Insulin immunogenicity in pregnancy: maternal and fetal studies.
Antibodies to insulin were found in 92% of the 138 insulin-treated pregnant diabetic patients studied. No effect of pregnancy was shown on insulin antibody levels. Higher insulin antibody levels were significantly associated with the previous use of conventional insulins. Change from conventional to highly purified porcine insulin during pregnancy produced a significant reduction in insulin antibody levels. The combination of protamine zinc and soluble insulin used before pregnancy was found to be the most immunogenic. Insulin antibodies were freely transferred to the fetus but not detectable after the first 8 months of life. No insulin antibodies were found in the cord blood or during the next few weeks in the infants of mothers who had no antibodies to their injected insulin. There was a tendency for higher insulin antibody levels to be associated with indices of neonatal morbidity but not with percentile birth weights and C-peptide levels in cord sera.


Viscoelasticity evaluation of rubber by surface reflection of supersonic wave.
The main characteristic of rubber is a viscoelasticity. So it is important to research the characteristic of the viscoelasticity of the high frequency band for the friction between a rubber material and the hard one with roughness, for instance, the tire and the road. As for the measurement of the viscoelasticity of rubber, DMA (dynamic mechanical analysis) is general. However, some problems are pointed out to the measurement of the high frequency band by DMA. Then, we evaluated the viscoelasticity characteristic by the supersonic wave measurement. However, attenuation of rubber is large, and when the viscoelasticity is measured by the supersonic wave therefore, it is inconvenient and limited in a past method by means of bottom reflection. In this report, we tried the viscoelasticity evaluation by the method of using complex surface reflection coefficient and we compared with the friction coefficient under wide-range friction velocity. As a result, some relationships had been found for two properties. We report the result that character of viscoelasticity of rubber was comparable to friction coefficient.


Seasonal patterns in newborns' health: Quantifying the roles of climate, communicable disease, economic and social factors.
Poor health at birth can have long-term consequences for children's development. This paper analyses an important factor associated with health at birth: the time of year that the baby is born, and hence seasonal risks they were exposed to in utero. There are multiple potential explanations for seasonality in newborns' health. Most previous research has examined these in isolation. We therefore do not know which explanations are most important - and hence which policy interventions would most effectively reduce the resulting early-life inequalities. In this paper, I use administrative data to estimate and compare the magnitudes of several seasonal risks, seeking to identify the most important drivers of seasonality in the Northern Territory of Australia, a large territory spanning tropical and arid climates and where newborn health varies dramatically with the seasons. I find that the most important explanations are heat exposure and disease prevalence. Seasonality in food prices and road accessibility have smaller effects on some outcomes. Seasonal fertility patterns, rainfall and humidity do not have statistically significant effects. I conclude that interventions that protect pregnant women from seasonal disease and heat exposure would likely improve newborn health in the Northern Territory, with potential long-term benefits for child development. It is likely that similar impacts would apply in other locations with tropical and arid climates, and that, without action, climate change will accentuate these risks.


Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis.
Obesity causes cardiovascular diseases, including cardiac hypertrophy and remodeling, via chronic tissue inflammation. Myeloid differentiation factor-2 (MD2), a binding protein of lipopolysaccharide, is functionally essential for the activation of proinflammatory pathways in endotoxin-induced acute inflammatory diseases. Here we tested the hypothesis that MD2 plays a central role in obesity-induced cardiomyopathy. Wildtype or MD2 knockout mice were fed with a high fat diet (HFD) or normal diet (Control) for total 16weeks, and MD2 inhibitor L6H21 (20mg/kg) or vehicle (1% CMC-Na) were administered from the beginning of the 9th week. HFD induced significant weight gain and cardiac hypertrophy, with increased cardiac fibrosis and inflammation. L6H21 administration or MD2 knockout attenuated HFD-induced obesity, inflammation and cardiac remodeling. In vitro exposure of H9C2 cells to high lipids induced cell hypertrophy with activated JNK/ERK and NF-κB pathways, which was abolished by pretreatment of MD2 inhibitor L6H21. Our results demonstrate that MD2 is essential to obesity-related cardiac hypertrophy through activating JNK/ERK and NF-κB-dependent cardiac inflammatory pathways. Targeting MD2 would be a therapeutic approach to prevent obesity-induced cardiac injury and remodeling.


Spectrophotometric determination of theophylline formulations.
Minophylline (theophylline ethanoate of piperazine) and aminophylline (theophylline ethylenediamine) were determined spectrophotometrically in dosage forms without interference from excipients and/or preservatives. A mixture of minophylline, in about 30-fold concentration, with phenobarbital was assayed for both components with good accuracy and high reproducibility.


Atherosclerotic calcification relates to cognitive function and to brain changes on magnetic resonance imaging.
Increasing evidence suggests a role of atherosclerosis in the pathogenesis of cognitive impairment and dementia. Calcification volume measured with computed tomography (CT) is a valid marker of atherosclerosis. This study investigates associations of atherosclerosis (measured using CT) at four locations with cognition and brain changes on magnetic resonance imaging (MRI). To quantify calcification volume, 2414 nondemented people from the Rotterdam Study underwent CT of the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries. To assess global cognition and performance on memory, executive function, information processing speed, and motor speed, they also underwent neuropsychological tests. In a random subgroup of 844 participants, brain MRI was performed. Automated segmentation and quantification of brain MRI scans yielded brain tissue volumes in milliliters. Diffusion tensor imaging was used to measure the microstructural integrity of the white matter. Relationships of atherosclerotic calcification with cognition, brain tissue volumes, and diffusion tensor imaging measures were assessed with linear regression models and adjusted for relevant confounders. With larger calcification volumes, lower cognitive scores were observed. When calcification volumes were larger, total brain volumes were also smaller. Specifically, larger coronary artery calcification volumes related to smaller gray matter volumes, and extracranial and intracranial carotid calcification volumes related to smaller white matter volumes. Larger calcification volume in all vessel beds was accompanied by worse microstructural integrity of the white matter. Larger calcification volume is associated with worse cognitive performance. It also relates to smaller brain tissue volumes and worse white matter microstructural integrity, revealing possible mechanisms through which atherosclerosis may lead to poorer cognition.


Rotational isomerism of some chloroacetamides: theoretical and experimental studies through calculations, infrared and NMR.
The geometries involved in the conformational equilibria of 2,2-dichloro-N-cyclohexyl-N-methyl-acetamide (DCCMA) and 2-chloro-N,N-dicyclohexylacetamide (CDCA) were investigated. Theoretical calculations at the B3LYP/cc-pVDZ level of theory showed that gauche forms (ClCCO) are the most stable and the predominant conformers in isolated phase. Both compounds had the conformational behavior in solvents of different polarities estimated from theoretical calculations with the PCM (Polarizable Continuum Model), at the same level of theory, using infrared data from deconvolution of the carbonyl absorption bands and (13)C NMR spectra. Their IR spectra showed two carbonyl absorptions and that the conformer with the highest dipole moment had its population increased when the most polar solvents were used, in accordance with the theoretical calculation in solution. (1)JCH coupling constants were obtained from their NMR spectra, and revealed that there was population variation of conformers with solvent exchange. Experimental data (NMR and IR) as well as calculations including the solvent effects followed the same trend.


Nuclear localization of the Epstein-Barr virus/C3d receptor (CR2) in the human Burkitt B lymphoma cell, Raji.
Epstein-Barr virus/C3d receptor (CR2) is a glycoprotein of mol. wt 140,000 expressed on the surface of Raji cells. We previously isolated phosphorylated CR2 from purified Raji cell nuclei. We have analyzed the nuclear localization of CR2 by electron microscope immunochemistry of thin sections of Raji cells and we have compared the binding properties of CR2 expressed on purified plasma membranes or nuclei. Anti-CR2 mAb immunogold labeling of thin sections of Raji cells identified CR2 at the nuclear surface and also within the nucleus. Nuclear envelope associated CR2 was localized mainly at nuclear pores. Within the nucleus, CR2 was associated with ribonucleoprotein (RNP) interchromatin fibrils. This labeling was preserved in nuclear matrix preparations. CR2 expressed on the surfaces of purified nuclei or on the cell surface interacted with soluble and particle-bound C3bi/C3d. Monoclonal anti-CR2 antibodies, which recognized extracellular domains of CR2, reacted differently with CR2 depending on its subcellular localization. The presence of CR2 in nuclei may be due to translocation of the cell surface CR2 and/or the presence of two distinct intracellular pathways for mature CR2.


Mitochondrial energy metabolism disorder and apoptosis: a potential mechanism of postoperative ileus.
To explore whether mitochondrial energy metabolism disorder and apoptosis of smooth muscle cells in intestinal muscularis are participated in pathogenesis of postoperative ileus (POI). Rats were randomized into three groups: naive controls (NC) group, sham controls (SC) group and intestinal manipulation (IM) group. Gastrointestinal transits were analyzed. Reactive oxygen species (ROS), malondialdehyde (MDA) and adenosine triphosphatases (ATPases) activity in intestinal muscularis were determined. The levels of aldehyde dehydrogenase 2 (ALDH2), Bcl-2 and Bax in intestinal muscularis were measured by real-time PCR assays and western blot analysis. The levels of ATP, ADP and AMP in intestinal muscularis were determined by high performance liquid chromatography. Transmission electron microscopic was used to observe ultrastructure of smooth muscle cells and mitochondria in intestinal muscularis. Delayed gastrointestinal transitoccurred only in IM groups. After IM, increased levels of ROS and MDA were observed in intestinal muscularis. In IM groups, we also observed decreased levels of ALDH2 and Bcl-2/Bax ratio. The levels of ATP and ADP were decreased and level of AMP was increased in IM groups. The activity of ATPases was decreased in IM groups. Abnormal morphological architecture of smooth muscle cells and mitochondria were found in intestinal muscularis of IM groups. Our results suggest that mitochondrial energy metabolism disorder and apoptosis of smooth muscle cells in intestinal muscularis may participate in the development of POI.


Biological importance of marine algae.
Marine organisms are potentially prolific sources of highly bioactive secondary metabolites that might represent useful leads in the development of new pharmaceutical agents. Algae can be classified into two main groups; first one is the microalgae, which includes blue green algae, dinoflagellates, bacillariophyta (diatoms)… etc., and second one is macroalgae (seaweeds) which includes green, brown and red algae. The microalgae phyla have been recognized to provide chemical and pharmacological novelty and diversity. Moreover, microalgae are considered as the actual producers of some highly bioactive compounds found in marine resources. Red algae are considered as the most important source of many biologically active metabolites in comparison to other algal classes. Seaweeds are used for great number of application by man. The principal use of seaweeds as a source of human food and as a source of gums (phycocollides). Phycocolloides like agar agar, alginic acid and carrageenan are primarily constituents of brown and red algal cell walls and are widely used in industry.


The long-term survival rates of patients after repair of abdominal aortic aneurysms.
This study was undertaken to examine the long-term survival rates of patients following abdominal aortic aneurysm (AAA) repair in comparison with an age-matched normal population, and to determine by multivariate analysis the factors influencing long-term survival. Of 125 patients who underwent AAA repair prior to July 1986, 13 died during hospitalization. Of these 13 patients, 6 who suffered aneurysmal rupture all died within 30 days. The survival rate of patients with ruptured aortic aneurysms was significantly lower than that of those with nonruptured aneurysms. Of the 112 patients surviving hospitalization, 85 died within 0.48 to 24 years after their operation. The long-term survival rate of patients who had suffered a preoperative cardiovascular event was significantly lower than that of those who had not suffered a preoperative cardiovascular event. The actual survival rate was significantly lower than the expected survival rate. According to a multivariate analysis, the significant predictors of late survival were age, aneurysmal rupture, and chronic renal failure in all the patients, and age, chronic renal failure, and pre- and postoperative cardiovascular events in patients who did not die in hospital. These findings indicate the importance of improving immediate perioperative management of ruptured AAA and that cardiovascular events should be prevented, or treated during long-term follow-up.


True and Perceived Synchrony are Preferentially Associated With Particular Sensory Pairings.
Perception and behavior are fundamentally shaped by the integration of different sensory modalities into unique multisensory representations, a process governed by spatio-temporal correspondence. Prior work has characterized temporal perception using the point in time at which subjects are most likely to judge multisensory stimuli to be simultaneous (PSS) and the temporal binding window (TBW) over which participants are likely to do so. Here we examine the relationship between the PSS and the TBW within and between individuals, and within and between three sensory combinations: audiovisual, audiotactile and visuotactile. We demonstrate that TBWs correlate within individuals and across multisensory pairings, but PSSs do not. Further, we reveal that while the audiotactile and audiovisual pairings show tightly related TBWs, they also exhibit a differential relationship with respect to true and perceived multisensory synchrony. Thus, audiotactile and audiovisual temporal processing share mechanistic features yet are respectively functionally linked to objective and subjective synchrony.


Control of neoplastic cell proliferation and differentiation by restoration of 4-hydroxynonenal physiological concentrations.
Several studies point to the existence of an inverse correlation between cellular lipid peroxidation and both cell proliferation and neoplastic transformation. In anaplastic cell lines products of membrane lipid peroxidation are very low or undetectable. Furthermore numerous results demonstrate effect of lipid peroxidation products on central biochemical pathways and intracellular signalling at physiological concentrations. 4-hydroxynonenal (HNE) is one of the most active products of lipid peroxidation. The restoration of HNE physiological concentrations in neoplastic cells may inhibit cell proliferation and modulate cell re-differentiation. This review try to summarize and critically discuss the effects of physiological concentrations of HNE on normal and neoplastic cell line.


Predicting Complicated Mild Traumatic Brain Injury in Adolescent Trauma to Enhance Clinical Decisions in Imaging.
The Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury algorithm is used to identify children at low risk of clinically significant traumatic brain injuries to reduce computed tomography (CT) exposure. Adapting PECARN rules based on population-specific risk stratification has been suggested to improve diagnostic accuracy. This study sought to identify center-specific patient variables, beyond PECARN rules, that may enhance the identification of patients requiring neuroimaging. This single-center, retrospective cohort study was conducted from July 1, 2016, to July 1, 2020, in a Southwestern U.S. Level II pediatric trauma center. The inclusion criteria were adolescents (10-15 years), Glasgow Coma Scale (13-15), with a confirmed mechanical blow to the head. Patients without a head CT were excluded. Logistic regression was performed to identify additional complicated mild traumatic brain injury predictor variables beyond the PECARN. There were 136 patients studied; 21 (15%) presented with a complicated mild traumatic brain injury. Relative to motorcycle collision or all-terrain vehicle trauma (odds ratio [OR] 211.75, 95% confidence interval, CI [4.51, 9931.41], p < .001), an unspecified mechanism (OR 42.0, 95% CI [1.30, 1350.97], p = .03) and consult activation (OR 17.44, 95% CI [1.75, 173.31], p = .01) were significantly associated with complicated mild traumatic brain injury. We identified additional factors associated with complex mild traumatic brain injury, including motorcycle collision and all-terrain vehicle trauma, unspecified mechanism, and consult activation that are not in the PECARN imaging decision rule. Adding these variables may aid in determining the need for appropriate CT scanning.


The interleukin-1 signalling pathway in astrocytes: a key contributor to inflammation in the brain.
A dysregulated inflammatory response in the central nervous system (CNS) lies at the heart of many neuropathological conditions such as multiple sclerosis and Alzheimer's disease. A key component of these inflammatory conditions is the accumulation of leukocytes in the CNS. The infiltration of leukocytes into the brain is dependent on the induction of leukocyte adhesion molecules and chemoattractant chemokines. Recent studies have suggested the astrocyte to be a key cell in mediating the inflammatory process in the brain and in expressing adhesion molecules and chemokines. Here I overview work in my laboratory and others that demonstrates interleukin-1 (IL-1) to be a key inducer of the expression of these molecules in astrocytes. The temporal expression is sustained in nature and this is due to prolonged activation of the transcription factor NFkappaB. The molecular basis to the sustained activation of NFkappaB is also discussed. The IL-1 signalling pathway thus emerges as a valuable therapeutic target in the treatment of presently incurable neuropathological conditions.


Trace analysis of sulfaquinoxaline in animal tissues by high-performance liquid chromatography.
Sulfaquinoxaline (in combination with diaveridine as a potentiating agent) was administered orally to broilers, 4-5 weeks old, and sulfonamide residues were determined in muscle and liver at 0, 1, 2, 4, 6, 7, 8, and 10 days post-treatment, using ion-pair extraction followed by high-performance liquid chromatography with UV detection. Improved recoveries (ca. 80%, at the 10 ppb level) were obtained after liquefaction of the tissues by the addition of 8 M urea and sodium hydroxide, prior to ion-pair extraction. A withdrawal period of seven days was found necessary in order to reduce drug residues in muscle and liver to 10 ppb, a level without hazard to humans.


Effects of different fragments of the fibronectin molecule on latex bead translocation along neural crest migratory pathways.
Previous studies from this laboratory have utilized latex beads as probes of embryonic migratory pathways. After microinjection into embryos at the time of neural crest migration, uncoated latex polystyrene beads were found to translocate to ventral sites and to settle in the vicinity of endogenous neural crest derivatives. However, latex beads coated with fibronectin did not translocate ventrally, but remained associated with cells surrounding the implantation site. Fibronectin is a large glycoprotein with a variety of biological activities and multiple binding domains. Here, the binding activities which might be responsible for immobilization of the fibronectin-coated beads are examined. Latex beads were coated with three types of fragments of the fibronectin molecule representing different functional domains: (i) a 66-kDa fragment containing collagen-binding activity; (ii) a mixture of 45- and 32-kDa fragments containing heparin-binding activity; and (iii) a 120-kDa fragment containing cell-binding activity. The beads coated with fibronectin fragments were injected into the newly formed trunk somites of avian embryos. After injection, beads coated with either the heparin- or the collagen-binding domain translocated ventrally and distributed analogously to uncoated latex beads. In contrast, the majority of beads coated with the fibronectin cell-binding domain did not translocate but remained associated with dermamyotomal cells surrounding the injection site. The cell-binding fragment, however, was not as effective as the intact fibronectin molecule in preventing translocation of the beads. The results suggest that the cell-binding domain is primarily responsible for restriction of fibronectin beads from the ventral neural crest pathway. Because intact fibronectin is more effective at immobilizing beads than is the cell-binding fragment, other binding domains of fibronectin, more efficient coating with intact fibronectin, or crosslinking of intact fibronectin molecules may also play some role in immobilization of the beads at the implantation site.


Bilateral brachial artery fibromuscular dysplasia.
Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease that usually involves medium- and small-sized arteries. It is most commonly observed in the renal, carotid, and intracerebral arteries, although it has been reported in other arterial beds. The most common form is characterized by medial fibrosis, with or without smooth muscle cell hyperplasia, which can result in luminal narrowing and turbulent flow. There is often a secondary aneurysmal degeneration of the artery, which may or may not be associated with thrombosis or obstruction of flow. This accounts for the typical "string-of-beads" appearance seen on arteriography. We describe a patient who presented with ischemia of the right hand secondary to fibromuscular dysplasia of the brachial artery. Subsequent studies also demonstrated fibromuscular dysplasia in the other brachial artery as well as mild involvement of the right renal artery. The patient was treated on the symptomatic side with dilatation of proximal lesions, resection of the thrombosed segment, and reconstruction with a reversed saphenous vein graft. Distal pulses were fully restored postoperatively. Pathologic examination confirmed the arteriographic and clinical diagnosis of fibromuscular dysplasia. The salient features of this case are reviewed in addition to the other cases reported in the literature.


Direct analysis of bromine and iodine in dried serum spots by laser ablation inductively coupled plasma mass spectrometry.
Accurate quantitative analysis of bromine and iodine in serum is an important aspect of monitoring body condition, but the volatile loss of halogen in sample pretreatment is a troublesome problem. We present a validated and flexible high-throughput method for quantification of bromine and iodine in dried serum spots (DSS) using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and an external aqueous standard calibration curve. The influence of serum matrix and laser ablation (LA) conditions on the analysis of bromine and iodine in DSS was researched systematically. Aqueous standards without matrix matching were used for calibration to analyze bromine and iodine in serum by LA-ICP-MS. 5-μL volumes of the aqueous standard solution and serum samples in 10 times diluted concentration were deposited on the PTFE paper to form dried standard calibration spots (DSCS) and DSS, of less than 2 mm in diameter. LA was performed using a focused Nd:YAG laser beam in raster lineal scan mode. The limits of detection (LODs) for bromine and iodine in DSS were 0.23 and 0.03 mg L-1 , respectively. The relative standard deviation (RSD) for this method was less than 10%. The samples were also detected with matrix matching calibration by ICP-MS. The accuracy of the method was verified by statistical analysis of these results from ICP-MS and LA-ICP-MS. The accuracy is satisfactory with recoveries ranging from 81.5% to 118%. A novel and simple approach for high-throughput screening of bromine and iodine in DSS has been established by LA-ICP-MS. Calibration could be achieved using an aqueous standard solution instead of a matrix-matching solution. The method allowed analysis of low-volume biological samples without derivatization and decreased the risk of contamination or loss.


[Search for genetic markers for precise diagnostics of keratoconus].
Keratoconus is a chronic disorder of the cornea, characterized by its progressive thinning, stretching, and conical protrusion. Diagnostics of subclinical keratoconus, as well as its early stages (forme fruste), is a complex problem. The presence of these forms of keratoconus in a patient is one of the reasons for the development of keratectasia after laser refractive surgery. Currently, the role of genetic factors in keratoconus development has been proven. This indicates the possibility of diagnostics of subclinical and forme fruste keratoconus using genetic markers. Knowledge about the patient's genetic susceptibility to keratoconus would allow correcting the tactics of treatment of refractive anomalies and avoiding serious side effects. The studies of causal mutations indicate the genetic heterogeneity of keratoconus, which complicates the development of a diagnostic panel. Selection of candidate variants from the currently known ones based on clear criteria may be one of the approaches for diagnostic markers search. In this review, we have analyzed articles on keratoconus markers in order to form a list of candidate variants for genotyping in the Russian population. The selection criteria took into account the complexes of symptoms in which a marker was found, populations in which a particular marker was investigated, the presence and results of replication studies. The analysis included markers in VSX1, SOD1, ZEB1, LOX, CAST, DOCK9, TGFBI, HGF, MAP3K19, KCND3, COL4A3, COL4A4, COL5A1, FNDC3B, FOXO1, BANP-ZNF469, MPDZ-NF1B, WNT10A genes. Based on the results of the analysis, the following candidate variants were selected for genotyping in the Russian population of patients with keratoconus: rs1536482 and rs7044529 in the COL5A1 gene, rs5745752 and rs2286194 in the HGF gene, rs4954218 in the MAP3K19 gene, rs4839200 near the KCND3 gene, rs2721051 near the FOXO1 gene, rs1324183 between the MPDZ and the NF1B genes, and rs121908120 in the WNT10A gene.


Customer, client, consumer, recipient, or patient.
Since the arrival of managed care, there has been a trend toward changing the basic terminology used to address clinicians and patients. Instead of the term "patient", third party payors frequently use terms such as "customer, client, consumer or recipient". One study demonstrated that patients prefer to be called patients. To investigate the preferred term to refer to patients and to be referred to by patients, we mailed a questionnaire to 100 physicians in four medical specialties each and to 100 psychologists. The overall response rate was 61%. Physicians overwhelmingly preferred to refer to patients by the patient's last name, their second preference was the patient's first name. Psychologists preferred to refer to the patients by first name, their second preference was the patient's last name. No group favored using terms such as client, customer, consumer, or recipient. Most physicians and psychologists preferred being referred to as doctors and nobody favored the term provider.


Intercountry adoption: young adult issues and transition to adulthood.
Intercountry adoption is an extremely sensitive and emotional issue for the citizens of the sending countries as well as for those in other, often more affluent, countries who adopt these children. It must be a priority to respect the dignity of the child's birth country as well as the dignity of the child.


Microphysiological testing for chemosensitivity of living tumor cells with multiparametric microsensor chips.
A constraint in the reliability of predictive chemosensitivity assays is linked to the fact that they analyze only a single cellular or biochemical parameter. A multiparametric test system using microsensor chips has been developed which can detect online microphysiological changes in living cells. Tumor cells were grown directly on glass- or silicon-based electronic sensor chips. Changes in extracellular pH and pO(2), reflecting metabolic activities, and changes in impedance, reflecting morphological properties, were monitored. In this study, colon and breast cancer cells as well as doxorubicin-sensitive and doxorubicin-resistant sarcoma cell lines were exposed to cytochalasin B, chloroacetaldehyde, or doxorubicin. Results show (1) reduction in medium acidification, (2) marked and rapid changes in O(2) consumption, and (3) modulations in impedance correlating with morphological changes observed in the microscope. Drug-resistant cells do not show these changes. Therefore, this microphysiological monitoring is a versatile tool for chemosensitivity testing of tumor cells.


Brain flexibility and balance and gait performances mark morphological and metabolic abnormalities in the elderly.
Although previous studies have found that cerebral white matter hyperintensities are associated with balance-gait disorders, no proton magnetic resonance spectroscopy data at the plane of the basal ganglia have been published. We investigated a possible relationship between balance performance and brain metabolite ratios or structural MRI measurements. We also included neuropsychological tests to determine whether such tests are related to structural or metabolic findings. All 80 participants were taken from the cohort of the Three-City study (Dijon-Bordeaux-Montpellier, France). The ratios of N-acetyl-aspartate to creatine (NAA/Cr) and choline to creatine (Cho/Cr) were calculated in the basal ganglia, thalami and insular cortex. We used univariate regression to identify which variables predicted changes in NAA/Cr and Cho/Cr, and completed the analysis with a multiple linear or logistic regression. After the multivariate analysis including hypertension, age, balance-gait, sex, white matter lesions, brain atrophy and body mass index, only balance-gait performance remained statistically significant for NAA/Cr (p=0.01) and for deep white-matter lesions (p=0.02). The Trail-Making Test is independently associated with brain atrophy and periventricular white-matter hyperintensities. Neuronal and axonal integrity at the plane of the basal ganglia is associated with balance and gait in the elderly, whereas brain flexibility is associated with structural MRI brain abnormalities.


Hyposensitivity to vasopressin in a hemorrhaged-transfused rat model of portal hypertension.
This study was designed to evaluate the hemodynamic response to vasopressin infusion during hemorrhage and blood transfusion in a rat model of portal hypertension. Portal pressure, arterial pressure, and regional and systemic blood flows were measured in a rat model of portal hypertension receiving placebo or vasopressin infusion. Effects of the drugs were compared in control rats and rats subjected to hemorrhage and blood transfusion. In a stable portal hypertensive rat group (no hemorrhage or transfusion) a standard vasopressin dose, 2.5 mU X kg-1 X min-1, resulted in a significantly lower portal pressure (11.5 +/- 0.7 vs. 14.4 +/- 0.6 mmHg) with a concomitantly lower portal venous inflow (8.5 +/- 0.3 vs. 11.1 +/- 0.6 ml X min-1 X 100 g body wt-1) when compared with rats receiving placebo. These findings are in contrast to the effects obtained with the same dose of vasopressin given during blood transfusion to hemorrhaged portal hypertensive rats. The standard dose of vasopressin had no effect on any of the splanchnic or systemic circulatory parameters. Only when a dose of vasopressin 10 times larger was used in the hemorrhaged-transfused animals were hemodynamic effects noted. A significant decrease in portal flow and pressure was noted. These findings suggest that vasopressin given during hemorrhage may be less effective than when given during a stable state. Larger doses of vasopressin may be needed during hemorrhage to produce the same effect as seen during a controlled stable state. Caution should be used in extrapolating the results of pharmacologic studies in stable portal-hypertensive models to hypovolemic states in humans.


Effect of Gram Stain-Guided Initial Antibiotic Therapy on Clinical Response in Patients With Ventilator-Associated Pneumonia: The GRACE-VAP Randomized Clinical Trial.
Gram staining should provide immediate information for detecting causative pathogens. However, the effect of Gram staining on restricting the initial antibiotic choice has not been investigated in intensive care units (ICUs). To compare the clinical response to Gram stain-guided restrictive antibiotic therapy vs guideline-based broad-spectrum antibiotic treatment in patients with ventilator-associated pneumonia (VAP). This multicenter, open-label, noninferiority randomized clinical trial (Gram Stain-Guided Antibiotics Choice for VAP) was conducted in the ICUs of 12 tertiary referral hospitals in Japan from April 1, 2018, through May 31, 2020. Patients aged 15 years or older with a VAP diagnosis and a modified Clinical Pulmonary Infection Score of 5 or higher were included. The primary analysis was based on the per-protocol analysis population. Patients were randomized to Gram stain-guided antibiotic therapy or guideline-based antibiotic therapy (based on the 2016 Infectious Disease Society of America and American Thoracic Society clinical practice guidelines for VAP). The primary outcome was the clinical response rate; clinical response was defined as completion of antibiotic therapy within 14 days, improvement or lack of progression of baseline radiographic findings, resolution of signs and symptoms of pneumonia, and lack of antibiotic agent readministration, with a noninferiority margin of 20%. Secondary outcomes were the proportions of antipseudomonal agents and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents as initial antibiotic therapies; 28-day mortality, ICU-free days, ventilator-free days; and adverse events. In total, 206 patients (median [IQR] age, 69 [54-78] years; 141 men [68.4%]) were randomized to the Gram stain-guided group (n = 103) or guideline-based group (n = 103). Clinical response occurred in 79 patients (76.7%) in the Gram stain-guided group and 74 patients (71.8%) in the guideline-based group (risk difference, 0.05; 95% CI, -0.07 to 0.17; P < .001 for noninferiority). Reduced use of antipseudomonal agents (30.1%; 95% CI, 21.5%-39.9%; P < .001) and anti-MRSA agents (38.8%; 95% CI, 29.4%-48.9%; P < .001) was observed in the Gram stain-guided group vs guideline-based group. The 28-day cumulative incidence of mortality was 13.6% (n = 14) in the Gram stain-guided group vs 17.5% (n = 18) in the guideline-based group (P = .39). Escalation of antibiotics according to culture results was performed in 7 patients (6.8%) in the Gram stain-guided group and 1 patient (1.0%) in the guideline-based group (P = .03). There were no significant differences between the groups in ICU-free days, ventilator-free days, and adverse events. Results of this trial showed that Gram stain-guided treatment was noninferior to guideline-based treatment and significantly reduced the use of broad-spectrum antibiotics in patients with VAP. Gram staining can potentially ameliorate the multidrug-resistant organisms in the critical care setting. ClinicalTrials.gov Identifier: NCT03506113.


[Hendrik Burger, editor-in-chief of the Dutch Journal of Medicine 1904- 1913].
Hendrik Burger (1864-1957) became the sixth editor-in-chief of the Journal before gaining international fame as a professor of otorhinolaryngology. He was more a teacher than researcher, and his clinic in Amsterdam became an internationally renowned training centre. He advocated better public healthcare for children who were deaf/mute or had impaired hearing and founded schools for these children. A prolific writer, Burger contributed more than 400 papers to the Journal.


Adult-onset type 1 diabetes: Predictors of glycaemic control.
Knowledge about adult-onset (AO) type 1 diabetes remains insufficient. We sought to characterize the initial 5 years of AO type 1 diabetes and hypothesized that initial factors predictive of subsequent glycaemic control might exist. A retrospective cohort study based on electronic medical records of 280 subjects with newly diagnosed AO type 1 diabetes (>18 years of age, excluding secondary and latent autoimmune diabetes) with available data for the initial 5-year treatment. Characteristics at diagnosis: 61% men, mean age 37 ± 12 years, BMI 23 ± 3.3 (kg/m2), systolic/diastolic blood pressure: 123 ± 15/76 ± 9 mm Hg and LDL cholesterol: 2.9 ± 0.9 mmol/L. HbA1c decreased from 106 mmol/mol (11.8%) at diagnosis to 52 mmol/mol (6.9%) at 6 months and then increased gradually to 67 mmol/mol (8.3%) after 5 years. Strict glycaemic control (<53 mmol/mol (7%)) was achieved by 66% within 6-9 months and 30% after 5 years. Comparing patients with and without strict glycaemic control after 5 years revealed no differences in HbA1c, C-peptide or any other diabetes-related parameter at the time of diagnosis. However, reaching strict control within 6-9 months after diagnosis was strongly associated with remaining in strict control after 5 years (OR: 9.2 (CI-95% 4.0-20.9; P < 0.0001)). Conversely, patients who did not achieve early strict control were very unlikely to be well controlled after 5 years. Long-term tight glycaemic control in subjects with AO type 1 diabetes is both achievable and to some extent predictable. Whether alternative strategies shortly after diagnosis would benefit patients with insufficient glycaemic control should be investigated.


New gene responsible for para-aminobenzoate biosynthesis.
Folate is an essential cofactor in all living cells for one-carbon transfer reactions. para-Aminobenzoate (pABA), a building block of folate, is usually derived from chorismate in the shikimate pathway by reactions of aminodeoxychorismate synthase (PabA and -B) and 4-amino-4-deoxychorismate lyase (PabC). We previously suggested that an alternative pathway for pABA biosynthesis would operate in some microorganisms such as Lactobacillus fermentum and Nitrosomonas europaea since these bacteria showed a prototrophic phenotype to pABA despite the fact that there are no orthologs of pabA, -B, and -C in their genome databases. In this study, a gene of unknown function, NE1434, was obtained from N. europaea by shotgun cloning using a pABA-auxotrophic Escherichia coli mutant (ΔpabABC) as a host. A tracer experiment using [U-(13)C6]glucose suggested that pABA was de novo synthesized in the transformant. An E. coli ΔpabABCΔaroB mutant carrying the NE1434 gene exhibited a prototrophic phenotype to pABA, suggesting that compounds in the shikimate pathway including chorismate were not utilized as substrates by NE1434. Moreover, the CT610 gene, an ortholog of NE1434 located in the folate biosynthetic gene cluster in Chlamydia trachomatis, also complemented pABA-auxotrophic E. coli mutants. Taken together, these results suggest that NE1434 and CT610 participate in pABA biosynthesis.


Information seeking behaviour of dental trauma patients and their parents.
Dental trauma is a common public health issue that can be associated with high costs and lifelong treatment. Children and parents should have the correct information regarding its management to reduce the potential long-term sequelae. Understanding their information seeking behaviour is therefore important to ensure that they are able to access, understand and retain the relevant information. The aim of this study was to investigate (a) the different ways that patients undertaking treatment for dental trauma, and their parents, look for relevant information, (b) their information needs, and (c) their preferred format of information. This was a two-phase study: Phase I involved in-depth interviews with 10 patients who were currently undergoing treatment for dental trauma, and 11 parents. In phase II, the themes and sub-themes identified from the interviews were used to develop patient and parent questionnaires, which were distributed to all trauma patients and parents who fulfilled the inclusion criteria and who were attending the dental clinics from March to May 2014. Patients and parents had different concerns immediately following the trauma, during treatment and in the long term, and they wanted different forms of information to answer their concerns. Reliability was the main issue about trusting the information available in the Internet, social media and other online sources. Therefore, patients preferred to obtain information verbally from their dentist, while parents preferred written information. Patients and parents have different information needs, and these also vary at different stages of treatment. It is therefore important to customize the way information is provided for each group accordingly.


What is the distribution of Aortic Dissection Detection Risk Score in an undifferentiated emergency department chest pain population?
To determine the distribution of Aortic Dissection Detection Risk Score (ADDRS) in undifferentiated chest pain patients. Prospective observational study of adult patients presenting to the ED with non-traumatic chest pain. Of 139 patients studied, more than 75% of patients has an ADDRS ≥1, mainly because of the report of severe pain. There were no aortic dissections. In patients with non-specific chest pain, testing driven by the ADDRS protocol would have seen a 280% increase in d-dimer testing and 2200% increase in computed tomography aortogram rates. Widespread use of the ADDRS and its investigation protocol cannot be supported.


A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy.
A randomised placebo controlled study was performed in 32 women with intrahepatic cholestasis of pregnancy. The population was divided into four groups: for 20 days each group was treated only with ursodeoxycholic acid, or S-adenosylmethionine, or a combination of both drugs, or a placebo (vitamin). Itching, standard liver function tests and serum total bile acids were measured before, during, and after treatment. Itching improved in all the women as well as the biochemical abnormalities. No side-effects in the mother or in the infant were recorded during and after therapy. A combination of ursodeoxycholic acid and S-adenosylmethionine is more effective than placebo and than either drug alone.


Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness.
The absence of endothelial cells at the luminal surface of a prosthetic vascular graft potentiates thrombosis and neointimal hyperplasia, which are common causes of graft failure in humans. This study tested the hypothesis that pretreatment with chronic in vitro shear stress enhances subsequent endothelial cell retention on vascular grafts implanted in vivo. Cultured endothelial cells derived from Fischer 344 rat aorta were seeded onto the luminal surface of 1.5-mm internal diameter polyurethane vascular grafts. The seeded grafts were treated for 3 days with 1 dyne/cm2 shear stress and then for an additional 3 days with 1 or 25 dyne/cm2 shear stress in vitro. The grafts then were implanted as aortic interposition grafts into syngeneic rats in vivo. Grafts that were similarly seeded with endothelial cells but not treated with shear stress and grafts that were not seeded with endothelial cells served as controls. The surgical hemostasis time was monitored. Endothelial cell identity, density, and graft patency rate were evaluated 24 hours after implantation. Endothelial cell identity in vivo was confirmed with cells transduced in vitro with beta-galactosidase complementary DNA in a replication-deficient adenoviral vector. Histologic, scanning electron microscopic, and immunohistochemical analyses were performed 1 week and 3 months after implantation to establish cell identity and to measure neointimal thickness. The pretreatment with 25 dyne/cm2 but not with 0 or 1 dyne/cm2 shear stress resulted in the retention of fully confluent endothelial cell monolayers on the grafts 24 hours after implantation in vivo. Retention of seeded endothelial cells was confirmed by the observation that beta-galactosidase transduced cells were retained as a monolayer 24 hours after implantation in vivo. In the grafts with adherent endothelial cells that were pretreated with shear stress, immediate graft thrombosis was inhibited and surgical hemostasis time was significantly prolonged. Confluent intimal endothelial cell monolayers also were present 1 week and 3 months after implantation. However, 1 week after implantation, macrophage infiltration was observed beneath the luminal cell monolayer. Three months after the implantation in vivo, subendothelial neointimal cells that contained alpha-smooth muscle actin were present. The thickness of this neointima averaged 41 +/- 12 micrometer and 60 +/- 23 micrometer in endothelial cell-seeded grafts that were pretreated with 25 dyne/cm2 shear stress and 1 dyne/cm2 shear stress, respectively, and 158 +/- 46 micrometer in grafts that were not seeded with endothelial cells. The effect of chronic shear stress on the enhancement of endothelial cell retention in vitro can be exploited to fully endothelialize synthetic vascular grafts, which reduces immediate in vivo graft thrombosis and subsequent neointimal thickness.


1989 Mary J. Nielubowicz Award winner. Today's role of the Navy nurse.
The ultimate Navy Nurse role would be described as the Nurse Corps officer who is known to be an expert nursing practitioner and simultaneously meeting all role expectations as a naval leader. Unclear or inaccurate expectations regarding the traditional Navy Nurse role may originate from expectations of peers or superiors. Role stress and strain results when role expectations are not or cannot be met, which may lead to loss of commitment and professional values both as an officer and as a nurse. Understanding the complicated dynamics and the many behaviors that contribute to the concept of the Navy Nurse, the role ultimately must be defined by each individual Nurse Corps officer.


Intrahepatic cholestasis of pregnancy after ovarian hyperstimulation syndrome with wild-type ABCB4 gene: a peculiar case and literature review.
Intrahepatic cholestasis of pregnancy (ICP) in the first trimester occurring after ovarian hyperstimulation syndrome (OHSS) is a rare condition and few cases are reported in the literature. Hyperestrogenism may explain this problem in genetically predisposed women. The objective of this article is to report one of these rare cases and offer an overview of the other published cases. We report a case of severe OHSS followed by ICP in the first trimester. The patient was admitted to the intensive care unit and was treated according to the guidelines for the management of OHSS. Moreover, the patient also received ursodeoxycholic acid for ICP, which brought to an improvement of her clinical conditions. The pregnancy continued without other complications until the 36th week of gestation, when the patient developed ICP in the third trimester and underwent cesarean section for increased bile acid levels and cardiotocographic (CTG) pathologic alterations. The newborn was a healthy baby weighing 2500 gr. We also reviewed other case reports published by other authors about this clinical condition. We present what is, to our knowledge, the first case of ICP developed in the first trimester of pregnancy after OHSS in which genetic polymorphisms of ABCB4 (MDR3) have been investigated. ICP in the first trimester might be induced by elevated serum estrogen levels after OHSS in genetically predisposed women. In these women, it might be useful to check for genetic polymorphisms to know if they have a predisposition for ICP recurrence in the third trimester of pregnancy.


Response of the L-arabinose forward mutation assay of Salmonella typhimurium to frameshift-type mutagens.
The present study was designed to evaluate the capacity of the L-arabinose resistance test of Salmonella typhimurium in the detection of frameshift-type mutagens. To this end the response of the Ara test was examined with respect to 15 chemicals which had been previously described as able to revert the Ames tester strain TA97. The mutagenicity of each compound was determined by the liquid test under experimental conditions which optimize the mutagenic response of the Ara test with the tester strain BA9. Strain TA97 was used simultaneously with BA9. The Ara forward-mutation assay efficiently detected the mutagenic activity of 14 out of the 15 chemicals assayed. PR toxin was the only compound which gave a weak dose response without doubling the spontaneous mutant level. In comparison with the Ara test, a total of 3 chemicals (HZ, PE and PR toxin) were not found to be mutagenic with strain TA97. In most cases (11/15) the mutagenic response of the Ara test was comparatively greater than that of strain TA97. Three chemicals (DEO, PRF and 9-AA) were detected with quite similar degrees of sensitivity by both mutation assays. ICR-191, which seems highly specific in reverting frameshift mutations with added cytosines in a run of cytosines, was the only chemical with a lower mutagenic activity in the Ara test than in strain TA97. The results enhance the interest of the L-arabinose forward-mutation assay as an alternative to the set of specific tester strains used by the histidine reverse-mutation assay in massive, general and primary screening for genotoxic agents.


A new series of steroidal antidysrhythmic agents.
With the aim of finding an antidysrhythmic agent suitable for intravenous or oral administration we have examined a range of steroids carrying basic substituents. The primary screen involved control of cardiac dysrhythmias induced by intravenous infusion of aconitine into pentobarbitone-anaesthetised artificially-respired rats. The best activity was found among a series of 11 alpha-alkylamino steroids and structure-activity studies included modification of the alkylamino group and variation of substituents in ring A and at the 17-position. Good oral and intravenous activity was found among 17 beta-methoxycarbonyl-5 alpha-androstanes and methyl 2 beta-ethoxy-3 alpha-hydroxy-11 alpha-(3-methylbutylamino)-5 alpha-androstane-17 beta-carboxylate hydrochloride (CCI 22277) was selected for more detailed pharmacological study.


Efficacy of doxorubicin-transferrin conjugate in apoptosis induction in human leukemia cells through reactive oxygen species generation.
Doxorubicin (DOX) is a small molecular cytotoxic agent that can be transferred efficiently to cancer cells by nanocarriers. This anthracycline antibiotic serves as an effective anti-neoplastic drug against both hematological and solid malignancies. Here, we set out to assess the capacity of a novel doxorubicin - transferrin conjugate (DOX-TRF) to provoke apoptosis in human normal and leukemia cells through free radicals produced via a redox cycle of doxorubicin (DOX) when released from its conjugate. After DOX-TRF exposure, we determined the time-course of apoptotic and necrotic events, the generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential, as well as alterations in cytochrome c levels and intracellular calcium concentrations in human leukemia-derived cell lines (CCRF-CEM, K562 and its doxorubicin-resistant derivative K562/DOX) and normal peripheral blood-derived mononuclear cells (PBMC). We found that DOX-TRF can induce apoptosis in all leukemia-derived cell lines tested, which was associated with morphological changes and decreases in mitochondrial membrane potential. In comparison to free DOX treated cells, we observed a time-dependency between a higher level of ROS generation and a higher drop in mitochondrial membrane potential, particularly in the doxorubicin-resistant cell line. In addition, we found that the apoptotic cell death induced by DOX-TRF was directly associated with a release of cytochrome c from the mitochondria and an increase in intracellular calcium level in all human leukemia-derived cell lines tested. Our data indicate that DOX-TRF is considerably more cytotoxic to human leukemia cells than free DOX. In addition, we show that DOX-TRF can effectively produce free radicals, which are directly involved in apoptosis induction.


REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial.
Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. ClinicalTrials.gov Identifier: NCT02638766.


Prevalence and host-parasite list of some nasal mites from birds (Acarina: Rhinonyssidae, Speleognathidae).
A survey of nasal mites, primarily from birds in Texas, was reported and comparisons with the other major studies were made. Of 103 host species examined, 40 were parasitized, and of 502 individual birds examined, 87 were parasitized (17% prevalence). It was shown that the prevalence of infection was significantly dependent on the bird taxa examined, which indicates that the evolution of the hosts has affected the nasal mites' ability to parasitize their avian hosts. It was also shown that the prevalence of rhinonyssid nasal mites in their hosts seems to differ significantly between geographic regions.


Population structure of some street rabies virus strains.
Street rabies virus strains can contain from one to three biological (clinical) variants as it has been estimated using random-bred white mice and dogs.


Kinetic behaviour of microsomal styrene monooxygenase and styrene epoxide hydratase in different animal species.
The apparent Km and Vmax values of styrene epoxide forming monooxygenase and styrene epoxide hydratase have been evaluated in the liver microsomes of male rats, mice, guinea-pigs and rabbits. Epoxide hydratase gave much higher and more uniform Km values than the monooxygenase in the species considered.


Bronchogenic cancer: It still exists.
Branchial cleft cysts rank among the most common differential diagnoses of cystic cervical masses. Rarely, classic cystic structures exhibit a squamous cell carcinoma differentiation that represents a bronchogenic carcinoma. The existence of bronchogenic carcinoma is controversial due to the lack of systematic immunohistologic workup. The present study aimed to identify the clinical and immunohistologic features of bronchogenic carcinoma to clearly distinguish this entity from other cystic cervical masses. Immunohistologic (epidermal growth factor receptor; cytokeratin 5, 6, 7, 13; and p16) and epidemiologic assessments were performed for branchial cleft cysts (n = 63), bronchogenic carcinomas (n = 5), cystic metastasized oropharyngeal carcinomas (n = 97), and carcinomas of unknown primary (n = 51). The study was conducted as a retrospective case series study with comparison. The patients with bronchogenic carcinomas differed significantly in age and in the number of involved lymph nodes compared with the cystic metastasized oropharyngeal carcinoma (and carcinoma of unknown primary) patients. Regular histologic wall structures were only observed in the bronchogenic carcinomas and branchial cleft cysts. Solitary cytokeratin-7 staining was only observed in the bronchogenic carcinomas, and all of the bronchogenic carcinomas were p16 negative. The existence of bronchogenic carcinoma seems to be plausible based on clinical findings. Cytokeratin-7 and p16 staining might be helpful in the diagnostic workflow. 4 Laryngoscope, 126:638-642, 2016.


Taste, smell and neuropsychological performance of individuals at familial risk for Alzheimer's disease.
The purpose of the study was to determine whether there are chemosensory and neuropsychological changes that predate the onset of Alzheimer's disease in individuals at enhanced risk of developing the condition. To study this question, a unique sample of individuals (n = 33) was studied who were genetically at-risk for AD by virtue of documented multigenerational evidence of the disease (so-called multiplex families). The performance of at-risk individuals was evaluated on various smell, taste, and neuropsychological measures at baseline and 18 months later. Their performance was compared to a control group (n = 32) that was matched in age, gender, education, and race. At baseline the at-risk group performed worse than the control group on the chemosensory measures of phenethyl alcohol smell detection, smell memory, and taste memory, and on a memory measure involving recall of narrative information (Logical Memory I from the Wechsler Memory Scale- Revised). Across both sessions, the at-risk group had lower smell memory scores than the control group. At-risk status was not significantly associated with APOE status. The results of this and other studies suggest that individuals who are genetically at risk for developing AD may perform more poorly on memory and smell measures compared to those not at risk. This effect may be separate from one known genetic risk factor of AD, APOE, and supports that multiple genes are likely responsible for the disease and its associated memory and other neurocognitive symptoms.


Dorsal and ventral cells of cleavage-stage Xenopus embryos show the same ability to induce notochord and somite formation.
Cells in the dorsal marginal zone of the amphibian embryo acquire the potential for mesoderm formation during the first few hours following fertilization. An examination of those early cell interactions may therefore provide insight on the mechanisms important for organization of axial structures. The formation of mesoderm (notochord, somites, and pronephros) was studied by combining blastomeres from the animal pole region of Xenopus embryos (32- to 512-cell stages) with blastomeres from different regions of the vegetal hemisphere. The frequency of notochord and somite development was similar in combinations made with dorsal or ventral blastomeres, or with both. Our results show that during early cleavage stages the ventral half of the vegetal hemisphere has the potential to organize axial structures, a property previously believed to be limited to the dorsal region.


Severe malformations of eelpout (Zoarces viviparus) fry are induced by maternal estrogenic exposure during early embryogenesis.
Pregnant eelpout were exposed via the water to known endocrine disrupting compounds (EDCs) to clarify if EDCs could be causing the increased eelpout fry malformation frequencies observed in coastal areas receiving high anthropogenic input. The presence of a teratogenic window for estrogen-induced malformations was also investigated by starting the exposure at different times during eelpout pregnancy. Both 17α-ethinylestradiol (EE2) (17.8 ng/L) and pyrene (0.5 μg/L) significantly increased fry malformation frequency whereas 4-t-octylphenol (4-t-OP) up to 14.3 μg/L did not. Vitellogenin was significantly induced by EE2 (5.7 and 17.8 ng/L) but not by 4-t-OP and pyrene. A critical period for estrogen-induced fry malformations was identified and closed between 14 and 22 days post fertilization (dpf). Exposure to 17β-estradiol (E2) between 0 and 14 dpf caused severe malformations and severity increased the closer exposure start was to fertilization, whereas malformations were absent by exposure starting later than 14 dpf. Data on ovarian fluid volume and larval length supported the suggested teratogenic window. Larval mortality also increased when exposure started right after fertilization.


Low temperature exposure inhibits proliferation and induces apoptosis of bovine subcutaneous preadipocytes via p38 MAPK/JNK activation.
Cold stress can cause changes in cell growth states. Cell proliferation and apoptosis are important physiological processes to maintain normal growth and development of cells and tissues. We sought to identify the impact of low temperature exposure on bovine subcutaneous preadipocyte proliferation and apoptosis. We first cultured preadipocytes at different low temperatures (35°C, 33°C, and 31°C) for 12 h, and then at 31°C for 24 and 48 h. The results showed that compared with the 37°C group, exposure to 31°C significantly reduced cell viability and number as well as inhibited cell cycle progression in preadipocytes. Moreover, low temperature also significantly upregulated the apoptosis rate of preadipocytes. After low temperature treatment, the mRNA levels of Cyclin E, CDK2 and B-cell lymphoma 2 (Bcl-2) were decreased in preadipocytes, whereas that of p53, p21 and Bcl-2 associated x protein (Bax) were increased in preadipocytes. Concurrently, low temperature increased the proteins levels of p53, Bax and Cleaved Caspase3, and reduced the protein level of Bcl-2 in preadipocytes. Furthermore, the elevated phosphorylation levels of p38 mitogen-activated protein kinases (p38 MAPK) and c-jun NH2-terminal kinase (JNK) were detected in cold-treated preadipocytes. The influence of low temperature exposure on preadipocyte proliferation and apoptosis were obviously weakened after blocking the p38 MAPK and JNK signaling pathways. In conclusion, low temperature exposure could inhibit proliferation and cell cycle progression and induce apoptosis through activation of p38 MAPK and JNK signaling pathways in bovine subcutaneous preadipocytes.


Pediatric primary Sjögren syndrome presenting with bilateral ranulas: A case report and systematic review of the literature.
Primary Sjögren syndrome is uncommon in children, and the standard clinical criteria used in diagnosis of adult Sjögren syndrome will miss many children with the disease. Floor of mouth ranulas have not been described in Sjögren syndrome. This study aims to describe a novel presentation of juvenile primary Sjögren syndrome, and to present a comprehensive systematic review of the literature regarding the presentation and diagnosis of Sjögren syndrome in children. Ovid MEDLINE. A MEDLINE literature search was performed using the following search terms: primary, Sjögren, disease, and children. Results were limited to human subjects and articles written in English between 1981 and 2014. Applicable articles were reviewed and qualitatively summarized. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRIMA). Initial MEDLINE search yielded 146 articles, 80 of which were excluded as not clinically pertaining to Sjögren syndrome. An additional 25 were excluded due to lack of pediatric-specific data. Systematic review of the literature revealed no reports of ranula in association with Sjögren syndrome. 6 papers were manually included from review of reference lists of included articles. Our review indicated that recurrent parotitis is the most commonly reported presenting symptom in children, followed by ocular and oral symptoms, musculoskeletal, and renal symptoms. Compared to adults, children are less likely to present with dry eyes and mouth. All studies were retrospective chart reviews, case series or case reports. This is the first report of a child presenting with floor of mouth ranulas in association with Sjögren syndrome. While recurrent parotitis is the most common presentation in children, other salivary gland and extra-salivary manifestations may be seen, and the clinician must maintain a high index of suspicion for underlying Sjögren syndrome.


[Radiation-induced sarcoma of the head and neck].
Radiation-induced sarcoma (RIS) of the head and neck is a late and rare complication of cancer treatment by radiation therapy. It occurs mostly within the limits of the irradiated area. Its incidence is increasing and related to an improved survival rate of treated patients. But it does not rule out the use of radiotherapy in the treatment of this cancer. We report two cases of sarcoma having appeared in the irradiated area, in patients treated by adjuvant radiotherapy for head and neck neoplasm. The prognosis for this sarcoma depends mainly on how early the diagnosis is made and the quality of surgical resection. Adjuvant chemotherapy or radiotherapy can be considered. Ongoing research on the expression of RIS genes could soon lead to new treatments.


rac-12-Selena-13,14-di-aza-tri-cyclo-[9.3.0.02,4]tetra-deca-11,13-diene.
The centrosymmetric crystal structure of the title compound, C11H16N2Se, is built up from alternating strands of (R,R)- and (S,S)-enanti-omers. These strands, which propagate along the c-axis direction, are composed of homochiral mol-ecules related to each other by twofold screw axes. The shape of the mol-ecule is an almost planar unit around the selena-diazole ring with a hexa-methyl-ene chain as an arched handle.


Health professional perceptions of opioid dependence among patients with pain.
The purpose of this study was to determine the percentage of patients perceived by health professionals to be opioid dependent among all patients presenting with pain and specifically among sickle cell patients with pain. Surveys were completed by all staff, residents, and nurses at an urban teaching hospital with an emergency department population consisting primarily of lower socioeconomic patients of African-American origin. The surveys requested a percentage estimate of all pain patients and sickle cell patients with pain presenting to this hospital who they perceived to be opioid dependent. The estimated percentage of opioid dependent patients presenting to the emergency department with pain was 4% for staff (P < .05, n = 14), 9% for residents (n = 31), and 7% for nurses (n = 41), and the estimates for sickle cell patients presenting with pain only were 8%, 17%, and 13% respectively (P < .05). All health professional groups surveyed estimated opioid dependence in patients with pain far in excess of that shown in previous studies. It is unknown whether pain medication are withheld inappropriately by physicians who perceived patients with pain to be opioid dependent, and that this deserved further study especially among sickle cell patients.


Triple arthrodesis.
A triple arthrodesis is a fusion of the talocalcaneal, calcaneal cuboid, and talonavicular joints. The purpose is to create a well-aligned, plantigrade, and stable foot for patients with deformity or progressive neurologic and arthritic conditions. This article is a comprehensive overview of the procedure. However effective, triple arthrodesis is a challenging procedure for even the most skilled surgeon.


HIV reservoirs: what, where and how to target them.
One of the main challenges in the fight against HIV infection is to develop strategies that are able to eliminate the persistent viral reservoir that harbours integrated, replication-competent provirus within host cellular DNA. This reservoir is resistant to antiretroviral therapy (ART) and to clearance by the immune system of the host; viruses originating from this reservoir lead to rebound viraemia once treatment is stopped, giving rise to new rounds of infection. Several studies have focused on elucidating the cells and tissues that harbour persistent virus, the true size of the reservoir and how best to target it, but these topics are the subject of ongoing debate. In this Viewpoint article, several experts in the field discuss the constitution of the viral reservoir, how best to measure it and the best ways to target this source of persistent infection.


Immunofluorescent evidence for exocytosis and internalization of secretory granule membrane in isolated chromaffin cells.
Cultured bovine adrenal medullary chromaffin cells were stimulated with the secretogogues Ba2+ or carbamyl choline plus Ca2+ in the presence of a monospecific rabbit IgG fraction directed against bovine dopamine beta-hydroxylase. The anti-dopamine beta-hydroxylase was labeled either with fluorescent protein A or with a fluorescent second antibody to rabbit IgG. Stimulation produced a patchy cell surface distribution of fluorescence. There was no noticeable internalization of the fluorescence for up to 2 h. In similar experiments using fluorescent monovalent fragments (Fab) of the same monospecificidopamine-beta-hydroxylase IgG, a more uniform distribution of the fluorescence was observed. A few min after a 5 min period of stimulation with Ba2+, the fluorescence appeared to be on or near the cell surface; however, after 20 min or more it was distributed throughout the cytoplasm except that the cell nuclei were not labeled. Thus, dopamine beta-hydroxylase which appeared on the cell surface as a consequence of exocytosis was internalized in the presence of monovalent antibody fragments, but not in the presence of the divalent (polyclonal) antibody, presumably because endocytosis of dopamine beta-hydroxylase was inhibited by crosslinking of the dopamine beta-hydroxylase molecules. The internalized anti-dopamine beta-hydroxylase Fab fragments were found to reappear on the cell surface during a second secretory response. It is concluded that the interior of the chromaffin granule membrane, for which dopamine beta-hydroxylase is a marker, becomes exposed on the surface of the cell during secretion and that the membrane is then retrieved back into the cell where it can be re-used in a further secretory cycle.


Pulmonary surfactant disaturated-phosphatidylcholine (DSPC) turnover and pool size in newborn infants with congenital diaphragmatic hernia (CDH).
In animal CDH models, surfactant deficiency contributes to the pathophysiology of the condition but information on human disease is very limited. The aim of our study was to investigate surfactant kinetics in CDH newborns. We studied surfactant disaturated-phosphatidylcholine (DSPC) half-life, turnover and apparent pool size by stable isotope methodology in CDH newborns with no ExtraCorporeal Membrane Oxygenation (ECMO) support (n = 13, birth weight (BW) 3.2 +/- 2.2 kg, gestational age (GA) 39 +/- 0.4 wks, postnatal age 43 +/- 11 h) and in 8 term infants with no lung disease (CONTROLS, BW 2.7 +/- 0 kg, GA 38 +/- 0.8 wks, postnatal age 96 +/- 26 h). We administered a trace dose of 13C-palmitic acid dipalmitoyl-phosphatidylcholine (DPPC) through the endotracheal (ET) tube and we measured DSPC kinetics by gas chromatography-mass spectrometry from DSPC13C-enrichment decay curves obtained from sequential tracheal aspirates. DSPC amount from tracheal aspirates (TA-DSPC) was measured by gas chromatography. In CDH infants DSPC half-life was shorter (24 +/- 4 and 53 +/- 11 h, p = 0.01), turnover faster (0.6 +/- 0.1 and 1.5 +/- 0.3 d-1 p = 0.01), apparent pool size smaller (34 +/- 6 and 57 +/- 7 mg/kg body weight, p = 0.02) and tracheal aspirates DSPC amount lower (2.4 +/- 0.4 and 4.6 +/- 0.5 mg/mL Epithelial Lining Fluid (ELF), p = 0.007) than in CONTROLS. In conclusion surfactant kinetics is grossly abnormal in mechanically ventilated CDH. Whether alterations of DSPC kinetics in CDH infants are caused by a primary surfactant deficiency or are secondary to oxygen therapy and ventilator support has still to be determined.


Langmuir-Blodgett films of 9-phenyl anthracene molecules incorporated into different matrices.
This communication reports the surface pressure (pi) versus area per molecule (A) isotherm characteristics of the mixed films of 9-phenyl anthracene (PA) in stearic acid (SA) and polymethyl methacrylate (PMMA) matrices, at the air-water interface. The mixed Langmuir films at the air-water interface have been observed to be easily transferred onto solid substrates to form uniform Langmuir-Blodgett films. By changing various parameters, namely molefraction, surface pressure of lifting and number of layers, the mixed Langmuir-Blodgett (LB) films of various types have been fabricated successfully and their spectroscopic characteristics have been reported. From the isotherm characteristics and the area per molecule versus molefraction plot, it is evident that the PA molecules are successfully incorporated into mixed Langmuir-Blodgett films. UV-vis absorption spectroscopic study of the mixed LB films at various molefractions of PA in two different matrices reveal that formation of I-type aggregate in PMMA matrix whereas both I- and H-type aggregates are playing their dominant role in SA matrix. Moreover, fluorescence spectroscopic study reveals reabsorption effect. Molecular movement persists in the freshly prepared LB films, as is evident from the time dependent changes in both UV-vis absorption and fluorescence spectra of the mixed LB films in both matrices. From our observation it is evident that about 200 h is required to get the LB films in a stable condition. Dimers and higher order n-mers are formed at a higher surface pressure of 30 mNm(-1).


Effect of 1,25-dihydroxycholecalciferol and 1,25-dihydroxycholecalciferol glycoside on 2,3-diphosphoglycerate levels of the rat erythrocyte.
The erythrocytes of rats treated with 1, 25-dihydroxycholecalciferol or 1, 25-dihydroxycholecalciferol glycoside showed decreased levels of 2, 3-diphosphoglycerate. The same result has been obtained in vitro, indicating a direct effect of the sterol on the red cell. The glycoside is less active than the free sterol in vivo and more active in vitro. The decreased levels of diphosphoglycerate induced tissue hypoxia as shown by a higher plasma lactate/pyruvate ratio and a three fold increase in plasma erythropoietin concentration.


Acquired Methemoglobinemia in an Infant: Consequence of Prolonged Application of Eutectic Mixture of Local Anesthetics (EMLA) Cream for Spontaneous Abscess Drainage.
Topical anesthetics are commonly used in emergency departments. One of the side effects can be methemoglobinemia if not appropriately used. We present a case of a six-week-old baby who developed methemoglobinemia with levels of 30.6% after prolonged (15 hours) application of Eutectic Mixture of Local Anesthetics (EMLA) cream. The cream was applied for spontaneous drainage of a perianal abscess. The patient received IV methylene blue with a resolution of methemoglobinemia.


Patients' willingness and ability to participate actively in the reduction of clinical errors: a systematic literature review.
This systematic review identifies the factors that both support and deter patients from being willing and able to participate actively in reducing clinical errors. Specifically, we add to our understanding of the safety culture in healthcare by engaging with the call for more focus on the relational and subjective factors which enable patients' participation (Iedema, Jorm, & Lum, 2009; Ovretveit, 2009). A systematic search of six databases, ten journals and seven healthcare organisations' web sites resulted in the identification of 2714 studies of which 68 were included in the review. These studies investigated initiatives involving patients in safety or studies of patients' perspectives of being actively involved in the safety of their care. The factors explored varied considerably depending on the scope, setting and context of the study. Using thematic analysis we synthesized the data to build an explanation of why, when and how patients are likely to engage actively in helping to reduce clinical errors. The findings show that the main factors for engaging patients in their own safety can be summarised in four categories: illness; individual cognitive characteristics; the clinician-patient relationship; and organisational factors. We conclude that illness and patients' perceptions of their role and status as subordinate to that of clinicians are the most important barriers to their involvement in error reduction. In sum, patients' fear of being labelled "difficult" and a consequent desire for clinicians' approbation may cause them to assume a passive role as a means of actively protecting their personal safety.


Nicotine dependence: intervention strategies for the physician.
Nicotine dependence is the most common serious medical problem in primary care. Its complications are common and far reaching, both for the person addicted to tobacco and for other people in the environment. Nicotine dependence is highly treatable.


The effects of sarin-like and soman-like organophosphorus agents on MAPK and JNK in rat brains.
One sarin-like and one soman-like organophosphorus agent [bis(isopropyl methyl)phosphonate, BIMP and bis(pinacolyl methyl)phosphonate, BPMP] were injected intravenously (iv) in rats. An increase in the tyrosine phosphorylation of several proteins in the cytosol fraction of the brain was observed. Activation of c-Jun N-terminal kinase (JNK) and slight activation of mitogen-activated protein kinase (MAPK) in the cytosol were also observed. The activation of these enzymes may be related to the high toxicity of these nerve agents.


CD4-CD8 lineage commitment: an inside view.
The mechanism of CD4-CD8 lineage commitment, which ensures the correlation between T cell receptor specificity and adoption of the T killer or T helper phenotype, has long been the subject of intense debate. Various approaches are slowly elucidating the underlying molecular pathways. Analysis of the function of T cell receptor signaling (the 'top-down' approach) supports the view that differences in signal strength and/or duration 'instruct' alternative commitment. Analysis of the transcriptional regulation of the genes encoding CD4 and CD8 (the 'bottom-up' approach) has identified critical cis-acting elements and their interacting factors. Finally, identification of the transcription factor Th-POK as a central component of the CD4 lineage-determining pathway has provided a new starting point from which to unravel this intriguing process 'from the inside out'.


WKGM: weighted k-space generative model for parallel imaging reconstruction.
Deep learning based parallel imaging (PI) has made great progress in recent years to accelerate MRI. Nevertheless, it still has some limitations: for example, the robustness and flexibility of existing methods are greatly deficient. In this work, we propose a method to explore the k-space domain learning via robust generative modeling for flexible calibrationless PI reconstruction, coined the weighted k-space generative model (WKGM). Specifically, WKGM is a generalized k-space domain model, where the k-space weighting technology and high-dimensional space augmentation design are efficiently incorporated for score-based generative model training, resulting in good and robust reconstructions. In addition, WKGM is flexible and thus can be synergistically combined with various traditional k-space PI models, which can make full use of the correlation between multi-coil data and realize calibrationless PI. Even though our model was trained on only 500 images, experimental results with varying sampling patterns and acceleration factors demonstrate that WKGM can attain state-of-the-art reconstruction results with the well learned k-space generative prior.


Estimation of blood-based biomarkers of glial activation related to neuroinflammation.
Neuroinflammation is a well-known feature of Alzheimer's disease (AD), and a blood-based test for estimating the levels of neuroinflammation would be expected. In this study, we examined and validated a model using blood-based biomarkers to predict the level of glial activation due to neuroinflammation, as estimated by 11C-DPA-713 positron emission tomography (PET) imaging. We included 15 patients with AD and 10 cognitively normal (CN) subjects. Stepwise backward deletion multiple regression analysis was used to determine the predictors of the TSPO-binding potential (BPND) estimated by PET imaging. The independent variables were age, sex, diagnosis, apolipoprotein E4 positivity, body mass index and the serum concentration of blood-based biomarkers, including monocyte chemotactic protein 1 (MCP-1), fractalkine, chitinase 3-like protein-1 (CHI3L1), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and clusterin. Sex, diagnosis, and serum concentrations of MCP1 and sTREM2 were determined as predictors of TSPO-BPND in the Braak1-3 area. The serum concentrations of MCP1 and sTREM2 correlated positively with TSPO-BPND. In a leave one out (LOO) cross-validation (CV) analysis, the model gave a LOO CV R2 of 0.424, which indicated that this model can account for approximately 42.4% of the variance of brain TSPO-BPND. We found that the model including serum MCP-1 and sTREM2 concentration and covariates of sex and diagnosis was the best for predicting brain TSPO-BPND. The detection of neuroinflammation in AD patients by blood-based biomarkers should be a sensitive and useful tool for making an early diagnosis and monitoring disease progression and treatment effectiveness.


Logic models of pathway biology.
Living systems seamlessly perform complex information processing and control tasks using combinatorially complex sets of biochemical reactions. Drugs that therapeutically modulate the biological processes of disease are developed using single protein target strategies, often with limited knowledge of the complex underlying role of the targets. Approaches that attempt to consider the combinatorial complexity from the outset might help identify any causal relationships that could lead to undesirable or adverse side effects earlier in the development pipeline. Such approaches, in particular logic methodologies, might also aid pathway selection and multiple target strategies during the drug discovery phase. Here, we describe the use of logic as a tractable and informative approach to modelling biological pathways that can allow us to improve our understanding of the dependencies in complex biological processes.


Glucose-insulin interactions on exocrine secretion from the perfused rat pancreas.
The effects of glucose and insulin on pancreatic enzyme release have been investigated using the isolated perfused rat pancreas. Basal and caerulein-stimulated secretion was significantly less in the presence of 15 mM glucose than with 5 mM glucose, except at a supramaximal concentration of caerulein (10(-9) M) where secretion was similar in both groups. Addition of exogenous insulin also caused a reduction in enzyme secretion, but the time of onset of the inhibitory action was delayed compared to that observed with glucose. Furthermore, it was found that the effects of 15 mM glucose and exogenous insulin were not additive at the concentration used in these experiments, and that the inhibitory action of insulin was glucose-dependent. Such glucose-insulin interactions must play an important role in the modulation of pancreatic enzyme secretion.


Stressors, self-reported overall health, potential protective factors and the workplace well-being of nurses during the COVID-19 pandemic in Switzerland: a longitudinal mixed-methods study protocol.
The COVID-19 pandemic was making a huge impact on Europe's healthcare systems in the spring of 2020, and most predictive models concurred that pandemic waves were in the offing. Most studies adopted a pathogenic approach to the subject; few used a salutogenic approach. These showed, however, that nurses can retain their health despite a pandemic by mobilising generalised resistance resources. Our study aims to understand how nurses working in Switzerland's hospitals protected their health and workplace well-being during the COVID-19 pandemic by investigating the moderating effects of the health resources they mobilised against the stressors inherent to the situation. The study aims to explore and describe the stressors and the resources nurses used to remain healthy during the COVID-19 pandemic. We will use a concurrent mixed-methods panel design with qualitative analyses ancillary to quantitative analyses. Quantitative data will be collected using electronic questionnaires at four time points over 2 years. Qualitative data will be collected using focus groups. Nurses from Switzerland's two main linguistic regions who had direct, indirect or no contact with patients with COVID-19 will be invited to participate. The a priori sample size will be at least 3631 participants at T0 and 1852 at T4. Longitudinal structural equation modelling and knowledge mapping will be used to analyse quantitative and qualitative data, respectively. The results derived from the two data types will then be compared and discussed using a side-by-side approach to determine whether they agree or disagree and how they complement each other to achieve our aims. Nurses will receive an electronic informed consent form. The data collected will be stored on a secure server at the authors' institution. This research project was approved by the Human Research Ethics Committee of the Canton of Vaud (2020-02845).


Hidrocolonic ultrasonography in the detection of tumoral processes in the inferior gastrointestinal tract.
To determine the value of hidrocolonic ultrasound in the detection of proliferative lesions in the colon and to compare it with other techniques of already proven value. We performed a prospective blinded trial including 155 patients (82 males and 73 females) with ages ranging from 33 to 94 years (average of 58) and clinical and analytical criteria suggesting the existence of colonic proliferative lesions. Patients with rectal mass or those with deficient bowel preparation were excluded. Ultrasound findings were compared to those obtained by colonoscopy (133 cases) and by Barium RX studies (22 cases) and all diagnoses were always confirmed by histologic exams. 155 patients were studied. 50 of them had cancer and 46 of these 50 were diagnosed by Hidrocolonic Ultrasound (92%); 19 had polyps > 7 mm. and 15 of these (78.9%) were diagnosed by Hidrocolonic Ultrasound. Hidrocolonic Ultrasound failed to detect all the polyps < 7 mm. The overall sensitivity, specificity, positive predictive value and negative predictive value for identifying colon carcinoma were 92%, 98%, 95.8% and 96.2% respectively and for polyps > 7 mm were 78.9%, 100%, 100% and 97.1%, respectively. The mean time for examination was 14 minutes. Tolerance was good in 114 patients (73.5%), 29 showed a slight discomfort (18.7%) and 12 (7.7%) showed a great discomfort. There were no complications. Hidrocolonic ultrasound is an innocuous, fast, well tolerated technique for detecting colonic proliferative lesions > 7 mm H.U. can be considered as a useful complementary technique to other more expensive and invasive ones, such as barium RX studies and Colonoscopy.


[Effectiveness of the eradication of Helicobacter pylori by treatment with omeprazol, amoxicillin, and clarithromycin according to dosage and administration schedule].
There are many reports that evaluate the efficacy of the combination of omeprazole, amoxicillin and clarithromycin in the eradication of Helicobacter pylori, but data about effectivity in clinical practice are sparse. The goal of our study is to evaluate the effectivity in the clinical setting of this combination with diverse durations and doses. This is a retrospective analysis of 187 patients (128 male and 59 female), with an endoscopic diagnosis of duodenal ulcer (156), gastric ulcer (25) and both (6) with Helicobacter pylori infection as defined by both: a positive ureasa test and histology. After diagnosis the patient were treated with one of three combinations: a) omeprazole: 20 mg/12 h + amoxicillin: 1 g/12 h + clarithromycin: 500 mg/12 h, during 6 days (n = 60); b) omeprazole: 20 mg/12 h + amoxicillin: 1 g/12 h + clarithromycin: 500 mg/12 h, during 7 days (n = 74), and c) omeprazole: 20 mg/12 h + amoxicillin: 1 g/8 h + clarithromycin: 500 mg/8 h, during 7 days (n = 53). After the 6 or 7 day treatment period the patients did not receive any further treatment until a follow-up control unit. Eradication was evaluated with one of two tests: endoscopy (with ureasa test and at least 4 histologic samples) (n = 90) or urea breath test according to european protocol (n = 97). No patient dropped out because of side effects and compliance was above 80% in all cases. The global eradication rate was 87.2% (CI 95%: 82.4-92%). According to treatment the rate were respectively 80% (CI 95%: 67.7-89.2%) with scheme A; 89.2% (CI 95%: 79.8-95.2%) with scheme B, and 92.5% (CI 95%: 81.8-97.9%) with scheme C, with no statistically significant differences among groups. Difference between schemes and C, however, was almost reached (p = 0.053). The combination of omeprazole, amoxicillin and clarithromycin at standard doses (scheme B) is effective in clinical practice. Higher dose of amoxicillin and clarithromycin does not improve the results, and shorter duration of therapy associated with lower, although not significant rate of eradication.


In-gel digestion coupled with mass spectrometry (GeLC-MS/MS)-based salivary proteomic profiling of canine oral tumors.
Various types of oral tumors, either benign or malignant, are commonly found in dogs. Since saliva directly contacts the tumors and saliva collection is non-invasive, easily accessible and cost effective, salivary biomarkers are practical to be used for the diagnosis and/or prognosis of these diseases. However, there is limited knowledge of protein expression in saliva for canine oral tumors. The present study aimed to investigate novel biomarkers from the salivary proteome of dogs with early- and late-stage oral melanoma (EOM and LOM, respectively), oral squamous cell carcinoma (OSCC), benign oral tumors (BN), and periodontitis and healthy controls (CP), using an in-gel digestion coupled with mass spectrometry (GeLC-MS/MS). The relationships between protein candidates and chemotherapy drugs were explored and the expression of potential biomarkers in saliva and tissues was verified by western blot analysis. For saliva samples, increased expression of protein tyrosine phosphatase non-receptor type 5 (PTPN5) was shown in all tumor groups compared with the CP group. Marked expression of PTPN5 was also observed in LOM and OSCC compared with that in BN and EOM. In addition, tumor protein p53 (p53), which appeared in the PTPN5-drug interactions, was exhibited to be expressed in all tumor groups compared with that in the CP group. For tissue samples, increased expression of p53 was shown in LOM compared with the control group. PTPN5 and p53 were proposed to be potential salivary biomarkers of canine oral tumors.


Effects of sample preparation on stable isotope ratios of carbon and nitrogen in marine invertebrates: implications for food web studies using stable isotopes.
Trophic ecology has benefitted from the use of stable isotopes for the last three decades. However, during the last 10 years, there has been a growing awareness of the isotopic biases associated with some pre-analytical procedures that can seriously hamper the interpretation of food webs. We have assessed the extent of such biases by: (1) reviewing the literature on the topic, and (2) compiling C and N isotopic values of marine invertebrates reported in the literature with the associated sample preparation protocols. The factors considered were: acid-washing, distilled water rinsing (DWR), sample type (whole individuals or pieces of soft tissues), lipid content, and gut contents. Two-level ANOVA revealed overall large and highly significant effects of acidification for both delta(13)C values (up to 0.9 per thousand decrease) and delta(15) N values (up to 2.1 per thousand decrease in whole individual samples, and up to 1.1 per thousand increase in tissue samples). DWR showed a weak overall effect with delta(13)C increments of 0.6 per thousand (for the entire data set) or decrements of 0.7 per thousand in delta(15) N values (for tissue samples). Gut contents showed no overall significant effect, whereas lipid extraction resulted in the greatest biases in both isotopic signatures (delta(13)C, up to -2.0 per thousand in whole individuals; delta(15)N, up to +4.3 per thousand in tissue samples). The study analyzed separately the effects of the various factors in different taxonomic groups and revealed a very high diversity in the extent and direction of the effects. Maxillopoda, Gastropoda, and Polychaeta were the classes that showed the largest isotopic shifts associated with sample preparation. Guidelines for the standardization of sample preparation protocols for isotopic analysis are proposed both for large and small marine invertebrates. Broadly, these guidelines recommend: (1) avoiding both acid washing and DWR, and (2) performing lipid extraction and gut evacuation in most cases.


Comprehensive analysis of shared genetic loci between hippocampal volume and schizophrenia.
Schizophrenia and hippocampal volume exhibit a genetic correlation, but the underlying genetic mechanisms remain unclear. Here, we investigated the shared genetic variants in schizophrenia and hippocampal volume using the largest genome-wide association studies (GWASs) data. We identified three genetic loci associated with both schizophrenia and hippocampal volume. Functional annotation analysis suggested that shared genetic variants play a major role via the regulatory effect on gene expression. Expression pattern analyses showed that candidate genes have a spatiotemporal and cell-specific expression pattern across human brain development. These findings provided deeper insights into the genetic mechanisms underlying hippocampus and schizophrenia risk.


Preliminary evaluation of the Moyo chart-a novel, low-cost, weight-for-height slide chart for the improved assessment of nutritional status in children.
The Moyo chart is a novel weight-for-height slide chart. We explore the hypothesis that it improves accuracy, speed and ease of nutritional assessment compared with traditional lookup tables. In a crossover randomised controlled trial, 61 medical students in Ethiopia diagnosed hypothetical cases of severe acute malnutrition, moderate acute malnutrition and normal nutrition in children. Mean accuracy of nutritional status diagnosis was 83.2% using the Moyo chart and 76.1% using lookup tables (P = 0.011). There was a trend towards a reduced time per correct diagnosis using the Moyo chart and 78% of participants preferred using it. These preliminary results suggest that the Moyo chart may aid frontline health workers classifying child nutritional status.


Tracking the speech signal--time-locked MEG signals during perception of ultra-fast and moderately fast speech in blind and in sighted listeners.
Blind people can learn to understand speech at ultra-high syllable rates (ca. 20 syllables/s), a capability associated with hemodynamic activation of the central-visual system. To further elucidate the neural mechanisms underlying this skill, magnetoencephalographic (MEG) measurements during listening to sentence utterances were cross-correlated with time courses derived from the speech signal (envelope, syllable onsets and pitch periodicity) to capture phase-locked MEG components (14 blind, 12 sighted subjects; speech rate=8 or 16 syllables/s, pre-defined source regions: auditory and visual cortex, inferior frontal gyrus). Blind individuals showed stronger phase locking in auditory cortex than sighted controls, and right-hemisphere visual cortex activity correlated with syllable onsets in case of ultra-fast speech. Furthermore, inferior-frontal MEG components time-locked to pitch periodicity displayed opposite lateralization effects in sighted (towards right hemisphere) and blind subjects (left). Thus, ultra-fast speech comprehension in blind individuals appears associated with changes in early signal-related processing mechanisms both within and outside the central-auditory terrain.