Assessment of the potential for pathogen dispersal during high-flow nasal therapy.

High-flow nasal therapy is increasingly used in hospitals because of its effectiveness and patient comfort. However, pathogens in the patient's nasal and oral cavities may be dispersed by forced air. This study aimed to investigate the risk of pathogen dispersal during high-flow nasal therapy. Liquid and bacterial dispersal were assessed via in-vitro experimental set-ups using a manikin. Thickened water or fresh yeast solution mimicked saliva and nasal mucus secretions. Dispersal was limited to the proximal area of the face and nasal cannula, suggesting that high-flow nasal therapy does not increase the risk of droplet and contact infection.

Removal methods of rigid stylets to minimise adverse force and tracheal tube movement: a mathematical and in-vitro analysis in manikins.

This study investigated displacement of the tracheal tube caused by different methods of intubating stylet removal, using in-vitro experiments and mathematical analysis. In the first in-vitro experiment, we measured the distance travelled by the tube tip during stylet extraction. Then, we investigated the ideal technique for stylet extraction using mathematical analysis, which would cause minimal tube displacement. Then, using a training manikin, we measured the force applied to the vocal cords and stylet extraction force during tracheal intubation. When the stylet was extracted along a straight path towards the stylet end, the distance travelled by the tube tip significantly increased as the bending angle increased. Mathematical analysis revealed that the stylet should be diagonally extracted (in the sagittal plane) at an appropriate angle, rather than along a straight path towards the direction of the stylet end. In simulated tracheal intubation, extraction force and force applied to the vocal cords both significantly increased as the bending angle increased. Compared with the 'hockey stick'-shaped stylet, the arcuate-shaped stylet resulted in reduced force. Our results indicate the potential risk for vocal cord injury when using hockey stick-shaped stylets with large bending angles.

Translocator protein 18kDa antagonist ameliorates stress-induced stool abnormality and abdominal pain in rodent stress models.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by abdominal pain and abnormal bowel habits, both of which are exacerbated by psychological stress. The translocator protein 18kDa (TSPO) is a marker of reactive gliosis in a number of central nervous system (CNS) diseases and responsible for many cellular functions, including neurosteroidogenesis. Although it has been reported that psychological stress disturbs neurosteroids levels, the pathophysiological relevance of TSPO in IBS is poorly understood. METHODS: We examined the effects of a TSPO antagonist, ONO-2952, on stress-induced stool abnormality and abdominal pain in rats, and on anxiety-related behavior induced by cholecystokinin. KEY RESULTS: Oral administration of ONO-2952 attenuated stress-induced defecation and rectal hyperalgesia in rats with an efficacy equivalent to that of a 5-HT3 receptor antagonist. In addition, ONO-2952 suppressed cholecystokinin-induced anxiety-like behavior with an efficacy equivalent to that of psychotropic drugs. On the other hand, ONO-2952 did not affect spontaneous defecation, gastrointestinal transit, visceral nociceptive threshold, and neurosteroid production in non-stressed rats even at a dose 10 times higher than its effective dose in the stress models. CONCLUSIONS AND INFERENCES: These results suggest that TSPO antagonism results in antistress action, and that ONO-2952 is a promising candidate for IBS without side effects associated with current treatment.

Comparative study of 27-gauge vs 25-gauge vitrectomy for epiretinal membrane.

PURPOSE: The purpose of this study was to compare 27-gauge (27G) with 25-gauge (25G) microincision vitrectomy in patients with epiretinal membrane (ERM).ParticipantsSeventy-four eyes of 66 patients undergoing 3-port pars plana vitrectomy using 27G or 25G instrumentation. METHODS: Seventy-four eyes of 66 patients with ERM, who underwent 27G or 25G microincision vitrectomy were prospectively evaluated. RESULTS: The mean operation time for vitrectomy was significantly longer in the 27G group than in the 25G group (9.9±3.5 vs 6.2±2.7 min, respectively, P<0.0001). No statistically significant difference was found between the two groups in terms of the mean operation time for ERM-inner limiting membrane peeling (27G vs 25G: 20.2±9.9 vs 16.1±9.3 min, P=0.14), although the time for vitreous cutting was longer in the 27G group (9.9±3.5 vs 6.2±2.7 min, respectively, P<0.0001). The flare value, intraocular pressure (IOP), and rate of hypotony 1 day after surgery did not differ between the 27G and 25G groups (flare value: 18.7 vs 17.2; IOP: 8.8 vs 9.7 mm Hg; rate of hypotony: 30 vs 35%, respectively). There was no significant difference in the surgically induced astigmatism between the two groups in the follow-up period. The mean time required for wound closure did not show a significant difference between the 27G and 25G groups (7.7 vs 8.6 weeks, respectively). CONCLUSION: The 27G system is as safe and useful for ERM vitrectomy as the 25G system. Based on its potential, further improvement of 27G instruments could result in greater efficiency.

The effects of Patent Blue dye on peripheral and cerebral oxyhaemoglobin saturations.

We measured the effect of Patent Blue dye on oxyhaemoglobin saturations after injection into breast tissue: 40 women had anaesthesia for breast surgery maintained with sevoflurane or propofol (20 randomly allocated to each). Saturations were recorded with a digital pulse oximeter, in arterial blood samples and with a cerebral tissue oximeter before dye injection and 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 min afterwards. Patent Blue did not decrease arterial blood oxyhaemoglobin saturation, but it did reduce mean (SD) digital and cerebral oxyhaemoglobin saturations by 1.1 (1.1) % and 6.8 (7.0) %, p < 0.0001 for both. The falsely reduced oximeter readings persisted for at least 2 h. The mean (SD) intra-operative digital pulse oxyhaemoglobin readings were lower with sevoflurane than propofol, 97.8 (1.2) % and 98.8 (1.0) %, respectively, p < 0.0001.

Absorption spectroscopy of gold nanoisland films: optical and structural characterization.

Nanoisland films prepared by annealing thin gold films at high temperatures were imaged using scanning electron microscopy (SEM) and atomic force microscopy, and optically characterized through absorption spectroscopy. Thin gold films of effective thicknesses 2, 5 and 7 nm annealed at 500, 700 and 900 degrees C were fabricated and studied experimentally. The measured absorption characteristics in support of theoretical calculations showed that the shapes of gold islands were partial spheres. The position of the peak absorption wavelength measured with s-polarized light or at normal incidence confirmed that the island shape grew from a near-hemisphere towards a sphere with increasing annealing temperature. The SEM images confirmed that the size of islands increased from 15 nm in diameter to 40 nm in diameter as film thickness increased from 2 to 5 nm. The affect of the index of the substrate material on absorption characteristics were also studied by comparing the absorption spectra of gold island films on quartz and LaSF15 glass substrates. The use of gold nanoisland films for preparing localized surface plasmon resonance substrates was suggested as they held advantages over the gold colloid films.

Diagnosis and treatment of obscure gastrointestinal bleeding using combined capsule endoscopy and double balloon endoscopy: 1-year follow-up study.

BACKGROUND AND STUDY AIMS: Several studies have shown the value of capsule endoscopy and double balloon endoscopy (DBE) in small-intestinal bleeding. The purpose of this study was to evaluate the impact of capsule endoscopy results on subsequent DBE examination, and the 1-year clinical outcome of this combined approach in patients with obscure gastrointestinal bleeding (OGIB). PATIENTS AND METHODS: A total of 45 consecutive patients with OGIB underwent capsule endoscopy. Patients with positive capsule endoscopy results underwent DBE for biopsy or therapy, and those with negative results underwent further assessment for possible diagnostic misses on capsule endoscopy. Tumors, ulcerations, and vascular lesions were considered as sources of bleeding. Diagnoses of OGIB lesions and clinical outcome were assessed 1 year after these examinations. RESULTS: Responsible lesions were found in 22 patients (49 %): 19 lesions in 18/45 patients (40 %) undergoing capsule endoscopy, and 18/36 patients (50 %) undergoing subsequent DBE. In all, 10 tumors, nine vascular lesions, and four ulcerations were found. In two patients, vascular lesions were only later diagnosed by conventional methods (4 %). Capsule endoscopy results guided our choice of the proper DBE model for successful therapeutic intervention in five patients. Re-bleeding rates were low during 1-year follow-up of the entire group (mean follow-up, 18.8 months): 5 % in cases with positive diagnoses on capsule endoscopy and/or DBE, and 12 % in negative cases. CONCLUSIONS: A combined approach using capsule endoscopy followed by DBE proves valuable in the diagnosis and treatment of patients with OGIB, leaves a low rate of undiagnosed bleeding sources, and has a good long-term outcome.

Effect of common driving sources to the feedback analysis of heart rate variability.

OBJECTIVES: This paper examines the operational characteristics of the multivariate autoregressive analysis applied to the simultaneous recordings of the instantaneous heart rate (IHR) and the change in systolic blood pressure (SBP). METHODS: The multivariate autoregressive model has been utilized to reveal the feedback characteristics between IHR and SBP. The model assumes the presence of independent set of driving forces to activate the system. However, it is likely that the driving forces may have correlation due to the presence of a common fluctuation source. This paper examines the effect of the presence of correlated components in the driving forces to the estimation accuracy of impulse responses characterizing the feedback properties. The two-dimensional autoregressive model driven by two correlated 1/f noises was chosen for the analysis of operational characteristics. The driving force was generated by a moving average system which simulates non-integer order integration. RESULTS: Computer simulation revealed that the mean square estimation errors of impulse responses sharply increase as relative power of common driving force exceeds 50%. However, the estimation accuracy and bias are found to be in permissible range in practice. CONCLUSIONS: These findings ensure the practical validity of utilizing multivariate autoregressive models for the feedback analysis between IHR and SBP where both signals have the common driving force.

Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.

BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. CONCLUSIONS: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.

Primary invasive micropapillary carcinoma of the colon.

AIMS: Invasive micropapillary carcinoma (IMPC) is associated with frequent lymph node metastasis and adverse clinical outcome. IMPC has been reported in breast, urinary bladder, ureter, lung and parotid gland but not in colon. We present the clinicopathological features of three cases of primary IMPC of the colon with a review of the literature. METHODS AND RESULTS: The patients (one man and two women) were 53, 67 and 68 years old, respectively. The size of the tumour ranged from 20 to 100 mm in diameter. Histologically, all cases were composed predominantly of papillary tumour cell clusters with spaces in a background of fine fibrocollagenous stroma. One of the tumours (case 1) was nearly completely composed of IMPC, but the other two were associated with foci of adenocarcinoma and concurrent mucinous carcinoma, respectively. MUC1 was positive in all cases, suggestive of reverse cell orientation which is responsible for its unique histological features. CONCLUSIONS: We report three cases of primary IMPC of the colon. Its clinical significance remains undetermined but the presence of this component may represent a poor prognostic factor.

Purification and characterization of extracellular alkaline serine protease from Stenotrophomonas maltophilia strain S-1.

AIMS: The present study was conducted by screening soil bacteria in an attempt to isolate a bacterium that produced extracellular alkaline protease, and for purification and characterization of the protease. METHODS AND RESULTS: Soil bacteria were screened by growth on casein as the sole carbon source. Characterization of a strain isolated from soil of Abashiri, Japan indicated a taxonomic affiliation to Stenotrophomonas maltophilia, and was named S-1 strain. The purified S-1 protease, designed S. maltophilia Protease-1 (SmP-1), exhibited an optimal pH of 12.0, optimal reaction temperature of 50 degrees C and a molecular mass of approximately 40 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The cleavage sites of the oxidized-insulin B chain by SmP-1 were identified as Leu6-Cys7, Cys7-Gly8, Tyr16-Leu17 and Leu17-Val18. The N-terminal amino acid sequence of the purified alkaline protease was determined as NH2-SASAPMVSGVAALVLE. CONCLUSION: A novel extracellular alkaline serine protease was isolated from S. maltophilia strain S-1. The optimal pH of the proteolytic activity was pH 12.0. SIGNIFICANCE AND IMPACT OF THE STUDY: The extremely high optimal pH and heat stability of the alkaline serine protease SmP-1 might make it widely applicable to food and other industries.

Low atmospheric temperature dependence on photodegradation of wood.

This paper deals with the photodegradation of wood in low atmospheric temperature region (-40 to 50 degrees C), and discusses the changes in color and IR spectra. The color and IR spectra of wood hardly changed with photo-irradiation at -40 degrees C but did at -20 degrees C. Therefore, it is thought that the photo-energy causes the scission of chemical bonds or the production of radicals; however, heat energy is needed to yellow of wood (i.e., to produce quinone). In case of softwoods, the absorption of the carbonyl band consisted of two sub-bands, and the carbonyl band at around 1710 cm(-1) increased at lower temperature than that at around 1760 cm(-1) by light-irradiation. Such IR measurement due to lignin degradation means that the photodegradation of softwoods is faster than that of hardwoods. The color change by exposure to light in the low temperature was also caused by the degradation of lignin.

Phenylalanine ammonia-lyase modified with polyethylene glycol: potential therapeutic agent for phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by the defects in the phenylalanine hydroxylase (PAH) gene. Individuals homozygous for defective PAH alleles show elevated levels of systemic phenylalanine and should be under strict dietary control to reduce the risk of neuronal damage associated with high levels of plasma phenylalanine. Researchers predict that plant phenylalanine ammonia-lyase (PAL), which converts phenylalanine to nontoxic t-cinnamic acid, will be an effective therapeutic enzyme for the treatment of PKU. The problems of this potential enzyme therapy have been the low stability in the circulation and the antigenicity of the plant enzyme. Recombinant PAL originated from parsley (Petroselinum crispum) chemically conjugated with activated PEG2 [2,4-bis(O-methoxypolyethyleneglycol)-6-chloro-s-triazine] showed greatly enhanced stability in the circulation and was effective in reducing the plasma concentration of phenylalanine in the circulation of mice. PEG-PAL conjugate will be an effective therapeutic enzyme for the treatment of PKU.

Can ataxin-2 be down-regulated by allele-specific de novo DNA methylation in SCA2 patients?

Spinocerebellar ataxia type 2 (SCA2) is caused by a CAG trinucleotide repeat expansion within the coding region of the ataxin-2 gene. Affected individuals typically have between 34 and 57 CAG repeats. Signs of the disorder generally begin in adulthood and include progressive ataxia, dysarthria, tremor, hyporeflexia, and slow saccades. As with other trinucleotide repeat disorders, SCA2 exhibits an inverse correlation between the size of the CAG repeat and the age at onset of clinically detectable disease, with neonatal cases of SCA2 being reported in individuals harboring over 200 CAG repeats. However, a wide range of age at onset is typically observed, especially in individuals with < 40 CAG repeats. CAG repeat number alone explains approximately 25-80% of the variability. In this paper, we hypothesize that the level of mutant ataxin-2 protein in affected cells contributes to these differences. One of the mechanisms that might influence this protein levels is de novo DNA methylation, which would specifically target the allele with the expanded CAG repeat leading to transcriptional silencing. Consequently, the symptoms of SCA2 would occur later in the patient's life history. Our postulations, as well as those previously reported to account for the phenotype of SCA2, are discussed.

Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity.

Recent work on isolated sinoatrial node cells from rabbit has suggested that sarcoplasmic reticulum Ca2+ release plays a dominant role in the pacemaker potential, and ryanodine at a high concentration (30 micromol/L blocks sarcoplasmic reticulum Ca2+ release) abolishes pacemaking and at a lower concentration abolishes the chronotropic effect of beta-adrenergic stimulation. The aim of the present study was to test this hypothesis in the intact sinoatrial node of the rabbit. Spontaneous activity and the pattern of activation were recorded using a grid of 120 pairs of extracellular electrodes. Ryanodine 30 micromol/L did not abolish spontaneous activity or shift the position of the leading pacemaker site, although it slowed the spontaneous rate by 18.9+/-2.5% (n=6). After ryanodine treatment, beta-adrenergic stimulation still resulted in a substantial chronotropic effect (0.3 micromol/L isoproterenol increased spontaneous rate by 52.6+/-10.5%, n=5). In isolated sinoatrial node cells from rabbit, 30 micromol/L ryanodine slowed spontaneous rate by 21.5+/-2.6% (n=13). It is concluded that sarcoplasmic reticulum Ca2+ release does not play a dominating role in pacemaking in the sinoatrial node. The full text of this article is available at http://www.circresaha.org.

Influence of alcohol consumption on the association between serum lipids and colorectal adenomas.

BACKGROUND: There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma. METHODS: The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did. RESULTS: In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without. CONCLUSIONS: Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.

Treatment of oligoasthenozoospermia with tranilast, a mast cell blocker, after long-term administration.

The authors retrospectively examined whether long-term administration of tranilast improves semen parameters in severe oligoasthenozoospermia. Fifty-two patients presenting with sperm concentration of less than 10 x 10(6) sperm/mL were enrolled. Subjects were partitioned into 3 groups as follows: patients displaying an atrophic testis with elevated (FSH) (group 1), patients exhibiting normal testicular volume with elevated FSH (group 2), and patients with normal testicular volume and normal FSH levels (group 3). Tranilast (300mg/day) was administered until pregnancy was achieved or for a period of up to 12 months. Sperm concentration was significantly increased at 3 months in 16 subjects (44%) in groups 1 and 3. In group 2, sperm concentration was increased at 12 months (5 of 16 subjects; 31%). Total sperm count was obviously elevated at 3 months in groups 1 and 2, and at 6 months in group 3. Six pregnancies were achieved via natural intercourse. Tranilast, a mast cell blocker, demonstrates a certain clinical benefit in terms of improvement of semen parameters involving severe oligoasthenozoospermia, but it does not appear to afford clinical benefit in long-term administration.

An ARL1 mutation affected autophagic cell death in yeast, causing a defect in central vacuole formation.

When the cdc28 strain of Saccharomyces cerevisiae is incubated at restrictive temperatures, the yeasts digest themselves in 7 days by activating autophagic machinery. In parallel, the cell-proliferative activity decreases progressively after about 48 h. We have previously referred to this phenomenon as autophagic death. In the present study, we isolated and characterized a recessive mutant strain, dlp2, which delays the progression toward autophagic death. The cdc28 dlp2 cells contain many small vesicles instead of the large central vacuoles that are usually found in parental cdc28 cells. We showed that the dlp2 phenotype results from the presence of a single mutation in the gene ARL1 (ADP-ribosylation factor-like protein 1). Morphological and biochemical analyses of cdc28 dlp2 suggested that a defect in central vacuole formation is caused by aberrant membrane trafficking, although the protein-sorting to vacuoles is not affected. After a shift to a restrictive temperature, the components of the cytoplasm and nucleus of cdc28 dlp2 were condensed, with an accompanying formation of vesicles in the periphery (epiplasm) of the cells rather than an activation of the autophagic machinery. Introducing this ARL1 mutation into the normal ARL1 locus of the wild-type W303 strain again inhibited the progression of apoptotic cell death due to a defect in vacuole formation, which in this case was induced by the proapoptotic protein Bax. Thus, the ARL1 gene plays an important role in the formation of central vacuoles and in the progression of programmed cell death induced by cell-cycle arrest or Bax. These results suggested the presence of a programmed-cell death machinery in yeast that is similar to that related to the Type II cell death of mammalian cells characterized by autophagocytosis.