Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents.
Propolis has been used as a folk medicine for centuries around the world due to its wide spectrum of biological activities. The red propolis, a new Brazilian variety of this apimaterial, has presented an unusual chemical composition, including isoflavones such as formononetin and biochanin A. Since both the green and red varieties of propolis are traditionally used as medicine and commercialized with no label differentiation, the study of the activities of red propolis extract has become important in order to clarify whether this product has the same activities as commercial ones. In this work, we demonstrated the potential action of the hydroalcoholic extract of red propolis (HERP) and its biomarker, formononetin, as antinociceptive and anti-inflammatory drugs on experimental models. The HERP was chemically characterised by HPLC/DAD analyses. The biological activities of the HERP (3, 10, and 30mg/kg) and formononetin (10mg/kg) were evaluated using the antinociceptive (acetic acid, formalin, and glutamate injections) and anti-inflammatory (carrageenan-induced hindpaw oedema and peritonitis) models in mice after oral administration. The open field test was also performed. Formononetin, one of the main biomarker of red propolis, was identified in the HERP (21.62mg/g). Pretreatment with the HERP (10 and 30mg/kg) and formononetin (10mg/kg) produced reduction (P<0.001) in the number of abdominal writhes, but the HERP was more effective (P<0.001) than formononetin. In the formalin test, all HERP doses (3, 10, and 30mg/kg, P<0.001) inhibited the late phase (inflammatory pain) of formalin-induced licking, but the inhibition of neurogenic pain was observed only when the higher doses (10 and 30mg/kg; P<0.05) were used. Formononetin caused inhibition (P<0.001) only in the second phase of formalin-induced nociception similarly at all HERP doses in the same phase of the test. The responses in glutamate-induced model presented crescent inhibition (P<0.05) with 10 and 30mg/kg of HERP. Also, formononetin inhibited (P<0.001) the nociception induced by glutamate similarly to 30mg/kg of HERP. There were no significant differences in the open field test after HERP administration, but formononetin decrease the spontaneous motor behaviour. Regarding the anti-inflammatory assessment, the HERP (10 and 30mg/kg, P<0.05) and formononetin (P<0.001) treatments caused a significant inhibition of the oedema response. All doses of HERP (3, 10, and 30mg/kg, P<0.05) and formononetin (P<0.001) also inhibited the carrageenan-induced leukocyte migration. In both cases, the results for the HERP at 30mg/kg and formononetin were similar. The HERP and formononetin presented significant anti-inflammatory activity. Moreover, the HERP presented antinociceptive action on inflammatory and neurogenic pain without motor side effects, possibly due to the action of other constituents present in the extract. These results, together, support the popular usage of this natural product.


Antigenic relationship between H1 and H2 of influenza A virus.
Using cloned viruses of proven purity, and by the methods of hemagglutination inhibition, single radial hemolysis, strain-specific complement fixation and neutralization tests we have demonstrated the serological cross reaction between late H1N1 variant (Dutch/56) and H2N2 of influenza A virus with fowl and hamster antisera. Such a cross reaction is not detected with earlier H1N1 variants. Serological crossing covers variants of H2N2 virus isolated from 1957-1966 but in decreasing titers, and disappears with the last variant of H2N2 isolated late in 1967. Analysis with mono-specific antisera or antigens prepared with recombinants reveal that the hemagglutinins of late H1N1 and H2N2 are related, while their neuraminidases are distinct. We have discussed the bearing of such antigenic relationships to previous epidemiological observations on the partial protection of patients convalescent from late H1N1 disease against H2N2 and to the recombination theory for the origin of H2N2 virus.


Evolution of abdominal pigmentation differences across species in the Drosophila dunni subgroup.
The Drosophila dunni subgroup displays a nearly perfect latitudinal cline in abdominal pigmentation that likely resulted from selective forces acting in the habitat of each species during speciation. Here we characterize the nature of this clinal variation by developing a quantitative measure to assess variation in abdominal pigmentation within and between the D. dunni subgroup species. Using discriminant analysis, we confirm the existence of a cline and find that our quantitative measure of pigmentation distinguishes each of the species with singular efficacy. We then combine our quantitative phenotypic analysis of pigmentation with the phylogeny of the D. dunni subgroup species and map the species relationships into the three-dimensional morphological space defined by our pigmentation measures. In this manner, we can visualize how the species have traversed the morphological pigmentation space during the course of speciation. Our analysis reveals that natural selection has caused overall intensity of pigmentation among the northernmost species of the cline to converge. Along with this convergence in phenotype has been a relaxation in expression of sexual dimorphism in these species, indicating a possible shift in the relative intensity of natural and sexual selection. Our analysis indicates an accelerated rate of change in pigmentation for the darkest species in addition to this species evolving a novel abdominal pigmentation trait.


Estrogens in schizophrenia: progress, current challenges and opportunities.
Schizophrenia is a heterogeneous psychiatric disorder with a different, but not necessarily milder clinical presentation in women as compared to men. These sex differences have largely been attributed to the protective role of estrogens. This article reviews the current state of estrogen research in schizophrenia. Estrogens regulate important pathophysiological pathways in schizophrenia, including dopamine activity, mitochondrial function, and the stress system. Estrogen deficiency is common in both sexes and is associated with increases in psychotic symptoms. Hyperprolactinemia causes secondary estrogen deficiency and can be a reaction to stress, or secondary to prolactin-raising antipsychotics. Therefore, prolactin-sparing antipsychotics should be preferred especially in premenopausal women, who are more prone to hyperprolactinemia. Premenopausal women furthermore require lower doses of antipsychotics than men, since estrogens raise the availability and efficacy of antipsychotics. The past years have established the importance of estrogens in the pathophysiology of schizophrenia and have shown its relevance to clinical practice through its influence on antipsychotic drug efficacy. Future research should focus on the neurobiological and clinical effect of contraceptives in premenopausal women with schizophrenia. Furthermore, the potential of estrogen-like augmentation with raloxifene and phytoestrogens in schizophrenia should be established in the coming years.


Reforming the health care system: the universal dilemma.
This Article surveys alternative approaches by which the advanced industrialized nations seek to cope with the twin problems that health care poses everywhere: the provision of universal access to health care and the control of national spending on health care. Although approaches to these twin problems vary considerably among nations at this time, there may well be a convergence toward a common approach in the next century. Under that approach, all health care systems will be subject to top-down global budgets and will put their health care providers into "statistical fishbowls" that reveal just how effectively these providers allocate the global budgets at their disposal.


Massive Hemorrhage and Mortality Following Thyroid Radiofrequency Ablation.
Radiofrequency ablation (RFA) provides a relatively safe and noninvasive option for treating benign thyroid nodules and thyroid cancer that is cosmetically superior to surgery. Following a loss of consciousness 1 h after thyroid RFA, a 56-year-old patient was transferred to the emergency room. Despite undergoing coronary angiography due to 3 cardiac arrests, the results were normal. Although brain, chest, and abdominal computed tomography scans were performed, the emergency physician failed to detect any hematoma formation. Despite the use of mechanical ventilation and extracorporeal membrane oxygenation, the patient exhibited persistent hypoventilation. It was later discovered that an aggravated massive hemorrhage had occurred, due to which inferior thyroid artery embolization and surgical hematoma evacuation were performed. Unfortunately, prolonged brain hypoperfusion resulting from airway compromise and common carotid artery occlusion resulted in brain death and, ultimately, the patient's demise. In conclusion, massive hemorrhages caused by RFA require immediate diagnosis and hemostasis.


Assessment of the impact of phenylketonuria and its treatment on quality of life of patients and parents from seven European countries.
The strict and demanding dietary treatment and mild cognitive abnormalities seen in PKU treated from a young age can be expected to affect the health-related quality of life (HRQoL) of patients and their families. Our aim was to describe the HRQoL of patients with PKU from a large international study, using generic HRQoL measures and an innovative PKU-specific HRQoL questionnaire (PKU-QOL). Analyses were exploratory, performed post-hoc on data collected primarily to validate the PKU-QOL. A multicentre, prospective, non-interventional, observational study conducted in France, Germany, Italy, The Netherlands, Spain, Turkey and the UK. Patients diagnosed with PKU aged ≥9 years old and treated with a Phe-restricted diet and/or Phe-free amino acid protein supplements and/or pharmacological therapy were included in the study; parents of at least one patient with PKU aged <18 years were also included. HRQoL was assessed by generic measures (Pediatric Quality-of-Life Inventory; Medical Outcome Survey 36 item Short Form; Child Health Questionnaire 28 item Parent Form) and the newly developed PKU-QOL. Mean generic domain scores were interpreted using published reference values from the general population. PKU-QOL domain scores were described overall and in different subgroups of patients defined according to severity of PKU, overall assessment of patient's health status by the investigator and treatment with tetrahydrobiopterin (BH4). Data from 559 subjects were analysed: 306 patients (92 children, 110 adolescents, 104 adults) and 253 parents. Mean domain scores of generic measures in the study were comparable to the general population. The highest PKU-QOL impact scores (indicating greater impact) were for emotional impact of PKU, anxiety about blood Phe levels, guilt regarding poor adherence to dietary restrictions or Phe-free amino acid supplement intake and anxiety regarding blood Phe levels during pregnancy. Patients with mild/moderate PKU and those receiving BH4 reported lower practical and emotional impacts of the diet and Phe-free amino acid supplement intake. Patients with PKU showed good HRQoL in the study, both with the generic and PKU-specific measures. Negative impacts of PKU on a patient's life, including the emotional impact of PKU and its management, was delineated by the PKU-QOLs across all age groups.


The Use of Direct Oral Anticoagulants in the Management of Venous Thromboembolism in Patients With Obesity.
Introduction The use of direct oral anticoagulants (DOACs) has gained significant traction given the lack of therapeutic monitoring and the need for anticoagulant bridging. There is a paucity of data on their effectiveness in obese patients with venous thromboembolism (VTE). Preliminary subgroup and pharmacokinetic analyses suggest reduced efficacy in those with a bodyweight >120 kg or body mass index (BMI) ≥40 kg per m2 and it is currently not recommended that these agents be used as first-line agents. We aimed to assess the rate of VTE recurrence in obese patients diagnosed with VTE and treated with DOAC therapy. Methods We utilized the Health Facts Center National Data Warehouse (Cerner) to perform a retrospective analysis of patients with VTE (acute deep venous thrombosis (DVT) or pulmonary embolism) that presented to the hospital between 2010 and 2016 and were managed with DOACs. The cohort of patients diagnosed with DVT or PE were identified using International Classification of Disease (ICD-9-CM, ICD-10-CM). Patients were divided into two groups based on their weight: 1) weight <120 kg or 2) weight>120 kg. Six-month VTE recurrence rates were recorded. Summary and univariate statistics were performed. Results A total of 18,147 patients with a mean (±SD) age of 62 (17) years were included; 48% (n=8732) were male. A total of 2,419 (13%) patients weighed >120 kg while the rest (N=15,728, 87%) weighed <120 kg. There were significantly more female patients weighing<120 kg (54% vs 42%, p<0.0001); otherwise, there was no significant difference in age or tobacco use between both groups (p>0.05). There was no significant difference in six-month readmission rates for VTE recurrence in patients that weighed <120 kg (34%) in comparison with patients >120 kg (36%) (p=0.08). Conclusion Our study suggests that the use of DOACs in obese patients is equally efficacious with similar VTE recurrence rates in comparison with non-obese patients. This study paves the way for prospective multi-institutional randomized control trials to further reinforce the safe use of such agents in this patient population.


Construction of an efficient biologically contained pseudomonas putida strain and its survival in outdoor assays
Active biological containment systems consist of two components, a killing element designed to induce cell death and a control element which modulates the expression of the killing function. We constructed a mini-Tn5 transposon bearing a fusion of the Plac promoter to the gef killing gene and a fusion of the Pm promoter to the lacI gene plus the positive regulator of the Pm promoter, the xylS gene. This mini-Tn5 transposon was transferred to the chromosome of Pseudomonas putida CMC4, and in culture this strain survived in the presence of 3-methylbenzoate (an XylS effector) and committed suicide in the absence of this aromatic compound. The rate of killing escape was on the order of 10(-8) per cell and per generation. This contained strain and an uncontained control strain were used in outdoor tests performed in the spring-summer and autumn-winter periods to determine their survival in planted and unplanted soils with and without 3-methylbenzoate. In unplanted soils the numbers of both the contained strain and the uncontained strain per gram of soil tended to decrease, but the numbers of the contained strain decreased faster in soils without 3-methylbenzoate. The decrease in the number of CFU per gram of soil was faster in the spring-summer period than in the autumn-winter period. In planted soils survival in the rhizosphere and survival in bulk soil were studied. In the rhizosphere the uncontained control strain tended to become established at levels on the order of 10(5) to 10(6) CFU/g of soil regardless of the presence of 3-methylbenzoate. In the bulk soil the numbers of bacterial cells were 2 to 3 orders of magnitude lower. In planted soils the contained strain tended to disappear, but this tendency was more pronounced in the absence of 3-methylbenzoate and occurred faster in the summer assay than in the winter assay. We found no evidence of dispersal of the test strains outside the experimental plots.


Structured Expert Consensus on Actinic Keratosis: Treatment Algorithm Focusing on Daylight PDT.
A practical and up-to-date consensus among experts is paramount to further improve patient care in actinic keratosis (AK). To develop a structured consensus statement on the diagnosis, classification, and practical management of AK based on up-to-date information. A systematic review of AK clinical guidelines was conducted. This informed the preparation of a 3-round Delphi procedure followed by a consensus meeting, which combined the opinions of 16 clinical experts from 13 countries, to construct a structured consensus statement and a treatment algorithm positioning daylight photodynamic therapy (dl-PDT) among other AK treatment options. The systematic review found deficiencies in current guidelines with respect to new AK treatments such as ingenol mebutate and dl-PDT. The Delphi panel established consensus statements across definition, diagnosis, classification, and management of AK. While the diagnosis of AK essentially rests on the nature of lesions, treatment decisions are based on several clinical and nonclinical patient factors and diverse environmental attributes. Participants agreed on ranked treatment preferences for the management of AK and on classifying AK in 3 clinical situations: isolated AK lesions requiring lesion-directed treatment, multiple lesions within a small field, and multiple lesions within a large field, both requiring specific treatment approaches. Different AK treatment options were discussed for each clinical situation. The results provide practical recommendations for the treatment of AK, which are readily transferable to clinical practice, and incorporate the physician's clinical judgement. The structured consensus statement positioned dl-PDT as a valuable option for patients with multiple AKs in small or large fields.


Blind tracheal intubation by paramedics through the LMA-Unique.
The manufacturer of the laryngeal mask airway (LMA) reports success rates of 30-93% by practitioners attempting tracheal intubation through the LMA-Classic. No prior studies describe success rates through the (disposable) LMA-Unique by paramedics. The objective of this study was to measure the success rate of paramedics attempting to intubate the trachea blindly through the LMA-Unique. During a paramedic refresher class and an emergency medical services teaching day conference, paramedics previously trained in the use of the LMA-Unique as a "rescue" airway device were instructed in the technique of tracheal intubation through the LMA-Unique. A Laerdal LMA-mannequin was immobilized with an extrication collar and held by an investigator in the head-neutral position. Paramedics were first asked to insert the LMA-Unique as previously trained, and to confirm adequate ventilation by seeing inflation of the mannequin's lungs. Then, subjects were asked to pass a well-lubricated 6-0 Mallinckrodt endotracheal tube through the LMA-Unique within a 60-second period. Tracheal placement of the endotracheal tube was then confirmed by visualization of the expanding mannequin lungs. Rates of success of LMA-Unique placement and endotracheal tube placement were measured. Fifty of the 52 (96%; CI 91% to 100%) paramedics successfully inserted the LMA-Unique on the first attempt. Only 11 of the 52 (21%; CI 10% to 32%) paramedics were successful in blind placement of the endotracheal tube into the trachea through the LMA-Unique within a 60-second period. The failures (41 of the 52) were visually confirmed to be located in the esophagus. In this study, when attempting blind tracheal intubation through the LMA-Unique, paramedics were rarely successful in tracheal placement. Basic LMA-Unique insertion, however, had a very high success rate.


Identification of salt-tolerant QTLs with strong genetic background effect using two sets of reciprocal introgression lines in rice.
Effect of genetic background on detection of quantitative trait locus (QTL) governing salinity tolerance (ST) was studied using two sets of reciprocal introgression lines (ILs) derived from a cross between a moderately salinity tolerant japonica variety, Xiushui09 from China, and a drought tolerant but salinity susceptible indica breeding line, IR2061-520-6-9 from the Philippines. Salt toxicity symptoms (SST) on leaves, days to seedling survival (DSS), and sodium and potassium uptake by shoots were measured under salinity stress of 140 mmol/L of NaCl. A total of 47 QTLs, including 26 main-effect QTLs (M-QTLs) and 21 epistatic QTLs (E-QTLs), were identified from the two sets of reciprocal ILs. Among the 26 M-QTLs, only four (15.4%) were shared in the reciprocal backgrounds while no shared E-QTLs were detected, indicating that ST QTLs, especially E-QTLs, were very specific to the genetic background. Further, 78.6% of the M-QTLs for SST and DSS identified in the reciprocal ILs were also detected in the recombinant inbred lines (RILs) from the same cross, which clearly brings out the background effect on ST QTL detection and its utilization in ST breeding. The detection of ILs with various levels of pyramiding of nonallelic M-QTL alleles for ST from Xiushui09 into IR2061-520-6-9 allowed us to further improve the ST in rice.


Electrophoretic and immunological analyses of almond (Prunusdulcis l.) genotypes and hybrids.
Aqueous extracts from sixty almond samples representing various genotypes and interspecies hybrids of almond, including almond-peach, were analyzed for protein and peptide content using electrophoresis, Western immunoblotting, and enzyme-linked immunosorbent assay (ELISA). Nondenaturing nondissociating polyacrylamide gel electrophoresis (NDND-PAGE) of the aqueous extracts indicated that a single major storage protein (almond major protein -- AMP or amandin) dominated the total soluble protein composition. Denaturing SDS--PAGE analyses of the aqueous extracts revealed that the AMP was mainly composed of two sets of polypeptides with estimated molecular masses in the ranges of 38--41 kDa and 20--22 kDa, regardless of the source; however, distinct variations in the intensity and electrophoretic mobility of some bands were noted between samples. In addition to AMP, several minor polypeptides were also present in all the genotypes, and variations were seen in these as well. Regardless of the genotype, AMP was recognized in Western blots by rabbit polyclonal anti-AMP antibodies, mouse monoclonal anti-AMP antibodies (mAbs), and serum IgE from patients displaying strong serum anti-almond IgE reactivity. As with protein staining results, antibody reactivity also revealed common patterns but displayed some variation between samples. An anti-AMP inhibition ELISA was used to quantify and compare aqueous extracts for various samples. All samples (n = 60) reacted in this assay with a mean +/- standard deviation (sigma n) = 0.82 +/- 0.18 when compared to reference aqueous extract from Nonpareil designated as 1.0.


Shaping thin nematic films with competing boundary conditions.
Free interfaces of liquid crystals tend to minimise both capillarity and anchoring forces. Here we study nematic films in planar and radial geometries with antagonistic anchoring boundary conditions and one deformable interface. Assuming a perturbation ansatz we study possible couplings of the director configuration with the shape of free interfaces. In the long-wavelength limit independent of the surface tension, we find analytically the threshold thickness when the flat film becomes unstable. Next we quantify the bifurcation of a circular ring towards structures with m-fold rotational symmetry, induced by elastic anisotropy of the nematic director in the bulk. We believe that our simplified approach can give additional insight into elastic and capillary phenomena of materials with inherent liquid crystalline order and free interfaces.


Metabolomic and transcriptomic changes induced by overnight (16 h) fasting in male and female Sprague-Dawley rats.
The overnight (16-h) fast is one of the most common experimental manipulations performed in rodent studies. Despite its ubiquitous employment, a comprehensive evaluation of metabolomic and transcriptomic sequelae of fasting in conjunction with routine clinical pathology evaluation has not been undertaken. This study assessed the impact of a 16-h fast on urine and serum metabolic profiles, transcript profiles of liver, psoas muscle, and jejunum as well as on routine laboratory clinical pathology parameters. Fasting rats had an approximate 12% relative weight decrease compared to ad libitum fed animals, and urine volume was significantly increased. Fasting had no effect on hematology parameters, though several changes were evident in serum and urine clinical chemistry data. In general, metabolic changes in biofluids were modest in magnitude but broad in extent, with a majority of measured urinary metabolites and from 1/3 to 1/2 of monitored serum metabolites significantly affected. Increases in fatty acids and bile acids dominated the upregulated metabolites. Downregulated serum metabolites were dominated by diet-derived and/or gut-microflora derived metabolites. Major transcriptional changes included genes with roles in fatty acid, carbohydrate, cholesterol, and bile acid metabolism indicating decreased activity in glycolytic pathways and a shift toward increased utilization of fatty acids. Typically, several genes within these metabolic pathways, including key rate limiting genes, changed simultaneously, and those changes were frequently correlative to changes in clinical pathology parameters or metabolomic data. Importantly, up- or down-regulation of a variety of cytochrome P450s, transporters, and transferases was evident. Taken together, these data indicate profound consequences of fasting on systemic biochemistry and raise the potential for unanticipated interactions, particularly when metabolomic or transcriptomic data are primary end points.


Basic fibroblast growth factor inhibits osteoclast-like cell formation.
Basic fibroblast growth factor (bFGF) inhibited osteoclast-like cell formation in co-cultures of mouse bone marrow cells either with the mouse stromal cell line, ST2, or with primary osteoblastic cells. Basic FGF significantly inhibited the osteoclast-like cell formation, induced by 1 alpha,25-dihydroxyvitamin D3[1 alpha, 25(OH)2D3] when the cytokine was added to the culture, at an intermediate stage, suggesting that bFGF inhibits the differentiation of the osteoclast progenitors. With regard to target cells, bFGF directly affected ST2; it increased [3H] thymidine uptake and decreased the number of alkaline phosphatase-positive cells. In contrast, bFGF had no inhibitory effect on the colony formation of bone marrow cells induced by macrophage colony stimulating factor in methylcellulose culture. In addition, ST2 cells treated with bFGF produced similar amounts of colony forming activity to those without the cytokine. These findings indicated that the bFGF is not involved in the proliferation of progenitor cells even in the presence of ST2 cells. Furthermore, bFGF inhibited osteoclast-like cell formation induced not only by 1 alpha,25(OH)2D3, but also by prostaglandin E2 and by interleukin-11. These results suggest that bFGF inhibits the common site of osteoclast-like cell formation, as induced by different mechanisms. Our data also indicated that the target cells for bFGF in inhibiting osteoclast formation are not osteoclast progenitors but stromal cells such as ST2 and osteoblastic cells, which support osteoclast development.


[Physiopathology of Vascular Complications of Diabetic Foot].
To review the literature on vascular complications of diabetic foot with special interest in ulcerative lesions and their prevention and treatment. Representative papers were selected through a computer MEDLINE search from 1980 to 2001. In diabetes mellitus, physiologic and biochemical mechanisms that regulate coordinated behavior between blood circulation and vessel wall are damaged, both in small and large vessels. Vascular alterations observed in patients with diabetes result in peripheral vascular disease with special characteristics in these patients that produce a greater tendency in diabetic than non-diabetic patients for chronic ulcerative lesions of foot and lesser capacity for healing. These lesions frequently result in amputation of the lower limb. Nevertheless efforts made for preventing and healing ulcerative complications, results are unsatisfactory. It is necessary to research new methods for preventing and healing vascular complications of diabetic foot with special attention to improving damaged physiologic and biochemical mechanisms in diabetes mellitus.


Is it the inventory, the meta-analysis, or the construct? Reply to the comments on Marcus, Fulton, and Edens.
Replies to comments by Neumann et al. (see record 2013-01797-001), Patrick et al. (see record 2013-01797-002), Benning (see record 2013-01797-003), Lilienfeld (see record 2013-01797-004), and Blonigen (see record 2013-01797-005) on the original article by Marcus, Fulton, and Edens (see record 2011-23134-001). We wish to thank all of the authors for their thought-provoking and insightful comments about our meta-analysis. All of the comments addressed two of the major findings from our meta-analysis: (a) that the two factors of the Psychopathic Personality Inventory (PPI; Lilienfeld & Andrews, 1996; Lilienfeld & Widows, 2005), Fearless Dominance (FD) and Self-Centered Impulsivity (SCI), are orthogonal or weakly correlated; and (b) that FD was positively correlated with desirable traits indicative of psychological health (i.e., positive emotionality) and negatively associated with traits indicative of distress and psychopathology (i.e., negative emotionality; NEM). Where the commentators differed was in the meaning that they ascribed to this pattern of results.


Correlates of lateral ventricular size in chronic schizophrenia, II: biological measures.
CSF homovanillic acid levels showed a significant negative correlation with ventricle-brain ratios (VBRs) in a group of drug-free chronic schizophrenic male veterans, while CSF 5-hydroxyindoleacetic acid levels showed a similar, nearly significant trend. The response of plasma human growth hormone to 0.75 mg of apomorphine also demonstrated a significant negative correlation with VBR in this group, but other measures of central neurotransmitter activity were unrelated to ventricular size.


The range and distribution of murine central nervous system cells infected with the gamma(1)34.5- mutant of herpes simplex virus 1.
Wild-type herpes simplex virus 1 (HSV-1) multiplies, spreads, and rapidly destroys cells of the murine central nervous system (CNS). In contrast, mutants lacking both copies of the gamma(1)34.5- gene have been shown to be virtually lacking in virulence even after direct inoculation of high-titered virus into the CNS of susceptible mice (J. Chou, E. R. Kern, R. J. Whitley, and B. Roizman, Science 250:1262-1266, 1990). To investigate the host range and distribution of infected cells in the CNS of mice, 4- to 5-week-old mice were inoculated stereotaxically into the caudate/putamen with 3 x 10(5) PFU of the gamma(1)34.5- virus R3616. Four-micrometer-thick sections of mouse brains removed on day 3, 5, or 7 after infection were reacted with a polyclonal antibody directed primarily to structural proteins of the virus and with antibodies specific for neurons, astrocytes, or oligodendrocytes. This report shows the following: (i) most of the tissue damage caused by R3616 was at the site of injection, (ii) the virus spread by retrograde transport from the site of infection to neuronal cell nuclei at distant sites and to ependymal cells by cerebrospinal fluid, (iii) the virus infected neurons, astrocytes, oligodendrocytes, and ependymal cells and hence did not discriminate among CNS cells, (iv) viral replication in some neurons could be deduced from the observation of infected astrocytes and oligodendrocytes at distant sites, and (v) infected cells were being efficiently cleared from the nervous system by day 7 after infection. We conclude that the gamma(1)34.5- attenuation phenotype is reflected in a gross reduction in the ability of the virus to replicate and spread from cell to cell and is not due to a restricted host range. The block in viral replication appears to be a late event in viral replication.


Old and new mechanisms of antiepileptic drug actions.
At the present time, between 30% and 50% of individuals with epilepsy continue to have seizures and among those who are considered "controlled", a good many unpleasant side effects are endured. It is clear that we need more and better antiepileptic drugs. The virtual explosion in knowledge about the cellular and molecular mechanisms underlying both normal and pathological reactions of the brain provides encouragement that we are on the right path towards developing new, effective and safe agents. Whether we continue to use "model-based" screening or "mechanism-based screening", or both, we must not go another 14 years without the introduction of a new antiepileptic drug. The problem is too large, our patients are too impatient and our responsibilities are clear.


Use of the radioreceptor assay for human chorionic gonadotropin in the diagnosis of ectopic pregnancy.
Since unrecognized ectopic pregnancy is a potentially lethal condition, there is a need for an accurate, rapid, sensitive and specific method for measuring low levels of human chorionic gonadotropin that may be observed in ectopic pregnancy. The Biocept-G test is a commercial modification of the radioreceptor assay for human chorionic gonadotropin. The test is performed in one hour and has a sensitivity of 200 milliinternational units of human chorionic gonadotropin per milliliter of serum. This study consisted of 15 patients with proved tubal ectopic pregnancies who were evaluated with the Biocept-G assay. All of the patients had a positive test result. By comparison, the two hour urine tube test result was positive in only eight and negative in seven patients. The two minute urine slide test result was positive in only six and negative in nine patients. The Biocept-G test was found to be simple to perform, quick and reliable, and the cost was comparable with that of the less accurate immunoassays. With the advent of the radioreceptor assay for human chorionic gonadotropin and the radioimmunoassays for the beta subunit of human chorionic gonadotropin, the presence of a positive pregnancy test result may be the most reliable diagnostic aid in helping to recognize early ectopic pregnancy.


Breast Cancer Navigation: Using Physician and Patient Surveys to Explore Nurse Navigator Program Experiences.
Patient navigators can improve patient experiences of care and outcomes, but little is known about how navigation programs may affect physician workflows and experience. This study aimed to understand patient and physician experiences with a breast cancer navigation (BCN) program using Lean design principles. Surveys were developed and distributed from 2019 to 2020 to 255 patients diagnosed with breast cancer and 128 physicians in primary care and cancer-related specialties. Descriptive analyses were conducted. Eighty-three physicians and 94 patients completed the survey. A large majority of physicians reported that the BCN program "made their day easier" and improved flow, care coordination, and patient experience. A large majority of patients reported receiving the right level of support during diagnosis communication and high satisfaction in other domains measured.


The Role of Physical Activity for the Management of Sarcopenia in People Living with HIV.
Sarcopenia is a physiopathological process associated with aging, caused by reduction of muscle strength, muscle quality and physical performance, and associated with an increased risk of falls, physical disability and premature death. There is no effective treatment for sarcopenia, but physical exercise seems to be highly effective at counteracting the decline in muscle mass and strength associated with aging. Recently, sarcopenia has been recognized as an emerging issue in people living with HIV (PLWH). Despite adequate treatment with combination antiretroviral therapy (cART), PLWH may exhibit an early occurrence of some aging-related conditions, including sarcopenia, frailty and falls, and this is likely resulting from high rates of comorbidities, high-risk behaviours, chronic immune activation and cART-specific factors. In this review, we discuss the potential mechanisms and the clinical relevance of sarcopenia in PLWH, and present data from longitudinal studies of physical activity in this population. Despite none of these studies having specifically addressed the benefits of physical exercise on sarcopenia, there is evidence that exercise is effective to increase aerobic capacity and muscle strength, and to improve body composition and inflammatory outcomes in PLWH. Therefore, the expected benefits of physical exercise are likely to translate into a successful and specific intervention for prevention and treatment of sarcopenia in this population.


[Nutrition of man and animals (author's transl)].
Information on daily nutrient requirements is more complete for farm animals than for horses, pets and man. Very little is known, particularly in man, horses and pets of the relationship between nutrition and longevity. Therefore, a slightly higher intake of essential nutrients would appear to be preferable, the more so as the body can readily remove any surpluses. This also holds true for man and animals in suboptimum living conditions. Inadequate information on this relationship in man as well as the current concern of the consumer regarding the safety of his food are the reasons for which animal production should be very cautious regarding the use of additives and drugs. Investigations on the effects of nutrition on longevity and resistance, immunity, food-intake regulation and other complicated problems should be directed towards understanding and require thorough and extensive preliminary studies covering all species of animal, including man. Animal husbandry as a whole contributes materially to world food production because of its use of many feeds which are unacceptable to or cannot be utilized by man. Further possibilities of increasing the conversion of feed into food are presented. However, ensuring an optimum world food supply to defeat famine not only involves the technical problems referred to but also has several economic and sociological aspects and requires united international efforts.


Noninvasively diagnosed peripheral arterial disease as a predictor of mortality: results from a prospective study.
Intermittent claudication has been reported in previous studies to approximately double the risk of subsequent mortality. However, a history of claudication is often present in the absence of significant peripheral arterial disease (PAD) and absent in the presence of PAD. For this reason we evaluated the association between large-vessel and small-vessel PAD, measured by highly reliable and valid noninvasive tests, and mortality in 567 older subjects from a defined population followed-up for an average of 4 years. Large-vessel PAD was strongly and significantly predictive of all-cause mortality in both men and women with a relative risk of 4 to 5, and this finding was independent of other cardiovascular disease risk factors in multivariable analysis. In addition, this finding persisted after exclusion of subjects with extant cardiovascular disease at baseline. The associations of both claudication and abnormal peripheral pulses with mortality were weaker than the large-vessel PAD association. Isolated small-vessel PAD was unrelated to subsequent mortality. These findings suggest older subjects of both sexes at a high risk of impending mortality can be identified through noninvasive testing for large-vessel PAD.


A treatment selection protocol for recurrent ovarian cancer patients: the role of FDG-PET/CT and staging laparoscopy.
To investigate the best diagnostic and staging strategy for recurrent ovarian cancer. The negative predictive value, specificity, positive predictive value, sensitivity, and accuracy rates of the fluorine-18-fluorodeoxyglucose positive emission tomography computed tomography (FDG-PET/CT) and staging laparoscopy in identifying surgically treatable/untreatable patients are assessed in a consecutive series of 70 recurrent ovarian cancer cases. Moreover, the diagnostic performance of each staging procedure in the evaluation of the number of nodules is analyzed. The negative predictive value of the FDG-PET/CT was 83.3%, whereas the positive predictive value was 76.9%. Specificity was 55.6%, whereas sensitivity was 93.0%. Accuracy rate was 78.6%. Negative predictive value, specificity, positive predictive value, sensitivity, and accuracy rate of staging laparoscopy were 88.9, 64.0, 80.8, 95.0 and 83.1%, respectively. Combined radiological and laparoscopic evaluation showed a negative predictive value of 88.9%, a specificity of 59.3%, a positive predictive value of 78.8%, a sensitivity of 95.3%, and an accuracy rate of 81.4%. The number of nodules identified by FDG-PET/CT corresponded in only 23 patients (40.3%) at laparotomy, whereas 15 of 30 patients were correctly diagnosed (50.0%) by staging laparoscopy. The combination of FDG-PET/CT and staging laparoscopy has a significant effect on the multimodal approach to the population of patients with recurrent ovarian cancer. Such techniques should be considered complementary, because of the potential of each one to identify a different setting of the disease.


Predictability of action sub-steps modulates motor system activation during the observation of goal-directed actions.
Action perception and execution are linked in the human motor system, and researchers have proposed that this action-observation matching system underlies our ability to predict observed behavior. If the motor system is indeed involved in the generation of action predictions, activation should be modulated by the degree of predictability of an observed action. This study used EEG and eye-tracking to investigate whether and how predictability of an observed action modulates motor system activation as well as behavioral predictions in the form of anticipatory eye-movements. Participants were presented with object-directed actions (e.g., making a cup of tea) consisting of three action steps which increased in their predictability. While the goal of the first step was ambiguous (e.g., when making tea, one can first grab the teabag or the cup), the goals of the following steps became predictable over the course of the action. Motor system activation was assessed by measuring attenuation of sensorimotor mu- and beta-oscillations. We found that mu- and beta-power were attenuated during observation, indicating general activation of the motor system. Importantly, predictive motor system activation, indexed by beta-band attenuation, increased for each action step, showing strongest activation prior to the final (i.e. most predictable) step. Sensorimotor activity was related to participants' predictive eye-movements which also showed a modulation by action step. Our results demonstrate that motor system activity and behavioral predictions become stronger for more predictable action steps. The functional roles of sensorimotor oscillations in predicting other's actions are discussed.


Designing human-AI systems for complex settings: ideas from distributed, joint, and self-organising perspectives of sociotechnical systems and cognitive work analysis.
Real-world events like the COVID-19 pandemic and wildfires in Australia, Europe, and America remind us that the demands of complex operational settings are met by multiple, distributed teams interwoven with a large array of artefacts and networked technologies, including automation. Yet, current models of human-automation interaction, including those intended for human-machine teaming or collaboration, tend to be dyadic in nature, assuming individual humans interacting with individual machines. Given the opportunities and challenges of emerging artificial intelligence (AI) technologies, and the growing interest of many organisations in utilising these technologies in complex operations, we suggest turning to contemporary perspectives of sociotechnical systems for a way forward. We show how ideas of distributed cognition, joint cognitive systems, and self-organisation lead to specific concepts for designing human-AI systems, and propose that design frameworks informed by contemporary views of complex work performance are needed. We discuss cognitive work analysis as an example.


Formation of an ion-pair molecule with a single NH(+)...Cl(-) hydrogen bond: Raman spectra of 1,1,3,3-tetramethylguanidinium chloride in the solid state, in solution, and in the vapor phase.
Some ionic compounds (salts) form liquids when heated to temperatures in the range of 200-300 degrees C. They may be referred to as moderate temperature ionic liquids. An example of such a compound is the 1,1,3,3-tetramethylguanidinium chloride, [TMGH]Cl, melting at approximately 212 degrees C. The chemistry of this compoundcontaining a dimeric ion-pair "molecule"was investigated in the solid state, in solutions in water and ethanol, and in the vapor phase, based on ab initio molecular orbital density functional theory (DFT)-type calculations with 6-311+G(d,p) basis sets. Calculations on the monomeric [TMGH] (+) ion and the dimeric chloride ion-pair salt converged to give geometries near the established crystal structure of [TMGH]Cl. The structures and their binding energies are given as well as calculated vibrational harmonic normal modes (IR and Raman band wavenumbers and intensities). Experimentally obtained Raman scattering spectra are presented and assigned, by comparing to the quantum mechanical calculations. It is concluded that dimeric molecular ion pairs with four N-H (+)...Cl (-) hydrogen bonds probably exist in the solutions and are responsible for the relatively high solubility of the "salt" in ethanol. It was discovered that the compound can be easily sublimed by heating to about 200-230 degrees C. In the Raman spectrum of the vapor at 225 degrees C, a characteristic strong band at 2229 cm (-1) was found and interpreted to show that the gas phase consists of monomeric ion-pair "molecules" held together by a single N-H (+)...Cl (-) hydrogen bond, the stretching band of which is causing the band.


Red cell morphologic alterations in cats with hepatic disease.
Medical records from 39 cats with hepatic disease, examined at the Veterinary Medical Teaching Hospital, University of Florida, between 1987 and 1992 were retrospectively evaluated for alterations in red blood cell (RBC) morphology. Diagnoses included: hepatic lipidosis, neoplasia, cholangiohepatitis, hepatitis/hepatopathy, systemic histoplasmosis, and portocaval shunt. A total of 56 laboratory data sets were studied which included complete blood counts and serum chemistry results. Stained blood smears were evaluated from 51 of the data sets. Twenty-two cats (56%) were determined to have poikilocytosis on the basis of blood smear evaluation. Eleven (28%) cats had moderate to marked poikilocytosis (2+ to 4+). Acanthocytes accounted for 62.6 -/+ 22.1% of morphologically abnormal RBC and were observed in blood smears from 100% of cats with poikilocytosis. Elliptocytes (ovalocytes) comprised 19.5 -/+ 15.8% of poikilocytes and were found in smears from 82% of cats with poikilocytosis. Keratocytes (7.0 -/+ 6.8%), schistocytes (3.6 -/+ 4.4%), and blister cells (2.6 -/+ 6.4%) were present in lower numbers and in fewer cats. Serum total cholesterol values were significantly greater (p < 0.05) in cats with moderate to marked alterations in RBC morphology. Cats with hepatic lipidosis were significantly (p < 0.04) more likely to have poikilocytosis than cats with other types of hepatic disease.


Hydatidiform mole and gestational trophoblastic disease in Southern Connecticut.
Of 127 patients with hydatidiform mole in southern Connecticut, 34 (28%) received chemotherapy for persistently elevated human chorionic gonadotropin (hCG) titers. An hCG regression curve was found to be useful if not mandatory for following patients. Excess uterine size, theca lutein cysts, uterine bleeding, and histologic trophoblastic hyperplasia were relative discriminators of the need for chemotherapy. In the absence of metastases, an hCG titer was the only valid discriminator for initiating chemotherapy, provided the patient could be followed consistently and reliably. The indications for initiating chemotherapy are discussed. Early diagnosis and close follow-up were associated with low morbidity. Five of 6 patients with metastatic disease were referred from outside the center.


Individual patient education for low back pain.
While many different types of patient education are widely used, the effect of individual patient education for low-back pain (LBP) has not yet been systematically reviewed. To determine whether individual patient education is effective in the treatment of non-specific low-back pain and which type is most effective. A computerized literature search of MEDLINE (1966 to July 2006), EMBASE (1988 to July 2006), CINAHL (1982 to July 2006), PsycINFO (1984 to July 2006), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2) was performed. References cited in the identified articles were screened. Studies were selected if the design was a randomised controlled trial; if patients experienced LBP; if the type of intervention concerned individual patient education, and if the publication was written in English, German, or Dutch. The methodological quality was independently assessed by two review authors. Articles that met at least 50% of the quality criteria were considered high quality. Main outcome measures were pain intensity, global measure of improvement, back pain-specific functional status, return-to-work, and generic functional status. Analysis comprised a qualitative analysis. Evidence was classified as strong, moderate, limited, conflicting or no evidence. Of the 24 studies included in this review, 14 (58%) were of high quality. Individual patient education was compared with no intervention in 12 studies; with non-educational interventions in 11 studies; and with other individual educational interventions in eight studies. Results showed that for patients with subacute LBP, there is strong evidence that an individual 2.5 hour oral educational session is more effective on short-term and long-term return-to-work than no intervention. Educational interventions that were less intensive were not more effective than no intervention. Furthermore, there is strong evidence that individual education for patients with (sub)acute LBP is as effective as non-educational interventions on long-term pain and global improvement and that for chronic patients, individual education is less effective for back pain-specific function when compared to more intensive interventions. Comparison of different types of individual education did not show significant differences. For patients with acute or subacute LBP, intensive patient education seems to be effective. For patients with chronic LBP, the effectiveness of individual education is still unclear.


Long-Acting Somatostatin Analog Therapy Differentially Alters 68Ga-DOTATATE Uptake in Normal Tissues Compared with Primary Tumors and Metastatic Lesions.
Synthetic somatostatin analogs have been posed as a potential source of error in somatostatin receptor imaging through interference with tumor detection; however, experimental models and clinical studies have shown a complex mechanism of the effect of octreotide on tumors. The aim of this study was to assess whether 68Ga-DOTATATE uptake before treatment with long-acting somatostatin analogs differs from that after treatment. Methods: Thirty patients (15 men; age [mean ± SD], 64.6 ± 13.4 y) who had intermediately differentiated to well-differentiated neuroendocrine tumors and who underwent 68Ga-DOTATATE PET/CT scanning before and after receiving long-acting repeatable octreotide (Sandostatin LAR) were included in the study. The SUVmax and SUVmean of healthy target organs, residual primary tumor, and up to 5 lesions with the highest SUVmax in each organ were compared before and after octreotide treatment. Results: The mean time interval between the 2 68Ga-DOTATATE studies was 9.6 ± 7.2 mo, and the mean time gap between the last Sandostatin LAR injection and the second 68Ga-DOTATATE study was 25.1 ± 14.8 d. The pretreatment mean SUVmax and SUVmean were both significantly higher in the thyroid, liver, and spleen (P < 0.05) than the values measured after the administration of Sandostatin LAR. No significant differences were found among the uptake indices for residual primary tumor or any metastatic lesions in the liver, bone, lung, or lymph nodes before and after Sandostatin LAR administration (P > 0.05). Conclusion: Long-acting octreotide treatment diminished 68Ga-DOTATATE uptake in the liver, spleen, and thyroid but did not compromise tracer uptake in residual primary tumor and metastatic lesions. These findings have a direct impact on the interpretation of 68Ga-DOTATATE PET/CT scans.


Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm.
Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, p<0.001) levels. Adjustment for circadian BP rhythm status ascribed this finding exclusively to non-dippers (p<0.01). Two months after delivery, in 11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.


Effects of edible bird's nest on hippocampal and cortical neurodegeneration in ovariectomized rats.
The aim of this research is to investigate whether edible bird's nest (EBN) attenuates cortical and hippocampal neurodegeneration in ovariectomized rats. Ovariectomized rats were randomly divided into seven experimental groups (n = 6): the ovariectomy (OVX) group had their ovaries surgically removed; the sham group underwent surgical procedure similar to OVX group, but ovaries were left intact; estrogen group had OVX and received estrogen therapy (0.2 mg kg(-1) per day); EBN treatment groups received 6%, 3%, and 1.5% EBN, respectively. Control group was not ovariectomized. After 12 weeks of intervention, biochemical assays were performed for markers of neurodegeneration, and messenger ribonucleic acid (mRNA) levels of oxidative stress-related genes in the hippocampus and frontal cortex of the brain were analysed. Caspase 3 (cysteine-aspartic proteases 3) protein levels in the hippocampus and frontal cortex were also determined using western blotting. The results show that EBNs significantly decreased estrogen deficiency-associated serum elevation of advanced glycation end-products (AGEs), and they changed redox status as evidenced by oxidative damage (malondialdehyde content) and enzymatic antioxidant defense (superoxide dismutase and catalase) markers. Furthermore, genes associated with neurodegeneration and apoptosis were downregulated in the hippocampus and frontal cortex by EBN supplementation. Taken together, the results suggest that EBN has potential for neuroprotection against estrogen deficiency-associated senescence, at least in part via modification of the redox system and attenuation of AGEs.


Biochemical characterization and histochemical localization of nitric oxide synthase in the nervous system of the snail, Helix pomatia.
Nitric oxide synthase (NOS) in the snail Helix pomatia was characterized by biochemical and molecular biological techniques and localized by histochemical methods. Central ganglia contained particulate paraformaldehyde-sensitive and cytosolic paraformaldehyde-insensitive NADPH-diaphorase. The cytosolic NADPH-diaphorase activity coeluted with NOS activity. The activity of NOS was dependent on Ca2+ and NADPH and was inhibited by N(G)-nitro-L-arginine (L-NNA). Proteins purified by 2',5'-ADP affinity chromatography were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and migrated at 150, 60, 40, and 30 kDa. An antibody to mammalian NOS exclusively labeled the 60-kDa protein. Characterization of the cDNA of the corresponding 60-kDa NOS-immunoreactive protein revealed no sequence homology with any known NOS isoform. The recombinant protein exhibited Ca2+- and NADPH-dependent NOS activity, which was partially inhibited by EGTA and L-NNA. Histochemistry showed NADPH-diaphorase activity in discrete regions of the central and peripheral nervous system. About 60% of the NADPH-diaphorase-positive neurons colocalize with immunoreactive material detected by antibodies to mammalian NOS. Comparison of organs showed the highest NADPH-diaphorase activity in the nervous system, whereas moderate activity was present in muscle tissue, digestive tract, and gonads. Our study suggests the presence of NOS and a putative NOS-associated/regulating protein in mollusk nervous tissue.


Seroprevalence of antibodies against the cat lungworm Aelurostrongylus abstrusus in cats from endemic areas of Italy.
Aelurostrongylus abstrusus (Nematoda, Metastrongyloidea) is a worldwide occurring lungworm causing verminous pneumonia in cats. To date the Baermann method is the most used procedure to diagnose A. abstrusus infection by isolating first stage larvae from faeces, though its sensitivity and specificity can be impaired by several factors. An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against A. abstrusus has been recently developed as a diagnostic alternative. The present study evaluated the seroprevalence for A. abstrusus infection in cats from two endemic areas of Italy. Overall, 250 sera were sampled and tested for the presence of antibodies against A. abstrusus. Based on the results obtained from 20 cats proven to be infected by A. abstrusus using Baermann technique and molecular methods, and from 20 negative cats (Subset A), a cut off value of 0.347 optical density (OD) was determined, leading to a sensitivity of 95% and a specificity of 100%. Two-hundred and ten cats (142 and 68 from Abruzzo and Umbria regions, respectively) were included in Subset B (i.e. 202 negative by Baermann examination and 8 positive for Troglostrongylus brevior). Antibodies against A. abstrusus were detected in forty-five (21.4%, 95% CI: 16.1-27.6%) samples. This study confirms the occurrence of A. abstrusus in endemic areas of Italy and indicates that one-fifth of randomly selected cats have or had a lungworm infection with production of antibodies.


A tribosphenic mammal from the Mesozoic of Australia.
A small, well-preserved dentary of a tribosphenic mammal with the most posterior premolar and all three molars in place has been found in Aptian (Early Cretaceous) rocks of southeastern Australia. In most respects, dental and mandibular anatomy of the specimen is similar to that of primitive placental mammals. With the possible exception of a single tooth reported as Eocene in age, terrestrial placentals are otherwise unknown in Australia until the Pliocene. This possible Australian placental is similar in age to Prokennalestes from the late Aptian/early Albian Khoboor Beds of Mongolia, the oldest currently accepted member of the infraclass Placentalia.


Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia.
Data from nine patients with leukemia participating in a phase I activity-escalation study of HuM195, labeled with the alpha-particle emitter 213Bi (half-life = 45.6 min), were used to estimate pharmacokinetics and dosimetry. This is the first trial using an alpha-particle emitter in humans. The linear energy transfer of alpha particles is several hundredfold greater than that of beta emissions. The range in tissue is approximately 60-90 microm. The activity administered to patients ranged from 0.6 to 1.6 GBq. Patient imaging was initiated at the start of each injection. Thirty 1-min images followed by ten 3-min images were collected in dynamic mode; a 20% photopeak window centered at 440 keV was used. Blood samples were collected until 3 h postinjection and counted in a gamma counter. Contours around the liver and spleen were drawn on the anterior and posterior views and around a portion of the spine on the posterior views. No other organs were visualized. The percentage injected dose in the liver and spleen volumes increased rapidly over the first 10-15 min to a constant value for the remaining hour of imaging, yielding a very rapid uptake followed by a plateau in the antibody uptake curves. The kinetic curves were integrated to yield cumulated activity. The mean energy emitted per nuclear transition for 213Bi and its daughters, adjusted by a relative biologic effectiveness of 5 for alpha emissions, was multiplied by the cumulated activity to yield the absorbed dose equivalent. Photon dose to the total body was determined by calculating a photon-absorbed fraction. The absorbed dose equivalent to liver and spleen volumes ranged from 2.4 to 11.2 and 2.9 to 21.9 Sv, respectively. Marrow (or leukemia) mean dose ranged from 6.6 to 12.2 Sv. The total-body dose (photons only) ranged from 2.2 x 10(-4) to 5.8 x 10(-4) Gy. This study shows that patient imaging of 213Bi, an alpha-particle emitter, labeled to HuM195 is possible and may be used to derive pharmacokinetics and dosimetry. The absorbed dose ratio between marrow, liver and spleen volumes and the whole body for 213Bi-HuM195 is 1000-fold greater than that commonly observed with beta-emitting radionuclides used for radioimmunotherapy.


Development and validation of the Italian version of the Intermittent Self-Catheterization Questionnaire.
Intermittent self catheterization questionnaire (ISC-Q) is a questionnaire exploring four issues related to self-intermittent catheterization (ISC): ease of use, convenience, discreteness and psychological well-being. The aim of the study was to develop and validate the Italian version of the ISC-Q. Two independent translations of the ISC-Q were performed and compared by an expert committee. A back translation to English was made by a linguistic expert, blinded to the original version. Patients using ISC to void their bladder were from 19 different spinal cord units; questionnaires were examined anonymously in a single center. A subgroup of 47 patients repeated the test at 2 weeks distance and completed the Qualiveen questionnaire to assess the convergent validity of ISC-Q. The internal consistency was determined from Cronbach's α coefficient. Criterion validity was determined through the concurrent use of Qualiveen. Reliability was performed by Intraclass Correlation Coefficient and test-retest. The sensitivity was determined by the effect size-based estimate for small change (ES) and Minimal Detectable Change 95 (MDC95). In the study 217 subjects (65.6% males, 34.4% females) were enrolled. Mean age: 43±10.1 years. Mean duration of ISC: 3.3±6.9 years. Cronbach's α ranged from 0.79 to 0.81. Pearson correlation between the different parts of ISC-Q and total score ranged from 0.24 to 0.78. ICC values were higher than 0.9. Convergent validity was faint to null. ES ranged from 3.8 to 6 points. MDC95 ranged from 4.1 to 12.1. The Italian ISC-Q has the same psychometric characteristics of the original questionnaire. ISC-Q is a valid, reliable and sensitive patient related outcome, specifically focused on ISC. our work provides a new validated measure for Italian patients to explore in future studies the role and impact of ISC.


Experimental evolution of human influenza virus H3 hemagglutinin in the mouse lung identifies adaptive regions in HA1 and HA2.
The genetic basis for virulence and host switching in influenza A viruses (FLUAV) is largely unknown. Because the hemagglutinin (HA) protein is a determinant of these properties, HA evolution was mapped in an experimental model of mouse lung adaptation. Variants of prototype A/Hong Kong/1/68 (H3N2) (wild-type [wt] HK) human virus were selected in both longitudinal and parallel studies of lung adaptation. Mapping of HA mutations found in 11 independently derived mouse-adapted populations of wt HK identified 27 mutations that clustered within two distinct regions in or near the globular frameworks of the HA1 and HA2 subunits. The adaptive mutations demonstrated multiple instances of convergent evolution involving four amino acid positions (162, 210, and 218 in HA1 and 154 in HA2). By use of reverse genetics, convergent HA mutations were shown to affect cell tropism by enhancing infection and replication in primary mouse tracheal epithelial cells in vitro and mouse lung tissue in vivo. Adaptive HA mutations were multifunctional, affecting both median pH of fusion and receptor specificity. Specific mutations within both adaptive regions were shown to increase virulence in a mouse lung model. The occurrence of mutations in the HA1 and HA2 adaptive regions of natural FLUAV host range and virulent variants of avian and mammalian viruses is discussed. This study has identified adaptive sites and regions within the HA1 and HA2 subunits that may guide future studies of viral adaptation and evolution in nature.


Early CA-125 fluctuations in patients with recurrent ovarian cancer receiving chemotherapy.
The objective of this study was to analyze retrospective populations with recurrent ovarian cancer to assess differences in CA-125 patterns during chemotherapy. The populations included all patients treated between January 1994 and January 2004, who received liposomal doxorubicin and topotecan, and all patients treated between July 1997 and June 2001, who received carboplatin. Prognostic variables were abstracted from the medical records. Eighty-nine patients received liposomal doxorubicin and topotecan therapy and 21 received carboplatin; of these, 59 (liposomal doxorubicin), 60 (topotecan), and 17 (carboplatin) patients had evaluable CA-125 patterns. Patients given liposomal doxorubicin were more likely to have received only one or two cycles of therapy (37/89 [42%]) than patients receiving either carboplatin (5/21 [24%]) or topotecan (20/89[22%]). In cycle 1, CA-125 increases in patients were carboplatin, 4/17 (24%); liposomal doxorubicin, 41/59 (69%); and topotecan, 11/60 (18%). In cycle 2, CA-125 increases were carboplatin, 2/16 (13%); liposomal doxorubicin, 19/37 (51%); and topotecan, 9/50 (18%). In cycle 3, CA-125 increases were carboplatin, 0/12 (0%); liposomal doxorubicin, 7/23 (30%); and topotecan, 6/38 (16%). Of patients having any CA-125 decrease and given two or more cycles, fewer declines were seen in those given liposomal doxorubicin precycle 2 (18/35[51%]) than in those given carboplatin (13/16[81%]) or topotecan (49/56[88%]). The most prominent delay in CA-125 decline was in patients given liposomal doxorubicin compared with those given topotecan or carboplatin. In the entire population, only 3 of 107 (2.8%) patients demonstrated first CA-125 decline precycle 4. Discontinuation of therapy solely on the basis of early CA-125 increase (precycle 3), particularly with liposomal doxorubicin chemotherapy, may exclude some patients who will benefit from continued therapy.


Flavin-photosensitized reactions of retinol and stilbene.
1. Retinol and stilbene are both isomerized when they are illuminated anaerobically in the presence of flavins. 2. Triplet quenchers (e.g. oxygen, potassium iodide and paramagnetic ions) inhibit the reaction more efficiently than they quench flavin fluorescence. At 77 degrees C in a diethyl ether-isopentane-ethanol (5:5:2) glass retinol quenches flavin phosphorescence, but not its fluorescence. 3. For the stilbene reaction cis/trans photostationary-state mixtures are obtained with different flavins and these are linearly related to the phosphorescence transition energies of the flavins used. 4. The reaction involves the triplet state of flavin and a scheme for the reaction is suggested. 5. The dependence of the rate of reaction on substrate concentration is explicable in terms of this scheme. 6. The photobleaching of rhodopsin sensitized by flavin is also demonstrated.


A prospective study of postconcussive outcomes after return to play in Australian football.
Decisions regarding safe return to play after concussion in sport remain difficult. To determine whether a concussed player returned to play using an individual clinical management strategy is at risk of impaired performance or increased risk of injury or concussion. Cohort study; Level of evidence, 3. All elite Australian football players were followed for 4 seasons. Players were recruited into the study after sustaining a concussive injury. Outcome measures included performance statistics (disposals per hour match-time), injury rates, and recurrence of concussion on return to play. A subset of players had brief screening cognitive tests performed at baseline and after their concussion. Noninjured players matched for team, position, age, and size were chosen as controls. A total of 199 concussive injuries were observed in 158 players. Sixty-one concussive injuries were excluded from analysis because of incomplete data (45 players) or presence of concurrent injury (16 players). Of the 138 concussive injuries assessed, 127 players returned to play without missing a game (92%). The remainder of concussed players returned to play after missing a single game (8%). Overall, there was no significant decline in disposal rates in concussed players on return to competition. Furthermore, there were no significant differences in injury rates between concussed and team, position, and game-matched controls. In the subset of players who had completed screening cognitive tests, all had returned to their individual baseline performance before being returned to play. Return to play decisions based on individual clinical assessment of recovery allows safe and appropriate return to sport following a concussive injury.


Effect of Pre-Treatment with a Combination of Fentanyl and Midazolam for Prevention of Etomidate-Induced Myoclonus.
Pre-treatment with either fentanyl or midazolam has previously been used to prevent etomidate-induced myoclonus (EIM). The aim of the present study was to determine the effect of pre-treatment with a combination of midazolam and fentanyl in reducing the incidence and severity of EIM. This prospective, randomised, double-blind study was conducted on 210 surgical patients allocated to three study groups. Group F patients received fentanyl 2 μg kg-1 and 5 mL saline. Group M patients received midazolam 0.03 mg kg-1 and 5 mL saline. Group FM patients received fentanyl 2 μg kg-1 plus midazolam 0.03 mg kg-1. The study drugs were administered intravenously over 30 s. Five minutes after study drug administration, etomidate 0.3 mg kg-1 was administered over 60 s. Patients were observed for 1 min for occurrence and severity of EIM. The incidence of EIM was 34/70 (48.6%), 55/70 (78.6%) and 11/70 (15.7%) in groups F, M and FM, respectively (p=0.001). Myoclonus of moderate or severe grade occurred in 23/70 (32.9%), 45/70 (64.3%) and 6/70 (8.6%) in groups F, M and FM, respectively (p=0.001). Patients who experienced myoclonus exhibited a significantly higher percentage change in post-induction heart rate (p=0.02), systolic blood pressure (p=0.001) and mean blood pressure (p=0.001) from pre-induction values than those who did not. Pre-treatment with a combination of fentanyl and midazolam is more effective than that with fentanyl or midazolam alone in reducing the incidence and severity of EIM. Myoclonus is associated with a higher post-induction haemodynamic variation.


Inhibitory functioning in Alzheimer's disease.
We present a comprehensive review of studies assessing inhibitory functioning in Alzheimer's disease. The objectives of this review are: (i) to establish whether Alzheimer's disease affects all inhibitory mechanisms equally, and (ii) where possible, to assess whether any effects of Alzheimer's disease on inhibition tasks might be caused by other cognitive deficits, such as slowed processing. We review inhibitory mechanisms considered to play a crucial role in various domains of cognition, such as inhibition involved in working memory, selective attention and shifting abilities, and the inhibition of motor and verbal responses. It was found that whilst most inhibitory mechanisms are affected by the disorder, some are relatively preserved, suggesting that inhibitory deficits in Alzheimer's disease may not be the result of a general inhibitory breakdown. In particular, the experimental results reviewed showed that Alzheimer's disease has a strong effect on tasks requiring controlled inhibition processes, such as the Stroop task. However, the presence of the disease appears to have relatively little effect on tasks requiring more automatic inhibition, such as the inhibition of return task. Thus, the distinction between automatic, reflexive inhibitory mechanisms and controlled inhibitory mechanisms may be critical when predicting the integrity of inhibitory mechanisms in Alzheimer's disease. Substantial effects of Alzheimer's disease on tasks such as negative priming, which are not cognitively complex but do require some degree of controlled inhibition, support this hypothesis. A meta-analytic review of seven studies on the Stroop paradigm revealed substantially larger effects of Alzheimer's disease on the inhibition condition relative to the baseline condition, suggesting that these deficits do not simply reflect general slowing.


Inspection of Ureteral Orifices: The Pearl of Flexible Cystoscopy.
Cystoscopy is most common diagnostic investigation. The examination technique and the findings, both normal and pathological, were well described described a hundred years ago. With technological advances, there has been over-emphasis on imaging modalities for diagnostic purposes. A basic maneuver of examining the ureteral orifices is sometimes rushed through when in fact careful examination can clinch the diagnosis. The importance is exemplified by two cases, one of which is a rare case of Xanthoma of the ureter.


[UROLOGICAL ASPECTS OF THE FOX - FORDYCE DISEASE].
The article presents the description of the clinical observation of the patient 28 years old with multiple granulomatous eruptions on the skin of the scrotum, accompanied by itching and pain when walking. Surgical treatment consisted of excising the skin of the scrotum and substitution dermatoplasty was performed. Fox - Fordyce disease was confirmed by histological examination of tissue removed: advanced cystic sebaceous gland duct with calcifications in its lumen was revealed. The were no relapses during follow-up of 15 months.


Acute in vivo elevation of insulin-like growth factor (IGF) binding protein-1 decreases plasma free IGF-I and muscle protein synthesis.
This study examined whether the acute elevation of IGF-binding protein-1 (IGFBP-1) decreases the plasma free IGF-I concentration and alters in vivo rates of muscle protein synthesis and glucose uptake. The plasma concentration of human IGFBP-1 was increased to approximately 95 ng/ml in conscious catheterized rats infused iv with human IGFBP-1 for 4 h. Infusion of IGFBP-1 also increased the concentration of endogenous (e.g. rat) IGFBP-1 in the blood, and this response was associated with a 2- to 3-fold elevation of IGFBP-1 mRNA in liver and kidney. IGFBP-1 did not significantly alter the plasma concentration of total IGF-I, but decreased circulating free IGF-I levels by about 50%. IGFBP-1 decreased protein synthesis in the predominantly fast-twitch gastrocnemius muscle (20%), and this change resulted from a decreased translational efficiency that was associated with a decreased phosphorylation of S6K1, but not 4E-BP1. Complementary studies demonstrated that IGFBP-1 also decreased the rates of protein synthesis under basal conditions and in response to stimulation by IGF-I when added in vitro to the fast-twitch epitrochlearis muscle. In contrast, IGFBP-1 did not alter in vivo-determined rates of protein synthesis in the slow-twitch soleus muscle, heart, liver, or kidney. The infusion of IGFBP-1 did not significantly alter the plasma glucose or lactate concentration or the whole body rate of glucose production or disposal. The above-mentioned changes were not mediated indirectly by changes in the plasma insulin or corticosterone concentrations, decreased high energy phosphate content in muscle, or hepatoxicity produced by the infused IGFBP-1. These results demonstrate that acute in vivo elevation in IGFBP-1, of the magnitude observed in various catabolic conditions, is capable of selectively decreasing protein synthesis in fast-twitch skeletal muscle and up-regulating the hepatic and renal syntheses of IGFBP-1 per se. Hence, elevations in circulating and tissue levels of IGFBP-1 may be an important mediator for the muscle catabolism observed in various stress conditions.


The Ethics of Perinatal Care for Black Women: Dismantling the Structural Racism in "Mother Blame" Narratives.
Perinatal and neonatal nurses have a critical role to play in effectively addressing the disproportionate prevalence of adverse pregnancy outcomes experienced by black childbearing families. Upstream inequities in maternal health must be better understood and addressed to achieve this goal. The importance of maternal health before, during, and after pregnancy is illustrated with the growing and inequitable prevalence of 2 common illnesses, pregestational diabetes and chronic hypertension, and 2 common conditions during and after pregnancy, gestational diabetes and preterm birth. New care models are needed and must be structured on appropriate ethical principles for serving black families in partnership with nurses. The overarching purpose of this article is to describe the ethics of perinatal care for black women; to discuss how social determinants of health, health disparities, and health inequities affecting women contribute to poor outcomes among their children; and to provide tools to dismantle structural racism specific to "mother blame" narratives." Finally, strategies are presented to enhance the provision of ethical perinatal care for black women by nurses.


Dose evaluation of Grid Therapy using a 6 MV flattening filter-free (FFF) photon beam: A Monte Carlo study.
Spatially fractionated radiotherapy is a strategy to overcome the main limitation of radiotherapy, i.e., the restrained normal tissue tolerances. A well-known example is Grid Therapy, which is currently performed at some hospitals using megavoltage photon beams delivered by Linacs. Grid Therapy has been successfully used in the management of bulky abdominal tumors with low toxicity. The aim of this work was to evaluate whether an improvement in therapeutic index in Grid Therapy can be obtained by implementing it in a flattening filter-free (FFF) Linac. The rationale behind is that the removal of the flattening filter shifts the beam energy spectrum towards lower energies and increase the photon fluence. Lower energies result in a reduction of lateral scattering and thus, to higher peak-to-valley dose ratios (PVDR) in normal tissues. In addition, the gain in fluence might allow using smaller beams leading a more efficient exploitation of dose-volume effects, and consequently, a better normal tissue sparing. Monte Carlo simulations were used to evaluate realistic dose distributions considering a 6 MV FFF photon beam from a standard medical Linac and a cerrobend mechanical collimator in different configurations: grid sizes of 0.3 × 0.3 cm2 , 0.5 × 0.5 cm2 , and 1 × 1 cm2 and a corresponding center-to-center (ctc) distance of 0.6, 1, and 2 cm, respectively (total field size of 10 × 10 cm2 ). As figure of merit, peak doses in depth, PVDR, output factors (OF), and penumbra values were assessed. Dose at the entrance is slightly higher than in conventional Grid Therapy. However, it is compensated by the large PVDR obtained at the entrance, reaching a maximum of 35 for a grid size of 1 × 1 cm2 . Indeed, this grid size leads to very high PVDR values at all depths (≥ 10), which are much higher than in standard Grid Therapy. This may be beneficial for normal tissues but detrimental for tumor control, where a lower PVDR might be requested. In that case, higher valley doses in the tumor could be achieved by using an interlaced approach and/or adapting the ctc distance. The smallest grid size (0.3 × 0.3 cm2 ) leads to low PVDR at all depths, comparable to standard Grid Therapy. However, the use of very thin beams might increase the normal tissue tolerances with respect to the grid size commonly used (1 × 1 cm2 ). The gain in fluence provided by FFF implies that the important OF reduction (0.6) will not increase treatment time. Finally, the intermediate configuration (0.5 × 0.5 cm2 ) provides high PVDR in the first 5 cm, and comparable PVDR to previous Grid Therapy works at depth. Therefore, this configuration might allow increasing the normal tissue tolerances with respect to Grid Therapy thanks to the higher PVDR and thinner beams, while a similar tumor control could be expected. The implementation of Grid Therapy in an FFF photon beam from medical Linac might lead to an improvement of the therapeutic index. Among the cases evaluated, a grid size of 0.5 × 0.5 cm2 (1-cm-ctc) is the most advantageous configuration from the physics point of view. Radiobiological experiments are needed to fully explore this new avenue and to confirm our results.


Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study.
The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was < 1 microg on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk.


Impact of Grapevine (Vitis vinifera) Varieties on Reproduction of the Northern Root-Knot Nematode (Meloidogyne hapla).
One of the most commonly encountered plant-parasitic nematodes in eastern Washington Vitis vinifera vineyards is Meloidogyne hapla; however, limited research exists on the impact of this nematode on V. vinifera. The objectives of this research were to determine the impact of M. hapla on Chardonnay and Cabernet Sauvignon vine establishment and to determine the host status of V. vinifera varieties/clones predominantly grown in Washington to M. hapla. In a microplot experiment, Chardonnay and Cabernet Sauvignon vines were planted into soil inoculated with different densities of M. hapla; population dynamics of M. hapla and vine performance were monitored over 3 yr. In greenhouse experiments, several clones representing five V. vinifera varieties, Chardonnay, Riesling, Cabernet Sauvignon, Merlot, and Syrah, were evaluated as hosts for M. hapla. In both microplot and greenhouse experiments, white varieties were significantly better hosts than red varieties. In the greenhouse experiments, Chardonnay and Riesling had 40% higher reproduction factor values than Syrah and Merlot, however, all varieties/clones screened were good hosts for M. hapla (reproduction factors > 3). In the microplot experiment, M. hapla eggs/g root were 4.5 times greater in Chardonnay compared to Cabernet Sauvignon 3 yr after planting but there was no evident impact of M. hapla on vine establishment.


A guide to the identification of the terrestrial Isopoda of Maryland, U.S.A. (Crustacea).
The terrestrial isopod fauna of Maryland is inferred using the taxonomic literature, internet-based citizen science projects, and original collecting. Twenty-two species are either known or are likely to occur in the state. This includes 17 mostly-European adventive species that comprise the vast majority of records. Of the five expected native species, three occur in or near marine or estuarine littoral habitats and each has yet to be recorded or recorded from only a single locality. This situation likely reflects the long history of systematic work on the European fauna and the availability of keys for the identification of these taxa, which contrasts with the limited taxonomic work on native species. A taxonomic key, illustrations, and brief descriptions of species known or expected to occur in Maryland are provided.


The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas.
Aims of the study were: 1. to establish the prevalence of CD44 protein expression in human astrocytomas; 2. to compare the distribution of the extracellular matrix in these tumors; 3. to investigate the relation between CD 44, the extracellular matrix proteins and the histological grade of the tumor. CD44, Type IV Collagen (Col IV), Laminin (LN), Fibronectin (FN), and Tenascin (TN) expression were detected by immunohistochemistry in formalin fixed paraffin embedded tissue samples of 52 astrocytic tumors: 35 glioblastomas (GB), 7 Anaplastic astrocytomas (AA) and 10 astrocytomas (A). The localization of Col IV was observed in the basement membrane of the vessel walls in most of the astrocytomas (88.4%) with a similar pattern obtained with LN staining. 7 of 10 A (70%), 2 of 7 AA (28%) and 9 of 35 GB (25.7%) showed LN positivity. There was a negative correlation between LN expression and tumor grade (p=0.03). FN was either localized in the basement membrane or showed thick multi-layered immunoreactivity of the vessel walls. FN expression was seen in 6 A (60%), 4 AA (57%) and all of 35 GB (100%). The FN distribution was not uniform and its staining intensity showed decrease in GB. 3A (30%), 3 AA (42%), 27 GB (77.1%) showed TN expression in the vessel walls and in some tumor cells of 19 GBs. TN expression was positively correlated with the degree of vascular endothelial proliferation in GB (p<0.05). The expression of CD44s wasseen as plasma membrane positivity of glioma cells in 5 of 10A (50%), 3 of 7AA (42.3%) and 29 of 35 GB (82.8%). The intensity of immunoreaction was quite strong especially near the vessels. There was a good correlation between TN and CD44s expression in human astrocytic tumors (p=0.005). No relationship was observed between GFAP, ECM proteins and CD44s expression. Both CD44s and TN expression showed increase with malignancy in astrocytomas. These findings indicated that the histological malignancy of the astrocytomas was correlated with expression of TN and CD44s. It was suggested that in astrocytomas there was a biological relationship only between CD44 and TN, but none with the other ECM proteins. TN may play a role in angiogenesis in human astrocytic tumors.


Scanning Proton-Induced X-ray Microspectrometry in an Atmospheric Environment.
Collimated million-electron-volt proton beams, brought out into air, can be used as a scanning microprobe to examine specimens with a spatial resolution of the order of 1 micrometer. Trace elements at concentrations as low as 1 part per million can be detected. Some preliminary results based on the use of this simple method are presented.


Directional synthetic aperture flow imaging.
A method for flow estimation using synthetic aperture imaging and focusing along the flow direction is presented. The method can find the correct velocity magnitude for any flow angle, and full color flow images can be measured using only 32 to 128 pulse emissions. The approach uses spherical wave emissions with a number of defocused elements and a linear frequency-modulated pulse (chirp) to improve the signal-to-noise ratio. The received signals are dynamically focused along the flow direction and these signals are used in a cross-correlation estimator for finding the velocity magnitude. The flow angle is manually determined from the B-mode image. The approach can be used for both tissue and blood velocity determination. The approach was investigated using both simulations and a flow system with a laminar flow. The flow profile was measured with a commercial 7.5 MHz linear array transducer. A plastic tube with an internal diameter of 17 mm was used with an EcoWatt 1 pump generating a laminar, stationary flow. The velocity profile was measured for flow angles of 90 and 60 degrees. The RASMUS research scanner was used for acquiring radio frequency (RF) data from 128 elements of the array, using 8 emissions with 11 elements in each emission. A 20-micros chirp was used during emission. The RF data were subsequently beamformed off-line and stationary echo canceling was performed. The 60-degree flow with a peak velocity of 0.15 m/s was determined using 16 groups of 8 emissions, and the relative standard deviation was 0.36% (0.65 mm/s). Using the same setup for purely transverse flow gave a standard deviation of 1.2% (2.1 mm/s). Variation of the different parameters revealed the sensitivity to number of lines, angle deviations, length of correlation interval, and sampling interval. An in vivo image of the carotid artery and jugular vein of a healthy 29-year-old volunteer was acquired. A full color flow image using only 128 emissions could be made with a high-velocity precision.


The Ontario universal typing of tuberculosis (OUT-TB) surveillance program--what it means to you.
Tuberculosis (TB) is a serious disease that is transmitted primarily by the airborne route. Effective disease control and outbreak management requires the timely diagnosis, isolation and treatment of infected individuals with active disease; contact tracing to identify secondary cases likely to benefit from treatment of latent infection; and laboratory identification or confirmation of epidemiologically linked cases. TB genotyping enables the comparison of Mycobacterium tuberculosis complex (MTBC) strains and the identification of cases that may or may not be linked. The increased availability of molecular methods for genotyping has allowed for greater discrimination of MTBC strains and greatly enhanced understanding of TB transmission patterns. To improve TB surveillance and control in Ontario, the Public Health Laboratories of the Ontario Agency for Health Protection and Promotion has introduced the Ontario Universal Typing of Tuberculosis (OUT-TB) Surveillance Program. The first isolate from every new TB case will be genotyped with two rapid molecular methods: spoligotyping and mycobacterial interspersed repetitive unit-variable-number tandem repeat typing. MTBC isolates with nonunique genotypes and, thus, potentially linked to other TB cases, will also be genotyped by IS6110 restriction fragment length polymorphism analysis. By providing TB control programs using these new genotyping tools, and using traditional and new case investigation methods (eg, social network analysis), this new program will provide a clearer picture of TB in Ontario, and permit more effective use of public health resources and improve disease control.


The role of gamma-hydroxybutyric acid in the treatment of alcoholism: from animal to clinical studies.
Since its discovery nearly 40 years ago, gamma-hydroxybutyric acid (GHB) has attracted several waves of scientific interest due to new developments in the knowledge of its mechanisms of action and ideas for its potential use in clinical practice. Its effects have been claimed to treat different psychiatric conditions, but over time its use has become limited to a few specific situations (e.g. sedating patients in non-painful surgical procedures and narcolepsy). New interest in the drug derives from its potential use in the treatment of alcoholism. Recent studies demonstrated a marked effect of the substance in suppressing ethanol (ETOH) withdrawal symptoms and in reducing craving for alcohol, compared to other available drugs. However, GHB has to be given under very careful supervision because of its side-effects, including the risk of abuse and dependence and possible interference with the metabolic pathways of endogenous GHB and ETOH. This short review discusses these and related issues and we hope that it will stimulate further interest in GHB.


Review of major endocrine abnormalities in patients with systemic lupus erythematosus.
Systemic lupus erythematosus is associated with an increased risk of developing an endocrine disease. These endocrinopathies can closely mimic SLE symptoms ranging from fatigue to renal involvement but the treatment is often very different. A careful review of the PubMed and MEsH databases linking endocrine disease to SLE was performed. A retrospective analysis of the 708 SLE patient cohort at University College London Hospital (UCLH) has been completed. They have been followed for at least one year from 1978 to 2017. In our study, we report how often these endocrine diseases are identified in lupus patients compared to the general population and whether these patients with both diseases had a poorer prognosis. We have attempted to establish if the endocrine diseases develop before or after the lupus diagnosis. The literature search produced some conflicting results. 708 SLE patients were included in our study. We found 67 endocrine diseases in 55 different patients of our cohort. The most common endocrinopathy was hypothyroidism (5.22%) followed by type 2 diabetes mellitus (1.41%) and hyperthyroidism (1.41%). Other endocrine disorders also identified were type 1 diabetes mellitus (0.42%) and hyperparathyroidism (0.70%). In terms of mortality, lupus patients with concomitant endocrine disease had similar outcomes compared to those without endocrine disease (16.36% died vs. 15.16%). In general terms, these endocrine diseases were developed after the lupus diagnosis. We found that the 21.8% of our SLE plus endocrinopathy patients also have an increased risk of developing a second endocrine disease. We report concomitant endocrine disease in 7.76 % of our 708 SLE cohort followed, for almost 40 years, at UCLH. These patients have increased liability to develop a second endocrine disease, but overall there is no difference in terms of mortality between SLE patients with or without an endocrinopathy. It is important to capture endocrine diseases in SLE as the symptoms they cause may mimic SLE features, but require quite distinct treatment.


Human immunodeficiency virus type 1 clade A and D neurotropism: molecular evolution, recombination, and coreceptor use.
Human immunodeficiency virus type 1 (HIV-1) non-B clade viral infections of the brain have not been studied to date. Among nine AIDS patients from Nairobi, Kenya, infected with HIV-1 A (N = 5) or D (N = 4) clade strains, brain-derived HIV-1 env sequences displayed greater evolutionary distance than B clade brain-derived viruses (P < 0.001). Similarly, molecular diversity between matched brain and spleen env clones was clade-dependent and concentrated in the hypervariable V4 region (P < 0.001), with phylogenetic clustering of sequences derived from the same organ. Brain-derived A and D clade sequences displayed significantly lower ratios of nonsynonymous/synonymous substitution rates (d(N)/d(S)) compared to matched spleen-derived clones and brain-derived B clade viruses. Interclade recombination events were infrequently observed among the present env sequences. A chimeric virus containing the C2V3 region from an A clade brain-derived sequence preferentially used CD4 and CCR5 for infection. These findings demonstrate that differences in molecular diversity in brain-derived sequences were dependent on the individual clade and domain within the env gene, but both B and non-B clade brain-derived viruses exhibit a preference for CCR5 as a coreceptor.