Interaction of strain AD169 and a clinical isolate of cytomegalovirus with peripheral monocytes: the effect of lipopolysaccharide stimulation.
The effect of human cytomegalovirus (CMV) infection on lipopolysaccharide (LPS)-stimulated and unstimulated monocytes from seronegative donors was studied by using the laboratory-adapted strain AD169 and a recent clinical isolate. LPS-stimulated and unstimulated monocytes infected with the isolate showed expression of immediate-early CMV antigens and were significantly more suppressive for lymphocyte proliferation than were strain AD169-infected monocytes, which rarely expressed detectable viral protein. Human CMV infection of LPS-stimulated and unstimulated monocytes resulted in abrogation of interleukin-1 activity, with the effect being marked in LPS-stimulated monocytes infected with the clinical isolate of CMV. Addition of interleukin-1 to infected, stimulated monocytes completely restored lymphoproliferative responses to phytohemagglutinin, whereas addition of this leukokine to infected, unstimulated cells could not restore this response.


Erythromycin infusion prior to endoscopy for acute nonvariceal upper gastrointestinal bleeding: a pilot randomized controlled trial.
The aim of this study was to compare the effects of erythromycin infusion and gastric lavage in order to improve the quality of visualization during emergency upper endoscopy. We performed a prospective randomized pilot study. Patients presented with hematemesis or melena within 12 hours and were randomly assigned to the erythromycin group (intravenous infusion of erythromycin), gastric lavage group (nasogastric tube placement with gastric lavage), or erythromycin + gastric lavage group (both erythromycin infusion and gastric lavage). The primary outcome was satisfactory visualization. Secondary outcomes included identification of a bleeding source, the success rate of hemostasis, duration of endoscopy, complications related to erythromycin infusion or gastric lavage, number of transfused blood units, rebleeding rate, and bleeding-related mortality. A total of 43 patients were randomly assigned: 14 patients in the erythromycin group; 15 patients in the gastric lavage group; and 14 patients in the erythromycin + gastric lavage group. Overall satisfactory visualization was achieved in 81% of patients: 92.8% in the erythromycin group; 60.0% in the gastric lavage group; and 92.9% in the erythromycin + gastric lavage group, respectively (p = 0.055). The identification of a bleeding source was possible in all cases. The success rate of hemostasis, duration of endoscopy, and number of transfused blood units did not significantly differ between groups. There were no complications. Rebleeding occurred in three patients (7.0%). Bleeding-related mortality was not reported. Intravenous erythromycin infusion prior to emergency endoscopy for acute nonvariceal upper gastrointestinal bleeding seems to provide satisfactory endoscopic visualization.


Modification of Green's one-step-late algorithm for attenuated emission data.
Green's one-step-late (OSL) algorithm is a popular image reconstruction algorithm in emission-data tomography, in spite of its convergence issues. One drawback of Green's algorithm is that the algorithm exhibits non-stationary regularization when the algorithm's projector and backprojector model the attenuation effects in single photon emission computed tomography (SPECT). This paper suggests a remedy to improve Green's OSL algorithm so that stationary regularization can be obtained. This paper also observes some similarities between the modified Green's OSL algorithm and the gradient descent algorithm.


Stimulatory effects of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs.
We examined the effect of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs. Bombesin significantly increased plasma immunoreactive trypsin (IRT). Atropine significantly inhibited the response of plasma IRT to bombesin. Pancreatic trypsin secretion was also increased by bombesin, as well as bicarbonate and protein outputs. Atropine failed to inhibit pancreatic trypsin secretion. In conclusion, bombesin has a stimulatory effect on plasma trypsin release mediated by a cholinergic mechanism and different from pancreatic secretion.


Two new antibiotics, A-218 and K-41. Isolation and characterization.
Two new antibiotics, A-218 and K-41, were isolated from strains identified as Streptomyces hygroscopicus. The antibiotics are characterized as polycyclic polyether compounds and are active against gram-positive bacteria.


The role of genetic factors in patients with hepatocellular carcinoma and iron overload - a prospective series of 234 patients.
Iron overload (IO) in HFE-related hereditary haemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/L (females) and/or transferrin saturation ≥50% (males) or ≥45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC. A total of 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, three were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. Thirteen patients with a LIC>70 μmol/g were enrolled in further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe haemochromatosis. Specific haplotypes of SLC40A1 were also studied. Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and the associated at-risk genotypes in patients who have developed HCC, is useful for both determining etiologic diagnosis and enabling family screening and possibly primary prevention in relatives.


Timing and the transition between modes in the defensive behavior system.
Antipredator defense is organized in a way that mirrors Timberlake's feeding behavior system because the goal of defense is to thwart predatory behavior. Each predatory mode has a corresponding antipredator mode. Like appetitive behavior systems, the defensive behavior system is organized around distinct modes along a spatiotemporal continuum we call the predatory imminence continuum. Behavior systems theory directs investigation toward the factors that lead to transitions between modes. In the feeding and sex systems the time between Conditional Stimulus (CS) and Unconditional Stimulus (US; e.g., CS-US interval or CS duration) is an important factor. Short CSs elicit conditional responses (CR) characteristic of more terminal modes and long CSs provoke CRs belonging to initial modes. Therefore, we asked if short CSs (10 s) would provoke CRs like the vigorous activity bursts and escape-like responses characteristic of the terminal mode of the predatory imminence continuum (Circa-Strike Behavior). Also, via analogy to appetitive systems, long CSs (3 min) were predicted to favor the intermediate mode, post-encounter behavior, which is characterized by freezing. Instead we found that both CSs produced freezing but not activity burst CRs and that freezing was actually greater with the short CS. We suggest that this difference between behavior systems flows from selection pressure that favors moving toward terminal modes in appetitive systems but away from terminal modes in the antipredator system. In addition, since appetitive reinforcers are more likely to be repeatedly experienced than predators, the learning of timing may be less relevant to defense. We also found that shock produced activity bursts and argue that when you are in the post-encounter mode (freezing) a sudden change in stimulation causes an immediate transition to circa-strike (terminal) behavior.


Clinical impact of timing of surgery on outcomes in preterm infants with surgical necrotizing enterocolitis.
The clinical impact of the timing of surgery on outcomes in preterm infants with surgical necrotizing enterocolitis (NEC) is not well defined. We sought to investigate the impact of the different timing of surgery from the day of NEC diagnosis on clinical outcomes in preterm infants with surgical NEC. Retrospective Cohort Study. Preterm 75 infants admitted between January 2013 and December 31, 2018, with an NEC (Bell stage III) diagnosis. Comparison of clinical information by the timing of surgery at three different time points (less and more than 48 hours, 96 hours, and 168 hours) in preterm infants with surgical NEC. 75 infants were included in the analysis. Those who received surgery after 48 hours (n= 29/75) had lower median gestational age, lower birth weight, had less pneumoperitoneum, were out born less frequently, had higher acute kidney injury, were intubated and ventilated more frequently, and had higher hemorrhagic and reparative lesions on histopathology than those receiving surgery after 48 hours. Infants receiving surgery after 96 hours had similar trends expect had significantly lower hematocrit and more prolonged parenteral nutrition dependence than less than 96 hours group. The infants receiving surgery after one week had significantly lower birth weight and had higher reparative changes and cholestasis than those receiving surgery < 1 week.There was no significant impact of surgery timing on the length of bowel loss, surgical morbidity, Bronchopulmonary dysplasia, white matter injury, and mortality. The infants receiving surgery later were young and smaller and received parenteral nutrition longer with no significant impact on morbidities and mortality. Our data point out that there are advantages of operating early with fewer morbidities which need further confirmation and evaluation in large multicentric prospective studies or clinical trials.


Effects of centrifugation leukapheresis with hydroxyethyl starch on the complement system of granulocyte donors.
In granulocyte donors during centrifugation leukapheresis (CL), total hemolytic complement, Clq, C3, factor B, and properdin decreased, but only to the extent expected from hemodilution. Crossed immunoelectrophoresis showed no C3 conversion in plasma obtained from the leukapheresis appeared during CL or in donor plasma immediately after CL. When serum was incubated with hydroxyethyl starch, total hemolytic complement did not decrease and C3 conversion was not detected by crossed immunoelectrophoresis. This investigation revealed no evidence that complement activation is associated with CL.


Xylan-degrading enzymes from Aspergillus terreus: Physicochemical features and functional studies on hydrolysis of cellulose pulp.
Two endo-β-1,4-xylanases named XylT1 and XylT2, previously purified from Aspergillus terreus, were structurally investigated by fluorescence quenching and characterized with respect to their binding properties with phenolic compounds. Neutral and charged quenchers had access to both enzymes in neutral and alkaline pHs. The greatest access was noted for the negative quencher, possibly due to positive amino acid residues in the vicinity of tryptophan. These tryptophan environments may partially explain the conformational differences and lower binding constants of phenolic compounds for XylT2 than XylT1Phenolic compounds had lower binding constants for XylT2 than XylT1. These results show that xylanases present structural and functional differences, despite belonging to similar families. XylT1 and XylT2 were also evaluated for their ability to hydrolyze cellulose pulp in different stages of bleaching. Both enzymes promoted hydrolysis of cellulose pulps, which was confirmed by the release of total reducing sugars, pentoses and chromophoric material. Analysis of released xylooligosaccharides demonstrated a preferential release of xylobiose. None of xylanases released glucose, showing that they do not hydrolyze the cellulose present in the pulp, making both enzymes excellent choices for bio-bleaching applications.


Prevention of the respiratory distress syndrome in premature infants by antepartum glucocorticoid therapy.
A trial of antepartum dexamethasone therapy was carried out in 55 mothers in whom premature delivery threatned between 28 to 36 weeks gestation in the hope of reducing the incidence of respiratory distress syndromes (RDS). The control group was made up of 62 mothers who delivered prematurely in the same gestational age without any treatment. In the treated group isoxsuprine was used to delay delivery when necessary. The respiratory dif infants (8.3 per cent) than in the controls (35.2 per cent; p less than 0.001). The difference was more marked in babies of under 32 weeks gestation. Considering only cases with intact membranes the incidence of RDS was significantly (p less than 0.01) lower in the treated group. Early neonatal mortality was 6.6 per cent in the treated group and 38 per cent (p less than 0.0001) in the controls. In 12 cases the L/S ratio was measured during dexamethasone administration and in the majority of these the L/S ratio rose sharply to mature values following treatment. This rise was observed as soon as 48 hours after beginning of dexamethasone. Antepartum isoxsuprine in the treated group had no apparent effect on the incidence of RDS. No adverse effects of steroid therapy were observed. This trial confirms the studies of others that antepartum glucocorticoid can significantly reduce the incidence of RDS in premature infants.


[Screening for microalbuminuria in diabetic patients in the primary health care system].
In order to detect the prevalence of microalbuminuria, a screening procedure was carried out in 1016 adult (age > 14 years) diabetic patients registered in primary health care system at the 17st district of the capital. The clinical characteristics of patients were investigated and microalbuminuria was measured by immunoturbidimetric method using first void morning urinary samples. In this way, the urinary albumin/creatinine ratio was calculated (abnormal value in men > or = 2.5 mg/mmol, in women > or = 3.5 mg/mmol). Moreover, serum creatinine, blood glucose, serum cholesterol and triglycerides were measured in fasting blood samples. After applying exclusion criteria data of 933 diabetic patients [129 insulin-dependent (IDDM) and 804 non-insulin-dependent (NIDDM) patients; 424 men, 509 women] were analysed. Abnormal urinary albumin/creatinine ratio was found in 315 (33.8%) patients. Microalbuminuria was detected in 32 (24.8%) IDDM and in 201 (25.0%) NIDDM patients. Macroalbuminuria was found in 13 (10.1%) IDDM and in 69 (8.6%) NIDDM patients. Abnormal urinary albumin/creatinine ratio was more often found in men than in women (IDDM men 41.3%, IDDM women 28.8%; NIDDM men 38.0%, NIDDM women 30.0%). Significant difference was found between diabetic patients with (n = 315) and without (n = 618) abnormal urinary albumin/creatinine ratio regarding age (64.3 +/- 0.7 years vs. 61.4 +/- 0.5 years; p < 0.001), duration of diabetes (10.3 +/- 0.5 years vs 7.9 +/- 0.3 years; p < 0.001) systolic blood pressure (151 +/- 1 mmHg vs 146 +/- 1 mmHg; p < 0.01), serum creatinine (99 +/- 2 mumol/l vs 88 +/- 1 mumol/l; p < 0.001) and blood glucose (10.4 +/- 0.2 mmol/l vs 9.4 +/- 0.1 mmol/l; p < 0.001). One third (33.8%) of diabetic patients in primary health care setting exhibited signs or were at risk of renal involvement of diabetes. Diabetic patients with micro- or macroalbuminuria should be carefully controlled in order to prevent or to decrease deterioration of renal function due to diabetic nephropathy.


Evolution of Cost-Free Resistance under Fluctuating Drug Selection in Pseudomonas aeruginosa.
Antibiotic resistance evolves rapidly in response to drug selection, but it can also persist at appreciable levels even after the removal of the antibiotic. This suggests that many resistant strains can both be resistant and have high fitness in the absence of antibiotics. To explore the conditions under which high-fitness, resistant strains evolve and the genetic changes responsible, we used a combination of experimental evolution and whole-genome sequencing to track the acquisition of ciprofloxacin resistance in the opportunistic pathogen Pseudomonas aeruginosa under conditions of constant and fluctuating antibiotic delivery patterns. We found that high-fitness, resistant strains evolved readily under fluctuating but not constant antibiotic conditions and that their evolution was underlain by a trade-off between resistance and fitness. Whole-genome sequencing of evolved isolates revealed that resistance was gained through mutations in known resistance genes and that second-site mutations generally compensated for costs associated with resistance in the fluctuating treatment, leading to the evolution of cost-free resistance. Our results suggest that current therapies involving intermittent administration of antibiotics are contributing to the maintenance of antibiotic resistance at high levels in clinical settings. IMPORTANCE Antibiotic resistance is a global problem that greatly impacts human health. How resistance persists, even in the absence of antibiotic treatment, is thus a public health problem of utmost importance. In this study, we explored the antibiotic treatment conditions under which cost-free resistance arises, using experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to the evolution of cost-free resistance and demonstrate that compensatory evolution is the mechanism responsible for cost-free resistance. Our results suggest that discontinuous administration of antibiotic may be contributing to the high levels of antibiotic resistance currently found worldwide.


Sulfonation of phenols extracted from the pyrolysis oil of oil palm shells for enhanced oil recovery.
The cost of chemicals prohibits many technically feasible enhanced oil recovery methods to be applied in oil fields. It is shown that by-products from oil palm processing can be a source of valuable chemicals. Analysis of the pyrolysis oil from oil palm shells, a by-product of the palm oil industry, reveals a complex mixture of mainly phenolic compounds, carboxylic acids, and aldehydes. The phenolic compounds were extracted from the pyrolysis oil by liquid-liquid extraction using alkali and an organic solvent and analyzed, indicating the presence of over 93% phenols and phenolic compounds. Simultaneous sulfonation and alkylation of the pyrolysis oil was carried out to produce surfactants for application in oil fields. The lowest measured surface tension and critical micelle concentration was 30.2 mNm(-1) and 0.22 wt%, respectively. Displacement tests showed that 7-14% of the original oil in place was recovered by using a combination of surfactants and xanthan (polymer) as additives.


Measurement of differential cross-sections of a single top quark produced in association with a W boson at s = 13 TeV with ATLAS.
The differential cross-section for the production of a W boson in association with a top quark is measured for several particle-level observables. The measurements are performed using 36.1 fb - 1 of pp collision data collected with the ATLAS detector at the LHC in 2015 and 2016. Differential cross-sections are measured in a fiducial phase space defined by the presence of two charged leptons and exactly one jet matched to a b-hadron, and are normalised with the fiducial cross-section. Results are found to be in good agreement with predictions from several Monte Carlo event generators.


Purkinje Cell Pathology and Loss in Multiple Sclerosis Cerebellum.
Cerebellar ataxia commonly occurs in multiple sclerosis, particularly in chronic progressive disease. Previous reports have highlighted both white matter and grey matter pathological changes within the cerebellum; and demyelination and inflammatory cell infiltrates appear commonly. As Purkinje cell axons are the sole output of the cerebellar cortex, understanding pathologic processes within these cells is crucial to develop strategies to prevent their loss and thus reduce ataxia. We studied pathologic changes occurring within Purkinje cells of the cerebellum. Using immunohistochemic techniques, we found changes in neurofilament phosphorylation states within Purkinje cells, including loss of dephosphorylated neurofilament and increased phosphorylated and hyperphosphorylated neurofilament. We also found Purkinje axonal spheroids and Purkinje cell loss, both of which occurred predominantly within areas of leucocortical demyelination within the cerebellar cortex. These changes have important implications for the study of cerebellar involvement in multiple sclerosis and may help design therapies to reduce the burden of ataxia in the condition.


Occurrence and distribution of Arcobacter species in poultry processing.
A total of 16 broiler flocks slaughtered in the morning in eight Belgian poultry slaughterhouses were examined for the presence of Campylobacteraceae. In samples collected before and after chilling, the prevalence of arcobacters was found to be higher than the prevalence of thermophilic campylobacters, with the slaughter procedure used having no clear effect. Two slaughterhouses were selected for a detailed investigation of the occurrence and distribution of arcobacters. Sampling carried out before slaughter revealed that both Arcobacter butzleri and Arcobacter cryaerophilus were commonly present on the slaughter equipment in both plants. These findings indicate inadequate decontamination of the slaughterhouse environment and suggest potential Arcobacter contamination of broiler carcasses through the slaughter equipment. Even before evisceration, contamination levels of hundreds to several thousands of arcobacters per gram of neck skin were detected. It appears unlikely that contamination through slaughter equipment alone explains the high contamination levels found for poultry products. Arcobacters were not isolated from the 30 intestinal tracts sampled for each broiler flock examined. A. cryaerophilus was the only Arcobacter species recovered from the transport crate samples collected before and after washing. Arcobacter contamination during slaughter, either direct (from chicken intestinal content or feces) or indirect (from equipment), was not confirmed. The origin and the precise routes of contamination remain to be determined.


Delayed inflammatory and cell death responses are associated with reduced pathogenicity in Lujo virus-infected cynomolgus macaques.
To identify host factors associated with arenavirus virulence, we used a cynomolgus macaque model to evaluate the pathogenesis of Lujo virus (LUJV), a recently emerged arenavirus that caused an outbreak of severe viral hemorrhagic fever in southern Africa. In contrast to human cases, LUJV caused mild, nonlethal illness in macaques. We then compared this to contrasting clinical outcomes during arenavirus infection, specifically to samples obtained from macaques infected with three highly pathogenic lines of Lassa virus (LASV), the causative agent of Lassa fever (LF). We assessed gene expression in peripheral blood mononuclear cells (PBMC) and determined genes that significantly changed expression relative to that in uninfected animals over the course of infection. We detected a 72-h delay in the induction of host responses to infection during LUJV infection compared to that of the animals infected with LASV. This included genes associated with inflammatory and antiviral responses and was particularly apparent among groups of genes promoting cell death. We also observed early differential expression of a subset of genes specific to LUJV infection that accounts for the delayed inflammatory response. Cell type enrichment analysis suggested that host response induction delay and an LUJV-specific profile are due to a different proportion of natural killer cells responding in LUJV infection than that in the LASV-infected animals. Together, these data indicate that delayed proinflammatory and proapoptotic host responses to arenavirus infection could ameliorate disease severity. This conclusion provides insight into the cellular and molecular mechanisms of arenaviral hemorrhagic fever and suggests potential strategies for therapeutic development. Old World arenaviruses are significant human pathogens that often are associated with high mortality. However, mechanisms underlying disease severity and virulence in arenavirus hemorrhagic fever are largely unknown, particularly regarding host responses that contribute to pathogenicity. This study describes a comparison between Lujo and Lassa virus infection in cynomolgus macaques. Lujo virus-infected macaques developed only mild illness, while Lassa virus-infected macaques developed severe illness consistent with Lassa fever. We determined that mild disease is associated with a delay in host expression of genes linked to virulence, such as those causing inflammation and cell death, and with distinct cell types that may mediate this delay. This is the first study to associate the timing and directionality of gene expression with arenaviral pathogenicity and disease outcome and evokes new potential approaches for developing effective therapeutics for treating these deadly emerging pathogens.


Fabrication of Novel Avermectin Nanoemulsion Using a Polyurethane Emulsifier with Cleavable Disulfide Bonds.
In this study, a polyurethane emulsifer with various functional groups was prepared from isophorone diisocyanate, avermectin, 2,2-dimethylol propionic acid, and bis(2-hydroxyethyl) disulfide. The chemical structure of the polymer was confirmed by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, and element analysis. The polymer exhibited adequate emulsification ability for avermectin after neutralization with triethylamine. A satisfaying nanoemulsion was obtained, in which avermectin was encapsulated in nanoparticles with 50 wt % drug loading, low organic solvent content, and high stability under dilution and centrifuging treatment in addition to low surface tension, high affinity to crop leaf, and improved avermectin photostability. The resulting nanoparticles showed degradability in the presence of dl-dithiothreitol or inside the insect as a result of the disulfide bonds, promoting the release of avermectin. As a result, the avermectin nanoparticles showed higher insecticidal ability compared to both the avermectin nanoparticles without a disulfide group and the avermectin emulsifiable concentrate.


Unilateral or asymmetric congenital ptosis, head posturing, and amblyopia.
To determine the prognostic implication of compensatory head posturing in patients with unilateral or asymmetric congenital ptosis. A retrospective review of 80 consecutive patients with unilateral or asymmetric congenital ptosis was performed. The presence of documented compensatory head posturing, age of onset, age of presentation, visual acuity, refraction, and amblyopia were recorded, and binocularity was tested. Five of seven (71%), patients with unilateral or asymmetric congenital ptosis and compensatory head posturing had amblyopia. All of these patients had straight eyes and four of the five amblyopic patients had anisometropia of less than 2 diopters (D). The high incidence of amblyopia in this group can occur in the absence of significant anisometropia and strabismus. This unusually high incidence of amblyopia in this subgroup of patients with unilateral or asymmetric congenital ptosis and compensatory head posturing warrants compulsive examination and prophylactic part-time occlusion therapy of the nonptotic eye until reliable vision testing can be performed.


Glycemic control, coping, and internalizing and externalizing symptoms in adolescents with type 1 diabetes: a cross-lagged longitudinal approach.
This study examines how active coping and withdrawal, psychological (internalizing and externalizing) symptoms, and glycemic control (A1C values) influence each other across time in adolescents with type 1 diabetes. One hundred and nine adolescents participated in a four-wave longitudinal study spanning four years (mean age at Time 1 was 13.77). Patients were visited at home and completed questionnaires measuring coping and psychological symptoms. The treating physicians were contacted to obtain A1C values. Cross-lagged path analysis from a structural equation modeling approach was used for data analysis. Clinically meaningful pathways between coping and glycemic control were found across time. Active coping prospectively predicted lower A1C levels, which, in turn, predicted active coping. Higher A1C levels and higher psychological symptoms consistently predicted avoidance coping across time. Finally, psychological symptomatology constituted an important link in the observed longitudinal chain of effects. More specifically, higher A1C values and symptomatology at Time 1 positively predicted withdrawal at Time 2, which, in turn, positively predicted symptomatology at Time 3. Next, symptomatology at Time 3 positively predicted higher A1C values at Time 4, thus coming full circle. Coping with everyday stress, psychological symptoms, and glycemic control were interrelated across time. Evidence was obtained for reciprocal pathways and mutually reinforcing mechanisms, indicating the need to monitor coping strategies and psychological symptoms along with glycemic control in optimizing clinical care in adolescents with type 1 diabetes.


Formal lithium fixation improves direct analysis of lipids in tissue by mass spectrometry.
Mass spectrometry imaging is a powerful method for imaging and in situ characterization of lipids in thin tissue sections. Structural elucidation of lipids is often achieved via collision induced dissociation, and lithium-lipid adducts have been widely reported as providing the most structurally informative fragment ions. We present a method for the incorporation of lithium salts into tissue imaging experiments via fixation of samples in formal lithium solutions. The method is suitable for preparation of single tissue sections, or as an immersion fixation method for whole tissue blocks or organs prior to sectioning. We compare lithium adduct detection and MALDI-MSI of murine brain from analysis of tissues prepared in different ways. Tissues prepared in formal solutions containing lithium or sodium salts before coating in matrix via air-spray deposition are compared with fresh samples coated in lithium-doped matrix preparations by either dry-coating or air-spray deposition. Sample preparation via fixation in formal lithium is shown to yield the highest quality images of lithium adducts, resulting in acquisition of more informative product ion spectra in MALDI MS/MS profiling and imaging experiments. Finally, the compatibility of formal lithium solutions with standard histological staining protocols (hemotoxylin and eosin, Van Giessen and Oil Red O) is demonstrated in a study of human liver tissue.


Alcohol and dietary factors in cirrhosis. An epidemiological study of 304 alcoholic patients.
Alcohol intakes and dietary habits of 304 alcoholic, hospitalized patients were evaluated. There were 195 patients with hepatic cirrhosis, 40 precirrhotics, and 69 noncirrhotics. Alcohol contributed 50% to 58% of total calories. Two thirds of the patients drank excessively for more than 20 years. There were no statistically significant differences between the three groups in the duration or degree of alcohol excess. Dietary intakes were assessed for a period of at least two years before the presenting illness. Noncirrhotics had higher food caloric intakes and higher protein intakes than the cirrhotics (P less than .05). The findings suggest that dietary factors may be involved in the pathogenesis of the disease.


Aggregation and fragmentation dynamics in random flows: From tracers to inertial aggregates.
We investigate the aggregation and fragmentation dynamics of tracers and inertial aggregates in random flows leading to steady-state size distributions. Our objective is to elucidate the impact of changes in aggregation rates due to differences in advection dynamics, especially with respect to the influence of inertial effects. This aggregation process is, at the same time, balanced by fragmentation triggered by local hydrodynamic stress. Our study employs an individual-particle-based model, tracking the position, velocity, and size of each aggregate. We compare the steady-state size distribution formed by tracers and inertial aggregates, characterized by different sizes and densities. On the one hand, we show that the size distributions change their shape with changes in the dilution rate of the suspension. On the other hand, we obtain that the size distributions formed with different binding strengths between monomers can be rescaled to a single form with the use of a characteristic size for both dense inertial particles and tracer monomers. Nevertheless, this last scaling relation also fails if the size distribution contains aggregates that behave as tracer-like and inertial-like, which results in a crossover between different scalings.


[Study of the function of coagulation, fibrinolysis and pulmonary vascular endothelium before and after experimental pulmonary thromboembolism in rabbits].
To study the functional changes and the significance of coagulation, fibrinolysis and pulmonary vascular endothelium before and after experimental pulmonary thromboembolism in rabbits. Rabbit pulmonary thromboembolism models by injection of auto-blood clots into femoral vein were used to observe the dynamical changes of activity of coagulation and fibrinolysis and endothelin-1 (ET-1), nitrogen monoxide (NO), von Willebrand factor (vWF) in blood. Petechial and patchy hemorrhages were observed on the surfaces of embolic lungs. The injected blood clots and secondary thrombosis in the pulmonary arteries, inflammatory cell infiltration around alveoli, local hemorrhages in the alveoli and interstitial tissue could be found by microscopy. The concentration of D-dimer, ET-1 and vWF in blood were significantly elevated, and the tissue-type plasminogen activator (t-PA), NO and antithrombin III (AT-III) decreased significantly after embolism (P < 0.05). After administration of urokinase, the pathological injuries relieved, and the concentration of D-dimer was higher at 1 h and 2 h after embolization than that before embolization (P < 0.05), and reduced to the level of pre- embolization at 4 h after embolization. The levels of t-PA, NO and AT-III after embolization were lower than those before embolization (P < 0.05). The level of ET-1 was higher at 2 h after embolization (P < 0.05) and reduced to the level of pre-embolization at 4 h. PTE has important impacts on coagulation, fibrinolysis and pulmonary vascular endothelial function. Thrombolysis with urokinase could keep the balance between coagulation and fibrinolysis and protect pulmonary vascular endothelial function.


Relationships between paternal attitudes, paternal involvement, and infant-feeding outcomes: Mixed-methods findings from a global on-line survey of English-speaking fathers.
The breastfeeding intention-behaviour gap remains wide in developed countries. Current studies have focused on maternal attitudes and behaviours concerning infant feeding in order to explore barriers to breastfeeding continuation. There has been limited consideration of the impact of paternal attitudes and behaviours, despite contemporary parenthood evolving and evidence indicating that there are greater levels of paternal involvement in routine childcare tasks. This mixed-methods study used a triangulation design to examine the associations between paternal attitudes towards parenthood and infant-feeding methods, levels of paternal involvement, infant-feeding outcomes, and father-infant relationships. Fathers of infants <52 weeks completed an online survey providing quantitative data (N = 212) and qualitative data (N = 208). For the quantitative data, fathers completed validated measures about their attitude towards parenthood and infant feeding, levels of paternal involvement, and infant-feeding history. For the qualitative data, questions explored influences on paternal attitudes towards infant feeding and the father-infant relationship. After controlling for covariates, regression analyses found egalitarian attitudes towards parenthood were positively associated with both attitudes towards breastfeeding and levels of paternal involvement. Positive paternal attitudes towards breastfeeding were significantly associated with increased likelihood of breastfeeding. A thematic framework analysis indicated fathers' attitudes towards infant feeding were largely influenced by their families and partners or healthcare professionals. Polarised views were expressed about the impact infant-feeding methods had on the father-infant relationship, although fathers were united in their desire to bond with their infant. Addressing paternal attitudes and the importance of father-infant involvement in domains other than feeding maybe beneficial in supporting breastfeeding and the father-infant relationship.


A structured workshop to improve the quality of resident discharge summaries.
Poor communication at hospital discharge can increase the risk of adverse events. The hospital discharge summary is the most common tool for detailing events related to hospitalization in preparation for postdischarge follow-up, yet deficiencies in discharge summaries have been widely reported. Resident physicians are expected to dictate discharge summaries but receive little formal training in this arena. We hypothesized that implementation of an educational program on chart documentation skills would result in improvements in the quality of hospital discharge summaries in a community hospital internal medicine residency program. A monthly, 1-hour workshop was launched in August 2007 to provide consistent and ongoing instruction on chart documentation. Guided by a faculty moderator, residents reviewed 2 randomly selected peer chart notes per session using instruments developed for that purpose. After the workshop had been in place for 2 years, 4 faculty members reviewed 63 randomly selected discharge summaries from spring 2007, spring 2008, and spring 2009 using a 14-item evaluation tool. Mean scores for 10 of the 14 individual items improved in a stepwise manner during the 3 years of the study. Items related to overall quality of the discharge summary showed statistically significant improvement, as did the portion of the summaries "carbon copied" to the responsible outpatient physician. The quality of hospital discharge summaries improved following the implementation of a novel, structured program to teach chart documentation skills. Ongoing improvement was seen 1 and 2 years into the program, suggesting that continuing instruction in those skills was beneficial.


Engineering metal-binding sites of bacterial CusF to enhance Zn/Cd accumulation and resistance by subcellular targeting.
The periplasmic protein CusF acts as a metallochaperone to mediate Cu resistance in Escherichia coli. CusF does not contain cysteine residues and barely binds to divalent cations. Here, we addressed effects of cysteine-substitution mutant (named as mCusF) of CusF on zinc/cadmium (Zn/Cd) accumulation and resistance. We targeted mCusF to different subcellular compartments in Arabidopsis. We found that plants expressing vacuole-targeted mCusF were more resistant to excess Zn than WT and plants with cell wall-targeted or cytoplasmic mCusF. Under long-term exposure to excess Zn, all transgenic lines accumulated more Zn (up to 2.3-fold) in shoots than the untransformed plants. Importantly, plants with cytoplasmic mCusF showed higher efficiency of Zn translocation from root to shoot than plants with secretory pathway-targeted-mCusF. Furthermore, the transgenic lines exhibited enhanced resistance to Cd and significant increase in root-to-shoot Cd translocation. We also found all transgenic plants greatly improved manganese (Mn) and iron (Fe) homeostasis under Cd exposure. Our results demonstrate heterologous expression of mCusF could be used to engineer a new phytoremediation strategy for Zn/Cd and our finding also deepen our insights into mechanistic basis for relieving Cd toxicity in plants through proper root/shoot partitioning mechanism and homeostatic accumulation of Mn and Fe.


Acute Cardiopulmonary, Metabolic, and Neuromuscular Responses to Severe-Intensity Intermittent Exercises.
Lisbôa, FD, Raimundo, JAG, Salvador, AF, Pereira, KL, Turnes, T, Diefenthaeler, F, Oliveira, MFMd, and Caputo, F. Acute cardiopulmonary, metabolic, and neuromuscular responses to severe-intensity intermittent exercises. J Strength Cond Res 33(2): 408-416, 2019-The purpose of this study was to compare cardiopulmonary, neuromuscular, and metabolic responses to severe-intensity intermittent exercises with variable or constant work rate (CWR). Eleven cyclists (28 ± 5 years; 74 ± 7 kg; 175 ± 5 cm; 63 ± 4 ml·kg·min) performed the following tests until exhaustion on separate days: (a) an incremental test; (b) in random order, 2 CWR tests at 95 and 110% of the peak power for the determination of critical power (CP); (c) 2-4 tests for the determination of the highest power that still permits the achievement of maximal oxygen uptake (PHIGH); and (d) 2 random severe-intensity intermittent exercises. The last 2 sessions consisted of a CWR exercise performed at PHIGH or a decreasing work rate (DWR) exercise from PHIGH until 105% of CP. Compared with CWR, DWR presented higher time to exhaustion (635 ± 223 vs. 274 ± 65 seconds), time spent above 95% of V[Combining Dot Above]O2max (t95% V[Combining Dot Above]O2max) (323 ± 227 vs. 98 ± 65 seconds), and O2 consumed (0.97 ± 0.41 vs. 0.41 ± 0.11 L). Electromyography amplitude (root mean square [RMS]) decreased for DWR but increased for CWR during each repetition. However, RMS and V[Combining Dot Above]O2 divided by power output (RMS/PO and V[Combining Dot Above]O2/PO ratio) increased in every repetition for both protocols, but to a higher extent and slope for DWR. These findings suggest that the higher RMS/PO and V[Combining Dot Above]O2/PO ratio in association with the longer exercise duration seemed to have been responsible for the higher t95% V[Combining Dot Above]O2max observed during severe DWR exercise.


Pemphigus vegetans. Neumann type and Hallopeau type.
Two cases of pemphigus vegetans are presented, one of the Neumann type and one of the Hallopeau type. The differences between the two subsets are clinical presentation and course. Patients with the Hallopeau type often have a relatively benign disease, require lower doses of systemic corticosteroids, and usually have a prolonged remission. Patients with the Neumann type have a course similar to pemphigus vulgaris, need higher doses of systemic corticosteroids, and have relapses and remissions. The histologic findings in the vegetating lesions are similar in both types. The immunopathologic features of both types are indistinguishable and similar to pemphigus vulgaris. IgM staining of eosinophilic microabscesses was observed in one case.


Whispering-gallery mode resonators for highly unidirectional laser action.
Optical microcavities can be designed to take advantage of total internal reflection, which results in resonators supporting whispering-gallery modes (WGMs) with a high-quality factor (Q factor). One of the crucial problems of these devices for practical applications such as designing microcavity lasers, however, is that their emission is nondirectional due to their radial symmetry, in addition to their inefficient power output coupling. Here we report the design of elliptical resonators with a wavelength-size notch at the boundary, which support in-plane highly unidirectional laser emission from WGMs. The notch acts as a small scatterer such that the Q factor of the WGMs is still very high. Using midinfrared (λ ∼ 10 μm) injection quantum cascade lasers as a model system, an in-plane beam divergence as small as 6 deg with a peak optical power of ∼5 mW at room temperature has been demonstrated. The beam divergence is insensitive to the pumping current and to the notch geometry, demonstrating the robustness of this resonator design. The latter is scalable to the visible and the near infrared, thus opening the door to very low-threshold, highly unidirectional microcavity diode lasers.


Converting inactive peptides into potent transcriptional activators.
Significant efforts have been devoted to the development of artificial transcriptional activators for use as mechanistic tools, as therapeutic agents, and for biomanufacturing applications. One of the primary challenges has been the development of artificial activators that exhibit potency in cells comparable to that of endogenous activators; the vast majority function only moderately in the cellular context. Here we demonstrate that the superimposition of two distinct binding modes, a masking interaction and an interaction with the transcriptional machinery, has a profoundly positive effect on the cellular activity of artificial activators, with up to 600-fold enhancement observed. Incorporation of this feature into future generations of small molecule transcriptional activators should increase their nuclear uptake and facilitate their accessibility to their target proteins, thus significantly augmenting both their activity and utility.


Complications after operative treatment of femoral shaft fractures in childhood and adolescence.
Purpose of the study was to retrospectively analyze the complication rates after operatively treated femoral shaft fractures in childhood and adolescence. Retrospective evaluation of 42 children with operatively treated femoral shaft fractures between 2000 and 2014. Fractures were classified as 27 A type, 12 B type and 3 C type fractures according the OTA/AO classification. 8 (19.05%) fractures were open. Age averaged 10.2 years (3-16). Fracture treatment was recorded as temporary or definitive external fixation, ESIN, plate fixation or IMN. Complications such as wound infection, re-fractures, nonunion and malunion were analyzed. Six (14.29%) fractures were temporarily stabilized using an external fixator. In 22 (52.38%) children the femoral shaft fracture was stabilized using ESINs. 10 (23.81%) children had a plate fixation and 9 (21.43%) adolescents were treated using an IMN. ESIN treated children were significantly younger (P=0.000) and had less weight (P=0.000) than children treated with both other methods. Complications were two (4.76%) superficial and two deep (4.76%) wound infections, one (2.38%) re-fracture with the ESIN in situ, one (2.38%) nonunion and one (2.38%) malunion. Six (14.29%) children required a reoperation for a complication. Risk factors for complications were temporarily applied external fixators, open fractures, C Type fractures (P=0.031) and an increasing age (P=0.048) and weight (P=0.047) of the child. The majority of children in our study population were successfully treated using ESIN presenting a low complication rate. Complications were observed following open fractures and more complex fracture types. Furthermore we observed an increasing complication rate with increasing ages and weights of the children.


Effect of different salts on foaming properties of model protein system for infant formula.
This multiscale study aimed to evaluate the effect of different salts (NaCl, KCl, MgCl2, and CaCl2) on foaming capacity (FC) and foam stability (FS) of model protein system (MPS) for infant formula via the changes of surface and structural properties. Results showed that the FC and FS of MPS were increased at NaCl, KCl, and MgCl2 condition, whereas CaCl2 significantly (P < 0.05) decreased FC (79.5 ± 10.6%) and increased FS (93.2 ± 2.2%). The H0 was increased, while the net charge and surface tension was reduced after addition of salts. Structural analysis revealed the reduction of intensity of intrinsic fluorescence spectroscopy and UV (UV) absorption, and the conversion of α-helix into β-strand, which was attributed to protein agglomeration. Additionally, MgCl2 and CaCl2 exhibited larger size and lower net charge compared with NaCl and KCl, indicating a greater ability to bind to charged amino acids and formed larger aggregates. Correlation analysis indicated that FC was positively related to adsorbed protein and β-turn, while negatively correlated with particle size. FS showed a positive correlation with β-strand, apparent viscosity, and zeta potential. However, it exhibited a negative correlation with β-turn, α-helix, and SH content. These results provide a theoretical reference for further understanding of the effect of salts on the foaming properties of MPS.


Staining of the conjunctiva and conjunctival tear film.
Both the distribution of tear fluid over the conjunctiva and any injury to the conjunctival epithelium can be made visible by instilling a fluorescent solution into the eye and observing with an appropriate combination of excitation and barrier filters. Sulphorhodamine B, which has an orange fluorescence that can be separated from the green natural fluorescence of the ocular tissues, gives a greater contrast than fluorescein. The tear film is seen to cover the surface of the conjunctiva and to be concentrated in its folds. Small circular areas of thin tear film appear transiently in the neighbourhood of the limbus after a blink. Occasional cells stain on the normal conjunctiva, particularly in the interpalpebral area. The density of the staining increases in dry eye conditions. Conjunctival trauma is sensitively revealed by the method, and its healing can be followed. Hard contact lenses are seen to traumatize continually the inferior limbal conjunctiva in symptomless wearers.


Circadian rhythm of TSH in adult onset non-insulin dependent (type II) diabetics with altered thyroid state.
Twenty adult onset non-insulin dependent (Type II) diabetic patients and twenty non-diabetic subjects matched for sex, age, height and weight were studied. The diabetes was controlled by diet only in 10 patients and by oral hypoglycemic agents in 10. All patients were diurnally active and rested at night. Blood was sampled at 4-hour intervals over a 24-hour span (6 samples). TSH, total T3 and total T4 were determined by radioimmunoassay. The circadian rhythm in TSH was statistically significant by cosinor analysis and was comparable in all rhythm parameters in diabetics and non-diabetics. The rhythms of total T3 and T4 also seem to persist with comparable timing although the small number of subjects did not allow rhythm detection at the 5 per cent level in all groups. The circadian mean of the total T3 plasma concentration in the diabetics, however, was statistically significantly lower than the usual range of this laboratory and the total T4 was elevated but within the usual range. The changes in total T3 and T4 were most pronounced in the patients on oral hypoglycemic agents. This study indicates persistence of a circadian rhythm in TSH (and presumably also in the plasma concentrations of total T3 and T4) in non-insulin dependent diabetic patients in spite of a lowered circadian mean concentration of total T3 and a slightly but statistically significantly higher total T4 than in the matched non-diabetic subjects. The altered thyroidal state in the diabetic patients thus does not interfere with the circadian periodic secretion of TSH.


Internet images of the speech pathology profession.
Objective The Internet provides the general public with information about speech pathology services, including client groups and service delivery models, as well as the professionals providing the services. Although this information assists the general public and other professionals to both access and understand speech pathology services, it also potentially provides information about speech pathology as a prospective career, including the types of people who are speech pathologists (i.e. demographics). The aim of the present study was to collect baseline data on how the speech pathology profession was presented via images on the Internet. Methods A pilot prospective observational study using content analysis methodology was conducted to analyse publicly available Internet images related to the speech pathology profession. The terms 'Speech Pathology' and 'speech pathologist' to represent both the profession and the professional were used, resulting in the identification of 200 images. These images were considered across a range of areas, including who was in the image (e.g. professional, client, significant other), the technology used and the types of intervention. Results The majority of images showed both a client and a professional (i.e. speech pathologist). While the professional was predominantly presented as female, the gender of the client was more evenly distributed. The clients were more likely to be preschool or school aged, however male speech pathologists were presented as providing therapy to selected age groups (i.e. school aged and younger adults). Images were predominantly of individual therapy and the few group images that were presented were all paediatric. Conclusion Current images of speech pathology continue to portray narrow professional demographics and client groups (e.g. paediatrics). Promoting images of wider scope to fully represent the depth and breadth of speech pathology professional practice may assist in attracting a more diverse group of people into the profession in the future. What is known about the topic? To date, research has not considered the promotional profile of allied health professionals on the Internet. There has been a lack of consideration of whether the way in which the professions are promoted may affect clients accessing allied health services or people entering careers. What does this paper add? This paper raises awareness of the lack of promotion of a diverse workforce in speech pathology and considers how this may affect changing the professional demographics in the future. It also provides a starting point for documentation in the form of a baseline for tracking future changes. It allows consideration of the fact that when designing health promotional and educational materials, it is crucial that diversity is displayed in the professional role, the client role and the setting in order to provide information and education to the general public about the health services provided. What are the implications for practitioners? The presentation of narrow demographics of both the professional and client may potentially affect people considering speech pathology as a future career. The appearance of narrow client demographics and diagnosis groups may also deter people from accessing services. For example, if the demonstrated images do not show older people accessing speech pathology services, then this may suggest that services are only for children. The results from the present case example are transferrable to other health professions with similar professional demographic profiles (e.g. occupational therapy). Consideration of the need to display a diverse client profile is relevant to all health and medical services, and demonstrates steps towards inclusiveness and increasing engagement of clients who may be currently less likely to access health services (including people who are Aboriginal or from a culturally and linguistically diverse background).


A review and survey of policies utilized for interventional pain procedures: a need for consensus.
Other than the newly published anticoagulation guidelines, there are currently few recommendations to assist pain medicine physicians in determining the safety parameters to follow when performing interventional pain procedures. Little information exists regarding policies for oral intake, cumulative steroid dose limits, driving restrictions with and without sedation, and routine medication use for interventional procedures. A 16-question survey was developed on common policies currently in use for interventional pain procedures. The questionnaire was distributed through the American Society of Regional Anesthesia and Pain Medicine and American Academy of Pain Medicine. We sought to statistically analyze the range of policies being used by pain medicine physicians and to determine if there are any commonly accepted standards. A total of 337 physicians out of 4037 members responded to our survey with a response rate of 8.4%. A total of 82% of these respondents used a sedative agent while performing an interventional pain procedure. The majority of respondents required drivers after procedures, except after trigger points. A total of 47% indicated that they have an nil per os (NPO) policy for procedures without sedation. A total of 98% reported that they had an anticoagulation policy before an interventional procedure. A total of 17% indicated that the interval between steroid doses was <2 weeks, while 53% indicated that they waited 2-4 weeks between steroid doses. Our study has clearly demonstrated a wide variation in the current practice among physicians regarding sedation, NPO status, steroid administration, and the need for designated drivers. There was much higher endorsement of policies regarding anticoagulation. There is an obvious need for evidence-based guidelines for these aspects of interventional pain care to improve patient safety and minimize the risk of adverse events.


Oligoazobenzenes--switching in a new dimension.
A new synthesis of cyclotrisazobenzene with different substituents was developed with yields of up to 30%. Solid-state structures of cyclotrisazobenzene as well as the tert-butyl derivative were obtained. Also, the photochromic properties and the complexation behaviour with alkali metal ions of this class of molecules were investigated.


Carryover of maduramicin from feed containing cross-contamination levels into eggs of laying hens.
Maduramicin is a coccidiostat authorized as feed additive in the European Union for chickens and turkeys for fattening but not for laying hens, considering the risk of residues in eggs. The unavoidable cross-contamination of non-target feed with coccidiostats is regulated by Commission Directive 2009/8/EC and resulting carry-over in food by Commission Regulation (EC) No. 124/2009. To verify the compliance of the maximum levels for maduramicin in feed (50 μg/kg) and eggs (2 μg/kg), the carry-over from feed into eggs was investigated. Diets containing 10, 30, and 50 μg of maduramicin/kg of feed were fed to laying hens. Feed, egg white, and yolk were analyzed by LC-MS/MS. Maduramicin residues were only detected in in egg yolk. Feeding the 10 μg/kg maduramicin diet resulted in maduramicin concentrations up to 2.5 μg/kg in whole eggs, already exceeding the maximum level. A carry-over rate of 8% maduramicin from feed into eggs was calculated.


Simultaneous visual diagnosis of acute hepatopancreatic necrosis disease and Enterocytozoon hepatopenaei infection in shrimp with duplex recombinase polymerase amplification.
Shrimp is a globally popular seafood. Shrimp farming has been challenged by various infectious diseases that lead to significant economic losses. The prevention of two important shrimp infectious diseases, the acute hepatopancreatic necrosis disease (AHPND) and the Enterocytozoon hepatopenaei (EHP) infection, is highly dependent on early and accurate diagnostic. On-site monitoring of the two diseases in shrimp farming facilities demands point-of-care-testing (POCT) type of diagnostic assays. This study established a duplex recombinase polymerase amplification (RPA) and lateral flow dipstick (LFD) combined assay that could simultaneously diagnose the two diseases. The optimized RPA-LFD assay could finish the diagnostic in 35 min with good specificity, and the sensitivity reached 101 and 102 gene copies per reaction for EHP and AHPND, respectively, which were at the same level as the currently available molecular diagnostic assays. Test results of clinical samples showed 100% agreement of this assay with the industrial standard nested polymerase chain reaction (PCR) assays, and samples with both diseases were simultaneously identified. Because of the isothermal 37℃ amplification and the visual reading of the signal on dipsticks, the dependence on equipment is minimal. This duplex RPA-LFD assay is well suited for simultaneous POCT diagnostic of the two important shrimp infectious diseases. Moreover, the principle can be applied to multiplex POCT diagnostic of other infectious diseases in aquaculture.


Disseminated pulmonary aspergillosis in a previously healthy young woman.
A young woman presented with widespread bilateral infiltrates on chest X-ray and a high fever. Investigations for bacterial, mycobacterial, and fungal infections were negative. A biopsy of the lung showed granulomas, and corticosteroid medication was given on vital indication because of the rapidly progressive disease. There was a dramatic response, with regression of the chest X-ray changes and the fever and the patient was discharged on her own request with a tentative diagnosis of acute sarcoidosis. One month later she was admitted in an alarming state with almost completely consolidated lung and died a few hours later. Autopsy revealed generalized aspergillosis. Renewed extensive investigation of the earlier lung biopsy revealed hyphae. After her death, the case history of an elder brother was traced and revealed that he had died at early age in a generalized granulomatous disease. Although no definite diagnosis can be made, it seems likely that both siblings suffered from a defect in the immune system, probably chronic granulomatous disease of the autosomal recessive type. This disease is sometimes found in young adults without a clear history of earlier infections.


Establishing a gingival fibroblast phenotype in a perfused degradable polyurethane scaffold: mediation by TGF-β1, FGF-2, β1-integrin, and focal adhesion kinase.
Medium perfusion has been shown to enhance cell proliferation and matrix protein production. In more recent work, under perfusion, a degradable/polar/hydrophobic/ionic polyurethane (D-PHI) scaffold was shown to enhance growth and production of collagen by human gingival fibroblasts (HGFs). However, the nature of the HGFs cultured in the perfused D-PHI scaffolds, and the mechanisms by which medium perfusion activates these cells to facilitate proliferation and collagen production are not defined. The current study sought to investigate HGF interaction within the D-PHI scaffolds under perfusion by examining the production and the spatial distribution of α-smooth muscle actin (α-SMA) and type I collagen (Col I), the secretion of transforming growth factor (TGF)-β1 and basic fibroblast growth factor (FGF-2) in the conditioned medium, with a goal of defining the mechanistic pathways affecting the production of these markers in the dynamic culture. It was found that the perfused D-PHI scaffold shifted the HGF phenotype from myofibroblast-like (upregulation of α-SMA) to fibroblast-like (downregulation of α-SMA) over the course of 28 days. Both TGF-β1 and FGF-2 were significantly greater in the dynamic vs. static culture at day 1. Although TGF-β1 has been often reported to increase α-SMA and collagen expression, the D-PHI material and significant high level of FGF-2 at day 1 of dynamic culture appear to play a role in regulating α-SMA production while allowing HGFs to increase Col I production. β1-integrin production was increased and focal adhesion kinase (FAK) were activated 2 h after HGFs were exposed to medium perfusion, which may have in part promoted cell growth, α-SMA and Col I production in the early dynamic culture. Consequently, the D-PHI material and medium perfusion has modulated fibroblast phenotype, and enhanced cell growth and Col I production through the coordinated actions of TGF-β1, FGF-2, β1-integrin and FAK.


Intima-media thickness: correlation between carotids, vertebral artery, aorta and femoral arteries.
Compare the intima-media thickness (IMT) of the internal carotid artery with the IMT of the common and external carotid, vertebral and femoral arteries and the abdominal aorta to assess the possibility of using these arteries as markers of atherosclerotic disease. Fifty patients with atherosclerosic risk factors were examined and the IMT was determined in the carotid arteries and compared with the values of IMT of the vertebral and femoral arteries and the abdominal aorta. The Spearman correlation coefficient and Kappa index were used for statistical analysis. Considering IMT equal or greater than 0,8mm, there was positive and significant correlation between the values obtained for the examined arteries. The best agreement was found between the external and common carotid artery as compared to the internal carotid. (accuracy of 73.5% and 79.2%, respectively). For all arteries the was a positive correlation of the values of the EMI. There is positive and significant correlation between the IMT of the internal carotid artery and the vertebral and femoral arteries and abdominal aorta. Routine examinations of either one of these arteries can ad important findings regarding early diagnosis for higher risk patients concerning atherosclerotic disease.


[Prenatal maternal blood screening for the detection of fetal chromosomal abnormalities: clinical importance of the rate of false positives].
Maternal serum screening to identify fetal aneuploidies is now routinely offered during the second trimester of pregnancy in developed countries. The purpose of this prospective study was to assess the value of maternal serum screening between 15 and 20 weeks of gestation to detect fetal aneuploidies and to determine the false positive rate (FPR). Blood samples were collected from 1,062 pregnant women between 15 and 20 weeks of gestation. Samples were assayed for alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (beta-hCG) and unconjugated estriol (uE3). Medians were established at each week from 200 normal, singleton pregnancies. Second trimester risk was calculated using the maternal age and different combinations of AFP, beta-hCG and uE3. Screening results calculated by likelihood ratio to be equal to or greater than 1:270 were considered positive. If the gestational age was confirmed by ultrasonography, genetic counselling and amniocentesis were offered. Ten fetal chromosomal abnormalities were detected with maternal serum screening. Sample's size does not allow a correct detection rate estimation, but false positive rate (FPR) was found to be 6.5%. This FPR has a clinical application. At a cut-off of 1:270, second trimester screening best results were obtained using a combination of all three biochemical markers. These results confirm the efficacy of maternal serum screening for fetal chromosomal abnormalities with a low FPR. The measurement of AFP, beta-hCG and uE3 is an effective prenatal screening test.


Artificial saliva and its use in biological experiments.
Examination of dental materials and their properties at the initial stage of the digestive process requires the development of conditions that mimic the environment of the oral cavity. One of the main components of this area is saliva, where many reactions occur under natural conditions. Human saliva is an important physiological fluid that is essential for the maintenance of good oral health and of the entire human body; it is the place where digestion begins and thus contributes to the supply of those nutrients and health-promoting substances that are essential to the body but may also cause release of potential toxins. Thereby, the main aim of the study was to review the use of artificial saliva models in the context of stomatological and biological research. Biological studies have shown that the amount of biologically active substances in biological material is not the same as their quantity released under the conditions of the human digestive system and thus bioavailable to it. These results show that tables of active ingredients in drugs and food stuffs do not present their actual usefulness and availability to the human body.


Exploration of interlacing and avoided crossings in a manifold of potential energy curves by a unitary group adapted state specific multi-reference perturbation theory (UGA-SSMRPT).
The Unitary Group Adapted State-Specific Multi-Reference Perturbation Theory (UGA-SSMRPT2) developed by Mukherjee et al. [J. Comput. Chem. 36, 670 (2015)] has successfully realized the goal of studying bond dissociation in a numerically stable, spin-preserving, and size-consistent manner. We explore and analyze here the efficacy of the UGA-SSMRPT2 theory in the description of the avoided crossings and interlacings between a manifold of potential energy curves for states belonging to the same space-spin symmetry. Three different aspects of UGA-SSMRPT2 have been studied: (a) We introduce and develop the most rigorous version of UGA-SSMRPT2 that emerges from the rigorous version of UGA-SSMRCC utilizing a linearly independent virtual manifold; we call this the "projection" version of UGA-SSMRPT2 (UGA-SSMRPT2 scheme P). We compare and contrast this approach with our earlier formulation that used extra sufficiency conditions via amplitude equations (UGA-SSMRPT2 scheme A). (b) We present the results for a variety of electronic states of a set of molecules, which display the striking accuracy of both the two versions of UGA-SSMRPT2 with respect to three different situations involving weakly avoided crossings, moderate/strongly avoided crossings, and interlacing in a manifold of potential energy curves (PECs) of the same symmetry. Accuracy of our results has been benchmarked against IC-MRCISD + Q.


AMP-activated protein kinase activator AICAR attenuates hypoxia-induced murine fetal growth restriction in part by improving uterine artery blood flow.
Pregnancy at high altitude is associated with a greater incidence of fetal growth restriction due, in part, to lesser uterine artery blood flow. AMP-activated protein kinase (AMPK) activation vasodilates arteries and may increase uterine artery blood flow. In this study, pharmacological activation of AMPK by the drug AICAR improved fetal growth and elevated uterine artery blood flow. These results suggest that AMPK activation is a potential strategy for improving fetal growth and raising uterine artery blood flow in pregnancy, which may be important in pregnancy disorders characterized by uteroplacental ischaemia and/or fetal hypoxia. Uteroplacental hypoxia is associated with pregnancy disorders such as intrauterine growth restriction and preeclampsia, which are characterized by uteroplacental ischaemia and/or fetal hypoxia. Activation of AMP-activated protein kinase (AMPK) results in vasodilatation and is therefore a potential therapeutic strategy for restoring uteroplacental perfusion in pregnancy disorders. In this study, C57Bl/6 mice were treated with subcutaneous pellets containing vehicle, the AMPK activator AICAR (200 mg kg-1 day-1 ), or the AMPK inhibitor Compound C (20 mg kg-1 day-1 ) beginning on gestational day 13.5, and were exposed to hypoxia starting on gestational day 14.5 that induced intrauterine growth restriction. Pharmacological AMPK activation by AICAR partially prevented hypoxia-induced fetal growth restriction (P < 0.01), due in part to increased uterine artery blood flow (P < 0.0001). The proportion of total cardiac output flowing through the uterine artery was increased with AICAR in hypoxic mice (P < 0.001), suggesting that the vasodilator effect of AICAR was selective for the uterine circulation. Further, pharmacological inhibition of AMPK with Compound C reduced uterine artery diameter and increased uterine artery contractility in normoxic mice, providing evidence that physiological levels of AMPK activation are necessary for vasodilatation in healthy pregnancy. Two-way ANOVA analyses indicated that hypoxia reduced AMPK activation in the uterine artery and placenta, and AICAR increased AMPK activation in these tissues compared to vehicle. These findings provide support for further investigation into the utility of pharmacological AMPK activation for treatment of fetal growth restriction.


Hemolytic uremic syndrome in adults: A case report.
Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by platelet aggregation and mechanical damage to erythrocytes, clinically characterized by microangiopatic haemolytic anemia, thrombocytopenia and organ injury. We are reporting a case of a woman patient with severe hemolytic uremic syndrome associated to infectious diarrhoea caused by Shiga toxin-producing pathogen, who were admitted to our intensive care unit. The patient described developed as organ injury, neurological failure and acute renal failure, with need of haemodialysis technique. Due to the severity of the case and the delay in the results of the additional test that help us to the final diagnose, we treated her based on a syndromic approach of TMA with plasma exchange, with favourable clinical evolution with complete recovery of organ failures. We focus on the syndromic approach of these diseases, because thrombotic thrombocytopenic purpura, one of the disorders that are included in the syndromes of TMA, is considered a haematological urgency given their high mortality without treatment; and also review the TMA in adults: Their pathogenesis, management and outcomes.


A regulatory perspective on essential considerations in design and analysis of subgroups when correctly classified.
This regulatory research provides possible approaches for improvement to conventional subgroup analysis in a fixed design setting. The interaction-to-overall effects ratio is recommended in the planning stage for potential predictors whose prevalence is at most 50% and its observed ratio is recommended in the analysis stage for proper subgroup interpretation if sample size is only planned to target the overall effect size. We illustrate using regulatory examples and underscore the importance of striving for balance between safety and efficacy when considering a regulatory recommendation of a label restricted to a subgroup. A set of decision rules gives guidance for rigorous subgroup-specific conclusions.


Anesthetic challenges of extrinsic trachea-bronchial compression due to posterior mediastinal mass: Our experience with a large esophageal mucocele.
Large posterior mediastinal masses may lead threatening complications such as critical tracheobronchial compression. Airway management in these individuals is a challenge and being a lower airway obstruction; rescue strategies are limited. We encountered one such case of a large esophageal mucocele causing extrinsic tracheobronchial compression. We have described the anesthetic management of this case using awake fiber-optic assessment followed by intubation. Close communication with the surgical team, meticulous planning of airway management, and early drainage of the mucocele are the cornerstones of management in such patients.


Comparison of several methods for the isolation of salmonellae from egg products.
Lactose broth and buffered peptone water proved to be equally effective as preenrichment media in the isolation of salmonellae from egg products. With tetrathionate bile brilliant green broth, incubated at 43 degrees C as enrichment medium, more samples were found to be positive than with selenite cystine broth incubated at 37 degrees C or 43 degreesC and selenite brilliant green broth incubated at 37 degrees C. As selective agar, brilliant green agar proved to be more reliable than bismuth sulfite agar. These results indicate that the ISO method for the isolation of salmonellae from meat and meat products can be successfully used for the examination of egg products.


Association between diabetes mellitus and lung cancer: Meta-analysis.
This study aimed to summarize the association between diabetes mellitus (DM) and the incidence of lung cancer using a meta-analysis of cohort studies. We systematically searched PubMed, Embase and the Cochrane Library to identify potential cohort studies. Relative risk (RR) was used to calculate the association between DM and the risk of lung cancer. Subgroup analysis, sensitivity analysis and test for publication bias were performed. Twenty cohort studies were selected. The participants with DM showed little or no significant effect on the risk of lung cancer (RR: 1.10; 95% CI: 0.99-1.23; P = .087). DM was not associated with the risk of lung cancer in men (RR: 1.11; 95%CI: 0.92-1.35; P = .270), but a significant association was observed in women (RR: 1.18; 95%CI: 1.10-1.28; P < .001). Subgroup analysis suggested that smoker status was confounding variables that could bias the relationship between DM and the incidence of lung cancer. This meta-analysis suggests that DM has no significant impact on the incidence of lung cancer in men but has a harmful effect on women.


[Unusual variation of popliteal arterial branches: 4 axes by early division of the peroneal artery].
Embryonic development of arteries of the lower limb results from the union of dorsal and ventral systems, explaining many variations at different levels. Some of these are important to recognize during the radiological exam because they can affect therapeutic management. These variations are most often bilateral and symmetrical predominating at the popliteal and subpopliteal levels. Lippert classified them into three types: normal level of popliteal arterial branching, high division of popliteal artery, hypoplastic or aplastic branching with altered distal supply. The length of the tibioperoneal trunk may also vary, rarely measuring more than 5 cm. We report a case combining three variations, two of them previously described in the literature and the third one not yet reported: our patient presented four arteries due to early bifurcation of the peroneal artery.


Geometrical envelopes: Extending graphical contemporary niche theory to communities and eco-evolutionary dynamics.
Contemporary niche theory is a powerful structuring framework in theoretical ecology. First developed in the context of resource competition, it has been extended to encompass other types of regulating factors such as shared predators, parasites or inhibitors. A central component of contemporary niche theory is a graphical approach popularized by Tilman that illustrates the different outcomes of competition along environmental gradients, like coexistence and competitive exclusion. These food web modules have been used to address species sorting in community ecology, as well as adaptation and coexistence on eco-evolutionary time scales in adaptive dynamics. Yet, the associated graphical approach has been underused so far in the evolutionary context. In this paper, we provide a rigorous approach to extend this graphical method to a continuum of interacting strategies, using the geometrical concept of the envelope. Not only does this approach provide community and eco-evolutionary bifurcation diagrams along environmental gradients, it also sheds light on the similarities and differences between those two perspectives. Adaptive dynamics naturally merges with this ecological framework, with a close correspondence between the classification of singular strategies and the geometrical properties of the envelope. Finally, this approach provides an integrative tool to study adaptation between levels of organization, from the individual to the ecosystem.


CTRR-ncRNA: A Knowledgebase for Cancer Therapy Resistance and Recurrence Associated Non-coding RNAs.
Cancer therapy resistance and recurrence (CTRR) are the dominant causes of death in cancer patients. Recent studies have indicated that non-coding RNAs (ncRNAs) can not only reverse the resistance to cancer therapy but also are crucial biomarkers for the evaluation and prediction of CTRR. Herein, we developed CTRR-ncRNA, a knowledgebase of CTRR-associated ncRNAs, aiming to provide an accurate and comprehensive resource for research involving the association between CTRR and ncRNAs. Compared to most of the existing cancer databases, CTRR-ncRNA is focused on the clinical characterization of cancers, including cancer subtypes, as well as survival outcomes and responses to personalized therapy of cancer patients. Information pertaining to biomarker ncRNAs has also been documented for the development of personalized CTRR prediction. A user-friendly interface and several functional modules have been incorporated into the database. Based on the preliminary analysis of genotype-phenotype relationships, universal ncRNAs have been found to be potential biomarkers for CTRR. The CTRR-ncRNA is a translation-oriented knowledgebase and it provides a valuable resource for mechanistic investigations and explainable artificial intelligence-based modeling. CTRR-ncRNA is freely available to the public at http://ctrr.bioinf.org.cn/.


Door-to-Balloon ST-Elevation Myocardial Infarction Interventions: Illustrated Cases.
ST-elevation myocardial infarction (STEMI) intervention comprises 2 components, the STEMI procedure and the STEMI process, which have unique aspects that can be modified and improved, ultimately affecting patient outcome. The 15 illustrated cases in this article highlight suggested improvements mainly in the STEMI procedure, with some references as to how the authors practically improved the STEMI process for the described procedure. The illustrated procedures have been meticulously selected from more than 1000 short door-to-balloon STEMI interventions recorded in the Single Individual Community Experience Registry (SINCERE) database, and are aimed at educating the reader about unique STEMI skills.


First Tissue-Agnostic Drug Approval Issued.
The PD-1 inhibitor pembrolizumab received accelerated approval for adult and pediatric patients with solid tumors that are mismatch repair-deficient or microsatellite instability-high. This is the first time the FDA has greenlighted a drug based not on tumor type, but on a common biomarker.


Recurrence of cervical artery dissection: An underestimated risk.
To explore the recurrence of cervical artery dissection (CeAD). A single-center consecutive series of 282 CeAD patients was prospectively recruited during first admission from 1995 to 2012. Patients with a follow-up of at least 1 year (n = 238) were eligible for the current analysis. All patients with clinical symptoms or signs of recurrent CeAD on ultrasound were examined by MRI. Dermal connective tissue morphology was studied in 108 (45.4%) patients. Median follow-up was 52 months (range 12-204 months). In all, 221 (92.8%) patients presented with monophasic CeAD, including 188 (79.0%) patients with a single CeAD event, 11 (4.6%) with simultaneous dissections in multiple cervical arteries, and 22 (9.2%) with subsequent events within a single phase of 4 weeks. Seventeen patients (7.1%) had late (>1 month after the initial event) recurrent CeAD events, including 5 (2.1%) with multiple recurrences. Patients with late recurrences were younger (37.5 ± 6.9 years) than those without (43.8 ± 9.9; p = 0.011). Ischemic stroke occurred in 164 (68.9%) patients at first diagnosis, but only 4 of 46 (8.7%) subsequent events caused stroke (p < 0.0001), while 19 (41.3%) were asymptomatic. Connective tissue abnormalities were found in 54 (56.3%) patients with monophasic and 8 (66.7%) with late recurrent dissections (p = 0.494). Twenty-two (9.2%) patients had new CeAD events within 1 month and 17 (7.1%) later recurrences. The risk for new events was significantly higher (about 60-fold) during the acute phase than during later follow-up. Connective tissue abnormalities were not more frequent in patients with late recurrent events than in those with monophasic CeAD.


Nonlocal electron kinetics and excited state densities in a magnetron discharge in argon.
The densities of argon metastable (3)P(2), and resonance (1)P(1), (3)P(1) states were measured along a cylindrical magnetron discharge radius by absorption spectroscopy using a narrow bandwidth single mode diode laser. The theoretical treatment includes calculations of the rates of numerous excitation and decay processes based on nonlocal electron kinetics, and analysis of the transport equations for the resonance and metastable atoms. The solution technique of the Biberman-Holstein equation of radiation transport is developed in conformity with magnetron discharge geometry. The radial profile of the effective lifetime is obtained, taking into account radiation escape on the inner and outer electrodes. The distinction in formations of the radial profiles of the resonance and metastable atoms caused by specifics of radiation transport and diffusion is demonstrated. The results of experiments and calculations are compared.


Increased augmentation index of the radial pressure waveform in patients with paroxysmal atrial fibrillation.
The augmentation index, a marker of wave reflection, has been reported to reflect vascular properties and to determine left ventricular (LV) characteristics. We investigated the relationship between the augmentation index and paroxysmal atrial fibrillation (AF). A total of 244 outpatients (122 patients with paroxysmal AF and 122 age-, and gender-matched controls without paroxysmal AF) were examined during sinus rhythm. The augmentation index was calculated from the radial arterial waveform using applanation tonometry methods. After adjusting for age, gender, heart rate, and medications, the augmentation index was significantly higher in patients with paroxysmal AF than in subjects without paroxysmal AF (means +/- SE: 88.9 +/- 1.0 and 81.8 +/- 1.0%, respectively; p < 0.001). In all subjects, an increase in the augmentation index was significantly correlated with LV hypertrophy and left atrial enlargement. Multiple logistic analysis revealed that an increase in the augmentation index was significantly related with paroxysmal AF, and the adjusted odds ratio of paroxysmal AF was approximately 1.8 for each 10% augmentation index increase (p < 0.01). An increase in the augmentation index was independently associated with paroxysmal AF. This result suggests that enhanced wave reflection may be related to the development of AF.


Nature and nurture in neuropsychiatric genetics: where do we stand?
Both genetic and nongenetic risk factors, as well as interactions and correlations between them, are thought to contribute to the etiology of psychiatric and behavioral phenotypes. Genetic epidemiology consistently supports the involvement of genes in liability. Molecular genetic studies have been less successful in identifying liability genes, but recent progress suggests that a number of specific genes contributing to risk have been identified. Collectively, the results are complex and inconsistent, with a single common DNA variant in any gene influencing risk across human populations. Few specific genetic variants influencing risk have been unambiguously identified, Contemporary approaches, however hold great promise to further elucidate liability genes and variants, as well as their potential inter-relationships with each other and with the environment. We will review the fields of genetic epidemiology and molecular genetics, providing examples from the literature to illustrate the key concepts emerging from this work.


Robust nondimensional estimators to assess the nasal airflow in health and disease.
There are significant variations of both human nose shapes and airflow patterns inside nasal cavities, so it is difficult to provide a comprehensive medical identification using a universal template for what otolaryngologists consider normal breathing at rest. In addition, airflow patterns present even more random characteristics in diseased nasal cavities. To give a medical assessment to differentiate the nasal cavities in health and disease, we propose 2 nondimensional estimators obtained from both medical images and computational fluid dynamics. The first mathematical estimator ϕ is a function of geometric features and potential asymmetries between nasal passages, while the second estimator R represents in fluid mechanics terms the total nasal resistance that corresponds to the atmosphere-choana pressure drop. These estimators only require global information such as nasal geometry and magnitudes of flow determined by simulations under laminar conditions. We find that these estimators take low and high values for healthy and diseased nasal cavities, respectively. Our study, based on 24 healthy and 25 diseased Caucasian subjects, reveals that there is an interval of values associated with healthy cavities that clusters in a small region of the plane ϕ-R. Therefore, these estimators can be seen as a first approximation to provide nasal airflow data to the clinician in a noninvasive method, as the computed tomography scan that provides the required images is routinely obtained as a result of the preexisting naso-sinusal condition.


Molecular cloning and sequencing of a canine tracheobronchial mucin cDNA containing a cysteine-rich domain.
To date the complete sequence of only one mammalian mucin cDNA, MUC1, has been reported, although several mucin proteins have been partially characterized. Here we report the nucleotide sequence of a canine tracheal mucin cDNA containing two potential translation initiation codons, one translation termination codon and a poly(A) tail. A lambda gt11 cDNA library prepared from canine tracheal epithelial cells was screened with polyclonal anti-apo-canine tracheal mucin antibodies with the aim of obtaining the deduced amino acid sequence of the mucin core protein. Antibody-positive clones containing overlapping inserts of various lengths were purified and used for nucleotide sequencing. Based on the sequencing data, synthetic oligonucleotide primers were constructed and both ends (5' and 3') of the cDNA were determined. The complete sequence was 3.7 kb and included an open reading frame with coding capacity for 1118 aa, two translation initiation ATG codons in context with Kozak consensus sequences, one polyadenylylation site, and a poly(A) stretch. The protein was rich in Thr, Pro, Ser, Gly, and Ala and poor in Tyr, Phe, and Trp. Although tandem repeats of amino acids were absent in the deduced canine tracheal mucin sequence, motifs TPTPTP and TTTTPV appeared 13 and 19 times, respectively. The C-terminal region contained a Cys-rich domain (although a few Cys residues were also present in the middle of the protein) as has been reported for bovine submaxillary mucin, porcine submaxillary mucin, rat intestinal mucin, human intestinal mucin, and frog skin mucin. This suggested that a broad group of mucins contain such a Cys-rich domain whose functional significance is yet to be understood. Three potential N-glycosylation sites were present in canine tracheal mucin and the amino acid sequence showed homology with both human tracheal and intestinal mucins. The N-terminal domain showed more flexibility (probably due to a high number of Pro residues in this region) when analyzed by the University of Wisconsin Genetics Computer Group program package to determine the predicted secondary structure. Evaluation of the transcripts using the canine mucin cDNA as a probe indicated a polydisperse message with total RNA.


Geographic access to hospital care: a 30-minute travel time standard.
A review of literature focusing upon geographic accessibility to health facilities indicates that while distance has been the traditional measure, travel time may now be a more meaningful indicator. Applying a 30-minute travel time standard to general hospitals, as advocated by various health plans, this paper illustrates an approach to the determination of geographic accessibility through a combination of a travel time file and sociodemographic profiles. Focusing upon all residents of West Virginia, the study identifies the number and characteristics of persons who reside within and beyond the 30-minute standard. More than 10 per cent of the entire population and nearly 20 per cent of the rural residents live in areas which are, by this standard, inaccessible to general hospitals. The "inaccessible" populations are characterized as having sociodemographic attributes associated with high medical needs. Other applications of travel time data are discussed.


Constitutive tyrosine phosphorylation of the GABA(A) receptor gamma 2 subunit in rat brain.
GABA(A) receptors are the major sites of fast synaptic inhibition in the brain, where they are predominantly composed of alpha, beta and gamma2 subunits. A role for direct tyrosine phosphorylation of residues 365 and 367 (Y365/367) within the intracellular domain of the gamma2 subunit has been suggested to be important in modulating GABA(A) receptor function, based on the study of recombinant receptors. To address the relevance of these observations for neuronal GABA(A) receptors we have studied the phosphorylation of the gamma2 subunit in the brain. In adult rat brain the gamma2 subunit is phosphorylated on tyrosine residues, including Y365/367 as defined using a phosphospecific antisera. In cultured cortical neurones, phosphorylation of Y365/367 is highly regulated and was only evident upon inhibition of tyrosine phosphatases. We also establish that the tyrosine kinase Src is capable of specifically interacting with the intracellular domains of receptor beta and gamma2 subunits. This may specifically localise tyrosine kinase activity to GABA(A) receptors, facilitating rapid receptor tyrosine phosphorylation upon kinase activation. Together our results suggests that tyrosine phosphorylation of the gamma2 subunit, possibly by closely associated Src, may be a dynamic mechanism for regulating GABA(A) receptor function in the brain.


Use of the Novel Derivatizing Agent 1,8-Diaminonapthalene With the CIP10 Sampler to Measure 4,4'-Methylene Diphenyl Diisocyanate Atmospheres.
DAN is a novel derivatizing agent for isocyanate sampling which targets total reactive isocyanate group (TRIG). Field evaluations have been conducted for 4,4'-Methylene diphenyl diisocyanate (MDI) sampling using DAN as the derivatizing agent in a CIP10. The perimidone formed, selective of TRIG, was analyzed in laboratory by liquid chromatography coupled to tandem mass spectrometry. Workplaces using MDI-based polyurethane spray foam and MDI wood product binder were studied. Each study compared the data obtained between the CIP10/DAN, the CIP10/MP, and a reference method. As a first evaluation, the CIP10/DAN sampled simulated MDI spray foam atmosphere in parallel with impingers (reference method) and CIP10/MP. The mean of the TRIG concentration values measured was 16% (95% confidence interval [CI], [1, 31]) higher for the CIP10/MP samples as compared to the impinger samples, while the mean TRIG concentrations found were 98% (95% CI [63, 133]) higher for the CIP10/DAN samples as compared to the impinger samples. For sampling done in a real workplace using MDI-based spray foam, the CIP10/DAN method showed lower results than the CIP10/MP method. The presence of hygroscopic DMSO used in the DAN approach is a limitation and may prevent obtaining accurate results in the spray foam atmosphere. CIP10/DAN was also studied in MDI wood product binder atmosphere. Mean TRIG concentrations found were 80% (95% CI [51, 110]) and 79% (95% CI [50, 108]) lower for the CIP10/MP and CIP10/DAN method, respectively, as compared to the reference method (a 13-mm filter coated with MP). In this case, the CIP10 may have reached its limit in this last evaluation where vapors and particles below 1 µm were not collected as efficiently as they were with the reference method.


Variability in low altitude astronomical refraction as a function of altitude.
Low altitude astronomical refraction (LAAR) of the setting Sun was measured over a sea horizon from a coastal location in Barbados, West Indies. The altitude of the upper limb of the Sun and the apparent horizon were determined using a digital video camera (Canon XL2) and a digital SLR camera (Canon EOS 5D). A total of 14 sunsets were measured between 2005 and 2007. From these measurements LAAR variability was estimated at 14 standard altitudes of the refracted Sun between 0 degrees .01 and 4 degrees .5. The relative variability decreases with increasing altitude from +/- 0.0195 of mean refraction at an altitude of 0 degrees .01 to +/- 0.0142 at 4 degrees .5. If extrapolated to an altitude of 15 degrees , a linear fit to the data produces a relative variability of +/- 0.0038 and an absolute variability of +/- 0(").45. Statistical analysis of the relative variability in LAAR appears to support the decreasing trend. However, error propagation analysis further suggests that the observed values of refraction may exceed the accuracy of the measurement system at altitudes higher than 2 degrees .


Assessment of the Correlation between Severity of Coronary Artery Disease and Waist-Hip Ratio.
This study was conducted to investigate the correlation between waist/hip ratio (WHR) as a measurement of obesity and severity of coronary artery disease (CAD) assessed by angiography in Kosovo. The study included 82 patients with suspected or known CAD who were referred for coronary angiography. All patients were subjected to full individual medical history, clinical examination including measurement of arterial blood pressure, body weight, height, body mass index (BMI), waist circumference, hip circumference, waist/hip ratio, and waist/height ratio. Coronary angiography was performed using standard techniques to determine the presence and severity of coronary artery lesions with the Gensini score. Among the 82 patients in the study, the mean age in the CAD group was 66.76 ± 9.12 years and the mean age in the non-CAD group was 64.80 ± 8.30 years. Patients in the CAD group had a mean BMI of 28.17 ± 3.32 kg/m2 and those in the non-CAD group had a mean BMI of 28.76 ± 4.68 kg/m2. Patients in the CAD group had a mean waist/height ratio of 1.76 ± 7.56 and those in the non-CAD group had a mean waist/height ratio of 0.57 ± 0.08. Patient in the CAD group had a mean waist/hip ratio of 0.93 ± 0.06 and those in the non-CAD group had a mean waist/hip ratio of 0.88 ± 0.07. Thirty-seven patients (45.1%) had no coronary artery disease (Gensini score = 0), 15 (18.3%) had mild disease (Gensini score = 1-32), 14 (17.1%) had moderate disease (Gensini score = 32-58), and 16 (19.5%) had severe disease (Gensini score ≥ 58). There was a significant positive correlation between waist/hip ratio and presence of CAD in Kosovar patients.