Endocardial pacemaker or defibrillator leads with infected vegetations: a single-center experience and consequences of transvenous extraction.
Removal of infected endovascular leads if often required for cure of systemic infection, but the perceived risk of embolic events in the presence of large (>10 mm) vegetations has been considered a relative contraindication to transvenous removal. Surgical removal of pacemaker leads has been suggested in this situation to avoid occurrence of pulmonary embolization. Of 38 patients with infection of implanted pacemaker or cardioverter-defibrillator devices, those with evidence for systemic infection underwent transesophageal echocardiography to assess for the presence of vegetations. Vegetations on endocardial leads or right-sided cardiac structures ranging in size from 10 mm to 38 mm in their largest dimension were detected in 9 patients. All patients underwent successful transvenous removal of endocardial leads. Five of 9 patients (55%) had evidence of pulmonary embolism. However, all 5 patients made a full recovery with antibiotic treatment and anticoagulation. Among patients with endocardial vegetations, there was no difference in hospitalization periods between those with or without pulmonary embolism (14.6 +/- 0.8 days vs 18.0 +/- 4.5 days, P =.7). Transvenous removal of infected pacemaker leads is an alternative to open-thoracotomy removal of infected leads. Fifty-five percent of patients with vegetations on endocardial leads in our series experienced pulmonary embolism, but neither survival nor length of hospital stay were affected by this complication.


MicroRNAs encoded by Kaposi's sarcoma-associated herpesvirus regulate viral life cycle.
Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with Kaposi's sarcoma and lymphomas. The pathogenesis of KSHV depends on the balance between two phases of the viral cycle: latency and lytic replication. In this study, we report that KSHV-encoded microRNAs (miRNAs) function as regulators by maintaining viral latency and inhibiting viral lytic replication. MiRNAs are short, noncoding, small RNAs that post-transcriptionally regulate the expression of messenger RNAs. Of the 12 viral miRNAs expressed in latent KSHV-infected cells, we observed that expression of miR-K3 can suppress both viral lytic replication and gene expression. Further experiments indicate that miR-K3 can regulate viral latency by targeting nuclear factor I/B. Nuclear factor I/B can activate the promoter of the viral immediate-early transactivator replication and transcription activator (RTA), and depletion of nuclear factor I/B by short hairpin RNAs had similar effects on the viral life cycle to those of miR-K3. Our results suggest a role for KSHV miRNAs in regulating the viral life cycle.


Distinct clinical features of infectious complications in adult T cell leukemia/lymphoma patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis in the Nagasaki transplant group.
Although allogeneic hematopoietic stem cell transplantation (allo-SCT) is performed as a curative option in adult T cell leukemia-lymphoma (ATL) patients, its high transplantation-related mortality raises a serious issue. The clinical features of infectious complications after transplantation are not well known. To analyze the impact of infections after allo-SCT for ATL, we retrospectively compared infectious complications in 210 patients at 3 institutions in Nagasaki prefecture between 1997 and 2009. There were 91 patients with acute myeloid leukemia (AML), 51 with acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL), and 68 with ATL. No patient received ganciclovir or foscarvir as prophylaxis, and most patients received antifungal prophylaxis with fluconazole or itraconazole. The cumulative incidence of cytomegalovirus (CMV) infection at 3 years was 69.2% in ATL patients versus 54.4% in AML patients (P = .0255). Cumulative infection-related mortality was significantly higher in ATL patients than in the 2 other groups (ATL versus AML, P = .0496; ATL versus ALL/LBL, P = .0075), and most death-causing pathogens were bacteria and fungus. The appearance of CMV infection was negatively associated with infectious mortality in ATL patients, but the P value for this association was near the borderline of significance (P = .0569). In multivariate analysis, transplantation using unrelated bone marrow and episodes of CMV infection were associated with worse overall survival in ATL patients, but were not in either AML or ALL/LBL patients. Collectively, the impact of infectious complications after transplantation in ATL patients was different from that in AML and ALL/LBL patients, suggesting that a more intensive strategy for infection control in ATL patients is required to reduce infectious mortality.


Spatiotemporal variations in mean height of 17-year-old students born in 1957-2002 across 47 Japanese prefectures: Evidence from School Health Surveys.
This paper examines the secular trends and variations in mean height of 17-year-old students born in 1957-2002 across 47 prefectures in Japan. Mean height is consistently lower in southwest prefectures and greater in prefectures in the Greater Tokyo Area and from the south-central area to the north-western area facing Eurasia in the main island. Both the range and the coefficient of variation stay constant in the cohorts born during the 1970s or later, following rapid increases of mean height in the prefectures that initially have the lowest means. A comprehensive policy framework may be needed to address diverse factors affecting the physical growth of adolescents at the subnational level.


Differential proteome profile of skin mucus of gilthead seabream (Sparus aurata) after probiotic intake and/or overcrowding stress.
Gilthead seabream (Sparus aurata L.) is the major cultured fish species in the Mediterranean area. High density stocking causes stress and increases the impact of diseases leading to economic losses. Probiotics could represent a solution to prevent diseases through several mechanisms such as improving the immune status and/or mucosal microbiota or competing with pathogens. The probiotic Shewanella putrefaciens, also known as Pdp11, was firstly isolated from the skin of healthy gilthead seabream. Our study focuses on the skin mucus proteome after dietary probiotic Pdp11 intake in fish maintained under normal or overcrowding conditions. 2-DE of skin mucus followed by LC-MS/MS analysis was done for each experimental group and differentially expressed proteins were identified. The results showed differentially expressed proteins especially involved in immune processes, such as lysozyme, complement C3, natural killer cell enhancing factor and nonspecific cytotoxic cell receptor protein 1, whose transcript profiles were studied by qPCR. A consistency between lysozyme protein levels in the mucus and lysozyme mRNA levels in skin was found. Further research is necessary to unravel the implications of skin mucosal immunity on fish welfare and disease. The present work reveals the proteomic changes, which are taking place in the skin mucus of stressed and non-stressed gilthead seabream after Pdp11 probiotic intake. The study contributes to improving the knowledge on skin mucosal immunology of this relevant farmed fish species. Furthermore, the paper shows for the first time how a suitable proteomic methodology, in this case 2-DE followed by LC-MS/MS is useful to perform a comparative study with a non-invasive technique of skin mucus of gilthead seabream.


[Clinical outcomes of 2 pediatric patients with Gaucher's disease in enzyme replacement therapy for 9 years].
We report two cases of type 1 Gaucher's disease in childhood and their outcomes after 9 years of enzyme replacement therapy. The first case concerns a 6-year-old boy who was diagnosed with Gaucher's disease after developing petechial exanthema, thrombocytopenia, anemia and hepatosplenomegaly, coinciding with chickenpox. The second case involves a 9-year-old girl who was referred to our unit. She had hepatosplenomegaly since 4-month-old and subsequently developed thrombocytopenia. Both patients have the N370S/L444P mutation. Enzyme replacement therapy was started with 60 U/kg imiglucerase every 2 weeks at the age of 6 and 9 years, respectively. In both patients, the therapeutic goals were achieved and maintained throughout treatment with a dose of 30 U/kg.


A Simple, Personalized Opioid Stratification Pathway Dramatically Reduces Opioid Utilization.
Orthopaedic surgeons account for the largest proportion of opioid prescriptions in the United States among surgical specialties. In total joint arthroplasty, increased opioid use has been associated with poorer clinical and functional outcomes. Despite an abundance of literature on opioid mitigation strategies, most fail to provide personalized prescriptions. Typically, most protocols prescribe the same opioid regimen regardless of patient factors or the extent of the planned procedure. We present a simple opioid stratification pathway that can be used by physicians and office staff as they prepare patients for arthroplasty. We have found this to be easy to implement, effective, and sustainable at a tertiary academic institution and allows for iterative improvements over time.


A statistical model for predicting the inter-annual variability of birch pollen abundance in Northern and North-Eastern Europe.
The paper suggests a methodology for predicting next-year seasonal pollen index (SPI, a sum of daily-mean pollen concentrations) over large regions and demonstrates its performance for birch in Northern and North-Eastern Europe. A statistical model is constructed using meteorological, geophysical and biological characteristics of the previous year). A cluster analysis of multi-annual data of European Aeroallergen Network (EAN) revealed several large regions in Europe, where the observed SPI exhibits similar patterns of the multi-annual variability. We built the model for the northern cluster of stations, which covers Finland, Sweden, Baltic States, part of Belarus, and, probably, Russia and Norway, where the lack of data did not allow for conclusive analysis. The constructed model was capable of predicting the SPI with correlation coefficient reaching up to 0.9 for some stations, odds ratio is infinitely high for 50% of sites inside the region and the fraction of prediction falling within factor of 2 from observations, stays within 40-70%. In particular, model successfully reproduced both the bi-annual cycle of the SPI and years when this cycle breaks down.


Copper(I) Forms a Redox-Stable 1:2 Complex with α-Synuclein N-Terminal Peptide in a Membrane-Like Environment.
α-Synuclein (αS) is the main protein component of Lewy bodies, characterizing the pathogenesis of Parkinson's disease. αS is unstructured in solution but adopts a helical structure in its extended N-terminal segment upon association with membranes. In vitro the protein binds avidly Cu(II), but in vivo the protein is N-acetylated, and Cu(II) binding is lost. We have now clarified the binding characteristics of the Cu(I) complex with the truncated αS peptide 1-15, both in N-acetylated and free amine forms, in a membrane mimetic environment and found that complexation occurs with a 1:2 Cu(I)-αS stoichiometry, where Cu(I) is bound to Met1 and Met5 residues of two helical peptide chains. The resulting tetrahedral Cu(I) center is redox-stable, does not form reactive oxygen species, and is unreactive against dopamine in the presence of O2. This suggests that, unlike cytosolic Cu(I)-αS, which retains the capacity to activate O2 and promote oxidative reactions, membrane-bound Cu(I)-αS may serve as a sink for unreactive copper.


Comparison of the keyhole trans-middle temporal gyrus approach and transsylvian approach for selective amygdalohippocampectomy: A single-center experience.
Several approach routes exist for selective amygdalohippocampectomy (SAH); however, previous reports regarding a comparison of these routes are limited. Here, we compared trans-middle temporal gyrus (T2) SAH and transsylvian (TS) SAH in terms of seizure outcome, visual-field defect, memory function, and operation time in our institution. This retrospective study examined the data of 16 patients with medically intractable mesial temporal lobe epilepsy. Six patients underwent trans-T2 SAH and 10 patients underwent TS SAH between July 2014 and February 2019 in Osaka City University Hospital. In trans-T2 SAH, we performed a keyhole temporal craniotomy and a small corticotomy on T2. In TS SAH, we performed a 1.5 cm corticotomy along the inferior periinsular sulcus after opening the sylvian fissure. Amygdalohippocampectomy after reaching the inferior horn of the lateral ventricle was performed in the same manner in both procedures. The seizure outcome, visual-field defect, memory function, and operation time were retrospectively compared between the procedures. Seizure-free outcomes were achieved for six patients in the trans-T2 SAH and eight patients in the TS SAH group. There were no significant differences in the seizure outcome, visual-field defect, and memory function. The operation time was significantly shorter for trans-T2 SAH than TS SAH. The postoperative scar was less conspicuous for trans-T2 SAH. Trans-T2 SAH and TS SAH were comparable in terms of the seizure outcome, visual-field defect, and memory function. The operation time and length of the skin incision were shorter for trans-T2 SAH, suggesting that it may be preferable for general epilepsy surgeons.


Bis(μ4-adamantane-1,3-di-carboxyl-ato-1κO 1:2κO 1':3κO 3:4κO 3')octa-carbonyl-1κ2 C,2κ2 C,3κ2 C,4κ2 C-tetra-kis-[tris-(4-methyl-phen-yl)phosphane]-1κP,2κP,3κP,4κP-tetra-osmium(I)(2 Os-Os).
The title complex, [{Os2(CO)4(C21H21P)2}2(C12H14O4)2], is a centrosymmetric mol-ecular loop consisting of two Os-Os sawhorse units linked by two adamantane di-carboxyl-ato bridges. It was synthesized by the microwave-mediated reaction between Os3(CO)12 and adamantane-1,3-di-carb-oxy-lic acid. In contrast to the related complex [{Os2(CO)6}2(μ4-adamantane-1,3-di-acetate)2], the metal-metal axes within each mol-ecule are oriented parallel rather than perpendicular to one another. The crystal structure exhibits cavities that contain residual electron density peaks, but it was not possible to unambiguously identify the solvent therein. The contribution of the disordered solvent mol-ecules to the scattering was removed using the SQUEEZE (Spek (2015 ▸). Acta Cryst. C71, 9-18) routine in PLATON [Spek (2020 ▸). Acta Cryst. E76, 1-11]. These solvent mol-ecules are not considered in the given chemical formula and other crystal data.


Fusion of median and bilateral filtering for range image upsampling.
We present a new upsampling method to enhance the spatial resolution of depth images. Given a low-resolution depth image from an active depth sensor and a potentially high-resolution color image from a passive RGB camera, we formulate it as an adaptive cost aggregation problem and solve it using the bilateral filter. The formulation synergistically combines the median and bilateral filters thus it better preserves the depth edges and is more robust to noise. Numerical and visual evaluations on a total of 37 Middlebury data sets demonstrate the effectiveness of our method. A real-time high-resolution depth capturing system is also developed using commercial active depth sensor based on the proposed upsampling method.


Platelet factor 4 triggers thrombo-inflammation by bridging innate and adaptive immunity.
Platelet factor 4 (PF4, synonym: CXCL4) is an evolutionary old chemokine with proposed roles in hemostasis and antimicrobial defense. In addition, PF4 has attracted considerable attention as a crucial mediator of one of the most prothrombotic adverse drug effects affecting blood cells, heparin-induced thrombocytopenia (HIT). Interest in PF4 substantially increased in 2021 when it was identified as the target antigen in the life-threatening adverse effect, vaccine-induced immune thrombotic thrombocytopenia (VITT). We address the concept that a major biological function of PF4-a strongly cationic chemokine-is to bind to negatively-charged prokaryotic microorganisms, resulting in structural changes in PF4 that trigger a danger signal recognized by the adaptive immune system. Application of biophysical tools has provided substantial insights into the molecular mechanisms by which PF4 becomes immunogenic, providing insights into a new mechanism of autoimmunity. Binding of autoantibodies with high affinity induces conformational change(s) in the endogenous protein, which are then recognized as foreign antigen, as exemplified by the prothrombotic disorders, autoimmune HIT and VITT. The final part of our review summarizes current assays for HIT and VITT, explaining how structural aspects of anti-PF4 pathobiology relate to assay design and performance characteristics. Currently, functional (platelet activation) assays using washed platelets detect HIT antibodies when heparin is added, and VITT antibodies when PF4 is added. Solid-phase PF4-dependent immunoassays using microtiter plates are sensitive for both HIT and VITT antibodies, while rapid immunoassays, in which the PF4/heparin antigen is coated on beads, are sensitive and specific for HIT, but not for VITT antibodies.


Mild hypothermia reduces the inflammatory response and hepatic ischemia/reperfusion injury in rats.
Hypothermia is known to protect against ischemia/reperfusion (I/R) injury. The mechanisms of protection are incompletely understood and a temperature threshold for protection has not been established. In anesthetized Wistar rats, partial (70%) hepatic ischemia was applied for 45 min. Three study groups were used. Group T31 (n = 6) spontaneously cooled to 31.3 +/- 0.8 degrees C, while group T34 (n = 6) spontaneously cooled to 34 degrees C and was then maintained at 34.0 +/- 0.1 degrees C using a heat lamp. The normothermic group (T37, n = 6) was maintained at 37.1 +/- 0.3 degrees C. Hepatic injury, inflammation, lipid peroxidation and metabolic function (using quantitative 1H-NMR) were assessed 24 h after reperfusion. At 24 h following reperfusion, alanine aminotransferase and aspartate aminotransferase increased to 5101 +/- 2378 and 6409 +/- 4202 U/l in the normothermic T37 group (P < 0.05 vs. T34 and T31), whereas transaminases in hypothermic groups (T31 and T34) were significantly lower. Severe liver necrosis was only noted with T37. Myeloperoxidase activity was increased in the T37 group when compared with hypothermic groups (223 +/- 161 (T37) vs. 16 +/- 10 (T31) and 8 +/- 5 (T34) mU/min/mg of tissue, P<0.05 vs. T31 and T34). 1H-NMR analysis of the blood of normothermic animals revealed metabolic changes consistent with increased ischemic injury, which was almost completely ameliorated in T34 and T31 groups. Mild hypothermia of 34 degrees C is sufficient to reduce I/R injury by inhibiting the inflammatory response. Further spontaneous cooling to 31 degrees C did not demonstrate any additional protective effect.


Multi-parametric analysis and registration of brain tumors: constructing statistical atlases and diagnostic tools of predictive value.
We discuss computer-based image analysis algorithms of multi-parametric MRI of brain tumors, aiming to assist in early diagnosis of infiltrating brain tumors, and to construct statistical atlases summarizing population-based characteristics of brain tumors. These methods combine machine learning, deformable registration, multi-parametric segmentation, and biophysical modeling of brain tumors.


Can throat swab after physiotherapy replace sputum for identification of microbial pathogens in children with cystic fibrosis?
To compare cultures throat swab after physiotherapy with results of sputum culture in identification of lower airway pathogens in children with cystic fibrosis. 387 samples of sputum cough swabs, throat swab and throat swab after physiotherapy were collected from 48 patients of cystic fibrosis and cultured for aerobic bacteria. The results of cultures of cough swabs, throat swab and throat swab after physiotherapy were compared with results of sputum culture. There was good concordance between culture results of sputum and other methods. Over all concordance was 70%, 81% and 92% with cough swab, throat swab and throat swab after physiotherapy. Sensitivity for isolation of Pseudomonas aeruginosa by throat swab, cough swab and throat swab after physiotherapy was 40%, 42% and 82% respectively. Specificity for isolation of Pseudomonas by throat swab, cough swab and throat swab after physiotherapy was 99%, 100% and 99% respectively. Sensitivity for isolation of Staphylococcus aureus by throat swab, cough swab and throat swab after physiotherapy was 57%, 50% and 100% respectively. Specificity for isolation of Staphylococcus by throat swab, cough swab and throat swab after physiotherapy was 99% for all these methods. It is concluded that throat swab after physiotherapy in a child with CF can be used reliably for identification of lower airway pathogens.


Effects of single and repeated electroconvulsive shock administration on inositol phosphate accumulation in rat brain slices.
Accumulation of inositol-1-phosphate after labeling with [3H]inositol and stimulation with noradrenaline, carbachol, and serotonin was measured in rat cortical, caudate nucleus, and hippocampal slices. The response to noradrenaline was significantly increased in cortical slices from animals that had received either a single electroconvulsive shock (ECS) or a series of 10 daily ECS but was unchanged in caudate nucleus or hippocampal slices. The response to carbachol, a muscarinic cholinergic agonist, was unchanged in cortical or caudate nucleus slices but was significantly reduced in hippocampal slices from animals that had received chronic ECS. The response to serotonin in cortical slices was not affected by the treatment. The results are correlated with changes in receptor number, which have been demonstrated to occur after administration of ECS.


Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin.
Hematopoietic stem cell transplantation (HSCT) offers curative therapy for patients with hemoglobinopathies, congenital immunodeficiencies, and other conditions, possibly including AIDS. Autologous HSCT using genetically corrected cells would avoid the risk of graft-versus-host disease (GVHD), but the genotoxicity of conditioning remains a substantial barrier to the development of this approach. Here we report an internalizing immunotoxin targeting the hematopoietic-cell-restricted CD45 receptor that effectively conditions immunocompetent mice. A single dose of the immunotoxin, CD45-saporin (SAP), enabled efficient (>90%) engraftment of donor cells and full correction of a sickle-cell anemia model. In contrast to irradiation, CD45-SAP completely avoided neutropenia and anemia, spared bone marrow and thymic niches, enabling rapid recovery of T and B cells, preserved anti-fungal immunity, and had minimal overall toxicity. This non-genotoxic conditioning method may provide an attractive alternative to current conditioning regimens for HSCT in the treatment of non-malignant blood diseases.


A tumor-associated antigen expressed in melanoma cells with lower malignant potential.
The antigen K-1-2, detectable by a MAb is found in nevi and melanomas. It is associated with melanoma cells of low invasive and metastatic potential as shown by immunoperoxidase studies with cell lines, biopsies and autopsies: K-1-2 occurs in melanoma cell line SK-Mel 25, but not in cell line A-375. A-375 has a higher malignant potential than SK-Mel 25 because, in contrast to SK-Mel 25, it produces plasminogen activator and grows in nude mice. K-1-2 was frequently strongly expressed (greater than or equal to 50% cells positive) in flat (less than 1.5 mm) and less frequently in medium and thick primary tumors. In thick primary melanomas K-1-2 positive cells were confined to the junctional zone or to marginal, flat areas of the tumor. Only rarely does K-1-2 occur in metastases. Strong expression of the K-1-2 antigen was found less often in primary melanomas, which develop early metastases, than in tumors that had not metastasized during an observation period of 18 months. In 5 patients with disseminated metastatic disease, metastases strongly expressing K-1-2 and those negative for this marker or containing only a minor percentage of K-1-2 positive cells were observed simultaneously or at different times. These findings suggest that a change from high malignancy to low malignancy--as observed in animal systems--may also occur in human melanoma.


How is your sleep: a neglected topic for health care screening.
Inadequate sleep, whether it is caused by voluntary sleep curtailment or specific sleep disorders, is highly prevalent, has wide-ranging negative consequences for human health and well-being, and is greatly under-diagnosed. The objective of this study was to determine the frequency of inquiry by family medicine clinics about unhealthy sleep patterns and symptoms in their health history database questionnaires. This study surveyed health history database forms used by family medicine clinics in the 7-county Minneapolis/St. Paul metropolitan area for questions related to sleep disorders. Fourteen distinct database batteries that are used in 121 primary care clinics and employ 935 family medicine doctors (roughly 75% of physicians practicing in this region) were analyzed. Direct questions about sleep health are often not included in health history questionnaires. Eight of 14 (57%) database batteries reviewed in this study featured no sleep-related questions. Other lifestyle issues were screened with much greater frequency. For example, questions about healthy eating patterns and regular physical activity were present in 13 and 12 of the 14 batteries (93% and 86%), respectively. Despite the significant burden that sleep disorders place on human health, this study found that family medicine clinics do not screen for them as frequently as they do for other lifestyle/behavioral issues when they establish a health history database for new patients.


Psoriasis and Nonalcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects.


PLA as a suitable 3D printing thermoplastic for use in external beam radiotherapy.
The purpose of this paper is to investigate the tissue equivalence and radiological properties of Polylactic Acid (PLA) to determine if this material is suitable for use as a 3D printing thermoplastic for radiotherapy applications. Profiles and percentage depth-dose measurements (PDDs) were analysed for photon and electron modalities with PLA samples (~ 1.25 g/cm3) to determine material dosimeteric characteristics. Beam profiles and PDDs from treatment planning system (TPS) simulations, water tank measurements and radiochromic film measurements were compared. Tissue equivalence was determined through CT scanning several PLA samples and measuring the Hounsfield units (HUs) to determine relative electron density (RED), mass density and mass attenuation, these results were compared to several commercial tissue phantoms with varying properties. Geometric accuracy was tested by comparing digitally planned dimensions to physical and CT image measurements. Finally, resistance to radiation damage was tested by exposing PLA samples to several thousand monitor units (MUs) over several weeks and inspecting for damage. It was determined that PLA is a safe and effective thermoplastic for use as a patient specific bolus for both electron and photon treatment modalities. The material properties have been characterised and can be accurately modelled in the MONACO TPS.


Identification of the receptor-binding protein in lytic Leuconostoc pseudomesenteroides bacteriophages.
Two phages, P793 and ΦLN04, sharing 80.1% nucleotide sequence identity but having different strains of Leuconostoc pseudomesenteroides as hosts, were selected for identification of the host determinant gene. Construction of chimeric phages leading to the expected switch in host range identified the host determinant genes as ORF21P793/ORF23ΦLN04. The genes are located in the tail structural module and have low sequence similarity at the distal end.


Cooperative environmental governance in urban South Asia: implications for municipal waste management and waste-to-energy.
This paper critically discusses the importance of cooperative environmental governance (CEG) for efficient waste management and waste-to-energy (WtE) generation in the context of growing urban South Asia. Focusing on Bangladesh, India and Pakistan experiences, the paper reveals that even though much progress has been done in the urbanisation in the selected countries, the process of waste management (mainly municipal solid waste) has not been effective due to low level of local inclusion. As a result, the WtE generation potential has not been realised to its fullest. In addition, it has been argued that institutional and social reforms are extremely important for strengthening the CEG, and it will eventually lead to effective and optimal WtE generation in the urban cities of the selected South Asian countries for green transition and urban sustainability. Finally, an integrated solid waste management framework has been formulated for policy implications in South Asia.


On the origins of tandemly repeated genes: does histone gene copy number in Drosophila reflect chromosomal location?
Widely regarded beliefs about Drosophila histone gene copy numbers and developmental requirements have been generalized from fairly limited data since studies on histone gene arrangements and copy numbers have been largely confined to a single species, D. melanogaster. Histone gene copy numbers and chromosomal locations were examined in three species: D. melangaster, D. hydei and D. hawaiiensis. Quantitative whole genome blot analysis of DNA from diploid tissues revealed a tenfold variability in histone gene copy numbers for these three species. In situ hybridization to polytene chromosomes showed that the histone DNA (hDNA) chromosomal location is different in all three species. These observations lead us to propose a relationship between histone gene reiteration and chromosomal position.


Cooperative Palladium/Isothiourea Catalyzed Enantioselective Formal (3+2) Cycloaddition of Vinylcyclopropanes and α,β-Unsaturated Esters.
A protocol for the enantioselective synthesis of substituted vinylcyclopentanes has been realised using cooperative palladium and isothiourea catalysis. Treatment of vinylcyclopropanes with Pd(PPh3 )4 generates a zwitterionic π-allyl palladium intermediate that intercepts a catalytically generated α,β-unsaturated acyl ammonium species prepared from the corresponding α,β-unsaturated para-nitrophenyl ester and the isothiourea (R)-BTM. Intermolecular formal (3+2) cycloaddition between these reactive intermediates generates functionalised cyclopentanes in generally good yields and excellent diastereo- and enantiocontrol (up to >95 : 5 dr, 97 : 3 er), with the use of LiCl as an additive proving essential for optimal stereocontrol. To the best of our knowledge a dual transition metal/organocatalytic process involving α,β-unsaturated acyl ammonium intermediates has not been demonstrated previously.


A global field study of the international classification of diseases (ICD-11) mood disorders clinical descriptions and diagnostic guidelines.
We report results of an internet-based field study evaluating the diagnostic guidelines for ICD-11 mood disorders. Accuracy of clinicians' diagnostic judgments applying draft ICD-11 as compared to the ICD-10 guidelines to standardized case vignettes was assessed as well as perceived clinical utility. 1357 clinician members of the World Health Organization's Global Clinical Practice Network completed the study in English, Spanish, Japanese or Russian. Participants were randomly assigned to apply ICD-11 or ICD-10 guidelines to one of eleven pairs of case vignettes. Clinicians using the ICD-11 and ICD-10 guidelines achieved similar levels of accuracy in diagnosing mood disorders depicted in vignettes. Those using the ICD-11 were more accurate in identifying depressive episode in recurrent depressive disorder. There were no statistically significant differences detected across classifications in the accuracy of identifying dysthymic or cyclothymic disorder. Circumscribed problems with the proposed ICD-11 guidelines were identified including difficulties differentiating bipolar type I from bipolar type II disorder and applying revised severity ratings to depressive episodes. Clinical utility of ICD-11 bipolar disorders was found to be significantly lower than for ICD-10 equivalent categories. Standardized case vignettes were manipulated to evaluate specific changes. The degree of accuracy of clinicians' diagnostic judgments may not reflect clinical decision-making with patients. Alignment of the ICD-11 with current research appears to have been achieved without sacrificing diagnostic accuracy or clinical utility though specific training may be necessary as ICD-11 is implemented worldwide. Areas in which the ICD-11 guidelines did not perform as intended resulted in further revisions.


Decontamination of multispecies oral biofilm from rough implant surface by airflow with glycine.
Decontamination of biofilm-colonized rough implant surfaces remains challenging. We investigated the effect of airflow with glycine powder (AFG) on decontamination of mature oral multispecies biofilm from a sandblasted and acid etched (SLA) titanium surface. Subgingival dental plaque was cultured on SLA disks anaerobically for 21 days. AFG with various settings and distances was applied directly on the disks with or without previous rinse of 0.9% NaCl. The specimens were then analyzed through scanning electron microscope and remaining bacteria on the implant surface were quantified and statistically compared. Mature oral biofilm with cocci and rods as major morphotypes, as well as spiral- and filamentous-shaped organisms, was formed on the untreated disks. Saline rinsing removed the thick biofilm layer but left numerous of coccoid bacteria in rough surface pits. AFG effectively removed most of the bacteria from the pits. Both 25% and 50% power settings were equally effective at 3-mm distance. With 50% power, AFG successfully removed bacteria at both 3- and 6-mm distance. When AFG was applied on native biofilm without prior rinsing with saline, it effectively removed the biofilm including bacteria in the pits. Application of AFG appears effective in removing bacteria from rough implant surfaces.


Retracing migration pattern in reproductive and non-reproductive female kutum Rutilus frisii, in south Caspian Sea, using otolith microchemistry.
Because trace elements of otoliths are considered a natural marker capable of recognizing the chemical composition of ambient water and fish migration history, these elements could be potentially used to analyse the movement of reproductive (R) and non-reproductive (NR) mature-sized fish. Supposedly, it is not essential for NR individuals to migrate to rivers for spawning because they do not have developed gonads. To investigate the potential differences in migration history between female R and NR kutum, Rutilus frisii, in the southwest waters of the Caspian Sea, the ratios of Sr, Ba, Mg, Na, K and P to Ca in otoliths (from the core to the edge) were examined using laser ablation-inductively coupled plasma-mass spectrometry. In NR fish, a significant increase in Sr:Ca ratio in the otoliths' growth rings, likely due to greater seawater residency, and an increase in Ba:Ca ratio in the last two rings were observed. Increased Ba:Ca ratio could be due to the movement of NR mature-sized fish to the coastal zones for foraging. Seasonal physiological factors such as gonad maturation and spawning activity are more likely to be involved in differences in the other elemental ratios (Mg, Na, K and P). These results suggest that microchemical analyses of growth rings of otolith can be used as a valuable tool for better understanding the movement pattern of different types of adult fish, which could be completed with data from other methods like tagging.


Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions.
An efficient deracemization method for conversion of the racemate to the desirable (R)-enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5-15 °C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)-enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization.


Using MEDLINE as a knowledge source for disambiguating abbreviations and acronyms in full-text biomedical journal articles.
Biomedical abbreviations and acronyms are widely used in biomedical literature. Since many of them represent important content in biomedical literature, information retrieval and extraction benefits from identifying the meanings of those terms. On the other hand, many abbreviations and acronyms are ambiguous, it would be important to map them to their full forms, which ultimately represent the meanings of the abbreviations. In this study, we present a semi-supervised method that applies MEDLINE as a knowledge source for disambiguating abbreviations and acronyms in full-text biomedical journal articles. We first automatically generated from the MEDLINE abstracts a dictionary of abbreviation-full pairs based on a rule-based system that maps abbreviations to full forms when full forms are defined in the abstracts. We then trained on the MEDLINE abstracts and predicted the full forms of abbreviations in full-text journal articles by applying supervised machine-learning algorithms in a semi-supervised fashion. We report up to 92% prediction precision and up to 91% coverage.


Glutaraldehyde-tanned microvascular grafts.
In this study the efficacy of preserving microvascular heterografts with glutaraldehyde tanning was investigated. These were compared with glutaraldehyde-tanned autografts. Previous studies have found that untreated autograft veins maintain a 95% patency rate, whilst untreated heterograft veins (Group 1) had a 15% patency rate at 4 weeks in this study. Autogenous glutaraldehyde-tanned rabbit carotid arterial grafts (Group 2) and glutaraldehyde-tanned human chorionic veins (Group 3) were interposed in rabbit femoral or carotid arteries. Fifty per cent and 75% patency rates were achieved respectively at 4 weeks. The low patency rate of the autogenous group suggests that the glutaraldehyde tanning technique itself is largely responsible for the low patency of glutaraldehyde-tanned human chorionic veins rather than any immunological response. Therefore if human chorionic veins are to be used as a readily available preserved microvascular graft, further investigation is required to develop another technique which will reduce antigenicity without promoting thrombosis.


Clonal analysis of mouse intestinal epithelial progenitors.
Little is known about the cell lineages leading from stem cells to the various terminally differentiated cell types of the intestinal epithelium. In particular, the existence and characterization of intermediate progenitor types remain open issues, which are discussed in this study. Chemical mutagenesis was used to genetically mark random intestinal epithelial cells by somatic mutation of the Dlb-1 locus. Intact epithelium was isolated at various times thereafter, and the composition, size, and location of mutant clones were scored. Analysis of clone dynamics showed short-lived (days) progenitors (C1, M1, and Mix) yielding one or two cell types and long-lived (months) mucous cell progenitors (M0), columnar cell progenitors (C0), and pluripotential stem cells (S) capable of giving rise to all epithelial cell types. Furthermore, study of clonal dispersion, during crypt branching morphogenesis or cell migration, shows that mutant progenitors usually partition into only one of the two daughter crypts and that cells are often widely dispersed in spite of the extensive intercellular junctions in the epithelium.


The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results.
The Cholesterol Lowering Atherosclerosis Study (CLAS) is a prospective, placebo-controlled, angiographic trial designed to test the hypothesis that aggressive lowering of LDL cholesterol with concomitant increase in HDL cholesterol will reverse or retard the atherosclerotic process. Specifically, CLAS was designed to determine whether combined therapy with colestipol plus niacin will produce clinically significant change in coronary, carotid, and femoral artery atherosclerosis and coronary bypass graft lesions. To this purpose, 188 subjects were randomized to diet plus drug or diet plus placebo. We report on methodological aspects of planning and evaluating this study, including the choice of the study population, procedures for recruitment, the experimental design including sample size considerations, methods for evaluating outcome, and methods for evaluating compliance to treatment. Comparison of baseline data indicated no significant differences between groups at the time of randomization. Subjects were predominantly male, Caucasian, 54 years of age, 20% above ideal weight, with normal blood pressure. The average age at bypass was 50 years. The average lipids were cholesterol (243 mg/dL), HDL (45 mg/dL), and LDL (168 mg/dL). Finally, the distribution of baseline coronary stenosis was equivalent between the two groups (average number of lesions per subject = 10.6).


Zinc oxide nanoparticles catalyzed condensation reaction of isocoumarins and 1,7-heptadiamine in the formation of bis-isoquinolinones.
The diversified bis-isoquinolinones were obtained in two steps, utilizing homophthalic acid and various acid chlorides providing 3-substituted isocoumarins in the first step which on further condensation with 1,7-heptadiamine involving C-N bond formation from the lactone in the presence of 10 mol% zinc oxide nanoparticles (ZnO NPs) (<150 nm) afforded the desired bis-isoquinolinones in high yield and purity. The synthesized compounds were then characterized using FTIR, (1)H NMR, (13)C NMR, and HRMS techniques.


Krametosan, a new trinorlignan from the roots of Krameria tomentosa.
A new phenylcoumarone type trinorlignan, krametosan (1), along with the known norlignans, ratanhiaphenol I (2) and 2-(2'-hydroxy-4',6'-dimethoxyphenyl)-5-(E)-propenylbenzofuran (3), the lignan conocarpan (4) and dinorlignan decurrenal (5), were isolated from the CHCl3 extract of the roots of Krameria tomentosa. The structure of these compounds were elucidated by the spectroscopic methods.


A Patient with Severe Cervicofacial Subcutaneous Emphysema Associated with Munchausen's Syndrome: A Case Report.
Subcutaneous cervicofacial emphysema is a rare and life-threatening condition that results from various causes. In this report, we documented a case of a patient with severe subcutaneous cervicofacial emphysema a condition that falls under the umbrella of Munchausen's syndrome and discussed the workup of this patient. Thorough diagnostic investigations seeking the etiology of the condition proved unsuccessful. When faced with cases of recurring subcutaneous cervicofacial emphysema, where the root cause remains ambiguous a diagnosis of Munchausen's Syndrome should be considered.


Transarterial embolization for traumatic intractable oronasal hemorrhage.
Severe craniofacial injury may cause intractable oronasal bleeding, a rare but life-threatening surgical emergency that may occur in the Emergency Department (ED). Uncontrolled massive bleeding is the major cause of mortality. This kind of trauma is usually associated with the transfer of high kinetic energy such as a motor vehicle collision. We report an unusual case of intractable oronasal bleeding diagnosed by angiography. A 43-year-old man was brought to the ED after being in a high-energy motor vehicle collision. He had suffered severe craniofacial trauma, including intracranial hemorrhage and intractable oronasal bleeding; he later developed a large pseudoaneurysm arising from the right internal maxillary artery. In the ED, the patient successfully underwent endovascular treatment (EVT) using angiography with transarterial embolization (TAE) therapy to control the bleeding. EVT by TAE for intractable oronasal bleeding was an effective treatment in this life-threatening situation.


Cutting-edge capillary electrophoresis characterization of monoclonal antibodies and related products.
Out of all categories, monoclonal antibodies (mAbs), biosimilar, antibody-drug conjugates (ADCs) and Fc-fusion proteins attract the most interest due to their strong therapeutic potency and specificity. Because of their intrinsic complexity due to a large number of micro-heterogeneities, there is a crucial need of analytical methods to provide comprehensive in-depth characterization of these molecules. CE presents some obvious benefits as high resolution separation and miniaturized format to be widely applied to the analysis of biopharmaceuticals. CE is an effective method for the separation of proteins at different levels. capillary gel electrophoresis (CGE), capillary isoelectric focusing (cIEF) and capillary zone electrophoresis (CZE) have been particularly relevant for the characterization of size and charge variants of intact and reduced mAbs, while CE-MS appears to be a promising analytical tool to assess the primary structure of mAbs and related products. This review will be dedicated to detail the current and state-of-the-art CE-based methods for the characterization of mAbs and related products.


The relationship of the dexamethasone suppression test (1 mg and 2 mg) to basal plasma cortisol levels in endogenous depression.
The 1 mg and 2 mg dexamethasone suppression tests (DST) were evaluated in two groups of endogenously depressed patients (n = 39 and n = 30, respectively) who also had a 1300-1600 hr basal cortisol assessment. Non-suppressors (on both DSTs) had significantly higher basal plasma cortisol levels and thus were significantly associated with relative cortisol hypersecretion. However, there was only a partial overlap between DST response and basal plasma cortisol, with a large variation of cortisol levels among non-suppressors. The 2 mg DST appears to be more specific for cortisol hypersecretion than the 1 mg DST. If cortisol hypersecretion is to be identified, neither the 1 mg or 2 mg DST is an adequate assessment nor a substitute for a basal cortisol assessment.


der(16)t(1;16)/der(1;16) in breast cancer detected by fluorescence in situ hybridization is an indicator of better patient prognosis.
By two-color fluorescence in situ hybridization (FISH), der(16)t(1;16) or der(1;16) was frequently detected in low-grade papillary carcinoma but not in benign intraductal papilloma of the breast. In order to clarify the incidence and clinicopathological significance of der(16)t(1;16)/der(1;16) in common breast cancers, der(16)t(1;16)/der(1;16) was examined by two-color FISH in breast cancers resected from 51 patients by using DNA probes for 16cen, 16q11.2, and 1q12 labeled with biotin or digoxigenin. der(16)t(1;16)/der(1;16) was clonally detected in 16 cancers (31%), being more frequent in ductal carcinomas of lower grade and invasive lobular carcinoma than in high-grade invasive ductal carcinoma (P<0.001). der(16)t(1;16)/der(1;16) was also correlated with a higher amount of hormone receptors in the tumor (P<0.05). Disease-free and overall survival rates of the patient group with der(16)t(1;16)/der(1;16)-positive cancer were higher (88% and 94%) than those of the group with der(16)t(1;16)/der(1; 16)-negative cancer (39% and 68%) (P<0.05). Among the 16 patients with lymph node metastasis who received one of two similar forms of postsurgical adjuvant chemo-endocrine therapy, the prognosis of those with der(16)t(1;16)/der(1;16)-positive cancer was better than that of those with der(16)t(1;16)/der(1;16)-negative cancer (P<0.05). der(16)t(1;16)/der(1;16) detected by FISH is considered helpful in identifying patients with a better prognosis and for stratification of patients in randomized clinical trials of adjuvant chemo-endocrine therapies.


[Rupture of a splenic artery aneurysm in full term pregnancy--case report].
A case of a primigravida with hypovolemic shock symptoms and acute intrauterine fetal hypoxia was described. Emergency caesarean section, during which a hemorrhage to the peritoneal cavity caused by an unrecognized splenic artery aneurysm rupture was diagnosed, was immediately performed.


Phenylenediamine catalysis of "click glycosylations" in water: practical and direct access to unprotected neoglycoconjugates.
Phenylenediamine-catalyzed click chemistry leads to the efficient, practical, and column-free preparation of neoglycoconjugates from unprotected glucosyl azide, in pure water when aglycon solubility permits.


Gastric duplication presenting as a double esophagus.
Duplications of the stomach are infrequent and, when present, usually become clinically manifest as an abdominal mass. Other clinical presentations have rarely been described. This report illustrates the case of a patient who presented with occult blood loss and radiographic evidence of esophageal duplication. A technetium scan demonstrated gastric duplication with mediastinal extension. Operative management and a review of the literature are described.


Biomarkers of Thrombotic Status Predict Spontaneous Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction.
Spontaneous reperfusion, seen in ∼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related artery, with or without ST-segment resolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown. The authors sought to relate spontaneous reperfusion to the thrombotic profile. In a prospective study, blood from STEMI patients (n = 801) was tested pre-PCI to assess in vitro, point-of-care, occlusion times (OT) and endogenous lysis times (LT). Spontaneous reperfusion was defined as infarct-related artery Thrombolysis In Myocardial Infarction flow grade 3 before PCI. Patients were followed for major cardiovascular events (death, myocardial infarction, or stroke). Spontaneous reperfusion was associated with a longer OT (435 seconds vs 366 seconds; P < 0.001) and a shorter LT (1,257 seconds vs 1,616 seconds; P < 0.001), lower troponin, and better left ventricular function. LT was superior to OT for predicting spontaneous reperfusion (area under the curve for LT: 0.707; 95% CI: 0.661-0.753; area under the curve for OT: 0.629; 95% CI: 0.581-0.677). Among patients with spontaneous reperfusion, those with complete, vs partial ST-segment resolution, had a longer OT (P = 0.002) and a shorter LT (P < 0.001). Spontaneous reperfusion was unrelated to clinical characteristics or pain-to-angiography times. Over 4 years, patients with spontaneous reperfusion experienced fewer major adverse cardiovascular events than those without (4.1% vs 10.6%; P = 0.013), especially in those with both spontaneous reperfusion and complete ST-segment resolution (1.5% vs 10.1%; P = 0.029). We demonstrate a novel hematological signature in STEMI patients with spontaneous reperfusion, namely, decreased platelet reactivity and faster endogenous fibrinolysis, relating to smaller infarcts and improved survival. This finding indicates a role for modulating thrombotic status early after STEMI onset, to facilitate spontaneous reperfusion and improve outcomes.


As good as it gets? Folding molecular dynamics simulations of the LytA choline-binding peptide result to an exceptionally accurate model of the peptide structure.
Folding simulations of a choline-binding peptide derived from the Streptococcus pneumoniae LytA protein converged to a model of the peptide's folded state structure which is in outstanding agreement with the experimentally-determined structures, reaching values for the root mean squared deviation as low as 0.24Å for the peptide's backbone atoms and 0.65Å for all non-hydrogen atoms.


Synchronous and 'early' metachronous carcinomas of the colon and rectum.
In a review of cases of colorectal cancer presenting to St. Mark's Hospital over the 16-year period 1970-85, 59 patients were found to have a synchronous carcinoma (3.4 per cent). Although 82 per cent of these synchronous tumours were distal to the splenic flexure (and hence within reach of a 60 cm flexible sigmoidoscope) only 42 per cent were detected pre-operatively: the remaining tumours were noted at surgery (24 per cent) or found incidentally on pathological examination of the resected specimen (34 per cent). Histological examination of these synchronous lesions revealed a high proportion with favourable stage (Dukes' A-75 per cent) and grade (well or moderate differentiation-90 per cent). Over the same 16-year period, 10 patients presented with an 'early' metachronous lesion (less than 3 years from initial surgery). Review of these cases noted negative findings on the initial barium studies in four patients and a failure to conduct full examination of the colon at initial presentation in the remaining six. It is concluded that full examination of the colon in all patients presenting with primary colorectal cancer is mandatory and that, in the light of this experience and recent reports in the literature, this should be by pre- or peroperative colonoscopy.


beta-Naphthoflavone and benzo(a)pyrene alter dopaminergic, noradrenergic, and serotonergic systems in brain and pituitary of rainbow trout (Oncorhynchus mykiss).
In the present study we evaluate for the first time the potential of the flavonoid compound beta-naphthoflavone (BNF) and the high molecular weight- Polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BaP) to alter brain neurotransmitter metabolism in fish. Fish of three different groups were intraperitoneally (i.p.) injected (2 microl g(-1)) with vegetable oil alone (control) or containing BNF or BaP (10 mg kg(-1)) and sacrificed 3, 24, and 72 h after treatment. Contents of dopamine (DA), noradrenaline (NA) and serotonin (5HT), as well as the amine oxidative metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5HIAA) were assayed in telencephalon, hypothalamus, preoptic region, optic tectum, and brain stem, as well as the pituitary. Fish treated with PAHs showed after 3h decreases in 5HT content in telencephalon, hypothalamus, preoptic region (with both BNF and BaP), and pituitary (with BaP), resulting in increased 5HIAA/5HT ratio. An increased ratio was also observed in hypothalamus 24h after BaP, and in preoptic region 72 h after BNF, in both cases due to an increased 5HIAA content. In other brain regions PAHs effects on 5-HT metabolism were less consistent. With respect to the dopaminergic system, changes induced by PAHs mainly occurred after 24 and 72 h of treatment, with increased DOPAC/DA ratio in preoptic region and brain stem. In hypothalamus, tectum, and pituitary, changes in DA metabolism showed strong variability. Finally, a decreased content of NA was evident in preoptic region (3h) and in telencephalon (24h) after both BNF and BaP treatments. Therefore, both BNF and BaP seem to act in rainbow trout brain by impairing 5HT availability at short term (3h) and increasing neuronal metabolic utilization of both 5HT and DA after 24 and 72 h. Data collected in the present study suggest that brain monoamine neurotransmitters are potential targets of BNF and BaP, and their alteration could have a role in known effects of PAHs on several neuroendocrine processes that are centrally regulated or modulated by brain monoamines.


Protein N-Terminal Acetylation: Structural Basis, Mechanism, Versatility, and Regulation.
N-terminal acetylation (NTA) is one of the most widespread protein modifications, which occurs on most eukaryotic proteins, but is significantly less common on bacterial and archaea proteins. This modification is carried out by a family of enzymes called N-terminal acetyltransferases (NATs). To date, 12 NATs have been identified, harboring different composition, substrate specificity, and in some cases, modes of regulation. Recent structural and biochemical analysis of NAT proteins allows for a comparison of their molecular mechanisms and modes of regulation, which are described here. Although sharing an evolutionarily conserved fold and related catalytic mechanism, each catalytic subunit uses unique elements to mediate substrate-specific activity, and use NAT-type specific auxiliary and regulatory subunits, for their cellular functions.


Genetic variants in Mammalian STE20-like protein kinase 2 were associated with risk of NSCL/P.
Mammalian STE20-like protein kinase 2 (MST2) plays an important role in apoptosis and the development of many disorders. Here, we aim to explore if genetic variants in MST2 are associated with the risk of non-syndromic cleft lip with or without palate (NSCL/P). The association study was performed in a two-stage study of 1,069 cases and 1,724 controls to evaluate the association between genetic variants in the MST2 and NSCL/P risk. The potential function of the candidate single nucleotide polymorphism (SNP) was predicted using HaploReg, RegulomeDB, and public craniofacial histone chromatin immunoprecipitation sequencing (ChIP-seq) data. Haploview was used to perform the haplotype of risk alleles. The expression quantitative trait loci (eQTL) effect was assessed using the Genotype-Tissue Expression (GTEx) project. Gene expression in mouse embryo tissue was performed using data downloaded from GSE67985. The potential role of candidate gene in the development of NSCL/P was assessed by correlation and enrichment analysis. Among SNPs in MST2, rs2922070 C allele (Pmeta = 2.93E-04) and rs6988087 T allele (Pmeta = 1.57E-03) were linked with significantly increased risk of NSCL/P. Rs2922070, rs6988087 and their high linkage disequilibrium (LD) SNPs constituted a risk haplotype of NSCL/P. Individuals carrying 3-4 risk alleles had an elevated risk of NSCL/P compared to those who carried less risk alleles (P = 2.00E-04). The eQTL analysis revealed a significant association between these two variants and MST2 in muscle tissue of the body. The MST2 expressed during mouse craniofacial development and over-expressed in the human orbicularis oris muscle (OOM) of NSCL/P patients compared to controls. MST2 was involved in the development of NSCL/P by regulating the mRNA surveillance pathway, the MAPK signaling pathway, the neurotrophin signaling pathway, the FoxO signaling pathway and the VEGF signaling pathway. MST2 was associated with the development of NSCL/P.


Integrating vegetation suitability in sustainable revegetation for the Loess Plateau, China.
Revegetation is accelerating globally due to its benefits for ecosystem restoration, desertification prevention, and climate change mitigation. The Loess Plateau has suffered serious erosion in the past decades, and revegetation projects, such as those under the 'Grain for Green' program, have been conducted for soil erosion prevention. The irrational distribution of artificial plantations had negative consequences, including vegetation degradation, soil drying, and decreases in streamflow. Determining the suitable plant species is critical in guiding the design of revegetation programs and may help delimit the suitable boundaries for artificial plantations. In this study, we used an eco-hydrological model to quantify the suitability of two typical revegetation species (Robinia pseudoacacia and Stipa bungeana) using a developed vegetation suitability equation, which estimates the water use/water stress trade-off. The results showed that R. pseudoacacia was more sensitive to water stress than S. bungeana. The water use of both species varied along the precipitation gradient, and S. bungeana generally had a higher water use than R. pseudoacacia. Suitable areas for R. pseudoacacia were mainly located in the northeastern part of the plateau. By overlaying the suitable boundaries for R. pseudoacacia on the current land cover, we found that the area of forests distributed in unsuitable regions reached 7.31% of the entire Loess Plateau. Converting forests beyond the suitable boundary to grasslands would increase the water yield (0.51%-12.23%) and slightly decrease the soil retention capacity (0.01%-0.08%), resulting in a 'win-win' situation for sustainable plant-soil ecosystems and soil-water conservations. Additionally, the suitable area of R. pseudoacacia is predicted to shrink under projected future drying trends. In conclusion, vegetation suitability in the future planning and design of revegetation projects should be considered to effectively tackle the impacts of environmental degradation and climate change in the Loess Plateau.


Magnetic covalent organic framework as a solid-phase extraction absorbent for sensitive determination of trace organophosphorus pesticides in fatty milk.
A simple and efficient magnetic solid-phase extraction (MSPE) method was established with magnetic covalent organic framework (COF) as adsorbent to enrich organophosphorus pesticides from fatty milk samples, followed by the sensitive determination via LC-MS/MS. The key parameters influencing the MSPE efficiency were comprehensively investigated to afford an optimized procedure. All the target analytes could be captured directly by magnetic COF from milk without protein precipitation, making the pretreatment rapid and convenient. Systematic method validation demonstrated its satisfactory linearity, recoveries (80.0-105 %), and precision (RSDs <12.3 %). The method limits of quantification were 0.2-0.5 μg L-1. A comparison experiment to the reported solid-phase extraction fully verified the present MSPE more rapid, accurate, and environment-friendly. Furthermore, FT-IR and XPS analysis were performed to reveal the adsorption mechanisms of magnetic COF to organophosphorus pesticides, which could offer guidance on the rational design of COF adsorbent for various target analytes.


Aortic valve stenosis: etiology, pathophysiology, evaluation, and management.
More patients with valvular aortic stenosis are being recognized, especially elderly patients with degenerative disease of the aortic valve. For nearly all patients with aortic valvular stenosis, 2-D and Doppler echocardiography have been found to be reliable for both the diagnosis and the establishment of severity (by gradient and valve area) of stenosis as well as for assessment of left ventricular function. Therefore, we project a lesser role for cardiac catheterization in the future, limited to definition of the coronary anatomy. Aortic valve replacement remains the proven therapy for patients with symptomatic aortic stenosis, although the decalcification/lithotripsy and balloon valvuloplasty techniques appear to be promising options in selected patients.


Micromotion-induced strain fields influence early stages of repair at bone-implant interfaces.
Implant loading can create micromotion at the bone-implant interface. The interfacial strain associated with implant micromotion could contribute to regulating the tissue healing response. Excessive micromotion can lead to fibrous encapsulation and implant loosening. Our objective was to characterize the influence of interfacial strain on bone regeneration around implants in mouse tibiae. A micromotion system was used to create strain under conditions of (1) no initial contact between implant and bone and (2) direct bone-implant contact. Pin- and screw-shaped implants were subjected to displacements of 150 or 300 μm for 60 cycles per day for 7 days. Pin-shaped implants placed in five animals were subjected to three sessions of 150 μm displacement per day, with 60 cycles per session. Control implants in both types of interfaces were stabilized throughout the healing period. Experimental strain analyses, microtomography, image-based displacement mapping, and finite element simulations were used to characterize interfacial strain fields. Calcified tissue sections were prepared and Goldner trichrome stained to evaluate the tissue reactions in higher and lower strain regions. In stable implants bone formation occurred consistently around the implants. In implants subjected to micromotion bone regeneration was disrupted in areas of high strain concentrations (e.g. >30%), whereas lower strain values were permissive of bone formation. Increasing implant displacement or number of cycles per day also changed the strain distribution and disturbed bone healing. These results indicate that not only implant micromotion but also the associated interfacial strain field contributes to regulating the interfacial mechanobiology at healing bone-implant interfaces.


Triple mosaicism 45,XY,--18/46, XY/47,XY,+18.
A patient with symptoms clinically resembling Edwards's syndrome is presented. Cranial asymmetry, thoracic and lumbar hemivertebrae, and an additional rib were the unusual features. The cytogenetic studies revealed the coexistence of three separate cell lines with 45,XY,--18/46,XY/47,XY,+18 complement.


Development of a high resolution melting method for the detection of genetic variations in Long QT Syndrome.
Inherited Long QT Syndrome (LQTS) is a cardiac channelopathy associated with a high risk of sudden death. The prevalence has been estimated at close to 1:2000. Due to large cohorts to investigate, the size of the 3 prevalent mutated genes, and the presence of a large spectrum of private mutations, mutational screening requires an extremely sensitive and specific scanning method. Efficiency of high resolution melting (HRM) analysis was evaluated for the most prevalent LQTS-causing genes (KCNQ1, KCNH2) using control DNAs and DNAs carrying previously identified gene variants. A cohort of 34 patients with a suspicion of LQTS was further blindly screened. To evaluate HRM sensitivity, this cohort was also screened using an optimized DHPLC strategy. HRM analysis was successfully optimized for KCNQ1 but optimisation of KCNH2 was more laborious as only 3 KCNH2 exons could be finally optimized. Remaining KCNH2 exons were analysed by direct sequencing. This molecular approach, which combined HRM and direct sequencing, was applied on the cohort of 34 cases and 9 putative mutations were identified. Using this approach, molecular investigation was completed faster and cheaper than using DHPLC strategy. This HRM/sequencing procedure represents an inexpensive, highly sensitive and high-throughput method to allow identification of mutations in the coding sequences of prevalent LQTS genes.


Modified double face onlay island preputial skin flap with augmented glanuloplasty for hypospadias repair.
To present and evaluate our initial results with a modified double face onlay preputial flap (DOPF) for repair of different degrees of hypospadias. From April 2004 to April 2009, 182 patients with different degrees of hypospadias (distal penile hypospadias = 122, mid penile hypospadias = 38, proximal penile hypospadias = 22) were included in our study. All patients were treated with a modified DOPF. Their age ranged from 6 months to 10 years (mean 3.03 years). Selection criteria were those cases with urethral plate<8 mm with either flat or conical glans, and non-circumcised patients. The technique of repair was to use the distally tapered inner preputial mucosa as onlay to augment the narrow urethral plate, while the outer face was tapered distally to augment the closed proximal part of the glanular wings and as skin cover. Suitable urethral catheter was inserted for 3-5 days. Follow-up duration was 27-30 months (mean 24 months). Functional and cosmetic success was reported in 176 patients (96.6%). Six patients (3.29%) had developed complications that affected the success rate: 1 (0.5%) glanular disruption, 2 (1.09%) fistula, 1 (0.5%) urethral diverticulum and 2 (1.09%) lateral penile torsion. Three (1.6%) patients had developed minor complications with no effect on functional and cosmetic success in form of superficial epidermal loss. Modified DOPF is a suitable technique for repair of different types of hypospadias as it results in satisfactory functioning and an acceptable cosmetic appearance.


The physical state and plasma biochemical profile of young calves on arrival at a slaughter plant.
To determine the welfare of calves arriving at a slaughter plant by assessing their physical state and plasma biochemical profile. Calves (n=7,169) aged 4-10 days, were examined immediately after they were unloaded from trucks (n=20) and categorised on physical grounds as being in an 'unacceptable', 'marginal' or 'acceptable' state. 'Unacceptable' calves were lying down, unable to walk, extremely weak or seriously injured. 'Marginal' calves had a wet umbilicus, were hollow sided, apparently immature, or weak and slow and unsteady on their feet. 'Acceptable' calves were strong, walked freely, round-sided, bright and alert and had a dry umbilicus. After unloading, 27 'unacceptable', 306 'marginal' and 289 'acceptable' calves were weighed, examined clinically and a blood sample was taken from each. A second blood sample was taken from 118 of these calves, 12-15 hours later. The packed cell volume (PCV) and plasma concentrations of glucose, beta-hydroxybutyrate (BHB), total plasma proteins (TPP), gamma-glutamyl transferase (GGT), urea, creatine kinase (CK) and lactate were measured. Only 27 of the 7,169 calves examined (0.4%) were categorised as being in an 'unacceptable' state on arrival and these were euthanased shortly after unloading. Generally, the plasma biochemical profiles of the 'acceptable' calves were similar to those of 'marginal' animals. However the glucose concentration of 'marginal' calves was lower than that of 'acceptable' calves, suggesting that they had lower energy reserves. After 12-15 h in lairage, plasma glucose concentration decreased and the BHB concentration increased in both 'acceptable' and 'marginal' calves compared with concentrations measured on arrival. The percentage of calves presented for slaughter in an 'unacceptable' state was small (0.4%). However, 4% of calves were classified as 'marginal' and failed to meet all the requirements of the code of recommendations and minimum standards governing the welfare of young calves in New Zealand. The categorisation of calves by a physical assessment was supported by results of plasma biochemistry. As a result, plasma biochemical profiles are considered unnecessary for making decisions regarding the welfare status of calves arriving at a slaughter plant; an assessment of their physical state is sufficient.


Development of a Conceptual Etiological Model of Treatment Regimen Fatigue Among Patients Engaged in HIV Care: A Qualitative Study.
Treatment regimen fatigue (TRF) is a decreased desire and motivation to maintain vigilance in adhering to treatment, and little is known about TRF in people living with HIV. We aimed to develop a conceptual framework of TRF. Five focus groups were conducted in 2014. Eligible participants were (a) HIV infected, (b) at least 18 years of age, (c) prescribed antiretroviral therapy, and (d) fluent in English. Data were analyzed using thematic analysis. Analyses revealed these themes: patient experiences of TRF; etiological factors at the systems, provider, and patient levels; strategies to manage TRF; consequences of TRF; and protective factors that prevent the occurrence of TRF. The results provided a conceptual framework for future investigations to build on in an effort to improve adherence and retention in HIV care. Study results indicate avenues for intervention at multiple levels (systems, provider, and patient) to reduce treatment burden and improve patient resources and capacity.


Detergent-induced changes in the mapping of certain enzymes in various cell types of Rita rita. II. Gill epithelium.
Rita rita were exposed to 6.9 mg/liter (96-hr LC50 of an anionic detergent, dodecylbenzene sodium sulfonate). Loss of activity of certain enzymes responsible for various metabolic processes in fish gill epithelium was observed using a battery of histochemical techniques. The information of this investigation may possibly add to an understanding of the as yet unknown mechanism of detergent action.


Complete Genome Sequence of Stenotrophomonas maltophilia Podophage Paxi.
Stenotrophomonas maltophilia is a multidrug-resistant nosocomial pathogen that can cause life-threatening infections among immunocompromised populations. This report presents the complete 74,962-bp genome of S. maltophilia podophage Paxi, an N4-like phage sharing 85.3% nucleotide similarity to S. maltophilia podophage Pokken.


Sledding while towed behind motorized vehicles associates with more severe and lethal injuries☆.
Our institution has recently experienced an increase in sledding-related injuries, particularly when towed behind motorized vehicles. The purpose of this study was to characterize injury severity and clinical outcomes between pediatric patients who sustain injuries owing to motorized sledding accidents to aid in injury prevention messaging. This retrospective study queried all patients who presented with a sledding-related injury to a single ACS-verified Level 1 Pediatric Trauma Center located in the Southeastern United States between 01/2015 and 01/2022. Demographics, injury details, and clinical outcomes were compared between two groups: patients towed behind a motorized vehicle (MOTOR) and those who were not (GRAVITY). Of the 67 patients included in our analysis, 15 (22%) were in the MOTOR group. Patients in the MOTOR group presented with significantly higher injury severity (ISS) and lower Glasgow coma scale (GCS) scores. Additionally, patients in this MOTOR group more often received a blood transfusion and intubation, had longer intensive care and overall hospital lengths of stay, and incurred higher hospital costs. In a multivariate analysis, the use of a motorized vehicle to sled was independently associated with increased ISS (OR: 9.7, 95% CI 1.9-17.5; p = 0.02). Two deaths occurred after sledding while being towed behind a motorized vehicle. Children experiencing sledding accidents while being towed by motorized vehicles sustain significantly more severe injuries and require more intensive treatments that together lead to increased hospital costs. These findings provide the framework for community educational initiatives and injury prevention measures to mitigate risk among children engaged in sledding. IV retrospective cohort study.


Cellular expression of gH confers resistance to herpes simplex virus type-1 entry.
Entry of herpes simplex virus-1 (HSV-1) into cells requires a concerted action of four viral glycoproteins gB, gD, and gH-gL. Previously, cell surface expression of gD had been shown to confer resistance to HSV-1 entry. To investigate any similar effects caused by other entry glycoproteins, gB and gH-gL were coexpressed with Nectin-1 in Chinese hamster ovary (CHO) cells. Interestingly, cellular expression of gB had no effect on HSV-1(KOS) entry. In contrast, entry was significantly reduced in cells expressing gH-gL. This effect was further analyzed by expressing gH and gL separately. Cells expressing gL were normally susceptible, whereas gH-expressing cells were significantly resistant. Further experiments suggested that the gH-mediated interference phenomenon was not specific to any particular gD receptor and was also observed in gH-expressing HeLa cells. Moreover, contrary to a previous report, gL-independent cell surface expression of gH was detected in stably transfected CHO cells, possibly implicating cell surface gH in the interference phenomenon. Thus, taken together these findings indicate that cellular expression of gH interferes with HSV-1 entry.


Membrane fusion-inhibiting peptides do not inhibit influenza virus fusion or the Ca(2+)-induced fusion of negatively charged vesicles.
Short hydrophobic N-carbobenzoxy oligopeptides are known to inhibit the infectivity of several enveloped viruses. Recently, it was shown that they inhibited the fusion of Sendai virus with N-methyl-dioleoylphosphatidylethanolamine (N-methyl-DOPE) liposomes as well as the low pH-induced fusion of these liposomes with each other (Kelsey, D.R., Flanagan, T. D., Young, J. E., and Yeagle, P. L. (1990) J. Biol. Chem. 265, 12178-12183). Therefore it was concluded that the peptides inhibit membrane fusion, an important step in viral infectivity. Here, it is shown that this peptide and a series of similar peptides did not inhibit influenza virus fusion with N-methyl-DOPE or other liposomes. In fact, some peptides enhanced the overall rate of fusion of influenza virus with N-methyl-DOPE liposomes. In our hands, the peptides did not inhibit influenza infectivity in Madin-Darby canine kidney cells or influenza-induced hemolysis either. They also did not inhibit the Ca(2+)-induced fusion between cardiolipin or phosphatidylserine liposomes. However, the inhibitory effect of one of the peptides on the fusion of Sendai virus with N-methyl-DOPE liposomes and on N-methyl-DOPE liposome-liposome fusion could be reproduced. These data indicate that the peptides do not, as had been suggested (Yeagle, P.L., Young, J.E., Hui, S.W., and Epand, R. M. (1992) Biochemistry 31, 3177-3183), act by preventing the formation of lipid structures with small radii of curvature, such as the inverted phase intermediates that are thought to be involved in N-methyl-DOPE fusion. The results also suggest that the mechanism of inhibition of Sendai virus infection and N-methyl-DOPE fusion by the peptides may be different after all.


Implications of COVID-19 on oxbow lake (Baors) Fisher's community, Bangladesh: resilience to food security against probable natural calamities.
The purpose of studying the consequence of COVID-19 on oxbow lake (Baor) fisher's community is to counteract the negative impacts on livelihoods with food security and figure out diversified resilience options for sustaining basic needs of life. Individual questionnaire interviews, oral history, focus group discussion, and telephonic interviews were among the methodological techniques used to gather primary data. The Baor fisher's community was impaired with income, food and feeding habit, health and marketing. The Baor fishers had to stop harvesting or reducing the amount of fish harvest because of gradual decreasing of consumer demand and prices of fish during the course of COVID-19 pandemic period. The transportation costs were raised up to 50%-80%, while the prices of fish decreased by 15%-30% prior to the onset of COVID-19 pandemic. The frequency of fish consumption was significantly come down to 37.5%. Many households substituted fish to farm reared hens, eggs, domestic hens and ducks, lentils, and vegetables during the period of lockdown across the country. Supply chains of fish and fish culture inputswere disrupted due to inadequacy of transportation facilities. Many school- and college-going students were dropped outduring the ongoing pandemic situation due to their financial problems (10%) and early marriage (7.5%). The secondary sources of income (labor of netting in other aquaculture farms) of Baor fisher's community were also impaired. The resilience options of this study will be helpful to minimize the sudden economic crises, ensure dynamic fish value chains and food security, protect individuals from ongoing health hazards, and promote sustainable food production systems followed by social cohesion and stabilityagainst the prevailing challenges owing to the pandemic and other natural calamities.


Development of a laboratory robotic system for automated bioanalytical methods--I. The determination of theophylline in human plasma: a comparison between the robotized and manual method.
The quality of bioanalytical methods is often determined by the quality of sample preparation. Using a robot for sample treatment may give better results than manual sample preparation, since the robot lacks human behaviour and incidental errors that are part of it. The use of a laboratory robot has the additional advantage of giving each sample the same analytical history, resulting in better reproducibility. An automated method has been developed for the analysis of drugs in plasma using a laboratory robot. Theophylline was used as a probe drug. Sample preparation was automated with a Zymate II robot, followed by separation and quantitation on an HPLC-system. The robotic method showed a good correlation with the manual method, while sample throughput was doubled.


Biomechanics of spinal cord injury.
This article summarizes the biomechanical relationship of the spinal column to load stresses with respect to column failure, and the resulting associated central nervous system injury. In addition, it presents pertinent animal research, which has focused onto the development standardized animal spinal cord injury model.


Different effects on human topoisomerase I by minor groove and intercalated deoxyguanosine adducts derived from two polycyclic aromatic hydrocarbon diol epoxides at or near a normal cleavage site.
Topoisomerase I (top1) relieves supercoiling in DNA by forming transient covalent cleavage complexes. These cleavage complexes can accumulate in the presence of damaged DNA or anticancer drugs that either intercalate or lie in the minor groove. Recently we reported that covalent diol epoxide (DE) adducts of benzo[a]pyrene (BaP) at the exocyclic amino group of G(+1) block cleavage at a preferred cleavage site ( approximately CTT-G(+1)G(+2)A approximately ) and cause accumulation of cleavage products at remote sites. In the present study, we have found that the 10S G(+2) adduct of BaP DE, which lies toward the scissile bond in the minor groove, blocks normal cleavage, whereas the 10R isomer, which orients away from this bond, allows normal cleavage but blocks religation. In contrast to BaP, the pair of benzo[c] phenanthrene (BcPh) DE adducts at G(+2), which intercalate from the minor groove either between G(+1)/G(+2) or between G(+2)/A, allow normal cleavage but block religation. Both intercalated BcPh DE adducts at G(+1) suppress normal cleavage, as do both groove bound BaP DE adducts at this position. These studies demonstrate that these DE adducts provide a novel set of tools to study DNA topoisomerases and emphasize the importance of contacts between the minor groove and top1's catalytic site.


Lignocellulosic nanomaterials production from wheat straw via peracetic acid pretreatment and their application in plastic composites.
Cellulose nanofibrils are typically prepared from high-purity bleached pulp through harsh chemical treatments (e.g., TEMPO oxidation), resulting in high costs and environmental impact. In this work, we utilize inexpensive wheat straw feedstock and alkaline peroxide pulping followed by mild peracetic acid (PAA) pretreatment to produce lignocellulosic nanomaterials (nano and microfibrils) with potential bioplastics applications. PAA was chosen due to its biodegradability, non-toxicity, and high reaction selectivity. As-synthesized lignocellulosic nanomaterials were thoroughly characterized and compared to nanofibrils produced via TEMPO oxidation pretreatment and then applied as reinforcing agents in plastic composites. A remarkable case of simultaneous strengthening and toughening of the polymer nanocomposite was achieved with high specific tensile strength (up to 59.5 MPa g-1 cm3), elastic modulus (up to 2.6 GPa g-1 cm3), and fracture strain (up to 138 %). This work is a comprehensive investigation of all process steps involved in lignocellulosic nanomaterials production, from original residue feedstock to final product application.


Removal of soil biota alters soil feedback effects on plant growth and defense chemistry.
We examined how the removal of soil biota affects plant-soil feedback (PSF) and defense chemistry of Jacobaea vulgaris, an outbreak plant species in Europe containing the defense compounds pyrrolizidine alkaloids (PAs). Macrofauna and mesofauna, as well as fungi and bacteria, were removed size selectively from unplanted soil or soil planted with J. vulgaris exposed or not to above- or belowground insect herbivores. Wet-sieved fractions, using 1000-, 20-, 5- and 0.2-μm mesh sizes, were added to sterilized soil and new plants were grown. Sieving treatments were verified by molecular analysis of the inocula. In the feedback phase, plant biomass was lowest in soils with 1000- and 20-μm inocula, and soils conditioned with plants gave more negative feedback than without plants. Remarkably, part of this negative PSF effect remained present in the 0.2-μm inoculum where no bacteria were present. PA concentration and composition of plants with 1000- or 20-μm inocula differed from those with 5- or 0.2-μm inocula, but only if soils had been conditioned by undamaged plants or plants damaged by aboveground herbivores. These effects correlated with leaf hyperspectral reflectance. We conclude that size-selective removal of soil biota altered PSFs, but that these PSFs were also influenced by herbivory during the conditioning phase.


Localized calcium spikes and propagating calcium waves.
Ca2+ signals control or modulate diverse cellular processes such as cell growth, muscle contraction, hormone secretion, and neuronal plasticity. Elevations in intracellular Ca2+ concentrations can be highly localized to micron and submicron domains or propagated as intra- and intercellular waves over distances as large as 1 mm. Localized, subcellular Ca2+ spikes are thought to selectively activate effector systems such as Ca2+ activated chloride currents in pancreatic acinar cells, neurotransmitter release in synaptic nerve terminals, and morphological changes in neural growth cones. In contrast, long-ranged Ca2+ waves synchronize the activities of different cytoplasmic regions of a single cell, such as cortical granule exocytosis after egg fertilization or coordinate the activities of many cells, such as ciliary beating in pulmonary epithelium. The purpose of this review is to delineate the role of Ca2+ in the generation of localized, subcellular Ca2+ spikes and long-ranged intracellular and intercellular Ca2+ waves.


Dissemination and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in water and sediment of Buriganga and Dhaleswari rivers of Dhaka, Bangladesh.
Concentration, source, ecological and health risks of sixteen polycyclic aromatic hydrocarbons (PAHs) were estimated for water and sediment samples of two urban rivers namely Buriganga River (BR) and Dhaleswari River (DR). The mean concentration of ∑PAHs in BR water and sediment were 9619.2 ngL-1 and 351.6 ngg-1, respectively. Furthermore, the average PAH concentrations detected in DR water and sediment were 1979.1 ngL-1 and 792.9 ngg-1, respectively. The composition profile showed that 3-ring PAHs were dominant in the water matrix; however, 5-ring PAHs were prevalent in the sediment samples of both rivers. Sources apportion study of PAHs indicated that mixed combustion and petroleum sources are responsible for PAHs contamination in the rivers. Ecological risk study of water suggested that the aquatic lives of both rivers are threatened by Fla, BbF, BkF, DahA, and IcdP, as presented above the threshold level. Comparison with sediment quality guidelines (SQGs) indicated that adverse effects might cause occasionally in the sediment ecosystem in DR at certain sampling sites for Nap, Acy, Fl, Phe, Ant, Pyr, Chr, BaP, and DahA. On the other hand, the presence of Nap, Acy and DahA might occasionally cause adverse biological effects in the BR sediment ecosystem. Estimated hazard quotient (HI > 1) and carcinogenic risk (CRtotal > 10-4) values indicated that local inhabitants living in the vicinity of the rivers are prone to high health risks.


Methylene blue functionalized graphene as binder-free electrode for high-performance solid state supercapacitors.
Electrochemical active small organic molecules are potential electrode materials for supercapacitors due to their sustainable and good redox reversibility. However, the poor electrical conductivity restricts their application in supercapacitors. Herein, a water soluble organic dye of methylene blue (MB) has been supported on graphene (GR) through a facile ultrasonic method to form a methylene blue/graphene (MB/GR) composite. A small amount of MB (13%) in MB/GR composite improves the wettability of GR and supplies pseudocapacitance. The MB/GR composite can be used as a binder-free electrode for supercapacitors, and gives a high specific capacitance of 517 F g-1 at 0.5 A g-1 in 0.5 mol L-1 H2SO4 aqueous electrolyte with a satisfactory capacitive retention of 91% after 2000 consecutive cyclic voltammetry tests at 10 mV s-1. Benefiting from the high specific capacitance of MB/GR composite, the as-assembled symmetrical solid-state supercapacitor (MB/GR//MB/GR) delivers a high energy density of 30.36 Wh kg-1 at 0.7 kW kg-1, and excellent cycle stability (nearly 27% drop after 10,000 consecutive constant current charge-discharge at 5 A g-1). This work offers some enlightenment to design and preparation of high-performance electrode materials for supercapacitors.


Modeling the Spatial Spread of Chagas Disease.
The aim of this work is to understand the spatial spread of Chagas disease, which is primarily transmitted by triatomines. We propose a mathematical model using a system of partial differential reaction-diffusion equations to study and describe the spread of this disease in the human population. We consider the respective subclasses of infected and uninfected individuals within the human and triatomine populations. The dynamics of the infected human subpopulation considers two disease phases: acute and chronic. The human population is considered to be homogeneously distributed across a space to describe the local propagation of Chagas disease by triatomines during a short epidemic period. We determine the basic reproduction number that allows us to assess Chagas disease control measures, and we determine the speed of disease propagation by using traveling wave solutions for our model.


Habitat association of Klebsiella species.
The genus Klebsiella is seemingly ubiquitous in terms of its habitat associations. Klebsiella is a common opportunistic pathogen for humans and other animals, as well as being resident or transient flora (particularly in the gastrointestinal tract). Other habitats include sewage, drinking water, soils, surface waters, industrial effluents, and vegetation. Until recently, almost all these Klebsiella have been identified as one species, ie, K. pneumoniae. However, phenotypic and genotypic studies have shown that "K. pneumoniae" actually consists of at least four species, all with distinct characteristics and habitats. General habitat associations of Klebsiella species are as follows: K. pneumoniae--humans, animals, sewage, and polluted waters and soils; K. oxytoca--frequent association with most habitats; K. terrigena--unpolluted surface waters and soils, drinking water, and vegetation; K. planticola--sewage, polluted surface waters, soils, and vegetation; and K. ozaenae/K. rhinoscleromatis--infrequently detected (primarily with humans).


Gum Arabic in combination with IFN-γ promotes the M1 polarization in macrophage.
Gum Arabic, a mixture of polysaccharide and glycoprotein, is used as an emulsifying stabilizer in the food industry. It might have immunomodulatory effects. We hypothesized that the combination of IFN-γ and Gum Arabic promotes the production of pro-inflammatory factors in RAW 264.7 cells. Treatment of RAW 264.7 cells with the combination of 3% Gum Arabic and 40 ng/mL IFN-γ resulted in a drastic increase (320%) in nitric oxide production compared with that induced by IFN-γ alone. PGE-2 was produced after the cells were treated with 3% Gum Arabic and 40 ng/mL IFN-γ for 6 h. Gum Arabic and IFN-γ increased the production of iNOS and COX-2 proteins, and triggered TNF-α release. Apart from TNF-α, the release of both G-CSF and IL-6 increased by more than 100 times. The release of IL-3, RANTES, and IL-10 increased by more than ten times. Gum Arabic and IFN-γ also increased the secretion of IL-10, IL-1α, IL-1β, IL-13, KC, IL-5, IL-4, IL-12, Eotaxin, IL-9, MCP-1, and ROS. Cytokines associated with M1 polarization of macrophages such as TNF-α, IL-1β, IL-12, NO, and ROS were induced by Gum Arabic and IFN-γ. Our findings help to explore the inflammatory reaction caused by Gum Arabic in cosmetics.


The relationship between epilepsy and religiosity illustrated by the story of the visionary mystic Wise-Knut.
The story of Wise-Knut is remarkable. He was born in a poor mountain district in Norway in 1792 and lived for 84years. He had severe and untreated epilepsy with apparent ictal, postictal, and interictal religious symptoms. He heard voices and had religious delusions; a spiritual awakening after a seizure cluster was a turning point in his life. Contemporary biographers have narrated his major life events in detail, but without a precise separation between ictal and postictal spiritual symptoms. Religious and supernatural significance was attributed to his experiences; he himself believed that his extraordinary abilities were a gift from God: "The prophets have had it like myself." His story corroborates the impression that epilepsy may have had a considerable role in the history of religions. However, apart from anecdotes on visionary and healing abilities, his biographies contain nothing that is miraculous or incredible. He falls into the line of various mystics and religious figures of the past that are currently thought to have had epilepsy. Apparently, the advancing understanding of epilepsy and its complications have influenced the dynamic balance between faith, superstition, and rationalism.


Absolute requirement for iron in the development of chemically induced uroporphyria in mice treated with 3-methylcholanthrene and 5-aminolevulinate.
Accumulating evidence, including experiments using cytochrome P450 1a2 (Cyp1a2) gene knock-out mice (Cyp1a2(-/-)), indicates that the development of chemically induced porphyria requires the expression of CYP1A2. It has also been demonstrated that iron enhances and expedites the development of experimental uroporphyria, but that iron alone without CYP1A2 expression, as in Cyp1a2(-/-) mice, does not cause uroporphyria. The role of iron in the development of porphyria has not been elucidated. We examined the in vivo effect of iron deficiency on hepatic URO accumulation in experimental porphyria. Mice were fed diets containing low (iron-deficient diet (IDD), 8.5 mg iron/kg) or normal (normal diet (ND), 213.7 mg iron/kg) levels of iron. They were treated with 3-methylcholanthrene (MC), an archetypal inducer of CYP1A, and 5-aminolevulinate (ALA), precursors of porphyrin and heme. We found that uroporphyrin (URO) levels and uroporphyrinogen oxidation (UROX) activity were markedly increased in ND mice treated with MC and ALA, while the levels were not raised in IDD mice with the same treatments. CYP1A2 levels and methoxyresorufin O-demethylase (MROD) activities, the CYP1A2-mediated reaction, were markedly induced in the livers of both ND and IDD mice treated with MC and ALA. UROX activity, supposedly a CYP1A2-dependent activity, was not enhanced in iron-deficient mice in spite of the fact of induction of CYP1A2. We showed that a sufficient level of iron is essential for the development of porphyria and UROX activity.