Antinociceptive, antiinflammatory and antidiabetic effects of Leonotis leonurus (L.) R. BR. [Lamiaceae] leaf aqueous extract in mice and rats.
The present study was undertaken to investigate the antinociceptive, antiinflammatory, and antidiabetic properties of the aqueous leaf extract of Leonotis leonurus (L.) R. BR. (Lamiaceae) in mice and rats, to scientifically appraise some of the plant's ethnomedical uses, and its safety and efficacy. The leaf powder of the plant was Soxhlet extracted with distilled water and used. The antinociceptive effect of the plant's extract was evaluated by the "hot-plate" and "acetic acid" test models of pain in mice, while the antiinflammatory and antidiabetic effects of the leaf extract were investigated in rats, using fresh egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), and chlorpropamide (250 mg/kg p.o.) were used, respectively, as reference analgesic, antiinflammatory, and hypoglycemic agents for comparison. L. leonurus leaf aqueous extract (LLE, 50-800 mg/kg i.p.) produced dose-dependent and significant (p < 0.05-0.001) antinociceptive effects against thermally and chemically induced nociceptive pain stimuli in mice. LLE (50-800 mg/kg i.p.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced paw edema, and caused significant (p < 0.05-0.001) hypoglycemic effects in rats. It is suggested that the analgesic effects of LLE (50-800 mg/kg i.p.) may be peripherally and centrally mediated. The different flavonoids, diterpenoids, polyphenolics, and other chemical constituents of the plant may be involved in the observed antinociceptive, antiinflammatory, and antidiabetic effects of the plant's extract. However, the results of this experimental animal study suggest that the aqueous leaf extract of L. leonurus possesses antinociceptive, antiinflammatory, and hypoglycemic properties, and thus lend pharmacological credence to the suggested folkloric uses of the herb in the management and/or control of painful, arthritic, and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.


Adding fuel to the fire: the impacts of non-native grass invasion on fire management at a regional scale.
Widespread invasion by non-native plants has resulted in substantial change in fire-fuel characteristics and fire-behaviour in many of the world's ecosystems, with a subsequent increase in the risk of fire damage to human life, property and the environment. Models used by fire management agencies to assess fire risk are dependent on accurate assessments of fuel characteristics but there is little evidence that they have been modified to reflect landscape-scale invasions. There is also a paucity of information documenting other changes in fire management activities that have occurred to mitigate changed fire regimes. This represents an important limitation in information for both fire and weed risk management. We undertook an aerial survey to estimate changes to landscape fuel loads in northern Australia resulting from invasion by Andropogon gayanus (gamba grass). Fuel load within the most densely invaded area had increased from 6 to 10 t ha(-1) in the past two decades. Assessment of the effect of calculating the Grassland Fire Danger Index (GFDI) for the 2008 and 2009 fire seasons demonstrated that an increase from 6 to 10 t ha(-1) resulted in an increase from five to 38 days with fire risk in the 'severe' category in 2008 and from 11 to 67 days in 2009. The season of severe fire weather increased by six weeks. Our assessment of the effect of increased fuel load on fire management practices showed that fire management costs in the region have increased markedly (∼9 times) in the past decade due primarily to A. gayanus invasion. This study demonstrated the high economic cost of mitigating fire impacts of an invasive grass. This study demonstrates the need to quantify direct and indirect invasion costs to assess the risk of further invasion and to appropriately fund fire and weed management strategies.


Role of clay content in partitioning, uptake and toxicity of zinc in the earthworm Eisenia fetida.
We studied the effect of clay content on the bioavailability of zinc to pre-clitellate earthworm, Eisenia fetida in the laboratory using OECD artificial soil adjusted to 5%, 20%, and 40% clay. Batches of worms were exposed to a wide range of zinc concentrations. Mortality, growth, maturation (% clitellate), cocoon production, and body zinc concentrations were assessed over and after a period of 4 weeks. Total, DTPA, and CaCl(2) extractable zinc in the substrates were also determined. The results of the biological responses showed that interaction of clay and zinc had a significant influence on mortality but not on the other biological parameters. None of the three extraction methods showed consistent and significant effect of clay content on zinc partitioning. Although total, DTPA, and CaCl(2) extracts of zinc correlated strongly with one another and were in similar relation with the observed biological responses, only the CaCl(2) extract revealed a time dependent availability of this metal. It is concluded that clay content had no significant influence on sub-lethal toxicity of zinc to this earthworm over the range of exposure concentrations.


Micro/nanomotors towards in vivo application: cell, tissue and biofluid.
Inspired by highly efficient natural motors, synthetic micro/nanomotors are self-propelled machines capable of converting the supplied fuel into mechanical motion. A significant advance has been made in the construction of diverse motors over the last decade. These synthetic motor systems, with rapid transporting and efficient cargo towing abilities, are expected to open up new horizons for various applications. Utilizing emergent motor platforms for in vivo applications is one important aspect receiving growing interest as conventional therapeutic methodology still remains limited for cancer, heart, or vasculature diseases. In this review we will highlight the recent efforts towards realistic in vivo application of various motor systems. With ever booming research enthusiasm in this field and increasing multidisciplinary cooperation, micro/nanomotors with integrated multifunctionality and selectivity are on their way to revolutionize clinical practice.


Transient transfection of the human myeloid cell line Mono Mac 6 using electroporation.
Leukemic cell lines such as Mono Mac 6 provide an excellent model for studying changes in gene expression during induction of cell differentiation. Mono Mac 6 cells can be induced to differentiate from their immature state to cells resembling morphologically and functionally mature monocytes and macrophages by various stimuli such as calcitriol and transforming growth factor-beta. During differentiation, the expression of differentiation markers such as the cell surface antigen CD14 or other differentiation-related genes such as 5-lipoxygenase are strongly increased. Thus, this cell line constitutes an excellent model system to study the regulation of gene expression by inducers of cell differentiation. However, myeloid cell lines are often refractory to transfection by calcium phosphate or DEAE dextran so that reporter gene assays are difficult to perform. We have established a transient transfection protocol for Mono Mac 6 cells using electroporation, a 5-lipoxygenase promoter luciferase reporter gene construct, and the secreted alkaline phosphatase as an internal standard.


Inhibition of cADPR-Hydrolase by ADP-ribose potentiates cADPR synthesis from beta-NAD+.
Cyclic adenosine 5'-diphosphate ribose (cADPR) is a potent Ca2+ releasing agent in a number of tissues. A particular bifunctional NAD+ glycohydrolase is responsible for both the cyclase and hydrolase activity necessary for its synthesis from beta-NAD and degradation to ADPR. We now report that ADPR, the end-product of this enzyme, releases Ca2+ at high concentrations (above 100 microM), and at lower concentrations (10-100 microM) inhibits the hydrolysis of cADPR and potentiates the production of cADPR from NAD+. This evidence suggests that ADPR may be an important modulator of the NAD+ glycohydrolase responsible for the production of cADPR.


Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis.
Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined.


Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery.
To evaluate the response of cavernous sinus meningiomas to stereotactic radiosurgery, we reviewed our 54-month experience with 34 patients. All patients underwent radiosurgery with a 201-source cobalt-60 gamma unit. Twenty-eight patients (82%) had previous histological confirmation of a meningioma (1 to 5 cranial base craniotomies per patient); 6 (18%) were treated on the basis of neuroimaging criteria alone. The single-fraction radiation tumor margin dose (10 to 20 Gy) was designed to conform to the irregular tumor volumes in all patients. The maximum radiation dose to the optic nerve or tract was reduced to 9 Gy in 31 patients. No patient had tumor growth (100% tumor control) during the follow-up interval (median, 26 mo). Tumor regression was observed in 56% of patients imaged at an average of 18 months. Eight patients (24%) improved clinically at follow-up examinations. Four patients developed new or worsened cranial nerve deficits during the follow-up interval; two had subsequent full improvement. No patient developed an endocrinopathy or new extraocular muscle paresis. Stereotactic radiosurgery, using multiple isocenter dosimetry facilitated by the gamma unit, is an accurate, safe, and effective technique to prevent the growth of tumors involving the cavernous sinus. Despite the proximity of such tumors to adjacent cranial nerves, complications were rare. The maximum length of hospital stay was 36 hours, and all patients returned to their preoperative employment status within 3 to 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)


Supernatants of human leukocytes contain mediator, different from interferon gamma, which induces expression of MHC class II antigens.
In this report, data are presented on the regulation of MHC class II antigen expression by a mediator present in supernatants of human mixed leukocyte cultures (MLC-SN), and which is different from IFN-gamma. The capacity of supernatants to induce antigen expression did not correspond to titers of IFN-gamma. Removal of IFN-gamma using either dialysis against pH 2 or neutralizing mAb against human IFN-gamma did not abrogate the MHC class II antigen expression-inducing capacity of MLC-SN when tested on adenocarcinoma cell lines, kidney epithelial cells, and fibroblasts in vitro in an indirect immunofluorescence assay. Therefore, supernatants of human leukocytes contain a mediator, different from IFN-gamma, which induces expression of MHC class II antigens. Dose-response studies revealed that the mediator is produced after allogeneic and lectin stimulation of human leukocytes, and by unstimulated leukocytes. Activation of leukocytes resulted in increased titers of the mediator. The mediator markedly enhances expression of both HLA-DR and HLA-DQ antigens, whereas IFN-gamma had a similar effect on HLA-DR antigens, and only a minor effect on HLA-DQ antigens. Interaction of the mediator and IFN-gamma resulted in a potentiating effect of these two factors on MHC class II antigen expression. Biochemical analysis revealed a mediator, distinguishable by FPLC from IL-1, IL-2, and human IFN-gamma, and which has a molecular mass of 32 kD.


Combined effects of hydrogen sulfide and lipopolysaccharide on osteoclast differentiation in rats.
Lipopolysaccharide (LPS) stimulates osteoclast differentiation through toll-like receptors (TLRs) 2 and 4, and hydrogen sulfide (H(2)S) induces osteoclast differentiation. If H(2)S activates TLRs, H(2)S may enhance the effects of LPS on osteoclast differentiation. The purpose of the present study is to examine the combined effects of sodium hydrogen sulfide (NaHS, an H(2)S donor drug) and LPS on osteoclast differentiation and TLR expression in rat periodontal tissue. Twenty-eight male Wistar rats (8 weeks old) were divided into four groups (n = 7 per group): a control (no treatment) group and three experimental groups (NaHS group, LPS group, and a combination [NaHS + LPS] group). At 1 day after topical application of NaHS and/or Porphyromonas gingivalis LPS into the gingival sulcus of first molars, the number of tartrate-resistant acid phosphate (TRAP)-positive osteoclasts in the periodontal tissue was counted. Expression of TLR2 and TLR4 mRNAs and proteins in the gingival was also assessed. The number of TRAP-positive osteoclasts was significantly higher in the combination group than in any other group (P <0.01). The combination group had 11.0-fold higher TLR4 mRNA levels than the control group. TLR4 protein levels were also higher in the combination group than in the NaHS or LPS group. However, the TLR2 mRNA and protein levels were not significantly different in the combination group and the LPS group. In rat periodontal tissue, NaHS and LPS had an additive effect on osteoclast differentiation through activation of the TLR4 pathway but not the TLR2 pathway.


Hypnosis for symptom management in women with breast cancer: a pilot study.
Eight women who were in treatment for breast cancer (n = 4) or breast cancer survivors (n = 4), presenting with 1 or more of 4 symptoms (chronic pain, fatigue, hot flashes, and sleep difficulties), were given 4 to 5 sessions of self-hypnosis training for symptom management. Analyses revealed (a) significant pre- to posttreatment decreases in pain intensity, fatigue, and sleep problems and (b) that pain intensity continued to decrease from posttreatment to 6-month follow-up. Although there was a slight increase in fatigue severity and sleep problems from posttreatment to 6-month follow-up, the follow-up scores did not return to pretreatment levels. The findings provide initial support for using hypnosis to manage symptoms in women who are breast cancer survivors. Clinical trials evaluating hypnosis efficacy over and above other treatments are warranted.


Neurovascular manifestations of heritable connective tissue disorders. A review.
Heritable disorders of connective tissue are recognized in a small minority of patients with neurovascular diseases. In this report, we review the neurovascular manifestations of four heritable connective tissue disorders: Ehlers-Danlos syndrome, Marfan's syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum, as well as two other systemic disorders with potential vascular manifestations: neurofibromatosis and polycystic kidney disease. Typical neurovascular complications of Ehlers-Danlos syndrome are carotid-cavernous fistulae, intracranial aneurysms, and cervical artery dissections. Arterial dissections and intracranial aneurysms cause the majority of neurovascular symptoms in Marfan's syndrome. Neurovascular disease is uncommon in osteogenesis imperfecta, although carotid-cavernous fistulae and vertebral artery dissections have been reported. Neurovascular disease in pseudoxanthoma elasticum is characterized by intracranial aneurysms and cerebral ischemia caused by premature arterial occlusive disease. Intracranial occlusive arterial disease is the most common neurovascular manifestation of neurofibromatosis, followed by cervical arteriovenous fistulae and aneurysms and intracranial aneurysms. Intracranial aneurysms are the hallmark of polycystic kidney disease. Recognition of an underlying generalized connective tissue disorder may be of considerable importance, although marked phenotypic heterogeneity often complicates the diagnosis of these disorders. Conversely, the association of certain neurovascular anomalies with generalized connective tissue disorders and recognition of their basic molecular defect may offer clues to the etiology and pathogenesis of these neurovascular diseases in general.


Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos.
Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), are pervasive, lifelong disorders for which pharmacological interventions are not readily available. Substantial increases in the prevalence of NDDs over a relatively short period may not be attributed solely to genetic factors and/or improved diagnostic criteria. There is now a consensus that multiple genetic loci combined with environmental risk factors during critical periods of neurodevelopment influence NDD susceptibility and symptom severity. Organophosphorus (OP) pesticides have been identified as potential environmental risk factors. Epidemiological studies suggest that children exposed prenatally to the OP pesticide chlorpyrifos (CPF) have significant mental and motor delays and strong positive associations for the development of a clinical diagnosis of intellectual delay or disability, ADHD, or ASD. We tested the hypothesis that developmental CPF exposure impairs behavior relevant to NDD phenotypes (i.e., deficits in social communication and repetitive, restricted behavior). Male and female rat pups were exposed to CPF at 0.1, 0.3, or 1.0 mg/kg (s.c.) from postnatal days 1-4. These CPF doses did not significantly inhibit acetylcholinesterase activity in the blood or brain but significantly impaired pup ultrasonic vocalizations (USV) in both sexes. Social communication in juveniles via positive affiliative 50-kHz USV playback was absent in females exposed to CPF at 0.3 mg/kg and 1.0 mg/kg. In contrast, this CPF exposure paradigm had no significant effect on gross locomotor abilities or contextual and cued fear memory. Ex vivo magnetic resonance imaging largely found no differences between the CPF-exposed rats and the corresponding vehicle controls using strict false discovery correction; however, there were interesting trends in females in the 0.3 mg/kg dose group. This work generated and characterized a rat model of developmental CPF exposure that exhibits adverse behavioral phenotypes resulting from perinatal exposures at levels that did not significantly inhibit acetylcholinesterase activity in the brain or blood. These data suggest that current regulations regarding safe levels of CPF need to be reconsidered.


Sedation with Dexmedetomidine or Propofol Impairs Hypoxic Control of Breathing in Healthy Male Volunteers: A Nonblinded, Randomized Crossover Study.
In contrast to general anesthetics such as propofol, dexmedetomidine when used for sedation has been put forward as a drug with minimal effects on respiration. To obtain a more comprehensive understanding of the regulation of breathing during sedation with dexmedetomidine, the authors compared ventilatory responses to hypoxia and hypercapnia during sedation with dexmedetomidine and propofol. Eleven healthy male volunteers entered this randomized crossover study. Sedation was administered as an intravenous bolus followed by an infusion and monitored by Observer's Assessment of Alertness/Sedation (OAA/S) scale, Richmond Agitation Sedation Scale, and Bispectral Index Score. Hypoxic and hypercapnic ventilatory responses were measured at rest, during sedation (OAA/S 2 to 4), and after recovery. Drug exposure was verified with concentration analysis in plasma. Ten subjects completed the study. The OAA/S at the sedation goal was 3 (3 to 4) (median [minimum to maximum]) for both drugs. Bispectral Index Score was 82 ± 8 and 75 ± 3, and the drug concentrations in plasma at the sedation target were 0.66 ± 0.14 and 1.26 ± 0.36 μg/ml for dexmedetomidine and propofol, respectively. Compared with baseline, sedation reduced hypoxic ventilation to 59 and 53% and the hypercapnic ventilation to 82 and 86% for dexmedetomidine and propofol, respectively. In addition, some volunteers displayed upper airway obstruction and episodes of apnea during sedation. Dexmedetomidine-induced sedation reduces ventilatory responses to hypoxia and hypercapnia to a similar extent as sedation with propofol. This finding implies that sedation with dexmedetomidine interacts with both peripheral and central control of breathing.


Clinical Characteristics and Lung Function in Older Children Vertically Infected With Human Immunodeficiency Virus in Malawi.
Antiretroviral therapy (ART) has led to increased survival of children with vertically acquired human immunodeficiency virus infection. Significant morbidity arises from respiratory symptoms, but aetiology and pulmonary function abnormalities have not been systematically studied. Human immunodeficiency virus-positive children aged 8-16 years were systematically recruited within clinics in Blantyre, Malawi. Clinical review, quality of life assessment, spirometry, and chest radiography were performed. One hundred sixty participants had a mean of age 11.1 (range, 8-16) years and 50.0% were female. Cough was present in 60 (37.5%) participants, and 55 (34.4%) had moderate or severe dyspnoea. Thirty-four (22.1%) participants had digital clubbing. Thirty-three (20.6%) participants were hypoxic at rest. One hundred eighteen (73.8%) of the children were receiving ART; median CD4 count was 698 cells/µL in these compared with 406 cells/µL in ART-naive individuals (P < .001). From 145 spirometry traces (90.6%), mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were 1.06 and 0.89 standard deviations below predicted mean, respectively. Twenty-one (14.5%) traces demonstrated obstructive defects and 26 (17.9%) reduced FVC. Lung function abnormality was not associated with any clinical findings. Of the 51 individuals with abnormal lung function, the mean increase in FEV1 after salbutamol was 3.8% (95% confidence interval, 0.02-7.53). "Tramlines" and ring shadows were seen on chest radiographs in over half of cases. Symptoms of chronic lung disease were highly prevalent with 2 main clinical phenotypes: "cough" and "hypoxia". Lung function abnormalities are common, poorly responsive to bronchodilators, and apparent throughout the age range of our cohort. Pathological causes remain to be elucidated. Cough and hypoxic phenotypes could be a useful part of diagnostic algorithms if further validated.


Overexpression of synapsin Ia in the rat calyx of Held accelerates short-term plasticity and decreases synaptic vesicle volume and active zone area.
Synapsins are synaptic vesicle (SV) proteins organizing a component of the reserve pool of vesicles at most central nervous system synapses. Alternative splicing of the three mammalian genes results in multiple isoforms that may differentially contribute to the organization and maintenance of the SV pools. To address this, we first characterized the expression pattern of synapsin isoforms in the rat calyx of Held. At postnatal day 16, synapsins Ia, Ib, IIb and IIIa were present, while IIa-known to sustain repetitive transmission in glutamatergic terminals-was not detectable. To test if the synapsin I isoforms could mediate IIa-like effect, and if this depends on the presence of the E-domain, we overexpressed either synapsin Ia or synapsin Ib in the rat calyx of Held via recombinant adeno-associated virus-mediated gene transfer. Although the size and overall structure of the perturbed calyces remained unchanged, short-term depression and recovery from depression were accelerated upon overexpression of synapsin I isoforms. Using electron microscopic three-dimensional reconstructions we found a redistribution of SV clusters proximal to the active zones (AZ) alongside with a decrease of both AZ area and SV volume. The number of SVs at individual AZs was strongly reduced. Hence, our data indicate that the amount of synapsin Ia expressed in the calyx regulates the rate and extent of short-term synaptic plasticity by affecting vesicle recruitment to the AZ. Finally, our study reveals a novel contribution of synapsin Ia to define the surface area of AZs.


Expectations and Projections for the Future of Nongynecolgical Cytology 10 Years Ago: Did They Materialize and How Did We Do?
In 2007, an article entitled "How Technology Is Reshaping the Practice of Nongynecologic Cytology: Frontiers of Cytology Symposium" [Bibbo: Acta Cytol 2007;51:123-152] was published. The moderator and editor was Marluce Bibbo, previous Editor-in-Chief of Acta Cytologica, and 17 participants from countries throughout the world were asked to answer how new technologies were being applied in their respective laboratories and whether future advances and challenges can be predicted. Ten years later, two previous participants in this Golden Anniversary Cytology Symposium were asked by Kari Syrjänen, current Editor-in-Chief of Acta Cytologica, to make a reappraisal of the 2007 predictions.


Effects of co-application of biosolids and water treatment residuals on corn growth and bioavailable phosphorus and aluminum in alkaline soils in egypt.
The co-application of biosolids and water treatment residuals (WTRs) has been previously trialed to reduce excessive bioavailable P in the soil treated with biosolids. However, uncertainty still exists regarding the environmental consequences of the co-application of biosolids and WTRs, especially in alkaline soils in Egypt or the Middle East region. A greenhouse pot study was conducted with Egyptian alkaline soils to (i) quantify the effects of co-application of biosolids and drinking WTRs on biomass production of corn (Zea mays L. cultivar single hybrid 10), (ii) determine the co-application effects on Olsen-P and KCl-extractable Al in relation to their accumulation in plant tissues, and (iii) optimize the co-application ratio of biosolids to WTRs for the best yield and effective reduction of soil bioavailable P. The results show that, among the studied soils treated with 1% biosolids along with various rates of WTRs, the corn yield increased significantly (P < 0.01) with increasing WTR application rate from 0 to 3% (w/w), but decreased at 4% application rate. The corn yield also significantly correlated with soil water holding capacity that increased with the addition of WTRs. Phosphorus uptake by plants significantly (P < 0.01) increased when the biosolid application rate was increased from 1 to 3% in the three studied soils that were treated with 1, 2, or 3% WTRs. The application of 4% WTRs in the biosolid-amended soils resulted in a significant reduction in soil Olsen-P values, but without having observable phytotoxicity of metals (such as Al) to corn during the growth period. The effective co-application ratio of biosolids to WTRs, for increasing corn yield and minimizing the potential for bioavailable P in runoff, was approximately 1:1 at the application rate of 3% biosolids and 4% WTRs in the alkaline soils.


Candidate genes in polycystic ovary syndrome.
The candidate gene approach has already paid some dividends in trying to understand the complex genetics of polycystic ovary syndrome (PCOS). In terms of steroidogenic abnormalities, CYP11a-encoding P450 side chain cleavage-appears to be a major susceptibility locus. In relation to the well-described metabolic disturbances in PCOS, the insulin gene variable number tandem repeat (VNTR) appears to be a promising candidate, at least in populations studied in the UK. Finally, genes implicated in ovarian follicular development may have a role in the aetiology of PCOS, as demonstrated by recent identification of the follistatin gene as a potential disease locus. It seems unlikely that PCOS can be explained on the basis of a single gene disorder although, in a given family, one gene may have a predominant effect. An oligogenic model seems the most appropriate basis on which to understand the genetic origins of this very common disorder. The candidate gene approach has been useful to date, but it may prove important in the near future to perform an anonymous genome-wide scan to identify hitherto unheralded susceptibility loci.


Dexmedetomidine attenuates tourniquet-induced hyperdynamic response in patients undergoing lower limb surgeries: a randomized controlled study.
Activation of sympathetic nervous system has a crucial role in mediating the pneumatic tourniquet inflation induced hyperdynamic response. Dexmedetomidine, a selective α(2)-adrenergic receptor agonist, has potent sympatholytic effects. We conducted this prospective, randomized, placebo-controlled, double-blinded study to elucidate the effects of dexmedetomidine on attenuating the tourniquet-induced hyperdynamic response during general anesthesia. We included a total of 72 healthy adult patients undergoing elective lower limb surgery. Under general anesthesia, patients were randomized to the dexmedetomidine or the control group (n = 36 in each group). The dexmedetomidine group received a loading dose of dexmedetomidine (0.8 μg·kg(-1) over 10 min) followed by continuous infusion of dexmedetomidine (0.4 μg·kg(-1).h(-1)) until tourniquet deflation. The control group received normal saline instead. We compared tourniquet-induced changes in hemodynamic parameters between groups to elucidate the effects of dexmedetomidine. Tourniquet inflation induced significant increases in hemodynamic parameters, including heart rate, systolic arterial pressure, mean arterial pressure, diastolic arterial pressure, rate pressure product, cardiac output, and stroke volume in the control group. The effects of tourniquet inflation on increasing hemodynamic parameters were significantly attenuated by dexmedetomidine: heart rate (P < 0.001), systolic arterial pressure (P = 0.002), mean arterial pressure (P = 0.042), diastolic arterial pressure (P = 0.012), rate pressure product (P < 0.001), and cardiac output (P = 0.001) of the dexmedetomidine group were significantly lower than those of the control group. However, the stroke volume of these groups was comparable. Dexmedetomidine attenuates tourniquet-induced hyperdynamic response in general anesthesia patients undergoing lower limb surgeries.


Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in neuroblastoma.
Loss of heterozygosity (LOH) on chromosome 18q21 is found frequently in various human cancers. Three candidate tumor suppressor genes, DCC (deleted in colorectal carcinomas), DPC4 (deleted in pancreatic carcinomas, locus 4), and MADR2/JV18-1 (MAD-related gene 2), have been cloned and identified from this chromosome region. We have reported recently that LOH on chromosome 18q is observed frequently in neuroblastoma. Alterations of DCC are involved in many human tumors. DPC4 and MADR2/JV18-1 are recently demonstrated to be altered in pancreatic and colorectal cancers, respectively. To confirm if inactivation of the DCC, DPC4, and MADR2/JV18-1 genes is involved in the pathogenesis of neuroblastoma and to clarify the mechanism of inactivation, we analyzed the expression of DCC, DPC4, and MADR2/JV18-1 in neuroblastoma cell lines and primary tumors by reverse transcription-PCR and investigated the mutations in the coding regions of these genes by PCR/reverse transcription-PCR single-strand conformation polymorphism. We found that 12 of 25 (48%) cell lines and 14 of 32 (44%) primary tumors, including 3 with 18q LOH, had absent or reduced expression of DCC mRNA. Expression was more likely to be reduced in advanced (67%) than in early stage neuroblastomas (24%) (P = 0.036), suggesting that inactivation of the DCC gene plays an important role in the progression of neuroblastoma. Altered expression of DPC4 was found in six (24%) cell lines and six (19%) tumors. MADR2/JV18-1 expression was reduced or absent only in four (16%) cell lines and three (9%) tumors. Mutations of the DCC genes were examined in 25 of 29 exons in neuroblastoma cell lines, and those exons in which mutations were found were further examined in primary tumors. We found missense mutations of AAC (Asn) to AGC (Ser) at DCC codon 176 in one cell line and ACC (Thr) to ATC (Ile) at codon 1105 in one cell line and tumor, respectively; polymorphisms of CGA (Arg) to GGA (Gly) at codon 201 and TTT (Phe) to TTG (Leu) at codon 951 in most of the cell lines and tumors; and a silent mutation of GAG (Glu) to GAA (Glu) at codon 118 in four cell lines and five primary tumors. We did not identify any mutations in the DPC4 and MADR2/JV18-1 genes in neuroblastoma. Our results suggested that mutations of the DCC gene may be involved in the pathogenesis of neuroblastomas but failed to account for the relatively high frequency of the altered expression, implying that other mechanisms are responsible for the inactivation of the DCC gene in neuroblastoma. Low frequency of reduced or absent mRNA expression and lack of mutations in DPC4 and MADR2/JV18-1 genes suggested a limited role for these two genes in neuroblastoma.


Combined mining: discovering informative knowledge in complex data.
Enterprise data mining applications often involve complex data such as multiple large heterogeneous data sources, user preferences, and business impact. In such situations, a single method or one-step mining is often limited in discovering informative knowledge. It would also be very time and space consuming, if not impossible, to join relevant large data sources for mining patterns consisting of multiple aspects of information. It is crucial to develop effective approaches for mining patterns combining necessary information from multiple relevant business lines, catering for real business settings and decision-making actions rather than just providing a single line of patterns. The recent years have seen increasing efforts on mining more informative patterns, e.g., integrating frequent pattern mining with classifications to generate frequent pattern-based classifiers. Rather than presenting a specific algorithm, this paper builds on our existing works and proposes combined mining as a general approach to mining for informative patterns combining components from either multiple data sets or multiple features or by multiple methods on demand. We summarize general frameworks, paradigms, and basic processes for multifeature combined mining, multisource combined mining, and multimethod combined mining. Novel types of combined patterns, such as incremental cluster patterns, can result from such frameworks, which cannot be directly produced by the existing methods. A set of real-world case studies has been conducted to test the frameworks, with some of them briefed in this paper. They identify combined patterns for informing government debt prevention and improving government service objectives, which show the flexibility and instantiation capability of combined mining in discovering informative knowledge in complex data.


Plasmon resonances in gold-coated tilted fiber Bragg gratings.
The transmission spectrum of fiber Bragg gratings with gratings planes tilted at a small angle (2 degrees -10 degrees) relative to the fiber axis shows a large number of narrowband cladding mode resonances within a 100 nm wide spectrum. When a gold coating with a thickness between 10 and 30 nm is deposited on the fiber, the transmission spectrum shows anomalous features for values of the outside medium refractive index between 1.4211 and 1.4499. These features are shown to correspond to the excitation of surface plasmon resonances at the external surface of the gold film.


Economic consequences for other family members of mental health problems in older people.
We estimated the effects of poor mental health among older family members on the labour supply and incomes of younger family members living in the same household. Due to policy differences, effects for Scotland were compared with other parts of the UK. Effects were estimated using the British Household Panel Survey (waves 1999-2006), with data from 621 older respondents and 800 younger family members. Mental health was assessed using the General Health Questionnaire (GHQ), together with self-reported presence of depression, anxiety, or other mental health problems. The associations between labour supply and mental ill-health were found to vary by gender and region of the UK. For men, there were larger negative effects in Scotland relative to the rest of the UK. For women, mental ill-health was associated with increased labour supply in Scotland, while in the remainder of the UK, a negative association was observed. Income losses accrued across all groups except among Scottish females, with the largest significant negative effects observed among men living in the remainder of the UK. Mental health problems among older family members are associated with significant labour market effects for younger family members. To reduce the economic consequences, better assessment of mental health among older people may be warranted. Further employment support for younger family members, in the form of more flexible work policies, might also serve to ameliorate economic losses.


Automated measurement of intima-media thickness of carotid arteries in ultrasonography by computer software.
Intima-media thickness (IMT) has been proposed to be a morphological criterion of atherosclerosis. The purpose of this study was to investigate the interobserver variability of manual and also of computer software measurements of IMT. High-resolution common carotid artery (CCA) images of 88 patients that have been obtained by a linear broadband L5-12 MHz transducer and archived in PACS were retrospectively evaluated. Two separate investigators, who were unaware of the former results, evaluated the same images by using computer software that had a dedicated tool for automatic measurement of IMT. The results of the investigators were compared. According to the two investigators who have performed manual measurements, mean values of IMT of right CCA were 0.6396 mm and 0.6356 mm; of the left CCA were 0.6662 mm and 0.6575 mm, respectively. The interobserver variability of measurements revealed the mean IMT as 0.6071 mm and 0.6048 mm for the right, 0.6216 mm and 0.6227 mm for the left CCA. Manual measurements of both investigators were found to be higher than the automatic measurements and the differences were statistically significant. Interobserver correlation of manual measurements was between 0.80-0.88 and of the automated measurements was between 0.93-0.98. Manual measurements reveal higher values than the automated measurements of IMT. The interobserver correlation of automated measurements is higher than manual measurements. The use of dedicated software may be proposed to reduce the measurement errors.


Review of triage reform: the case for national consensus on a single triage scale for clients with a mental illness in Australian emergency departments.
The aim of this paper is to examine the use of mental health triage scales in Australian emergency departments (EDs) and to explore the use of the Australasian Triage Scale (ATS) with existing mental health triage scales. Since the introduction of mainstreaming and deinstitutionalisation in Australian mental health care, the number of clients presenting to Australian EDs has been increasing. It has become apparent that the lack of mental health descriptors in existing triage scales diminishes the ability of ED triage staff to accurately assess clients with a mental illness. In response to this, specialised mental health triage scales have been developed and introduced into practice. Concurrently, mental health descriptors have been incorporated into the ATS used across Australian EDs. A review of English language literature was conducted. The data bases Proquest, Synergy and CINAHL were searched using the key words 'emergency department', 'triage', 'mental health' and again using the term 'emergency mental health triage'. There is a paucity of literature surrounding the use of mental health triage scales in Australian EDs; 18 articles were found to be directly relevant to the subject matter. Currently clients with a mental illness presenting to the ED may be triaged against one of four mental health triage scales. Research has shown that the mental health descriptors in the ATS are not as reliable as a specialised mental health triage scale. This has implications for clinical practice on two levels. First, it affects the initial triage assessment in the ED and the ability for mental health clinicians to respond in a timely manner and this will have an impact on clinical outcomes. Second, the use of the mental health triage criteria in the ATS may misrepresent ED workloads and affect data pertaining to ED performance.


Perceptions and estimates of error rates in forensic science: A survey of forensic analysts.
Every scientific technique features some error, and legal standards for the admissibility of scientific evidence (e.g., Daubert v. Merrill Dow Pharmaceuticals, Inc., 1993; Kumho Tire Co v. Carmichael, 1999) guide trial courts to consider known error rates. However, recent reviews of forensic science conclude that error rates for some common techniques are not well-documented or even established (e.g., NAS, 2009; PCAST, 2016). Furthermore, many forensic analysts have historically denied the presence of error in their field. Therefore, it is important to establish what forensic scientists actually know or believe about errors rates in their disciplines. We surveyed 183 practicing forensic analysts to examine what they think and estimate about error rates in their various disciplines. Results revealed that analysts perceive all types of errors to be rare, with false positive errors even more rare than false negatives. Likewise, analysts typically reported that they prefer to minimize the risk of false positives over false negatives. Most analysts could not specify where error rates for their discipline were documented or published. Their estimates of error in their fields were widely divergent - with some estimates unrealistically low.


Micropatterned charge heterogeneities via vapor deposition of aminosilanes.
Aminosilanes are routinely employed for charge reversal or to create coupling layers on oxide surfaces. We present a chemical vapor deposition method to pattern mica surfaces with regions of high-quality aminosilane (3-aminopropyltriethoxysilane, APTES) monolayers. The approach relies on the vapor deposition of an aminosilane through a patterned array of through-holes in a PDMS (poly(dimethylsiloxane)) membrane that acts as a mask. In aqueous solutions the surfaces have regular patterns of charge heterogeneities with minimal topographical variations over large areas. This versatile dry lift-off deposition method alleviates issues with multilayer formation and can be used to create charge patterns on curved surfaces. We identify the necessary steps to achieve high quality monolayers and charge reversal of the underlying mica surface: (1) hexane extraction to remove unreacted PDMS oligomers from the membrane that would otherwise deposit on and contaminate the substrate, (2) oxygen plasma treatment of the top of the membrane surfaces to generate a barrier layer that blocks APTES transport through the PDMS, and (3) low of the vapor pressure of APTES during deposition to minimize APTES condensation at the mica-membrane-vapor contact lines and to prevent multilayer formation. Under these conditions, AFM imaging shows that the monolayers have a height of 0.9 ± 0.2 nm with an increase in height up to 3 nm at the mica-membrane-vapor contact lines. Fluorescence imaging demonstrates pattern fidelity on both flat and curved surfaces, for feature sizes that vary between 6.5 and 40 μm. We verify charge reversal by measuring the double layer forces between a homogeneous (unpatterned) APTES monolayers and a mica surface in aqueous solution, and we characterize the surface potential of APTES monolayers by measuring the double-layer forces between identical APTES surfaces. We obtain a surface potential of +110 ± 6 mV at pH 4.0.


Relationship of Autophagy and Apoptosis with Total Occlusion of Coronary Arteries.
BACKGROUND The primary aim of this study was to evaluate the level of autophagy and apoptosis enzymes in patients with coronary artery disease (CAD). Furthermore, we investigated the role of autophagy and apoptosis in the progression of coronary collateral and coronary total occlusion (TO). MATERIAL AND METHODS We enrolled 115 patients in this prospective, observational, controlled study, who were categorized into 3 groups as follows: group 1, patients with chronic TO (n=49); group 2, patients with acute TO such as myocardial infarction (n=36); and group 3, healthy control patients (n=30). We used the enzyme-linked immunosorbent assay (ELISA) kit for autophagy-related protein 5 (ATG5) and apoptosis (M30) in the plasma for these 3 groups. RESULTS Autophagy levels significantly varied among the groups (13.7±5.3 ng/mL, 11.7±3.4 ng/mL, and 7.5±3, respectively; P<0.001). In addition, apoptosis levels significantly varied among the groups (78.6±33.4 ng/mL, 64.9±30.6 ng/mL, and 47.6±18.2, respectively; P<0.001). The subgroup analysis revealed significant positive correlations between the autophagy level and the Rentrop score in contrast to apoptosis in group 1 (r=0.463; P<0.001). CONCLUSIONS This study determined that autophagy and apoptosis levels were higher in patients with CAD than in healthy controls. In contrast to the serum apoptosis level, serum autophagy levels demonstrated a significant positive correlation with the Rentrop score. Hence, an elevated autophagy level might be a potential activator and marker of the process by which the body protects itself in CAD.


Windows of vulnerability: Seasonal mismatches in exposure and resource identity determine ocean acidification's effect on a primary consumer at high latitude.
It is well understood that differences in the cues used by consumers and their resources in fluctuating environments can give rise to trophic mismatches governing the emergent effects of global change. Trophic mismatches caused by changes in consumer energetics during periods of low resource availability have received far less attention, although this may be common for consumers during winter when primary producers are limited by light. Even less is understood about these dynamics in marine ecosystems, where consumers must cope with energetically costly changes in CO2 -driven carbonate chemistry that will be most pronounced in cold temperatures. This may be especially important for calcified marine herbivores, such as the pinto abalone (Haliotis kamschatkana). H. kamschatkana are of high management concern in the North Pacific due to the active recreational fishery and their importance among traditional cultures, and research suggests they may require more energy to maintain their calcified shells and acid/base balance with ocean acidification. Here we use field surveys to demonstrate seasonal mismatches in the exposure of marine consumers to low pH and algal resource identity during winter in a subpolar, marine ecosystem. We then use these data to test how the effects of exposure to seasonally relevant pH conditions on H. kamschatkana are mediated by seasonal resource identity. We find that exposure to projected future winter pH conditions decreases metabolism and growth, and this effect on growth is pronounced when their diet is limited to the algal species available during winter. Our results suggest that increases in the energetic demands of pinto abalone caused by ocean acidification during winter will be exacerbated by seasonal shifts in their resources. These findings have profound implications for other marine consumers and highlight the importance of considering fluctuations in exposure and resources when inferring the emergent effects of global change.


Expression analysis of chick Frizzled receptors during spinal cord development.
Frizzleds (Fzds) are transmembrane receptors that can transduce signals dependent upon binding of Wnts, a large family of secreted glycoproteins homologous to the Drosophila wingless gene. FZDs are critical for a wide variety of normal and pathological developmental processes. In the nervous system, Wnts and Frizzleds play an important role in anterior-posterior patterning, cell fate decisions, proliferation, and synaptogenesis. Here, we preformed a comprehensive expression profile of Wnt receptors (FZD) by using situ hybridization to identify FZDs that are expressed in dorsal-ventral regions of the neural tube development. Our data show specific expression for FZD1,2,3,7,9 and 10 in the chick developing spinal cord. This expression profile of cFZD receptors offers the basis for functional studies in the future to determine roles for the different FZD receptors and their interactions with Wnts during dorsal-ventral neural tube development in vivo. Furthermore, we also show that co-overexpression of Wnt1/3a by in vivo electroporation affects FZD7/10 expression in the neural tube. This illustrates an example of Wnts-FZDs interactions during spinal cord neurogenesis.


Navigating in a volumetric world: metric encoding in the vertical axis of space.
Animals navigate through three-dimensional environments, but we argue that the way they encode three-dimensional spatial information is shaped by how they use the vertical component of space. We agree with Jeffery et al. that the representation of three-dimensional space in vertebrates is probably bicoded (with separation of the plane of locomotion and its orthogonal axis), but we believe that their suggestion that the vertical axis is stored "contextually" (that is, not containing distance or direction metrics usable for novel computations) is unlikely, and as yet unsupported. We describe potential experimental protocols that could clarify these differences in opinion empirically.


Angular Synchronization by Eigenvectors and Semidefinite Programming.
The angular synchronization problem is to obtain an accurate estimation (up to a constant additive phase) for a set of unknown angles θ(1), …, θ(n) from m noisy measurements of their offsets θ(i) - θ(j) mod 2π. Of particular interest is angle recovery in the presence of many outlier measurements that are uniformly distributed in [0, 2π) and carry no information on the true offsets. We introduce an efficient recovery algorithm for the unknown angles from the top eigenvector of a specially designed Hermitian matrix. The eigenvector method is extremely stable and succeeds even when the number of outliers is exceedingly large. For example, we successfully estimate n = 400 angles from a full set of m=(4002) offset measurements of which 90% are outliers in less than a second on a commercial laptop. The performance of the method is analyzed using random matrix theory and information theory. We discuss the relation of the synchronization problem to the combinatorial optimization problem Max-2-Lin mod L and present a semidefinite relaxation for angle recovery, drawing similarities with the Goemans-Williamson algorithm for finding the maximum cut in a weighted graph. We present extensions of the eigenvector method to other synchronization problems that involve different group structures and their applications, such as the time synchronization problem in distributed networks and the surface reconstruction problems in computer vision and optics.


Omics of endothelial cell dysfunction in sepsis.
During sepsis, defined as life-threatening organ dysfunction due to dysregulated host response to infection, systemic inflammation activates endothelial cells and initiates a multifaceted cascade of pro-inflammatory signaling events, resulting in increased permeability and excessive recruitment of leukocytes. Vascular endothelial cells share many common properties but have organ-specific phenotypes with unique structure and function. Thus, therapies directed against endothelial cell phenotypes are needed to address organ-specific endothelial cell dysfunction. Omics allow for the study of expressed genes, proteins and/or metabolites in biological systems and provide insight on temporal and spatial evolution of signals during normal and diseased conditions. Proteomics quantifies protein expression, identifies protein-protein interactions and can reveal mechanistic changes in endothelial cells that would not be possible to study via reductionist methods alone. In this review, we provide an overview of how sepsis pathophysiology impacts omics with a focus on proteomic analysis of mouse endothelial cells during sepsis/inflammation and its relationship with the more clinically relevant omics of human endothelial cells. We discuss how omics has been used to define septic endotype signatures in different populations with a focus on proteomic analysis in organ-specific microvascular endothelial cells during sepsis or septic-like inflammation. We believe that studies defining septic endotypes based on proteomic expression in endothelial cell phenotypes are urgently needed to complement omic profiling of whole blood and better define sepsis subphenotypes. Lastly, we provide a discussion of how in silico modeling can be used to leverage the large volume of omics data to map response pathways in sepsis.


Combining in silico and in vitro models to inform cell seeding strategies in tissue engineering.
The seeding density of therapeutic cells in engineered tissue impacts both cell survival and vascularization. Excessively high seeded cell densities can result in increased death and thus waste of valuable cells, whereas lower seeded cell densities may not provide sufficient support for the tissue in vivo, reducing efficacy. Additionally, the production of growth factors by therapeutic cells in low oxygen environments offers a way of generating growth factor gradients, which are important for vascularization, but hypoxia can also induce unwanted levels of cell death. This is a complex problem that lends itself to a combination of computational modelling and experimentation. Here, we present a spatio-temporal mathematical model parametrized using in vitro data capable of simulating the interactions between a therapeutic cell population, oxygen concentrations and vascular endothelial growth factor (VEGF) concentrations in engineered tissues. Simulations of collagen nerve repair constructs suggest that specific seeded cell densities and non-uniform spatial distributions of seeded cells could enhance cell survival and the generation of VEGF gradients. These predictions can now be tested using targeted experiments.


Discrimination of spectral reflectance under environmental illumination.
Color constancy is the ability to recover a stable perceptual estimate of surface reflectance, regardless of the lighting environment. However, we know little about how observers make judgments of the surface color of glossy objects, particularly in complex lighting environments that introduce complex spatial patterns of chromatic variation across an object's surface. To address this question, we measured thresholds for reflectance discrimination using computer-rendered stimuli under environmental illumination. In Experiment 1, we found that glossiness and shape had small effects on discrimination thresholds. Importantly, discrimination ellipses extended along the direction in which the chromaticities in the environmental illumination spread. In Experiment 2, we also found that the observers' abilities to judge surface colors were worse in lighting environments with an atypical chromatic distribution.


Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations.
Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism's fitness. Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well.Genet Med 18 10, 1029-1036.


The importance of health for persons with psychiatric disabilities.
Persons with psychiatric disabilities often lead an isolated life, and their living conditions are usually not as good as those of other people. There are few studies that describe these individuals' own opinions of what can contribute to increased health. The aim of this study was therefore to describe the importance of health for persons with psychiatric disabilities. The study group comprised 12 persons, living in the community in west of Sweden, who were interviewed during 2005. The data were analysed by means of qualitative content analysis. The findings revealed five categories: (1) help and support in daily life; (2) being part of a social context; (3) having a meaningful daily life; (4) using resources in the right way; and (5) experiencing well-being. The result showed that interventions that promote health need to be clarified and strengthened by means of coordinated efforts from the healthcare services and the local community. In addition, persons with psychiatric disabilities should be invited and encouraged to participate in society as well as being listened to and having their needs addressed.


The neural site of binocular rivalry relative to the analysis of motion in the human visual system.
Neural processing is disrupted during suppression phases of binocular rivalry, as evidenced by the temporary invisibility of an otherwise complex, high-contrast visual stimulus. This paper investigates the locus of this disruption relative to the processing of information about image motion. In one experiment, observers tracked binocular rivalry between a stationary textured field and a plaid composed of 2 drifting cosine gratings, with the angle between components varied to produce different pattern speeds. (Plaid speed is given by the ratio of the component speed to the cosine of the angle between the 2 directions of motion.) Predominance of the moving plaid increased with pattern speed, even though the speed of the individual components remained constant. Control measures verified that this influence of plaid speed was not attributable to specific component orientations. Information about coherent motion influences the rivalry process, implying that the site of coherent motion analysis, presumably the middle temporal area (MT), received input during dominance phases of rivalry. A second experiment investigated the effect of suppression on the processing of complex, nonlinear motion. Observers tracked rivalry phases for a rotating spiral, then indicated the duration of the subsequently perceived spiral aftereffect (SAE) for both rivalry and nonrivalry conditions. The SAE was reduced when adaptation occurred under the rivalry condition, with aftereffect duration proportional to the total duration of spiral visibility during adaptation. Earlier work places rivalry after the site of the linear motion aftereffect, and the present results show that rivalry suppression occurs prior to the site of spiral motion processing.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of affirm VP Microbial Identification Test for Gardnerella vaginalis and Trichomonas vaginalis.
A commercial system (Affirm VP Microbial Identification Test; MicroProbe Corp.) for detection of vaginal pathogens was evaluated with 176 consecutive women attending a sexually transmitted disease clinic for genital complaints. Vaginal swab specimens were used for culture of Gardnerella vaginalis and Trichomonas vaginalis, preparation of a vaginal smear for Gram stain interpretation, and wet mount evaluation. An additional swab was used to evaluate the 30-min nonisotopic oligonucleotide probe test. The automated probe system detected G. vaginalis in 69 (95%) of 73 women having > 5 x 10(5) CFU of G. vaginalis per ml by culture, and 20 (43%) of 47 specimens with < or = 5 x 10(5) CFU of G. vaginalis per ml. There were three false positives and four false negatives for the Affirm VP test compared with > 5 x 10(5) CFU of G. vaginalis per ml. The probe system detected G. vaginalis in 57 (90%) of 63 vaginal specimens from women having clue cells on wet mount examination, and in only 3 (3%) of 113 women without clue cells, suggesting that the Affirm probe for G. vaginalis could be used as a surrogate for wet mount examination for clue cells. The T. vaginalis probe was positive for 12 of 12 specimens positive by wet mount and 12 of 15 specimens positive by culture. There were no false positives and three false negatives for the Affirm VP test compared with culture and/or wet mount for T. vaginalis. The Affirm VP Microbial Identification System is a rapid, objective, and automated test for the detection of T. vaginalis and clinically significant levels of G. vaginalis that is comparable to wet mount examination for clue cells and is superior to wet mount examination for the detection of trichomonads.


Citizens' Perspectives on Disinvestment from Publicly Funded Pathology Tests: A Deliberative Forum.
Deliberative forums can be useful tools in policy decision making for balancing citizen voice and community values against dominant interests. To describe the use of a deliberative forum to explore community perspectives on a complex health problem-disinvestment. A deliberative forum of citizens was convened in Adelaide, South Australia, to develop criteria to support disinvestment from public funding of ineffective pathology tests. The case study of potential disinvestment from vitamin B12/folate pathology testing was used to shape the debate. The forum was informed by a systematic review of B12/folate pathology test effectiveness and expert testimony. The citizens identified seven criteria: cost of the test, potential impact on individual health/capacity to benefit, potential cost to society, public good, alternatives to testing, severity of the condition, and accuracy of the test. The participants not only saw these criteria as an interdependent network but also questioned "the authority" of policymakers to make these decisions. Coherence between the criteria devised by the forum and those described by an expert group was considerable, the major differences being that the citizens did not consider equity issues and the experts neglected the "cost" of social and emotional impact of disinvestment on users and the society.


A case of bow hunter's stroke caused by non-dominant vertebral artery.
Rotational movements in the territory of vertebrobasilar artery of the head and neck can induce vertebrobasilar insufficiency (VBI) or infarction. The term "bow hunter's stroke" or "rotational VBI" has been used to describe this clinical syndrome. In most cases, symptoms were provoked because of involvement of a dominant vertebral artery (VA) with hypoplasia or occlusion of the contralateral VA. The author presented a case in which bow hunter's stroke was caused by occlusion of a non-dominant VA ending in the posterior inferior cerebellar artery (PICA). Diagnosis of rotational VBI was based on stereotypical clinical symptoms related to head rotation and hemodynamic study of the effects of head rotation. VA compression was documented in dynamic ultrasonography including the disappearance of end-diastolic flow in extracranial portion of VA and marked reduction in blood flow velocity (more than 50%) in the intracranial portion of VA upon head rotation. We emphasize that rotational occlusion of this anatomical variation is an important cause of VBI. This may cause permanent neurological deficits if left undiagnosed.


Co-administration of cholera toxin and apple polyphenol extract as a novel and safe mucosal adjuvant strategy.
Although native cholera toxin (CT) is an extremely effective adjuvant, its toxicity prevents its use in humans. We report here that apple polyphenol extract (APE), obtained from unripe apples, reduces CT-induced morphological changes and cAMP accumulation. Based upon this finding, we have attempted to design a novel, effective and safe mucosal vaccine by using CT with several dosages of APE as nasal adjuvants. Mice nasally immunized with OVA plus CT and an optimal dosage of APE showed significantly reduced levels of inflammatory responses as well as total and OVA-specific IgE antibodies when compared with mice given without APE. However, levels of both mucosal and systemic OVA-specific antibody responses were maintained. Further, APE significantly down-regulated accumulation of CT in the olfactory nerves and epithelium. In summary, an optimal dosage of APE would take full advantage of mucosal adjuvanticity of native CT without any toxicity for application in humans.


The recommodification of healthcare? A case study of user charges and inequalities in access to healthcare in Sweden 1980-2005.
User charges in Swedish healthcare have increased during recent decades. This can be seen in terms of the recommodification of healthcare: making healthcare access more dependent on market position. This study investigates whether the increase in user charges had an impact on educational inequalities in access to healthcare in Sweden between 1980 and 2005. Data from the Swedish Living Conditions Survey were used to calculate the odds ratios of access to healthcare for the low and higher educated in Sweden, and the results were stratified by health status (Good and Not good health) for each year 1980-2005. These odds ratios were correlated with the average user charge for healthcare. There were no educational differences in healthcare access in the group with Good health. In the group with Not good health, the higher educated had higher rates of healthcare access than the lower educated. Inequalities in access to healthcare were relatively stable over time, with a slight increase among those with Not good health. Recommodification has had only a small association with access to healthcare in Sweden. The Swedish system has integral protections that protect the vulnerable against rising healthcare costs. This is an important caveat for other countries that are considering introducing or raising user charges.


A comparison of head movement during back boarding by motorized spine-board and log-roll techniques.
In a patient with a potential cervical spine injury, minimizing or eliminating movement at the head and neck during stabilization and transport is paramount because movement can exacerbate the condition. Any equipment or technique creating less movement will allow for a more effective and safe stabilization of an injured patient, reducing the likelihood of movement and potential secondary injury. To compare the amount of head movement created during the log-roll and motorized spine-board (MSB) stabilization techniques. A 2-condition, repeated-measures design. Laboratory. Thirteen certified athletic trainers, emergency first responders, and emergency medical technicians (6 men, 7 women). Subjects rotated through 4 positions for the log roll and 2 positions for the MSB. Each subject performed 3 trials while maintaining manual, inline stabilization of the model's head for each condition. Three-dimensional head movement was measured and expressed as degrees of motion. The log roll created significantly more motion in the frontal and transverse planes compared with the MSB (P = .001 for both measures). No significant difference was noted for sagittal-plane motion (P = .028). The MSB created less movement at the head than did the log roll in 2 planes of motion and created slightly more motion in 1 plane, although this difference was not significant. The MSB may provide emergency responders with an appropriate alternative method for stabilizing and transporting a supine injured athlete without requiring a log roll.


TFF2 (trefoil family factor2) inhibits apoptosis in breast and colorectal cancer cell lines.
We have recently demonstrated that human TFF2 inhibits apoptosis in the non-TFF2 expressing breast adenocarcinoma cell line MCF-7. In this study we examined the impact of TFF2 and an anti-TFF2 antibody (hSP3) on the survival of other human adenocarcinoma cell lines; TFF2-positive (LS174T and SW480) and TFF2-negative (MCF-7 and T47D). Addition of TFF2 protected the (TFF2-) lines but had no effect on those constitutively expressing TFF2. Blocking with hSP3 significantly increased apoptosis in the (TFF2+) cell lines with minimal effect on the (TFF2-) cells. Our results show that the cytoprotective effect of TFF2 seen in MCF-7 cells is not cell line-specific and can be abrogated by inhibition of its expression.


Conservation of the OmpC Porin Among Typhoidal and Non-Typhoidal Salmonella Serovars.
Salmonella enterica infections remain a challenging health issue, causing significant morbidity and mortality worldwide. Current vaccines against typhoid fever display moderate efficacy whilst no licensed vaccines are available for paratyphoid fever or invasive non-typhoidal salmonellosis. Therefore, there is an urgent need to develop high efficacy broad-spectrum vaccines that can protect against typhoidal and non-typhoidal Salmonella. The Salmonella outer membrane porins OmpC and OmpF, have been shown to be highly immunogenic antigens, efficiently eliciting protective antibody, and cellular immunity. Furthermore, enterobacterial porins, particularly the OmpC, have a high degree of homology in terms of sequence and structure, thus making them a suitable vaccine candidate. However, the degree of the amino acid conservation of OmpC among typhoidal and non-typhoidal Salmonella serovars is currently unknown. Here we used a bioinformatical analysis to classify the typhoidal and non-typhoidal Salmonella OmpC amino acid sequences into different clades independently of their serological classification. Further, our analysis determined that the porin OmpC contains various amino acid sequences that are highly conserved among both typhoidal and non-typhoidal Salmonella serovars. Critically, some of these highly conserved sequences were located in the transmembrane β-sheet within the porin β-barrel and have immunogenic potential for binding to MHC-II molecules, making them suitable candidates for a broad-spectrum Salmonella vaccine. Collectively, these findings suggest that these highly conserved sequences may be used for the rational design of an effective broad-spectrum vaccine against Salmonella.


Maternal underweight and the risk of preterm birth and low birth weight: a systematic review and meta-analyses.
Despite the current obesity epidemic, maternal underweight remains a common occurrence with potential adverse perinatal outcomes. Our objective was to determine the relationship between maternal underweight and preterm birth (PTB) and low birth weight (LBW) in singleton pregnancies in developing and developed countries. We followed the MOOSE consensus statement. We searched MEDLINE and EMBASE from their inceptions. We included studies that assessed the effect of maternal underweight compared with normal weight according to body mass index in singleton gestations on our two primary outcomes: PTB (<37 weeks) and LBW (<2500 g). Two assessors independently reviewed citations, extracted data and assessed quality. A total of 78 studies were included involving 1 025 794 women. The overall risk of PTB was increased in the cohort studies of underweight women [adjusted relative risk (RR) 1.29, 95% confidence interval (CI) 1.15-1.46], as were the risks of spontaneous PTB (adjusted RR 1.32, 95% CI 1.10-1.57) and induced PTB (adjusted RR 1.21, 95% CI 1.07-1.36). Underweight women had an increased risk of an LBW infant (adjusted RR 1.64, 95% CI 1.38-1.94). In developed countries, underweight women had an increased risk of PTB (RR 1.22, 95% CI 1.15-1.30) but not in developing countries (RR 0.99, 95% CI 0.67-1.45). In both developed and developing countries, underweight women were at increased risk of having an LBW infant (RR 1.48, 95% CI 1.29-1.68, and RR 1.52, 95% CI 1.25-1.85, respectively). In this systematic review and meta-analyses, we determined that singletons born to underweight women have higher risks of PTB (overall, spontaneous and induced) and LBW than those born to women with normal weight.


Human listeriosis and animal models.
Human listeriosis is a potentially fatal foodborne infection caused by Listeria monocytogenes, an opportunistic psychrophile bacterium that is widespread in the environment. It has only recently emerged as a significant cause of human infection in industrialized countries, owing to appearance of a vulnerable population of immunocompromised individuals, and the concomitant development of large-scale agro-industrial plants and refrigerated food. Here we review the main clinical features of human listeriosis and highlight specificities and similarities with animal listeriosis in diverse species. Finally, we present some of the critical determinants for the choice of an appropriate animal model to study human listeriosis.


Feedback regulation of ALDOA activates the HIF-1α/MMP9 axis to promote lung cancer progression.
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC). We validated our in silico findings with an immunohistochemical analysis of clinical samples. Aldolase A silencing significantly suppressed metastatic potential both in vitro and in vivo, whereas the ectopic overexpression of Aldolase A resulted in the opposite phenotype. Furthermore, our microarray and Ingenuity Pathway Analyses (IPA) revealed that Aldolase A-driven lung cancer metastasis was closely linked to hypoxia inducible factor 1 alpha (HIF-1α)-downstream signaling. Importantly, Aldolase A overexpression may promote the release of lactate to block PHD activities and further induce HIF-1α stabilization. Aldolase A and nuclear HIF-1α overexpression levels were positively correlated and were significantly associated with a poorer survival rate in lung cancer patients (P = 0.008 for Overall Survival, P = 0.021 for Disease-free Survival). Furthermore, MMP9, a downstream target of HIF-1α, was significantly upregulated after ALDOA overexpression. A MMP9 inhibitor significantly inhibited cell invasion and migration in ALDOA-HIF-1α axis-induced lung cancer. In summary, our results reveal the molecular mechanism of Aldolase A in promoting lung cancer metastasis via PHD-mediated stabilization of HIF-1α and the subsequent activation of MMP9. The ALDOA-HIF-1α axis may provide a new therapeutic target for metastatic lung cancer treatment.


Healthy lifestyle behaviors among older U.S. adults with and without disabilities, Behavioral Risk Factor Surveillance System, 2003.
Little is known about the relationship between healthy behaviors and the prevalence of chronic diseases in older adults with disabilities. This study examines the prevalence of selected healthy lifestyle behaviors related to chronic diseases among adults aged 65 years and older with and without disabilities. Data from the 2003 Behavioral Risk Factor Surveillance System (BRFSS) were used to assess having a healthy weight and six behaviors: current cigarette smoking status, consumption of at least one alcoholic beverage daily, consumption of at least five fruits or vegetables daily, physical activity during the average week, influenza immunization in the past year, and lifetime pneumococcal immunization. People with a disability were less likely than people without a disability to have a healthy weight (28.5% vs 37.2%) and to engage in the recommended level of weekly physical activity (14.7% vs 26.2%). However, people with a disability were more likely than those without a disability to be nonsmokers (91.8% vs 89.9%), to consume up to one alcoholic beverage daily (95.1% vs 91.5%), to have received their influenza immunization in the past year (72.7% vs 69.0%), and to have received a lifetime pneumococcal immunization (72.1% vs 63.0%). There was no difference between people with and without a disability in the prevalence rates of consuming at least five fruits or vegetables daily. The prevalence of having a healthy weight and six chronic-disease related behaviors among adults aged 65 years and older varies by disability status and by specific modifiable lifestyle behavior. Screening older adults with and without disabilities and counseling them about health behaviors should be integrated into every interaction between older adults and their health care providers to potentially lower the rates of morbidity and mortality related to chronic diseases in the later years.


The interaction of Escherichia coli O157 :H7 and Salmonella Typhimurium flagella with host cell membranes and cytoskeletal components.
Bacterial flagella have many established roles beyond swimming motility. Despite clear evidence of flagella-dependent adherence, the specificity of the ligands and mechanisms of binding are still debated. In this study, the molecular basis of Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium flagella binding to epithelial cell cultures was investigated. Flagella interactions with host cell surfaces were intimate and crossed cellular boundaries as demarcated by actin and membrane labelling. Scanning electron microscopy revealed flagella disappearing into cellular surfaces and transmission electron microscopy of S. Typhiumurium indicated host membrane deformation and disruption in proximity to flagella. Motor mutants of E. coli O157:H7 and S. Typhimurium caused reduced haemolysis compared to wild-type, indicating that membrane disruption was in part due to flagella rotation. Flagella from E. coli O157 (H7), EPEC O127 (H6) and S. Typhimurium (P1 and P2 flagella) were shown to bind to purified intracellular components of the actin cytoskeleton and directly increase in vitro actin polymerization rates. We propose that flagella interactions with host cell membranes and cytoskeletal components may help prime intimate attachment and invasion for E. coli O157:H7 and S. Typhimurium, respectively.


Supramolecular control of the magnetic anisotropy in two-dimensional high-spin Fe arrays at a metal interface.
Magnetic atoms at surfaces are a rich model system for solid-state magnetic bits exhibiting either classical or quantum behaviour. Individual atoms, however, are difficult to arrange in regular patterns. Moreover, their magnetic properties are dominated by interaction with the substrate, which, as in the case of Kondo systems, often leads to a decrease or quench of their local magnetic moment. Here, we show that the supramolecular assembly of Fe and 1,4-benzenedicarboxylic acid molecules on a Cu surface results in ordered arrays of high-spin mononuclear Fe centres on a 1.5 nm square grid. Lateral coordination with the molecular ligands yields unsaturated yet stable coordination bonds, which enable chemical modification of the electronic and magnetic properties of the Fe atoms independently from the substrate. The easy magnetization direction of the Fe centres can be switched by oxygen adsorption, thus opening a way to control the magnetic anisotropy in supramolecular layers akin to that used in metallic thin films.


Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase.
Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. We report herein the isolation of a cDNA encoding a novel protein kinase designated MAPKKK5 from a human macrophage library. The nucleotide sequence predicts that MAPKKK5 encodes an open reading frame of 1374 amino acids with all 11 kinase subdomains. The putative catalytic domain of MAPKKK5 shows significant sequence homology to the kinase domains of the MAPKKK/MEKK level protein kinases from mouse MEKK2 and -3, Drosophila melanogaster PK92B, Saccharomyces cerevisiae STE11, and Schizosaccharomyces pombe BYR2. Northern blot analysis showed that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. When transiently expressed in COS and 293 cells, MAPKKK5 markedly activated c-Jun N-terminal kinase or stress-activated protein kinase, but not MAPK/ERK. Furthermore, MAPKKK5 that was immunoprecipitated from transfected 293 cells was able to phosphorylate and activate MKK4 in vitro, suggesting that MAPKKK5 may be an upstream activator of MKK4 in the c-Jun N-terminal kinase pathway.


High glucose alters Cx43 expression and gap junction intercellular communication in retinal Müller cells: promotes Müller cell and pericyte apoptosis.
To investigate whether high glucose (HG) alters connexin 43 (Cx43) expression and gap junction intercellular communication (GJIC) activity in retinal Müller cells, and promotes Müller cell and pericyte loss. Retinal Müller cells (rMC-1) and cocultures of rMC-1 and retinal pericytes were grown in normal (N) or HG (30 mM glucose) medium. Additionally, rMC-1 transfected with Cx43 small interfering RNA (siRNA) were grown as cocultures with pericytes, and rMC-1 transfected with Cx43 plasmid were grown in HG. Expression of Cx43 was determined by Western blotting and immunostaining and GJIC was assessed by scrape-loading dye transfer (SLDT) technique. Apoptosis was analyzed by TUNEL or differential staining assay, and Akt activation by assessing Akt phosphorylation. In monocultures of rMC-1 and cocultures of rMC-1 and pericytes, Cx43 protein level, number of Cx43 plaques, GJIC, and Akt phosphorylation were significantly reduced in HG medium. Number of TUNEL-positive cells was also significantly increased in rMC-1 monocultures and in rMC-1 and pericyte cocultures grown in HG medium. Importantly, when rMC-1 transfected with Cx43 siRNA were grown as cocultures with pericytes, a significant decrease in GJIC, and increase in TUNEL-positive cells was observed, concomitant with decreased Akt phosphorylation. Upregulation of Cx43 rescued rMC-1 from HG-induced apoptosis. Gap junction communication between Müller cells and pericytes is essential for their survival. Downregulation of Cx43 that is HG induced and impairment of GJIC activity in Müller cells contributes to loss of glial and vascular cells associated with the pathogenesis of diabetic retinopathy.


Onychomycosis: modern diagnostic and treatment approaches.
The medical term onychomycosis should be understood as chronic infection of the nails caused by a fungus. The most common causative agents are the dermatophytes and Candida species. The less common are certain types of moulds (nondermatophyte moulds or NDMs). In approximately 60-80 % of the cases, onychomycosis is due to dermatophytes. Among dermatophytes, the most often isolated causative pathogen is Trichophyton (T.) rubrum. Other common species are T. interdigitale (formerly T. mentagrophytes), Epidermophyton floccosum, and T. tonsurans. The most significant yeasts causing onychomycosis are Candida albicans and Candida parapsilosis. Predisposing factors for onychomycosis include mainly diseases such as diabetes mellitus, peripheral vascular arterial disease, chronic venous insufficiency, polyneuropathies of diverse etiologies, and immunosuppression, e.g., myeloproliferative diseases (such as lymphoma and paraproteinemia), HIV/AIDS, etc. Other factors facilitating the fungal infection are frequent trauma in professional sportsmen, often accompanied by excessive perspiration. The diagnostic methods that are often applied in different dermatologic departments and ambulatory units are also different. This precludes the creation of a unified diagnostic algorithm that could be used everywhere as a possible standard. In most of the cases, the method of choice depends on the specialist's individual experience. The therapeutic approach depends mostly on the fungal organism identified by the dermatologist or mycologist. This review hereby includes the conventional as well as the newest and most reliable and modern methods used for the identification of the pathogens causing onychomycosis. Moreover, detailed information is suggested, about the choice of therapeutic scheme in case whether dermatophytes, moulds, or yeasts have been identified as causative agents. A thorough discussion of the schemes and duration of the antifungal therapy in certain groups of patients have been included.


Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation.
Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (I(max)) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for I(max) were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of I(max) during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy.


The persistence of component Theileria parva stocks in cattle immunized with the 'Muguga cocktail' live vaccine against East Coast fever in Uganda.
The 'Muguga cocktail' live vaccine comprises three Theileria parva stocks (Muguga, Kiambu 5 and the buffalo-derived Serengeti-transformed) and has been used extensively in Eastern, Central and Southern Africa with an infection and treatment protocol to protect cattle against East Coast fever. We report the characterization of the three component vaccine stocks using a panel of polymorphic micro-satellite and mini-satellite markers and the development of a stock-derived PCR method that distinguishes two of the vaccine stocks. These markers, with the use of a recently developed Reverse Line Blot assay, have enabled us to address four important questions in relation to vaccination. First, how closely related are the vaccine stocks, secondly do all three stocks persist post-vaccination and induce a carrier state, thirdly is there evidence for the transmission of the vaccine stocks and fourthly does vaccination prevent infection with local genotypes? The results show that Muguga and Serengeti-transformed stocks are highly related but very distinct from Kiambu 5 that persists in vaccinated cattle establishing a carrier state. No evidence was obtained for the transmission of vaccine stocks to co-grazed animals, although these animals were infected with up to 8 different T. parva genotypes showing there was a significant level of tick challenge. Some of the vaccinated animals become infected with a subset of local genotypes providing evidence for limited vaccine 'breakthrough'.


Determinants of airborne benzene evaporating from fresh crude oils released into seawater.
Benzene, toluene, ethylbenzene, xylenes, naphthalene and n-hexane evaporating from a thin oil film was measured for 30 min in a small-scale test system at 2 and 13 °C and the impact of physicochemical properties on airborne benzene with time after bulk oil release was studied. Linear mixed-effects models for airborne benzene in three time periods; first 5, first 15 and last 15 min of sampling, indicated that benzene content in fresh oil, oil group (condensate/light crude oil) and pour point were significant determinants explaining 63-73% of the total variance in the outcome variables. Oils with a high pour point evaporated considerably slower than oils with a low pour point. The mean air concentration of total volatile organic compounds was significatly higher at 13 °C (735 ppm) compared to 2 °C (386 ppm) immediately after release of oil, but at both temperatures the concentration rapidly declined.


Relationship between ureB Sequence Diversity, Urease Activity and Genotypic Variations of Different Helicobacter pylori Strains in Patients with Gastric Disorders.
Association of the severity of Helicobacter pylori induced diseases with virulence entity of the colonized strains was proven in some studies. Urease has been demonstrated as a potent virulence factor for H. pylori. The main aim of this study was investigation of the relationships of ureB sequence diversity, urease activity and virulence genotypes of different H. pylori strains with histopathological changes of gastric tissue in infected patients suffering from different gastric disorders. Analysis of the virulence genotypes in the isolated strains indicated significant associations between the presence of severe active gastritis and cagA+ (P = 0.039) or cagA/iceA1 genotypes (P = 0.026), and intestinal metaplasia and vacA m1 (P = 0.008) or vacA s1/m2 (P = 0.001) genotypes. Our results showed a 2.4-fold increased risk of peptic ulcer (95% CI: 0.483-11.93), compared with gastritis, in the infected patients who had dupA positive strains; however this association was not statistically significant. The results of urease activity showed a significant mean difference between the isolated strains from patients with PUD and NUD (P = 0.034). This activity was relatively higher among patients with intestinal metaplasia. Also a significant association was found between the lack of cagA and increased urease activity among the isolated strains (P = 0.036). While the greatest sequence variation of ureB was detected in a strain from a patient with intestinal metaplasia, the sole determined amino acid change in UreB sequence (Ala201Thr, 30%), showed no influence on urease activity. In conclusion, the supposed role of H. pylori urease to form peptic ulcer and advancing of intestinal metaplasia was postulated in this study. Higher urease activity in the colonizing H. pylori strains that present specific virulence factors was indicated as a risk factor for promotion of histopathological changes of gastric tissue that advance gastric malignancy.


Psychometric properties and health correlates of the Geriatric Anxiety Inventory in Australian community-residing older women.
To assess the psychometric properties and health correlates of the Geriatric Anxiety Inventory (GAI) in a cohort of Australian community-residing older women. Cross-sectional study of a population-based cohort of women aged 60 years and over (N = 286). The GAI exhibited sound internal consistency and demonstrated good concurrent validity against the state half of the Spielberger State Trait Anxiety Inventory and the neuroticism domain of the NEO five-factor inventory. GAI score was significantly associated with self-reported sleep difficulties and perceived memory impairment, but not with age or cognitive function. Women with current DSM-IV Generalized Anxiety Disorder (GAD) had significantly higher GAI scores than women without such a history. In this cohort, the optimal cut-point to detect current GAD was 8/9. Although the GAI was designed to have few somatic items, women with a greater number of general medical problems or who rated their general health as worse had higher GAI scores. The GAI is a new scale designed specifically to measure anxiety in older people. In this Australian cohort of older women, the instrument had sound psychometric properties.


The role of collagen abnormalities in ultrasound and densitometry assessment: In vivo evidence.
There is little information concerning how the mutation of collagen affects bone mineralization and the assessment of bone properties. To estimate these influences, we performed ultrasonic assessments of the calcaneus and bone mineral density (BMD) measurements of the hip and lumbar spine. Females with diseases related to the mutation of collagen [Ehlers-Danlos syndrome (EDS) type III and systemic sclerosis (SSc)] participated in this study. We compared the broadband ultrasound attenuation (BUA and UBI-4), the average transit time through the heel (TTH), and a multiple factor index (UBI-4T) with control subjects matched on age, race, and menstrual status. Both groups of patients had BMD of the spine (L2-L4) within the normal range for their age and sex (for EDS: n = 23, 1.14 +/- 0. 14 g/cm2 and z-score = 0.37; for SSc: n = 15, 0.98 +/- 0.15 g/cm2 and z-score = 0.20). EDS and SSc subjects had lower BMD of the femoral neck (FN) compared with controls (for EDS: 0.91 +/- 0.13 g/cm2, z-score = -0.41, P = 0.025; for SSc 0.67 +/- 0.13 g/cm2, z-score = -0.92, P = 0.006). Subjects with EDS and SSc also had lower BUA values (P = 0.051-0.001) compared with controls. After adjusting for body weight, height, and the level of physical activity, the difference in FN BMD between EDS or SSc and controls became marginal (EDS: P = 0.072; SSc: P = 0.086). However, the significant difference for BUA between subjects and controls remained for EDS (P = 0.008), and disappeared for SSc (0.70) after adjusting for weight, height, level of physical activity, and BMD. These results suggest that the abnormalities of collagen may impact on bone mass measurements differently depending on skeletal site, modality of the assessment, and the source and nature of collagen defects. To determine whether collagen properties influence QUS, proper models in vivo and in vitro should be used.


Time to End Physician Sexual Abuse of Patients: Calling the U.S. Medical Community to Action.
Despite the strict prohibition against all forms of sexual relations between physicians and their patients, some physicians cross this bright line and abuse their patients sexually. The true extent of sexual abuse of patients by physicians in the U.S. health care system is unknown. An analysis of National Practitioner Data Bank reports of adverse disciplinary actions taken by state medical boards, peer-review sanctions by institutions, and malpractice payments shows that a very small number of physicians have faced "reportable" consequences for this unethical behavior. However, physician self-reported data suggest that the problem occurs at a higher rate. We discuss the factors that can explain why such sexual abuse of patients is a persistent problem in the U.S. health care system. We implore the medical community to begin a candid discussion of this problem and call for an explicit zero-tolerance standard against sexual abuse of patients by physicians. This standard must be coupled with regulatory, institutional, and cultural changes to realize its promise. We propose initial recommendations toward that end.