Dietary recommendations regarding pilot whale meat and blubber in the Faroe Islands.
For centuries the pilot whale has been an important part Faroese life--both in regard to food and culture. However, studies dating back to 1977 have shown an increase in contamination of the meat, blubber, liver and kidneys of pilot whales. Several birth cohorts have been established in the Faroes in order to discover the health effects related to mercury and organchlorine exposure. In short the results have so far shown that: mercury from pilot whale meat adversely affects the foetal development of the nervous system; the mercury effect is still detectable during adolescence; the mercury from the maternal diet affects the blood pressure of the children; the contaminants of the blubber adversely affect the immune system so that the children react more poorly to immunizations; contaminants in pilot whales appear to increase the risk of developing Parkinson's disease in those who often eat pilot whale; the risk of hypertension and arteriosclerosis of the carotid arteries is increased in adults who have an increased exposure to mercury; septuagenarians with type 2 diabetes or impaired fasting glycaemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. Also impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants. From the latest research results, the authors consider that the conclusion from a human health perspective must be to recommend that pilot whale is no longer used for human consumption.


Impact of killer immunoglobulin-like receptor-human leukocyte antigens ligand incompatibility among renal transplantation.
Killer immunoglobulin-like receptor (KIR) gene shows a high degree of polymorphism. Natural killer cell receptor gets activated once they bind to self-human leukocyte antigens (HLAs) with specific ligand. KIR gene and HLA ligand incompatibility due to the presence/absence of KIR in the recipient and the corresponding HLA ligand in the allograft may impact graft survival in solid organ transplantation. This study evaluates the effect of matches between KIR genes and known HLA ligands. KIR genotypes were determined using sequence specific primer polymerase chain reaction. Presence of certain KIR in a recipient, where the donor lacked the corresponding HLA ligand was considered a mismatch. The allograft was considered matched when both KIR receptor and HLA alloantigen reveald compatibility among recipient and donor. The data revealed better survival among individuals with matched inhibitory KIR receptors and their corresponding HLA ligands (KIR2DL2/DL3-HLAC2, KIR3DL1-HLABw4). On the contrary, no adverse effect was seen for matched activating KIR receptors and their corresponding HLA ligands. One of the activating gene KIR2DS4 showed risk (P = 0.0413, odds ratio = 1.91, 95% confidence interval = 1.02-3.57) association with renal allograft rejection. We conclude that the presence of inhibitory KIR gene leads to better survival; whereas activating motifs show no significant role in renal allograft survival.


Failure of Chlamydia trachomatis to pass transplacentally to fetuses of TO mice infected during pregnancy.
Mice (strain TO) were inoculated with a human strain of Chlamydia trachomatis (serovar E) either 14 days before the detection of a vaginal plug (day 1 of pregnancy), or from one to nine days thereafter. The organisms were given via the intraperitoneal route (ip) or intravenously with an additional intravaginal inoculum (iv + ivag). Mice were killed on day 18 of pregnancy and the contents of the uterus examined. Chlamydiae were isolated from at least one placental disk of about a quarter of the mice. Organisms given via the ip route established placental colonisation more effectively. Thus, placental colonisation was detected in five of 16 mice given chlamydiae by the ip route (in six of eight placentas in one mouse), whereas colonisation occurred in only a single placenta from one of nine mice infected via the iv + ivag routes. Chlamydiae were isolated from 13 (6.25%) of 208 placentas examined; the degree of colonisation was variable and the individual placentas were colonised independently. Chlamydiae were not recovered from fetal tissue, even when there was heavy placental colonisation. Nor were they isolated from maternal spleens, even though there was antibody to C. trachomatis in all maternal sera; the titres were in the range 4-2048, depending on the time of chlamydial challenge. These experiments show that C. trachomatis did not cross the placenta and that the pregnancy outcome in these mice was not affected.


Clinical Long-Term Response to Cardiac Resynchronization Therapy Is Independent of Persisting Echocardiographic Markers of Dyssynchrony.
The aim of the study was to prove the concept that correction of established parameters of dyssynchrony is a requirement for favorable long-term outcome in patients with cardiac resynchronization therapy (CRT), whereas patients with persisting dyssynchrony should have a less favorable response. After CRT implantation and optimization of dyssynchrony parameters, we evaluated whether correction or persistence of dyssynchrony predicted long-term outcome. Primary endpoint was a combination of cardiac mortality/heart transplantation and hospitalization due to worsening heart failure, and secondary endpoint was NYHA class. One hundred twenty-eight consecutive patients (mean age 68 ± 10 years) undergoing CRT with a mean left ventricular ejection fraction of 27±9% were followed for 27 ± 19 months. All cause mortality was 17.2%, cardiac mortality was 7.8% and 3.1% had to undergo heart transplantation. Rehospitalization due to worsening heart failure was observed in 14.8%. NYHA class before CRT implantation was 2.8 ± 0.8 and improved during follow-up to 2.0 ± 0.8 (P < 0.001). A clinical response was observed in 76% (n = 97) and an echocardiographic response was documented in 66% (n = 85). After individually optimized AV and VV intervals with echocardiography, atrioventricular dyssynchrony was still present in 7.2%, interventricular dyssynchrony in 13.3% and intraventricular dyssynchrony in 16.4%. Despite persistent atrioventricular, interventricular and intraventricular dyssynchrony at long-term follow-up, the combined primary and secondary endpoints did not differ compared to the group without mechanical dyssynchrony (P = ns). QRS duration with biventricular stimulation did not differ between responders vs. nonresponders. After successful CRT implantation, clinical long-term response is independent of correction of dyssynchrony measured by echocardiographic parameters and QRS width.


Identification of the major structural and nonstructural proteins encoded by human parvovirus B19 and mapping of their genes by procaryotic expression of isolated genomic fragments.
Plasma from a child with homozygous sickle-cell disease, sampled during the early phase of an aplastic crisis, contained human parvovirus B19 virions. Plasma taken 10 days later (during the convalescent phase) contained both immunoglobulin M and immunoglobulin G antibodies directed against two viral polypeptides with apparent molecular weights of 83,000 and 58,000 which were present exclusively in the particulate fraction of the plasma taken during the acute phase. These two protein species comigrated at 110S on neutral sucrose velocity gradients with the B19 viral DNA and thus appear to constitute the viral capsid polypeptides. The B19 genome was molecularly cloned into a bacterial plasmid vector. Restriction endonuclease fragments of this cloned B19 genome were treated with BAL 31 and shotgun cloned into the open reading frame expression vector pJS413. Two expression constructs containing B19 sequences from different halves of the viral genome were obtained, which directed the synthesis, in bacteria, of segments of virally encoded protein. These polypeptide fragments were then purified and used to immunize rabbits. Antibodies against a protein sequence specified between nucleotides 2897 and 3749 recognized both the 83- and 58-kilodalton capsid polypeptides in aplastic plasma taken during the acute phase and detected similar proteins in the tissues of a stillborn fetus which had been infected transplacentally with B19. Antibodies against a protein sequence encoded in the other half of the B19 genome (nucleotides 1072 through 2044) did not react specifically with any protein in plasma taken during the acute phase but recognized three nonstructural polypeptides of 71, 63, and 52 kilodaltons present in the liver and, at lower levels, in some other tissues of the transplacentally infected fetus.


Calibration and validity of an eccentric photorefractor.
A new graphical calibration method was developed to convert the photorefractive reflex into refractive error. With this graphical method, the refractive error can be obtained for pupil sizes and for photorefractive reflex sizes which have not been precalibrated. In the conventional method, the refractive error associated with non-precalibrated pupil and reflex sizes is obtained by interpolating between neighbouring precalibrated points. This introduces error because the relationship between refractive error and pupil and reflex size is not linear. Three hundred and sixty-one children aged between 36 and 65 months were clinically examined and photorefracted. The refractive error obtained using retinoscopy and the eccentric photorefractor agreed well with each other, although the photorefractor tended to under-estimate refractive error. Using the referral criteria developed by Chan, O.Y.C. and Edwards, L.M. (Refraction referral criteria for Hong Kong Chinese Children. Ophthal. Physiol. Opt. 14, 259-256, 1994), the photorefractor had a sensitivity of 74.6% and a specificity of 96.4%. All the under-referred cases were borderline, having just failed the referral criteria. All the cases with hyperopia of > + 2.0 D, astigmatism of > 1.25 D and visual acuity of worse than 6/18 were identified.


Somatotype and Body Composition in Young Soccer Players According to the Playing Position and Sport Success.
Cárdenas-Fernández, V, Chinchilla-Minguet, JL, and Castillo-Rodríguez, A. Somatotype and body composition in young soccer players according to the playing position and sport success. J Strength Cond Res 33(7): 1904-1911, 2019-Soccer players undergo an evolution in their body composition throughout the growth and passage through the different base stages, that is, childhood, puberty, and adolescence. The aim of this study was to analyze the morphology and body composition of U14, U16, and U19 soccer players, taking into account in addition, their sport success endorsed through the regularity participation and their relation with the different playing positions occupied during competition (goalkeeper, external defender, central defender, midfielder, and forward/extreme). For that, a total of 174 male young soccer players were evaluated anthropometrically. Dominant somatotype of the players was, according to their playing position, meso-endomorphic in goalkeepers, central for external defenders, balanced ectomorph in central defenders, balanced mesomorph in the case of midfielders, and meso-ectomorph in forwards/extremes. Taking into account that sport performance is directly mediated by the body composition of athletes, the differences found suggest a marked specialization between the goalkeepers and forwards, establishing significant differences between them. Further studies would be needed to evaluate the influence of individual maturation development vs. sports training on the conformation of a certain anthropometric profile of a soccer player and its relation with the different playing positions occupied on the pitch during the game.


Enhanced suppressor T cell activity resulting in increased IgM and decreased IgG productions in children with minimal change nephrotic syndrome.
In order to clarify the cellular basis accounting for the decreased serum IgG and increased serum IgM in children with minimal change nephrotic syndrome (MCNS), peripheral blood mononulcear cells (MNC) were obtained from 15 children with biopsy-proved MCNS and 15 age- and sex-matched normals. MNC were then separated into helper (OKT4) T cells, suppressor (OKT8) T cells, B cells and monocytes. Different cell populations from patients and normals were then recombined and pokeweed mitogen-stimulated in vitro immunoglobulin biosynthesis was studied. The results strongly suggest the presence of isotype-specific suppressor T cells which may affect the switch of IgM B cells to IgG B cells in patients with MCNS and may be used to explain partly the clinical findings of lowered serum IgG and increased IgM in those individuals.


Inferring data-specific micro-RNA function through the joint ranking of micro-RNA and pathways from matched micro-RNA and gene expression data.
In practice, identifying and interpreting the functional impacts of the regulatory relationships between micro-RNA and messenger-RNA is non-trivial. The sheer scale of possible micro-RNA and messenger-RNA interactions can make the interpretation of results difficult. We propose a supervised framework, pMim, built upon concepts of significance combination, for jointly ranking regulatory micro-RNA and their potential functional impacts with respect to a condition of interest. Here, pMim directly tests if a micro-RNA is differentially expressed and if its predicted targets, which lie in a common biological pathway, have changed in the opposite direction. We leverage the information within existing micro-RNA target and pathway databases to stabilize the estimation and annotation of micro-RNA regulation making our approach suitable for datasets with small sample sizes. In addition to outputting meaningful and interpretable results, we demonstrate in a variety of datasets that the micro-RNA identified by pMim, in comparison to simpler existing approaches, are also more concordant with what is described in the literature. This framework is implemented as an R function, pMim, in the package sydSeq available from http://www.ellispatrick.com/r-packages. email@example.com Supplementary data are available at Bioinformatics online.


Sphingosine-1-phosphate mediates ICAM-1-dependent monocyte adhesion through p38 MAPK and p42/p44 MAPK-dependent Akt activation.
Up-regulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Sphingosine-1-phosphate (S1P) has been shown to play a key role in inflammation via adhesion molecules induction, and then causes lung injury. However, the mechanisms underlying S1P-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. The effect of S1P on ICAM-1 expression was determined by Western blot and real-time PCR. The involvement of signaling pathways in these responses was investigated by using the selective pharmacological inhibitors and transfection with siRNAs. S1P markedly induced ICAM-1 expression and monocyte adhesion which were attenuated by pretreatment with the inhibitor of S1PR1 (W123), S1PR3 (CAY10444), c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), PI3K (LY294002), or AP-1 (Tanshinone IIA) and transfection with siRNA of S1PR1, S1PR3, c-Src, EGFR, PDGFR, p38, p42, JNK1, c-Jun, or c-Fos. We observed that S1P-stimulated p42/p44 MAPK and p38 MAPK activation was mediated via a c-Src/EGFR and PDGFR-dependent pathway. S1P caused the c-Src/EGFR/PDGFR complex formation. On the other hand, we demonstrated that S1P induced p42/p44 MAPK and p38 MAPK-dependent Akt activation. In addition, S1P-stimulated JNK1/2 phosphorylation was attenuated by SP600125 or PP1. Finally, S1P enhanced c-Fos mRNA levels and c-Jun phosphorylation. S1P-induced c-Jun activation was reduced by PP1, AG1478, AG1296, U0126, SP600125, SB202190, or LY294002. These results demonstrated that S1P-induced ICAM-1 expression and monocyte adhesion were mediated through S1PR1/3/c-Src/EGFR, PDGFR/p38 MAPK, p42/p44 MAPK/Akt-dependent AP-1 activation.


New Evidence-Based Treatment Approach in Behçet's Disease.
Behçet's disease (BD) is a chronic, relapsing, and debilitating systemic vasculitis of unknown aetiology with the clinical features of mucocutaneous lesions, ocular, vascular, articular, neurologic, gastrointestinal, urogenital, and pulmonary involvement. The disease is much more frequent along the ancient "Silk Route" extending from Eastern Asia to the Mediterranean basin, compared with Western countries. The disease usually starts around the third or fourth decade of life. Male sex and a younger age of onset are associated with more severe disease. Although the treatment has become much more effective in recent years, BD is still associated with severe morbidity and considerable mortality. The main aim of the treatment should be the prevention of irreversible organ damage. Therefore, close monitoring, early, and appropriate treatment is mandatory to reduce morbidity and mortality. The treatment is mainly based on the suppression of inflammatory attacks of the disease using immunomodulatory and immunosuppressive agents. In this paper, current state of knowledge regarding the therapeutic approaches is outlined. To provide a rational framework for selecting the appropriate therapy along the various treatment choices, a stepwise, symptom-based, evidence-based algorithmic approach was developed.


Occurrence of articulins and epiplasmins in protists.
The cortex of ciliates. dinoflagellates, and euglenoids comprises a unique structure called the epiplasm, implicated in pattern-forming processes of the cell cortex and in maintaining cell shape. Articulins, a novel class of cytoskeletal proteins, are major constituents of the epiplasm in the flagellate Euglena gracilis and the ciliate Pseudomicrothorax dubius. The hallmark of articulins is a core domain of repetitive motifs of alternating valine and proline residues, the VPV-motif. The VPV-motif repeats are 12 residues long. Positively and negatively charged residues segregate in register with valine and proline positions. The VPV-motif is unique to articulins. The terminal domains flanking the core are generally hydrophobic and contain a series of hexa- or heptapeptide repeats rich in glycine and hydrophobic residues. Using molecular and immunological tools we show that articulins are also present in the dinoflagellate Amphidinium carterae and the ciliates Paramecium tetraurelia and Paramecium caudatum, Tetrahymena pyriformis, and Euplotes aediculatus. Our analysis further shows that epiplasmins, a group of epiplasmic proteins first characterized in Paramecium, are also present in all these species. Moreover, we present evidence that epiplasmins and articulins represent two distinct classes of cytoskeletal proteins.


Spatial connectivity in a large river system: resolving the sources and fate of dissolved organic matter.
Large rivers are generally heterogeneous and productive systems that receive important inputs of dissolved organic matter (DOM) from terrestrial and in situ sources. Thus, they are likely to play a significant role in the biogeochemical cycling of the DOM flowing to the oceans. The asymmetric spatial gradient driven by directional flow and environmental heterogeneity contributes to the fate of DOM flowing downstream. Yet, the relative effects of spatial connectivity and environmental heterogeneity on DOM dynamics are poorly understood. For example, since environmental variables show spatial heterogeneity, the variation explained by environmental and spatial variables may be redundant. We used the St. Lawrence River (SLR) as a representative large river to resolve the unique influences of environmental heterogeneity and spatial connectivity on DOM dynamics. We used three-dimensional fluorescence matrices combined with parallel factor analysis (PARAFAC) to characterize the DOM pool in the SLR. Seven fluorophores were modeled, of which two were identified to be of terrestrial origin and three from algal exudates. We measured a set of environmental variables that are known to drive the fate of DOM in aquatic systems. Additionally, we used asymmetric eigenvector map (AEM) modeling to take spatial connectivity into account. The combination of spatial and environmental models explained 85% of the DOM variation. We show that spatial connectivity is an important driver of DOM dynamics, as a large fraction of environmental heterogeneity was attributable to the asymmetric spatial gradient. Along the longitudinal axis, we noted a rapid increase in dissolved organic carbon (DOC), mostly controlled by terrestrial input of DOM originating from the tributaries. Variance partitioning demonstrated that freshly produced protein-like DOM was found to be the preferential substrate for heterotrophic bacteria undergoing rapid proliferation, while humic-like DOM was more correlated to the diffuse attenuation coefficient of UVA radiation.


Von Willebrand factor collagen-binding (activity) assay in the diagnosis of von Willebrand disease: a 15-year journey.
The correct diagnosis and classification of von Willebrand disease (vWD) is crucial because the presenting biological activity of von Willebrand factor (vWF) determines both the hemorrhagic risk and the subsequent clinical management. A variety of laboratory assays may be employed, not necessarily restricted to assessments of vWF. This article discusses the relative strengths and limitations of various functional or discriminatory vWF assays with a special focus on the vWF:collagen-binding activity (vWF:CBA) assay. This is a functional vWF assay that relies on the property of vWF adhesion to collagen. The vWF:CBA was first described approximately 15 years ago. The journey from that time point has been an interesting one, and the vWF:CBA is now gaining more widespread acceptance. There are now many published studies confirming the superiority of the vWF:CBA over the vWF ristocetin cofactor (vWF:RCof) activity as a functional screening diagnostic test process for vWD. However, both tests may be required in order to appropriately diagnose all forms of vWD. The relationship of these assays with multimer analysis is also discussed. In summary, an optimized vWF:CBA detects primarily high-molecular-weight (HMW) vWF forms and probably only about 30% of the total plasma vWF pool detected by vWF antigen (vWF:Ag). Because these HMW vWF forms are missing in types 2A and 2B vWD, the vWF:CBA is extremely useful in the detection of these qualitative vWD subtypes. In addition, however, concordance of vWF:CBA with vWF:Ag in unison with low vWF levels may alternatively suggest a type 1 vWD, and an absence of both vWF:Ag and vWF:CBA will suggest type 3 vWD. The vWF:CBA is also being investigated in various disease states, as is its usefulness as an effective marker of functional HMW vWF in both desmopressin (DDAVP) and factor-concentrate therapy in vWD.


Infection and cancer following renal transplantation.
Ever increasingly potent but non-specific immunosuppression has necessarily brought with it the continuing risk of opportunistic infections and virus-induced malignancies. The improvement in graft and patient survival rates from transplantation has depended to a certain extent on parallel improvements in the diagnosis and treatment of infectious complications. This review will highlight some of the current problems and progress. The risks of infection are largely related to the total burden of immunosuppression rather than any particular drug, although sirolimus and the anti CD25 antibodies may be an exception. Almost all the post-transplant infections are treatable; a precise microbiological diagnosis is essential so that specific therapy can be used. Newer molecular diagnostic techniques are increasingly widely available, e.g.quantitative polymerase chain reaction. The transplant community will inevitably be faced with highly resistant bacteria such as. Methicillin resistant Staphylococcus Aureus (MRSA) and will have to develop appropriate strategies. New infectious organisms continue to be identified [e.g. Burkitt's Virus (BKV), West Nile virus and Avian influenza) and will continue to tax the ingenuity of transplant physicians and microbiologists.


[Autoradiographic demonstration of the passage of vincamin through the blood-brain barrier].
Autoradiographies of the brain and of the cerebellum were performed in 8-month old rats after intraperitoneal injection of 3H-labelled vincamine. Only those samples that were processed by freezedrying or by freezesubstitution gave interpretable results. Some specifically labelled cells were found in the molecular layer of the cerebellar cortex as well as in the internal granular and in the deeper layers of the cerebral cortex. they did not belong to the vascular system. It was concluded that vincamine or its metabolites crosses the blood-brain barrier. Any attempt to explain a possible action of the substance on the brain function should thus also consider the cellular components of the central nervous system and not only the haemodynamics of the cerebral circulation.


Production of cold bromine atoms at zero mean velocity by photodissociation.
The production of a translationally cold (T < 1 K) sample of bromine atoms with estimated densities of up to 10(8) cm(-3) using photodissociation is presented. A molecular beam of Br(2) seeded in Kr is photodissociated into Br + Br* fragments, and the velocity distribution of the atomic fragments is determined using (2 + 1) REMPI and velocity map ion imaging. By recording images with varying delay times between the dissociation and probe lasers, we investigate the length of time after dissociation for which atoms remain in the laser focus, and determine the velocity spread of those atoms. By careful selection of the photolysis energy, it is found that a fraction of the atoms can be detected for delay times in excess of 100 μs. These are atoms for which the fragment recoil velocity vector is directly opposed and equal in magnitude to the parent beam velocity leading to a resultant lab frame velocity of approximately zero. The FWHM velocity spreads of detected atoms along the beam axis after 100 μs are less than 5 ms(-1), corresponding to temperatures in the milliKelvin range, opening the possibility that this technique could be utilized as a slow Br atom source.


On model specification and selection of the Cox proportional hazards model.
Prognosis plays a pivotal role in patient management and trial design. A useful prognostic model should correctly identify important risk factors and estimate their effects. In this article, we discuss several challenges in selecting prognostic factors and estimating their effects using the Cox proportional hazards model. Although a flexible semiparametric form, the Cox's model is not entirely exempt from model misspecification. To minimize possible misspecification, instead of imposing traditional linear assumption, flexible modeling techniques have been proposed to accommodate the nonlinear effect. We first review several existing nonparametric estimation and selection procedures and then present a numerical study to compare the performance between parametric and nonparametric procedures. We demonstrate the impact of model misspecification on variable selection and model prediction using a simulation study and an example from a phase III trial in prostate cancer.


[Pancreatic Adenosquamous Carcinoma That Developed after Resection of IPMA in the Pancreatic Tail].
Pancreatic adenosquamous carcinoma coexisting with intraductal papillary mucinous neoplasm(IPMN)is extremely rare. We report a rare case of pancreatic adenosquamous carcinoma that developed after resection of intraductal papillary mucinous adenoma(IPMA). A 67-year-old man was suspected of having a pancreatic cystic lesion. MRCP demonstrated a cystic lesion measuring 25mm in the pancreatic tail, which had an enhanced nodule. We therefore diagnosed branch duct type IPMN of the pancreas. Although pancreatic juice cytology did not indicate malignancy, we performed laparoscope-assisted distal pancreatectomy. The reason why the IPMN lesion had an enhanced nodule. The histopathological diagnosis was IPMA without malignancy. One year and 5 months after surgery, blood analysis showed an elevated tumor marker level, and abdominal CT demonstrated a pancreatic head tumor with lymphadenopathy. EUS-FNA was performed and the patient was diagnosed with pancreatic adenosquamous carcinoma based on immunohistochemical staining. We administered chemotherapy with gemcitabine and S-1. After 3 courses of this chemotherapy, the size of the pancreatic tumor and the tumor marker level decreased. The patient achieved a partial response. He is still receiving chemotherapy after 7 courses.


Nano-Enable Materials Promoting Sustainability and Resilience in Modern Agriculture.
Intensive conventional agriculture and climate change have induced severe ecological damages and threatened global food security, claiming a reorientation of agricultural management and public policies towards a more sustainable development model. In this context, nanomaterials promise to support this transition by promoting mitigation, enhancing productivity, and reducing contamination. This review gathers recent research innovations on smart nanoformulations and delivery systems improving crop protection and plant nutrition, nanoremediation strategies for contaminated soils, nanosensors for plant health and food quality and safety monitoring, and nanomaterials as smart food-packaging. It also highlights the impact of engineered nanomaterials on soil microbial communities, and potential environmental risks, along with future research directions. Although large-scale production and in-field testing of nano-agrochemicals are still ongoing, the collected information indicates improvements in uptake, use efficiency, targeted delivery of the active ingredients, and reduction of leaching and pollution. Nanoremediation seems to have a low negative impact on microbial communities while promoting biodiversity. Nanosensors enable high-resolution crop monitoring and sustainable management of the resources, while nano-packaging confers catalytic, antimicrobial, and barrier properties, preserving food safety and preventing food waste. Though, the application of nanomaterials to the agri-food sector requires a specific risk assessment supporting proper regulations and public acceptance.


Preclinical pharmacology of albumin-free B-domain deleted recombinant factor VIII.
A second-generation recombinant factor VIII molecule was developed with an albumin-free formulation. In this modified form of factor VIII, the N- and C-terminal sections of the B-domain are retained and fused at serine 743 and glutamine 1638, resulting in a B-domain deleted factor VIII protein known as ReFacto (Genetics Institute, Andover, MA). Preclinical studies of ReFacto have focused on efficacy of the product for the hemophilia A patient population. The efficacy and pharmacokinetic profiles of ReFacto were similar to plasma-derived factor VIII in correcting the hemostatic defect of hemophilia A dogs. Both ReFacto and plasma-derived human factor VIII (Octonativ-M7, Pharmacia, Stockholm, Sweden) were found to associate with von Willebrand factor (vWF) after infusion into hemophilia A dogs as demonstrated by size exclusion chromatography. Infusion of either ReFacto or Octonativ-M7 quickly corrected factor VIII coagulant activity (FVIIIc), whole blood clotting time (WBCT), and activated partial thromboplastin time (aPTT). No obvious differences were seen between ReFacto and Octonativ-M7. Both ReFacto and Octonativ-M7 treatment reduced secondary bleeding time to less than 6 minutes. The clearance was faster and the volume of distribution at steady state was larger for plasma-derived factor VIII compared with ReFacto. The half-life was similar between Octonativ-M7 and ReFacto. These data predict that ReFacto will be effective in correcting human factor VIII deficiency states.


Beta2-adrenergic receptor agonists and cAMP arrest human cultured airway smooth muscle cells in the G(1) phase of the cell cycle: role of proteasome degradation of cyclin D1.
Hyperplasia of airway smooth muscle (ASM) contributes to the airway hyperresponsiveness that characterizes asthma. We have investigated the relationship between cAMP-induced growth arrest of ASM cells and thrombin-stimulated, extracellular-regulated protein kinase (ERK) activity, cyclin D1, and the restriction protein retinoblastoma. The beta(2)-adrenergic receptor agonist albuterol (100 nM) inhibited DNA synthesis after incubation with ASM for periods as brief as 1 h when these coincided with the timing of the restriction point. Inhibition of thrombin-stimulated DNA synthesis by albuterol (1-100 nM), 8-bromo-cAMP (300 microM), or prostaglandin E(2) (1 microM) was accompanied by a reduction in cyclin D1 protein levels. The ERK kinase inhibitor PD98059 (3-30 microM) attenuated thrombin-stimulated ERK phosphorylation and activity and the increase in cyclin D1 protein levels, as did albuterol (1-100 nM) or 8-bromo-cAMP (300 microM). In contrast, neither albuterol (100 nM) nor PD98059 (30 microM) reduced cyclin D1 mRNA levels between 4 and 20 h after thrombin addition, which suggests that elevation of cAMP regulates cyclin D1 by a post transcriptional mechanism. The proteasome inhibitor MG132 (30 and 100 nM) and the calpain I inhibitor N-acetyl-Leu-Leu-leucinal (10 microM) attenuated the reduction in thrombin-stimulated cyclin D1 levels in ASM exposed to albuterol (100 nM), 8-bromo-cAMP (300 microM), or the phosphodiesterase inhibitor isobutylmethylxanthine (100 microM). Thus, the cAMP-induced arrest of ASM in the G(1) phase of the cell cycle is associated with a proteasomal degradation of cyclin D1 protein and a reduced protein retinoblastoma phosphorylation that prevents passage through the restriction point.


Of Humans and Gerbils- Independent Diversification of Neuroligin-4 Into X- and Y-Specific Genes in Primates and Rodents.
The neural cell adhesion protein neuroligin-4 has puzzled neuroscientists and geneticist alike for almost two decades. Its clinical association with autism spectrum disorders (ASD) is well established, however, its diversification into sex chromosome-specific copies, NLGN4X and NLGN4Y, remains uncharted territory. Just recently, the presence of substantial neuroligin-4 sequence differences between humans and laboratory mice, in which Nlgn4 is a pseudoautosomal gene, could be explained as a consequence of dramatic changes affecting the pseudoautosomal region on both sex chromosomes in a subset of rodents, the clade eumuroida. In this study, we describe the presence of sex chromosome-specific copies of neuroligin-4 genes in the Mongolian gerbil (Meriones unguiculatus) marking the first encounter of its kind in rodents. Gerbils are members of the family Muridae and are closely related to mice and rats. Our results have been incorporated into an extended evolutionary analysis covering primates, rodents, lagomorphs, treeshrews and culogos comprising together the mammalian superorder euarchontoglires. We gathered evidence that substantial changes in neuroligin-4 genes have also occurred outside eumuroida in other rodent species as well as in lagomorphs. These changes feature, e.g., a general reduction of its gene size, an increase in its average GC-content as well as in the third position (GC3) of synonymous codons, and the accumulation of repetitive sequences in line with previous observations. We further show conclusively that the diversification of neuroligin-4 in sex chromosome-specific copies has happened multiple times independently during mammal evolution proving that Y-chromosomal NLGN4Y genes do not originate from a single common NLGN4Y ancestor.


GRF increases release of growth hormone and arachidonate from anterior pituitary cells.
Arachidonate and its metabolites increase growth hormone release in vitro. A study was designed to determine whether arachidonate release from anterior pituitary cells is modified by growth hormone-releasing factor (GRF) or somatostatin (SRIF). Cultured pituitary cells were incubated with [3H]arachidonate to esterify the long-chain fatty acid into cellular lipids. The cells were extensively washed with medium containing no [3H]arachidonate and then incubated with GRF and/or SRIF for 30 min. The incubation medium was then extracted with ethyl acetate, and following thin-layer chromatographic separation, the radioactivity in the [3H]arachidonate band was measured. GRF in a concentration-dependent manner (1-30 nM) stimulated growth hormone and arachidonate release, whereas SRIF (100 nM) blocked the GRF-induced increase of growth hormone and arachidonate release. The effects of GRF on growth hormone and arachidonate were evident at time intervals as brief as 5 min. These findings support the hypothesis that arachidonate may play a role in the GRF-induced growth hormone release.


Articulated coralline algae of the genus Amphiroa are highly effective natural inducers of settlement in the tropical abalone Haliotis asinina.
The initiation of metamorphosis in marine invertebrates is strongly linked to the environment. Planktonic larvae typically are induced to settle and metamorphose by external cues such as coralline algae (Corallinaceae, Rhodophyta). Although coralline algae are globally abundant, invertebrate larvae of many taxa settle in response to a very limited suite of species. This specificity impacts population structure, as only locations with the appropriate coralline species can attract new recruits. Abalone (Gastropoda, Haliotidae) are among those taxa in which closely related species are known to respond to different coralline algae. Here we identify highly inductive natural cues of the tropical abalone Haliotis asinina. In contrast to reports for other abalone, the greatest proportion of H. asinina larvae are induced to settle and metamorphose (92.8% to 100% metamorphosis by 48 h postinduction) by articulated corallines of the genus Amphiroa. Comparison with field distribution data for different corallines suggests larvae are likely to be settling on the seaward side of the reef crest. We then compare the response of six different H. asinina larval families to five different coralline species to demonstrate that induction by the best inductive cue (Amphiroa spp.) effectively extinguishes substantial intraspecific variation in the timing of settlement.


Brainstem gliomas in children. A Children's Cancer Group review of 119 cases.
Brainstem gliomas (BSG) with intrinsic and extensive brainstem involvement continue to have a poor outlook despite current treatment approaches. Neuroimaging studies have aided in the differentiation of malignant brainstem tumors from more 'benign' subgroups. A Children's Cancer Group protocol evaluating outcome in children with BSG after treatment with hyperfractionated radiotherapy (7,200-7,800 cGy) was recently completed. The clinical aspects of 119 children entered into this study were reviewed in an attempt to determine risk groups and prognostic indicators. The overall survival of this group was very poor and there was no statistically significant correlation of survival with age, sex, clinical symptoms and signs, or tumor grade. Longer survival was only associated with prolonged duration of brainstem symptoms and signs greater than 1 month prior to diagnosis of the tumor. Improved outlook for children with BSG will require further research in tumor biology and newer therapeutic modalities.


A prospective randomised controlled clinical trial comparing the efficacy of different molecular weight hyaluronan solutions in the treatment of knee osteoarthritis.
Viscosupplementation consists of injecting exagenous hyaluronan (HA) into the synovial joints to restore the normal rheological environment which deteriorates severely in osteoarthritic (OA) joints. Efficacy might be related to the rheological properties and molecular weight (MW) of the hyaluronan preparations. This prospective, controlled, double-blind, randomised clinical trial was aimed at comparing the elastoviscous properties of a high molecular weight viscosupplement, hylan G-F 20, with that of a lower molecular weight hyaluronan product in order to determine the relationship of elastoviscosity to efficacy, alongside placebo, in the treatment of patients with knee OA. The results were analysed as a "completers" analysis with 59 patients. Primary outcome measures included the Western Ontario and Mc Master Universities' Osteoarthritis Index (WOMAC) for pain, stiffness and function scores, and patient and physician global assessments (0-100 scale). For patient (PGA) and physician global assessments (PhGA), the 0-100 scale was used, with 100 being the worst. Follow-up assessments were made at intervals of 1, 3 and 6 months after the first injection. Local adverse events, such as transient pain at the injection site or warm knee lasting for one night, were recorded in two patients (3%). In all groups, the WOMAC pain score exhibited a significant difference from the baseline value; neither treatment group was significantly different from the placebo group, but total pain score was significantly better than baseline for both of the HA groups at the end of 6 months (p < 0.05). Improvement in WOMAC physical function score favoured both sodium hyaluronate and hylan G-F 20 after the first month, and remained significant until the end of 6 months (p < 0.01). In the placebo group, the physical function scores became worse after the end of the 1st month; the scores at the end of 6 months were no different from those at the beginning. The WOMAC stiffness scores of both of the hyaluronic acid groups improved with the first injection, and remained significantly better than the placebo group until the end of the survey (p < 0.001). All groups expressed improvement with PGA scores after the first injection. At the end of 6 months all three groups were similar, but the treatment groups were significantly better than the placebo group (p < 0.05), and all were significantly better than at the beginning (p < 0.05). The PhGA scores were similar in all groups until after the third injection. The second group was slightly better in the controls at 1 and 3 months, but all the groups were similar at the end of 6 months. Although the placebo group seemed worse, it was not statistically significant. Compared with lower molecular weight HA, the higher molecular weight HA might be more efficacious in treating knee OA, but heterogeneity of previous studies limited definitive conclusions. Patients treated by injection of either of two hyaluronan preparations showed clinical improvement for pain, though no different from the placebo group; WOMAC stiffness scores were better than placebo in the HA groups, whereas PGA scores showed improvement in all groups but HA groups were better than placebo. PhGA scores were worse in the placebo group, but not to a statistically-significant extent. The HA groups did not differ in terms of clinical efficacy.


The protooncogene MYC can break B cell tolerance.
The protooncogene MYC has been implicated in both the proliferation and programmed cell death of lymphoid cells, and in the genesis of lymphoid tumors. Here, we report that overexpression of MYC, as found in many lymphomas, can break immune tolerance. Mice that would otherwise be tolerant to a transgenic autoantigen mounted an immune response to the antigen if MYC was vigorously expressed in the B cell lineage. The responsive B cells converted to an activated phenotype and produced copious amounts of autoantibody that engendered immune complex disease of the kidney. MYC was required to both establish and maintain the breach of tolerance. These effects may be due to the ability of MYC to serve as a surrogate for cytokines. We found that the gene could mimic the effects of cytokines on both B cell proliferation and survival and, indeed, was required for those effects. These findings demonstrate a critical role for MYC in the response of B cells to antigen and expand the potential contributions of MYC to the genesis of lymphomas.


Experimental and natural host specificity of Loma salmonae (Microsporidia).
The microsporidian Loma salmonae (Putz, Hoffman & Dunbar, 1965) Morrison & Sprague, 1981 has caused significant gill disease in Pacific salmon Oncorhynchus spp. Host specificity of the parasite was examined experimentally by per os challenge of selected salmonids and non-salmonids with infective chinook salmon O. tshawytscha gill material. Pink Oncorhynchus gorbuscha and chum salmon O. keta, brown Salmo trutta and brook trout Salvelinus fontinalis, and chinook salmon (controls) were positive, whereas Atlantic salmon Salmo salar and Arctic char Salvelinus alpinus were negative. In addition, no non-salmonids were susceptible to experimental exposure. Wild Pacific salmon species in British Columbia, Canada, were examined for L. salmonae during their freshwater life history stages (smolts, prespawning, spawning). All stages were infected, although infections in smolts were only detectable using a L. salmonae-specific PCR test. Many previous Loma spp. described from Oncorhychus spp. are likely L. salmonae based on host, parasite morphology, and site of infection.


Correlations between drug use, HIV disclosure and interpersonal communication on sexual risk behaviour of HIV-positive men who have sex with men.
The Human Immunodeficiency Virus (HIV) epidemic is a global health problem whose number of cases are always higher among men who have sex with men (MSM). Most existing MSM have moderate and very high risk behaviour in HIV transmission. This study was designed to identify correlations between drug use, HIV disclosure and interpersonal communication patterns on sexual risk behaviour among HIV-positive MSM. This study used a cross sectional design with a purposive sampling technique for participants who visited the voluntary counselling and testing (VCT) clinic in a referral hospital and snowball sampling technique for participants in the work area of a community health centre in Batam involving 126 HIV-positive MSM. Data were collected by 5 part questionnaire, namely demographic questionnaire, drug screening questionnaire, brief scale for HIV self disclosure, communication pattern questionnaire-short form, and safe sex behaviour questionnaire. Bivariate analysis was applied to determine whether there is a relationship between drug use, HIV disclosure, interpersonal communication and demographic characteristics (ethnicity, educational status) with sexual risk behaviour of MSM. Logistic regression analysis was used to explore the variables that most associated variable to sexual risk behaviour. The results showed that there was significant correlation between HIV disclosure and sexual risk behaviour (p = 0.019, α = 0.05, OR = 2.530) and significant correlation between interpersonal communication patterns and sexual risk behaviour (p = 0.016, α = 0.05, OR = 2.589). There is no significant correlation between demographic characteristics, namely: ethnicity and educational status with sexual behaviour at risk of MSM. In multiple logistic regression analysis, educational status was the factor that most associated with sexual risk behaviour among HIV-positive MSM (p = 0.027, α = 0.05, OR = 2.807, 95% CI = 1.125-7.006). HIV disclosure and interpersonal communication patterns have a significant negative correlation with sexual risk behaviour among HIV-positive MSM. MSM with low HIV disclosure have high risk sexual behaviour opportunities. MSM with the closed interpersonal communication pattern also has a high risk of sexual behaviour. Education status was the most associated variable to sexual risk behaviour of HIV-positive MSM. Nurses as professional health workers need to improve comprehensive assessment, personal counselling and plan specific learning model by involving HIV-positive MSM in reducing HIV transmission from risky behaviour.


Biomarkers of inflammation, metabolism, and oxidative stress in blood, liver, and milk reveal a better immunometabolic status in peripartal cows supplemented with Smartamine M or MetaSmart.
The peripartal dairy cow experiences a state of reduced liver function coupled with increased inflammation and oxidative stress. This study evaluated the effect of supplementing basal diets with rumen-protected Met in the form of MetaSmart (MS) or Smartamine M (SM) (both from Adisseo Inc., Antony, France) during the peripartal period on blood and hepatic biomarkers of liver function, inflammation, and oxidative stress. Thirty-seven multiparous Holstein cows were fed the same basal diet from -50 to -21 d relative to expected calving [1.24 Mcal/kg of dry matter (DM); no Met supplementation]. From -21 d to calving, the cows received diets (1.54 Mcal/kg of DM) with no added Met (control, CON; n=13), CON plus MS (n=11), or CON plus SM (n=13). From calving through 30 d in milk (DIM), the cows received the same postpartal diet (1.75 Mcal/kg of DM; CON), or CON plus MS or CON plus SM. Liver and blood samples were harvested at various time points from -21 to 21 d relative to calving. Preplanned contrasts of CON versus SM + MS during prepartum (-21 and -10 d before calving) and postpartum (7, 14, and 21 d after calving) responses were evaluated. Cows fed MS or SM compared with CON had lower overall concentrations of plasma ceruloplasmin and serum amyloid A (SAA). Compared with CON, Met-supplemented cows had greater overall plasma oxygen radical absorbance capacity. Liver concentrations of glutathione and carnitine also were greater overall with Met supplementation. Milk choline and liver phosphatidylcholine were lower overall in cows fed Met compared with controls. Liver tissue choline concentrations did not differ. Data indicate that supplemental Met enhanced de novo glutathione and carnitine synthesis in liver and, thus, increased antioxidant and β-oxidation capacity. The greater decrease of IL-6 after calving coupled with lower ceruloplasmin and SAA in Met-supplemented cows indicated a reduction in proinflammatory signaling within liver. The lower hepatic phosphatidylcholine in Met-supplemented cows might have been associated with greater assembly or export of very low density lipoproteins. Overall, biomarker analyses in blood and tissue indicate that the beneficial effect of feeding SM and MS on postpartal cow performance is due in part to a better immunometabolic status.


[The specific features of bacillary excretion and drug sensitivity in Mycobacterium tuberculosis in patients with recurrent pulmonary tuberculosis].
Data on 485 patients with recurrent pulmonary tuberculosis were studied. At the beginning of the study, all the patients underwent a triple sputum smear test and sputum was cultured in 338 cases. Among persons with a negative smear, sputum inoculation yielded Mycobacterium tuberculosis (MBT) in 50%. By taking into account these observations, bacillary excretion was detected in 72.2%. It was established most frequently by both methods (42%), slightly less frequently by the smear test (38%) and inoculation (20%). Drug resistance in MBT was revealed almost equally frequently in bacillary recurrences in patients with positive and negative sputum smear tests (68 and 62.3%, respectively). The bulk of the strains obtained were found to be polyresistant as well as quite often multiresistant. In the group of patients who had received chemotherapy by the WHO standards at primary detection of tuberculosis, polyresistance and multiresistance were encountered significantly more frequently in those who had been treated in previous years. The resistance of MBT to various drugs was also studied. Recommendations are given on the basis of the results of the study.


Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nerves.
Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K(+)-Cl(-) cotransporter (KCC) family includes four isoforms (KCC1-4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K(+) and Cl(-) with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2-4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na(+)-K(+)-2Cl(-)-cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3(-/-) mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3(-/-) mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K(+)-Cl(-) cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves.


[Cardiorespiratory capacity in children living at moderate altitude].
To determine the cardiorespiratory capacity of school children living at moderate altitude. 795 children (394 children and 401 girls) were selected from urban public schools in Arequipa, Peru at moderate altitude (2,320 m). Anthropometric variables (body mass, height, body fat percentage) and cardiorespiratory capacity were assessed using the Course Navette test, considering the following categories: deficient, poor, fair, good, very good and excellent. The results showed significant differences in all categories (p<0.05). It was described that the median values of the poor and deficient categories in both gender were lower than what is considered acceptable (p<0.05). It was concluded that 19% of boys and 21% of girls showed low level of cardiorespiratory capacity and a low negative correlation with overweight (r=-0.20 to -0.22) and a moderate negative correlation with obesity (r=-0.39 to -0.42) were described for both genders. Low levels of cardiorespiratory capacity in boys and girls living at moderate altitude are observed, which is negatively correlated with excess body weight. The results suggest that 1 in 5 children are likely to suffer some type of cardiovascular event.


Transient Loss-Induced Non-Hermitian Degeneracies for Ultrafast Terahertz Metadevices.
Non-Hermitian degeneracies, also known as exceptional points (EPs), have attracted considerable attention due to their unique physical properties. In particular, metasurfaces related to EPs can open the way to unprecedented devices with functionalities such as unidirectional transmission and ultra-sensitive sensing. Herein, an active non-Hermitian metasurface with a loss-induced parity-time symmetry phase transition for ultrafast terahertz metadevices is demonstrated. Specifically, the eigenvalues of the non-Hermitian transmission matrix undergo a phase transition under optical excitation and are degenerate at EPs in parameter space, which is accompanied by the collapse of chiral transmission. Ultrafast EP modulation on a picosecond time scale can be realized through variations in the transient loss at a non-Hermitian metasurface pumped by pulsed excitation. Furthermore, by exploiting the physical characteristics of chiral transmission EPs, a switchable quarter-wave plate based on the photoactive metasurface is designed and experimentally verified and realized the corresponding function of polarization manipulation. This work opens promising possibilities for designing functional terahertz metadevices and fuses EP physics with active metasurfaces.


Determinants of duration of ICU stay after coronary artery bypass graft surgery.
Prediction of duration of a patient's stay in the ICU after cardiac surgery is difficult. In 652 consecutive adult patients undergoing elective coronary artery bypass graft (CABG) surgery, we analysed prospectively preoperative and immediate postoperative variables thought to influence duration of stay in the ICU. With univariate analysis, we found that age, preoperative left ventricular ejection fraction, bypass time, aortic cross-clamp time, blood transfusions and the number of inotropic agents administered in the immediate postoperative period (for at least 6 h) were significant correlates of duration of stay in the ICU. However, logistic regression analysis showed that the number of inotropes was the most important determinant of stay in the ICU, with an overall prediction accuracy of 94.8%. The main cause of prolonged stay in the ICU (more than 2 days) was low cardiac output syndrome. We conclude that analysis of perioperative variables enhanced our ability to accurately predict duration of stay in the ICU in cardiac surgery patients. The number of inotropic agents administered during the first 6 h after operation was the most important determinant of duration of stay in the ICU.


Seasonal exposures to triazine and other pesticides in surface waters in the western Highveld corn-production region in South Africa.
The objective of this study was to characterize concentrations of atrazine, terbuthylazine, and other pesticides in amphibian habitats in surface waters of a corn-production area of the western Highveld region (North-West Province) of South Africa. The study was conducted from November 2001 to June 2002, coinciding with the corn-production season. Pesticide residues were measured at regular intervals in surface water from eight ponds, three in a non-corn-growing area (NCGA) and five within the corn-growing area (CGA). Measured atrazine concentrations differed significantly among sites and between samples. In the five CGA sites, the maximum atrazine concentrations measured during the study ranged from 1.2 to 9.3 microg/L. Although no atrazine was recorded as being applied in the catchment of the three NCGA sites, maximum concentrations from 0.39 to 0.84 microg/L were measured during the study, possibly as a result of atmospheric transport. Maximum measured concentrations of terbuthylazine ranged from 1.22 to 2.1 microg/L in the NCGA sites and from 1.04 to 4.1 microg/L in the CGA sites. The source of terbuthylazine in the NCGA sites may have been in use other than in corn. The triazine degradation products, deisopropylatrazine (DIA) and deethylatrazine (DEA) and diaminochlorotriazine (DACT) were also found in water from both the CGA and NCGA sites. Concentrations of DIA were > or = 1 microg/L throughout the season, while DEA concentrations were mostly <0.5 microg/L before planting but increased after planting and application of herbicides to concentrations >2 microg/L in some locations. Concentrations of DACT were highly variable (LOD to 8 microg/L) both before and after planting and application, suggesting that they resulted from historical use of triazines in the area. Other herbicides such as simazine and acetochlor were only detected infrequently and pesticides such as S-metolachlor, cypermethrin, monocrotophos, and terbuphos, known to be used in the CGA, were not detected in any of the samples. Because of dilution by higher than normal rainfall in the study period, these concentrations may not be predictive of those in years of normal rainfall.


Longitudinal associations between stressors and work ability in hospital workers.
This study sought to assess associations between work stressors and work ability in a cohort (2009-2012) of 498 hospital workers. Time-dependent variables associated with the Work Ability Index (WAI) were evaluated using general linear mixed models. Analyses included effects of individual and work characteristics. Except for work demands, the work stressors (job control, social support, effort-reward imbalance, overcommitment and work-related activities that cause pain/injury) were associated with WAI (p < 0.050) at intercept and in the time interaction. Daytime work and morning shift work were associated with decreased WAI (p < 0.010). Work stressors negatively affected work ability over time independently of other variables.


An mHealth App for Self-Management of Chronic Lower Back Pain (Limbr): Pilot Study.
Although mobile health (mHealth) interventions can help improve outcomes among patients with chronic lower back pain (CLBP), many available mHealth apps offer content that is not evidence based. Limbr was designed to enhance self-management of CLBP by packaging self-directed rehabilitation tutorial videos, visual self-report tools, remote health coach support, and activity tracking into a suite of mobile phone apps, including Your Activities of Daily Living, an image-based tool for quantifying pain-related disability. The aim is to (1) describe patient engagement with the Limbr program, (2) describe patient-perceived utility of the Limbr program, and (3) assess the validity of the Your Activities of Daily Living module for quantifying functional status among patients with CLBP. This was a single-arm trial utilizing a convenience sample of 93 adult patients with discogenic back pain who visited a single physiatrist from January 2016 to February 2017. Eligible patients were enrolled in 3-month physical therapy program and received the Limbr mobile phone app suite for iOS or Android. The program included three daily visual self-reports to assess pain, activity level, and medication/coping mechanisms; rehabilitation video tutorials; passive activity-level measurement; and chat-based health coaching. Patient characteristics, patient engagement, and perceived utility were analyzed descriptively. Associations between participant characteristics and program interaction were analyzed using multiple linear regression. Associations between Your Activities of Daily Living and Oswestry Disability Index (ODI) assessments were examined using Pearson correlation and hierarchical linear modeling. A total of 93 participants were enrolled; of these, 35 (38%) completed the program (age: mean 46, SD 16 years; female: 22/35, 63%). More than half of completers finished assessments at least every 3 days and 70% (19/27) used the rehabilitation component at least once a week. Among respondents to a Web-based feedback survey, 76% (16/21) found the daily notifications helped them remember to complete their exercises, 81% (17/21) found the system easy to use, and 62% (13/21) rated their overall experience good or excellent. Baseline Your Activities of Daily Living score was a significant predictor of baseline ODI score, with ODI increasing by 0.30 units for every 1-unit increase in Your Activities of Daily Living (P<.001). Similarly, hierarchical linear modeling analysis indicated that Your Activities of Daily Living daily assessment scores were significant predictors of ODI scores over the course of the study (P=.01). Engagement among participants who completed the Limbr program was high, and program utility was rated positively by most respondents. Your Activities of Daily Living was significantly associated with ODI scores, supporting the validity of this novel tool. Future studies should assess the effect of Limbr on clinical outcomes, evaluate its use among a wider patient sample, and explore strategies for reducing attrition. ClinicalTrials.gov NCT03040310; https://clinicaltrials.gov/ct2/show/NCT03040310 (Archived by WebCite at http://www.webcitation.org/722mEvAiv).


Clinical and epidemiologic investigation of two Legionella-Rickettsia co-infections.
We treated two patients diagnosed with legionellosis and simultaneous Rickettsia conorii co-infection. To report the clinical and laboratory characteristics of this unusual combination, and to describe the execution and results of our environmental and epidemiologic investigations. Serial serologic testing was conducted 1, 4 and 7 weeks after initial presentation. Water samples from the patients' residence were cultured for Legionella. Follow-up cultures were taken from identical points at 2 weeks and at 3 months after the initial survey. Both patients initially expressed a non-specific rise in anti-Legionella immunoglobulin M titers to multiple serotypes. By week 4 a definite pattern of specifically elevated IgG titers became apparent, with patient 1 demonstrating a rise in specific anti-L. pneumophila 12 IgG titer and patient 2 an identical response to L. jordanis. At 4 weeks both patients were positive for both IgM and IgG anti-R. conorii antibodies at a titer > or = 1:100. Heavy growth of Legionella was found in water sampled from the shower heads in the rooms of both patients. Indirect immunofluorescence of water cultures was positive for L. pneumophila 12 and for L. jordanis. Although most cases of community-acquired Legionella pneumonia in our region appear simultaneously with at least one other causative agent, co-infection with R. conorii is unusual and has not been reported to date. This report illustrates the importance of cooperation between clinicians and public health practitioners.


Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry.
Autofluorescence (lambda = 530 nm) of the human lens was determined as a function of age by fluorophotometry in insulin-dependent diabetics and in healthy controls. Statistical analysis revealed a significant linear age dependency for both groups (7.98 ng eq X ml-1 y-1 for diabetic patients, P less than 0.001 and 6.36 ng eq X ml-1 y-1 for healthy controls, P less than 0.001) and a significant dependency on diabetes duration (8.78 ng eq X ml-1 per year of diabetes duration, P less than 0.001). The increase with age was found from about zero value at early childhood.


Rhizosphere mediated biodegradation of benzo(A)pyrene by surfactin producing soil bacilli applied through Melia azadirachta rhizosphere.
Benzo(a)pyrene is a high-molecular-weight polycyclic aromatic hydrocarbon highly persistent in the environment as a biohazard. The present research emphasizes on rhizodegradation of BaP using bacterial isolates, Bacillus flexus S1I26 (NCBI accession no- KX692271), and Paenibacillus sp. S1I8 (KX602663) with plant Melia azadirachta. The isolates produced surfactin type bio-surfactant with high emulsification index that could solubilize BaP efficiently. The extracted crude bio-surfactants could solubilize BaP up to 24.41%, which was higher than the efficiency of synthetic surfactant SDS (9.7%) but less than other synthetic surfactant, tweens 80 (42.79%). The isolates showed excellent degradation of BaP after 21 days in laboratory conditions where B. flexus S2I26 showed degradation of BaP up to 70.7% and isolates Paenibacillus sp. S1I8 showed degradation rate of 76.76% in a liquid medium. Pot trial experiment showed efficient rhizodegradation of BaP in the soil after 60 days in the rhizosphere of plant Melia azadirachta. After application of S1I8 and S1I26, the rate of degradation was found to be much higher (87.42 and 86.08%) than in bulk (68.22%). Therefore, the results suggest that the bio-surfactant producing isolates could be a promising biodegradation tool for benzo(a)pyrene in soil and may be used for bioremediation of hydrocarbon contaminated sites.


Influence of delivery method on neuroprotection by bone marrow mononuclear cell therapy following ventral root reimplantation with fibrin sealant.
The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results.


Comparative evaluation of carbosulfan- and permethrin-impregnated curtains for preventing house-entry by the malaria vector Anopheles gambiae in Burkina Faso.
Pyrethroid-impregnated bednets and curtains are widely employed to reduce the risk of malaria transmission, but pyrethroid-resistance is becoming more prevalent among malaria vector Anopheles mosquitoes (Diptera: Culicidae). As an alternative treatment for curtains, we assessed carbosulfan (a carbamate insecticide) in comparison with permethrin as the standard pyrethroid, against endophilic female mosquitoes of the Anopheles gambiae Giles complex in a village near Ouagadougou, Burkina Faso. The main criterion evaluated was the impact of curtains (hung inside windows, eaves and doorways) on the number of An. gambiae s.l. females active indoors at night. Light-traps were operated overnight (21.00-06.00 hours beside occupied untreated bednets) to sample mosquitoes in houses fitted with net curtains treated with carbosulfan 0.2 g ai/m2 or permethrin 1 g ai/m2 or untreated, compared with houses without curtains. The treated and untreated curtains significantly reduced the numbers of mosquitoes collected indoors, compared with houses without curtains. Carbosulfan-treated curtains had a highly significantly greater effect than permethrin-treated or untreated curtains, the scale of the difference being estimated as three-fold. However, there was no significant difference between the impact of untreated and permethrin-treated curtains on densities of An. gambiae s.l. trapped indoors. Samples of the An. gambiae complex comprised An. arabiensis Patton and both the S- and M-forms of An. gambiae Giles s.s. Susceptibility tests revealed some resistance to DDT and low frequencies of permethrin-resistance, insufficient to explain the poor performance of permethrin on curtains. Among survivors from the diagnostic dosage of permethrin were some specimens of all three members of the An. gambiae complex, but the kdr resistance mechanism was detected only in the S-form of An. gambiae s.s. Questions arising for further investigation include clarification of resistance mechanisms in, and foraging behaviour of, each member of the An. gambiae complex in this situation and the need to decide whether carbosulfan-treated curtains are acceptably safe for use to reduce risks of malaria transmission.


The fabM gene product of Streptococcus mutans is responsible for the synthesis of monounsaturated fatty acids and is necessary for survival at low pH.
Previously, it has been demonstrated that the membrane fatty acid composition of Streptococcus mutans is affected by growth pH (E. M. Fozo and R. G. Quivey, Jr., Appl. Environ. Microbiol. 70:929-936, 2004; R. G. Quivey, Jr., R. Faustoferri, K. Monahan, and R. Marquis, FEMS Microbiol. Lett. 189:89-92, 2000). Specifically, the proportion of monounsaturated fatty acids increases when the organism is grown in acidic environments; if the shift to increased monounsaturated fatty acids is blocked by the addition of a fatty acid biosynthesis inhibitor, the organism is rendered more acid sensitive (E. M. Fozo and R. G. Quivey, Jr., Appl. Environ. Microbiol. 70:929-936, 2004). Recently, work with Streptococcus pneumoniae has identified a novel enzyme, FabM, responsible for the production of monounsaturated fatty acids (H. Marrakchi, K. H. Choi, and C. O. Rock, J. Biol. Chem. 277:44809-44816, 2002). Using the published S. pneumoniae sequence, a putative FabM was identified in the S. mutans strain UA159. We generated a fabM strain that does not produce unsaturated fatty acids as determined by gas chromatography of fatty acid methyl esters. The mutant strain was extremely sensitive to low pH in comparison to the wild type; however, the acid-sensitive phenotype was relieved by growth in the presence of long-chain monounsaturated fatty acids or through genetic complementation. The strain exhibited reduced glycolytic capability and altered glucose-PTS activity. In addition, the altered membrane composition was more impermeable to protons and did not maintain a normal DeltapH. The results suggest that altered membrane composition can significantly affect the acid survival capabilities, as well as several enzymatic activities, of S. mutans.


Investigation of the human oesophagus as a new monitoring site for blood oxygen saturation.
Pulse oximeter probes placed peripherally may fail to give accurate values of arterial blood oxygen saturation (SpO2) when peripheral perfusion is poor. Since central blood flow may be preferentially preserved, the oesophagus was suggested as an alternative monitoring site. A reflectance oesophageal photoplethysmographic (PPG) probe and a multiplexed data acquisition system, operating simultaneously at two wavelengths and incorporating an external three-lead electrocardiogram (ECG) reference channel, has been developed. It has been used to investigate the suitability of the oesophagus as a possible monitoring site for SpO2 in cases of compromised peripheral perfusion. Oesophageal PPG signals and standard ECG traces were obtained from 16 anaesthetized patients and displayed on a laptop computer. Measurable PPG signals with high signal-to-noise ratios at both infrared and red wavelengths were obtained from all five oesophageal depths investigated. The maximum PPG amplitude occurred at 25 cm from the upper incisors in the mid-oesophagus. The measured pulse transit times (PTTs) to the oesophagus were consistent with previous measurements at peripheral sites and had a minimum value of 67 +/- 30 ms at a depth of 30 cm. There was broad agreement between the calculated values of oesophageal SpO2 and those from a commercial finger pulse oximeter.


Screening for mutations in exons encoding the ligand-binding domain of the LDL receptor gene using PCR-CFLP and PCR-SSCP.
Primary hypercholesterolemia includes both monogenic disorders and polygenic conditions. Two well defined monogenic disorders are familial hypercholesterolemia (FH) and familial defective apolipoprotein (apo) B-100 (FDB). Both disorders convey high risk of premature coronary artery disease. FH and FDB are caused by mutations in LDL receptor and apo B-100 genes, respectively. In the present study, mutations in both genes in Thai subjects with primary hypercholesterolemia were screened. For apo B-100 gene, a common mutation R3500Q was screened. This mutation was not observed in the patients (n = 45). For LDL receptor gene, mutations in the exons encoding the ligand-binding domain were screened. By PCR-CFLP analysis, 18 abnormal CFLP patterns in exon 4, the hot spot for mutations, were found in patients (n=45). One of the DNA samples with abnormal CFLP patterns was previously identified and reported as a possible disease-causing mutation, namely D151Y. For the other exons, the screening technique was PCR-SSCP. Abnormal SSCP patterns in DNA samples from patients (n=20) were found as follows, two in exon 3, one in exon 5 and another one in exon 6. Further characterization by DNA sequencing and family studies for these abnormal patterns are underway.


Inhibitory Effects of Trifluoperazine on Peripheral Proinflammatory Cytokine Expression and Hypothalamic Microglia Activation in Obese Mice Induced by Chronic Feeding With High-Fat-Diet.
Microglia and astrocytes are the glial cells of the central nervous system (CNS) to support neurodevelopment and neuronal function. Yet, their activation in association with CNS inflammation is involved in the initiation and progression of neurological disorders. Mild inflammation in the periphery and glial activation called as gliosis in the hypothalamic region, arcuate nucleus (ARC), are generally observed in obese individuals and animal models. Thus, reduction in peripheral and central inflammation is considered as a strategy to lessen the abnormality of obesity-associated metabolic indices. In this study, we reported that acute peripheral challenge by inflammagen lipopolysaccharide (LPS) upregulated the expression of hypothalamic dopamine type 2 receptor (D2R) mRNA, and chronic feeding by high-fat-diet (HFD) significantly caused increased levels of D2R in the ARC. The in vitro and in vivo studies indicated that an FDA-approved antipsychotic drug named trifluoperazine (TFP), a D2R inhibitor was able to suppress LPS-stimulated activation of microglia and effectively inhibited LPS-induced peripheral inflammation, as well as hypothalamic inflammation. Further findings showed daily peripheral administration intraperitoneally (i.p.) by TFP for 4 weeks was able to reduce the levels of plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in accompany with lower levels of plasma glucose and insulin in obese mice receiving HFD for 16 weeks when compared those in obese mice without TFP treatment. In parallel, the activation of microglia and astrocytes in the ARC was also inhibited by peripheral administration by TFP. According to our results, TFP has the ability to suppress HFD-induced ARC gliosis and inflammation in the hypothalamus.


KCNT1 epilepsy with migrating focal seizures shows a temporal sequence with poor outcome, high mortality and SUDEP.
Epilepsy of infancy with migrating focal seizures was first described in 1995. Fifteen years later, KCNT1 gene mutations were identified as the major disease-causing gene of this disease. Currently, the data on epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations are heterogeneous and many questions remain unanswered including the prognosis and the long-term outcome especially regarding epilepsy, neurological and developmental status and the presence of microcephaly. The aim of this study was to assess data from patients with epilepsy in infancy with migrating focal seizures with KCNT1 mutations to refine the phenotype spectrum and the outcome. We used mind maps based on medical reports of children followed in the network of the French reference centre for rare epilepsies and we developed family surveys to assess the long-term outcome. Seventeen patients were included [age: median (25th-75th percentile): 4 (2-15) years, sex ratio: 1.4, length of follow-up: 4 (2-15) years]. Seventy-one per cent started at 6 (1-52) days with sporadic motor seizures (n = 12), increasing up to a stormy phase with long lasting migrating seizures at 57 (30-89) days. The others entered this stormy phase directly at 1 (1-23) day. Ten patients entered a consecutive phase at 1.3 (1-2.8) years where seizures persisted at least daily (n = 8), but presented different semiology: brief and hypertonic with a nocturnal (n = 6) and clustered (n = 6) aspects. Suppression interictal patterns were identified on the EEG in 71% of patients (n = 12) sometimes from the first EEG (n = 6). Three patients received quinidine without reported efficacy. Long-term outcome was poor with neurological sequelae and active epilepsy except for one patient who had an early and long-lasting seizure-free period. Extracerebral symptoms probably linked with KCNT1 mutation were present, including arteriovenous fistula, dilated cardiomyopathy and precocious puberty. Eight patients (47%) had died at 3 (1.5-15.4) years including three from suspected sudden unexpected death in epilepsy. Refining the electro-clinical characteristics and the temporal sequence of epilepsy in infancy with migrating focal seizures should help diagnosis of this epilepsy. A better knowledge of the outcome allows one to advise families and to define the appropriate follow-up and therapies. Extracerebral involvement should be investigated, in particular the cardiac system, as it may be involved in the high prevalence of sudden unexpected death in epilepsy in these cases.


[Reproducibility of lumbar spine kinematics in clinical gait analysis].
The objective measurement of functional lumbopelvical movements enables the evaluation of the quantity and quality of movements referring to functional disorders in dynamic test-situations. The goal of the present study is the determination of the reproducibility of time-continuous movement analysis of the pelvic region during walking and the determination of possible errors. The movements of the thoracic (Th12), lumbar and sacrum-region (S1) of 17 healthy subjects (age: 32.1 +/- 2.3 years) during walking on a treadmill (4.5 km/h) were investigated twice in an interval of 24 hours by means of a 3D ultrasonic movement analysis system. The ensemble averages of the low-pass filtered and time-normalized angle-time sequences of all anatomical planes and regions showed high test-retest correlations (r > or = 0.92, p < 0.01) except fo the lumbar movement in the sagittal plane (r = 0.79, p < 0.01). A paired t-test showed no significant differences for the amplitudes of test and retest measurements except for the thoracolumbar movement in the sagittal plane (p < .05). The results show that the evaluation of lumbar movement patterns can be regarded as admissible and desirable for clinical movement analysis. The data can be used as a diagnostic tool for the planning and control of therapeutic interventions.


[Thermal sensitivity of aldolase isoenzymes in the organs of cattle, sheep and swine].
During the investigation of homogenates from organs of cattle, sheep and swine (a heart, a kidney, a pancreas, a liver, a thigh muscle, a spleen, a lung) the highest activity of aldolase was proved in the bodily muscles, whereas in the other organs it did not show great differences. Thus it is determined as an ubiquitous enzyme in all these kinds of farm animals. After heating at 61 degrees C for 15 min. aldolase from the bodily muscles of cattle, sheep and swine, showed a high degree of thermostability (residual activity of 86 = 92%), whereas in the parenchymatous organs the enzyme was considerably thermosensitive (residual activity of 15.2--48.4%). The liver isoenzyme of aldolase showed the highest degree of thermosensitivity and had a residual activity of hardly 8--12%. A viewpoint is endorsed, namely that on that basis can be differentiated some pathological processes in the musculature from the pathological processes in the parenchymatous organs.


The Role of Adjuvant Acid Suppression on the Outcomes of Bleeding Esophageal Varices after Endoscopic Variceal Ligation.
The impact of adjuvant acid suppression via proton pump inhibitors or histamine-2 receptor antagonists after endoscopic variceal ligation remains uncertain. We therefore aimed to evaluate the effect of adjuvant acid suppression on the rebleeding and mortality rates in patients who received endoscopic variceal ligation and vasoconstrictor therapy for bleeding esophageal varices. Data from 1997 to 2011 were extracted from the National Health Insurance Research Database in Taiwan. A total of 1576 cirrhotic patients aged > 18 years with a primary diagnosis of acute esophageal variceal bleeding who received endoscopic variceal ligation therapy were screened. After strict exclusion, 637 patients were recruited. The exclusion criteria included patients with gastric variceal bleeding, failure in the control of bleeding, mortality within 12 hours, and history of hepatocellular carcinoma or gastric cancer. Patients were divided into two groups: the vasoconstrictors group (n = 126) and vasoconstrictors plus acid suppression group (n = 511). We observed that the rebleeding and mortality rates were not significantly different between 2 groups during hospitalization and the 15-year follow-up period after discharge. A Charlson score ≥3 (odds ratio: 2.42, 95% confidence interval: 1.55 ~3.79, P = 0.0001), presence of hepatitis C virus (odds ratio: 1.70, 95% confidence interval: 1.15 ~2.52, P = 0.0085), and cirrhosis (odds ratio: 1.69, 95% confidence interval: 1.08 ~2.66, P = 0.0229) were the independent risk factors of mortality after discharge. In conclusion, the results of the current study suggest that adjuvant acid suppression prescription to patients who received endoscopic variceal ligation and vasoconstrictor therapy for bleeding esophageal varices may not change the rebleeding and mortality outcomes compared to that for those who received endoscopic variceal ligation and vasoconstrictor agents without acid suppression.


Emergency diagnosis of cancer and previous general practice consultations: insights from linked patient survey data.
Emergency diagnosis of cancer is common and aetiologically complex. The proportion of emergency presenters who have consulted previously with relevant symptoms is uncertain. To examine how many patients with cancer, who were diagnosed as emergencies, have had previous primary care consultations with relevant symptoms; and among those, to examine how many had multiple consultations. Secondary analysis of patient survey data from the 2010 English Cancer Patient Experience Survey (CPES), previously linked to population-based data on diagnostic route. For emergency presenters with 18 different cancers, associations were examined for two outcomes (prior GP consultation status; and 'three or more consultations' among prior consultees) using logistic regression. Among 4647 emergency presenters, 1349 (29%) reported no prior consultations, being more common in males (32% versus 25% in females, P<0.001), older (44% in ≥85 versus 30% in 65-74-year-olds, P<0.001), and the most deprived (35% versus 25% least deprived, P = 0.001) patients; and highest/lowest for patients with brain cancer (46%) and mesothelioma (13%), respectively (P<0.001 for overall variation by cancer site). Among 3298 emergency presenters with prior consultations, 1356 (41%) had three or more consultations, which were more likely in females (P<0.001), younger (P<0.001), and non-white patients (P = 0.017) and those with multiple myeloma, and least likely for patients with leukaemia (P<0.001). Contrary to suggestions that emergency presentations represent missed diagnoses, about one-third of emergency presenters (particularly those in older and more deprived groups) have no prior GP consultations. Furthermore, only about one-third report multiple (three or more) consultations, which are more likely in 'harder-to-suspect' groups.


Binuclear ruthenium complexes of a neutral radical bridging ligand. A new "spin" on mixed valency.
The electronic structures of (LX)2Ru(Vd)Ru(LX)2 complexes (Vd = 1,5-diisopropyl-3-(4,6-dimethyl-2-pyrimidinyl)-6-oxoverdazyl radical; LX = acac (acetylacetonate) or hfac (hexafluoroacetylacetonate)) in multiple charge states have been investigated experimentally and computationally. The main focus was to probe the consequences of the interplay between the ruthenium ions and the redox-active verdazyl ligand for possible mixed-valent behavior. Cyclic voltammetry studies reveal one reversible reduction and one reversible oxidation process for both complexes; in addition the acac-based derivative possesses a second reversible oxidation. Analysis of a collection of experimental (X-ray structures, EPR, electronic spectra) and computational (TD-DFT (PCM)) data reveal that the ruthenium ancillary ligands (acac vs hfac) have dramatic consequences for the electronic structures of the complexes in all charge states studied. In the hfac series, the neutral complex is best regarded as a binuclear Ru(II) species bridged by a neutral radical ligand. Reduction to give the anionic complex takes place on the verdazyl ligand, whereas oxidation to the cation (a closed shell species) is shared between Vd and ruthenium. For the acac-based complexes, the neutral species is most accurately represented as a Ru(II)/Ru(III) mixed valent complex containing a bridging verdazyl anion, though some bis(Ru(II))-neutral radical character remains. The monocation complex contains a significant contribution from a "broken symmetry" singlet diradical structure, best represented as a bis-Ru(III) system with an anionic ligand, with significant spin coupling of the two Ru(III) centers via the Vd(-1) ligand (calculated J = -218 cm(-1)). The dication, a spin doublet, consists of two Ru(III) ions linked (and antiferromagnetically coupled) to the neutral radical ligand. Computed net σ- and π-back-donation, spin densities, and orbital populations are provided. Time dependent DFT is used to predict the optical spectra and assign experimental data.


Effects of anti-inflammatory treatment on efficacy of selective laser trabeculoplasty: a systematic review and meta-analysis.
Selective laser trabeculoplasty (SLT) can evidently reduce intraocular pressure (IOP) in cases of open-angle glaucoma. Several studies have investigated the effectiveness of anti-inflammatory treatment to relieve discomfort after SLT, but whether such treatments affect the response of SLT remains uncertain. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library for relevant studies published before 31 March 2021. The major outcomes were the efficacy of post-SLT anti-inflammatory treatment on IOP reduction, incidence of discomfort, and anterior chamber inflammation compared with those of placebo agents. Five randomized controlled trials with 235 eyes receiving anti-inflammatory treatment and 170 eyes receiving placebo agents were included in the meta-analysis. Compared with placebo, no significant differences were present in IOP reduction effects upon using topical non-steroidal anti-inflammatory drugs or steroid post-SLT. The results were consistent from 1 to 6 months during follow-up. Furthermore, anti-inflammatory treatment had no significant effects on pain or discomfort or the presence of anterior chamber cells 1 h to 1 week post-SLT. Topical anti-inflammatory treatment after SLT for patients with glaucoma neither significantly affected IOP reduction nor remarkably relieved clinical discomfort and anterior chamber inflammation. Hence, regular use of post-SLT anti-inflammatory treatment may be unnecessary.


Training medical students in the social determinants of health: the Health Scholars Program at Puentes de Salud.
Given the large influence of social conditions on health, physicians may be more effective if they are trained to identify and address social factors that impact health. Despite increasing interest in teaching the social determinants of health in undergraduate medical education, few models exist. We present a 9-month pilot course on the social determinants of health for medical and other health professional students, which is based at Puentes de Salud, Philadelphia, PA, USA, a community health center serving a Latino immigrant population. This service-learning course, called the Health Scholars Program (HSP), was developed and implemented by volunteer medical and public health faculty in partnership with the community-based clinic. The HSP curriculum combines didactic instruction with service experiences at Puentes de Salud and opportunities for critical reflection. The HSP curriculum also includes a longitudinal project where students develop, implement, and evaluate an intervention to address a community-defined need. In our quantitative evaluation, students reported high levels of agreement with the HSP meeting stated course goals, including developing an understanding of the social determinants of health and working effectively with peers to implement community-based projects. Qualitative assessments revealed students' perception of learning more about this topic in the HSP than in their formal medical training and of developing a long-term desire to serve vulnerable communities as a result. Our experience with the HSP suggests that partnerships between academic medical centers and community-based organizations can create a feasible, effective, and sustainable platform for teaching medical students about the social determinants of health. Similar medical education programs in the future should seek to achieve a larger scale and to evaluate both students' educational experiences and community-defined outcomes.


Management of auditory hallucinations as a sequela of traumatic brain injury: a case report and a relevant literature review.
A patient with progressively worsening auditory hallucinations and 30-year history of traumatic brain injury (TBI) was reported. To formulate a comprehensive diagnostic and treatment approach to patients with auditory sensory disturbances and other neuropsychiatric sequela of a TBI, an electronic search of the major behavioral science databases (PubMed, PsycINFO, Medline) and a textbook review were conducted to retrieve studies detailing the clinical characteristics, biological mechanisms, and therapeutic approaches to post-TBI psychosis. Additional references were incorporated from the bibliographies of the retrieved articles. Although infrequent, auditory hallucinations is a debilitating complication of TBI that can manifest itself 4-5 years after the occurrence of TBI. Because the age range of TBI survivors is 15-24 years, and the chance of developing post-TBI psychosis is reported to be up to 20%, this chronic neuropsychiatric complication and the available treatment options warrant close scrutiny from the clinical and the biomedical research community. Our case report and literature review demonstrates a clear need for a large, well-designed randomized trials to compare properties and efficacies of different, available, and promising pharmacotherapy agents for the treatment of post-TBI psychosis.


Communicative interaction between teachers and children with severe handicaps.
The content and structure of teacher input language to children with severe handicaps during early stages of language development were examined. Teacher-child dyads (N = 21) were videotaped during interactions in a semi-structured play setting. Each child was ranked as to level of communicative abilities on a scale of early communicative behaviors. Results showed that teachers adjusted the complexity of their linguistic requests based on the child's level of communication and modulated their requests based on children's responses from one moment to the next. The structure of the teacher's utterances was not as closely attuned to the communicative levels of the children. Issues and problems relating to adults' linguistic interaction with children with handicaps were discussed.


Patterns of helminth infection and relationship to BCG vaccination in Karonga District, northern Malawi.
Surveys of enteric and urinary helminth infections were carried out in 1999 among 501 schoolchildren and among 320 adolescents and young adults participating in a study of immune responses to BCG vaccine in Karonga District, northern Malawi. Hookworm, Schistosoma mansoni and S. haematobium infections were detected in 64%, 27% and 20% of schoolchildren and in 55%, 40% and 25% of the immunology study subjects, respectively. Other helminths were appreciably less common. The prevalence of 'at least one' helminth infection was 76% among schoolchildren, ranging from 60% to 92% in the 4 schools, and was 79% in the immunology study participants. There was no evidence for an association between the presence of a BCG scar and presence or intensity of infection with worms in the schoolchildren, nor evidence that BCG vaccination of adolescents and young adults had any effect on the prevalence of helminth infections 1 year later.


Pacific oyster polyamine oxidase: a protein missing link in invertebrate evolution.
Polyamine oxidases catalyse the oxidation of polyamines and acetylpolyamines and are responsible for the polyamine interconversion metabolism in animal cells. Polyamine oxidases from yeast can oxidize spermine, N(1)-acetylspermine, and N(1)-acetylspermidine, while in vertebrates two different enzymes, namely spermine oxidase and acetylpolyamine oxidase, specifically catalyse the oxidation of spermine, and N(1)-acetylspermine/N(1)-acetylspermidine, respectively. In this work we proved that the specialized vertebrate spermine and acetylpolyamine oxidases have arisen from an ancestor invertebrate polyamine oxidase with lower specificity for polyamine substrates, as demonstrated by the enzymatic activity of the mollusc polyamine oxidase characterized here. This is the first report of an invertebrate polyamine oxidase, the Pacific oyster Crassostrea gigas (CgiPAO), overexpressed as a recombinant protein. This enzyme was biochemically characterized and demonstrated to be able to oxidase both N(1)-acetylspermine and spermine, albeit with different efficiency. Circular dichroism analysis gave an estimation of the secondary structure content and modelling of the three-dimensional structure of this protein and docking studies highlighted active site features. The availability of this pluripotent enzyme can have applications in crystallographic studies and pharmaceutical biotechnologies, including anticancer therapy as a source of hydrogen peroxide able to induce cancer cell death.