A mitochondrial marker for red algal intraspecific relationships.
Intraspecific studies of red algae have relied on nuclear or plastid markers rather than mitochondrial data to address questions of systematics, biogeography or population genetics. In this study, primers were developed that spanned the noncoding intergenic region between the mitochondrial cytochrome oxidase subunit 2 and cytochrome oxidase subunit 3 genes. These primers were demonstrated to be successful on a variety of red algae in different orders: Gracilariales, Bonnemaisoniales and Ceramiales (families: Delesseriaceae, Ceramiaceae and Rhodomelaceae). Amplification products were between 450 and 320 bp in length, with variation in length shown among geographically distant isolates within a species. The region was variable within a single species, as shown for Bostrychia moritziana and B. radicans, and within populations of Caloglossa leprieurii. In the latter species, four mitochondrial haplotypes were observed in isolates from a single locality in Woolooware Bay, New South Wales, Australia. Analysis of hybrids between different mitochondrial haplotypes of B. moritziana revealed that the mitochondria are maternally inherited in this species. This is the first report of a mitochondrial marker that is variable within red algal populations and may lead to a better understanding of the population ecology of these important marine organisms.


Hepatic stellate cells limit hepatocellular carcinoma progression through the orphan receptor endosialin.
Hepatocellular carcinoma (HCC) is among the most common and deadliest cancers worldwide. A major contributor to HCC progression is the cross talk between tumor cells and the surrounding stroma including activated hepatic stellate cells (HSC). Activation of HSC during liver damage leads to upregulation of the orphan receptor endosialin (CD248), which contributes to regulating the balance of liver regeneration and fibrosis. Based on the established role of endosialin in regulating HSC/hepatocyte cross talk, we hypothesized that HSC-expressed endosialin might similarly affect cell proliferation during hepatocarcinogenesis. Indeed, the histological analysis of human HCC samples revealed an inverse correlation between tumor cell proliferation and stromal endosialin expression. Correspondingly, global genetic inactivation of endosialin resulted in accelerated tumor growth in an inducible mouse HCC model. A candidate-based screen of tumor lysates and differential protein arrays of cultured HSC identified several established hepatotropic cytokines, including IGF2, RBP4, DKK1, and CCL5 as being negatively regulated by endosialin. Taken together, the experiments identify endosialin-expressing HSC as a negative regulator of HCC progression.


Genetic determinants of right-ventricular remodeling after tetralogy of Fallot repair.
Hypoxia-inducible factor (HIF1A) regulates the myocardial response to hypoxia and hemodynamic load. We investigated the association of HIF1A variants with right-ventricular (RV) remodeling after tetralogy of Fallot (TOF) repair. Children with TOF were genotyped for three single-nucleotide polymorphisms in HIF1A. Genotypes were analyzed for association with RV myocardial protein expression and fibrosis at complete repair (n = 42) and RV dilation, fractional area change, and freedom from pulmonary valve/conduit replacement on follow-up. In 180 TOF patients, mean age at repair was 1.0 ± 0.8 y with follow-up at 9.0 ± 3.5 y; 82% had moderate to severe pulmonary insufficiency. Freedom from RV reinterventions at 5, 10, and 15 y was 92, 84, and 67%, respectively. Patients with more functioning HIF1A alleles had higher transforming growth factor β1 expression and more fibrosis at initial repair as compared with controls (P < 0.05). During follow-up, patients with more functioning HIF1A alleles showed less RV dilation, better preservation of RV function, and greater freedom from RV reinterventions (P < 0.05). This was confirmed in a replication cohort of 69 patients. In children who have had TOF repair, a lower number of functioning HIF1A alleles was associated with RV dilation and dysfunction, suggesting that hypoxia adaptation in unrepaired TOF may influence RV phenotype after repair.


Wideband Tympanometry in Meniere's Disease.
The aim of our study was to obtain wideband tympanometry (WBT) findings in Meniere's disease (MD). It also aimed to evaluate whether the data obtained have diagnostic significance. 21 patients who were followed-up for unilateral Meniere's Disease were evaluated. The ears with Meniere disease were grouped as the MD group and the opposite ears were grouped as the control group. WBT results were recorded as resonance frequency (RF) and frequency-specific absorbance values at 10 different frequencies in the 0.25-8.0 kHz range. Statistical analysis was performed with t test and receiver-operating characteristic analysis. Considering the WBT results, RF was significantly lower in the MD group compared to the control group (p < 0.001). Frequency-specific absorbance values at 0.25, 0.5, 0.75 and 1 kHz were significantly lower in the MD group compared to the control group (p < 0.05). No significant difference was found at 1.5 kHz and above (p > 0.05). For the MD, the RF below 598 Hz was 85.7% sensitive and 76.2% specific, the absorbance at 0.25 kHz below 8% was 66.7% sensitive and 61.9% specific, the absorbance below 17% at 0.5 kHz was 71.4% sensitive and 62.1% specific, the absorbance below 36% at 0.75 kHz was 81% sensitive and 57.8% specific, and the absorbance below 46% at 1 kHz was 71.5% sensitive and 66.7% specific. When MD was compared with intact ears, it was observed that RF was lower, and absorbance decreased in low frequencies. These data is statistically significant, but the sensitivity level is not enough for diagnostic use. Therefore, it is considered as an complementary test for the diagnosis.


Dominance and queen succession in captive colonies of the eusocial naked mole-rat, Heterocephalus glaber.
Naked mole-rat colonies exhibit a high reproductive skew, breeding being typically restricted to one female (the 'queen') and one to three males. Other colony members are reproductively suppressed, although this suppression can be reversed following the removal or death of the queen. We examined dominance and queen succession within captive colonies to investigate the relationship between urinary testosterone and cortisol, dominance rank and reproductive status; and to determine if behavioural and/or physiological parameters can be used as predictors of queen succession. Social structure was characterized by a linear dominance hierarchy before and after queen removal. Prior to queen removal, dominance rank was negatively correlated with body weight and urinary testosterone and cortisol titres in males and females. Queen removal results in social instability and aggression between high ranking individuals. Dominance rank appears to be a good predictor of reproductive status: queens are the highest ranking colony females and are succeeded by the next highest ranking females. The intense dominance-related aggression that accompanies reproductive succession in naked mole-rats provides empirical support for optimal skew theory.


[Morphological characteristics of hyperplastic and adenomatous stomach polyps].
A morphological study of biopsy samples of gastric polyps from 224 patients was carried out. Four stages in gastric polyp morphogenesis were distinguished: foveolar hyperplasia, hyperplastic polyp, "two-floor" adenoma and adenoma. The correlation was established between the degree of Helicobacter pylori infection in the polyp mucous membrane on the one hand, and epithelial and stromal reactions (immuno-inflammatory reaction of stroma, chronic inflammation, formation of Russel bodies, cystes and chronic erosions) on the other. Greater content of stromal collagens, type IV collagen in case of gastric hyperplastic lesions was observed. Appearance and progression of gastric adenomatous growth in hyperplastic polyp correlates with an increase of type III collagen content, decrease of types I, IV, V collagens and fibronectin.


Gastric Duplication Cyst in a man Presenting with Elevated Liver Enzymes and Icterus.
Gastric duplication cysts comprise 2-7% of gastrointestinal duplications, rare congenital malformations that can be present at almost any part of the alimentary tract. They mostly present with gastrointestinal obstruction symptoms, ulceration, and painless hemorrhage. Symptoms include nausea, vomiting, and fullness sensation. Gastric duplications are mostly cystic in shape. Herein, we present a 58-year-old man with a gastric duplication cyst, 70×30×35 mm in size, with the initial presentation of abdominal pain, icterus, and elevated liver enzymes. The patient provided informed consent for this report.


Parent and professional perspectives on behavioral inflexibility in autism spectrum disorders: A qualitative study.
Restricted and repetitive behaviors are a core feature of autism spectrum disorder; however, research on the functional impact of these behaviors on the quality of life for individuals with autism spectrum disorder and their families remains scarce. We conducted focus groups with parents of children with autism spectrum disorder and clinicians in order to better characterize the functional impact of behavioral inflexibility, which represents one potential dimensional construct that could account for the breadth of behaviors comprising the restricted and repetitive behavior domain. Transcripts of the focus groups were analyzed using qualitative analysis coding methods to determine parent and clinician beliefs on a range of issues related to behavioral inflexibility including overall impact, types of child behaviors, and strategies for managing behavioral inflexibility. Thematic analysis revealed that parents and clinicians view behavioral inflexibility as an important behavior that impacts multiple areas of functioning, relates to other restricted and repetitive behaviors as well as social communication behaviors, and warrants targeted treatment. Notably, many parents and clinicians emphasized some positive consequences of behavioral inflexibility as well. These findings add crucial insights into the functional impact of behavioral inflexibility and restricted and repetitive behaviors as a whole and suggest that behavioral inflexibility represents an important avenue for future research.


Molecularly imprinted polymers and capillary electrophoresis for sensing phytoestrogens in milk.
Dairy cow feed contains, among other ingredients, soybeans, legumes, and clover, plants that are rich in phytoestrogens. Several publications have reported a positive influence of phytoestrogens on human health; however, several unfavorable effects have also been reported. In this work, a simple, selective, and eco-friendly method of phytoestrogen isolation based on the technique of noncovalent molecular imprinting was developed. Genistein was used as a template, and dopamine was chosen as a functional monomer. A layer of molecularly imprinted polymers was created in a microtitration well plate. The binding capability and selective properties of obtained molecularly imprinted polymers were investigated. The imprinted polymers exhibited higher binding affinity toward chosen phytoestrogen than did the nonimprinted polymers. A selectivity factor of 6.94 was calculated, confirming satisfactory selectivity of the polymeric layer. The applicability of the proposed sensing method was tested by isolation of genistein from a real sample of bovine milk and combined with micellar electrokinetic capillary chromatography with UV-visible detection.


Cations Control Lipid Bilayer Memcapacitance Associated with Long-Term Potentiation.
Phospholipid bilayers can be described as capacitors whose capacitance per unit area (specific capacitance, Cm) is determined by their thickness and dielectric constant─independent of applied voltage. It is also widely assumed that the Cm of membranes can be treated as a "biological constant". Recently, using droplet interface bilayers (DIBs), it was shown that zwitterionic phosphatidylcholine (PC) lipid bilayers can act as voltage-dependent, nonlinear memory capacitors, or memcapacitors. When exposed to an electrical "training" stimulation protocol, capacitive energy storage in lipid membranes was enhanced in the form of long-term potentiation (LTP), which enables biological learning and long-term memory. LTP was the result of membrane restructuring and the progressive asymmetric distribution of ions across the lipid bilayer during training, which is analogous, for example, to exponential capacitive energy harvesting from self-powered nanogenerators. Here, we describe how LTP could be produced from a membrane that is continuously pumped into a nonequilibrium steady state, altering its dielectric properties. During this time, the membrane undergoes static and dynamic changes that are fed back to the system's potential energy, ultimately resulting in a membrane whose modified molecular structure supports long-term memory storage and LTP. We also show that LTP is very sensitive to different salts (KCl, NaCl, LiCl, and TmCl3), with LiCl and TmCl3 having the most profound effect in depressing LTP, relative to KCl. This effect is related to how the different cations interact with the bilayer zwitterionic PC lipid headgroups primarily through electric-field-induced changes to the statistically averaged orientations of water dipoles at the bilayer headgroup interface.


Carrier detection in ornithine transcarbamylase deficiency.
We have studied six known heterozygotes for ornithine transcarbamylase (McKusick 31125; OTC) deficiency. All had abnormal results when tested by measurement of urine orotic acid after protein loading. Duodenal mucosa OTC assay detected fewer of the known heterozygotes but was a useful supplementary test. Urine orotic acid excretion after protein loading is influenced by age and results from women being tested must be compared with those from controls of appropriate age.


The resting electrophysiological profile in adults with ADHD and comorbid dysfunctional anger: a pilot study.
Although dysfunctional anger is not a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision [DSM-IV-TR]) diagnosis, it sometimes presents as a primary clinical complaint and as a comorbid feature in a subset of adults with attention-deficit/hyperactivity disorder (ADHD). No known studies have examined electroencephalographic (EEG) profiles in adults with comorbid dysfunctional anger and ADHD (ADHD + anger). Resting EEG was recorded in 14 ADHD + anger adults (11 males) and 14 controls. Relative power was assessed at standard frequencies, as was frontal absolute α power asymmetry. A modest increase was noted in β1 power in the ADHD + anger group. Unexpectedly, relatively decreased left (or increased right) frontocortical activity (α assessed) was noted in the ADHD + anger group, which was also characterized by a more diffuse θ/β ratio scalp distribution. Nonmedicated ADHD + anger adults exhibited modest resting cortical hyperarousal, consistent with the findings in a subset of children with ADHD characterized by anger-associated problems. The unexpected frontal α asymmetry may reflect enhanced activity of frontal inhibitory mechanisms.


Interposed abdominal compression CPR: a comprehensive evidence based review.
Interposed abdominal compression (IAC)-CPR includes all steps of standard external CPR with the addition of manual mid-abdominal compressions in counterpoint to the rhythm of chest compressions. IAC-CPR can increase blood flow during CPR about 2-fold compared with standard CPR without IAC, as shown by six of six studies in computer models and 19 of 20 studies in various animal models. The addition of IAC has clinical benefit in humans, as indicated in 10 of 12 small to medium sized clinical studies. The technique increases the frequency of immediate return of spontaneous circulation for in-hospital resuscitations from roughly 25 to 50%. Improved survival to discharge is also likely on the basis of two small in-hospital trials. Possible harm from abdominal compression is minimal on the basis of 426 humans, 151 dogs and 14 pigs that received IAC in published reports. The complexity of performing IAC is similar to that of opening the airway and is less than that of other basic life support maneuvers. The aggregate evidence suggests that IAC-CPR is a safe and effective means to increase organ perfusion and survival, when performed by professionally trained responders in a hospital and when initiated early in the resuscitation protocol. Cost and logistical considerations discourage use of IAC-CPR outside of hospitals.


Nested positive feedback loops in the maintenance of major depression: An integration and extension of previous models.
Several theories of Major Depressive Disorder (MDD) have previously been proposed, focusing largely on either a psychological (i.e., cognitive/affective), biological, or neural/computational level of description. These theories appeal to somewhat distinct bodies of work that have each highlighted separate factors as being of considerable potential importance to the maintenance of MDD. Such factors include a range of cognitive/attentional information-processing biases, a range of structural and functional brain abnormalities, and also dysregulation within the autonomic, endocrine, and immune systems. However, to date there have been limited efforts to integrate these complimentary perspectives into a single multi-level framework. Here we review previous work in each of these MDD research domains and illustrate how they can be synthesized into a more comprehensive model of how a depressive episode is maintained. In particular, we emphasize how plausible (but insufficiently studied) interactions between the various MDD-related factors listed above can lead to a series of nested positive feedback loops, which are each capable of maintaining an individual in a depressive episode. We also describe how these different feedback loops could be active to different degrees in different individual cases, potentially accounting for heterogeneity in both depressive symptoms and treatment response. We conclude by discussing how this integrative model might extend understanding of current treatment mechanisms, and also potentially guide the search for markers to inform treatment selection in individual cases.


[Causes of death of persons exposed to health hazards in the area of the Chernobyl Accident].
Causes of death were analysed for two groups of subjects exposed to radiation in 1986 because of the Chernobyl accident. 27 victims were exposed to external gamma-radiation (4.3-13.7 Gy) in the moment of or few hours after the accident. Most of these subjects had radiation sickness of different severity in combination with local radiation lesions. 2 victims had severe thermal burns. 405 victims worked as wreckers or emergency teams members in the contaminated area in different time after the accident. They died most frequently of traumas, accidents, cancer, cardiovascular diseases. Most of deaths in this group were attributed to general somatic causes unrelated to the hazards of the ionizing radiation.


Response rates to a mailed survey of a representative sample of cancer patients randomly drawn from the Pennsylvania Cancer Registry: a randomized trial of incentive and length effects.
In recent years, response rates to telephone surveys have declined. Online surveys may miss many older and poorer adults. Mailed surveys may have promise in securing higher response rates. In a pilot study, 1200 breast, prostate and colon patients, randomly selected from the Pennsylvania Cancer Registry, were sent surveys in the mail. Incentive amount ($3 vs. $5) and length of the survey (10 pages vs. 16 pages) were randomly assigned. Overall, there was a high response rate (AAPOR RR4 = 64%). Neither the amount of the incentive, nor the length of the survey affected the response rate significantly. Colon cancer surveys were returned at a significantly lower rate (RR4 = 54%), than breast or prostate surveys (RR4 = 71%, and RR4 = 67%, respectively; p < .001 for both comparisons). There were no significant interactions among cancer type, length of survey and incentive amount in their effects on response likelihood. Mailed surveys may provide a suitable alternative option for survey-based research with cancer patients.


Association of Religious Participation With Mortality Among Chinese Old Adults.
This research examines the association of religious participation with mortality using a longitudinal data set collected from 9,017 oldest-old aged 85+ and 6,956 younger elders aged 65 to 84 in China in 2002 and 2005 and hazard models. Results show that adjusted for demographics, family/social support, and health practices, risk of dying was 24% (p < 0.001) and 12% (p < 0.01) lower among frequent and infrequent religious participants than among nonparticipants for all elders aged 65+. After baseline health was adjusted, the corresponding risk of dying declined to 21% (p < 0.001) and 6% (not significant), respectively. The authors also conducted hazard models analysis for men versus women and for young-old versus oldest-old, respectively, adjusted for single-year age; the authors found that gender differentials of association of religious participation with mortality among all elderly aged 65+ were not significant; association among young-old men was significantly stronger than among oldest-old men, but no such significant young-old versus oldest-old differentials in women were found.


Long-Term Exposure to Air Pollutants and Cancer Mortality: A Meta-Analysis of Cohort Studies.
The aim of this study was to examine the relationship between main air pollutants and all cancer mortality by performing a meta-analysis. We searched PubMed, EMBASE (a biomedical and pharmacological bibliographic database of published literature produced by Elsevier), and the reference lists of other reviews until April 2018. A random-effects model was employed to analyze the meta-estimates of each pollutant. A total of 30 cohort studies were included in the final analysis. Overall risk estimates of cancer mortality for 10 µg/m³ per increase of particulate matter (PM)2.5, PM10, and NO₂ were 1.17 (95% confidence interval (CI): 1.11⁻1.24), 1.09 (95% CI: 1.04⁻1.14), and 1.06 (95% CI: 1.02⁻1.10), respectively. With respect to the type of cancer, significant hazardous influences of PM2.5 were noticed for lung cancer mortality and non-lung cancer mortality including liver cancer, colorectal cancer, bladder cancer, and kidney cancer, respectively, while PM10 had harmful effects on mortality from lung cancer, pancreas cancer, and larynx cancer. Our meta-analysis of cohort studies indicates that exposure to the main air pollutants is associated with increased mortality from all cancers.


Reconstitution of Monocyte Subsets and PD-L1 Expression but Not T Cell PD-1 Expression in Obstructive Sleep Apnea Patients upon PAP Therapy.
Obstructive sleep apnea (OSA) is characterized by nocturnal breathing intermissions resulting in oxidative stress and eventually, a low-grade systemic inflammation. The study aimed to investigate the impact of positive airway pressure (PAP) therapy on the inflammatory milieu as measured by monocyte and T cell phenotypic alterations. Participants were assessed for their OSA severity before PAP therapy and about six months later, including patient-reported outcome and therapy usage by telemetry readout. The distributions of the CD14/CD16-characterized monocyte subsets as well as the CD4/CD8-characterized effector T cell subsets with regard to their PD-1 and PD-L1 expression were analyzed by flow cytometry from blood samples. Data of 25 patients revealed a significant reconstitution of the monocyte subset distribution and a decrease in PD-L1 expression on pan-monocytes and CD8+ T cells without an association to initial AHI and overweight. The PD-1 expression was still increased on T cell subsets, especially on CD4+ TH17/22 cells. We conclude that PAP therapy might have a rapid effect on the monocyte phenotype and overall PD-L1 expression levels. However, T cell immune alterations especially on TH17/22 cells persist longer, indicating an ongoing disturbance of the adaptive immune system.


Near infrared optical projection tomography for assessments of β-cell mass distribution in diabetes research.
By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR); 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans.


Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats.
Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury. This study was undertaken to determine the neuroprotective effects and mechanisms of TBHQ post-treatment on neonatal HI brain damage. Using a neonatal HI rat model, we demonstrated that TBHQ markedly abated oxidative stress compared to the HI group, as evidenced by decreased oxidative stress indexes, enhanced Nrf2 nuclear accumulation and DNA binding activity, and up-regulated expression of Nrf2 downstream antioxidative genes. Administration of TBHQ likewise significantly suppressed reactive gliosis and release of inflammatory cytokines, and inhibited apoptosis and neuronal degeneration in the neonatal rat cerebral cortex. In addition, infarct size and neuronal damage were attenuated distinctly. These beneficial effects were accompanied by improved neurological reflex and motor coordination as well as amelioration of spatial learning and memory deficits. Overall, our results provide the first documentation of the beneficial effects of TBHQ in neonatal HI model, in part conferred by activation of Nrf2 mediated antioxidative signaling pathways.


Time-lapse imagery and volunteer classifications from the Zooniverse Penguin Watch project.
Automated time-lapse cameras can facilitate reliable and consistent monitoring of wild animal populations. In this report, data from 73,802 images taken by 15 different Penguin Watch cameras are presented, capturing the dynamics of penguin (Spheniscidae; Pygoscelis spp.) breeding colonies across the Antarctic Peninsula, South Shetland Islands and South Georgia (03/2012 to 01/2014). Citizen science provides a means by which large and otherwise intractable photographic data sets can be processed, and here we describe the methodology associated with the Zooniverse project Penguin Watch, and provide validation of the method. We present anonymised volunteer classifications for the 73,802 images, alongside the associated metadata (including date/time and temperature information). In addition to the benefits for ecological monitoring, such as easy detection of animal attendance patterns, this type of annotated time-lapse imagery can be employed as a training tool for machine learning algorithms to automate data extraction, and we encourage the use of this data set for computer vision development.


Health care experiences of mothers of children with bronchiectasis in Counties Manukau, Auckland, New Zealand.
Bronchiectasis is a worsening public health problem in New Zealand. This study aimed to explore the health care experiences of mothers of children with bronchiectasis in the Counties Manukau District Health Board area of Auckland, New Zealand. Semi-structured interviews were undertaken with ten mothers of children with bronchiectasis. Data were analysed using thematic analysis. Five themes emerged: 1) Searching for answers, describing mothers' search for a diagnosis; 2) (Dis)empowerment, describing mothers' acquisition of knowledge, leading to empowerment; 3) Health care and relationships, describing the impact of relationships on the mother's health care experiences; 4) A juggling act, describing the challenges of juggling health care with school, work and family; 5) Making it work, describing how mothers overcome barriers to access health care for their child. The health provider-parent relationship was crucial for fostering positive health care experiences. Mothers' acquisition of knowledge facilitated empowerment within those relationships. Additionally, mothers' perceptions of the quality and benefit of health services motivated them to overcome barriers to accessing care. Study findings may help to improve health care experiences for parents of children with bronchiectasis if identified issues are addressed.


Cross-frequency coupling in mesiotemporal EEG recordings of epileptic patients.
Semi-invasive foramen ovale (Fov) electrodes were used to record electrical activity in the vicinity of the inferior mesial temporal region of epileptic patients, in addition to standard scalp EEG. Third order cumulant analysis was used to measure the phase-coupled frequencies corresponding to non-linear coupling of spectral frequency components, somewhat analogous to frequencies of resonance. On the basis of the distribution of these frequencies, an index of resonance (IR) is defined as the ratio between the number of peaks in the gamma-band (40-55Hz) vs. the number of peaks in the beta-band (15-30Hz). The epileptogenic focus was located in the hemisphere with lower resonant frequencies because these frequencies were characteristic of a spread of the seizure over a broader area. In the case of Fov electrodes IR could differentiate a group of patients affected by a tumor compared to patients with mesial temporal sclerosis. The novel index IR appears as an interesting parameter to evaluate the level of interareal functional connectivity in Fov recordings in epileptic patients, but its usage is likely to be extended in electrophysiological studies.


The mechanism of oleic acid nitration by *NO(2).
Fatty acid nitration is a recently discovered process that generates biologically active nitro lipids; however, its mechanism has not been fully characterized. For example, some structural details such as vinyl and allyl isomers of the nitro fatty acids have not been established. To characterize lipids that originated from a biomimetic reaction of *NO(2) with oleic acid, we synthesized several isomers of nitro oleic acids and studied their chromatography and mass spectra by various techniques of mass spectrometry. LC/MS analysis performed on a high resolution micro column detected molecular carboxylic anions of various oleic acid nitro isomers (NO(2)OA). Esterification of NO(2)OA with pentafluorobenzyl bromide and diisopropylethylamine as a catalyst produced a unique isoxazole ester derivative exclusively from allyl NO(2)OA isomers via dehydration of the nitro group at ambient temperatures. This new analytical procedure revealed that *NO(2) generated two vinyl and two allyl isomers of NO(2)OA. The vinyl isomers showed high regioselectivity with the 1.8:1 preference for the 10-NO(2)OA isomer that was absent among allylic isomers. The nitration also generated elaidic acid via cis-trans isomerization and diatereoisomers of vicinal nitro hydroxy, nitro keto and alpha-nitro epoxy stearic acids with high stereo and regioselectivity. Nitration of small unilamelar phospholipid vesicles resulted in several phospholipids containing nitro lipids and elaidic acid amenable to hydrolysis by phospholipase A(2).


Role of atrial natriuretic peptide in natriuresis in volume-expanded rats.
Continuous intravenous infusion of rat atrial natriuretic peptide (rANP) was carried out for 60 min in urethan-anesthetized rats. Plasma rANP (PANP) levels during 0, 12.5, and 50 ng/min rANP infusion reached 20.9 +/- 3.4, 61.2 +/- 12.3, and 228 +/- 30.6 pg/ml, respectively. Urinary sodium excretion (UNaV) remained unchanged during the 0 and 12.5 ng/min rANP infusion. In contrast, the 50 ng/min rANP infusion resulted in a 5.6-fold increase in UNaV without significant changes in plasma aldosterone levels and glomerular filtration rate. Isotonic saline infusion (116 microliter/min for 60 or 120 min) caused a significant increase in UNaV. UNaV in an experimental model of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was 5.0 times greater than in control animals. PANP levels in 60- or 120-min saline-infused and SIADH rats were 46.3 +/- 6.7, 39.0 +/- 9.0, and 35.6 +/- 3.2 pg/ml, respectively. These values were significantly higher than control values but failed to achieve a level at which natriuresis occurred during the infusion of rANP. These results suggest that endogenous ANP may not play a critical role in the induction of acute natriuresis in volume-expanded states, although it could be partially involved in such a natriuretic response.


Premalignant Gastric Lesions in Patients Included in National Colorectal Cancer Screening.
Gastric cancer is the fifth most common malignancy in the world with almost one million new cases annually. Helicobacter pylori infection causes 89% of all gastric cancers. Premalignant lesions (atrophy and intestinal metaplasia) develop after several decades of inflammation. Secondary prevention with gastroscopy is possible, but it is costly and has a low compliance rate. Alternative procedures like serology testing for pepsinogen I and II and pepsinogen I/II ratio are available to select patients for surveillance gastroscopies. In seven outpatient endoscopic units, 288 patients (154 men; 53.5%), average age 60.68 years, tested positive in National colorectal cancer screening programme SVIT, were included in the study. Gastropanel (BioHit, Finland) was used as a serologic biopsy method. We found 24 patients (12 men, mean age 63.7 years) with pepsinogen (pepsinogen I/II < 3 and/or pepsinogen I < 30 μg/L). Premalignant changes were found on gastric biopsies in 21 patients (7.3% incidence). Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) ≥ 1 was found in 20 patients; Operative Link for Gastritis Assessment (OLGA) ≥ 1 was found in 19 patients. Combined accuracy for preneoplastic lesions in Gastropanel positive patients was 87.5%. H. pylori seropositivity was found in 219 patients (76%). Only 24% of our population had normal results. Gastropanel test has proven to be a reliable non-invasive test for advanced gastric preneoplastic lesions that can select patients for further gastroscopy. We found high H. pylori seropositivity in older age groups in Slovenia.


An integrative review of facilitators and barriers influencing collaboration and teamwork between general practitioners and nurses working in general practice.
To identify facilitators and barriers influencing collaboration and teamwork between general practitioners and nurses working in general (family) practice. Internationally, a shortage of doctors entering and remaining in general practice and an increasing burden of chronic disease has diversified the nurse's role in this setting. Despite a well-established general practice nursing workforce, little attention has been paid to the ways doctors and nurses collaborate in this setting. Integrative literature review. CINAHL, Scopus, Web of Life, Cochrane Library, Joanna Briggs Institute Library of Systematic Reviews and Trove (dissertation and theses) were searched for papers published between 2000 and May 2014. This review was informed by the approach of Whittemore and Knafl (2005). All included papers were assessed for methodological quality. Findings were extracted, critically examined and grouped into themes. Eleven papers met the inclusion criteria. Thematic analysis revealed three themes common to the facilitators of and barriers to collaboration and teamwork between GPs in general practice: (1) roles and responsibilities; (2) respect, trust and communication; and (3) hierarchy, education and liability. This integrative review has provided insight into issues around role definition, communication and organizational constraints which influence the way nurses and general practitioners collaborate in a team environment. Future research should investigate in more detail the ways doctors and nurses work together in general practice and the impact of collaboration on nursing leadership and staff retention.


Anatomical and biochemical characterisation of a barrier to radial O2 loss in adventitious roots of two contrasting Hordeum marinum accessions.
A barrier to radial O2 loss (ROL) in roots is an adaptive trait of waterlogging-tolerant plants. Hordeum marinum Huds. is a waterlogging-tolerant species that, in contrast to its waterlogging-sensitive cultivated relatives, forms a tight barrier to ROL in basal root zones. To evaluate the nature of the barrier to ROL in roots, we combined measurements of ROL with histochemical and biochemical studies of two contrasting H. marinum accessions. H21 formed greater aerenchyma (up to 38% of cross-sectional area) and a tight barrier to ROL when grown under deoxygenated stagnant conditions, whereas the barrier was only partially formed in roots of H90 and aerenchyma was up to 26%. A tight barrier to ROL in roots of H21 corresponded with strong suberisation of the exodermis. In agreement with anatomical studies, almost all aliphatic suberin quantities were greater in roots of H21 grown under stagnant conditions compared with roots from aerated controls, and also to those in H90. By contrast to suberin, no differences in root lignification were observed between the two accessions raised in either aerated or stagnant conditions. These findings show that in adventitious roots of H. marinum, suberisation rather than lignification restricts ROL from the basal root zones.


Modeling the effect of forward scatter and aberrations on visual acuity after endothelial keratoplasty.
To evaluate the effects on visual acuity of forward scatter and aberrations typical of those after Descemet stripping endothelial keratoplasty (DSEK). Twenty normal eyes of 20 subjects (ages 22-57 years) were examined with best spectacle correction. Under photopic conditions, high-contrast visual acuities (HCVAs) were measured by using ETDRS charts. Visual acuity was also measured by using aberrated charts that simulated the typical high-order aberrations at 12 months after DSEK. Forward scatter was induced by viewing the eye charts through a 1-mm-thick layer of scattering solution (Amco Clear, at a concentration of 4000 nephelometric turbidity units) and was measured with a straylight meter. Forward scatter increased from 1.19 ± 0.11 log straylight parameter (log[s]; mean ± SD) without induced scatter to 1.57 ± 0.06 log(s) with induced scatter (P < 0.001). Induced scatter reduced HCVA on the nonaberrated chart by 2.7 Snellen letters, from 20/19 (Snellen equivalent) to 20/21 (P < 0.001) and by 2.1 letters on the aberrated chart, from 20/25 to 20/28 (P = 0.005). Addition of aberrations reduced HCVA by more than twice the number of Snellen letters than did induced scatter, by 6.4 letters with low scatter (P < 0.001), and by 5.8 letters with high scatter (P < 0.001). Under typical clinical testing conditions, increased forward scatter has minimal effect on visual acuity. High-order aberrations are a more likely cause of degraded visual acuity than is forward scatter in eyes with clear corneas after DSEK.


Ionic Strength Effects on Cation Sorption to Oxides: Macroscopic Observations and Their Significance in Microscopic Interpretation
Sorption of metal ions at oxide mineral-water interfaces is a complex process involving many possible variables, one of them being ionic strength. Depending on the system, adsorption of metal ions at these interfaces has been reported to increase or decrease with increasing ionic strength. However, in most cases it appears to be insensitive to ionic strength. Insensitivity to ionic strength has been taken as an indication for inner sphere surface complexation. Decrease of sorption with increasing ionic strength has been interpreted as outer sphere surface complexation. Promotive effects of ionic strength have not been discussed at all in terms of conventional surface complexation theory. The present paper shows that the classical example of Ba sorption to goethite, where increasing ionic strength decreases Ba adsorption, can be alternatively explained by an inner sphere mechanism if ion pair formation in solution between Ba and nitrate of the swamping electrolyte is taken into account. This suggests that macroscopic observations in cation uptake experiments should not be used to obtain mechanistic interpretations, even for ionic strength effects. Promotive effects of ionic strength on Cd sorption to goethite are also discussed. The present modeling exercises with the help of a conventional one-site surface complexation model suggest that promotive ionic strength effects may be explained in terms of more effective shielding of highly charged surface complexes at high ionic strength. Copyright 1997 Academic Press. Copyright 1997Academic Press


High-grade glioma in very young children: a rare and particular patient population.
In the past years, pediatric high-grade gliomas (HGG) have been the focus of several research articles and reviews, given the recent discoveries on the genetic and molecular levels pointing out a clinico-biological uniqueness of the pediatric population compared to their adult counterparts with HGG. On the other hand, there are only scarce data about HGG in very young children (below 3 years of age at diagnosis) due to their relatively low incidence. However, the few available data suggest further distinction of this very rare subgroup from older children and adults at several levels including their molecular and biological characteristics, their treatment management, as well as their outcome. This review summarizes and discusses the current available knowledge on the epidemiological, neuropathological, genetic and molecular data of this subpopulation. We discuss these findings and differences compared to older patients suffering from the same histologic disease. In addition, we highlight the particular clinical and neuro-radiological findings in this specific subgroup of patients as well as their current management approaches and treatment outcomes.


Patient considerations and drug selection in the treatment of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown cause. Approximately 5,000 people are diagnosed with IPF in the UK every year. People with IPF suffer significant morbidity and, without any curative treatment at present, survival rates remain poor with a median survival of 3 years. While treatment remains largely supportive, many drug therapies have been trialed in IPF over the years. Pirfenidone and nintedanib are newly licensed treatments for IPF and the first drugs to have shown convincing evidence of slowing disease progression. In addition to evaluating clinical evidence, we also discuss elements affecting drug choice from the viewpoint of patients and health care professionals. We discuss pharmacological and nonpharmacological aspects of providing best supportive care for patients with IPF. However, few good quality studies exist focusing on controlling symptoms specifically in patients with IPF, and recommendations are often extrapolated from evidence in other chronic diseases. In covering these topics, we hope to provide readers with a comprehensive review of the available evidence pertaining to all aspects of care for patients suffering with IPF.


[Inhibitory effect of deoxyadenylyl-(3'-5')-deoxyguanosine on the RNA-polymerase activity of influenza virus A].
Deoxyadenylylguanosine (dAdG, 0.2-0.4 mM), affecting the RNA polymerase activity, caused inhibition of transcription of the influenza A virus in presence of precursor AdG by 50-60% and a 80-85% inhibition in absence of the precursor. The inhibitor exhibited its effect independently on the time of addition into an incubation mixture. Addition of 0.5 mM inhibitor into a cultural medium inhibited reproduction of the influenza A virus in a culture of chicken embryonal fibroblasts.


Noncytolytic control of viral infections by the innate and adaptive immune response.
This review describes the contribution of noncytolytic mechanisms to the control of viral infections with a particular emphasis on the role of cytokines in these processes. It has long been known that most cell types in the body respond to an incoming viral infection by rapidly secreting antiviral cytokines such as interferon alpha/beta (IFN-alpha/beta). After binding to specific receptors on the surface of infected cells, IFN-alpha/beta has the potential to trigger the activation of multiple noncytolytic intracellular antiviral pathways that can target many steps in the viral life cycle, thereby limiting the amplification and spread of the virus and attenuating the infection. Clearance of established viral infections, however, requires additional functions of the immune response. The accepted dogma is that complete clearance of intracellular viruses by the immune response depends on the destruction of infected cells by the effector cells of the innate and adaptive immune system [natural killer (NK) cells and cytotoxic T cells (CTLs)]. This notion, however, has been recently challenged by experimental evidence showing that much of the antiviral potential of these cells reflects their ability to produce antiviral cytokines such as IFN-gamma and tumor necrosis factor (TNF)-alpha at the site of the infection. Indeed, these cytokines can purge viruses from infected cells noncytopathically as long as the cell is able to activate antiviral mechanisms and the virus is sensitive to them. Importantly, the same cytokines also control viral infections indirectly, by modulating the induction, amplification, recruitment, and effector functions of the immune response and by upregulating antigen processing and display of viral epitopes at the surface of infected cells. In keeping with these concepts, it is not surprising that a number of viruses encode proteins that have the potential to inhibit the antiviral activity of cytokines.


Relapsing polychondritis: state of the art on clinical practice guidelines.
Due to the rarity of relapsing polychondritis (RP), many unmet needs remain in the management of RP. Here, we present a systematic review of clinical practice guidelines (CPGs) published for RP, as well as a list of the most striking unmet needs for this rare disease. We carried out a systematic search in PubMed and Embase based on controlled terms (medical subject headings and Emtree) and keywords of the disease and publication type (CPGs). The systematic literature review identified 20 citations, among which no CPGs could be identified. We identified 11 main areas with unmet needs in the field of RP: the diagnosis strategy for RP; the therapeutic management of RP; the management of pregnancy in RP; the management of the disease in specific age groups (for instance in paediatric-onset RP); the evaluation of adherence to treatment; the follow-up of patients with RP, including the frequency of screening for the potential complications and the optimal imaging tools for each involved region; perioperative and anaesthetic management (due to tracheal involvement); risk of neoplasms in RP, including haematological malignancies; the prevention and management of infections; tools for assessment of disease activity and damage; and patient-reported outcomes and quality of life indicators. Patients and physicians should work together within the frame of the ReCONNET network to derive valuable evidence for obtaining literature-informed CPGs.


Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease.
Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD. Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögren's syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA(®) (Memory Lymphocyte Immuno Stimulation Assay). In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P<0.0001). The most frequent allergens were nickel, mercury, gold and palladium. Patients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies.


Emotions correlate with perceived mental effort and concentration disruption in adult sport performers.
Two studies explored the relationship between emotions, perceived mental effort and concentration disruption in adult sport performers. In Study 1, semi-professional association football players completed questionnaire measures before and after a competitive match. In Study 2, student athletes completed questionnaire measures for two performance scenarios: one in which they were performing above their normal level and one in which they were performing below their normal level. Findings demonstrated that cognitive trait anxiety was associated with greater disruptions in concentration but was unrelated to mental effort. For state measures, athletes reported greater levels of concentration disruption when experiencing high levels of anxiety or high levels of happiness, and fewer disruptions in concentration when experiencing high levels of excitement. Findings also showed that excitement was associated with low levels of mental effort during good performances and high levels of mental effort during poor performances; anxiety and happiness were associated with high levels of mental effort during good performances and low levels of mental effort during poor performances. Taken together, these studies point towards potential benefits accompanying high levels of excitement and potential disadvantages accompanying high levels of anxiety and happiness.


Extreme coronary radiation doses from intravascular brachytherapy.
To evaluate coronary artery integrity after very high radiation doses from intravascular brachytherapy (IVBT) in the setting of source asymmetry. Ten patients treated for right coronary artery (RCA) in-stent restenosis (ISR) between 2017 and 2021 and for whom follow-up angiograms were available were identified from departmental records. Procedural angiograms, taken to document source position, were used to estimate vascular wall doses. The 2.5 mm proximal source marker was used to estimate the distance from source center to the media and adventitia. Distances were converted to dose (Gy) using the manufacturers' dose fall-off table, measured in water. Follow-up films were scrutinized for any sign of late vascular damage. The average minimal distance from catheter center to the adjacent media and the adventitia was 0.9 mm (±0.2) mm and 1.4 mm (±0.2), respectively. The average maximum media and adventitial doses adjacent to the source were 75 Gy (±26) and 39 Gy (±14), respectively. Follow-up angiograms were available from 0.6 years to 3.9 years following IVBT (median: 1.6 years). No IVBT-treated vascular segment showed signs of degeneration, dissection or aneurysm. IVBT vascular wall doses are frequently far higher than prescribed. The lack of complications in this unselected group of patients gives a modicum of reassurance that raising the prescription dose is unlikely to lead to a sudden appearance of complications.


Concomitant "Ear Bleed and Styloid Fracture": An Unusual Complication of Impacted Mandibular Third Molar Removal.
The removal of impacted mandibular third molar is associated with potential complications such as dry socket, paresthesia, uncontrolled socket bleeding, angle fracture, etc., which are commonly encountered in dental practice. This article presents a peculiar case of "ear bleed" concomitant with "isolated styloid" fracture following removal of impacted mandibular third molar, not reported in the literature till date. Ear bleed is a bothersome clinical sign that requires thorough investigation and prompt treatment because it is frequently related to fractures of the skull base. Isolated fracture of the styloid process is rare; its diagnosis, impact on adjacent vital structures, and treatment protocol are less discussed in maxillofacial literature. The case report elucidates the etiopathogenesis of ear bleed and styloid fracture which have great clinical implications. The clinical correlation between the two entities and dental extraction is discussed in this report to guide a dental practitioner in its management.


A picture may be worth a thousand texts: obese adolescents' perspectives on a modified photovoice activity to aid weight loss.
In an effort to enhance the vividness and personal relevance of a text messaging intervention to promote weight loss among obese adolescents, a modified Photovoice process was evaluated with adolescents in a weight management program. Photovoice is a method using photography to generate relevant images and stories from users. Participants were recruited from the Michigan Pediatric Outpatient Weight Evaluation and Reduction (MPOWER) program, a multidisciplinary weight management program for obese adolescents and their parents. Twenty-three adolescents with a mean BMI of 40 were asked to take pictures on three to five randomly assigned weight-related topics, such as "something that reminds you to exercise," and to text them to a research assistant. Adolescents then engaged in semistructured interviews about the experience. Detailed notes of the interviews were analyzed to identify themes. Participants generally provided high ratings of the process, indicating that (1) deciding what pictures to take caused them to reflect on their weight loss experience, and (2) a mobile intervention incorporating personally relevant images (e.g., basketball as their favorite sport rather than sports in general) would increase treatment adherence. The submitted photographs frequently featured family members and friends, and participants indicated that family and friends played a major role in motivating and supporting them. This study suggests that a Photovoice component has the potential to enhance weight management programs for teens as part of a text messaging intervention and as an independent entity. Further work should evaluate the effect of this promising intervention on weight loss.


[Relationship between the effect of bradykinin on microvessels and their initial tonus].
The effect of bradykinin on microcirculation was studied in vivo on the rat mesentery. Bradykinin (0.01--10 micrograms) caused three types of reactions of arterioles and venules (constriction, dilatation, no changes in the diameter) in relation to the dose used. Preliminary application of noradrenaline changed the sensitivity of microvessels to bradykinin towards the increased frequency of dilatation. The increased permeability by red cells in postcapillaries and in venules arose in the areas of the greatest stretch (sites of confluences and ridges of vessels wavy in outline) and was accompanied by deformation and shortening of venules. It was disclosed that bradykinin exerted a pronounced pain effect that promoted awakening of the animals from anesthesia.


Nucleo-cytoplasmic relationships of high-molecular-weight ribonucleic acid, including polyadenylated species, in the developing rat brain.
The metabolism of high-molecular-weight RNA in the nuclear and cytoplasmic fractions of newborn and adult rat brain was investigated after the intracranial administration of [32P]Pi. In young brain, a considerable proportion of the newly synthesized radioactive RNA is transferred to the cytoplasm, in contrast with the adult brain, where there appears to be a high intranuclear turnover. Electrophoretic analysis of the newly synthesized RNA showed that processing of the rRNA precursor to yield the 28S and 18S rRNA may be more rapid in the adult than in the young, although most of the adult rRNA in the nucleus is not transferred to the cytoplasm. In young brain, processing is probably tightly coupled to transport of rRNA into the cytoplasm, so that 28S and 18S rRNA are not subjected to possible degradation within the nucleus. Polyadenylated RNA turns over in concert with high-molecular-weight RNA in the nuclei of the adult rat brain. In the cytoplasm the polyadenylated RNA has a higher turnover rate relative to rRNA. In the young brain the polyadenylated RNA is transferred to the cytoplasm along with rRNA, although polyadenylated RNA is transported into the cytoplasm at a faster rate. The nuclear and cytoplasmic polyadenylated RNA species of young brain are larger than their corresponding adult counterparts. These results suggest that there are considerable changes in the regulation of the nucleo-cytoplasmic relationship of rRNA and polyadenylated RNA during the transition of the brain from a developing replicative phase to an adult differentiated and non-dividing state.


Molecular characterization of Plasmodium falciparum S-adenosylmethionine synthetase.
S-Adenosylmethionine (AdoMet) synthetase (SAMS: EC 184.108.40.206) catalyses the formation of AdoMet from methionine and ATP. We have cloned a gene for Plasmodium falciparum AdoMet synthetase (PfSAMS) (GenBank accession no. AF097923), consisting of 1209 base pairs with no introns. The gene encodes a polypeptide (PfSAMS) of 402 amino acids with a molecular mass of 44844 Da, and has an overall base composition of 67% A+T. PfSAMS is probably a single copy gene, and was mapped to chromosome 9. The PfSAMS protein is highly homologous to all other SAMS, including a conserved motif for the phosphate-binding P-loop, HGGGAFSGKD, and the signature hexapeptide, GAGDQG. All the active-site amino acids for the binding of ADP, P(i) and metal ions are similarly preserved, matching entirely those of human hepatic SAMS and Escherichia coli SAMS. Molecular modelling of PfSAMS guided by the X-ray crystal structure of E. coli SAMS indicates that PfSAMS binds ATP/Mg(2+) in a manner similar to that seen in the E. coli SAMS structure. However, the PfSAMS model shows that it can not form tetramers as does E. coli SAMS, and is probably a dimer instead. There was a differential sensitivity towards the inhibition by cycloleucine between the expressed PfSAMS and the human hepatic SAMS with K(i) values of 17 and 10 mM, respectively. Based on phylogenetic analysis using protein parsimony and neighbour-joining algorithms, the malarial PfSAMS is closely related to SAMS of other protozoans and plants.


Biliary sequelae of endoscopic sphincterotomy.
Twenty five patients were reviewed a mean of 36 months after successful endoscopic sphincterotomy for the removal of bile duct stones. All the patients had improved symptomatically but 20% had episodes of mild abdominal pain and a similar number had elevated serum gamma glutamyltranspeptidase activities (up to 3 times normal). In 12 patients (50%) biliary gas was demonstrated indicating reflux of duodenal contents. Clinical cholangitis did not occur. Aspiration liver biopsy revealed mild portal tract fibrosis and inflammation in patients with biliary reflux. Biliary reflux was significantly associated with mild upper abdominal pain (P less than 0.05). This study has shown that mild abnormalities of biliary function persist after endoscopic sphincterotomy. The long term consequence of these changes is unclear.


Malignant Hyperthermia-Susceptible Adult Patient and Ambulatory Surgery Center: Society for Ambulatory Anesthesia and Ambulatory Surgical Care Committee of the American Society of Anesthesiologists Position Statement.
This document represents a joint effort of the Society for Ambulatory Anesthesia (SAMBA) and the Ambulatory Surgical Care Committee of the American Society of Anesthesiologists (ASA) concerning the safe anesthetic care of adult malignant hyperthermia (MH)-susceptible patients in a free-standing ambulatory surgery center (ASC). Adult MH-susceptible patients can safely undergo a procedure in a free-standing ASC assuming that proper precautions for preventing, identifying, and managing MH are taken. The administration of preoperative prophylaxis with dantrolene is not indicated in MH-susceptible patients scheduled for elective surgery. There is no evidence to recommend an extended stay in the ASC, and the patient may be discharged when the usual discharge criteria for outpatient surgery are met. Survival from an MH crisis in an ASC setting requires early recognition, prompt treatment, and timely transfer to a center with critical care capabilities.


[Susceptibility of rat thymocyte subpopulations to thymosine affecting their protein synthesis and dexamethasone receptors].
Protein synthesis and reception for 1,2-3H-(N)-dexamethasone were studied in A, B, C, D subpopulations of rat thymocytes after treatment with thymosine, cyclic adenosine-3,' 5'-monophosphate (cAMP) and caffeine. Thymosine inhibited the 1,2-3H-(N)-dexamethasone reception in rat thymocyte subpopulations A, B and C by 30-40%, stimulated the protein synthesis in A and B fractions by 30% as well as inhibited the synthesis in D fraction by 14%. Caffeine, administered together with thymosine, inhibited the protein synthesis by 80% in C and D thymocyte subpopulations and - by 47% in B subpopulations. After simultaneous treatment with exogenous cAMP, thymosine and caffeine the protein synthesis was inhibited by 14% in all the thymocyte subpopulations. The data obtained suggest that thymosine and caffeine affect the various lymphocyte T subpopulations, dissimilar in their differentiation.


Comparison and characterization of soybean and sunflower lecithins used for chocolate production by high-performance thin-layer chromatography with fluorescence detection and electrospray mass spectrometry.
The scarce availability of nongenetically modified soybeans on the world market represents a growing problem for food manufacturers. Hence, in this study the effects of substituting soybean with sunflower lecithin were investigated with regard to chocolate production. The glycerophospholipid pattern of the different lecithin samples was investigated by high-performance thin-layer chromatography fluorescence detection (HPTLC-FLD) and by HPTLC-positive ion electrospray ionization mass spectrometry (ESI(+)-MS) via the TLC-MS Interface and by scanning HPTLC-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOFMS). Especially, the contents of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were of interest due to the influencing effects of these two glycerophospholipids on the rheological parameters of chocolate production. The lecithin substitution led to only slight differences in the rheological parameters of milk and dark chocolate. Limits of detection (LODs) and limits of quantification (LOQs) of seven glycerophospholipids were studied for three detection modes. Mean LODs ranged from 8 to 40 mg/kg for HPTLC-FLD and, using a single-quadrupole MS, from 10 to 280 mg/kg for HPTLC-ESI(+)-MS as well as from 15 to 310 mg/kg for HPTLC-FLD-ESI(+)-MS recorded after derivatization with the primuline reagent.


Trialing the feasibility of a critical time intervention for youth transitioning out of homelessness.
Little is known regarding the specific types of service models and collaborations that are necessary to support diverse populations of youth in transition out of homelessness. Transitional supports addressing the complex needs of this population are needed to stabilize the array of housing arrangements that youth access. This study was a pilot randomized controlled trial of one such critical time intervention, called the Housing Outreach Program-Collaboration (HOP-C). HOP-C is a multicomponent, multidisciplinary intervention that provides 6 months of mental health and peer support, along with transitional case management to youth who have transitioned into some form of stable housing out of homelessness. In this trial, 65 youth were randomized to receive HOP-C plus treatment as usual or transitional case management plus treatment as usual. Outcome assessments were completed by 30 treatment and 28 control participants. The findings suggest that this intervention is feasible with mental health, employment or education, and housing metrics favoring HOP-C with odds ratios ranging from 2.28 to 3.18 and better subjective housing stability. Other indicators showed less change. HOP-C appears feasible and should be tested in a fully powered trial, providing the intervention for a duration longer than 6 months. Overall, these data suggest the potential benefit in fostering city-level, multidisciplinary teams sourced from several organizations to support youth transitioning out of homelessness. Pragmatic trial method considerations for this population are also addressed as are the ethical considerations pertinent to engaging highly marginalized youth in clinical trials. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Temporal control of rhythmic performance: a comparison between young and old adults.
Young (20-30-year-old) and older (60-76-year-old) adults were tested on two measures of rhythmic performance. The first involved tapping at the subject's own preferred rate, a measure of so-called internal tempo. Over five sessions of testing, tapping rates were consistently and significantly slower on average in the older subjects than the younger ones, but rates were not relatively more variable in older subjects (i.e., coefficients of variation, standard deviation/mean, did not differ between the older and young people). In addition, both old and younger subjects performed on a synchronized-tapping and continuation task of the type used by Wing and Kristofferson (1973, Perception and Psychophysics, 14, 3-12). Target interresponse times were 300, 400, 500, 600, and 700 ms, and in all cases interresponse intervals produced by both the old and young adults matched the target times very closely. Wing and Kristofferson's analytical procedure was used to decompose tapping variance into that attributable to timing processes and that resulting from motor implementation of the timing signal. Both sorts of variance increased with increasing target interresponse time (with timer variance increasing most markedly), but no difference was found in either type of variance in comparisons between the old and younger subjects. If the internal tempo measure directly reflects the speed of internal timing processes, the data suggest that such processes are slower, but not relatively more variable, in older than younger subjects (consistent with some previous evidence and speculation), but that the calibration of performance forced by the synchronization task will make such an age-related difference in "internal clock speed" unobservable on synchronized-tapping tasks.


The geometric transfer function component for scintillation camera collimators with straight parallel holes.
A theoretical approach has been developed that allows the geometric transfer function component for conventional scintillation camera collimators to be predicted in closed form. If transfer function analysis is to be useful in describing imaging system performance, the image of a point source must not depend on source position in a plane parallel to the detection plane. This shift invariance can be achieved by analysis of system response in terms of an effective point spread function, defined as the normalised image of a point source that would be obtained if the camera collimator were uniformly translated (but not rotated) during image formation. The geometric component of the corresponding effective transfer function is shown to be expressed simply by the absolute square of the two-dimensional Fourier transform of a collimator hole aperture, with the spatial frequency plane scaled by a factor which depends on collimator length, source-to-collimator distance, and collimator-to-detection plane distance. Closed form algebraic expressions of the geometric transfer function have been obtained for all four common hold shapes (circular, hexagonal, square and triangular). Monte Carlo simulations and experimental measurements have shown these theoretical expressions to be highly accurate.


Prognostic utility of fluorescence in situ hybridization for determining HER2 gene amplification in breast cancer.
An accurate investigation of the HER2 proto-oncogene is extremely important for the therapy and prognostication of breast cancer. Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard methods for this purpose. The aim of this study was to detect the expression and amplification of HER2 in paraffin-embedded samples of breast cancer tissue and to investigate the relationship between HER2 amplification and various clinicopathological parameters in advanced breast cancers. We used FISH to examine the HER2 gene amplification and IHC to examine the expression of HER2 protein, estrogen receptor (ER) and progesterone receptor (PR) in 62 advanced breast cancers. HER2 gene amplification was detected by FISH in 12 breast cancers (19%) and HER2 protein expression with a score of 3+ was detected by IHC in 11 (17%). There was a significant correlation between the HER2 gene amplification and HER2 protein overexpression in breast cancers (P<0.0001). However, some mismatching was evident: 3 cases, negative for the HER2 gene, showed a HER2 protein expression score of 3+ and 2 cases, positive for HER2 gene amplification, had HER2 protein expression scores of 0 and 1+ (negative), respectively. ER and PR were expressed in 41 (66%) and 46 (74%) cancers, respectively. No correlation was observed between the HER2 gene amplification and any of the clinicopathological parameters examined, including age, histopathological type, TNM stage, tumor size, lymph node status, relapse and expression of PR. We observed three patterns among the 6 deceased cases: i) triple negativity for HER2, ER and PR, ii) positivity for HER2 gene amplification with a mismatching HER2 protein expression, and iii) positivity for the HER2 gene amplification with a matching HER2 protein expression score of 2+ or 3+. The triple negative cases and HER2 gene amplification positive cases with a mismatching HER2 protein expression had a poor outcome. These results suggest that in breast cancer, the detection of HER2 gene amplification by FISH is desirable compared with the HER2 protein expression determined by IHC. Moreover, triple negativity for HER2, ER and PR is a potentially very important prognostic marker.


Targeting cancer with nano-bullets: curcumin, EGCG, resveratrol and quercetin on flying carpets.
It is becoming progressively more understandable that different phytochemicals isolated from edible plants interfere with specific stages of carcinogenesis. Cancer cells have evolved hallmark mechanisms to escape from death. Concordant with this approach, there is a disruption of spatiotemproal behaviour of signaling cascades in cancer cells, which can escape from apoptosis because of downregulation of tumor suppressor genes and over- expression of oncogenes. Genomic instability, intra-tumor heterogeneity, cellular plasticity and metastasizing potential of cancer cells all are related to molecular alterations. Data obtained through in vitro studies has convincingly revealed that curcumin, EGCG, resveratrol and quercetin are promising anticancer agents. Their efficacy has been tested in tumor xenografted mice and considerable experimental findings have stimulated researchers to further improve the bioavailability of these nutraceuticals. We partition this review into different sections with emphasis on how bioavailability of curcumin, EGCG, resveratrol and quercetin has improved using different nanotechnology approaches.


Functionalized iron oxide nanoparticles for controlling the movement of immune cells.
Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed "cell box" was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.


Empiric combination antibiotic therapy is associated with improved outcome against sepsis due to Gram-negative bacteria: a retrospective analysis.
The optimal approach for empirical antibiotic therapy in patients with severe sepsis and septic shock remains controversial. A retrospective cohort study was conducted in the intensive care units of a university hospital. The data from 760 patients with severe sepsis or septic shock associated with Gram-negative bacteremia was analyzed. Among this cohort, 238 (31.3%) patients received inappropriate initial antimicrobial therapy (IIAT). The hospital mortality rate was statistically greater among patients receiving IIAT compared to those initially treated with an appropriate antibiotic regimen (51.7% versus 36.4%; P < 0.001). Patients treated with an empirical combination antibiotic regimen directed against Gram-negative bacteria (i.e., beta-lactam plus aminoglycoside or fluoroquinolone) were less likely to receive IIAT compared to monotherapy (22.2% versus 36.0%; P < 0.001). The addition of an aminoglycoside to a carbapenem would have increased appropriate initial therapy from 89.7 to 94.2%. Similarly, the addition of an aminoglycoside would have increased the appropriate initial therapy for cefepime (83.4 to 89.9%) and piperacillin-tazobactam (79.6 to 91.4%). Logistic regression analysis identified IIAT (adjusted odds ratio [AOR], 2.30; 95% confidence interval [CI] = 1.89 to 2.80) and increasing Apache II scores (1-point increments) (AOR, 1.11; 95% CI = 1.09 to 1.13) as independent predictors for hospital mortality. In conclusion, combination empirical antimicrobial therapy directed against Gram-negative bacteria was associated with greater initial appropriate therapy compared to monotherapy in patients with severe sepsis and septic shock. Our experience suggests that aminoglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection.


The Role of TTP Phosphorylation in the Regulation of Inflammatory Cytokine Production by MK2/3.
Tristetraprolin (TTP) is an RNA-binding protein and an essential factor of posttranscriptional repression of cytokine biosynthesis in macrophages. Its activity is temporally inhibited by LPS-induced p38MAPK/MAPKAPK2/3-mediated phosphorylation, leading to a rapid increase in cytokine expression. We compared TTP expression and cytokine production in mouse bone marrow-derived macrophages of different genotypes: wild type, MAPKAP kinase 2 (MK2) deletion (MK2 knockout [KO]), MK2/3 double deletion (MK2/3 double KO [DKO]), TTP-S52A-S178A (TTPaa) knock-in, as well as combined MK2 KO/TTPaa and MK2/3 DKO/TTPaa. The comparisons reveal that MK2/3 are the only LPS-induced kinases for S52 and S178 of TTP and the role of MK2 and MK3 in the regulation of TNF biosynthesis is not restricted to phosphorylation of TTP at S52/S178 but includes independent processes, which could involve other TTP phosphorylations (such as S316) or other substrates of MK2/3 or p38MAPK Furthermore, we found differences in the dependence of various cytokines on the cooperation between MK2/3 deletion and TTP mutation ex vivo. In the cecal ligation and puncture model of systemic inflammation, a dramatic decrease of cytokine production in MK2/3 DKO, TTPaa, and DKO/TTPaa mice compared with wild-type animals is observed, thus confirming the role of the MK2/3/TTP signaling axis in cytokine production also in vivo. These findings improve our understanding of this signaling axis and could be of future relevance in the treatment of inflammation.


Effects of a therapeutic intervention for foster preschoolers on diurnal cortisol activity.
Atypical diurnal patterns of hypothalamic-pituitary-adrenal (HPA) axis activity have been observed in samples of individuals following early life adversity. A characteristic pattern arising from disrupted caregiving is a low early-morning cortisol level that changes little from morning to evening. Less well understood is the plasticity of the HPA axis in response to subsequent supportive caregiving environments. Monthly early-morning and evening cortisol levels were assessed over 12 months in a sample of 3-6-year-old foster children enrolled in a randomized trial of a family-based therapeutic intervention (N=117; intervention condition, n=57; regular foster care condition, n=60), and a community comparison group of same-aged, non-maltreated children from low-income families (n=60). Latent growth analyses revealed stable and typical diurnal (morning-to-evening) cortisol activity among non-maltreated children. Foster children in the intervention condition exhibited cortisol activity that became comparable to the non-maltreated children over the course of the study. In contrast, children in regular foster care condition exhibited increasingly flattened morning-to-evening cortisol activity over the course of the study. In sum, improvements in caregiving following early adversity appear to have the potential to reverse or prevent disruptions in HPA axis functioning.


Polo-like kinase 1 regulates activation of AMP-activated protein kinase (AMPK) at the mitotic apparatus.
AMP-activated protein kinase (AMPK) is being primarily studied as a central metabolic stress sensor, which regulates cell survival and growth-related metabolic pathways to preserve intracellular ATP levels in response to energy deprivation. Evidence is now accumulating that AMPK plays also an obligatory role to ensure proper cell division and faithful chromosomal segregation during mitosis. Increased phosphorylation in the AMPK catalytic subunit (AMPKα) was found in a proteomic study for kinases activated during G2/M and, more recently, activated AMPKα (PP-AMPKα(Thr172)) has been observed to transiently associate with several mitotic structures including centrosomes, spindle poles, the central spindle midzone and the midbody throughout all of the mitotic stages and cytokinesis. How AMPKα activation is controlled spatially and temporally during mitosis, however, remained undiscovered. Because Polo-like Kinases (PLKs) regulate many aspects of mitotic progression including centrosome maturation, bipolar spindle assembly, chromosome congression & segregation, and cytokinesis, we decided to combine an immunofluorescence microscopy analysis with a chemical biology approach employing a small-molecule PLK1 inhibitor to dissect a putative relationship between PLK1 and AMPKα during G2/M transition. PLK1 and PP-AMPKα(Thr172) were found to display a major spatio-temporal overlap early at centrosomes, from prophase until anaphase, and late at the midbody, during telophase and cytokinesis. Moreover, short-term treatment with the thiophene derivative GW843682X, a selective PLK inhibitor that has 400-fold greater potency for PLK1 than for PLK2 or PLK3, fully abolished mitotic activation of AMPKα. Upon long-term PLK1 inhibition, PP-AMPKα(Thr172) was barely detected surrounding the spindle poles of prometaphase-like arrested cells displaying the "polo" phenotype. Similarly, PP-AMPKα(Thr172) was largely inhibited in GW843682X-treated cells exhibiting cytokinesis failure and binucleate cell formation. Given that PLK1 is a well-recognized master regulatory kinase for the numerous protein substrates involved in mitosis, our current description of a causal link between PLK1 activity and mitotic phosphorylation of AMPKα may provide fundamental insights into how the energy sensor AMPK is directly coupled to mitotic cell division and cell cycle exist.


Repeated endotracheal intubations and bronchial lavage in the postoperative treatment of tracheoesophageal fistula.
Recurrent pulmonary atelectasis occurs often in neonates following primary repair of esophageal atresia, leading to massive pneumonia and respiratory failure. The atelectasis is caused by tenacious mucous plugs which are presumably formed as a result of ciliary mucosal damage secondary to reflux of gastric fluid through a tracheo-esophageal fistula. Early aggressive treatment of the atelectasis by repeated gentle tracheal intubation with bronchial lavage and suction is advocated. This treatment is well tolerated and is preferred to continuous intubation with its inherent dangers for the neonatal patient.


Camptocormia in a patient with Parkinson disease and a myopathy with nemaline rods.
Camptocormia, also referred to as bent spine, is a gait disorder characterized by hyperflexion of the thoracolumbar spine that develops in recumbent position while walking and that disappears in supine position. Myopathy is one of the frequent causes of camptocormia. A 77-yr-old male patient who was followed up with the diagnosis of rheumatoid arthritis for 2 yrs was admitted with progressive gait deterioration. Hyperflexion of trunk, disappearing in supine position, was detected and diagnosed as camptocormia. He also exhibited the signs of parkinsonism. A paraspinal muscle biopsy showed myopathy with rods in many muscle fibers. Camptocormia in this patient may be attributable to the myopathic weakness of thoracolumbar paraspinal muscles. The normal biceps brachii muscle biopsy refers to the isolated affection of paraspinal muscles in this patient. A camptocormia (bent spine) case of myopathy with nemaline rods associated with Parkinson disease is presented.


Sperm-egg fusion: a molecular enigma of mammalian reproduction.
The mechanism of gamete fusion remains largely unknown on a molecular level despite its indisputable significance. Only a few of the molecules required for membrane interaction are known, among them IZUMO1, which is present on sperm, tetraspanin CD9, which is present on the egg, and the newly found oolema protein named Juno. A concept of a large multiprotein complex on both membranes forming fusion machinery has recently emerged. The Juno and IZUMO1, up to present, is the only known extracellular receptor pair in the process of fertilization, thus, facilitating the essential binding of gametes. However, neither IZUMO1 nor Juno appears to be the fusogenic protein. At the same time, the tetraspanin is expected to play a role in organizing the egg membrane order and to interact laterally with other factors. This review summarizes, to present, the known molecules involved in the process of sperm-egg fusion. The complexity and expected redundancy of the involved factors makes the process an intricate and still poorly understood mechanism, which is difficult to comprehend in its full distinction.


[Comparative effects of flavonoids on cell cycle passage and apoptosis induction in human acute lymphoblastic leukemia MT-4 cells].
In the present study, 8 flavonoids of three major flavonoid subgroups, namely flavones, flavonols and flavanones were tested for their cytotoxic and apoptogenic effects in human acute lymphoblastic leukemia MT-4 cells in vitro. Apoptotic cells were identified by DNA flow cytometric analysis. The effects of the flavonoids on the cell cycle patterns and activation of caspase-3 were also examined. Among the flavonoids tested, 7,8-benzoflavone, flavone, quercetin, chrysin, and galangine were shown to be effective apoptosis inducers. At concentrations corresponding to ED50, the flavonoids mentioned above exerted varying degrees of caspase-3 activation in MT-4 cells. The flavonoid-treated cells demonstrated different cell cycle profiles with accumulation in either G0/G1 (flavone, morin) or G2/M (7,8-benzoflavone, naringenin, quercetin, apigenin) phase. The induction of apoptosis did not correlate with phase-specific effects of flavonoid assayed. The relationship between chemical structure and apoptogenic activity of flavonoids tested is discussed.


Flagella and chemotaxis are required for efficient induction of Salmonella enterica serovar Typhimurium colitis in streptomycin-pretreated mice.
Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of gastrointestinal infections. The host's innate immune system and a complex set of Salmonella virulence factors are thought to contribute to enteric disease. The serovar Typhimurium virulence factors have been studied extensively by using tissue culture assays, and bovine infection models have been used to verify the role of these factors in enterocolitis. Streptomycin-pretreated mice provide an alternative animal model to study enteric salmonellosis. In this model, the Salmonella pathogenicity island 1 type III secretion system has a key virulence function. Nothing is known about the role of other virulence factors. We investigated the role of flagella in murine serovar Typhimurium colitis. A nonflagellated serovar Typhimurium mutant (fliGHI) efficiently colonized the intestine but caused little colitis during the early phase of infection (10 and 24 h postinfection). In competition assays with differentially labeled strains, the fliGHI mutant had a reduced capacity to get near the intestinal epithelium, as determined by fluorescence microscopy. A flagellated but nonchemotactic cheY mutant had the same virulence defects as the fliGHI mutant for causing colitis. In competitive infections, both mutants colonized the intestine of streptomycin-pretreated mice by day 1 postinfection but were outcompeted by the wild-type strain by day 3 postinfection. Together, these data demonstrate that flagella are required for efficient colonization and induction of colitis in streptomycin-pretreated mice. This effect is mostly attributable to chemotaxis. Recognition of flagellar subunits (i.e., flagellin) by innate immune receptors (i.e., Toll-like receptor 5) may be less important.


Relationship between orally administered dose, surface emission rate for gamma radiation, and urine radioactivity in radioiodine-treated hyperthyroid cats.
To determine the relationship between surface emission rate of gamma radiation and urine concentration of I131 (urine radioactivity) during the period 7 to 21 days after oral or SC administration of I131 to hyperthyroid cats. 47 hyperthyroid cats administered I131 PO and 24 hyperthyroid cats administered I131 SC. A dose of I131 (1.78 to 2.04 X 10(2) MBq [4.8 to 5.5 mCi]) was administered orally. Surface emission at the skin adjacent to the thyroid gland on days 7, 10, 14, 18, and 21 and number of counts/30 s in a urine sample (1 mL, obtained via cystocentesis) on days 7, 14, and 21 after oral administration were measured. Effective half-life (T1/2E) was derived for each point. Surface emission thresholds for maximum urine radioactivity values were established. A dose of I131 (1.48 X 10(2) MBq [4.0 mCi]) was administered SC. Urine radioactivity and surface emission rates for SC administration were compared with values for oral administration. The T1/2E for surface emissions and urine radioactivity progressively increased toward values for physical T1/2 over time. The T1/2E for surface emissions was 2.19 to 4.70 days, and T1/2E for urine radioactivity was 2.16 to 3.67 days. Surface emission rates had a clinically useful threshold relationship to maximum urine concentrations of I131. Surface emission rates for cats administered I131 appeared useful in determining upper limits (threshold) of urine radioactivity and are a valid method to assess the time at which cats can be discharged after I131 administration.


Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection.
Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this diverse infectious capability is not accompanied by extensive variation in genomic content, suggesting that the genetic capacity to be an acute or a chronic pathogen is present in most P. aeruginosa strains. To investigate the genetic requirements for acute and chronic pathogenesis in P. aeruginosa infections, we combined high-throughput sequencing-mediated transcriptome profiling (RNA-seq) and genome-wide insertion mutant fitness profiling (Tn-seq) to characterize gene expression and fitness determinants in murine models of burn and non-diabetic chronic wound infection. Generally we discovered that expression of a gene in vivo is not correlated with its importance for fitness, with the exception of metabolic genes. By combining metabolic models generated from in vivo gene expression data with mutant fitness profiles, we determined the nutritional requirements for colonization and persistence in these infections. Specifically, we found that long-chain fatty acids represent a major carbon source in both chronic and acute wounds, and P. aeruginosa must biosynthesize purines, several amino acids, and most cofactors during infection. In addition, we determined that P. aeruginosa requires chemotactic flagellar motility for fitness and virulence in acute burn wound infections, but not in non-diabetic chronic wound infections. Our results provide novel insight into the genetic requirements for acute and chronic P. aeruginosa wound infections and demonstrate the power of using both gene expression and fitness profiling for probing bacterial virulence.


Cost Estimates for Designing and Implementing a Novel Team Care Model for Chronically Ill Patients.
Little is known about the cost of implementing chronic care models. We estimate the human resource cost of implementing a novel team-based chronic care model "Champion," at a large multispecialty group practice. We used activity-based costing to calculate costs from development through rollout and stabilization in 1 clinic with 12 000 chronic care patients. Data analyzed included Microsoft Outlook meeting metadata, supporting documents, and 2014 employee wages. Implementation took more than 29 months, involved 168 employees, and cost the organization $2 304 787. Payers may need to consider a mixed-payment model to support the both implementation and maintenance costs of team-based chronic care.


Does rapid volume loading during transesophageal echocardiography differentiate constrictive pericarditis from restrictive cardiomyopathy?
Respiratory variation of the pulmonary venous (PV) peak flow velocities can be used to distinguish constrictive pericarditis (constriction) from restrictive cardiomyopathy (restriction). Rapid volume expansion has been used successfully to enhance diastolic pressure equalization in occult constriction. The effect of volume on the respiratory variation in constriction has not been studied previously. This study assessed the utility of volume in enhancing the PV respiratory variation of constriction to further separate it from restriction. The study population consisted of 15 patients referred to the echocardiography laboratory for further evaluation of clinically suspected diastolic dysfunction. Pulsed-Doppler transesophageal echocardiography (TEE) of the left or right upper pulmonary vein and mitral inflow was performed with respiratory monitoring before and after infusion of 1 liter of normal saline over 5 to 10 minutes. The classification of patients as constriction (n = 8) or restriction (n = 7) was confirmed independently by cardiac catheterization or surgery. Peak velocities of the PV systolic and diastolic waves and the mitral inflow E were measured during inspiration and expiration. A mean of 3-6 respiratory cycles was obtained for each value before and after volume loading. The percent change from expiration to inspiration (%E) was calculated using the formula %E = expiration - inspiration / expiration. At baseline, patients with constrictive pericarditis can be separated reliably from those with restrictive cardiomyopathy based on a higher systolic/diastolic ratio and greater respiratory variation of their PV diastolic flow velocity. There were no complications in any patient due to volume expansion. Although the change from baseline to volume expansion was not statistically significant in either constriction or restriction, the %E of the PV diastolic wave became significantly higher in constriction than in restriction (P < 0.05). Rapid volume expansion is relatively safe during TEE and can be used for further separation of constrictive pericarditis from restrictive cardiomyopathy by significantly enhancing the respiratory variation of the PV diastolic flow velocity in constrictive pericarditis.


A literature review of economic evaluations for a neglected tropical disease: human African trypanosomiasis ("sleeping sickness").
Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and key funders. These analyses would be of use, as HAT is currently being prioritized as a neglected tropical disease (NTD) to reach elimination by 2020.