A review of the 1918 herald pandemic wave: importance for contemporary pandemic response strategies.
Mounting epidemiological evidence supports the occurrence of a mild herald pandemic wave in the spring and summer of 1918 in North America and Europe, several months before the devastating autumn outbreak that killed an estimated 2% of the global population. These epidemiological findings corroborate the anecdotal observations of contemporary clinicians who reported widespread influenza outbreaks in spring and summer 1918, with sporadic occurrence of unusually severe clinical manifestations in young adults. Initially seen as controversial, these findings were eventually confirmed by retrospective identification of influenza specimens collected from U.S. soldiers who died from acute respiratory infections in May-August 1918. Other studies found that having an episode of influenza illness during the spring herald wave was highly protective in the severe autumn wave. Here, we conduct a systematic review of the clinical, epidemiological, and virological evidence supporting the global occurrence of mild herald waves of the 1918 pandemic and place these historic observations in the context of pandemic preparedness. Taken together, historic experience with the 1918 and subsequent pandemics shows that increased severity in second and later pandemic waves may be the rule rather than the exception. Thus, a sustained pandemic response in the first years following a future pandemic is critical; conversely, multiwave pandemic patterns allow for more time to rollout vaccines and antivirals.


Chromosome deletion 1q42-43.
We report on a newborn male and a female of 3 years 9 months with de novo 1q42 or 43-qter deletions. These cases are compared with ten other reported cases.


Real-space imaging of two-dimensional antiferromagnetism on the atomic scale
A two-dimensional antiferromagnetic structure within a pseudomorphic monolayer film of chemically identical manganese atoms on tungsten(110) was observed with atomic resolution by spin-polarized scanning tunneling microscopy at 16 kelvin. A magnetic superstructure changes the translational symmetry of the surface lattice with respect to the chemical unit cell. It is shown, with the aid of first-principles calculations, that as a result of this, spin-polarized tunneling electrons give rise to an image corresponding to the magnetic superstructure and not to the chemical unit cell. These investigations demonstrate a powerful technique for the understanding of complicated magnetic configurations of nanomagnets and thin films engineered from ferromagnetic and antiferromagnetic materials used for magnetoelectronics.


Monoclonal gammopathy associated membranous glomerulonephritis: A rare entity.
A 40-year-old male presented with nephrotic syndrome. Light microscopic analysis of the renal biopsy showed thickening of the glomerular capillary wall. Immunofluorescence examination revealed granular deposition of monoclonal immunoglobulin (Ig) G3-kappa and complement C3 along the glomerular basement membrane. Electron microscopy showed subepithelial electron dense deposits, thus confirming membranous glomerulonephritis (MGN) with monoclonal gammopathy. MGN with monoclonal gammopathy is an extremely rare but distinctive entity. This patient was treated with a combination of bortezomib, thalidomide and dexamethasone and showed partial remission of his nephrotic state and dysproteinemia.


Nutritionally relevant supplementation of vitamin B6 in lactating women: effect on plasma prolactin.
Pharmacologic doses of vitamin B6 administered to lactating women have been reported to suppress plasma prolactin. As a result, some physicians have recommended restriction of vitamin B6 intake for lactating women. In the present investigation, 20 lactating women were given supplemental doses of vitamin B6, 0.5 to 4.0 mg/d, beginning 24 hours after delivery. Plasma prolactin, plasma pyridoxal phosphate, and breast milk total vitamin B6 concentrations were determined during the first 9 months postpartum. Women receiving the supplement of 4.0 mg compared with 0.5 mg of vitamin B6 per day had significantly higher plasma pyridoxal phosphate (P less than .01) and breast milk total vitamin B6 concentrations (P less than .05) beginning at 1 month postpartum and continuing through the duration of the study. Plasma prolactin concentrations were not significantly different between the two groups. The percentage of all women, regardless of treatment, in whom lactation persisted at 1 and 2 weeks and 1, 3, 6, and 9 months were 100%, 100%, 100%, 90%, 80%, and 65%, respectively. All women who ceased to lactate during the study reported doing so by choice. Nutritionally relevant doses of vitamin B6 elevated plasma pyridoxal phosphate and breast milk total vitamin B6 concentrations of lactating women without reducing plasma prolactin concentration or halting lactation.


Genetic diversity of the planthopper, Sogatella furcifera in the Greater Mekong Subregion detected by inter-simple sequence repeats (ISSR) markers.
The white backed planthopper, Sogatella furcifera (Hemiptera: Delphacidae), is a serious pest of rice in Asia. In the present study, inter-simple sequence repeat (ISSR) markers were employed to investigate the genetic diversity and differentiation of 47 populations sampled from 14 prefectures of the Greater Mekong Subregion. A total of 14 selected primers yielded 121 bright and discernible bands, with an average of 8.6 bands per primer. According to the hierarchical analysis of molecular variance (AMOVA), the genetic variation among geographic regions (79.84%) was higher than that of among populations within region (20.16%), and the FST value was 0.72, indicating a high level of genetic differentiation. Neighbor-Joining cluster analysis of the 47 populations showed two major clusters, one consisting of mostly southwestern Yunnan Province and Myanmar populations; and the other one consisting of southeastern and central of Yunnan Province plus Vietnam and Laos populations. No significant positive correlation was observed between genetic and geographic distances by Mantel test (r = 0.2230, p = 0.8448), indicating the role of geographic isolation did not shape the genetic structure of the sampled S. furcifera populations. This paper provides useful data for understanding and speculating the migration of S. furcifera and reveals available information to develop sustainable strategies for manage this long-range migratory pest.


Prevention of thrombotic disorders in cancer patients undergoing chemotherapy.
The etiology of thrombosis in malignancy is multi-factorial, and mechanisms include release of procoagulants by tumor cells, comorbid predisposing factors in anti-cancer drugs. The most reliable information on the incidence of thromboembolism in patients receiving chemotherapy comes from breast cancer. The rate of thrombosis in women with Stage II breast cancer receiving adjuvant chemotherapy is approximately 5%. The highest risk is in postmenopausal women and the addition of tamoxifen to chemotherapy increases the thrombotic risk over chemotherapy alone. The rate of thrombosis in metastatic breast cancer is likely to be much higher than that in Stage II breast cancer. Cancer patients with central venous catheters, e.g. Hickman, portacath, should receive 1 mg of warfarin daily. A recent trial has demonstrated that low molecular weight heparin can prevent catheter-related clots. There has been only one trial conducted evaluating prophylaxis in ambulatory cancer patients receiving chemotherapy. In this study, very low dose warfarin (INR 1.3-1.9) substantially reduced the risk of venous thromboembolism in breast cancer patients receiving chemotherapy.


[Forward about long duration anesthesia (author's transl)].
The duration of anesthesia and surgical operation increased considerably during the last decennia. Such a long duration induces pathophysiological phenomenons unapparent for shorter operation and which are responsible of complications during or after the operation (cellular hypoxia, arrest of mitosis, deviation of any metabolisms). We speak then of anesthesia for very long duration operation and we fixe arbitrarily this duration to eight hours, the risks are considered as acceptable and without loud sequellas. It is necessary to precise the physiological abnormal causes which occurs for proposing means of prevention; there are both anesthetic and surgical. They show the necessity of pre-operatory concentration between medical, anesthesiological and surgical staffs for evaluating acceptable risks. We emphasize the necessity to forsee a change of the working staff after a reasonable time as in the high collective responsibility organisms.


Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs.
The FYVE domain mediates the recruitment of proteins involved in membrane trafficking and cell signaling to phosphatidylinositol 3-phosphate (PtdIns(3)P)-containing membranes. To elucidate the mechanism by which the FYVE domain interacts with PtdIns(3)P-containing membranes, we measured the membrane binding of the FYVE domains of yeast Vps27p and Drosophila hepatocyte growth factor-regulated tyrosine kinase substrate and their mutants by surface plasmon resonance and monolayer penetration analyses. These measurements as well as electrostatic potential calculation show that PtdIns(3)P specifically induces the membrane penetration of the FYVE domains and increases their membrane residence time by decreasing the positive charge surrounding the hydrophobic tip of the domain and causing local conformational changes. Mutations of hydrophobic residues located close to the PtdIns(3)P-binding pocket or an Arg residue directly involved in PtdIns(3)P binding abrogated the penetration of the FYVE domains into the monolayer, the packing density of which is comparable with that of biological membranes and large unilamellar vesicles. Based on these results, we propose a mechanism of the membrane binding of the FYVE domain in which the domain first binds to the PtdIns(3)P-containing membrane by specific PtdIns(3)P binding and nonspecific electrostatic interactions, which is then followed by the PtdIns(3)P-induced partial membrane penetration of the domain.


Some extensions of a new method to analyze complete stability of neural networks.
In a recent work, a new method has been introduced to analyze complete stability of the standard symmetric cellular neural networks (CNNs), which are characterized by local interconnections and neuron activations modeled by a three-segment piecewise-linear (PWL) function. By complete stability it is meant that each trajectory of the neural network converges toward an equilibrium point. The goal of this paper is to extend that method in order to address complete stability of the much wider class of symmetric neural networks with an additive interconnecting structure where the neuron activations are general PWL functions with an arbitrary number of straight segments. The main result obtained is that complete stability holds for any choice of the parameters within the class of symmetric additive neural networks with PWL neuron activations, i.e., such a class of neural networks enjoys the important property of absolute stability of global pattern formation. It is worth pointing out that complete stability is proved for generic situations where the neural network has finitely many (isolated) equilibrium points, as well as for degenerate situations where there are infinite (nonisolated) equilibrium points. The extension in this paper is of practical importance since it includes neural networks useful to solve significant signal processing tasks (e.g., neural networks with multilevel neuron activations). It is of theoretical interest too, due to the possibility of approximating any continuous function (e.g., a sigmoidal function), using PWL functions. The results in this paper confirm the advantages of the method of Forti and Tesi, with respect to LaSalle approach, to address complete stability of PWL neural networks.


Empathy in Negative and Positive Interpersonal Interactions. What is the Relationship Between Central (EEG, fNIRS) and Peripheral (Autonomic) Neurophysiological Responses?
Emotional empathy is crucial to understand how we respond to interpersonal positive or negative situations. In the present research, we aim at identifying the neural networks and the autonomic responsiveness underlying the human ability to perceive and empathize with others' emotions when positive (cooperative) or negative (uncooperative) interactions are observed. A multimethodological approach was adopted to elucidate the reciprocal interplay of autonomic (peripheral) and central (cortical) activities in empathic behavior. Electroencephalography (EEG, frequency band analysis) and hemodynamic (functional Near-Infrared Spectroscopy, fNIRS) activity were all recorded simultaneously with systemic skin conductance response (SCR) and heart rate (HR) measurements as potential biological markers of emotional empathy. Subjects were required to empathize in interpersonal interactions. As shown by fNIRS/EEG measures, negative situations elicited increased brain responses within the right prefrontal cortex (PFC), whereas positive situations elicited greater responses within the left PFC. Therefore, a relevant lateralization effect was induced by the specific valence (mainly for negative conditions) of the emotional interactions. Also, SCR was modulated by positive/negative conditions. Finally, EEG activity (mainly low-frequency theta and delta bands) intrinsically correlated with the cortical hemodynamic responsiveness, and they both predicted autonomic activity. The integrated central and autonomic measures better elucidated the significance of empathic behavior in interpersonal interactions.


Changes in HDL cholesterol and cardiovascular outcomes after lipid modification therapy.
Lipid modification therapy (LMT) produces cardiovascular benefits principally through reductions in low density lipoprotein cholesterol. While recent evidence, using data from 454 participants in the Framingham Offspring Study, has suggested that increases in high density lipoprotein cholesterol (HDL-C) are also associated with a reduction in cardiovascular outcomes, independently of changes in low density lipoprotein cholesterol, replication of this finding is important. The authors therefore present further results using data from the EPIC-Norfolk (UK) and Rotterdam (The Netherlands) prospective cohort studies. A total of 1148 participants, 446 from the EPIC-Norfolk and 702 from the Rotterdam study, were assessed for lipids before and after starting LMT. Subsequent risk of cardiovascular events, ascertained through linkage with mortality records and hospital databases, was investigated using Cox proportional hazards regression. Random effects meta-analysis was used to combine results across studies. Based on combined data from the EPIC-Norfolk and Rotterdam studies there was some evidence that change in HDL-C resulting from LMT was associated with reduced cardiovascular risk (HR per pooled SD (=0.34 mmol/l) increase=0.74, 95% CI 0.56 to 0.99, adjusted for age, sex and baseline HDL-C). However, this association was attenuated and was not (statistically) significant with further adjustments for non-HDL-C and for cigarette smoking history, prevalent diabetes, systolic blood pressure, body mass index, use of antihypertensive medication, previous myocardial infarction, prevalent angina and previous stroke (0.92, 0.701.20). Following adjustment for conventional non-lipid risk factors of cardiovascular disease, this study provides no evidence to support a significant benefit from increasing HDL-C independent of the effect of lowering non-HDL-C.


Current status of pharmacotherapy against metastatic renal cell carcinoma in Japan.
So far, metastatic renal cell carcinoma has been one of the most treatment-resistant cancers. The extensive use of cytokines, such as interferon-α and interleukin-2, were carried out for metastatic renal cell carcinoma. However, significant advances in understanding the molecular mechanisms underlying renal cell carcinoma have led to the development of molecular target-based drugs, which were desperately awaited for a long time, and now two types of molecular target-based drugs are available. Two vascular endothelial growth factor receptor tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors have been approved and available in Japan. The molecular target-based drugs have unique and characteristic adverse events, whose profile are not well understood in Japanese patients, because most of the clinical trials were carried out in Europe and America. In contrast, immunotherapy is being reconsidered in the selection of more appropriate patients or as a combined treatment form with other drugs, because of few complete responses obtained and unexpected adverse events by molecular targeted treatments. We have several molecular targeted-drugs available at present and will have more, and we will actually use these drugs in various clinical settings, such as the presurgical setting, the adjuvant setting, sequential administration and combined administration, in addition to cytokines. Therefore, we need more elaborate studies to obtain the optimal treatment methods to maximize the effect of such agents to extend overall survival while maintaining quality of life of metastatic renal cell carcinoma patients. In this article, we reviewed the issues related to the current status of pharmacotherapy available for metastatic renal cell carcinoma.


A review of consumer awareness, understanding and use of food-based dietary guidelines.
Food-based dietary guidelines (FBDG) have primarily been designed for the consumer to encourage healthy, habitual food choices, decrease chronic disease risk and improve public health. However, minimal research has been conducted to evaluate whether FBDG are utilised by the public. The present review used a framework of three concepts, awareness, understanding and use, to summarise consumer evidence related to national FBDG and food guides. Searches of nine electronic databases, reference lists and Internet grey literature elicited 939 articles. Predetermined exclusion criteria selected twenty-eight studies for review. These consisted of qualitative, quantitative and mixed study designs, non-clinical participants, related to official FBDG for the general public, and involved measures of consumer awareness, understanding or use of FBDG. The three concepts of awareness, understanding and use were often discussed interchangeably. Nevertheless, a greater amount of evidence for consumer awareness and understanding was reported than consumer use of FBDG. The twenty-eight studies varied in terms of aim, design and method. Study quality also varied with raw qualitative data, and quantitative method details were often omitted. Thus, the reliability and validity of these review findings may be limited. Further research is required to evaluate the efficacy of FBDG as a public health promotion tool. If the purpose of FBDG is to evoke consumer behaviour change, then the framework of consumer awareness, understanding and use of FBDG may be useful to categorise consumer behaviour studies and complement the dietary survey and health outcome data in the process of FBDG evaluation and revision.


The p38 mitogen-activated protein kinase is involved in stress-induced phospholipase D activation in vascular smooth muscle cells.
Oxidative stress has been implicated in mediation of vascular disorders. Earlier study showed that the exposure of vascular smooth muscle cells (VSMC) to pervanadate (hydrogen peroxide plus orthovanadate) resulted in the accumulation of [3H]phosphatidylbutanol. In this study, the effect of pervanadate on the activation of p38 mitogen-activated protein kinase (p38 MAPK) was studied in the VSMC. Pervanadate treatment activated p38 MAPK in a dose-and time-dependent manner. Interestingly, specific inhibition of p38 MAPK with SB203580 attenuated pervanadate-induced PLD activation. This correlates with the finding that expression of dominant negative mutants of MKK3/6 inhibited the PLD activation. SB203580 pretreatment also inhibited other cellular stressors (i.e. high osmolarity and UV light)-induced PLD activation. The possible correlationship of p38 MAPK activation with PKC was examined since PKC is reported to be involved in the pervanadate-induced PLD activation. Calphostin C, a PKC inhibitor, suppressed pervanadate-induced p38 MAPK and PLD activation in a dose-dependent manner. These results suggest that PKC-p38 MAPK may represent an upstream pathway of PLD in the signal transduction of cellular stress.


The Impact of Storage Conditions on the Stability of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis Bb12 in Human Milk.
Human milk is the optimal source of complete nutrition for neonates and it also guides the development of infant gut microbiota. Importantly, human milk can be supplemented with probiotics to complement the health benefits of breastfeeding. Storage of human milk for limited periods of time is often unavoidable, but little is known about the effect of different storage conditions (temperature) on the viability of the added probiotics. Therefore, in this study, we evaluated how different storage conditions affect the viability of two specific widely used probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis (Bb12), in human milk by culturing and quantitative polymerase chain reaction. Our results indicate that LGG and Bb12 remained stable throughout the storage period. Thus, we conclude that human milk offers an appropriate matrix for probiotic supplementation.


Serum erythropoietin levels in patients with congenital heart disease.
Serum erythropoietin levels were measured by radioimmunoassay in 146 children and young adults with congenital heart disease to assess the relationship between erythropoietin and clinical factors (heart failure, anemia, cyanosis) and hemodynamic variables affecting oxygen delivery and utilization. Erythropoietin values were in the normal range (10 to 30 microU/mL) in 73% (58 of 80) of the patients with and 82% (54 of 66) of those without cyanosis. Elevated erythropoietin values in cyanotic patients were associated with lower mixed venous oxygen saturation and tension than in cyanotic patients with normal erythropoietin levels, even though the degree of polycythemia was similar. In contrast, most of the acyanotic patients who had elevated erythropoietin levels were anemic. Of the blood oxygen measurements, mixed venous oxygen saturation and tension had the closest inverse correlation with erythropoietin values. The normal erythropoietin values in most patients are in accord with other observations that show that an elevation in erythropoietin level in response to hypoxia will be transient if it results in a rise in hemoglobin concentration "appropriate" to the degree of hypoxia. Persistent elevation of erythropoietin in patients with congenital heart disease may indicate harmful impairment of hemoglobin production that is potentially correctable.


Is VEGF a potential therapeutic target in asthma?
Asthma is currently affecting approximately 300 million people worldwide and is expected to rise to 400 million over the next couple decades. Airway remodelling in asthma consists of mucus hypersecretion, epithelium erosion, extracellular matrix protein deposition under the basement membrane, smooth muscle proliferation and angiogenesis. The vascular endothelial growth factor (VEGF) plays a part in remodelling through its effect upon angiogenesis, but the extent of its contribution to asthma pathology is not yet completely understood. Irreversible airway remodelling seems to be an important contributor to asthma progressive worsening, so further developments in preventing remodelling are warranted. A better understanding of VEGF mechanisms in asthma could aid such therapeutic developments.


Mouth breathing evaluation: use of Glatzel mirror and peak nasal inspiratory flow.
To compare the use of the Glatzel mirror and peak nasal inspiratory flow in the evaluation of mouth-breathing participants and to analyze the correlation between these instruments. Sixty-four children were evaluated--32 mouth breathers and 32 nasal breathers; the children were aged 4 to 12 years. The mouth breathers were subdivided according to the cause of obstruction by a multidisciplinary team. The Glatzel mirror and peak nasal inspiratory flow were used in both groups to evaluate patency and nasal airflow. Data were then subjected for statistical analysis. The Glatzel mirror allowed us to differentiate the breathing mode considering gender, age, weight, height, and body mass index, but it did not help in identifying the cause of mouth breathing. The peak nasal inspiratory flow did not allow differentiation of the breathing mode and identification of the cause of mouth breathing. In our sample, there was no correlation between the instruments used. The Glatzel mirror was reliable in identifying participants with and without nasal obstruction, although it was not possible to differentiate subgroups of mouth breathers using this instrument. The peak nasal inspiratory flow showed differences only between nasal breathers and surgical mouth breathers. Low correlation was found between these two instruments.


Activation of lysophosphatidic acid receptor by gintonin inhibits Kv1.2 channel activity: involvement of tyrosine kinase and receptor protein tyrosine phosphatase α.
Gintonin is a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand. The primary action of gintonin is to elicit a transient increase in [Ca(2+)]i via activation of LPA receptor subtypes. Voltage-gated potassium (Kv) channels play important roles in synaptic transmission in nervous systems. The previous reports have shown that Kv channels can be regulated by Gαq/11 protein-coupled receptor ligands. In the present study, we examined the effects of gintonin on Kv1.2 channel activity expressed in Xenopus oocytes after injection of RNA encoding the human Kv1.2 α subunit. Gintonin treatment inhibited Kv1.2 channel activity in reversible and concentration-dependent manners. The inhibitory effect of gintonin on Kv1.2 channel activity was blocked by active phospholipase C inhibitor, inositol 1,4,5-triphosphate receptor antagonist, and intracellular Ca(2+) chelator. The co-expression of active receptor protein tyrosine phosphatase α (RPTPα) with Kv1.2 channel greatly attenuated gintonin-mediated inhibition of Kv1.2 channel activity, but attenuation was not observed with catalytically inactive RPTPα. Furthermore, neither genistein, a tyrosine kinase inhibitor, nor site-directed mutation of a tyrosine residue (Y132 to Y132F), which is phosphorylated by tyrosine kinase of the N-terminal of the Kv1.2 channel α subunit, significantly attenuated gintonin-mediated inhibition of Kv1.2 channel activity. These results indicate that the gintonin-mediated Kv1.2 channel regulation involves the dual coordination of both tyrosine kinase and RPTPα coupled to this receptor. Finally, gintonin-mediated regulation of Kv1.2 channel activity might explain one of the modulations of gintonin-mediated neuronal activities in nervous systems.


A critical review of the effectiveness of educational interventions applied in HIV/AIDS prevention.
A critical review of issues around the effectiveness of educational approaches applied in the field of HIV/AIDS prevention. Published papers, systematic reviews and technical reports were reviewed. The review has identified the large gap between the current state of the art and the ultimate goal of the education-based approaches contributing to the reduction of HIV incidence rates. Significant positive impact has been reported mainly on mediating factors to behavioural change (knowledge, attitude, and intentions). The reported impact on actual behaviour change has been weak and short-lived. Biological markers are not used in many studies as outcome measures and follow-up period is too short to facilitate the measurement of impact on behaviour change or biological markers. Several methodological flaws and cultural issues militate against effective programming. A guideline for standardising practice and research in school-based programme is available for use. There is only very modest evidence of the effectiveness of educational interventions as a result of several gaps in project design, implementation and follow-up. There is urgent need to raise practice and research standards. Educational interventions should utilise scientifically valid data gathering methods. Follow-up period should be long enough to allow for impact measurement.


Meganema perideroedes gen. nov., sp. nov., a filamentous alphaproteobacterium from activated sludge.
An industrial wastewater treatment plant at Grindsted, Denmark, has suffered from bulking problems for several years caused by filamentous bacteria. Five strains were isolated from the sludge by micromanipulation. Phylogenetic analysis of the 16S rRNA gene sequences showed that the strains formed a monophyletic cluster in the Alphaproteobacteria, and they were phenotypically different from their closest relatives and from all hitherto known filamentous bacteria described (closest relative Brevundimonas vesicularis ATCC 11426(T), 89.8 % sequence similarity). In pure culture, the cells (1.5-2.0 microm) in filaments are Gram-negative and contain polyphosphate and polyhydroxyalkanoates. The optimum temperature for growth is 30 degrees C and the strains grow in 2 % NaCl and are oxidase- and catalase-positive. Ubiquinone 10 is the major quinone. The major fatty acid (C(18 : 1)omega7c) and smaller amounts of unsaturated fatty acids, 3-hydroxy fatty acids with a chain length of 16 and 18 carbon atoms and small amounts of 10-methyl-branched fatty acids with 18 carbon atoms (C(19 : 0) 10-methyl) affiliated the strains with the Methylobacterium/Xanthobacter group in the Alphaproteobacteria. The G+C content of the DNA is 42.9 mol% (for strain Gr1(T)). The two most dissimilar isolates by 16S rRNA gene comparison (Gr1(T) and Gr10; 97.7 % identical) showed 71.5 % DNA-DNA relatedness. Oligonucleotide probes specific for the pure cultures were designed for fluorescence in situ hybridization and demonstrated that two filamentous morphotypes were present in the Grindsted wastewater treatment plant. It is proposed that the isolates represent a new genus and species, Meganema perideroedes gen. nov., sp. nov. The type strain of Meganema perideroedes is strain Gr1(T) (=DSM 15528(T)=ATCC BAA-740(T)).


Dr. Sait Bilal Golem (1899-1955): Veterinarian and pioneer researcher of public health in Albania and Turkey.
Sait Bilal Golem is an Albanian veterinarian who graduated from the Military Veterinary School in 1920. Golem started his doctorate in microbiology at Alfort Veterinary School. In this process, he worked as an assistant to the world-renowned French microbiologist Dr Gaston Ramon at the Pasteur Institute. After his doctorate, he returned to Albania and established the Veterinary Affairs Organization and made significant contributions to its structuring in international standards. Dr Golem returned to Türkiye in 1926 and started working at the Central Institute of Hygiene. Dr Golem, together with physicians and veterinarians at this institute, diagnosed brucellosis in animals and humans with serological methods for the first time in Türkiye. Moreover, he isolated Newcastle virus from embryonated eggs for the first time and prepared Komarov type attenuated dry vaccine against this virus for the first time in Türkiye. He conducted the first research on the diagnosis of Q fever and prepared the first intradermal BCG vaccine in Türkiye. Through his studies for both public and animal health in Türkiye, he has contributed to the One Health concept with an understanding that transcends time.


Child health of Great Barrier Island.
The health of 69 children on Great Barrier Island was studied. This is an isolated community without a permanent doctor, and most children were healthy. Ear disease was the commonest problem, especially in Maori children. Problems of impetigo, scabies, rheumatic fever and dental caries were not present. Comparisons are made with the results of a recent Auckland study.


Antibodies to a specific surface antigen of T cells in human sera inhibiting mixed leukocyte culture reactions.
Surface radioiodination of lymphocytes by the lactoperoxidase procedure has permitted demonstration of an assortment of different antibodies to lymphocytes in the sera of patients with systemic lupus erythematosus. One type of antibody proved of special interest because it appeared to be associated with inhibition of the responder cells in the mixed leukocyte culture reactions. This reacted with an antigen on T cells and thymocytes which on sodium dodecyl sulfate acrylamide gel electrophoresis showed a molecular weight of approximately 15,000 daltons. The possible relation of this antigen to T cell receptors and products of immune response genes is discussed.


CT prognostic factors in acute subdural haematomas: the value of the 'worst' CT scan.
The relationship between radiological findings and outcome in patients with acute posttraumatic subdural haematomas (SDH) has been based on CT obtained upon hospital admission. This study was undertaken to investigate the effects on prognosis of SDH patients of lesions not present on admission, but detected by subsequent CT. We have also studied those findings present on admission CT that could predict worsening of the associated lesions. From 1 May 1989 to 30 April 1996, we admitted 206 patients harbouring acute SDH of thickness 5 mm or more. The admission GCS score ranged from 3 to 15. Each patient underwent CT on admission (always within 3 h from injury). Follow-up CT was performed within 12-24 h after injury and in the following days (an average of 4.3 examinations for each patient). These examinations were reviewed by a neuroradiologist and the 'worst' CT was determined. We defined the 'worst' examination as that showing the largest haematoma thickness/midline shift and/or with the most extensive degree of parenchymal damage. Clinical factors related to prognosis in this series are age, hypoxia/hypotension, GCS motor score and pupillary abnormalities. Time from injury to treatment was found relevant only in patients with isolated SDH. CT findings on admission that correlated with outcome were haematoma thickness, midline shift and status of the basal cisterns. Prognosis was also worsened by the presence of associated lesions; SAH alone or associated with brain contusions. The last of these was the single most powerful predictor of worse outcomes (Odds ratio 0.37, p < 0.004). Whereas the first CT showed parenchymal associated damage in 56 patients, the 'worst CT' showed such damage in 105 patients. Presence of SAH on admission was found significant (p < 0.02) in predicting evolving parenchymal damage. Haematoma thickness, midline shift, status of the basal cisterns and presence of SAH are related to outcome when identified on the initial (early) CT examination. However, early (within 3 h from injury) CT under-estimates the ultimate size of parenchymal contusions. Patients with SAH on early CT are those at highest risk for associated evolving contusions. The use of sequential CT should be included in the routine management of head-injured patients.


Genome-based estimates of fungal rDNA copy number variation across phylogenetic scales and ecological lifestyles.
Ribosomal DNA (rDNA) copy number variation (CNV) has major physiological implications for all organisms, but how it varies for fungi, an ecologically ubiquitous and important group of microorganisms, has yet to be systemically investigated. Here, we examine rDNA CNV using an in silico read depth approach for 91 fungal taxa with sequenced genomes and assess copy number conservation across phylogenetic scales and ecological lifestyles. rDNA copy number varied considerably across fungi, ranging from an estimated 14 to 1,442 copies (mean = 113, median = 82), and copy number similarity was inversely correlated with phylogenetic distance. No correlations were found between rDNA CNV and fungal trophic mode, ecological guild or genome size. Taken together, these results show that like other microorganisms, fungi exhibit substantial variation in rDNA copy number, which is linked to their phylogeny in a scale-dependent manner.


Substrate specificity and regulation of the maize (Zea mays) leaf ADP: protein phosphotransferase catalysing phosphorylation/inactivation of pyruvate, orthophosphate dikinase.
The protein substrate specificity of the maize (Zea mays) leaf ADP: protein phosphotransferase (regulatory protein, RP) was studied in terms of its relative ability to inactivate/phosphorylate pyruvate, orthophosphate dikinase from Zea mays and the non-sulphur purple photosynthetic bacterium Rhodospirillum rubrum. The dimeric bacterial dikinase was inactivated by the maize leaf RP via phosphorylation, with a stoichiometry of approximately 1 mol of phosphate incorporated/mol of 92.7-kDa protomer. Inactivation required both ADP and ATP, with ADP being the specific donor for regulatory phosphorylation. The requirements for inactivation/phosphorylation in this heterologous system were identical with those previously established for the tetrameric maize leaf dikinase. The ADP-dependent maize leaf RP did not phosphorylate alternative protein substrates such as casein or phosvitin, and its activity was not affected by cyclic nucleotides, Ca2+ or calmodulin. The regulation of the maize leaf ADP: protein phosphotransferase was studied in terms of changes in adenylate energy charge and pyruvate concentration. The change in adenylate energy charge necessary to substantially inhibit phosphorylation of maize leaf dikinase was not suggestive of it being a physiological modulator of phosphotransferase activity. Pyruvate was a potent competitive inhibitor of regulatory phosphorylation (Ki = 80 microM), consistent with its interaction with the catalytic phosphorylated intermediate of dikinase, the true protein substrate for ADP-dependent phosphorylation/inactivation.


Electromagnetic Fields of Mobile Phone Jammer Exposure on Blood Factors in Rats.
The increasing demand for using mobile phones has led to increasing mobile phone jammers as well. On the other hand, reports show that exposure to electromagnetic field causes an increase in the incidence of diseases such as leukemia, cancer, depression and failure in pregnancy outcomes; therefore, the aim of this study is to investigate the effects of exposure to electromagnetic fields of mobile phone jammers on blood factors. Thirty male Wistar immature and thirty mature rats were selected randomly and each one was divided into three groups of ten. The control group did not receive any radiation; the sham group was exposed to a switched-off jammer device and the experimental group was exposed to electromagnetic fields (EMF) radiated by Mobile Phone Jammer daily eight hours for five days a week during forty days. Blood sample was taken from heart and blood factors including PLT, MCHC and RDWCV were measured. The data were analyzed by ANOVA which was followed by Duncan's test. The data from mature rats revealed that jammer usage led to a significant difference in blood factors including RBC, platelet, hemoglobin, hematocrit, MCV and RDWCV (P≤0.05); however, the number of lymphocytes, WBC and MCVH in the blood was the same in all groups. In immature rats, the exposure to jammer did not change RBC, lymphocyte and WBC count, hemoglobin and hematocrit; while, the platelet count along with MCHC, MVC and RDWCV changed by jammer radiation. The results exhibited that mobile phone jammer caused frequent changes in blood cell factors.


Fine mapping genetic associations between the HLA region and extremely high intelligence.
General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ > 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h2 = 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence.


Echinococcus multilocularis Detection in Live Eurasian Beavers (Castor fiber) Using a Combination of Laparoscopy and Abdominal Ultrasound under Field Conditions.
Echinococcus multilocularis is an important pathogenic zoonotic parasite of health concern, though absent in the United Kingdom. Eurasian beavers (Castor fiber) may act as a rare intermediate host, and so unscreened wild caught individuals may pose a potential risk of introducing this parasite to disease-free countries through translocation programs. There is currently no single definitive ante-mortem diagnostic test in intermediate hosts. An effective non-lethal diagnostic, feasible under field condition would be helpful to minimise parasite establishment risk, where indiscriminate culling is to be avoided. This study screened live beavers (captive, n = 18 or wild-trapped in Scotland, n = 12) and beaver cadavers (wild Scotland, n = 4 or Bavaria, n = 11), for the presence of E. multilocularis. Ultrasonography in combination with minimally invasive surgical examination of the abdomen by laparoscopy was viable under field conditions for real-time evaluation in beavers. Laparoscopy alone does not allow the operator to visualize the parenchyma of organs such as the liver, or inside the lumen of the gastrointestinal tract, hence the advantage of its combination with abdominal ultrasonography. All live beavers and Scottish cadavers were largely unremarkable in their haematology and serum biochemistry with no values suspicious for liver pathology or potentially indicative of E. multilocularis infection. This correlated well with ultrasound, laparoscopy, and immunoblotting, which were unremarkable in these individuals. Two wild Bavarian individuals were suspected E. multilocularis positive at post-mortem, through the presence of hepatic cysts. Sensitivity and specificity of a combination of laparoscopy and abdominal ultrasonography in the detection of parasitic liver cyst lesions was 100% in the subset of cadavers (95%Confidence Intervals 34.24-100%, and 86.7-100% respectively). For abdominal ultrasonography alone sensitivity was only 50% (95%CI 9.5-90.6%), with specificity being 100% (95%CI 79.2-100%). For laparoscopy alone sensitivity was 100% (95% CI 34.2-100%), with specificity also being 100% (95% CI 77.2-100%). Further immunoblotting, PCR and histopathological examination revealed one individual positive for E. multilocularis, whilst the other individual was positive for Taenia martis.


[Social profile of the black population in Brazil: implications for the nursing profession].
The discussion about the inequality conditions in which black population lives in Brazil, has been disguised by today's economical conjuncture which apparently sets with no restrictions the white, black and mestizos in absolute destitution conditions. Considered unracist, entitled by 'Folha de Sao Paulo/Datafolha' as Kind Racist, Brazil has being instituting way of living among races whose discrimination is expressed by the lack of opportunity and access to consumption services. This way, the insertion of the black in Brazilian society after slavery abolition is our study object. This bibliographical discusses social indicators aiming at describing this population strategies in conquering a social space. This study shows up the difficulties faced by this populational group regarding to its insertions to the work market as determinant factor to its social rising. We have included black male and female as citizens which compose the labor force in Nursing.


Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice.
Development of a vaccine that targets blood-stage malaria parasites is imperative if we are to sustainably reduce the morbidity and mortality caused by this infection. Such a vaccine should elicit long-lasting immune responses against conserved determinants in the parasite population. Most blood-stage vaccines, however, induce protective antibodies against surface antigens, which tend to be polymorphic. Cell-mediated responses, on the other hand, offer the theoretical advantage of targeting internal antigens that are more likely to be conserved. Nonetheless, few of the current blood-stage vaccine candidates are able to harness vigorous T cell immunity. Here, we present what we believe to be a novel blood-stage whole-organism vaccine that, by combining low doses of killed parasite with CpG-oligodeoxynucleotide (CpG-ODN) adjuvant, was able to elicit strong and cross-reactive T cell responses in mice. Our data demonstrate that immunization of mice with 1,000 killed parasites in CpG-ODN engendered durable and cross-strain protection by inducing a vigorous response that was dependent on CD4+ T cells, IFN-gamma, and nitric oxide. If applicable to humans, this approach should facilitate the generation of robust, cross-reactive T cell responses against malaria as well as antigen availability for vaccine manufacture.


Initial studies on the contributions of body size and gastrointestinal passage rates to dietary flexibility among gorillas.
Large body size has been traditionally seen as the primary dietary adaptation of gorillas, facilitating their consumption of fibrous foods (Schaller ¿1963 The Mountain Gorilla; Watts ¿1990 Int. J. Primatol. 11:21-45). Nevertheless, recent research has emphasized frugivory among western lowland gorillas, as well as the influence of habitat and seasonality on gorilla diet and behavior across subspecies (Watts ¿1990 Int. J. Primatol. 11:21-45; Tutin et al. ¿1991 Philos. R. Soc. Trans. Lond. Biol. 334:179-186; Remis ¿1994 Ph.D. Thesis, ¿1997a Am. J. Primatol. 43:87-109, ¿1997b Am. J. Primatol. 43:111-133, ¿1998 Primate Locomotion: Recent Advances, p 95-(1)108, ¿1999 Primates 40:383-396; Nishihara ¿1995 Primates 36:151-168; Goldsmith ¿1999a Int. J. Primatol. 20:1-23, Goldsmith [1999b] Nonhuman Primates, p 58-63). This study provides preliminary data to address the physiological underpinnings of dietary flexibility among gorillas, and their consumption of a broad range of fibrous and tannin-rich foods. To date, little is known about the digestive physiology of the African apes (but see Milton ¿1984 Adaptations for Foraging in Nonhuman Primates, p 249-279, Milton [1984] ¿1999Evol. Anthropol. 8:11-20; Milton and Demment ¿1988 J. Nutr. 118:1082-1088; Lambert ¿1997 Ph.D. Dissertation), although gastrointestinal morphology and proportions are roughly similar among species ( Chivers and Hladik ¿1980 J. Morphol. 166:337-386). This study provides additional experimental data on the gastrointestinal passage times of gorillas (Gorilla gorilla gorilla) fed a captive diet in a zoological park setting and discusses results in relation to field research on gorilla feeding ecology. In this study, 480 small plastic markers were fed to six captive gorillas. The mean gut retention time (MRT) of the adult gorillas in this study was 50 hr, longer than the 31 hr reported for chimpanzees fed a similar diet (Lambert ¿1997 Ph.D. Dissertation). These data suggest that gorillas may retain foods in their gastrointestinal tracts longer than smaller hominoids, and that the large body size likely forms the primary basis for consumption of fiber. This research provides additional data to contribute to our understanding of the relationships of body size and morphology to ecology, and the evolution of body size, foraging strategy and social organization among the African apes.


Application of visible and near-infrared spectroscopy to classification of Miscanthus species.
The feasibility of visible and near infrared (NIR) spectroscopy as tool to classify Miscanthus samples was explored in this study. Three types of Miscanthus plants, namely, M. sinensis, M. sacchariflorus and M. fIoridulus, were analyzed using a NIR spectrophotometer. Several classification models based on the NIR spectra data were developed using line discriminated analysis (LDA), partial least squares (PLS), least squares support vector machine regression (LSSVR), radial basis function (RBF) and neural network (NN). The principal component analysis (PCA) presented rough classification with overlapping samples, while the models of Line_LSSVR, RBF_LSSVR and RBF_NN presented almost same calibration and validation results. Due to the higher speed of Line_LSSVR than RBF_LSSVR and RBF_NN, we selected the line_LSSVR model as a representative. In our study, the model based on line_LSSVR showed higher accuracy than LDA and PLS models. The total correct classification rates of 87.79 and 96.51% were observed based on LDA and PLS model in the testing set, respectively, while the line_LSSVR showed 99.42% of total correct classification rate. Meanwhile, the lin_LSSVR model in the testing set showed correct classification rate of 100, 100 and 96.77% for M. sinensis, M. sacchariflorus and M. fIoridulus, respectively. The lin_LSSVR model assigned 99.42% of samples to the right groups, except one M. fIoridulus sample. The results demonstrated that NIR spectra combined with a preliminary morphological classification could be an effective and reliable procedure for the classification of Miscanthus species.


Holographic Bragg grating input-output couplers for polymer waveguides at an 850-nm wavelength.
Bragg gratings used as input-output couplers in polymeric waveguides have been demonstrated at infrared wavelengths. These Bragg grating couplers were holographically formed volume phase gratings with a near-45 degrees fringe slant angle embedded directly into a waveguide layer. A photopolymer was used for both producing a planar waveguide and constructing the embedded Bragg grating coupler. A coupling efficiency of 23% for input and 5% for output has been achieved at 850 nm. The output-coupling beam profiles are also discussed.


Depression and anxiety in patients with hereditary angioedema.
Hereditary angioedema (HAE) is characterized by edematous swelling attacks of the face, extremities, abdomen, genitalia, and upper airway. The potential for laryngeal swelling makes the disease life-threatening, and the swelling elsewhere contributes to the significant burden of illness. The increased risk for mental health disorders in HAE is due to the burden of disease and possibly associated activation of the immune system. To determine the prevalence of depression and anxiety in HAE patients and the most high-yield features of depression to target in a clinical encounter. Depression and anxiety symptoms were evaluated using the 29 items of the Hamilton Depression Rating Scale along with the 14-item Hamilton Anxiety Rating Scale. The sample size was 26 participants with a diagnosis of type 1 or 2 HAE drawn from a cohort of 60 adult patients. In addition, a literature search was performed regarding how immune modulation affects depression and anxiety. A total of 39% of participants were identified as experiencing depression of mild (50%), moderate (40%), or severe (10%) levels. Fifteen percent of participants displayed prominent anxiety, half of whom had mild anxiety, 25% moderate anxiety, and 25% severe anxiety. The literature on inflammation and depression suggests a possible link between HAE and depression. Our data and the literature support that depression and anxiety symptoms are common in patients with HAE and may be secondary to chronic disease burden, associated pathophysiologic features, or both. Treatment that addresses the psychosocial and mental health of HAE patients is critical for best practice.


Detection of anti-influenza A nucleoprotein antibodies in pigs using a commercial influenza epitope-blocking enzyme-linked immunosorbent assay developed for avian species.
Influenza virus causes acute respiratory disease in pigs and is of concern for its potential public health significance. Many subtypes of influenza virus have been isolated from pigs, and the virus continues to evolve in swine populations. Current antibody assays have limited antigenic recognition, and accurate, broad-spectrum, high through-put screening tests are needed to detect infections in swine herds and to aid in the implementation of control measures. In the current study, a commercial blocking enzyme-linked immunosorbent assay (ELISA) developed for the detection of Influenza A virus nucleoprotein antibodies in avian species was evaluated for the detection of anti-influenza serum antibodies in swine. Serum samples used to evaluate the test were archived samples from influenza research conducted at the U.S. Department of Agriculture-Agricultural Research Service-National Animal Disease Center and included samples from influenza-inoculated pigs (H1N1, H1N2, H2N3, and H3N2), contact-infected pigs, vaccinated pigs, and negative controls. Based on samples of known status (n = 453), a receiver operating characteristic (ROC) curve analysis of the ELISA results estimated the optimized diagnostic sensitivity and specificity at 96.6% (95% confidence interval [CI]: 92.3, 98.9) and 99.3% (95% CI: 97.6, 99.9), respectively. By using the cutoff established in the ROC analysis, the assay was evaluated in pigs infected with 2 isolates of the 2009 pandemic H1N1 virus. Overall, the assay showed excellent diagnostic performance against the range of influenza subtypes investigated and could serve as a useful screening assay for swine.


Inequalities in the social determinants of health and Chagas disease transmission risk in indigenous and creole households in the Argentine Chaco.
The social determinants of health (SDHs) condition disease distribution and the ways they are handled. Socio-economic inequalities are closely linked to the occurrence of neglected tropical diseases, but empirical support is limited in the case of Chagas disease, caused by the protozoan Trypanosoma cruzi. Herein we assessed the relationship between key structural SDHs and the risk of T. cruzi vector-borne transmission in rural communities of the Argentine Chaco occupied by creoles and an indigenous group (Qom). We used multiple correspondence analysis to quantify the household-level socio-economic position (social vulnerability and assets indices), access to health and sanitation services, and domestic host availability. We identified the most vulnerable population subgroups by comparing their demographic profiles, mobility patterns and distribution of these summary indices, then assessed their spatial correlation and household-level effects on vector domiciliary indices as transmission risk surrogates. Qom households had higher social vulnerability and fewer assets than creoles, as did local movers and migrant households compared with non-movers. We found significantly positive effects of social vulnerability and domestic host availability on infected Triatoma infestans abundance, after adjusting for ethnicity. Access to health and sanitation services had no effect on transmission risk. Only social vulnerability displayed significant global spatial autocorrelation up to 1 km. A hotspot of infected vectors overlapped with an aggregation of most vulnerable households. This synthetic approach to assess socio-economic related inequalities in transmission risk provides key information to guide targeted vector control actions, case detection and treatment of Chagas disease, towards sustainability of interventions and greater reduction of health inequalities.


Interpretation and knowledge of human rights in mental health practice.
The Human Rights Act is sometimes misunderstood as being an obstruction to the provision of safe and effective mental health care, allowing patients to cry 'human rights abuse' too easily. In reality, however, little is known about how human rights are protected and promoted in psychiatric care. This article provides an overview, for nurses, of how human rights are currently understood to be protected in mental health care and steps that could improve the protection of rights. Additionally, an overview of the relevant case law is presented to enable nurses to understand how human rights law is ever-evolving, how cases may be interpreted, and the implications that this has for mental health nursing practice.


Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders.
This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics. In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies. We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel-group and cross-over study designs. We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach. We included eight randomized controlled trials (four of which were cross-over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta-analysis due to important clinical heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine. Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.


Multipurpose heterofunctional dendritic scaffolds as crosslinkers towards functional soft hydrogels and implant adhesives in bone fracture applications.
Two sets of heterofunctional dendritic frameworks displaying an inversed and exact number of ene and azide groups have successfully been synthesized and post-functionalized with biorelevant molecules. Their facile scaffolding ability enabled the fabrication of soft and azide functional dendritic hydrogels with modulus close to muscle tissue. The dendritic scaffolds are furthermore shown to be promising primers for the development of novel bone fracture stabilization adhesives with shear strengths succeeding commercial Histroacryl®.


Studies on the mechanism of neutralization of influenza virus by antibody: evidence that neutralizing antibody (anti-haemagglutinin) inactivates influenza virus in vivo by inhibiting virion transcriptase activity.
Influenza viruses, which had lost up to 99.999% infectivity by incubation with antibody (a) specific for the haemagglutinin (HA) or with monoclonal alpha-HA, attached on to and penetrated chick embryo fibroblast (CEF) cells to the same extent as non-neutralized virus. Neutralized virus was also uncoated efficiently as shown by the accumulation of virion RNA in the nucleus and virion envelope in the cytoplasm. Polyacrylamide gel electrophoresis of virion RNA segments recovered from the nucleus or cytoplasm of cells inoculated with neutralized or non-neutralized virus showed that antibody did not potentiate degradation of RNA. However, these RNAs were not expressed since virus-induced proteins were not detected in cells to which neutralized virus had been added. Assay of virion transcriptase of neutralized virus in vitro showed that its activity was reduced up to sevenfold compared with non-neutralized virus, and annealing studies showed that no detectable transcription took place in vivo with neutralized virus. These studies support the conclusion that antibody directed specifically against the HA protein on the outer surface of the influenza virus particle neutralizes infectivity by inactivating virion transcriptase activity and it is suggested that antibody to HA brings about allosteric rearrangements in the HA molecule which are transmitted across the virus envelope to the interior of the particle.


Distant Pituitary Adenoma Spread: A Systematic Review and Report of 2 Cases.
Distant spread of pituitary adenoma outside the sellar/suprasellar region is classified as pituitary carcinoma. Cerebrospinal fluid (CSF)-born spread of pituitary adenoma can occur after tumor cell spillage into the CSF space after surgery, irradiation, or apoplexy and is not necessarily related to intrinsic tumor biology. To systematically review the literature and describe the clinical characteristics and treatment strategies of patients with pituitary carcinomas. We further present 2 cases from our institution. A single-center retrospective review of patients with pituitary adenoma spread to distant intracranial locations between 2000 and 2020 was performed. Electronic databases were searched from their inception to May 25, 2021, and studies describing patients with pituitary spread to distant locations were included. Of 1210 pituitary adenoma cases reviewed, 2 (0.16%) showed tumor spread to distant locations. We found 134 additional cases (from 108 published articles) resulting in a total of 136 cases (61.9% were male). The time to tumor spread ranged between 0 and 516 months (median: 96 months). The follow-up duration ranged between 0 and 240 months (median: 11.5 months). All but 2 patients (98.5%) underwent surgical resection before adenoma spread. The 2 exceptions included a patient with evidence of an apoplectic event on autopsy and another patient with leptomeningeal pituitary spread but an unclear history of apoplexy. Elevated tumor markers were not linked to poor outcomes. Distant spread of pituitary adenoma may occur after surgery, irradiation, or apoplexy. It is not necessarily associated with a malignant clinical course.


Muscle performance and enzymatic adaptations to sprint interval training.
Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance. Twelve healthy men (22 +/- 2 yr of age) underwent intense interval training on a cycle ergometer for 7 wk. Training consisted of 30-s maximum sprint efforts (Wingate protocol) interspersed by 2-4 min of recovery, performed three times per week. The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7. Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption (VO2 max) were measured before and after the training program. Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase, total glycogen phosphorylase, phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase. The training program resulted in significant increases in peak power output, total work over 30 s, and VO2 max. Maximal enzyme activity of hexokinase, phosphofructokinase, citrate synthase, succinate dehydrogenase, and malate dehydrogenase was also significantly (P < 0.05) higher after training. It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity, maximum short-term power output, and VO2 max.


Health care costs and the socioeconomic consequences of work injuries in Brazil: a longitudinal study.
Work injuries are a worldwide public health problem but little is known about their socioeconomic impact. This prospective longitudinal study estimates the direct health care costs and socioeconomic consequences of work injuries for 406 workers identified in the emergency departments of the two largest public hospitals in Salvador, Brazil, from June through September 2005. After hospital discharge workers were followed up monthly until their return to work. Most insured workers were unaware of their rights or of how to obtain insurance benefits (81.6%). Approximately half the cases suffered loss of earnings, and women were more frequently dismissed than men. The most frequently reported family consequences were: need for a family member to act as a caregiver and difficulties with daily expenses. Total costs were US$40,077.00 but individual costs varied widely, according to injury severity. Out-of-pocket costs accounted for the highest proportion of total costs (50.5%) and increased with severity (57.6%). Most out-of-pocket costs were related to transport and purchasing medicines and other wound care products. The second largest contribution (40.6%) came from the public National Health System - SUS. Employer participation was negligible. Health care funding must be discussed to alleviate the economic burden of work injuries on workers.


Lyophilized microculture susceptibility test for ketoconazole, miconazole, clotrimazole, and griseofulvin against dermatophytes.
A lyophilized microculture antimycotic susceptibility testing system for ketoconazole, miconazole, griseofulvin, and clotrimazole is described. Microculture plates were loaded with 100 microliters of medium and 10 microliters of appropriate concentrations of the four antimycotics and were lyophilized to complete dryness. The lyophilized plates were stored at -70 degrees C or 4 degrees C or in a desiccator at 25 degrees C. Samples from each storage condition were rehydrated at 1, 2, 3, 4, 5, 6, 8, 10, and 12 months and inoculated with Trichophyton mentagrophytes (Robin) Blanchard ATCC 18748. All of the minimal inhibitory concentrations (MICs) generated from the lyophilized microcultures were within one experimental dilution of MICs derived from fresh microcultures. The ability of reconstituted lyophilized microcultures to consistently produce MICs comparable to MICs derived from fresh microcultures was characterized. Nine dermatophyte isolates were tested five times each over a 70-day period. The MICs derived were reproducible and comparable to MICs determined by freshly prepared microculture tests. Lyophilization of freshly prepared antimycotic-containing microcultures does not alter the MIC resolution of the testing system and provides an effective method of storage of prepared antimycotic tests for ketoconazole, miconazole, clotrimazole, and griseofulvin.


Improving the CAC Score by Addition of Regional Measures of Calcium Distribution: Multi-Ethnic Study of Atherosclerosis.
The aim of this study was to investigate whether inclusion of simple measures of calcified plaque distribution might improve the ability of the traditional Agatston coronary artery calcium (CAC) score to predict cardiovascular events. Agatston CAC scoring does not include information on the location and distributional pattern of detectable calcified plaque. We studied 3,262 (50%) individuals with baseline CAC >0 from MESA (Multi-Ethnic Study of Atherosclerosis). Multivessel CAC was defined by the number of coronary vessels with CAC (scored 1 to 4, including the left main). The "diffusivity index" was calculated as: 1 - (CAC in most affected vessel/total CAC), and was used to group participants into concentrated and diffuse CAC patterns. Multivariable Cox proportional hazards regression, area under the curve, and net reclassification improvement analyses were performed for both coronary heart disease (CHD) and cardiovascular disease (CVD) events to assess whether measures of regional CAC distribution add to the traditional Agatston CAC score. Mean age of the population was 66 ± 10 years, with 42% women. Median follow-up was 10.0 (9.5 to 10.7) years and there were 368 CHD and 493 CVD events during follow-up. Considerable heterogeneity existed between CAC score group and number of vessels with CAC (p < 0.01). Addition of number of vessels with CAC significantly improved capacity to predict CHD and CVD events in survival analysis (hazard ratio: 1.9 to 3.5 for 4-vessel vs. 1-vessel CAC), area under the curve analysis (C-statistic improvement of 0.01 to 0.033), and net reclassification improvement analysis (category-less net reclassification improvement 0.10 to 0.45). Although a diffuse CAC pattern was associated with worse outcomes in participants with ≥2 vessels with CAC (hazard ratio: 1.33 to 1.41; p < 0.05), adding this variable to the Agatston CAC score and number of vessels with CAC did not further improve global risk prediction. The number of coronary arteries with calcified plaque, indicating increasingly "diffuse" multivessel subclinical atherosclerosis, adds significantly to the traditional Agatston CAC score for the prediction of CHD and CVD events.


Psychosocial and behavioural correlates of attitudes towards antiretroviral therapy (ART) in a sample of South African mineworkers.
Despite being one of the worst affected sectors in South Africa, the mining sector has proven to be one of the most active in intervention efforts in the fight against HIV and AIDS (Ellis, 2007). Owing to low uptake rates of antiretroviral therapy (ART) in mining companies in recent years (Connelly & Rosen, 2006) and the positive relationship between attitudes towards ART and ART uptake (Cooper et al., 2002; Horne, Cooper, Gellaitry, Leake, & Fisher, 2007), this study sought to describe and investigate the psychosocial and behavioural correlates of attitudes towards ART in a sample of South African mineworkers. A total of 806 mineworkers from a large South African mine participated in this quantitative study. Despite a high rate of HIV testing behaviour (83.0%) as well as favourable attitudes towards ART, analysis indicated that temporary employees and contractors were more vulnerable in terms of HIV risk, HIV testing behaviours and ART knowledge and attitudes. Employees who had more positive attitudes towards ART were more knowledgeable of ART and, importantly, had a more favourable attitude towards the mine's HIV/AIDS treatment programme. These findings are discussed in relation to the low ART uptake rates in this context and recommendations for the improvement of ART uptake amongst employees at this mining site.


[The Child and Adolescent Health Survey--a foundation for prevention, health promotion and health goals].
At the beginning of the 21st century, the German Health Interview and Examination Survey of Children and Adolescents will for the first time provide the data essential for programmes of disease prevention and health promotion as well as for the development of health targets. This it will create key information for an evidence-based health policy. The results of the study can be projected to the general population of children and adolescents in Germany. The data will be collected conjunct at the level of the individual subject. They will facilitate valid and distinct description of prevalent physical, psychological and social health problems, as well as on who has them under which circumstances and settings. Information on the impact, e.g., in terms of utilisation of the health system or impairments of quality of life, will also be available from the same subjects. In addition, indicators of risks to health in later life are included. Hence, the data will support prevention of health problems in infancy, childhood and adolescence as well as of chronic diseases in later life. Finally, the data shall be a basis for the definition of new reference values for many variables. This will improve valid and clear judgement not only in epidemiological studies but also in medical care.


Mediator release after nasal aspirin provocation supports different phenotypes in subjects with hypersensitivity reactions to NSAIDs.
Multiple NSAID-induced urticaria/angioedema (MNSAID-UA) is an entity well differentiated from aspirin-exacerbated respiratory disease (AERD), although no detailed phenotype analysis has yet been performed. The objective was to evaluate the functional characteristics of MNSAID-UA subjects by analyzing the response to nasal lysine-aspirin challenge and measurement of nasal inflammatory mediator release compared with AERD subjects and controls. The study included 85 subjects with confirmed hypersensitivity to NSAIDs (≥3 episodes with >2 different NSAIDs or positive drug provocation) with either cutaneous (MNSAID-UA, n = 25) or respiratory manifestations (AERD, n = 60) and 30 tolerant controls (15 aspirin-tolerant asthmatic patients and 15 healthy controls). Nasal lavages at 0, 15, 60, and 120 min after lysine-aspirin challenge were analyzed for ECP, tryptase, PGE2 , PGD2 , LTD4 , and LTE4 . Lysine nasal challenge was positive in 80% of the AERD cases but positive only in 12% of the MNSAID-UA group. MNSAID-UA subjects showed no changes in nasal ECP, whereas subjects with AERD had increased levels of ECP, with the highest peak at 15 min after challenge (P < 0.05). Tryptase levels were higher in AERD compared with MNSAID-UA and controls with the highest release of tryptase at 60 min (P < 0.05). Significant increases in PGD2 , LTD4 , and LTE4 were observed in AERD (at 60 min for PGD2 , LTD4 , and LTE4 ) but not in MNSAID-UA or control subjects (P < 0.05). Data support the observation that MNSAID-UA, although sharing a common response with AERD to COX inhibitors, seems to have a distinctive phenotype, based on the response to nasal challenge and the release of inflammatory mediators.


Glucose-induced endothelial heparanase secretion requires cortical and stress actin reorganization.
Heparanase, which specifically cleaves carbohydrate chains of heparan sulfate, has been implicated in the pathology of diabetes-associated complications. Using high glucose (HG) to replicate hyperglycaemia observed following diabetes, the present study was designed to determine the mechanism by which HG initiates endothelial heparanase secretion. To examine the effect of HG on endothelial heparanase, bovine coronary artery endothelial cells were incubated with 25 mM glucose. Strategies using different agonists and antagonists were used to determine the mechanism behind HG-induced heparanase secretion. In endothelial cells, heparanase colocalized with lysosomes predominately around the nucleus, and HG caused its dispersion towards the plasma membrane for subsequent secretion. ATP release, purinergic receptor activation, cortical actin disassembly, and stress actin formation were essential for this HG-induced heparanase secretion. With HG, phosphorylation of filamin likely contributed to the cortical actin disassembly, whereas Ca(2+)/calmodulin-dependent protein kinase II and p38 mitogen-activated protein kinase /heat shock protein 25 phosphorylation mediated stress actin formation. The endothelial secreted heparanase in response to HG demonstrated endoglucuronidase activity, cleaved heparan sulfate, and released attached proteins like lipoprotein lipase and basic fibroblast growth factor. Our results suggest that HG is a potent stimulator of endothelial heparanase secretion. These data may assist in devising new therapeutic strategies to prevent or delay the cardiovascular complications associated with diabetes.


Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer.
Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II "Phoenix" definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and may assist clinicians in predicting an outcome. Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes.


Spontaneous Activity as a Determinant of Axonal Connections.
To investigate the role of spontaneous retinal activity in map refinement, we studied goldfish kept in darkness during regeneration of a cut optic nerve. In one experiment, such fish (with lenses ablated to blur vision) were maintained for 70 days in stroboscopic light, diurnal light, or total darkness interrupted daily by 15 minutes of stroboscopic light. The retinotectal projection was then assessed for retinotopy by standard methods, using retrograde transport of wheat germ agglutinin-horseradish peroxidase. As in previous work, significantly more refinement was found in diurnal than in stroboscopic light. In darkness, refinement was as complete as in diurnal light. In a second experiment, similar fish were kept in stroboscopic light for 63 days. Some were then assessed to confirm that refinement had been delayed, while others were transferred to darkness or diurnal light for assessment later. After 7 days in either environment, no further refinement was seen; but after 21 days, substantial and significant refinement has occurred in both. Thus the effects of darkness and diurnal light were indistinguishable, and very different from those of stroboscopic light and (in previous studies) tetrodotoxin. Map refinement is evidently activity-dependent but not experience-dependent, and can effectively use the correlated spontaneous firing of neighbouring ganglion cells as its basis. Locally correlated spontaneous activity, which appears also to drive eye- and class-specific axon segregation in mammals, occurs widely in the nervous system. It could potentially generate systematic interconnection patterns even between neuronal populations without an overtly topographic organization.


Reliable safety assessment depends on species differences in epigenetic mechanisms of gene regulation.
The potential carcinogenic hazard of chemical agents to humans is presently based primarily on the results of long-term animal bioassays. The validity of this toxicologic approach to human risk assessment depends on two fundamental assumptions. First, the results of an animal bioassay are directly applicable to humans (interspecies extrapolation). Second, the doses used in an animal bioassay are relevant for estimating risk at known or expected human exposure levels (dose extrapolation). Although progress has been made over the past four decades in understanding the mode of action of chemical carcinogens, it is increasingly important to determine mechanistically the relevance of these modes of action in humans. There is now evidence that M6P/IGF2R functions as a novel tumor-suppressor gene in a variety of human and rodent cancers. M6p/Igf2r is imprinted in rodents and expressed only from the maternal allele after embryonic implantation. In contrast, both alleles are functional in humans. This marked species difference in M6P/IGF2R imprinting has important implications for human carcinogen risk assessment since only one rather than two alleles needs to be mutated in rodents to completely inactivate the function of this tumor suppressor gene. This striking species difference in the imprint status of M6P/IGF2R clearly demonstrates that we need to understand better variations in epigenetic mechanisms of gene regulation between rodents and humans to perform accurately chemical safety assessments.


Genetics of primary aldosteronism.
Primary aldosteronism (PA) accounts for ∼10% of hypertension, which is commonly caused by an aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Germline mutations producing PA are considered rare and termed familial hyperaldosteronism (FH) [1, 2, 3]. Since early 2011, a series of somatic mutations confined to the adrenal cortex has been reported, accounting for about half of APA. These mutations are in genes encoding components of the Kir 3.4 (GIRK4) potassium channel (KCNJ5), sodium/potassium and calcium ATPases (ATP1A1 and ATP2B3) and a voltage-dependent C-type calcium channel (CACNA1D). FH-1 (glucocorticoid-remediable hyperaldosteronism) results from a chimeric gene (5'-end of CYP11B1 fused to 3'-end of CYP11B2) and accounts for ∼1% of PA. FH-3 is very rare, is caused by bilateral expression of mutant KCNJ5 and usually results in florid hyperaldosteronism requiring early bilateral adrenalectomy. FH-2 is the most common form of hereditary PA (2 first-degree relatives with either an APA or bilateral adrenal hyperplasia) and currently thought to represent ∼6% of PA; the true prevalence may be considerably higher. The mutation(s) causing FH-2 are unknown but appear dominant, as is the case for FH-1 and FH-3. No studies have been done on possible recessive forms of PA.


Rethinking scholarship in medical education during the era of the COVID-19 pandemic.
This article was migrated. The article was marked as recommended. The COVID-19 pandemic has significantly disrupted society and communities across the world requiring new and innovative approaches for healthcare, work, education and leisure. Similar changes have been precipitated in medical education, producing a rapid and major impact on students, educators and institutions. However, institutions still require educators to engage with scholarship in medical education, including providing evidence for promotion and tenure. We propose that resolving this tension between the demands of delivering a high quality curriculum and maintaining scholarship in medical education during the era of the COVID-19 pandemic requires urgent consideration of a transformational change in the scholarship in medical education. Key aspects of this change are a focus on rapid cycles of research to inform teaching, with local and wider dissemination using newer rapid approaches to publication and social media, and acceptability of these changes by institutions.


In vitro ictogenesis is stochastic at the single neuron level.
Seizure initiation is the least understood and most disabling element of epilepsy. Studies of ictogenesis require high speed recordings at cellular resolution in the area of seizure onset. However, in vivo seizure onset areas cannot be determined at the level of resolution necessary to enable such studies. To circumvent these challenges, we used novel GCaMP7-based calcium imaging in the organotypic hippocampal slice culture model of post-traumatic epilepsy in mice. Organotypic hippocampal slice cultures generate spontaneous, recurrent seizures in a preparation in which it is feasible to image the activity of the entire network (with no unseen inputs existing). Chronic calcium imaging of the entire hippocampal network, with paired electrophysiology, revealed three patterns of seizure onset: (i) low amplitude fast activity; (ii) sentinel spike; and (iii) spike burst and low amplitude fast activity onset. These patterns recapitulate common features of human seizure onset, including low voltage fast activity and spike discharges. Weeks-long imaging of seizure activity showed a characteristic evolution in onset type and a refinement of the seizure onset zone. Longitudinal tracking of individual neurons revealed that seizure onset is stochastic at the single neuron level, suggesting that seizure initiation activates neurons in non-stereotyped sequences seizure to seizure. This study demonstrates for the first time that transitions to seizure are not initiated by a small number of neuronal 'bad actors' (such as overly connected hub cells), but rather by network changes which enable the onset of pathology among large populations of neurons.


Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats.
We have reported that a deficiency of tetrahydrobiopterin (BH(4)), an active cofactor of endothelial NO synthase (eNOS), contributes to the endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O(2)(-)) generation in the insulin-resistant state. To further confirm this hypothesis, we investigated the effects of dietary treatment with BH(4) on endothelium-dependent arterial relaxation and vascular oxidative stress in the aortas of insulin-resistant rats. Oral supplementation of BH(4) (10 mg. kg(-1). d(-1)) for 8 weeks significantly increased the BH(4) content in cardiovascular tissues of rats fed high levels of fructose (fructose-fed rats). Impairment of endothelium-dependent arterial relaxation in the aortic strips of the fructose-fed rats was reversed with BH(4) treatment. The BH(4) treatment was associated with a 2-fold increase in eNOS activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats. The BH(4) treatment also partially improved the insulin sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats. Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and activating protein-1, which were increased in fructose-fed rats. The BH(4) treatment of control rats did not have any significant effects on these parameters. These results indicate that BH(4) augmentation is essential for the restoration of eNOS function and the reduction of vascular oxidative stress in insulin-resistant rats.


Training Health Professionals to Deliver Healthy Living Medicine.
The growing incidence and prevalence of unhealthy living behaviors leading to compromised health, along with unhealthy supportive environments, are the primary reasons for the current chronic disease crisis in almost all countries. Over the course of health professions training across disciplines, a large amount about information regarding various aspects of chronic disease is introduced, from pathophysiology to a broad array of approaches to examinations (focused on diagnosis and prognosis) and interventions. Currently, a late primary or secondary prevention focus is the primary educational approach in the health professions. In either scenario, the health professional is often trained to approach their discipline from a catch up approach, with little focus on how an individual's health condition, at the time of presentation, came to be. It is unfortunate that so little educational time and effort are devoted to train future health professionals on how to practice Healthy Living Medicine (HLM) and, deliver healthy living (HL) interventions. The primary goal should be to keep individuals healthy where they live, work and go to school and minimize initiating care in the hospital and outpatient clinical setting. The current review describes current trends in training health professionals in HLM and the delivery of HL interventions.


Film characteristics pertinent to coherent optical data processing systems.
Photographic film is studied quantitatively as the input mechanism for coherent optical data recording and processing systems. The two important film characteristics are the amplitude transmission vs exposure (T(A) - E) curve and the film noise power spectral density. Both functions are measured as a function of the type of film, the type of developer, developer time and temperature, and the exposing and readout light wavelengths. A detailed analysis of a coherent optical spatial frequency analyzer reveals that the optimum do bias point for 649-F film is an amplitude transmission of about 70%. This operating point yields minimum harmonic and intermodulation distortion, whereas the 50% amplitude transmission bias point recommended by holographers yields maximum diffraction efficiency. It is also shown that the effective ac gain or contrast of the film is nearly independent of the development conditions for a given film. Finally, the linear dynamic range of one particular coherent optical spatial frequency analyzer is shown to be about 40-50 dB.


Levels of drug and antidrug antibodies are associated with outcome of interventions after loss of response to infliximab or adalimumab.
There is controversy about whether levels of anti-tumor necrosis factor (TNF) and antidrug antibodies (ADAs) are accurate determinants of loss of response to therapy. We analyzed the association between trough levels of anti-TNF agents or ADAs and outcomes of interventions for patients with loss of response to infliximab or adalimumab. We performed a retrospective study of pediatric and adult patients with inflammatory bowel disease and suspected loss of response to anti-TNF agents treated at medical centers throughout Israel from October 2009 through February 2013. We examined the correlation between outcomes of different interventions and trough levels of drug or ADAs during loss of response. An additional subanalysis was performed including only patients with a definite inflammatory loss of response (clinical worsening associated with increased levels of C-reactive protein or fecal calprotectin, or detection of inflammation by endoscopy, fistula discharge, or imaging studies). Among 247 patients (42 with ulcerative colitis), there were 330 loss-of-response events (188 to infliximab and 142 to adalimumab). Trough levels of adalimumab greater than 4.5 mcg/mL and infliximab greater than 3.8 mcg/mL identified patients who failed to respond to an increase in drug dosage or a switch to another anti-TNF agent with 90% specificity; these were set as adequate trough levels. Adequate trough levels identified patients who responded to expectant management or out-of-class interventions with more than 75% specificity. Levels of antibodies against adalimumab >4 microgram per mL equivalent (mcg/mL-eq) or antibodies against infliximab >9 mcg/mL-eq identified patients who did not respond to an increased drug dosage with 90% specificity. Patients with high titers of ADAs had longer durations of response when anti-TNF agents were switched than when dosage was increased (P = .03; log-rank test), although dosage increases were more effective for patients with no or low titers of ADAs (P = .02). An analysis of definite inflammatory loss-of-response events (n = 244) produced similar results; patients with adequate trough levels had a longer duration of response when they switched to a different class of agent than when anti-TNF was optimized by either a dosage increase or by a switch within the anti-TNF class (P = .002; log-rank test). The results of this retrospective analysis suggest that trough levels of drug or ADAs may guide therapeutic decisions for more than two-thirds of inflammatory bowel disease patients with either clinically suspected or definite inflammatory loss of response to therapy.


Comparison of CT and MRI for the diagnosis recurrent esophageal carcinoma after operation.
Despite an increase in radical surgery for esophageal carcinoma, many patients continue to develop recurrent disease. Some reports have suggested that recurrent tumors should be treated aggressively with a combination of chemotherapy and radiotherapy. The aim of this study was to assess the comparative utility of computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of recurrence after curative resection of cancer of the esophagus and gastroesophageal junction. To maximize survival benefit, detection of tumor recurrence as early and accurately as possible is important. Twenty-three patients who developed recurrent tumors after curative transthoracic esophagogastrectomy for esophageal carcinoma were analyzed retrospectively. The CT and MRI findings were correlated with pathology or with endoscopic and clinical follow-up. Primary tumor recurrence was detected at the anastomosis side in 19 patients (intraluminal mass in 13 and as diffuse or focal wall thickening in six). Distant recurrence was seen in the liver (n = 5), lung (n = 4), bone (n = 3), abdominal lymph node (n = 4), pleural effusion (n = 2) and pericardial effusion (n = 1). CT and MRI were found equal in showing the intraluminal mass, liver metastasis, pleural and pericardial effusion. Thickening of esophageal wall was demonstrated in nine patients using CT, but only seven of these tumor recurrences were confirmed by MRI, the remaining two were related to secondary fibrosis. Both CT and MRI showed diffuse gastric wall thickening determined as false tumor recurrence due to severe gastritis in one case. There were two (50%) false negatives for lung metastasis in MRI and one bone metastasis (33%) false negative in CT. CT was found superior in the demonstration of lung metastasis and MRI was superior in the evaluation of wall thickening and bone metastasis.