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Photoinduced decarbonylation of 2,4-bis(spirocyclohexyl)-1,3-cyclobutanedione 1 in the crystalline solid state resulted in formation of a deep blue transient with lambda(max) = 550 nm and a half-life of 42 min at 298 K, identified as kinetically stabilized oxyallyl. Support for an open-shell singlet species was obtained by spectroscopic analysis and (4/4) CASSCF calculations with the 6-31+G(d) basis set and multireference MP2 corrections. The electronic spectrum of the singlet biradical, confirmed by femtosecond pump-probe studies in solution, was matched by coupled cluster calculations with single and double corrections. | Butanones |
Pseudomonas pseudoalcaligenes JS45 utilizes nitrobenzene as the sole source of nitrogen, carbon, and energy. Previous studies have shown that degradation of nitrobenzene involves the reduction of nitrobenzene to nitrosobenzene and hydroxylaminobenzene, followed by rearrangement to 2-aminophenol, which then undergoes meta ring cleavage to 2-aminomuconic semialdehyde. In the present paper, we report the enzymatic reactions responsible for the release of ammonia after ring cleavage. 2-Aminomuconic semialdehyde was oxidized to 2-aminomuconate in the presence of NAD by enzymes in crude extracts. 2-Aminomuconate was subsequently deaminated stoichiometrically to 4-oxalocrotonic acid. No cofactors are required for the deamination. Two enzymes, 2-aminomuconic semialdehyde dehydrogenase and a novel 2-aminomuconate deaminase, distinguished by partial purification of the crude extracts, catalyzed the two reactions. 4-Oxalocrotonic acid was further degraded to pyruvate and acetaldehyde. The key enzyme, 2-aminomuconate deaminase, catalyzed the hydrolytic deamination that released ammonia, which served as the nitrogen source for growth of the organism." | Aminomuconate-Semialdehyde Dehydrogenase |
The specificities of antisera against digoxin C-3' or C-3'' hemisuccinate-bovine serum albumin (BSA) conjugate were assessed by cross-reactivity studies with digoxin metabolites by radioimmunoassay (RIA) using the homologous and the site heterologous tritium-labeled antigens. One of the tracers used was digoxin 3'-hemisuccinyl-[3H]-leucine; the other was digoxin 3''-hemisuccinyl-[3H]-leucine, which had been prepared from digoxin 3''-hemisuccinate. When the tracer with [3H]-leucine at the C-3' position was used, antisera (I-1, I-3) elicited by digoxin 3'-hemisuccinate-BSA conjugate showed the following cross-reactivity: digoxigenin bisdigitoxoside (0.34%, 76%), digoxigenin monodigitoxoside (0.11%, 65%), digoxigenin (0.02%, 26%) and dihydrodigoxin (9.4%, 1.2%). However, when using the homologous antigen, antiserum (I-1) was highly specific against the digitoxose chain. When the site heterologous antigen, digoxin 3''-hemisuccinyl-[3H]-leucine was combined, this antiserum showed high cross-reactivity to digoxin degradation products. This digoxin RIA using antiserum (I-1) with the homologous antigen measures unmetabolized digoxin. On the other hand, the RIA system using antiserum (I-3) with the homologous antigen had cross-reactivity with the metabolites in accordance with their relative cardio-activities, so this system would be useful in therapeutic drug monitoring of digoxin. | Antigens, Heterophile |
Respiratory syncytial virus (RSV) infection potentiates neurogenic inflammation in rat airways. Because some vascular effects of sensory nerves are mediated by cysteinyl leukotrienes (cysLTs), we studied whether the receptor antagonist montelukast inhibits neurogenic plasma extravasation in RSV-infected rats. Pathogen-free rats were inoculated at 2 wk (weanlings) or 12 wk (adults) of age with RSV or virus-free medium and treated with montelukast or its vehicle starting 1 day before inoculation. Five days postinoculation, we measured the extravasation of Evans blue-labeled albumin in the respiratory tract after stimulation of sensory nerves with capsaicin. Montelukast had no effect in the extrapulmonary airways but abolished albumin extravasation in the intrapulmonary airways of RSV-infected rats, with a larger effect in weanlings than in adults. Increased concentrations of 5-lipoxygenase-encoding mRNA and cysLTs, as well as numerous mast cells, were detected in the lung tissues of RSV-infected weanling rats. These observations suggest that the release of neuropeptides from capsaicin-sensitive sensory nerves and nonneuronal cells in the lungs of RSV-infected young rats increases vascular permeability by promoting the release of leukotrienes from mast cells. | Neurogenic Inflammation |
A human Tay-Sachs disease (TSD) fetal-brain-cell line is a useful model for the disease since the cells lack hexosaminidase A and accumulate the ganglioside, GM2. This brain-cell line was used to assess the effect of hexosaminidase A treatment on GM2 storage material. Entry of placental hexosaminidase A into the cells was obtained by pretreatment of the cultures with concanavalin A. Cells were analyzed periodically during six days. During the course of the experiment, GM2 in the cells decreased by approximately 50%. A substantial amount of hexosaminidase A was maintained in the cultures throughuot the experiment. This strategy was successful in mobilizing stored GM2 in TSD brain-cell cultures. Therefore, the activating factor needed for hexosaminidas A activity must be present in TSD-cultured brain cells. | Tay-Sachs Disease |
Actinobacillus suis is an opportunistic pathogen that resides in the tonsils of the soft palate of swine. Unknown stimuli can cause this organism to invade the host, resulting in septicaemia and sequelae including death. To better understand its pathogenesis, the expression of several adhesin genes was evaluated by semi-quantitative real-time PCR in A. suis grown in conditions that mimic the host environment, including different nutrient and oxygen levels, exponential and stationary phases of growth, and in the presence of the stress hormone epinephrine. Fifty micromolar epinephrine did not affect the growth rate or expression of A. suis adhesin genes, but there was a significant growth phase effect for many genes. Most adhesin genes were also differentially expressed during anoxic static growth or aerobic growth, and in this study, all genes were differentially expressed in either exponential or stationary phase. Based on the time*treatment interactions observed in the anoxic study, a model of persistence of A. suis in the host environment in biofilm and planktonic states is proposed. Biofilm dynamics were further studied using wild type and isogenic mutants of the type IVb pilin (Delta flp1), the OmpA outer membrane protein (DeltaompA), and the fibronectin-binding (DeltacomE1) genes. Disruption of these adhesin genes affected the early stages of biofilm formation, but in most cases, biofilm formation of the mutant strains was similar to that of the wild type by 24h of incubation. We postulate that other adhesins may have overlapping functions that can compensate for those of the missing adhesins. | Actinobacillus suis |
Various methods of cardioplegia administration have been used in cardiac surgery: crystalloid, blood and mixed crystalloid/blood. Each of these types of cardioplegia administration typically needs a different circuit. This may correspond to an increase in cost and the time needed to change the circuit if required. When various modifications are performed on the circuit, this also increases the risk of contamination. In order to simplify the management of differing cardioplegia circuits, we devised one circuit for all solutions in all situations by adding one modification. The ReVerse cardioplegia circuit system is a description of a two-pump cardioplegia circuit which is adaptable to either blood or crystalloid cardioplegia. The change from one mode to another requires a manoeuvre of two clamps, allowing the blood solution to travel through shunt tubing into the apposite pumphead. In our experience the versatility of this circuit is a fast, safe method to administrate all types of cardioplegia solution, saving the space taken up by storing multiple circuits. | Cardioplegic Solutions |
The T3SS is a syringe-shaped nanomachine essential for the progression of many Gram-negative bacterial infections including plague, typhoid fever, and dysentery. It spans both bacterial membranes and that of the host allowing delivery of proteins that modulate cell function to aid bacterial survival. Its structure has been the focus of scrutiny for 20 years; however, limitations in purification and structure determination techniques have restricted understanding to atomic structures of individual components and subcomplexes or lower resolution information of the more complete assembly. The recent cryo-EM resolution revolution has facilitated dramatic advances in our structural understanding of the T3SS with complimentary techniques of single particle cryo-EM and cryo-ET revealing structures of isolated complexes to near-atomic resolutions or the architecture of the entire T3SS in its native cellular environment. Here we present an overview of these advances and discuss how these structures further understanding of the dynamic process of injectisome assembly. | Secretin |
The paper discusses the major Argentineans contributors, medical physicists and scientists, in medical imaging and the development of medical imaging in Argentina. The following are presented: history of medical imaging in Argentina: the pioneers; medical imaging and medical revolution; nuclear medicine imaging; ultrasound imaging; and mathematics, physics, and electronics in medical image research: a multidisciplinary endeavor. | Biomedical Engineering |
The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience. | Ethylene Glycol |
Since the seminal 1993 demonstrations o f Murphy an d Zajonc, researchers have replicated and extended findings concerning subliminal affective priming. So far, however, no data on test-retest reliability of affective priming effects are available. A subliminal facial affective priming task was administered to 22 healthy individuals (15 women and 7 men) twice about 7 wk. apart. Happy and sad facial expressions were used as affective primes and neutral Chinese ideographs served as target masks, which had to be evaluated. Neutral facial primes and a no-face condition served as baselines. All participants reported not having seen any of the prime faces at either testing session. Priming scores for affective faces compared to the baselines were computed. Acceptable test-retest correlations (rs) of up to .74 were found for the affective priming scores. Although measured almost 2 mo. apart, subliminal affective priming seems to be a temporally stable effect. | Sublimation, Psychological |
o-[131I] iodohippurate [OIH(I-131)] has been used for many years in the estimation of effective renal plasma flow. This compound suffers from low photon yield and poor images when the quantity used is limited to stay within a reasonable radiation dose. To test the validity of substituting I-123 for I-131, a series of experiments was performed in a surgically prepared dog model. The extraction ratios and clearance values OIH(I-123) prepared from radionuclidically pure I-123 were compared with those of commercial OIH(I-131) and PAH. The extraction ratios for OIH(I-123) and OIH(I-131) were 0.65 and 0.67, representing 0.86 and 0.88 that of PAH, respectively. The clearance values (cc/min/kg) for the I123 and I-123) can be used to estimate effective renal plasma flow; moreover, because of the high yield within an acceptable radiation dose range, images of good quality can be produced. | Hippurates |
To define the quantitative aspects of ossification of human fetal spine, we performed a high resolution densitometric study by lateral and postero-anterior scanning of five fetal spines (18-36 weeks of conceptual age) and one spine of a 4-month-old infant. The data were plotted against developmental age for each spine and vertebra. Bone mineral content increased with developmental age, with a peak at the upper lumbar level, in agreement with the ossification pattern of the spine, reported in embryological literature. Bone mineral density (BMD) was unrelated to developmental age, and showed similar trends for each vertebra in all the vertebral columns examined. The changes of BMD seems to be a phenomenon related to individual variability. This study also demonstrates that densitometric techniques may provide useful and interesting information in studies on skeletal development. | Spine |
Transcription and its regulation pose challenges related to DNA torsion and supercoiling of the DNA template. RNA polymerase tracking the helical groove of the DNA introduces positive helical torsion and supercoiling upstream and negative torsion and supercoiling behind its direction of travel. This can inhibit transcriptional elongation and other processes essential to transcription. In addition, chromatin remodeling associated with gene activation can generate or be hindered by excess DNA torsional stress in gene regulatory regions. These topological challenges are solved by DNA topoisomerases via a strand-passage reaction which involves transiently breaking and re-joining of one (type I topoisomerases) or both (type II topoisomerases) strands of the phosphodiester backbone. This review will focus on one of the two mammalian type II DNA topoisomerase enzymes, DNA topoisomerase II beta (TOP2B), that have been implicated in correct execution of developmental transcriptional programs and in signal-induced transcription, including transcriptional activation by nuclear hormone ligands. Surprisingly, several lines of evidence indicate that TOP2B-mediated protein-free DNA double-strand breaks are involved in signal-induced transcription. We discuss the possible significance and origins of these DSBs along with a network of protein interaction data supporting a variety of roles for TOP2B in transcriptional regulation. | DNA Topoisomerases, Type II |
Total internal reflection fluorescence microscopy (TIRFM) is an important method in surface science and for the analysis of surface-bound macromolecules. Here, we developed and explored the use of a novel fluorescein isothiocyanate isomer I (FITC)-adsorbed monolayer for alignment and validation of TIRFM measurements and configurations. Aqueous solutions of FITC exist as several different protolytic forms (dianionic, anionic, neutral, and cationic) with each form having different emission characteristics. However, the emission behavior of FITC adsorbed on hydrophilic, hydrophobic, and unmodified glass surfaces at different pH was unknown. TIRFM imaging and spectroscopy were used to study FITC and FITC-labeled bovine serum albumin (BSA-FITC) monolayers generated on three different glass surfaces. Monolayer emission intensity, spectra, and the photobleaching profiles were all dependent on pH and the surface properties of the glass. Very strangely, however, at pH 5.0 on hydrophobic surfaces, the FITC monolayers produced were both bright and apparently unbleachable over approximately 20 min of imaging (60 s total exposure). During monolayer formation at pH 5.0, we saw clear evidence for concentration-based quenching, indicating high surface coverage. When the monolayer had been rinsed with buffer to remove unbound FITC, we observed an increase in emission intensity during illumination indicative of some form of photoactivated species being present. Eventually, the fluorescence emission stabilized and remained constant for extended periods of time with no evidence of photobleaching. We hypothesize that during the adsorption process (a hydrophobic-hydrophobic interaction) there was conversion to the fluorescent quinoid form of FITC. In contrast, at pH 7.4 and 9.6 on hydrophobic surfaces, FITC monolayers had well-defined, fast photobleaching kinetics (decay to approximately 50% intensity in 5-10 s). The equivalent BSA-FITC monolayers were slightly brighter, with similar photobleaching kinetics. While the precise mechanism for this unusual behavior is still unknown, all these low-cost monolayers were easily prepared, were reproducible, and can serve as convenient test samples for TIRFM alignment, calibration, and validation prior to undertaking measurements with more sensitive biogenic or biological specimens. | Fluorescein-5-isothiocyanate |
Growth of the human MCF-7 breast cancer cell line is highly dependent on L-arginine. We have reported that L-arginine, released from extracellular substrates by prolactin (PRL)- and 17beta-estradiol (E2)-induced carboxypeptidase-D in the cell membrane, promotes nitric oxide (NO) production for MCF-7 cell survival. Arginine uptake is mediated by members of the cationic amino acid transporter (CAT) family and may coincide with induction of nitric oxide synthase (NOS) for the production of NO. The present study investigated the CAT isoforms and PRL/E2 regulation of CAT and NOS in breast cancer cell lines. Using RT-PCR analysis, CAT-1, CAT-2A, and CAT-2B transcripts were detected in MCF-7, T47D, and MDA-MB-231 cells. The CAT-4 transcript was detected in MDA-MB-231 only. CAT-3 was not detected in any of these cells. PRL and E2 did not significantly alter levels of CAT-1 mRNA and protein, nor CAT-2A and CAT-2B mRNAs in MCF-7 and T47D cells. PRL and E2 also had no effect on the overall uptake of L-[2,3,4,5-H(3)] arginine into these cells. However, confocal immunofluorescent microscopy showed that PRL and E2 upregulated eNOS and iNOS proteins, which distributed in the cytoplasm and/or nucleus of MCF-7 cells. Knockdown of CAT-1 gene expression using small interfering RNA significantly decreased L-[2,3,4,5-H(3)]-arginine uptake, decreased viability and increased apoptosis of MCF-7 and T47D cells. In summary, several CAT isoforms are expressed in breast cancer cells. The CAT-1 isoform plays a role in arginine uptake and, together with PRL/E2-induced NOS, contribute to NO production for the survival of MCF-7 and T47D cells." | Cationic Amino Acid Transporter 1 |
Large-scale composting of source-separated household waste has expanded in recent years in the Nordic countries. One problem can be low pH at the start of the process. Incoming biowaste at four composting plants was characterised chemically, physically and microbiologically. The pH of food waste ranged from 4.7 to 6.1 and organic acid concentration from 24 to 81 mmol kg(-1). The bacterial diversity in the waste samples was high, with all samples dominated by Gammaproteobacteria, particularly Pseudomonas and Enterobacteria (Escherichia coli, Klebsiella, Enterobacter). Lactic acid bacteria were also numerically important and are known to negatively affect the composting process because the lactic acid they produce lowers the pH, inhibiting other bacteria. The bacterial groups needed for efficient composting, i.e. Bacillales and Actinobacteria, were present in appreciable amounts. The results indicated that start-up problems in the composting process can be prevented by recycling bulk material and compost. | Environmental Microbiology |
OBJECTIVE: The aim of this study was to evaluate the feasibility, morbidity and survival outcome of laparoscopy-assisted vaginal pelvic exenteration. METHODS: Since 2000, we have performed 5 cases of en-bloc pelvic exenteration combining a vaginal or perineal approach and laparoscopic approach. All patients had received previous pelvic irradiation. One patient underwent a total type II exenteration with ileal-loop diversion, an omental flap and a temporary colostomy. Two patients underwent a middle and posterior exenteration: one was a type III exenteration with perineal rectal resection and a gracilis myocutaneous flap; the second one was a type II exenteration with a colorectal anastomosis and a vaginal reconstruction using a gluteal thigh flap. Two patients underwent a type I anterior and middle exenteration with continent Miami pouch and vaginal reconstruction by omental cylinder. RESULTS: Mean time of the procedure was 6 h (range: 4.5-9). Peroperative bleeding was less than 500 cm3. Two patients presented minor complications: a perineal abscess after perineal rectal resection and an abdominal wound abscess. Mean length of hospital stay was 27 days. Three patients are free of disease. Two patients presented groin metastasis. One patient died of disease after 8 months. CONCLUSION: Laparoscopic or laparoscopy-assisted vaginal pelvic exenteration followed by reconstruction is feasible with curative intent in selected patients. | Pelvic Exenteration |
Due to the growing field of digital pathology, more and more digital histology slides are becoming available. This improves the accessibility, allows teleconsultations from specialized pathologists, improves education, and might give urologist the possibility to review the slides in patient management systems. Moreover, by stacking multiple two-dimensional (2D) digital slides, three-dimensional volumes can be created, allowing improved insight in the growth pattern of a tumor. With the addition of computer-aided diagnosis systems, pathologist can be guided to regions of interest, potentially reducing the workload and interobserver variation. Digital (3D) pathology has the potential to improve dialog between the pathologist and urologist, and, therefore, results in a better treatment selection for urologic patients. | Diagnosis, Computer-Assisted |
In August 2018, a fatal autochthonous case of Crimean-Congo hemorrhagic fever was confirmed in western Spain. The complete sequence of the viral genome revealed circulation of a new virus because the genotype differs from that of the virus responsible for another case in 2016. Practitioners should be alert to possible new cases." | Hemorrhagic Fever Virus, Crimean-Congo |
The hypothesis that there might occur selective defeminization by social class between childhood and adulthood among homosexual men was explored. Interview data on 686 homosexual men were employed. It was found that there is a greater tendency for cross-gender propensities to persist into adulthood among respondents from blue-collar backgrounds. Effeminate respondents from such backgrounds were found to be disproportionately involved in same-sex sexual activities during adolescence. They were also sexually responsive to same-sex persons earlier. The interpretation is offered that early homosexual experiences reinforce cross-gender propensities among blue-collar respondents because of the greater gender role dichotomization found in blue-collar culture. Such reinforcement may explain the tendency for there to be greater persistence of cross-gendering among blue-collar men. | Psychosexual Development |
Occludin, tricellulin, and marvelD3 belong to the tight junction (TJ)-associated MARVEL protein family. Occludin and tricellulin jointly contribute to TJ strand branching point formation and epithelial barrier maintenance. However, whether marvelD3 has the same function remains unclear. Furthermore, the roles of the carboxy-terminal cytoplasmic tail, which is conserved in occludin and tricellulin, on the regulation of TJ strand morphology have not yet been explored in epithelial cells. We established tricellulin/occludin/marveld3 triple-gene knockout (tKO) MDCK II cells and evaluated the roles of marvelD3 in the TJ strand structure and barrier function using MDCK II cells and a mathematical model. The complexity of TJ strand networks and paracellular barrier did not change in tKO cells compared to that in tricellulin/occludin double-gene knockout (dKO) cells. Exogenous marvelD3 expression in dKO cells did not increase the complexity of TJ strand networks and epithelial barrier tightness. The expression of the carboxy-terminal truncation mutant of tricellulin restored the barrier function in the dKO cells, whereas occludin lacking the carboxy-terminal cytoplasmic tail was not expressed on the plasma membrane. These data suggest that marvelD3 does not affect the morphology of TJ strands and barrier function in MDCK II cells and that the carboxy-terminal cytoplasmic tail of tricellulin is dispensable for barrier improvement." | MARVEL Domain Containing 2 Protein |
Scutellarin, a flavone glycoside, popularly applied for the treatment of cardiopathy, has been purified in two-step purification by high-speed counter-current chromatography (HSCCC) from Erigeron breviscapus (vant.) Hand. Mazz. (Deng-zhan-hua in Chinese), a well-known traditional Chinese medicinal plant for heart disease. Two solvent systems, n-hexane-ethyl acetate-methanol-acetic acid-water (1:6:1.5:1:4, v/v/v/v/v) and ethyl acetate-n-butanol-acetonitrile-0.1% HCl (5:2:5:10, v/v/v/v) were used for the two-step purification. The purity of the collected fraction of scutellarin was 95.6%. This study supplies a new alternative method for purification of scutellarin. | Glucuronates |
The withdrawal reflex system has been extensively used as a model system for studies of pain related mechanisms, sensorimotor integration, learning and memory. For a long time, this system was assumed to be organised as a flexion reflex system. However, recent studies indicate that this system has a modular organisation, each module performing a detailed and functionally adapted sensorimotor transformation related to the withdrawal efficacy of its output muscle(s). Each module appears to be a self-organising circuitry that uses sensory feedback on single muscle contractions to adjust its synaptic organisation during development. These findings and their implications for the understanding of higher motor functions as well as clinical aspects will be discussed. | Imprinting, Psychological |
Studies of breast self-examination (BSE) in older women have revealed deficiencies in both frequency and proficiency of practice. Current data from an ongoing study indicate that practice is sufficiently poor as to make the detection of lumps difficult. Interventions to increase frequency and proficiency, however, have been encouraging. Several studies are reporting significant improvement in practice following specific strategies. Barriers such as forgetting and embarrassment need to be addressed when attempting to increase frequency and proficiency. The efficiency of BSE cannot be adequately addressed until women are trained at a proficient level. | Self-Examination |
A comparative study was performed with the venoms of newborn Crotalus durissus durissus, adult Crotalus durissus terrificus and adult Crotalus durissus durissus snakes. Venom of newborn specimens of C.d. durissus is very similar to that of adult specimens of C.d. terrificus, since they have strong lethal and myotoxic activities, and weak proteolytic, hemorrhagic and edema-forming effects, in contrast to venom of adult specimens of C.d. durissus. In addition, the two former venoms have high amounts of the neurotoxic complex crotoxin, whereas venom from adult C.d. durissus has a low concentration of crotoxin. Electrophoretic analysis corroborates the strong similarities between the former two venoms. It is concluded that venom of newborn C.d. durissus contains high concentrations of crotoxin and low amounts of hemorrhagic and proteolytic components, and that a drastic ontogenetic change takes place in the venom composition of this subspecies. | Crotoxin |
You are leading a negotiating team for your company. When you sit down with the other party, someone on your side of the table blurts out: "Just tell us--what do we need to do to get more of your business?" And in that moment, you know you've lost the upper hand. Gaffes like this are more common than most businesspeople would care to admit, management professors Brett, Friedman, and Behfar have found in their research. Even though team members are all technically on the same side, they often have different priorities and imagine different ideal outcomes: Business development just wants to close the deal. Finance is most concerned about costs. Legal is focused on patents and intellectual property. The authors recommend taking four steps, either singly or in tandem, to align those goals: Map out each person's priorities, work out conflicts directly with departments, employ a mediator if that doesn't work, and use data to resolve differences. Once you are all on the same page, you can take steps to make sure everyone is coordinated during the negotiations themselves. Try simulating the negotiation beforehand, assigning roles to team members that take advantage of their strengths, and establishing the signals you will use to communicate with one another during the session. The payoff from working as a cohesive group is clear. With access to greater expertise and the ability to assign members to specialized roles, teams can implement more-complex strategies than a sole negotiator could ever pull off." | Institutional Management Teams |
This research article describes an approach to modify the thiazolidinedione scaffold to produce test drugs capable of binding to, and inhibit, the in vitro transcriptional activity of the oncogenic protein FOXM1. This approach allowed us to obtain FOXM1 inhibitors that bind directly to the FOXM1-DNA binding domain without targeting the expression levels of Sp1, an upstream transcription factor protein known to activate the expression of FOXM1. Briefly, we modified the chemical structure of the thiazolidinedione scaffold present in anti-diabetic medications such as pioglitazone, rosiglitazone and the former anti-diabetic drug troglitazone, because these drugs have been reported to exert inhibition of FOXM1 but hit other targets as well. After the chemical synthesis of 11 derivatives possessing a modified thiazolidinedione moiety, we screened all test compounds using in vitro protocols to measure their ability to (a) dissociate a FOXM1-DNA complex (EMSA assay); (b) decrease the expression of FOXM1 in triple negative-breast cancer cells (WB assay); (c) downregulate the expression of FOXM1 downstream targets (luciferase reporter assays and qPCR); and inhibit the formation of colonies of MDA-MB-231 cancer cells (colony formation assay). We also identified a potential binding mode associated with these compounds in which compound TFI-10, one of the most active molecules, exerts binding interactions with Arg289, Trp308, and His287. Unlike the parent drug, troglitazone, compound TFI-10 does not target the in vitro expression of Sp1, suggesting that it is possible to design FOXM1 inhibitors with a better selectivity profile. | Troglitazone |
The regulated proliferation and differentiation of neural stem cells before the generation and migration of neurons in the cerebral cortex are central aspects of mammalian development. Periventricular neuronal heterotopia, a specific form of mislocalization of cortical neurons, can arise from neuronal progenitors that fail to negotiate aspects of these developmental processes. Here we show that mutations in genes encoding the receptor-ligand cadherin pair DCHS1 and FAT4 lead to a recessive syndrome in humans that includes periventricular neuronal heterotopia. Reducing the expression of Dchs1 or Fat4 within mouse embryonic neuroepithelium increased progenitor cell numbers and reduced their differentiation into neurons, resulting in the heterotopic accumulation of cells below the neuronal layers in the neocortex, reminiscent of the human phenotype. These effects were countered by concurrent knockdown of Yap, a transcriptional effector of the Hippo signaling pathway. These findings implicate Dchs1 and Fat4 upstream of Yap as key regulators of mammalian neurogenesis." | Periventricular Nodular Heterotopia |
The number of patients with the diagnosis of lumbar spinal stenosis (LSS) is steadily increasing and simultaneously, the patients' expectations are also increasing. Nevertheless, evidence from studies for the appropriate treatment is still lacking. Treatment options mainly result from the practitioner 's experience and the clinical focus. The findings described in magnetic resonance imaging (MRI) often do not correlate with the patient's symptoms. Basically, the treatment should be started with a conservative treatment and preferably with a multimodal approach. Severe pain with extensive neurogenic claudication symptoms and unsuccessful conservative treatment should be treated surgically. Absolute indications for surgery, such as a conus-cauda syndrome are rare. The goal of all surgical procedures is to decompress the spinal canal without compromising the stability of the motion segment. Instability can also make an additional fusion necessary. | Spinal Stenosis |
Normal weight obesity (NWO) is a new emerging phenotype of obesity, defined as a normal body mass index with a high body fat percentage. While several studies have described the impact of NWO on cardiometabolic risk factors, the association between them remains uncertain. This meta-analysis systematically evaluated cardiometabolic risk factors in adults with NWO compared to adults with normal weight lean (NWL). A systematic literature search was performed from the inception until September 21, 2021 in order to comprehensively search for all observational studies that had three important variables, including adults (age >/=18 years old), NWO and cardiometabolic risk factors including metabolic syndrome, hypertension, diabetes mellitus, dyslipidaemia or all laboratory findings related to cardiometabolic risk factors. Twenty-four cross-sectional studies with a total of 75 201 subjects are included in the qualitative and quantitative analysis. Overall, older age and female sex are more likely in NWO population. Compared to NWL, NWO is significantly associated with cardiometabolic risk factors, including metabolic syndrome (OR = 2.24 [1.74, 2.89]; p < .001; I(2) = 76%, P(heterogeneity) < 0.001), hypertension (OR = 1.60[1.36, 1.89]; p < .001; I(2) = 76%, P(heterogeneity) < 0.001), diabetes mellitus (OR = 1.72[1.54, 1.92]; p < .001; I(2) = 47%, P(heterogeneity) < 0.001), dyslipidaemia (OR = 1.50 [1.03, 2.18]; p = .03; I(2) = 94%, P(heterogeneity) < 0.001) and other laboratory findings, except for C-reactive protein in both sexes group; and adiponectin levels in female group. Our meta-analysis showed that NWO was associated with cardiometabolic risk factors. Thus, the traditional definition of obesity using the BMI criteria should be challenged, as those with NWO might still be exposed to a heightened risk of cardiometabolic disorders. Nonetheless, further prospective cohort studies are needed better to understand this syndrome. | Cardiometabolic Risk Factors |
Iron-sulfur proteins are ubiquitous catalysts of a wide range of biological reactions, and are particularly abundant in clostridia which lack the ability to synthesize hemes. The development of research on these metalloproteins has therefore been strongly associated with biochemical investigations of clostridial metabolism. Major breakthroughs in the field, from the first isolation of an iron-sulfur protein in 1962, to the recent determination of an Fe-hydrogenase structure, have been made with clostridia. These data, as well as others obtained through studies on clostridia, are transferable to many other bioenergetic machineries, due to the strong phylogenetic conservation of some important components. For instance, clear homologies exist between constituents of the anaerobic electron transfer chains in clostridia and aerobic respiratory chains. The contribution of iron-sulfur proteins to the biotechnological and medical significance of clostridia is also discussed. Structural and functional genomics are expected to bring forth a wealth of novel data on clostridia and iron-sulfur proteins. | Rubredoxins |
OBJECTIVES: The P300 component of the auditory event-related potential (ERP) is a large amplitude positive wave peaking at approximately 300 ms following detection of a rare significant stimulus. Although P300 is typically only evoked when the subject attends to the stimulus, it may also be elicited in an awake, inattentive subject if the stimulus is sufficiently intrusive. We therefore employed an oddball task to determine if high intensity stimuli would elicit the P300 during sleep. METHODS: A loud 90 dB SPL tone pip was presented infrequently (P = 0.05) in a train of lower intensity 70 dB SPL standard stimuli. A multiple channel EEG was recorded from 8 good sleepers during a single night. RESULTS: A large amplitude parieto-central P300, peaking at 321 ms, was apparent in REM sleep to the loud deviant stimulus. In stage two non-REM sleep, a later positive wave, peaking at 446 ms, was apparent even after K-Complexes were removed from the average. This non-REM P450 was however maximum over occipito-parietal areas of the scalp. CONCLUSION: The presence of a P300 in REM sleep following a loud, rare stimulus indicates that sensory discrimination capabilities remain intact during this state. This may be associated with either pre- or conscious processing of relevant stimuli. | Sleep Stages |
A case of unicystic ameloblastoma of the mandible is presented. Enucleation would appear to be the treatment of choice. Difficulty may be encountered in establishing a histological diagnosis. Long term follow up is desirable. | Mandibular Neoplasms |
PURPOSE: Beta-ray imaging systems are widely used for various biological objects to obtain a two-dimensional (2D) distribution of beta-ray emitting radioisotopes. However, a conventional beta-ray imaging system is unsuitable for multiple-tracer imaging, because the continuous energy distribution of beta-rays complicates distinguishing among different tracers by energy information. Therefore, we developed a new type of beta-ray imaging system, which is useful for multiple tracers by detecting coincidence gamma-rays with beta-rays, and evaluated its imaging performance. METHODS: Our system is composed of position-sensitive beta-ray and gamma-ray detectors. The former is a 35 x 35 x 1-mm(3) Ce-Doped((La, Gd)(2) Si(2) O(7) ) (La-GPS) scintillation detector, which has a 300-microm pitch of pixels. The latter is a 43 x 43 x 16-mm(3) bismuth germanium oxide (BGO) scintillation detector. Both detectors are mounted on a flexible frame and placed in a user-selectable position. We experimentally evaluated the performance of the beta-ray detector and the gamma-ray efficiencies of the gamma-ray detector with different energies, positions, and distances. We also conducted point sources and phantom measurements with dual isotopes to evaluate the system performance of multiple-tracer imaging. RESULTS: For the beta-ray detector, the beta-ray detection efficiencies for (45) Ca (245-keV maximum energy) and (90) Sr/(90) Y (545 and 2280-keV maximum energy) were 14.3% and 21.9%, respectively. The total gamma-ray detection efficiency of the gamma-ray detector for all gamma-rays from (22) Na (511-keV annihilation gamma-rays and a 1275-keV gamma-ray) in the center position with a detector distance of 20 mm was 17.5%. From a point-source measurement using (22) Na and (90) Sr/(90) Y, we successfully extracted the position of a positron-gamma emitter (22) Na. Furthermore, for a phantom experiment using (45) Ca and (18) F or (18) F and (22) Na, we successfully extracted the distribution of the second tracer using the annihilation gamma-ray or de-excitation gamma-ray coincidence. In all the imaging experiments, the event counts of the extracted images were consistent with the counts estimated by the measured gamma-ray efficiencies. CONCLUSIONS: We successfully demonstrated the feasibility of our beta-ray autoradiography system for imaging multiple isotopes. Since our system can identify not only a beta-gamma emitter but also a positron emitter using the coincidence detection of annihilation gamma-rays, it is useful for PET tracers and various new applications that are otherwise impractical. | Calcium Radioisotopes |
Executor (E) genes comprise a new type of plant resistance (R) genes, identified from host-Xanthomonas interactions. The Xanthomonas-secreted transcription activation-like effectors (TALEs) usually function as major virulence factors, which activate the expression of the so-called susceptibility" (S) genes for disease development. This activation is achieved via the binding of the TALEs to the effector-binding element (EBE) in the S gene promoter. However, host plants have evolved EBEs in the promoters of some otherwise silent R genes, whose expression directly causes a host cell death that is characterized by a hypersensitive response (HR). Such R genes are called E genes because they trap the pathogen TALEs in order to activate expression, and the resulting HR prevents pathogen growth and disease development. Currently, deploying E gene resistance is becoming a major component in disease resistance breeding, especially for rice bacterial blight resistance. Currently, the biochemical mechanisms, or the working pathways of the E proteins, are still fuzzy. There is no significant nucleotide sequence homology among E genes, although E proteins share some structural motifs that are probably associated with the signal transduction in the effector-triggered immunity. Here, we summarize the current knowledge regarding TALE-type avirulence proteins, E gene activation, the E protein structural traits, and the classification of E genes, in order to sharpen our understanding of the plant E genes." | Xanthomonas |
Removal of the pineal gland produces stereotyped tonic convulsions in parathyroidectomized rats. Inasmuch as central levels of norepinephrine (NE) are decreased in these animals, the purpose of this study was to investigate the effects of alterations in central catecholamine function on convulsions produced by pinealectomy in parathyroidectomized rats. The treatment of rats with alpha-methyl-p-tyrosine or FLA-63 produced large reductions in forebrain levels of both NE and dopamine or NE alone, respectively, which were not associated with facilitation of convulsions. However, the incidence of convulsions was increased by FLA-63 in rats pretreated with the catecholamine precursor L-dihydroxyphenylalanine. Reserpine, a monoamine depleter, had no effect on either the incidence or severity of convulsions. An acute injection of desipramine, an inhibitor of the reuptake of NE, however, significantly lowered the incidence of convulsions. Timolol, a beta-adrenergic receptor antagonist, reduced, in a dose-dependent manner, the average latency to onset of convulsions and increased the average number of convulsions each rat experienced. Clonidine, an alpha 2-adrenergic agonist, did not significantly alter convulsions. Thus presynaptic mechanisms such as synthesis and storage of both NE and DA appear to have little, if any, effect on pinealectomy-induced convulsions, whereas enhancing synaptic levels of NE by blocking its reuptake into adrenergic axons had an anticonvulsant effect. Further evidence suggesting a role for NE in modulating these convulsions is provided by the proconvulsant effect of blocking central beta-adrenergic receptors." | Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide |
This article presents a formula for modeling the lifetime incidence of cancer in humans. The formula utilizes a Poisson distribution-based np" model to predict cancer incidence, with "n" representing the effective number of cell turnover and "p" representing the probability of single-cell transformation. The model accurately predicts the observed incidence of cancer in humans when a reduction in cell turnover due to aging is taken into account. The model also suggests that cancer development is ultimately inevitable. The article proposes a theory of aging based on this concept, called the "np" theory. According to this theory, an organism maintains its order by balancing cellular entropy through continuous proliferation. However, cellular "information entropy" in the form of accumulated DNA mutations increases irreversibly over time, restricting the total number of cells an organism can generate throughout its lifetime. When cell division slows down and fails to compensate for the increased entropy in the system, aging occurs. Essentially, aging is the phenomenon of running out of predetermined cell resources. Different species have evolved separate strategies to utilize their limited cell resources throughout their life cycle." | Poisson Distribution |
In MALDI TOF MS analysis, complicated mass spectra can usually be recorded for polymers with high affinities to protons and alkali metal ions. For these polymers, protonated ions and sodium and potassium adducts can often be formed concomitantly. By distributing these ions into three separate spectra of protonated ions, sodium adducts, and potassium adducts, significantly simplified spectra can be acquired. Mass spectra consisting of only sodium or potassium adducts can often be obtained by simply adding sodium salt and potassium salt, respectively. We report here a method to selectively generate protonated ions. A polyethylene glycol (PEG) sample with amino end groups was selected as the model polymer and alpha-cyano-4-hydroxycinnamic acid (CHCA) as the matrix. Octadecylamine (ODA) or a mixture of a tetrabutylammonium (TBA) salt and an ammonium salt was used as the co-matrix to inhibit the release of sodium and potassium ions and their related adducts into the MALDI gas phase plume. By depositing the polymer sample on top of a preloaded layer of CHCA with a co-matrix, the generation of Na(+) and K(+) adducts is suppressed, while [ODA + H](+) and NH(4)(+) released from the preloaded matrix layer can serve as protonation reagents to protonate the polymer molecules via proton transfer reactions. It is clearly demonstrated that disentangling a complex mass spectrum filled densely with various series of ions into three separate spectra, with each one consisting of only one type of ions, allows unambiguous identification of mass peaks and greatly helps the interpretation of MS results. | Metals, Alkali |
PURPOSE: To assess the biomechanical deterioration arising from keratoconus progression in-vivo. METHODS: The preoperative examinations of 32 progressive KC cases that were submitted to corneal cross-linking were evaluated. The examinations included the corneal tomography using the Pentacam HR and biomechanical parameters assessed by the Corvis ST (Oculus, Wetzlar, Germany). The results were recorded at two time points, the latter of which was at the last visit before the CXL procedure. Keratoconus progression was characterised by a significant change in the ABCD system. RESULTS: At the last follow-up visit (41.4 +/- 40.9 months) all morphological parameters of the ABCD grading system showed significant deterioration (p < 0.001). The comparative analyses revealed a significant reduction in corneal stiffness expressed by a significant reduction in the stress-strain index (SSI: -0.10 +/- 0.06, p < 0.001), the Stiffness parameter A1 (SP-A1: -6.1 +/- 12.0 mmHg/mm, p = 0.011), by a significant increase in the integrated Inverse Radius (IIR: 0.95 +/- 1.04 mm-1, p < 0.001) and in the deflection amplitude (DA) ratio (0.23 +/- 0.58, p = 0.034). A barely significant increase in the DA also pointed towards corneal stiffness reduction. (0.04 +/- 0.13 mm, p = 0.056). The SSI and the IIR were the indices with the smallest overlaps between the two examinations. CONCLUSIONS: It has been demonstrated in-vivo that corneal biomechanical deterioration occurs with keratoconus progression. The larger changes observed in the SSI and the IIR when compared to the remaining biomechanical parameters suggests that these parameters could be suitable to assess the corneal stiffness reduction in keratoconus natural progression. | Corneal Topography |
BACKGROUND: Successful anastomotic healing is critical to preventing complications after intestinal surgery. We aimed to compare the early healing of end-to-end small bowel anastomosis by self-forming magnets with surgical stapling in a porcine model. METHOD: Six Yorkshire pigs underwent 2 simultaneous small bowel anastomoses using a circular stapler and self-forming magnet technique. The primary outcome was healing quality, measured by 4 histologic features: inflammatory cell infiltration, collagen formation, grade of inflammation, and bacterial infiltration at the anastomosis. The samples were evaluated at days 1, 3, and 7. Gross evaluation of anastomotic integrity was a secondary outcome. RESULTS: The self-forming magnet group displayed significant differences at each time point. On day 1, the stapled group displayed dense inflammatory cell infiltration and extensively ulcerated intestinal layers with significant edema. The self-forming magnet group showed less inflammatory infiltrate, and all intestinal layers remained compressed in direct apposition. By day 3, the self-forming magnet group already exhibited neovascularization with scant bacterial colonies. By contrast, stapled anastomoses had large areas of inflammation separating collagen fibers with prevalent bacterial infiltrations. On day 7, self-forming magnet anastomoses were characterized by robust neovascularization, maturing granulation tissue, and mucosal re-epithelization without significant inflammation. Meanwhile, stapled samples had persisting dense inflammation, tissue cavities with hemorrhage, and immature fibrous tissue. Grossly, the self-forming magnet created a patent lumen without defect, whereas stapled anastomoses demonstrated focal areas of serosal separation. CONCLUSION: Bowel anastomosis by self-forming magnets is associated with superior early histologic healing metrics, including early seal generation through mechanical compression, decreased inflammation, early neovascularization, lower bacterial infiltration, and faster re-epithelization. | Surgical Stapling |
The presence of anti-Tax antibody responses in human T cell leukemia virus type I (HTLV-I)-infected individuals has been correlated with increased proviral load, increased risk of transmitting infection, and increased risk of developing tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In this study, a rabbit model of HTLV-I infection was used to determine whether anti-Tax antibody responses could predict the presence of virus with the potential to replicate. Seven of 14 HTLV-I-infected rabbits developed anti-Tax antibody responses. The onset of Tax reactivity was variable, but once detected remained constant throughout the remainder of the 60-week course of the study. All anti-Tax antibody positive rabbits produced virus as measured by p19 expression upon coculture, while p19 was detected in only one of the Tax antibody negative animals. Thus the presence of an anti-Tax antibody response correlates with p19 expression following cocultivation, and may be a useful predictor of virus replication in HTLV-I infected individuals. | HTLV-I Antigens |
Pharmaceutical facilities on board French Navy Vessels must be adapted to the constraints of medical quarters when they exist, or to the lack of such quarters when there are not any. They must meet the demands of the vessel's mission take into account, the number of people on board and the means of members of the Navy Medical Corps. In our ever changing world, the recent increase of female crew members has made it necessary to alter the list of medicines usually taken on board. Because of the advent of nuclear power, it has become necessary to take on board new kinds of medicines against radio-active elements and their pathological effects. | Naval Medicine |
Merging polymer-supported asymmetric organocatalysis with continuous flow in a packed bed reactor has been used as the key, enantiodetermining step in a short synthesis of indoloquinolizidines. Using this approach, a highly enantioselective, solvent-free and rapid conjugate addition of dimethyl malonate to a diverse family of cinnamaldehydes in continuous flow, allowing the preparation of relevant oxodiesters in multigram amounts has been developed. The obtained Michael adducts have been used to complete an expedient diastereoselective synthesis of indoloquinolizidine via cascade Pictet-Splengler cyclisation-lactamisation in continuous flow. The conversion of enantiopure Michael adducts into delta-lactones via telescoped reduction/cyclisation in continuous flow has also been explored. | Stereoisomerism |
The article presents data on Saint Petersburg memorial and sign places related to distinguished dentists and maxillofacial surgeons of Russia." | Oral and Maxillofacial Surgeons |
P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases. P-gp is a major cause of drug resistance in cancer, parasitic diseases, epilepsy and other disorders. This review article aims to summarize the research findings on the marine natural products with P-glycoprotein inhibitor properties. Natural compounds that modulate P-gp offer great possibilities for semi-synthetic modification to create new drugs and are valuable research tools to understand the function of complex ABC transporters." | ATP Binding Cassette Transporter, Subfamily B, Member 1 |
Genes for five somatostatin receptor subtypes, designated sst1-5, have been cloned and shown to belong to the seven transmembrane domain receptor family. The sst2 mRNA transcript is alternatively spliced to generate two related receptor products (sst2A and sst2B) which differ in their carboxylterminal sequence whereas each of the other genes is transcribed to give a single unique receptor protein. The six sst receptor subtypes all bind SRIF14, SRIF28 and the cortistatins with high affinity but vary in their affinity for analogs, such as octreotide. Although the tissue distribution of sst mRNAs has been extensively examined, much less is known about the cellular distribution of the individual receptor proteins. Recent studies with sst subtype specific antibodies have localized individual sst receptors to specific cell types within the rat gastrointestinal tract, pancreas, pituitary and brain. Furthermore, sst receptors have recently been identified in human tumors by immunocytochemistry, providing a significantly improved method for sst receptor detection. All six sst receptor subtypes are linked to guanine nucleotide binding proteins (G proteins) and lead to inhibition of adenylyl cyclase following hormone binding. The sst receptors also regulate a variety of different effectors via G proteins, including calcium and potassium channels and serine and tyrosine phosphatases. In addition to signalling, two other processes are activated by hormone binding: receptor desensitization and receptor internalization. The extent to which these occur seems to vary for the different receptor subtypes. Recent studies have shown that the sst2A receptor is rapidly phosphorylated upon hormone binding, suggesting that this phosphorylation may be responsible for the desensitization and/or internalization of this receptor. The importance of receptor regulation in cellular responsiveness to somatostatin and for receptor detection as well as the molecular mechanisms by which these processes occur provide important areas for future investigations. | Receptors, Neuropeptide |
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately needed. In our present study, three datasets including GSE33630, GSE29265, and GSE65144 were retrieved from Gene Expression Omnibus with a total of 32 ATC samples and 78 normal thyroid tissues. A total of 1804 consistently changed differentially expressed genes (DEGs) were identified from three datasets. KEGG pathways enrichment suggested that upregulated DEGs were mainly enriched in ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, focal adhesion, and p53 signaling pathway. Furthermore, key gene modules in PPI network were identified by Cytoscape plugin MCODE and they were mainly associated with DNA replication, cell cycle process, collagen fibril organization, and regulation of leukocyte migration. Additionally, TOP2A, CDK1, CCNB1, VEGFA, BIRC5, MAPK1, CCNA2, MAD2L1, CDC20, and BUB1 were identified as hub genes of the PPI network. Interestingly, module analysis showed that 8 out of 10 hub genes participated in Module 1 network and more than 70% genes of Module 2 consisted of collagen family members. Notably, transcription factors (TFs) regulatory network analysis indicated that E2F7, FOXM1, and NFYB were master regulators of Module 1, while CREB3L1 was the master regulator of Module 2. Experimental validation showed that CREB3L1, E2F7, and FOXM1 were significantly upregulated in ATC tissue and cell line when compared with normal thyroid group. In conclusion, the TFs regulatory network provided a more detail molecular mechanism underlying ATC occurrence and progression. TFs including E2F7, FOXM1, CREB3L1, and NFYB were likely to be master regulators of ATC progression, suggesting their potential role as molecular therapeutic targets in ATC treatment. | E2F7 Transcription Factor |
A new and general methodology is described for the targeted enrichment and subsequent direct mass spectrometric characterization of sample subsets bearing various chemical functionalities from highly complex mixtures of biological origin. Specifically, sample components containing a chemical moiety of interest are first selectively labeled with perfluoroalkyl groups, and the entire sample is then applied to a perfluoroalkyl-silylated porous silicon (pSi) surface. Due to the unique hydrophobic and lipophobic nature of the perfluorinated tags, unlabeled sample components are readily removed using simple surface washes, and the enriched sample fraction can then directly be analyzed by desorption/ionization on silicon mass spectrometry (DIOS-MS). Importantly, this fluorous-based enrichment methodology provides a single platform that is equally applicable to both peptide as well as small molecule focused applications. The utility of this technique is demonstrated by the enrichment and mass spectrometric analysis of both various peptide subsets from protein digests as well as amino acids from serum. | Affinity Labels |
BACKGROUND: Protein pulldown using Methyl-CpG binding domain (MBD) proteins followed by high-throughput sequencing is a common method to determine DNA methylation. Algorithms have been developed to estimate absolute methylation level from read coverage generated by affinity enrichment-based techniques, but the most accurate one for MBD-seq data requires additional data from an SssI-treated Control experiment. RESULTS: Using our previous characterizations of Methyl-CpG/MBD2 binding in the context of an MBD pulldown experiment, we build a model of expected MBD pulldown reads as drawn from SssI-treated DNA. We use the program BayMeth to evaluate the effectiveness of this model by substituting calculated SssI Control data for the observed SssI Control data. By comparing methylation predictions against those from an RRBS data set, we find that BayMeth run with our modeled SssI Control data performs better than BayMeth run with observed SssI Control data, on both 100 bp and 10 bp windows. Adapting the model to an external data set solely by changing the average fragment length, our calculated data still informs the BayMeth program to a similar level as observed data in predicting methylation state on a pulldown data set with matching WGBS estimates. CONCLUSION: In both internal and external MBD pulldown data sets tested in this study, BayMeth used with our modeled pulldown coverage performs better than BayMeth run without the inclusion of any estimate of SssI Control pulldown, and is comparable to - and in some cases better than - using observed SssI Control data with the BayMeth program. Thus, our MBD pulldown alignment model can improve methylation predictions without the need to perform additional control experiments. | Methyl CpG Binding Domain |
Transcatheter electrosurgery refers to a family of procedures using radiofrequency energy to vaporize and traverse or lacerate tissue despite flowing blood. The authors review theory, simulations, and benchtop demonstrations of how guidewires, insulation, adjunctive catheters, and dielectric medium interact. For tissue traversal, all but the tip of traversing guidewires is insulated to concentrate current. For leaflet laceration, the Flying V" configuration concentrates current at the inner lacerating surface of a kinked guidewire. Flooding the field with non-ionic dextrose eliminates alternative current paths. Clinical applications include traversing occlusions (pulmonary atresia, arterial and venous occlusion, and iatrogenic graft occlusion), traversing tissue planes (atrial and ventricular septal puncture, radiofrequency valve repair, transcaval access, Potts and Glenn shunts), and leaflet laceration (BASILICA, LAMPOON, ELASTA-Clip, and others). Tips are provided for optimizing these techniques. Transcatheter electrosurgery already enables a range of novel therapeutic procedures for structural heart disease, and represents a promising advance toward transcatheter surgery." | Prosthesis Design |
Molecular chaperones are essential for guarding proteins that are indispensable for normal cellular functions. Heat shock protein 90 (Hsp90) is a vital molecular chaperone in eukaryotes that participates in stabilizing and activating approximately 200 target proteins, called clients," many of which are involved in signal transduction pathways. Cancer cells however utilize Hsp90 to chaperone an array of mutated and overexpressed oncoproteins to protect them from misfolding and degradation. Therefore, Hsp90 is an attractive target in cancer therapy. Hsp90 chaperone function relies on ATP binding and hydrolysis, which in turn guides its carefully orchestrated conformational changes. This chaperone cycle is fine-tuned by another group of proteins called co-chaperones. They are able to accelerate or decelerate the cycle, allowing Hsp90 to chaperone different clients. Posttranslational modifications (PTMs) can also regulate the chaperone cycle at an epigenetic level thereby tailoring Hsp90 function to suit a specific cell type or environmental condition. Recent evidence suggests that inhibition of the enzymes that catalyze the PTM of Hsp90 can act synergistically with Hsp90 inhibitors, providing a novel therapeutic strategy to enhance the efficacy of Hsp90 inhibitors in cancer cells." | HSP90 Heat-Shock Proteins |
BACKGROUND: We previously demonstrated the convergent validity of a fully automated voice recognition analogue of the Symbol Digit Modalities Test (VR-SDMT) for evaluating processing speed in people with multiple sclerosis (pwMS). OBJECTIVE/METHODS: We aimed to replicate these results in 54 pwMS and 18 healthy controls (HCs), demonstrating the VR-SDMT's reliability. RESULTS: Significant correlations were found between the VR-SDMT and the traditional oral SDMT in the multiple sclerosis (MS) (r = -0.771, p < 0.001) and HC (r = -0.785, p < 0.001) groups. CONCLUSION: Taken collectively, our two studies demonstrate the reliability and validity of the VR-SDMT for assessing processing speed in pwMS. | Voice Recognition |
During their lifetime, superorganisms, like unitary organisms, undergo transformations that change the machinery of their collective behaviour. Here, we suggest that these transformations are largely understudied and propose that more systematic research into the ontogeny of collective behaviours is needed if we hope to better understand the link between proximate behavioural mechanisms and the development of collective adaptive functions. In particular, certain social insects engage in self-assemblage, forming dynamic and physically connected architectures with striking similarities to developing multicellular organisms, making them good model systems for ontogenetic studies of collective behaviour. However, exhaustive time series and three-dimensional data are required to thoroughly characterize the different life stages of the collective structures and the transitions between these stages. The well-established fields of embryology and developmental biology offer practical tools and theoretical frameworks that could speed up the acquisition of new knowledge about the formation, development, maturity and dissolution of social insect self-assemblages and, by extension, other superorganismal behaviours. We hope that this review will encourage an expansion of the ontogenetic perspective in the field of collective behaviour and, in particular, in self-assemblage research, which has far-reaching applications in robotics, computer science and regenerative medicine. This article is part of a discussion meeting issue 'Collective behaviour through time'. | Mass Behavior |
Marine bivalves are exposed to different types of bacteria in the surrounding waters, in particular of the Vibrio genus. In the hemocytes of the mussel Mytilus spp. immune responses to different vibrios have been largely characterized. However, little information is available on the hemocyte responses to human pathogenic vibrios commonly detected in coastal waters and bivalve tissues that are involved in seafood-borne diseases. In this work, functional parameters of the hemocytes from the Mediterranean mussel M. galloprovincialis were evaluated in response to in vitro challenge with different vibrios isolated from environmental samples of the Adriatic sea (Italy): V. parahaemolyticus Conero, V. alginolyticus 1513 and V. vulnificus 509. V. parahaemolyticus ATCC 43996 was used for comparison. At the 50:1 bacteria hemocyte ratio, only V. parahaemolyticus strains induced significant lysosomal membrane destabilisation. Stimulation of extracellular lysozyme release, total ROS, O(2)(-) and NO production were observed, although to different extents and with distinct time courses for different vibrios, V. vulnificus 509 in particular. Further comparisons between V. parahaemolyticus Conero and V. vulnificus 509 showed that only the latter induced dysregulation of the phosphorylation state of p38 MAP Kinase and apoptotic processes. The results indicate that mussel hemocytes can mount an efficient immune response towards V. parahaemolyticus and V. alginolyticus strains, whereas V. vulnificus 509 may affect the hemocyte function. This is the first report on immune responses of mussels to local environmental isolates of human pathogenic vibrios. These data reinforce the hypothesis that Mytilus hemocytes show specific responses to different vibrio species and strains. | Mytilus |
Endometrial cancers with peritoneal spread are stage IVB of FIGO classification. Their pattern is similar to that of ovarian cancer. Optimal debulking surgery and chemotherapy are predictor of better overall and disease free survival. Despite the poor outcome, there is a need for new treatment options. Recommended management for this group of patients should consist of surgical cytoreduction followed by chemotherapy. There may be a role for neoadjuvant chemotherapy followed by interval surgery in selected subgroups of patients. | Endometrial Neoplasms |
AIM: To evaluate the risk factors and incidence of Asherman Syndrome in women with post-abortion uterine evacuation and curettage. METHODS: A total of 2546 patients who had surgical abortion (uterine evacuation and curettage) before the 20th gestational week with indications of missed abortion, anembryonic pregnancy, incomplete abortion, and elective curettage in a tertiary antenatal care center were recruited. The patients were called and surveyed for their symptoms; including infertility, oligo-amenorrhea and recurrent pregnancy loss, preterm birth and intrauterine growth retardation and abnormal placentation as criteria of Asherman Syndrome. Diagnostic (office) hysteroscopy was performed for 177 who had one of those complaints. RESULTS: The incidence of Asherman Syndrome was 1.6% (n = 43/2546). History of >/=3 abortions was the main factor that increased the risk of Asherman Syndrome for by 4.6 times. Use of vacuum aspiration or sharp curettage, premedication for cervical priming, and having a pregnancy >10th gestational weeks were not risk factors for Asherman Syndrome. CONCLUSION: When the diagnosis was based on presence of symptoms who underwent uterine instrumentation, the incidence of Asherman Syndrome was found to be 1.6%. Repeated abortions were the main risk factor for Asherman Syndrome and avoiding from repeated uterine instrumentations may have a role in prevention. | Vacuum Curettage |
This study examined implementation of an evidence-based home reading program by caregivers of children with language impairment. Caregivers received materials and supports to read with their children for 15 weeks, four times weekly; in total, 128 caregivers were enrolled. Survival analysis showed that 55% of caregivers completed the program, and the majority of dropouts did so early in the intervention. Mulitnominal logistic regression results showed that dropout was associated with household income, child literacy skills, and receipt of behavior-change techniques by caregivers, especially financial incentives (50 cents per book reading). Results may advance the science of implementation in the area of early childhood disability and could provide suggestions to improve caregivers' effectiveness in implementing interventions to their children. | Literacy |
A key process in the tsetse reproductive cycle is the transfer of essential nutrients and bacterial symbionts from mother to intrauterine offspring. The tissue mediating this transfer is the milk gland. This work focuses upon the localization and function of two milk proteins (milk gland protein (GmmMGP) and transferrin (GmmTsf)) and the tsetse endosymbionts (Sodalis and Wigglesworthia), in the context of milk gland physiology. Fluorescent in situ hybridization (FISH) and immunohistochemical analysis confirm that the milk gland secretory cells synthesize and secrete milk gland protein and transferrin. Knockdown of gmmmgp by double stranded RNA (dsRNA) mediated RNA interference results in reduction of tsetse fecundity, demonstrating its functional importance in larval nutrition and development. Bacterial species-specific in situ hybridizations of milk gland sections reveal large numbers of Sodalis and Wigglesworthia within the lumen of the milk gland. Sodalis is also localized within the cytoplasm of the secretory cells. Within the lumen, Wigglesworthia localize close to the channels leading to the milk storage reservoir of the milk gland secretory cells. We discuss the significance of the milk gland in larval nutrition and in transmission of symbiotic bacteria to developing offspring. | Wigglesworthia |
We examined Swainson's warblers (Limnothlypis swainsonii (Audubon, 1834), Aves: Parulidae) for lice fauna during 2 yr at three study sites in Arkansas, USA. A total of 66 individuals were examined; eight birds (10.6%) were parasitized with 16 lice of two new species belonging to two genera Myrsidea Waterson, 1915 (Amblycera: Menoponidae) and Brueelia Keler, 1936 (Ischnocera: Philopteridae). Parasitological parameter data are given on the prevalence of lice on Swainson's warblers. Species descriptions and illustrations are provided for Myrsidea bensoni sp. nov. and Brueelia limnothlypiae sp. nov.; including a key for females of the genus Myrsidea that parasitize Parulidae (Passeriformes). | Ischnocera |
E. Dhooge and R. J. Hartsuiker (2010) reported experiments showing that picture naming takes longer with low- than high-frequency distractor words, replicating M. Miozzo and A. Caramazza (2003). In addition, they showed that this distractor-frequency effect disappears when distractors are masked or preexposed. These findings were taken to refute models like WEAVER++ (A. Roelofs, 2003) in which words are selected by competition. However, Dhooge and Hartsuiker do not take into account that according to this model, picture-word interference taps not only into word production but also into attentional processes. Here, the authors indicate that WEAVER++ contains an attentional mechanism that accounts for the distractor-frequency effect (A. Roelofs, 2005). Moreover, the authors demonstrate that the model accounts for the influence of masking and preexposure, and does so in a simpler way than the response exclusion through self-monitoring account advanced by Dhooge and Hartsuiker. | Field Dependence-Independence |
Ferritin is a class of naturally occurring iron storage proteins, which is distributed widely in animal, plant, and bacteria. It usually consists of 24 subunits that form a hollow protein shell with high symmetry. One holoferritin molecule can store up to 4500 iron atom within its inner cavity, and it becomes apoferritin upon removal of iron from the cavity. Recently, scientists have subverted these nature functions and used reversibly self-assembled property of apoferritin cage controlled by pH for the encapsulation and delivery of bioactive nutrients or anticancer drug. In all these cases, the ferritin cages shield their cargo from the influence of external conditions and provide a controlled microenvironment. More importantly, upon encapsulation, ferritin shell greatly improved the water solubility, thermal stability, photostability, and cellular uptake activity of these small bioactive compounds. This review aims to highlight recent advances in applications of ferritin cage as a novel vehicle in the field of food science and nutrition. Future outlooks are highlighted with the aim to suggest a research line to follow for further studies. | Ferritins |
OBJECTIVES: The primary objective of the study was to assess whether the Availability, Responsiveness and Continuity (ARC) organizational intervention improved youth outcomes in community based mental health programs. The second objective was to assess whether programs with more improved organizational social contexts following the 18-month ARC intervention had better youth outcomes than programs with less improved social contexts. METHOD: Eighteen community mental health programs that serve youth between the ages of 5 and 18 were randomly assigned to ARC or control conditions. Clinicians (n = 154) in the participating programs completed the Organizational Social Context (OSC) measure at baseline and following the 18-month ARC organizational intervention. Caregivers of 393 youth who were served by the 18 programs (9 in ARC and 9 in control) completed the Shortform Assessment for Children (SAC) once a month for six months beginning at intake. RESULTS: Hierarchical linear models (HLM) analyses indicated that youth outcomes were significantly better in the programs that completed the 18 month ARC intervention. HLM analyses also showed that youth outcomes were best in the programs with the most improved organizational social contexts following the 18 month ARC intervention. CONCLUSIONS: Youth outcomes in community mental health programs can be improved with the ARC organizational intervention and outcomes are best in programs that make the most improvements in organizational social context. The relationships linking ARC, organizational social context, and youth outcomes suggest that service improvement efforts will be more successful if those efforts include strategies to improve the organizational social contexts in which the services are embedded. | Social Medicine |
Although allergen exposure can clearly aggravate the condition of sensitized patients with asthma, there is uncertainty and controversy about exactly which allergen avoidance interventions should be recommended to patients with asthma. Interventions that appear logical may fail to be clinically efficacious for several reasons. Although narrow interventions, such as allergen-impermeable mattress covers to reduce exposure to dust mite allergens, may offer little benefit if used alone, recent evidence suggests that a multifaceted, home-based environmental intervention focusing on multiple exposures may provide clinical benefits to patients with asthma. The role of allergen avoidance in infancy in the primary prevention of asthma is a subject of active investigation, but data remain too preliminary to make public health recommendations in this regard. | Pyroglyphidae |
Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment. | Laron Syndrome |
BACKGROUND: Reduced surface tension of liquids results in higher surface wetting ability and diffusivity by the substrate. OBJECTIVES: The objective of this study was to evaluate the influence of the Grander Technology in reducing the surface tension of adhesive systems. METHODS: Two adhesive systems (self-etch and total-etch) were modified by physical contact with the Grander system Flexible unit to revitalize water, for 48 h. Surface tension of adhesive systems and water in normal and grander-modified conditions was measured with a goniometer. RESULTS: The results showed a reduction of surface tension for all conditions grander-modified between 3-15%. CONCLUSIONS: Grander Technology was effective in reducing the surface tension of the Single Bond and Clearfil SE Bond adhesive systems. Clinical significance. Grander technology was employed to restructure the molecular structure of water-based adhesive systems, which can increase their wetness capacity and therefore ensure a greater diffusibility. | Surface Tension |
Reverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNA(Lys)(3) primer bound to the vRNA genome and is the target of key antivirals, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Initiation proceeds slowly with discrete pausing events along the vRNA template. Despite prior medium-resolution structural characterization of reverse transcriptase initiation complexes (RTICs), higher-resolution structures of the RTIC are needed to understand the molecular mechanisms that underlie initiation. Here we report cryo-EM structures of the core RTIC, RTIC-nevirapine, and RTIC-efavirenz complexes at 2.8, 3.1, and 2.9 A, respectively. In combination with biochemical studies, these data suggest a basis for rapid dissociation kinetics of RT from the vRNA-tRNA(Lys)(3) initiation complex and reveal a specific structural mechanism of nucleic acid conformational stabilization during initiation. Finally, our results show that NNRTIs inhibit the RTIC and exacerbate discrete pausing during early reverse transcription. | RNA, Transfer, Lys |
The design of zein-based nanoparticles to encapsulate bioactive molecules has gained great attention in recent years. However, the use of ethanol to dissolve zein presents flammability concerns and the scale-up production of zein-based nanoparticles is also a concern. In our study, propolis loaded zein/caseinate/alginate nanoparticles were fabricated using a facile one-step procedure: a well-blended solution was prepared containing deprotonated propolis, soluble zein, dissociated sodium caseinate micelles (NaCas) and alginate at alkaline pH, and then this alkaline solution was added to 0.1 M citrate buffer (pH 3.8) to fabricate composite nanoparticles without using organic solvents and sophisticated equipment. During acidification, the alginate molecules adsorbed on the zein/NaCas surfaces by electrostatic complexation, which improved the stability towards aggregation of zein/NaCas nanoparticles under gastrointestinal (GI) or acidic pH. The nanoparticles prepared under the optimized method (method 3 sample) were of spherical morphology with a particle size around 208 nm and a negative zeta potential around -27 mV. The encapsulation efficiency (EE) and loading capacity (LC) of propolis reached 86.5% and 59.6 mug mg-1 by zein/NaCas/alginate nanoparticles, respectively. These nanoparticles were shown to be stable towards aggregation over a wide range of pH values (2-8) and salt concentrations (0-300 mM NaCl). Compared to free propolis, the bioaccessibility of propolis encapsulated with nanoparticles was increased to 80%. Our results showed a promising clean and scalability strategy to encapsulate hydrophobic nutraceuticals for applications in foods, supplements, and pharmaceuticals. | Zein |
This paper will explore how the practice of ritual healing (sazuke) has played a prominent part in the propagation of a Japanese new religious movement (Tenrikyo) in Taiwan. The author firstly unravels the mystery of Tenrikyo's healing ritual (sazuke) and its role in enabling Taiwanese followers' potential to re-establish their relationship with the world. The author points out that sazuke is similar to Taiwanese folk therapy and fits into Taiwan's multi-medical systems. The author also examines the features of Tenrikyo's healing practice in Taiwan and discusses the evolution of sazuke from a non-institutionalised practice to a bureaucratised one. The author then advances to a more widely theoretical consideration by discussing how sazuke became a force that enabled Taiwanese people to respond to the changing world and how it facilitated peoples' transformation when they were confronted by daily troubles and difficulties. | Ceremonial Behavior |
Malignant gliomas persist as a major disease of morbidity and mortality in adult. Differentiation therapy has emerged as a promising candidate modality. However, the mechanism related is unknown. Here, we show that glycogen synthase kinase-3beta (GSK-3beta) is highly expressed and activated during the cholera toxin-induced differentiation in sensitive C6 and U87-MG malignant glioma cells, whereas the GSK-3alpha activity remains stable. GSK-3beta inhibitors or small interfering RNA suppress the induced-differentiation in sensitive C6 cells. Conversely, overexpression of a constitutively active form of human GSK-3beta (pcDNA3-GSK-3beta-S9A) mutant in resistant U251 glioma cells restores their differentiation capabilities. In addition, GSK-3beta triggers cyclin D1 nuclear export and subsequent degradation, which is necessary for differentiation in C6 and U251 glioma cells. Analysis of human glioma tissues further revealed overexpression of active GSK-3beta. These findings suggest that GSK-3beta is a differentiation fate determinant, and shed new lights on the mechanism by which GSK-3beta regulates cyclin D1 degradation and cellular differentiation in gliomas. | Glycogen Synthase Kinases |
Duodenal ulcers were produced in rats following either an oral or parenteral administration of 200 mg/kg of mepirizole, a nonsteroidal antiinflammatory agent. Deep ulcers, including perforated ones, were induced in the proximal duodenum with an incidence of over 90%. Mortality due to perforation was less than 5%. The agent also induced several erosions in the antrum. Feeding of animals after the ingestion of mepirizole markedly suppressed the development of both duodenal ulcers and gastric erosions. Antacids, anticholinergic agents, a histamine H2-receptor antagonist and 16-DMPGE2 dose-dependently inhibited mepirizole-induced duodenal ulcers. Gastric erosions were also significantly inhibited by antacids and anticholinergic agents but not by a histamine H2-receptor antagonist and 16-DMPGE2. Intraduodenally administered mepirizole dose-dependently inhibited the gastric secretion in pylorus-ligated rats. This ulcer model should be useful for screening antiulcer agents and for the study of pathogenesis of duodenal ulcers and gastric erosions. | Epirizole |
Adult acquired flatfoot deformity is a debilitating condition typically affecting middle-aged patients. The multiple components include hindfoot valgus, first ray elevation, medial soft tissue compromise, and forefoot abduction. As the foot becomes unbalanced, the deformity progresses with repetitive loading and time. Untreated patients often need significant reconstructions or extensive arthrodesis after arthritis and joint contractures present. Medializing calcaneal osteotomy is the workhorse operation for correction of hindfoot valgus, reliably correcting deformity with a relatively low complication risk. This article reviews indications, techniques, complications, and outcomes for the medializing calcaneal osteotomy. | Foot Deformities, Acquired |
Reality is what makes it possible to exist as a human being; every form of psychosis is characterized by a loss of reality. Human reality is the social reality of one's fellow-creatures. It is always rooted in the corporeal, the soma which is the manifestation within the individual of the unity of physis, bios, and mind. This complex manifestation (or gestalt in a broader sense) is unstable. It must be maintained by means of a constant supply of emotional stimuli, which is aesthetically mediated by communicative intercourse. Schizophrenia signifies the rupture of interpersonal relationships, a breakdown in the process of emotional refuelling. A marked diminution of clear contours in physiognomic manifestations also has somatically perceivable consequences in the case of the chronically ill. Not only does gestalt thus help form the basis of relationships; relationships, for their part, are instrumental in shaping gestalt. | Reality Testing |
During a 6-month study we critically evaluated the accuracy of the AutoMicrobic system Gram-Negative Identification Card (Vitek Systems, Inc., Hazelwood, Mo.) in identifying glucose-nonfermenting gram-negative bacilli by testing 419 selected isolates in parallel with a conventional reference method. Of 356 isolates included in the AutoMicrobic system profile, a total of 307 (86.2%) were correctly identified, 36 (10.1%) were not identified, and 13 (3.7%) were misidentified. Fifty-eight of 63 (92%) isolates not included in the profile were correctly reported as "unidentified organisms." Overall, if the first-choice identification was always accepted, only 18 (4.3%) isolates would have been incorrectly reported. When first-choice identifications appended with the special message "questionable biopattern" were rejected, and organisms were screened for characteristic odor and antimicrobial susceptibility before final acceptance of the AutoMicrobic system report, the number of misidentifications was reduced to 5 (1.2%). The average time to identification with the AutoMicrobic system Gram-Negative Identification Card was 15 h. This compares favorably with the 65 h required by the reference method." | Gram-Negative Aerobic Rods and Cocci |
The scapholunate ligament stabilizes the scaphoid and lunate of the proximal row in the wrist which allows for proper force transmission with the radius and ulna. Damage to this structure degenerates into arthritis and disability. Controversy exists over the best technique to restore function and reduce pain. A three-dimensional computational model of the wrist and hand was used to investigate the biomechanical effects of scapholunate ligament dissociation and its repair. The model replicated 3D bony anatomy, soft tissue structures, and muscle loading. The model predicted the increased instability caused by the injury, consistent with experimental and clinical evidence, and a return of more healthy kinematics with the repair. Changes to load transmission across the radiocarpal joints were noted with the injury, only some of which were mitigated by the repair. As better understanding of the biomechanics of the wrist joint is achieved, this model could prove to be an important tool to further investigate wrist mechanics and inform the effects of treatment options. Graphical abstract 3D computational model of all bones in the wrist/hand permitted simulation of five major motions-wrist flexion/extension, radial/ulnar deviation, and clenched fist. Shown are the array of tensile elements representing ligaments and capsule, as well as muscle force vectors for the desired motions. SL (scapholunate) separation (interval) predicted by the model for one motion compared well to an experimental study showing the instability induced by an injured (cut) SL ligament and returned stability by a clinical repair procedure, MBT (Modified Brunelli technique). | Wrist |
While Gilbert's syndrome is extremely common and benign, its pathogenesis may not be as straightforward as once believed. It has been used as a model to examine aberrations of virtually every step in bilirubin metabolism. The clinical hallmarks are of a hereditary, chronic, mild unconjugated hyperbilirubinaemia. Not infrequently subclinical haemolysis may coexist. Liver histology is normal although some minor ultrastructural abnormalities may be evident. The universal defect appears to be a reduction in hepatic bilirubin-GT activity. However, other associated abnormalities in bilirubin metabolism, which occur less consistently, suggest that this may not be the sole defect in all patients. The syndrome is almost certainly part of a spectrum which includes the Crigler-Najjar syndromes; molecular biology data suggests that there is an absence of one (or even more) GT isoenzymes in these disorders. Whether one or more genes is consistently culpable remains open to speculation. Despite the complicated pathogenesis of Gilbert's syndrome, management remains simply reassurance alone. | Gilbert Disease |
Neurotensin (NT) when injected in a dose of 5 micrograms into the third cerebral ventricle of conscious, unrestrained male rats, outfitted with chronic third ventricle and jugular cannulae, decreased the resting prolactin (PRL) levels. NT (5 micrograms) also markedly inhibited the PRL-releasing effect of activation of central serotonin receptors by 5-hydroxytryptophan (5HTP, 15 mg/kg) in animals pretreated with fluoxetine (4 mg/kg). however, interruption of dopamine (DA) neurotransmission by either alpha-methyl-p-tyrosine (alpha MT, 250 mg/kg) or spiroperidol (0.3 mg/kg) led to a blockade of the PRL-inhibiting effect of NT. Treatment of animal with alpha MT prior to the injection of fluoxetine and 5HTP also blocked the PRL-inhibiting effect of NT. These results suggest that the central dopaminergic system mediates the PRL-inhibitory effect of NT. | Methyltyrosines |
PURPOSE OF REVIEW: To summarize what is known about the use of MRI in acute stroke treatment (predominantly thrombolysis), to examine the assumptions and theories behind the interpretation of magnetic resonance images of acute ischemic stroke and how they are used to select patients for therapies, and to suggest directions for future research. RECENT FINDINGS: Recent studies have been contradictory about the usefulness of MRI in selecting patients for treatment. New MRI models for selecting patients have emerged that focus not only on the ischemic penumbra but also on the infarct core. Fixed time-window selection parameters are being replaced by timing-based individualized MRI stroke features. New ways to interpret traditional MRI stroke sequences are emerging. SUMMARY: Although the efficacy of acute stroke treatment is time dependent, the use of fixed time windows cannot account for individual differences in infarct evolution, which could potentially be detected with MRI. Although MRI shows promise for identifying patients who should be treated, as well as excluding patients who should not be treated, definitive evidence is still lacking. Future research should focus on validating the use of MRI to select patients for intravenous therapies in extended time windows. | Stroke |
Open-chest dogs anesthetized with pentobarbital were treated with saline or N-acetylprocainamide (20 mg/kg, i.v.) 10 min prior to simultaneous ligation of the left anterior descending and septal coronary arteries. Ventricular fibrillation occurred in 20 of 26 control dogs but in only 6 of 15 dogs treated with N-acetylprocainamide (P less than 0.05). Since N-acetylprocainamide significantly reduced spontaneous heart rate this may have contributed to its antifibrillatory effect. | Acecainide |
Hepatocellular carcinoma is the most common primary liver cancer in patients with cirrhosis and is the leading cause of mortality in these patients. Despite existence of robust clinical practice guidelines for surveillance, diagnosis, and management for hepatocellular carcinoma (HCC), the quality of care received by patients with HCC has been inconsistent. Several studies have reported disappointingly low surveillance rates in high-risk groups which likely contribute to most HCC cases being diagnosed at advanced stages. There is also data from large studies showing that significant under-referral to specialists and delay in initiation of treatment are linked to poor clinical outcomes. Given above circumstances, it is very important to perform studies which can identify areas in need of improvement in the care processes of HCC and design interventions to enhance quality of care. Unfortunately, data on validated quality indicators and quality metrics for HCC are non-existent. In this article, we review the existing literature pertaining to this issue and identify areas that need further research. | Carcinoma, Hepatocellular |
In this paper, we review three different approaches to disclosure and privacy: a) an individualistic approach, which emphasizes an individual's control over information access and flow, b) a networked approach focused on information flow in horizontal relations between people, and c) an institutional approach concerned with public and societal privacy risks from platforms, providers, and governments. These approaches co-exist largely independently of each other in privacy and disclosure literature. However, with overlapping public and private spheres of communication where a presumption of individual agency over personal information is no longer tenable, we argue for the importance of bridging these perspectives towards a more multifaceted view on online disclosure and privacy in a networked ecology. | Confidentiality |
Resident immune cells (e.g., macrophages [MPhis]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MPhi function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter-mediated MPhi depletion was generated, characterized, and crossed with the sodium channel beta subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A-mediated depletion of LysM(+) pulmonary MPhis in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM(+) MPhi depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM(+) MPhi-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM(+) MPhi-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM(+) MPhi-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MPhi-mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease. | Pasteurella pneumotropica |
Ventilator associated pneumonia (VAP) is a common complication in mechanically ventilated children and adults. There remains much controversy in the literature over the definition, treatment and prevention of VAP. The incidence of VAP is variable, depending on the definition used and can effect up to 12% of ventilated children. For the prevention and reduction of the incidence of VAP, ventilation care bundles are suggested, which include vigorous hand hygiene, head elevation and use of non-invasive ventilation strategies. Diagnosis is mainly based on the clinical presentation with a lung infection occurring after 48hours of mechanical ventilation requiring a change in ventilator settings (mainly increased oxygen requirement, a positive culture of a specimen taken preferentially using a sterile sampling technique either using a bronchoscope or a blind lavage of the airways). A new infiltrate on a chest X ray supports the diagnosis of VAP. For the treatment of VAP, initial broad-spectrum antibiotics should be used followed by a specific antibiotic therapy with a narrow target once the bacterium is confirmed." | Pneumonia, Ventilator-Associated |
AIM: To evaluate a possible role of CYP2C9 genotyping for sulfonylureas (SUs) prescription in Russia. MATERIALS & METHODS: We have collected the current data on correlation between SUs pharmacodynamics and CYP2C9 polymorphisms. We have evaluated the frequency of CYP2C9 polymorphisms in Russia by reviewing the literature published from 2004 to 2015 on Russian CYP2C9. RESULTS: The genotype *1/*1, which confers risk for treatment failure, has a higher frequency (81.92%) in the non-Caucasians than that (64.92%) in the Caucasians. The Caucasians have a frequency (3.58%) of the poor metabolizers (*2/*2, *2/*3 and *3/*3) eight-times higher than that (0.44%) in the non-Caucasians, predisposing an increased risk of hypoglycemia. CONCLUSION: Considering the received data and the existed knowledge on CYP2C9 influence on SUs pharmacokinetics and pharmacodynamics, we propose a possible approach to CYP2C9-guided SUs prescription for Russians. | Cytochrome P-450 CYP2C9 |
In this article, a discussion of the definition and description of brief interventions is followed by broad reviews of their effectiveness in the cigarette smoking and alcohol fields. It is then argued that brief interventions should not be justified only in terms of early intervention; that there is at present insufficient evidence to warrant the abandonment of conventional outpatient treatment for clinic attenders; and that the relative contribution of motivational and active behaviour-change components of brief interventions is an important area for research. | Psychotherapy, Brief |
Fatigue is a significant clinical problem for medical-surgical patients experiencing acute and chronic health problems. Fatigue can cause nutritional intake to suffer and compromises overall functional status. A thorough assessment of the factors associated with a patient's fatigue enables the nurse to develop a fatigue management plan and implement other strategies to minimize the negative consequences of fatigue. | Fatigue |
Four adult, full-sibling slender-tailed meerkats (Suricata suricatta) were diagnosed with acute pancreatitis. The incident case presented with lethargy, anorexia, abdominal guarding, and a cranial abdominal mass. Serum was grossly lipemic, with elevated cholesterol and triglyceride concentrations and increased amylase and lipase activity. An exploratory laparotomy confirmed chylous peritonitis and included excision of a saponified spleno-duodenal mass, a partial pancreatectomy, and a splenectomy. Histopathology revealed severe, multifocal, subacute necrotizing and granulomatous pancreatitis. Within 13 days of the incident case, the second meerkat was identified with essentially identical clinical, surgical, and histologic findings. During subsequent physical examinations of apparently unaffected cohorts (n=12), physical and hematologic findings suggestive of pancreatitis were identified in the two remaining siblings of the first two cases. The definitive cause for these four cases is undetermined; however, common risk factors identified were obesity and hyperlipidemia, a change to a higher-fat diet, and genetic predisposition. To assess its usefulness in the diagnosis of meerkat pancreatitis, serum canine and feline pancreatic lipase immunoreactivity (cPLI and fPLI) concentrations were measured in serum samples (n=61) from two unrelated meerkat populations. Although these assays are highly sensitive and specific for the diagnosis of pancreatitis in domestic carnivores, similar correlation was not apparent for meerkats. In addition, hyperlipidemia was inconsistently present in many meerkats, with no apparent correlation to the development of clinical illness. Based on these observations, sensitive and specific diagnostic tests for pancreatitis in meerkats are currently unavailable. | Herpestidae |
The following report contains all of the recommendations of the working group on oral health that met during the Surgeon General's Workshop on Health Promotion and Aging, March 20-23, 1988, in Washington, DC, under the direction of Surgeon General C. Everett Koop and a number of leaders in geriatrics and gerontology. The working group was composed of 17 specialists, including Frank Martin, technical manager; Scott Presson, reporter; James Beck, chairman; and group members Ronald Ettinger, Jean Frazier, Mary Alice Gaston, Helen Gift, Neville Gilmore, Marc Heft, H. Asuman Kiyak, James Marshall, Roseann Mulligan, Linda Niessen, Vincent Rogers, Michele Saunders, Ruth Seigler, and Hongying Wang. The report also includes dental-related recommendations made by the working groups on medication, preventive health services, alcohol, physical fitness and exercise, injury prevention, mental health, smoking cessation, and nutrition. Eight workshops have been sponsored by the surgeon general since his appointment to office in 1981; this workshop was the first to focus on dentistry and aging. | Geriatric Dentistry |
Roof-harvested rainwater (RHRW) has been considered an effective alternative water source for drinking and various nonpotable uses in a number of countries throughout the world. The most significant issue in relation to using untreated RHRW for drinking or other potable uses, however, is the potential public health risks associated with microbial pathogens. This paper reviews the available research reporting on the microbial quality of RHRW and provides insight on the capacity of fecal indicator bacteria to monitor health risks and disease outbreaks associated with the consumption of untreated RHRW. Several zoonotic bacterial and protozoan pathogens were detected in individual and communal rainwater systems. The majority of the studies reported in the literature assessed the quality of rainwater on the basis of the presence or absence of specific pathogens, with little information available regarding the actual numbers of such pathogens. In addition, no information is available concerning the ongoing prevalence of different pathogens in RHRW over time. The published data suggest that the microbial quality of RHRW should be considered less than that expected for potable water and that the commonly used indicators may not be suitable to indicate the presence of pathogens in RHRW. Several case control studies established potential links between gastroenteritis and consumption of untreated RHRW. Therefore, health risks assessment models, such as those using Quantitative Microbial Risk Assessment, should be used to manage and mitigate health risks associated with drinking and nonpotable uses of RHRW. | Rain |
The genetic control of embryonic organization is far better understood for the fruit fly Drosophila melanogaster than for any other metazoan. A gene hierarchy acts during oogenesis and embryogenesis to regulate the establishment of segmentation along the anterior-posterior axis, and homeotic selector genes define developmental commitments within each parasegmental unit delineated. One of the most intensively studied Drosophila segmentation genes is fushi tarazu (ftz), a pair-rule gene expressed in stripes that is important for the establishment of the parasegmental boundaries. Although ftz is flanked by homeotic selector genes conserved throughout the metazoa, there is no evidence that it was part of the ancestral homeotic complex, and it has been unclear when the gene arose and acquired a role in segmentation. We show here that the beetle Tribolium castaneum has a ftz homolog located in its Homeotic complex and expressed in a pair-rule fashion, albeit in a register differing from that of the fly gene. These and other observations demonstrate that a ftz gene preexisted the radiation of holometabolous insects and suggest that it has a role in beetle embryogenesis which differs somewhat from that described in flies." | Fushi Tarazu Transcription Factors |
Volatile oil composition of hydro-distilled (HD) and supercritical carbon dioxide (SC-CO(2)) essential oil of freshly collected aerial parts of Heracleum thomsonii (Umbeliferae) from the western Himalayas was studied by GC-FID and GC-MS. Results revealed qualitative and quantitative dissimilarity in the composition of hydro-distilled and SC-CO(2) extracted oils. Nineteen constituents, which accounted for 89.32% of total constituents in HD oil, represented by limonene (4.31%), (Z)-beta-ocimene (3.69%), terpinolene (22.24%), neryl acetate (36.19%), nerol (9.51%) and p-cymene-8-ol (2.61%) were identified. In SC-CO(2) extracted oil, 24 constituents representing 89.95% of total constituents were identified. Terpinolene (5.08%), germacrene D (2.17%), neryl acetate (51.62%), nerol (9.78%), geranyl acetate (2.06%), alpha-bisabolol (2.48%) and 1-nonadecanol (4.96%) were the dominating constituents. In vitro antimicrobial activity of hydro-distilled oil was conducted against microrobial strains including two Gram-positive (Staphylococcus aureus and Bacillus subtilis) and five Gram-negative (Burkholderia cepacia, Escherichia coli, Enterobacter cloacae, Klebseilla pneumoniae and Pseudomonas aeruginosa) bacteria as well as seven fungi (Candida albicans, Issatchenkia orientalis, Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Aspergillus sydowii and Trichophyton rubrum) using broth microdilution method. The results of bioassay showed that the oil exhibited moderate to high antimicrobial activity against fungi C. albicans (MIC 625 microg ml(-1)), A. parasiticus (MIC 312.5 microg ml(-1)), A. sydowii (MIC 312.5 microg ml(-1)), T. rubrum (MIC 625 microg ml(-1)), Gram-positive bacteria B. subtilis (MIC 625 microg ml(-1)) and Gram-negative bacteria P. aeruginosa (MIC 312.5 microg ml(-1)). | Heracleum |
AIMS: To characterize the population pharmacokinetics of netilmicin, an aminoglycoside antibiotic, in adult urology patients and to develop a covariate model for improved dose titration. METHODS: Data from 62 adult patients (55 male, seven female), undergoing urological surgery and treated with netilmicin for short-term prophylaxis, were evaluated retrospectively. The group had (median, range) ages 68, 31-92 years, weights 72, 43-106 kg and heights 167, 148-182 cm. No patient showed renal impairment before netilmicin treatment (serum creatinine </=1.9 mg dl-1). Netilmicin (100 mg) was administered as a maximum of four successive intravenous infusions of 30 min, at 8-h intervals. A total of five blood samples were collected from each patient. Prior to analysis, the dataset was divided into 'index' (n = 44) and 'validation' (n = 18) groups at random. The time courses of netilmicin concentrations from all subjects were analysed using a mixed effects, population, nonlinear modelling package (WinNonMix). For covariate model development, a stepwise procedure was used with backward elimination followed by forward inclusion based on age, sex, weight, height, creatinine clearance and type of surgery. The final covariate model parameters from the index group were used to simulate concentrations in the validation group and the bias and precision were compared with the observations. RESULTS: A bi-compartmental open model with a proportional residual error best described the data. The population parameters for central and peripheral volumes of distribution were (typical population value [interindividual CV%]) Vc = 14.5 l [56%] and Vp = 10.2 l [not estimated], and the systemic and intercompartmental clearances were CL = 3.9 l h-1[42%] and CLQ = 10.1 l h-1[not estimated], respectively. The final population covariate relationships were based on sex (SEX) and creatinine clearance (CrCL): (Vc, l) = 18.9 - 5.9 x SEX [29%] and (CL, l h-1) = 0.06 x CrCL [33%]. Compared with the observations in the validation group, this model showed a bias (95% confidence interval) of -0.028 (-0.28, 0.25) and precision of 1.22 (0.78, 1.34). CONCLUSION: Bi-compartmental pharmacokinetic parameters of netilmicin have been estimated from clinical data in urological surgery patients using a population approach. A given single dose results in large variability in plasma concentrations and thus the population covariate final model can be used for direct estimation of initial dosing in patients. | Netilmicin |
The immunocytochemical localization of cathepsin E, a non-lysosomal aspartic proteinase, was investigated in rat osteoclasts using the monospecific antibody to this protein. At the light-microscopic level, the preferential immunoreactivity for cathepsin E was found at high levels in active osteoclasts in the physiological bone modeling process. Neighboring osteoblastic cells were devoid of its immunoreactivity. At the electron-microscopic level, cathepsin E was exclusively confined to the apical plasma membrane at the ruffled border of active osteoclasts and the eroded bone surface. Cathepsin E was also concentrated in some endocytotic vacuoles of various sizes in the vicinity of the ruffled border membrane, some of which appeared to be secondary lysosomes containing the phagocytosed materials. These results strongly suggest that this enzyme is involved both in the extracellular degradation of the bone organic matrix and in the intracellular breakdown of the ingested substances in osteoclasts. | Cathepsin E |
Deoxyribozymes are synthetic enzymes made of DNA that can catalyze the cleavage or formation of phosphodiester bonds and are useful tools for RNA biochemistry. Herein, we report new RNA-cleaving deoxyribozymes to interrogate the methylation status of target RNAs, thereby providing an alternative method for the biochemical validation of RNA methylation sites containing N(6) -methyladenosine, which is the most wide-spread and extensively investigated natural RNA modification. The developed deoxyribozymes are sensitive to the presence of N(6) -methyladenosine in RNA near the cleavage site. One class of these DNA enzymes shows faster cleavage of methylated RNA, while others are strongly inhibited by the modified nucleotide. The general applicability of the new deoxyribozymes is demonstrated for several examples of natural RNA sequences, including a lncRNA and a set of C/D box snoRNAs, which have been suggested to contain m(6) A as a regulatory element that influences RNA folding and protein binding. | Adenosine |
To assess characteristics of Chinese costal cartilage and costa calcification using Dual-Energy computed tomography(DECT). 154 patients who underwent chest DECT scanning were included in our study. They were divided into following groups: less than 30 years old, 31-40 years old, 41-50 years old, 51-60 years old and over 60 years old. The sixth, seventh and eighth costal cartilages and costas were evaluated. Calcification patterns of cartilage were classified as central(C), peripheral(P), mixed(M) and no calcification(N) types. Calcification degree of cartilage was distinguished as 1(0-25%), 2(26-50%) and 3(>50%). CT value, calcium and water concentrations were measured in costal cartilage, cortical or cancellous bone respectively. An increasing C pattern of cartilage was displayed in females, while P type preferred in males as age increased. Calcification degree generally changed from 1 to 2 or 3 in females. CT value and calcium concentration of cartilage went through a gradual rising course and peaked in their 40-50 years, while those two indices of cancellous bone decreased gradually since their 50 years in females. The findings suggest a gradual calcification of the costal cartilage took place before 40-50 years old and a sharp bone loss of the costa happened after 40-50 years old in females. | Costal Cartilage |
Differentiated NG108-15 neuroblastoma x glioma hybrid cells were whole-cell voltage-clamped. Hyperpolarizing pulses, superimposed on a depolarized holding potential (-30 or -20 mV), elicited deactivation currents which consisted of two components, distinguishable by fitting with two exponential functions. Linopirdine [DuP 996, 3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one), a neurotransmitter-release enhancer known as potent and selective blocker of the M-current of rat sympathetic neurons, in concentrations of 5 or 10 microM selectively inhibited the fast component (IC50 = 14.7 microM). The slow component was less sensitive to linopirdine (IC50>20 microM). The class III antiarrhythmics [(4-methylsulphonyl)amido]benzenesulphonamide (WAY-123.398) and 1-[2-(6-methyl-2-pyrydinil)ethyl]-4-(4-methylsulphonylaminobenz oyl) piperidine (E-4031), selective inhibitors of the inwardly rectifying ERG (ether-a-go-go-related gene) potassium channel, inhibited predominantly the slow component (IC50 = 38 nM for E-4031). The time constant of the WAY-123.398-sensitive current resembled the time constant of the slow component in size and voltage dependence. Inwardly rectifying ERG currents, recorded in K+ -rich bath at strongly negative pulse potentials, resembled the slow component of the deactivation current in their low sensitivity to linopirdine (28% inhibition at 50 microM). The size of the slow component varied greatly between cells. Accordingly, varied the effect of WAY-123.398 on deactivation current and holding current. RNA transcripts for the following members of the ether-a-go-go gene (EAG) K+ channel family were found in differentiated NG108-15 cells: ERG1, ERG2, EAGI, EAG-like (ELK)1, ELK2; ERG3 was only present in non-differentiated cells. In addition, RNA transcripts for KCNQ2 and KCNQ3 were found in differentiated and non-differentiated cells. We conclude that the fast component of the deactivation current is M-like current and the slow component is deactivating ERG current. The molecular correlates are probably KCNQ2/KCNQ3 and ERG1/ERG2, respectively. | KCNQ3 Potassium Channel |
We have examined the effect of neutrophil concentration on killing of a clinical isolate of Staphylococcus epidermidis. Human neutrophils at concentrations varying from 10(5) to 10(7) per ml were mixed in suspension with S. epidermidis at concentrations varying from 10(3) to 10(8) colony-forming units/ml, and the concentration of viable bacteria was assayed after various times at 37 degrees C. The rate of bacterial killing depended on the concentration of neutrophils and not on the ratio of neutrophils to bacteria. Below a critical concentration of neutrophils, bacteria growth was greater than neutrophil killing of bacteria even when the ratio of neutrophils to bacteria was 100:1. We fitted the time course of bacterial concentration and its dependence on neutrophil concentration with an exponential function, the exponent of which is (-kp + g)t, where k is the second-order rate constant for bacterial killing, p is the neutrophil concentration, g is the first-order rate constant for bacterial growth, and t is time. We found that k approximately 2 x 10(-8) ml per neutrophil per min, and g approximately 8 x 10(-3)/min. Only when p is greater than g/k, which we call the critical neutrophil concentration, does the bacterial concentration fall. Under optimal assay conditions, the critical neutrophil concentration was 3-4 x 10(5) per ml, a value very close to that (< or =5 x 10(5) per ml) known to predispose humans to bacterial and fungal infections. | Blood Bactericidal Activity |
The gastric emptying rate is a carefully regulated process consisting of different mathematically defined phases. The gastric metabolic load, as well as neural regulatory mechanisms and hormonal influences, cooperate in order to achieve a well-balanced emptying of contents from the stomach into the duodenum for absorption in the small intestine. This finely tuned regulation is primarily regulated by the release of gastrointestinal peptide hormones which serve to counteract the emptying process in the fed state and to stimulate sweeping contractions in the fasted state, most likely in order to prepare the stomach for another meal. We have found that the two peptide hormones ghrelin and glucagon-like peptide- I (GLP- I) have a great impact on the regulation of gastric emptying: ghrelin is a most potent stimulator of gastric contractions and emptying, and GLP- I profoundly inhibits this emptying process. These data suggest possibilities for governing the rate of gastric emptying as a natural step in achieving metabolic balance and control. | Gastric Emptying |
The paper describes the changes in the cricopharyngeal muscle in seven cases of dysphagia resulting from obstruction at this level which was relieved by myotomy. Histological features included degeneration and regeneration in the muscle fibres with interstitial fibrosis which was severe in some of the cases. It is considered that this restrictive fibrosis is the cause of the dysphagia and that it is secondary to muscle fibre damage, the cause of which is at present obscure. Minor degrees of muscle damage and regeneration were seen rarely in controls and fibrosis was never present. There was no evidence of underlying vascular or neurological disease in six cases; the seventh had a previous history of scleroderma but this was not thought to be the cause of the cricopharyngeal lesion. The age incidence ranged from 1 to 5 years at the onset of dysphagia; in six of the seven it was 50 years or more. | Pharyngeal Diseases |
Our study attempted to compare the efficacies of bone morphogenetic protein (BMP) 2, 6, and 9 in inducing osteogenic differentiation of preodontoblasts (PDBs). We immortalized PDBs by introducing a reversible SV40 T antigen-based immortalization system. Cell proliferation capability was examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The effects of BMP2, 6, and 9 on the osteogenic differentiation of immortalized preodontoblasts (iPDBs) were measured by alkaline phosphatase (ALP) activity assays and alizarin red S staining. The expression of osteogenic markers was evaluated by semiquantitative real-time polymerase chain reaction analysis. To assess ectopic bone formation, rat-derived iPDBs were transfected in culture with adenoviral vectors designated Ad-BMP2, 6, and 9 and subcutaneously or intramuscularly injected into mice. Several BMPs retained endogenous expression in PDBs and regulated the mRNA expression of mineralized tissue-associated proteins. ALP activity and mineralized nodule formation were significantly increased in the Ad-BMP9-transfected group relative to the control group. In addition, the most significant hard tissue formation was in this group. The results indicated that BMP signaling was involved in the osteogenic differentiation of iPDBs. BMP9 could be an efficacious accelerant of the osteogenic differentiation of iPDBs. | Bone Morphogenetic Proteins |
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