"Fooling fido"--chemical and behavioral studies of pseudo-explosive canine training aids.
Genuine explosive materials are traditionally employed in the training and testing of explosive-detecting canines so that they will respond reliably to these substances. However, challenges arising from the acquisition, storage, handling, and transportation of explosives have given rise to the development of "pseudo-explosive" training aids. These products attempt to emulate the odor of real explosives while remaining inert. Therefore, a canine trained on a pseudo-explosive should respond to its real-life analog. Similarly, a canine trained on an actual explosive should respond to the pseudo-explosive as if it was real. This research tested those assumptions with a focus on three explosives: single-base smokeless powder, 2,4,6-trinitrotoluene (TNT), and a RDX-based plastic explosive (Composition C-4). Using gas chromatography-mass spectrometry with solid phase microextraction as a pre-concentration technique, we determined that the volatile compounds given off by pseudo-explosive products consisted of various solvents, known additives from explosive formulations, and common impurities present in authentic explosives. For example, simulated smokeless powders emitted terpenes, 2,4-dinitrotoluene, diphenylamine, and ethyl centralite. Simulated TNT products emitted 2,4- and 2,6-dinitrotoluene. Simulated C-4 products emitted cyclohexanone, 2-ethyl-1-hexanol, and dimethyldinitrobutane. We also conducted tests to determine whether canines trained on pseudo-explosives are capable of alerting to genuine explosives and vice versa. The results show that canines trained on pseudo-explosives performed poorly at detecting all but the pseudo-explosives they are trained on. Similarly, canines trained on actual explosives performed poorly at detecting all but the actual explosives on which they were trained.


Band structure of surface electric potential in growing roots.
For growing roots of azuki bean (Phaseolus chrysanthos), an electric potential is measured minutely along the surface of the root, together with the surface pH. It was found that the root begins to display a band-type pattern of potential with a spatial period of about 2 cm in a mature region as soon as it grows to about 10 cm in root length, while the surface potential shows only one convex peak around a position 5-20 mm behind a root tip and a succeeding concave peak around 20-35 mm, providing the length of root is shorter than about 10 cm. Since the surface potential takes a relatively positive value on average at the side of the root base compared with that in an elongation zone near the tip, electric current is supposed to flow into the elongation zone, accompanied by some local current loops in the mature region. The present band-type pattern observed first in multi-cell systems seems to be a kind of dissipative structure appearing far from equilibrium, and hence its relationship to growth is discussed.


Intraoperative dexmedetomidine attenuates norepinephrine levels in patients undergoing transsphenoidal surgery: a randomized, placebo-controlled trial.
Dexmedetomidine has sympatholytic effects. We investigated whether dexmedetomidine could attenuate stress responses in patients undergoing endoscopic transnasal transseptal transsphenoidal surgery. Forty-six patients were randomized to receive a continuous infusion of 0.9% saline (n = 23) or dexmedetomidine (n = 23). Immediately after general anesthesia induction, the dexmedetomidine group received a loading dose of 1 mcg/kg dexmedetomidine over 10 min, followed by a maintenance dose of 0.2-0.7 mcg/kg/h and the control group received 0.9% saline at the same volume until 30 min before the end of surgery. Serum levels of epinephrine, norepinephrine, and glucose were assessed before surgery (T1) and the end of drug infusion (T2). The primary outcome was the change in norepinephrine levels between the two time points. Changes (T2-T1 values) in perioperative serum norepinephrine levels were significantly greater in the dexmedetomidine group than in the control group (median difference, 56.9 pg/dL; 95% confidence interval, 20.7 to 83.8 pg/dL; P = 0.002). However, epinephrine level changes did not show significant intergroup differences (P = 0.208). Significantly fewer patients in the dexmedetomidine group than in the control group required rescue analgesics at the recovery area (4.3% vs. 30.4%, P = 0.047). Intraoperative dexmedetomidine administration reduced norepinephrine release and rescue analgesic requirement. Dexmedetomidine might be used as an anesthetic adjuvant in patients undergoing transnasal transseptal transsphenoidal surgery. Clinical Trial Registry of Korea, identifier: KCT0003366; registration date: 21/11/2018; presenting author: Ji Seon Jeong.


Leveraging Big Data and Electronic Health Records to Enhance Novel Approaches to Acute Kidney Injury Research and Care.
While acute kidney injury (AKI) has been poorly defined historically, a decade of effort has culminated in a standardized, consensus definition. In parallel, electronic health records (EHRs) have been adopted with greater regularity, clinical informatics approaches have been refined, and the field of EHR-enabled care improvement and research has burgeoned. Although both fields have matured in isolation, uniting the 2 has the capacity to redefine AKI-related care and research. This article describes how the application of a consistent AKI definition to the EHR dataset can accurately and rapidly diagnose and identify AKI events. Furthermore, this electronic, automated diagnostic strategy creates the opportunity to develop predictive approaches, optimize AKI alerts, and trace AKI events across institutions, care platforms, and administrative datasets.


Multispectral tissue characterization for intestinal anastomosis optimization.
Intestinal anastomosis is a surgical procedure that restores bowel continuity after surgical resection to treat intestinal malignancy, inflammation, or obstruction. Despite the routine nature of intestinal anastomosis procedures, the rate of complications is high. Standard visual inspection cannot distinguish the tissue subsurface and small changes in spectral characteristics of the tissue, so existing tissue anastomosis techniques that rely on human vision to guide suturing could lead to problems such as bleeding and leakage from suturing sites. We present a proof-of-concept study using a portable multispectral imaging (MSI) platform for tissue characterization and preoperative surgical planning in intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI system coupled with polarizers and image analysis software. The system is tested on ex vivo porcine intestine tissue, and we demonstrate the feasibility of identifying optimal regions for suture placement.


Single (sub)species then and now: An examination of the nonracial perspective of C. Loring Brace.
C. Loring Brace's writings on the concept of race have been among the most influential within anthropology. A review of the development of Brace's perspective on race shows that his philosophical approaches to fossil and modern human variation are consistent and integrated. Brace's views on race are compared with those of Ashley Montagu and Frank Livingstone, who also proposed eliminating "race" from anthropology, and with those of Stanley Garn and Alice Brues, who accepted "racial" subdivisions of humans. Carleton Coon's writings are more divergent; the aftermath of the publication of his Origin of Races highlights significant political tensions of the 1960s that intersected with scientific changes in anthropology emanating from the Evolutionary Synthesis. Recent forensic and "no race" positions are compared to explore their differences and the possibility of reconciliation, and the role of Brace and others in combating proposals of intellectual differences among human groups is discussed. While a spectrum of anthropological opinion regarding race exists, the commonalities are sufficient to allow valuable, united commentary emphasizing the complexity of modern human cultural and biological variation.


Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies.
The consumption of fruit and vegetables is associated with a reduced rate of coronary heart disease (CHD) in observational cohorts. The purpose of this study was to assess the strength of this association in a meta-analysis. Cohort studies were selected if they reported relative risks (RRs) and 95% CI for coronary heart disease or mortality and if they presented a quantitative assessment of fruit and vegetable intake. The pooled RRs were calculated for each additional portion of fruit and/or vegetables consumed per day, and the linearity of the associations were examined. Nine studies were eligible for inclusion in the meta-analysis that consisted of 91,379 men, 129,701 women, and 5,007 CHD events. The risk of CHD was decreased by 4% [RR (95% CI): 0.96 (0.93-0.99), P = 0.0027] for each additional portion per day of fruit and vegetable intake and by 7% [0.93 (0.89-0.96), P < 0.0001] for fruit intake. The association between vegetable intake and CHD risk was heterogeneous (P = 0.0043), more marked for cardiovascular mortality [0.74 (0.75-0.84), P < 0.0001] than for fatal and nonfatal myocardial infarction [0.95 (0.92-0.99), P = 0.0058]. Visual inspection of the funnel plot suggested a publication bias, although not statistically significant. Therefore, the reported RRs are probably overestimated. This meta-analysis of cohort studies shows that fruit and vegetable consumption is inversely associated with the risk of CHD. The causal mechanism of this association, however, remains to be demonstrated.


[Atypical benign partial epilepsy of childhood. Clinical follow-up EEG study of 3 patients].
Between 369 cases of benign partial epilepsy of the childhood with Rolandic spikes (BECRS) diagnosed in our hospital, we have been able to study three patients that have presented a neurophysiological and clinical presentation that was compatible with the form described by Aicardi and Chevrie in 1982. None of our patients had familial epilepsy precedents. There were no pathological birth or previous neurological disorders. The neurophysiological development was normal until the beginning of the clinical picture. The seizures began when the patients were 3 years and 4 months, and 5 years, with partial seizures of the same characteristic that present patients with BECRS. Two of them had generalized tonic-clonic seizures during sleep. All the patients presented throughout the evolution absences myoclonic and/or atonic seizures. The awake EEG patterns showed normal background activity and paroxysms of focal spike were complexes with diffusion to central areas. During the slow wave sleep, every cases showed paroxysms of diffuse and generalized slow spike and wave complexes practically continuous. The partial seizures were scarce, but the absences and the atonicas seizures presented several times every day, and in one case appeared in the form of a grand mal state. The evolution of the patients was favourable, as they were free of seizures, with a normal neurophysiological development. At the beginning, the seizures were resistant to treatment with several antiepileptics drugs (AED). The treatment with valproic acid (VPA) and clonazepam (CZP), has been very effective.


Single-virus fusion experiments reveal proton influx into vaccinia virions and hemifusion lag times.
Recent studies have revealed new insights into the endocytosis of vaccinia virus (VACV). However, the mechanism of fusion between viral and cellular membranes remains unknown. We developed a microfluidic device with a cell-trap array for immobilization of individual cells, with which we analyzed the acid-dependent fusion of single virions. VACV particles incorporating enhanced green fluorescent protein (EGFP) and labeled with self-quenching concentrations of R18 membrane dye were used in combination with total internal reflection fluorescence microscopy to measure the kinetics of R18 dequenching and thus single hemifusion events initiated by a fast low-pH trigger. These studies revealed unexpectedly long lag phases between pH change and hemifusion. In addition, we found that EGFP fluorescence in the virus was quenched upon acidification, indicating that protons could access the virus core, possibly through a proton channel. In a fraction of virus particles, EGFP fluorescence was recovered, presumably after fusion-pore formation and exposure of the core to the physiological pH of the host-cell cytosol. Given that virus-encoded cation channels play a crucial role in the life cycle of many viruses and can serve as antiviral drug targets, further investigations into a potential VACV viroporin are justified. Our findings indicate that the microfluidic device described may be highly beneficial to similar studies requiring fast kinetic measurements.


Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure.
Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for heart failure (HF). Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission) was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona) over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR) for the associations between NAFLD and the outcome(s) of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes). Patients with NAFLD (n = 109; 51.4%) had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, p<0.0001) after adjustment for established risk factors and potential confounders. Similar results were found for 1-year cardiac re-hospitalization (adjusted-hazard ratio 8.05, 95% confidence intervals 3.77-15.8, p<0.0001). In conclusion, NAFLD and its severity were strongly and independently associated with an increased risk of 1-year all-cause and cardiac re-hospitalization in elderly patients admitted with acute HF.


6-(methylamino)hexane-1,2,3,4,5-pentanol 4-(((1S,2S)-1-hydroxy-2,3-dihydro-1H,1'H-[2,2-biinden]-2-yl)methyl)benzoate (PH46A): a novel small molecule with efficacy in murine models of colitis.
The indane skeleton is found naturally and in several therapeutic molecules in medicinal chemistry. During our work on the anti-inflammatory activity of naturally occurring and synthetic indanes, we have synthesized a novel indane scaffold that has been optimized for both anti-inflammatory activity and bioavailability. We have evaluated our lead molecule, PH46A, in in vivo models of inflammatory bowel disease (IBD), an area of considerable unmet clinical need; current therapies are often unable to control the course of the disease. The compound significantly reduced histological damage and serum amyloid A (SAA) levels in IL-10(-/-) colitis mice, was efficacious in the 5% dextran sulfate sodium (DSS) colitis model, and compared favorably with prednisolone in this model and supports its potential use to treat acute exacerbations of the disease. Further, the graded response to the compound may also lend itself to be used at a lower dose to maintain periods of remission.


Cloning and nucleotide sequencing of genes for a second type of small, acid-soluble spore proteins of Bacillus cereus, Bacillus stearothermophilus, and "Thermoactinomyces thalpophilus".
The nucleotide sequences of the single genes coding for the B-type small, acid-soluble spore proteins (SASP) of Bacillus cereus, B. stearothermophilus, and "Thermoactinomyces thalpophilus" were determined, and the amino acid sequences of all B-type SASP were compared. While this type of SASP showed significant sequence conservation around the two spore protease cleavage sites, alignment of these sequences required the introduction of gaps, and even then only 19 of the residues were conserved exactly in all five proteins. However, all five B-type SASP did contain a large (27 to 35-residue), rather well-conserved amino acid sequence repeat, and four of the five proteins had well-conserved regions of 14 to 17 amino acids which appeared three times.


Genome-Wide DNA Methylation and Its Effect on Gene Expression During Subclinical Mastitis in Water Buffalo.
Subclinical mastitis (SCM) in buffalo is one of the most challenging paradoxes for the dairy sector with very significant milk production losses and poses an imminent danger to milch animal's milk-producing ability. We present here the genome-wide methylation specific to SCM in water buffalo and its consequential effect on the gene expression landscape for the first time. Whole-genome DNA methylation profiles from peripheral blood lymphocytes and gene expression profiles from milk somatic cells of healthy and SCM cases were catalogued from the MeDIP-Seq and RNA-Seq data. The average methylation in healthy buffaloes was found to be higher than that in the SCM-infected buffaloes. DNA methylation was abundant in the intergenic region followed by the intronic region in both healthy control and SCM groups. A total of 3,950 differentially methylated regions (DMRs) were identified and annotated to 370 differentially methylated genes (DMGs), most of which were enriched in the promoter region. Several important pathways were activated due to hypomethylation and belonged to the Staphylococcus aureus infection, Th17 cell differentiation, and antigen processing and presentation pathways along with others of defense responses. DNA methylome was compared with transcriptome to understand the regulatory role of DNA methylation on gene expression specific to SCM in buffaloes. A total of 4,778 significant differentially expressed genes (DEGs) were extracted in response to SCM, out of which 67 DMGs were also found to be differentially expressed, suggesting that during SCM, DNA methylation could be one of the epigenetic regulatory mechanisms of gene expression. Genes like CSF2RB, LOC102408349, C3 and PZP like, and CPAMD8 were found to be downregulated in our study, which are known to be involved in the immune response to SCM. Association of DNA methylation with transposable elements, miRNAs, and lncRNAs was also studied. The present study reports a buffalo SCM web resource (BSCM2TDb) available at http://webtom.cabgrid.res.in/BSCM2TDb that catalogues all the mastitis-related information of the analyses results of this study in a single place. This will be of immense use to buffalo researchers to understand the host-pathogen interaction involving SCM, which is required in endeavors of mastitis control and management.


Fractionation of cadmium in tobacco and cigarette smoke condensate using XANES and sequential leaching with ICP-MS/MS.
Fractionation data for cadmium in tobacco products, as obtained by sequential leaching of cadmium species with ICP-MS/MS analysis, and separately by X-ray absorption near edge structure (XANES) are presented here for the first time. The total amount of cadmium found in 3R4F cigarette cut tobacco was 1526 ± 42 μg kg-1, of which 5% was found in the smoke under ISO smoking conditions. XANES analysis showed that Cd in tobacco, cigarette smoke and ash was present in the + 2 oxidation state. Examination of the gas-particle partitioning of smoke cadmium suggests that Cd in mainstream smoke is best viewed as semi-volatile, existing in both particulate and gas phases. Sequential extraction of trapped tobacco smoke was carried out to get a deeper insight into the chemistry of cigarette smoke cadmium compounds. Consecutive extractions with ultrapure water, dilute (1%) nitric acid and 10% nitric acid led to extraction of a total amount of Cd which agreed with that obtained after microwave digestion of the whole sample, suggesting that cadmium was quantitatively leachable into aqueous/acidic solutions. Most Cd (~ 90% of the total Cd in the smoke condensate) was extracted into dilute nitric acid (likely as CdO, Cd(OH)2 and CdCO3) with a minor percentage (3%) extracted into water (likely as CdCl2) and in 10% nitric acid (likely as CdS). Extraction of trapped mainstream smoke with pentane, followed by ICP-MS/MS analysis, to examine the possible presence of organocadmium in 3R4F tobacco smoke, did not show the presence of organocadmium compounds above the method LOQ (2 μg kg-1), possibly due to their reactivity under the experimental conditions. The high selectivity with sufficient sensitivity achieved by ICP-MS/MS was invaluable to quantify Cd (at low μg kg-1levels) simultaneously with sulphur and chlorine in the tobacco smoke fractions of complex matrix. The cadmium chemistry in the smoke, identified in this study, is consistent with both relatively high lung absorption and DNA binding; both potentially important factors for disease progression in smokers. Graphical Abstract This paper provides quantitative fractionation data for cadmium in tobacco and smoke by using sequential leaching with ICPMS and XANES.


Ectopic production of human chorionic gonadotropin in transitional cell carcinoma of the bladder. An immunohistochemical study.
A retrospective histopathological and clinical analysis of 43 patients with transitional cell carcinoma of the bladder, attending our institution between March 1986 and April 1989, was performed. The indirect immunoperoxidase method was used for the demonstration of human chorionic gonadotropin production in transitional cell carcinoma cells. Nine of the 16 grade III tumors stained positive for human chorionic gonadotropin, while grade I and grade II tumors remained unstained. Our results suggest that the presence of human chorionic gonadotropin in tumor cells is a strong evidence of dedifferentiation, and its association with patient prognosis needs further investigation, especially in high-grade, low-stage tumors.


Fatal Primary Amebic Meningoencephalitis in Nebraska: Case Report and Environmental Investigation, August 2022.
Primary amebic meningoencephalitis (PAM) is a rare and lethal infection caused by Naegleria fowleri. We report an epidemiological and environmental investigation relating to a case of PAM in a previously healthy boy age 8 years. An interview of the patient's family was conducted to determine the likely exposure site and to assess risk factors. Data from the United States Geological Survey site at Waterloo, NE, on the Elkhorn River were used to estimate water temperature and streamflow at the time and site of exposure. Data from the National Weather Service were used to estimate precipitation and ambient air temperature at the time and site of exposure. Despite conventional treatment, the patient died 2 days after hospital admission. The patient participated in recreational water activities in the Elkhorn River in northeastern Nebraska 5 days before symptom onset. In the week before exposure, water and ambient air high temperatures reached annual highs, averaging 32.4°C and 35.8°C, respectively. The day before infection, 2.2 cm of precipitation was reported. Streamflow was low (407 ft3/s). Infections in several northern states, including Nebraska, suggest an expanding geographic range of N. fowleri transmission, which may lead to increased incidence of PAM in the United States. Similar environmental investigations at suspected exposure sites of future cases will allow data aggregation, enabling investigators to correlate environmental factors with infection risk accurately.


Comparison of age at first full-term pregnancy between women with breast cancer and women with benign breast diseases.
Benign breast diseases have a broadly similar risk profile to that of breast cancer, possibly reflecting a similar underlying endocrine milieu. We have hypothesized that a crucial distinction between breast cancer and benign breast diseases is that mammary gland terminal differentiation has not been successfully accomplished among women who tend to develop breast cancer. From October 2001 to December 2002, information concerning breast cancer risk factors and sociodemographic characteristics was collected from 174 women with breast cancer and 116 women with benign breast diseases, all 30 years old or older, who were histologically diagnosed at a major prevention center in Athens, Greece. Among the examined breast cancer risk factors, only age at first full-term pregnancy was significantly associated with the odds of having breast cancer rather than benign breast disease, and the association was evident among premenopausal [odds ratio (OR) per 5 years = 1.76, 95% confidence interval (CI) 1.10-2.93] and postmenopausal (OR = 2.10, 95% CI 1.16-3.71) women, as well as among all women (OR = 1.93, 95% CI 1.34-2.70). There was no evidence that any of the remaining breast cancer risk factors could discriminate between breast cancer and benign breast diseases. We conclude that early age at first pregnancy may convey substantial protection against breast cancer risk among women with benign breast diseases, probably operating through induction of terminal differentiation of mammary gland cells. The finding is accentuated by the fact that women with benign breast diseases are already at a relatively high risk for breast cancer.


Plasmacup--special design. Aspects of the dysplastic acetabulum.
In Japan, the main reason for osteoarthritis of the hip joint is caused by dysplastic deformities. The implantation technique of cementless press-fit cup with multi-screw fixation and acetabular bone graft to reconstruct the true acetabular center is described. In addition, special design aspects of the BiCONTACT-N stem were optimized for these patients. Between January 1997 and December 1999, 29 patients (33 hips) received a BiCONTACT-N/Plasmacup-M total hip replacement. There were 28 women and one man. Average age at the time of THA of 64 (range 51-76) years. Average time of follow-up was 41 (range 25-59) months. According to the Crowe classification, 18 hips where classified as type 1 (less than 50% subluxation of the femoral head from the acetabulum), nine type 2 (50-75% subluxation), five type 3 (75-100% subluxation), and one type 4 (complete dislocation). At time of follow-up, there was no loosening of the acetabular implant or collapse of the acetabular bone graft. In the radiographic examination, 80% of the femoral implants showed spot welds in the transitional zone of the coated and uncoated area, and 96% sclerotic lines in the coated area. At the uncoated surface, radiolucent lines were seen in 12% and a cortical hypertrophy in 24%. No stress shielding could be observed. Stem subsidence was measured with an average value of 0.32 (range 0-1.6) mm. No patient complained about thigh pain, and no intraoperative complications were observed. Postoperative complications were two anterior dislocations due to cup malposition and excessive lumbar hypnosis. Three deep-venous thromboses where found with venography and treated with warfarin therapy. The limited experience indicates that BiCONTACT-N stem design in combination with the Plasmacup multihole implant is appropriate for the treatment of dysplastic hip deformities in Japanese patients. However, a long-term follow-up study is needed.


Thyroglobulin as a Rapid and Cost-Effective Biomarker for Diagnosis of Thyroid Carcinoma Brain Metastasis: A Case Report of a Patient with Metastatic Hurthle Cell Thyroid Carcinoma.
BACKGROUND Brain metastasis of papillary thyroid cancer (PTC) is rare. Treatment of these patients is challenging due to the lack of specific guidelines. Early diagnosis is accompanied by immediate treatment and less morbidity. Total resection of brain lesions may be unattainable when they include infiltration of eloquent areas. This report is of an 81-year-old man who had undergone total thyroidectomy for goiter in the past and presented with metastatic papillary thyroid carcinoma (PTC) to the neck after a gap of 16 years. After two years, the patient developed a solitary cystic brain PTC metastasis associated with raised thyroglobulin (Tg) inside the cystic lesion aspirated during brain surgery. CASE REPORT An 81-year-old male patient was admitted for a space-occupying brain lesion in the right frontal lobe. The patient's history included metastatic disease of PTC to the neck with cervical lymph node metastasis and local recurrence after surgery and radioactive iodine-131 treatment. The patient underwent craniotomy and removal of the lesion. The aspirated fluid was sent for cytological examination and measurement of Tg levels, which were interestingly high. Pathology of the brain lesion revealed infiltration of brain parenchyma from a metastatic lesion characterized by eosinophilic cells with irregular contours forming grooves, resulting in cytoplasmic pseudo-inclusions, an oncotic variant of PTC. CONCLUSIONS This report has shown that residual tissue may be present following total thyroidectomy and may be the origin of PTC with metastasis to the brain. The patient in this study suffered from a brain lesion that could be excised. However, aspiration of cystic compartments could provide a rapid diagnosis in patients with non-removable brain lesions.


Cortical metabolic and nigrostriatal abnormalities associated with clinical stage-specific dementia with Lewy bodies.
The aims of this study were to investigate the hypometabolic regions of FDG PET compared with the nigrostriatal dopamine pathway abnormalities in TRODAT-1 scan in patients with dementia with Lewy bodies (DLBs) at mild and dementia stages as well as to validate the correlation among networks being constructed with clinical data. A total of 25 DLB patients were classified into 2 functional groups stratified by the Clinical Dementia Rating (CDR) Scale (CDR 0.5: n = 14, mild stage; CDR 1 or 2: n = 11, dementia stage) compared with 9 age-matched controls. Neuroimaging survey was applied using information derived from FDG PET by performing voxel-based analysis and a semiquantitative Tc-TRODAT-1 scan to correlate these results with the cognitive and Unified Parkinson's Disease Rating Scale. Compared with normal database, the patients with mild stage showed hypometabolism in the temporal regions, anterior cingulate cortex, inferior orbital region, thalamus, and caudate nucleus. Although at the dementia stage, more extensive cortical hypometabolism involving occipital region were found. The dopamine transporter levels derived from TRODAT-1 scan had excellent discrimination in diagnosing DLB compared with age-matched normal controls (1.58 [0.2] and 1.84 [0.1], P < 0.01) but without significant differences between mild and dementia stages. The sophisticated cortical-brainstem networks by FDG PET and TRODAT-1 yielded good clinical correlation. The networks yielded from FDG PET and TRODAT-1 revealed good correlation with clinical data and that nigrostriatal pathway abnormalities are preceded by typical occipital hypometabolism in mild stage of DLB. Dopamine transporter levels may serve as early diagnostic tool and FDG PET as staging indicator for DLB pathology.


A molecular site-site integral equation that yields the dielectric constant.
Our recent derivation [K. M. Dyer et al., J. Chem. Phys. 127, 194506 (2007)] of a diagrammatically proper, site-site, integral equation theory using molecular angular expansions is extended to polar fluids. With the addition of atomic site charges we take advantage of the formal long-ranged potential field cancellations before renormalization to generate a set of numerically stable equations. Results for calculations in a minimal (spherical) angular basis set are presented for the radial distribution function, the first dipolar (110) projection, and the dielectric constant for two model diatomic systems. All results, when compared to experiment and simulation, are a significant quantitative and qualitative improvement over previous site-site theories. More importantly, the dielectric constant is not trivial and close to simulation and experiment.


Synaptic association of dopaminergic axon terminals and neurokinin-1 receptor-expressing intrinsic neurons in the striatum of the rat.
We examined if axon terminals of dopaminergic neurons might make synapses upon neurokinin-1 receptor (NK1R)-expressing intrinsic neurons in the rat striatum. In a double-immunocytochemical ultrastructural study, dopaminergic terminals were labeled by the immunoperoxidase method for tyrosine hydroxylase (TH), while NK1R-immunoreactivity (-IR) was revealed by the immunogold-silver labeling method. Some TH-immunoreactive (-ir) axon terminals formed synapses of the symmetric or intermediate type on NK1R-ir neuronal profiles; usually on dendritic profiles and rarely on somatic profiles. It was further confirmed by means of triple-immunofluorescence histochemistry that NK1R-ir neurons in close association with TH-ir axon terminals showed nitric oxide synthase (NOS)- or vesicular acetylcholine transporter-IR. Since NK1R-expressing striatal neurons are segregated into cholinergic and somatostatin/NOS-containing intrinsic neurons (Brain Res. 631 (1993) 297; Neurosci. Lett. 310 (2001) 109), the present results indicate that dopaminergic neurons make synapses upon these intrinsic neurons in the striatum.


Recovery of the ascending reticular activating system and consciousness following comprehensive management in a patient with traumatic brain injury: a case report.
We report on changes in the ascending reticular activating system (ARAS) concurrent with the recovery of impaired consciousness following rehabilitation and cranioplasty in a patient with traumatic brain injury (TBI), which were demonstrated on diffusion tensor tractography (DTT). A 34-year-old male patient was diagnosed with a traumatic intracerebral hemorrhage after falling from a height of approximately 7 m and underwent a right frontoparietotemporal decompressive craniectomy and hematoma removal. At 5 months after onset, when starting rehabilitation, the patient showed impaired consciousness, with a Glasgow Coma Scale (GCS) score of 4. Comprehensive rehabilitative therapy was provided until 14 months after onset, and his GCS score improved to 8. Cranioplasty was performed using auto-bone at 14 months after onset. One month after cranioplasty, his GCS score improved to 12. On the 15-month DTT, the deviated lower dorsal ARAS was restored on both sides, and the right side had become thicker. The right lower ventral ARAS was reconstructed, and increased neural connectivity of the upper ARAS was detected in both the prefrontal cortices. Thus, changes in the ARAS were demonstrated in a patient with TBI during recovery of consciousness following rehabilitation and cranioplasty.


The clinical utility of nuclear medicine imaging for the detection of occult gastrointestinal haemorrhage.
Acute gastrointestinal bleeding is often intermittent and the bleeding source may be difficult to locate, resulting in delay of potentially life-saving treatment. The aim of this study was to determine the clinical utility of 99mTc labelled red blood cell imaging and [99mTc]pertechnetate (Meckel's scan) imaging in a series of 137 patients admitted over a 5 year period to hospital for management of acute gastrointestinal bleeding. Of the 137 patients, 70 had positive 99mTc red blood cell studies. Eleven of 24 patients who had imaging performed beyond 3 h had positive scans that would otherwise have been missed. Only 47 patients had a definite final diagnosis at the time of hospital discharge, of which six were negative on 99mTc red blood cell imaging. The correct site of bleeding was localized in seven of 21 patients with foregut bleeding, and 15 of 20 patients with colonic bleeding. Endoscopy yielded a diagnosis in 13 of the 47 patients (28%). Eleven patients had Meckel's scans but all were negative. Angiography was diagnostic in one of 17 patients studied. 99mTc red blood cell imaging is a useful test in the management of acute gastrointestinal bleeding. Imaging beyond 3 h may further improve the bleeding detection rate. This test, however, may be an unreliable means of localization of bleeding, particularly in the foregut.


Interaction of Erp Protein of Mycobacterium tuberculosis with Rv2212 Enhances Intracellular Survival of Mycobacterium smegmatis.
The Mycobacterium tuberculosis exported repetitive protein (RvErp) is a crucial virulence-associated factor as determined by its role in the survival and multiplication of mycobacteria in cultured macrophages and in vivo Although attempts have been made to understand the function of Erp protein, its exact role in Mycobacterium pathogenesis is still elusive. One way to determine this is by searching for novel interactions of RvErp. Using a yeast two-hybrid assay, an adenylyl cyclase (AC), Rv2212, was found to interact with RvErp. The interaction between RvErp and Rv2212 is direct and occurs at the endogenous level. The Erp protein of Mycobacterium smegmatis (MSMEG_6405, or MsErp) interacts neither with Rv2212 nor with Ms_4279, the M. smegmatis homologue of Rv2212. Deletion mutants of Rv2212 revealed its adenylyl cyclase domain to be responsible for the interaction. RvErp enhances Rv2212-mediated cyclic AMP (cAMP) production. Also, the biological significance of the interaction between RvErp and Rv2212 was demonstrated by the enhanced survival of M. smegmatis within THP-1 macrophages. Taken together, these studies address a novel mechanism by which Erp executes its function. RvErp is one of the important virulence factors of M. tuberculosis This study describes a novel function of RvErp protein of M. tuberculosis by identifying Rv2212 as its interacting protein. Rv2212 is an adenylyl cyclase (AC) and produces cAMP, one of the prime second messengers that regulate the intracellular survival of mycobacteria. Therefore, the significance of investigating novel interactions of RvErp is paramount in unraveling the mechanisms governing the intracellular survival of mycobacteria.


[Malignant small bowel ileus caused by local recurrence after colorectal cancer surgery].
We assessed 5 consecutive patients operated for local recurrence of small bowel obstruction after previous operation for colorectal cancer. Case 1 involved a 71-year-old man who presented with local recurrence with invasion of the ileum after low anterior resection( D3) for rectal cancer( Rb[rectum/below the peritoneal reflection]). Case 2 involved a 51-year-old woman; case 3, a 54-year-old woman; and case 4, a 60-year-old woman, all showing local recurrence with invasion of the jejunum and ureter after high anterior resection (D3) for rectal cancer (Ra[rectum/above the peritoneal reflection]). Case 5 involved a 58-year-old man who showed local recurrence of descending colon cancer with invasion of the jejunum, liver metastasis, and brain metastasis after left hemicolectomy( D3) for descending colon cancer. For the treatment of local recurrence in the patient referred to in case 1, amputation recti with partial resection of the ileum was performed. Partial resection of the ileum was performed in the patients referred to in cases 2 and 3. Nephrostomy was performed in patients referred to in cases 2, 3, and 4. Partial resection of the anastomotic colon and jejunum was performed in the patient referred to in case 5. The patient involved in case 5 underwent radiotherapy for brain metastasis. In the patient referred to in case 1, only radical surgery was performed, which is associated with a good prognosis. The estimated survival after the operation for local recurrence, except for the patient referred to in case 1, was 2 to 15 months( mean, 11.5 months). Oral intake periods, except for the patient referred to in case 1, were 0 to 4 months (mean, 2.3 months). Postoperative complication rates were 80%( 4/5). Our findings suggest that radical operation leads to a good quality of life( QOL) in patients with malignant small bowel obstruction.


Exercise hyperthermia induces greater changes in gastrointestinal permeability than equivalent passive hyperthermia.
Hyperthermia and exertional heat illness increase gastrointestinal (GI) permeability, although whether the latter is only via hyperthermia is unclear. The aim of this pilot study was to determine whether different changes in GI permeability, characterized by an increased plasma lactulose:rhamnose concentration ratio ([L:R]), occurred in exercise hyperthermia in comparison to equivalent passive hyperthermia. Six healthy adult male participants (age 25 ± 5 years, mass 77.0 ± 6.7 kg, height 181 ± 6 cm, peak oxygen uptake [ V·O2peak ] 48 ± 8 ml.kg-1 .min-1 ) underwent exercise under hot conditions (Ex-Heat) and passive heating during hot water immersion (HWI). Heart rate (HR), rectal temperature (TCORE ), rating of perceived exertion (RPE), and whole-body sweat loss (WBSL) were recorded throughout the trials. The L:R ratio, peak HR, change in HR, and change in RPE were higher in Ex-Heat than HWI, despite no differences in trial duration, peak core temperature or WBSL. L:R was strongly correlated (p < 0.05) with HR peak (r = 0.626) and change in HR (r = 0.615) but no other variable. The greater L:R in Ex-Heat, despite equal TCORE responses to HWI, indicates that increased cardiovascular strain occurred during exercise, and exacerbates hyperthermia-induced GI permeability at the same absolute temperature.


[MicroRNA-671-3p suppresses proliferation and invasion of breast cancer cells by targeting DEPTOR].
To investigate the effects of miR-671-3p on the proliferation and invasion of breast cancer cells and explore the possible mechanism. We examined the expressions of miR-671-3p in human normal epithelial cells (MCF-10A) and breast cancer cell lines (MCF-7, MDA-MB-231, and SK-BR3) using RT-PCR. The effects of transfection with a miR-671-3p mimic or inhibitor on the proliferation, migration and invasion of MCF-7 cells were evaluated using CCK-8 assay and Transwell chamber assay. The target gene of miR-671-3p was predicated with Targetscan and validated by a dual luciferase reporter system and Western blotting. The expression of miR-671-3p was significantly lower in breast cancer cells than in normal breast epithelial cells. Compared with negative control group, MCF-7 cells with miR-671-3p overexpression exhibited significantly reduced proliferation and invasion, whereas inhibition of miR-671-3p obviously promoted the cell proliferation and invasion. Luciferase reporter assay demonstrated that DEPTOR was the target gene of miR-671-3p, and miR-671-3p overexpression caused significant down-regulation of the protein expression of DEPTOR. MiR-671-3p suppresses the proliferation and invasion of breast cancer cell line MCF-7 by directly targeting DEPTOR protein.


Natural hybridization between Senecio jacobaea and Senecio aquaticus: molecular and chemical evidence.
Hybridization is known to be involved in a number of evolutionary processes, including species formation, and the generation of novel defence characteristics in plants. The genus Senecio of the Asteraceae family is highly speciose and has historically demonstrated significant levels of interspecific hybridization. The evolution of novel chemical defence characteristics may have contributed to the success of Senecio hybrids. Chemical defence against pathogens and herbivores has been studied extensively in the model species Senecio jacobaea, which is thought to hybridize in nature with Senecio aquaticus. Here, we use amplified fragment length polymorphisms (AFLPs) and pyrrolizidine alkaloid (PA) composition to confirm that natural hybridization occurs between S. jacobaea and the closely related species S. aquaticus. AFLPs are also used to estimate the ancestry of hybrids. We also demonstrate that even highly back-crossed hybrids can possess a unique mixture of defence chemicals specific to each of the parental species. This hybrid system may therefore prove to be useful in further studies of the role of hybridization in the evolution of plant defence and resistance.


The airway dimension in ordinary human lungs. A standardized morphometry of lung sections.
In chronic obstructive pulmonary disease, obscurities remain in the degree of obstruction and its distribution in the airway tree. To overcome these obscurities, a technique was introduced to estimate the original diameter of an airway in lung sections; this technique involved measurement of the accompanying artery. Ordinary lungs had been obtained at autopsy from 17 deceased patients of various ages; from these lungs, 695 pairs of airways and pulmonary arteries were subjected to computer-assisted measurement of their diameters: the whole range of airways from the segmental bronchi to the respiratory bronchioles was sampled. We proved that a log-log regression existed between the diameter of an airway and that of the pulmonary artery; this regression was sufficiently close to allow one to estimate the diameter of an airway from the diameter of the pulmonary artery, even in chronic obstructive pulmonary disease, in which airways are usually strongly stenosed or dilated. In an additional study of three lungs with various types of chronic obstructive pulmonary disease, the diameters of the pulmonary arteries were shown to remain essentially unaffected.


Effects of proton acceptors on formation of a non-heme iron(IV)-oxo complex via proton-coupled electron transfer.
Rates of formation of a non-heme iron(IV)-oxo complex, [Fe(IV)(O)(N4Py)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), via electron-transfer oxidation of [Fe(III)(OH)(N4Py)](2+) in acetonitrile (MeCN) containing H2O (0.56 M) were accelerated as much as 390-fold by addition of proton acceptors such as CF3COO(-), TsO(-) (p-MeC6H4SO3(-)), NsO(-) (o-NO2C6H4SO3(-)), DNsO(-) (2,4-(NO2)2C6H3SO3(-)), and TfO(-) (CF3SO3(-)). The acceleration effect of proton acceptors increases with increasing basicity of the proton acceptors. The one-electron oxidation potential of [Fe(III)(OH)(N4Py)](2+) was shifted from 1.24 to 0.96 V vs SCE in the presence of TsO(-) (10 mM). The electron-transfer oxidation of Fe(III)-OH complex was coupled with the deprotonation process by proton acceptors in which deuterium kinetic isotope effects were observed when H2O was replaced by D2O.


Thromboelastometry Based Early Goal-Directed Coagulation Management Reduces Blood Transfusion Requirements, Adverse Events, and Costs in Acute Type A Aortic Dissection: A Pilot Study.
BACKGROUND: In aortic surgery bleeding complications can be fatal. Therefore, rotational thromboelastometry(ROTEM™)-based coagulation management was introduced. METHODS: After 5 cases of acute type A aortic dissection and aortic arch replacement had been treated based on ROTEM findings (ROTEM group; RG), 5 cases without ROTEM were matched as control group (CG). CG treatment was based on conventional tests and clinical findings. Blood component and coagulation factor requirements, ventilation time, duration of stay at intensive care unit (ICU), hospitalization, and thrombotic or bleeding incidents as well as transfusion-associated costs were compared. RESULTS: Administration of blood products and coagulation factor concentrates, ventilation time, ICU length of stay, and hospitalization tended to be lower in RG. Postoperative plasma transfusion (p = 0.038), recognized incidents (p = 0.048), and resulting costs on coagulation treatment (p = 0.049) were significantly reduced. CONCLUSION: Our data suggest that ROTEM-based coagulation management can reduce transfusion requirements and corresponding costs in patients with aortic arch replacement. These data has to be confirmed by prospective randomized trials.


Dietary pollutants induce oxidative stress, altering maternal antioxidant provisioning and reproductive output in the temperate sea urchin Evechinus chloroticus.
Evidence is growing to suggest that the capacity to withstand oxidative stress may play an important role in shaping life-history trade-offs, although little is known on the relationship in broadcast spawning marine invertebrates. In this group, variation in gamete quantity and quality are important drivers of offspring survival and successful recruitment. Therefore the provisioning of eggs with antioxidants may be an important driver of life history strategies because they play a critical role in preventing damage from reactive oxygen species to macromolecules. In this study, a suite of oxidative stress biomarkers was measured in the gonads and eggs of the sea urchin Evechinus chloroticus exposed to polycyclic aromatic hydrocarbons (PAHs). Links between oxidative stress markers and core components of fitness including fecundity, gamete quality and maternal transfer of antioxidants were assessed. Experimental induction of oxidative stress was achieved via exposure to a mix of four PAHs over a 21-day period. In PAH exposed individuals, we observed a significant upregulation of the antioxidant defence and detoxification enzymes SOD, CAT, GR, GPx and GST, as well as a greater pool of the non-enzymatic antioxidant glutathione in gonad tissue and eggs. In contrast, glutathione redox status was not affected by PAH exposure, with the percentage of reduced glutathione remaining at approximately 80% in both gonad tissue and released eggs. PAH-exposed adults experienced greater than three- and five-fold increases in oxidative protein and lipid damage, respectively, in gonad tissue. In contrast, eggs maintained low levels of damage, not differing from baseline levels found in eggs released from PAH-naïve mothers. PAH exposure also resulted in a 2-fold reduction in fecundity of reproductively mature females but no significant alteration to egg diameter. Although PAH-exposed females released fewer eggs, successful fertilisation of those eggs was slightly enhanced with average rates ranging from 90-99% in comparison to 76-90% in control eggs. Early-stage offspring reflected maternal antioxidant status with populations derived from PAH-exposed mothers demonstrating significantly higher antioxidant levels than those derived from PAH-naïve mothers. This maternally inherited protection enhanced the capacity of embryos to minimise oxidative damage to lipids and proteins during early development but, despite this, did not reduce the proportion of morphological abnormalities in the population. Overall, these findings indicate that when faced with short-term contaminant stress E. chloroticus has the capacity to trade high reproductive output during a spawning event for a greater antioxidant investment in eggs. However, this production of potentially more resilient offspring did not translate to a fitness gain, at least for the early larval stages in the present experimental conditions.


Functional lateralization of the human premotor cortex during sequential movements.
A neurological truism is that each side of the brain controls movements on the opposite side of the body. Yet some left hemisphere brain lesions cause bilateral impairment of complex motor function and/or ideomotor apraxia. We report that the left dorsal premotor cortex of normal right-handed people plays a fundamental role in sequential movement of both right and left hands. Subjects performed sequential finger movements during functional magnetic resonance imaging of the motor cortices. In right-handed subjects, the volume of activated dorsal premotor cortex showed a left hemispheric predominance during hand movements. We suggest that the observed left premotor dominance contributes to the lateralization found in lesion studies.


Fungal Keratitis, or Misled by a Small Insect?
The pine processionary caterpillar is an insect that has multiple small, thin hairs around its body as a defense mechanism. These hairs have a hazardous effect on ocular structures and cause a broad range of reactions from conjunctivitis to endophthalmitis, referred to as ophthalmia nodosa. The diagnosis of the disease is based on the patient's history and the detection of the hairs on ocular structures. In this report, we present a patient with ophthalmia nodosa misdiagnosed as fungal keratitis, and the actual diagnosis was made by in vivo confocal microscopy. We also would like to increase awareness among ophthalmologists about the disease which has a growing distribution area due to climate change.


The Brownian and Flow-Driven Rotational Dynamics of a Multicomponent DNA Origami-Based Rotor.
Nanomechanical devices are becoming increasingly popular due to the very diverse field of potential applications, including nanocomputing, robotics, and drug delivery. DNA is one of the most promising building materials to realize complex 3D structures at the nanoscale level. Several mechanical DNA origami structures have already been designed capable of simple operations such as a DNA box with a controllable lid, bipedal walkers, and cargo sorting robots. However, the nanomechanical properties of mechanically interlinked DNA nanostructures that are in general highly deformable have yet to be extensively experimentally evaluated. In this work, a multicomponent DNA origami-based rotor is created and fully characterized by electron microscopy under negative stain and cryo preparations. The nanodevice is further immobilized on a microfluidic chamber and its Brownian and flow-driven rotational behaviors are analyzed in real time by single-molecule fluorescence microscopy. The rotation in previous DNA rotors based either on strand displacement, electric field or Brownian motion. This study is the first to attempt to manipulate the dynamics of an artificial nanodevice with fluidic flow as a natural force.


Tennessee Williams.
Tennessee Williams was one of the greatest American playwrights of all time. Born into a family with a strong history of serious mental illness, Williams seemed to have had several major depressive episodes during his early adulthood, along with severe and worsening alcohol and drug dependence and abuse involving sedatives and stimulants throughout his adult life. He received treatment of variable quality and duration in middle and old age. Despite his mental illness, Williams continued to be a productive writer even after age 60, although his later works were less successful. The authors consider both the strengths and limitations of Williams' coping mechanisms.


Production of potent antimicrobial agent by actinomycete, Streptomyces sannanensis strain SU118 isolated from phoomdi in Loktak Lake of Manipur, India.
Actinomycetes have provided a wealth of bioactive secondary metabolites with interesting activities such as antimicrobial, antiviral and anticancer. The study aims at isolation, characterization and the antimicrobial potentiality of Streptomyces sannanensis SU118 obtained from Phoomdi, a unique habitat of Loktak Lake of Manipur, India. An actinomycete strain isolated from Phoomdi soil of Loktak Lake of Manipur, India was identified as Streptomyces sannanensis SU118. It is a Gram-positive filamentous bacterium which exhibits antimicrobial activity only against Gram-positive bacteria, while Gram-negative organisms were not affected. Glucose Soyabean meal broth was found to be the suitable medium for antibiotic production at 28°C for seven days of incubation. The antimicrobial agent produced by the strain was extracted with ethyl acetate as solvent and purified by thin layer chromatography. Screening and bioassay - guided fractionation of the ethyl acetate extract from the culture filtrate led to the isolation of an active potential compound (R f value 0.56) with λmax 275.0 nm which has got the lowest minimum inhibitory concentration (0.5 μg/ml) against Staphylococcus aureus MTCC 96 and Staphylococcus aureus (clinical isolate), whereas highest (3.0 μg/ml) was recorded against Mycobacterium smegmatis MTCC 6 and Bacillus circulans MTCC 8074. This study has therefore uncovered the potential of exploring virgin untapped habitats in the Indo-Burma biodiversity hot spot region as reservoir of promising antimicrobial metabolite producer. These results highlighted the scope for further characterization of the metabolite and could be a candidate in the generation of new antimicrobial agents.


[Expression of SM30 (A-F) Genes Encoding Spicule Matrix Proteins in Intact and Damaged Sea Urchin Strongylocentrotus intermedius (A. Agassiz, 1863) at the Six-Arm Pluteus].
In this study we investigated expression of the SM30(A-F) gene family encoding Strongylocentrotus intermedius spicule matrix proteins during the normal and regenerative pluteus II stage (three pairs of arms). We found that SiSM30A and SiSM30B genes are expressed at high levels in the normal pluteus II sea urchin. SiSM30A is expression was also significantly upregulated in the reparative pluteus II stage 3 hours after damage. Conversely, SiSM30B was downregulated during the reparative pluteus II stage. Our findings reveal a substantial similarity between the activity of SiSM30A and SiSM30B activity in the processes of regenerative growth during the pluteus II stage and during normal development at the prism stage in Strongylocentrotus purpuratus. On the basis of our findings, we propose that normal developmental mechanisms corresponding to the preceding developmental stage are reactivated during pluteus regeneration.


Long-term results of saphenous vein graft for coronary stenosis caused by Kawasaki disease.
Although saphenous vein grafts (SVG) have been used from 1975 to treat coronary stenosis caused by Kawasaki disease, long-term results after more than 20 years remain unknown. From 1981 to 1997, 13 patients underwent coronary artery bypass grafting using SVG (n=20). The age at operation ranged from 2 to 20 years (median 11 years), the age at latest angiography from 15 to 36 years (median 30 years) and the postoperative follow-up period was from 10 to 26 years (median 22 years). The patency rate of the SVG was determined by postoperative angiography, graft wall morphology was graded and the late clinical course was reviewed. The patency rates at 1, 10, and 25 years after operation were 84.4%, 57.2%, and 51.5%, respectively. Irregularity of the SVG wall was slight in 3 of 7 patients with long-term patency. One patient with obesity and hyperlipidemia underwent stent implantation in the SVG because of graft stenosis. Although the patency rates for SVG are low, there are patients with long-term patency over 20 years. Obesity and hyperlipidemia in these patients should be vigorously pursued.


A Human-Derived, Collagen-Rich Hydrogel Augments Wound Healing in a Diabetic Animal Model.
Application of collagen products to wounds has been shown to improve wound healing. Using a collagen-based hydrogel (cHG) capable of cellular support previously developed by our laboratory, we hypothesize that our hydrogel will increase the speed of wound healing by providing a 3-dimensional framework for cellular support, increasing angiogenesis and cell-proliferation at the wound bed. Two, 10-mm excisional wounds were created over the dorsum of 12 male, genetically modified Zucker diabetic rats. Wounds were splinted open to limit healing by wound contracture. One wound was treated with an occlusive dressing (OD), whereas the adjacent wound was treated with an OD plus cHG. Occlusive dressings were changed every other day. Hydrogel was applied on day 2 and every 4 days after until complete wound closure. Rate of wound closure was monitored with digital photography every other day. Wounds were harvested at days 10 and 16 for histological and immunohistochemical analysis. Wound closure was significantly faster in cHG-treated wounds compared with OD-treated wounds. By day 10, cHG-treated wounds achieved 63% wound closure, compared with 55% wound closure in OD-treated wounds (P < 0.05). By day 16, cHG-treated wounds achieved 84% wound closure, compared with 68% wound closure in OD-treated wounds (P < 0.05).Histologically, wound depth was not different between the cHG and OD groups on days 10 and 16. However, wound length was significantly less in the cHG group compared with the OD group (P < 0.05) consistent with digital photographic analysis. Immunohistochemical analysis for RECA-1 demonstrated that blood vessel density in the wound bed was 2.3 times higher in the cHG group compared with the OD group (P = 0.01) on day 16. Cell proliferation was 3.8 times higher in the cHG group versus the OD group (P < 0.05) on day 10. Collagen-based hydrogel-treated wounds demonstrated significantly improved healing compared with control. The thermoresponsive feature of collagen hydrogel and its structural stability at body temperature demonstrate promising clinical potential as a vehicle for the delivery of therapeutic cells to the wound bed.


Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults.
Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947-1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22-56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatory defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3-8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0-8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.


Developmental and hormonal regulation of progesterone receptor A-form expression in female mouse lung in vivo: interaction with glucocorticoid receptors.
Progesterone (P(4)) regulates many aspects of physiological functions via two nuclear P(4) receptors (PR), PRA and PRB, which are members of a structurally related nuclear hormone receptor superfamily that includes glucocorticoid receptors (GR). The regulation and cellular distribution of PR protein isoforms have been extensively studied in reproductive tissues, but this is not the case in the lung. In the present study, reverse transcriptase (RT)-PCR, Western blotting, and immunolocalization supported the presence of PRA in the lung of female mice, with PRA protein levels significantly increased between postnatal day 7 and 12, declined at postnatal day 26, and minimal in adults when compared to postnatal day 2. The peak was temporally related to postnatal lung maturation in rodents. Immunoreactivity for PR was detected in the alveolar and bronchial epithelia. We then extended this study to examine, for the first time, the regulation of PRA protein expression in female mouse lung in vivo. Neither the increase in endogenous P(4) nor treatment with exogenous P(4) regulated PRA protein expression in female mouse lung. However, treatment of mice with the GR/PR antagonist RU 486, but not Org 31710 (a specific PR antagonist), significantly increased PRA protein expression in parallel to a decrease in GR protein expression. In addition, treatment with the synthetic glucocorticoid dexamethasone led to a decrease in PRA protein expression independent of endogenous P(4) levels. Furthermore, immunoprecipitation followed by Western blot analysis revealed that, under in vivo conditions, PRA physically interacted with GR in mouse lung. Confocal laser microscopy revealed that PRA and GR co-localized in the nuclei of alveolar epithelia cells, whereas nuclear PR and cytoplasmic GR were detected in bronchial epithelium. Taken together, our observations suggest that PRA may be an important physiological factor involved in postnatal lung development and that the regulation of PRA protein expression is not dependent on P(4), but rather on functional glucocorticoid/GR signaling mediated by protein-protein interaction in the mouse lung.


The human pituitary proteome: the characterization of differentially expressed proteins in an adenoma compared to a control.
In order to clarify the basic molecular mechanisms that participate in the formation of human pituitary macroadenomas, this study, for the first time, describes the comparative proteomics between a pituitary adenoma tissue and a control tissue. A vertical, two-dimensional polyacrylamide gel electrophoresis system and PDQuest image analysis software were used to provide a high level of between-gel reproducibility and electrophoretic separation to accurately locate each differentially expressed protein. Mass spectrometry (MALDI-TOF and LC-ESI-Q-IT) and protein databases were used to characterize each differentially expressed protein. A total of 137 differential gel spots (37 increased spot volumes, 39 decreased, 19 new and 42 lost) were found when we compared an adenoma proteome to a control proteome. Seventy-one spots (20 increased, 27 decreased, 13 new, 11 lost), representing 39 differentially regulated proteins, were identified. Five differentially regulated proteins (prolactin, cellular retinoic acid-binding protein II, G-protein beta subunit 3, secretagogin and calreticulin) were also validated with results from a comparative transcriptomics study of pituitary adenomas and controls. The functional characteristics of these differentially expressed proteins provide a differential proteomic profile between a pituitary adenoma and a control.


Histamine: the case for a photoreceptor's neurotransmitter.
The evidence is strong that histamine is the transmitter from photoreceptors of the barnacle, several insect species, and Limulus. Histamine is synthesized and stored in the photoreceptors and mimics the effect of the natural transmitter on the postsynaptic cell. An activity-dependent uptake mechanism exists to recapture the histamine for reuse at this continuously active synapse. Only light-dependent release of this compound remains to be demonstrated. A primary job of the photoreceptor's synapse in the barnacle and also in insects is to convert photoreceptor hyperpolarizations at the offset of light (which presumably lead to decreases in transmitter release) to a depolarizing off-response in the postsynaptic cell. Hardie (10) has established that histamine has cooperative binding and a relatively low affinity for its receptor, leading to a short open time for the postsynaptic channel. These features could allow the postsynaptic cell to respond relatively quickly to decreases in transmitter concentration. Perhaps the uptake mechanism demonstrated in barnacle photoreceptors will also prove to be important in the generation of the postsynaptic response by quickly clearing the cleft of released histamine. It will be of interest to determine what factors control the rate of uptake of histamine and whether blocking the uptake mechanism affects signals set up in the postsynaptic cell.


Approach to COVID-19 in older adults and indications for improving the outcomes.
Background: COVID-19 continues to present challenges in the care of older adults with frailty and/or comorbidities and very old patients, who can be hospitalized with severe COVID-19 despite full vaccination. Frailty is a heterogeneous syndrome characterized by an increased aging-related vulnerability due to a reduced physiological reserve and function of systemic organs, and is associated with an impairment of activities of daily living. Frail older adults remain at elevated risk of mortality from COVID-19 compared to older adults without frailty, and some pre-existing risk factors such as malnutrition, prolonged bed rest, and the association with comorbidities can aggravate the SARS-CoV-2 infection. Furthermore, the severity of COVID-19 can impact on long-term functioning of older patients surviving from the infection. Persistent symptoms are another emerging problem of the post-vaccination phase of pandemic, as most patients suffer from chronic symptoms which can become debilitating and affect the daily routine. Aim of this review: In this complex relationship, the evaluation of COVID-19 in vulnerable categories is still a matter of high interest and personalized care plans based on a comprehensive geriatric assessment, tailored interventions; specific therapeutic algorithms among older adults are thus recommended in order to improve the outcomes.


Dual (Anticoagulant Plus Single Antiplatelet) vs Triple (Anticoagulant Plus Dual Antiplatelet) Antithrombotic Therapy - "Real World" Experience.
Atrial fibrillation (AF) is a common arrhythmia that increases in prevalence with advancing age and in patients with coronary artery disease, revascularization, particularly with percutaneous coronary intervention (PCI), is also common. Both disease states have thrombosis as a core pathophysiologic process which requires treatment - low sheer stress thrombi in AF and intracoronary high sheer stress thrombi in PCI. For the 10-20% of patients who have both AF and undergo PCI, preventing thrombotic complications will require inhibition of both processes requiring simultaneous use of anticoagulation and antiplatelet therapy. There is a broad experience of combining oral anticoagulation therapy, used to prevent stroke and systemic embolization, in AF with dual antiplatelet therapy, used to prevent stent thrombosis and thrombotic coronary events. This "triple antithrombotic therapy" (TT) has been evaluated through many observation studies, both small and large. TT has more frequently been associated with a significant increase in bleeding events with non-significant reduction in thrombotic events. Current guidelines recommend shorter duration of TT, especially in patients with high risk of bleeding.


TAS2R activation promotes airway smooth muscle relaxation despite β(2)-adrenergic receptor tachyphylaxis.
Recently, bitter taste receptors (TAS2Rs) were found in the lung and act to relax airway smooth muscle (ASM) via intracellular Ca(2+) concentration signaling generated from restricted phospholipase C activation. As potential therapy, TAS2R agonists could be add-on treatment when patients fail to achieve adequate bronchodilation with chronic β-agonists. The β(2)-adrenergic receptor (β(2)AR) of ASM undergoes extensive functional desensitization. It remains unknown whether this desensitization affects TAS2R function, by cross talk at the receptors or distal common components in the relaxation machinery. We studied intracellular signaling and cell mechanics using isolated human ASM, mouse tracheal responses, and human bronchial responses to characterize TAS2R relaxation in the context of β(2)AR desensitization. In isolated human ASM, magnetic twisting cytometry revealed >90% loss of isoproterenol-promoted decrease in cell stiffness after 18-h exposure to albuterol. Under these same conditions of β(2)AR desensitization, the TAS2R agonist chloroquine relaxation response was unaffected. TAS2R-mediated stimulation of intracellular Ca(2+) concentration in human ASM was unaltered by albuterol pretreatment, in contrast to cAMP signaling, which was desensitized by >90%. In mouse trachea, β(2)AR desensitization by β-agonist amounted to 92 ± 6.0% (P < 0.001), while, under these same conditions, TAS2R desensitization was not significant (11 ± 3.5%). In human lung slices, chronic β-agonist exposure culminated in 64 ± 5.7% (P < 0.001) desensitization of β(2)AR-mediated dilation of carbachol-constricted airways that was reversed by chloroquine. We conclude that there is no evidence for physiologically relevant cross-desensitization of TAS2R-mediated ASM relaxation from chronic β-agonist treatment. These findings portend a favorable therapeutic profile for TAS2R agonists for the treatment of bronchospasm in asthma or chronic obstructive lung disease.


Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1.
Mutations in the parkin gene are linked to autosomal-recessive juvenile parkinsonism (AR-JP). Parkin functions as a ubiquitin protein ligase in the degradation of several proteins, including the neuron-specific septin CDCrel-1. AR-JP-associated parkin mutations inhibit ubiquitination and degradation of CDCrel-1 and other parkin target proteins. Here we show that recombinant adeno-associated virus-mediated CDCrel-1 gene transfer to the substantia nigra of rats results in a rapid onset (6-10 days) of nigral and striatal CDCrel-1 expression that is followed by a progressive loss of nigral dopaminergic neurons and a decline of the striatal dopamine levels. In contrast, neurons of the globus pallidus are spared from CDCrel-1 toxicity. Furthermore, CDCrel-1 inhibits the release of dopamine from stably-transfected PC12 cells, and pharmacological inhibition of tyrosine hydroxylase and dopamine synthesis in rats prevents CDCrel-1-induced nigral neurodegeneration. These results show that CDCrel-1 overexpression exerts dopamine-dependent neurotoxicity and suggest that inhibition of dopamine secretion by CDCrel-1 may contribute to the development of AR-JP.


Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3.
1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has potent antiproliferative effects characterized by a hampered G(1)/S transition. cDNA microarrays were used to monitor expression of 21,492 genes in MC3T3-E1 mouse osteoblasts at 1, 6, 12, 24, and 36 h after treatment with 1,25(OH)(2)D(3). Statistical analysis revealed a cluster of genes that were strongly down-regulated by 1,25(OH)(2)D(3) and which not only function in cell cycle regulation and DNA replication but also mediate checkpoint control, DNA repair, chromosome modifications, and mitosis. Because many of these genes were shown earlier to be regulated by the transcriptional repressor E2F4, the intergenic regions of these 1,25(OH)(2)D(3)-down-regulated genes were searched for the presence of E2F binding sites. This led to the characterization of two novel E2F target genes, chromosome condensation-related SMC-associated protein 1 (Cnap1) and maternal embryonic leucine zipper kinase (Melk). Transfection studies and site-directed mutagenesis confirmed Cnap1 and Melk to be bona fide E2F targets. Repression of Cnap1 and Melk by 1,25(OH)(2)D(3) was confirmed not only in MC3T3-E1 cells but also in several other bone-unrelated cell types. This down-regulation as well as the antiproliferative effect of 1,25(OH)(2)D(3) depended on the pocket proteins p107 and p130 because 1,25(OH)(2)D(3) failed to repress these E2F target genes and lost its antiproliferative action in p107(-/-);p130(-/-) cells but not in pRb(-/-) cells.


[Overexpression of mitofusion 2 inhibits acute respiratory distress syndrome pulmonary fibrosis and its mechanism].
To study the inhibitory effect of overexpression of mitofusion 2 (Mfn2) protein on acute respiratory distress syndrome (ARDS) pulmonary fibrosis and its mechanism. Human embryo lung fibroblasts (HELF) were cultured in vitro, and digested and passaged when the adherent rate of HELF reached 80%, and then the cells in good condition were selected for experiment. The ARDS cell model was reproduced by 5 mg/L of lipopolysaccharide (LPS, LPS group); 75 mol/L adenovirus vector carrying mitofusion 2 (Adv-Mfn2) was transfected into HELF (Adv-Mfn2+LPS group); at the same time, blank control group (complete medium culture) and Adv-vector+LPS group were set as controls. The cell proliferation was observed by sulforhodamine B (SRB) method at 0, 12, 24, 36 and 48 hours. After Hoechst 33342 staining, the morphological changes were observed under confocal microscope. Western blotting was used to detect the protein expressions of Bcl-2 and caspase-3. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expressions of Bcl-2 and caspase-3. After LPS stimulation for 12-48 hours, the cell proliferation rates in the LPS group increased gradually, which were significantly higher than those in the blank control group [12 hours: (10.75±1.51)% vs. (0.73±1.22)%, 24 hours: (20.09±1.71)% vs. (1.15±1.12)%, 36 hours: (20.58±1.55)% vs. (1.20±1.12)%, 48 hours: (21.30±1.51)% vs. (1.23±1.10)%, all P < 0.01]. There was no statistically significant difference in the cell proliferation rate between the LPS group and the Adv-vector+LPS group. After overexpression of Mfn2, the cell proliferation rates at 12, 24, 36, 48 hours in the Adv-Mfn2+LPS group were (8.93±1.14)%, (10.52±1.24)%, (10.72±1.30)%, and (10.91±1.20)%, which were significantly lower than those in the LPS group (all P < 0.05). Confocal microscopy showed that some cells in the blank control group had nuclei of different sizes, and some nuclei fragmented or shrank to form apoptotic bodies. The nuclei of the cells in the LPS and Adv-vector+LPS groups were round or oval in size, and only a few apoptotic cells appeared. When Mfn2 was overexpressed, there were more apoptotic cells in the visual field in the Adv-Mfn2+LPS group than LPS group. Western blotting and RT-qPCR results showed that Bcl-2 expressions increased significantly after LPS stimulation in the LPS group as compared with the blank control group [Bcl-2 protein (Bcl-2/GAPDH): 0.68±0.01 vs. 0.29±0.01, Bcl-2 mRNA (2-ΔΔCT): 2.23±0.34 vs. 1.00±0.00, both P < 0.01], and caspase-3 expressions decreased significantly [caspase-3 protein (caspase-3/GAPDH): 0.37±0.02 vs. 0.66±0.02, caspase-3 mRNA (2-ΔΔCT): 0.31±0.05 vs. 1.00±0.00, both P < 0.01]. Compared with LPS group, the expressions of Bcl-2 after overexpression of Mfn2 in the Adv-Mfn2+LPS group were down-regulated [Bcl-2 protein (Bcl-2/GAPDH): 0.46±0.01 vs. 0.68±0.01, Bcl-2 mRNA (2-ΔΔCT): 1.45±0.14 vs. 2.23±0.34, both P < 0.01], and the expressions of caspase-3 were up-regulated [caspase-3 protein (caspase-3/GAPDH): 0.54±0.02 vs. 0.37±0.02, caspase-3 mRNA (2-ΔΔCT): 0.88±0.10 vs. 0.31±0.05, both P < 0.01]. Mfn2 protein is involved in ARDS pulmonary fibrosis, which may be related to mitochondrial mediated inhibition of cell proliferation.


The effect of intermittent and variable negative pressure wound therapy on wound edge microvascular blood flow.
Negative pressure wound therapy (NPWT) alters wound edge microvascular blood flow. Some preclinical data suggest that cycling between low and high negative pressure may be more beneficial than continuous NPWT. The purpose of this in vivo study was to compare the effect of intermittent negative pressure (cycled either from 0 to -75 or to -125 mm Hg) and variable negative pressure (cycled from -10 to -75 or -125 mm Hg or from -45 to -75 or -125 mm Hg) on wound edge microvascular blood flow. Using a peripheral wound model (n = 8 domestic 70-kg pigs), intermittent and variable NPWT was applied to surgically created wounds (5 cm diameter, 2 cm depth) for five cycles of 5 minutes of high and 2 minutes of low pressure. Blood flow was measured using laser Doppler velocimetry in subcutaneous and muscle tissue at 0.5 and 2.5 cm from the wound edge. When NPWT was applied, blood flow decreased an average of 29% +/- 2% in muscle tissue and 22 % +/- 4% in subcutaneous tissue at -75 mm Hg at 0.5 cm from the wound edge and increased an average of 20% +/- 6% for -75 mm Hg at 2.5 cm from the wound edge. Blood flow changed repeatedly when negative pressure was cycled. Large gradients between the cycled pressures (eg, -10 to -75 mm Hg) resulted in greater blood flow alterations than smaller (eg, -45 to -75 mm Hg) gradients. Blood flow alternations were similar between low-pressure settings of -10 mm Hg (variable NPWT) and 0 mm Hg (intermittent NPWT) and between high-pressure settings of -75 or -125 mm Hg. Both intermittent and variable NPWT result in a beneficial combination of increased blood flow, known to facilitate oxygenation and nutrient supply, and decreased blood flow, known to stimulate angiogenesis and granulation tissue formation. Cycling the negative pressure may be especially advantageous when treating poorly vascularized tissue. In cases where intermittent therapy causes patient discomfort, variable therapy may be superior.


Transient crossed cerebellar diaschisis due to cerebral hyperperfusion following surgical revascularization for moyamoya disease: case report.
Crossed cerebellar diaschisis (CCD) often occurs after ischemic or hemorrhagic stroke that damages the cortico-ponto-cerebellar pathway. However, CCD due to cerebral hyperperfusion following cerebrovascular reconstruction is rare. A 61-year-old woman presented with transient CCD due to cerebral hyperperfusion following bypass surgery for adult moyamoya disease. She developed transient weakness of the right extremities and was diagnosed with moyamoya disease. First, she underwent superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis with indirect synangiosis on the left. Postoperative course was uneventful. Subsequently, she underwent STA-MCA anastomosis with indirect synangiosis on the right. She complained of mild headache on the right, and single photon emission computed tomography (SPECT) performed on the 7th postoperative day demonstrated hyperperfusion in the right frontal and temporal lobes associated with hypoperfusion in the left cerebellum. Magnetic resonance (MR) imaging demonstrated no new lesions and MR angiography showed patent STA-MCA bypass. Subsequent SPECT showed disappearance of both hyperperfusion and CCD. This case strongly suggests that cerebral hyperperfusion after bypass surgery for moyamoya disease may cause transient CCD. Although the clinical significance is still obscure, this phenomenon indicates the cortico-ponto-cerebellar pathway is interrupted due to hyperperfusion, suggesting the development of hyperperfusion syndrome. Careful observation of cerebral hemodynamics after bypass surgery is warranted to avoid hyperperfusion-related complications.


Oxygen requirement for acetylene reduction by pure cultures of rhizobia.
The oxygen and nutritional requirements for acetylene reduction by Rhizobium japonicum and Rhizobium sp. in liquid culture are described. The optimal oxygen concentration was about 0.1% in the gas phase, which is lower than that of any other known aerobic nitrogen-fixing microorganism. these organisms are also unique in that nitrogenase synthesis is not repressed in the presence of ammonium chloride under certain cultural conditions, in contrast to other wild-type bacteria.


Gastrointestinal manifestations of HIV infection.
Gastrointestinal symptoms are pervasive in patients with AIDS. Organ-specific symptoms, particularly dysphagia, postprandial emesis, hematemesis, biliary colic, increasing abdominal girth, and small volume diarrhea, are usually easy to diagnose definitively and may respond to specific therapy. Thorough invasive and noninvasive investigation is warranted.


Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis.
Lung inflammatory cells of patients with idiopathic pulmonary fibrosis (IPF) were evaluated for their ability to injure 51Cr-labeled AKD alveolar epithelial cells in the presence and absence of IPF alveolar epithelial lining fluid (ELF). The IPF cells were spontaneously releasing exaggerated amounts of superoxide (O.2) and hydrogen peroxide (H2O2) compared with normal (P less than 0.02). Cytotoxicity of the AKD cells was markedly increased when the IPF inflammatory cells were incubated with autologous ELF (P less than 0.02). The majority of IPF patients had ELF myeloperoxidase levels above normal (P less than 0.002). Incubation of IPF ELF with AKD cells in the presence of H2O2 caused increased cellular injury (P less than 0.01 compared with control), which was suppressed by methionine, a myeloperoxidase system scavenger. IPF patients with high concentrations of ELF myeloperoxidase deteriorated more rapidly than those with low ELF myeloperoxidase (P less than 0.05). Thus, IPF is characterized by an increased spontaneous production of oxidants by lung inflammatory cells, the presence of high concentrations of myeloperoxidase in the ELF of the lower respiratory tract, and a synergistic cytotoxic effect of alveolar inflammatory cells and ELF on lung epithelial cells, suggesting oxidants may play a role in causing the epithelial cell injury of this disorder.


A new species of Hymeraphia Bowerbank, 1864 (Axinellida: Raspailiidae) from a deep-water canyon southwest off Ireland.
The genus Hymeraphia currently comprises three species and all records of the genus are from the northeast Atlantic and the Mediterranean Sea. The present paper describes a new species, H. vaceleti sp. nov. from a deep-water canyon, off southwest Ireland. H. vaceleti sp. nov. is morphologically distinct from other Hymeraphia species and 28S rRNA sequences show substantial differences between our new species and other Hymeraphia spp. We present data on the prevalence of sponge species established on the basis of single specimens (singletons) or uniques (species only known from a single locality). We argue for the recognition of singletons for species that are rare or from habitats that are very difficult to survey or sample, such as the deep sea.


Improved functional properties of the ovoinhibitor by conjugating with galactomannan.
The chicken egg white ovoinhibitor, a multi-type proteinase inhibitor, was conjugated with galactomannan through the Maillard reaction in a controlled dry heating state at 60 degrees C and 65% relative humidity. The formation of an ovoinhibitor-galactomannan conjugate during dry heating was confirmed by SDS-PAGE. The resulting ovoinhibitor-galactomannan conjugate showed almost the same inhibitory activity toward trypsin, chymotrypsin and elastase as that of the untreated ovoinhibitor, while the conjugate showed stronger heat stability and better emulsifying properties than the untreated ovoinhibitor. These results suggest that the ovoinhibitor-galactomannan conjugate can be used as a protease inhibitor having heat stability and outstanding emulsifying properties for industrial application.


A general model for selectivity in olefin cross metathesis.
In recent years, olefin cross metathesis (CM) has emerged as a powerful and convenient synthetic technique in organic chemistry; however, as a general synthetic method, CM has been limited by the lack of predictability in product selectivity and stereoselectivity. Investigations into olefin cross metathesis with several classes of olefins, including substituted and functionalized styrenes, secondary allylic alcohols, tertiary allylic alcohols, and olefins with alpha-quaternary centers, have led to a general model useful for the prediction of product selectivity and stereoselectivity in cross metathesis. As a general ranking of olefin reactivity in CM, olefins can be categorized by their relative abilities to undergo homodimerization via cross metathesis and the susceptibility of their homodimers toward secondary metathesis reactions. When an olefin of high reactivity is reacted with an olefin of lower reactivity (sterically bulky, electron-deficient, etc.), selective cross metathesis can be achieved using feedstock stoichiometries as low as 1:1. By employing a metathesis catalyst with the appropriate activity, selective cross metathesis reactions can be achieved with a wide variety of electron-rich, electron-deficient, and sterically bulky olefins. Application of this model has allowed for the prediction and development of selective cross metathesis reactions, culminating in unprecedented three-component intermolecular cross metathesis reactions.


3D Tdoa Problem Solution with Four Receiving Nodes.
Time difference of arrival (TDOA) positioning methods have experienced growing importance over the last few years due to their multiple applications in local positioning systems (LPSs). While five sensors are needed to determine an unequivocal three-dimensional position, systems with four nodes present two different solutions that cannot be discarded according to mathematical standards. In this paper, a new methodology to solve the 3D TDOA problems in a sensor network with four beacons is proposed. A confidence interval, which is defined in this paper as a sphere, is defined to use positioning algorithms with four different nodes. It is proven that the separation between solutions in the four-beacon TDOA problem allows the transformation of the problem into an analogous one in which more receivers are implied due to the geometric properties of the intersection of hyperboloids. The achievement of the distance between solutions needs the application of genetic algorithms in order to find an optimized sensor distribution. Results show that positioning algorithms can be used 96.7% of the time with total security in cases where vehicles travel at less than 25 m/s.


Anti-interferon gamma treatment blocks the ability of glutaraldehyde-polymerized allergens to inhibit specific IgE responses.
The lymphokines interleukin 4 and interferon gamma (IFN-gamma) have been shown to play an important role in regulation of polyclonal immunoglobulin E (IgE) and IgG2a responses in vitro and in vivo. We demonstrate here that treatment with chemically modified ovalbumin (OA) results in long-lived, 97-99% inhibition of allergen-specific murine IgE responses and 10(3)-10(4)-fold increases in anti-OA IgG2a. Responses to unrelated antigens are not affected. Treatment with unmodified OA under the same conditions fails to inhibit primary or secondary IgE responses or to increase IgG2a but does lead to pronounced increases in OA-specific IgG1 production. Glutaraldehyde-polymerized ovalbumin (OA-POL)-induced changes in IgE and IgG2a responses are abrogated by in vivo treatment with purified monoclonal anti-IFN-gamma antibody (XMG 1.2), a finding indicative of preferential IFN-gamma production upon exposure to chemically modified, but not native, allergen. The results suggest the possibility that the pattern of cytokine synthesis elicited after exposure to protein antigens, and the resulting immune response, may be dependent upon the form of antigen to which the individual is exposed and consequently may be subject to manipulation.


Orthodontic treatment demand in young adolescents - Are parents familiar with their children's desires and reasons?
To assess the levels of agreement between parents and adolescents about young adolescents' orthodontic treatment demand and to what extent is treatment demand conditioned by family and psychosocial impacts and oral function. This cross-sectional study included 221 adolescents (11-14 years, 54% female) and their parents. A 5-point scale was used to assess orthodontic treatment demand. Adolescents self-administered the Child Perceptions Questionnaire, and parents self-administered the Parental-Caregivers Perceptions Questionnaire and Family Impact Scale. The Index of Orthodontic Treatment Need Dental Health Component (IOTN DHC) was used for determining malocclusion severity. Intraclass correlation coefficient and Cohen's kappa coefficient were used for the assessment of agreement between two informants. The parent-child agreement on children's orthodontic treatment demand was weak, concording in 67.4% of cases. The most common reasons for seeking orthodontic treatment derive from the emotional (EW) and social well-being domains for both informants. In linear regression, the adolescent's reporting of impaired EW and IOTN DHC was the only significant linear predictor of orthodontic treatment demand. Parents cannot correctly assess the orthodontic treatment demand of their children. Impaired EW is the most significant self-reported determinant of adolescents' demand for orthodontic treatment. Family relationships and parental perspective have a low influence.


A Comparative Study on the Roll-to-Roll Processing of a Silicate-Polyvinyl Alcohol Composite Barrier Lacquer Using Slot-Die and Reverse Gravure Coating Techniques.
The integration of platelet-shaped montmorillonite particles to improve the oxygen barrier of polyvinyl-alcohol-based barrier layers is state-of-the-art, but research on roll-to-roll coatings of such composite barrier lacquers has not been widely published. In this study, two different coating techniques, slot-die and reverse gravure, were used on a roll-to-roll scale to apply barrier lacquers comprising polyvinyl alcohol and montmorillonite. The lacquers were analyzed regarding viscosity at certain shear rates and surface energy and the dried coating layers regarding oxygen barrier, surface morphology, and particle orientation. Low permeability coefficients delivering a high oxygen barrier of 0.14 and 0.12 cm3 (STP) 1 μmm2 d bar were achieved for the coating layers with slot-die and reverse gravure coating, respectively. It turned out that the properties of the barrier lacquer need to be adjusted to the coating technique to achieve high oxygen barrier performance. By tailoring the barrier lacquer formulation, the orientation of the platelet-shaped montmorillonite particles can be achieved using both techniques. A low solid content of down to 3 wt% is preferable for the premetered slot-die coating, because it results in low agglomeration quantity in the coating layer. A high solid content of up to 9 wt% is preferable for the self-metered reverse gravure coating to assure a homogeneously coated layer.


Two-Dimensional High-Performance Liquid Chromatography as a Powerful Tool for Bioanalysis: The Paradigm of Antibiotics.
The technique of two-dimensional high-performance liquid chromatography has managed to gain the recognition it deserves thanks to the advantages of satisfactory separations it can offer compared to simple one-dimensional. This review presents in detail key features of the technique, modes of operation, and concepts that ensure its optimal application and consequently the best possible separation of even the most complex samples. Publications focusing on the separation of antibiotics and their respective impurities are also presented, providing information concerning the analytical characteristics of the technique related to the arrangement of the instrument and the chromatographic conditions.


Cholesteatoma vs. cholesterol granuloma of the petrous apex.
Lesions involving the petrous apex are rarely encountered in clinical practice. This directly affects the ability of the otolaryngologist to diagnose and effectively treat these lesions. Greater physician awareness and increased technologic capability are leading to more effective management of pathologic conditions involving this area of the temporal bone.


Receiver operating characteristic estimation and threshold selection criteria in three-class classification problems for clustered data.
Statistical evaluation of diagnostic tests, and, more generally, of biomarkers, is a constantly developing field, in which complexity of the assessment increases with the complexity of the design under which data are collected. One particularly prevalent type of data is clustered data, where individual units are naturally nested into clusters. In these cases, Bias can arise from omission, in the evaluation process, of cluster-level effects and/or individual covariates. Focusing on the three-class case and for continuous-valued diagnostic tests, we investigate how to exploit the clustered structure of data within a linear-mixed model approach, both when the assumption of normality holds and when it does not. We provide a method for the estimation of covariate-specific receiver operating characteristic surfaces and discuss methods for the choice of optimal thresholds, proposing three possible estimators. A proof of consistency and asymptotic normality of the proposed threshold estimators is given. All considered methods are evaluated by extensive simulation experiments. As an application, we study the use of the Lysosomal Associated Membrane Protein Family Member 5 gene expression as a biomarker to distinguish among three types of glutamatergic neurons.


Aorto-esophageal fistula: successful open surgical management of two cases.
An aorto-esophageal fistula (AEF) is a rare yet life-threatening cause of upper gastrointestinal bleeding. We report our experience with open surgical management of two cases of AEF. Both cases presented with almost identical presentations: hematemesis and hemodynamic instability. The aorta in the first patient was normal; the defect was small and was repaired with a Dacron patch. The second patient had an aneurysmal aorta, which was replaced with a Dacron graft. Both cases were performed under partial bypass. The esophageal rent in both patients was debrided, primarily closed and buttressed with a vascularized intercostal pedicle. Nonavailability of endovascular personnel and equipment along with hemodynamic instability of the patient influenced our surgical strategy. Long-term follow-up of these patients is necessary to analyze the outcomes of our surgical repair.