Trans-scale thermal signaling in biological systems.
Biochemical reactions in cells serve as the endogenous source of heat, maintaining a constant body temperature. This process requires proper control; otherwise, serious consequences can arise due to the unwanted but unavoidable responses of biological systems to heat. This review aims to present a range of responses to heat in biological systems across various spatial scales. We begin by examining the impaired thermogenesis of malignant hyperthermia in model mice and skeletal muscle cells, demonstrating that the progression of this disease is caused by a positive feedback loop between thermally driven Ca2+ signaling and thermogenesis at the subcellular scale. After we explore thermally driven force generation in both muscle and non-muscle cells, we illustrate how in vitro assays using purified proteins can reveal the heat-responsive properties of proteins and protein assemblies. Building on these experimental findings, we propose the concept of 'trans-scale thermal signaling'.


Crystal Structure of Photosystem I Monomer From Synechocystis PCC 6803.
A single histidine addition to the C-terminus of PsaL of Synechocystis sp. PCC 6803 was previously reported by our lab to shift the trimer-to-monomer ratio of PSI in favor of the monomeric form. P700 re-reduction and NADP+ photo-reduction measurements of the PsaLHIS strain show no effect on PSI activity in comparison to the WT trimeric PSI. Crystal structure of the PsaLHIS monomeric PSI reveals several alterations that occurred in the trimerisation site of PSI, primarily a deformation of the C-terminus of PsaL and loss of chlorophyll a and β-carotene molecules.


Microbial kinetics of drug action against gram-positive and gram-negative organisms. III: Effect of lincomycin and clindamycin combinations on Staphylococcus aureus and Escherichia coli.
The functional dependencies of apparent first-order generation rate constants kapp, of drug-affected cultures on drug concentrations indicate that lincomycin and clindamycin possess the same mechanism of action, which is bacteriostatic, against Staphylococcus aureus. Clindamycin also possesses another mechanism of action, which is bactericidal, at high concentration levels. However, clindamycin possesses only one of the two mechanisms of lincomycin action, which is bacteriostatic, against Escherichia coli. The relative potency of action of a clindamycin-lincomycin combination against Staph. aureus is variable, and the effective ratio ranges between 5:1 and 9:1; the effective ratio against E. coli is fixed at 6:1 over a wide concentration range. This difference is attributed to differences in bioavailability and/or binding characteristics of the drugs for bioreceptors, as a consequence of structural modifications in the drug molecules, and to differences in modes of action in the respective organisms. Mixtures containing equipotent fractions of clindamycin and lincomycin show "equivalence" or "indifference" of effects on Staph. aureus. The combined action of the mixtures can be quantitatively predicted from the separate dose-response curves of either component drug alone. Therefore, it is concluded that clindamycin and lincomycin may bind to the same receptor site that is engaged in microbial protein synthesis to inhibit the generation of Staph. aureus. However, combinations of clindamycin and lincomycin are less active than the a priori equipotent concentration of either drug alone in their action against E. coli, demonstrating unequivocally an antagonism of effects. Furthermore, the degree of antagonism is dependent on the order of addition of the drugs, which is attributed to the possibility that clindamycin and lincomycin bind differently on active and allosteric loci of the same receptor site functionally engaged in protein synthesis in E. coli. A rational approach to the quantification and prediction of combined antibiotic action must, therefore, be based not only on the kinetics and mechanisms of action as well as on the dose-response relationship over a wide concentration range for the separate antibiotics but also on the strain and species of the test organism.


DNA-dependent adenosinetriphosphatase B from mouse FM3A cells has DNA helicase activity.
We have detected at least four forms of DNA-dependent ATPase in mouse FM3A cell extracts [Tawaragi, Y., Enomoto, T., Watanabe, Y., Hanaoka, F., & Yamada, M. (1984) Biochemistry 23, 529-533]. The purified fraction of one of the four forms, ATPase B, has been shown to have DNA helicase activity by using a DNA substrate which permits the detection of limited unwinding of the helix. The DNA substrate consists of single-stranded circular fd DNA and the hexadecamer complementary to the fd DNA, which bears an oligo(dT) tail at the 3' terminus. The helicase activity and DNA-dependent ATPase activity cosedimented at 5.5 S on glycerol gradient centrifugation. The helicase required a divalent cation for activity (Mg2+ congruent to Mn2+ greater than Ca2+). The optimal concentrations of these divalent cations were 5 mM. The requirement of divalent cations of the DNA helicase activity was very similar to that for the DNA-dependent ATPase activity of ATPase B. The helicase activity was absolutely dependent on the presence of a nucleoside triphosphate. ATP was the most effective cofactor among the ribo- and deoxyribonucleoside triphosphates tested, and considerable levels of helicase activity were observed with other ribo- and deoxyribonucleoside triphosphates. The efficiency of a nucleoside triphosphate to serve as cofactor for the helicase activity correlated with the capacity of the nucleotide to serve as substrate for the DNA-dependent ATPase activity. The nonhydrolyzable ATP analogues such as adenosine 5'-O-(3-thiotriphosphate) were not effective for the helicase activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Abomasal and uterine adenocarcinomas with ovarian metastasis in a captive elk (Cervus elaphus nelsoni).
A captive, 20-year-old female elk (Cervus elaphus nelsoni) euthanized due to progressive lameness and weight loss was presented to Colorado State University Veterinary Diagnostic Laboratory for postmortem examination. Within the uterus there was a poorly demarcated, multilobulated mass measuring 10 cm in diameter. Histologically the tumor was an adenocarcinoma. Histologic examination of the ovaries revealed unilateral metastasis. A focal, 1-cm diameter adenocarcinoma was identified within the abomasum; this tumor was histologically distinct from the neoplasm found in the uterus and ovary. Although this elk had a history of experimental reproductive treatments, including leuprolide, gonadotropin-releasing hormone vaccine, and Brucella abortus vaccination, it was most likely that both tumors represent spontaneous, independent neoplastic transformations and were unrelated.


Motivation key to use of new technologies.
Researchers and academics discuss how to get health care personnel motivated to adopt technological innovation. Physicians, they say, get a bad rap as the most techophobic players in the health care arena.


Effects of dextran on microvascular ischemia-reperfusion injury in striated muscle.
The objectives of this study were 1) to elucidate the effects of dextran (Dx) at a nonhemodiluting dose of 5 mg/kg on ischemia-reperfusion injury in striated muscle and 2) to investigate whether the effects are dependent on the molecular weight of Dx. We used the model of a 4-h pressure-induced ischemia in the hamster skinfold chamber. By means of intravital microscopy the following parameters were assessed: vessel diameter, red blood cell velocity, rolling and adherent leukocytes, macromolecular extravasation, and functional capillary density. The animals received a continuous infusion (total dose 5 mg/kg) of dextran of different molecular weights or equivalent volumes of saline. Seven groups were studied: NaCl (control, n = 6), Dx 1 (n = 6), Dx 40 (n = 7), Dx 60 (n = 6), Dx 70 (n = 7), Dx 110 (n = 7), and Dx 150 (n = 7). Leukocyte rolling was reduced by all Dx fractions, the difference from the control reaching significance 0.5 h after reperfusion in the Dx 60, Dx 70, and Dx 110 group, whereas leukocyte adherence was attenuated by > 40,000-mol-wt Dx at 0.5 h after reperfusion. Concomitantly, functional capillary density tended to improve after treatment with > or = 40,000-mol-wt Dx. However, all Dx fractions studied failed to reduce postischemic macromolecular extravasation. These results provide evidence that Dx at 5 mg/kg attenuates postischemic microvascular disturbances; this effect is molecular weight dependent.


Endogenous occurrence of protein S-guanylation in Escherichia coli: Target identification and genetic regulation.
8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a nitrated cGMP derivative formed in response to nitric oxide (NO) and reactive oxygen species (ROS). It can cause a post-translational modification (PTM) of protein thiols through cGMP adduction (protein S-guanylation). Accumulating evidence has suggested that, in mammals, S-guanylation of redox-sensor proteins may implicate in regulation of adaptive responses against ROS-associated oxidative stress. Occurrence as well as protein targets of S-guanylation in bacteria remained unknown, however. Here we demonstrated, for the first time, the endogenous occurrence of protein S-guanylation in Escherichia coli (E. coli). Western blotting using anti-S-guanylation antibody clearly showed that multiple proteins were S-guanylated in E. coli. Interestingly, some of those proteins were more intensely S-guanylated when bacteria were cultured under static culture condition than shaking culture condition. It has been known that E. coli is deficient of guanylate cyclase, an enzyme indispensable for 8-nitro-cGMP formation in mammals. We found that adenylate cyclase from E. coli potentially catalyzed 8-nitro-cGMP formation from its precursor 8-nitroguanosine 5'-triphosphate. More importantly, E. coli lacking adenylate cyclase showed significantly reduced formation of S-guanylated proteins. Our S-guanylation proteomics successfully identified S-guanylation protein targets in E. coli, including chaperons, ribosomal proteins, and enzymes which associate with protein synthesis, redox regulation and metabolism. Understanding of functional impacts for protein S-guanylation in bacterial signal transduction is necessary basis for development of potential chemotherapy and new diagnostic strategy for control of pathogenic bacterial infections.


Gendered Organizations in the New Economy.
Gender scholars draw on the "theory of gendered organizations" to explain persistent gender inequality in the workplace. This theory argues that gender inequality is built into work organizations in which jobs are characterized by long-term security, standardized career ladders and job descriptions, and management controlled evaluations. Over the past few decades, this basic organizational logic has been transformed. in the so-called new economy, work is increasingly characterized by job insecurity, teamwork, career maps, and networking. Using a case study of geoscientists in the oil and gas industry, we apply a gender lens to this evolving organization of work. This article extends Acker's theory of gendered organizations by identifying the mechanisms that reproduce gender inequality in the twenty-first-century workplace, and by suggesting appropriate policy approaches to remedy these disparities.


Assessment and verification of chemical inactivation of peste des petits ruminants virus by virus isolation following virus capture using Nanotrap magnetic virus particles.
This study reports development and optimization of a new method for the assessment and verification of the inactivation of peste des petits ruminants virus (PPRV) by chemical agents, including Triton X-100 and commercially available viral lysis buffers. Virus inactivation was confirmed by virus isolation (VI) on Vero cells following capture of the potential residual viruses from treated samples using Nanotrap magnetic virus particles (NMVPs). Since chemical agents are cytotoxic, treated PPRV samples could not be used directly for VI on Vero cell monolayers; instead, they were diluted in Eagle's Minimum Essential Medium (EMEM) to neutralize cytotoxicity and then subjected to virus capture using NMVPs. The NMVPs and the captured viruses were then clarified on a magnetic stand, reconstituted in EMEM, and inoculated onto Vero cells that were examined for cytopathic effect (CPE). No CPE was observed on cells inoculated with treated viruses captured by NMVPs; but CPE was observed on cells inoculated with untreated viruses, including those captured by NMVPs. For further verification, the supernatants of the VI cultures (treated or untreated) were subjected to RNA extraction and PPRV-specific real-time RT-PCR (RT-qPCR). The cycle threshold values were undetectable for the supernatants of VI cultures inoculated with NMVPs reconstituted from treated PPRV but detectable for the supernatants of VI cultures inoculated with untreated PPRV or the NMVPs reconstituted from untreated PPRV, indicating complete inactivation of PPRV. This new method of verification of virus inactivation using NMVPs can be applied to other high impact viruses of agricultural or public health importance. IMPORTANCE Research including diagnosis on highly contagious viruses at the molecular level such as PCR and next-generation sequencing requires complete inactivation of the virus to ensure biosafety and biosecurity so that any accidental release of the virus does not compromise the safety of the susceptible population and the environment. In this work, peste des petits ruminants virus (PPRV) was inactivated with chemical agents, and the virus inactivation was confirmed by virus isolation (VI) using Vero cells. Since the chemical agents are cytotoxic, inactivated virus (PPRV) was diluted 1:100 to neutralize cytotoxicity, and the residual viruses (if any) were captured using Nanotrap magnetic virus particles (NMVPs). The NMVPs and the captured viruses were subjected to VI. No CPE was observed, indicating complete inactivation, and the results were further supported by real-time RT-PCR. This new protocol to verify virus inactivation can be applicable to other viruses.


Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia.
1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm. 2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E-like substances (PLS) in the venous effluent from the muscle was analysed using bio-assay. For inhibition of PG biosynthesis, indomethacin (1-25 mg/kg body weight) was administered. 3. Following 5 min of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Indomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml./100 ml. tissue before, and 13 ml./100 ml. tissue after administration of indomethacin. 4. During sustained isometric forearm contraction, and following isometric and dynamic forearm muscle activity, a moderate hyperaemia was observed. This was significantly diminished when indomethacin had been administered, although not to the same extent as the reactive hyperaemia. The total hyperaemia in the absence and presence of indomethacin was 113 and 77 ml./100 ml. tissue, respectively, in connexion with isometric contraction and 206 and 120 ml./100 ml. tissue, respectively, following dynamic work. 5. The venous concentration of PLS was very low at rest. A significantly increased concentration was observed after ischaemia. This increased release of PLS was entirely suppressed by indomethacin. With the present assay method, muscular activity elicited no detectable change in the venous concentration of PLS. 6. It is concluded that reactive hyperaemia depends to a considerable extent on an intact PGE synthesis. It is furthermore suggested that endogenous PGE may contribute to the functional hyperaemia that appears during and after muscle activity.


Limit cycles, noise, and chaos in hearing.
Based on insight obtained from a newly developed cochlea model, we argue that noise-driven limit cycles are the basic ingredient in the mammalian cochlea hearing process. For insect audition, we provide evidence in favor of the persistence of this principle. We emphasize the role of bifurcations for the emergence of broad-range sound perception, both in the frequency and amplitude domain, and indicate that this crucially depends on the correct coupling between limit cycles. We review the limit-cycle coupling universality, and outline how it can be used to encode information. Cortical noise is the microscopic basis for this encoding, whereas chaos emerges as the macroscopic expression of computation being done in the network. Large neuron firing variability is one possible consequence of the proposed mechanism that may apply to both vertebrate and insect hearing.


Comment on "Old is Gold: Electrolyte Aging Influences the Topography, Chemistry, and Bioactivity of Anodized TiO2 Nanopores".
Self-organized anodic TiO2 nanostructures, in the form of nanopores, nanotubes, mesosponge, etc., obtained by electrochemical anodization have in the past two decades attracted tremendous focus and the number of publications based on such structures for various applications is remarkable. Guo et al. in ACS Appl. Mater. Interfaces 2021, 13 (7), 7897-7912 discuss the obtaining of TiO2 nanopores by anodization in an aged electrolyte and its influence on the nanopores' topography, chemistry, and bioactivity. Guo et al. do not include in their study sufficient SEM characterization to confirm the claimed nanopore morphology. This comment clarifies the difference between a nanotube and a nanopore structure, both by already existing literature and reproduced experimental results. In fact, anodization on similar substrates and in similar anodization conditions leads to a nanotube morphology covered at the top by an initiation layer, depending on the anodization duration and post-treatments, such as ultrasonication. It is noted that the type of nanostructure has a clear influence on the available inner surface area for porosity computation or biomedical applications, for example, targeting drug delivery and interactions with proteins. Here, a clearer classification into nanopores and nanotubes─with an open top or an initiation layer─is established and explained.


Postburn Neck Lateral Contracture Anatomy and Treatment: A New Approach.
Lateral contracture of the neck is a rare and insufficiently researched burn consequent. Contracture restricts head motion, can cause a secondary face deformity, presents severe cosmetic defects, and, therefore, requires surgical reconstruction. Literature does not sufficiently address the issue; therefore, anatomy not researched and treatment techniques not developed. The anatomy of postburn lateral cervical flexion contracture was studied in 21 operated patients. Using obtained data, new approaches were investigated, which were directed toward maximal efficacy of the local tissues use. Follow-up results were observed from 6 months to 9 years. Lateral cervical contractures were divided into two types based on their anatomy: edge and medial. Edge contractures were caused by burns and scars located on the posterior neck surface and were characterized by the presence of the fold in central lateral zone. In the fold, only one (posterior) sheet is scars that cause the contracture. Medial contractures were caused by scars located on the lateral cervical surface and were characterized by the presence of the fold in which both sheets were scars. In both types, contracture was caused by scar sheet surface deficiency in length, which has a trapezoid form (contracture cause). In all cases, there was surface surplus in the fold's sheets allowed contracture release with local tissue. The technique that allows the maximum local tissue use and ensures full contracture elimination is the trapeze-flap plasty. Two anatomic types of lateral cervical scar contractures were identified: edge and medial. An anatomically justified efficacy reconstructive technique for both types is trapeze-flap plasty.


Effect of Helicobacter pylori infection on iron absorption in asymptomatic adults consuming wheat flour fortified with iron and zinc.
Helicobacter pylori infection could impair iron absorption from fortified products. The objective of the study was to determine the effect of H. pylori infection on iron absorption from asymptomatic adults consuming wheat flour fortified with iron and zinc. The (13)C urea breath test was used to assess H. pylori infection. Twenty-four H. pylori-positive and 26 H. pylori-negative volunteers completed the study. On day 1, the subjects were randomized to receive for breakfast bread fortified with either ferrous sulfate and zinc sulfate or ferrous fumarate and zinc oxide. Bread fortified with ferrous sulfate was labeled with (59)Fe as sulfate, and bread fortified with ferrous fumarate was labeled with (55)Fe as fumarate. On day 3, they received the other type of bread, with the respective tracers. On days 18-23, a proton pump inhibitor was administered to all subjects. On day 24, all subjects received bread fortified with ferrous fumarate and zinc oxide labeled with (55)Fe as fumarate. H. pylori prevalence was 77.6%. The geometric mean (±1 SD) of iron absorption was significantly higher for ferrous sulfate than fumarate (6.9 ± 2.9% vs. 0.5 ± 3.5%, p < 0.001). The H. pylori-negative subjects absorbed significantly more iron from bread fortified with either ferrous sulfate (10.5 ± 3.1% vs. 4.4 ± 2.2%, p < 0.001) or ferrous fumarate (0.6 ± 3.9% vs. 0.4 ± 3.1%, p < 0.001). Iron absorption was not significantly different between groups after administration of a proton pump inhibitor (0.3 ± 3.3% vs. 0.3 ± 2.7%, p = 0.11). H. pylori infection has a negative effect on iron absorption in asymptomatic adults consuming iron- and zinc-fortified wheat flour.


Number of inseminations to conception in Holstein cows using censored records and time-dependent covariates.
Three methodologies that accommodate censoring or time-dependent covariates were used to estimate variance components for number of inseminations to conception. Data included 80,071 lactation records and 143,927 artificial inseminations in 47,509 Spanish Holstein cows. Up to 4 inseminations to conception, along with their respective censoring information, were analyzed. An ordinal-censored threshold model (CTM), a sequential threshold model (STM), and a grouped survival analysis via a discrete proportional hazards model (DPH) were implemented. Sire variance estimates on the liability scale were 0.016 and 0.010 for CTM and STM, respectively, and 0.012 for DPH on the logarithmic scale. Heritability estimates on the liability scale were 0.050 and 0.038 with CTM and STM, respectively. All models led to similar rankings of sires, and the strong correlations (0.97 to 0.98) between methodologies suggested robustness in ranking of sires of cows. Service sire variance estimates were 0.021 for both CTM and STM; DPH led to an approximate service sire variance of 0.020. Rankings for service sires between methodologies ranged from 0.76 to 0.90. These lower values are most likely due to differences in the treatment of time-dependent covariates. The STM had greater predictive ability of daughter fertility at first insemination than the other methodologies. However, the CTM predicted daughter fertility more accurately in subsequent inseminations. The DPH and STM had a similar predictive ability of daughter fertility in second and subsequent inseminations.


Effects of reinforcement scheduling on simultaneous discrimination performance.
Pigeons were trained on a discrete-trials, simultaneous discrimination procedure, with confusable stimuli such that asymptotic performance was about 85% correct. Trials were terminated if no response occurred within 2 sec of stimulus onset, so that probability of responding was free to vary. The schedule of reinforcement for correct responses was varied, with the following results: (1) there was no relation between frequency of reinforcement and accuracy of responding. (2) In extinction, the probability of responding fell to low levels, but accuracy remained roughly constant. (3) When reinforcement was available after a fixed number of trials or after a fixed number of correct responses, the probability of responding increased with successive trials after reinforcement, but accuracy was generally constant. (4) When every fifth correct response was reinforced, accuracy decreased immediately after reinforcement if the birds were required to respond on every trial.


Ecological Drivers and Sex-Based Variation in Body Size and Shape in the Queensland Fruit Fly, Bactrocera tryoni (Diptera: Tephritidae).
The Queensland fruit fly (Bactrocera tryoni; Q-fly) is an Australian endemic horticultural pest species, which has caused enormous economic losses. It has the potential to expand its range to currently Q-fly-free areas and poses a serious threat to the Australian horticultural industry. A large number of studies have investigated the correlation between environmental factors and Q-fly development, reproduction, and expansion. However, it is still not clear how Q-fly morphological traits vary with the environment. Our study focused on three morphological traits (body size, wing shape, and fluctuating asymmetry) in Q-fly samples collected from 1955 to 1965. We assessed how these traits vary by sex, and in response to latitude, environmental variables, and geographic distance. First, we found sexual dimorphism in body size and wing shape, but not in fluctuating asymmetry. Females had a larger body size but shorter and wider wings than males, which may be due to reproductive and/or locomotion differences between females and males. Secondly, the body size of Q-flies varied with latitude, which conforms to Bergmann's rule. Finally, we found Q-fly wing shape was more closely related to temperature rather than aridity, and low temperature and high aridity may lead to high asymmetry in Q-fly populations.


High-resolution microspectrometer with an aberration-correcting planar grating.
A concept for a highly miniaturized spectrometer featuring a two-component design is presented. The first component is a planar chip that integrates an input slit and aberration-correcting diffraction grating with an image sensor and is fabricated using microelectromechanical systems (MEMS) technologies. Due to the fabrication in a simple MEMS batch process the essential elements of the spectrometer are automatically aligned, and a low fabrication cost per device can be achieved. The second component is a spherical mirror, which is the only external part. The optimized grating structure compensates for aberrations within the spectrometer operating range, resulting in a diffraction-limited performance of the spectrometer optics. The prototype of the device has been fabricated and characterized. It takes a volume of 0.5 cm(3) and provides a FWHM spectral resolution of 0.7 nm over a 350 nm bandwidth from 420 nm to 770 nm combined with an etendue of 7.4x10(-5) mm(2) sr.


POSS Compounds as Modifiers for Rigid Polyurethane Foams (Composites).
Three types of polyhedral oligomeric silsesquioxanes (POSSs) with different functional active groups were used to modify rigid polyurethane foams (RPUFs). Aminopropylisobutyl-POSS (AP-POSS), trisilanoisobutyl-POSS (TS-POSS) and octa(3-hydroxy-3-methylbutyldimethylsiloxy-POSS (OH-POSS) were added in an amount of 0.5 wt.% of the polyol weight. The characteristics of fillers including the size of particles, evaluation of the dispersion of particles and their effect on the viscosity of the polyol premixes were performed. Next, the obtained foams were evaluated by their processing parameters, morphology (Scanning Electron Microscopy analysis, SEM), mechanical properties (compressive test, three-point bending test, impact strength), viscoelastic behavior (Dynamic Mechanical Analysis, DMA), thermal properties (Thermogravimetric Analysis, TGA, thermal conductivity) and application properties (contact angle, water absorption). The results showed that the morphology of modified foams is significantly affected by the fillers typology, which resulted in inhomogeneous, irregular, large cell shapes and further affected the physical and mechanical properties of the resulting materials. RPUFs modified with AP-POSS represent better mechanical properties compared to the RPUFs modified with other POSS.


The development of grammatical case distinctions in the use of personal pronouns by Spanish-speaking preschoolers.
Data on personal pronoun development in Spanish-speaking children was obtained in this study. Forty monolingual Puerto Rican Spanish-speaking children between the ages of 2;0 and 3;11 participated in the investigation. Two tasks were designed to obligate production of nominative and object pronouns in both reflexive and non-reflexive forms. Productive use and error analysis data were obtained and compared to previous data on pronoun development in English. By contrast with the order of productive use of grammatical case distinctions reported in the literature for English-speaking children, the children in the present study demonstrated a pattern in which nominative pronoun use preceded object case use. Implications of these findings for developmental theories that have been presented to explain pronoun development are discussed.


Double-blind, placebo-controlled trial of sildenafil in phallometric testing.
Not all males undergoing phallometric testing for assessment of deviant sexual interests respond adequately to test stimuli. As poor response may be linked to hormonal, neurologic, vascular, or psychogenic causes, we studied the ability of sildenafil, an effective proerectile agent, to increase penile blood flow during phallometric testing. Twenty-two males completed this double-blind, placebo-controlled trial of sildenafil (100 mg). Each participant underwent phallometric testing with and without sildenafil. On average, each subject's peak response was 50 percent greater in the sildenafil condition than it was in the placebo condition (p < .05). Correlations between participants' penile response to human stimulus categories, with or without treatment, were all very high (r = 0.77-0.89) and statistically significant, thus indicating excellent reliability between the two test conditions. These results support earlier findings that sildenafil significantly increases phallometric response among middle-aged males. Moreover, pharmacologic treatment did not compromise the reliability of phallometric diagnosis.


Dose response considerations in risk assessment--an overview of recent ILSI activities.
This paper will provide some perspective on the role that a consideration of the dose-response has played (past), is playing (present) and will play (future) in human risk assessment with special emphasis on a number of recent activities undertaken by various components of the International Life Sciences Institute (ILSI). The dose-response is a critically important concept in every aspect of biomedical science, including toxicology. A characterization of the dose response has been recognized as one of the four essential components of risk assessment since the release of the NRC/NAS report in 1983, and understanding the dose-response curve is the basis for regulatory toxicology. The introduction of concepts such as hormesis, thresholds of toxicological concern (TTC), and dose-dependent transitions in mechanisms of toxicity have emphasized the complexities associated with a characterization of the dose-response. The transitions to emphasizing predictive toxicology, systems biology, the new 'omics technologies, and high-throughput screening (HTS) have provided a new vision for toxicity testing. One impact of fully integrating these new concepts and technologies is that we will have unprecedented capabilities to explore the dose-response relationship, especially at low doses. How these new insights into the dose-response will affect our definition of threshold, and our understanding of the distinction between adverse and adaptive effects remain to be determined.


Minimum United States Medical Licensing Examination and Comprehensive Osteopathic Medical Licensing Examination Scores Often Do Not Align.
Background Many residency programs do not accept the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) alone for osteopathic applicants. Furthermore, among those programs that do accept the COMLEX-USA, it is unknown how programs scale their minimum COMLEX-USA scores compared to their minimum United States Medical Licensing Examination (USMLE) scores. Objective Our objective was to examine the variation of relative within-program differences between minimum USMLE Step and COMLEX-USA Level scores required for consideration by United States residency programs. Methods We performed a cross-sectional analysis of the Fellowship and Residency Electronic Interactive Database Access (FREIDA) database from April 2023, including the 10 specialties with the most training spots in 2022. These specialties were internal medicine, family medicine, pediatrics, emergency medicine, psychiatry, surgery, anesthesiology, obstetrics-gynecology, orthopedic surgery, and neurology. Within-program differences were calculated by subtracting the minimum USMLE Step 1 and 2 scores from the converted minimum USMLE Step 1 and 2 scores calculated from the minimum COMLEX-USA Level 1 and 2 scores using two conversion tools. We present differences as medians with interquartile ranges (IQR). Additionally, we report the proportion of programs with greater than 10-point differences for each step (1 and 2). Results Of the 3,364 accredited programs from the examined specialties, we included 1,477 in the Step 1 analysis and 1,227 in the Step 2 analysis with complete data. The median within-program difference between the minimum Step 1 score and the predicted Step 1 score was 12.0 (IQR 2.0, 17.0) using the Barnum and colleagues' conversion tool and -1.7 (IQR -6.2, 6.3) using the Smith and colleagues' tool. The median differences for Step 2 were 2.0 (IQR -8.0, 12.0) and -6.5 (IQR -13.9, -1.5) for each tool, respectively. Using the Barnum and Smith conversion tools, 937 (63%) and 435 (29%) programs had a greater than 10-point Step 1 score difference, respectively. Similarly, for Step 2, 564 (46%) and 515 (42%) programs had a greater than 10-point difference with each conversion tool. Conclusion There is wide variation in the within-program differences between minimum USMLE and predicted minimum USMLE (from COMLEX-USA) scores. Many programs have greater than 10-point differences, which may be a source of bias in osteopathic applicant selection.


Risk and protective factors for substance use among urban African American adolescents considered high-risk.
This exploratory study examined the relative contribution of academic achievement, peer drug use, and neighborhood attachment on alcohol and marijuana use among African American adolescents considered high-risk. Participants were 291 urban African American adolescents (ages 11 to 18 years) who were identified as at-risk. Youth were administered measures of the constructs of interest. Consistent with previous findings, regression findings revealed that academic achievement and peer drug use were significant predictors of alcohol and marijuana use among high-risk African American youth. However, neighborhood attachment was not significant. Our findings warrant further investigation into the different aspects of neighborhood contexts that may be protective or risk factors for substance use among African American youth considered high risk.


Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases.
Symptomatic, hormone refractory prostate cancer (HRCAP) is a major cause of morbidity with a median survival of less than 12 months and a 2-year survival of only up to 10% in most series. Mitoxantrone has been approved by the Food and Drug Administration for HRCAP. Preliminary data suggest that DPPE (N,N-diethyl-2-[4-(phenylmethyl) phenoxy]-ethanamine) or tesmilifene modulates cytotoxics to enhance the anticancer effect. In this phase II trial we assessed whether there is sufficient evidence of enhanced efficacy of DPPE and mitoxantrone to lead to a phase III clinical trial. A total of 29 patients with a median age of 73 years, of whom 10% were older than 80 years, with progressive HRCAP received 5.3 mg/kg DPPE intravenously every 3 weeks, 12 mg/m mitoxantrone intravenously every weeks and 5 mg prednisone orally twice daily. All patients had pain at presentation, while 97% had bone metastases, 10% had liver metastases and 17% had lung metastases. Median prostate specific antigen (PSA) was 210 ng/ml (IQR 77 to 430). Of the patients 75% had some pain improvement, 66% had decreased analgesia, 59% had a PSA decrease of 50% or greater and 45% had a PSA decrease of 75% or greater. Actual (not actuarial) 2-year survival was 21%. Despite major limitations of historical comparison the PSA decrease and decreased symptoms with DPPE-mitoxantrone-prednisone compare favorably to those of mitoxantrone-prednisone and docetaxel-estramustine in the literature. The 2-year survival rate of 21% mandates further assessment. This will be tested in a phase III Southwest Oncology Group trial.


Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.
Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiation in vitro required a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that the in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.


Interpreting estrogen screening assays in the context of potency and human exposure relative to natural exposures to phytoestrogens.
While the Environmental Protection Agency and the Organization for Economic Cooperation and Development have developed validated in vitro and in vivo screening assays to measure interaction of substances with estrogen, androgen and thyroid pathway components, to date, methods to contextualize such results in terms of potencies and actual human exposures are lacking. To place endocrine screening results in the context of potency and human exposure, we propose a method that entails (1) calculating a benchmark dose for a response measured in an endocrine screen; (2) estimating the human urinary concentration (biomonitoring equivalent, BE) expected to correspond to this dose (BEBMD ); (3) deriving the exposure:activity ratio (EAR) by comparing actual urinary values from human biomonitoring studies (e.g., National Health and Nutrition Examination Survey (NHANES)) to the BEBMD . Using OECD uterotrophic assay validation studies and NHANES results, we calculated EARs for genistein (EARGEN = 6.6 × 10(-4) ) and bisphenol A (EARBPA = 8.8 × 10(-7) ). The EARGEN is more than 700-fold greater than the EARBPA . Not only can these methods be applied to additional endocrine assays and compounds, they can contribute to weight of evidence decisions regarding the need for additional endocrine screening and testing-substances with low EARs may not warrant additional testing.


Chitosan-PEG hydrogel with sol-gel transition triggerable by multiple external stimuli.
Smart hydrogels play an increasingly important role in biomedical applications, since materials that are both biocompatible and multi-stimuli-responsive are highly desirable. A simple, organic solvent-free method is presented to synthesize a biocompatible hydrogel that undergoes a sol-gel transition in response to multiple stimuli. Methoxy-poly(ethylene glycol) (mPEG) is modified into carboxylic-acid-terminated-methoxy-poly(ethylene glycol) (mPEG-acid), which is then grafted onto chitosan via amide linkages yielding mPEG-g-chitosan. Grafting of mPEG onto hydrophobic chitosan imparts hydrophilic properties to the resultant polymer. The mPEG-g-chitosan gel exhibits a controllable multi-stimuli-responsive property. The balance between hydrophilicity and hydrophobicity is believed to confer mPEG-g-chitosan with stimuli-responsive behavior. The effect of salt concentration, solute concentration, temperature, and pH on the sol-gel transition of mPEG-g-chitosan is evaluated and the underlying mechanisms of mPEG-g-chitosan polymer packing and gelation property is discussed.


Topiramate induced histopathological changes in placenta of rats.
Effect of topiramate, an antiepileptic drug, on the development of conceptus and its safety during pregnancy has been investigated in experimental rats. Rats were treated with topiramate dissolved in tap water in the doses of 40. 100 and 200 mg/kg body weight from day 9 to 12 of gestation through oral route. Fetuses along with placenta were collected for examination on day 21 of gestation after sacrificing the pregnant rats with deep ether anaesthesia. The placenta showed neither significant reduction in weight as compared to the controls nor any overt anomaly. However. on microscopic examination all treated groups showed similar structural changes which increased in severity with increase in the dose of the drug. The deciduas basalis showed thickening, heamorrhage and increased fibrinoid deposit. Disproportionately increased frequency of vacuolated giant cells was observed in the basal zone whereas frequently broken trichorial membrane. homogenous labyrinthine septa and increased fetal mesenchyme were observed in the placental barrier. The results suggested that topiramate induced dose dependent deleterious changes in the structure of placenta, therefore it should be used with caution during pregnancy.


Size matters in the water uptake and hygroscopic growth of atmospherically relevant multicomponent aerosol particles.
Understanding the interactions of water with atmospheric aerosols is crucial for determining the size, physical state, reactivity, and climate impacts of this important component of the Earth's atmosphere. Here we show that water uptake and hygroscopic growth of multicomponent, atmospherically relevant particles can be size dependent when comparing 100 nm versus ca. 6 μm sized particles. It was determined that particles composed of ammonium sulfate with succinic acid and of a mixture of chlorides typical of the marine environment show size-dependent hygroscopic behavior. Microscopic analysis of the distribution of components within the aerosol particles show that the size dependence is due to differences in the mixing state, that is, whether particles are homogeneously mixed or phase separated, for different sized particles. This morphology-dependent hygroscopicity has consequences for heterogeneous atmospheric chemistry as well as aerosol interactions with electromagnetic radiation and clouds.


[Postoperative supraventricular arrhythmias in atrial septal defects].
Before operation as well as over a mean postoperative period of 8.9 years 222 adults with atrial septal defects underwent a follow-up examination concerning frequency and clinical significance of supraventricular dysrhythmias. Thereby disturbances of the formation of stimuli were found before the operative procedure in 60 patients and after the correction in 115 patients. Disturbances of the sinoatrial and atrioventricular conduction were registered preoperatively in 53 cases and postoperatively in 81 cases. Within these statistically significant increases in particular the significant forms of dysrhythmia elevated after the atrial septal defect closure. Thus the tachycardiac atrial dysrhythmias increased from 7 to 28%, complex arrhythmias even from 2 to 16%. Of dysrhythmias to be taken seriously patients with IAVC and supraventricular defect are significantly more frequently affected than those with interatrial septal defects. Size of the defect, shunt volume and pressure of the pulmonary artery did not show any connections with the frequency of dysrhythmia. On the other hand, when accompanying cardiac anomalies, symptoms of a manifest heart insufficiency were present and at an operation age over 40 years arrhythmias were proved more frequently. The complaints of the patients did not correlate with the endangering, but are imprinted by the haemodynamics and its postoperative normalization. By the established profile of complaints and a decrease of frequency from 76% pre- to only 40% postoperative the patient with atrial septal defect cannot estimate his individual risk and needs an adapted long-term concept for his cardiological care.


Patient evaluation and comparison of the recovery profile between propofol and thiopentone as induction agents in day surgery.
The patient's subjective perception of the quality of his/her recovery after day case anaesthesia with propofol or thiopentone as induction agents is still controversial. The authors investigated the perception and quality of awakening after anaesthesia during the recovery period and at 24 hours and 72 hours, in outpatients undergoing anaesthesia induced either with propofol or thiopentone and maintained with a volatile anaesthetic. In a double-blind study in adults undergoing knee arthroscopy in a day surgery unit, propofol and thiopentone were compared as induction agents in 60 randomized outpatients. A Critical Flicker Fusion Threshold test (CFFT), verbal test for anxiety, visual analog scale for anxiety and pain, and questionnaires were used to assess objectively and subjectively the quality of anaesthesia and awakening during the postoperative period. Demographic data and mean duration of anaesthesia were similar. In the propofol group, patients awoke more rapidly (9.2 +/- 5.8 vs 12.3 +/- 5.8 min) (P < 0.05); however, the CFFT measurements did not show any significant difference between the groups, except at time = 0 min, when 17 patients in the propofol group were able to perform the test versus only 10 patients in the thiopentone group (P < 0.05). At 4, 24, and 72 hours postoperatively, the authors were unable to detect any difference between the two groups. Except for early recovery, there were no differences between the intermediate and late recovery profiles, when propofol or thiopentone was used as the anaesthetic induction agent in day surgery.


Networks of ProteinProtein Interactions: From Uncertainty to Molecular Details.
Proteins are the bricks and mortar of cells. The work of proteins is structural and functional, as they are the principal element of the organization of the cell architecture, but they also play a relevant role in its metabolism and regulation. To perform all these functions, proteins need to interact with each other and with other bio-molecules, either to form complexes or to recognize precise targets of their action. For instance, a particular transcription factor may activate one gene or another depending on its interactions with other proteins and not only with DNA. Hence, the ability of a protein to interact with other bio-molecules, and the partners they have at each particular time and location can be crucial to characterize the role of a protein. Proteins rarely act alone; they rather constitute a mingled network of physical interactions or other types of relationships (such as metabolic and regulatory) or signaling cascades. In this context, understanding the function of a protein implies to recognize the members of its neighborhood and to grasp how they associate, both at the systemic and atomic level. The network of physical interactions between the proteins of a system, cell or organism, is defined as the interactome. The purpose of this review is to deepen the description of interactomes at different levels of detail: from the molecular structure of complexes to the global topology of the network of interactions. The approaches and techniques applied experimentally and computationally to attain each level are depicted. The limits of each technique and its integration into a model network, the challenges and actual problems of completeness of an interactome, and the reliability of the interactions are reviewed and summarized. Finally, the application of the current knowledge of protein-protein interactions on modern network medicine and protein function annotation is also explored.


The Beckwith-Wiedemann syndrome phenotype and the risk of cancer.
Beckwith-Wiedemann syndrome (BWS) comprises of a number of childhood abnormalities, often associated with one or more tumors. Thirty-eight patients were investigated to determine clinical and/or biological signs associated with a tumor presence. Our patients exhibited a higher incidence of tumor development (21%) than that previously reported, underlying the care with which such patients should be followed, when particular clinical features are observed: visceromegaly affecting three organs (liver, kidney, spleen), and also family history with sign of BWS such as macroglossia, omphalocele, hemihypertrophy, embryonic tumor), high body weight at birth (> or = +2 standard deviations and diastasis recti.


[Effects of earthworm (Eisennia foetida ) on As, P uptake by maize and As, P fractional transformation in the rhizosphere].
A pot experiment was conducted to examine the roles of earthworm in As uptake from original As-polluted soil by maize (Zea mays L.), and their effects on As, P fractions in the rhizosphere. The As-polluted soils with three As levels were collected from the arable soil near As mine. The plants were harvested after 10 weeks of growth. Dry weight (DW) and P, As concentrations of plants, as well as As and P fractions of the rhizospheric soil, were determined. The results showed that inoculated earthworm or appended rice straw increased maximal 149%, 222% DW of root and shoot, respectively. At the medium and high soil As levels, root As concentration in the soil treated by earthworm and rice straw was highest among all treatments, and earthworm increased more As concentration of shoot than rice straw did. In different soil As levels, root P concentration in the soil treated by earthworm was highest, and shoot P by rice straw. Ca-P affected maize absorbing As at the low soil As level(r = 0.981), and maize absorbing Al-P was restrained by As involved in well-crystallized hydrous oxides of Fe and Al at the medium (r = 0.953)and high (r = 0.997)soil As levels. The concentration of non-specially absorbed As and As combined with Fe or Al and of O-P increased at the soil inoculated earthworm or/and appended rice straw at the same time. These results indicated that earthworm was more valuable for plant developing than rice straw was.


[Association of alpha-adducin gene and G-protein beta3-subunit gene with essential hypertension in Chinese].
To investigate the relationship between the alpha-adducin (ADD1) gene G460W and the G-protein beta 3-subunit (GNB3) gene C825T polymorphisms and essential hypertension (EH) in a northern Chinese Han population. Peripheral blood samples were collected from 256 hypertensive patients and 495 normotensive controls. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphisms of ADD1 and GNB3 genes. Their body mass index, blood lipids, blood glucose and blood uric acid levels were also determined. The allele frequencies of the ADD1 gene G460W and the GNB3 gene C825T polymorphisms were in Hardy-Weinberg equilibrium. The WW frequency in the EH group was 35.2%, significantly higher than that in the normal group (27.4%, chi(2) = 4.768, P = 0.029, OR = 1.43). Adjusted for the conventional risk factors of hypertension, alpha-adducin polymorphism still played an independent role on systolic blood pressure. The genotypes CC, CT, and TT of the GNB3 gene in the EH group were 20%, 52%, and 28% respectively, not significantly different from those in the control group (21%, 53%, and 26% respectively, P = 0.755). The frequencies of the alleles C and T of the GNB3 gene C825T were 46% and 54% respectively, not significantly different from those of the normotensive controls (47% and 53% respectively, P = 0.561). Body mass index, blood lipids, and glucose level did not differ significantly among the three genotype groups in both EH and normotensive control groups. The alpha-adducin gene may be a susceptible gene to EH in northern Chinese Han population, however, the GNB3 gene C825T polymorphism may not play a significant role in EH in the same population.


Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness.
Protectins are newly identified natural chemical mediators that counter leukocyte activation to promote resolution of inflammation. In this study, we provide the first evidence for protectin D1 (PD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid) formation from docosahexaenoic acid in human asthma in vivo and PD1 counterregulatory actions in allergic airway inflammation. PD1 and 17S-hydroxy-docosahexaenoic acid were present in exhaled breath condensates from healthy subjects. Of interest, levels of PD1 were significantly lower in exhaled breath condensates from subjects with asthma exacerbations. PD1 was also present in extracts of murine lungs from both control animals and those sensitized and aerosol challenged with allergen. When PD1 was administered before aeroallergen challenge, airway eosinophil and T lymphocyte recruitment were decreased, as were airway mucus, levels of specific proinflammatory mediators, including IL-13, cysteinyl leukotrienes, and PGD(2), and airway hyperresponsiveness to inhaled methacholine. Of interest, PD1 treatment after aeroallergen challenge markedly accelerated the resolution of airway inflammation. Together, these findings provide evidence for endogenous PD1 as a pivotal counterregulatory signal in allergic airway inflammation and point to new therapeutic strategies for modulating inflammation in asthmatic lung.


Endoplasmic reticulum stress-mediated autophagy alleviates lipopolysaccharide-induced nucleus pulposus cell pyroptosis by inhibiting CHOP signaling in vitro.
Pyroptosis, a newly discovered pro-inflammatory programmed necrosis of cells, serves as an initiating and promoting event that leads to intervertebral disc (IVD) degeneration (IDD). Endoplasmic reticulum stress (ERS) and autophagy are vital regulatory mechanisms of cellular homeostasis, which is also closely related to IDD. However, the role and relationship of ERS and autophagy in the pyroptosis of nucleus pulposus cell (NPC) are not well understood. In this research, we aimed to elucidate the role and mechanism of ERS-C/EBP homologous protein (CHOP) in lipopolysaccharide (LPS)-induced cell pyroptosis and determine its interaction with autophagy. ERS and autophagy inducers or inhibitors were used or not in the preconditioning of rat NPCs. Cell viability, pyroptosis-related protein expression, caspase-1 activity assay, and enzyme-linked immunosorbent assay were performed to observe rat NPC pyroptosis after the treatment of LPS. Activation of the ERS pathway and autophagy were assessed by quantitative real-time PCR, western blot analyses, and immunofluorescence staining assay to classify the molecular mechanisms. Our results showed that LPS stimulation induced NPC pyroptosis with concomitant activation of the ERS-CHOP pathway and initiated autophagy. Activation of the ERS-CHOP pathway exacerbated rat NPC pyroptosis, whereas autophagy inhibited cell pyroptosis. LPS-induced cell pyroptosis and CHOP upregulation were negatively regulated by autophagy. LPS-induced autophagy was depressed by the ERS inhibitor but aggravated by the ERS inducer. Taken together, our findings suggested that LPS induced NPC pyroptosis by activating ERS-CHOP signaling and ERS mediated LPS-induced autophagy, which in turn alleviated NPC pyroptosis by inhibiting CHOP signaling.


Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma.
Administration of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) to melanoma patients causes selective disruption of the tumor vasculature but the mechanism of this disruption is unknown. Here we report that exposure of human endothelial cells to TNF and IFN-gamma results in a reduced activation of integrin alphaVbeta3, an adhesion receptor that plays a key role in tumor angiogenesis, leading to a decreased alphaVbeta3-dependent endothelial cell adhesion and survival. Detachment and apoptosis of angiogenic endothelial cells was demonstrated in vivo in melanoma metastases of patients treated with TNF and IFN-gamma. These results implicate integrin alphaVbeta3 in the anti-vascular activity of TNF and IFN-gamma and demonstrate a new mechanism by which cytokines control cell adhesion.


Clinical characteristics of the patients with Hodgkin's lymphoma involving extranodal sites.
Differences between Hodgkin's lymphoma (HL) patients in China and Western countries are known to exist, but data on Chinese patients with HL are limited. It is not clear whether there are clinical and histological differences in patients with HL involving different extranodal sites. This is the first study to analyze Chinese patients with HL involving different extranodal sites. We selected 22 HL patients with extranodal involvement from more than 250 previously untreated HL patients. Most patients were young males, and 20 of the 22 patients had stage IV disease. The major pathologic types were nodular sclerosis classical HL (NSCHL) and mixed cellularity classical HL(MCCHL). At diagnosis, the most commonly involved extranodal sites were the liver and lung, followed by the bones. There was no significant association between the international prognostic score(IPS) and survival in patients with different extranodal sites. Our data showed the overall survival (OS) and disease-free survival (DFS) rates of low-risk group (IPS = 0-2) were relatively higher than those of high-risk group (IPS ≥ 3), but the IPS did not show predictive power for survival. Although HL with extranodal involvement is rare, it should be considered as a unique form of HL.


Visual Dysfunction in Chinese Children With Developmental Dyslexia: Magnocellular-Dorsal Pathway Deficit or Noise Exclusion Deficit?
Many studies have suggested that children with developmental dyslexia (DD) not only show phonological deficit but also have difficulties in visual processing, especially in non-alphabetic languages such as Chinese. However, mechanisms underlying this impairment in vision are still unclear. Visual magnocellular deficit theory suggests that the difficulties in the visual processing of dyslexia are caused by the dysfunction of the magnocellular system. However, some researchers have pointed out that previous studies supporting the magnocellular theory did not control for the role of "noise". The visual processing difficulties of dyslexia might be related to the noise exclusion deficit. The present study aims to examine these two possible explanations via two experiments. In experiment 1, we recruited 26 Chinese children with DD and 26 chronological age-matched controls (CA) from grades 3 to 5. We compared the Gabor contrast sensitivity between the two groups in high-noise and low-noise conditions. Results showed a significant between-group difference in contrast sensitivity in only the high-noise condition. In experiment 2, we recruited another 29 DD and 29 CA and compared the coherent motion/form sensitivity in the high- and low-noise conditions. Results also showed that DD exhibited lower coherent motion and form sensitivities than CA in the high-noise condition, whereas no evidence was observed that the group difference was significant in the low-noise condition. These results suggest that Chinese children with dyslexia have noise exclusion deficit, supporting the noise exclusion hypothesis. The present study provides evidence for revealing the visual dysfunction of dyslexia from the Chinese perspective. The nature of the perceptual noise exclusion and the relationship between the two theoretical hypotheses are discussed.


[Comparative analysis of the value of information provided by anterior segment optical coherence tomography and confocal laser scanning microscopy for identifying the palisades of Vogt in normal limbus].
to conduct a comparative analysis of the value of information provided by anterior segment optical coherence tomography (AS-OCT) and in vivo confocal laser scanning microscopy (CLSM) for identifying the palisades of Vogt (POV) in normal limbus. POV were studied in 15 healthy participants (30 eyes) without any anterior segment disease. Two examination methods were used: AS-OCT En Face imaging (RTVue XR Avanti, 3D Cornea protocol) and CLSM (HRT3). Concordance of the results was then analyzed. Structural features of POV were distinguishable by both methods. CLSM was able to visualize POV in both the superior and inferior limbi of all the 15 patients (30 eyes). Within the inferior corneal hemisphere, POV had the appearance of well-differentiated hyperreflective double-contoured structures organized in parallel lines at the level of basal epithelium. The structure of the superior limbus, as judged from CLSM data, varied significantly: «classic» palisades were seen in only 13 eyes (43%), while in the other 17 cases (57%) POV were atypical. On OCT, POV structure was seen in detail in 29 eyes. By comparing the abilities of CLSM and OCT to visualize POV, a strong positive correlation (rS=0.99, p<0.05) was revealed between the results obtained in both the superior and inferior limbi. OCT data provide a detailed understanding of POV structure and strongly correlate with CLSM results. Taking into consideration the noninvasiveness, demonstrativeness, and repeatability of AS-OCT En Face imaging as well as the high value of provided information, the method cay be recommended as an alternative in POV diagnostics.


Public familiarity with the terms somatoform disorder and functional disorder in Germany: results from a representative population survey.
The terms somatoform disorder and functional disorder have been criticized for hindering rather than facilitating clinical communication, and physicians may rarely use these terms when communicating with patients who might be eligible for these diagnoses. However, no study has yet examined the extent to which patients at risk for these disorders are familiar with the diagnostic terms. Therefore, the primary aim of this study was to examine whether people at risk for a somatoform disorder (ie, those with medically unexplained somatic symptoms) are more familiar with the 2 terms than others. Participants in a representative German population sample (N = 2,471) were asked whether they were familiar with the terms somatoform disorder and functional disorder. The mean (SD) age of the sample was 50.5 (18.6) years, and 53.9% were women. Sociodemographic variables, (unexplained) physical ailments, doctor visits, depression, and anxiety were also assessed. Data were collected from November 2009 to December 2009. Of the sample, 19.5% and 54.0% reported being familiar with the terms somatoform disorder and functional disorder, respectively. Participants with medically unexplained symptoms did not have a higher probability of knowing the terms somatoform disorder (odds ratio = 0.98, 95% CI = 0.57-1.68) or functional disorder (odds ratio = 1.32, 95% CI = 0.86-2.04) compared to all others. Participants with a potential somatoform disorder did not differ in their familiarity ratings from others. We conclude that these diagnostic terms are probably not commonly used by physicians in routine clinical communication with patients suffering from unexplained medical symptoms. Future empirical research should investigate whether the currently proposed diagnosis complex somatic symptom disorder can solve current problems of acceptability, communication, and adequate treatment.


[Features of nano aerosols action and safety measures].
The article presents results of studies concerning influence of high-dispersed aerosol formed in traditional plasma processes on operators' health. Consideration also includes new technologies to obtain metall-containing nanoproducts; the authors recommend protection measures for workers, methods and devices to control nano aerosols in air.


An NTP-driven mechanism for the nucleotide addition cycle of Escherichia coli RNA polymerase during transcription.
The elementary steps of transcription as catalyzed by E. coli RNA polymerase during one and two rounds of the nucleotide addition cycle (NAC) were resolved in rapid kinetic studies. Modelling of stopped-flow kinetic data of pyrophosphate release in a coupled enzyme assay during one round of the NAC indicates that the rate of pyrophosphate release is significantly less than that for nucleotide incorporation. Upon modelling of the stopped-flow kinetic data for pyrophosphate release during two rounds of the NAC, it was observed that the presence of the next nucleotide for incorporation increases the rate of release of the first pyrophosphate equivalent; incorrect nucleotides for incorporation had no effect on the rate of pyrophosphate release. Although the next nucleotide for incorporation increases the rate of pyrophosphate release, it is still significantly less than the rate of incorporation of the first nucleotide. The results from the stopped-flow kinetic studies were confirmed by using quench-flow followed by thin-layer chromatography (QF-TLC) with only the first nucleotide for incorporation labeled on the gamma phosphate with 32P to monitor pyrophosphate release. Collectively, the results are consistent with an NTP-driven model for the NAC in which the binding of the next cognate nucleotide for incorporation causes a synergistic conformational change in the enzyme that triggers the more rapid release of pyrophosphate, translocation of the enzyme along the DNA template strand and nucleotide incorporation.


Effects of a single intravenous bolus of fentanyl on the minimum anesthetic concentration of isoflurane in chickens (Gallus gallus domesticus).
To assess the temporal effects of a single fentanyl intravenous (IV) bolus on the minimum anesthetic concentration (MAC) of isoflurane in chickens and to evaluate the effects of this combination on heart rate (HR) and rhythm, systemic arterial pressures (sAP) and ventilation. Prospective experimental trial. Seventeen adult chickens weighing 1.8±0.2 kg. Individual isoflurane MAC for 17 chickens was previously determined using the bracketing method. Chickens were anesthetized with isoflurane to evaluate the effects of a single IV fentanyl bolus (10 or 30 μg kg-1) on isoflurane MAC over time using the up-and-down method. Ventilation was controlled. The isoflurane MAC reduction was estimated by logistic regression at 5 and 15 minutes after fentanyl administration. In the second phase, seven chickens were anesthetized with isoflurane, and fentanyl was administered (30 μg kg-1) IV over 1 minute during spontaneous ventilation and HR and rhythm, sAP and ventilation variables were measured. At 5 minutes after IV administration of fentanyl (10 or 30 μg kg-1), isoflurane MAC was significantly reduced by 17.6% (6.1-29.1%) [logistic regression estimate (95% Wald confidence interval)] and 42.6% (13.3-71.9%), respectively. Isoflurane MAC reduction at 15 minutes after IV administration of fentanyl (10 or 30 μg kg-1) was 6.2% (-0.6 to 12.9%) and 13.2% (-0.9 to 27.3%), respectively; however, this reduction was not significant. No clinically significant cardiopulmonary changes or arrhythmias were detected after the administration of fentanyl (30 μg kg-1). Administration of a single fentanyl bolus induced a dose-dependent and short-lasting reduction in isoflurane MAC. The higher dose induced no significant cardiopulmonary depression in isoflurane-anesthetized chickens during spontaneous ventilation. In chickens anesthetized with isoflurane, the clinical usefulness of a single fentanyl bolus is limited by its short duration of effect.


Serum lipid concentrations in the Koki community: a preliminary report.
Serum cholesterol and triglyceride concentrations were estimated in a self-selected sample of 9% of the adults over the age of 18 years in the urban community of Koki in Port Moresby, in which there is a high prevalence of diabetes. There were 84 males and 58 females in the sample. The mean age was 32.6 years, with the males significantly older than the females. Mean cholesterol and triglyceride levels were 4.7 mmol/l and 1.2 mmol/l respectively, and significant sex differences were observed, with males demonstrating higher levels, even in the younger age group. A high prevalence of obesity was observed in both males (40%) and females (55%). The prevalence of hyperlipidaemia was higher in males than females and was also more frequently observed in obese than non-obese subjects of either sex. A significant number (25%) of young subjects (18-30 years) exhibited serum lipid concentrations in excess of recommended levels. Our results suggest that, in contrast to previous reports, elevated serum cholesterol and triglyceride levels are present in this community, and may represent an increased risk for the development of ischaemic heart disease.


Assessing the impact of cigarette smoking on β-cell function and risk for type 2 diabetes in a non-diabetic Chinese cohort.
Although the impact of cigarette smoking on glucose homeostasis has been extensively studied, the results, however, are still not conclusive. We, therefore, conducted a cross-sectional analysis of a non-diabetic Chinese cohort collected by the China Health and Nutrition Survey (CHNS 2009) to comprehensively assess the relationship between smoking, Hemoglobin A1c, β-cell function and insulin sensitivity. The cohort included a total of 5965 individuals (47.4% male) with a mean age of 49.23 years, and 4140 of which were non-smokers (69.4%), 834 were current light smokers (13.9%) and 991 were current heavy smokers (16.6%). Current smokers were predominantly males (93.6%) with a lower BMI (22.95 versus 23.42 kg/m2). HbA1c levels were dose-dependently increased with smoking exposure (5.39%, 5.42% and 5.45%, respectively, P = 0.007). Non-smokers were served as a referent, the adjusted ORs for type 2 diabetes were 1.12 (P = 0.256, light smokers) and 1.26 (P = 0.014, heavy smokers), indicating a positive relationship between cigarette smoking and incidence of diabetes. HOMA%B was decreased in a dose-responsive manner with cigarette smoking (4.80, 4.79 and 4.76, P = 0.036), suggesting an adverse effect of smoking on β-cell function. Collectively, cigarette smoking is dose-dependently associated with decreased HOMA%B, and current smokers were clearly in a higher risk for diabetes as manifested by the elevated HbA1c.


Predictors of hazardous drinking behavior in 1,340 adult trauma patients: a computerized alcohol screening and intervention study.
Alcohol screening and brief intervention (SBI) is used to decrease alcohol consumption, health care costs, and injury recidivism in trauma patients. Despite SBI being mandated for trauma centers, various concerns have led many centers to conduct SBI only on patients with a detectable blood alcohol concentration (BAC). We sought to determine the predictive nature of BAC on hazardous drinking behavior. Adult trauma patients were included if they received an SBI before discharge. SBI was administered using a computerized alcohol screening and intervention (CASI) system with the Alcohol Use Disorder Identification Test (AUDIT). Data regarding demographics, injuries, and BAC were prospectively collected. Multivariate analyses were performed to identify independent predictors of hazardous drinking behavior. Data were complete for 1,340 patients, with a mean age of 43 years (SD 20 years). Sixty-eight percent were male, 33% had detectable BAC, and 19% had hazardous drinking behavior. Multivariate analysis identified age (odds ratio [OR] 0.97 per year), male sex (OR 3.1), BAC (OR 1.009 per mg/dL), detectable BAC (OR 3.9), and legal intoxication (OR 7.8) as independent predictors of hazardous drinking behavior. Asian/Pacific Islander ethnicity was a significant negative predictor (OR 0.53) compared with white. Thirty-eight percent of patients with hazardous drinking behavior had no detectable BAC. Younger age, male sex, and higher BAC are early predictors of hazardous drinking behavior in adult trauma patients. Asian/Pacific Islander patients are half as likely to report hazardous drinking behavior compared with white patients. More than one-third of patients with hazardous drinking behavior do not have detectable BAC on admission and are not receiving interventions in centers that screen solely based on BAC.


Recognizing, reporting and reducing the data curation debt of cohort studies.
Good data curation is integral to cohort studies, but it is not always done to a level necessary to ensure the longevity of the data a study holds. In this opinion paper, we introduce the concept of data curation debt-the data curation equivalent to the software engineering principle of technical debt. Using the context of UK cohort studies, we define data curation debt-describing examples and their potential impact. We highlight that accruing this debt can make it more difficult to use the data in the future. Additionally, the long-running nature of cohort studies means that interest is accrued on this debt and compounded over time-increasing the impact a debt could have on a study and its stakeholders. Primary causes of data curation debt are discussed across three categories: longevity of hardware, software and data formats; funding; and skills shortages. Based on cross-domain best practice, strategies to reduce the debt and preventive measures are proposed-with importance given to the recognition and transparent reporting of data curation debt. Describing the debt in this way, we encapsulate a multi-faceted issue in simple terms understandable by all cohort study stakeholders. Data curation debt is not only confined to the UK, but is an issue the international community must be aware of and address. This paper aims to stimulate a discussion between cohort studies and their stakeholders on how to address the issue of data curation debt. If data curation debt is left unchecked it could become impossible to use highly valued cohort study data, and ultimately represents an existential risk to studies themselves.


Blood-brain barrier integrity in Alzheimer's disease patients and elderly control subjects.
A defective blood-brain barrier (BBB) has been postulated to be present in Alzheimer's disease (AD), which would allow circulating beta-amyloid peptide to enter the brain. The authors tested this hypothesis by studying BBB function in 14 individuals with probable AD and 9 elderly control subjects. A computed tomographic method was used to measure blood-to-brain transport (K1), tissue-to-blood efflux (k2), tissue plasma space (Vp), and tissue extracellular space (Ve) of meglumine iothalamate. Repeated-measures analysis of variance indicated no significant differences between the groups for any of the measures. The authors conclude that there is no generalized abnormality of the blood-brain barrier in AD.


The P wave and P-R interval. Effects of the site of origin of atrial depolarization.
The atria of 37 patients were paced from selected sites during cardiac surgery. When the atria were paced from endocardial sites low in the right atrium, the P waves in ECG leads II, III, and aVF were shown to be either negative, biphasic, or positive, depending on the site paced. When the endocardial sites were paced, the P-R intervals were, almost without exception, less than 0.12 sec. When those endocardial sites closest to the A-V junction were paced, the P-R intervals were always less than 0.12 sec. When the atria were paced, from the epicardial sites, the P-R intervals were always greater than 0.12 sec. Negative P waves in ECG leads II, III, and aVF were recorded when the atria were paced from the postero-inferior left atrium and the caudal right atrium. The P-R interval did not always reflect the initial period of atrial activation because an isoelectric interval, generally of 0.01 to 0.025 sec, was frequently present between the onset of atrial stimulation and the first clear evidence of the P wave in the ECG. The implications of these results are discussed.


Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program.
Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's<0.05). European ancestry (EA) analysis identified GWS loci on chromosomes 6 and 9, as well as GWS gene associations in EXD3, DRD2, and DCC. No other ancestry-specific GWS results were identified, underscoring the need to increase representation of diverse individuals. The genetic correlation of SI and SA within MVP was high (rG = 0.87; p = 1.09e-50), as well as with post-traumatic stress disorder (PTSD; rG = 0.78; p = 1.98e-95) and major depressive disorder (MDD; rG = 0.78; p = 8.33e-83). Conditional analysis on PTSD and MDD attenuated most pan-ancestry and EA GWS signals for SI without SA to nominal significance, with the exception of EXD3 which remained GWS. Our novel findings support a polygenic and complex architecture for SI without SA which is largely shared with SA and overlaps with psychiatric conditions frequently comorbid with suicidal behaviors.


Insomnia, daytime sleepiness and cardio-cerebrovascular diseases in the elderly: a 6-year prospective study.
To examine 1) the associations between history of cardio-cerebrovascular diseases (CVD) and insomnia complaints and excessive daytime sleepiness (EDS), and 2) the relationships between sleep complaints and future CVD in persons over 65. CVD was assessed at baseline and during two, four, and six-year follow-up in 5494 non-demented subjects. Self-reported insomnia complaints (poor sleep quality, difficulty in initiating sleep, difficulty in maintening sleep, and early morning awakening), EDS and sleep medication use were evaluated at baseline. Logistic regression models and Cox proportional hazard models, with delayed entry and age of participants as the time scale, were adjusted for socio-demographic, lifestyle and clinical variables. At baseline, 748 participants had a past-history of CVD. A past-history of CVD was associated with EDS (OR = 1.28 95%CI = [1.05-1.57]) and the number of insomnia complaints (OR = 1.26 95%CI = [1.03-1.55] for 1-2 insomnia complaints; OR = 1.32 95%CI = [1.03-1.71] for ≥3 complaints). In longitudinal analyses, neither the four components of insomnia nor the number of insomnia complaints were significantly associated with first or recurrent CVD events (n = 391 events). EDS was independently associated with future CVD events even after adjusting for prescribed sleep medication and past-history of CVD (HR = 1.35 95%CI = [1.06-1.71]). Our results suggest that the relationships between sleep complaints and CVD could be complex. Insomnia complaints are more likely a consequence of CVD, whereas EDS appears to be a determinant of CVD independently of past-history of CVD. EDS screening may thus constitute a means of detecting persons at high risk of CVD.


Quasi-classical approaches to vibronic spectra revisited.
The framework to approach quasi-classical dynamics in the electronic ground state is well established and is based on the Kubo-transformed time correlation function (TCF), being the most classical-like quantum TCF. Here we discuss whether the choice of the Kubo-transformed TCF as a starting point for simulating vibronic spectra is as unambiguous as it is for vibrational ones. Employing imaginary-time path integral techniques in combination with the interaction representation allowed us to formulate a method for simulating vibronic spectra in the adiabatic regime that takes nuclear quantum effects and dynamics on multiple potential energy surfaces into account. Further, a generalized quantum TCF is proposed that contains many well-established TCFs, including the Kubo one, as particular cases. Importantly, it also provides a framework to construct new quantum TCFs. Applying the developed methodology to the generalized TCF leads to a plethora of simulation protocols, which are based on the well-known TCFs as well as on new ones. Their performance is investigated on 1D anharmonic model systems at finite temperatures. It is shown that the protocols based on the new TCFs may lead to superior results with respect to those based on the common ones. The strategies to find the optimal approach are discussed.


Endocrine pancreatic function during atrophy of the exocrine gland.
Serum levels of glucose, insulin, and gastric inhibitory polypeptide (GIP) in response to intraduodenal and intravenous glucose loads have been examined in rats with exocrine pancreatic atrophy induced by feeding them a copper-deficient diet supplemented with D-penicillamine for 10-12 weeks. Whereas pancreatic weight and protein and trypsin content were drastically reduced as compared with pair-fed controls, insulin content was not significantly different between experimental (1.10 U) and control (1.40 U) rats. The intravenous glucose infusion was given in a dose (1.2 g/kg/h) simulating the glucose concentrations observed in response to an intraduodenal glucose load of 2.0 g/kg body weight. Both basal and stimulated insulin concentrations were lower in experimental animals as compared with controls. However, if the relative insulin response is considered, insulin secretion was almost identical in experimental and control animals. Both groups released significantly more insulin after intraduodenal glucose load than after intravenous glucose application. It is concluded that the entero-insular axis is intact in rats with exocrine pancreatic atrophy.


Characteristics and outcome of hemolytic uremic syndrome in Sudanese children in a single Centre in Khartoum State.
Hemolytic uremic syndrome (HUS) is one of the important causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in children. Proposed prognostic features are controversial. We reviewed, retrospectively, the records of children with HUS seen at Soba hospital, Khartoum (2004-2012). We aimed to study demographics, clinical/ laboratory features, outcome and prognostic risk factors. Thirty-nine children with HUS were recorded; 59% had diarrhoea positive (D+) and 41% diarrhoea negative (D-) HUS. The mean age was 65.4 months and males were 61.5%. At the acute phase seizures, coma, anuria/oliguria and hypertension were present in 25%, 17.9%, 51.3% and 53.8% respectively. Severe anaemia, thrombocytopenia, and leukocytosis were present in 71.8%, 97.4%, and 28.2% respectively. On discharge, hypertension was detected in 23.1%. Clinical and laboratory features were not significantly different in D+ and D- cases (P > 0.05 for all parameters). Dialysis was undertaken in 84.6% and acute mortality was 12.8% being significantly higher in D+ (P = 0.002). Demographic, clinical and laboratory features, late referral or need for dialysis were not significantly associated with higher risk of acute mortality (p > 0.05 for all). At short-term follow up (mean period ± SD of 18.54 ± 13.21 months), 51.3% had complete renal recovery, 15.4% CKD 3-4, 12.8% CKD 5 requiring renal replacement therapy (RRT), and 20.5% died. Higher mean serum creatinine and hypertension on discharge were risk factors for adverse outcome (CKD5 requiring RRT or death), P = 0.011 and 0.00 respectively. In spite of institution of RRT and supportive therapy, our data showed less favourable outcome of HUS.


[Antihypertensive effect of trifluoropentoxypicolinic acid: a pharmacokinetic study].
Two drugs, trifluoropentoxypicolinic acid (TFP) and 5-butoxypicolinic acid, which are composed of a picolinic acid skeleton and an alkoxyl group, were studied to determine characteristics of their antihypertensive effect. The study was carried out using normotensive rats and experimental hypertensive rats (DOCA type hypertensive, one-kidney type hypertensive and spontaneous hypertensive), and effects of these drugs were compared with those of fusaric acid (5-butylpicolinic acid), which is known as a hypotensive agent inhibiting dopamine beta-hydroxylase. The hypotensive effect of the drugs (10, 30 and 100 mg/kg, p.o.) on normotensive rats was weaker than on hypertensive rats. TFP showed a dose-dependent hypotensive effect which was not influenced by reserpine pretreatment. Though TFP showed the same inhibitory effect on serum dopamine beta-hydroxylase as fusaric acid, it had only approximately 0.5 times the inhibitory activity. However, TFP had a hypotensive effect which was 1.4 times stronger than that of fusaric acid. According to pharmacokinetic analysis based on the determination of blood drug concentration, the transfer rate of fusaric acid from the digestive tract to the blood was much higher than TFP by 1.6 X 10(4) times. Moreover, fusaric acid had a 4.5 times greater disappearance rate than TFP. From the above results, first of all, it is supposed that the antihypertensive effect of TFP is related to inhibition of dopamine beta-hydroxylase. In addition, it is suggested that prolonged presence of unchanged TFP in the blood increases its immediate depressive effect on the cardiovascular system, thereby causing a strong hypotensive effect.


A switch of microbial flora coupled with ontogenetic niche shift in Leptinotarsa decemlineata.
In Leptinotarsa decemlineata, a final-instar wandering larva typically undergoes an ontogenetic niche shift (ONS), from potato plant during the foraging stage to its pupation site below ground. Using high-throughput sequencing of the bacterial 16S ribosomal RNA gene, we determined the hypothesis that the L. decemlineata pupae harbor stage-specific bacteria to meet the physiological requirements for underground habitat. We identified 34 bacterial phyla, comprising 73 classes, 208 orders, 375 families, and 766 genera in the collected specimens. Microbes across phyla Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were enriched in the pupae, while those in the phylum Proteobacteria, Tenericutes, Firmicutes, and Bacteroidetes dominated in the larvae and adults. A total of 18 genera, including Blastococcus, Corynebacterium_1, Gordonia, Microbacterium, Nocardia, Nocardioides, Rhodococcus, Solirubrobacter, Tsukamurella, Enterococcus, Acinetobacter, Escherichia_Shigella, Lysobacter, Pseudomonas, and Stenotrophomonas, were specifically distributed in pupae. Moreover, soil sterilizing removed a major portion of bacteria in pupae. Specifically, both Enterococcus and Pseudomonas were eliminated in the soil sterilizing and antibiotic-fed beetle groups. Furthermore, the pupation rate and fresh pupal weight were similar, whereas the emergence rate and adult weight were decreased in the antibiotic-fed beetles, compared with controls. The results demonstrate that a switch of bacterial communities occurs in the pupae; the pupal-specific bacteria genera are mainly originated from soil; this bacterial biodiversity improves pupa performance in soil. Our results provide new insight into the evolutionary fitness of L. decemlineata to different environmental niches.


High frequency of endothelial colony forming cells marks a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis.
Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54-17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×10(9)/L or lower, and platelet count of 400×10(9)/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45-13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment.


How Does the P7C3-Series of Neuroprotective Small Molecules Prevent Membrane Disruption?
Molecular dynamics (MD) simulations are conducted to suggest a mechanism of action for the aminopropyl dibromocarbazole derivative (P7C3) small molecule, which protects neurons from apoptotic cell death. At first, the influence of embedded Aβ42 stacks on the structure of membrane is studied. Then, the effect of P7C3 molecules on the Aβ42 fibril enriched membrane and Aβ42 fibril depleted membrane (when Aβ42 fibrils are originally dissolved in the aqueous phase) are evaluated. Also, the formation of an amyloid ion channel in the Aβ42 enriched membrane is examined by calculating deuterium order parameter, density profile, and surface thickness. For Aβ42 in the fully inserted state, ion channel-like structures are formed. The presence of P7C3 molecules in this case just postpones membrane destruction but could not prevent pore formation. In contrast, when both Aβ42 and P7C3 molecules are embedded in the aqueous solution, the P7C3 molecules are self-assembled at membrane/ionic aqueous solution interface and prevent the precipitation and deposition of Aβ42 fibrils into the membrane.


Composition and Function of Mutant Swi/Snf Complexes.
The 12-subunit Swi/Snf chromatin remodeling complex is conserved from yeast to humans. It functions to alter nucleosome positions by either sliding nucleosomes on DNA or evicting histones. Interestingly, 20% of all human cancers carry mutations in subunits of the Swi/Snf complex. Many of these mutations cause protein instability and loss, resulting in partial Swi/Snf complexes. Although several studies have shown that histone acetylation and activator-dependent recruitment of Swi/Snf regulate its function, it is less well understood how subunits regulate stability and function of the complex. Using functional proteomic and genomic approaches, we have assembled the network architecture of yeast Swi/Snf. In addition, we find that subunits of the Swi/Snf complex regulate occupancy of the catalytic subunit Snf2, thereby modulating gene transcription. Our findings have direct bearing on how cancer-causing mutations in orthologous subunits of human Swi/Snf may lead to aberrant regulation of gene expression by this complex.


Impact of minimally invasive surgery on healthcare utilization, cost, and workplace absenteeism in patients with Incisional/Ventral Hernia (IVH).
Incisional hernia repair is one of the most common general surgery operations being performed today. With the advancement of laparoscopy since the 1990s, we have seen vast improvements in faster return to normal activity, shorter hospital stays and less post-operative narcotic use, to name a few. The key aims of this review were to measure the impact of minimally invasive surgery versus open surgery on health care utilization, cost, and work place absenteeism in the patients undergoing inpatient incisional/ventral hernia (IVH) repair. We analyzed data from the Truven Health Analytics MarketScan® Commercial Claims and Encounters Database. Total of 2557 patients were included in the analysis. Of the patient that underwent IVH surgery, 24.5% (n = 626) were done utilizing minimally invasive surgical (MIS) techniques and 75.5% (n = 1931) were done open. Ninety-day post-surgery outcomes were significantly lower in the MIS group compared to the open group for total payment ($19,288.97 vs. $21,708.12), inpatient length of stay (3.12 vs. 4.24 days), number of outpatient visit (5.48 vs. 7.35), and estimated days off (11.3 vs. 14.64), respectively. At 365 days post-surgery, the total payment ($27,497.96 vs. $30,157.29), inpatient length of stay (3.70 vs. 5.04 days), outpatient visits (19.75 vs. 23.42), and estimated days off (35.71 vs. 41.58) were significantly lower for MIS group versus the open group, respectively. When surgical repair of IVH is performed, there is a clear advantage in the MIS approach versus the open approach in regard to cost, length of stay, number of outpatient visits, and estimated days off.


Lysis of human malignant mesothelioma cells by natural killer (NK) and lymphokine-activated killer (LAK) cells.
Malignant mesothelioma is an aggressive tumor of the pleura for which, at present, there is no effective therapy. As interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells lyse many solid tissue malignancies that are unresponsive to conventional forms of therapy, the aim of this study was to evaluate the susceptibility of human malignant mesothelioma cells to lysis by natural killer (NK) and LAK cells. Using a 4-h 51Cr release assay, malignant mesothelioma cell lines grown from six different patients were found to be resistant to NK cell lysis (less than 10% lysis as compared to 50 +/- 3% lysis of the standard NK-sensitive target, K562, p less than 0.001). These malignant mesothelioma cells were, however, susceptible to lysis by LAK cells (58 +/- 4% lysis, p less than 0.001 compared to NK lysis). Similar results were seen using fresh mesothelioma cell targets (4 +/- 2% and 34 +/- 12% lysis for NK and LAK cells, respectively). Optimal LAK cell activation against these targets was achieved by incubating peripheral blood mononuclear cells (2 to 4 x 10(6)/ml) in culture medium containing 1,000 units/ml IL-2 for 3 to 14 days. The degree of LAK cell activation was dependent on the serum source used in culture, with autologous serum being more effective than pooled human AB serum or fetal calf serum at generating LAK cell activity in vitro (p less than 0.05). The results of this study demonstrate that although human malignant mesothelioma cells are resistant to NK cell lysis, IL-2-activated LAK cells effectively kill these targets.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment of pagetoid reticulosis with intensity modulated radiation therapy.
Pagetoid reticulosis, also known as Woringer-Kolopp disease, is a rare variant of cutaneous T-cell lymphoma usually presenting as an isolated patch or plaque on the extremities. Immunohistochemical staining of T-cell markers can be variable, but as the name implies the epidermotropic lymphocytes consistently display a "pagetoid" appearance. The following case demonstrates clearance of this condition with intensity modulated radiation therapy, whereas most cases are managed with electron beam therapy if radiation therapy is implemented.