Calcium channel blockers correct acidosis in ischemic rat brain without altering cerebral blood flow.
We compared the effects of intravenous infusions of 40 micrograms/kg/min verapamil (n = 5), 0.5 microgram/kg/min nimodipine (n = 5), and 5 ng/kg/min prostacyclin (n = 6) and no treatment (n = 6) on local cerebral pH and local cerebral blood flow in middle cerebral artery-occluded rats 90 minutes after the ischemic insult. Local cerebral pH and local cerebral blood flow were determined simultaneously by a double-label autoradiographic technique. The infusions were started 15 minutes after completion of the occlusion and ended at decapitation 90 minutes after completion of the occlusion. Cortical pH for four regions in the ischemic middle cerebral artery territory of rats receiving verapamil or nimodipine was normalized (mean +/- SEM 6.90 +/- 0.02 and 7.01 +/- 0.01, respectively, for the parietal, sensorimotor, frontal, and auditory cortexes), while mean +/- SEM pH in rats receiving prostacyclin was 6.79 +/- 0.01; in untreated rats, mean +/- SEM pH in the same brain regions was 6.72 +/- 0.01. Local cerebral pH in the verapamil- or nimodipine-treated rats was thus significantly different from that in untreated rats (p less than 0.05). Local cerebral blood flow in treated rats was not different from that in untreated ones. Our findings suggest that calcium channel blockers correct ischemic cerebral acidosis by metabolic mechanisms rather than by changes in blood flow.


Structure of mouse IP-10, a chemokine.
Interferon-gamma-inducible protein (IP-10) belongs to the CXC class of chemokines and plays a significant role in the pathophysiology of various immune and inflammatory responses. It is also a potent angiostatic factor with antifibrotic properties. The biological activities of IP-10 are exerted by interactions with the G-protein-coupled receptor CXCR3 expressed on Th1 lymphocytes. IP-10 thus forms an attractive target for structure-based rational drug design of anti-inflammatory molecules. The crystal structure of mouse IP-10 has been determined and reveals a novel tetrameric association. In the tetramer, two conventional CXC chemokine dimers are associated through their N-terminal regions to form a 12-stranded elongated beta-sheet of approximately 90 A in length. This association differs significantly from the previously studied tetramers of human IP-10, platelet factor 4 and neutrophil-activating peptide-2. In addition, heparin- and receptor-binding residues were mapped on the surface of IP-10 tetramer. Two heparin-binding sites were observed on the surface and were present at the interface of each of the two beta-sheet dimers. The structure supports the formation of higher order oligomers of IP-10, as observed in recent in vivo studies with mouse IP-10, which will have functional relevance.


Effects of gamma-irradiation on biosynthesis of different types of ribonucleic acids in normal and regenerating rat liver.
1. The effect of gamma-irradiation (4000rd) on the synthesis of ribosomal (pre-rRNA) and heterogeneous nuclear RNA (pre-mRNA) in normal and in regenerating rat liver was studied by using 40 min labelling with [6(-14)C]orotic acid. 2. Partial hepatectomy caused a sharp transient increase in the specific radioactivity of the endogenous low-molecular-weight RNA precursors in the livers of both normal and irradiated rats. Irradiation of intact animals did not affect the pool. 3. Irradiation enhanced the synthesis of pre-rRNA for at least 12h. The synthesis of pre-mRNA was also enhanced, but only in the first 3h after irradiation. 4. Partial hepatectomy strongly stimulated the synthesis of both pre-rRNA and pre-mRNA. 5. The synthesis of pre-rRNA was enhanced also in regenerating liver of animals irradiated before or after the operation. The conclusion can be drawn that the early increase in the synthesis of ribosomal RNA is a non-specific cellular response to different injuring factors. 6. The only case where irradiation caused an early inhibition of RNA synthesis was that of pre-mRNA in regenerating liver. This supports the hypothesis that ionizing radiation does not suppress the transcription per se but affects the mechanisms of activation of new genes (cellular programming).


Long-term water quality monitoring in agricultural catchments in Sweden: Impact of climatic drivers on diffuse nutrient loads.
Water quality related to non-point source pollution continues to pose challenges in agricultural landscapes, despite two completed cycles of Water Framework Directive actions by farmers and landowners. Future climate projections will cause new challenges in landscape hydrology and subsequently, the potential responses in water quality. Investigating the nutrient trends in surface waters and studying the efficiency of mitigation measures revealed that loads and measures are highly variable both spatially and temporally in catchments with different agro-climatic and environmental conditions. In Sweden, nitrogen and phosphorus loads in eight agricultural catchments (470-3300 ha) have been intensively monitored for >20 years. This study investigated the relationship between precipitation, air temperature, and discharge patterns in relation to nitrogen (N) and phosphorus (P) loads at catchment outlets. The time series data analysis was carried out by integrating Mann-Kendall test, Pettitt break-points, and Generalized Additive Model. The results showed that the nutrient loads highly depend on water discharge, which had large variation in annual average (158-441 mm yr-1). The annual average loads were also considerably different among the catchments with total N (TN) loads ranging from 6.76 to 35.73 kg ha-1, and total P (TP) loads ranging from 0.11 to 1.04 kg ha-1. The climatic drivers were highly significant indicators of nutrient loads but with varying degree of significance. Precipitation (28-962 mm yr-1) was a significant indicator of TN loads in five catchments (loamy sand/sandy loam) while annual average temperature (6.5-8.7 °C yr-1) was a significant driver of TN loads in six out of eight catchments. TP loads were associated with precipitation in two catchments and significantly correlated to water discharge in six catchments. Considering the more frequent occurrence of extreme weather events, it is necessary to tailor N and P mitigation measures to future climate-change features of precipitation, temperature, and discharge.


The Role of Personal Risk Experience-An Investigation of Health and Terrorism Risk Perception in Germany and Israel.
The present study examined the relationship between risk experience and risk perceptions in relation to the target (risk to the self vs. others) and for two different types of risk: acute risks (i.e., terrorist attacks) and cumulative health risks (i.e., alcohol consumption, tobacco consumption, and unhealthy eating) in two countries (Israel and Germany). An online survey (N = 571) was conducted to assess participants' previous personal experience with acute and cumulative risks and their personal and general risk perceptions. The results showed that personal experience with terrorism was related to increased personal and general risk perceptions, while personal experience with cumulative health risks was related to increased personal but not general risk perceptions. It is argued that an increase in risk perception with more risk experience can be explained by the amount of available information about people's personal as well as other people's risk status. The findings emphasize that the experience-risk perception relationship depends on the target of the risk and the type of risk experience.


Radiotherapy planning for glioblastoma based on a tumor growth model: implications for spatial dose redistribution.
Gliomas differ from many other tumors as they grow infiltratively into the brain parenchyma rather than forming a solid tumor mass with a well-defined boundary. Tumor cells can be found several centimeters away from the central tumor mass that is visible using current imaging techniques. The infiltrative growth characteristics of gliomas question the concept of a radiotherapy target volume that is irradiated to a homogeneous dose-the standard in current clinical practice. We discuss the use of the Fisher-Kolmogorov glioma growth model in radiotherapy treatment planning. The phenomenological tumor growth model assumes that tumor cells proliferate locally and migrate into neighboring brain tissue, which is mathematically described via a partial differential equation for the spatio-temporal evolution of the tumor cell density. In this model, the tumor cell density drops approximately exponentially with distance from the visible gross tumor volume, which is quantified by the infiltration length, a parameter describing the distance at which the tumor cell density drops by a factor of e. This paper discusses the implications for the prescribed dose distribution in the periphery of the tumor. In the context of the exponential cell kill model, an exponential fall-off of the cell density suggests a linear fall-off of the prescription dose with distance. We introduce the dose fall-off rate, which quantifies the steepness of the prescription dose fall-off in units of Gy mm(-1). It is shown that the dose fall-off rate is given by the inverse of the product of radiosensitivity and infiltration length. For an infiltration length of 3 mm and a surviving fraction of 50% at 2 Gy, this suggests a dose fall-off of approximately 1 Gy mm(-1). The concept is illustrated for two glioblastoma patients by optimizing intensity-modulated radiotherapy plans. The dose fall-off rate concept reflects the idea that infiltrating gliomas lack a defined boundary and are characterized by a continuous fall-off of the density of infiltrating tumor cells. The approach can potentially be used to individualize the prescribed dose distribution if better methods to estimate radiosensitivity and infiltration length on a patient by patient basis become available.


Control of zoonoses in Britain: past, present, and future.
In the past zoonoses that caused serious human illness also caused serious loss of animal production, but there is growing awareness of the public health problems arising from infections that cause little or no such loss. Much can be learnt from the history of the control of bovine tuberculosis and brucellosis. In both cases there was reluctance to accept that animals were the principal cause of infection, and the earliest attempts at control failed because measures were taken only against clinical cases of the disease. The essential features in control of both infections were: official recognition of a problem, willingness of governments to allocate resources, and cooperation between the medical and veterinary professions. Salmonellosis is the most important zoonotic infection in Britain today, though several Orders have reduced the reservoir of infection in food animals. It is suggested that a national team of doctors should be set up to investigate and control zoonoses, that this team should be answerable to a central agency, and that it should build up close working relationships with the nominated officers of the veterinary profession.


[Bony metaplasia of the endometrium. Report of two cases].
We report a 28 year old female consulting for infertility and a 26-year-old woman consulting for severe dysmenorrhea. In both patients a osseous metaplasia of the endometrium was found. Both patients were subjected to a hysteroscopic resection of the osseous material and both achieved spontaneous pregnancies and term deliveries following the procedures. If the bony material is removed, normal pregnancies and deliveries are feasible afterwards, no matter how extensive is the the osseus metaplasia.


Quitting-unmotivated and quitting-motivated cigarette smokers exhibit different patterns of cue-elicited brain activation when anticipating an opportunity to smoke.
The authors examined the effects of smoking expectancy on cue-reactivity among those motivated and those unmotivated to quit smoking using functional MRI. Cue-elicited activation was observed in the rostral prefrontal cortex (PFC) in smokers who expected to smoke within seconds, but not in those who expected to have to wait hours before having the chance to smoke, regardless of quitting motivation. For quitting-unmotivated smokers expecting to smoke, rostral PFC activation was strongly positively correlated with the activation of several areas previously linked to cue-reactivity, including the medial orbitofrontal cortex (OFC) and rostral anterior cingulate cortex (ACC). In contrast, there was a nonsignificant negative relationship between activation of the rostral PFC and activation of the medial OFC/rostral ACC in quitting-motivated smokers expecting to smoke. Results extend previous work examining the effects of smoking expectancy and highlight the utility of examining interregional covariation during cue exposure. Findings also suggest that investigators may need to pay close attention to the motivational contexts associated with their experiments when studying cue-reactivity, as these contexts can modulate not only responses to drug cues, but perhaps also the functional implications of observed activity.


Microwaves and the cell membrane. II. Temperature, plasma, and oxygen mediate microwave-induced membrane permeability in the erythrocyte.
Microwaves (2450 MHz) are shown to increase 22Na permeability of rabbit erythrocytes for exposures only within the narrow temperature range of 17.7 to 19.5 degrees C (Tc) which coincides with a nonlinearity in the Arrhenius plot reflecting an apparent membrane phase transition. Significantly, this response is not observed for cholesterol-loaded erythrocyte membranes which exhibit a linear Arrhenius plot and no apparent phase transition at Tc. The permeability increase at Tc is a nonlinear function of absorbed power but is a linear function of the internal electric field strength of the sample and saturates at approximately 400 mW/g and 600 V/m, respectively. The permeability increase was found to be reversible and transient in that immediately following termination of exposure sodium influx is significantly reduced but returns to normal within 60 min. Extracellular factors exert a significant influence on the microwave effect. The presence of plasma markedly potentiates the increase in 22Na permeability at Tc. Oxygen also modulates the microwave effect with relative hypoxia (5 mm Hg) and hyperoxia (760 mm Hg) enhancing the permeability increase. In contrast, the presence of two antioxidants, ascorbic acid or mercaptoethanol, inhibits the effect. These findings raise important questions about the physical and chemical nature of microwave interactions with cell membranes and also shed light on earlier studies reporting either positive or negative effects on membrane permeability.


Race and Hepatitis C Care Continuum in an Underserved Birth Cohort.
Birth cohort screening is recommended for hepatitis C virus (HCV) and underserved populations are disproportionally affected by HCV. Little is known about the influence of race on the HCV care continuum in this population. To assess the cascade of HCV care in a large racially diverse and underserved birth cohort. Retrospective cohort study using electronic medical record data abstracted until August 31, 2017. 34,810 patients born between 1945 and 1965 engaged in primary care between October 1, 2014, and October 31, 2016, within the safety-net clinics of the San Francisco Health Network. Rate of hepatitis C testing, hepatitis C treatment, and response to therapy. Cohort characteristics were as follows: median age 59 years, 57.6% male, 25.5% White (20.6% Black, 17.7% Latino, 33.0% Asian/Pacific Islander (API), 2% other), and 32.6% preferred a non-English language. 99.7% had an HCV test (95.4% HCV antibody, 4.3% HCVRNA alone). Among HCV antibody-positive patients (N = 4587), 22.9% were not tested for confirmatory HCVRNA. Among viremic patients (N = 3673), 20.8% initiated HCV therapy, 90.6% achieved sustained virologic response (SVR) and 8.1% did not have a SVR test. HCV screening and treatment were highest in APIs (98.7 and 34.7% respectively; p < 0.001). Blacks had the highest chronic HCV rate (22.2%; p < 0.001). Latinos had the lowest SVR rate (81.3%; p = 0.01). On multivariable analysis, API race (vs White, OR 1.20; p = 0.001), presence of HIV co-infection (OR 1.58; p = 0.02), presence of chronic kidney disease (OR 0.47; p < 0.001), English (vs non-English) as preferred language (OR 0.54; p = 0.002), ALT (OR 0.39 per doubling; p < 0.001), and HCVRNA (OR 0.83 per 10-fold increase; p < 0.001) were associated with HCV treatment. Despite near-universal screening, gaps in active HCV confirmation, treatment, and verification of cure were identified and influenced by race. Tailored interventions to engage and treat diverse and underserved populations with HCV infection are needed.


Parafoveal vessel changes in primary open-angle glaucoma and normal-tension glaucoma using optical coherence tomography angiography.
To evaluate parafoveal and peripapillary perfusion in healthy, glaucoma suspect, normal-tension glaucoma, and primary open-angle glaucoma subjects. This was a retrospective cross-sectional study with optical coherence tomography angiography imaging with RTVue XR Avanti (Optovue, Inc., Fremont, CA) of 56 eyes (14 healthy, 14 glaucoma suspect, 16 normal-tension glaucoma, and 12 primary open-angle glaucoma) at a tertiary academic referral center. Parafoveal and peripapillary superficial vessel density and parafoveal superficial retinal thickness were the main parameters of interest. Area under receiver operating characteristic curves were calculated. There were significant decreases in parafoveal superficial vessel density in primary open-angle (40.06±4.54%, P<0.001) and normal-tension glaucoma (42.82±5.16%, P=0.010) but not suspect eyes (45.72±4.37%, P=0.916) compared to healthy eyes (48.10±2.82%). Similarly, decreases were observed in parafoveal inner retinal thickness in primary open-angle (83.19±14.29 μm, P<0.001) and normal-tension glaucoma eyes (94.97±12.44 μm, P=0.035), but not suspect eyes (99.93±9.00 μm, P=0.648), compared to healthy controls (107.00±9.55 μm). Only primary open-angle glaucoma eyes displayed significant changes in peripapillary vessel density (37.63±7.19%) compared to healthy controls (49.12±2.80%, P<0.001). Further statistical adjustment for sex and age revealed a significant decrease in parafoveal vessel density in suspects relative to controls (P=0.039). Diagnostic accuracy of parafoveal vessel density was high with an area under the curve of 0.833±0.073 for normal-tension glaucoma and 0.946±0.049 for primary open-angle glaucoma. Parafoveal vessel density was significantly reduced in glaucomatous eyes, with good diagnostic accuracy. These findings provide further evidence that these changes may be useful in the diagnosis and monitoring of disease in glaucoma patients.


Implementing primary care diabetes prevention for women with previous gestational diabetes: a mixed-methods study.
The implementation of diabetes prevention for women with previous gestational diabetes (GDM) has been stymied by many barriers that are located within routine general practice (GP). We aimed to unpack the GP factors and understand the mechanisms that explain why a diabetes prevention intervention for this population succeeds or fails. We performed a mixed-methods study with a Normalization Process Theory framework that included clinical audits, semistructured interviews, and focus groups within mixed urban and rural primary care practices in Victoria, Australia. Staff of primary care practices and external support staff who provide services to women with previous GDM participated in a 12-month quality improvement collaborative intervention. We compared diabetes screening and prevention activity planning with the strategies and factors identified through a process evaluation of full-, moderate-, and low-active participating practices. The intervention doubled screening rates (26%-61%) and 1-in-10 women received a diabetes prevention planning consultation. Critical improvement factors were: mothers being seen as participants in the quality improvement work; staff collectively building care strategies; staff taking a long-term care of a community perspective rather than episodic service delivery; and feedback processes being provided and acted on across the practice. The observable factors from the external perspective were: leadership by identified practice staff, reminder systems in action and practice staff driving the process collectively. Successful engagement in diabetes prevention for women with previous GDM requires proactive building of the critical improvement factors and audit feedback into routine GP.


Magnetic Particle Imaging for Real-Time Perfusion Imaging in Acute Stroke.
The fast and accurate assessment of cerebral perfusion is fundamental for the diagnosis and successful treatment of stroke patients. Magnetic particle imaging (MPI) is a new radiation-free tomographic imaging method with a superior temporal resolution, compared to other conventional imaging methods. In addition, MPI scanners can be built as prehospital mobile devices, which require less complex infrastructure than computed tomography (CT) and magnetic resonance imaging (MRI). With these advantages, MPI could accelerate the stroke diagnosis and treatment, thereby improving outcomes. Our objective was to investigate the capabilities of MPI to detect perfusion deficits in a murine model of ischemic stroke. Cerebral ischemia was induced by inserting of a microfilament in the internal carotid artery in C57BL/6 mice, thereby blocking the blood flow into the medial cerebral artery. After the injection of a contrast agent (superparamagnetic iron oxide nanoparticles) specifically tailored for MPI, cerebral perfusion and vascular anatomy were assessed by the MPI scanner within seconds. To validate and compare our MPI data, we performed perfusion imaging with a small animal MRI scanner. MPI detected the perfusion deficits in the ischemic brain, which were comparable to those with MRI but in real-time. For the first time, we showed that MPI could be used as a diagnostic tool for relevant diseases in vivo, such as an ischemic stroke. Due to its shorter image acquisition times and increased temporal resolution compared to that of MRI or CT, we expect that MPI offers the potential to improve stroke imaging and treatment.


Prolonged airway retention of insoluble particles in cystic fibrosis versus primary ciliary dyskinesia.
Patients with cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) have been shown to have impaired large airway clearance of radiolabelled particles as measured by external gamma camera scanning up to 6 hours post deposition. Recent studies suggest that 24-hour retention of particles may reflect some airway retention in addition to alveolar retention. In a retrospective study, we analyzed the relationship between the deposition pattern and 24-hour retention (Ret24 hr) of technetium 99-radiolabelled iron oxide (99Tc-Fe2O3) particles in 20 patients with CF, 12 patients with PCD, and 17 normal subjects. By gamma camera analysis, initial aerosol deposition was analyzed in terms of central-peripheral (C/P) activity within the lungs. Gamma camera scanning was performed immediately following deposition and again at 24 hours to assess residual retention (Ret24 hr) as a percent of initial deposition. C/P analysis was also performed on the 24-hour scan (C/P24). For all subjects, initial deposition pattern (C/P) was inversely related to lung function (forced expiratory volume in 1 second [FEV1]%pred vs. C/P, r = -.54). Ret24 hr was also inversely related to initial deposition pattern for all subjects (Ret24 hr vs. C/P ratio, r = -.42). Analysis of covariance showed that for a given C/P ratio, CF patients had significantly greater Ret24 hr compared to normal subjects (9.8 +/- 2.8 [SE]%). In addition, the CF patients had similar C/P24 as the normal subjects (1.35 +/- 0.40 [SD] vs. 1.10 +/- 0.39, respectively). These results suggest that small airway clearance is compromised in CF patients compared to normal subjects. On the other hand, PCD patients had C/P24 similar to their initial deposition C/P ratios (2.78 +/- 1.72 vs. 2.45 +/- 0.87, respectively), significantly greater than 1.0, and significantly greater than CF or normal subjects, suggesting that PCD patients have prolonged particle retention associated with their large bronchial airways.


Drug use and intimate partner violence among college students: an in-depth exploration.
College students experience an extremely high level of violence among intimate partners during their college careers, with prevalence rates ranging between 20% and 50%. Because intimate partner violence (IPV) among college students is such a widespread problem, it is important to understand the factors that contribute to this type of abuse. Studies using a variety of samples demonstrate that drug use is one such factor. However, research to date fails to identify specific types of drugs linked to college students' use of violence against intimates. In an attempt to fill this void, this exploratory study uses data from the Relationship Characteristics Study, which was conducted in 2001 and includes a sample of 1,938 college students, to provide a more comprehensive understanding of the relationship between college students' drug use and IPV perpetration than the current literature allows.


A Simple Field Tapping Test for Evaluating Frequency Qualities of the Lower Limb Neuromuscular System in Soccer Players: A Validity and Reliability Study.
Over the years, the foot tapping test protocol has been proposed by scientists to identify the capabilities of the lower limb neuromuscular system in the medical context; however, to our knowledge, no studies have established its usefulness and relationship to athletic performance. The aim of the present study was to test the reliability, criterion validity and sensitivity of a new foot tapping (TAP) test, and to examine its relationship with proxies of athletic performance in soccer players. Forty voluntary soccer players of two different levels participated in this study (20 players from the national level: age: 22.6 ± 2.5 years and 20 players from regional level: 25.1 ± 3.6 years). They performed the TAP test on two separate occasions to test its relative and absolute reliability. To examine the criterion validity of the TAP test, all participants performed four types of jumps, sprint tests, agility tests, the Wingate test and the finger tapping test considered a gold standard tapping test. The sensitivity was assessed with national and regional player levels. The TAP test presented a high relative and absolute reliability with intra-class correlation coefficient ICC > 0.90, standard errors of measurement SEM < 5% and mean difference ±95% limits of agreement equal to 0.2 ± 0.8 tap·s−1. National level players showed a higher TAP score (p < 0.001; dz = 1.96, large) compared to regional players (9.68 ± 1.41 tap·s−1 vs. 7.28 ± 1.01 tap·s−1, respectively) and the value of area under curve measured by the receiver operating characteristic curve technique was 0.95 (95% CI: 0.827−0.990). The TAP test showed a significant association with the finger tapping test (r = 0.84, p < 0.001), whereas no correlation was seen between the TAP test and all the other physical tests measured. The TAP test could be considered a valid and reliable test to assess lower limb neuromuscular ability in soccer players.


Ki67 index changes, pathological response and clinical benefits in primary breast cancer patients treated with 24 weeks of aromatase inhibition.
Aromatase inhibitor shows efficacy for hormone receptor positive postmenopausal breast cancer. We evaluated the activity of 24 weeks of aromatase inhibition with exemestane for primary breast cancer in a neoadjuvant setting. Patients with stage II/IIIA invasive breast cancer with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive status were eligible. Primary endpoints were objective response rate (ORR) and safety. A steroidal aromatase inhibitor exemestane of 25 mg/day was administered for 16 weeks with an 8-week extension. Secondary endpoints were rates of breast-conserving surgery (BCS), and change of Ki67 index and ER/PgR expression in central laboratory analyses. Between March 2006 and December 2007, 116 patients were enrolled. Among those, 102 patients completed 24 weeks of administration. The ORR was 47% (55/116) at Week 16 and 51% (59/116) at Week 24, respectively. No serious toxicity was seen. ORR was associated with ER Allred scores but not with PgR scores. The significant reduction in Ki67 index was confirmed. No progression was experienced in tumors with less than 15% Ki67 index. Pathological response was observed in 28 (30%) of 94 evaluated cases. No statistical correlation between pre-treatment Ki67 index and pathological response was detected; however, a trend of correlation was found between the post-treatment preoperative endocrine prognostic index (PEPI), a prognostic score and the pathological response. At diagnosis, 59 patients (51%) would have required mastectomy but 40 patients were converted to BCS, showing an increase in the rate of BCS (77%). The 24-week aromatase inhibition provided preferable clinical benefits with significant reduction in Ki67 index. More precise mechanisms of the response need to be investigated.


Regulation of gastric and pancreatic lipase secretion by CCK and cholinergic mechanisms in humans.
Gastric lipase (HGL) contributes significantly to fat digestion. However, little is known about its neurohormonal regulation in humans. We studied the role of CCK and cholinergic mechanisms in the postprandial regulation of HGL and pancreatic lipase (HPL) secretion in six healthy subjects. Gastric emptying of a mixed meal and outputs of HGL, pepsin, acid, and HPL were determined with a double-indicator technique. Three experiments were performed in random order: intravenous infusion of 1) placebo, 2) low-dose atropine (5 micrograms.kg-.h-1), and 3) the CCK-A receptor antagonist loxiglumide (22 mumol.kg-.h-1). Atropine decreased postprandial outputs of HGL, pepsin, gastric acid, and HPL (P < 0.03) while slowing gastric emptying (P < 0.05). Loxiglumide markedly increased the secretion of HGL, pepsin, and acid while distinctly reducing HPL outputs and accelerating gastric emptying (P < 0.03). Plasma CCK and gastrin levels increased during loxiglumide infusion (P < 0.03). Atropine enhanced gastrin but not CCK release. Postprandial HGL, pepsin, and acid secretion are under positive cholinergic but negative CCK control, whereas HPL is stimulated by cholinergic and CCK mechanisms. We conclude that CCK and cholinergic mechanisms have an important role in the coordination of HGL and HPL secretion to optimize digestion of dietary lipids in humans.


Copper-zinc superoxide dismutase prevents the early decrease of apurinic/apyrimidinic endonuclease and subsequent DNA fragmentation after transient focal cerebral ischemia in mice.
DNA damage and its repair mechanism are thought to be involved in ischemia/reperfusion injury in the brain. We have previously shown that apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, rapidly decreased after transient focal cerebral ischemia (FCI) before the peak of DNA fragmentation. To further investigate the role of reactive oxygen species in APE/Ref-1 expression in vivo, we examined the expression of APE/Ref-1 and DNA damage after FCI in wild-type and transgenic mice overexpressing copper-zinc superoxide dismutase. Transgenic mice overexpressing copper-zinc superoxide dismutase and wild-type littermates were subjected to 60 minutes of transient FCI by intraluminal blockade of the middle cerebral artery. APE/Ref-1 protein expression was analyzed by immunohistochemistry and Western blot analysis. DNA damage was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL). A similar level of APE/Ref-1 was detected in the control brains from both groups. APE/Ref-1 was significantly reduced 1 hour after transient FCI in both groups, whereas the transgenic mice had less reduction than that seen in wild-type mice 1 and 4 hours after FCI. DNA laddering was detected 24 hours after FCI and was decreased in transgenic mice. Double staining with APE/Ref-1 and TUNEL showed that the neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive. These results suggest that reactive oxygen species contribute to the early decrease of APE/Ref-1 and thereby exacerbate DNA fragmentation after transient FCI in mice.


An lrp-like gene of Bacillus subtilis involved in branched-chain amino acid transport.
The azlB locus of Bacillus subtilis was defined previously by a mutation conferring resistance to a leucine analog, 4-azaleucine (J. B. Ward, Jr., and S. A. Zahler, J. Bacteriol. 116:727-735, 1973). In this report, azlB is shown to be the first gene of an operon apparently involved in branched-chain amino acid transport. The product of the azlB gene is an Lrp-like protein that negatively regulates expression of the azlBCDEF operon. Resistance to 4-azaleucine in azlB mutants is due to overproduction of AzlC and AzlD, two novel hydrophobic proteins.


[Physiologically active argon-based gas mixtures as a means of creating fire-safe gaseous environments in pressurized modules of varying purpose].
Development of acute hypoxic hypoxia in consequence of fire in various pressurized modules was studied. The investigation was aimed to look into the effects of inert argon and dramatic oxygen reduction in gaseous environment on animals (Wistar rats, mice c57bl/6, balb/c and f1cbaxbalb/c hybrids, Japanese quail embryos) and microorganism (Escherichia coli strains k-12 jf 238 and k-12 jm 83). Also, inflammability of some widely used materials was assessed in order to provide inputs to developers of fire-safe gaseous mixtures for pressurized habitats. It was shown that argon is favorable to survivability of animals and to maintenance of a high level of oxygen consumption. Gaseous mixtures with oxygen content less than 15 volume % suppressed burning of selected materials. Results of the investigation offer possibilities for designing new hypoxic fire-safe gas mixtures that will provide adequate human performance and ensure survival in extreme situations.


The validity of compliance monitors to assess wearing time of thoracic-lumbar-sacral orthoses in children with spinal cord injury.
Prospective multicenter observation. To determine the validity of 3 commercially available at recording thoracic-lumbar-sacral orthosis (TLSO) wearing time of children with spinal cord injury (SCI) and to assess each monitor's function during daily activities. A major limitation to studies assessing the effectiveness of spinal prophylactic bracing is the patient's compliance with the prescribed wearing time. Although some studies have begun to use objective compliance monitors, there is little documentation of the validity of the monitors during activities of daily life and no comparisons of available monitors. Fifteen children with SCI who wore a TLSO for paralytic scoliosis were observed for 4 days during their rehabilitation stay. Three compliance monitors (2 temperature and 1 pressure sensitive) were mounted onto each TLSO. Time of brace wear from the monitors was compared with the wear time per day recorded in diaries. Observed versus monitored duration of brace wear found the HOBO (temperature sensitive) to be the most valid compliance monitor. The HOBO had the lowest average of difference and variance of difference scores. The correlation between the recorded daily entries and monitored brace wear time was also highest for the HOBO in analysis of dependent and independent scores. Bland-Altman plots showed that the pressure sensitive monitor underestimated wear time whereas the temperature monitors overestimated wear time. Compliance to prescribed wearing schedule has been a barrier to studying TLSO efficacy. All 3 monitors were found to measure TLSO compliance, but the 2 temperature monitors were more in agreement with the daily diaries. Based on its functional advantages compared with the HOBO, the StowAway TidbiT will be used to further investigate the long-term compliance of TLSO bracing in children with SCI.


A Tetratricopeptide Repeat Protein Regulates Carotenoid Biosynthesis and Chromoplast Development in Monkeyflowers (Mimulus).
Little is known about the factors regulating carotenoid biosynthesis in flowers. Here, we characterized the REDUCED CAROTENOID PIGMENTATION2 (RCP2) locus from two monkeyflower (Mimulus) species, the bumblebee-pollinated species Mimulus lewisii and the hummingbird-pollinated species Mimulus verbenaceus We show that loss-of-function mutations of RCP2 cause drastic down-regulation of the entire carotenoid biosynthetic pathway. The causal gene underlying RCP2 encodes a tetratricopeptide repeat protein that is closely related to the Arabidopsis (Arabidopsis thaliana) REDUCED CHLOROPLAST COVERAGE proteins. RCP2 appears to regulate carotenoid biosynthesis independently of RCP1, a previously identified R2R3-MYB master regulator of carotenoid biosynthesis. We show that RCP2 is necessary and sufficient for chromoplast development and carotenoid accumulation in floral tissues. Simultaneous down-regulation of RCP2 and two closely related paralogs, RCP2-L1 and RCP2-L2, yielded plants with pale leaves deficient in chlorophyll and carotenoids and with reduced chloroplast compartment size. Finally, we demonstrate that M. verbenaceus is just as amenable to chemical mutagenesis and in planta transformation as the more extensively studied M. lewisii, making these two species an excellent platform for comparative developmental genetics studies of closely related species with dramatic phenotypic divergence.


Low-level pyrene exposure causes cardiac toxicity in zebrafish (Danio rerio) embryos.
It is widely accepted that the most abundant polycyclic aromatic hydrocarbons (PAHs) in weathered crude oils is cardiotoxic. Although PAHs toxic endpoints show strong correlation with the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor, and is thought to be a potent inducer of cytochrome P4501A, the action mechanism of PAHs on vertebrate cardiovascular development and disease is unclear. Herein, we address the cardiac developmental effects of exposure to the weak AhR agonist pyrene on the early life-stages of zebrafish. Embryos were exposed to 0, 0.05, 0.5, 5, and 50 nmol/L pyrene up to 72h post-fertilization (hpf). Pyrene-treated embryos showed dose-dependent heart abnormalities, such as pericardial edema and cardiac looping defects. Changes in AhR1a, AhR1b, AhR2, and Cyp1A expression were assessed by real-time RT-PCR. The results showed that low-level pyrene failed to alter these genes expression. However, the homeodomain transcription factor Nkx2.5, which plays an essential role in the development of the cardiovascular system, was down-regulated in a dose-dependent manner by pyrene exposure. The bone morphogenetic protein 2b (Bmp2b), which has been identified as the upstream gene of Nkx2.5, also was inhibited in a dose-dependent manner after treatment with pyrene. Taken together, these data indicated that embryonic exposure of zebrafish to low-level environmental pyrene disrupt normal cardiac development and alter expression of defective cardiac differentiation related genes.


The Clinicopathological Features and Prognostic Significance of HER2-Low in Early Breast Tumors Patients Prognostic Comparison of HER-Low and HER2-Negative Breast Cancer Stratified by Hormone Receptor Status.
There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p = 0.008). Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses.


A review of Shamosuchus and Paralligator (Crocodyliformes, Neosuchia) from the Cretaceous of Asia.
The crocodyliform Shamosuchus is known from numerous Late Cretaceous localities in southern and eastern Mongolia and fragmentary remains from Uzbekistan. Seven species of Shamosuchus have been named from six localities in Mongolia and three in Uzbekistan. Six species originally described as Paralligator were later referred to Shamosuchus. Only the type species, Shamosuchus djadochtaensis has been examined in detail. Many of the named species of Shamosuchus show striking similarity in size and cranial morphology but most are based on partial remains suggesting that the true species diversity is overestimated. A review of all species referred to Shamosuchus recognizes three valid taxa: Shamosuchus djadochtaensis, S. gradilifrons, and S. major. Shamosuchus sungaricus, S. borealis, and S. karakalpakensis are nomena dubia, whereas S. ancestralis, S. ulgicus, S. tersus, and S. ulanicus are junior subjective synonyms of S. gradilifrons. Phylogenetic analysis of 318 phenotypic characters recovers a Paralligatoridae clade consisting of Shamosuchus, Rugosuchus, Batrachomimus, Glen Rose Form, and Wannchampsus. Shamosuchus is non-monophyletic: S. djadochtaensis is near the base of Paralligatoridae whereas S. gradilifrons + S. major are the most deeply nested. The name Paralligator is resurrected for this clade. Rugosuchus and Batrachomimus are sister taxa to Paralligator. Paralligatoridae is closely related to Theriosuchus, hylaeochampsids and a speciose Allodaposuchus clade, which together are the sister group of Borealosuchus plus Crocodylia. These results support the presence of a diverse clade in eastern Asia and western North America throughout the Cretaceous with origins in the Late Jurassic.


Behavioral side effects of prophylactic therapies against soman-induced seizures and lethality in rats.
Four medical therapies previously shown to exert varying degrees of protection against a convulsant dose of soman were assessed for potential behavioral side effects in a novelty test. In Experiment 1, HI-6 (1-[([4-(aminocarbonyl)pyridino] methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium) (125 mg/kg), scopolamine (1 mg/kg), physostigmine (0.1 mg/kg), levetiracetam (50 mg/kg), and procyclidine (20 mg/kg) were tested separately. In Experiment 2, the combination of HI-6, scopolamine, and physostigmine (termed the physostigmine regimen) or HI-6, levetiracetam, and procyclidine (termed the procyclidine regimen) were tested. In Experiment 3, the metabotropic glutamate modulators DCG-IV ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine) (4 mg/kg) and MPEP (2-Methyl-6-(phenylethynyl)pyridine hydrochloride) (30 mg/kg) were tested separately or each drug in combination with HI-6 and procyclidine (termed the DCG-IV regimen and the MPEP regimen, respectively). The results showed that the physostigmine and procyclidine regimens both produced severe cognitive impairment (lack of preference for novelty) and reduced locomotor and rearing activities. The DCG-IV and MPEP regimens caused milder deficits on the same behavioral measures. Some relations were seen between prophylactic capacity and degree of behavioral side effects. Only HI-6 or levetiracetam had no adverse effects on behavior. DCG-IV or MPEP produced some impairment, whereas the detrimental effects of scopolamine or procyclidine were pronounced. The relatively high dose of procyclidine (anticholinergic and antiglutamatergic) needed for prophylactic efficacy may have played a major role for the side effects of the regimens in which the drug was used. It was concluded that behavioral side effects are inevitable for potent prophylactic therapies against soman intoxication.


Pheromonal influences on sociosexual behavior in men.
This study tested whether synthesized human male pheromones increase the sociosexual behavior of men. Thirty-eight heterosexual men, ages 26-42, completed a 2-week baseline period and 6-week placebo-controlled, double-blind trial testing a pheromone "designed to improve the romance in their lives." Each subject kept daily behavioral records for 6 sociosexual behaviors: petting/affection/kissing, formal dates, informal dates, sleeping next to a romantic partner, sexual intercourse, and self-stimulation to ejaculation (masturbation) and FAXed them each week. Significantly more pheromone than placebo users increased above baseline in sexual intercourse and sleeping with a romantic partner. There was a tendency for more pheromone than placebo users to increase above baseline in petting/affection/kissing, and informal dates, but not in self-stimulation to ejaculation or in formal dates. A significantly larger proportion of pheromone than placebo users increased in > or = 2 and > or = 3 of the 5 sociosexual behaviors involving a female partner. Thus, there was a significant increase in male sociosexual behaviors in which a woman's sexual interest and cooperation plays a role but not in male masturbation which involves only the man. These initial data need replication but suggest that human male pheromones affected the sexual attractiveness of men to women.


Diurnal Plasma Cortisol Measurements Utility in Differentiating Various Etiologies of Endogenous Cushing Syndrome.
Cortisol diurnal variation may be abnormal among patients with endogenous Cushing syndrome (CS). The study objective was to compare the plasma cortisol AM/PM ratios between different etiologies of CS. This is a retrospective cohort study, conducted at a clinical research center. Adult patients with CS that underwent adrenalectomy or trans-sphenoidal surgery (n=105) were divided to those with a pathologically confirmed diagnosis of Cushing disease (n=21) and those with primary adrenal CS, including unilateral adrenal adenoma (n=28), adrenocortical hyperplasia (n=45), and primary pigmented nodular adrenocortical disease (PPNAD, n=11). Diurnal plasma cortisol measurements were obtained at 11:30 PM and midnight and at 7:30 and 8:00 AM. The ratios between the mean morning levels and mean late-night levels were calculated. Mean plasma cortisol AM/PM ratio was lower among CD patients compared to those with primary adrenal CS (1.4±0.6 vs. 2.3±1.5, p<0.001, respectively). An AM/PM cortisol ratio≥2.0 among patients with unsuppressed ACTH (>15 pg/ml) excludes CD with a 85.0% specificity and a negative predictive value (NPV) of 90.9%. Among patients with primary adrenal CS, an AM/PM cortisol≥1.2 had specificity and NPV of 100% for ruling out a diagnosis of PPNAD. Plasma cortisol AM/PM ratios are lower among patients with CD compared with primary adrenal CS, and may aid in the differential diagnosis of endogenous hypercortisolemia.


Modulation of apoptosis-associated genes bcl-2, bcl-x, and bax during rat liver regeneration.
Liver regeneration (LR) after 70% partial hepatectomy (PH) represents a unique in vivo model of cell cycle and gene regulation. This study was conducted to characterize apoptosis-associated gene expression during LR. The results indicated that transcripts for both bcl-x and bcl-2 exhibited similar patterns of expression during LR with peaks at 6 h post-PH. In contrast, the major 1.1-kb bax transcript exhibited peaks at 18 (P < 0.05) and 72 h (P < 0.001) post-PH. Nuclear run-on analyses for all three genes indicated no detectable transcription rate changes during LR. At 6 h post-PH, when bcl-x mRNA levels were increased by 25-fold (P < 0.001), bcl-x mRNA half-life was elevated 4-fold (P < 0.001). Similarly, bax transcript half-life increased from 2.8 h at 0 h to 4.3 h at 24 h (P < 0.001) and > 8 h at 40 h (P < 0.001) post-PH, coincident with increases in steady-state levels of mRNA. Western blot analyses of Bcl-2 and Bcl-x proteins showed no significant change through 96 h of LR, whereas Bax protein levels cycled in parallel with its mRNA. Interestingly, novel Bax- and Bcl-2-cross-reactive proteins of 31 and 32 kDa, respectively, were detected in nuclei isolated from quiescent liver. When liver growth was induced by the peroxisome proliferator clofibrate, transcript and protein levels were coupled for bcl-x but not for bax. In conclusion, the apoptosis-associated genes bcl-2, bcl-x and bax are modulated at the transcript and protein levels during LR, suggesting a role for these gene products in normal liver growth. The alterations in transcript levels occur posttranscriptionally and involve changes in mRNA stability. Furthermore, unlike bax, steady-state protein and transcript levels are uncoupled for both bcl-2 and bcl-x, suggesting a role for translational regulation during LR after PH.


TIMAP is a positive regulator of pulmonary endothelial barrier function.
TGF-beta-inhibited membrane-associated protein, TIMAP, is expressed at high levels in endothelial cells (EC). It is regarded as a member of the MYPT (myosin phosphatase target subunit) family of protein phosphatase 1 (PP1) regulatory subunits; however, its function in EC is not clear. In our pull-down experiments, recombinant TIMAP binds preferentially the beta-isoform of the catalytic subunit of PP1 (PP1cbeta) from pulmonary artery EC. As PP1cbeta, but not PP1calpha, binds with MYPT1 into functional complex, these results suggest that TIMAP is a novel regulatory subunit of myosin phosphatase in EC. TIMAP depletion by small interfering RNA (siRNA) technique attenuates increases in transendothelial electrical resistance induced by EC barrier-protective agents (sphingosine-1-phosphate, ATP) and enhances the effect of barrier-compromising agents (thrombin, nocodazole) demonstrating a barrier-protective role of TIMAP in EC. Immunofluorescent staining revealed colocalization of TIMAP with membrane/cytoskeletal protein, moesin. Moreover, TIMAP coimmunoprecipitates with moesin suggesting the involvement of TIMAP/moesin interaction in TIMAP-mediated EC barrier enhancement. Activation of cAMP/PKA cascade by forskolin, which has a barrier-protective effect against thrombin-induced EC permeability, attenuates thrombin-induced phosphorylation of moesin at the cell periphery of control siRNA-treated EC. On the contrary, in TIMAP-depleted EC, forskolin failed to affect the level of moesin phosphorylation at the cell edges. These results suggest the involvement of TIMAP in PKA-mediated moesin dephosphorylation and the importance of this dephosphorylation in TIMAP-mediated EC barrier protection.


Differential roles of TNFα-TNFR1 and TNFα-TNFR2 in the differentiation and function of CD4+Foxp3+ induced Treg cells in vitro and in vivo periphery in autoimmune diseases.
Tumor Necrosis Factor (TNF) α is a multifunctional cytokine with pro-inflammatory and anti-inflammatory characteristics. Increasing evidence suggests that thymus-derived, natural regulatory T cells (nTreg) express a remarkably high level of TNF Receptor 2 (TNFR2) and TNFα modulates the number or function of nTreg via TNFR2 in autoimmune diseases. Nonetheless, Treg cells consist of at least nTreg and iTreg that are induced in the periphery or in vitro and two subsets may have different biological characteristics. However, the role of TNF-TNFR signaling in development and function of these iTreg cells is less clear. In this study, we systemically studied the effect of TNFα and its receptor signals on iTreg differentiation, proliferation, and function in vitro and in vivo. We further investigated the expression and requirement of TNFR1 or TNFR2 expression on iTreg by utilizing TNFR1-/- and TNFR2-/- mice. We found that exogenous TNFα facilitated iTreg differentiation and function in vitro. TNFR2 deficiency hampered iTreg differentiation, proliferation, and function, while TNFR1 deficiency decreased the differentiation of inflammatory T cells such as Th1 and Th17 cells but maintained the regulatory capabilities of iTreg both in vitro and in vivo. Using colitis model, we also revealed TNFR2 but not TNFR1 deficiency compromised the iTreg functionality. Interestingly, inflammation affects TNFR expression on nTreg but not iTreg subset. Our results demonstrate that exogenous TNFα may enhance the differentiation and function of iTreg via TNFR2 signaling. The expression of TNFR2 on Treg might be downregulated in some autoimmune diseases, accompanied by an increased level of TNFR1. Thus, TNFR2 agonists or TNFR1-specific antagonists hold a potential promise for clinical application in treating patients with autoimmune diseases.


[Upper lateral incisor with 2 canals].
Clinical case summary of the patient with an upper lateral incisor with two root canals. The suspicion that there might be an anatomic anomaly in the root that includes a complex root canal system was made when an advanced radicular groove was detected in the lingual surface or an excessively enlarged cingulum.


Rapid re-amplification of PCR products purified in low melting point agarose gels.
A rapid, simple method is described for performing sequential amplifications of purified products produced by the PCR. After the initial amplification, an aliquot of the reaction is run on a low melting point agarose gel. A Pasteur pipet is used to punch out a gel plug from the amplified band. The DNA in this plug is then used directly as the template for a second round of amplification. Relatively large amounts of agarose can be tolerated without noticeable effects on amplification. Use of a composite gel made from agarose and linear polyacrylamide increases the ease and utility of this technique. These gels are simple to cast, easier to handle and permit several replicate plugs to be obtained from a single band. This method is well suited to experiments which use "nested" primers to increase the sensitivity and specificity of amplification or any method in which PCR amplification follows DNA purification by electrophoresis in LMP agarose gels.


Low Dimensional Magnetic Lattice and Room Temperature Magneto(di)electric Effect in Polyanion Ruddlesden-Popper Iron Oxides.
We have shown a new design strategy which exploits different oxyanions in a Ruddlesden-Popper (RP)-type phase to modulate the local crystal structure and magnetic lattice. Material (Sr4Fe2(SO4)0.5O6.5) with the larger voluminous oxyanion (SO4, S-O distance = 1.49 Å) as separating blocks between magnetic FeO layers shows a two-dimensional magnetic lattice. A three-dimensional magnetic lattice and spin reorientation transition is observed for the Sr4Fe2(CO3)O6, having CO3 (C-O distance = 1.25 Å), a smaller oxyanion, as a separating layer. Using mixed oxyanions (SO4 and CO3) in the central perovskite block of the RP3 phase, we have demonstrated a facile strategy to modulate the local crystal structure. The modulated displacement of the magnetic cations, which can break the local centrosymmetry, is suggested to originate the magnetodielectric effect near the magnetic ordering temperatures (higher than room temperature). Further, all CO3 containing samples show magnetodielectric coupling below room temperature due to the spin reorientation transition. The room temperature magnetodielectric effect coupled to the targeted local modulation of the crystal structure by oxyanions (in the absence of second-order Jahn-Teller active "distortion centers") opens a new door to the design of new multifunctional materials with the possibility for the room temperature application.


Alcoholic liver disease: Utility of animal models.
Alcoholic liver disease (ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.


PATTERN OF REFERRALS OF HEAD INJURY TO THE UNIVERSITY COLLEGE HOSPITAL, IBADAN.
Although there are now many neurosurgical units in Nigeria, cases of head injury (HI) continue to present in the University College Hospital, UCH, Ibadan, from hospitals all over the country. This report aims to highlight the contemporary patterns of referrals of cases of head injury for neurosurgery in Ibadan. The study emanated from an analysis of registry of cases of head injury managed in our practice covering a 7-year period at the UCH Ibadan. The clinical/ trauma-demography of cases of head injury referred were analyzed quantitatively and then compared with head injury cases that presented primarily to UCH Ibadan during the same period. An alpha value of <0.05 was considered significant for associations for pattern of referrals. Of the 1034 cases of head injuries in the registry, 23.6% presented primarily to UCH, Ibadan; 423 (40.1%) were from outside Ibadan/Oyo state. Most of the cases were earlier seen in other health facilities in four out of Nigeria's six geopolitical zones including other teaching hospitals with practicing neurosurgeons. The reasons for these inter-hospital, inter-state referrals included absence of neurosurgical expertise (67%) or lack of other logistics like neuroimaging, bed space and intensive care unit services. Head Injury was caused by road accidents in more than 85% of the cases. The patients referred inter-state had more severe injuries, more delayed attainment of critical milestones in their trauma care, and higher frequency of neurosurgical operative interventions. They also had worse in-hospital outcome and longer length of stay. The University College Hospital, Ibadan continues to play a pivotal role in the management of head injury in Nigeria. The results support an urgent need for stakeholders in the health sector to provide all that is required to uphold the status of the Hospital as a center of excellence in neurosurgery and neurosciences.


Depression and insomnia in cancer: prevalence, risk factors, and effects on cancer outcomes.
Over two-thirds of the 11.4 million cancer survivors in the United States can expect long-term survival, with many others living with cancer as a chronic disease controlled by ongoing therapy. Behavioral comorbidities often arise during treatment and persist long term to complicate survival and reduce quality of life. This review focuses on depression and insomnia with an emphasis on understanding the role of cancer-specific factors and their contribution to the prevalence of these behavioral comorbidities in cancer patients following cancer diagnosis and treatment. The clinical significance of depression and insomnia for cancer patients is further stressed by epidemiological observations that link depression and insomnia to cancer morbidity and mortality risk.


Removing patients from the liver transplant wait list: A survey of US liver transplant programs.
Guidelines are in place regarding who is a candidate for liver transplantation. Once a potential candidate is listed, there are no uniform guidelines indicating when he should be removed from the list because of a change in clinical status. A survey with 14 scenarios was sent to the medical and surgical directors of all liver transplant programs in the United States. In each scenario, clinical information was provided about a patient active on the transplant wait list. Data regarding a clinical change were provided, and responders were questioned whether they would remove the patient from the wait list. The scenarios were designed to address the issues of age, etiology of liver disease, renal dysfunction, respiratory failure, infection, failure to thrive, and social support. Two hundred four questionnaires were mailed with 47 responses (23%): 8 return to sender, 24 surgeons, and 15 hepatologists. All 11 United Network for Organ Sharing regions were represented. The responders were well distributed among university programs (n = 28), private practice programs (n = 10), and health maintenance organization programs (n = 1). Nine responses were from small-volume programs (< or =25 transplants), 12 were from medium-volume programs (26-50 transplants), and 18 were from large-volume programs (> or =51 transplants). There was wide variability between responders regarding which patients should be removed from the transplant wait list. Patient age and etiology of liver disease led to the greatest discordance among responders. In conclusion, there is a lack of agreement and standardization among US liver transplant programs regarding who should be removed from the wait list for a change in clinical status.


Sandwiched spherical tin dioxide/graphene with a three-dimensional interconnected closed pore structure for lithium storage.
Low reversion of lithium oxide (Li2O) and the tin (Sn) coarsening causing irreversible capacity loss is the main reason for the poor cycle performance in tin dioxide (SnO2) based composites. In this research, a novel sandwiched spherical tin dioxide/graphene with a three-dimensional interconnected closed pore structure is synthesized. The microstructural characterization shows that the spherical graphene with submicron sized diameters interconnects with each other forming an interconnected flexible conductive network, whereas a large number of SnO2 nanoparticles (approximately 5 nm) are limited homogeneously in between the interlayers of the sphere-like graphene shell. The sandwich structure of the SnO2/graphene and the closed graphene sphere can provide double protection for the SnO2. When it is used as an anode material for energy storage, the generated Li2O can remain in close contact with Sn to make the conversion reaction (SnO2 + 4Li+ + 2e- ↔ Sn + Li2O) highly reversible in situ and the reversibility even does not diminish markedly after 100 cycles. A high reversible specific capacity of 914.8 mA h g-1 is expressed in the sandwiched spherical SnO2/graphene composite at 100 mA g-1 after 100 cycles, which is significantly higher than that of a SnO2/graphene aerogel with an open pore structure.


The Ross-Konno procedure for congenital aortic stenosis.
Left ventricular outflow tract (LVOT) obstruction can result from supravalvular, valvular and/or subvalvular etiologies. Congenital aortic valvular stenosis is frequently associated with aortic annular hypoplasia. Aortoventriculoplasty with pulmonary autograft, "The Ross-Konno" operation, provides more or less a radical solution to multilevel LVOT obstruction by enlarging the aortic annulus and the subvalvular area, thus relieving both valvular and subvalvular obstructions. In addition to this, the procedure carries the major advantage of having a competent autograft in the LVOT. An autograft that has the potential for growth and provides excellent quality of life without the need for anticoagulation. The procedure is most commonly performed as a complete root implantation, harvesting the coronary arteries as buttons, and harvesting the autograft with a muscle skirt to allow a single unit reconstruction of the LVOT. The procedure has been modified over time to minimize the risk of conduction tissue injury and the development of complete heart block by modifying the interventricular septal incision. The Ross-Konno procedure has changed the approach to patients with complex multilevel LVOT obstruction. However, while it can be performed early in life, one should be aware that this procedure is technically demanding and can be associated with a higher surgical risk. Nevertheless, it is considered "the ultimate solution" for those with complex multilevel LVOT obstruction.


Hypermethylation of tumor suppressor and tumor-related genes in neoplastic and non-neoplastic gastric epithelia.
A number of tumor suppressor and tumor-related genes exhibit promoter hypermethylation with resultant gene silencing in human cancers. The frequencies of methylation differ among genes and genomic regions within CpG islands in different tissue types. Hypermethylation initially occurs at the edge of CpG islands and spreads to the transcription start site before ultimately shutting down gene expression. When the degree of methylation was quantitatively evaluated in neoplastic and non-neoplastic gastric epithelia using DNA microarray analysis, high-level methylation around the transcription start site appeared to be a tumor-specific phenomenon, although multiple tumor suppressor genes became increasingly methylated with patient age in non-neoplastic gastric epithelia. Quantitative analysis of DNA methylation is a promising method for both cancer diagnosis and risk assessment.


A novel force-constrained non-negative matrix factorization algorithm reveals the effectiveness of muscle synergies in the task space.
According to the synergy hypothesis, the motor system recruits a small number of synergies in a task-dependent manner. Existing synergy extraction algorithms typically only consider the muscle pattern and it remains unclear to which extent muscle synergies encode task-relevant variations of muscle activity. We propose a novel force-constrained non-negative matrix algorithm (FCNMF) based on a gradient descent update rule that considers also the task space by adding a term penalizing force reconstruction error in the cost function. We validated the FCNMF algorithm using simulated muscle data and corrupted them by noise. We compared task performances with reconstructed trajectories using synergies (RS) extracted from the FCNMF algorithm and from the standard multiplicative non-negative matrix factorization NMF algorithm. We found that FCNMF outperforms NMF for different types of noise. Finally, we demonstrated the effectiveness of FCNMF on EMG data collected during an isometric reaching task. The new algorithm accurately reconstructs the trajectories in all participants, even in those for which the NMF algorithm fails. These findings show the effectiveness of muscle synergies extracted considering the task space, possibly thanks to the robustness of FCNMF against non-isotropic noise present in muscle data, suggesting that they provide an effective strategy for motor coordination.


Cell suspensions from porcine olfactory mucosa. Changes in membrane potential and membrane fluidity in response to various odorants.
A suspension of olfactory epithelial cells was prepared from porcine olfactory mucosa and the physiological functions of the suspension were examined. The membrane potential of the cell suspension, which was monitored by measuring the fluorescence changes of rhodamine 6G, was depolarized by an increase in the K+ concentration in the external medium. Various odorants depolarized the cell suspension in a dose-dependent fashion. The magnitude of depolarization by odorants was either unchanged or slightly increased by a reduction of the concentration of Na+, Ca2+, and Cl- in the external medium, which suggests that changes in the permeabilities of specific ions are not involved in depolarization by odorants. The application of various odorants to the cell suspension induced changes in the membrane fluidity at different sites of the membrane that were monitored with various fluorescent dyes [8-anilino-1-naphthalene sulfonate, n-(9-anthroyloxy) stearic acids, 12-(9-anthroyloxy) oleic acid, and (1,6-diphenyl-1,3,5-hexatriene)], which suggests that the odorants having different odors are adsorbed on different sites in the membrane. On the basis of these results, a possible mechanism of odor discrimination is discussed.


Antibodies against phosphorylcholine are not altered in plasma of patients with Alzheimer's disease.
Phosphorylcholine is one of the major epitopes of oxidised low density lipoprotein. Low levels of IgM antibodies against phosphorylcholine (anti-PC) are associated with development of myocardial infarction and stroke. It has been shown that patients with Alzheimer's disease and other dementias have significantly lower serum anti-PC levels compared to controls, suggesting that low levels of atheroprotective anti-PC may play a role in AD and dementia. We quantified levels of anti-PC levels using an ELISA in plasma from 176 controls, 125 patients with Alzheimer's disease, 19 patients with vascular dementia and 63 patients with other dementias. We observed similar plasma anti-PC levels in controls, patients with Alzheimer's disease, and other dementias. Our data suggests that anti-PC is not useful as a biomarker for Alzheimer's disease.


First-principles modeling of chemistry in mixed solvents: Where to go from here?
Mixed solvents (i.e., binary or higher order mixtures of ionic or nonionic liquids) play crucial roles in chemical syntheses, separations, and electrochemical devices because they can be tuned for specific reactions and applications. Apart from fully explicit solvation treatments that can be difficult to parameterize or computationally expensive, there is currently no well-established first-principles regimen for reliably modeling atomic-scale chemistry in mixed solvent environments. We offer our perspective on how this process could be achieved in the near future as mixed solvent systems become more explored using theoretical and computational chemistry. We first outline what makes mixed solvent systems far more complex compared to single-component solvents. An overview of current and promising techniques for modeling mixed solvent environments is provided. We focus on so-called hybrid solvation treatments such as the conductor-like screening model for real solvents and the reference interaction site model, which are far less computationally demanding than explicit simulations. We also propose that cluster-continuum approaches rooted in physically rigorous quasi-chemical theory provide a robust, yet practical, route for studying chemical processes in mixed solvents.


Genes and nonalcoholic fatty liver disease.
Whereas most individuals with nonalcoholic fatty liver disease (NAFLD) will have steatosis, only a minority will ever develop progressive disease. Family studies and interethnic variations in susceptibility suggest that genetic factors may be important in determining disease risk. Although no genetic associations with advanced NAFLD have been replicated in large studies, preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, tumor necrosis factor-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis. With the advent of high-throughput gene analyses and the reduced cost of whole genome-wide scans, it seems likely that genes contributing to inherited susceptibility to this common disease will be identified in the near future.


Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx.
Transient receptor potential (TRP) mucolipins (TRPMLs), encoded by the MCOLN genes, are patho-physiologically relevant endo-lysosomal ion channels crucial for membrane trafficking. Several lines of evidence suggest that TRPMLs mediate localised Ca2+ release but their role in Ca2+ signalling is not clear. Here, we show that activation of endogenous and recombinant TRPMLs with synthetic agonists evoked global Ca2+ signals in human cells. These signals were blocked by a dominant-negative TRPML1 construct and a TRPML antagonist. We further show that, despite a predominant lysosomal localisation, TRPML1 supports both Ca2+ release and Ca2+ entry. Ca2+ release required lysosomal and ER Ca2+ stores suggesting that TRPMLs, like other endo-lysosomal Ca2+ channels, are capable of 'chatter' with ER Ca2+ channels. Our data identify new modalities for TRPML1 action.


[The expertise of quality of diagnostics of bronchial asthma in ambulatory polyclinic institutions].
The article deals with the comprehensive expertise of quality of diagnostics of bronchial asthma in ambulatory polyclinic institutions of pediatric profile. The following techniques were applied: the retrospective analysis of all cases of bronchial asthma among children of City of Yugorsk of Hanti-Mansiisky autonomous okrug (n = 92), expertise of the causes of late diagnostics and possible ways of optimization of earlier diagnostics of bronchial asthma in ambulatory polyclinic institution (20 experts), testing the pediatricians working in children polyclinics (n = 95) on the knowledge of dealing with bronchial asthma. The late diagnostics is ascertained in 95% of cases and average period of diagnostics delay consisted 3 days. The leading role of inadequate theoretical background of pediatricians as a "triggering device" in progressive development of disease is established. The necessity to develop various forms of ongoing training of physicians of primary care for optimizing modern diagnostics of bronchial asthma in polyclinic conditions is justified.


Evaluation of activated charcoal and magnesium citrate in the prevention of aspirin absorption in humans.
Inhibition of aspirin absorption by activated charcoal and magnesium citrate solution was compared with the inhibition produced by activated charcoal alone. Following an overnight fast, eight healthy male volunteers were given three 325-mg aspirin tablets under four study regimens: (1) water 360 ml; (2) water 300 ml and activated charcoal 10 g in water 60 ml; (3) water 105 ml, activated charcoal 10 g in water 60 ml, and magnesium citrate solution 200 ml; and (4) same as (3) except that administration of magnesium citrate was delayed 30 minutes. At least one week separated each regimen. Urine samples were collected at 0, 2, 4, 8, 12, 24, 36, and 48 hours, and percent of the aspirin dose excreted in the urine was determined. The data were analyzed using analysis of variance for Latin-square design and Newman-Keuls test. The salicylate excreted with regimens 2, 3, and 4 was each significantly less compared with that excreted following regimen 1 (p less than 0.001). Salicylate excretion percentages when magnesium citrate was given with activated charcoal in regimens 3 and 4 were not significantly different from each other or the salicylate excretion with activated charcoal alone (p greater than 0.05). These findings apply only to the dose of aspirin tested, and it is possible that magnesium citrate and activated charcoal may decrease aspirin absorption to a greater extent when aspirin is taken in overdose. Hence, it is recommended that this study not be used to justify discontinuing the combined use of magnesium citrate and activated charcoal to treat aspirin overdose.


What an otolaryngologist should know about evaluation of a child referred for delay in speech development.
Otolaryngologists are asked to evaluate children who a parent, physician, or someone else believes is slow in developing speech. Therefore, an otolaryngologist should be familiar with milestones for normal speech development, the causes of delay in speech development, and the best ways to help assure that children develop the ability to speak in a normal way. To provide information for otolaryngologists that is helpful in the evaluation and management of children perceived to be delayed in developing speech. Data were obtained via literature searches, online databases, textbooks, and the most recent national guidelines on topics including speech delay and language delay and the underlying disorders that can cause delay in developing speech. Emphasis was placed on epidemiology, pathophysiology, most common presentation, and treatment strategies. Most of the sources referenced were published within the past 5 years. Our article is a summary of major causes of speech delay based on reliable sources as listed herein. Speech delay can be the manifestation of a spectrum of disorders affecting the language comprehension and/or speech production pathways, ranging from disorders involving global developmental limitations to motor dysfunction to hearing loss. Determining the cause of a child's delay in speech production is a time-sensitive issue because a child loses valuable opportunities in intellectual development if his or her communication defect is not addressed and ameliorated with treatment. Knowing several key items about each disorder can help otolaryngologists direct families to the correct health care provider to maximize the child's learning potential and intellectual growth curve.


Self-sampling versus health care professional-guided swab collection for SARS-CoV-2 testing.
To evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure. Hospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire. The test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals. Oropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity.


Partial regulatory T cell depletion prior to acute feline immunodeficiency virus infection does not alter disease pathogenesis.
Feline immunodeficiency virus (FIV) infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4(+)CD25(hi)FoxP3(+) immunosuppressive regulatory T (Treg) cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4(+) T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection.


Correlations between AFM and SEM imaging of acid-etched tooth enamel.
Enamel bond strength is an important factor in restorative dentistry and crucially depends on the enamel roughness. To increase roughness, different etching procedures are employed and profilometric estimations, with probe profilometers, including atomic force microscopy (AFM), have been made. However, no correlation between roughness and bond strength has been found. To search for a possible error source leading to the underestimation of enamel roughness when utilizing probe profilometers, the authors compared scanning electron microscopy and AFM images of acid-etched tooth enamel. The results showed that AFM imaging cannot correctly depict the acid-etched enamel surface, because of the high steepness of the enamel crystallites and the generation of convolute images. This leads to a large underestimation of the profilometric parameters measured with AFM, or other profilometers, on acid-etched tooth enamel surfaces.


The Arabidopsis wall associated kinase-like 10 gene encodes a functional guanylyl cyclase and is co-expressed with pathogen defense related genes.
Second messengers have a key role in linking environmental stimuli to physiological responses. One such messenger, guanosine 3',5'-cyclic monophosphate (cGMP), has long been known to be an essential signaling molecule in many different physiological processes in higher plants, including biotic stress responses. To date, however, the guanylyl cyclase (GC) enzymes that catalyze the formation of cGMP from GTP have largely remained elusive in higher plants. We have identified an Arabidopsis receptor type wall associated kinase-like molecule (AtWAKL10) as a candidate GC and provide experimental evidence to show that the intracellular domain of AtWAKL10(431-700) can generate cGMP in vitro. Further, we also demonstrate that the molecule has kinase activity indicating that AtWAKL10 is a twin-domain catalytic protein. A co-expression and stimulus-specific expression analysis revealed that AtWAKL10 is consistently co-expressed with well characterized pathogen defense related genes and along with these genes is induced early and sharply in response to a range of pathogens and their elicitors. We demonstrate that AtWAKL10 is a twin-domain, kinase-GC signaling molecule that may function in biotic stress responses that are critically dependent on the second messenger cGMP.


Post-exercise syncope: Wingate syncope test and visual-cognitive function.
Adequate cerebral perfusion is necessary to maintain consciousness in upright humans. Following maximal anaerobic exercise, cerebral perfusion can become compromised and result in syncope. It is unknown whether post-exercise reductions in cerebral perfusion can lead to visual-cognitive deficits prior to the onset of syncope, which would be of concern for emergency workers and warfighters, where critical decision making and intense physical activity are combined. Therefore, the purpose of this experiment was to determine if reductions in cerebral blood velocity, induced by maximal anaerobic exercise and head-up tilt, result in visual-cognitive deficits prior to the onset of syncope. Nineteen sedentary to recreationally active volunteers completed a symptom-limited 60° head-up tilt for 16 min before and up to 16 min after a 60 sec Wingate test. Blood velocity of the middle cerebral artery was measured using transcranial Doppler ultrasound and a visual decision-reaction time test was assessed, with independent analysis of peripheral and central visual field responses. Cerebral blood velocity was 12.7 ± 4.0% lower (mean ± SE; P < 0.05) after exercise compared to pre-exercise. This was associated with a 63 ± 29% increase (P < 0.05) in error rate for responses to cues provided to the peripheral visual field, without affecting central visual field error rates (P = 0.46) or decision-reaction times for either visual field. These data suggest that the reduction in cerebral blood velocity following maximal anaerobic exercise contributes to visual-cognitive deficits in the peripheral visual field without an apparent affect to the central visual field.


Behaviourally mediated predation avoidance in penguin prey: in situ evidence from animal-borne camera loggers.
Predator dietary studies often assume that diet is reflective of the diversity and relative abundance of their prey. This interpretation ignores species-specific behavioural adaptations in prey that could influence prey capture. Here, we develop and describe a scalable biologging protocol, using animal-borne camera loggers, to elucidate the factors influencing prey capture by a seabird, the gentoo penguin (Pygoscelis papua). From the video evidence, we show, to our knowledge for the first time, that aggressive behavioural defence mechanisms by prey can deter prey capture by a seabird. Furthermore, we provide evidence demonstrating that these birds, which were observed hunting solitarily, target prey when they are most discernible. Specifically, birds targeted prey primarily while ascending and when prey were not tightly clustered. In conclusion, we show that prey behaviour can significantly influence trophic coupling in marine systems because despite prey being present, it is not always targeted. Thus, these predator-prey relationships should be accounted for in studies using marine top predators as samplers of mid- to lower trophic-level species.


A review on phytoremediation of contaminants in air, water and soil.
There is a global need to use plants to restore the ecological environment. There is no systematic review of phytoremediation mechanisms and the parameters for environmental pollution. Here, we review this situation and describe the purification rate of different plants for different pollutants, as well as methods to improve the purification rate of plants. This is needed to promote the use of plants to restore the ecosystems and the environment. We found that plants mainly use their own metabolism including the interaction with microorganisms to repair their ecological environment. In the process of remediation, the purification factors of plants are affected by many conditions such as light intensity, stomatal conductance, temperature and microbial species. In addition the efficiency of phytoremediation is depending on the plants species-specific metabolism including air absorption and photosynthesis, diversity of soil microorganisms and heavy metal uptake. Although the use of nanomaterials and compost promote the restoration of plants to the environment, a high dose may have negative impacts on the plants. In order to improve the practicability of the phytoremediation on environmental restoration, further research is needed to study the effects of different kinds of catalysts on the efficiency of phytoremediation. Thus, the present review provides a recent update for development and applications of phytoremediation in different environments including air, water, and soil.


Treatment of pulmonary aspergilloma with itraconazole.
In a 12 month open study of itraconazole in pulmonary aspergilloma nine patients received oral itraconazole 200 mg daily for six months followed by further itraconazole or observation for a further six months. There was no change in the serum IgG specific for Aspergillus fumigatus (mean (SE) change -4% (10%)) or symptoms of chronic cough and haemoptysis. In two of the three patients who continued treatment beyond six months symptoms and radiographic appearances improved and a temporary reduction in A fumigatus specific IgG occurred in one patient. Further experience of the effects of longer treatment are needed before oral itraconazole can be recommended for aspergilloma.


From challenges to advanced practice registered nursing role development: Qualitative interview study.
The aim of this study is to describe the factors hindering and facilitating the implementation of the advanced practice registered nurses role at Finnish university hospitals, and to examine the implications for its future development. A descriptive qualitative approach, using thematic individual interviews, was conducted in 2011 with a sample of 11 advanced practice registered nurses. The data were analysed using qualitative content analysis. The advanced practice registered nurses role barriers had an impact on the role development needs. In turn, the facilitating factors helped encounter the challenges of the role, therefore having an impact on both the current role achievement, as well as contributing to the future role development. The factors hindering and facilitating the advanced practice registered nurses role need to be acknowledged to support the role implementation and planning of the future of the role.


Change in daytime sleepiness and cognitive function in a 6-month, double-blind study of lurasidone and quetiapine XR in patients with schizophrenia.
Daytime sleepiness is a commonly reported adverse effect associated with psychotropic agents that may impair cognitive performance and functioning. The objective of this post-hoc analysis was to evaluate the long-term effects of lurasidone and quetiapine XR on daytime sleepiness and neurocognitive performance during a 6-month, double-blind continuation study, in subjects who completed an initial 6-week, randomized, placebo-controlled trial comparing these agents. Daytime sleepiness, cognitive performance, and health-related quality of life were assessed with the Epworth Sleepiness Scale (ESS), CogState computerized battery, and the Quality of Well-Being (QWB-SA) Scale, respectively. Treatment with flexible-dose lurasidone 40-160 mg/d, administered once daily in the evening, was associated with significantly reduced daytime sleepiness compared with flexibly dosed quetiapine XR 200-800 mg/d (p = 0.03, effect size = 0.36) at week 32 (month 6 of the continuation study endpoint). Incidence of markedly high sleepiness (ESS > 10) was significantly higher in the quetiapine XR (200-800 mg/d) group compared with the lurasidone (40-160 mg/day) group at both months 3 and 6 visits (p < 0.05). Lurasidone (40-160 mg/d) significantly improved neurocognitive performance compared to quetiapine XR (200-800 mg/d) before (effect size = 0.49) and after adjustment (effect size = 0.45) for sleepiness effect (p = 0.008 and 0.010, respectively). Increased daytime sleepiness was significantly associated with reduced neurocognitive performance (p = 0.019) and quality of well-being (p = 0.05). Our findings suggest that clinicians should actively monitor patients for the presence of daytime sleepiness due in part to its potential impact on neurocognitive performance and well-being.


Factors affecting quality of life in patients on haemodialysis: a cross-sectional study from Palestine.
Haemodialysis (HD) is a life-sustaining treatment for patients with end-stage renal disease (ESRD). HD can bring about significant impairment in health-related quality of life (HRQOL) and outcomes. Therefore, we sought to describe the patterns of HRQOL and determine the independent factors associated with poor HRQOL in Palestinian patients on HD. A multicenter cross-sectional study was performed from June 2014 to January 2015 using the EuroQOL-5 Dimensions instrument (EQ-5D-5L) for the assessment of HRQOL. ESRD patients undergoing HD in all dialysis centres in the West Bank of Palestine were approached and recruited for this study. Multiple linear regression was carried out to identify factors that were significantly associated with HRQOL. Two hundred and sixty-seven patients were participated in the current study giving response rate of 96 %. Overall, 139 (52.1 %) were male, and the mean ± standard deviation age was 53.3 ± 16.2 years. The reported HRQOL as measured by mean EQ-5D-5L index value and Euro QOL visual analogue scale (EQ-VAS) score was 0.37 ± 0.44 and 59.38 ± 45.39, respectively. There was a moderate positive correlation between the EQ-VAS and the EQ-5D-5L index value (r = 0.42, p < 0.001). The results of multiple linear regression showed a significant negative association between HRQOL with age, total number of chronic co-morbid diseases and the total number of chronic medications. However, a significant positive association was found between HRQOL with male gender, university education level and patients who live in village. Our results provided insight into a number of associations between patient variables and their HRQOL. Healthcare providers should be aware of low HRQOL among patients with no formal education, female gender, patient's residents of refugee camps, multiple co-morbid diseases, multiple chronic medications, and elderly patients to improve their quality of life.


Survival Benefit of Multiple Arterial Revascularization With and Without Supplementary Saphenous Vein Graft.
Background It is unknown if the presence of saphenous vein grafting (SVG) adversely affects late survival following coronary surgery with multiple arterial grafting (MAG) versus single arterial grafting. Methods and Results A retrospective, observational, multicenter cohort study from 2001 to 2020 was conducted using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Database linked to the National Death Index. Patients undergoing primary isolated coronary artery bypass grafting with ≥2 grafts were included, and exclusions were patients aged <18 years, reoperations, concomitant or previous cardiac surgery, and the absence of arterial grafting. Demographics, comorbidities, medication, and operative configurations were propensity score matched between cohorts. The primary outcome was all-cause late death. Of 59 689 eligible patients, 35 113 were MAG (58.8%), and 24 576 were single arterial grafting (41.2%). Of the MAG cohort, 17 055 (48.6%) patients did not receive supplementary SVG (total arterial revascularization). Matching separately generated 22 764 patient pairs for MAG versus single arterial grafting, and 11 137 patient pairs for MAG with total arterial revascularization versus MAG with ≥1 supplementary vein grafts. At a median follow-up duration of 5.0 years postoperatively, the mortality rate was significantly lower for MAG than single arterial grafting (hazard ratio [HR], 0.79 [95% CI, 0.76-0.83]; P<0.001). The stratified MAG analysis found that MAG with total arterial revascularization had a lower risk of late death (HR, 0.85 [95% CI, 0.80-0.91]; P<0.001) compared with MAG with ≥1 supplementary vein grafts. Sensitivity analyses produced consistent outcomes as the primary analysis. Following adjustment for the presence of SVG in the Cox model, the survival advantage of incremental number of arteries was lost. Conclusions Multiple arterial grafting has significantly improved long-term survival compared with single arterial grafting. A further incremental survival benefit exists when no SVG is used.