A Review of the Effect of Classroom Sound-Field Amplification on Children in Primary School.
Being able to hear the teacher clearly is an important factor for children's learning. However, classrooms often have suboptimal listening conditions. Sound-field amplification systems (SFAS) can help improve classroom listening conditions by increasing the level of the teacher's speech compared to the background noise throughout the classroom. The aim of this review article was to review the effect of SFAS on children in primary school. A comprehensive search of four online databases (ERIC, PubMed, Scopus, and Web of Science) was conducted. The search terms were classroom sound-field amplification and classroom amplified distribution system. Twenty-one articles were deemed relevant for the review plus an additional six from their references. Most articles were published between 1996 and 2015. Only one article was published since 2016. A range of child populations were studied including typically developing children and children with difficulties and disabilities such as hearing loss, developmental language disorders, attention-deficit/hyperactivity disorder, emotional and behavior disorders, Down syndrome, and developmental disabilities. There were several different measures that were used to evaluate the effectiveness of SFAS including speech perception assessments, language assessments, academic and comprehension assessments, classroom observations, interviews, and questionnaires. Improvements with SFAS were found for speech perception, listening comprehension and auditory analysis, language outcomes, academic outcomes, and behavior. SFAS can benefit children's listening and learning; however, the child's background, classroom reverberation time (limit to < 1 s), and layout and type of learning activities, especially in modern classrooms, need to be taken into consideration.


IgM anti-HBc in acute and chronic hepatitis B virus (HBV) infection: diagnostic value and correlation with viral replication and disease activity.
IgM antibody to hepatitis B core antigen (IgM anti-HBc) was determined in 348 subjects with hepatitis B virus infection, in order to evaluate, in an area of high hepatitis D virus (HDV) endemicity, its usefulness in discriminating acute HBV hepatitis from HDV superinfection of HBsAg carriers, and to see whether in chronic HBV infection IgM anti-HBc can be related to viral replication, disease activity, or risk of neoplastic transformation. The positive predictive value (PV) of IgM anti-HBc for acute hepatitis was low at the standard 2.1 cut-off (35.2%), but a cut-off of 7 raised the positive PV, retaining a negative PV of above 90% and a sensitivity of 59.5%. No significant relationship was found in chronic infection between IgM anti-HBc, the level of HBV replication or the type of liver disease. Patients with HDV infection were mostly IgM anti-HBc negative. Hepatocellular carcinoma was not associated with a raised prevalence of IgM anti-HBc.


Relationship between nutritional biomarkers and occlusal status in gastric cancer patients using the Eichner index: Observational study.
Systemic inflammatory responses and nutritional status are useful prognostic factors in gastric cancer patients. Since oral hypofunction causes undernutrition, we cross-sectionally investigated whether nutritional biomarkers were affected by the occlusal supporting zone status.In 114 gastric cancer patients, the gastric cancer stage, body mass index, albumin levels, total lymphocyte counts, cholesterol levels, C-reactive protein levels, and 4 nutritional biomarkers - the Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio, prognostic nutrition index (PNI), and controlling nutritional status (CONUT) - were evaluated. Oral conditions were assessed by determining the number of remaining teeth. The occlusal supporting status was based on the Eichner classification. Patients were assigned into 3 groups per their occlusal status, and mean values were compared using the Kruskal-Wallis test. The mean age and body mass index were 72.2 ± 8.5 (50-89) years and 22.0 ± 3.6 (14.8-33.4), respectively. There were 42, 39, 23, and 10 patients in stages I, II, III, and IV, respectively. The mean number of remaining teeth was 18.1 ± 9.5. According to the Eichner classification, there were 45, 42, and 27 patients in groups A, B, and C, respectively. The GPS and neutrophil-lymphocyte ratio values and CONUT frequencies between groups A and C were significantly different (P = .033, P = .00097, P = .04, respectively; Mann-Whitney U test). PNI values were lower in group C with poor occlusal support zones than in group A with stable occlusal support zones.Occlusal supporting zone reductions were undernutrition associated. Eichner Class C patients with few occlusal supporting zones had poor GPS, PNI, and CONUT values and were undernourished.


Surgical management of the severely contracted socket following reconstruction.
To present a surgical technique for the early maintenance of the severely contracted socket following reconstruction. Two patients with severely contracted sockets following multiple procedures and recurrent failure were identified over a 1 year period. Following fornix and eyelid reconstruction, silicone fixative was injected into the fornix through a standard conformer. The silicone fixed around a pre-placed K-wire passed from the lateral orbital rim to the posterior lacrimal crest. Both silicone and wire were removed at 3 months. Both patients were able to wear and maintain an acceptable prosthesis following the surgical procedure. This is a safe and effective method for the early maintenance of a severely contracted socket. This technique minimizes cheesewiring or extrusion and avoids damage to superior and inferior muscles and structures.


Static postural sway of women with and without fibromyalgia syndrome: A cross-sectional study.
There is a frequent complaint about balance problems among fibromyalgia syndrome patients; however, there are not enough studies that have shown static postural sway of women with fibromyalgia syndrome. This study aimed to compare static postural sway of women with and without fibromyalgia syndrome. This is a cross-sectional study in which twenty-nine women with fibromyalgia syndrome and 20 without took part. A posturography evaluation was performed in six different situations (bipedal, right tandem and left tandem, with eyes opened and closed), and questionnaires for clinical depression symptoms, clinical anxiety symptoms, sleep quality, and Visual Analogue Scales for Pain and Fatigue were applied. Mann-Whitney U test was used to check differences among groups; Wilcoxon matched-pair test was used to check differences intragroup; Cohen d coefficient was used to measure effect sizes and Pearson Correlation Coefficient was used for correlations among variables. Level of significance adopted was 5%. Women with fibromyalgia syndrome have presented worse postural sway than women without fibromyalgia syndrome in all situations (P<0.05), and worse scores in all questionnaires (P<0.05). In the eyes closed situations, women with fibromyalgia syndrome presented worse postural sway than women without in the same conditions. Women with fibromyalgia syndrome have worse performance in the static posture test, more prominent in reduced support bases with eyes closed. Pain, fatigue, depression and anxiety may have directly influenced postural sway in fibromyalgia syndrome patients.


Homeostatic control of lymphocyte survival: potential origins and implications.
Lymphocytes depend on extracellular ligands to maintain their viability. Structurally diverse lymphocyte receptors transmit survival signals through separate signal transduction cascades, which all share the ability to sustain viability by maintaining the sequestration of apoptogenic factors within mitochondria. Receptors can induce cellular survival either by promoting the expression and/or function of anti-apoptotic Bcl-2 family proteins or by activating the phosphatidylinositol-3 kinase Akt pathway. Either of these events represses the function of the pro-apoptotic proteins Bax and Bak, which are required for mitochondrial release of cytochrome c. As we discuss here, the apparently redundant functions of Bax and Bak may have evolved to prevent lymphocyte mitochondria from adapting to loss of receptor mediated signal transduction and thus keep lymphocytes from accumulating in a cell-autonomous manner.


Continuous insulin infusion reduces infectious complications in diabetics following coronary surgery.
This study was undertaken to evaluate the effects of a continuous insulin infusion protocol on postoperative infection and mortality. Patients who underwent coronary artery bypass grafting from January 1997 until December 1998 were included in this study (n = 761). A continuous insulin drip protocol (IDP) designed to titrate blood sugar levels to 120-160 mg/dL in the immediate postoperative period was instituted in 1998. Comparisons of diabetic and nondiabetic data before and after initiation of the IDP were made. Of the 761 patients who underwent coronary revascularization, diabetics accounted for 32%. There was no significant difference in age, gender, diabetic status, urgency of operation, or operative time between 1997 and 1998 diabetics and nondiabetics. Overall, wound infections occurred in 3% (23/761) of patients. In 1997, the infection rate was significantly higher in diabetics than nondiabetics (p = 0.0007). After initiation of the IDP in 1998, the infection rate for the diabetic population was reduced to that of the nondiabetic population. There was no significant difference in the mortality rate between 1997 diabetics (4%) and 1998 diabetics (5%) (p = 0.5759) or in the length of stay for 1997 diabetics versus nondiabetics (p = 0.1906). There were no mortalities among patients with wound infections. Initiation of the IDP and the subsequent tight control of blood sugars in the immediate postoperative period proved to reduce the incidence of wound infection in the diabetic population. There was no significant difference in the mortality rate or length of hospitalization.


Quantitative Analysis of Depth, Distribution, and Density of Cysts in Acanthamoeba Keratitis Using Confocal Microscopy.
To quantify the density, distribution, and depth of invasion of cysts in the corneas of eyes with acanthamoeba keratitis (AK) by in vivo confocal microscopy (IVCM) with a novel scanning pattern. The medical records of patients with AK evaluated at the Doheny Eye Center UCLA between September 2014 and July 2016 were reviewed retrospectively. Patients with clinically diagnosed AK underwent IVCM at various time points during their clinical course. Five corneal locations were scanned at each time point: the central area and 4 standard points on the peripheral cornea corresponding to temporal, nasal, inferior, and superior locations. The IVCM scans were manually graded to quantify the maximum depth of invasion and density of cysts. Twenty-one eyes of 18 patients with visible cysts on IVCM were included. Mean cyst density at presentation was 214.1 ± 120.2/mm (range: 64-484 cells/mm), and the average cyst depth was 164.3 ± 81.2 μm (range: 17-290 μm). In 17 eyes, the average cyst depth was 139.4 ± 68.6 μm (range: 17-245 μm), mean cyst density was 177.9 ± 99.6/mm, and an average of 1.4 ± 1.3 quadrants was infiltrated at presentation, and reached clinical resolution with medical treatment without surgical intervention. Four eyes that ultimately underwent therapeutic penetrating keratoplasty had cysts in all 4 quadrants and deeper cyst infiltration; the average cyst depth in these corneas was 270.5 ± 17.5 μm (range: 252-290). Eyes with AK requiring therapeutic keratoplasty were more likely to have a deeper and more diffuse penetration of cysts in the cornea compared with those resolving with medical treatment.


Swelling-induced modulation of static and dynamic fluctuations in polyacrylamide gels observed by scanning microscopic light scattering.
The nature of inhomogeneities in vinylpolymer gels has hardly been clarified yet. Inhomogeneities on submicron and nanometer scales in polyacrylamide gels have been investigated by using a scanning microscopic light-scattering system and applying a general formula for an ensemble-averaged correlation function. The network structure of the gels is modified by varying the preparation conditions and can be roughly divided into two types. Swelling-induced modulation of inhomogeneities depends on the type of the network structure. At low monomer concentrations in preparation, both submicron- and nanometer-scale inhomogeneities increase with swelling. At high monomer concentrations in preparation, submicron-scale inhomogeneities increase with swelling, but nanometer-scale inhomogeneities decrease anomalously. This behavior is explained by a model of inhomogeneous network structure of vinylpolymer gels, where macrogel is formed from a large number of microgel particles.


Impact performance of bicycle helmets.
Seven brands of bicycle helmets were compared by means of a drop test using an instrumented Hodgson-WSU headform, on the front (F), rear (R) and left side (LS) locations from a height of 1.0m and on the right front boss (RFB) from either 1.0m or 1.75m. Acceleration signals from the headform were computer processed to yield peak acceleration and the Gadd Severity Index (GSI). Significant differences between helmets and within helmets at different locations were found. Helmets with crushable polystyrene liners were much superior to those with soft foam liners. The superiority of the polystyrene liners disappeared however when helmets were subjected to two consecutive drops to the same location (R). The results also indicated that for most cases the GSI was between 800-1200 but there were two helmets that had values in excess of 1500. Clearly not all bicycle helmets provide equivalent levels of protection and some are much superior to others.


Brain irradiation leads to persistent neuroinflammation and long-term neurocognitive dysfunction in a region-specific manner.
Long-term cognitive deficits are observed after treatment of brain tumors or metastases by radiotherapy. Treatment optimization thus requires a better understanding of the effects of radiotherapy on specific brain regions, according to their sensitivity and interconnectivity. In the present study, behavioral tests supported by immunohistology and magnetic resonance imaging provided a consistent picture of the persistent neurocognitive decline and neuroinflammation after the onset of irradiation-induced necrosis in the right primary somatosensory cortex of Fischer rats. Necrosis surrounded by neovascularization was first detected 54 days after irradiation and then spread to 110 days in the primary motor cortex, primary somatosensory region, striatum and right ventricle, resulting in fiber bundle disruption and demyelination in the corpus callosum of the right hemisphere. These structural damages translated into selective behavioral changes including spatial memory loss, disinhibition of anxiety-like behaviors, hyperactivity and pain hypersensitivity, but no significant alteration in motor coordination and grip strength abilities. Concomitantly, activated microglia and reactive astrocytes, accompanied by infiltration of leukocytes (CD45+) and T-cells (CD3+) cooperated to shape the neuroinflammation response. Overall, our study suggests that the slow and gradual onset of cellular damage would allow adaptation in brain regions that are susceptible to neuronal plasticity; while other cerebral structures that do not have this capacity would be more affected. The planning of radiotherapy, adjusted to the sensitivity and adaptability of brain structures, could therefore preserve certain neurocognitive functions; while higher doses of radiation could be delivered to brain areas that can better adapt to this treatment. In addition, strategies to block early post-radiation events need to be explored to prevent the development of long-term cognitive dysfunction.


[The Library of Medicine of Córdoba, witness and protagonist of knowledge from the end of the 19th Century to the beginning of 21st Century].
In the nineteenth century, was founded the Medicine's Library of the National University Faculty of Medicine, center of knowledge, new ideas and teaching. The history library sector hold the valuable inheritance that represent the collection of Teachers Doctors, Pablo Mirizzi, Temístocles Castellano, Pedro Ara, José F. Verna, Juan Martín Allende located with the books and thesis of the XIX century and beginning of XX century. In 1986 it integrates the National Health Science Information Network and also, the Latino American and the Caribbean Health Science Information Network. The health libraries are in front of a new paradigm. The technologies of information and communication require new methods for administration of the information's resources and services, to answer the society information needs in the knowledge age. The traditional and virtual library is one unit that complement sources in different supports, electronic publications and interactive networks. It is the nexus between the scientific inheritance and the society, and it's mission is: Give local and virtual information's services and management the information's resources, basis of the knowledge society, support of teaching, investigation and extension of the Medical Sciences Faculty of the Córdoba National University.


TAR and Sp1-independent transactivation of HIV long terminal repeat by the Tat protein in the presence of human cytomegalovirus IE1/IE2.
The HIV Tat protein is a transcriptional transactivator of the HIV-1 long terminal repeat (LTR) promoter element. Its activity depends on its direct interaction with the trans-activation response (TAR) element, although TAR-independent activation by Tat has been demonstrated in different cells. Herpesviruses in general and human cytomegalovirus (HCMV) in particular are often isolated from HIV-1-infected patients and could play a role in the activation of latent HIV and in a subsequent increase in HIV replication. HCMV immediate early gene products (IE1 and IE2) are nuclear phosphoproteins that play a pivotal role in HCMV replication and have been shown to transregulate both viral and cellular gene expression. It has repeatedly been shown that HCMV IE1/IE2 can independently transactivate HIV-1 LTR. The aim of this study was to investigate IE1/IE2 transactivation of HIV-1 LTR in a CD4+ T-cell line in the absence and presence of HIV-1 Tat to establish whether IE1/IE2 can synergize with Tat. HIV-1 LTR transactivation by HCMV IE1/IE2 in the presence and absence of HIV-1 Tat was determined by transient transfection experiments of J-Jhan lymphoblastoid cells with a series of different expression vectors. We found a strong synergistic transactivation between HIV Tat and the IE1-IE2 complex on HIV LTR activity using vectors driven either by wild-type LTR or by the nuclear factor NF-kappa(B) response element-mutated HIV LTR. IE1/IE2 synergism with HIV Tat was also observed in Sp1 binding site-mutated for TAR-deleted LTR, which cannot be activated by Tat alone. This cooperation is abolished when the region in IE2 that binds the TATA box binding protein is deleted. The results obtained indicate that Sp1-binding and TAR sequences are not strictly required for Tat responsiveness when Tat is directed to the HIV promoter by HCMV IE1-IE2. This synergistic effect is mediated by the IE2 and TATA-binding region, and could play a major role in HIV activation when cells are infected by both viruses, a feature often observed in AIDS patients.


Cholecystokinin-1 receptor protein up-regulation during pancreatic regeneration after acute haemorrhagic pancreatitis in rats.
Cholecystokinin (CCK) plays an important role in regeneration after acute pancreatitis in rats. The present study was aimed to elucidate the role of CCK-1 receptor (CCK-1R) in acute pancreatitis. We investigated the serial changes in CCK-1R mRNA and protein levels and their immunolocalization after acute haemorrhagic pancreatitis induced in male Wistar rats by retrograde intraductal infusion of 4% sodium taurocholate (100 micro L 100 g(-1) body weight). Histological changes were evaluated by haematoxylin and eosin staining. Pancreatic CCK-1R mRNA was determined by Northern blot analysis. Pancreatic CCK-1R protein was evaluated by immunoblot analysis and immunohistochemistry with a polyclonal antibody against rat CCK-1R protein. Histological findings revealed that newly formed acinar cells were detected at the periphery of tubular complexes on day 14, and normal architecture of lobules was observed focally on day 21. Pancreatic CCK-1R mRNA peaked on day 3 and thereafter gradually decreased. Cholecystokinin-1R protein rapidly increased after induction of pancreatitits, reaching a maximal level on day 3. On day 3, intense immunoreactivity for CCK-1R protein was observed in both the cytoplasm of vacuolized acinar cells and the tubular complexes. In the regenerative process after acute haemorrhagic pancreatitis in rats, the expression of pancreatic CCK-1R mRNA and protein increased, and intense immunoreactivity for CCK-1R protein was observed in tubular complexes in the cytoplasm of regenerated acinar cells. These results suggest that CCK-1R contributes to pancreatic regeneration after acute haemorrhagic pancreatitis and that tubular complexes are involved in the process of acinar cell regeneration following pancreatic injury.


Pro-con debate on regionalization of emergency general surgery: controversy or common sense?
More than three million patients every year develop emergency general surgical (EGS) conditions and this number is rising. EGS diseases range from straightforward to potentially life-threatening, and if severe or complex may require extensive resources. Given the looming surgeon shortage and concerns about access to care, regionalization of EGS care, in a manner similar to trauma care, has been proposed. We present a unique pro-con debate highlighting the salient arguments for and against regionalization of EGS care in the USA.


Analysis of the risk transmission mechanism of monetary policy in the monetary and financial service sectors from the perspective of asset-liability management.
The Silicon Valley Bank crisis that occurred in March 2023 highlights the importance of studying the risk transmission mechanism underlying monetary policy. To explore this mechanism in the monetary and financial services sector from the perspective of asset-liability management, the relationships between asset- and liability-side risks and the corresponding action direction of those risks were empirically studied based on the risk-taking channel theory of monetary policy using publicly available information on 176 Chinese monetary and financial services companies covering the period of 2000 to 2022. The analysis shows that asset-side risks are transmitted through monetary policy as liability-side risks in the monetary and financial service sectors. If the liability side passively takes on these risks, the action direction of monetary policy to asset-side risks is determined; when the liability side actively takes on these risks, monetary policy exerts opposite effects on both types of risks. This conclusion somewhat deepens our understanding of the risk transmission mechanism of monetary policy, which is helpful in better formulating and implementing monetary policy.


Current status of endoscopic diagnosis and treatment for superficial non-ampullary duodenal epithelial tumors.
Though superficial non-ampullary duodenal epithelial tumors (SNADETs) have been traditionally considered rare, there is a growing detection under the development and widespread of endoscopic techniques in recent times. Many case studies have revealed early manifestations of lesions through advanced endoscopic technology, however, because of the low incidence of duodenal tumors and challenges in diagnosing, the preoperative diagnosis criteria have not been established so far. In spite of this, recently the increasing detection rate of early duodenal epithelial lesions enhances the demand for minimally invasive treatment as well. The most suitable therapeutic endoscopic modality to remove duodenal lesions should be selected according to the size, location and histological invasive depth of duodenal lesions. Nevertheless, due to the special anatomical structure of the duodenum, the incidence of complications is much higher than in any other part of the digestive tract. To prevent these adverse events prophylactically, a few novel strategies have been applied effectively after resection. This review describes the current status of preoperative endoscopic diagnosis and endoscopic resection approaches, as well as countermeasures for avoiding procedure-related complications.


Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells.
It is believed that P-glycoprotein (P-gp) is an energy-dependent drug efflux pump responsible for decreased drug accumulation in multidrug resistant (MDR) cells. In this study, we investigated whether azidopine, a photoactive dihydropyridine calcium channel blocker, is transported by P-gp in MDR Chinese hamster lung cells, DC-3F/VCRd-5L, and whether its binding site(s) on P-gp are distinct from those of Vinca alkaloids and cyclosporins. The efflux of azidopine from MDR cells was energy-dependent and inhibited by the cytotoxic agent vinblastine (VBL). Cyclosporin A (CsA), a modulator of MDR, also increased azidopine accumulation in MDR cells by decreasing the energy-dependent efflux of azidopine. P-gp in these cells was the only protein specifically bound to [3H]azidopine in photoaffinity experiments. The specific photoaffinity labeling of P-gp by [3H]azidopine was inhibited by CsA, SDZ 33-243, nonradioactive azidopine, and VBL with median concentrations (IC50) of 0.5, 0.62, 1.7, and 25 microM, respectively. The equilibrium binding of azidopine to plasma membranes of MDR variant DC-3F/VCRd-5L cells showed a single class of specific binding sites having a dissociation constant of 1.20 microM and a maximum binding capacity of 4.47 nmol/mg of protein. Kinetic analysis indicated that the inhibitory effect of VBL and CsA on azidopine binding to plasma membranes of MDR cells was noncompetitive, indicating that azidopine binds to P-gp at a binding site(s) different from the binding site(s) of these drugs.


Planococcus rifietensis sp. nov, isolated from algal mat collected from a sulfurous spring in Campania (Italy).
The taxomony of strain M8, isolated from algal mat formed at the origin of a sulfurous spring in Rifieto (Savignano Irpino, Campania, Italy), was investigated in a polyphasic approach. The morphological, physiological and genetic characteristics were compared with of Planococcus and Planomicrobium species. The isolate grew optimally at pH 9.0, 1.8 M NaCl at 37 degrees C. The cells were Gram-positive cocci that form pairs, tetrads and aggregates of several cells. The isolate was aerobic/microaerophilic and accumulated glycine-betaine, as a major osmolyte, with minor components glutamate and an unknown compound. M8 was able to hydrolyse X-Glc (5-bromo-4-chloro-3-indoyl beta-d-glucopyranoside). The polar lipid profile consisted of phosphatidylglycerol and diphosphatidylglycerol as major components, and phosphocholine as a minor compound. MK8 was the only quinone found and the fatty acid composition was dominated by branched acids, mainly aiC15:0. The G+C content of DNA was 47.9% and its phylogenetic position was established by 16S rRNA gene sequencing as a member of the genus Planococcus. The DNA/DNA similarity of M8 to the type species Planococcus citreus was less than 55%. For this reason and for physiological and chemotaxonomic features, it is proposed to create a new species Planococcus rifietensis sp. nov.


Black silicon significantly enhances phosphorus diffusion gettering.
Black silicon (b-Si) is currently being adopted by several fields of technology, and its potential has already been demonstrated in various applications. We show here that the increased surface area of b-Si, which has generally been considered as a drawback e.g. in applications that require efficient surface passivation, can be used as an advantage: it enhances gettering of deleterious metal impurities. We demonstrate experimentally that interstitial iron concentration in intentionally contaminated silicon wafers reduces from 1.7 × 1013 cm-3 to less than 1010 cm-3 via b-Si gettering coupled with phosphorus diffusion from a POCl3 source. Simultaneously, the minority carrier lifetime increases from less than 2 μs of a contaminated wafer to more than 1.5 ms. A series of different low temperature anneals suggests segregation into the phosphorus-doped layer to be the main gettering mechanism, a notion which paves the way of adopting these results into predictive process simulators. This conclusion is supported by simulations which show that the b-Si needles are entirely heavily-doped with phosphorus after a typical POCl3 diffusion process, promoting iron segregation. Potential benefits of enhanced gettering by b-Si include the possibility to use lower quality silicon in high-efficiency photovoltaic devices.


[Syndromic surveillance for the detection of outbreaks of unusual infectious diseases].
Syndromic surveillance has been developed in order to detect outbreaks of unusual infectious diseases such as severe acute respiratory syndrome (SARS) or anthrax at an early stage. Whereas the usual surveillance systems are based on established diagnoses and emergency department discharge data, syndromic surveillance uses preliminary outcomes and derived data such as absenteeism, prescription medication and requests for laboratory tests. Investigations abroad have indicated the potential ofsyndromic surveillance. In the Netherlands, the National Institute of Public Health and Environment (RIVM) is examining the feasibility of implementing syndromic surveillance.


Embryonic stem cell research: the relevance of ethics in the progress of science.
Experimentation with embryonic stem (ES) cells has become an important breakthrough in medical research. However, it is also a source of controversy, because it requires the destruction of the human embryos used to derive ES cells. This paper deals with some of the ethical issues concerning ES cell research. To begin with, the terms used in the debate on the ethical status of the human embryo need to be defined. Apart from the presumed benefits of ES cell research, we should also consider such issues as the strong opposition to this research by a large part of society, who argue in favour of protecting and respecting human embryos; the fragility and defenseless of human embryos; and the contradiction in terms inherent in the statement that human embryos must be treated with respect. Secondly, we should focus on possible conflicts between the financial, scientific, and ethical aspects of this debate. Thirdly, the significance of social and political debate requires clear and complete information that takes all consequences into account. Finally, the paper suggests how multipotent adult stem cell research may be an optimal and realistic alternative to ES cell research.


Fault diagnosis method and application based on unsaturated piecewise linear stochastic resonance.
Signal detection and processing have become an important way to diagnose mechanical faults. The classical bistable stochastic resonance (CBSR) method for signal detection can become saturated, where the amplitude of the output signal gradually stabilizes at a relatively low level instead of increasing with further increases of the input signal amplitude. This leads to difficulty in extracting the weak signals from strong background noise. We studied a new mechanism based on unsaturated piecewise linear stochastic resonance (PLSR). The piecewise linear potential model has a unique structure, which can independently adjust the barrier height and potential wall inclination, so the piecewise linear potential model has a rich potential structure. The rich potential structure makes the potential model unsaturated, thus ensuring that the output signals increase as the input signals increase. In addition, according to the piecewise linear model, the output signal-to-noise ratio (SNR) of the system is deducted. Analysis of the influence of signal strength, potential parameters, and angular frequency on the SNR shows that the optimal SNR can be obtained by adjusting the potential parameters. We propose a weak signal detection method for bearing fault diagnosis. This method can effectively extract the weak fault signals from rolling bearings in a strong noise background. The simulated and experimental bearing fault signals verify that the proposed PLSR method is superior to the CBSR method.


Serum lactate dehydrogenase isoenzyme 1 in patients with seminoma stage I followed with surveillance.
Serum lactate dehydrogenase isoenzyme I catalytic concentration (S-LD-1) was measured in patients with testicular seminoma clinical stage I followed with surveillance after orchiectomy. The serum samples were obtained before orchiectomy in 110 patients (group A) and soon after orchiectomy in 55 patients (group B). In group A, 60 patients (55%) had elevated S-LD-1 and 10 patients (9%) had elevated serum human chorionic gonadotropin concentrations (S-hCG). In group B, median S-LD-1 was lower than that of group A and decreased with increasing time after orchiectomv (p = 0.001, Jonckheere-Terpstra test, one-sided). After a median follow-up of 5.1 years, 23 patients (21%) in group A had relapses. The patients with elevated S-LD-1 and those with normal S-LD-1 had a similar relapse-free survival (p = 0.79, log-rank test). Thus patients with seminoma stage I had elevated S-LD-1 more often than elevated S-hCG but an elevation in S-LD-1 did not predict a relapse during follow-up with surveillance. Further studies are required to elucidate the value of S-LD-1 in monitoring the surveillance of patients with seminoma stage I.


Functional Analysis of Helicase Gene Promoter and Homologous Region 3 Enhancer in Bombyx mori Nuclear Polyhedrosis Virus.
The promoter of the helicase gene, including 510 bp upstream of ATG,was cloned and sequenced, and was found that it had both early and late RNA initiation sites. The initiation codon ATG was deleted by using point mutation. Luciferase gene, as a reporter gene, was fused with the promoter region to construct the plsmid pBm hel 510 luc. When pBm hel 510 luc was transfected into Bm-5 and Sf-21 cell lines, the helicase gene promoter was recognized by cellular RNA polymerase and transactivated by viral factors. Baculovirus homologous regions (hrs) act as viral DNA replication start sites, which also have been shown to alter the rate of transcription for cis-linked promoters. BmNPV hr3 was cloned into a downstream site of luc gene, to study the effect of this enhancer on hel 510 promoter activity. The transient expression in transfected insect cell lines and silkworm larvae indicated that hr 3 could enhance the transcriptional level of hel 510 promoter by about 7 000 and 1 000 fold, respectively.


WHY ARE CLUTCH SIZES MORE VARIABLE IN SOME SPECIES THAN IN OTHERS?
Animal species differ in the variability of their clutch sizes, as well as in mean clutch sizes. This phenomenon is particularly obvious in lizards, where virtually invariant clutch sizes have evolved independently in at least 23 lineages in seven families. Reduced variance in clutch size may arise either as an adaptation (because females with less variable clutch sizes have higher fitness) or as an indirect by-product of selection on other life-history characteristics. Comparative data on Australian scincid lizards indicate that variance in clutch sizes is lowest among species with low mean clutch sizes, small body sizes and a low variance in body sizes of adult females. Phylogenetic analysis shows that evolutionary decreases in the variance of clutch size have accompanied decreases in mean clutch sizes and decreases in the variance of adult female body sizes. Tropical lizards may also exhibit lower variance in clutch size. Most of these characteristics are correlated in occurrence, and may be allometrically tied to small body size. Hence, low variance in clutch size may be a consequence of allometric effects on a correlated suite of life-history characteristics. Exceptions to the general patterns noted above-especially, lizard species with invariant clutch sizes but large body sizes-may be due to loss of genetic variance for clutch sizes in lineages that have passed through a "bottleneck" of small body sizes and hence, low variance in clutch sizes.


Corneal endothelial viability after femtosecond laser preparation of posterior lamellar discs for Descemet-stripping endothelial keratoplasty.
To evaluate the feasibility of the femtosecond (FS) laser in preparation of posterior lamellar discs (PLDs) and to study the effect on endothelial cell (EC) viability for Descemet-stripping endothelial keratoplasty. Fourteen human donor bulbi unsuitable for transplantation were used. A horizontal lamellar cut was prepared in the donor cornea with an FS laser by using a raster and/or a spiral spot pattern. The control group consisted of the paired cornea of the same donor. EC density was evaluated before and after preservation in organ culture. The PLD was stripped from the anterior part by using either a forceps or a blunt dissection technique. The damage to the endothelium was evaluated. EC loss after organ storage was not statistically significant between the FS cornea group and the control group in the 15- (7.7% +/- 6.9% and 8.9% +/- 8.1%, respectively; P = 0.78) and 30-kHz (4.3% +/- 4.0% and 3.7% +/- 3.6%, respectively; P = 0.75) group. There was no significant effect of laser frequency (15 vs. 30 kHz) on EC loss (7.7% vs. 4.3%, P = 0.25). Dissection by using a forceps stripping technique resulted in higher EC loss than that with a blunt dissection technique (13.0% vs. 6.5%, P = 0.03). EC loss after FS laser lamellar cutting is not dependent on the frequency (ie, energy level) of the laser. A blunt dissection technique of PLDs resulted in acceptable EC loss and supports the clinical use of the FS laser for the preparation of PLDs.


The reduction of tris-dithiolene complexes of molybdenum(VI) and tungsten(VI) by hydroxide ion: kinetics and mechanism.
The kinetic study of the spontaneous reduction of some neutral tris-dithiolene complexes [ML3] of molybdenum(VI) and tungsten(VI), (L = S2C6H4(2-), S2C6H3CH3(2-) and S2C2(CH3)2(2-); M = Mo or W) by tetrabutylammonium hydroxide in tetrahydrofuran-water solutions demonstrates that OH- is an effective reductant. Their reduction is fast, clean and quantitative. Depending upon both the molar ratio in which the reagents are mixed and the amount of water present, one- or two-electron reductions of these tris-dithiolene complexes were observed. If Bu4NOH is present in low concentration or/and at high concentrations of water, the total transformation of the neutral M(VI) complex into the monoanionic M(V) complex is the only observed process. Stopped-flow kinetic data for this reaction are consistent with the rate law: -d[ML3]/dt = d[ML3-]/dt = k[ML3][Bu4NOH]. The proposed mechanism involves nucleophilic attack of OH- to form a mono-anionic seven-coordinate intermediate [ML3OH]-, which interacts with another molecule of [ML3] to generate the monoanionic complex [ML3]- transfering the oxygen from coordinated OH- to water. Hydrogen peroxide was identified as the reaction product. The molybdenum complexes are more difficult to reduce than their corresponding tungsten complexes, and the values of k obtained for the molybdenum and tungsten series of complexes increase as the ene-1,2-dithiolate ligand becomes more electron-withdrawing (S2C6H4(2-) > S2C6H3CH3(2-) > S2C2(CH3)2(2-)). This investigation constitutes the only well-established interaction between hydroxide ion and a tris(dithiolene) complex, and supports a highly covalent bonding interaction between the metal and the hydroxide ion that modulates electron transfer reactions within these complexes.


Leptin and old person's nutrition.
The leptin, protein of 146 amino acids, produced gene ob (chromosome 7) acts via the hypothalamus on the control of energy balance. It is implied in the adequacy between the food intake and the energy expenditure, and maintains stable body mass. We studied leptine's diurnal rhythm in old person of more than 75 years in institution, according to its state of nutrition and the undercurrent events likely to modify it. The study subjects were divided in two groups according to BMI < or superior 20 kg/m2. In the group of the patients with BMI higher than 20 kg/m2, there exists a correlation of the variation of the plasma leptin levels according to the BMI. At the subjects having a BMI lower than 20 kg/m2, the plasma leptin level is higher than the awaited value and the Leptin/BMI ratio is increased significantly compared to the subjects having a BMI higher than 20 kg/m2 (p < 0,05). Reduced nutritional status has largely exceeded capacities of adaptation to the nutritional needs and the capacity of response to the stress via the leptin is very disturbed.


Access to general practice for Pacific peoples: a place for cultural competency.
Access to primary health care services has been identified as a problem for Pacific peoples. Although cost is the most frequently cited barrier to Pacific service utilisation, some research has indicated that access may also be influenced by features of mainstream primary care services. This study aimed to identify features of mainstream general practice services that act as barriers to accessing these services for Pacific peoples in order to explore strategies that providers could adopt to enable their practices to be more welcoming, accessible and appropriate for Pacific peoples. Pacific participants were recruited through Pacific networks known to Pegasus Health and via 'snowball' sampling. In total, 20 participants participated in one of three focus groups. A semi-structured interview explored the participants' views and experiences of mainstream general practice care. Thematic analysis was utilised to interpret the data. The analysis revealed five themes highlighting non-financial features of mainstream general practice services that may influence the availability and acceptability of these services to Pacific peoples: language and communication; rushed consultations; appointment availability; reception; and Pacific presence. The findings indicate that all personnel within the primary care setting have the ability to directly engage in the improvement of the health status of Pacific peoples in New Zealand by developing cultural competency and incorporating flexibility and diversity into the care and service they provide.


Randomized, double-blind trial comparing topical nitroglycerine with xylocaine and Proctosedyl in idiopathic chronic anal fissure.
To compare symptomatic relief, healing, and changes in maximal anal resting pressure with the use of topical formulations in patients with chronic anal fissure. Sixty-four consecutive patients with chronic anal fissure were randomized into 4 groups that received, in a double-blind manner, a topical ointment that contained 0.2% nitroglycerine (GTN), 5% xylocaine, Proctosedyl (hydrocortisone acetate, heparin, framycetin sulfate, esculoside, ethoform, butoform) or petroleum jelly (Vaseline), to be applied twice daily. Patients were reviewed at 2-week intervals for 6 weeks. Anal manometry was done before, and 20 minutes after, the first application of the ointment. There was significant (p < 0.0001) reduction in mean anal resting pressure after application of GTN, but not any other ointment. Of 16 patients receiving GTN, complete pain relief occurred in 6 and 15 patients after 2 and 4 weeks of treatment, respectively; this was more frequent than in the other 3 groups. At 6 weeks also, complete pain relief occurred more often with GTN than with Vaseline or xylocaine. After 4 weeks of treatment, 3 patients on GTN had complete healing of fissure as compared to one each in the xylocaine and Proctosedyl groups and none in the Vaseline group. At 6 weeks, healing of fissure had occurred in 15 of 16 patients receiving GTN as compared to 4 receiving Vaseline, 11 receiving xylocaine, and 12 on Proctosedyl. Topical nitroglycerine produces 'chemical sphincterotomy' with reduction in mean anal resting pressure. Pain relief and healing of fissure occurred earlier with GTN than with other treatments. GTN should be considered as the treatment of choice for the non-surgical management of patients with chronic anal fissure.


Factors Regulating microRNA Expression and Function in Multiple Myeloma.
Intensive research has been undertaken during the last decade to identify the implication of microRNAs (miRNAs) in the pathogenesis of multiple myeloma (MM). The expression profiling of miRNAs in MM has provided relevant information, demonstrating different patterns of miRNA expression depending on the genetic abnormalities of MM and a key role of some miRNAs regulating critical genes associated with MM pathogenesis. However, the underlying causes of abnormal expression of miRNAs in myeloma cells remain mainly elusive. The final expression of the mature miRNAs is subject to multiple regulation mechanisms, such as copy number alterations, CpG methylation or transcription factors, together with impairment in miRNA biogenesis and differences in availability of the mRNA target sequence. In this review, we summarize the available knowledge about the factors involved in the regulation of miRNA expression and functionality in MM.


Role of the Go/i signaling network in the regulation of neurite outgrowth.
Neurite outgrowth is a complex differentiation process stimulated by many neuronal growth factors and transmitters and by electrical activity. Among these stimuli are ligands for G-protein-coupled receptors (GPCR) that function as neurotransmitters. The pathways involved in GPCR-triggered neurite outgrowth are not fully understood. Many of these receptors couple to Galphao, one of the most abundant proteins in the neuronal growth cones. We have studied the Go signaling network involved in neurite outgrowth in Neuro2A cells. Galphao can induce neurite outgrowth. The CB1 cannabinoid receptor, a Go/i-coupled receptor expressed endogenously in Neuro2A cells, triggers neurite outgrowth by activating Rap1, which promotes the Galphao-stimulated proteasomal degradation of Rap1GAPII. CB1-receptor-mediated Rap1 activation leads to the activation of a signaling network that includes the small guanosine triphosphate (GTP)ases Ral and Rac, the protein kinases Src, and c-Jun N-terminal kinase (JNK), which converge onto the activation of signal transducer and activator of transcription 3 (Stat3), a key transcription factor that mediates the gene expression process of neurite outgrowth in Neuro2A cells. This review describes current findings from our laboratory and also discusses alternative pathways that Go/i might mediate to trigger neurite outgrowth. We also analyze the role neurotransmitters, which stimulate Go/i to activate a complex signaling network controlling neurite outgrowth, play in regeneration after neuronal injury.


Reaction kinetics in a tight spot.
The standard analysis of reaction networks based on deterministic rate equations fails in confined geometries, commonly encountered in fields such as astrochemistry, thin-film growth and cell biology. In these systems the small reactant population implies anomalous behavior of reaction rates, which can be accounted for only by following the full distribution of reactant numbers.


[Radioprotection in dentistry offices].
In 1998, the Brazilian Ministry of Health established the Guidelines for Protection in Medical and Odontological Radiography, aimed at ensuring the quality of radiological procedures provided to the population as well as radiological protection for the health professionals. The purpose of this study was to verify the current situation in the dental offices with regard to the technical specifications and the adopted protective measures, using a questionnaire including questions about equipments, techniques and radiological protection. The investigated universe consisted of the surgeon dentists of the city of Aracaju using radiographic examination as a routine, resulting in a final sample of 103 professionals. The results showed that a high percentage of these professionals ignore the current norms (64.1%) as well as the technical specifications of their equipment (51.5% ignored the peak kilovoltage and 57.3% the milliamperage of their equipment), besides examining the radiographs visually (67%) As positive behaviors, the paralleling technique was preferred by 62.1% and the lead apron was used by 98.1%. We conclude that, despite the limited knowledge about the Guidelines, some measures are being correctly adopted but that the dentists have to be more aware of the necessary protective measures.


In situ Poly(methyl methacrylate)/Graphene Composite Gel Electrolytes for Highly Stable Dye-Sensitized Solar Cells.
Dye-sensitized solar cells (DSCs) with long-term stability are produced using polymer-gel electrolytes (PGEs). In this study, we introduce the formation of PGEs using in situ gelation with poly(methyl methacrylate) (PMMA) particles and graphene fillers that are pre-deposited on the counter electrodes. We obtain a high concentration PMMA-based PGEs (i.e., over 10 wt%). A DSC composed of a PMMA/graphene composite PGEs exhibits an 8.49% photon-to-electric conversion efficiency, which is comparable to conventional liquid electrolyte DSCs. This finding is attributed to increased ion diffusivity and conductivity of the PMMA-based PGEs resulting from the incorporation of graphene nanofillers. The PMMA-based PGE DSCs exhibit highly stable long-term efficiencies, maintaining up to 90% of their initial efficiency during thermal soaking, whereas the efficiencies of liquid electrolyte cells decrease significantly, by up to 60%.


Simultaneous enhancement of tensile/compressive strength and ductility of magnesium alloy AZ31 using carbon nanotubes.
AZ31 nanocomposite containing carbon nanotube (CNT) reinforcement was fabricated using solidification processing followed by hot extrusion. The CNT reinforcement was integrated with AZ31 using an Al foil method. The AZ31 nanocomposite exhibited slightly smaller grain and intermetallic particle sizes than monolithic AZ31, reasonable CNT distribution, dominant (10 - 11) texture in the transverse and longitudinal directions unlike monolithic AZ31, and 48% higher hardness than monolithic AZ31. Compared to monolithic AZ31, the AZ31 nanocomposite exhibited higher 0.2%TYS, UTS, tensile failure strain and tensile work of fracture (WOF) (+10%, +17%, +68% and +92%, respectively). Similarly, compared to monolithic AZ31, the AZ31 nanocomposite exhibited higher 0.2%CYS, UCS, average compressive failure strain and compressive WOF (+58%, +3%, +5% and +17%, respectively). Inclusive of crystallographic texture changes, the effect of CNT integration on the enhancement of tensile and compressive properties of AZ31 is investigated in this paper.


Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice.
Epilepsy is a chronic neurological disorder and generally associated with certain psychiatric comorbidities. Among several comorbidities depressive behavior and cognitive impairment has been reported to be most debilitating comorbidity associated with epilepsy. This study was envisaged to evaluate the ameliorative effect of Curcumin on depression like behavior and cognitive impairment observed in pentylenetetrazole kindled animals. Male Swiss Albino mice were kindled with subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.). Successfully kindled animals were used in the study to observe the effect of different treatments. Treatment groups received phenytoin (30 mg/kg) and Curcumin (50, 100 and 200mg/kg) for 15 days. The animals were challenged with pentylenetetrazole (35 mg/kg, i.p.) on day 5, 10 and 15 and seizure severity score, immobility period, number of mistakes and step down latency were recorded. On 15th day, all the animals were sacrificed after behavioral evaluations and their brain was isolated and homogenized to estimate brain norepinephrine, serotonin, total nitrite level and acetylcholinesterase activity. Phenytoin treatment significantly improved the depressive like behavior along with its anticonvulsant effect, however was unable to improve memory impairment. Curcumin significantly attenuated seizure severity, depression like behavior and memory impairment in kindled animals, in dose dependent manner. These results were supported by the biochemical modulation of brain monoamine, nitrosative stress level and acetylcholinesterase activity. Thus present study concluded that Curcumin has the ameliorative effect on seizure severity, depression like behavior and memory impairment in pentylenetetrazole kindled mice, possibly via central monoaminergic modulation and inhibitory effect on nitrosative stress and acetylcholinesterase activity.


Phylogeny of Lantana, Lippia, and related genera (Lantaneae: Verbenaceae).
Lantana and Lippia (Verbenaceae) are two large Linnean genera whose classification has been based on associated fruit traits: fleshy vs. dry fruits and one vs. two seed-bearing units. We reconstruct evolutionary relationships and the evolution of the two fruit traits to test the validity of these traits for classification. Previous studies of plastid DNA sequences provided limited resolution for this group. Consequently, seven nuclear loci, including ITS, ETS, and five PPR loci, were sequenced for 88 accessions of the Lantana/Lippia clade and three outgroups. Neither Lantana nor Lippia is monophyletic. Burroughsia, Nashia, Phyla, and several Aloysia species are included within the clade comprising Lantana and Lippia. We provide a hypothesis for fruit evolution and biogeographic history in the group and their relevance for classification. Fleshy fruits evolved multiple times in the Lantana/Lippia clade and thus are not suitable taxonomic characters. Several sections of Lantana and Lippia and the small genera are monophyletic, but Lippia section Zappania is broadly paraphyletic, making circumscription of genera difficult. Lippia sect. Rhodolippia is a polyphyletic group characterized by convergence in showy bracts. Species of Lantana sect. Sarcolippia, previously transferred to Lippia, are not monophyletic. The clade originated and diversified in South America, with at least four expansions into both Central America and the Caribbean and two to Africa. The types species of Lantana and Lippia occur in small sister clades, rendering any taxonomy that retains either genus similar to its current circumscription impossible.


Adenovirus-based vaccine with epitopes incorporated in novel fiber sites to induce protective immunity against Pseudomonas aeruginosa.
Adenovirus (Ad) vector-based vaccines displaying pathogen-derived epitopes on Ad capsid proteins can elicit anti-pathogen immunity. This approach seems to be particularly efficient with epitopes incorporated into the Ad fiber protein. Here, we explore epitope insertion into various sites of the Ad fiber to elicit epitope-specific immunity. Ad vectors expressing the 14-mer Pseudomonas aeruginosa immune-dominant outer membrane protein F (OprF) epitope 8 (Epi8) in five distinct sites of the Ad5 fiber, loops CD (AdZ.F(CD)Epi8), DE (AdZ.F(DE)Epi8), FG (AdZ.F(FG)Epi8), HI (AdZ.F(HI)Epi8) and C terminus (AdZ.F(CT)Epi8), or the hexon HVR5 loop (AdZ.HxEpi8) were compared in their capacity to elicit anti-P. aeruginosa immunity to AdOprF, an Ad expressing the entire OprF protein. Intramuscular immunization of BALB/c mice with AdZ.F(FG)Epi8 or AdZ.F(HI)Epi8 elicited higher anti-OprF humoral and cellular CD4 and CD8 responses as well as enhanced protection against respiratory infection with P. aeruginosa compared to immunization with AdZ.F(CD)Epi8, AdZ.F(DE)Epi8, AdZ.F(CT)Epi8 or AdZ.HxEpi8. Importantly, repeat administration of the fiber- and hexon-modified Ad vectors boosted the OprF-specific humoral immune response in contrast to immunization with AdOprF. Strikingly, following three doses of AdZ.F(FG)Epi8 or AdZ.F(HI)Epi8 anti-OprF immunity surpassed that induced by AdOprF. Furthermore, in the presence of anti-Ad5 immunity, immunization with AdZ.F(FG)Epi8 or AdZ.F(HI)Epi8, but not with AdOprF, induced protective immunity against P. aeruginosa. This suggests that incorporation of epitopes into distinct sites of the Ad fiber is a promising vaccine strategy.


Primary leiomyosarcoma of the spine: A case report and literature review.
Primary leiomyosarcoma of the bone was firstly reported by Evans and Sanerkin in 1965, whereas primary leiomyosarcoma of the vertebra is extremely rare. Because of the rarity of primary vertebral leiomyosarcoma, the diagnosis, treatment, and clinical outcome still remain controversial. Here we report a special case of primary leiomyosarcoma in the thoracic vertebra. A 47-year-old female patient was admitted to our institution with the chief complaint of persistent back pain for 4 weeks. She had no symptoms of numbness, weakness, pain, and abnormal sensation in her extremities. Neurological examination on admission revealed no obvious abnormality. Magnetic resonance imaging showed a bone destruction of the T11 vertebral body and the right pedicle. Therefore, primary vertebral leiomyosarcoma was suspected. Pathological hematoxylin and eosin staining of the resected tumor revealed a diagnosis of polymorphic undifferentiated sarcoma. Furthermore, to identify the subtype of this sarcoma, the immunohistochemical staining of the tumor was performed with each of the various antibodies and the results are epithelial membrane antigen (-), H-caldesmon (-), desmin (+), smooth muscle actin (+), S-100 (-), myogenin (-), pan-keratin (-), and Ki-67 (positive rate: 20%). Finally, the patient was diagnosed as primary vertebral leiomyosarcoma. the anterior corpectomy and autogenous iliac bone graft with instrumentation combined with the posterior spinal canal decompression and fusion with the pedicle screw system were performed through an anterior-posterior union approach. Neither clinical symptoms nor signs of tumor recurrence were detected within the follow-up of 6 months. In addition, 11 cases of the primary vertebral leiomyosarcoma reported in the literature were reviewed and summarized. Exclusion of metastatic leiomyosarcoma by various imaging modalities and histopathological examinations, especially the immunohistochemical staining with various antibodies against the epithelial and mesenchymal cell markers, are critical for establishing the correct diagnosis of the primary vertebral leiomyosarcoma. Surgical resection, especially the total en bloc spondylectomy, is the main treatment option with a good outcome, albeit with a limited follow-up duration.


Canagliflozin in the treatment of type 2 diabetes: an evidence-based review of its place in therapy.
Deciding on an optimal medication choice for type 2 diabetes is often challenging, due to the increasing number of treatment options. Canagliflozin is a novel glucose-lowering agent belonging to sodium-glucose co-transporter 2 (SGLT2) inhibitors. The aim of this study was to examine and summarize the evidence based on the efficacy, safety, and cost-effectiveness of canagliflozin for type 2 diabetes. Compared to placebo, canagliflozin 100 and 300 mg lower glycated hemoglobin (HbA1c) by ~0.6%-0.8%, respectively. Canagliflozin appears to be slightly more effective than dipeptidyl peptidase-4 (DPP-4) inhibitors in reducing HbA1c. It also has a favorable effect on body weight and blood pressure, both versus placebo and most active comparators. However, treatment with canagliflozin is associated with increased incidence of genital tract infections and osmotic diuresis-related adverse events. Based on short-term data, canagliflozin is not associated with increased risk for all-cause mortality and cardiovascular outcomes. Economic evaluation studies from various countries indicate that canagliflozin is a cost-effective option in dual- or triple-agent regimens. As monotherapy, canagliflozin could be used in patients for whom metformin is contraindicated or not tolerated. For patients on background treatment with metformin, canagliflozin appears to be superior to sulfonylureas with respect to body weight, blood pressure and risk for hypoglycemia, and to DPP-4 inhibitors in terms of lowering HbA1c, body weight, and blood pressure. Canagliflozin also seems to be cost-effective compared with sulfonylureas and DPP-4 inhibitors as add-on to metformin monotherapy, and compared with DPP-4 inhibitors as add-on to metformin and sulfonylurea. Current evidence on intermediate efficacy outcomes, short-term safety and cost-effectiveness support the use of canagliflozin in patients on background treatment with metformin. Robust long-term data regarding the effect of canagliflozin on cardiovascular endpoints will be available upon completion of the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial.


Ambient UVA-induced expression of p53 and apoptosis in human skin melanoma A375 cell line by quinine.
This study aimed to analyze the phototoxic mechanism and photostability of quinine in human skin cell line A375 under ambient intensities of UVA (320-400 nm). Photosensitized quinine produced a photoproduct 6-methoxy-quinoline-4-ylmethyl-oxonium identified through LC-MS/MS. Generation of (1)O2, O2(•-), and (•)OH was measured and further substantiated through their respective quenchers. Photosensitized Quinine (Q) caused degradation of 2-deoxyguanosine, the most sensitive nucleotide to UV radiation. The intracellular ROS was increased in a concentration-dependent manner. Significant reduction in metabolic status measured in terms of cell viability (54%) at 25 μg mL(-1) was observed through MTT assay. Results of MTT assay accord NRU assay. Single strand DNA breaks and apoptosis were increased significantly (P < 0.01) as observed through comet assay and EB/AO double staining. Photosensitized quinine caused cells to arrest in G2 phase of cell cycle and induced apoptosis (5.08%) as revealed through FACS. Real-Time PCR showed upregulation of p21 (4.56 folds) and p53 (2.811 folds) genes expression. Thus, our study suggests that generation of reactive oxygen species by quinine under ambient intensity of UVA may result into deleterious phototoxic effects among human population.


An Unusual Presentation of Primary B-cell Lymphoma of the Small Bowel in an Immunosuppressant-Naive Patient With Newly Diagnosed Crohn's Disease.
Inflammatory bowel disease (IBD) consists of two primary conditions: ulcerative colitis (UC) and Crohn's disease (CD). UC primarily impacts the colon, leading to inflammation of the mucosal layer. Conversely, CD involves transmural inflammation and can affect any segment of the gastrointestinal tract, ranging from the oral cavity to the perianal region. Patients with CD can have symptoms for many years prior to diagnosis, or they may present acutely. We present the case of a 31-year-old male with a recent CD diagnosis and otherwise, no past medical history presenting with a week-long history of bilateral lower extremity swelling that started in the thighs and progressed downward, accompanied by a heavy sensation in the legs and intermittent numbness. Less than 24 hours into his hospital course, the patient experienced progressive bilateral numbness, saddle anesthesia, and urinary incontinence. Subsequently, the patient was taken for STAT MRI and emergent neurosurgery to alleviate the spinal cord compression and remove/biopsy a mass at the T6-T7 level that was later defined as a B-cell lymphoma. Our objectives are to describe the etiology of IBD complicated by lymphoma, to analyze the association between IBD and lymphoma, and to investigate the role that immunosuppressants play in the development of lymphoma from IBD, which we achieve through retrospective case analysis and associated literature review on symptom constellation. There is good evidence that malignant lymphoma of the bowel is a rare but significant complication of IBD in immunosuppressant-naive patients, apparently being more common in chronic UC. We suggest increased surveillance for this disease in immunosuppressant-naive patients, as the prognosis of lymphoma depends on the time of diagnosis.


[Epidemiology of hand injuries based on surveys in Vas County].
Authors have found in a 1 year survey in the county Vas 7580 hand injuries. The major proportion of young men and adolescents in the material was conspicuous. The types of accidents were investigated together with the place of the accident and types of the injury. The material shows that in contrary to the accidents of the work in the recent past the number of the accidents at home has increased--and so their prophylaxis became the main point.


Identification of a voltage-responsive segment of the potential-gated colicin E1 ion channel.
The voltage dependence of channel activity of the bactericidal protein colicin E1 was found to be correlated with insertion into the membrane bilayer of a specific segment of the 178-residue COOH-terminal thermolytic colicin channel peptide. The insertion into the bilayer was detected by an increase in labeling by one of two different lipophilic photoaffinity probes or by a decrease in iodination of peptide tyrosines from the external solution. Imposition of a potassium diffusion potential of -100 mV resulted in an increase of 35-60% in the labeling of the peptide by the lipophilic probe in the bilayer and a concomitant decrease in labeling of Tyr residues in the peptide by the iodination reagent in the external solution. The change in labeling decreased upon dissipation of the membrane potential with a half-time of about 1 min. The labeling change was localized to a 36-residue peptide segment bounded by alanine-425 and by tryptophan-460. This segment containing seven positively charged residues at low pH is a voltage-sensitive region that inserts into the membrane bilayer when the channel is turned on by the potential and is extruded from it when the voltage is removed and the channel is turned off.


Analysis of safety and efficacy of pegylated-interferon alpha-2a in hepatitis C virus positive hemodialysis patients: results from a large, multicenter audit.
Hepatitis C virus (HCV) infection rates are still high in hemodialysis (HD) centers in developing countries. Standard interferon (IFN) monotherapy is associated with good results in HCV-positive patients (more than 30% rate of sustained virological response) but with poor tolerance. Pegylated interferon (PEG-IFN) is better tolerated and has a more sustained antiviral effect in the general population. There have been no large trials to date with PEG-IFN in hemodialysis populations. We report the largest series to date of HCV+ HD patients (n=78) treated with PEG-IFN alfa -2a 135 microg s.c. weekly monotherapy. The primary outcomes were (a) efficacy - assessed by the viral response at 12, 48 weeks and 6 months after completion of therapy, and (b) rate of serious adverse events. In 48/78 (61.5%) patients an early (12 weeks) viral response was obtained. Viral end-of-treatment response (ETR) was evaluated in the 21 patients (26.9%) who reached week 48 on therapy: only 15 subjects (19.2% of the initial population) had undetectable HCV-RNA levels. In these 15 patients, a sustained viral response (SVR) was recorded in 11 - i.e. 14.1% of the initial intention-to-treat (ITT) population. A high prevalence of noncompliance (32%) and of adverse events (83%) was recorded; minor adverse effects (flu-like syndrome, mild-to-moderate thrombocytopenia, leukopenia and anemia) responded to symptomatic therapy or dose reduction, but often caused lack of compliance. The incidence rate of serious adverse events was 0.19/patient-year (median time to event 20.5 weeks), and incidence of deaths was 0.11/patient-year. In dialysis patients, PEG-IFN alfa -2a is poorly tolerated and associated with a high number of serious adverse events, causing a significant lack of compliance/discontinuation of therapy. In this largest HCV-positive hemodialysis population survey, we report a low sustained viral response in an ITT analysis, compared with previously published historical data using non-PEG-IFN, a low compliance rate and an unsatisfactory overall safety profile, not supporting the superiority of PEG-IFN monotherapy.


Semiclassical approximations based on complex trajectories.
The semiclassical limit of the coherent state propagator <z" absolute value of e(-i H T/Planck's over 2 pi) z'> involves complex classical trajectories of the Hamiltonian H(u,v) = <v absolute value of H u> satisfying u(0) = z' and v(T) = z"*. In this work we study mostly the case z' = z". The propagator is then the return probability amplitude of a wave packet. We show that a plot of the exact return probability brings out the quantal images of the classical periodic orbits. Then we compare the exact return probability with its semiclassical approximation for a soft chaotic system with two degrees of freedom. We find two situations where classical trajectories satisfying the correct boundary conditions must be excluded from the semiclassical formula. The first occurs when the contribution of the trajectory to the propagator becomes exponentially large as Planck's over 2 pi goes to zero. The second occurs when the contributing trajectories undergo bifurcations. Close to the bifurcation the semiclassical formula diverges. More interestingly, in the example studied, after the bifurcation, where more than one trajectory satisfying the boundary conditions exist, only one of them in fact contributes to the semiclassical formula, a phenomenon closely related to Stokes lines. When the contributions of these trajectories are filtered out, the semiclassical results show excellent agreement with the exact calculations.


PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.
The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo) level in leukocyte DNA of healthy controls (138 individuals), patients with benign adenomas (AD, 137 individuals) and with malignant carcinomas (CRC, 169 individuals) revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.


Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation.
Malignant glioma is a formidable disease that commonly leads to death, mainly due to the invasion of tumor cells into neighboring tissues. Therefore, inhibition of tumor cell invasion may provide an effective therapy for malignant glioma. Here we report that nicotinic acid (NA), an essential vitamin, inhibits glioma cell invasion in vitro and in vivo. Treatment of the U251 glioma cells with NA in vitro results in reduced invasion, which is accompanied by a loss of mesenchymal phenotype and an increase in cell-cell adhesion. At the molecular level, transcription of the adherens junction protein E-cadherin is upregulated, leading to accumulation of E-cadherin protein at the cell-cell boundary. This can be attributed to NA's ability to facilitate the ubiquitination and degradation of Snail1, a transcription factor that represses E-cadherin expression. Similarly, NA transiently inhibits neural crest migration in Xenopus embryos in a Snail1-dependent manner, indicating that the mechanism of action for NA in cell migration is evolutionarily conserved. We further show that NA injection blocks the infiltration of tumor cells into the adjacent brain tissues and improves animal survival in a rat model of glioma. These results suggest that NA treatment may be developed into a potential therapy for malignant glioma.


Cloning, characterization and expression of wheat EDR1 (enhanced disease resistance) gene.
To investigate if there is an EDR1 pathway in wheat (Triticum aestivum L.), a pair of degenerate primers was designed according to the cDNAs of Arabidopsis thaliana EDR1 gene and its homologs were used to isolate EDR1 gene homologs from wheat. RT-PCR was conducted on the cDNA template synthesized with RNA of wheat leaves. A 627-bp cDNA fragment representing an EDR1 gene (named as TaEDR1) was isolated (GenBank accession number: AY743662). Subsequently, the 3050-bp full-length cDNA sequence of TaEDR1, which encodes a polypeptide consisting of 959 amino acid residues, was obtained by RACE technique. The amino acid sequence of TaEDR1 and that of barley (Hordeum vulgare) EDR1 (signed as HvEDR1) show 92% identity. There is a highly conserved catalytic domain of serine/threonine protein kinases in the C-terminus of TaEDR1. Because this protein has a putative nuclear localization motif, it probably functions in the nucleus. This study provides the first molecular biological evidence of the presence of an EDR1 homolog in common wheat. The transcription pattern of TaEDR1 was investigated in leaves after inoculation with Blumeria graminis (DC.) E.O. Speer f. sp. tritici Em. Marchal (Bgt) through semi-quantitative RT-PCR (semi-QRT-PCR). The result showed that the transcribing of TaEDR1 was enhanced by Bgt. The expression pattern of the TaEDR1 gene in different tissues showed that it expressed in leaves, stems, spikes and roots. This study suggests that the TaEDR1, a MAP kinase kinase kinase, may function in wheat defense responses.


Exhaled nitric oxide in single and repetitive prolonged exercise.
This study was performed to determine the influence of single and repetitive exercise on nitric oxide (NO) concentration in the lung. Exhaled NO concentration (FE(NO)) was measured during a constant-flow exhalation manoeuvre (170 ml x s(-1), against a 10 cmH2O resistance) in healthy individuals (a) during and after a 100-min square-wave exercise of between 25 and 60% of maximal power output (n = 18) and (b) before and after five successive prolonged exercises (90-120 min, 75-85% of maximal heart rate) separated by 48 or 24 h (n = 8). The FE(NO0.170) was decreased during and after the 100-min exercise test (mean +/- s(x): 58.5 +/- 3.7% and 76.7 +/- 5.2% of resting value at 90 min of exercise and 15 min post-exercise, respectively; P < 0.05). The five successive exercise sessions induced a similar post-exercise FE(NO0.170) decrement (73.1 +/- 2.9% of resting value 15 min post-exercise), while basal FE(NO0.170) values were not different between the five sessions (P > 0.05). These results suggest that prolonged exercise induces a reduction in NO concentration within the lung that lasts for several minutes after the end of exercise. However, repetitive exercises (at least every 24 h) allow complete NO recovery from one session to another. The implication of such a decrease in NO availability within the lung remains to be clarified.


Influence of captopril and enalapril on some central effects of ethanol.
The influence of captopril and enalapril on acute toxicity of ethanol, ethanol-induced hypothermia, ethanol sleeping time has been investigated in mice. Moreover, the combined effect of captopril and enalapril on spontaneous locomotor activity in mice has been examined. The captopril (5 and 20 mg/kg) and enalapril (5 and 20 mg/kg) were injected intraperitoneally i.p. The drugs were given as single or repeated doses for 10 days. It has been shown that the captopril and enalapril administered in single doses decreases, but chronic administration increases acute toxicity of ethanol. Captopril and enalapril in single doses enhanced, but chronic administration inhibits hypothermic effect of ethanol. Captopril and enalapril reduces ethanol sleeping time. Captopril and enalapril administered for 10 days and enalapril in a single dose 20 mg/kg decreases ethanol induced hyperactivity.


Report: Clinical characteristics and treatment experience report of severe pulmonary infection after renal transplantation.
This study was to discuss the clinical diagnosis and treatment features of severe pulmonary infections after renal transplantation, in order to improve the cure rate. Retrospective research was applied to analyze the 52 cases of patients with serve pulmonary infection after renal transplantation in the department of organ transplantation in People's Hospital of Zhengzhou from July, 2008 to December, 2013. The pathogens which caused the pulmonary infection after renal transplantation were bacteria, virus, fungi, mycobacterium tuberculosis, combined infection and unknown pathogens, and the rate were respectively 28.85%, 15.38%, 7.69%, 3.85%, 21.15% and 23.08%. In the 52 cases, there were 41 cases of patients successfully survived, which was 78.85% and 11 cases died, which was 21.15%. The mortality rate of combined infection and unknown pathogens infection was significantly higher than that of single pathogen infection. Pulmonary infection after renal transplantation was of rapid deteriorated progress and high mortality rate. It was significant for patients to receive the comprehensive and integrated treatment.


Why financial incentives did not reach the poor tuberculosis patients? A qualitative study of a Fidelis funded project in Shanxi, China.
A project implemented in 50 counties of Shanxi province provided incentives to poor TB patients for their first trip to tuberculosis (TB) dispensaries. Incentives were also given to doctors for referring and supervising TB patients. A previous quantitative evaluation identified no improvement on TB case detection and management. This qualitative study was then conducted to explore reasons for project failure. To understand how the incentives were distributed to and viewed by their recipients and the implications for TB and health systems. Qualitative in-depth interviews were conducted with 32 TB patients, 13 village doctors, 12 village leaders, 8 TB doctors and 8 TB programme managers. The study revealed a lack of operational tools on how to evaluate patients' economic status and how to publicise the incentives. As a result, patients did not know the level of incentives in advance and regarded the amount as inadequate. Patients faced a huge financial burden and a long delay in treating TB, dwarfing the benefits of travel incentives. The referral and case supervision incentives were not implemented. Doctors did not receive any referral and supervision incentives in addition to those already existing. Strategies to address health system and TB programme issues should be implemented before or alongside financial incentives. Operational details and tools for any intervention should be developed, field-tested and revised prior to wide-scale use.


Novel triazole based inhibitors of Ras farnesyl transferase.
A novel series of potent inhibitors of Ras farnesyl transferase possessing a 1,2,4-triazole pharmacophore is described. These inhibitors were discovered from a parallel synthesis effort and were subsequently optimized to in vitro IC(50) value of less than 1nM.


Psychosocial thriving during late pregnancy: relationship to ethnicity, gestational weight gain, and birth weight.
To test the relationships between psychosocial thriving (depressive symptoms, health-related lifestyle) and gestational weight gain and birth weight. To test the influences of ethnicity on the relationships between psychosocial thriving and gestational weight gain and birth weight. Baseline data taken from the Austin New Mothers Study. A community hospital in Texas. 305 low-risk African American, Hispanic, and White women with full-term pregnancies, singleton births, and Medicaid coverage. Center for Epidemiologic Studies Depression Scale, Self Care Inventory, Food Habits Questionnaire, gestational weight gain, and birth weight. Newborns of African American women had lower birth weights (3,240 g) than newborns of Hispanic (3,422 g) or White women (3,472 g), even though no ethnic differences were found among the mothers on psychosocial variables. Late in pregnancy, women had high levels and prevalence (> 70%) of depressive symptoms regardless of ethnicity, and 50% exceeded recommended gestational weight gains. In full regression models, psychosocial variables were not significant predictors of gestational weight gain or birth weight. Ethnicity also was not a significant moderator of weight outcomes. Psychosocial thriving late in pregnancy was unrelated to gestational weight gain or birth weight. Ethnicity did not moderate psychosocial-weight relationships. Although ethnic differences were not found on psychosocial variables, high levels of depressive symptoms and greater than recommended gestational weight gains were prevalent. These findings have implications for maternal health during and beyond pregnancy.


A case of amebiasis with negative serologic markers that caused intra-abdominal abscess.
A 23-year-old Japanese woman presented with abdominal distention following fever, diarrhea, and abdominal pain during a stay in Taiwan. Serology for the detection of amebic-antibodies and stool microscopic examination were both negative. A computed tomography scan showed a 13 cm diameter abscess spreading from the lower abdominal wall to the pelvic retroperitoneal space. Needle aspiration of the abscess was done under computed tomography guidance, and microscopy of the aspirated fluid revealed trophozoites of Entamoeba. The patient was diagnosed as amebiasis with negative serologic markers that caused intra-abdominal abscess. Intravenous metronidazole treatment for two weeks did not result in any improvement of the abscess. After irrigation and drainage of the abscess, her symptoms resolved. This case report highlights that amebiasis should be considered when indicated by patient history, including travelers returning from endemic areas, and that further evaluation is necessary for diagnosis, even if the serology and stool test are negative.


Noninvasive imaging of transgene expression by use of positron emission tomography in a pig model of myocardial gene transfer.
Radionuclide imaging of reporter gene expression may be useful for noninvasive monitoring of clinical cardiac gene therapy. Experience until now, however, has been limited to small animals. To evaluate feasibility in a clinically applicable setting, pigs were studied by conventional positron emission tomography (PET) 2 days after regional intramyocardial injection of control adenovirus or adenovirus carrying herpesviral thymidine kinase reporter gene (HSV1-tk). Myocardial blood flow was quantified by use of [13N]ammonia. Subsequently, kinetics of the reporter substrate [124I]-2'-fluoro-2'-deoxy-5-iodo-1-beta-d-arabino-furanosyluracil (FIAU) were assessed over a period of 2 hours. Areas infected with adenovirus expressing HSV1-tk showed significantly elevated FIAU retention during the first 30 minutes after injection. At later times, washout was observed, and retention was not different from that in areas infected with control virus or remote myocardium. Early in vivo FIAU uptake correlated with ex vivo images, autoradiography, and immunohistochemistry for reporter gene product after euthanasia. After intramyocardial injection of both adenoviruses, myocardial blood flow was mildly elevated compared with that in remote areas, consistent with histological signs of regional inflammation. In vivo quantification of regional myocardial transgene expression is feasible with clinical PET methodology, the radioiodinated reporter probe FIAU, and the HSV1-tk reporter gene. Radioactivity efflux after specific initial uptake was not observed previously in tumor studies, suggesting that tissue-specific differences in nucleoside metabolism influence reporter probe kinetics. By coregistering reporter gene expression with additional biological parameters such as myocardial blood flow, PET allows for noninvasive characterization of the success of cardiac gene transfer along with its functional correlates.


Psychological distress and amniocentesis.
40 women who underwent amniocentesis were administered the Symptom Questionnaire to evaluate changes in psychological distress. Anxiety, depression, somatic symptoms and hostility significantly decreased after the results of the procedure were communicated to the patient, replicating the findings in a previous study. Psychological distress, however, returned to the initial levels in the third trimester of pregnancy. Women whose only indication for amniocentesis was an age of 35 years or older displayed significantly higher hostility and somatic symptoms and less contentment before the procedure than the other women. Subsequently these differences lost their significance and the two groups showed similar patterns of psychological distress throughout the pregnancy.


[Research progress of IQGAP1 in the pathogenesis of ARDS induced by sepsis].
Sepsis is one of the main cause of patients' death. Lung is the most vulnerable target organ during sepsis, and sepsis patients are often complicated with acute respiratory distress syndrome (ARDS), of which the main mechanism is vascular leakage caused by cytoskeleton rearrangement and cell-to-cell connection changes. IQ-guanosine triphosphatease-activating protein 1 (IQGAP1) has become the key component of cytoskeleton dynamics regulation in recent years. At present, the relationship between IQGAP1 and ARDS induced by sepsis is not yet clear. In this article, we will review the mechanism of the interaction between IQGAP1 and pathogenic microorganisms, changes of pulmonary micro vascular barrier function and cyto-skeleton at the molecular level.


Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma.
A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective. Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B). Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8-20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12-43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor-1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival. Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months.


Recruitment & retention program for the NeuroNEXT SMA Biomarker Study: Super Babies for SMA!
Recruitment and retention of research participants are challenging and critical components of successful clinical trials and natural history studies. Infants with spinal muscular atrophy (SMA) have been a particularly challenging population to study due to their fragile and complex medical issues, poor prognosis and, until 2016, a lack of effective therapies. Recruitment of healthy infants into clinical trials and natural history studies is also challenging and sometimes assumed to not be feasible. In 2011, our group initiated a two-year, longitudinal natural history study of infants with SMA and healthy infant controls to provide data to assist in the analysis and interpretation of planned clinical trials in infants with SMA. The recruitment goal was to enroll 27 infants less than 6 months of age with SMA and 27 age-matched healthy infants within the two-year enrollment period. A detailed recruitment and retention plan was developed for this purpose. In addition, a survey was administered to participant families to understand the determinants of participation in the study. All healthy infants were recruited within the study's first year and 26 SMA infants were recruited within the two-year recruitment period. Thirty-eight participant families responded to the recruitment determinants survey. Nearly half of respondents (18/38, 48%) reported that they first heard of the study from their physician or neurologist. The most common reason to decide to enroll their infant (22/38, 58%) and to remain in the study (28/38, 74%) was their understanding of the importance of the study. Thematic recruitment tools such as a study brochure, video on social media, and presentations at advocacy meetings were reported to positively influence the decision to enroll. A proactive, thematic and inclusive recruitment and retention plan that effectively communicates the rationale of a clinical study and partners with patients, advocacy groups and the local communities can effectively recruit participants in vulnerable populations. Recommendations for the proactive integration of recruitment and retention plans into clinical trial protocol development are provided.


[Anti-stigmatization and ethical perspectives on mental illness and genetic technologies].
People with mental illness suffer from their disorder as well as from social stigma. This paper explores the bio-psycho-social reasons that underlie human stigma and proposes potential anti-stigmatization strategies. Furthermore, this paper presents a multi-component, multi-level intervention genetic psychiatry protocol addressing stigma prevention. Significant levels of social stigma still pervade Taiwanese culture, and a potential crisis of genetic psychiatry exists in cases where mental illness is identified. Promoting humanistic, ethical, and caring attitudes and enhancing genetic nursing education at both the community level and amongst health professional are central to ensuring the rights and quality of life of the mentally ill in Taiwan society.


Safety of an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food pursuant to Regulation (EU) 2015/2283.
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ethanolic extract of the dried biomass of the microalga P. tricornutum diluted in a medium-chain triglyceride oil carrier, with standardised fucoxanthin and tocopherol content. The main component of the NF is fat (78% on average), followed by crude protein (10% on average). The Panel is of the view that a consistent and safe production process has not been demonstrated. Additionally, the Panel considers that the information provided on the composition of the NF is not complete and may raise safety concerns. The applicant proposed to use the NF as a food supplement at the use level of 437 mg/day, with the target population being adults, excluding pregnant and breastfeeding women. There is no history of use of the NF or of its source, i.e. P. tricornutum. The Panel notes that the source of the NF, P. tricornutum, was not granted the qualified presumption of safety (QPS) status by the EFSA Panel on Biological Hazards (BIOHAZ), due to the lack of a safe history of use in the food chain and on its potential for production of bioactive compounds with toxic effects. There were no concerns regarding genotoxicity of the NF. In the 90-day study provided, a number of adverse effects were observed, some of them seen already at the lowest dose tested (750 mg/kg body weight (bw) day), which was identified by the Panel as the lowest-observed-adverse-effect-level (LOAEL). The potential phototoxicity of pheophorbide A and pyropheophorbide A in the NF was not addressed in this study. Although noting the uncertainties identified by the Panel regarding the analytical determination of these substances in the NF and the limitations in the publicly available toxicity data, a low margin of exposure (MoE) was calculated for these substances at the proposed use levels. The Panel concludes that the safety of the NF under the proposed uses and use levels has not been established.


Femoral anastomotic false aneurysms. An 11-year experience analyzed with a case control study.
Eighty-three femoral anastomotic false aneurysms occurring in 51 patients were diagnosed from 1972 through 1982. Twenty-two (27%) presented with acute events. Seventy (84%) were confirmed by sonography and/or arteriography. Bilaterality (29%), recurrence (18%), and associated aortic false aneurysms (8%) were significant problems. Eight-one were repaired with a six per cent complication rate, including one death related to preoperative rupture. The 51 patients were evaluated for associated illnesses, risk factors, and etiologies of their false aneurysms. The most common single cause (61%) was host vessel degeneration with an intact suture line remaining attached to a disrupted Dacron limb. Twenty-three patients with host vessel degeneration were matched with case controls not developing false aneurysms. These two groups were matched for gender, age, and year of AFB and compared for associated illnesses and risk factors. Incidences of cigarette smoking, hypertension, cerebrovascular disease, coronary artery disease, diabetes mellitus, previous femoral endarterectomy, outflow disease, other aneurysmal disease, multiple groin operations, wound complications, and training levels of surgeons performing initial AFBs were similar for both groups. Factors observed significantly more often in patients who developed false aneurysms included serum lipid abnormalities (p less than 0.05), braided synthetic suture material as opposed to monofilament polypropylene (p less than 0.05), and continued abuse of tobacco following AFB (p less than 0.005).


The effect of preterm birth on vestibular evoked myogenic potentials in children.
Preterm birth is a significant global health problem with serious short- and long-term consequences. This study examined the long term effects of preterm birth on vestibular evoked myogenic potentials (VEMPs) among preschool-aged children. Thirty-one children with preterm and 20 children with term birth histories aged 5.5 to 6.5 years were studied. Each child underwent VEMPs testing using a 500 Hz tone-burst stimulus with a 95 dB nHL (normal hearing level) intensity level. The mean peak latencies of the p13 and n23 waves in the very preterm group were significantly longer than for the full-term group (p≤ 0.041). There was a significant difference between very and mildly preterm children in the latency of peak p13 (p= 0.003). No significant differences existed between groups for p13-n23 amplitude and the interaural amplitude difference ratio. The tested ear and gender did not affect the results of the test. Prolonged VEMPs in very preterm children may reflect neurodevelopmental impairment and incomplete maturity of the vestibulospinal tract (sacculocollic reflex pathway), especially myelination. VEMPs is a non-invasive technique for investigating the vestibular function in young children, and considered to be an appropriate tool for evaluating vestibular impairments at the low brainstem level. It can be used in follow-ups of the long-term effects of preterm birth on the vestibular system.