An evaluation of PCR methods to detect strains of Mycoplasma fermentans.
A panel of 30 putative Mycoplasma fermentans strains, isolated from various sources including human, ovine and cell lines, were tested by a previously described polymerase chain reaction (PCR) to confirm their identity by amplification of a conserved 206 bp region of the insertion sequence IS1550. In addition, the application of another PCR based on the major part of the IS1550 element showed one or two products of different length (1144 and 1341 bp) enabling M. fermentans strains to be divided into two types designated as Type A and Type B. A PCR, which amplifies the macrophage activating lipopeptide gene (malp), supported the identification of all the strains as M. fermentans. Thirteen other species of Mycoplasma from human sources gave negative results in these tests, with the exception of Mycoplasma orale, which was detected by both IS1550-PCRs based on the major part and the conserved 206 bp region of the IS1550 element. This study suggests that all M. fermentans isolates possess both the IS1550 element and the malp gene. In contrast to the IS1550, the malp gene is shown to be species-specific and the use of a malp PCR described here could prove to be a useful adjunct to IS1550 detection as confirmation of the presence of M. fermentans in clinical material.


[Cribra orbitalia (Porotic hyperostosis) in a prehistoric population of Parana Medio].
The observation of porotic hyperostosis in the orbits (criba orbitalia) in bone remains of a funeral site at the north of the Santa Fe province strongly suggests the occurrence of severe anemia among dwellers. Intestinal parasitosis (by Ancylostoma duodenalis or Necator americanus) is deemed the most likely cause of the anemia.


Morphological and immunological similarity of the monocytes from pure and mixed monocytic leukaemias.
Morphological and immunological marker data on a patient with 'pure' monocytic leukaemia are presented and compared with those of 6 cases of clearly mixed myelomonocytic leukaemia with a variable monocytic component. In all patients studied, the leukaemic monocytes expressed a receptor for the Fc of IgG, and IgG sensitization markedly enhanced phagocytosis of ox erythrocytes. A variable, but lower, percentage of the leukaemic monocytes had a receptor for mouse C3, but the cells uniformly lacked surface immunoglobulin and receptors for the Fc of IgM and for unsensitised mouse erythrocytes. Cytochemical and ultrastructural study also showed no clear difference between the monocytes of the 'pure' and mixed monocytic leukaemias. This report therefore lends no support to the concept of distinct types of monocytic leukaemia.


The Evolution of Tumor Formation in Humans and Mice with Inherited Mutations in the p53 Gene.
While tumors are very heterogeneous in their origins, mutations in the p53 gene and inactivation of p53 gene functions are the most common feature that predispose to the formation of cancers in humans. Inherited p53 mutations lead to different tumor types at very different frequencies and at very different ages than somatic p53 mutations. The reasons for this are explored. When the first mutation arises in a stem cell (a gatekeeper mutation) it selects for a specific subset of second mutations which in turn select for mutations in a third subset of genes. The nature of the first mutation in a tumor determines, by selection, the functional types of subsequent mutations. Inherited mutations occur at different developmental times and in different orders of mutational sequences than somatic mutations. The excess risk of developing a cancer with an inherited p53 mutation is two- to three-fold in endodermal derived tissues compared with 100- to 1000-fold for ectodermal and mesenchymal derived tissues. By contrast, endodermal derived tumors with somatic p53 mutations occur at very high frequencies (70-100%). These evolutionary restrictions upon the mutational path that tumor development may take could open up new avenues for therapy and prevention.


Predictors of postoperative outcome after general surgical procedures in patients with congenital heart disease.
This study was undertaken to evaluate factors predictive of postoperative outcome after general surgical (GS) procedures in patients with congenital heart disease (CHD). All patients with a diagnosis of CHD who underwent a GS procedure under general anesthesia during a consecutive 10-year period were considered eligible for the study The congenital heart defect was classified as either simple (ASD, VSD, PDA) or complex (endocardial cushion defects, transposition of the great vessels, tetralogy of Fallot), and the GS procedure as either major (intraperitoneal, intrathoracic, or vascular reconstructive) or minor (inguinal herniorrhaphy, vascular access). The overall mortality rate for the patient population was 12% (27 deaths among 226 procedures), minor procedures being associated with a 3% mortality rate (2 of 70 procedures), and major procedures with a 16% mortality rate (25 of 156 procedures). Incremental risk factors for mortality included a preoperative American Society of Anesthesiologists' (ASA) physical status class of IV or higher (P = .0003), a preoperative in-hospital stay of 10 or more days (P = .004), birth at a tertiary care center (P = .04), and emergency operations (P = .05). In the subgroup of patients less than 6 months old, weight of less than 2.4 kg at the time of surgery and a 1-minute Apgar score of less than 4 were additional independent risk factors (P = .04 and .01, respectively). By logistic analysis, previous corrective cardiac procedures, whether complete or palliative, did not significantly alter the postoperative outcome. The authors conclude that physiologically well-compensated patients with CHD can undergo elective operations at a low operative risk; however, poorly compensated patients undergoing urgent or emergent operations are at high risk.(ABSTRACT TRUNCATED AT 250 WORDS)


Microbial contamination in inoculated shell eggs: I. Effects of layer strain and hen age.
Three Ottawa control strains and a current commercial laying stock were reared and housed under identical environmental and management conditions. Eggs were collected from each strain when hens were 32, 45, 58, 71, and 84 wk of age. The eggs were inoculated with Salmonella enteritidis (SE), Pseudomonasfluorescens (PF), or a combination of the two. After storage at 26 C, bacterial counts were obtained from the exterior shell surfaces (rinse), air cell, egg contents, and shell structure. SE and PF survived at different rates on the shell surface with as much as a 1 log difference during a given collection period. Egg content counts tended to be higher than eggshell counts in PF, whereas the opposite was true for SE. These data suggest that PF is a primary invader of eggs that is more capable of contaminating egg contents through the shell membranes than SE. The PF and SE data suggest that bacterial contamination of air cells, shells, and egg contents is more easily achieved in eggs from older hens than from younger hens. There were also differences between the strains. Control Strain 10 consistently maintained a lower level of contamination for both organisms in each sampling location. The overall results of this study suggest that genetic selection has altered the ability of eggs to resist microbial contamination and that screening for microbial integrity should be considered in the selection process among the laying egg breeders.


Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism.
The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.


Involvement of phospholipases C and D in the defence responses of riboflavin-treated tobacco cells.
Riboflavin is an activator of defence responses in plants that increases resistance against diseases caused by fungal, oomycete, bacterial and viral pathogens. However, the mechanisms driving defence activation by riboflavin are poorly understood. We investigated the signal transduction pathways of phospholipase C (PLC) and phospholipase D (PLD) in tobacco (Nicotiana tabacum) suspension cells using a pharmacological approach to confirm whether riboflavin-mediated activation of the defence response is dependent on both PLC and PLD. The expression patterns analysed by quantitative reverse transcription-polymerase chain reaction demonstrated that the tobacco PLC and PLD gene families were differentially expressed in riboflavin-treated tobacco cells. PLC and PLD expression accompanied defence responses including the expression of defence response genes (PAL, PR-1a and PR-1b), the production of hydrogen peroxide and the accumulation of the phytoalexin scopoletin in tobacco cells treated with riboflavin. These defence responses were significantly inhibited in the presence of the PLC inhibitor U73122 and the PLD inhibitor 1-butanol; however, inhibitor analogues had no effect. Moreover, treating tobacco cells with phosphatidic acid, a signalling molecule produced by phospholipase catalysis, induced the accumulation of the phytoalexin scopoletin and compensated for the suppressive effects of U73122 and 1-butanol on riboflavin-induced accumulation of the phytoalexin. These results offer pharmacological evidence that PLC and PLD play a role in riboflavin-induced defences of tobacco.


Comparison of Distichlis spicata and Suaeda aegyptiaca in response to water salinity: Candidate halophytic species for saline soils remediation.
Distichlis spicata and Suaeda aegyptiaca are two potential halophytic plant species for bioremediation of salt degraded soils, and development of saline agriculture. The physiological responses of the species to different levels of salinity (EC 0, 12, 24, 36, and 48 dS/m) in a controlled environment experiment were studied. Both species showed a high level of tolerance to elevated concentrations of salt in the irrigation water. The shoot fresh and dry weights in S. aegyptiaca increased till 36 dS/m and were sustained under 48 dS/m while in D. spicata, both parameters decreased as salinity increased. Glycine betaine accumulation did not change in D. spicata with increasing salinity, whereas proline content revealed a marked increase of 7.13 fold in 48 dS/m salinity compared to the control, which showed its critical osmoprotection role in the plant. In S. aegyptiaca, both osmolytes content significantly increased at high salinity levels (36 and 48 dS/m) up to 3.22 and 2.0 folds, respectively. Overall, S. aegyptiaca had a better potential of Na+ phytoremediation, and tolerated higher salinity compared to D. spicata. In contrast, the vigorous root and rhizome growth in D. spicata made it a proper solution for protecting the soils against further erosion under saline conditions.


Prospects for Neurotrophic Factor-Based Early Intervention in Schizophrenia: Lessons Learned from the Effects of Antipsychotic Drugs on Cognition, Neurogenesis, and Neurotrophic Factors.
Although reducing psychotic symptoms in schizophrenia has been a major focus of therapeutic interventions for decades, improving cognition is considered a better predictor of functional outcomes. However, the most commonly prescribed antipsychotic drugs (APDs) show only marginal beneficial effects on cognition in patients with schizophrenia. The neural mechanisms underlying cognitive disturbances in schizophrenia remain unknown that making drug development efforts very challenging. Since neurotrophic factors are the primary architects of neurogenesis, synaptic plasticity, learning, and memory, the findings from preclinical and clinical studies that assess changes in neurogenesis and neurotrophic factors and their relationship to cognitive performance in schizophrenia, and how these mechanisms might be impacted by APD treatment, may provide valuable clues in developing therapies to combat cognitive deficit in schizophrenia. Numerous evidence produced over the years suggests a deficit in a wide spectrum of neurotrophic factors in schizophrenia. Since schizophrenia is considered a neurodevelopmental disorder, early intervention with neurotrophic factors may be more effective in ameliorating the cognitive deficits and psychopathological symptoms associated with this pathology. In this context, results from initial clinical trials with neurotrophic factors and their future potential to improve cognition and psychosocial functioning in schizophrenia are discussed.


Lung volumes in swimmers performing different styles of swimming.
The alteration of lung volumes in swimmers performing different strokes was the theme of the present study. The study was carried out due to lack of knowledge regarding the lung volumes of different strokers. As the energy expenditure, O2 consumption rate, body movements, viz. arm and leg movements differ with each stroke, the lung function status and mechanics of breathing in swimmers has to cope up with the stroke techniques. Lung volumes, viz. VC, FVC, FEV1 and RVind decrease from resting condition to after swimming performance in freestyle swimmers and butterfly stroke swimmers. The primary reason for the decline in lung volumes after exercise bout, found out from several reports is that it may be due to the fatigue of respiratory muscle. When lung volumes of different swimming strokers were compared with age and height matched controls a higher lung volume were observed in swimmers performing different strokes. Higher breath holding ability of swimmers may facilitate the increase in the strength of respiratory musculature. This may have lead to higher lung volumes in swimmers. From the results of different strokers of swimmers, it is clear that lung volumes differ with respect to the stroke technique employed by the swimmer. Here the age and height, training duration of the swimmers performing different strokes were almost matched, so it is more or less clear that lung volumes are influenced by different swarming strokes. The results of the study can be utilised for the selection trials of swimmers. The study outlines the need for research work in swimmers to be more specific with regard to strokes than generalizing swimmers of different strokes as a category together.


Training and the attentional blink: Raising the ceiling does not remove the limits.
The attentional blink (AB) is a widely studied deficit in reporting the second of two sequentially presented targets when they occur within 500 milliseconds. The AB often is interpreted to index a structural limit in sequential visual processing. However, this interpretation is challenged by reports that the deficit can be reduced with several hundred trials of specific training (Braun in Nature, 393(6684), 424-425, 1998; Choi et al. in Proceedings of the National Academy of Sciences, 109(30), 12242-12247, 2012; Taatgen et al. in Cognitive Psychology, 59(1), 1-29, 2009) and other reports that some individuals experience very little or no deficit, even without specific training (Martens et al. in Journal of Cognitive Neuroscience, 18(9), 1423-1438, 2006). Yet neither of these claims has been studied when the artifact of ceiling effects has been removed. We sent a small number of participants (n = 5) home to practice an AB task on their mobile phones for 3,000-6,000 trials (Experiment 1) and trained a much larger number of participants (n = 48) in a similar way for 1,200-1,800 trials (Experiment 2). Both experiments used adaptive procedures to equate task difficulty throughout training to keep second-target accuracy below ceiling levels. The results showed strong training effects on the rate of processing sequential information. Despite this, there were (a) robust AB effects after training for most participants, (b) no benefit for training on difficult versus easy target tasks, and (c) substantial correlations between the magnitude of the AB before and after extensive training. These findings support the interpretation that the AB is an index of a structural limit in the ability to consciously process rapid visual sequences.


The influence of the living conditions on the diagnostics process and treatment of bronchial asthma of developmental age based on the author's own material.
Bronchial asthma is one of the most frequent chronic diseases of developmental age. The occurrence of bronchial asthma with children is connected with individual predisposition to development of atopic disease as well as with the presence of specific environmental conditions. Specific factors include food, inhalatory and contact allergens. Non-specific factors include infections, air pollution, and passive smoking. Environment conditions have the significant influence on the course of the disease. The aim of this work is to estimate the frequency of occurring bronchial asthma with children and the influence of living conditions on the diagnosis and treatment processes. The researches were completed on the group of 43 children aged from 8 months to 14 years. The children attended the Paediatric Counselling and complained about chronic cough or symptoms of wheezing breath. The initial diagnosis included taking a history of a patient and his/her family, physical examinations, and supplementary investigation. The final diagnosis was confirmed after a specialist consultation. After introduction of medical treatment, the follow-up examinations were recommended every 4-6 weeks. In the examined group the children with proper birth weight (89%) who were breast-fed at least for 6 months (78%) predominated. In 23% of cases the living conditions were qualified as inconvenient. 63% of children were in a risk of passive smoking in their place of living. In all age groups the children from the families burdened with atopy dominated (98%). In 44% of cases a pet was present in the place of living. In the examined material the highest percentage of children with diagnosis was observed in groups of children aged 7-10. In this group the boys living in difficult conditions prevailed. A high percentage of young children aged 2-3 years were observed. In this group the girls living in good living conditions prevailed. On the basis of the present experience it has been possible to claim that parents of children aged 4-6 have had the highest consciousness of necessity of urgent diagnosis and medical treatment. Treatment of bronchial asthma was introduced at 98% of cases. In the examined group no essential statistical effectiveness of treatment regarding to sex or the living conditions was found. The presented analysis confirms the role of environmental epidemiology in the setting of true relationship between the diagnosis of asthma and the exposure to specific environmental factors.


HES-Mediated Repression of Pten in Caenorhabditis elegans.
The hairy/enhancer-of-split (HES) group of transcription factors controls embryonic development, often by acting downstream of the Notch signaling pathway; however, little is known about postembryonic roles of these proteins. In Caenorhabditis elegans, the six proteins that make up the REF-1 family are considered to be HES orthologs that act in both Notch-dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the REF-1 family works to coordinate postembryonic cellular events, we performed a functional characterization of the REF-1 family member, HLH-25. We show that, after embryogenesis, hlh-25 expression persists throughout every developmental stage, including dauer, into adulthood. Like animals that carry loss-of-function alleles in genes required for normal cell-cycle progression, the phenotypes of hlh-25 animals include reduced brood size, unfertilized oocytes, and abnormal gonad morphology. Using gene expression microarray, we show that the HLH-25 transcriptional network correlates with the phenotypes of hlh-25 animals and that the C. elegans Pten ortholog, daf-18, is one major hub in the network. Finally, we show that HLH-25 regulates C. elegans lifespan and dauer recovery, which correlates with a role in the transcriptional repression of daf-18 activity. Collectively, these data provide the first genetic evidence that HLH-25 may be a functional ortholog of mammalian HES1, which represses PTEN activity in mice and human cells.


[Spondylodiscitis after surgery of lumbar disk hernia. Apropos of 12 cases in 1796 operations].
Discitis is a rare complication of disc operation. The incidence rate varies from 0.2 to 0.8% according to the series. During a 6 year period (1980-1986) 1,796 patients were operated for lumbar disc protrusion at our institution and twelve of them (0.66%) developed a post operative discitis. Bacteriologic verification due to the infection was ascertained in ten cases. Direct contamination during surgical time is likely far more frequent than hematogenous contamination because the liable germ was staphylococcus in 9 cases. Ascertaining the diagnosis is base upon clinical picture and some selected investigations. It may be earlier than it has been said before. Discitis may be suspected within a week after operation in two cases out of three. The most prominent clinical feature is back pain with muscle spasm but sometimes diagnosis may be misled to a psychiatric condition or a visceral disorder. Among conclusive investigations we range in the first place the needle aspiration of the disc which permitted to isolate a germ nine times out of eleven. Next the bone scan with H.M.D.P. Te 99 (8 Mbq/kg) which revealed a significant uptake pattern in eight cases out of eight. Finally the blood culture which grew five times out of ten. Risks of discitis, i.e septicemia, polysegmental infection or death justify in our opinion an appropriate antibiotherapy during at least 8 weeks. Moreover, in our experience, it is the best antalgic treatment that we can offer and back pain decreases as soon as the second day with antibiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)


A safety, length of stay, and cost analysis of minimally invasive microsurgery for anterior circulation aneurysms.
The aim of our study was to evaluate minimally invasive techniques for the treatment of anterior circulation aneurysms versus standard surgery, and to calculate the impact of these techniques on health resources, length of stay, and treatment costs. A consecutive series of 24 patients with ruptured and 30 with unruptured anterior circulation aneurysms treated with minimally invasive microsurgery (MIM) by the same surgeon was compared with a matched series of standard microsurgeries (SM) conducted for 23 ruptured and 22 unruptured aneurysms. Complication rates, aneurysm obliteration, modified Rankin Scale (mRS) outcomes, length of stay, and treatment costs were assessed. Surgical complications, aneurysm obliteration rates and mRS outcomes were comparable between MIM and SM groups in ruptured and unruptured aneurysm cohorts. MIM resulted in shorter operative times both in unruptured (102.7 ± 4.35 vs 194.7 ± 10.26 min, p < 0.0001) and ruptured aneurysms (124.3 ± 827 vs 209 ± 13.84 min, p < 0.0001). Length of stay was reduced in patients with MIM for unruptured aneurysms (1.55 ± 24 vs 4.28 ± 0.71 days, p < 0.000,1) but not in those with ruptured aneurysms. MIM reduced treatment costs of unruptured aneurysm patients, mainly through reduced utilization of inpatient resources (non-acute bed costs in CAD: 371.2 ± 80.99 vs 1440 ± 224.1, p < 0.0001), whereas costs were comparable in patients with ruptured aneurysms. Minimally invasive surgery is a safe and effective approach for the treatment of ruptured and unruptured aneurysms of the anterior circulation. In patients with unruptured aneurysms, reduced invasiveness and shorter operative times decreased length of stay, which reflects improved patient postoperative recovery. Overall, this translated into bed resource economy and cost reduction.


Endocannabinoid-mediated neuromodulation in the main olfactory bulb at the interface of environmental stimuli and central neural processing.
The olfactory system has become an important functional gateway to understand and analyze neuromodulation since olfactory dysfunction and deficits have emerged as prodromal and, at other times, as first symptoms of many of neurodegenerative, neuropsychiatric and communication disorders. Considering olfactory dysfunction as outcome of altered, damaged and/or inefficient olfactory processing, in the current review, we analyze how olfactory processing interacts with the endocannabinoid signaling system. In the human body, endocannabinoid synthesis is a natural and on-demand response to a wide range of physiological and environmental stimuli. Our current understanding of the response dynamics of the endocannabinoid system is based in large part on research advances in limbic system areas, such as the hippocampus and the amygdala. Functional interactions of this signaling system with olfactory processing and associated pathways are just emerging but appear to grow rapidly with multidimensional approaches. Recent work analyzing the crystal structure of endocannabinoid receptors bound to their agonists in a signaling complex has opened avenues for developing specific therapeutic drugs that could help with neuroinflammation, neurodegeneration, and alleviation/reduction of pain. We discuss the role of endocannabinoids as signaling molecules in the olfactory system and the relevance of the endocannabinoid system for synaptic plasticity.


The complement system in uremia.
Plasma C1q, C1 esterase inactivator, C4, C3 and C3 proactivator were measured in 20 chronic uremic patients on maintenance hemodialysis, in 10 conservatively treated chronic uremic patients and in 20 healthy volunteers. There was no statistical significant difference between the patient groups in any of the measured complement components. The C1q, C1 esterase inactivator and C4 concentration were found to be the same in the patient and the control groups. The C3 and C3 proactivator levels were equally and significantly lower in both patient groups compared with the healthy volunteers.


Exercise therapy for sarcopenia in rheumatoid arthritis: A meta-analysis and meta-regression of randomized controlled trials.
Rheumatoid arthritis and age are associated with high sarcopenia risk. Exercise is an effective treatment for preventing muscle mass loss in older adult populations. It remains unclear whether exercise affects muscle mass in people with rheumatoid arthritis. Thus, this meta-analysis investigated the effect of exercise on muscle mass gain in patients with rheumatoid arthritis. PubMed, EMBASE, the Cochrane Library, the Physiotherapy Evidence Database (PEDro), the China Knowledge Resource Integrated Database, and Google Scholar were systematically searched until June 2021. The present study was conducted according to the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Randomized controlled trials (RCTs) that reported the effects of exercise on muscle mass for rheumatoid arthritis were identified. The included RCTs were subject to meta-analysis and risk of bias assessment. Subgroup and random-effects meta-regression analyses were performed to identify any heterogeneity (I2) of treatment effects across studies. We included nine RCTs with a median PEDro score of 6/10 (range: 4/10-8/10). The weighted mean effect size for muscle mass was 0.77 (95% CI: 0.30-1.24; P = 0.001; I2 = 77%). Meta-regression analyses indicated that the disease duration significantly explained variance of treatment effects across studies (β = -0.006, R2 = 69.7%, P = 0.005). Exercise therapy effectively increased muscle mass in patients with rheumatoid arthritis. Treatment effects may be attenuated in those who have had rheumatoid arthritis for a relatively long time.


Should the cardiotomy suction blood be cell-saver processed before retransfusion? A clinico-pathologic mystery.
The use of cardiotomy suction (CS) in cardiopulmonary bypass (CPB) surgery is associated with a pronounced systemic inflammatory response and a resulting coagulopathy as well as exacerbating the microembolic load. However, CS is yet been employed to preserve autologous blood during on-pump surgery. Though processing CS blood with a cell saving device is considered paramount in significantly reducing the inflammatory effects, yet this might also have potential harmful effects on the outcome of the patient. Here we discuss the results of the different prospective and randomized studies to address these issue if the cell saver technique in processing CS blood before retransfusion is to establish its identity and role in the CPB surgery.


Deciphering molecular properties and docking studies of hepatitis C and non-hepatitis C antiviral inhibitors - A computational approach.
Hepatitis C is an infectious liver disease with high mortality rate which is caused by Hepatitis C virus. Several treatment methods have been applied to combat this deadly virus including interferons, vaccine and direct acting antivirals (DAAs). However, the later shows promising effects in HCV treatment with lower adverse effect. Specifically, the DAAs target the non-structural proteins (NS3 and NS5B). The objective of the present study is to hypothesize an alternative antiviral inhibitor for HCV from the available other antivirals. Computation of 2D molecular descriptors for the selected antiviral inhibitors followed by clustering the descriptor features. The closely clustered compounds were subjected to the interaction studies against the HCV target protein to validate the cluster result. The clustering result showed that indinavir (HIV inhibitor) and AT130 (HBV inhibitor) molecule are close to the HCV inhibitor. The indinavir complexed with NS3 protein shows -5.33kcal/mol and AT-130 complexed with NS5B protein possess the binding energy of -8.87kcal/mol. The docking interaction study indicated a better binding affinity than other viral inhibitors. From the descriptor based feature similarity analysis and the interaction study, it can be concluded that indinavir and AT-130 could be a potential alternative agent for HCV treatment.


Fabrication of an electrically-resistive, varistor-polymer composite.
This study focuses on the fabrication and electrical characterization of a polymer composite based on nano-sized varistor powder. The polymer composite was fabricated by the melt-blending method. The developed nano-composite was characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FeSEM), and energy-dispersive X-ray spectroscopy (EDAX). The XRD pattern revealed the crystallinity of the composite. The XRD study also showed the presence of secondary phases due to the substitution of zinc by other cations, such as bismuth and manganese. The TEM picture of the sample revealed the distribution of the spherical, nano-sized, filler particles throughout the matrix, which were in the 10-50 nm range with an average of approximately 11 nm. The presence of a bismuth-rich phase and a ZnO matrix phase in the ZnO-based varistor powder was confirmed by FeSEM images and EDX spectra. From the current-voltage curves, the non-linear coefficient of the varistor polymer composite with 70 wt% of nano filler was 3.57, and its electrical resistivity after the onset point was 861 KΩ. The non-linear coefficient was 1.11 in the sample with 100 wt% polymer content. Thus, it was concluded that the composites established a better electrical non-linearity at higher filler amounts due to the nano-metric structure and closer particle linkages.


MANF Is Required for the Postnatal Expansion and Maintenance of Pancreatic β-Cell Mass in Mice.
Global lack of mesencephalic astrocyte-derived neurotropic factor (MANF) leads to progressive postnatal loss of β-cell mass and insulin-dependent diabetes in mice. Similar to Manf-/- mice, embryonic ablation of MANF specifically from the pancreas results in diabetes. In this study, we assessed the importance of MANF for the postnatal expansion of pancreatic β-cell mass and for adult β-cell maintenance in mice. Detailed analysis of Pdx-1Cre+/- ::Manffl/fl mice revealed mosaic MANF expression in postnatal pancreata and a significant correlation between the number of MANF-positive β-cells and β-cell mass in individual mice. In vitro, recombinant MANF induced β-cell proliferation in islets from aged mice and protected from hyperglycemia-induced endoplasmic reticulum (ER) stress. Consequently, excision of MANF from β-cells of adult MIP-1CreERT::Manffl/fl mice resulted in reduced β-cell mass and diabetes caused largely by β-cell ER stress and apoptosis, possibly accompanied by β-cell dedifferentiation and reduced rates of β-cell proliferation. Thus, MANF expression in adult mouse β-cells is needed for their maintenance in vivo. We also revealed a mechanistic link between ER stress and inflammatory signaling pathways leading to β-cell death in the absence of MANF. Hence, MANF might be a potential target for regenerative therapy in diabetes.


Corticosteroids inhibit lymphocyte binding to endothelium and intercellular adhesion: an additional mechanism for their anti-inflammatory and immunosuppressive effect.
Glucocorticosteroids (GCS) are potent anti-inflammatory and immunosuppressive agents widely used in the treatment of many medical conditions, but their mechanism of action is not yet fully understood. Some of the anti-inflammatory effects of GCS have been attributed to the synthesis of lipocortins, whereas the immunosuppressive effects are thought to be mediated through the inhibition of several immune functions through a down-regulation of cytokine gene expression. Another important mechanism of action of GCS may relate to their ability to interfere with the phenomena of adhesion and migration of inflammatory cells. In this study, the direct effects of GCS on lymphocyte adhesion capacity in vitro were investigated. We demonstrate that GCS inhibit lymphocyte adhesion to endothelium through the down-modulation of lymphocyte adhesion molecules. We also provide evidence that GCS inhibit cell aggregate formation induced by TCR ligation, which directly correlates with the down-modulation of LFA-1 and CD2, but not LFA-3 or ICAM-1. Such down-modulation was paralleled by a decrease in the steady state mRNA level of LFA-1 and CD2 gene products, which suggests a direct GCS control of the expression of these genes. Finally, we show that GCS effects are mediated through the GCS receptor, since they can be completely reversed by the GCS-R antagonist RU-486. This study supports the concept that some of the immunosuppressive and anti-inflammatory effects of GCS are likely to be exerted by the inhibition of adhesion-dependent lymphocyte functions.


Institutionalization of Migration Policy Frameworks in Armenia, Azerbaijan and Georgia.
This article is a comparative study of the institutionalization of the migration policy frameworks of post-Soviet states Armenia, Azerbaijan and Georgia since the collapse of the Soviet Union in 1991. All three countries share common historical legacies: a Soviet past, wars and conflicts, unemployment, high emigration, and commitment to integration into European bodies. To what extent do the migration policies of these three countries (driven by contextual forces, i.e. domestic challenges) address country-specific migration dynamics? Or are they imposed by the European Union? In which dimensions have the national policies on migration of Armenia, Azerbaijan and Georgia evolved, and around which issues have they converged or diverged? Have these trends led to an integration of migration policymaking at the regional level in the South Caucasus?


Assisted hatching.
Assisted hatching entails the opening or thinning of the zona pellucida before embryo transfer in order to improve the results of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). The technique can be performed mechanically, chemically or with a laser beam. A piezoelectric method has also been described. Meta-analyses of randomised trials have shown that assisted hatching increases the clinical pregnancy, implantation and on-going pregnancy rates in patients with poor prognosis for IVF and ICSI, particularly those with repeated implantation failure. The technique is not without risks, and has been associated with an increased incidence of monozygotic twinning. Nevertheless, it remains an invaluable tool in assisted reproductive technology.


Trimanual Anterior Vitrectomy: A Novel Technique to Manage Vitreous Loss during Phacoemulsification.
We report 2 cases illustrating the use of a new technique to manage vitreous loss during phacoemulsification, which we have termed 'trimanual' anterior vitrectomy. In each case, after recognizing posterior capsule tear, the remaining nuclear pieces were removed with low-parameter phacoemulsification. The remaining cortical material was then removed using bimanual irrigation and aspiration handpieces while the assistant surgeon inserted the vitrectomy probe through a separate 1-mm limbal incision. The vitrectomy probe was held below the plane of the posterior capsule tear, used to cut the vitreous and to provide a mechanical blockade to potentially descending lens material. While this technique involves the potentially awkward simultaneous use of 3 intraocular instruments, we believe that there are several advantages over standard bimanual anterior vitrectomy.


[Comparative temperature measurement by thermoprobes and infrared pyrometry in the rewarming of frozen kidneys using short wave generators].
Mini pigs' kidneys were frozen to -20 degrees C after initial hypothermic perfusion and cryopreparation with dimethyl sulphoxide. They were subsequently thawed out with short-wave radiation. During this procedure continuous temperature measurement is only possible using infra-red pyrometry without physical contact. After completion of short-wave irradiation at ca. 4 degrees C the surface and internal temperatures are measured with thermoelements. In comparison with measurement by thermoprobes, infra-red pyrometry proves to be quite practicable, with certain limitations. If a homogeneous distribution of temperature in the organ is assumed; the internal temperature could be calculated from the surface temperature. Also, continuous observation of temperature changes ist possible.


Effect of gonadal steroid hormone levels during pubertal development on social behavior of adult mice toward pups and synaptic transmission in the rhomboid nucleus of the bed nucleus of the stria terminalis.
Sexually immature male mice exhibit parenting behavior toward unfamiliar pups; however, the percentage of males that engage in infanticidal behavior gradually increases with age. We previously reported that excitatory synaptic transmission of the rhomboid nucleus of the bed nucleus of the stria terminalis (BSTrh), a brain region implicated in infanticidal behavior, is reinforced during pubertal development. However, it remains unclear how gonadal steroid hormones mediate this behavioral transition and neural plastic change during pubertal development. Here we revealed that administration of either 17β-estradiol (E2) or 5α-dihydrotestosterone (DHT) to gonadectomized mice during pubertal development induced infanticidal behavior in adulthood (about 7 weeks old). Next, we performed whole-cell patch clamp recording in the BSTrh to study the effect of gonadal steroid hormones on neural synaptic transmission. We found that E2 but not DHT administration during pubertal development considerably enhanced excitatory synaptic transmission in the BSTrh by increasing the probability of excitatory neurotransmitter release from the presynaptic terminalis. These data suggest that reinforcement of excitatory synaptic transmission by estrogen-receptor-dependent signaling in the BSTrh during puberty may contribute to the development of infanticidal behavior.


Non-motor behavioural impairments in parkin-deficient mice.
Mutations in the parkin gene are the major cause of early-onset familial Parkinson's disease (PD). We previously reported the generation and analysis of a knockout mouse carrying a deletion of exon 3 in the parkin gene. F1 hybrid pa+/- mice were backcrossed to wild-type C57Bl/6 for three more generations to establish a pa-/-(F4) mouse line. The appearance of tyrosine hydroxylase-positive neurons was normal in young and aged pa-/- (F4) animals. Loss of parkin function in mice did not enhance vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. However, the pa-/- (F4) mice displayed impaired exploration and habituation to a new environment and exhibited thigmotaxis behaviour in the open field and Morris water maze. Abnormal anxiety-related behaviour of pa-/- (F4) mice was also observed in the light/dark exploration test paradigm. Dopamine metabolism was enhanced in the striatum of pa-/- (F4) mice, as revealed by increased homovanillic acid (HVA) content and a reduced ratio of dihydroxyphenylacetic acid (DOPAC)/HVA. The alterations found in the dopaminergic system could be responsible for the behavioural impairments of pa-/- (F4) mice. Consistent with a recent observation of cognitive dysfunction in parkin-linked patients with PD, our findings provide evidence of a physiological role of parkin in non-motor behaviour, possibly representing a disease stage that precedes dopaminergic neuron loss.


[Proliferative and secretory activity of human umbilical vein endothelial cells cultured under varying degrees of hypoxia].
In this study we examined the impact of 3-day hypoxia of varying degrees on the viability, proliferative and secretory activity of endothelial cells in human umbilical vein (HUVEC). The gas mixture of the three components (%) was used: 1) 10 O2, 5 CO2, 85 Ar; 2) 5 O2, 5 CO2, 90 Ar and 3) 1 O2, 5 CO2, 94 Ar. The HUVEC, cultivated in CO2-incubator under conditions of atmospheric oxygen (21% O2) were the controls. Comprehensive assessment of the results after has shown that 3-day HUVEC cultivating in the presence of 1% O2 led to pathological activation of endotheliocytes: increased NO synthesis combined with the marked secretion of endothelin-1, IL-6, IL-8 and TNF-alpha, sVCAM-1, sE-cadherin and of sE-selectin, VEGF-A and bFGF, and slow proliferation. When HUVEC were cultivated at 10% O2 and 5% O2, the level of basal secretion of the substances listed above was the least against the background of increased proliferative activity. The results showing the changes in the secretory activity of endothelial cells when cultivated under the conditions of atmospheric oxygen levels have demonstrate HUVEC activation, because the secretion of NO, IL-6, IL-8 and von Willebrand factor after 3 days of cultivation in 21% 02 exceeded that in the case of 10 and 5% O2. Thus, a gaseous medium with reduced oxygen content of up to 5% provides more physiological conditions for HUVEC cultivation. The maximum proliferative activity of HUVEC with minimal basal secretion proved such a composition to be comfortable. Increasing the oxygen content to the atmospheric level leads to the activation of endotheliocytes with signs of endothelial dysfunction, and the critical reduction in oxygen to 1% causes the development of endothelial dysfunction and reduces the proliferative potential.


APOE Alleles and Diet in Brain Aging and Alzheimer's Disease.
The APOE gene alleles modify human aging and the response to the diet at many levels with diverse pleotropic effects from gut to brain. To understand the interactions of APOE isoforms and diet, we analyze how cellular trafficking of apoE proteins affects energy metabolism, the immune system, and reproduction. The age-accelerating APOE4 allele alters the endosomal trafficking of cell surface receptors that mediate lipid and glucose metabolism. The APOE4 allele is the ancestral human allele, joined by APOE3 and then APOE2 in the human species. Under conditions of high infection, uncertain food, and shorter life expectancy, APOE4 may be adaptive for reducing mortality. As humans transitioned into modern less-infectious environments and longer life spans, APOE4 increased risks of aging-related diseases, particularly impacting arteries and the brain. The association of APOE4 with glucose dysregulation and body weight promotes many aging-associated diseases. Additionally, the APOE gene locus interacts with adjacent genes on chromosome 19 in haplotypes that modify neurodegeneration and metabolism, for which we anticipate complex gene-environment interactions. We summarize how diet and Alzheimer's disease (AD) risk are altered by APOE genotype in both animal and human studies and identify gaps. Much remains obscure in how APOE alleles modify nutritional factors in human aging. Identifying risk variant haplotypes in the APOE gene complex will clarify homeostatic adaptive responses to environmental conditions.


Pharmacologic treatment of acute pediatric methamphetamine toxicity.
To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.


Effects of acute blood pressure elevation on biochemical-metabolic parameters in individuals with hypertensive crisis.
Hypertensive crisis is a common clinical situation that presents a high rate of morbidity and mortality and it is characterized by symptomatic rise of blood pressure (BP), systolic (SBP) ≥ 180 mmHg and/or diastolic (DBP) ≥ 120 mmHg. It is classified as emergency (HE) or hypertensive urgency (HU). There is no description of laboratory findings in patients who present acute BP elevation. Thus, this study had the objective to assess the biochemical-metabolic parameters of patients with HC. We studied 74 normotensive individuals (NT), 74 controlled hypertensive patients (ContrHT), 50 subjects with HU, and 78 with HE for evaluating biochemical-metabolic parameters. HE occurs in older individuals and more frequently in those with known hypertension. More patients with HE had dyslipidemia than those with HU (58% vs. 38%). The diastolic BP and heart rate were higher in the HE group (120 mmHg and 87 bpm) compared to ContrHT (71 mmHg and 71 bpm; p < 0.0001) and NT groups (75 mmHg and 68 bpm; p < 0.0001). Glycemia was higher in HE vs. NT and ContrHT (p < 0.05). HDL cholesterol was lower in HE than NT (p = 0.0088). Potassium was lower in HE vs. NT, ContrHT and HU groups (p < 0.05). Creatinine was higher in the HC group vs. NT and ContrHT (p < 0.05). The GFR was significantly lower in HE group vs. HU, ContrHT and NT (p < 0.001). In conclusion, individuals with HC show biochemical alterations when compared to ContrHT and NT. Acute BP elevations are associated with hyperglycemia, dyslipidemia, and higher potassium and creatinine levels and lower renal function. Abbreviations BMI = body mass index BP = blood pressure CH = hypertensive crisis ContrHT = controlled hypertensive DBP = diastolic blood pressure GFR = glomerular filtration rate HbA1c = glycated hemoglobin HDLc = high-density lipoprotein cholesterol HE = hypertensive emergency HPLC = high-performance liquid chromatography HR = heart rate HU = hypertensive urgency JNC 7 = VII Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure LDLc = low-density lipoprotein cholesterol MDRD = Modification of Diet in Renal Disease NT = normotensive RASB = renin-angiotensin system blockers SBP = systolic blood pressure TC = total cholesterol TG = triglycerides.


Tetra-aqua-bis-[2-(2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)acetato]-zinc.
The Zn(II) ion in the title compound, [Zn(C(9)H(6)NO(4))(2)(H(2)O)(4)], is located on an inversion center and is octa-hedrally coordinated by two 2-(2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)acetate anions in axial sites and four water mol-ecules in equatorial positions. In the crystal, O-H⋯O hydrogen bonds between the coordinated water mol-ecules and carbon-yl-carboxyl-ate O atoms lead to pleated sheets parallel to (001).


Final infarct volume discriminates outcome in mild strokes.
Knowledge of whether final infarct volume (FIV) predicts disability after mild stroke is limited. We sought to determine if FIV could differentiate good versus poor outcome after mild stroke. We retrospectively identified 65 patients with mild stroke (National Institutes of Health Stroke Scale≤5) in a multicenter registry of 2453 patients. We evaluated associations between FIV and clinical outcome and evaluated the optimal FIV threshold that discriminated favorable (modified Rankin scale (mRS) 0-1) versus poor (mRS 2-6) outcome. The FIV cut-point of 20 mL differentiated favorable and poor outcomes (area under curve (AUC) 0.73, 95% confidence interval: 0.58-0.88). Favorable outcome was observed in 37/45 (82%) with FIV<20 mL, compared to 5/14 (36%) with FIV≥20 mL (p<0.01). FIV≥20 mL remained strongly associated with poor outcome independent of age, gender, stroke severity, Alberta Stroke Program Early CT Score (ASPECTS), and proximal arterial occlusion. In our small sample size, an FIV of 20 mL best differentiated between the likelihood of good versus poor outcome in patients with mild stroke. Further validation of infarct volume as a surrogate marker in mild stroke is warranted.


Mechanism of high-affinity potassium uptake in roots of Arabidopsis thaliana.
Potassium is a major nutrient in higher plants, where it plays a role in turgor regulation, charge balance, leaf movement, and protein synthesis. Terrestrial plants are able to sustain growth at micromolar external K+ concentrations, at which K+ uptake across the plasma membrane of root cells must be energized despite the presence of a highly negative membrane potential. However, the mechanism of energization has long remained obscure. Therefore, whole-cell mode patch clamping has been applied to root protoplasts from Arabidopsis thaliana to characterize membrane currents resulting from the application of micromolar K+. Analysis of whole cell current/voltage relationships in the presence and absence of micromolar K+ enabled direct testing of K+ transport for possible energization by cytoplasmic ATP and the respective trans-membrane gradients of Na+, Ca2+, and H+. Subtracted current/voltage relations for K(+)-dependent membrane currents are independent of ATP and reverse at potentials that imply H(+)-coupled K+ transport with a ratio of 1 H+:K+. Furthermore, the reversal potential of the K+ current shifts negative as external H+ activity is decreased. K(+)-dependent currents saturate in the micromolar concentration range with an apparent Km of 30 microM, a value in close agreement with previously reported Km values for high-affinity K+ uptake. We conclude that our results are consistent with the view that high-affinity K+ uptake in higher plants is mediated by a H+:K+ symport mechanism, competent in driving K+ accumulation to equilibrium ratios in excess of 10(6)-fold.


Parental evaluation of quality of life measures following pediatric dental treatment using general anesthesia.
The purpose of this study was to examine (a) parental satisfaction with the dental care their child received under general anesthesia, and (b) perception of the impact of this care on physical and social quality of life. The sample included 45 children (median age 50 months, 26 boys and 19 girls). Data were collected using a 1-page survey instrument completed by the parent at the first follow-up appointment. Dichotomous dependent variables were developed to measure parental satisfaction, dental outcome, and social impact of treatment. There was an overwhelmingly positive impression with dental outcomes (pain relief and improved masticatory efficiency). Parental perceptions in the social dimension were also positive. Parents reported more smiling, improved school performance, and increased social interaction. Relative to overall health, the majority of parents reported an improvement. Logit regression analysis revealed that absence of pain (P < .05) and increased social interaction (P < .01) had a significant impact on parents' perception of overall health. Our findings indicate that dental care under general anesthesia for preschool children has a high degree of acceptance by parents and is perceived to have a positive social impact on their child.


Palliative care and its emerging role in Multiple System Atrophy and Progressive Supranuclear Palsy.
Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are sporadic, neurodegenerative conditions and belong to a group known as the atypical Parkinsonian disorders. The atypical Parkinsonian (AP) disorders have some features of idiopathic Parkinson's disease (PD) but often with poor or transient levodopa response [1], distinct symptom profiles, more rapid progression and reduced survival. They have significant symptom burden [2]. It is beginning to be appreciated that AP disorders not only carry a heavy symptom burden equivalent to that of patients with advanced cancer but that AP patients experience significant morbidity for an extended period of time. PSP and MSA patients reach clinical milestones such as wheelchair-dependence or frequent falls early in the course of their disease and can live with these accumulating burdens for some years [3]. The acknowledgement of the benefits of emphasizing quality of life in progressive disorders and the growing evidence for palliative care need in non-malignant conditions suggests that MSA and PSP would benefit from an integrated palliative approach. Studies to determine palliative need and possibility of benefit from intervention are beginning to yield results in Parkinsonian conditions. This review aims to discuss the trajectory of disease in MSA and PSP, explore significant symptoms and summarize some evidence which exists for palliative care need and quality of life in these conditions. The challenges of a palliative approach with this group including advance care planning will also be discussed.


WHEN MORPHOLOGY MISLEADS: INTERPOPULATION UNIFORMITY IN SEXUAL SELECTION MASKS GENETIC DIVERGENCE IN HARLEQUIN BEETLE-RIDING PSEUDOSCORPION POPULATIONS.
Differences in secondary sexual characteristics of males often provide the most conspicuous means of distinguishing between closely related species. Does this therefore imply that the absence of differentiation in exaggerated male traits between allopatric populations provides evidence of a single, genetically cohesive species? We addressed this question with a comprehensive investigation of two populations (French Guiana and Panama) of the harlequin beetle-riding pseudoscorpion, Cordylochernes scorpioides. This highly sexually dimorphic pseudoscorpion is currently described as a single species, ranging throughout the Neotropics. Our morphometric analyses detected minimal differentiation between the two populations in all nine external morphological characters measured, including sexually dimorphic traits in males. Only in traits of the spermatophore was there any appreciable level of differentiation. Behavior differentiation and prezygotic reproductive isolation were also limited: 78.3% of males successfully transferred sperm to "foreign" females, and in 63.9% of these cases, females' eggs were successfully fertilized. By contrast, extensive divergence existed in two of nine electrophoretic loci, including an essentially fixed-allele difference at the Ldh locus. Most significantly, postzygotic reproductive isolation was complete, with heteropopulation zygotes invariably aborting early in development. These results strongly suggest that the two populations are, in fact, sibling species, a conclusion supported by our recently published findings on their marked divergence in minisatellite DNA. How can such interpopulation homogeneity in male sexually dimorphic traits exist in the face of strong genetic divergence? We propose that sexual selection, oscillating between favoring small and then large males, maintains such high levels of male variability within each population that it has obscured a speciation event in which genetic divergence and postzygotic incompatibility have clearly outpaced the evolution of prezygotic reproductive isolation.


Abiotic and biotic stresses and changes in the lignin content and composition in plants.
Lignin is a polymer of phenylpropanoid compounds formed through a complex biosynthesis route, represented by a metabolic grid for which most of the genes involved have been sequenced in several plants, mainly in the model-plants Arabidopsis thaliana and Populus. Plants are exposed to different stresses, which may change lignin content and composition. In many cases, particularly for plant-microbe interactions, this has been suggested as defence responses of plants to the stress. Thus, understanding how a stressor modulates expression of the genes related with lignin biosynthesis may allow us to develop study-models to increase our knowledge on the metabolic control of lignin deposition in the cell wall. This review focuses on recent literature reporting on the main types of abiotic and biotic stresses that alter the biosynthesis of lignin in plants.


The paediatric clinic as negotiated social space.
Contemporary urban diversity combined with increasing specialisation in tertiary care, technological innovations, and complexity of pathologies, render patient-physician relations challenging for both patients and practitioners. Based on ongoing research in a university paediatric hospital in Montreal, this paper examines how patient-physician relations are played out in the space of the clinic in which a set of social, cultural, structural and asymmetrical relations intertwine. Through an ethnographic approach, which includes the observation of multi-disciplinary clinical settings as well as interviews with clinicians and families (migrants and non-migrants), the paper examines how the 'images' of both the patient (his family) and the physician play an active role in the clinical encounter. Interpretations of parental attitudes by practitioners are linked to their perceived background within the local and institutional configuration of norms and values, including the notion of a 'good parent'. This research problematises the concept of culture as it is engaged by clinicians (by excluding their own) and promotes reflection on an anthropologically informed clinical practice.


High Trap Formation and Low Metabolite Production by Disruption of the Polyketide Synthase Gene Involved in the Biosynthesis of Arthrosporols from Nematode-Trapping Fungus Arthrobotrys oligospora.
A group of morphology regulatory arthrosporol metabolites have been recently characterized from carnivorous fungus Arthrobotrys oligospora that can develop trapping networks to capture their prey. A combination of genetic manipulation and chemical analyses was applied to characterize the function of one polyketide synthase (PKS) gene AOL_s00215g283 in A. oligospora, which was putatively involved in the production of 6-methylsalicylic acid. High-performance liquid chromatography analysis showed that the disruption of the PKS gene not only led to the total loss of the arthrosporol A but also resulted in significant reduction in the production of secondary metabolites in the cultural broth of the mutant ΔAOL_s00215g283 strain. Interestingly, the mutant strain displayed significant increases in the trap formation and the nematicidal activity by 10 and 2 times, respectively, higher than the wild-type strain. These findings revealed a pathogenicity-related biosynthetic gene of this agriculturally important biological agent and have implications for establishment of efficient fungal biocontrol agents.


Modeling high-biomass-density cell recycle fermentors.
Since intrinsic models, which take into account cell volume fraction, follow from proper application of the law of conservation of mass to a multiphase system, the intrinsic modeling approach should be used whenever biomass occupies a significant volume fraction of the culture. A recent report(11) offers the first comparison of intrinsic and nonintrinsic model predictions to actual experimental data gathered from a high-density yeast recycle fermentor. Here, the analysis of Jarzebski et al.(11) has been carried further to show that the improper nonintrinsic model predicts a steady-state culture glucose concentration that differs from that given by the fundamentally correct intrinsic model by over 60% at the optimal, bleed stream flow rate. In addition, a revised formulation for an intrinsic ethanol mass balance is presented.


Inoculation with Actinobacteria spp. Isolated from a Hyper-Arid Environment Enhances Tolerance to Salinity in Lettuce Plants (Lactuca sativa L.).
Irrigated agriculture is responsible for a third of global agricultural production, but the overuse of water resources and intensification of farming practices threaten its sustainability. The use of saline water in irrigation has become an alternative in areas subjected to frequent drought, but this practice affects plant growth due to osmotic impact and excess of ions. Plant-growth-promoting rhizobacteria (PGPR) can mitigate the negative impacts of salinity and other abiotic factors on crop yields. Actinobacteria from the hyper-arid Atacama Desert could increase the plant tolerance to salinity, allowing their use as biofertilizers for lettuce crops using waters with high salt contents. In this work, rhizosphere samples of halophytic Metharme lanata were obtained from Atacama Desert, and actinobacteria were isolated and identified by 16S gene sequencing. The PGPR activities of phosphate solubilization, nitrogen fixation, and the production of siderophore and auxin were assessed at increasing concentrations of NaCl, as well as the enhancement of salt tolerance in lettuce plants irrigated with 100 mM of NaCl. Photosynthesis activity and chlorophyll content, proline content, lipid peroxidation, cation and P concentration, and the identification and quantification of phenolic compounds were assessed. The strains S. niveoruber ATMLC132021 and S. lienomycini ATMLC122021 were positive for nitrogen fixation and P solubilization activities and produced auxin up to 200 mM NaCl. In lettuce plants, both strains were able to improve salt stress tolerance by increasing proline contents, carotenoids, chlorophyll, water use efficiency (WUE), stomatal conductance (gs), and net photosynthesis (A), concomitantly with the overproduction of the phenolic compound dicaffeoylquinic acid. All these traits were positively correlated with the biomass production under saltwater irrigation, suggesting its possible use as bioinoculants for the agriculture in areas where the water resources are scarce and usually with high salt concentrations.


Resistance Profile of Neisseria gonorrhoeae in KwaZulu-Natal, South Africa Questioning the Effect of the Currently Advocated Dual Therapy.
We report on the antimicrobial resistance profile of Neisseria gonorrhoeae isolates and the distribution of tetM genes in isolates with high-level tetracycline resistance in KwaZulu-Natal, South Africa. Male and female patients presenting with urethral and/or vaginal discharge were recruited into the study. Urethral and cervical secretions were cultured on New York City agar. Confirmatory tests for N. gonorrhoeae included Gram stain, catalase, oxidase, and carbohydrate utilization tests. Beta-lactamase was tested by means of the chromogenic cephalosporin test. Minimum inhibitory concentrations were determined using agar dilution with multipoint inoculation. Polymerase chain reaction with gel electrophoresis was used to detect the presence and type of the tetM gene. N. gonorrhoeae was isolated from the specimens of 319 (26%) of the 1220 recruited patients. Of these 319 isolates, 71% were resistant to 3 or more drugs. Resistance to azithromycin was found in 68% of the isolates. All isolates showed high-level tetracycline resistance with minimum inhibitory concentration values of 16 and 32 mg/mL. The tetM gene was present in 293 (92%). The American type was found in 264 (90%) and the Dutch type in 29 (10%). Twenty-six (8%) did not carry a tetM gene. The current syndromic management with dual ceftriaxone and azithromycin is due to the high level of azithromycin resistance factually single-drug therapy. High-level tetracycline resistance based on a resistance mechanism other than ribosome protection by the tetM gene product is present in N. gonorrhoeae infecting South African patients.


Removal of geosmin and 2-methylisoborneol by biological filtration.
The quality of drinking water is sometimes diminished by the presence of certain compounds that can impart particular tastes or odours. One of the most common and problematic types of taste and odour is the earthy/musty odour produced by geosmin (trans-1, 10-dimethyl-trans-9-decalol) and MIB (2-methylisoborneol). Taste and odour treatment processes including powdered activated carbon, and oxidation using chlorine, chloramines, potassium permanganate, and sometimes even ozone are largely ineffective for reducing these compounds to below their odour threshold concentration levels. Ozonation followed by biological filtration, however, has the potential to provide effective treatment. Ozone provides partial removal of geosmin and MIB but also creates other compounds more amenable to biodegradation and potentially undesirable biological instability. Subsequent biofiltration can remove residual geosmin and MIB in addition to removing these other biodegradable compounds. Bench scale experiments were conducted using two parallel filter columns containing fresh and exhausted granular activated carbon (GAC) media and sand. Source water consisted of dechlorinated tap water to which geosmin and MIB were added, as well as, a cocktail of easily biodegradable organic matter (i.e. typical ozonation by-products) in order to simulate water that had been subjected to ozonation prior to filtration. Using fresh GAC, total removals of geosmin ranged from 76 to 100% and total MIB removals ranged from 47% to 100%. The exhausted GAC initially removed less geosmin and MIB but removals increased over time. Overall the results of these experiments are encouraging for the use of biofiltration following ozonation as a means of geosmin and MIB removal. These results provide important information with respect to the role biofilters play during their startup phase in the reduction of these particular compounds. In addition, the results demonstrate the potential biofilters have in responding to transient geosmin and MIB episodes.


[Vitamin D deficiency and osteoporosis in a rural population of Cordoba province, Argentina].
Vitamin D deficiency is defined when blood levels of 25-hydroxyvitamin D (25 (OH) D) is less than ng / mmol/L. The status of Vitamin D level is associated with clinical, pathological and physiological changes as increased of parathyroid hormone, bone remodeling, osteoporosis and increased risk of fractures. Moreover,vitamin D and its metabolites are known to be associated with multiple chronic diseases as diabetes mellitus, autoimmune, cardiovascular and neoplasia diseases. To assess the vitamin D status in a rural population of Córdoba Province in Argentina and its relation with bone mineral density. We prospectively studied 31 patients over 50 years old who live in a rural population of Pampa de Achala in Córdoba Province, Argentina. This city is located in Córdoba High mountains. Blood vitamin D levels were tested in 24 patients and Bone mineral density in 31 patients. Vitamin D level was determined by HPLC. The vitamin D level were considered normal between 20-50 ng/ml in the winter season and 20-80 ng/ml in the summer season. Bone mineral density of lumbar spine and femoral neck was measured by DXA GE LUNAR DPX-L, according to World Health organization classification (37). The data were analyzed by Spearman coefficient and Chi cuadrado. The vitamin D levels samples were available in 24 patients. Mean blood Vitamin D level was 24.54 ng /ml. 8 of them (33%) had vitamin D level less than 20ng/ ml. 83% (20) of the analysed patients had vitamin D level less than 30 ng/ml and only 4 patients has vitamin D level more than 30 ng/ml. Low bone mineral density of lumbar spine and femoral neck was found in 66 % of the patients. 19 % of the patients were diagnosed of lumbar spine and femoral neck osteoporosis and 29 % of them had lumbar spine meanwhile 25 % had femoral neck. There was not statistically significant association between vitamin D level and bone mineral density analysed by Chi Cuadrado (p<0.07). A significant association was found between blood vitamin D level and low bone mineral density of femoral neck (Spearman 0.51) CONCLUSIONS: Vitamin D insufficiency is high in the rural adult population of Pampa de Achala in Córdoba and it could be a major health problem in this population.


Eroticism in group psychotherapy: psychoanalytic reflections on desire, agony, and ecstasy.
To fully understand the complexities of eroticism in groups, it may be necessary to review a conceptual differentiation of desire and its allies: agony and ecstasy. This article suggests that psychoanalytic group psychotherapy is made for neither agony nor ecstasy. Sexual excitement maybe; eroticism and desire, yes; agony and ecstasy, no. While agony or ecstasy imply a threat to the survival of the group, eroticism and desire reaffirm its existence. In this manner the group may be converted into a theater where desire may be celebrated, while the threat of being dissolved in the depths or exaltation of agony and ecstasy is elaborated and worked through: "Desire is desire only if it succeeds in postponing something".


Involvement of Na+/Ca2+ exchanger in catecholamine-induced increase in intracellular calcium in cardiomyocytes.
Although sarcolemmal (SL) Na+/Ca2+ exchanger is known to regulate the intracellular Ca2+ concentration ([Ca2+]i), its involvement in catecholamine-induced increase in [Ca2+]i is not fully understood. To gain some information in this regard, isolated rat cardiomyocytes were treated with different agents, which are known to modify Ca2+ movements, in the absence or presence of a beta-adrenoceptor agonist, isoproterenol, and [Ca2+]i in cardiomyocytes was determined spectrofluorometrically with fura-2 AM. Treatment with isoproterenol did not alter [Ca2+]i in quiescent cardiomyocytes, whereas the ATP (purinergic receptor agonist)-induced increase in [Ca2+]i was significantly potentiated by isoproterenol. Unlike ryanodine and cyclopiazonic acid, which affect the sarcoplasmic reticulum function, SL L-type Ca2+ channel blockers verapamil and diltiazem, as well as a SL Ca2+-pump inhibitor, vanadate, caused a significant depression in the isoproterenol-induced increase in [Ca2+]i. The SL Na+/Ca2+ exchange blockers amiloride, Ni2+, and KB-R7943 also attenuated the isoproterenol-mediated increase in [Ca2+]i. Combination of KB-R7943 and verapamil showed additive inhibitory effects on the isoproterenol-induced increase in [Ca2+]i. The isoproterenol-induced increase in [Ca2+]i in KCl-depolarized cardiomyocytes was augmented by low Na+; this augmentation was significantly depressed by treatment with KB-R7943. The positive inotropic action of isoproterenol in isolated hearts was also reduced by KB-R7943. These data suggest that in addition to SL L-type Ca2+ channels, SL Na+/Ca2+ exchanger seems to play an important role in catecholamine-induced increase in [Ca2+]i in cardiomyocytes.


Gender comparisons in children with ASD entering early intervention.
Males are diagnosed with Autism Spectrum Disorder (ASD) approximately four times as often as females. This has led to interest in recent years of potential under-diagnosis of females, as well as negative consequences for females with ASD due to under-identification. A number of potential explanations for gender bias in diagnosis are discussed including that females and males may present differently despite showing the same core symptoms. Previous research has shown inconsistent findings in comparisons between genders in young children with ASD for whom early intervention is vital. Thus, the aim of the present study was to investigate the social, communication, and cognitive functioning, as well as level of ASD symptoms, in a cohort of children who presented for early intervention to inform understanding of gender differences in this population, as well as to inform understanding of the mechanisms by which gender bias may occur. Participants included 254 children (42 females) aged 29-74 months who completed measures of cognition, communication skills, adaptive behaviour, and ASD symptoms on entry to early intervention. Consistent with hypotheses, no significant gender differences were found both overall, and when split by functioning level. However, a similar ratio of males and females was found in both high- and low-functioning groups contrary to predictions. These results are consistent with some of the previous research that suggests gender differences may not be apparent in clinical samples at this young age. We highlight a need for further research that may use universal screening or longitudinal methods to understand the trajectory of development for females with ASD specifically. Such research could better inform timely and tailored intervention from the preschool years onwards.


[Comparison of different housing systems for laying hens in respect to economic, health and welfare parameters with special regard to organized cages (literature review)].
In conventional cages laying hens are subjected to restricted movement and a lack of ability to fulfil most of their natural behaviours. Thus, welfare and health of laying hens can be highly limited in conventional cages. Due to the rising criticism of conventional cages the EU passed a directive in 1999 (CEC, 1999) in order to ban conventional cages by the beginning of 2012. Because of this decision alternative housing systems like floor pens, aviaries or free range systems will gain importance in the future. In these housing systems laying hens have the opportunity to live out their natural behaviours to a higher extent. But also alternative housing systems have some disadvantages. Frequent infections leading to higher mortalities can be detected. Besides that egg production in alternative systems is often not so high and stable like in cages. Furnished cages and small-group-systems represent the attempt to retain the high economic and hygiene standards of conventional cages, while offering the hens the possibility to exercise and fulfil some of their natural behaviours. With regard to productivity, egg quality and bone strength this attempt seems to function, whereas keel bone deformities and the lack of ability to live out natural behaviours are still problems in furnished cages.


The interface between benzenes (C6H6;C6H5Cl;2-C6H4OHCl) and amorphous solid water studied with metastable impact electron spectroscopy and ultraviolet photoelectron spectroscopy (HeI and II).
Interfaces between films of benzenes (C(6)H(6);C(6)H(5)Cl;2-C(6)H(4)OHCl) and solid H(2)O on tungsten substrates were studied between 80 and 200 K with metastable impact electron spectroscopy (MIES) and ultraviolet photoelectron spectroscopy [UPS(HeI and II)]. The following cases were studied in detail: (i) Adsorption of the benzenes on solid water in order to simulate their interaction with ice particles, and (ii) deposition of water on benzene films in order to simulate the process of water precipitation. In all cases the prepared interfacial layers were annealed up to 200 K under in situ control of MIES and UPS. The different behavior of the interfaces for the three studied cases is traced back to the different mobilities of the molecules with respect to that of water. The interaction between H(2)O and the benzenes at the interfaces is discussed on the basis of a qualitative profile for the free energy of that component of the interface which has the larger mobility. Possible implications of the present results for atmospheric physics are briefly mentioned.


Visual field changes after vitrectomy with internal limiting membrane peeling for epiretinal membrane or macular hole in glaucomatous eyes.
To investigate visual field changes after vitrectomy for macular diseases in glaucomatous eyes. A retrospective review of 54 eyes from 54 patients with glaucoma, who underwent vitrectomy for epiretinal membrane (ERM; 42 eyes) or macular hole (MH; 12 eyes). Standard automated perimetry (Humphrey visual field 24-2 program) was performed and analyzed preoperatively and twice postoperatively (1st and 2nd sessions; 4.7 ± 2.5, 10.3 ± 3.7 months after surgery, respectively). Postoperative visual field sensitivity at each test point was compared with the preoperative value. Longitudinal changes in mean visual field sensitivity (MVFS) of the 12 test points within 10° eccentricity (center) and the remaining test points (periphery), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and ganglion cell complex (GCC) thickness, and the association of factors with changes in central or peripheral MVFS over time were analyzed using linear mixed-effects models. In addition, 45 eyes from 45 patients without glaucoma who underwent vitrectomy for epiretinal membrane (ERM; 34 eyes) or macular hole (MH; 11 eyes) were similarly examined and statistically analyzed (control group). In glaucomatous eyes, visual field test points changed significantly and reproducibly; two points deteriorated only at the center and twelve points improved only at the periphery. Central MVFS decreased (p = 0.03), whereas peripheral MVFS increased postoperatively (p = 0.010). In the control group, no visual field test points showed deterioration, and central MVFS did not change significantly after vitrectomy. BCVA improved, GCC thickness decreased, and IOP did not change postoperatively in both groups. The linear mixed-effects models identified older age, systemic hypertension, longer axial length, and preoperative medication scores of ≥2 as risk factors for central MVFS deterioration in glaucomatous eyes. Visual field sensitivity within 10° eccentricity may deteriorate after vitrectomy for ERM or MH in glaucomatous eyes.


Perceptions and experiences of first sexual intercourse in Australian adolescent females.
To better understand the factors that influence the initiation of first intercourse among adolescent females and to explore the context in which this occurs. A purposive sample of sexually active female teenagers aged between 14 and 19 years were recruited from sexual and reproductive health clinics across the Perth metropolitan area. Sixty-eight in-depth, semistructured interviews were conducted. Thematic analysis was employed to analyze the narrative data. Meanings and interpretations that emerged were constantly verified through subsequent inquiry. The degree of personal control over the factors that led to their first experience of intercourse determined how teenagers reflected upon the experience. Those who were "ready" were more likely to have delayed intercourse until they were comfortable with both when and with whom this occurred. In contrast, conforming to peer norms, coercion from sexual partners and being intoxicated were common reasons for premature and unwanted first experience of sexual intercourse. The explorative approach used in this study deepens current understanding of the factors influencing and associated with intercourse initiation, and how these reflect different aspects of adolescent development. In particular, the role of young peoples' sociocultural environment, including peer interaction and alcohol intoxication, alongside pressure from sexual partners in premature and unwanted sexual activity may assist in informing educational interventions of greater personal relevance and impact.


Origin of friction anisotropy on a quasicrystal surface.
Wearless friction force experiments [Science 309, 1354 (2005)10.1126/science.1113239] have recently demonstrated that tribological response in quasicrystals could be related to the exotic atomic structure of the bulk material. Here, by numerical simulations, we address the origin of the experimentally observed friction anisotropy on a twofold decagonal quasicrystal surface. We predict the distinct stick-slip patterns in the lateral force along the periodic and quasiperiodic directions, specifically exploring the temperature dependence that rules the transitions between single and multiple-slip regimes of motion.


DOSCATs: Double standards for protein quantification.
The two most common techniques for absolute protein quantification are based on either mass spectrometry (MS) or on immunochemical techniques, such as western blotting (WB). Western blotting is most often used for protein identification or relative quantification, but can also be deployed for absolute quantification if appropriate calibration standards are used. MS based techniques offer superior data quality and reproducibility, but WB offers greater sensitivity and accessibility to most researchers. It would be advantageous to apply both techniques for orthogonal quantification, but workflows rarely overlap. We describe DOSCATs (DOuble Standard conCATamers), novel calibration standards based on QconCAT technology, to unite these platforms. DOSCATs combine a series of epitope sequences concatenated with tryptic peptides in a single artificial protein to create internal tryptic peptide standards for MS as well as an intact protein bearing multiple linear epitopes. A DOSCAT protein was designed and constructed to quantify five proteins of the NF-κB pathway. For three target proteins, protein fold change and absolute copy per cell values measured by MS and WB were in excellent agreement. This demonstrates that DOSCATs can be used as multiplexed, dual purpose standards, readily deployed in a single workflow, supporting seamless quantitative transition from MS to WB.


Isolation and characterization of the cDNAs encoding two isoforms of subunit CIX of bovine cytochrome c oxidase.
The smallest subunit of bovine cytochrome c oxidase (CIX or VIII in different nomenclatures) occurs in two isoforms, a heart (H) form and a liver (L) form. The cDNAs for both of these forms have been isolated and sequenced. The cDNA for the H form encodes a protein 70 amino acids long with a 24-residue presequence and a mature polypeptide of 46 amino acids; that of liver encodes a protein of 69 amino acids, a 25-residue presequence and a mature polypeptide of 44 amino acids. The leader sequences of the H and L forms are 40% homologous with an abundance of positively charged residues but no negatively charged amino acids. These features are typical of polypeptides targeted to the mitochondrion for processing in the matrix space. The homology of the two isoforms is 52% in the mature subunit with most of the differences occurring in the N-terminal hydrophilic domain of the protein. Evidence has been obtained of polymorphisms of both the H and L forms of the subunit. Protein chemical analyses show that the H isoform is the predominant if not the exclusive form of subunit CIX in heart and skeletal muscle tissue. The L form is the predominant form in liver, kidney, and brain. Northern analyses, using cDNAs to the two forms to screen whole cell RNA preparations, show that the transcript of the H isoform is present in heart and skeletal muscle but not in other tissues examined. The mRNA of the L form was found in brain, kidney, and liver and also in heart and skeletal muscle. These results indicate that the synthesis of the H isoform of CIX is controlled transcriptionally while the L form is under post-transcriptional regulation at least in heart and muscle tissue.


Analysis of the CO2 and NH3 reaction in an aqueous solution by 2D IR COS: formation of bicarbonate and carbamate.
The two-dimensional (2D) infrared correlation spectra obtained from the reaction time- and concentration-dependent IR spectra elucidates the reaction of CO2 and NH3 in an aqueous solution for CO2 absorption. In the synchronous 2D correlation spectra, the interrelation of the proton with carbamate and bicarbonate indicates that the pH level affected the formation reactions of the two products. Furthermore, the interrelation of carbamate with bicarbonate confirmed the conversion of carbamate into bicarbonate with the release of protons (or the decrease of the pH). From the experimental results including the asynchronous 2D correlation spectra, the reaction of the CO2 and aqueous ammonia proceeded through the following steps: formation of carbamate, formation of bicarbonate, release of protons, and conversion of carbamate into bicarbonate. The analysis of the formation of carbamate and bicarbonate by 2D infrared correlation spectroscopy provides useful information on the reaction mechanism of CO2 and NH3 in aqueous solutions.


FLT3 antibody-based therapeutics for leukemia therapy.
Antibodies represent a unique class of therapeutics because of their high specificity toward a defined target antigen. Recent clinical success with antibody-based cancer therapeutics has led to an upsurge in the development of these agents. Antibodies directed against FLT3 represent a promising approach for the treatment of human leukemia. We discuss some basic aspects of antibody-based cancer therapeutics, including their mechanisms of action, with a focus on recent progress in the generation and development of anti-FLT3 antibodies as well as their therapeutic potentials in the treatment of human hematologic malignancies.


[Antibiotic Resistance of Microbial Isolates from Long-Term Healing Wounds Exposed to Light of Various Wave Lengths].
The data on inhibition of the growth of microorganisms of a characteristic spectrum and antibiotic resistance isolated from long-term healing wounds by light of various wave ranges are presented. The growing cultures on blood agar were exposed to polarized light, red and infrared, ultraviolet of medium- and short-wave continuous modes accustomed in physiotherapy of wounds.The effect of light in some way induced inhibition of the growth, but complete recovery was stated only after the use of ultraviolet light when confirmed quantitatively in terms of the CFU.


Gold nanoparticles: A critical review of therapeutic applications and toxicological aspects.
Gold (Au) compounds have been utilized as effective therapeutic agents for the treatment of some inflammatory diseases such as rheumatoid arthritis. However, Au compound use has become limited due to associated high incidence of side effects. Recent development of nanomaterials for therapeutic use with Au-containing drugs is improving the beneficial actions and reducing toxic properties of these agents. Lower toxicity in conjunction with anti-inflammatory and antiangiogenic effects was reported to occur with gold nanoparticles (AuNP) treatment. However, despite this therapeutic potential, safety of AuNP remains to be determined, since the balance between therapeutic properties and development of adverse effects is not well established. Several variables that drive this benefit-risk balance, including physicochemical characteristics of nanoparticles such as size, shape, surface area, and chemistry, are poorly described in the scientific literature. Moreover, therapeutic and toxicological data were obtained employing nonstandardized or poorly described protocols with different experimental settings (animal species/cell type, route and time of exposure). In contrast, effective and safe application of AuNP may be established only after elucidation of various physicochemical properties of each specific AuNP, and determination of respective kinetics and interaction of compound with target tissue. This critical review conveys the state of the art, the therapeutic use, and adverse effects mediated by AuNP, with primary emphasis on anti-inflammatory and antiangiogenic potential, highlighting the limitations/gaps in the scientific literature concerning important points: (i) selection of experimental designs (in vitro and in vivo models) and (ii) consideration of different physicochemical properties of AuNP that are often disregarded in many scientific publications. In addition, prospects and future needs for research in this area are provided.


A Radiomics Approach to Assess High Risk Carotid Plaques: A Non-invasive Imaging Biomarker, Retrospective Study.
This study aimed to construct a radiomics-based MRI sequence from high-resolution magnetic resonance imaging (HRMRI), combined with clinical high-risk factors for non-invasive differentiation of the plaque of symptomatic patients from asyptomatic patients. A total of 115 patients were retrospectively recruited. HRMRI was performed, and patients were diagnosed with symptomatic plaques (SPs) and asymptomatic plaques (ASPs). Patients were randomly divided into training and test groups in the ratio of 7:3. T2WI was used for segmentation and extraction of the texture features. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were employed for the optimized model. Radscore was applied to construct a diagnostic model considering the T2WI texture features and patient demography to assess the power in differentiating SPs and ASPs. SPs and ASPs were seen in 75 and 40 patients, respectively. Thirty texture features were selected by mRMR, and LASSO identified a radscore of 16 radiomics features as being related to plaque vulnerability. The radscore, consisting of eight texture features, showed a better diagnostic performance than clinical information, both in the training (area under the curve [AUC], 0.923 vs. 0.713) and test groups (AUC, 0.989 vs. 0.735). The combination model of texture and clinical information had the best performance in assessing lesion vulnerability in both the training (AUC, 0.926) and test groups (AUC, 0.898). This study demonstrated that HRMRI texture features provide incremental value for carotid atherosclerotic risk assessment.


Procalcitonin levels in migraine patients.
Migraine is a risk factor for ischemic stroke. Sterile vascular inflammation may develop during migraine attacks. This study aims to investigate procalcitonin (PCT) levels amongst migraine patients as they are important markers for infection and sepsis, but can also be found at elevated levels in various cases of inflammation. Eighty adult migraine patients participated in our study. Patients were initially separated into two main groups; Group-1 consisted of 34 patients who had migraines during the attack period. Group-2 consisted of 46 patients during the period in-between attacks. Afterwards, patients were further divided into four subgroups based on their aura status; Group-1a Migraine without aura, 27 patients during attack period, Group-1b Migraine with aura, 7 patients during attack period, Group-2a Migraine without aura, 40 patients during the period in-between attacks, Group-2b Migraine with aura, 6 patients during the period in-between attacks. Average PCT levels in patients during attack periods were found to be higher than the average PCT levels of patients during the period in-between attacks. These elevated levels were determined to be statistically significant(p<0.01). Serum PCT levels of the patients with migraine without aura during the attack period were significantly higher than those of patients during the period in-between attacks(p<0.01). Based on significantly high levels of PCT, our results support the idea that sterile inflammation plays a role in migraine pathogenesis. Further studies are necessary to understand whether PCT is a marker for ischemic stroke risk in patients who go through frequent migraine attacks.


Disseminated candidiasis 18 years after renal transplantation.
Although mucocutaneous candidiasis is a common infection in renal transplant recipients, disseminated candidiasis is rare. Candida pnemonia causing miliary mottling on X-ray chest with the central nervous system involvement is still rarer. We report an unusual case with disseminated candidiasis that presented 18 years after renal transplantation and improved on conventional antifungal therapy; the relevant literature is reviewed.


Differentiation between porcine reproductive and respiratory syndrome virus isolates by restriction fragment length polymorphism of their ORFs 6 and 7 genes.
Three distinct antigenic profiles were identified by comparing the reactivities of 15 Canadian field isolates, the attenuated U.S. vaccine (Ingelvac MLV) strain and 2 European reference strains (Lelystad and Weybridge) of the porcine reproductive and respiratory syndrome virus (PRRSV) by indirect immunofluorescence with a set of 4 monoclonal antibodies to the nucleocapsid (N) protein and 2 other to the matrix (M) protein. In the present study, 9 Canadian isolates for which the sequences were determined appeared closely related to 2 U.S. reference strains (ATCC VR-2332 and ATCC VR-2385) with amino acid identities varying between 90 to 98% for the M and N proteins; substitutions in the nucleotide sequences were distributed randomly throughout the ORFs 6 and 7 genes, and most were 3rd base silent mutations. In comparison, more than 30% divergence was demonstrated with the Lelystad virus. Furthermore, differentiation between North American and European isolates, and between field isolates and the MLV strain could be achieved by cutting PCR-amplified products encompassing both ORFs 6 and 7 genes with 4 restriction endonucleases. When taken individually, BsaJI and AluI were the more appropriate restriction enzymes for distinguishing the vaccine strain from field isolates. The results obtained suggest that the restriction fragment length polymorphism of the genomic region covering the ORFs 6 and 7 genes may be a valuable tool to differentiate among PRRSV isolates.


1 alpha,25-dihydroxyvitamin D3 suppresses interleukin-1beta-induced interleukin-8 production in human whole blood: an involvement of erythrocytes in the inhibition.
Interleukin (IL)-8, which is involved in inflammatory responses, is produced by a variety of cell types, monocytes/macrophages and neutrophils, in response to inflammatory stimuli including lipopolysaccharide, IL-1, and tumor necrosis factor alpha. Here we report the inhibitory effects of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) on IL-8 production in human whole blood culture. 1,25(OH)2D3 inhibited only the late phase of the biphasic IL-8 production in lipopolysaccharide-stimulated human whole blood. It also effectively inhibited IL-8 production induced by IL-lbeta compared with that induced by tumor necrosis factor alpha. IL-8 mRNA expression in IL-lbeta-stimulated whole blood was found to require de novo protein synthesis. Although monocytes were found to be mainly responsible for IL-1beta-induced IL-8 production in whole blood, 1,25(OH)2D3 inhibited IL-8 production by isolated mononuclear cells only marginally. The inhibitory effect of 1,25(OH)2D3 on mononuclear cells was restored by adding erythrocytes. These results suggest that erythrocytes play a role in mediating the inhibitory effects of 1,25(OH)2D3 on IL-8 production in IL-1beta-stimulated whole blood.


Do Mammalian Cells Really Need to Export and Import Heme?
Heme is a cofactor that is essential to almost all forms of life. The production of heme is a balancing act between the generation of the requisite levels of the end-product and protection of the cell and/or organism against any toxic substrates, intermediates and, in this case, end-product. In this review, we provide an overview of our understanding of the formation and regulation of this metallocofactor and discuss new research on the cell biology of heme homeostasis, with a focus on putative transmembrane transporters now proposed to be important regulators of heme distribution. The main text is complemented by a discussion dedicated to the intricate chemistry and biochemistry of heme, which is often overlooked when new pathways of heme transport are conceived.