency at any age and did not moderate the relationships between drinking frequency and adverse consequences. Our results suggest that the relationship between intelligence and drinking frequency is age dependent. Discrepancies with earlier findings from Sweden may be driven by changes in drinking patterns.


Alpha- and gamma-interferon inhibit plasminogen activator inhibitor-1 gene expression in human retinal pigment epithelial cells.
The effect of interferons IFN-alpha and IFN-gamma on the production of plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs) was examined in human retinal pigment epithelial (RPE) cells in culture. Cultures of human RPE cells were incubated with either of the interferons for 48-96 h. The cell cultures were assayed using mRNA analysis and solid-phase immunocapture assay. Both interferons caused a marked decrease in PAI-1 mRNA expression after 48 h with no change in urokinase-type plasminogen activator (u-PA) mRNA expression. A marked decrease in PAI-1 activity and concomitant increase in u-PA activity in the culture medium appeared only after 72-96 h. We conclude that IFN-alpha and IFN-gamma stimulate plasminogen-mediated pericellular proteolysis of human RPE cells in culture by inhibiting PAI-1 gene expression.


Rates of unconventional medical therapy use in patients with prostate cancer: standard history versus directed questions.
The use of unconventional medical therapies (UMTs) in the general population has increased dramatically in the past decade. Studies have estimated that 9% to 64% of patients with cancer use UMTs, and many do not disclose this information to their physicians. This study was designed to evaluate the rates of UMT use by patients with prostate cancer revealed by standard versus directed questioning and to identify demographic markers that may predict use. A prospective study of 287 consecutive patients with cancer presenting to the Department of Radiation Oncology was performed. The prostate cancer population was 29% (84 of 287) of the total cancer patient population. Each patient underwent the standard history interview, including questions regarding prescription and over-the-counter medication. At the completion of the standard history interview, patients were then asked a set of directed questions regarding the use of UMTs. Of the 84 patients with prostate cancer, 31 (37%) used unconventional therapies. The standard history revealed that 6 (19%) of 31 used UMTs, and directed questioning revealed an additional 25 patients (81%) used UMTs in the study population (P <0.001). Of those using UMTs, 65% used megavitamins, 49% used herbal remedies, 13% used meditation or guided imagery, and 20% used nonherbal natural supplements. UMT use is prevalent among patients with prostate cancer. Some of these treatments may have a potential biologic impact on tumor behavior, therapeutic endpoints, and measured prostate-specific antigen values. The use of directed questioning during the patient evaluation significantly increases the physician's ability to identify patients with prostate cancer using UMTs.


[Status of the autonomic nervous system and its correction in complex treatment of patients with occupational cervical dorsopathy].
The authors studied features of vegetative regulation in patients with occupational cervical dorsopathy and specified differentiated rehabilitation programs proved to be more efficient than the conventional treatment.


Increased frequency of Ig heavy-chain HS1,2-A enhancer *2 allele in dermatitis herpetiformis, plaque psoriasis, and psoriatic arthritis.
The enhancer DNase-hypersensitive region 1,2 (HS1,2), a member of the Ig heavy-chain 3' regulatory region (3'RR) cluster, is active in human B cells transfected with reporter genes and in mouse is activated in late maturation. HS1,2-A contains binding sites for several transcription factors. There are four known alleles, that is, (*)1, (*)2, (*)3, and (*)4, which differ in their lengths in transcription factor binding. We showed that in celiac disease the frequency of the (*)2 allele is increased. Both dermatitis herpetiformis (DH) and psoriasis can be associated with different frequencies with celiac disease. Thus, we further investigate the frequency of allele (*)2 in DH, plaque psoriatic, and psoriatic arthritis patients. HS1,2-A allele frequencies were investigated in 37 DH, 61 plaque psoriatic, 28 psoriatic arthritis patients, and 265 healthy donors, age- and sex-matched, from the same geographical area. The frequency of the (*)2 allele changes from 0.39 in controls to 0.63 in DH, 0.59 in plaque psoriasis and 0.75 in psoriatic arthritis (P between 10(-4)-10(-5)). Our data evidence an increased frequency of the (*)2 allele of HS1,2-A in these cutaneous immune-related disorders. We suggest a related genetic predisposition in these pathogeneses.


The Incidence and Associated Factors of Early Neurological Deterioration After Thrombolysis: Results From SITS Registry.
Early neurological deterioration (END) after stroke onset may predict severe outcomes. Estimated rates of END after intravenous thrombolysis among small patient samples have been reported up to 29.8%. We studied the incidence and factors associated with END among patients following intravenous thrombolysis. We analyzed SITS-International Stroke Thrombolysis registry patients with known outcomes enrolled in 2010 to 2017. END was defined as an increase in National Institutes of Health Stroke Scale score ≥4 or death within 24 hours from baseline National Institutes of Health Stroke Scale. We determined the incidence of END and used logistic regression models to inspect its associated factors. We adjusted for variables found significant in univariate analyses (P<0.05). Main outcomes were incidence of END, associated predictors of END, ordinal day-90 mRS, and day-90 mortality. We excluded 53 539 patients and included 50 726 patients. The incidence of END was 3415/50 726 (6.7% [95% CI, 6.5%-7.0%]). Factors independently associated with END on multivariate analysis were intracerebral hemorrhage (OR, 3.23 [95% CI, 2.96-3.54], P<0.001), large vessel disease (LVD) with carotid stenosis (OR, 2.97 [95% CI, 2.45-3.61], P<0.001), other LVD (OR, 2.41 [95% CI, 2.03-2.88], P<0.001), and ischemic stroke versus transient ischemic attack (TIA)/stroke mimics (OR, 16.14 [95% CI, 3.99-65.3], P<0.001). END was associated with worse outcome on ordinal mRS: adjusted OR 2.48 (95% CI, 2.39-2.57, P<0.001) by day-90 compared with no END. The adjusted OR for day-90 mortality was 9.70 (95% CI, 8.36-11.26, P<0.001). The routinely observed rate of END reflected by real-world data is low, but END greatly increases risk of disability and mortality. Readily identifiable factors predict END and may help with understanding causal mechanisms to assist prevention of END.


Albumin, a biologically active protein acting on Leydig cells.
The objective of the present study was to characterize further the albumin fraction of rat testicular fluid (rTF), which can enhance luteinizing hormone (LH)-stimulated pregnenolone production by immature Leydig cells in vitro. Testicular fluid, obtained from 300 rat testes was fractionated by sequential ammonium sulfate precipitation, dye-affinity, anion-exchange chromatography, chromatofocussing and an additional heat treatment. The final fraction showed a single band when analyzed on a silver-stained sodium dodecyl sulfate-polyacrylamide gel and isoelectric focussing gel. The protein had a molecular weight of 67 kDa, an isoelectric point of 5.0 and was identified as albumin after Western blotting using an antibody against rat serum albumin. Albumin in this fraction gave a dose-dependent (0.1-2% protein, w/v) increase in LH-induced pregnenolone production, up to 4-fold, and the increase in specific bioactivity when compared to rTF was 1.4-fold. Selective depletion of albumin from testicular fluid was used as another approach to confirm that albumin itself is the main biologically active component in rTF. rTF from mutant analbuminemic rats (albumin content 0.02 mg/ml) did not stimulate LH-induced steroid production in our assay, in contrast to rTF from normal rats (albumin content 40 mg/ml). Albumin fractions obtained from rat, bovine and human sera were also effective in stimulation of steroid production in the presence of LH, in contrast to chicken serum albumin which gave no stimulation. The stimulatory effect of albumin is not caused by bound fatty acids, nor by the presence of modified forms of albumin such as testibumin or the albumin-bilirubin complex. Our results indicate that Leydig cells are more active in steroid production when surrounded by high but physiological concentrations of albumin.


Cingulate-centered large-scale networks: Normal functions, aging, and neurodegenerative disease.
In this chapter, we review evidence from structural and functional neuroimaging in humans to consider the role of the cingulate cortex subregions (i.e., subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, anterior midcingulate cortex, and dorsal posterior cingulate cortex) as major hubs anchoring multiple large-scale brain networks. We begin with a review of evidence from intrinsic functional connectivity and diffusion tensor imaging studies to show how connections within and between cingulate-centered networks contribute to processing and integrating signals related to autonomic, affective, executive, and memory functions. We then consider how variability in cingulate-centered networks could contribute to a range of aging outcomes, including typical aging and unusually successful aging (dubbed "superaging"), as well as early neurodegenerative dementias, including frontotemporal dementia and Alzheimer's disease.


Density gradient equilibrium methods applied to blood-group specific glycoproteins.
The blood-group specific glycoproteins of human ovarian cyst fluids have been isolated by equilibrium density gradient centrifugation in CsCl; they have been characterised in terms of buoyant density, selective salvation and apparent molecular weight, both in CsCl and Cs(2)SO(4).


Issues in clinical trial design: stopping a trial early and the large and simple trial.
During the conduct of a clinical trial, a primary function of the Data Safety and Monitoring Committee is to select the trial conduct and the accumulating data to determine whether the trial should continue or be discontinued earlier than planned. Reasons for early discontinuation of a trial include: evidence of benefit, evidence of harm, and evidence of futility. More than 1 of these elements will often be present. These principles will be illustrated with examples from National Institute of Child Health and Human Development-Maternal-Fetal Medicine Units clinical trials. The "large and simple clinical trial" is a study design rarely undertaken in the United States but commonly used elsewhere. The principles of this type of trial will be introduced and contrasted with those of the "conventional clinical trial."


Access to healthcare system of indigenous communities with musculoskeletal disorders and rheumatic disease in Chaco, Argentina: a qualitative study.
The objective of this study is to describe the local healthcare system from the perspective of the health professionals, community health workers, and local representatives of the qom community living in the province of Chaco, Argentina. A qualitative study, with an ethnographic approach, was carried out using two techniques: non-participant observations and semi-structured interviews. A guide for the interviews was designed and developed by a multidisciplinary group of GLADERPO researchers. The main aspects included were the following: reference into the local healthcare system and accessibility to the system. Andersen's base conceptual model of health service utilization was applied for the analysis and for structuring the results. A total of 21 people were interviewed, twelve women and nine men with an age ranging between 25 and 60 years old. The main findings were different barriers (communication and cultural) between the community and the healthcare system; "navigation" within the health system carried out by the qom community; and migration and bureaucratization of the health system. These findings should be incorporated into educational strategies to improve access to healthcare system and adherence to medical treatment, establishing an interaction between the different levels of the local care system and providing community health workers with an appropriate training with the support of the community representatives. Key Points • The different barriers between the community and the healthcare system were described. • The "navigation" within the health system carried out by the qom community and the migration were relevant points. • The bureaucratization of the health system and the need to design and implement educational strategies in the future were highlighted.


A cerebrospinal fluid microRNA signature as biomarker for glioblastoma.
To develop a cerebrospinal fluid (CSF) miRNA diagnostic biomarker for glioblastoma. Glioblastoma tissue and matched CSF from the same patient (obtained prior to tumor manipulation) were profiled by TaqMan OpenArray® Human MicroRNA Panel. CSF miRNA profiles from glioblastoma patients and controls were created from three discovery cohorts and confirmed in two validation cohorts. miRNA profiles from clinical CSF correlated with those found in glioblastoma tissues. Comparison of CSF miRNA profiles between glioblastoma patients and non-brain tumor patients yielded a tumor "signature" consisting of nine miRNAs. The "signature" correlated with glioblastoma tumor volume (p=0.008). When prospectively applied to cisternal CSF, the sensitivity and specificity of the 'signature' for glioblastoma detection were 67% and 80%, respectively. For lumbar CSF, the sensitivity and specificity of the signature were 28% and 95%, respectively. Comparable results were obtained from analyses of CSF extracellular vesicles (EVs) and crude CSF. We report a CSF miRNA signature as a "liquid biopsy" diagnostic platform for glioblastoma.


Cochlear implantation after surgery for bilateral jugular foramen paragangliomas: a case report.
This paper describes a case of cochlear implantation for deafness due to bilateral glomus jugulare tumors (paragangliomas) as well as an unusual complication after cochlear implantation in a 31-year-old male. A 31-year-old male with profound sensorineural hearing loss on the right side and deafness on the left side, caused by bilateral jugular foramen paragangliomas, was implanted with a multi-channel cochlear implant (Combi 40+, Med-El) on the right side during subtotal petrosectomy for removal of the right-sided glomus jugulare tumor. No postoperative medical complications were observed. The patient responded to acoustic stimuli. Postoperative computed tomography (CT) did not show any misplacement of the electrode. Three years after implantation, an acute, rapidly progressive hearing impairment with pain to acoustic stimuli was observed. A CT scan at that time showed cochlear bone resorption. No radiologic evidence of paraganglioma recurrence was observed. The implant was removed and a biopsy of the cochlea was performed which on histologic examination showed fibrosis without any sign of any tumor recurrence. Cochlear implantation can restore hearing in deafness due to bilateral glomus jugulare tumors. Cochlear resorption may occur as a late complication in the implanted side in the patients.


Somatic variation of H-2Kk expression and structure in a T-cell lymphoma: instability, stabilization, high production and structural mutation.
In the heterozygous T lymphoma line LDHB, variants which have lost the expression of individual H-2 class I genes are spontaneously generated in vitro at a frequency of 10(-1)-10(-2). A cell line (HK13) in which the class I gene Kk is stably expressed (frequency of loss variants less than 10(-4) was selected from LDHB cells by fluorescence activated cell sorting. Further selection of HK13 cells for high Kk expression led to the isolation of the HK22 line which expresses twice as much Kk as HK13. From HK13 and HK22 cells, spontaneous structural variants of Kk having lost individual serological determinants of the Kk wild-type molecule, were isolated by fluorescence activated cell sorting. Such variants occur at a frequency of 10(-6)-10(-7) per cell per generation. The analysis of these variants indicates that they carry mutations in the Kk structural gene and that HK13 cells express a single Kk gene which appears to be duplicated in HK22 cells. We did not find evidence for the generation of variants expressing 'alien' class I products in the LDHB cell line. The instability of class I gene expression in LDHB cells and the transition to stable expression may represent steps of T-cell differentiation in the thymus.


Abnormalities in cerebral hemodynamics and changes with surgical intervention in neonates with congenital heart disease.
To use novel optical techniques to measure perioperative cerebral hemodynamics of diverse congenital heart disease (CHD) groups (two-ventricle, d-transposition of the great arteries [TGA], and single ventricle [SV]) and (1) compare CHD groups with healthy controls preoperatively and (2) compare preoperative and postoperative values within each CHD group. Frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy were used to measure cerebral oxygen saturation, cerebral blood volume, cerebral blood flow index, cerebral oxygen extraction fraction (OEF, calculated using arterial oxygen saturation and cerebral oxygen saturation), and an index of cerebral metabolic rate of oxygen consumption in control and CHD neonates. Preoperative CHD measures were compared with controls. Preoperative and postoperative measures were compared within each CHD group. In total, 31 CHD neonates (7 two-ventricle, 11 TGA, 13 SV) and 13 controls were included. Only neonates with SV CHD displayed significantly lower preoperative cerebral blood flow index (P < .04) than controls. TGA and SV groups displayed greater OEF (P < .05) during the preoperative period compared with controls. Compared with the preoperative state, postoperative neonates with TGA had a greater arterial oxygen saturation with lower OEF. Differences in cerebral hemodynamics and oxygen metabolism were observed in diverse CHD groups compared with controls. Increased OEF appears to be a compensatory mechanism in neonates with TGA and SV. Studies are needed to understand the relationship of these metrics to outcome and their potential to guide interventions to improve outcome.


Long-term central venous catheters in patients with acquired immunodeficiency syndrome.
As long-term vascular access becomes more prevalent among patients with AIDS, it is becoming more important to consider their potential complications. One hundred two central venous access devices placed in 84 patients with AIDS were reviewed for septic and mechanical complications. Catheters were inserted by one surgeon by means of the cephalic vein cutdown technique. The sample included 88 implanted venous reservoir catheters (86.3%) and 14 tunneled central venous catheters (13.7%). Mean catheter life was 141 +/- 15 days. Total number of catheter days was 14,383. The catheter-related infection rate was 0.125 episodes/100 catheter-days. Staphylococcus aureus was the most commonly isolated pathogen in the sample. Mechanical complications were rare (0.05 episodes/100 catheter-days). When these data are compared with other, smaller series in the literature, the findings suggest that long-term central venous catheters inserted in patients with AIDS are safe and effective for the multiple infusion therapies required in these patients.


Antioxidant activity and structural modifications of serum chondroitin sulfate in Graves' disease.
Disturbances in the metabolism of proteoglycans/glycosaminoglycans related to free radical overproduction can be detected in Graves' ophthalmopathy. However, it is not evident whether these disorders appear before the clinical manifestation of ophthalmopathy and contribute to the development of nonthyroidal symptoms. They might also reflect the body's defence against the effects of an autoimmune attack, or they merely result from these disorders. Our study conducted in Graves' patients, free of ocular changes at the time of recruitment, is an attempt at explaining these ambiguities. We decided to investigate the relation between the changes in extracellular matrix components, namely the total glycosaminoglycans (GAGs) and chondroitin sulfates (CS), as well as parameters characterising oxidative stress, i.e. the total antioxidant status (TAS), and the thiol group (TG) concentration. GAGs, TAS and TG were quantified in serum samples obtained from 30 healthy subjects and 30 Graves' patients before and after treatment. An increased serum concentration of total GAGs and CS in Graves' patients before and after treatment was observed. Additionally, increased sulfation of CS in both Graves' patient groups was recorded. The serum TG and TAS concentrations in untreated patients were significantly decreased. Subsequent euthyreosis led to the normalisation of TG concentration. We have revealed a significant correlation between changes of extracellular matrix components, especially chondroitin-4-sulfate, thyroid status parameters, and parameters characterising oxidative stress. The structural modifications of serum CS in Graves' patients clinically free of ocular complications are probably the expression of systemic connective tissue remodelling. Simultaneously, these modifications may participate in a defence response to free radical damage underlying this pathology.


The biochemical basis for the apparent defect of soluble mutant tissue factor in enhancing the proteolytic activities of factor VIIa.
Tissue factor (TF), an integral membrane protein, is the cofactor for the serine protease, coagulation factor VIIa (FVIIa). Previous studies of the isolated extracellular domain of TF (sTF) reported a kcat for factor X (FX) activation by the sTF.VIIa complex only 4% that of wild-type TF.VIIa and furthermore, a complete inability of sTF to support FVII autoactivation. We now report that in the presence of poly(L-lysine), sTF promoted both FX activation and FVII autoactivation, the latter with an apparent second-order rate constant higher than reported previously for wild-type TF in phospholipid vesicles. This led us to reexamine the cofactor ability of sTF, using high concentrations of phospholipid to promote nearly quantitative binding of sTF.VII(a) complexes to the phospholipid surface. Rate constants for the activation of FX or FVII by sTF.VIIa were similar to those of wild-type TF.VIIa, indicating that the apparent deficiency of sTF is largely attributable to kinetic consequences of relatively weak affinity of FVIIa (and sTF.VIIa) for phospholipid surfaces in these surface-dependent reactions, compared with TF being embedded in the membrane. This supports the notion that sTF recapitulates the protein-protein interactions of wild-type TF with high, and possibly full, catalytic activity. It also provides a biochemical explanation for the specificity of our recently described, sTF-based clotting assay for plasma FVIIa.