Microscopic dual-energy CT (microDECT): a flexible tool for multichannel ex vivo 3D imaging of biological specimens.
Dual-energy computed tomography (DECT) uses two different x-ray energy spectra in order to differentiate between tissues, materials or elements in a single sample or patient. DECT is becoming increasingly popular in clinical imaging and preclinical in vivo imaging of small animal models, but there have been only very few reports on ex vivo DECT of biological samples at microscopic resolutions. The present study has three main aims. First, we explore the potential of microscopic DECT (microDECT) for delivering isotropic multichannel 3D images of fixed biological samples with standard commercial laboratory-based microCT setups at spatial resolutions reaching below 10 μm. Second, we aim for retaining the maximum image resolution and quality during the material decomposition. Third, we want to test the suitability for microDECT imaging of different contrast agents currently used for ex vivo staining of biological samples. To address these aims, we used microCT scans of four different samples stained with x-ray dense contrast agents. MicroDECT scans were acquired with five different commercial microCT scanners from four companies. We present a detailed description of the microDECT workflow, including sample preparation, image acquisition, image processing and postreconstruction material decomposition, which may serve as practical guide for applying microDECT. The MATLAB script (The Mathworks Inc., Natick, MA, USA) used for material decomposition (including a graphical user interface) is provided as a supplement to this paper (https://github.com/microDECT/DECTDec). In general, the presented microDECT workflow yielded satisfactory results for all tested specimens. Original scan resolutions have been mostly retained in the separate material fractions after basis material decomposition. In addition to decomposition of mineralized tissues (inherent sample contrast) and stained soft tissues, we present a case of double labelling of different soft tissues with subsequent material decomposition. We conclude that, in contrast to in vivo DECT examinations, small ex vivo specimens offer some clear advantages regarding technical parameters of the microCT setup and the use of contrast agents. These include a higher flexibility in source peak voltages and x-ray filters, a lower degree of beam hardening due to small sample size, the lack of restriction to nontoxic contrast agents and the lack of a limit in exposure time and radiation dose. We argue that microDECT, because of its flexibility combined with already established contrast agents and the vast number of currently unexploited stains, will in future represent an important technique for various applications in biological research.


Mobility and asymmetry effects in one-dimensional rock-paper-scissors games.
As the behavior of a system composed of cyclically competing species is strongly influenced by the presence of fluctuations, it is of interest to study cyclic dominance in low dimensions where these effects are the most prominent. We here discuss rock-paper-scissors games on a one-dimensional lattice where the interaction rates and the mobility can be species dependent. Allowing only single site occupation, we realize mobility by exchanging individuals of different species. When the interaction and swapping rates are symmetric, a strongly enhanced swapping rate yields an increased mixing of the species, leading to a mean-field-like coexistence even in one-dimensional systems. This coexistence is transient when the rates are asymmetric, and eventually only one species will survive. Interestingly, in our spatial games the dominating species can differ from the species that would dominate in the corresponding nonspatial model. We identify different regimes in the parameter space and construct the corresponding dynamical phase diagram.


Embelin-loaded guar gum microparticles for the management of ulcerative colitis.
The aim of the present study is to develop embelin-loaded guar gum microparticles through emulsification technique. The in vitro release of the optimised formulation was found to be 88.5 ± 3.8% in 24 h, has exhibited remarkably sustain and delayed the release of embelin at a specific site. Embelin-loaded microparticles showed average particle size of 12.9 ± 0.75 µm. The statistical analysis was carried out by one-way ANOVA followed by comparison test of Bonferroni. P values < 0.05 were considered as significant. The in vivo study concluded that pre-treatment of embelin prevents dinitrobenzenesulfonic acid (DNBS)-induced colitis in rats and depicts protective activity against ulcerative colitis due to its antioxidant and anti-inflammatory actions. This approach produces comparatively less side effect to another conventional dosage form.


[Pituicytoma: a clinicopathological analysis of twenty-one cases].
Objective: To investigate the clinicopathological features and treatment strategies of pituicytoma. Methods: Twenty-one cases of pituicytoma were collected at the First Affiliated Hospital of Nanjing Medical University and Jinling Hospital, Nanjing, China from 2009 to 2020. The clinical data of 21 pituicytoma patients was retrospectively analyzed, and the relevant literature was reviewed. Results: Twenty-one patients aged 4 to 68 years, including 8 males and 13 females. All patients underwent surgical treatment. Histologically, the tumor was consisted almost entirely of elongate, bipolar spindle cells arranged in a fascicular or storiform pattern. Mitotic figures were rare. Immunohistochemically, tumor cells were diffusely positive for S-100 protein (21/21), vimentin (15/15) and TTF1 (14/14), while they were weakly or focally positive for GFAP (13/16) and EMA (6/12). CKpan was negative in all cases and Ki-67 proliferation index was low (<5%). Among the 18 patients with follow-up, all survived and 2 relapsed after surgery. Conclusions: Pituicytoma is a rare low-grade glioma of the sellar area. It is easily confused with other sellar tumors. Preoperative diagnosis is difficult. It needs to be confirmed by histopathology and immunohistochemistry. Microsurgery is the main treatment method at present.


Analysis of growth resistance mechanisms and causes in tea plants (Camellia sinensis) in high-pH regions of Northern China.
In tea plantations with high-pH (pH > 6.5) in Northern China, tea plants are prone to yellowing disease, albinism, and reductions in components that contribute to plant quality, which affect the scale and rate of tea plantation development in Northern China. To investigate the potential causes of these issues, Camellia sinensis cv. Pingyang Tezao and Camellia sinensis cv. Ruixue were planted in Shouguang city (a high-pH area, soil pH > 6.5) and Rizhao city (a normal-pH area, soil pH is 4.5-5.5), respectively; differences in growth morphology, pigment content, cell structure, quality-determining components, and element content of the two varieties in the two areas were analyzed. The results showed that tea leaves planted in Shouguang had varying degrees of yellowing disease and albinism; the pigment content in both varieties was significantly lower when planted in Shouguang compared with Rizhao. The cell structure was severely damaged and the main quality-determining components were decreased. Nitrogen (N), phosphorus (P), potassium (K), zinc (Zn), copper (Cu) and manganese (Mn) contents in the leaves of the two tea plant varieties were significantly lower when planted in Shouguang compared with those in Rizhao; the levels of these elements in Shouguang soil were significantly higher than in Rizhao soil. Calcium (Ca) contents in Shouguang soil was 9.90 times higher than that of Rizhao soil. We conclude that the soil in high-pH areas hindered tea plant uptake of N, Zn, Cu, and Mn, which had a detrimental effect on chloroplasts and reductions in chlorophyll synthesis, contributing to yellowing disease and albinism. In addition, excessive calcium (Ca) in Shouguang soil was also an important contributor to these negative effects. High-pH soil hindered tea plant uptake of P and K, resulting in reductions in tea polyphenols, amino acids, and other major quality components.


Models for the Yielding Behavior of Amorphous Solids.
Investigations of plastic deformation and yielding of amorphous solids reveal a strong dependence of their yielding behavior on the degree of annealing. Above a threshold degree of annealing, the nature of yielding changes qualitatively, becoming progressively more discontinuous. Theoretical investigations of yielding in amorphous solids have almost exclusively focused on uniform deformation, but cyclic deformation reveals intriguing features that remain uninvestigated. Focusing on athermal cyclic deformation, I investigate a family of models, which reproduce key features observed in simulations, and provide an interpretation for the intriguing presence of a threshold energy.


[Study of the characteristics of various hematologic diseases using monoclonal antibodies LT1, LT2 and LT7].
Monoclonal antibodies (MCA) LT1, LT2 and LT7 were characterized. It was established that MCA LT1 and LT2 (IgG1 and IgM classes, respectively) interacted with antigen 67 kD, and MCA LT7 (IgGZa)--with antigen 40 kD. MCA LT1, LT2 and LT7 were shown to identify normal and neoplastic cells of T-lymphoid type. MCA LT1 and LT2 also reacted with B-lymphocytes of chronic lymphocytic leukemic patients. MCA LT1 and LT2 were referred to CD5 (Cluster of Differentiation) and MCA LT7--to CD7 by the molecular weight of an identified antigen and the spectrum of its expression. The importance of MCA studied in the diagnosis of subtypes of acute and chronic lymphocytic leukemia has been confirmed.


The relationship between smoking status and cortisol secretion.
Evidence for an association of smoking status with cortisol secretion is mixed. The objective of the study was to assess the relationship between smoking status and salivary cortisol. This was a cross-sectional study of smoking status and cortisol secretion from phase 7 (2002-2004) of the Whitehall II study. An occupational cohort was originally recruited in 1985-1987. The study population consisted of 3103 men (1514 never-smokers, 1278 ex-smokers, and 311 smokers) and 1128 women (674 never-smokers, 347 ex-smokers, and 107 smokers). Information was collected on smoking status, average number of cigarettes smoked, and additional covariates. Saliva samples were taken on waking; waking + 0.5, 2.5, 8, and 12 h; and bedtime for the assessment of cortisol. Smoking status was significantly associated with increased salivary cortisol release throughout the day (P < 0.001) adjusted for covariates; this was apparent for the cortisol awakening response (P < 0.001) when examined separately. Compared with never-smokers, smokers had higher release of total cortisol (P = 0.002), whereas no difference was observed between never-smokers and ex-smokers (P = 0.594): mean release per hour (nanomoles per liter), never-smokers, 4.13 [confidence interval (CI) 4.02-4.24]; ex-smokers, 4.21 (CI 4.08-4.35); smokers, 4.63 (CI 4.35-4.93). There was no significant relationship between number of cigarettes smoked and total cortisol release. However, a difference was observed for the cortisol awakening response: mean release by tertiles of cigarettes smoked (nanomoles per liter): high, 13.49 (CI 10.74-16.23); medium, 9.58 (CI 7.40-11.76); low, 8.49 (CI 5.99-10.99), P = 0.029. Salivary cortisol is increased in current smokers, compared with nonsmokers; no differences were observed between ex-smokers and never-smokers, suggesting that smoking has a short-term effect on the neuroendocrine system.


Preparation of Rat Skeletal Muscle Homogenates for Nitrate and Nitrite Measurements.
Nitrate ions (NO3-) were once thought to be inert end products of nitric oxide (NO) metabolism. However, previous studies demonstrated that nitrate ions can be converted back to NO in mammals through a two-step reduction mechanism: nitrate being reduced to nitrite (NO2-) mostly by oral commensal bacteria, then nitrite being reduced to NO by several mechanisms including via heme- or molybdenum-containing proteins. This reductive nitrate pathway contributes to enhancing NO-mediated signaling pathways, particularly in the cardiovascular system and during muscular exercise. The levels of nitrate in the body before such utilization are determined by two different sources: endogenous NO oxidation and dietary nitrate intake, principally from plants. To elucidate the complex NO cycle in physiological circumstances, we have examined further the dynamics of its metabolites, nitrate and nitrite ions, which are relatively stable compared to NO. In previous studies skeletal muscle was identified as a major storage organ for nitrate ions in mammals, as well as a direct source of NO during exercise. Therefore, establishing a reliable methodology to measure nitrate and nitrite levels in skeletal muscle is important and should be helpful in extending its application to other tissue samples. This paper explains in detail the preparation of skeletal muscle samples, using three different homogenization methods, for nitrate and nitrite measurements and discusses important issues related to homogenization processes, including the size of the samples. Nitrate and nitrite concentrations have also been compared across four different muscle groups.


Prevalence of fatigue among cancer patients receiving various anticancer therapies and its impact on quality of life: a cross-sectional study.
Fatigue is disabling and continuous phenomenon in cancer patients during and after various anticancer treatments which can continue for many years after treatment and definitely it has profound effect on Quality of Life (QOL). However, determining its severity is still underestimated among the cancer patients and also very few studies in the literature exist reporting on Cancer-Related Fatigue (CRF) among Indian population. To find out the prevalence of rate of fatigue in cancer patient receiving various anti cancer therapies. To find out the relative impact of fatigue on QOL. This cross-sectional observational study included a total 121 cancer patients receiving radiotherapy, chemotherapy, and concurrent chemo-radiation with the age group of above 15 years who fulfilled the inclusion and exclusion criteria. All the patients were assessed for severity of fatigue using Brief Fatigue Inventory (BFI) and for QOL using FACT-G scale while they were receiving the anticancer therapies as an in-patient in the regional cancer centers in Madhya Pradesh, India. The severe fatigue was more prevalent in chemotherapy [58/59 (98.30%)], and concurrent chemo-radiation (33/42 (78.57%)) as compared to radiotherapy (Moderate-9/20 (45%) and Severe-9/20 (45%)). Moderate correlations were exhibited between fatigue due to radiotherapy and QOL (r = -0.71, P < 0.01), whereas weak correlation was found between fatigue due to chemotherapy and concurrent chemo-radiation (r = -0.361, P < 0.01 and r = -0.453, P < 0.01, respectively). Severity of fatigue was found more after chemotherapy and concurrent chemo-radiation therapy while impact on QOL was more after the radiotherapy.


Carcinoma of the gallbladder with an anomalous connection between the choledochus and the pancreatic duct. Report of 10 cases and review of the literature in Japan.
During the last 8 years, the authors had experience with 10 cases of carcinoma of the gallbladder with an anomalous connection between the choledochus and the pancreatic duct. These cases were studied in reference to age, sex, frequency of gallstones and dilatation of the bile duct, amylase levels in bile, direct cholangiograms, histologic findings, methods of treatment, and prognosis. Histologically, intestinal metaplasia was noticed in cancerous areas and also in noncancerous areas of differentiated adenocarcinomas. These facts suggest that in carcinoma of the gallbladder with this anomaly, reflux and stasis of pancreatic juice in the gallbladder may induce chronic cholecystitis which leads to mucosal metaplasia and, eventually, to differentiated adenocarcinoma.


[Plate thermography in the assessment of changes in the female breast. 1. The value of malignancy criteria using Tricoire's technic].
In a retrospective study on 19,641 patients of which 2702 were clarified by morphology criteria of malignancy by Tricoire were examined. Nearly all criteria were relevant. Only the "mild circumscript heatness " and "one atypical vessel" have failed as criteria of malignancy. The vascular pattern D + E ( Bourjat ) is shown as an additive sign of malignancy. The correct classification in typical and atypical vascular patterns depends from a decisive dynamic test.


Lung abscess secondary to lung cancer with a coinfection of Granulicatellaadiacens and other bacteria: a case report.
Granulicatella adiacens is facultative anaerobic Gram-positive bacteria, which mainly involve bacterial endocarditis and bacteremia, but there are few reports of local suppurative infection. A case of lung abscess with a coinfection of Granulicatella adiacens and other bacteria in a lung cancer patient will be reported in this paper. To our knowledge, this is the first case report describing lung abscess due to G.adiacens. A 52-year-old Chinese woman was admitted to the hospital, She complained of coughing and expectoration for 1 month, shortness of breath for half a month, and dyspnea for 1 day. After a series of examinations, she was diagnosed with lung abscess, pleural effusion, and bronchogenic carcinoma. Draining pus culture demonstrated Granulicatella adiacens. After more than 5 weeks of antibiotic therapies in total, she gradually recovered to fight against lung cancer. This is the first reported lung abscess caused by G.adiacens. In immunosuppressed hosts, G.adiacens is a virulent pathogen associated with a spectrum of intrathoracic suppurative. Earlier diagnosis and proper drainage surgery with effective antibiotics treatment are very important, and antimicrobial treatment should be more than 5 weeks. When complex pulmonary infection interferes with the CT diagnosis, clinical suspicion of lung cancer should be increased if G.adiacens or Eikenella corrodens is detected from a pulmonary infection.


The role of LRP8 (ApoER2') in the pathophysiology of the antiphospholipid syndrome.
One of the greatest enigmas in thrombosis research is the observation that one can diagnose a person with a thrombotic risk with a prolongation of the clotting time. Our textbooks have taught us that prolongation of clotting correlates with a tendency to bleed. To confuse our textbook knowledge further, the same patients often have a prolonged bleeding time, a diagnostic test to detect a dysfunction in primary haemostasis. In this paper we critically review the literature that tries to explain the contradiction that exists between in-vitro diagnostic tests and the observed clinical manifestations and discuss our current opinion on how antiphospholipid antibodies can disturb the haemostatic balance.


Eosinophilic ascites due to Strongyloides stercoralis.
We report the case of a patient with eosinophilic ascites in whom filariform larvae of Strongyloides stercoralis were found in smears of the ascitic fluid. The ascites resolved after therapy with albendazole. Eosinophilic ascites can rarely result from parasitic infections including Strongyloides stercoralis.


COMMD1: A Multifunctional Regulatory Protein.
The COMMD Protein Family is highly conserved among multicellular eukaryotic organisms and many orthologs of human COMMD genes have been found in different species of plants, invertebrates, lower vertebrates, and mammals. COMMD1 is the best characterized member of the family and is conserved among vertebrates. This protein represents a pleiotropic factor involved in the regulation of many cellular and physiological processes that include copper and cholesterol homeostasis, ionic transport, oxidative stress, protein aggregation, protein trafficking, NF-κB-mediated transcription, hypoxia induced transcription, DNA damage response, and oncogenesis. The present work reviews the molecular mechanisms and biological processes regulated by COMMD1 that have been described so far, emphasizing in the regulatory role of the protein and its importance for cellular homeostasis. J. Cell. Biochem. 119: 34-51, 2018. © 2017 Wiley Periodicals, Inc.


[The evaluation of the error of the thermal pulse technique used to measure moisture content of root substrates in space greenhouse].
Point thermopulse probes were used to monitor moisture level in the root substrates during cultivation of higher plants in a space greenhouse. Investigated were performance data of the thermopulse moisture probe in integration with the space greenhouse. It was shown that within the substrate moisture range from 20 up to 100% of the full saturation the technique error does not exceed 1.5%. The thermopulse technique bears much promise for metrologic monitoring of the root substrate moisture content in space greenhouses no matter water and air supply technology.


Consequences of induced brassinosteroid deficiency in Arabidopsis leaves.
The identification of brassinosteroid (BR) deficient and BR insensitive mutants provided conclusive evidence that BR is a potent growth-promoting phytohormone. Arabidopsis mutants are characterized by a compact rosette structure, decreased plant height and reduced root system, delayed development, and reduced fertility. Cell expansion, cell division, and multiple developmental processes depend on BR. The molecular and physiological basis of BR action is diverse. The BR signalling pathway controls the activity of transcription factors, and numerous BR responsive genes have been identified. The analysis of dwarf mutants, however, may to some extent reveal phenotypic changes that are an effect of the altered morphology and physiology. This restriction holds particularly true for the analysis of established organs such as rosette leaves. In this study, the mode of BR action was analysed in established leaves by means of two approaches. First, an inhibitor of BR biosynthesis (brassinazole) was applied to 21-day-old wild-type plants. Secondly, BR complementation of BR deficient plants, namely CPD (constitutive photomorphogenic dwarf)-antisense and cbb1 (cabbage1) mutant plants was stopped after 21 days. BR action in established leaves is associated with stimulated cell expansion, an increase in leaf index, starch accumulation, enhanced CO2 release by the tricarboxylic acid cycle, and increased biomass production. Cell number and protein content were barely affected. Previous analysis of BR promoted growth focused on genomic effects. However, the link between growth and changes in gene expression patterns barely provided clues to the physiological and metabolic basis of growth. Our study analysed comprehensive metabolic data sets of leaves with altered BR levels. The data suggest that BR promoted growth may depend on the increased provision and use of carbohydrates and energy. BR may stimulate both anabolic and catabolic pathways.


Lymphangioleiomyomatosis diagnosed by immunocytochemical and genetic analysis of lymphangioleiomyomatosis cell clusters found in chylous pleural effusion.
A 37-year-old woman presented with a cough and discomfort in the chest. Computed tomography revealed the right pleural effusion and a number of cysts in the lungs. Thoracentesis revealed LAM cell clusters (LCC) in chylous pleural effusion, confirmed by immunocytochemical examinations showing that the cells at the center of cluster were LAM cells positive for alpha-smooth muscle actin and HMB45 and the outer layer was lymphatic endothelium cells. When LCC were cultured in vitro, the loss of heterozygosity of TSC2 markers was detected. This case illustrates that LAM can be diagnosed by the identification of LCC without an invasive biopsy if complicated with chylous effusion.


Cerebrovascular abnormalities in adults born SGA at 12 years after growth hormone cessation compared to controls.
Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population.However, previous studies did not have an appropriate control group which is a major limitation. To study cerebrovascular abnormalities (aneurysms, previous intracerebral hemorrhages and microbleeds) using MRI in adults born SGA at 12 years after cessation of childhood GH-treatment (SGA-GH) compared to appropriate controls. In this prospective study, all brain MRIs were performed between May 2016 - December 2020 on a 3T MRI system. MRI images were scored by two neuro-radiologists who were blinded to patient groupings. Single-center study. Adults born SGA previously treated with GH and 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). Long-term GH-treatment during childhood. Cerebrovascular abnormalities. 301 adults were investigated. Aneurysms were found in 6 adults: 3 (3.6%) SGA-GH, 1 (2.9%) SGA-S and 2 (2.2%) AGA adults, without differences between SGA-GH adults and the controls. Previous intracerebral hemorrhages were only found in 2 SGA-S adults (4.8%). Microbleeds were found in 17 adults: 4 (4.3%) SGA-GH, 4 (9.5%) SGA-S, 3 (4.3%) SGA-CU and 6 (6.3%) AGA adults, without differences between SGA-GH adults and the controls. Our findings suggest that SGA-GH adults at 12 years after GH cessation have no increased prevalence of cerebrovascular abnormalities compared to appropriate controls. Further research is needed to confirm our findings.


Two new compounds from a marine-derived Streptomyces sp.
Two new long-chain unsaturated compounds, (2E, 6E)-10-methoxy-3,7-dimethyl-10-oxodeca-2,6-dienoic acid (1) and (2E, 6E)-3,7,11-trimethyldodeca-2,6-dienedioic acid (2), together with seven known compounds were isolated from a marine-derived Streptomyces sp. Their structures were determined by spectroscopic methods, including 2D NMR techniques. Compounds 1 and 2 were investigated for their antibacterial activities.


Long-term outcome of schizoaffective and schizophrenic disorders: a comparative study. II. Causal-analytical investigations.
The influence of symptomatological and non-symptomatological factors on the long-term outcome of schizoaffective and schizophrenic disorders was investigated using the Analysis of Linear Structural Relationships (LISREL). The outcome was assessed employing the GAS, WHO/DAS, PIRS and the Bonn Criteria of Outcome. The analysis produced some interesting results in both groups, separately and in comparison with each other. The most striking difference between the two disorders concerns the finding that only symptomatological parameters directly influence the long-term outcome of schizoaffective disorders - melancholic episodes are correlated with favourable outcome, symptoms typical of schizophrenia with a relatively unfavourable outcome. Both symptomatological parameters (such as schizophrenic first-rank symptoms during course) and non-symptomatological parameters (such as life events or acuteness of onset) have a direct impact on the outcome. It was also found that "simple" depressive symptomatology (the presence of depressive symptoms not fulfilling the criteria of melancholic episodes according to DSM-III-R) has no influence on the long-term outcome of schizophrenia.


Incidence of Venous Thromboembolism after Sternal Reconstruction: A Single-center Retrospective Review.
Deep sternal wound infection and mediastinitis following sternotomy are associated with significant morbidity and mortality, and often require sternal reconstruction by plastic surgeons. Despite this patient population having a substantial risk of venous thromboembolism, there are no reports of the incidence of venous thromboembolism in patients undergoing sternal reconstruction. The authors sought to evaluate the incidence of venous thromboembolism in sternal reconstruction patients and to identify common risk factors for venous thromboembolism in this patient population. A single-center retrospective review was completed of all patients who underwent sternal reconstruction by plastic surgeons between January 2012 and July 2020. Demographic data, antiplatelet and anticoagulant use, 2005 Caprini score, operative time, bleeding events, and postoperative venous thromboembolism events were recorded. A total of 44 patients were identified for analysis. The average 2005 Caprini score for the cohort was 10.9. In total, 93.2% of patients received perioperative antiplatelet and anticoagulant therapy (either chemoprophylaxis or systemic). Two patients developed postoperative venous thromboembolism events, for a total venous thromboembolism rate of 4.6%. Four patients had bleeding events requiring reoperation. No deaths were reported from either of these complications. Patients undergoing sternal reconstruction are at a high risk for venous thromboembolism and postoperative bleeding events. Despite the growing body of literature on venous thromboembolism in various surgical populations, the optimal management of thromboembolic risk in patients with high Caprini scores undergoing sternal reconstruction requires additional investigation.


Quantifying mechanical force in axonal growth and guidance.
Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight: (1) standing questions concerning the role of mechanical force in axonal growth and guidance; and (2) different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.


The gene encoding IFP 53/tryptophanyl-tRNA synthetase is regulated by the gamma-interferon activation factor.
We have obtained genomic DNA encoding the interferon-gamma (IFN-gamma)-inducible IFP 53/tryptophanyl-tRNA synthetase. Comparison with several different IFP 53 cDNA clones revealed a complex pattern of alternatively spliced 5'-untranslated regions. The interferon-responsive region within the IFP 53 promoter was found to contain a gamma-interferon activation site (GAS) but not the interferon-stimulated response element and to bind the gamma-interferon activation factor (GAF). GAF.GAS complexes contained the IFN-regulated 91-kDa protein. Competition experiments defined the GAS boundaries and showed that GAF binding to the IFP 53 GAS could be prevented by an excess of the IFN-gamma response regions of several other IFN-gamma-inducible genes. We thus provide evidence for a central role of GAS.GAF in gene transcription mediated by IFN-gamma and suggest a consensus sequence defining more precisely the requirements for GAF binding to DNA.


First Report of Tobacco Ringspot Virus Naturally Infecting Cotton (Gossypium hirsutum L.) in the United States.
Cotton (Gossypium hirsutum L.) is one of the major cash crops grown in the United States (U.S.) with a total acreage of over 11.5 million acres in 2021 (NASS, 2021). In Oklahoma, cotton represents an important economic crop and was grown on 490,000 acres during the 2021 growing season (NASS, 2021). In 2021, during a survey of a cotton field in Beckham County of Oklahoma, cotton plants showed typical virus-like symptoms including mosaic, yellow ring spots, discoloration and short internodes (Supplementary Fig. 1). Thirteen symptomatic and five asymptomatic samples were collected from cotton plants and brought to the University of Tulsa for further processing. Total RNA was extracted from all samples using the Spectrum Plant Total RNA Kit (Sigma-Aldrich). Total RNA from two symptomatic samples (named EC3 and EC4) were subjected to high-throughput sequencing (HTS) on the NextSeq 500/550 High-Output kit v2.5 (Illumina, USA) at the genomic facility, Oklahoma State University (Stillwater, OK, USA). A total of 17,542,322 and 22,572,118 trimmed pair-ends reads for both samples were assembled using CLC Genomics Workbench (v12.0.3) (Qiagen, Inc) and subjected to BLASTn analysis. Two contigs of 556 bp and 1062 bp (average coverage 2,799X) for sample EC3 showed 99% and 91% nucleotide (nt) identities with 3'-UTR, 5'-UTR and P1A gene respectively of the Tobacco ringspot virus (TRSV) RNA1 of isolates WA-AM1 (MW495243.1), and IA-1-2017 (MT563078.1) respectively. The other two contigs, 221 bp and 561 bp (average coverage 23,070X) for sample EC4 showed, 100% and 96% nt identities with 3'-UTR, protease, and RdRp genes of TRSV RNA1, isolates WA-AM1 and YW (MT042825.1) respectively. The HTS data did not reveal any other viral sequence in these two cotton samples. To further confirm the presence of TRSV in these samples, previously designed specific primers to TRSV (Forward: 5'-GGAAATTAACTGGGATGATTT-3' and Reverse: 5'-GAGCTCCAACCTTAAAACCA-3') for RNA1, targeting the P1A and helicase genes, and another primer pair (Forward: 5'-GCATCCTCCCATGTTTTCT-3' and Reverse: 5'-GGGACAAACACGACACTA-3') for RNA2, targeting the coat protein and 3'-untranslated region, of TRSV were tested by RT-PCR assay. The sizes of amplified PCR products obtained from both isolates (EC3 and EC4) on 1% agarose gel were approximately 1,000 bp for RNA1 and 1,100 bp for RNA2. The amplified PCR products were cloned and three independent recombinant clones for each primer set were analyzed by Sanger sequencing. The resulting consensus sequences were used in a BLASTn search against the Genbank and matched with TRSV sequences. Consensus nt sequences analysis specific to RNA1 of EC3 isolate (Accession no. OM563300) and EC4 isolate (Accession no OM563301) showed 97% nt identities with TRSV isolate IA-1-2017. Consensus nt sequences specific to RNA 2 of EC3 isolate (Accession no. OM630605) and EC4 isolate (Accession no OM5630606) showed 92% and 90% nt identities with the corresponding sequences of WA-AM1 and IA-1-2017 isolates respectively. Further screening of the remaining 11 symptomatic samples resulted in two more positive TRSV samples that were co-infected with Cotton leafroll dwarf virus (CLRDV), six were positive to only CLRDV, and three were negative to both viruses by RT-PCR assay using the above TRSV specific primers and CLRDV specific primers AL674F/1407R (Avelar et al. 2019). None of the asymptomatic cotton samples were positive by RT-PCR to TRSV or CLRDV. Our results confirmed the presence of TRSV infection in these symptomatic cotton plants. The presence of TRSV could pose a new threat to cotton crops in Oklahoma and the U.S. due to its wide host range (Adam and Antoniw, 2005), and transmission through many vectors including nematodes, (Keinath et al. 2017), and seed (Hill and Whitman, 2014). To the best of our knowledge, this is the first report of TRSV infecting cotton naturally in the U.S. and in the world.


Variations in clinical practice among the Hawaiian islands.
State health surveys and hospital discharge data suggest aspects of health care may vary by island in the state of Hawai'i. This study further examines the issue comparing O'ahu, Maui, Hawai'i, and Kaua'i on 15 indicators of recommended clinical care using data from a large insurer in Hawaii. The Hawaiian Islands differed to a statistically significant extent on 14 of the 15 indicators. O'ahu had the highest percentage of recommended care for six indicators, Maui for four, Kaua'i for three, and Hawai'i for two. In analyses adjusted for age, gender, morbidity, and health plan--and comparing the outer islands individually to O'ahu--O'ahu had more favorable care in 16 of 18 statistically significant comparisons. More focused geographic studies may be warranted to clarify where and why the variations in health care occur.


E-health, phase two: the imperative to integrate process automation with communication automation for large clinical reference laboratories.
The initial efforts of e-health have fallen far short of expectations. They were buoyed by the hype and excitement of the Internet craze but limited by their lack of understanding of important market and environmental factors. E-health now recognizes that legacy systems and processes are important, that there is a technology adoption process that needs to be followed, and that demonstrable value drives adoption. Initial e-health transaction solutions have targeted mostly low-cost problems. These solutions invariably are difficult to integrate into existing systems, typically requiring manual interfacing to supported processes. This limitation in particular makes them unworkable for large volume providers. To meet the needs of these providers, e-health companies must rethink their approaches, appropriately applying technology to seamlessly integrate all steps into existing business functions. E-automation is a transaction technology that automates steps, integration of steps, and information communication demands, resulting in comprehensive automation of entire business functions. We applied e-automation to create a billing management solution for clinical reference laboratories. Large volume, onerous regulations, small margins, and only indirect access to patients challenge large laboratories' billing departments. Couple these problems with outmoded, largely manual systems and it becomes apparent why most laboratory billing departments are in crisis. Our approach has been to focus on the most significant and costly problems in billing: errors, compliance, and system maintenance and management. The core of the design relies on conditional processing, a "universal" communications interface, and ASP technologies. The result is comprehensive automation of all routine processes, driving out errors and costs. Additionally, compliance management and billing system support and management costs are dramatically reduced. The implications of e-automated processes can extend beyond the specific transaction problems they are designed to solve. The ready access and communication of process details required by e-automation can apply to many other business functions.


Soluble tetraarylporphyrin-platinum conjugates as cytotoxic and phototoxic antitumor agents.
A series of asymmetric tetraarylporphyrins was synthesized from pyrrole, para-substituted oligo- or poly(ethylene glycol) monomethyl ether benzaldehyde and from 4-hydroxybenzaldehyde etherified with diethyl bromomalonate according to the Lindsey method. After hydrolysis of the tetraarylporphyrin esters, the resulting carboxylic acid groups were used to bind platinum fragments. In comparison to analogous hematoporphyrin-platinum conjugates, the title compounds are characterized by a 30 nm bathochromic shift of their absorption bands. The antiproliferative activity of 18 platinum complexes (1, 5, and 10 microM) differing in solubility, type of the platinum fragment, and the corresponding tetraarylporphyrin ligands were studied on TCC-SUP transitional bladder cancer cells in the dark and after irradiation (lambda = 600-730 nm; 24 J/cm(2)). The most active compounds were among the tetraarylporphyrin-platinum conjugates bearing the diammine and (RR/SS)-trans-1,2-diaminocyclohexane ligands.


Component distributions of body mass index defining moderate and extreme overweight in Danish women and men.
Skewness in the distribution of body mass index in a population of Danish men (n = 1,589) and women (n = 1,988) adopted in Copenhagen between 1923 and 1947 can be explained by mixture of three component distributions, after removing age and sex effects. Even when residual skewness was allowed for in component distributions, similar results were obtained. The upper component distributions corresponded to extreme overweight in both women and men. The results indicate that while there are differences in the means and ranges of body mass index in men and women, the component distributions are similar. Both genetic and environmental factors can produce such component distributions. The authors speculate that the underlying predisposition to obesity is distributed similarly in women and men. Finally, on the basis of the component distributions, the authors propose thresholds of body mass index which allow for 85-98 per cent separation of moderate and extreme overweight groups in men and women.


A novel HLA-B allele, HLA-B*35:279, identified by sequencing-based typing in a Czech patient.
The identification of a novel HLA-B*35:279 allele in a Czech patient is described. This allele is identical to the B*35:03:01 variant except the G/A nucleotide exchange at position 652 of the HLA-B gene that corresponds to the amino acid substitution from valine to isoleucine in alpha 3 domain of the HLA-B antigen.


Hyperbranched poly(ether amine) (hPEA)/poly(vinyl alcohol) (PVA) interpenetrating network (IPN) for selective adsorption and separation of guest homologues.
We here reported that hyperbranched poly(ether amine) (hPEA) and poly(vinyl alcohol) (PVA) interpenetrating network (hPEA/PVA-IPN) can be used for the selective adsorption and separation of guest homologues. A series of hyperbranched poly(ether amine) and poly(vinyl alcohol) interpenetrating networks (hPEA/PVA-IPNs) were fabricated by introducing poly(vinyl alcohol) chains into network of hyperbranched poly(ether amine), in which two independent networks of hyperbranched poly(ether amine) and poly(vinyl alcohol) were cross-linked through photodimerization of coumarin groups of hyperbranched poly(ether amine) and aldol condensation reaction between hydroxyl groups of poly(vinyl alcohol) and glutaraldehyde, respectively. The mechanical strength of interpenetrating networks can be enhanced by the introduction of poly(vinyl alcohol), and the tensile strength of interpenetrating networks increased with tens of times in compared with the pure hyperbranched poly(ether amine) network. The adsorption behavior of seven fluorescein dyes sharing with the same backbone and charge state onto hyperbranched poly(ether amine) and poly(vinyl alcohol) interpenetrating networks was then investigated in detail. Regardless of their charge states, these interpenetrating networks exhibited the quick adsorption to Rose Bengal (RB), Erythrosin B (ETB), Eosin B (EB), 4',5'-dibromofluorescein (DBF), and 4,5,6,7-tetrachlorofluorescein (TCF), with high adsorption capacity (Qeq) and very low adsorption of Calcein (Cal) and fluorescein (FR). The adsorption process was found to follow the pseudo-second-order kinetics, and the introduction of poly(vinyl alcohol) has no obvious effect on the adsorption behavior in this study. The big difference in the adsorption is indicative of the selective adsorption of hyperbranched poly(ether amine) and poly(vinyl alcohol) interpenetrating networks to fluorescein dyes. Based on the unique selective adsorption, the separation of several mixtures of fluorescein dyes such as RB/Cal, RB/FR, ETB/FR, and ETB/Cal was achieved by using hPEA/PVA-IPN as adsorbent.


Novel agents for the treatment of advanced kidney cancer.
Advanced kidney cancer accounts for over 12,000 deaths in the United States each year. Immunotherapy, typically interleukin-2 or interferon-alpha, have been the mainstay of treatment. Response rates are low for these immune-based treatments, and most patients with advanced kidney cancer succumb to their disease. There are several novel agents currently in clinical trials that show promise in this refractory disease. These compounds include antiangiogenic agents, raf kinase pathway inhibitors, and novel antimicrotubule agents. This review discusses some of the agents currently being explored for the treatment of advanced kidney cancer.


Racial differences in the causes of end-stage renal failure in Natal.
This study analyses the age, sex and race of end-stage renal failure ( ESRF ) patients who were referred to the two renal units in Durban from the whole of the province of Natal, as well of the aetiology of the disease. A striking feature was the high incidence of analgesic nephropathy in Whites; this did not cause ESRF in Black, Indian or Coloured patients. In contrast, hypertension was an important cause of ESRF in Black, Indian and Coloured patients. The control of analgesic abuse among Whites and the detection and screening of hypertension in all racial groups, particularly urban Blacks, are imperative. There are searching questions about whether developing countries can afford a chronic renal failure programme.


Multiclass, Multiresidue Method for the Quantification and Confirmation of 112 Veterinary Drugs in Game Meat (Bison, Deer, Elk, and Rabbit) by Rapid Polarity Switching Liquid Chromatography-Tandem Mass Spectrometry.
An analytical program for multiclass, multiresidue residue analysis to qualitatively and quantitatively determine veterinary drug compounds in game meats by LC-MS/MS has been developed and validated. The method was validated for the analysis of muscle from bison, deer, elk, and rabbit to test for 112 veterinary drug residues from the following drug classes: β-agonists, anthelmintics, anti-inflammatory drugs, corticosteroids, fluoroquinolones, β-lactams, macrolides, nitroimidazoles, phenicols, polypeptides, sulfonamides, tetracyclines, thyreostats, and tranquilizers. Muscle was extracted using a simple and quick procedure based on a solvent extraction with 80% ACN/water and sample cleanup with dispersive solid-phase extraction. The compounds of interest were separated using a Waters HSS T3 column and detected by tandem mass spectrometry with rapid polarity switching to detect both negatively and positively charged ions in a single run. Recoveries were calculated using extracted matrix-matched calibration curves for each type of matrix. The average accuracy of fortified compounds ranged from 95.6 to 101% at the target quantitative validation level in the four matrices. The method was also validated as a qualitative screening method where all sample responses were compared with a single extracted matrix-matched calibrant at the target testing level (5 or 25 ng/g). Samples demonstrating a presumptive positive above the threshold value were re-extracted and analyzed with a five-point matrix-matching extracted calibration curve. Since the beginning of this survey program, 360 samples have been analyzed for veterinary drug residues in game meats. Antibiotic or tranquilizer residues have been identified in deer (chlortetracycline, haloperidol, and tulathromycin) and rabbit (sulfadiazine).


Serotype and Genotype (Multilocus Sequence Type) of Streptococcus suis Isolates from the United States Serve as Predictors of Pathotype.
Streptococcus suis is a significant cause of mortality in piglets and growing pigs worldwide. The species contains pathogenic and commensal strains, with pathogenic strains causing meningitis, arthritis, endocarditis, polyserositis, and septicemia. Serotyping and multilocus sequence typing (MLST) are primary methods to differentiate strains, but the information is limited for strains found in the United States. The objective of this study was to characterize the diversity of 208 S. suis isolates collected between 2014 and 2017 across North America (mainly the United States) by serotyping and MLST and to investigate associations between subtype and pathotype classifications (pathogenic, possibly opportunistic, and commensal), based on clinical information and site of isolation. Twenty serotypes were identified, and the predominant serotypes were 1/2 and 7. Fifty-eight sequence types (STs) were identified, and the predominant ST was ST28. Associations among serotypes, STs, and pathotypes were investigated using odds ratio and clustering analyses. Evaluation of serotype and ST with pathotype identified a majority of isolates of serotypes 1, 1/2, 2, 7, 14, and 23 and ST1, ST13, ST25, ST28, ST29, ST94, ST108, ST117, ST225, ST373, ST961, and ST977 as associated with the pathogenic pathotype. Serotypes 21 and 31, ST750, and ST821 were associated with the commensal pathotype, which is composed of isolates from farms with no known history of S. suis-associated disease. Our study demonstrates the use of serotyping and MLST to differentiate pathogenic from commensal isolates and establish links between pathotype and subtype, thus increasing the knowledge about S. suis strains circulating in the United States.


Aberrant RNA splicing and its functional consequences in cancer cells.
Among the myriad of alterations present in cancer cells are an abundance of aberrant mRNA transcripts. Whether abnormal gene transcription is a by-product of cellular transformation or whether it represents an inherent element that contributes to the properties of cancer cells is not yet clear. Here, we present growing evidence that in many cases, aberrant mRNA transcripts contribute to essential phenotypes associated with transformed cells, suggesting that alterations in the splicing machinery are common and functionally important for cancer development. The proteins encoded by these abnormal transcripts are often truncated or missing domains, thereby altering protein function or conferring new functions altogether. Thus, aberrant splicing regulation has genome-wide effects, potentially altering gene expression in many cancer-associated pathways.


Investigation of the localized surface plasmon effect from Au nanoparticles in ZnO nanorods for enhancing the performance of polymer solar cells.
The organic polymer solar cell is recognized as one of the most competitive technologies of the next generation. Au nanoparticles and ZnO nanorods were combined to improve the inverted-structure low-bandgap polymer solar cells and enhance the absorption and efficiency of the devices. However, the Au nanoparticles tend to aggregate in solution, thus reducing the localized surface plasmon resonance (LSPR) effect. The cluster effect on the spectral range of enhancement in the absorption is investigated and the absorption characteristics of the LSPR receive proper modification through our experiment. After reducing the number of Au nanoparticle clusters, the LSPR effect in the devices was clearly verified. The proper combination of the Au nanoparticles and ZnO nanorods leads to the power conversion efficiency of the PTB7 : PC71BM inverted organic solar cell reaching 8.04% after optimizing the process conditions.


Function-Preserving Neurotized Lateral Arm Free Flap in the Reconstruction of Hemiglossectomy Defects.
Introduction and Methods The glabrous, thin, and pliable texture of lateral arm flap with no loss of any axial vessel of the limb renders it a good choice for hemiglossectomy defect reconstruction. The main caveat of this flap harvest is the loss of sensation in the distribution of posterior antebrachial cutaneous nerve (PABCN). In this article, we present two strategic sites and techniques to preserve the integrity of PABCN and at the same time harvesting lateral arm flap with a lengthy lower lateral cutaneous nerve of arm for the neurotization. The outcome of this function-preserving neurotized lateral arm free flap in the reconstruction of hemiglossectomy defects is analyzed and presented in this article. Results Ninety percent of the patients attained grade 3 score in objective assessment, leading to a significant p -value of 0.02 with this technique. All had preservation of sensation in the distribution of PABCN. Conclusion Our technique of harvest and neurotization has brought good functional recovery of the oral cavity with preservation of PABCN.


Paclitaxel in cancer therapy.
The last decade witnessed the introduction of exciting new chemotherapeutic agents. Among these, paclitaxel emerged as one of the most powerful compounds. Paclitaxel promotes the polymerisation of tubulin, thereby causing cell death by disrupting the normal microtubule dynamics required for cell division and vital interphase processes. Mechanisms of acquired resistance to paclitaxel include alterations of tubulin structure and the amplification of membrane phosphoglycoproteins that function as drug-efflux pumps. Toxicities associated with paclitaxel include hypersensitivity reaction, neurotoxicity and haematological toxicities. Toxicities may be both dose- and schedule-dependent. Paclitaxel has activity against a broad band of tumour types, including breast, ovarian, lung, head and neck cancers. Paclitaxel also has activity in other malignancies that are refractory to conventional chemotherapy, including previously-treated lymphoma and small cell lung cancers and oesophageal, gastric endometrial, bladder and germ cell tumours. Paclitaxel is also active against AIDS-associated Kaposi's sarcoma.


A Mechanistic Understanding of Hydrogen Peroxide Decomposition by Vanadium Minerals for Diethyl Phthalate Degradation.
The interaction of naturally occurring minerals with H2O2 affects the remediation efficiency of polluted sites in in situ chemical oxidation (ISCO) treatments. However, interactions between vanadium(V) minerals and H2O2 have rarely been explored. In this study, H2O2 decomposition by various vanadium-containing minerals including V(III), V(IV), and V(V) oxides was examined, and the mechanism of hydroxyl radical (•OH) generation for contaminant degradation was studied. Vanadium minerals were found to catalyze H2O2 decomposition efficiently to produce •OH for diethyl phthalate (DEP) degradation in both aqueous solutions with a wide pH range and in soil slurry. Electron paramagnetic resonance (EPR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) analyses, and free radical quenching studies suggested that •OH was produced via single electron transfer from V(III)/V(IV) to H2O2 followed a Fenton-like pathway on the surface of V2O3 and VO2 particles, whereas the oxygen vacancy (OV) was mainly responsible for •OH formation on the surface of V2O5 particles. This study provides new insight into the mechanism of interactions between vanadium minerals and H2O2 during H2O2-based ISCO.


[A Case of Chronic Myelogenous Leukemia That Developed Fibrous Pericarditis Owing to Nilotinib Use].
A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.


Investigation of the mutation points and effects of some drugs on glucose-6-phosphate dehydrogenase-deficient people in the Erzurum region.
We have carried out a systematic study of the molecular basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency on three samples of 1,183 children aged 0.5-6 years from Erzurum, in eastern Anatolia. Total genomic DNAs were isolated from the blood samples of a healthy person and the three persons determined with G6PD deficiency by examining the enzyme activity and hemoglobin ratio. Then PCR amplification of the entire coding region in eight fragments was carried out followed by Agarose gel electrophoresis. The 540-bp PCR fragment containing exons VI-VII and the 550bp PCR fragment containing exons XI-XIII were digested with EcoRI and with NIaIII, respectively. SSCP techniques for eight fragments (exons II, III-IV, V, VI-VII, VIII, IX, X, and XI-XIII) were employed to determine the mutations on the exons of the G6PD gene. A mutation occurred on the region of the exons 6 and 7 of one person (person-1) and exon 5 of two G6PD-deficient persons (person 2 and 3) examined. The sequential approach described is fast and efficient and could be applied to other populations. Effects of analgesic drugs on G6PD were studied on the purified enzyme (ammonium fractionation, dialysis and 2',5' ADP-Sepharose 4B affinity chromatography) for the healthy person and G6PD-deficient persons 1, 2 and 3. The effects of remifentanil hydrochloride, fentanyl citrate, alfentanil hydrochloride and pethidine hydrochloride, as analgesic drugs, on G6PD activity were tested. Although remifentanil hydrochloride, fentanyl citrate (I50 values; 1.45mM and 6.1 mM, respectively) inhibited the activity of the enzyme belonging to the healthy person, they did not alter enzyme activity on two of the three persons with G6PD deficiency. Other drugs (alfentanil hydrochloride and pethidine hydrochloride) did not effect the enzyme activity of the healthy or G6PD-deficient children.


Efficacy and safety of rituximab plus low-dose oral fludarabine and cyclophosphamide as first-line treatment of elderly patients with indolent non-Hodgkin lymphomas.
Indolent non-Hodgkin lymphomas (iNHLs) are B-cell neoplasms for which no consensus is available about optimal first-line therapy. Chemoimmunotherapy with fludarabine, cyclophospamide and rituximab is very effective, but may give severe hematological and non-hematological toxicity at standard doses, especially in elderly patients. In this phase II study, 25 untreated elderly patients with iNHL received rituximab (375 mg/m(2)) plus low-dose oral fludarabine (25 mg/m(2) for 4 consecutive days) and cyclophosphamide (150 mg/m(2) for 4 consecutive days) for four monthly cycles. Twenty-three patients were responsive (92%) and 12 patients achieved a complete remission (48%). Twenty-one patients (84%) were alive, median follow-up was 30 months and median event-free survival (EFS) was not reached. Patients who we previously treated with chemotherapy alone had a shorter EFS (median 20 months). Compliance was good, with mild toxicity. This regimen is effective for elderly patients with iNHL. The addition of rituximab results in long EFS without affecting toxicity.


Ag2O-Induced Regioselective Huisgen Cycloaddition for the Synthesis of Fully Substituted Pyrazoles as Potential Anticancer Agents.
Efficient regioselective synthesis of novel fully substituted pyrazoles has been achieved through Huisgen cycloaddition reaction of δ-acetoxy allenoates with hydrazonoyl chlorides by the addition of Ag2O. The present approach offers the advantages of simpleness, high efficiency, mild conditions, wide substrate scope, and good-to-excellent regioselectivities. The strategy could be performed on a large-scale pattern to allow access to structurally versatile pyrazoles, of which a key intermediate of lonazolac (303), a nonsteroidal anti-inflammatory drug, could be synthesized efficiently. Moreover, several pyrazoles show obvious growth-inhibitory activity of Huh-7 cells, expected as potential anticancer agents.


Redescription of Anomala eucoma Bates, 1888 and a description of three new species from Costa Rica (Coleoptera: Scarabaeidae: Rutelinae).
Anomala eucoma Bates, 1888 is redescribed and a lectotype from Guatemala is designated. Three new species from Costa Rica, A. flavacoma new species, A. megaparamera new species, and A. pseudoeucoma new species, are described, and a distribution map is given. The internal sac (endophallus) of the species covered is illustrated, and its use in separating closely related species in this region is discussed. An identification key for morphologically similar species from the Neotropical region is provided.


Multimodality imaging of vaginal rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor arising from the embryonal muscle cells (rhabdomyoblasts), and is the most common soft tissue sarcoma in children and young adults accounting for 4-6% of all malignancies in this age group. Though rare overall, embryonal rhabdomyosarcoma is the most common malignancy arising in the pediatric female genitourinary tract with sarcoma botryoides being the most common variant of the tumor. In young and adolescent individuals, the cervix and uterus are affected; whereas in infants, vaginal lesions are more common. Imaging plays a crucial role not only in the initial diagnosis but also in long-term follow-up of genital RMS. We describe a rare case of embryonal rhabdomyosarcoma of the vagina occurring in a 23-year-old female who presented with abnormal vaginal bleeding ever since she was a child.


An update on our understanding of Gram-positive bacterial membrane vesicles: discovery, functions, and applications.
Extracellular vesicles (EVs) are nano-sized particles released from cells into the extracellular environment, and are separated from eukaryotic cells, bacteria, and other organisms with cellular structures. EVs alter cell communication by delivering their contents and performing various functions depending on their cargo and release into certain environments or other cells. The cell walls of Gram-positive bacteria have a thick peptidoglycan layer and were previously thought to be unable to produce EVs. However, recent studies have demonstrated that Gram-positive bacterial EVs are crucial for health and disease. In this review, we have summarized the formation, composition, and characteristics of the contents, resistance to external stress, participation in immune regulation, and other functions of Gram-positive bacterial EVs, as well as their application in clinical diagnosis and treatment, to provide a new perspective to further our understanding of Gram-positive bacterial EVs.


The importance of managing the patient and not the gene: expanded phenotype of GLE1-associated arthrogryposis.
GLE1 encodes a protein important for mRNA export and appears to play roles in translation initiation and termination as well. Pathogenic variants in GLE1 mutations have been associated with lethal contracture syndrome and lethal arthrogryposis with anterior horn cell disease; phenotypes reported in individuals include fetal akinesia and a severe form of motor neuron disease, typically presenting with prenatal symptoms and perinatal lethality. In this article, we identified biallelic missense mutations in GLE1 by trio whole-exome sequencing in an individual affected with congenital motor weakness and contractures as well as feeding and respiratory difficulties. Muscle biopsy was consistent with anterior horn cell disease and supported the pathogenicity of the sequence variants. Importantly, this individual survived past the perinatal period with respiratory support and currently demonstrates age-appropriate cognition and slow but steady motor developmental progress. We propose that pathogenic variants in GLE1 can be associated with a nonperinatal lethal motor phenotype, and affected individuals can demonstrate motor skill progression, unlike prototypical anterior horn cell diseases such as spinal muscular atrophy.


Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in Huntington's disease.
There has been a longstanding debate regarding the role of proteolysis in Huntington's disease. The toxic peptide theory posits that N-terminal cleavage fragments of mutant Huntington's disease protein [mutant huntingtin (mhtt)] enter the nucleus to cause transcriptional dysfunction. However, recent data suggest a second model in which proteolysis of full-length mhtt is inhibited. Importantly, the two competing theories differ with respect to subcellular distribution of mhtt at initiation of toxicity: nuclear if cleaved and cytoplasmic in the absence of cleavage. Using quantitative single-cell analysis and time-lapse imaging, we show here that transcriptional dysfunction is "downstream" of cytoplasmic dysfunction. Primary and reversible toxic events involve destabilization of microtubules mediated by full-length mhtt before cleavage. Restoration of microtubule structure by taxol inhibits nuclear entry and increases cell survival.


Malnutrition and nutritional care practices in hospital wards for older people.
This paper is a report of a study conducted to gain a better insight into the current nutritional care practices in Belgian hospital wards for older people, and to study the association between these practices and the prevalence of malnutrition. In 1999, the Council of Europe assessed nutritional care practices and support in 12 European countries and showed them to be sparse and inconsistent. At the time of research, no studies had described the association between nutritional care practices and malnutrition prevalence in Belgium. In 2007, a cross-sectional survey was carried out in a representative sample of Belgian hospital wards for older people. In total, 2094 patients from 140 wards for older people were included. The overall prevalence rate of malnutrition in wards for older people was 31.9%. Nutritional care practices such as nutritional screening and assessment, use of a standardized screening instrument and a nutritional protocol were suboptimal. Multilevel analysis revealed that ward characteristics explained for 9.1% whether a patient was malnourished or not. None of the registered nutritional care practices could explain a patient's individual risk. Malnutrition is a frequently occurring problem on hospital wards for older people. Increased consciousness among healthcare professionals and hospital policy makers of the importance of nutritional care will contribute to further improvement in care quality.


Commencing one-handed chest compressions while activating emergency medical system using a handheld mobile device in lone-rescuer basic life support: a randomised cross-over simulation study.
In conventional basic life support (c-BLS), a lone rescuer is recommended to start chest compressions (CCs) after activating the emergency medical system. To initiate earlier CCs in lone-rescuer BLS, we designed a modified BLS (m-BLS) sequence in which the lone rescuer commences one-handed CCs while calling for help using a handheld cellular phone with the other free hand. This study aimed to compare the quality of BLS between c-BLS and m-BLS. This was a simulation study performed with a randomised cross-over controlled trial design. A total of 108 university students were finally enrolled. After training for both c-BLS and m-BLS, participants performed a 3-minute c-BLS or m-BLS on a manikin with a SkillReporter at random cross-over order. The paired mean difference with SE between c-BLS and m-BLS was assessed using paired t-test. The m-BLS had reduced lag time before the initiation of CCs (with a mean estimated paired difference (SE) of -35.0 (90.4) s) (p<0.001). For CC, a significant increase in compression fraction and a higher number of CCs with correct depth were observed in m-BLS (with a mean estimated paired difference (SE) of 16.2% (0.6) and 26.9% (3.3), respectively) (all p<0.001). However, no significant paired difference was observed in the hand position, compression rate and interruption time. For ventilation, the mean tidal volumes did not differ. However, the number of breaths with correct tidal volume was higher in m-BLS than in c-BLS. In simulated lone-rescuer BLS, the m-BLS could deliver significantly earlier CCs than the c-BLS while maintaining high-quality cardiopulmonary resuscitation.


U-Shaped Association Between Duration of Sports Activities and Mortality: Copenhagen City Heart Study.
To investigate the association between the duration of weekly leisure-time sports activity and all-cause mortality. As part of the prospective Copenhagen City Heart Study, 8697 healthy adults completed a comprehensive questionnaire about leisure-time sports activities. Duration (minutes per week) of leisure-time sports activities was recorded for tennis, badminton, soccer, handball, cycling, swimming, jogging, calisthenics, health club activities, weightlifting, and other sports. The primary end point was all-cause mortality, and the median follow-up was 25.6 years. The association between duration of leisure-time sports activities and all-cause mortality was studied using multivariable Cox proportional hazards regression analysis. Compared with the reference group of 2.6 to 4.5 hours of weekly leisure-time sports activities, we found an increased risk for all-cause mortality for those with 0 hours (hazard ratio [HR], 1.51; 95% CI, 1.29 to 1.76), for those with 0.1 to 2.5 hours (HR, 1.24; 95% CI, 1.05 to 1.46), and for those with more than 10 hours (HR, 1.18; 95% CI, 1.00 to 1.39) of weekly leisure-time sports activities. These relationships were generally consistent with additional adjustments for potential confounders among subgroups of age, sex, education, smoking, alcohol intake, and body mass index, when the first 5 years of follow-up were excluded, and for cardiovascular disease mortality. We observed a U-shaped association between weekly duration of leisure sports activities and cardiovascular and all-cause mortality, with lowest risk for those participating in 2.6 to 4.5 weekly hours, being consistent across subgroups. Participation in sport activities should be promoted, but the potential risk of very high weekly hours of sport participation should be considered for inclusion in guidelines and recommendations.


Vogt-Koyanagi-Harada disease in a patient of chronic myeloid leukemia.
This case report describes the concurrent development of Vogt-Koyanagi-Harada (VKH) disease in a 39 year old male patient of chronic myeloid leukemia (CML). The patient being reported was a known case of CML in remission with history of painless sudden loss of vision in both eyes. Cases of leukemia can present with visual loss due to multiple ocular manifestations of leukemia itself or side effects of modern drugs used for its treatment. Clinical examination and multimodal imaging of our patient were suggestive of concurrent development of VKH. The patient was started on oral steroids, to which he showed a good response. Thus, the cases of CML may rarely develop concurrent ocular disorders not related to leukemia. These associated ocular disorders need to be distinguished from the ocular manifestations of leukemia itself. Our case highlights the concurrent development of VKH as the etiology of visual loss in a case of CML.


Infantile hemangiomas: our current understanding and treatment options.
Infantile hemangioma (IH) is the most common vascular tumor of infancy, affecting up to 10% of all infants. Our understanding of IH and its management has greatly evolved. The etiology of IH is unclear but hypoxia is thought to play a key role. Furthermore, GLUT1, IGF2, and HIF-1-? are thought to be important mediators. Current management options include active observation, medical treatment, and surgical intervention. The goals of treatment are preventing cosmetic disfiguration, psychosocial distress, and life-threatening complications. Infantile hemangioma should be managed with an individual, patient-centered approach. Generally, uncomplicated IH can be observed up to 18 months. However, IH should be treated in the setting of bleeding, ulceration, functional compromise, or eventual failure to regress.


Uncoupling protein 2 regulates metabolic reprogramming and fate of antigen-stimulated CD8+ T cells.
Adoptive cell therapy (ACT) employing ex vivo-generated tumor antigen-specific CD8+ T cells shows tumor efficacy when the transferred cells possess both effector and memory functions. New strategies based on understanding of mechanisms that balance CD8+ T cell differentiation toward effector and memory responses are highly desirable. Emerging information confirms a central role for antigen-induced metabolic reprogramming in CD8+ T cell differentiation and clonal expansion. The mitochondrial protein uncoupling protein 2 (UCP2) is induced by antigen stimulation of CD8+ T cells; however, its role in metabolic reprogramming underlying differentiation and clonal expansion has not been reported. Employing genetic (siRNA) and pharmacologic (Genipin) approaches, we note that antigen-induced UCP2 expression reduces glycolysis, fatty acid synthesis and production of reactive oxygen species to balance differentiation with survival of effector CD8+ T cells. Inhibition of UCP2 promotes CD8+ T cell terminal differentiation into short-lived effector cells (CD62L(lo)KLRG1(Hi)IFNγ(Hi)) that undergo clonal contraction. These findings are the first to reveal a role for antigen-induced UCP2 expression in balancing CD8+ T cell differentiation and survival. Targeting UCP2 to regulate metabolic reprogramming of CD8+ T cells is an attractive new approach to augment efficacy of tumor therapy by ACT.


Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response.
Mechanisms of bile acid-induced (BA-induced) liver injury in cholestasis are controversial, limiting development of new therapies. We examined how BAs initiate liver injury using isolated liver cells from humans and mice and in-vivo mouse models. At pathophysiologic concentrations, BAs induced proinflammatory cytokine expression in mouse and human hepatocytes, but not in nonparenchymal cells or cholangiocytes. These hepatocyte-specific cytokines stimulated neutrophil chemotaxis. Inflammatory injury was mitigated in Ccl2-/- mice treated with BA or after bile duct ligation, where less hepatic infiltration of neutrophils was detected. Neutrophils in periportal areas of livers from cholestatic patients also correlated with elevations in their serum aminotransferases. This liver-specific inflammatory response required BA entry into hepatocytes via basolateral transporter Ntcp. Pathophysiologic levels of BAs induced markers of ER stress and mitochondrial damage in mouse hepatocytes. Chemokine induction by BAs was reduced in hepatocytes from Tlr9-/- mice, while liver injury was diminished both in conventional and hepatocyte-specific Tlr9-/- mice, confirming a role for Tlr9 in BA-induced liver injury. These findings reveal potentially novel mechanisms whereby BAs elicit a hepatocyte-specific cytokine-induced inflammatory liver injury that involves innate immunity and point to likely novel pathways for treating cholestatic liver disease.


Type IV collagenase activity of a primary HSV-2-induced hamster fibrosarcoma and its in vivo metastases and in vitro clones.
The expression of a basement membrane (BM) collagen-degrading metalloprotease (Type IV collagenase) was studied in a herpes simplex virus (HSV)-2 transformed hamster fibrosarcoma and its in vivo derived sublines and in vitro derived clones of varying metastatic potential. The primary parent tumor was shown to release more or less Type IV collagenolytic activity compared with its sublines (derived from lung nodules that developed after resection of the primary tumor). Normal baby hamster kidney and hamster embryo fibroblasts did not secrete detectable amounts of BM collagenase, whereas normal hamster lung fibroblast secreted intermediate levels of Type IV collagenase activity. The collagenase IV activity of the parent tumor and its in vivo and in vitro derived sublines was assayed in vitro and compared with the ability of the cells lines to spontaneously metastasize in vivo. No correlation between the ability to secrete type IV collagenase and metastatic propensity was detected. Although all cell lines secreted type IV collagenase, the highest activity was recorded for a nonmetastatic variant.


Desodification from calcareous saline sodic soil through phytoremediation with Phragmites australis (Cav.) Trin. ex Steud. and gypsum.
The reclamation of saline sodic soils requires sodium removal and the phytoremediation is one of the proven low-cost, low-risk technologies for reclaiming such soils. However, the role of Phragmites australis in reclaiming saline sodic soils has not been evaluated extensively. The comparative reclaiming role of P. australis and gypsum was evaluated in a column experiment on a sandy clay saline sodic soil with ECe 74.7 dS m-1, sodium adsorption ratio (SAR) 63.2, Na+ 361 g kg-1, and pH 8.46. The gypsum at 100% soil requirement, planting common reed (P. australis) alone, P. australis + gypsum at 50% soil gypsum requirements, and leaching (control without plant and gypsum) were four treatments applied. After 11 weeks of incubation, the results showed that all treatments including the control significantly reduced pH, EC, exchangeable Na+, and SAR from the initial values, the control being with least results. The gypsum and P. australis + gypsum were highly effective in salinity (ECe) reduction, while sodicity (SAR) and Na+ reductions were significantly higher in P. australis + gypsum treatment. The reclamation efficiency in terms of Na+ (83.4%) and SAR (86.8%) reduction was the highest in P. australis + gypsum. It is concluded that phytoremediation is an effective tool to reclaim saline sodic soil.


The role of femtolaser in cataract surgery.
Having been very successful in corneal surgery, femtolasers were recently introduced into the surgery of crystalline lens. The most important indications and advantages include: perfectly centered and sized capsulotomy, liquefaction of softer lenses and fragmentation of harder lenses which allows for chopping the nucleus without the use of phaco energy. Femtolaser can also be used for creating corneal wounds (tunnels) of any size at any location, and in order to manage the preoperative astigmatism using arcuate incisions at the desired depth within the cornea. Because of controlled steps in cataract surgery, wide acceptance and spread is to be expected.


Current and fluctuation in a two-state stochastic system under nonadiabatic periodic perturbation.
We calculate a current and its fluctuation in a two-state stochastic system under a periodic perturbation. The system could be interpreted as a channel on a cell surface or a single Michaelis-Menten catalyzing enzyme. It has been shown that the periodic perturbation induces a so-called pump current, and the pump current and its fluctuation are calculated with the aid of the geometrical phase interpretation. We give a simple calculation recipe for the statistics of the current, especially in a nonadiabatic case. The calculation scheme is based on the nonadiabatic geometrical phase interpretation. Using the Floquet theory, the total current and its fluctuation are calculated, and it is revealed that the average of the current shows a stochastic-resonance-like behavior. In contrast, the fluctuation of the current does not show such behavior.


Molecular cloning and expression of human and rat tumor necrosis factor receptor chain (p60) and its soluble derivative, tumor necrosis factor-binding protein.
Tumor necrosis factor-alpha (TNF-alpha), a protein released by activated macrophages, is involved in a wide variety of human diseases including septic shock, cachexia, and chronic inflammation. TNF binding protein (TNF-BP), a glycoprotein with high affinity to TNF-alpha isolated from urine, acts as an inhibitor of TNF-alpha by competing with the cell-surface TNF receptor. We report here the partial amino acid sequencing of human TNF-BP as well as the isolation, sequence, and expression of cDNA clones encoding a human and rat TNF receptor. The calculated Mr of the mature human and rat TNF receptor chains is 47,526 and 48,072, respectively. The extracellular ligand binding domain represents the soluble TNF-BP which is released by proteolytic cleavage. TNF-BP contains 24 cysteine residues and three potential N-glycosylation sites and shows sequence homology to the extracellular portions of TNF-R p80 chain and nerve growth factor receptor. Transfection of the human TNF receptor cDNA into mammalian cells resulted in increased binding capacity for TNF-alpha and increased reactivity with a monoclonal antibody directed against the human TNF receptor chain p60. When a stop codon was introduced into the cDNA at the site corresponding to the carboxyl terminus of TNF-BP, transfected cells secreted a protein that reacted with antibodies raised against natural TNF-BP.


Dopant distribution in a Tm(3+)-Yb(3+) codoped silica based glass ceramic: an infrared-laser induced upconversion study.
The optically active dopant distribution in a Tm(3+)-Yb(3+) doped silica based glass ceramic sample has been investigated. A systematic analysis of the upconversion fluorescence of the Tm(3+)-Yb(3+) codoped glass and glass ceramic has been performed at room temperature. Tm(3+) and Yb(3+) single doped glass and glass ceramics have also been included in the study. Upon infrared excitation at 790 nm into the (3)H(4) level of the Tm(3+) ions a blue upconversion emission is observed, which is drastically increased in the Yb(3+) codoped samples. A rate equation model confirmed the energy transfer upconversion mechanism. Based on these results, the temporal dynamic curves of the levels involved in the upconversion process, (3)H(4), (2)F(5/2), and (1)G(4) were interpreted in the glass ceramic samples. The contribution of the optically active Tm(3+) and Yb(3+) ions in the crystalline and in the vitreous phase of the glass ceramic was distinguished and the ratio of Tm(3+) ions in the crystalline phase could be quantified for the 1 mol % Tm(3+)-2.5 mol % Yb(3+) glass ceramic. A surprising result was obtained for that concentration: the main contribution to the upconversion emission of the glass ceramic is due to Tm(3+)-Yb(3+) ions in the vitreous phase.


Large subcortical hemispheric infarctions. Presentation and prognosis.
A specific form of large subcortical hemispheric infarction on computed tomography was identified in 24 of 2198 (1%) stroke registry patients. Combined with 13 cases from earlier literature reports, a characteristic neurologic picture developed. Severe face plus arm plus leg weakness at onset (76%), corticallike features of aphasia and/or contralateral neglect (68%), and premonitory transient ischemic attacks (24%) were frequent. Twenty-two patients (59%) had large vessel arterial occlusive disease. Eight patients (22%) had primary embolic occlusion in the middle cerebral artery territory. During an average follow-up of 16 months, five patients (14%) suffered recurrent stroke or death. The clinical presentation and prognostic features of this distinct stroke subtype are described.


Treatment of dentinal hypersensitivity using low-level laser therapy and 5% potassium nitrate: A randomized, controlled, three arm parallel clinical study.
The present randomized study was aimed to compare the efficacy 5% potassium nitrate (KNO3) toothpaste, low-level laser therapy (LLLT), and LLLT with 5% KNO3 toothpaste in the treatment of dentinal hypersensitivity (DH). Total of 45 patients complaining of DH with visual analog scale (VAS) score being ≥2 were recruited and were divided into three groups. Group A was treated with 5% KNO3 toothpaste, Group B using LLLT along with the application of 5% KNO3 toothpaste, and Group C using LLLT alone. VAS scores were recorded at the baseline, 1st, 2nd, and 3rd weeks by the examiner who is blinded toward the treatment. The sensitivity response was evaluated using air spray and tactile sensation (explorer). A greater reduction of DH was recorded at the end of 3 weeks in Group C and Group B when compared to Group A. Better results were noted in Group C at the end of the 1st week when compared to Group B. According to this study, there was no additional benefit of using toothpaste along with LLLT. A greater reduction of DH was recorded at the end of 3 weeks in Group C and Group B when compared to Group A. Better results were noted in Group C at the end of the 1st week when compared to Group B. According to this study, there was no additional benefit of using toothpaste along with LLLT.


Effect of the serum of rats treated with Suo Quan pill on embryonic stem cells.
Suo Quan pill(SQP), a well-known and classical traditional Chinese medicine compound, consists of three traditional Chinese medicine: Alpinia oxyphylla Miq., Lindera aggregata (Sims) Kosterm., Dioscorea opposite. Its effect was summarized as supplementing kidney-yang and shrinkaging urination. This study evaluated the effects of the serum of rats treated with Suo Quan pill on embryonic stem cells(ES cells). Cell proliferation was detected by MTT assay. Cell cycle and apoptosis of ES cells were evaluated with flow cytometry. Nanog mRNA expression was verified by fluorescence quantitative PCR and Nanog protein in ES cells was determined by Western blot. The serum of SQP-treated rats not only promoted ES cells proliferation and Nanog expression in ES cells, but also inhibited H202 stimulated cell apoptosis. Furthermore, the serum of rats containing SQP affected the cell cycle distribution of ES cells, reducing the percentage of cells in G0/G1phase and increasing the percentage of cells in G2/M phase, increasing the proliferation index of ES cells. These results illustrate that the enhanced effect of SQP on ES cells proliferation is in part due to the increased expression of Nanog in ES cells, the accelerated cell cycle period and the inhibited apoptosis of ES cells.


Process variables of the life review: counseling implications.
The concept of the life review as a developmental process is examined with three main objectives. First, the life review is placed within a developmental framework as a dynamic rather than static occurrence in which the individual is an active agent. Secondly, in order to clarify the possible process variables of the life review, three interactive stages are identified and elaborated. Finally, possible counseling interventions are suggested for practitioners working with elderly persons.


Inhibitory capacity of some fractions isolated from a green barley extract upon TNF alpha production by the cells of the THP-1 human monocytes line.
A green barley extract commercialized as an antiinflammatory product under the name of "Natural SOD" was fractionated based on the molecular weights principle. Knowing that the TNF alpha cytokine plays an important role in inducing inflammatory phenomena, by the use of two determination methods (ELISA and cytotoxicity), the fractions obtained were analysed for their capacity to modulate TNF alpha production/release by an LPS-activated human monocytes line (THP-1). The results pointed to the existence of 3 groups of substances (fractions 3, 4 and 9) apt to modulate TNF alpha production, fraction 4 being the most active. Of the TNF alpha determination methods, ELISA proved to be more sensitive as it detected not only free TNF alpha identified also by the cytotoxicity test, but also TNF alpha complexed with its soluble receptors. The presence of these substances in Natural SOD, fractions with modulatory action upon TNF alpha production, might partly account for the clinical efficiency of this product in the treatment of inflammatory affections reported in humans.


Chronic hepatitis B and viral genotype: the clinical significance of determining HBV genotypes.
The global health challenge posed by the hepatitis B virus (HBV) centres around the widespread distribution and the serious complications as a result of persistent infection with the virus. As with other chronic diseases mediated by pathogens such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), clinicians are searching for epidemiological, pathological and viral characteristics of HBV infection that may lead to more effective management of patients with chronic infection. Unlike HCV, the role of HBV genotype in disease progression, severity, response to therapy and drug resistance is still under investigation and just beginning to be clarified. This review examines the potential role of HBV genotype determination in the clinic with emphasis on how this genetic information may used to provide effective management for the treatment of patients with chronic hepatitis B.


Understanding the increasing incidence of neuroendocrine tumors.
Neuroendocrine tumors (NETs) are a diverse group of tumors with origins from different primary sites such as gastro-entero-pancreatic, lung and endocrine tissue. Worldwide, their incidence has increased in recent decades. Advances in imaging and better clinical awareness are traditionally attributed to this trend; however, other factors such as genetic and environmental contributors are appreciated as well. The purpose of this article is to review the worldwide epidemiologic trends in incidence of NET through the decades and discuss the various factors potentially contributing to the observed changes in incidence trends. Overall, the incidence of NET has increased across the globe over the last few decades. Although multiple genetics and environmental factors have been proposed, the majority of this increase in incidence is secondary to earlier detection. Future studies will help in more accurate assessments and an improved understanding of disease incidence among patients with different grades and differentiation.


A Novel PSEN1 K311R Mutation Discovered in Chinese Families with Late-Onset Alzheimer's Disease Affects Amyloid-β Production and Tau Phosphorylation.
Presenilin-1 (PSEN1) is the most frequently mutated gene in familial Alzheimer's disease (AD), whereas only several novel mutations have been reported in China and functional studies were seldom conducted. We describe a novel PSEN1 K311R mutation in two Chinese families with late-onset AD and its functional impact on amyloid-β protein precursor (AβPP) processing and tau phosphorylation. The mutation was detected by direct sequencing of PSEN1 exon 9. HEK293 cells stably expressing wild-type APP695 (HEK293-APP695wt) were transfected with plasmids containing human wild-type PSEN1, PSEN1 K311R mutation, and PSEN1 E280A mutation to compare the K311R mutation's effects on AβPP processing with other groups. In addition, each group of cells were co-transfected with plasmids harboring PSEN1 and human wild-type MAPT complementary DNA to study the mutation's impacts on tau phosphorylation. The K311R mutation was detected in probands of two late-onset AD families. Expression of the K311R or E280A mutation increased amyloid-β (Aβ)42 levels but decreased Aβ40 levels, resulting in an overall increase in the Aβ42/Aβ40 ratio compared to those in wild-type PSEN1 transfected cells (p < 0.05). The K311R or E280A mutation also increased the levels of phosphorylated tau compared to wild-type PSEN1 (p < 0.05). The K311R mutation might contribute to AD pathogenesis by overproducing toxic Aβ species and enhancing tau phosphorylation. Further in-depth studies are needed to decipher the pathogenic mechanisms of the K311R mutation in terms of AβPP cleavage, tau phosphorylation, and other presenilin-1 mediated functional pathways.


Reassortment process after co-infection of pigs with avian H1N1 and swine H3N2 influenza viruses.
The influenza A virus is highly variable, which, to some degree, is caused by the reassortment of viral genetic material. This process plays a major role in the generation of novel influenza virus strains that can emerge in a new host population. Due to the susceptibility of pigs to infections with avian, swine and human influenza viruses, they are considered intermediate hosts for the adaptation of the avian influenza virus to humans. In order to test the reassortment process in pigs, they were co-infected with H3N2 A/swine/Gent/172/2008 (Gent/08) and H1N1 A/duck/Italy/1447/2005 (Italy/05) and co-housed with a group of naïve piglets. The Gent/08 strains dominated over Italy/05, but reassortment occurred. The reassortant strains of the H1N1 subtype (12.5%) with one gene (NP or M) of swine-origin were identified in the nasal discharge of the contact-exposed piglets. These results demonstrate that despite their low efficiency, genotypically and phenotypically different influenza A viruses can undergo genetic exchange during co-infection of pigs.


Retrospective review of the reduction of oral pressure ulcers in mechanically ventilated patients: a change in practice.
Hospital-acquired pressure ulcers (HAPU) are a growing concern in patient care. Mucosal pressure ulcers (PUs) on the lips, mouth, gums, and tongue caused by oral intubation and their securement devices can be difficult to identify and prevent. In an effort to address this problem and reduce mucosal PU, implementation of an alternative securement device, the Hollister ETAD endotracheal (ET) tube securing device, in conjunction with the B&B Medical Universal Bite Block, was introduced at our institution, a level 1 trauma and burn center, in July 2007. The ETAD was later replaced by the Hollister AnchorFast ET tube securing device in December 2007. By April 2009, they became the standard devices and method used to secure oral ET tubes. We hypothesized the use of the new securement devices and bite block would lead to a decrease of HAPUs on the lips, mouth, gums, and tongue of orally intubated critical care patients because these allow for better oral assessment and ET tube manipulation to redistribute pressure. Using data collected from our electronic medical record and our HAPU incidence tracking system, we analyzed the number of PUs on the lips, mouth, gums, and tongue of orally intubated patients in our preintervention (phase 1) group compared with the data from our postintervention (phases 2 and 3) groups. A clinically significant decrease in the reported incidence of HAPUs on the lips, mouth, gums, and tongue was noted in our phases 2 and 3 groups following introduction of the ETAD, AnchorFast, and Universal Bite Block in our institution.


Laparoscopic fundoplication: the alternative to long-term medical therapy for severe gastroesophageal reflux disease.
Gastroesophageal reflux disease is common. Fundoplication is very effective for those patients who fail medical therapy, particularly those with an incompetent lower esophageal sphincter. Open surgery is reported to achieve cure rates in excess of 90 percent. Laparoscopic fundoplication has been performed since 1991. The early experience with this procedure is reviewed. 1992 cases were reported in the literature. The mortality rate was 0.1 percent. Operative complications occurred as follows: 0.9 percent esophagogastric perforation rate; 0.6 percent bleeding rate (requiring transfusion); and 0.6 percent pneumothorax rate. No splenectomies were reported. 4.8 percent of patients required conversion to the open procedure. As experience with the procedure is gained this conversion rate decreases. Recurrent reflux postoperatively is 3.4 percent, but follow-up is short (range: 0 to 36 months; mean: two years). Dysphagia requiring dilatation occurs in 3.5 percent of patients. Gas bloat occurs in 0 to 24 percent of patients. These results compare favorably with the published results of medical therapy and the open fundoplication. The early experience with laparoscopic fundoplication appears promising and provides an attractive alternative to long-term medical therapy and to open surgery in appropriate patients. Long-term follow-up is awaited.


Using curcumin to prevent structural impairments of testicles in rats induced by sodium metabisulfite.
Sodium metabisulfite (Na-MBS) is a disinfectant and preservative agent. Some organ including testicle would be in danger in the case of Na-MBS consumption. Curcumin (CUR) is the constituent of turmeric with protective properties. The effect of CUR on testicles in rats exposed to Na-MBS evaluated using stereological methods. Sprague-Dawley rats were divided into eight groups. The rats in groups I to VIII received the following respectively: distilled water, CUR (100 mg/kg/day), low (0.7 mg/kg/day: acceptable daily intake), intermediate (7 mg/ kg/day), and high (70 mg/kg/day) doses of Na-MBS, and low, intermediate, and high doses of Na-MBS plus CUR. After 7 weeks, the testicles were analyzed. The volume of seminiferous tubule, tubular epithelium and tubule length reduced (25-40 %) on average in the rats that received intermediate and high doses of Na-MBS, while the connective tissue volume increased (15-20 %) in both groups (P<0.01). Besides, 19-36 % and 41-57 % of the cells (spermatogonia types A and B, spermatids, Sertoli and Leydig) were lost in the rats that received intermediate and high doses of Na-MBS respectively in comparison to the control groups. Nonetheless, all the above-mentioned alterations ameliorated drastically in the rats that received Na-MBS plus CUR compared to those exposed to Na-MBS without CUR therapy (P<0.01). The acceptable daily intake of Na-MBS for 7 weeks did not affect on testicular parameters. CUR (100 mg/kg/day) could prevent structural impairments of testicles in the rats induced by Na-MBS (7 and 70 mg/kg/day).


Meiotic pairing error in an infertile male bearing reciprocal deletion of chromosome 13.
A series of complex processes takes place during the first meiotic division, including pairing, synapsis, recombination, and segregation of homologous chromosomes. When any of these processes is altered, cellular checkpoints arrest the progression of meiosis and induce cell loss, causing a severe reduction in fertility, or even sterility. In this study, we report on a 29-year-old, healthy, but severe oligozoospermic male with a supernumerary, ring-neocentric 13q12.3 → 13q22 chromosome and a reciprocal deletion, which interfere with the meiotic pairing of chromosomes 13, causing spermatogenesis failure.


Isolated posterior capsule rupture in blunt trauma: pathogenesis and management.
Although blunt ocular trauma frequently-damages the crystalline lens, isolated rupture of the posterior capsule is an infrequently reported occurrence. The authors describe three patients with this unusual presentation. All patients underwent cataract extraction and intraocular lens (IOL) implantation using a limbal approach. There were no intraoperative complications. All patients achieved good postoperative visual acuity with well-positioned posterior chamber IOLs (in-the-bag in two eyes, sulcus fixated in one eye). Isolated rupture of the posterior capsule in young patients can be safely managed using the limbal approach and implantation of posterior chamber IOLs, is possible.