TRPV4 plays an important role in rat prefrontal cortex changes induced by acute hypoxic exercise.
This study aims to investigate the effects of TRPV4 on acute hypoxic exercise-induced central fatigue, in order to explore the mechanism in central for exercise capacity decline of athletes in the early stage of altitude training. 120 male Wistar rats were randomly divided into 12 groups: 4 normoxia groups (quiet group, 5-level group, 8-level group, exhausted group), 4 groups at simulated 2500 m altitude (grouping as before), 4 groups at simulated 4500 m altitude (grouping as before), 10 in each group. With incremental load movement, materials were drawn corresponding to the load. Intracellular calcium ion concentration was measured by HE staining, enzyme-linked immunosorbent assay, immunohistochemistry, RT-qPCR, Fluo-4/AM and Fura-2/AM fluorescence staining. (1) Hypoxic 2-5 groups showed obvious venous congestion, with symptoms similar to normoxia-8 group; Hypoxic 2-8 groups showed meningeal loosening edema, infra-meningeal venous congestion, with symptoms similar to normoxia-exhausted group and hypoxic 1-exhaused group. (2) For 5,6-EET, regardless of normoxic or hypoxic environment, significant or very significant differences existed between each exercise load group (normoxic - 5 level 20.58 ± 0.66 pg/mL, normoxic - 8 level 23.15 ± 0.46 pg/mL, normoxic - exhausted 26.66 ± 0.71 pg/mL; hypoxic1-5 level 21.72 ± 0.43 pg/mL, hypoxic1-8 level 24.73 ± 0.69 pg/mL, hypoxic 1-exhausted 28.68 ± 0.48 pg/mL; hypoxic2-5 level 22.75 ± 0.20 pg/mL, hypoxic2-8 level 25.62 ± 0.39 pg/mL, hypoxic 2-exhausted 31.03 ± 0.41 pg/mL) and quiet group in the same environment(normoxic-quiet 18.12 ± 0.65 pg/mL, hypoxic 1-quiet 19.94 ± 0.43 pg/mL, hypoxic 2-quiet 21.72 ± 0.50 pg/mL). The 5,6-EET level was significantly or extremely significantly increased in hypoxic 1 environment and hypoxic 2 environment compared with normoxic environment under the same load. (3) With the increase of exercise load, expression of TRPV4 in the rat prefrontal cortex was significantly increased; hypoxic exercise groups showed significantly higher TRPV4 expression than the normoxic group. (4) Calcium ion concentration results showed that in the three environments, 8 level group (normoxic-8 190.93 ± 6.11 nmol/L, hypoxic1-8 208.92 ± 6.20 nmol/L, hypoxic2-8 219.13 ± 4.57 nmol/L) showed very significant higher concentration compared to quiet state in the same environment (normoxic-quiet 107.11 ± 0.49 nmol/L, hypoxic 1-quiet 128.48 ± 1.51 nmol/L, hypoxic 2-quiet 171.71 ± 0.84 nmol/L), and the exhausted group in the same environment (normoxic-exhausted 172.51 ± 3.30 nmol/L, hypoxic 1-exhausted 164.54 ± 6.01 nmol/L, hypoxic 2-exhausted 154.52 ± 1.80 nmol/L) had significant lower concentration than 8-level group; hypoxic2-8 had significant higher concentration than normoxic-8. Acute hypoxic exercise increases the expression of TRPV4 channel in the prefrontal cortex of the brain. For a lower ambient oxygen concentration, expression of TRPV4 channel is higher, suggesting that TRPV4 channel may be one important mechanism involved in calcium overload in acute hypoxic exercise.


Gas flow MRI using circulating laser-polarized 129Xe.
We describe an experimental approach that combines multidimensional NMR experiments with a steadily renewed source of laser-polarized 129Xe. Using a continuous flow system to circulate the gas mixture, gas phase NMR signals of laser-polarized 129Xe can be observed with an enhancement of three to four orders of magnitude compared to the equilibrium 129Xe NMR signal. Due to the fact that the gas flow recovers the nonequilibrium 129Xe nuclear spin polarization in 0.2 to 4 s, signal accumulation on the time scale of seconds is feasible, allowing previously inaccessible phase cycling and signal manipulation. Several possible applications of MRI of laser-polarized 129Xe under continuous flow conditions are presented here. The spin density images of capillary tubes demonstrate the feasibility of imaging under continuous flow. Dynamic displacement profiles, measured by a pulsed gradient spin echo experiment, show entry flow properties of the gas passing through a constriction under laminar flow conditions. Further, dynamic displacement profiles of 129Xe, flowing through polyurethane foams with different densities and pore sizes, are presented.


Accessory caudal axial and pelvic ribs.
Accessory caudal ribs are reported as an extremely curious anomaly in five patients. Once the fracture of this rib was a source of pains after injury. The different shapes of the ribs are documented in this clinical survey which is the most extensive in the present literature. Anomalous ribs arise due to inappropriate segmentation during the embryonal development of the axial skeleton.


[Cytopathology 2012: screening - education - diagnostics highlights of 37th European cytology congress, dubrovník - cavtat, croatia 30.9. -3.10.2012].
In Dubrovnik - Cavtat, Croatia more than 550 cytopathologists, representing 50 countries, met in the 37th European Cytology Congress. Three main topics dominated the programme: The cervical screening programmes focused on the optimal combination of HPV tests and screening cytology aimed at cost-effective and safe prolongation of the screening interval while still covering the target population. Regarding the mammary screening, the best organized "one day" diagnostic systems (French, Italian, Scandinavian) utilized sonography-guided fine needle diagnostics followed (only if needed) with a core biopsy.Great emphasis was placed on standardized European programmes of training and certification of cytotechnologists and pathologists. The role of cytotechnologists having a general education is increasing. The participation of clinical specialists will be limited to taking cytopathology samples.The strengthening role of cytodiagnostics was evident. Diagnostics is becoming a complex and multidisciplinary predictive process. Pathology lesions are regularly and routinely diagnosed with combined materials (smears, liquid based cytology, cytoblocks). ROSE (rapid on the spot evaluation) is performed - at minimum by a cytotechnician, but preferably by a pathologist with the rapid diagnosis made if possible. Cytotechnicians/cytopathologists are also responsible for optimal handling of these materials for molecular biology methods. The cooperation of the representatives of the Czech Society of Pathologists within working groups of EFCS (screening, education) represents an opportunity to improve the system of cytodiagnostics in the Czech Republic.


Evidence from catch-up growth and hoarding behavior of rats that exposure to hypobaric air lowers the body-mass set point.
The depression of body growth rate and the reduction of body mass for chronological age and gender in growing experimental animals exposed to hypobaric air (simulated high altitude = SHA) have been associated with hypophagia because of reduced appetite. Catch-up growth during protein recovery after a short period of protein restriction only occurs if food intake becomes super-normal, which should not be possible under hypoxic conditions if the set-point for appetite is adjusted by the level of SHA. The present investigation was designed to test the hypothesis that growth retardation during exposure to SHA is due to an alteration of the neural mechanism for setting body mass size rather than a primary alteration of the central set-point for appetite. One group of female rats aged 35 d were exposed to SHA (5460m) in a SHA chamber for 27 d (HX rats). Other group was maintained under local barometric pressure conditions (NX rats). One half of both NX and HX rats were fed a protein-free diet for the initial 9 d of the experimental period. From this time on, they were fed a diet containing 20% protein, as were the remaining rats of both groups during the entire experimental period. The growth rates of both mass and length of the body were significantly depressed in well-nourished rats exposed to SHA during the entire observation period when compared to normoxic ones. At its end, body mass and body length were 24% and 21% less in HX than in NX rats. Growth rates were negatively affected by protein restriction in both NX and HX rats. During protein recovery, they reached supernormal values in response to supernormal levels of energy intake that allowed a complete catch-up of both body mass and length. The finding that energy intake during the period of protein rehabilitation in HX rats previously stunted by protein restriction was markedly higher than in HX control ones at equal levels of hypoxia demonstrates that the degree of hypoxia does not determine directly the degree of appetite and energy intake. Furthermore, the finding that catch-up growth in the stunted HX rats returns the animal only to the stunted size appropriate for the hypoxic animal supports the hypothesis that hypoxia lowers the set-point for body mass size, which is reached by inhibition of appetite. Confirmation of the hypothesis was done by assessment of the set-point of body mass by the behavioral method of the weight threshold to hoard food. It was lowered by 17.0% in HX rats.


Clinical Characteristics of Patients Undergoing Right Heart Catheterizations in Community Hospitals.
Background Recognition of precapillary pulmonary hypertension (PH) has significant implications for patient management. However, the low a priori chance to find this rare condition in community hospitals may create a barrier against performing a right heart catheterization (RHC). This could result in misclassification of PH and delayed diagnosis/treatment of precapillary PH. Therefore, we investigated patient characteristics and echocardiographic parameters associated with the decision whether to perform an RHC in patients with incident PH in 12 Dutch community hospitals. Methods and Results In total, 275 patients were included from the OPTICS (Optimizing PH Diagnostic Network in Community Hospitals) registry, a prospective cohort study with patients with incident PH; 157 patients were diagnosed with RHC (34 chronic thromboembolic PH, 38 pulmonary arterial hypertension, 81 postcapillary PH, 4 miscellaneous PH), while 118 patients were labeled as probable postcapillary PH without hemodynamic confirmation. Multivariable analysis showed that older age (>60 years), left ventricular diastolic dysfunction grade 2-3, left atrial dilatation were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilatation, and tricuspid regurgitation velocity ≥3.7 m/s favor an RHC performance. Conclusions Older age and echocardiographic parameters of left heart disease were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilation, and severe PH on echocardiography favored an RHC performance. As such, especially elderly patients may be at an increased risk of diagnostic delays and missed diagnoses of treatable precapillary PH, which could lead to a worse prognosis.


Transcutaneous oxygen measurements: implications for nursing.
Transcutaneous oxygen measurement is a noninvasive diagnostic technique that records the partial pressure of oxygen at the skin surface. This measurement provides information regarding the supply and delivery of oxygen to the underlying microvascular circulation. It can be used for adults in wound evaluation, hyperbaric therapy, plastic surgery, amputation level determination, and peripheral vascular disease assessment, including the status of limb revascularization procedures. This article presents an overview of transcutaneous oxygen measurement and situations that influence measurement levels, including environmental, dermal, physiologic, and mechanical factors. Nursing considerations and indications for further research are also discussed.


Houttuynia cordata Extract Ameliorates Bladder Damage and Improves Bladder Symptoms via Anti-Inflammatory Effect in Rats with Interstitial Cystitis.
The mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear to date, but reports showed that bladder inflammation and increasing number of activating mast cells in bladder tissues were common in patients with IC/BPS. Houttuynia cordata is widely used in Chinese traditional medicine, and its function of anti-inflammation has been proved. The purpose of this study was to investigate the efficacy and possible mechanisms of the Houttuynia cordata (HC) extract in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). In the current study, a total of 30 adult female rats were randomly divided into three groups: sham group (n = 10), cyclophosphamide + saline (CYP + NS) group (n = 10), and cyclophosphamide + Houttuynia cordata extract (CYP + HC) group (n = 10). The animal model of IC/BPS was induced with cyclophosphamide (75 mg/kg, intraperitoneal injection, once every 3 days for 10 days) in the CYP + NS group and CYP + HC group, and sham rats received a volume-matched injection of saline. After anesthesia with urethane (0.8 g/kg, intraperitoneal injection), intravesical administration of either saline (1 ml) or Houttuynia cordata extract (1 ml, 2 g/ml) was continued once per day for a week in the CYP + NS group and CYP + HC group, respectively. Subsequently, urinary frequency, nociceptive behaviors, cystometry, bladder weight, histological changes, and cytokine (IL-6, IL-8, TNF-α) concentration were evaluated and compared among the three groups. Variables including inflammatory grade, mast cell number, proportion of activated mast cells, bladder weight, cytokine concentration of bladder homogenates, and frequency of urination significantly increased in the CYP + NS group compared with the sham group (P < 0.01) and CYP + HC group (P < 0.01). Besides, compared with the CYP + NS group, longer intercontraction interval, bigger bladder capacity, higher nociceptive threshold, fewer number of mast cells, and lower proportion of activated mast cells were found in the CYP + HC group (P < 0.01). Our study demonstrated that the Houttuynia cordata extract can effectively inhibit mast cell proliferation and activation and downregulate proinflammatory cytokine in a rat model of IC/BPS induced with cyclophosphamide and might be potentially valuable for the treatment of IC/BPS.


Hepatic capsular rupture in pregnancy.
The syndrome of haemolysis, elevated liver enzymes and low platelets is a rare condition specific to pregnancy, affecting approximately 5-20% of all pre-eclamptic pregnancies. Described here is a woman in her first pregnancy, who experienced an intrauterine death following a significant hepatic haematoma and capsular rupture, in the absence of classical clinical features suggestive of pre-eclampsia. The events that followed suggested haemolysis, elevated liver enzymes and low platelets syndrome as the likely diagnosis. The patient's clinical course highlights the difficulties that may be encountered when making decisions about pregnant women with complicated medical and obstetric issues.


Late endocrine, metabolic and skeletal sequelae following treatment of childhood cancer.
With an ever increasing adult population of childhood cancer survivors there is a need to focus on the late effects of cancer therapy. It is essential that, after discharge from the paediatric oncologists, the patients are not lost from the health system but are under continued surveillance with access to the appropriate physicians. Endocrine and metabolic consequences may affect a patient's life both soon after cancer treatment and also for many years in the future. In this review we consider the following potential problems: growth hormone deficiency and replacement in adulthood, cardiovascular risk factors, osteopaenia, thyroid and parathyroid dysfunction.


Concentrations of selenium and lipid peroxides and glutathione peroxidase activities in plasma of thermally injured pigs.
The mechanism of behaviour of parameters involved in protection of the cell from oxidative damage in burn disease remains unclear. Therefore, selenium and lipid peroxide (MDA) levels, and glutathione peroxidase (GSH-Px) activities have been measured for one month in plasma of thermally injured young pigs. Immediately post-burn mean MDA level and GSH-Px activity decreased, while Se concentration increased. After 3 week lipid peroxide levels reached top concentration. Only the enzyme activity returned to initial value at the end of the study, whereas the other two parameters were below the content noted at the beginning. The Se concentration was significantly and positively correlated with GSH-Px activity, and negatively with MDA levels. The similar relationship was also showed for the enzyme and lipid peroxides. The results indicate an interesting role of the studied agents in burn disease, but still suggestions of treatment of severely burned patients with antioxidants need to be supported by detailed studies.


Determination of five sulfonylurea herbicides in environmental waters and soil by ultra high performance liquid chromatography with tandem mass spectrometry after extraction using graphene.
A fast and novel analytical method was developed for the determination of trace levels of sulfonylurea herbicides in water and soil samples. Graphene was used as a sorbent for extraction, and ultra high performance liquid chromatography with tandem mass spectrometry was used for quantification. Five sulfonylurea herbicides were preconcentrated from water samples using a graphene-loaded packed cartridge, while extraction from soil samples was performed in a single step using graphene-supported matrix solid-phase dispersion. Under the optimized conditions, the calibration plots were linear in the range between 5 and 1000 ng/L for water samples, and between 1 and 200 ng/g for soil samples. All correlation coefficients (R) were >0.99. The limits of detection for water and soil samples were 0.28-0.53 ng/L and 0.08-0.26 ng/g, respectively. This method was successfully applied to the analysis of spiked samples of environmental water and soil, with recoveries ranging from 84.2-109.3 and 86.12-103.2%, respectively, all with relative standard deviations of <10%.


Theory of plasmonic femtosecond pulse generation by mode-locking of long-range surface plasmon polariton lasers.
We develop a semiclassical theory of passively mode-locked surface plasmon polariton (SPP) lasers based on a SPP Bragg resonator with a metal film deposited on a polymer host and adjacent layers of a slow saturable absorber and a slow saturable gain medium. The mode-locked laser dynamics is studied for the case that both the gain medium and the saturable absorber are solid-state dyes. The SPP laser pulse parameters are calculated in dependence on layer thicknesses of the metal film and pump parameters. We predict the possibility of SPP pulse generation with ∼ 100 fs pulse duration.


Mental Health Diagnoses and Seasonal Trends at a Pediatric Emergency Department and Hospital, 2015-2019.
Increasingly, youth with mental health disorders and suicidality are presenting to emergency departments (EDs) and requiring hospitalization. For youth with suicidality, studies reveal seasonal variations in frequency of presentations but do not identify associated diagnoses or whether other primary mental health complaints also reveal seasonal variations. Data were collected between January 2015 and December 2019 by a child and adolescent psychiatry consultation-liaison service in a pediatric ED and hospital. Descriptive analysis and multiple linear regression were performed to assess volume over time, seasonal trends, and associated diagnoses. A total of 2367 patients were included, with an average age of 13.9 years and female predominance (62.3%). During the study period, annual ED consultations increased 87.5% and hospital consultations increased 27.5%. Consultations revealed seasonal trends, with highest volumes during January, April, May, October, and November (P < .001; adjusted R 2 = 0.59). The most frequent diagnostic categories were depressive disorders and trauma- or stressor-related disorders. Thirty-six percent of patients presented after a suicide attempt, with the highest rates in spring (P = .03; adjusted R 2 = 0.19). Boarding rates revealed significant seasonality, with higher instances in February, March, April, May, and October (P = .009; adjusted R 2 = 0.32). Mental health presentations to a pediatric ED and hospital reveal seasonal trends, with the highest volumes in fall and spring and the most common diagnoses being depressive and trauma-related disorders. Suicide attempts are highest in late spring. Knowledge of these trends should inform hospitals, mental health services, and school systems regarding staffing, safety, surveillance, and prevention.


Initial characterization of a type I fatty acid synthase and polyketide synthase multienzyme complex NorS in the biosynthesis of aflatoxin B(1).
The biosynthesis of the potent environmental carcinogen aflatoxin B(1) is initiated by norsolorinic acid synthase (NorS), a complex of an iterative type I polyketide synthase and a specialized yeast-like pair of fatty acid synthases. NorS has been partially purified from Aspergillus parasiticus, has been found to have a mass of approximately 1.4 x 10(6) Da, and carries out the synthesis of norsolorinic acid in the presence of acetylCoA, malonylCoA, and NADPH where hexanoylCoA is not a free intermediate. The N-acetylcysteamine thioester of hexanoic acid can substitute for the catalytic functions of HexA/B to initiate norsolorinic acid synthesis by the complex in the presence of only malonylCoA. An alpha(2)beta(2)gamma(2) stoichiometry is proposed for NorS in keeping with its estimated mass and the observed dimeric or higher-order quarternary structures of PKS and FAS enzymes.


Acute infectious purpura fulminans associated with asplenism or hyposplenism.
Acute infectious purpura fulminans is a rapidly progressive syndrome of hemorrhagic skin necrosis associated with acute infection and disseminated intravascular coagulation. We report 5 cases of purpura fulminans and briefly review the literature. All cases were associated with encapsulated organisms (Streptococcus pneumoniae or Group A streptococcus), and 4 of the 5 patients had asplenism or functional hyposplenism.


Phosphorylation-induced conformational changes in a mitogen-activated protein kinase substrate. Implications for tyrosine hydroxylase activation.
Mitogen-activated protein (MAP) kinase-mediated phosphorylation of specific residues in tyrosine hydroxylase leads to an increase in enzyme activity. However, the mechanism whereby phosphorylation affects enzyme turnover is not well understood. We used a combination of fluorescence resonance energy transfer (FRET) measurements and molecular dynamics simulations to explore the conformational free energy landscape of a 10-residue MAP kinase substrate found near the N terminus of the enzyme. This region is believed to be part of an autoregulatory sequence that overlies the active site of the enzyme. FRET was used to measure the effect of phosphorylation on the ensemble of peptide conformations, and molecular dynamics simulations generated free energy profiles for both the unphosphorylated and phosphorylated peptides. We demonstrate how FRET transfer efficiencies can be calculated from molecular dynamics simulations. For both the unphosphorylated and phosphorylated peptides, the calculated FRET efficiencies are in excellent agreement with the experimentally determined values. Moreover, the FRET measurements and molecular simulations suggest that phosphorylation causes the peptide backbone to change direction and fold into a compact structure relative to the unphosphorylated state. These results are consistent with a model of enzyme activation where phosphorylation of the MAP kinase substrate causes the N-terminal region to adopt a compact structure away from the active site. The methods we employ provide a general framework for analyzing the accessible conformational states of peptides and small molecules. Therefore, they are expected to be applicable to a variety of different systems.


Naltrexone alters responses to social and physical warmth: implications for social bonding.
Socially warm experiences, when one feels connected to others, have been linked with physical warmth. Opioids, hypothesized to support social bonding with close others and, separately, physical warmth, may underlie both experiences. In order to test this hypothesis, 80 participants were randomly assigned to the opioid antagonist, naltrexone or placebo before neural and emotional responses to social and physical warmth were collected. Social and physical warmth led to similar increases in ventral striatum (VS) and middle-insula (MI) activity. Further, feelings of social connection were positively related to neural activity to social warmth. However, naltrexone (vs placebo) disrupted these effects by (i) reducing VS and MI activity to social and physical warmth, (ii) erasing the subjective experience-brain association to social warmth and (iii) disrupting the neural overlap between social and physical warmth. Results provide additional support for the theory that social and physical warmth share neurobiological, opioid receptor-dependent mechanisms and suggest multiple routes by which social connections may be maintained.


Characteristics of allergen profile, sensitization patterns and Allergic Rhinitis in SouthEast Asia.
To highlight the characteristics of allergic rhinitis, local allergic rhinitis (LAR), and importance of allergens in Southeast Asian countries. The Asia-Pacific region is very diverse with disparities in the epidemiological data between countries as well as in the unmet needs. The prevalence of allergic rhinitis has markedly increased in the past decades, with a high variation between countries, ranging from 4.5--80.3%. In terms of LAR, the reported prevalence in Southeast Asia is similar to that of other Asian countries (3.7-24.9%) but lower than that in western countries. House dust mites, cockroach, pollens, and molds are major allergens that are known triggers for of allergic rhinitis in this region, whereas the association with helminth infection requires further investigation. There are gaps and high variation between countries in Southeast Asia regarding the prevalence of allergic rhinitis and LAR. Further studies are needed to fully elucidate the association between allergens and allergic rhinitis in Southeast Asia.


Correction Without Consciousness in Complex Tasks: Evidence from Typing.
It has been demonstrated that with practice, complex tasks can become independent of conscious control, but even in those cases, repairing errors is thought to remain dependent on conscious control. This paper reports two studies probing conscious awareness over repairs in nearly 15,000 typing errors collected from 145 participants in a single-word typing-to-dictation task. We provide evidence for subconscious repairs by ruling out alternative accounts, and report two sets of analyses showing that a) such repairs are not confined to a specific stage of processing and b) that they are sensitive to the final outcome of repair. A third set of analyses provides a detailed comparison of the timeline of trials with conscious and subconscious repairs, revealing that the difference is confined to the repair process itself. We propose an account of repair processing that accommodates these empirical findings.


Failure of Fondaparinux in Autoimmune Heparin-Induced Thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin that is associated with life-threatening thrombotic complications. More rarely, HIT may begin after stopping of heparin or after flushes of heparin (autoimmune HIT). Fondaparinux has been proposed as a candidate treatment for HIT, but there are few data on its use in autoimmune HIT. An 86-year-old man with a history of diabetes mellitus, arterial hypertension, and hypercholesterolemia was admitted to our hospital for carotid endarterectomy. During surgery, only one heparin dose of 5,000 U was used. Platelet count started to decrease on the 11th day after surgery. Since the patient was not receiving heparin treatment/prophylaxis, HIT was not suspected. On day 19, platelet count was 61 × 10 3 /μL, and the patient was investigated for a diagnosis of HIT. Immunoglobulin (Ig)-G-specific enzyme-linked immunosorbent assay (ELISA) was positive and HIT was confirmed by a platelet aggregation test; fondaparinux 5 mg once a day was started. During fondaparinux treatment, platelet count did not increase and a lower leg deep vein thrombosis occurred. Fondaparinux was stopped and rivaroxaban 15 mg twice a day was started. Platelet count returned to base line after 10 days from fondaparinux withdrawal. There was no thrombotic event or bleeding complication during rivaroxaban treatment. Anecdotal evidence suggests risk of failure of fondaparinux treatment for autoimmune HIT and supports the use of rivaroxaban for treatment of HIT, justifying larger studies.


[Cerebral vascular complication of hyperhomocysteinemia. Controlling thromboembolic complications with folates].
Young patients who experience cardiovascular events may have raised levels of homocysteine. There may be several causes for this hyperhomocysteinemia. Cerebrovascular disease occurred in a 40-year-old female smoker with hyperhomocysteinemia. This patient subsequently had several episodes of thromboembolism involving the brain and lower limb arteries. Prothrombin concentration was difficult to control with antivitamin K anticoagulants. Investigations to identify a genetic cause of hyperhomocysteinemia revealed that she was homozygous for the C677T mutation on the methylenetetrahydrofolate reductase gene. There was no G1691A mutation of the factor V gene, a risk factor for familial thrombosis. Supplementation with folic acid successfully halted episodes of thromboembolism (follow-up 2 years) and prothrombin levels stabilized under treatment. The C677T mutation, which is common in the general population (15.7%), cannot explain the effect of folate supplementation alone. Other mutations affecting homocysteine metabolism could have a potentializing effect on vascular events.


Liver transplantation using young pediatric donor grafts in adults with hepatitis C infection.
The impact of using grafts from donor's age less than or equal to 13 years on adult hepatitis C virus (HCV) recipients in terms of survival and HCV recurrence is undefined. To determine if adults undergoing liver transplantation for HCV who receive a graft from a donor age less than or equal to 13 years have similar outcomes to recipients of organs from 18- to 35-year-old donors. Records from adult HCV patients undergoing liver transplantation between April 1998 and April 2004 who received whole grafts from non-HCV donors less than 35 years old after brain death were reviewed. Patients with donor age less than or equal to 13 years (group 1) and 18 to 35 years (group 2) were compared for patient and graft survival, allograft rejection, biliary complications, and HCV recurrence. Fifty-one HCV patients were analyzed. The two groups were similar except that group 1 donors and recipients were smaller in size. One year patient and graft survival for groups 1 vs. 2 were 93% vs. 94% and 93% vs. 83%, respectively (P=NS). Biliary complications, HCV recurrence, and advanced fibrosis free survival were not significantly different. Whole liver grafts from donors age less than or equal to 13 years can potentially be used in selected size-matched adult HCV patients in the absence of an acceptable pediatric recipient.


[Focusing on Recent Trends in Clinical Oncology and Palliative Care].
The integration of standard oncology and palliative care has become common around the world. Since the proposal of this approach by ASCO in the late 1990s, and studies by Temel, et al on EBM using RCT in 2010, and by Kaasa, et al at the Lancet Oncology Commission in 2018, it seems that most of the world agrees. Today, there are increasing expectations that comprehensive cancer care should be carried out by a multidisciplinary team. However, this has been challenging due to significant ideological differences between cancer treatment based on natural science and palliative care, which is mainly based on social science. From this, the idea of"palliative oncology"developed, which is built on the premise that palliative care should exist as a science derived from symptomatic treatment. Therefore, clinical oncologists should provide palliative care to enable better integration in cancer care.


Dementia and personhood: a focus for care?
The philosophy of nursing emphasizes the importance of holistic care delivered to an individual and their significant others through a shared understanding of the person. Dementia, however, strikes at the very nature of personhood, and carers are challenged to re-evaluate how care can be adjusted to help preserve dignity and independence during a very variable span of deteriorating mental function. This paper explores the impact of dementia on patients and carers through the meanings of self and body image which give individuality to each of us. It concludes by highlighting how recognition of this may assist carers to accommodate the necessary changes associated with the illness.


Assessment and management of the patient presenting with snoring.
Snoring is experienced regularly by approximately 30% of male adults, of whom one in seven will have obstructive sleep apnoea syndrome. Women experience snoring and apnoea at a rate of approximately half of that of men. General practitioners have a key role in the management of snoring. Patients whose symptoms of excessive sleepiness and loud habitual snoring more than three times per week, should alert the GP to the presence of apnoeas. The co-existence of systemic essential hypertension, especially if more than two drugs are required for its control, or any other cardiovascular disease, would increase suspicion of significant sleep apnoea. Conservative measures such as reduction in weight, alcohol and nasal resistance can be instigated in such patients immediately. Patients who have failed conservative treatment, or have suspected moderate to severe apnoea, need to be referred to a physician trained in sleep disorders for further evaluation and management. Snoring represents a trumpeters introduction to the three spectra of sleep related breathing disorders. These vary from simple snoring to profoundly severe snoring associated with obstructive sleep apnoea syndrome and cardiovascular sequelae, through to orthopnoea, paroxysmal nocturnal dyspnoea and fragmented sleep associated with unstable or decompensated cardiovascular and/or pulmonary disease.


Cross-cultural comparison of depressive symptoms on the Beck Depression Inventory-II, across six population samples.
The Beck Depression Inventory (BDI) and BDI-II (revised version) are some of the most widely used and comparable self-report scales for assessing the presence and severity of depressive symptoms in many countries. However, although the relative mean score of each symptom in different countries may vary, the cultural differences of BDI-II symptoms for each item have not been previously studied. To examine the overall picture of the magnitude of the symptoms in the Finnish population, and compare the relative mean score of each symptom between all published population-based samples from different countries fulfilling the search criteria. We conducted a search for population-based studies reporting BDI-II item, using Scopus, PsycINFO and PubMed, and five population-based samples were identified. Relative average scores for each item of the scale were calculated for the Finnish population and five populations from other countries. Meta-regression methods were used to test the differences in the relative score of each symptom between each country separately, and results were then visually compared with spider charts. We found significant differences in several BDI-II item scores between countries: lower indecisiveness, higher changes in sleep pattern and higher irritability in Finland; higher loss of pleasure in Norway; higher loss of interest in the Dominic Republic; higher self-criticalness and feelings of punishment in Mexico; and higher sadness in Japan. Based on the study fundings and including all currently published population-based samples with BDI-II scores, cultural differences in depressive symptoms should be considered when interpreting BDI-II item scores.


Advanced Copper Composites Against Copper-Tolerant Xanthomonas perforans and Tomato Bacterial Spot.
Bacterial spot, caused by Xanthomonas spp., is a widespread and damaging bacterial disease of tomato (Solanum lycopersicum). For disease management, growers rely on copper bactericides, which are often ineffective due to the presence of copper-tolerant Xanthomonas strains. This study evaluated the antibacterial activity of the new copper composites core-shell copper (CS-Cu), multivalent copper (MV-Cu), and fixed quaternary ammonium copper (FQ-Cu) as potential alternatives to commercially available micron-sized copper bactericides for controlling copper-tolerant Xanthomonas perforans. In vitro, metallic copper from CS-Cu and FQ-Cu at 100 μg/ml killed the copper-tolerant X. perforans strain within 1 h of exposure. In contrast, none of the micron-sized copper rates (100 to 1,000 μg/ml) from Kocide 3000 significantly reduced copper-tolerant X. perforans populations after 48 h of exposure compared with the water control (P < 0.05). All copper-based treatments killed the copper-sensitive X. perforans strain within 1 h. Greenhouse studies demonstrated that all copper composites significantly reduced bacterial spot disease severity when compared with copper-mancozeb and water controls (P < 0.05). Although there was no significant impact on yield, copper composites significantly reduced disease severity when compared with water controls, using 80% less metallic copper in comparison with copper-mancozeb in field studies (P < 0.05). This study highlights the discovery that copper composites have the potential to manage copper-tolerant X. perforans and tomato bacterial spot.


Coherence of marine alien species biosecurity legislation: A study of England and Wales.
The marine environment is particularly at risk from the intentional and unintentional introduction and spread of invasive alien species (IAS); preventing their introduction and spread from occurring is therefore, a key component in the on-going management of marine IAS. Ensuring legislation is coherent and consistent is essential to the success of managing the existing and future impacts of marine IAS. We explore the coherence (determined as consistency and interaction) of marine biosecurity legislation for IAS at different geopolitical scales. There was consistency between both the Bern Convention and Convention on Biological Diversity and European and national legislation that had been created in response. There was a lack of interaction evidenced by the Ballast Water Management Convention, which had not yet been transposed into regional (mainly European) or national legislation. Implementation measures such as legislation should be coherent as any failure in the chain could potentially weaken the overall effort to establish and maintain biosecurity and achieve behaviour change.


Collecting duct carcinoma of the kidney. A contribution of 4 new cases.
Collecting duct carcinoma of the kidney is a rare and aggressive subtype of renal cell carcinoma with low cancer-specific survival. We reviewed our series of collecting duct tumours retrospectively. We performed a retrospective analysis of the collecting duct carcinomas of the kidney treated in our unit between January 2007 and December 2012. The variables analysed were: age, gender, reason for consultation, side affected, ASA score according to anaesthetic risk, surgical treatment, tumour size, Fuhrman grade, lymphovascular invasion, TNM staging (2009 classification), adjuvant treatment and survival time. Four collecting duct carcinomas were identified. Mean patient age was 61 years. Constitutional syndrome and lower back pain were the most frequent reasons for consultation (75%), followed by hematuria. The surgical treatment was laparoscopic radical nephrectomy in 100% of the cases, with lymphadenectomy in 2 patients due to lymph node disease detected on imaging studies. The 4 patients were initially treated with temsirolimus as adjuvant therapy with no response. Two patients were given second-line treatment with sunitinib without any response. All 4 patients died from their disease with a mean survival of 9.5 months (rang: 4-15 months). Collecting duct carcinoma of the kidney is a rare and aggressive renal parenchymal tumour. Long-term survival rate is low, because the only potentially curative treatment seems to be surgery if it is performed in patients with localised tumours.


Self-construction of supramolecular polyrotaxane films by an electrotriggered morphogen-driven process.
The design of films using a one-pot process has recently attracted increasing interest in the field of polymer thin film formation. Herein we describe the preparation of one-pot supramolecular polyrotaxane (PRX) films using the morphogen-driven self-construction process. This one-pot buildup strategy where the film growth is triggered by the electrochemical formation and diffusion of a catalyst in close vicinity of the substrate has recently been introduced by our group. A one-pot mixture was used that contained (i) poly(acrylic acid) (PAA) functionalized by azide groups grafted on the polymer chain through oligo(ethylene glycol) (EG) arms, leading to PAA-EG13-N3, (ii) cyclodextrins (α and β CD), as macrocycles that can be threaded along EG arms, (iii) alkyne-functionalized stoppers (ferrocene or adamantane), to cap the PRX assembly by click chemistry, and (iv) copper sulfate. The one-pot mixture solution was brought into contact with a gold electrode. Cu(I), the morphogen, was generated electrochemically from Cu(II) at the electrode/one-pot solution interface. This electrotriggered click reaction leads to the capping of polypseudorotaxane yielding to PRXs. The PRXs can self-assemble through lateral supramolecular interactions to form aggregates and ensure the cohesion of the film. The film buildup was investigated using different types of CD and alkyne functionalized stoppers. Supramolecular PRX aggregates were characterized by X-ray diffraction measurements. The film topographies were imaged by atomic force microscopy. The influence of the concentration in CD and the presence of a competitor were studied as well. The stability of the resulting film was tested in contact with 8 M urea and during the electrochemical oxidation of ferrocene.


Electron microscopy and theoretical modeling of cochleates.
Cochleates are self-assembled cylindrical condensates that consist of large rolled-up lipid bilayer sheets and represent a novel platform for oral and systemic delivery of therapeutically active medicinal agents. With few preceding investigations, the physical basis of cochleate formation has remained largely unexplored. We address the structure and stability of cochleates in a combined experimental/theoretical approach. Employing different electron microscopy methods, we provide evidence for cochleates consisting of phosphatidylserine and calcium to be hollow tubelike structures with a well-defined constant lamellar repeat distance and statistically varying inner and outer radii. To rationalize the relation between inner and outer radii, we propose a theoretical model. Based on the minimization of a phenomenological free energy expression containing a bending, adhesion, and frustration contribution, we predict the optimal tube dimensions of a cochleate and estimate ratios of material constants for cochleates consisting of phosphatidylserines with varied hydrocarbon chain structures. Knowing and understanding these ratios will ultimately benefit the successful formulation of cochleates for drug delivery applications.


Acquired Lutembacher syndrome or mitral stenosis and acquired atrial septal defect after transseptal mitral valvuloplasty.
Critical mitral stenosis in selected patients may be treated successfully with percutaneous mitral valvuloplasty. Complications of this procedure, particularly an atrial septal defect following transseptal approach, are generally of minor clinical significance. We describe a woman who initially underwent a successful percutaneous double-balloon mitral valvuloplasty via the transseptal approach. Three months later she presented with right-sided heart failure. Color Doppler echocardiography and cardiac catheterization demonstrated an atrial septal defect (ASD) as well as restenosis of the mitral valve. We conclude that significant ASDs may occur following transseptal mitral valvuloplasty with appearance of right ventricular failure and that color Doppler imaging aids in the diagnosis of this new variant of the classical Lutembacher syndrome.


Animal and Cellular Studies Demonstrate Some of the Beneficial Impacts of Herring Milt Hydrolysates on Obesity-Induced Glucose Intolerance and Inflammation.
The search for bioactive compounds from enzymatic hydrolysates has increased in the last few decades. Fish by-products have been shown to be rich in these valuable molecules; for instance, herring milt is a complex matrix composed of lipids, nucleotides, minerals, and proteins. However, limited information is available on the potential health benefits of this by-product. In this context, three industrial products containing herring milt hydrolysate (HMH) were tested in both animal and cellular models to measure their effects on obesity-related metabolic disorders. Male C57Bl/6J mice were fed either a control chow diet or a high-fat high-sucrose (HFHS) diet for 8 weeks and received either the vehicle (water) or one of the three HMH products (HMH1, HMH2, and HMH3) at a dose of 208.8 mg/kg (representing 1 g/day for a human) by daily oral gavage. The impact of HMH treatments on insulin and glucose tolerance, lipid homeostasis, liver gene expression, and the gut microbiota profile was studied. In parallel, the effects of HMH on glucose uptake and inflammation were studied in L6 myocytes and J774 macrophages, respectively. In vivo, daily treatment with HMH2 and HMH3 improved early time point glycemia during the oral glucose tolerance test (OGTT) induced by the HFHS diet, without changes in weight gain and insulin secretion. Interestingly, we also observed that HMH2 consumption partially prevented a lower abundance of Lactobacillus species in the gut microbiota of HFHS diet-fed animals. In addition to this, modulations of gene expression in the liver, such as the upregulation of sucrose nonfermenting AMPK-related kinase (SNARK), were reported for the first time in mice treated with HMH products. While HMH2 and HMH3 inhibited inducible nitric oxide synthase (iNOS) induction in J774 macrophages, glucose uptake was not modified in L6 muscle cells. These results indicate that milt herring hydrolysates reduce some metabolic and inflammatory alterations in cellular and animal models, suggesting a possible novel marine ingredient to help fight against obesity-related immunometabolic disorders.


Injection of human primary effusion lymphoma cells or associated macrophages into severe combined immunodeficient mice causes murine lymphomas.
The pathogenesis of immunodeficiency-associated lymphoma is poorly understood. During the past several years, numerous lines of evidence implicating a multistep process of malignant transformation, also known as sequential pathogenesis, have emerged. Tumor-associated macrophage production of specific lymphostimulatory products has been demonstrated and hypothesized to be central to this process. While attempting to establish primary effusion lymphoma in severe combined immunodeficient (SCID) mice, we discovered a potential model of murine lymphomagenesis consistent with the sequential pathogenesis model. This pathogenesis-based model of lymphoma could significantly impact the current thinking about posttransplantation and other immunodeficiency-related lymphoproliferative disorders. Human primary effusion lymphoma-derived CD14+ cell-injected SCID mice developed aggressive murine large cell lymphomas. Tumor cell preparations containing CD14 cells or isolated CD14 cells induced lymphoma/lymphoproliferative diseases in 74% (20 of 27) of injected SCID mice. No tumors were induced by tumor-associated CD3 cells (0 of 4), normal human macrophages (0 of 13), or a murine macrophage cell line (0 of 10). Human macrophages were detected in tumor-bearing animals up to 6 months postinjection in association with the murine T-cell tumors but were not detected in controls or unaffected animals. These observations are consistent with the macrophage-initiated sequential pathogenesis model of disease (M. S. McGrath et al., Acquir. Immune Defic. Syndr., 8: 379-385, 1995; M. S. McGrath et al., Infectious Causes of Cancer: Targets for Intervention, pp. 231-242, Totowa, NJ: Humana Press, 2000).


Host-Symbiont Interactions: III. Purification and Partial Characterization of Rhizobium Lipopolysaccharides.
The lipopolysaccharides of three strains each of Rhizobium leguminosarum, R. phaseoli, and trifolii have been purified and partially characterized. The last step in the purification procedure is gel filtration column chromatography using Sepharose 4B with an elution buffer consisting of ethylenediaminetetraacetic acid and triethylamine. Each of the lipopolysaccharides reported in this paper elutes as a symmetrical peak in the partially included volume of this Sepharose 4B column. The ratio of 2-keto-3-deoxyoctonate acid (a sugar which is characteristic of lipopolysaccharides) to hexose is constant throughout the carbohydrate-containing peaks as they elute from the Sepharose 4B. The compositions and immunodominant structures of the purified lipopolysaccharides vary as much among strains of a single Rhizobium species as among the different species of Rhizobium. There is no obvious correlation between the nodulation group to which a Rhizobium belongs and the chemical composition or immunochemistry of the Rhizobium's lipopolysaccharide. There is extensive crosslysis by phage of strains of R. trifolii, R. phaseoli, and R. leguminosarum. This suggests that the receptors for these cross-lysing phage reside either in nonlipopolysaccharide structures or in common structures within the lipopolysaccharide which are not detected by compositional or immunochemical analysis.


The linking chain length in bridged aldehyde-substituted pyridinium dimers modulates a slow reversible binding that affects supercoiling of plasmid DNA.
Bridged aldehyde substituted pyridinium dimers bind to DNA. Binding induces retardation of the electrophoretic migration of circular plasmid due to relaxation of supercoiling. Binding to DNA is slow and reversible and depends on the length of linking chain, pH, ionic strength and temperature. It is postulated that release of topological stress results from the disruption of hydrogen bonding between complementary bases, a hypothesis consistent with facilitated attack of DNA by formaldehyde promoted by the bridged compounds.


A Nomogram Modeling 11C-MET PET/CT and Clinical Features in Glioma Helps Predict IDH Mutation.
Purpose: We developed a 11C-Methionine positron emission tomography/computed tomography (11C-MET PET/CT)-based nomogram model that uses easy-accessible imaging and clinical features to achieve reliable non-invasive isocitrate dehydrogenase (IDH)-mutant prediction with strong clinical translational capability. Methods: One hundred and ten patients with pathologically proven glioma who underwent pretreatment 11C-MET PET/CT were retrospectively reviewed. IDH genotype was determined by IDH1 R132H immunohistochemistry staining. Maximum, mean and peak tumor-to-normal brain tissue (TNRmax, TNRmean, TNRpeak), metabolic tumor volume (MTV), total lesion methionine uptake (TLMU), and standard deviation of SUV (SUVSD) of the lesions on MET PET images were obtained via a dedicated workstation (Siemens. syngo.via). Univariate and multivariate logistic regression models were used to identify the predictive factors for IDH mutation. Nomogram and calibration plots were further performed. Results: In the entire population, TNRmean, TNRmax, TNRpeak, and SUVSD of IDH-mutant glioma patients were significantly lower than these values of IDH wildtype. Receiver operating characteristic (ROC) analysis suggested SUVSD had the best performance for IDH-mutant discrimination (AUC = 0.731, cut-off ≤ 0.29, p < 0.001). All pairs of the 11C-MET PET metrics showed linear associations by Pearson correlation coefficients between 0.228 and 0.986. Multivariate analyses demonstrated that SUVSD (>0.29 vs. ≤ 0.29 OR: 0.053, p = 0.010), dichotomized brain midline structure involvement (no vs. yes OR: 26.52, p = 0.000) and age (≤ 45 vs. >45 years OR: 3.23, p = 0.023), were associated with a higher incidence of IDH mutation. The nomogram modeling showed good discrimination, with a C-statistics of 0.866 (95% CI: 0.796-0.937) and was well-calibrated. Conclusions: 11C-Methionine PET/CT imaging features (SUVSD and the involvement of brain midline structure) can be conveniently used to facilitate the pre-operative prediction of IDH genotype. The nomogram model based on 11C-Methionine PET/CT and clinical age features might be clinically useful in non-invasive IDH mutation status prediction for untreated glioma patients.


[Hexavalent combined vaccination].
Since January 2004, hexavalent combined vaccines are available in Belgium. They protect children simultaneously against 6 diseases (poliomyelitis, diphtheria, tetanus, pertussis, invasive infections with Haemophilus influenzae type b and hepatitis B) and reduce the number of needed injections. Acellular pertussis vaccine is the corner-stone of the combination. Theoretically, only 5 visits and 6 injections are needed to complete the vaccination of the children. In addition to the reduction of injections and consequently a better comfort for the child, Hexavalent vaccination favours an increase of immunization coverage, alleviation of the burden of diseases evitable by vaccination, simplification of immunisation programme and diminution of their cost. However an increased surveillance of the incidence of the diseases, particularly for pertussis and invasive Haemophilus influenzae type b disease is needed. As always for a new product, pharmacovigilance has to be able to detect any severe adverse event. Parent's information must be strengthened to maintain confidence in the immunization programme. Medical practice will have to adapt to the new vaccine because it reduces individual flexibility and modifies the catch-up immunization schedule.


Regional cerebral blood flow during signed and heard episodic and semantic memory tasks.
Ten deaf participants and 10 normal hearing participants performed 2 memory tasks during which their regional cerebral blood flow was measured with a high-resolution system. The deaf participants solved an episodic memory (i.e., recognition of words) and a semantic memory (i.e., classification of items into categories) task presented by means of sign language; the same material was presented to the hearing participants who heard the stimulus lists. The specific hypothesis that signed episodic recognition tasks would activate posterior, right-hemisphere cortical areas was supported. Expectedly, the remaining 3 memory activations were mainly located in the left hemisphere. Data from recent positron emission tomography studies suggest that one challenge for future research is to assess the relative localization for encoding and retrieval of signed episodes.


Anticancer Activity of a Novel High Phenolic Sorghum Bran in Human Colon Cancer Cells.
Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH2-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.


The Mycobacterium tuberculosis SecA2 system subverts phagosome maturation to promote growth in macrophages.
The ability of Mycobacterium tuberculosis to grow in macrophages is critical to the virulence of this important pathogen. One way M. tuberculosis is thought to maintain a hospitable niche in macrophages is by arresting the normal process of phagosomes maturing into acidified phagolysosomes. The process of phagosome maturation arrest by M. tuberculosis is not fully understood, and there has remained a need to firmly establish a requirement for phagosome maturation arrest for M. tuberculosis growth in macrophages. Other intracellular pathogens that control the phagosomal environment use specialized protein export systems to deliver effectors of phagosome trafficking to the host cell. In M. tuberculosis, the accessory SecA2 system is a specialized protein export system that is required for intracellular growth in macrophages. In studying the importance of the SecA2 system in macrophages, we discovered that SecA2 is required for phagosome maturation arrest. Shortly after infection, phagosomes containing a ΔsecA2 mutant of M. tuberculosis were more acidified and showed greater association with markers of late endosomes than phagosomes containing wild-type M. tuberculosis. We further showed that inhibitors of phagosome acidification rescued the intracellular growth defect of the ΔsecA2 mutant, which demonstrated that the phagosome maturation arrest defect of the ΔsecA2 mutant is responsible for the intracellular growth defect. This study demonstrates the importance of phagosome maturation arrest for M. tuberculosis growth in macrophages, and it suggests there are effectors of phagosome maturation that are exported into the host environment by the accessory SecA2 system.


Fentanyl-fluanisone-midazolam combination results in more stable hemodynamics than does urethane alpha-chloralose and 2,2,2-tribromoethanol in mice.
Near-physiologic hemodynamic conditions for several hours were needed to study cardiovascular physiology in a murine model. We compared two commonly used anesthetic treatments, urethane alpha-chloralose (U-alphaCh; 968 mg U and 65 mg alphaCh/kg) and 2,2,2-tribromoethanol (TBE; 435 mg/kg) and fentanyl fluanisone midazolam (FFM; 3.313 mg fentanyl, 104.8 mg fluanisone, and 52.42 mg midazolam/kg) with respect to mean arterial blood pressure (MAP) and heart rate (HR) for 100 min at similar levels of surgical anesthesia. Assessed every 10 to 15 min, the U-alphaCh+TBE group maintained a significantly (P < 0.001) lower mean MAP (49 4 mmHg) than did the FFM group (78 5 mmHg). Mean HR in the U-alphaCh+TBE group significantly (P < 0.001) increased from 308 34 bpm at the beginning to 477 43 bpm at the end of the experiment. In comparison, the FFM group showed a stable HR of 431 37 bpm. The MAP and HR of the U-alphaCh+TBE group were extremely unstable, with sudden and unpredictable changes in MAP when examined at 1-min intervals. The results of our study show that U-alphaCh+TBE anesthesia should not be used in murine models in which stable, near-physiologic hemodynamics are needed for cardiovascular studies.


Therapy of active chronic hepatitis with recombinant alpha 2b-interferon: an 18 month follow-up.
The aim of this study was to evaluate the efficacy of interferon therapy in patients with "active" chronic hepatitis. A total of 115 patients with histological diagnosis of active chronic hepatitis were enrolled in the study and treated with recombinant alpha 2b-interferon at a dosage of 3 MU, 3 times a week, for a 6 month period. Patients who showed a complete normalization of serum aminotransferase levels were followed for further 12 months, in which no treatment was performed. After 6 months of treatment, 50 (43.4%) patients showed normalized serum aminotransferase levels and among these "responders", 18 (36%) showed a persistent normalization 12 months after stopping interferon therapy. Only 7 patients at the end of the study agreed to a second liver biopsy which showed a decrease in Knodell's index and a clear-cut reduction of inflammation and lobular necrosis. Interferon is useful for the treatment of chronic active anti-HCV positive hepatitis but the beneficial responses are often transient. Future therapeutic strategies and the development of direct assay for HCV in serum and liver are necessary to understand the real role of interferon in chronic anti-HCV positive hepatitis.


NIR laser tissue welding of in vitro porcine cornea and sclera tissue.
The objective of this study was to test the hypothesis that an near infrared (NIR) laser system (1,455 nm) in combination with a motorized translational stage to control the position and speed of the laser beam and a shutter to control the laser exposure to the tissue being welded could be used to successfully weld ocular tissues. Seventy-five porcine corneas and 23 porcine scleral tissues were welded in vitro in this study. The welded tissues were examined using histopathology and tensile strength analysis. Eight different welding conditions were analyzed for porcine cornea and one for sclera tissues. The tensile strength of the welded groups was compared to a sutured cornea control group. The NIR laser welding system provides strong, full thickness welds and does not require the use of extrinsic dyes, chromophores, or solders. Mean weld strengths of 0.15-0.45 kg/cm(2) were obtained for the cornea and 1.01 kg/cm(2) for sclera welds. The native H(2)O in the ocular tissue serves as an absorber of the 1,455 nm radiation and helps to induce the welds. We conclude that an NIR laser system using an optimal laser radiation wavelength of 1,455 nm can effectively weld cornea and sclera tissue and that this laser tissue welding (LTW) methodology typically causes minimal disruption of tissue, and thus, avoids opacities and irregularities in the tissue which may result in decreased visual acuity. The optimization of a laser welding system that leads to a strong full thickness tissue bond without tissue destruction, an instant seal that promotes wound healing, and the absence of a continued presence of a foreign substance like a suture, is of considerable importance to the ophthalmology medical community. This need is especially apparent with respect to corneal transplantation and fixing the position of corneal flaps in Laser-Assisted In Situ Keratomileusis (LASIK), a laser procedure used to permanently change the shape of the cornea.


Audit of the support for breastfeeding mothers in Fife maternity hospitals using adapted 'Baby Friendly Hospital' materials.
The objective of this study was to assess the level of support given to breastfeeding mothers during their stay in maternity hospitals. The audit was carried out in maternity hospitals in Fife with the co-ordination of the Fife Joint Breastfeeding initiative. The subjects consisted of ten maternity hospital staff (medical and midwifery), and 12 antenatal and 21 postnatal women. The design of the study consisted of an audit of hospital policies and practices in comparison with ten internationally recognized standards. This was carried out by adapting the external evaluation instruments from the WHO-UNICEF "Baby Friendly Hospital" materials. Methods relied not only on reported practices but also on direct observation and enquiry. Action was taken to address areas of practice which fell below the WHO-UNICEF standards: supplementary feeding of breastfed babies, particularly overnight, was reduced; discharge "bounty packs" advertising baby milk manufacturer products were discontinued; a hospital breastfeeding support group was established; the hypoglycaemia policy was revised; and the need for an orientation session on breastfeeding policies for medical staff was recognized. This audit approach using "Baby Friendly Hospital' materials has helped to define policy, measure performance against recognized standards, identify quality specifications for maternity service agreements and has improved hospital support for breastfeeding mothers. This approach is suitable for maternity hospitals whose breastfeeding rates make them ineligible for "Baby Friendly Hospital" accreditation, and has the potential to be extended to encompass wider "health-promoting hospital" issues such as promotion of infant car seats.


Soluble Flavanthrone Derivatives: Synthesis, Characterization, and Application to Organic Light-Emitting Diodes.
Simple modification of benzo[h]benz[5,6]acridino[2,1,9,8-klmna]acridine-8,16-dione, an old and almost-forgotten vat dye, by reduction of its carbonyl groups and subsequent O-alkylation, yields solution-processable, electroactive, conjugated compounds of the periazaacene type, suitable for the use in organic electronics. Their electrochemically determined ionization potential and electron affinity of about 5.2 and -3.2 eV, respectively, are essentially independent of the length of the alkoxyl substituent and in good agreement with DFT calculations. The crystal structure of 8,16-dioctyloxybenzo[h]benz[5,6]acridino[2,1,9,8-klmna]acridine (FC-8), the most promising compound, was solved. It crystallizes in space group P1‾ and forms π-stacked columns held together in the 3D structure by dispersion forces, mainly between interdigitated alkyl chains. Molecules of FC-8 have a strong tendency to self-organize in monolayers deposited on a highly oriented pyrolytic graphite surface, as observed by STM. 8,16-Dialkoxybenzo[h]benz[5,6]acridino[2,1,9,8-klmna]acridines are highly luminescent, and all have photoluminescence quantum yields of about 80 %. They show efficient electroluminescence, and can be used as guest molecules with a 4,4'-bis(N-carbazolyl)-1,1'-biphenyl host in guest/host-type organic light-emitting diodes. The best fabricated diodes showed a luminance of about 1900 cd m(-12) , a luminance efficiency of about 3 cd A(-1) , and external quantum efficiencies exceeding 0.9 %.


Raising the Bar: Improving Antimicrobial Resistance Detection by Clinical Laboratories by Ensuring Use of Current Breakpoints.
Antimicrobial resistance (AMR) is a pressing global challenge detected by antimicrobial susceptibility testing (AST) performed by clinical laboratories. AST results are interpreted using clinical breakpoints, which are updated to enable accurate detection of new and emerging AMR. Laboratories that do not apply up-to-date breakpoints impede global efforts to address the AMR crisis, but the extent of this practice is poorly understood. A total of 1490 clinical laboratories participating in a College of American Pathologists proficiency testing survey for bacterial cultures were queried to determine use of obsolete breakpoints. Between 37.9% and 70.5% of US laboratories reported using obsolete breakpoints for the antimicrobials that were queried. In contrast, only 17.7%-43.7% of international laboratories reported using obsolete breakpoints (P < .001 for all comparisons). Use of current breakpoints varied by AST system, with more laboratories reporting use of current breakpoints in the US if the system had achieved US Food and Drug Administration clearance with current breakpoints. Among laboratories that indicated use of obsolete breakpoints, 55.9% had no plans to update to current standards. The most common reason cited was manufacturer-related issues (51.3%) and lack of internal resources to perform analytical validation studies to make the update (23.4%). Thirteen percent of laboratories indicated they were unaware of breakpoint changes or the need to update breakpoints. These data demonstrate a significant gap in the ability to detect AMR in the US, and to a lesser extent internationally. Improved application of current breakpoints by clinical laboratories will require combined action from regulatory agencies, laboratory accreditation groups, and device manufacturers.


Big Cat Coalitions: A Comparative Analysis of Regional Brain Volumes in Felidae.
Broad-based species comparisons across mammalian orders suggest a number of factors that might influence the evolution of large brains. However, the relationship between these factors and total and regional brain size remains unclear. This study investigated the relationship between relative brain size and regional brain volumes and sociality in 13 felid species in hopes of revealing relationships that are not detected in more inclusive comparative studies. In addition, a more detailed analysis was conducted of four focal species: lions (Panthera leo), leopards (Panthera pardus), cougars (Puma concolor), and cheetahs (Acinonyx jubatus). These species differ markedly in sociality and behavioral flexibility, factors hypothesized to contribute to increased relative brain size and/or frontal cortex size. Lions are the only truly social species, living in prides. Although cheetahs are largely solitary, males often form small groups. Both leopards and cougars are solitary. Of the four species, leopards exhibit the most behavioral flexibility, readily adapting to changing circumstances. Regional brain volumes were analyzed using computed tomography. Skulls (n = 75) were scanned to create three-dimensional virtual endocasts, and regional brain volumes were measured using either sulcal or bony landmarks obtained from the endocasts or skulls. Phylogenetic least squares regression analyses found that sociality does not correspond with larger relative brain size in these species. However, the sociality/solitary variable significantly predicted anterior cerebrum (AC) volume, a region that includes frontal cortex. This latter finding is despite the fact that the two social species in our sample, lions and cheetahs, possess the largest and smallest relative AC volumes, respectively. Additionally, an ANOVA comparing regional brain volumes in four focal species revealed that lions and leopards, while not significantly different from one another, have relatively larger AC volumes than are found in cheetahs or cougars. Further, female lions possess a significantly larger AC volume than conspecific males; female lion values were also larger than those of the other three species (regardless of sex). These results may reflect greater complexity in a female lion's social world, but additional studies are necessary. These data suggest that within family comparisons may reveal variations not easily detected by broad comparative analyses.


Enhancing the absorption capabilities of thin-film solar cells using sandwiched light trapping structures.
A novel structure for thin-film solar cells is simulated with the purpose of maximizing the absorption of light in the active layer and of reducing the parasitic absorption in other layers. In the proposed structure, the active layer is formed from an amorphous silicon thin film sandwiched between silicon nanowires from above and photonic crystal structures from below. The upper electrical contact consists of an indium tin oxide layer, which serves also as an antireflection coating. A metal backreflector works additionally as the other contact. The simulation was done using a new reliable, efficient and generic optoelectronic approach. The suggested multiscale simulation model integrates the finite-difference time-domain algorithm used in solving Maxwell's equation in three dimensions with a commercial simulation platform based on the finite element method for carrier transport modeling. The absorption profile, the external quantum efficient, and the power conversion efficiency of the suggested solar cell are calculated. A noticeable enhancement is found in all the characteristics of the novel structure with an estimated 32% increase in the total conversion efficiency over a cell without any light trapping mechanisms.


[In situ transcription and determination of mRNA in human thymic antigen 1a positive cells within epidermis].
This paper introduces a method of study on the characteristics of cell surface protein. We used human thymic antigen 1a anti-sense oligonucleotide primer, radiolabeled deoxynucleotide and in situ transcription with cells. The results of in situ transcription and determination of mRNA in CD1a positive cells isolated from the epidermis of the prepuce of normal neonate showed that most of the positive cells contained specific CD1a mRNA, and the specificity and sensitivity of this method were higher and the procedure was relatively simple.


Application of Autogenous Urine-Derived Stem Cell Sheet Enhances Rotator Cuff Healing in a Canine Model.
A repaired rotator cuff (RC) often heals with interposed scar tissue, making repairs prone to failure. Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for harvesting the cells. These advantages make it a novel cell source for autologous transplantation to enhance RC healing. Implantation of an autogenous USC sheet to the injury site will enhance RC healing. Controlled laboratory study. USCs isolated from urine were cultured using ascorbic acid and transforming growth factor β3 to form a cell sheet. Sixteen male mature beagles underwent bilateral shoulder surgery. The right shoulder underwent infraspinatus tendon (IT) insertion detachment and repair only, and the other was subjected to IT insertion detachment and repair, followed by autogenous USC sheet implantation. Among the animals, 3 received a Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate)- labeled USC sheet implant in the right shoulder and were sacrificed at postoperative 6 weeks for cell tracking. The other animals were sacrificed at postoperative 12 weeks, and the IT-humerus complexes were harvested for gross observation, micro-computed tomography evaluation and histological analysis (n = 5), and mechanical testing (n = 8). Additionally, 13 unpaired canine cadaveric shoulders were included as native controls. Micro-computed tomography analysis showed that the USC sheet group had a significant increase in bone volume/total volume and trabecular thickness at the RC healing site when compared with the control group (P < .05 for all). Histologically, the Dil-labeled USC sheet was still visible at the RC healing site, which suggested that the implanted USCs remained viable at postoperative 6 weeks. Meanwhile, the healing interface in the USC sheet group regenerated significantly more enthesis-like tissue than did that of the control group (P < .05). Additionally, the healing interface in the USC sheet group presented a larger fibrocartilage area, more proteoglycan deposition, and higher collagen birefringence than did that of the control group (P < .05 for all). Biomechanically, the USC sheet group showed significantly higher failure load and stiffness versus the control group (P < .05 for all). A USC sheet was able to enhance RC healing in a canine model. The findings of the study showed that USC sheet implantation could serve as a practical application for RC healing.


[Change test with DHEA-S in vivo and in vitro. Hypotrophy and utero-placental blood flow (author's transl)].
Using the method of Cedard and al., we perfused 18 placentas of women in which DHEA-S loading test has been performed during pregnancy. For each placenta, we measured the increase of estrogens in the perfusate (E1 + E2) 15 minutes after the injection of 10 mg of DHEA-S, and we calculated the half-life of the precursor in the system in well-standardized conditions. The comparison between: 1. Placentas of small for date babies and normal ones. 2. The increase of estrogens and the half-life of DHEA-S measured during pregnancy on the one hand and the same data obtained from the perfusion on the other, leads us to conclude that the capacity of the placenta to metabolize DHEA-S into estrogens is not diminished in small-for-date babies. The factor which modifies the response of the DHEA-S loading test in poor intrauterine growth seems to be due to a reduction of utero-placental blood flow.


Bicunningines A and B, two new dimeric diterpenes from Cunninghamia lanceolata.
Two unprecedented dimeric diterpenoids, with a 2,3-dihydrofuran ring fusing an abietane and a 4,5-seco-abietane diterpene, were isolated from Cunninghamia lanceolata. Their structures were elucidated by spectroscopic measurements, and their absolute configurations were determined by quantum chemical TDDFT ECD calculations, chemical transformations, and Mosher's method. The Mosher method carried out with MPA and MTPA esters of the sterically hindered sec-hydroxyl group gave contradictory results, while MPA afforded the correct absolute configuration.


Neural mechanisms of mental fatigue elicited by sustained auditory processing.
Despite growing evidence that prolonged episodes of effortful listening can lead to mental fatigue, little work has been done to examine the patterns of brain activation associated with listening over time. In order to gain a better understanding of the nature of listening-related mental fatigue, this study characterized the effects of sustained auditory processing on brain activation in 19 adults with normal hearing. A 50-min, auditory choice paradigm served as the fatiguing task. Mental fatigue was quantified using subjective (self-report) and behavioral (response time and accuracy) measures, as well as event-related potential (ERP) measures indexing motivation (error-related negativity; ERN) and general arousal (N1). Additional electrical neuroimaging analyses were carried out on ERP datasets. Subjective and behavioral results confirmed that participants became fatigued during the auditory task (data from the first 25min compared with the second 25min). ERPs revealed changes in neural activity consistent with decreased arousal (reduced N1 amplitude). Topographical analyses indicated decreased brain activation, without a change in underlying neural network configuration. Regions of decreased brain activation, as estimated via electrical neuroimaging, suggested a decrease in attention to task stimulus-response characteristics (reduced activation in regions associated with the dorsal attention network). The decrease in mean N1 amplitude revealed a significant, positive correlation with subjective report of reduced motivation. These findings support existing cognitive and neurophysiological models that suggest mental fatigue builds over time on task, and affects motivation to influence task performance. Furthermore, this study shows sustained auditory processing can elicit mental fatigue, and that dorsal parietal activity might provide a useful method of measuring its effects.


23Na nuclear magnetic resonance spectral changes during and after forebrain ischemia in hypoglycemic, normoglycemic, and hyperglycemic rats.
The severity of brain injury in animal models of forebrain ischemia increases with blood glucose level. During ischemia, energy failure is slower and maintenance of ion gradients is prolonged as the level of glycemia increases. It is not clear how the level of glycemia influences recovery of ion homeostasis on reperfusion. It has been shown that changes in the intensity of the multiple-quantum 23Na nuclear magnetic resonance (NMR) signals reflect changes in intracellular Na+ levels. We have used 23Na NMR spectroscopy to evaluate the influence of the level of glycemia on changes in Na+ concentration during and after forebrain ischemia in rats. Single-quantum (SQ) and double-quantum (DQ) 23Na NMR spectra were measured before and during 10-minute forebrain ischemia and during reperfusion in hypoglycemic, normoglycemic, and hyperglycemic rats. The DQ 23Na NMR signal increased to 210% of preischemia intensity in all rats, but a delay in this increase was observed in normoglycemic and hyperglycemic animals. The rate of the DQ 23Na NMR signal increase was fastest in hypoglycemic (apparent first-order rate constant 0.673 +/- 0.046 min-1, P < .002 compared with normoglycemic animals) and slowest in hyperglycemic (0.285 +/- 0.024 min-1, P < .03) rats. During reperfusion, the signal intensity recovered rapidly in hypoglycemic (0.385 +/- 0.050 min-1) and normoglycemic (0.464 +/- 0.047 min-1) rats, whereas in hyperglycemic animals recovery was slow (0.108 +/- 0.044 min-1, P < .0001 compared with normoglycemic animals). The SQ 23Na NMR signal intensity increased to 117% of preischemia level in hypoglycemic (P < .05 compared with normoglycemic animals) and to 107% in normoglycemic and hyperglycemic animals during reperfusion. The slower increase in the 23Na DQ NMR signal intensity during forebrain ischemia in rats with higher blood glucose levels suggests that Na+ homeostasis is maintained longer in these animals. On reperfusion, the slower recovery of the DQ 23Na NMR signal intensity in hyperglycemic animals likely indicates a slower recovery of Na+ homeostasis, perhaps contributing to the increased neuronal injury after cerebral ischemia in hyperglycemic animals.


Colistin powders with high aerosolisation efficiency for respiratory infection: preparation and in vitro evaluation.
In many respiratory infections caused by multi-drug-resistant Gram-negative bacteria, colistin is often the last-line drug for treatment despite its nephrotoxicity when administered parenterally. Inhalation therapy of colistin has great potential to improve the efficacy while reducing adverse effects. In this study, inhalable powder formulations of colistin (sulphate) were produced via spray drying. The colistin powders were found to have intact antimicrobial activity against Acinetobacter baumannii measured by broth micro-dilution. Both the raw material and spray-dried formulations were amorphous and absorbed significant amount of water up to 30% (w/w) at relative humidity (RH) of at least 70%. The spray-dried formulations were physically stable in the amorphous form at 60% RH and 25°C, having a high aerosol efficiency (emitted dose >86% and fine particle fraction total >83%) which remained unchanged after a 3-month storage. Storage at an elevated RH of 75% resulted in the aerosolisation performance significantly decreased, and at RH 90%, the formulation particles fused together (but without re-crystallisation). Although spray drying has been extensively used for generating inhalable drug particles, this is the first report that colistin powder can be physically stable in the amorphous form at ambient conditions, indicating that spray-drying approach is suitable for producing inhalable colistin powder formulation.


Relating the ontogeny of functional morphology and prey selection with larval mortality in Amphiprion frenatus.
Survival during the pelagic larval phase of marine fish is highly variable and is subject to numerous factors. A sharp decline in the number of surviving larvae usually occurs during the transition from endogenous to exogenous feeding known as the first feeding stage in fish larvae. The present study was designed to evaluate the link between functional morphology and prey selection in an attempt to understand how the relationship influences mortality of a marine fish larva, Amphiprion frenatus, through ontogeny. Larvae were reared from hatch to 14 days post hatch (DPH) with one of four diets [rotifers and newly hatched Artemia sp. nauplii (RA); rotifers and wild plankton (RP); rotifers, wild plankton, and newly hatched Artemia nauplii (RPA); wild plankton and newly hatched Artemia nauplii (PA)]. Survival did not differ among diets. Larvae from all diets experienced mass mortality from 1 to 5 DPH followed by decreased mortality from 6 to 14 DPH; individuals fed RA were the exception, exhibiting continuous mortality from 6 to 14 DPH. Larvae consumed progressively larger prey with growth and age, likely due to age related increase in gape. During the mass mortality event, larvae selected small prey items and exhibited few ossified elements. Cessation of mass mortality coincided with consumption of large prey and ossification of key elements of the feeding apparatus. Mass mortality did not appear to be solely influenced by inability to establish first feeding. We hypothesize the interaction of reduced feeding capacities (i.e., complexity of the feeding apparatus) and larval physiology such as digestion or absorption efficiency contributed to the mortality event during the first feeding period.


Nanostructured Ceria-Praseodymium and Ceria-Terbium Mixed Oxides: Relationship Between Structural Change and Catalytic Activity Towards CO Oxidation.
The structural and textural properties of the Ce0.9Pr0.1O2-δ (CP) and Ce0.9Pr0.1O2-δ (CT) solid solutions were investigated by X-ray diffraction (XRD), BET surface area, transmission electron microscopy (TEM-HRTEM), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), Raman spectra, and X-ray photoelectron spectroscopy (XPS). The redox recoverability and catalytic activity were analyzed by temperature-programmed reduction (TPR) and oxidation reaction using carbon monoxide as a probe molecule. It was found that the CP solid solution exhibited better structural thermal stability, oxygen storage/release capacity, as well as redox ability than that of CT solid solution, since that the microstructure and oxygen vacancy concentration of CP sample under actual using process could recover to its initial status more easily in oxygen, even at room temperature. Therefore, the CP sample presented better CO oxidation activity compared with that of CT solid solution.


RNA editing is abundant and correlates with task performance in a social bumblebee.
Colonies of the bumblebee Bombus terrestris are characterized by wide phenotypic variability among genetically similar full-sister workers, suggesting a major role for epigenetic processes. Here, we report a high level of ADAR-mediated RNA editing in the bumblebee, despite the lack of an ADAR1-homolog. We identify 1.15 million unique genomic sites, and 164 recoding sites residing in 100 protein coding genes, including ion channels, transporters, and receptors predicted to affect brain function and behavior. Some edited sites are similarly edited in other insects, cephalopods and even mammals. The global editing level of protein coding and non-coding transcripts weakly correlates with task performance (brood care vs. foraging), but not affected by dominance rank or juvenile hormone known to influence physiology and behavior. Taken together, our findings show that brain editing levels are high in naturally behaving bees, and may be regulated by relatively short-term effects associated with brood care or foraging activities.


An exploratory study to evaluate visual function endpoints in non-advanced age-related macular degeneration.
To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD. A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1-4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF™ test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated. There was no difference in standard ETDRS VA between non-advanced AMD (0.06 ± 0.02 logMAR) and normal groups (0.04 ± 0.02 logMAR) (p = 0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p > 0.05). Ora-VCF™ test was significantly worse in the non-advanced AMD group compared to normals (0.67 ± 0.07 in AMD; 0.45 ± 0.04 in normals, p = 0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55 ± 11.22 wpm in AMD; 145.17 ± 9.55 wpm in normals p = 0.049). No significant difference between the groups was noted using other tests. Repeatability was 82% for Ora-VCF™ test and 92% for Ora-tablet LL 2.0ND reading. Reproducibility was 89% for both Ora-VCF™ test and Ora-tablet LL 2.0ND reading. While there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF™ test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.


[Determination of bisphenol S in urine by vortex-assisted liquid-liquid microextraction with high performance liquid chromatography].
Objective: To establish a method for the determination of bisphenol S in urine using dispersive liquid-liquid microextraction (DLLME) coupled with high performance liquid chromatography (HPLC) . Methods: The acetonitrile, octanol were used as extraction solvent, dispersive solvent respectively, for the preconcentration of bisphenol S. The optimal extraction conditions were optimized by single factor rotations, and methodological performance index were tested. Results: The linear correlation coefficient of bisphenol S in the range of 0.0-160 μg/L is greater than 0.999. The detection limit of this method was 0.76 μg/L, and the recovery rates were 88.06%-103.81%. The intra-and inter-day precisions were 1.78%-2.85% and 2.65%-4.25%, respectively. Conclusion: The method is reliable and sensitive. It is suitable for the determination of bisphenol S in urine samples for occupational exposure populations and non-professional.


Drastic Change in Electronic Transition upon Hydrogen Bond Network Switching in 3-Aminopyridine-(H2O) n Clusters.
The hydration structures of 3-aminopyridine (3AP)-(H2O) n ( n = 2-4) in supersonic jets have been investigated by measuring the electronic and vibrational spectra with the aid of quantum chemical calculations. The S1-S0 electronic transition of 3AP-(H2O)2 is observed at a slightly red-shifted position from 3AP-(H2O)1, while further hydration induces drastic red shifts and complicated vibrational structures. We assign the cluster structures of 3AP-(H2O)2 as a cyclic structure composed of the homodromic hydrogen bond (H-bond) chain connecting the pyridyl CH bond acting as the proton donor toward a pyridyl nitrogen acceptor. For 3AP-(H2O) n ( n = 3, 4), on the other hand, the initial donor site in the H-bond network changes from a pyridyl CH group to an amino group. The observed red shift derived from H-bond network switching can be reproduced very well with the S1-S0 origin band estimation obtained by applying geometry optimization and subsequent harmonic vibrational analysis of (TD-)DFT calculations to each electronic state of the isomer structure. It is suggested that the drastic red shift of the electronic transition upon H-bond network switching is due to a much more stabilized "quinoid-like" structure in the ππ* state by the H-bond formation of an amino group.


Technical characterization of five x-ray detectors for paediatric radiography applications.
Physical image quality of five x-ray detectors used in the paediatric imaging department is characterized with the aim of establishing the range/scope of imaging performance provided by these detectors for neonatal imaging. Two computed radiography (CR) detectors (MD4.0 powder imaging plate (PIP) and HD5.0 needle imaging plate (NIP), Agfa HealthCare NV, B-2640 Mortsel, Belgium) and three flat panel detectors (FPD) (the Agfa DX-D35C and DX-D45C and the DRX-2530C (Carestream Health Inc., Rochester, NY 14608, USA)) were assessed. Physical image quality was characterized using the detector metrics given by the International Electrotechnical Commission (IEC 62220-1) to measure modulation transfer function (MTF), the noise power spectrum (NPS) and the detective quantum efficiency (DQE) using the IEC-specified beam qualities of RQA3 and RQA5. The DQE was evaluated at the normal operating detector air kerma (DAK) level, defined at 2.5 µGy for all detectors, and at factors of 1/3.2 and 3.2 times the normal level. MTF curves for the different detectors were similar at both RQA3 and RQA5 energies; the average spatial frequency for the 50% point (MTF0.5) at RQA3 was 1.26 mm-1, with a range from 1.20 mm-1 to 1.37 mm-1. The DQE of the NIP CR compared to the PIP CR was notably greater and similar to that for the FPD devices. At RQA3, average DQE for the FPD and NIP (at 0.5 mm-1; 2.5 µGy) was 0.57 compared to 0.26 for the PIP CR. At the RQA5 energy, the DRX-2530C and the DX-D45C had the highest DQE (~0.6 at 0.5 mm-1; 2.5 µGy). Noise separation analysis using the polynomial model showed higher electronic noise for the DX-D35C and DRX-2530C detectors; this explains the reduced DQE seen at 0.7 µGy/image. The NIP CR detector offers notably improved DQE performance compared to the PIP CR system and a value similar to the DQE for FPD devices at the RQA3 energy.


[Prevalence of antibodies against hepatitis C virus in a sample of homosexual males].
The finding of an important proportion of cases of hepatitis C without previous contact with blood or hemoderivates has led to suspect that there may be other routes of transmission among which sexual transmission may be found. The presence of antibodies against the hepatitis C virus (anti-HCV) and the association of this infection with certain epidemiologic parameters and sexual practice was determined in 184 homosexual males with no other risk factors for virasis of intravenous transmission. Moreover, the prevalence of anti-HCV was evaluated in 210 voluntary blood donors. Every homosexual was surveyed on sexual practice and the first serum sample available of each of these patients was analyzed for anti-HVC and anti-HIV-1. Twenty-two homosexual (12%) were anti-HCV positive while only one (0.5%) of the control was positive for this marker (p < 0.0001). Thirty-six cases (19%) were anti-HIV positive (none of the controls). No statistical association was found between both serologic markers or between the presence of anti-HCV and the epidemiologic parameters evaluated. Homosexuals constitute a risk group for hepatitis C virus infection although the sexual route is probably not effective for transmission of this entity.


Low-dose, short-term oral prednisone in the treatment of carpal tunnel syndrome.
We evaluated the effectiveness of low-dose, short-term oral prednisone in ameliorating the pain and other symptoms of carpal tunnel syndrome (CTS) in a randomized, double-blind, placebo-controlled study of patients with mild to moderate CTS. Prednisone, in doses of 20 mg daily for the first week and 10 mg daily for the second week, resulted in significant improvement in global symptom scores. The effect was rapid, but gradually waned over 8 weeks of observation. This approach may provide a treatment alternative in the short-term, conservative management of CTS.


Cloning and characterization of the sisomicin-resistance gene from Micromonospora inyoensis.
We cloned DNA fragments of sisomicin-producing Micromonospora inyoensis into Streptomyces plasmid vectors and identified Streptomyces lividans TK24 transformants expressing the M. inyoensis sisomicin-resistance (sisA) gene. The sisA gene was compared to the previously reported Micromonospora purpurea Kan-Gen (kanamycin-gentamicin)-resistance gene. While the restriction endonuclease digestion patterns of the two determinants appear to be divergent, the genes are nonetheless closely related, based on similar patterns and levels of aminoglycoside-resistance and their ability to cross-hybridize under stringent conditions. We have transformed recombinant plasmid pMD5-2, which carries the sisA gene, into our M. purpurea gentamicin-production strain and determined that gentamicin biosynthesis was not improved.


Co-pyrolysis of sewage sludge and food waste digestate to synergistically improve biochar characteristics and heavy metals immobilization.
Food waste digestate (FWD) is a desirable additive in sewage sludge (SS)-based biochar preparation owing to its high contents of intrinsic inorganic minerals and lignocellulosic compounds. In this study, we investigated the co-pyrolysis of SS with FWD at different mixing ratios (4:0, 3:1, 2:2, 1:3, and 0:4; SS:FWD w/w) at 550 °C to synergistically improve the biochar characteristics and immobilize the heavy metals in the SS. The results showed that co-pyrolysis of SS with FWD greatly increased the aromaticity and pH (by 13.22-26.56%) of the blended biochar, and significantly reduced the contents of total and bioavailable heavy metals. The addition of FWD effectively enhanced the conversion of heavy metals from less stable fractions to more stable forms, but led to the transformation of Cr from the residual fraction (F4) to the oxidizable fraction (F3) when the FWD:SS ratio was ≥ 3:1. Overall, the formation of co-crystal compounds, stable kaolinite, and metal oxides together with the enhancement of biochar characteristics during co-pyrolysis significantly reduced the heavy metal-associated ecological risk (potential ecological risk index lower than 15.51) and phytotoxicity (germination index higher than 139.41%) of the blended biochar. These findings suggest that high levels of mineral components in FWD greatly immobilize more heavy metals in biochar.