Monitoring supported-nanocluster heterogeneous catalyst formation: product and kinetic evidence for a 2-step, nucleation and autocatalytic growth mechanism of Pt(0)n formation from H2PtCl6 on Al2O3 or TiO2.
A pressing problem in supported-metal-nanoparticle heterogeneous catalysis--despite the long history and considerable fundamental as well as industrial importance of such heterogeneous catalysts--is how to monitor such catalysts' formation more routinely, rapidly, and in real time. Such information is needed to better control the size, shape, composition, and thus resultant catalytic activity, selectivity, and lifetime of these important catalysts. To this end, a study is reported of the formation of supported Pt(0)(n) nanoparticles by H(2) reduction of H(2)PtCl(6) on Al(2)O(3) (or TiO(2)) to give 6 equivalents of HCl plus supported Pt(0)(n)/Al(2)O(3) (or Pt(0)(n)/TiO(2)), all while in contact with a solution of EtOH and cyclohexene. The HCl and Pt(0)(n) products were confirmed, respectively, by the stoichiometry of HCl formation using pH(apparent) measurements, appropriate standards, and by TEM and EDX measurements. The hypothesis of this research is that the kinetics of formation of this supported heterogeneous catalyst could be successfully monitored by a fast cyclohexene hydrogenation catalytic reporter reaction method first worked out for monitoring transition-metal nanoparticle formation in solution (Watzky, M. A. and Finke, R. G. J. Am. Chem. Soc. 1997, 119, 10382-10400). Significantly, sigmoidal kinetics of Pt(0)(n)/Al(2)O(3) catalyst formation were in fact successfully monitored by the catalytic hydrogenation reporter reaction method and then found to be well fit to the Finke-Watzky (hereafter F-W) 2-step, slow continuous nucleation and then autocatalytic surface growth mechanism, A --> B (rate constant k(1)) and A + B --> 2B (rate constant k(2)), respectively, in which A is the H(2)PtCl(6) and B is the growing, catalytically active Pt(0) nanoparticle surface. The finding that the F-W mechanism is applicable is significant in that it, in turn, suggests that the > or = 8 insights from studies of the mechanisms of soluble nanocluster formation can likely also be applied to supported heterogeneous catalyst synthesis, including a recent equation that gives nanocluster size vs time in terms of k(1), k(2), [A](o) and other parameters (Watzky, M. A., Finney, E. E. and Finke, R. G. J. Am. Chem. Soc. 2008, 130, 11959-11969 ). Also presented are the use of the catalytic reporter reaction to reveal H(2) gas to-solution mass-transfer-limitations (MTL) in the system of H(2)PtCl(6) on TiO(2), results relevant to a recent communication in this journal. The use of the F-W 2-step nucleation and autocatalytic growth kinetic model to fit 3 literature examples of heterogeneous catalyst formation, involving H(2) reduction of both supported or bulk M(x)O(y) (i.e., and in gas-solid reactions), are also presented as part of the Supporting Information. A conclusion section is then provided summarizing the insights and caveats from the present work, as well as some needed future studies.


Short nucleotide sequences signal spliceosomal binding in nucleic acids.
We have explored the region around the splice sites of the human intron and exons from the exon-intron database (EID) and located a number of short 6-nucleotide and 7-nucleotide sequences that are relatively common in the regions. These short sequences, we expect play an important role in the selection of the appropriate splicing process. We propose that the external signals via short recognition sequences play the deterministic role in the actual splicing process. We have obtained 50 such sequences each from the exon and intron from the beginning and from the ending and noted a number of common features.


[Cardiovascular diseases and periodontal diseases].
Accumulated evidence has strongly suggested that the long-term effects of periodontal diseases can be linked to more serious systemic conditions such as cardiovascular diseases, diabetes, and complications of pregnancy. Especially, a prevalence of coronary heart disease was found to be significantly increased in patients with periodontitis after adjusting for risk factors such as smoking, diabetes, alcohol intake, obesity, and blood pressure. Furthermore, various studies have shown that Porphyromonas gingivalis, a major periodontal pathogen, is able to exacerbate atherosclerosis following oral-hematogenous spread due to the bacteremia. By P. gingivalis, endothelial cells activate and upregulate various adhesion molecules, thus increasing the likelihood of macrophage diapedesis and subsequent conversion to foam cells thus furthering athroma progression. These findings likely indicate the tight relationship between periodontitis/periodontal pathogens and cardiovascular diseases.


Use of EndoVac System for Aspiration of Exudates from a Large Periapical Lesion: A Case Report.
Large cyst-like periapical lesions can heal after nonsurgical root canal treatment. Decreasing the hydrostatic pressure within a periapical lesion can be achieved with the aspiration technique by using EndoVac when there is drainage of cystic fluid through the canals. Clinical examination of a 21-year-old male patient revealed a large periapical lesion extending from the distal aspect of tooth #26 and reaching the mesial surface of tooth #22. During root canal treatment of teeth #23, #24, and #26, serous exudate drained from the root canal of tooth #24. The MacroCannula component of EndoVac apical negative pressure irrigation system was used to aspirate the inflammatory fluid. The technique produces a vacuum effect in the periapical region through the root canal, which facilitates evacuation of large amounts of exudate. Two-year clinical and radiographic examinations revealed resolution of the mandibular radiolucency, and the adjacent tooth #25 retained its vitality. The healing of a large periapical lesion can be achieved by the correct diagnosis and the proper treatment approach, without the need for surgery. EndoVac negative irrigation system might be useful for intracanal aspiration of exudates.


Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their possible interaction in signalling cytokinesis.
TD-60 and INCENP are two members of the chromosome passenger protein family, and each has been suggested to play a role in the control of cytokinesis. Here we demonstrate by confocal immunofluorescence microscopy that TD-60 and INCENP distribute identically throughout the cell cycle. Both appear coordinately in G2-phase nuclei and become concentrated at centromeres during prophase. TD-60 and INCENP both then leave the chromosome together during anaphase and redistribute to the spindle midzone, as do other chromosome passenger proteins, and traverse the entire equatorial diameter from cortex to cortex. By image overlay and pixel count analysis we show that TD-60 and INCENP are distinct among known chromosome passenger proteins in extending beyond the spindle to the cortex. Further, we show that the cytokinesis-associated protein kinase AIM-1 also shares this distribution property. We suggest that this redistribution is required to signal cytokinesis. TD-60 and INCENP also show identical localization in cells that exit mitosis in the presence of dihydrocytochalasin B (DCB), an inhibitor of actin assembly. Such cells can resume cleavage upon removal of DCB and in a recovery subpopulation that cleaves only on one side, these proteins both colocalize to the cortex only where a cleavage furrow forms. Given the coincident distribution of TD-60 and INCENP during both interphase and mitosis, we suggest that these proteins may cooperate, perhaps within a protein complex, in signalling cytokinesis. Such a mechanism, using chromosome passenger proteins, may ensure that cytokinesis occurs only between the separated chromatids, and only after they have segregated.


Spatial and temporal groundwater level variation geostatistical modeling in the city of Konya, Turkey.
Groundwater is one of the most important resources used for drinking and utility and irrigation purposes in the city of Konya, Turkey, as in many areas. The purpose of this study is to evaluate spatial and temporal changes in the level of groundwater by using geostatistical methods based on data from 91 groundwater wells during the period 1999 to 2003. Geostatistical methods have been used widely as a convenient tool to make decisions on the management of groundwater levels. To evaluate the spatial and temporal changes in the level of the groundwater, a vector-based geographic information system software package, ArcGIS 9.1 (Environmental Systems Research Institute, Redlands, California), was used for the application of an ordinary kriging method, with cross-validation leading to the estimation of groundwater levels. The average value of variogram (spherical model) for the spatial analysis was approximately 2150 m. Results of ordinary kriging for groundwater level drops were underestimated by 17%. Cross-validation errors were within an acceptable level. The kriging model also helps to detect risk-prone areas for groundwater abstraction.


Afut1, a retrotransposon-like element from Aspergillus fumigatus.
A repeated DNA sequence used for epidemiological studies of the human opportunistic pathogen Aspergillus fumigatus has been characterized. It is a retroelement of 6914 bp in length, bounded by long terminal repeats of 282 bp, with sequence and features characteristic of retroviruses and retrotransposons. A 5 bp duplication site was found at its borders. This element, designated Afut1, encodes amino acid sequences homologous to the reverse transcriptase, RNase H and endonuclease encoded by the pol genes of retroelements. Comparison of the peptidic sequences with other putative polypeptides of fungal LTR retrotransposons showed that Afut1 is a member of the gypsy group. This is the first report of a transposable element in A.fumigatus. Afut1 is a defective element: the putative coding domains contain multiple stop codons due exclusively to transitions from C:G to T:A.


Heart rate variability in pubertal girls with type 1 diabetes: its relationship with glycaemic control, insulin resistance and hyperandrogenism.
To examine the association between glycaemic control, insulin resistance and hyperandrogenism on cardiac autonomic function in peripubertal girls with type 1 diabetes. Prospective, clinic-based study of 125 girls with diabetes and 46 age-matched nondiabetic girls. Heart rate variability (HRV) parameters derived from a 10-min ECG recording using LabChart Pro were as follows: standard deviation of mean NN intervals (SDNN), where NN = adjacent QRS complexes; root mean squared difference of successive NN intervals (RMSSD) - estimates of overall HRV; and low-/high-frequency (LF:HF) ratio - an estimate of the sympathovagal balance. Androgens and sex hormone binding globulin (SHBG) were measured in girls with diabetes, and free androgen index (FAI) calculated. HRV and anthropometry were measured in nondiabetic controls. Adolescents with diabetes (median age 15·1 years [13·3-16·0], diabetes duration 7·0 years [4·6-10·0] and median HbA1c 8·4% [7·5-9·3]) had higher HR and lower HRV compared with controls. Using multivariate models in the diabetes group, higher HR was associated with higher HbA1c, total daily dose insulin/kg body weight and systolic BP standard deviation scores (SDS), whilst reduced HRV was associated with higher HbA1c (SDNN, RMSSD and LF:HF ratio), lower SHBG (SDNN and RMSSD) and higher weight SDS (LF:HF ratio). Higher FAI was associated with higher HR and reduced HRV measures in the univariate analyses only. In adolescent girls with diabetes, reduced HRV parameters are associated with worse glycaemic control, lower SHBG and higher weight SDS. SHBG should be considered in the cardiac risk models for this population.


The cost of space independence in P300-BCI spellers.
Though non-invasive EEG-based Brain Computer Interfaces (BCI) have been researched extensively over the last two decades, most designs require control of spatial attention and/or gaze on the part of the user. In healthy adults, we compared the offline performance of a space-independent P300-based BCI for spelling words using Rapid Serial Visual Presentation (RSVP), to the well-known space-dependent Matrix P300 speller. EEG classifiability with the RSVP speller was as good as with the Matrix speller. While the Matrix speller's performance was significantly reliant on early, gaze-dependent Visual Evoked Potentials (VEPs), the RSVP speller depended only on the space-independent P300b. However, there was a cost to true spatial independence: the RSVP speller was less efficient in terms of spelling speed. The advantage of space independence in the RSVP speller was concomitant with a marked reduction in spelling efficiency. Nevertheless, with key improvements to the RSVP design, truly space-independent BCIs could approach efficiencies on par with the Matrix speller. With sufficiently high letter spelling rates fused with predictive language modelling, they would be viable for potential applications with patients unable to direct overt visual gaze or covert attentional focus.


Structural determination and promoter analysis of the chicken mitogen-inducible prostaglandin G/H synthase gene and genetic mapping of the murine homolog.
We have previously reported the isolation and characterization of a new form (PGHS-2) of prostaglandin G/H synthase (PGHS, cyclooxygenase) from chicken embryo fibroblasts. To further study the regulation and structure of the gene, we have cloned the entire chicken PGHS-2 (previously termed miPGHSch) gene with its 5'-flanking region from a chicken genomic library. A genomic Southern blot showed the existence of a single PGHS-2 gene. The size of the gene was estimated at 8.9 kb through DNA sequencing and polymerase chain reaction analysis. The PGHS-2 gene was found to contain 10 exons, giving it a structure similar to that of the human PGHS-1 and murine PGHS-2 genes. The transcription start site was determined by primer extension, and the nucleotide sequence of 1.6 kb of the 5'-flanking region immediately upstream of the transcription start site was determined. The promoter sequence contained a TATA box and a variety of enhancer elements, including a serum response element, an AP-1, an NF-kappa B, and several SP-1 and AP-2 sites. Chloramphenicol acetyltransferase (CAT) assays showed that the first 158 nucleotides of the promoter efficiently drove transcription of the CAT reporter gene in serum-stimulated cells. Dexamethasone, a potent inhibitor of prostaglandin synthesis, had no effect on CAT activity, although this drug is known to markedly decrease PGHS-2 mRNA in vivo. This suggests that dexamethasone may inhibit PGHS-2 mRNA expression at the post-transcriptional level. Analysis of hamster/mouse somatic cell hybrids with radiolabeled cDNA probes demonstrated that PGHS-1 mapped to chromosome 2 and PGHS-2 mapped to chromosome 1 of the mouse genome.


Serum S100 Protein Is a Reliable Predictor of Brain Injury After Out-of-Hospital Cardiac Arrest: A Cohort Study.
Purpose: To evaluate serum S100 protein at hospital admission and after 48 h in early neuroprognostication of comatose survivors of out-of-hospital cardiac arrest (OHCA). Methods: The study included 48 consecutive patients after OHCA, who survived for at least 72 h after the event. The patients were divided based on their best cerebral performance category (CPC) achieved over a 30 day follow-up period: favorable neurological outcome (CPC 1-2) vs. unfavorable neurological outcome (CPC 3-4). Predictors of an unfavorable neurological outcome were identified by multivariable regression analysis. Analysis of the receiver operating characteristic curve (ROC) was used to determine the cut-off value for S100, having a 0% false-positive prediction rate. Results: Of the 48 patients, 30 (63%) had a favorable and 18 (38%) had an unfavorable neurological outcome. Eleven patients (23%) died over the 30 day follow-up. Increased S100 levels at 48 h after OHCA, but not the baseline S100 levels, were independently associated with unfavorable neurological outcome, with an area under the ROC curve of 0.85 (confidence interval 0.74-0.96). A 48 h S100 value ≥0.37 μg/L had a specificity of 100% and sensitivity of 39% in predicting an unfavorable 30 day neurological outcome. Conclusion: This study showed that S100 values assessed 48 h after an OHCA could independently predict an unfavorable neurological outcome at 30 days.


The alternative pathway is critical for pathogenic complement activation in endotoxin- and diet-induced atherosclerosis in low-density lipoprotein receptor-deficient mice.
The early components of the classical and lectin complement pathways have been shown to protect low-density lipoprotein receptor-deficient mice (Ldlr(-/-)) from early atherogenesis. However, the role of the alternative pathway remained unknown, and that was investigated in this study. Mice lacking factor B (Bf(-/-)), the initiator of the alternative pathway, were crossed with Ldlr(-/-) mice and studied under different proatherogenic conditions. There was no statistically significant difference in lipid profiles or atherosclerotic lesion development between Bf(-/-)/Ldlr(-/-) and Ldlr(-/-) mice fed a low-fat diet. However, in these groups, administration of bacterial lipopolysaccharide led to a significant increase in atherosclerosis only in Ldlr(-/-) and not in Bf(-/-)/Ldlr(-/-) mice, indicating that the alternative pathway is necessary for endotoxin-mediated atherogenesis. Bf(-/-)/Ldlr(-/-) mice also had significantly decreased cross-sectional aortic root lesion fraction area and reduced lesion complexity compared with Ldlr(-/-) animals after a 12-week period of high-fat diet, although this was also accompanied by reduced levels of serum cholesterol. Under both experimental conditions, the atherosclerotic changes in the Bf(-/-)/Ldlr(-/-) mice were accompanied by a marked reduction in complement activation in the circulation and in atherosclerotic plaques, with no statistically significant differences in immunoglobulin G deposition or in the serum antibody response to oxidized low-density lipoprotein. These data demonstrate that amplification of complement activation by the alternative pathway in response to lipopolysaccharide or high-fat diet plays a proatherogenic role.


A Facile Strategy for Preparation of Yttrium-90 Therapeutic Sources for Radionuclide Therapy.
Background: Mold brachytherapy using high-energy β--emitting radioisotopes is a promising treatment modality for skin cancers and keloids. Simple methodologies for consistent and stable incorporation of radionuclides into the matrix are desired for preparation of therapeutic sources. Methods: The authors report a facile strategy for the stable incorporation of Yttrium-90 (90Y) into amidoxime-functionalized polyacrylonitrile-polyvinylidene fluoride (PAN-PVDF) membranes. The strategy consisted of surface modification of PAN-PVDF membranes by reaction with hydroxylamine, characterization of the functionalized membranes, and optimization of experimental variables for maximum loading of 90Y onto the membranes. Quality control tests essential for confirming the suitability of the 90Y therapeutic sources for human application, such as uniformity of activity distribution, absence of leaching of activity, and estimation of surface contamination, were performed. Theoretical calculations to estimate the dose imparted by the 90Y therapeutic sources at varying depths of tissue were also carried out to predict the possible therapeutic outcome of treatment. Results: A facile method for large-scale preparation of 90Y-based mold brachytherapy sources could be established. Conclusions: The source fabrication methodology standardized in this work could be tailored for fabrication of custom-made 90Y sources for individualized treatment of superficial tumors, Bowen's disease, and keloids.


Combined catheter ablation for atrial fibrillation and Watchman® left atrial appendage occlusion procedures: Five-year experience.
Patients with atrial fibrillation (AF) may benefit from undergoing concomitant interventions of left atrial catheter ablation and device occlusion of the left atrial appendage (LAA) as a two-pronged strategy for rhythm control and stroke prevention. We report on the outcome of combined procedures in a single center case series over a 5-year timeframe. Ninety-eight patients with non-valvular AF and a mean CHA2DS2-VASc score 2.6±1.0 underwent either first time, or redo pulmonary vein isolation (PVI) procedures, followed by successful implant of a Watchman® device. All procedures were generally uncomplicated with a mean case time of 213±40 min. Complete LAA occlusion was achieved at initial implant in 92 (94%) patients. Satisfactory LAA occlusion was achieved in 100% of patients at 12 months, with a complete LAA occlusion rate of 86%. All patients discontinued oral anticoagulation. Persistent late peri-device leaks were more frequently associated with device angulation or shoulder protrusion, and were associated with a significantly lower achieved device compression of 12±3% vs. 15±5% (p<0.01) than complete occlusion. One ischemic stroke was recorded over a mean follow-up time of 802±439 days. Twelve months׳ freedom from detectable AF was achieved in 77% of patients. Combined procedures of catheter ablation for AF and Watchman® LAA implant appear to be feasible and safe, with excellent rates of LAA occlusion achieved and an observed stroke rate of 0.5% per year during mid-term follow-up. Incomplete occlusion was associated with lower achieved device compression and was more frequently associated with suboptimal device position.


Buccal and lingual activity during mastication and swallowing in typical adults.
A non-invasive protocol was developed to assess tongue and cheek movements during mastication and to evaluate the temporal relationship between mastication and the initiation of pharyngeal swallowing. Typical adults (three males and three females) were monitored during chewing. Miniature pressure transducers were bonded unilaterally to the buccal and lingual surfaces of the first mandibular molar and the buccal surface of the first maxillary molar on each subject's preferred chewing side. Surface electromyography of the ipsilateral masseter muscle was recorded as an indicator of jaw-closing activity. Pressure and electromyography (EMG) recordings were time-linked to simultaneous B-mode ultrasound imaging of the oral cavity using a submental, coronal view aligned with the first mandibular molar. The intervals between peak pressure recorded at each pressure transducer and peak jaw-closing activity for each masticatory cycle were not statistically different [analysis of variance (anova), P=0.9856] and displayed large statistical variation. These intervals were not different at the beginning of the trials (hard biscuit) than they were at the completion of mastication when the cookie had been broken down to a paste/puree consistency bolus. The interval between the last chewing stroke and the initiation of swallowing was 0.92 +/- 0.34 s). No significant difference existed among subjects for this time interval (anova, P=0.382).


Synthetic peptides: managing lipid disorders.
Recent publications related to the potential use of synthetic peptides for the management of lipid disorders and their vascular complications are reviewed. The potential use of synthetic peptides for the management of lipid disorders and their vascular complications has emerged in recent years. These peptides are models of apolipoproteins, but are much smaller in size than the apolipoproteins. Oral peptides that improve the antiinflammatory properties of HDLs have been shown to potently inhibit atherosclerosis in mouse models. Injection of a peptide with a class A amphipathic helix in a rat model of diabetes dramatically reduced endothelial sloughing and improved vasoreactivity. Injected synthetic peptides have also been described that dramatically lower plasma cholesterol and restore endothelial function in a rabbit model of familial hypercholesterolemia. These studies suggest the therapeutic potential for synthetic peptides in the management of lipid disorders and their vascular complications. Synthetic peptides much smaller than exchangeable human plasma apolipoproteins but with physical and chemical characteristics similar to the plasma apolipoproteins have shown promise in the management of lipid disorders and their vascular complications in animal models. The initial success of these animal studies suggests that synthetic peptides have the potential to emerge as a new therapeutic class of agents in the management of patients with lipid disorders.


An in vitro study of the fracture resistance and the incidence ofvertical root fracture of pulpless teeth restored with six post-and-coresystems.
Posts and cores are often required with pulpless teeth to provide retention and resistance form for complete crowns. Nevertheless, conventional posts may increase the potential for root fracture. This study compared the resistance to vertical root fracture of extracted teeth treated with post-core systems that were modified with polyethylene woven fibers (Ribbond) with those treated with conventional post-and-core systems. Canal instrumentation was performed for 60 maxillary central incisors, and complete crown preparations were made. The coronal portion of each tooth was amputated, and 6 post-and-core systems were studied. Specimens were mounted in acrylic resin blocks with a layer of polyvinyl siloxane covering the roots. Loads were applied at an angle of 130 degrees and measured with a universal testing machine. Results were analyzed statistically with 1-way analysis of variance with Student-Newman-Keuls grouping and chi-square analysis. RESULTS. Cast posts and cores resulted in significantly higher failure thresholds than all others, except for prefabricated, comparably sized, parallel-sided posts with composite cores. All failures in the group with cast posts involved fracture of the teeth, whereas 70% of the teeth with comparably sized parallel-sided posts and composite cores failed as a result of tooth fractures and 30% experienced core fractures. The woven fiber post-core system was significantly lower in strength than all others, and exhibited significantly fewer vertical root fractures. Polyethylene woven fiber and composite resin without a prefabricated post resulted in significantly fewer vertical root fractures, but mean failure load was the lowest. Smaller diameter prefabricated posts combined with the polyethylene woven fiber and composite cores improved resistance to failure. Traditional cast posts and cores were the strongest of the 6 post-core systems.


Pituicyte modulation of neurohormone output.
Pituicytes have long been suspected to play a role in the regulation of neurohypophysial hormone output. This role has been mainly ascribed to morphological changes in these cells and subsequent modifications of their tight structural relationships with surrounding nerve terminals and capillaries. These entirely reversible changes are brought about by physiological states such as parturition, lactation, or dehydration, and it was inferred that they should facilitate neurohormone output, based on concerted analyses of in vitro, in situ, and ex vivo experiments. Pituicyte stellation, the in vitro counterpart of these morphological changes, can be induced by beta-adrenergic or A1-adenosine receptor activation, and appears to result from inhibition of the small GTPase RhoA. Actin depolymerization is the key event allowing stellation. Vasopressin and oxytocin reverse stellation and return pituicytes to their basal shape by activating Cdc42, another small GTPase that reorganizes the actin cytoskeleton in a cortical position. Adenosine and neurohormones also have opposite actions on the efflux of taurine, a local messenger that is released by pituicytes in hypotonic conditions and accordingly inhibits vasopressin output from axon terminals. As adenosine is likely generated from endogenous ATP co-released with neurohormones and broken down by local ectoATPases, these data suggest a subtle balance between a positive and a negative feedback on vasopressin output operated, respectively, by adenosine and vasopressin to maintain hydromineral homeostasis. A theoretical scenario is presented to account for the putative sequence of pituicyte-related events following disturbance of the hydromineral system.


The clinical course of alcohol dependence associated with a low level of response to alcohol.
To evaluate the clinical course of specific alcohol-related life problems and the risk for dependence on illicit drugs in individuals with relatively low and high levels of response (LR) to alcohol earlier in life. From among 439 men who were part of the 15-year follow-up of sons of alcoholics and controls, 108 were identified as having fulfilled criteria for DSM-III-R alcohol dependence. The LR to alcohol was originally evaluated following the consumption of 0.61 g/kg of ethanol at age 20 by determining the levels of change in subjective feelings of intoxication, body sway and several hormones such as cortisol. From the 453 original subjects, 450 completed a face-to-face 10-year follow-up evaluation, and 439 completed the 15-year protocol. A comparison of the clinical course of 50 alcohol-dependent men with clearly low LR values at age 20 with that for 42 individuals whose LR scores were above the median revealed few differences. Those with a low LR had a slightly earlier age of onset of alcohol dependence (24.8 +/- 3.41 vs. 26.6 +/- 4.48 years), and this finding was unrelated to the presence of an alcohol-dependent father. Otherwise the members of the two groups demonstrated a similar course of alcohol dependence. There was no relationship between a low LR at age 20 and either the pattern of substances used or the rate of dependence on illicit drugs. The results indicate that for this sample a low LR to alcohol, while associated with a high risk for alcohol dependence, was not related to most aspects of the course of alcohol problems once dependence developed.


Binding of antithyrotropin receptor autoantibodies in Graves' disease serum to nascent, in vitro translated thyrotropin receptor: ability to map epitopes recognized by antibodies.
The binding of Graves' disease autoantibodies and xenogeneic antibodies to the human TSH receptor (TSH-R) has been studied using receptor preparations generated in an in vitro transcription and translation reaction. The complementary DNAs encoding for the full-length (764 amino acids) and the extracellular region of TSH-R (amino acids 20-414, lacking the signal sequence) were used to generate the translated receptor antigen. Stable [35S]methionine-labeled nascent protein for full-length and extracellular regions of TSH-R of approximate size 87 and 50 kDa, respectively, together with other smaller proteins were generated. The 87- and 50-kDa translated receptor proteins react by immunoprecipitation analysis with monoclonal antibodies, polyclonal antisera, and unfractionated Graves' disease serum containing autoantibody to TSH-R. The translated products of the extracellular TSH-R were examined in detail. Using three well characterized murine monoclonal antibodies whose epitopes encompass the amino-, central, and carboxyl-terminals of the extracellular region of the receptor led to immunochemical identification of the smaller translated products to derive from internal methionine start sites of TSH-R. These smaller, N-terminal-truncated translated proteins were also recognized by polyclonal antisera generated against recombinant TSH-R, thus allowing epitope mapping of some antibodies. A large proportion of Graves' disease autoantibodies (> 70%) bind to the translated extracellular region of TSH-R. This indicates that the majority of pathogenic anti-TSH-R autoantibody binds the nascent translated extracellular region of TSH-R, which is not influenced by the lack of glycosylation of the receptor.


Effect of obesity on coronary collateral vessel development in patients with coronary artery disease.
The purpose of this study was to compare coronary collateral circulation and with other risk factors in patients with coronary artery disease and different body mass index. Between January 1999 and December 2001, of 867 patients who underwent angiography for the first time, 90 patients (24 women and 66 men), with occlusion in only 1 coronary artery participated in the study. Information regarding age, body mass index, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia, preinfarction angina, and use of oral beta blockers and nitrates were recorded for all patients. The patients were separated into 2 groups in accordance with development of their coronary collateral circulation; those with insufficient (Rentrop 0, 1, and 2) and those with sufficient coronary collateral circulation. They were also divided into 3 groups on the basis of body mass index as follows: (I) 18.0-24.9 kg/m(2), (II) 25.0-29.9 kg/m(2), and (III) more than 30 kg/m(2). In the obesity and overweight groups, hyperlipidemia, diabetes mellitus, and nitrate use were identified more frequently than in the other groups (p < 0.05). Use of oral nitrates more than 6 months before the myocardial infarction and existence of preinfarction angina affected collateral coronary vessel development in the positive direction (p = 0.01, p = 0.03, respectively). There was no correlation between coronary artery disease and coronary collateral vessel development in the obese patients (p = 0.6). Although it has been shown that coronary collateral vessel development was affected negatively in obese patients with coronary artery disease, no statistical significance was identified.


Effects of postchill application of acidified sodium chlorite to control Campylobacter spp. and Escherichia coli on commercial broiler carcasses.
Experiments were performed to assess the reduction of Campylobacter spp. and Escherichia coli in commercial broiler carcasses by postchill dip applications of acidified sodium chlorite. Carcass rinses were collected before the inside-outside-bird washer (IOBW), post-IOBW, postchill, and after the postchill application of acidified sodium chlorite. Prevalence and counts of Campylobacter spp. and E. coli were determined. The mean values for Campylobacter spp. and E. coli counts differed significantly at sampling sites. The IOBW reduced the bacterial counts significantly in only one experiment. The chiller reduced Campylobacter counts significantly in both experiments but failed to significantly reduce the counts of E. coli in one experiment. No major reduction in the prevalence after enrichment for Campylobacter spp. was detected post-IOBW or postchill. However, a significant reduction in Campylobacter spp. and in E. coli counts and Campylobacter spp. prevalence was seen after the postchill application of acidified sodium chlorite. These results demonstrate that the antimicrobial effect of acidified sodium chlorite applied postchill may be used to significantly reduce Campylobacter spp. and E. coli in commercial broiler carcasses. Postchill systems may eventually be used in different applications, such as mist, spray, or bath, which could be applied closer to the final stages in processing.


Efficacy of a Subcutaneous Implantable Cardioverter Defibrillator in a Child with Early Repolarization Syndrome.
An early repolarization (ER) pattern or J waves are considered to be a benign finding observed in the healthy population, however, it has been pointed out that the ER pattern seen in the inferolateral leads could be an independent risk factor for fatal arrhythmias. We present a pediatric case in which early repolarization syndrome (ERS) was suspected due to the presence of ER or J waves in the inferior leads, which eventually disappeared after the administration of pilsicainide. During the follow-up period, several fatal ventricular arrhythmias were recorded after implantation of a subcutaneous implantable cardiac defibrillator (S-ICD). This report describes the efficacy of S-ICDs in a child with an ER pattern after aborted sudden cardiac death.


[Effect of advanced glycosylation end products on oxidative stress and MCP-1 in human renal mesangial cells].
To investigate the effects of advanced glycosylation end products (AGEs) modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs). HRMCs were cultured in vitro with medium containing different doses of AGE-BSA or BSA (50,100, 200, 400 mg/L) for 48 hours, or with AGE-BSA (200 mg/L) for different times (12, 24, 48, 72 h). Immunocytochemistry assay was used to estimate the protein level of RAGE. The ROS in cells were measured by flow cytometry and the mRNA expression of MCP-1 were analyzed by semi-quantiative reverse transcription-polymerase chain reaction (RT-PCR) after treatment with AGE-BSA or BSA. The protein level of RAGE was upregulated in the HRMCs with AGE-BSA. The expression of ROS and MCP-1 significantly enhanced by incubation of AGE-BSA in a time- and dose-dependent manner. The effects of AGE-BSA-induced up-regulation of ROS and MCP-1 level was significantly blocked by neutralizing antibodies to RAGE, while the expression of ROS and MCP-1 stood nearly unchanged after cultured with huamn IgG. The expression of ROS and MCP-1 in HRMCs is induced by AGE-BSA through RAGE, which may have potential effects in the pathgenic mechanism of diabetic nephropathy.


In vitro analysis of roles of a disulfide bridge and a calcium binding site in activation of Pseudomonas sp. strain KWI-56 lipase.
The expression of lipase from Pseudomonas sp. strain KWI-56 (recently reclassified as Burkholderia cepacia) had been found to be dependent on an activator gene (act) downstream of its structural gene (lip). In this work, the mature lipase was synthesized in an enzymatically active form with a cell-free Escherichia coli S30 coupled transcription-translation system by expressing a recombinant lipase gene (rlip) encoding the mature lipase in the presence of its purified activator or by coexpression of rlip and act. The in vitro expression systems were used for studying the folding process of the lipase. The addition of dithiothreitol in the expression systems decreased the activity dramatically without affecting the synthesis level of the lipase, whereas the in vitro-synthesized active lipase was relatively stable even in the presence of dithiothreitol. This phenomenon was further investigated by constructing mutant lipase genes only in vitro by PCR without gene cloning. Replacements of cysteine residues (Cys190 and Cys270) forming a sole putative disulfide bond to serine residues decreased the lipase activity greatly, suggesting that the disulfide bond was essential for the proper folding of the lipase. In addition, replacing Asp242 and Asp288, which were deduced to be part of a Ca(2+) binding site, also greatly decreased the activities of the in vitro-synthesized lipases. The role of the Ca(2+) binding site in the activation of the lipase is also discussed.


Surgical antimicrobial prophylaxis in intensive care unit (ICU) patients: a preliminary, observational, retrospective study.
Surgical antimicrobial prophylaxis (SAP) is supported by evidence-based guidelines. Nevertheless, SAP guidelines do not cover all clinical scenarios. To our knowledge, no information is available regarding SAP in the critically ill patients. We designed a retrospective, observational and preliminary study which the objective was to describe our professional practices in intensive care unit (ICU) patients requiring SAP. All patients admitted for more than 48 h in the ICU and requiring surgery were retrospectively included from January 1st to December 31, 2016. We collected data related to infection, colonization and antimicrobial treatments pre- and post-operatively. We assessed the compliance of SAP to guidelines. Among 41 included patients, 13 (32%) were treated for an ongoing infection and 21 (51%) received at least one antibiotic during the ICU stay. Seven (17%) were colonized. Twenty-one (51%) patients received SAP according to guidelines. Thirteen postoperative infections including 1 surgical site infection were reported. For 10 (24%) patients, the ongoing antimicrobial treatment was continued in the operating room. No surgical site infection and 1 lung infection was reported. In 3 (7%) patients, no SAP was administered and 1 episode of bacteremia was noted. Three (7%) patients had their ongoing treatment changed in the operating room. Two of them developed a lung infection. The other patients were assessed individually due to complex conditions. These preliminary data showed a large heterogeneity in the management of SAP in the ICU, suggesting the need for specific guidelines based on clinical trials.


Uniform presentation of process evaluation results facilitates the evaluation of complex interventions: development of a graph.
Process evaluation is a highly essential element for the increasing number of studies regarding multi-component interventions. Yet, researchers are challenged to collect and present appropriate process outcomes in such way that it is easy and valuable to be used by other researchers and policy makers in interpreting and comparing intervention effects because of the absence of standards for conducting and publishing process evaluation. This article describes the development of a method to concisely summarize the results of process evaluations of complex multi-component interventions. Development of a graph with the aim to facilitate the reporting of process evaluation's results, based on a narrative review of the literature for process measures used in complex interventions for elderly people. Seventeen articles of process evaluations alongside effect studies of complex interventions were reviewed. From these articles, it was found that process evaluations should address whether the intervention (1) was implemented successfully; (2) was evaluated properly; and (3) can be continued in the future. A flow chart based on the essential components of an adequate process evaluation was developed. A simplified but highly informative figure reporting a summary of the results of the process evaluation is proposed and its use is explained by administering the figure to two studies including a process and effect evaluation of a complex intervention. A graphical approach - which includes the core results of process evaluation and can be used directly in reporting effectiveness studies - will help researchers and policy makers to interpret and compare effects of complex multi-component interventions.


Successful treatment of extensive intestinal perforations from Behcet's disease involving the whole gut: a case report.
Intestinal perforation resulting from Behcet's disease has been previously well recognized. To date, fewer than 100 cases of this nature have been reported. Nearly the entire digestive system can be involved, including esophageal, gastric, duodenal, ileum, colon and anal tissues. Most of the reported perforations are single or assembled. Herein, an 8-year-old Chinese girl who developed Behcet's disease with extensive intestinal perforations throughout the gut was successfully treated and is presented. The diagnosis of Behcet's disease was established based on the typical presentations of recurrent oral aphthous ulcers, genital ulcers, typical eye lesions and a positive skin prick test. The extensive intestinal perforations were confirmed by laparotomy. Taking her developmental requirements into consideration, a simple perforation repair was carried out, followed by routine administration of immunosuppressive treatment, and the symptoms were temporarily relieved. Unfortunately, another ileocecal perforation occurred after 1.5 years, and an ileocolectomy was carried out. After the procedure, the girl recovered well. Clinicians should be aware of Behcet's disease as a unique source of intestinal perforation. Although it is encountered rarely in clinical settings, this condition should be considered in each case of intestinal perforation. An ileocolectomy was the necessary choice for radical treatment, even in the case of a pediatric patient.


Discovery of runs-of-homozygosity diplotype clusters and their associations with diseases in UK Biobank.
Runs of homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE, to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number of individuals, in large cohorts. ROH-DICE identified over 1 million ROH diplotypes that span over 100 SNPs and shared by more than 100 UK Biobank participants. Moreover, we found significant associations of clustered ROH diplotypes across the genome with various self-reported diseases, with the strongest associations found between the extended HLA region and autoimmune disorders. We found an association between a diplotype covering the HFE gene and haemochromatosis, even though the well-known causal SNP was not directly genotyped nor imputed. Using genome-wide scan, we identified a putative association between carriers of an ROH diplotype in chromosome 4 and an increase of mortality among COVID-19 patients. In summary, our ROH-DICE method, by calling out large ROH diplotypes in a large outbred population, enables further population genetics into the demographic history of large populations. More importantly, our method enables a new genome-wide mapping approach for finding disease-causing loci with multi-marker recessive effects at population scale.


A groove technique for securing an electrode connector on the cranial bone: case analysis of efficacy.
A groove technique for securing an electrode connector was described as an alternative surgical technique in deep brain stimulation (DBS) surgery to avoid electrode connector-related complications, such as skin erosion, infection, and migration. We retrospectively reviewed 109 patients undergoing one of two techniques; the standard technique (52 patients using 104 electrodes) and the groove technique (57 patients using 109 electrodes) for securing the electrode connector in DBS surgery, regardless of patient disease. In the standard percutaneous tunneling technique, the connector was placed on the vertex of the cranial surface. The other technique, so called the groove technique, created a groove (about 4 cm long, 8 mm wide) in the cranial bone at the posterior parietal area. Wound erosion and migration related to the connectors were compared between the two techniques. The mean follow-up period was 73 months for the standard method and 46 months for the groove technique. Connector-related complications were observed in three patients with the groove technique and in seven patients with the standard technique. Wound erosion at the connector sites per electrode was one (0.9%) with the groove technique and six (5.8%) with the standard technique. This difference was statistically significant. The electrode connector was migrated in two patients with the groove technique and in one patient with the standard technique. The groove technique, which involves securing an electrode using a groove in the cranial bone at the posterior parietal area, offers an effective and safe method to avoid electrode connector-related complications during DBS surgery.


Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from chromosome 18 and associated with a reciprocal translocation involving chromosomes 17 and 18.
Prenatal diagnosis of small supernumerary marker chromosomes (sSMC) gives rise to difficulties in genetic counseling, and requires molecular cytogenetic technologies such as spectral karyotyping, fluorescence in situ hybridization, multicolor-fluorescence in situ hybridization, or array-comparative genomic hybridization to identify the nature of the aberrant chromosome. We report such a case associated with a reciprocal translocation. A 36-year-old woman, gravida 7, para 1, abortus 5, was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a reciprocal translocation between chromosomes 17q and 18q and an sSMC. The karyotype was 47,XY,t(17;18)(q11.1;q11.2), +mar. Chromosome preparations from blood lymphocytes revealed that she had the same reciprocal translocation and sSMC. Spectral karyotyping showed that the sSMC was derived from the centromeric region of chromosome 18, and there was a reciprocal translocation between chromosomes 17 and 18. The derivative chromosome 17 had positive 17p terminal (17pTEL) and chromosome 17 centromeric (cep17) signals but did not have a positive chromosome 18 centromeric signal (cep18). The derivative chromosome 18 had positive 18p terminal (18pTEL), chromosome 18 centromeric (cep18) and cep17 signals. The sSMC had only a positive cep18 signal. These findings suggested that a breakpoint occurred at 17q11.1 and another at 18q11.2 during translocation, and the sSMC originated from chromosome 18. The karyotype of the fetus was thus 47,XY,t(17;18)(q11.1;q11.2), +mar.ish der(17)t(17;18)(q11.1;q11.2)(17pTEL+,D17Z1+),der(18)t(17;18)(q11.1;q11.2)(18pTEL+,D18Z1+,D17Z1+), + der(18)(D18Z1+). Oligonucleotide-based array comparative genomic hybridization demonstrated no gain or loss of the gene dosage on chromosomes 17 and 18. Our case adds to the reported cases of sSMCs derived from the centromeric region of chromosome 18 without phenotypic consequences.


Neuro-invasion by a 'Trojan Horse' strategy and vasculopathy during intrauterine flavivirus infection.
The central nervous system (CNS) is a major target of several important human and animal viral pathogens causing congenital infections. However, despite the importance of neuropathological outcomes, for humans in particular, the pathogenesis, including mode of neuro-invasion, remains unresolved for most congenital virus infections. Using a natural model of congenital infection with an RNA virus, bovine viral diarrhoea virus in pregnant cattle, we sought to delineate the timing and mode of virus neuro-invasion of and spread within the brain of foetuses following experimental respiratory tract infection of the dams at day 75 of pregnancy, a time of maximal risk of tissue pathology without foetal death. Virus antigen was first detected in the foetal brains 14 days postinfection of dams and was initially restricted to amoeboid microglial cells in the periventricular germinal layer. The appearance of these cells was preceded by or concurrent with vasculopathy in the same region. While the affected microvessels were negative for virus antigen, they expressed high levels of the type I interferon-stimulated protein ISG15 and eventually disappeared in parallel with the appearance of microcavitary lesions. Subsequently, the virus spread to neurons and other glial cells. Our findings suggest that the virus enters the CNS via infected microglial precursors, the amoeboid microglial cells, in a 'Trojan horse' mode of invasion and that the microcavitary lesions are associated with loss of periventricular microvasculature, perhaps as a consequence of high, unrestricted induction of interferon-regulated proteins.


The Portuguese Model of Home Respiratory Care: Healthcare Professionals' Perspective.
Patients' and carers' views regarding the Portuguese model of home respiratory care were recently described, yet the complementary perspective of healthcare professionals (HCPs) is still to be investigated. Thus, this study explored HCPs experience in the management of patients needing home respiratory therapies (HRT), and their perspective about the Portuguese model. A phenomenological descriptive study, using focus groups, was carried out with 28 HCPs (median 42 y, 68% female) with distinct backgrounds (57% pulmonologists, 29% clinical physiologists, 7% physiotherapists, 7% nurses). Three focus groups were conducted in three regions of Portugal. Thematic analysis was performed by two independent researchers. HCPs have in general a positive view about the organization of the Portuguese model of home respiratory care, which was revealed in four major topics: Prescription (number of references, n = 171), Implementation and maintenance (n = 162), Carer involvement (n = 65) and Quality of healthcare (n = 247). Improvements needed were related to patients' late referral, HRT prescription (usability of the medical electronic prescription system and renewals burden), patients' education, access to hospital care team, lack of multidisciplinary work and articulation between hospital, primary and home care teams. This study describes the perspective of HCPs about the Portuguese model of home respiratory care and identifies specific points where improvements and reflections are needed. This knowledge may be useful to decision makers improve the current healthcare model.


Nuclear factor I-C is essential for odontogenic cell proliferation and odontoblast differentiation during tooth root development.
Our previous studies have demonstrated that nuclear factor I-C (NFI-C) null mice developed short molar roots that contain aberrant odontoblasts and abnormal dentin formation. Based on these findings, we performed studies to elucidate the function of NFI-C in odontoblasts. Initial studies demonstrated that aberrant odontoblasts become dissociated and trapped in an osteodentin-like mineralized tissue. Abnormal odontoblasts exhibit strong bone sialoprotein expression but a decreased level of dentin sialophosphoprotein expression when compared with wild type odontoblasts. Loss of Nfic results in an increase in p-Smad2/3 expression in aberrant odontoblasts and pulp cells in the subodontoblastic layer in vivo and primary pulp cells from Nfic-deficient mice in vitro. Cell proliferation analysis of both cervical loop and ectomesenchymal cells of the Nfic-deficient mice revealed significantly decreased proliferative activity compared with wild type mice. In addition, Nfic-deficient primary pulp cells showed increased expression of p21 and p16 but decreased expression of cyclin D1 and cyclin B1, strongly suggesting cell growth arrest caused by a lack of Nfic activity. Analysis of the pulp and abnormal dentin in Nfic-deficient mice revealed an increase in apoptotic activity. Further, Nfic-deficient primary pulp cells exhibited an increase in caspase-8 and -3 activation, whereas the cleaved form of Bid was hardly detected. These results indicate that the loss of Nfic leads to the suppression of odontogenic cell proliferation and differentiation and induces apoptosis of aberrant odontoblasts during root formation, thereby contributing to the formation of short roots.


Identification and detection of genetically modified papaya resistant to papaya ringspot virus strains in Thailand.
Many lines of genetically modified (GM) papaya (Carica papaya Linnaeus) have been developed worldwide to resist infection from various strains of papaya ringspot virus (PRSV). We found an unidentified and unauthorized GM papaya in imported processed papaya food. Transgenic vector construct that provides resistance to the PRSV strains isolated in Thailand was detected. An original and specific real-time polymerase chain reaction method was generated to qualitatively detect the PRSV-Thailand-resistant GM papaya.


[Role of pharmacists in the medical team--attempting palliative care].
The Pharmacy Department at our hospital is attempting to develop methods for palliative care, for example of cancer pain or smelly tumors. The participation of pharmacists on the medical team for home care is necessary, because the supply of proper drugs for patients' individual conditions is indispensable in palliative care. Communication between not only patients, but also between their families and us, as well as the maintenance of close contact with the medical team, are important in home care.


Target ability and therapy efficacy of immunoliposomes using a humanized antihepatoma disulfide-stabilized Fv fragment on tumor cells.
Recently the use of peptides in bee venom (PBV) for cancer therapy has attracted considerable attention. However, PBV's extensive use is prohibited by its intense hemolytic activity. In this study, the sterically stabilized liposomal PBV (PBV-SL) was prepared using soybean phosphatidylcholine, cholesterol, and cholesterol-PEG-COOH. The humanized antihepatoma disulfide-stabilized Fv (hdsFv25) was reengineered, expressed, and coupled to sterically stabilized liposomes using the N-hydroxysuccinimide ester method. The hdsFv25-immunoliposomes (SIL [hdscFv25]) were immunoreactive as determined by ELISA assay. PBV-SIL [hdscFv25] can kill SMMC-7721 cells in vitro with higher efficiency than nontargeted liposomes. PBV-SIL [hdsFv25] displayed high antitumor activity and resulted in a significant reduction in tumor size compared to nontargeted liposomes and PBV. These results indicated that this strategy should be applicable to applicable in the treatment of other cancers.


Abundant apoptosis in nutmeg liver of cardiomyopathic hamsters. Apoptotic cell death as a possible mechanism of hepatic remodeling by congestion.
Chronic congestive heart failure (CHF) causes structural remodeling of the liver, generally leading to nutmeg liver. Male UM-X7.1 hamsters, a strain developing cardiomyopathy, had no CHF and decompensated CHF (n = 6 each) at the age of 10 and 30 weeks, respectively. We used age-matched, male Syrian hamsters without CHF (n = 6 each) as controls. All the 30-week-old UM-X7.1 hamsters had a typical nutmeg liver in which the population of hepatocytes was decreased. Positive in situ nick end labeling (TUNEL) was found in 2.2 +/- 0.74% of hepatocytes in congestive livers, being significantly higher compared with the other groups without CHF (< 0.5%). DNA ladder pattern was also evident in the congestive livers. Electron microscopy revealed a typical apoptotic ultrastructure in the hepatocytes of the 30-week-old UM-X7.1 hamsters. However, many showed secondary necrotic changes. Although hepatocytes undergoing oncosis (primary necrosis) are rare, they were also found. The level of soluble Fas ligand in the plasma was increased, and Fas receptor in the liver was overexpressed in the CHF animals. In addition, both the Bax/Bcl-2 ratio and the Bad/Bcl-xL ratio were increased, and caspase-3 was activated in them. Our findings suggest that hepatocyte apoptosis contributes to hepatic remodeling under conditions of CHF.


Experimental study of vocal-ventricular fold oscillations in voice production.
Ventricular folds are located in the supraglottal region above the vocal folds. Although the ventricular folds do not vibrate under normal vocalizations, they vibrate under certain conditions, e.g., throat singing or ventricular fold dysphonia. In throat singing, the ventricular folds vibrate at the same frequency as (or at integer ratios of) the vocal fold vibration frequency. In ventricular fold dysphonia, on the other hand, the ventricular folds interfere with the vocal folds, giving rise to a hoarse voice. In the present study, the synthetic larynx model was utilized to examine the vocal-ventricular fold oscillations. Our experiments revealed that the vocal and ventricular folds can co-oscillate at the same frequency with an out-of-phase relation. Compared to the control condition, under which no ventricular folds exist, the phonation threshold pressure was increased in the presence of the ventricular folds. Acoustic analysis indicated that jitter was reduced and vocal efficiency was increased by the ventricular folds. Distance between the vocal and ventricular folds did not alter these oscillation properties. A computational model was further simulated to elucidate the mechanism underlying the observed vocal-ventricular fold oscillations. It has been suggested that out-of-phase oscillations of the vocal and ventricular folds are important for sustaining periodic laryngeal vibrations.


Donor-specific transfusion and donor bone marrow infusion in renal transplantation tolerance: a review of efficacy and mechanisms.
The ultimate goal in transplantation is modulation of the immune response to produce tolerance without immunosuppression. To date only a state of pseudotolerance for the allograft has been achieved through the use of potent pharmacologic and biologic manipulations. Despite these manipulations to prevent acute rejection, chronic rejection eventually results in graft failure. Thus, different strategies have been sought to induce tolerance and prevent acute and chronic rejection. Historically, donor-specific transfusion (DST) was one such strategy attempted. Donor-specific transfusion has been used primarily in living donor organ transplantation. With the concern that DST may sensitize patients, thereby preventing transplantation and introduction of cyclosporine, the use of DST was curtailed. More recently, donor bone marrow (DBM) infusion at the time of cadaveric transplantation has been used to facilitate development of microchimerism and tolerance to abrogate acute and chronic rejection. However, DBM infusion may predispose the recipient to graft-versus-host disease and is not easily accomplished in living donor organ transplantation. The potentially immunomodulating and tolerizing mechanisms of DST and DBM infusion are similar and include induction of anergy, stimulation of anti-anti-HLA antibodies, provision of soluble HLA antigen, suppressor cell and/or veto cell activity, clonal deletion, regulation of cell surface molecules, regulation of cytokines, promotion of microchimerism, or a combination of these. Of these mechanisms, microchimerism with the concomitant persistence of soluble donor HLA antigen is felt by many to be the most important. Although microchimerism is detectable in many patients who are tolerant of their grafts, there is no clear evidence that chimerism is responsible for the induction or maintenance of tolerance.


Chefs' opinions about reducing the calorie content of menu items in restaurants.
Modifying the energy content of foods, particularly foods eaten away from home, is important in addressing the obesity epidemic. Chefs in the restaurant industry are uniquely placed to influence the provision of reduced-calorie foods, but little is known about their opinions on this issue. A survey was conducted among chefs attending US culinary meetings about strategies for creating reduced-calorie foods and opportunities for introducing such items on restaurant menus. The 432 respondents were from a wide variety of employment positions and the majority had been in the restaurant industry for ≥ 20 years. Nearly all chefs (93%) thought that the calories in menu items could be reduced by 10-25% without customers noticing. To decrease the calories in two specific foods, respondents were more likely to select strategies for reducing energy density than for reducing portion size (P < 0.004). Low consumer demand was identified as the greatest barrier to including reduced-calorie items on the menu by 38% of chefs, followed by the need for staff skills and training (24%), and high ingredient cost (18%). The majority of respondents (71%) ranked taste as the most influential factor in the success of reduced-calorie items (P < 0.0001). The results of this survey indicate that opportunities exist for reducing the energy content of restaurant items. Ongoing collaboration is needed between chefs and public health professionals to ensure that appealing reduced-calorie menu items are more widely available in restaurants and that research is directed toward effective ways to develop and promote these items.


Increased Frontal Gamma and Posterior Delta Powers as Potential Neurophysiological Correlates Differentiating Posttraumatic Stress Disorder from Anxiety Disorders.
Posttraumatic stress disorder (PTSD) is distinct from anxiety disorders in its etiology and clinical symptomatology, and was reclassified into trauma- and stressor-related disorders in DSM-5. This study aimed to find neurophysiological correlates differentiating PTSD from anxiety disorders using resting-state quantitative electroencephalography (qEEG). Thirty-six patients with either PTSD or acute stress disorder and 79 patients with anxiety disorder were included in the analysis. qEEG data of absolute and relative powers and patients' medication status on the day of qEEG examination were obtained. Electrodes were grouped into frontal, central, and posterior regions to analyze for regional differences. General linear models were utilized to test for group differences in absolute and relative powers while controlling for medications. PTSD patients differed from those with anxiety disorders in overall absolute powers [F(5,327)=2.601, p=0.025]. Specifically, overall absolute delta powers [F(1,331)=4.363, p=0.037], and overall relative gamma powers [F(1,331)=3.965, p=0.047] were increased in PTSD group compared to anxiety disorder group. Post hoc analysis regarding brain regions showed that the increase in absolute delta powers were localized to the posterior region [F(1,107)=4.001, p=0.048]. Additionally, frontal absolute gamma powers [F(1,107)=4.138, p=0.044] were increased in PTSD group compared to anxiety disorder group. Our study suggests increased overall absolute delta powers and relative gamma powers as potential markers that could differentiate PTSD from anxiety disorders. Moreover, increased frontal absolute gamma and posterior delta powers might pose as novel markers of PTSD, which may reflect its distinct symptomatology.


Comparison of 6 and 8 hourly tobramycin dosing intervals in treatment of pulmonary exacerbations in cystic fibrosis patients.
The efficacy and toxicity of a shortened tobramycin dosing interval in the treatment of exacerbations of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis patients were evaluated prospectively. Patients ages 13 to 30 years received 34 treatment courses and were randomized by pairs to receive tobramycin administered either every 6 or 8 hours. Peak serum concentrations were adjusted to 8 to 10 micrograms/ml; thus a larger total daily dosage was administered to patients receiving tobramycin every 6 hours. The shorter dosing interval was associated with better pulmonary function at follow-up and significantly longer time before next hospital admission for a pulmonary exacerbation. During the study hospitalization there were no differences in pulmonary function tests, clinical score, sputum carriage of P. aeruginosa, toxicity or necessary length of hospitalization. A 6-hour tobramycin dosing interval was more efficacious than an 8-hour dosing interval in the treatment of cystic fibrosis patients.


Phosphorus and Zinc Are Strongly Associated with Belowground Fungal Communities in Wheat Field under Long-Term Fertilization.
Belowground fungi are closely related to crop growth, and agricultural fertilization is widely known to affect soil fungal communities. Yet it remains unclear whether fungal communities in differing belowground habitats-root endosphere, rhizosphere soil, and bulk soil-respond differently to long-term fertilization. Here we investigated the variation in fungal communities of root endosphere, rhizosphere soil, and bulk soil under 35 years of fertilization in wheat fields. Specifically, the fertilization regimes were applied as five treatments: soils receiving NPK fertilizer, NPK and cow manure (NPK+CM), NPK and pig manure (NPK+PM), NPK and wheat straw (NPK+WS), and no fertilizer (Control). Long-term fertilization significantly impacted fungal community composition in all three habitats, and these effects were stronger in the rhizosphere and bulk soils than root endosphere. Mantel test results showed that fungal community composition was significantly correlated with phosphorus and zinc contents. Further, fungal alpha diversity was lowest in the NPK+PM treatment and was negatively correlated with both phosphorus and zinc contents. Moreover, NPK+PM treatment had the lowest complexity of fungal co-occurrence network, and in general network complexity was significantly negatively correlated with the zinc and phosphorus contents. Taken together, these results suggest that long-term fertilization can impact fungal communities not only in soils but in root endosphere, and this is strongly associated with the contents of phosphorus and zinc there, a finding important for guiding fertilization management practices and supporting sustainable agriculture. IMPORTANCE Fungi, an essential component in nutrient cycling and plant growth, are highly sensitive to fertilization. However, there are limited studies on fungi in root endosphere under long-term fertilization management. Our research extended the study on the endophytic fungal community of crop roots under agricultural management and found that its responses were similar to the communities in soil habitats. In addition, the type of organic materials was reported as the main driver affecting soil fungal community under long-term fertilization. Our research further revealed that the underlying mechanism of affecting the fungal communities in the soils and roots was the differences in phosphorus and zinc contents caused by the application of different organic materials. Therefore, our results highlight that except for phosphorus, zinc content of the organic materials should be considered in long-term organic fertilization systems.


Circulating Tumor DNA as a Potential Marker to Detect Minimal Residual Disease and Predict Recurrence in Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death, partly due to the high recurrence rates for patients with PDAC. Current postoperative surveillance methods, including monitoring of clinical symptoms, tumor markers, and CT imaging, lack sensitivity and specificity for minimal residual disease (MRD). We investigated whether the detection of circulating tumor DNA (ctDNA) could identify MRD and predict relapse in postoperative patients with PDAC. In this study, we performed panel-captured sequencing to detect somatic mutations. Matched tissue samples were obtained to verify mutation. A total of 27 patients and 65 plasma samples were included. Among the somatic mutations, KRAS and TP53 were the most recurrent genes in both tissue and plasma samples. The detectable rate of ctDNA increased with the stage of PDAC. The maximal variant allele fraction (VAF) of ctDNA had a positive correlation with tumor largest diameter (p = 0.0101). Patients with ctDNA-positive status postoperatively had a markedly reduced disease-free survival (DFS) compared to those with ctDNA-negative status (HR, 5.20; p = 0.019). Positive vascular invasion significantly influenced disease-free survival (DFS) (p = 0.036), and positive postoperative ctDNA status was an independent prognostic factor for DFS (HR = 3.60; 95% CI, 1.15-11.28; p = 0.028). Postoperative ctDNA detection provides strong evidence of MRD and identifies patients with a high risk of relapse. ctDNA detection is a promising approach for personalized patient management during postoperative follow-up.


Motivation and fertility control behaviour in Pakistan.
Using data from the Population, Labor Force, and Migration (PLM) Survey of 1979-80, this paper examines the component of potential motivation for fertility limitation among Pakistani married women and then determines what factor are important in explaining the contraceptive use differentials among the potentially motivated subgroup of women. The analysis is conducted using logit regression models. The findings show that, among women wanting no additional children, a substantial proportion is reluctant to adopt fertility control behavior, confirming the existence of latent demand for contraception in all strata. A majority of those women report no exposure to the program or no contact with a family planning worker, and a large majority of those who have had exposure or have been contacted do not report contraceptive use, indicating a considerable shortfall of the program. Among the urban women wanting no more children, the important factors affecting contracepting use positively are education (both primary and secondary), household income, living in a nuclear family, exposure to the program, and contact with a family planning worker, for rural women, only nuclear family living and the program factors are significant in promoting contraceptive use. The suggestions likely to increase contraceptive prevalence are, first, to reach those women who have the potential motivation for contraception, and, second, to increase the quality and sources of the motivation efforts of the program to crystallize the latent demand among those who need it.


Molecular identification and antimicrobial activities of some wild Egyptian mushrooms: Bjerkandera adusta as a promising source of bioactive antimicrobial phenolic compounds.
The discovery of potential, new cost-effective drug resources in the form of bioactive compounds from mushrooms is one way to control the resistant pathogens. In the present research, the fruiting bodies of five wild mushrooms were collected from Egypt and identified using internal transcribed spacer region (ITS) of the rRNA encoding gene and their phylogenetic relationships, antimicrobial activities, and biochemical and phenolic compounds were evaluated. The sequences revealed identity to Bjerkandera adusta, Cyclocybe cylindracea, Agrocybe aegerita, Chlorophyllum molybdites, and Lentinus squarrosulus in which Cyclocybe cylindracea and Agrocybe aegerita were closely related, while Chlorophyllum molybdites was far distant. Cyclocybe cylindracea and Agrocybe aegerita showed 100% similarity based on the sequenced ITS-rDNA fragment and dissimilar antimicrobial activities and chemical composition were detected. Bjerkandera adusta and Cyclocybe cylindracea showed strong antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Micrococcus luteus, Streptococcus pneumoniae, and Candida albicans. This activity could be attributed to the detected phenolic and related compounds' contents. Our finding provides a quick and robust implement for mushroom identification that would facilitate mushroom domestication and characterization for human benefit.


Expression of cyclooxygenase-2 in intestinal goblet cells of pre-diabetic NOD mice.
Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is expressed in constitutive (COX-1) and inducible (COX-2) isoforms. The COX-2 has been proposed to be involved in development of autoimmune type 1 diabetes (T1D). We examined COX-2 expression in the gut-associated lymphoid tissue (GALT), and found COX-2 was strongly expressed in goblet cells of non-obese diabetic (NOD) mice at the apical villi at the age of 2.5 weeks, clearly before the onset of insulitis, while the expression in the control BALB/c mice was weak or absent at all ages (P < 0.001). Lipopolysaccharide (LPS) given intraperitoneally slightly increased COX-2 expression in the goblet cells and epithelium of both NOD and BALB/c mice. High-resolution confocal microscopy showed that the surroundings of the goblet cells contained no COX-2, implying that the enzyme is synthesized by the goblet cells. The COX-2 is secreted from goblet cells into the intestinal lumen along with mucins. The COX-2 concentration in the goblet cell of BALB/c and especially of NOD mice was markedly higher than that in the intraepithelial lymphocytes or lamina propria macrophages. High mucin COX-2 from goblet cells may increase luminal prostaglandin synthesis, alter epithelial permeability, modulate intestinal immune responses and modify functional properties of the lymphocytes in the GALT, which all may be important for the initiation of the autoimmune phenomenon in the NOD mice.


Pain and other cardinal TMJ dysfunction symptoms: a longitudinal survey of Japanese female adolescents.
Longitudinal data were obtained for 4 years from 361 Japanese high school girls between the ages of 12 and 16. The data were analysed for the occurrence of pain and its associations with the occurrence of other cardinal TMJ dysfunction symptoms and occlusal states. It was determined that even if pain or noise or jaw-deviation symptoms appeared, those symptoms did not necessarily last thereafter. The symptoms were not persistent but rather appeared and disappeared repetitively. Those who exhibited noise during at least one of the surveys of the 4-year survey period showed a significantly higher prevalence of pain than those who did not exhibit noise at all (P < 0.05). Those who exhibited noise by the age of 13 showed a significantly higher prevalence of pain than those who exhibited noise after age 14 (P < 0.1). The temporal occurrence of pain depended upon the appearance of noise and the age at which noise first appeared. On the other hand, the occurrence of pain symptoms was not necessarily related to specific types of malocclusions, which suggests the significance of multifactorial contributions in understanding the aetiology of pain rather than the occlusal factor.


Vacuole/Extravacuole distribution of soluble protease in hippeastrum petal and triticum leaf protoplasts.
The subcellular distribution of soluble protease in anthesis-stage, anthocyanin-containing Hippeastrum cv. Dutch Red Hybrid petal protoplasts has been reevaluated and that of Triticum aestivum L. var. Red Coat leaf protoplasts determined using (125)I-fibrin as a protease substrate and improved methods for protoplast and vacuole volume estimation. Results indicate that about 20% of the Hippeastrum petal-soluble protease and about 90% of the wheat leaf-soluble protease can be assigned to the vacuole. Protoplast isolation enzyme labeled with (125)I has been used to assess the efficiency of removing isolation enzyme from protoplasts by repeated washing and by separation of protoplasts from debris using density centrifugation. Results of these studies suggest that protoplasts prepared by both methods retain low levels of isolation enzyme. However, when protoplasts prepared by either method were lysed with washing medium lacking osmoticum, little isolation enzyme contaminated the lysates.


Building academic-practice partnerships: the Center for Public Health Preparedness at the Columbia University Mailman School of Public Health, before and after 9/11.
The Center for Public Health Preparedness at the Columbia University Mailman School of Public Health is part of a national network of academic centers established by the Centers for Disease Control and Prevention to strengthen links between public health practice and academe, especially for public health workforce development. Since its inception in Fall 2000, the Center has been working in partnership with the New York City Department of Health & Mental Hygiene (DOHMH) on planning and competency-based training in emergency preparedness (including bioterrorism and infectious diseases) and evaluation. Initial programs with DOHMH included development of a 3-hour orientation to basic emergency preparedness for their workforce. In the wake of 9/11 and the anthrax events, Center members gave over two dozen presentations at community forums, seminars, and clinical rounds, and over 100 press interviews, provided lay language information through community forum presentations and the School's Web site, and developed a database of volunteers for surge capacity. Subsequent programs include bioterrorism response training for clinicians and emergency medical services personnel, incident command for public health, and a study of evacuation from the World Trade Center on 9/11.


Rapidly progressive severe vascular calcification sparing the kidney allograft following warfarin initiation.
We describe a case of rapid onset of vascular calcification coincident with the initiation of warfarin therapy in a kidney transplant recipient. Calcification developed within the media of the blood vessel wall, with relative intimal sparing. Medium and small arteries were affected; however, the aorta was mostly free of calcifications, suggesting a differential response to warfarin between the intima and media and between different vascular beds. In addition, unlike the highly calcified native kidney's vessels, the kidney allograft was not calcified, suggesting local genetically determined mechanisms in preventing vascular calcification. Distal subcutaneous necrosis ultimately led to the patient's death.


A Case of Mesenchymal Hamartoma of the Chest Wall in a 4-Month-Old Infant.
BACKGROUND Mesenchymal hamartoma of the chest wall is a rare benign lesion that typically presents in early infancy. However, the clinical presentation can be atypical, with imaging features that mimic infection or malignancy. Imaging combined with histopathology is essential in the diagnosis. A case of mesenchymal hamartoma of the chest wall in a 4-month-old infant is presented. CASE REPORT A 4-month-old infant had an incidental finding of a large right-sided chest wall mass. Initial imaging included thoracoabdominal ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Histology of an initial open biopsy was inconclusive. The diagnosis of mesenchymal hamartoma was confirmed by histology of the resection specimen, which showed a benign, mixed, chondroid, mesenchymal, and cystic hamartoma with areas of calcification and ossification. CONCLUSIONS This case showed that the diagnosis of mesenchymal hamartoma of the chest wall, which is characterized by heterogeneous components, may require a combined approach for the diagnosis that includes imaging and histology. Increased clinical awareness of mesenchymal hamartoma in infants may help to guide the approach to the correct diagnosis and prevent unnecessarily radical treatment for this benign condition.


Approach to Limb Weakness.
"Approach to limb weakness" provides an overview of the pathways of the motor system and the type of weakness seen with pathology at each level from the cortex to the muscle. This article provides the clinical pearls needed to identify different patterns of weakness and accurately localize the level of weakness. It offers important pointers that help distinguish among the different etiologies of weakness at each level, as well as various diagnostic approaches and treatments of diseases that lead to limb weakness. The diagnoses discussed are meant to be representative and not exhaustive, as a complete differential for each pattern of weakness is beyond the scope of this article.


Evaluation of Serologic Cross-Reactivity Between Dengue Virus and SARS-CoV-2 in Patients with Acute Febrile Illness - United States and Puerto Rico, April 2020-March 2021.
The diagnosis of dengue disease, caused by the dengue virus (DENV) (a flavivirus), often requires serologic testing during acute and early convalescent phases of the disease. Some symptoms of DENV infection, such as nonspecific fever, are similar to those caused by infection with SARS-CoV-2, the virus that causes COVID-19. In studies with few COVID-19 cases, positive DENV immunoglobulin M (IgM) results were reported with various serologic tests, indicating possible cross-reactivity in these tests for DENV and SARS-CoV-2 infections (1,2). DENV antibodies can cross-react with other flaviviruses, including Zika virus. To assess the potential cross-reactivity of SARS-CoV-2, DENV, and Zika virus IgM antibodies, serum specimens from 97 patients from Puerto Rico and 12 U.S.-based patients with confirmed COVID-19 were tested using the DENV Detect IgM Capture enzyme-linked immunosorbent assay (ELISA) (InBios International).* In addition, 122 serum specimens from patients with confirmed dengue and 121 from patients with confirmed Zika virus disease (all from Puerto Rico) were tested using the SARS-CoV-2 pan-Ig Spike Protein ELISA (CDC).† Results obtained for DENV, Zika virus IgM, and SARS-CoV-2 antibodies indicated 98% test specificity and minimal levels of cross-reactivity between the two flaviviruses and SARS-CoV-2. These findings indicate that diagnoses of dengue or Zika virus diseases with the serological assays described in this report are not affected by COVID-19, nor do dengue or Zika virus diseases interfere with the diagnosis of COVID-19.


The effect of condoms on penile vibrotactile sensitivity thresholds in young, heterosexual men.
Investigating the ways in which barrier methods such as condoms may affect penile sensory thresholds has potential relevance to the development of interventions in men who experience negative effects of condoms on sexual response and sensation. A quantitative, psychophysiological investigation examining the degree to which sensations are altered by condoms has, to date, not been conducted. The objective of this study was to examine penile vibrotactile sensitivity thresholds in both flaccid and erect penises with and without a condom while comparing men who do and those who do not report condom-associated erection problems (CAEP). Penile vibrotactile sensitivity thresholds were assessed among a total of 141 young, heterosexual men using biothesiometry. An incremental two-step staircase method was used and repeated three times for each of four conditions. Intra-class correlation coefficients (ICCs) were calculated for all vibratory assessments. Penile vibratory thresholds were compared using a mixed-model analysis of variance. Penile vibrotactile sensitivity thresholds with and without a condom, erectile function measured by International Index of Erectile Function Questionnaire, and self-reported degree of erection. Significant main effects of condoms (yes/no) and erection (yes/no) were found. No main or interaction effects of CAEP were found. Condoms were associated with higher penile vibrotactile sensitivity thresholds (F[1,124] = 17.11, P < 0.001). Penile vibrotactile thresholds were higher with an erect penis than with a flaccid penis (F[1,124] = 4.21, P = 0.042). The current study demonstrates the feasibility of measuring penile vibratory thresholds with and without a condom in both erect and flaccid experimental conditions. As might be expected, condoms increased penile vibrotactile sensitivity thresholds. Interestingly, erections were associated with the highest thresholds. Thus, this study was the first to document that erect penises are less sensitive to vibrotactile stimulation than flaccid penises.


[Clinical analysis of 31 cases with rectal prolapse undergoing modified Gant-Miwa procedure and anal encircling].
To evaluate the efficacy of modified Gant-Miwa procedure with anal encircling for adults with rectal prolapse. Clinical and follow-up data of 31 adult patients with rectal prolapse undergoing modified Gant-Miwa procedure with anal encircling procedure between September 2005 and January 2012 were retrospectively analyzed. Operations were successfully performed in these 31 cases. The mean operation time was 75 (range 50-165) minutes. The mean estimated blood loss during operation was 50 (range 20-80) ml. There were no postoperative complications, such as hemorrhage, perianal abscess, anal fistula, intra-abdominal infection, or urogenital dysfunction, while only 7 patients developed urinary retention postoperatively. Rate of postoperative constipation improvement was 61.5% (8/13) and defecation difficulty improvement was 69.6% (16/23). Twenty-eight patients received anal manometry 2 months after operation and the result showed that rectal sensation threshold and rectal maximal tolerance decreased significantly, while anal resting pressure and anal squeeze pressure did not change significantly as compared to preoperative values. Six months after operation, anal function was Kirwan grade I in 22 cases and grade II in 8 cases. During a mean postoperative follow-up of 2.5 years (3 months-6.3 years), 2 of 26 patients developed recurrent prolapse. Modified Gant-Miwa procedure with anal encircling for adults of rectal prolapse is a simple and safe procedure with low recurrence rate, minimal invasion, no serious complication and mortality, especially suitable for the elderly patients, accompanied with underlying diseases or reluctant to undergo transabdominal operation.


PII signal transduction proteins: pivotal players in post-translational control of nitrogenase activity.
The fixation of atmospheric nitrogen by the prokaryotic enzyme nitrogenase is an energy- expensive process and consequently it is tightly regulated at a variety of levels. In many diazotrophs this includes post-translational regulation of the enzyme's activity, which has been reported in both bacteria and archaea. The best understood response is the short-term inactivation of nitrogenase in response to a transient rise in ammonium levels in the environment. A number of proteobacteria species effect this regulation through reversible ADP-ribosylation of the enzyme, but other prokaryotes have evolved different mechanisms. Here we review current knowledge of post-translational control of nitrogenase and show that, for the response to ammonium, the P(II) signal transduction proteins act as key players.


Prospective study of the risk of not using prophylactic antibiotics in nasal packing for epistaxis.
There is wide variation in UK prescribing practice regarding prophylactic antibiotics for nasal packing in spontaneous epistaxis. There are few published cases of infective complications in such patients. This prospective study examined 149 consecutive patients admitted to a tertiary otorhinolaryngology centre with spontaneous epistaxis, who underwent nasal packing, over a six-month period. In the first three-month period, 78 patients were routinely prescribed prophylactic antibiotics; in the second three months, 71 patients were not routinely prescribed antibiotics. Exclusion criteria included antibiotics prescribed for unrelated pathology and post-operative epistaxis. Signs and symptoms of acute otitis media, sinusitis and toxic shock syndrome were assessed using clinical examination and a questionnaire. Fourteen of the 149 patients experienced otalgia, most commonly following posterior nasal packing. No patient in either group had evidence of any infective complication. We do not recommend the routine prescription of prophylactic antibiotics for patients undergoing nasal packing for spontaneous epistaxis.


[The feasibility study of objective evaluation of the severity of motion sickness by quantitative analysis of the facial skin color].
Objective: To explore the feasibility of applying quantitative analysis of the facial skin color to evaluate the severity of motion sickness objectively and to seek objective indicators that can reflect the severity of motion sickness. Methods: Motion sickness was induced in 51 male adult subjects recruited at the Air Force Medical University by Coriolis acceleration stimulation, and facial skin colorimetric values were acquired using a portable spectrophotometer at five time points: before stimulation and at 0 min, 10 min, 20 min and 30 min after the end of stimulation. The Graybiel rating scales were applied to assess the severity of motion sickness in subjects at each time point after stimulation, and the correlation between the magnitude of change in each colorimetric value and the maximum Graybiel's score was analyzed. The ROC curves were used to compare the evaluation performance of colorimetric value indicators which could reflect the severity of motion sickness. Results: Each colorimetric value in the CIE-L*a*b* color system changed significantly after exposure to provocative motion stimuli, and the trend was consistent with the typical sign of pallor in motion sickness. The magnitudes of the increase in the colorimetric value CIE-L*, the decrease in CIE-a*, and the increase in CIE-b* were all significantly and positively correlated with the maximum of Graybiel's scores (r=0.490 0, P=0.000 3; r=0.549 3, P<0.000 1; r=0.540 9, P<0.000 1). Comparing the performance of three colorimetric indicators to assess the severity of motion sickness, CIE-a* had an area under the ROC curve of 0.875 0, a sensitivity of 85.71%, and a specificity of 87.50%, which was better than CIE-L* and CIE-b*. Conclusions: The CIE-L*a*b* colorimeter values can be considered as objective indicators of the severity of motion sickness, among which the colorimetric indicator CIE-a* has the most diagnostic significance, and the method of quantitative analysis of the facial skin color can provide a new reference for the objective evaluation of the severity of motion sickness.


[Vitreous and macular diseases].
We investigated the vitreous in its origin, morphology, metabolism and regeneration, and its role in various vitreomacular diseases. Focal vitreous liquefaction developed anterior to a laser induced chorioretinal scar in rabbit eyes, which suggested that a normal retina is necessary to maintain the integrity of the vitreous. We measured levels of hyaluronic acid and of the precursor of type II collagen in vitreous samples obtained by vitrectomy. Those levels declined with age in women. The precursor of type II collagen was at the same level in the samples from vitrectomy and those obtained by fluid air exchange, which suggested a persistent secretion of type II collagen into the vitreous cavity even after vitrectomy. We found a posterior precortical vitreous pocket in human autopsied eyes whose vitreous was stained with fluorescein. Using the same methods, we confirmed the presence of intravitreal fibrous membranes in the "tractus" in the anterior vitreous. In clinical studies using biomicroscopy, observations during surgery, scanning laser ophthalmoscopy, and optical coherence tomography (OCT), we clarified the role of premacular vitreous cortex which forms the posterior wall of the "pocket" in the premacular membrane and macular hole. The premacular vitreous cortex seems to be the main structure of the premacular membrane and its contraction may cause macular hole. Ring-shaped proliferation tends to develop along the outer margin of the "pocket". OCT demonstrated that some diabetic macular edema is caused by traction of the premacular vitreous cortex. Vitrectomy appear to be effective for diabetic macular edema by eliminating vitreous traction and the accumulated cytokine in the "pocket". The retina appears to have a program for vitreous metabolism throughout life, including the premacular pocket formation.


An Enhanced Sherwood Number to Model the Hydrogen Transport in Membrane Steam Reformers.
It is well known that membrane reactors are inherently two-dimensional systems in which species concentrations vary as a consequence of both the reaction and permeation across the membrane, which occurs in the direction perpendicular to that of the main gas flow. Recently, an expression for an enhanced Sherwood number was developed to describe the hydrogen concentration gradients arising in methane steam-reforming membrane reactors as a consequence of the combined effect of hydrogen production, dispersion, and permeation. Here, the analysis is developed in further detail with the aim of (i) assessing the validity of the simplifying assumptions made when developing the 1D model and (ii) identifying the operating conditions under which it is possible to employ the 1D model with the enhanced Sherwood number.


Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1-->q22.3: exclusion of GAS1 and XPA.
The peripheral neuropathy, hereditary sensory neuropathy type I (HSN-I) is an autosomal dominant degenerative disorder of sensory and motor neurons. The disease leads to distal sensory loss, distal muscle wasting and weakness, and variable neural deafness. The HSN-I locus was recently mapped to a large genetic interval on chromosome 9q22 that includes the candidate genes GAS1 and XPA. XPA mutations have been shown to cause peripheral neuropathy, and GAS1 is related to the PMP22 gene, which is critical in the pathogenesis of two other peripheral neuropathies. By undertaking extensive genetic linkage analysis within the candidate region, we have refined the HSN-I locus to a critical interval of 3-4 cM. GAS1, XPA, and several other genes that map within the interval initially identified for the disease locus have been investigated and excluded from playing a pathogenic role in HSN-I.


An analysis of 9,918 consecutive perioperative autotransfusions.
The efficacy of perioperative autotransfusion (PAT) can be evaluated by the reduction in homologous transfusion accompanying its use. An alternative approach is to evaluate the amount of blood salvaged and retransfused. An analysis of 9,918 consecutive PAT procedures in various surgical specialties revealed that the average return of autologous blood salvaged was equivalent to 2.61 units of erythrocytes ("packed cells"). Cardiac operation had the greatest average number of units recovered (4.65), while orthopedic operation had the least (1.05). This method of analysis demonstrates that significant quantities of blood can be salvaged during PAT procedures.


Evaluating recommended audiometric changes to candidacy using the speech intelligibility index.
The National Institute of Health and Care Excellence (NICE) has derived candidacy guidelines for cochlear implants in the UK based on audiometric thresholds (90 dB HL or above at 2 and 4 kHz; hereafter referred to as the 90 dB HL criteria). Recent research has proposed that these criteria should be changed to 80 dB HL at 2 and 4 kHz (hereafter referred to as the 80 dB HL criteria) in the ear to be implanted. In this study, we analysed aided SII scores derived for different hearing loss profiles falling within the current 90 dB HL criteria and equivalent profiles falling within the new 80 dB HL criteria. The aided SII scores demonstrated that the majority of potential hearing configurations falling within the new proposed 80 dB HL criteria have aided SII values of less than 0.65 (a recommended cut-off point below which there is not sufficient audibility to receive adequate benefit through hearing aids). This supports the proposed change to the 80 dB HL criterion level and also highlights the additional value of the SII score in supporting candidacy decisions for CI, especially for borderline candidates.