A bioinformatic approach to identify core genome difference between Salmonella Pullorum and Salmonella Enteritidis.
S. Pullorum and S. Enteritidis are closely related in genetic terms, but they show very different pathogenicity and host range. S. Enteritidis infects many different hosts, usually causing acute gastroenteritis, while S. Pullorum is restricted to avian, where it causes systemic disease in young animals. The reason why they differ in host range and pathogenicity is unknown. The core-genome denotes those genes that are present in all strains within a clade, and in the present work, an automated bioinformatics workflow was developed and applied to identify core-genome differences between these two serovars with the aim to identify genome features associated with host specificity of S. Pullorum. Results showed that S. Pullorum unique coding sequences (CDS) were mainly concentrated in three regions not present in S. Enteritidis, suggesting that such CDS were taken up probably during the separation of the two types from their common ancestor. One of the unique regions encoded Pathogenicity Islands 19 (SPI-19), which encodes a type VI secretion system (T6SS). Single-nucleotide polymorphism (SNP) analysis identified 1791 conserved SNPs in coding sequences between the two serovars, including several SNPs located in a type IV secretion system (T4SS). Analyzing of 100 bp regions upstream of coding sequences identified 443 conserved SNPs between the two serovars, including SNP variations in type III secretion system effector (T3SE). In conclusion, this analysis has identified genetic features encoding putative factors controlling host-specificity in S. Pullorum. The novel bioinformatic workflow and associated scripts can directly be applied to other bacteria to uncover the genome difference between clades.


A new approach to revealing point mutations in DNA analyzed by colorimetric detection.
A new approach to detection of point mutations in an amplified DNA was developed. The approach is based on highly selective ligation (T4 DNA ligase) of a tandem of short oligonucleotides one of which contains the biotin group. The ligation product is formed only when the hybridization complex DNA/tandem is formed and the tandem is perfect. The hybridization complex DNA/(biotinylated ligation product) was separated from the biotinylated component of the tandem by UV-immobilization of the reaction mixture on a nylon membrane. The immobilized hybridization complex was detected colorimetrically by a streptavidin-alkaline phosphatase cojugate with a chromogenic substrate.


Pulmonary artery banding for ventricular septal defect with pulmonary hypertension.
Sixty children in this series underwent pulmonary artery banding (PAB); isolated ventricular septal defect (VSD) was present in 24, and 20 were corrected seven months to ten years and eight months after PAB. Other anomalies were present in 37, and 15 were eventually totally corrected. Survival after PAB was 90% (95.8% with isolated VSD), and 94.3% (95% with isolated VSD) after total correction. Mean age at banding was 12.9 months, and 52.6 months at debanding. All patients underwent catheterization before PAB; 39 underwent catheterization after PAB, and ten after total correction. Pulmonary artery blood pressure was reduced from 53.5 mm Hg to 25.3 mm Hg by banding. Most patients had only moderately increased pulmonary blood flow. Banding at the altitude of Denver (1,600 m) appears to be an effective means to convert high-risk infants into lower-risk children for total correction. The cumulative mortality for two-stage treatment of VSD was 8.3%.


Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma.
LINC00426 is a newly identified long non-coding RNA (lncRNA) with unacknowledged biological roles. Here we set out to characterize the expression status of LINC00426 in osteosarcoma and understand its mechanistic involvement in incidence of doxorubicin (Dox) resistance. The relative expression of LINC00426 and miR-4319 was determined by real-time PCR. Cell viability and proliferation in response to LINC00426 silencing or miR-4319 over-expression was measured with CCK-8 kit and colony formation assay, respectively. The direct association between LINC00426 and miR-4319 was analyzed by pulldown assay with biotin-labelled probes. LINC00426 was significantly up-regulated in Dox-resistant osteosarcoma (OS) both in vitro and in vivo, which intimately associated with unfavorable prognosis. SiRNA-mediated knockdown of LINC00426 remarkably compromised cell viability and proliferation in Dox-resistant OS cells, which accompanied with decrease of IC50 and activation of caspase-3. We further predicted and validated the regulatory effects of miR-4319 on LINC00426 expression. Simultaneously, we provided evidences in support of direct binding between LINC00426 and miR-4319 by pulldown assay. Reciprocally negative regulation was observed between LINC00426 and miR-4319 each other. Ectopic introduction of miR-4319 significantly surmounted the Dox resistance in OS cells, while miR-4319 inhibition in LINC00426-deficient cells greatly restore this phenotype. We uncovered the important contribution of LINC00426/miR-4319 to Dox resistance in osteosarcoma. This article was reviewed by Bo Liang and Sinan Zhu.


Retrospective Screening for SARS-CoV-2 RNA in California, USA, Late 2019.
To investigate the possibility of earlier cases of severe acute respiratory syndrome coronavirus 2 infection than previously recognized, we retrospectively tested pooled samples from 1,700 persons with respiratory signs/symptoms seen at Stanford Health Care, Palo Alto, California, USA, during the last 2 months of 2019. We found no evidence of earlier infection.


Calix[4]arenes with intramolecularly bridged meta positions prepared via Pd-catalysed double C-H activation.
The introduction of a 2-pyridylsulfoxide moiety into the upper rim of calix[4]arenes enabled the synthesis of unprecedented derivatives with intramolecularly bridged meta positions of two neighbouring aromatic subunits. Palladium-catalysed double C-H activation thus represents a straightforward way to a completely novel type of calixarenes.


Development of modified voxel phantoms for the numerical dosimetric reconstruction of radiological accidents involving external sources: implementation in SESAME tool.
Estimating the dose distribution in a victim's body is a relevant indicator in assessing biological damage from exposure in the event of a radiological accident caused by an external source. When the dose distribution is evaluated with a numerical anthropomorphic model, the posture and morphology of the victim have to be reproduced as realistically as possible. Several years ago, IRSN developed a specific software application, called the simulation of external source accident with medical images (SESAME), for the dosimetric reconstruction of radiological accidents by numerical simulation. This tool combines voxel geometry and the MCNP(X) Monte Carlo computer code for radiation-material interaction. This note presents a new functionality in this software that enables the modelling of a victim's posture and morphology based on non-uniform rational B-spline (NURBS) surfaces. The procedure for constructing the modified voxel phantoms is described, along with a numerical validation of this new functionality using a voxel phantom of the RANDO tissue-equivalent physical model.


Percutaneous pedicle screw for unstable spine fractures in polytraumatized patients: A report of two cases.
Unstable spine fractures commonly occur in the setting of a polytraumatized patient. The aim of management is to balance the need for early operative stabilization and prevent additional trauma due to the surgery. Recent published literature has demonstrated the benefits of early stabilization of an unstable spine fracture particularly in patients with higher injury severity score (ISS). We report two cases of polytrauma with unstable spine fractures stabilized with a minimally invasive percutaneous pedicle screw instrumentation system as a form of damage control surgery. The patients had good recovery from the polytrauma injuries. These two cases illustrate the role of minimally invasive stabilization, its limitations and technical pitfalls in the management of unstable spine fractures in the polytrauma setting as a form of damage control surgery.


The von Economo neurons in apes and humans.
The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex (ACC) in great apes and humans but not other primates. We stereologically counted the VENs in FI and the limbic anterior (LA) area of ACC and found them to be more numerous in humans than in apes. In humans, VENs first appear in small numbers in the 36th week postconception are rare at birth and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than the left in FI and LA in postnatal brains; this may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, containing FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. In a preliminary diffusion tensor imaging study of the connections of FI, we found that the VEN-containing regions connect with the frontal pole as well as with other parts of frontal and insular cortex, the septum, and the amygdala. The VENs and a related cell population, the fork cells, selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing pepide, which signal satiety. The loss of VENs and fork cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. These cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals.


[Surveillance Bronchoscopy after Lung Transplantation].
Acute cellular rejection( ACR) is one of the major complications of the acute phase after lung transplantation. In addition, ACR is considered to be a major cause of chronic lung allograft dysfunction (CLAD). Therefore, the diagnosis and treatment for ACR are major issues at transplantation facilities. Surveillance bronchoscopy( SB) is performed at many institutions as the golden standard for ACR diagnosis, and our hospital also implements long-term post-transplant monitoring of ACR as a preventive measure for CLAD. However, the suitability of SB may be questioned due to the risk of complications such as bleeding and pneumothorax. Here, we would like to report the results of SB in our department and discuss future diagnosis and treatment policy for ACR.


Influence of extracellular matrix on cytokine stimulated pro-labour gene expression in human uterine myocytes.
Cellular function is modulated by the interaction with the extracellular matrix within the myometrium. We formed the hypothesis that the cytokine-stimulated pro-labour gene expression by human uterine smooth muscle cells would be increased by growing the cells on collagen-coated plates. Primary cultures of human uterine smooth muscle cells grown on uncoated plates and on plates coated with collagen were exposed to the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and interleukin-6) and assessed the messenger RNA expression of oxytocin receptor, interleukin-8, prostaglandin H synthase type-2 and prostaglandin F(2) alpha receptor. Basal pro-labour gene expression was unaffected by collagen coating and the response to the inflammatory cytokines was similar for oxytocin receptor and prostaglandin H synthase type-2, but appeared to be reduced for interleukin-8 and enhanced for FP. Collagen coating made no significant impact on basal integrin expression and interleukin-1beta induced phosphorylation of extracellular-regulated-kinase1/2 and RelA subunit of nuclear factor-kappa B (p65). We conclude that growing human uterine smooth muscle cells on collagen-coated plates may modulate the pro-labour gene response to the inflammatory cytokines.


Using novel click chemistry algorithm to design D3R inhibitors as blood-brain barrier permeants.
Dopamine receptor D3 (D3R) has gained attention as a promising therapeutic target for neurological disorders. In this study, an innovative in silico click reaction strategy was employed to identify potential D3R binders. The ligand template, 1-phenyl-4-[4-(1H-1,2,3-triazol-5-yl)butyl]piperazine, with substitution at the 1,2,3-triazole ring, served as the starting point. Generated compounds underwent filtration based on their brain-to-blood concentration ratio (logBB), leading to the identification of 1-{4-[1-(decahydronaphthalen-1-yl)-1H-1,2,3-triazol-5-yl]butyl}-4-phenylpiperazine as the most promising candidate, displaying superior D3R affinity and blood-brain barrier (BBB) permeability compared to the reference ligand, eticlopride. Molecular dynamics simulations further supported these findings. This study presents a novel hit for designing D3R ligands and establishes a workflow utilizing in silico click chemistry to screen compounds with BBB permeability. The proposed click reaction-based algorithm holds significant potential as a valuable tool in the development of effective antipsychotic compounds.


Bone scanning--who needs it among patients with newly diagnosed prostate cancer?
We evaluated the relationship between serum PSA and clinical variables to eliminate bone scanning in patients with prostate cancer having a low probability of bone metastasis. The study included 366 patients with newly diagnosed prostate cancer between 1999 and 2005. Bone metastasis was studied for its correlation with various clinical and pathological variables in these patients. Bone metastasis was found in 28 (7.7%) of 366 patients. Fourteen patients had skeletal symptoms related to bone metastasis. The risk for bone metastases increased considerably with increases of PSA level, clinical T stage and Gleason score. The metastasis was not found in 161 patients with serum PSA concentration of 10 ng/ml or lower. In 95 patients with the concentration between 10 and 20 ng/ml only two had the metastasis. These two patients had T2 disease and Gleason scores of 7 or greater. In 204 patients with clinical stage T1 disease, one (0.5%) had the metastasis. In 117 patients with Gleason scores of 6 or less, the metastasis was found in two (1.7%). For patients with serum PSA levels of 10 ng/ml or lower, bone scanning may be eliminated because of the negligible risk of bone metastases. In addition, scanning may not be necessary for those with PSA levels between 10 and 20 ng/ml, when they have T1 disease and Gleason scores of 6 or lower.


The perceived threat in adults with leukemia undergoing hematopoietic stem cell transplantation.
Leukemia and hematopoietic stem cell transplantation (HSCT) create physical, psychological, social, and spiritual distresses in patients. Understanding this threatening situation in adults with leukemia undergoing HSCT will assist health care professionals in providing holistic care to the patients. The aim of the present study was exploring the perceived threat in adults with leukemia undergoing HSCT. This article is part of a longitudinal qualitative study which used the grounded theory approach and was conducted in 2009-2011. Ten adults with acute leukemia scheduled for HSCT were recruited from the Hematology-Oncology Research Center and Stem Cell Transplantation, Shariati Hospital in Tehran, Iran. A series of pre-transplant and post-transplant in-depth interviews were held in the hospital's HSCT wards. Totally, 18 interviews were conducted. Three written narratives were also obtained from the participants. The Corbin and Strauss approach was used to analyze the data. Perceived threat was one of the main categories that emerged from the data. This category included four subcategories, "inattention to the signs and symptoms", "doubt and anxiety", "perception of danger and time limitation" and "change of life conditions", which occurred in linear progression over time. Suffering from leukemia and experiencing HSCT are events that are uniquely perceived by patients. This threatening situation can significantly effect perception of patients and cause temporary or permanent alterations in patients' lives. Health care professionals can help these patients by deeper understanding of their experiences and effective interventions.


[The role of endothelial lipase in atherogenesis].
Endothelial lipase (EL) is synthetized by endothelial cells and its main substrates are lipoprotein phospholipids. Over expression of EL reduces high density lipoprotein (HDL) cholesterol and phospholipids, in vivo and in vitro. Inhibition of the enzyme achieves the opposite effects. The synthesis of the enzyme is regulated by interleukin 1 and tumor necrosis factor a. These inflammatory cytokines play a role in diabetes and vascular disease. An increase in vascular mechanical forces, that play a role in atherogenesis, also increase the synthesis of EL. There is expression of EL in endothelial cells, macrophages and muscle cells of atherosclerotic lesions of coronary arteries of humans. This evidence leads to the suspicion that EL plays a role in atherogenesis. There are also higher plasma levels of EL in subjects with type 2 diabetes, who are especially susceptible to the development of vascular lesions. Therefore the inhibition of EL could play an important role in HDL metabolism and could be a new therapeutic strategy for the prevention of atherosclerosis.


Effects of octreotide on acute necrotizing pancreatitis in rabbits.
To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg.b.m. of 50 g/L sodium taurocholate (NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mg/kg.b.m. was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction. Serum activities of amylase, IL-6 and TNF-alpha and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-, Cu-, and Zn-SOD) in pancreatic tissue were measured. Serum TNF-alpha and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes. Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylactic octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.


Modelling antigenic drift in weekly flu incidence.
Since influenza in humans is a major public health threat, the understanding of its dynamics and evolution, and improved prediction of its epidemics are important aims. Underlying its multi-strain structure is the evolutionary process of antigenic drift whereby epitope mutations give mutant virions a selective advantage. While there is substantial understanding of the molecular mechanisms of antigenic drift, until now there has been no quantitative analysis of this process at the population level. The aim of this study is to develop a predictive model that is of a modest-enough structure to be fitted to time series data on weekly flu incidence. We observe that the rate of antigenic drift is highly non-uniform and identify several years where there have been antigenic surges where a new strain substantially increases infective pressure. The SIR-S approach adopted here can also be shown to improve forecasting in comparison to conventional methods.


Correlations between the expression of molecules in the TGF-β signaling pathway and clinical factors in adamantinomatous craniopharyngiomas.
To investigate the clinical and pathological factors associated with preoperative hypothalamus invasion and postoperative outcomes of adamantinomatous craniopharyngiomas (ACPs) after the expanded endonasal approach (EEA) resection. Ninety-three specimens of ACPs, consisting of 71 primary and 22 recurrent tumors, were investigated for the expression of TGF-β1, SMAD2, SMAD3, and β-catenin by immunohistochemistry staining. The clinical information of relevant patients, including the extent of resection, hypothalamus invasion, endocrinopathy, complications, and prognosis, was reviewed. The relationships between the expression of these immunopathological markers and clinical factors were analyzed. Endocrinological dysfunctions were more common in recurrent patients and primary patients with hypothalamus invasion in the comparisons. For recurrent patients, the rate of gross total resection (GTR) was significantly lower than for primary patients (63.6% vs. 90.1%, P = 0.007). According to radiological and intraoperative findings, invasive ACPs (IACPs) included 48 (67.6%) cases in primary tumors. The expression of TGF-β1 and β-catenin was significantly higher in recurrent tumors (P = 0.021 and P = 0.018, respectively) and IACPs (P = 0.008 and P = 0.004, respectively). The expression level of TGF-β1 was associated with hypothalamus involvement (Puget grade, P = 0.05; Vile grade, P = 0.002), postoperative endocrinopathy (P = 0.01), and pituitary stalk preservation (P = 0.008) in primary patients. In addition, the extent of resection, treatment history, hypothalamic invasion, and level of TGF-β1 expression had significant influences on tumor recurrence/progression after surgery separately. Our study demonstrated the potential role of TGF-β1 in the regulation of hypothalamus invasion in ACPs and the prediction of prognosis after EEA surgery. The TGF-β signaling pathway may represent a crucial mechanism in the aggressive behavior and progression of ACPs.


[Isolation and characteristics of the extracellular matrix of cultured cells].
Sodium deoxycholate extraction was used to isolate extracellular matrix from various cultured cells: human and murine embryonic fibroblasts, epithelial lines of mouse (MPTR), rat (IAR 2 and IAR 20), pig (SPEV) and cow (FBT). Protein composition of the matrix was studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunofluorescence. The matrix morphology was investigated by scanning electron microscopy. In cell lines FBT and MPTR the major component of the matrix was laminin, whereas in other lines and fibroblasts it was fibronectin. The matrix of the majority of lines had a fibrillar structure, and the fibrils usually formed networks. MPTR cells had a punctate matrix composed of laminin and collagen type IV, densely covering the substratum. The treatment of the matrix by hyaluronidase and/or DNAase I did not influence its protein composition. The isolated matrix of different structure and composition may serve a biological substratum in studies of normal tumor cell behavior in tissue culture.


Histidine-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma.
Addition of 0.05 IU of heparin per ml normal plasma prolongs its thrombin time from 20 to 27s , but that of plasma specifically depleted in histidine-rich glycoprotein (by immunoadsorption) from 20 to 180s . Reconstitution of the depleted plasma with normal plasma or with purified histidine-rich glycoprotein normalizes its thrombin time. In 54 plasma samples from hospitalized patients a significant negative correlation was found between the anticoagulant activity of heparin measured by thrombin inhibition and the plasma level of histidine-rich glycoprotein (r = 0.69). It is concluded that the level of histidine-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma to an extent which appears to be pharmacologically and possibly clinically relevant.


Sensory feedback in prosthetics: a standardized test bench for closed-loop control.
Closing the control loop by providing sensory feedback to the user of a prosthesis is an important challenge, with major impact on the future of prosthetics. Developing and comparing closed-loop systems is a difficult task, since there are many different methods and technologies that can be used to implement each component of the system. Here, we present a test bench developed in Matlab Simulink for configuring and testing the closed-loop human control system in standardized settings. The framework comprises a set of connected generic blocks with normalized inputs and outputs, which can be customized by selecting specific implementations from a library of predefined components. The framework is modular and extensible and it can be used to configure, compare and test different closed-loop system prototypes, thereby guiding the development towards an optimal system configuration. The use of the test bench was demonstrated by investigating two important aspects of closed-loop control: performance of different electrotactile feedback interfaces (spatial versus intensity coding) during a pendulum stabilization task and feedforward methods (joystick versus myocontrol) for force control. The first experiment demonstrated that in the case of trained subjects the intensity coding might be superior to spatial coding. In the second experiment, the control of force was rather poor even with a stable and precise control interface (joystick), demonstrating that inherent characteristics of the prosthesis can be an important limiting factor when considering the overall effectiveness of the closed-loop control. The presented test bench is an important instrument for investigating different aspects of human manual control with sensory feedback.


In silico insight into EGFR treatment in patients with lung carcinoma and T790M mutations.
The T790M mutational basis of treatment failure, following treatment via alteration of the epidermal growth factor receptor (EGFR) pathway, is a well-known anomaly in patients with non-small cell lung cancer (NSCLC). The T790M mutation activates the kinase domain, causing tyrosine kinase inhibitors, such as gefitinib, to elicit little or no response. To overcome this acquired resistance in NSCLC cells, the present study utilized a structure-based drug designing method to identify a novel lead compound. An in-house traditional Chinese medicinal compound database was used and following initial virtual screening, pre-absorption, distribution, metabolism and excretion/Tox and automated docking analyses, nardosinon was selected as the most appropriate candidate for further analysis. Two NSCLC cell lines, PC9GR4 and H2347, were used to test nardosinon and the results were compared with gefitinib. Results from an initial cell death assay revealed that nardosinon was able to induce cell death in NSCLC cells with and without the T790M mutation. These findings suggest that nardosinon may be an effective pharmacological compound for NSCLC treatment, including T790M EGFR mutant NSCLC cells.


Tandem Mass-Selective Cryogenic Digital Ion Traps for Enhanced Cluster Formation.
We present the implementation of tandem mass-selective cryogenic ion traps, designed to enhance the range of ion processing capabilities that can be performed prior to spectroscopic interrogation. We show that both the formation of ion clusters and mass filtering steps can be combined in a single cryogenic linear quadrupole ion trap driven by RF square waves. Mass filtering and mass isolation can be achieved by manipulation of the RF frequency and duty cycle. Very importantly, this scheme circumvents the need for high-amplitude RF voltages that can be incompatible with typical cryogenic ion processing conditions. In addition, proper adjustment of the stability boundaries during the clustering process allows for the preferential formation of a specific cluster size rather than a broad distribution of sizes. Lastly, we show that a specific cluster size can be formed, mass-selected, and then transferred to another ion trap for a second completely separate ion processing step. The instrumentation and modular design developed here expand the scope of ionic species and clusters that can be accessed by processing electrosprayed ions.


ENU large-scale mutagenesis and quantitative trait linkage (QTL) analysis in mice: novel technologies for searching polygenetic determinants of craniofacial abnormalities.
Discrepancies in size and shape of the jaws are the underlying etiology in many orthodontic and orthognathic surgery patients. Genetic factors combined with environmental interactions have been postulated to play a causal or contributory role in these craniofacial abnormalities. Along with the soon-to-be-available complete human and mouse genomic sequence data, mouse mutants have become a valuable tool in the functional mapping of genes involved in the development of human maxillofacial dysmorphologies. We review two powerful methods in such efforts: N-ethyl-N-nitrosourea (ENU) large-scale mutagenesis and quantitative trait linkage (QTL) analysis. The former aims at producing a plethora of novel variants of particular trait(s), and ultimately mapping the point mutations responsible for the appearance of these new traits. In contrast, the latter applies intensive breeding and mapping techniques to identify multiple loci (and, subsequently, genes) contributing to the phenotypic difference between the tested strains. A prerequisite for either approach to studying variations in the traits of interest is the application of effective mouse cephalometric phenotype analysis and rapid DNA mapping techniques. These approaches will produce a wealth of new data on critical genes that influence the size and shape of the human face.


Alveolar bone changes in the mandibular incisors after genioplasty, a three-dimensional study.
Functional genioplasty aims to achieve lip competence at rest and reduces lip pressure against the mandibular incisors. The purpose of this study was to describe the radiographic changes in alveolar bone of the mandibular incisors after functional genioplasty. Cone beam CT images from 36 patients were compared between immediate (T0) and delayed postoperative period (T1). The mean time to complete the second imaging was 10.9 ± 4.7 months. Dental and bone parameters were assessed: the vestibular bone height (BH), the bone thickness (BT) with regard to the apex of the central incisor (BT2) and at equidistance between the cementoenamel junction and the dental apex (BT1). The existence of fenestrations, the apical-root resorption and the incisor-mandibular plane angle (IMPA) were also collected. No significant change occurred in the BH. BT was improved of a mean 47.9% and 53.6% at the BT1 level on #31 and #41, respectively (p1=0.01 and p2=0.02, respectively); and of 53.0% at the level of the apex of both mandibular central incisors (p1=0.003 on #31 and p2=0.009 on #41). No difference in the number of fenestrations was observed between T0 and T1. A significant decrease in the root length on both mandibular incisors was observed on the delayed CBCT (from 21.96 ± 1.35 to 21.68 ± 1.32 mm for #31, p=0.0007; from 22.26 ± 1.66 to 21.96 ± 1.48 mm for #41, p=0.002). Finally, the IMPA remained stable between the two examinations with a mean 106.1 ± 7.38° vs 105.8 ± 6.51° (p=0.38). Functional genioplasty favours the alveolar bone formation of the mandibular central incisors, probably by direct bone grafting, but also by the relaxation of the perioral and chin musculature.


[Invasive Mechanical Ventilation Therapy in the Dying Process - Step by Step].
Invasive mechanical ventilation can be terminated by immediate (palliative) extubation or by gradual reduction of ventilation with the ventilation access left open (terminal weaning). Both procedures are ethically equivalent and can be performed in everyday life, so that individual patient factors and the experience of the treatment team are decisive. However, the primary goal is to ensure that the patient and relatives do not suffer. This article presents step by step which aspects are relevant: communication, adjust or stop monitoring, selection and implementation of the appropriate procedure, preparatory measures, recognition and treatment of distressing symptoms by means of drug or non-drug therapy options and last but not least accurate documentation.


Epidemiology and management practices for childhood-onset systemic lupus erythematosus patients: a survey in Latin America.
To assess epidemiology and management practices of Latin America Pediatric Rheumatologists (LAPR) about childhood-onset systemic lupus erythematosus (cSLE). A cross-sectional study was performed in 288 LAPR PANLAR members based on online survey about cSLE practices. The response rate of web-based survey by LAPR was 170/288(59%) and the majority worked in university hospitals (63%). The ACR and/or SLICC classification criteria (99%) and disease activity tools (97%) were almost universally used by LAPR, whereas damage index (70%) and CHAQ (58%) instruments were less frequently used. Laboratory exams, diagnostic imaging, and biopsies were generally available (> 75%), however low availability for densitometry (66%). Drug access was excellent for the most common prescribed medications (> 75%), except for belimumab (11%). Emerging mosquito-borne diseases were also reported: dengue (20%), chikungunya (11%), and Zika (8%). Groups were further divided in two, according to the median number of cSLE patients followed by LAPR in the last year: groups A and B (≥ 25 and < 25, respectively). Frequencies of condom in combination with other contraceptive methods were significantly higher in group A than B (p = 0.01). The frequencies of reported pregnancy (p < 0.001) and non-adherence to therapy were significantly higher in group A (p = 0.023). Alcohol intake (p = 0.004) and illicit drug use (p = 0.007) were also reported more frequently by LAPR of group A in at least one cSLE patient. This first large web-based survey demonstrated an overall excellent access for diagnosis and therapy by LAPR, probably related to their high rate of practices in tertiary care of university hospitals. Adherence to therapy, pregnancy, and substance abuse was identified as major challenges in this population, particularly in larger centers.


AoMedA has a complex regulatory relationship with AoBrlA, AoAbaA, and AoWetA in conidiation, trap formation, and secondary metabolism in the nematode-trapping fungus Arthrobotrys oligospora.
The asexual sporulation of filamentous fungi is an important mechanism for their reproduction, survival, and pathogenicity. In Aspergillus and several filamentous fungi, BrlA, AbaA, and WetA are the key elements of a central regulatory pathway controlling conidiation, and MedA is a developmental modifier that regulates temporal expression of central regulatory genes; however, their roles are largely unknown in nematode-trapping (NT) fungi. Arthrobotrys oligospora is a representative NT fungus, which can capture nematodes by producing adhesive networks (traps). Here, we characterized the function of AoMedA and three central developmental regulators (AoBrlA, AoAbaA, and AoWetA) in A. oligospora by gene disruption, phenotypic comparison, and multi-omics analyses, as these regulators are required for conidiation and play divergent roles in mycelial development, trap formation, lipid droplet accumulation, vacuole assembly, and secondary metabolism. A combined analysis of phenotypic traits and transcriptome showed that AoMedA and AoWetA are involved in the regulation of peroxisome, endocytosis, and autophagy. Moreover, yeast one-hybrid analysis showed that AoBrlA can regulate AoMedA, AoAbaA, and AoWetA, whereas AoMedA and AoAbaA can regulate AoWetA. Our results highlight the important roles of AoMedA, AoBrlA, AoAbaA, and AoWetA in conidiation, mycelia development, trap formation, and pathogenicity of A. oligospora and provide a basis for elucidating the relationship between conidiation and trap formation of NT fungi. IMPORTANCE Conidiation is the most common reproductive mode for many filamentous fungi and plays an essential role in the pathogenicity of fungal pathogens. Nematode-trapping (NT) fungi are a special group of filamentous fungi owing to their innate abilities to capture and digest nematodes by producing traps (trapping devices). Sporulation plays an important role in the growth and reproduction of NT fungi, and conidia are the basic components of biocontrol reagents for controlling diseases caused by plant-parasitic nematodes. Arthrobotrys oligospora is a well-known NT fungus and is a routinely used model fungus for probing the interaction between fungi and nematodes. In this study, the functions of four key regulators (AoMedA, AoBrlA, AoAbaA, and AoWetA) involved in conidiation were characterized in A. oligospora. A complex interaction between AoMedA and three central regulators was noted; these regulators are required for conidiation and trap formation and play a pleiotropic role in multiple intracellular activities. Our study first revealed the role of AoMedA and three central regulators in conidiation, trap formation, and pathogenicity of A. oligospora, which contributed to elucidating the regulatory mechanism of conidiation in NT fungi and helped in developing effective reagents for biocontrol of nematodes.


RNA-binding proteins of the NXF (nuclear export factor) family and their connection with the cytoskeleton.
The mutual relationship between mRNA and the cytoskeleton can be seen from two points of view. On the one hand, the cytoskeleton is necessary for mRNA trafficking and anchoring to subcellular domains. On the other hand, cytoskeletal growth and rearrangement require the translation of mRNAs that are connected to the cytoskeleton. β-actin mRNA localization may influence dynamic changes in the actin cytoskeleton. In the cytoplasm, long-lived mRNAs exist in the form of RNP (ribonucleoprotein) complexes, where they interact with RNA-binding proteins, including NXF (Nuclear eXport Factor). Dm NXF1 is an evolutionarily conserved protein in Drosophila melanogaster that has orthologs in different animals. The universal function of nxf1 genes is the nuclear export of different mRNAs in various organisms. In this mini-review, we briefly discuss the evidence demonstrating that Dm NXF1 fulfils not only universal but also specialized cytoplasmic functions. This protein is detected not only in the nucleus but also in the cytoplasm. It is a component of neuronal granules. Dm NXF1 marks nuclear division spindles during early embryogenesis and the dense body on one side of the elongated spermatid nuclei. The characteristic features of sbr mutants (sbr10 and sbr5 ) are impairment of chromosome segregation and spindle formation anomalies during female meiosis. sbr12 mutant sterile males with immobile spermatozoa exhibit disturbances in the axoneme, mitochondrial derivatives and cytokinesis. These data allow us to propose that the Dm NXF1 proteins transport certain mRNAs in neurites and interact with localized mRNAs that are necessary for dynamic changes of the cytoskeleton.


Direct refractive index retrieval from interferometry measurements.
We present an alternative numerical method to the Abel inversion technique, which can be applied to complex non-symmetrical systems. A comparison with the Abel inversion algorithm was conducted. For benchmarking, the method was applied to a synthetic trace representing a plasma waveguide characterized by a constant parabolic density profile. Furthermore, the temperature and refractive index of a plume of hot air surrounding a non-cylindrical soldering iron were retrieved. Temperatures between 50 °C and 200 °C were successfully retrieved within the instrument precision. The proposed method allows robust and fast data retrieval while maintaining the accuracy and resolution of well-known methods, as Abel inversion.


Delineation of the roles of paracrine and autocrine interleukin-6 (IL-6) in myeloma cell lines in survival versus cell cycle. A possible model for the cooperation of myeloma cell growth factors.
Primary myeloma cells rapidly apoptose as soon as they are removed from their bone-marrow environment. A likely explanation is that the tumor environment produces survival factors that may counteract a spontaneous activation of pro-apoptotic program. Additional factors may trigger cell cycling in surviving myeloma cells. Interleukin-6 (IL-6) is a well recognized myeloma cell growth factor produced mainly by the tumor environment. However, myeloma cells themselves may produce low levels of autocrine IL-6. The respective roles of paracrine versus autocrine IL-6 are a matter of debate. We investigated these roles using the XG-6 myeloma cell line whose growth is dependent on addition of exogenous IL-6, despite its weak IL-6 mRNA and protein expression. The apoptosis induced by exogenous IL-6 deprivation was blocked by transferring the Mcl-1 gene coding for an anti-apoptotic protein in XG-6 cells. An XG-6Mcl-1 cell line which can survive and grow without adding IL-6 was obtained. We show that anti-IL-6 or anti-gp130 antibodies abrogated cell cycling whereas they did not affect cell survival. These data indicate that the weak autocrine IL-6 produced by myeloma cells is sufficient to trigger cell cycling whereas their survival requires large exogenous IL-6 concentrations. This important role of autocrine IL-6 has to be considered when evaluating the mechanism of action of myeloma cell growth factors. These factors may actually block an activated pro-apoptotic program, making possible a weak production of autocrine IL-6 to promote cell cycling.


New insights into phenotype and genotype relationships in Neospora caninum.
The successful isolation of four new Neospora caninum strains from different regions and with different backgrounds (obtained from an abortion storm or congenitally infected and asymptomatic calves) allowed us previously to characterize natural isolates, finding differences in phenotype and microsatellites. Given the variability observed, we wondered in this work whether these differences had consequences in virulence, invasion and vertical transmission using cell cultures and murine neosporosis models. In addition, we performed the genomic analysis and SNP comparative studies of the NcURU isolates. The results obtained in this work allowed us to establish that NcURU isolates are of low virulence and have unique phenotypic characteristics. Likewise, sequencing their genomes has allowed us to delve into the genetic singularities underlying these phenotypes, as well as the common mutated genes. This work opens a new perspective for diagnostic purposes and formulating possible vaccines based on attenuated strains.


Modulation of ATP-sensitive K+ channels by internal acidification in insulin-secreting cells.
The effect of intracellular acidification (low pHi) on open probability of the ATP-sensitive K+ (KATP) channel was examined in insulin-secretion cells using an inside-out configuration of the patch-clamp technique. In an insulin-secreting cell line beta-TC3, KATP single-channel currents (IKATP) were readily recorded in the absence of internal ATP. ATP (50 microM and 0.5 mM) dramatically decreased the channel activity. A step decrease of intracellular pH (pHi) from 7.4 to 6.7 or 6.3 in the presence of ATP gradually increased the channel activity. In addition, low pHi in the presence of ATP could partially restore channel activity lost in a process called "rundown." Kinetic analysis revealed a change in channel gating at low pHi with ATP. The bursting durations of IKATP at pHi 6.3 in the presence of ATP were significantly longer than those at pHi 7.4 in the absence of ATP. These results suggest that the increased channel activity at low pHi might have resulted from a mechanism involving an alteration of channel conformation. We also observed an inhibitory effect of low pHi on channel activity. However, the inhibitory effect was much more apparent at pHi 5.7 and was only partially reversible. The activation effect of low pHi on IKATP in the presence of ATP was also observed in acutely isolated rat islet cells and in another insulin-secretion cell line RINm5F, although the effect was weaker and was variable among experiments. We conclude that, as in frog skeletal muscle and cardiac muscle, an increase in channel activity at low pHi is one of the mechanisms underlying proton modulation of IKATP in insulin-secreting cells.


Cingulin, paracingulin, and PLEKHA7: signaling and cytoskeletal adaptors at the apical junctional complex.
Cingulin, paracingulin, and PLEKHA7 are proteins localized in the cytoplasmic region of the apical junctional complex of vertebrate epithelial cells. Cingulin has been detected at tight junctions (TJs), whereas paracingulin has been detected at both TJs and adherens junctions (AJs) and PLEKHA7 has been detected at AJs. One function of cingulin and paracingulin is to regulate the activity of Rho family GTPases at junctions through their direct interaction with guanidine exchange factors of RhoA and Rac1. Cingulin also contributes to the regulation of transcription of several genes in different types of cultured cells, in part through its ability to modulate RhoA activity. PLEKHA7, together with paracingulin, is part of a protein complex that links E-cadherin to the microtubule cytoskeleton at AJs. In this paper, we review the current knowledge about these proteins, including their discovery, the characterization of their expression, localization, structure, molecular interactions, and their roles in different developmental and disease model systems.


Cerebral circulation during acute microgravity induced by free drop in anesthetized rats.
To evaluate changes in the cerebral circulation during acute microgravity (microG), we measured intracranial pressure (ICP), aortic pressure at the diaphragm level, and cerebral flow velocity (CFV) in anesthetized rats (n = 5) during 4.5 s of microG induced by free drop, then calculated arterial pressure at the eye level (AP(eye)) and cerebral perfusion pressure (CPP = AP(eye)-ICP), and estimated CPP-CFV relationship. The rats were placed in the flat and the 30 degrees head-up positions. In the head-up position, ICP, AP(eye), and CPP were significantly increased by 2.2 +/- 0.4, 12.3 +/- 2.0, and 10.1 +/- 1.7 mmHg respectively during microG, whereas the CFV did not change significantly. In the flat position, none of these variables were significantly affected by microG. The slope of the CPP-CFV relationship was decreased only in the head-up position, suggesting that the cerebrovascular resistance was increased by microG. These findings indicate that the change in gravitational (hydrostatic) pressure is a key factor in understanding the changes in cerebral circulation during acute microG.


Benzene and Its Principal Metabolites Modulate Proinflammatory Cytokines and Growth Factors in Human Epidermal Keratinocyte Cultures.
Benzene is an established leukemogen and hematotoxin in humans. However, the finding that benzene is a multiple-site carcinogen in rodents raises the possibility that other tissues could be susceptible to benzene-induced carcinogenicity, especially since a significant excess of squamous cell carcinomas and papillomas arise from epidermal and oral keratinocytes in benzene-exposed rats. Since inflammation and sustained hyperplasia are two integral components in carcinogenesis, the elaboration of proinflammatory cytokines and growth factors by keratinocytes might provide a mechanistic link between tumor initiation and promotion in benzene-induced cancers. We observed that the principal benzene metabolites, represented by hydroquinone, 1,4-benzoquinone, phenol, 1,2,4-benzenetriol, and catechol, significantly alters the production of transforming growth factor of (TGF)-α and interleukin (IL)-8 in human epidermal keratinocyte cultures. These cytokines represent the primary growth promoting factor and neutrophil chemotactant in the skin, respectively. Cytokine secretion correlated with the known redox potential of individual benzene metabolites and antioxidants, including dimethyl sulfoxide, 1,1,3,3-tetramethylthiourea, and N-acetylcysteine, attenuated the response. Binary combinations of selected benzene metabolites synergized in the induction of IL-8, while benzene, by itself, induced about a three-fold increase in IL-8 production. Taken together, our studies suggest that benzene and many of its phase I metabolites induce inflammatory cytokines and growth factors and this occurs through direct covalent binding or the generation of reactive oxygen species by autooxidation and reduction. The elaboration of proinflammatory cytokines and growth factors by keratinocytes in response to benzene and its principal metabolites may participate in benzene-induced skin carcinogenesis.


Approach for selective separation of thiophenic and sulfidic sulfur compounds from petroleum by methylation/demethylation.
Detailed characterization of petroleum derived sulfur compounds has been challenging, due to the complex composition of the hydrocarbon matrix. A novel method was developed for selective separation of thiophenic and sulfidic compounds from petroleum. Sulfur compounds were methylated to sulfonium salts by AgBF4 and CH3I, then the polar salts were separated by precipitation from petroleum matrix. The thiophenic and sulfidic sulfonium salts were sequentially demethylated with 7-azaindole and 4-dimethylaminopyridine, obtaining original thiophenic and sulfidic compounds, respectively. The method was validated by model compounds, and applied to a diesel and a vacuum distillation petroleum fraction. Sulfur fractions were characterized by gas chromatography (GC) coupled with a sulfur chemiluminescence detector (SCD) and quadrupole mass spectrometry (MS), and high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The technique was effective to selectively obtain high-purity thiophenic and sulfidic compounds and showed rare discrimination among sulfur compounds with ranging molecular weights and degrees of unsaturation. The method would facilitate multifaceted detailed characterization of sulfur compounds in an organic complex matrix.


Dark matter spikes and annihilation radiation from the galactic center.
The annihilation rate of weakly interacting cold dark matter particles at the galactic center could be greatly enhanced by the growth of a density spike around the central supermassive black hole (SBH). Here we discuss the effects of hierarchical mergers on the central spike. Mergers between halos containing SBHs lead to the formation of SBH binaries which transfer energy to the dark matter particles, lowering their density. The predicted flux of annihilation photons from the galactic center is several orders of magnitude smaller than in models that ignore the effects of SBHs and mergers. Measurement of the annihilation radiation could in principle be used to constrain the merger history of the galaxy.


An alternative technique for the fabrication of removable complete dentures.
The traditional approach for the fabrication of removable complete dentures has several principal limitations. It requires numerous clinical and laboratory steps, and is labor intensive and time consuming. It is obvious that the clinical practice would benefit from further technique optimization in denture fabrication. The authors present a technique in which a duplicate of the patient's existing maxillary denture is simultaneously used as an impression carrying tray, as a guide for placement of the denture teeth, and for maxillomandibular articulation. This article discusses an alternative approach for the fabrication of removable complete dentures. Upon reading this article, the reader should: Be able to identify disadvantages in the traditional approach. Become familiar with the steps required to Fabricate a duplicate denture. Understand the clinical applications for the proposed technique.


The crosstalk: Tumor-infiltrating lymphocytes rich in regulatory T cells suppressed cancer-associated fibroblasts.
The interactions between cancer-associated fibroblasts (CAFs) and cancer cells or tumor-infiltrating lymphocytes (TILs) and cancer cells play important roles in cancer progression and metastasis. However, studies related to the crosstalk between CAFs and TILs in tumor microenvironment (TME) are still lacking. In this study, we mainly investigated the interactions between CAFs and TILs. The distribution of TILs rich in regulatory T cells (Tregs) in breast cancer tissues was evaluated using hematoxylin-eosin staining and immunohistochemistry with anti-CD3, anti-Foxp3, and anti-α-smooth muscle actin antibodies. Homologous CAFs/normal fibroblasts (NFs) and TILs cultured in vitro were identified and detected using immunocytochemistry and flow cytometry (FCM). The direct interaction among these cell types was studied via a factorial design in a co-cultured system. Their indirect interaction was assayed using Transwell plates. The cell cycle and apoptosis of CAFs/NFs co-cultured with TILs was analyzed using propidium iodide staining. Histochemistry demonstrated most of the TILs including Tregs, were distributed in the cancer stroma, adjoining to CAFs. This finding implies that both cell types interact closely in the TME. Identification of the cultured cells showed that CAFs maintained their activated phenotype within limited passages in vitro, and that the TILs population contained a high percentage of Tregs. Data analysis of the factorial design suggests significant interactions among CAFs, NFs, and TILs in both direct and indirect contact ways. The CAFs and NFs were suppressed signally by TILs, which are probably induced by the secretory cytokines derived from TILs or Tregs. Although apoptosis was not detected in CAFs/NFs, the cell cycle assay suggested that the CAFs/NFs were arrested in the G2/M phase by the TILs and their secretory cytokines. CAFs and NFs were dramatically suppressed by Tregs-rich TILs. This suggests the interaction between TILs and CAFs might modify the TME in an unknown manner.


Performance Evaluation of Bruker Biotyper, ASTA MicroIDSys, and VITEK-MS and Three Extraction Methods for Filamentous Fungal Identification in Clinical Laboratories.
Filamentous fungi are a major cause of life-threatening infections in immunocompromised patients; thus, rapid and accurate identification is critical. Filamentous fungal identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been demonstrated with high sensitivity and reproducibility; however, its wider application has been limited in clinical laboratories because of practical challenges such as database availability or lack of standardization. In this study, we compared the performance of the Bruker Biotyper, ASTA MicroIDSys, and Vitek MS for 84 clinical filamentous fungal isolates. Moreover, the sensitivity of three independent sample preparation methods (direct, on plate, in tube) was compared. Bruker Biotyper identified 71.43% (60/84) of isolates correctly (species, genus, or complex/group level). ASTA MicroIDSys and Vitek MS showed accuracy rates of 70.24% (59/84) and 55.95% (47/84), respectively. We found that any difference in sensitivity may be attributed to the database of the systems. In addition, the "in tube" method showed the highest sensitivity among the three methods; however, there was no statistical difference among them. For the broader application of MALDI-TOF MS for filamentous fungal identification, further studies from multiple perspectives are required.


Response of pMOS dosemeters on gamma-ray irradiation during its re-use.
Response of pMOS dosemeters during two successive irradiations with gamma-ray irradiation to a dose of 35 Gy and annealing at room and elevated temperature has been studied. The response was followed on the basis of threshold voltage shift, determined from transfer characteristics, as a function of absorbed dose or annealing time. It was shown that the threshold voltage shifts during first and second irradiation for the gate bias during irradiation of 5 and 2.5 V insignificantly differ although complete fading was not achieved after the first cycle of annealing. In order to analyse the defects formed in oxide and at the interface during irradiation and annealing, which are responsible for threshold voltage shift, midgap and charge-pumping techniques were used. It was shown that during first irradiation and annealing a dominant influence to threshold voltage shift is made by fixed oxide traps, while at the beginning of the second annealing cycle, threshold voltage shift is a consequence of both fixed oxide traps and slow switching traps.


Reduced susceptibilities to biocides and resistance to antibiotics in food-associated bacteria following exposure to quaternary ammonium compounds.
Our aim was to assess the effects of step-wise exposure to didecyl dimethyl ammonium chloride (DDAC) on the antimicrobial (antibiotics and biocides) susceptibilities of food-associated bacterial strains. Adaptive responses of bacterial strains were investigated by exposing the strains daily to increasing subinhibitory concentrations of DDAC for 7 days. Following adaptation to DDAC, a threefold increase in the minimum inhibitory concentration (MIC) values for this biocide was observed in 48% of the Escherichia coli and Listeria monocytogenes strains, and 3% of the Salmonella strains. Reduced susceptibility to other biocides was found with the most important increase in MIC for benzalkonium chloride (BC) and a commercial biocide formulation (Galox Horizon) containing DDAC and glutaraldehyde, for all species except Salmonella. Increase in antibiotic MIC values was more pronounced in E. coli in terms of antibiotic numbers and of magnitude (from 4- to 32-fold increase) and, to a lesser extent, in Salmonella strains. Most of these strains had acquired resistance to ampicillin, cefotaxime, ceftazidime, chloramphenicol and ciprofloxacin. The effects of exposure to DDAC on biocides and antibiotics susceptibilities depend upon the bacteria species. Extensive use of DDAC at subinhibitory concentrations may lead to the development of antibiotic-resistant bacteria and may represent a public health issue.


Normative force of appeals to personhood in dementia care: A critical examination of Kitwood's account of personhood.
In this paper, I critically examine Kitwood's account of personhood for people with dementia. His account has been influential in supporting appeals to personhood in both clinical and bioethical literature on dementia care. I demonstrate that Kitwood's account does not run into common objections against invoking personhood as a normative notion, namely, the objection of exclusionary implications and the objection of redundancy. I argue, however, that Kitwood's account suffers from two other major conceptual issues. These include (a) unreasonable social contingency, and thus, precariousness, of his notion of personhood for people with dementia; and (b) insufficient theoretical connection between his account of personhood and his proposed list of indicators of well-being for people with dementia. Despite these issues, I do not agree with the following view: that, in the context of dementia care, scholars should refrain from appealing to personhood considerations. Instead, I defend the view that while Kitwood fails to offer a compelling theoretical account of personhood of people with dementia, his empirically driven list of indicators of well-being and his notion of malignant social phycology seem to be sensitive to key ethical considerations relevant to dementia care. I propose that we pursue alternative ways of explaining what is morally (un) desirable about them without (explicit) appeal to personhood.


Quality of life in women with endometriosis: a cross-sectional survey.
The aim of the study was to assess QoL and identify and analyse its determinants in women with endometriosis. The study was performed in 2019 in health centres in Lublin (Poland) on 309 women with diagnosed endometriosis. In order to verify which factors affect QoL of the study participants, regression for qualitative variables (CATREG) was used. The applied research instruments included the WHOQOL-BREF quality of life questionnaire, the Acceptance of Illness Scale (AIS), the Laitinen Pain Scale, and a general questionnaire. The overall QoL score of the respondents was 3.30, whereas their overall perceived health score was 2.37. The highest QoL scores were found for the psychological domain 13.33, whereas the lowest QoL were found for the physical domain 11.52. Women with endometriosis have a moderate level of illness acceptance (24.64) and experience daily pain of moderate intensity (5.83). Women with endometriosis rate their overall QoL higher than their overall perceived health. Perceived QoL in women with endometriosis is most commonly associated with their acceptance of illness, BMI, negative impact of symptoms on the relationship with the partner, and dyspareunia. To improve these women's lives, care should also respond to the social, emotional, and sexual issues resulting from the illness. Such interventions will contribute to improved comfort and QoL among these women.


Not All Generic Concerta Is Created Equal: Comparison of OROS Versus Non-OROS for the Treatment of ADHD.
Treatment effectiveness between equivalent doses of non-OROS (osmotic controlled release oral delivery system) methylphenidate ER and OROS methylphenidate ER (brand name Concerta) was examined in a clinical case series of children and adolescents followed for treatment of attention-deficit/hyperactivity disorder (ADHD). The Conners-Third Edition: Parent Rating Scale was used to compare ADHD symptoms when patients were taking non-OROS versus OROS at follow-up visits. A repeated-measures mixed-model approach was used to compare treatment effectiveness. The entire sample (N = 14) demonstrated a reduction in the mean score on the Inattention Scale from clinically significant (T-score > 65) to not clinically significant (T-score < 65) when patients were changed from non-OROS to OROS at the same dosage (mean T-score reduction = 23, p < .0001). The reduction in mean T-score after changing from non-OROS to OROS at the same dosage is indicative of improvement in symptoms of ADHD. Results provide empirical support for US Food and Drug Administration concerns regarding the therapeutic equivalence of non-OROS versus OROS for the treatment of ADHD.


Empathy, burnout, and antibiotic prescribing for acute respiratory infections: a cross-sectional primary care study in the US.
The impact of physician-patient relationship factors, such as physician empathy and burnout, on antibiotic prescribing has not been characterised. To assess associations between physician empathy and burnout and antibiotic prescribing for acute respiratory infections (ARIs) in primary care. Cross-sectional study of primary care practices in the Cleveland Clinic Health System in the US. Patient and prescribing data were obtained from the medical record. All patients with primary diagnoses of ARIs from 1 January 2012 to 31 December 2013, except those with chronic obstructive pulmonary disease (COPD) or who were immunocompromised, were included. Physician empathy was measured using the Jefferson Scale of Empathy while physician burnout was measured using the Maslach Burnout Inventory. The relationship between empathy and burnout and antibiotic prescribing, adjusted for patient and provider characteristics, was analysed using multiple linear regression. In 5937 ARI visits to 102 primary care physicians, the median proportion resulting in antibiotic prescribing was 48.6% (interquartile range [IQR] 24.1% to 70.0%). Neither physician empathy (correlation coefficient [β] 0.005, 95% confidence interval [CI] = -0.001 to 0.010, P = 0.07) nor any burnout measures were significantly associated with antibiotic prescribing: emotional exhaustion (β 0.001, 95% CI = -0.005 to 0.006, P = 0.79), tendency to depersonalise patients (β -0.009, 95% CI = -0.021 to 0.003, P = 0.13), and sense of personal accomplishment (β -0.004, 95% CI = -0.014 to 0.006, P = 0.44). The authors found no significant association between empathy or burnout measures and antibiotic prescribing for ARIs in primary care. Other physician characteristics should be investigated to explain individual variation in antibiotic prescribing.


Subepithelial connective tissue graft: an alternative application for treating endoperiodontal lesions.
This article presents an endoperiodontal lesion treated with a subepithelial connective tissue graft technique using periosteum. A patient with a right lateral maxillary incisor that had been retracted endodontically had gingival fenestration and recession, as well as an extensive apical lesion. Surgery was performed, and 5 months later a metal-ceramic crown was installed. At 6 years post-treatment, the periodontal tissues were stable and there was satisfactory new apical bone formation.


Interleukin-1alpha and tumor necrosis factor alpha modulate cytochrome P450 activities in carp (Cyprinus carpio).
In mammals, it has been shown that the activation of host defense mechanisms down-regulates microsomal cytochrome P450 by the liberation of cytokines. We investigated the effect of interleukin-1alpha (IL1alpha) and tumor necrosis factoralpha (TNFalpha) on constitutive and 3-methylcholanthrene (3-MC)-induced biotransformation activities in carp. We have first measured the time course response of ethoxyresorufine O-decthylase (EROD) activity in liver, head kidney, and spleen 1, 2, 3, 5, and 7 days after intraperitoneal injection of a prototypical Cyp 1A inducer (3-MC). This activity was compared to the rate of 3-MC accumulation in all organs tested. A correlation between a diminution of EROD activity and an increase in 3-MC concentration in each organ was observed. We have also tested the effects of two inflammatory cytokines (IL1alpha and TNFalpha) on biotransformation activities. Intravenous injection of these compounds resulted in a marked depression of 3-MC-induced glutathione S-transferase activity in all organs tested and in 3-MC-increased cytochrome P450 content in the liver and head kidney. TNFalpha produced an increase in basal EROD activity in the liver and head kidney. Taken together, these results suggested that, as in mammals, the activation of host defense mechanisms regulates microsomal cytochrome P450 and related enzymes in fish.


Performance analysis of anoxic selector in upgrading activated sludge process in tropical climate.
The paper describes and analyses the performance of anoxic selectors in upgrading activated sludge process in a municipal wastewater treatment plant under tropical climate, where poor sludge settleability is a problem due to elevated temperature. Site monitoring and laboratory experiment were conducted to study the denitrification, sludge settleability, kinetics, mass balance, pH and alkalinity variation in the system. The sludge settleability measured in Sludge Volume Index (SVI) was observed to improve with the increasing degree of denitrification in the anoxic selector. Under well-developed stable state, an average SVI value of 136 ml/g was achieved, which was significantly lower than the value of 250 ml/g before the application of anoxic selector. The specific reaction rates for denitrification and nitrification at 30 degrees C were 0.06 mg NO3-N/mg MLSS day and 0.08 mg NH4-N/mg MLSS day, respectively. The overall efficiencies of nitrification and denitrification were 86 percent and 55.4 percent, respectively, with an alkalinity recovery ratio of 15.4 percent. 32 percent of total COD removed was used up as electron donor in the denitrification process. However, due to absence of the internal Mixed Liquor Recirculation (MLR), a higher degree of denitrification occurred in the secondary sedimentation tank than in the anoxic zone. Issues for further studies are also discussed.


Size- and shape-controlled synthesis of monodisperse vanadium dioxide nanocrystals.
Highly monodisperse VO2 nanocrystals with finely defined sizes and shapes were synthesized for the first time by thermolysis of single source vanadium precursor in high boiling point solvents of oleic acid (OA), oleylamine (OM), and octadence (ODE). The resulting VO2 nanocrystals were characterized by means of powder X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X-Ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). It was revealed that the low valence vanadium oxide of VO2 nanocrystals was successfully synthesized via this approach, and the obtained VO2 nanocrystals displayed uniform sizes and narrow size distribution with size variation in range of approximately 4-20 nm under various synthetic conditions. The previously unknown cubic, polyhedral shaped VO2 nanocrystals were achieved as well through modulating the preparative conditions. The solvent composition and precursor concentration are found to have profound effects on the sizes and shapes of the final VO2 nanocrystals. It is expected that the obtained VO2 nanocrystals with finely controlled sizes and shapes may be valuable candidates for studying and realizing the new size- and shape- dependent optical and electrical properties of VO2 materials in the nanoscale realm, and the novel synthetic method is potentially useful for the controlled synthesis of high quality doped VO2 and other vanadium oxides nanocrystals.


Rituximab in adult minimal change disease and focal segmental glomerulosclerosis.
Treatment of nephrotic syndrome due to minimal change disease and focal segmental glomerulosclerosis remains a challenge since steroid dependence, steroid resistance and a relapsing disease course exhibits a high cumulative steroid dosage. The necessity of using alternative steroid-sparing immunosuppressive agents with potential toxic side effects also restricts their long-term use. Rituximab, a monoclonal antibody targeting CD20, has been increasingly used in the therapy of difficult-to-treat nephrotic syndrome. A clinical response has been shown for patients with steroid-dependent or frequently relapsing nephrotic syndrome, whereas the benefit seems to be limited in steroid-resistant patients, especially those with underlying focal segmental glomerulosclerosis. No potentially life-threatening adverse events have been observed in the treatment of adult minimal change disease and focal segmental glomerulosclerosis following rituximab administration. Since most reports are retrospective and evidence of efficacy is derived from small case series, more prospective trials in a controlled, randomized manner are highly desirable to delineate the use of rituximab or other B cell-depleting agents in steroid-dependent, frequently relapsing or steroid-resistant patients.


Smart Meeting Room Usage Information and Prediction by Modelling Occupancy Profiles.
The monitoring of small houses and rooms has become possible due to the advances in IoT sensors, actuators and low power communication protocols in the last few years. As buildings are one of the biggest energy consuming entities, monitoring them has great interest for trying to avoid non-necessary energy waste. Moreover, human behaviour has been reported as being the main discrepancy source between energy usage simulations and real usage, so the ability to monitor and predict actions as opening windows, using rooms, etc. is gaining attention to develop stronger models which may lead to reduce the overall energy consumption of buildings, considering buildings thermal inertia and additional capabilities. In this paper, a case study is described in which four meeting rooms have been monitored to obtain information about the usage of the rooms and later use it to predict their future usage. The results show the possibility to deploy a simple and non-intrusive sensing system whose output could be used to develop advanced control strategies.


A Novel Vaccine Delivery Model of the Apicomplexan Eimeria tenella Expressing Eimeria maxima Antigen Protects Chickens against Infection of the Two Parasites.
Vaccine delivery is critical in antigen discovery and vaccine efficacy and safety. The diversity of infectious diseases in humans and livestock has required the development of varied delivery vehicles to target different pathogens. In livestock animals, previous strategies for the development of coccidiosis vaccines have encountered several hurdles, limiting the development of multiple species vaccine formulations. Here, we describe a novel vaccine delivery system using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria maxima. In this delivery system, the immune mapped protein 1 of E. maxima (EmIMP1) was delivered by the closely related species of E. tenella to the host immune system during the whole endogenous life cycle. The overexpression of the exogenous antigen did not interfere with the reproduction and immunogenicity of transgenic Eimeria. After immunization with the transgenic parasite, we detected EmIMP1's and E. maxima oocyst antigens' specific humoral and cellular immune responses. In particular, we observed partial protection of chickens immunized with transgenic E. tenella against subsequent E. maxima infections. Our results demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen delivery vehicle and represents a new type of coccidiosis vaccines. In addition, this model could potentially be used in the development of malaria live sporozoite vaccines, in which antigens from different strains can be expressed in the vaccine strain.


Salvage of a severely ischemic limb by arteriovenous revascularization: a case report.
Severe ischemia in a limb that cannot be revascularized almost inevitably leads to gangrene and eventual amputation. For decades, surgeons have considered utilizing the venous system to revascularize ischemic tissue in numerous areas, including the lower limb, but with very limited success. This report documents the successful revascularization of a severely ischemic pregangrenous limb with a bypass graft from the femoral artery to a tibial vein. The authors believe this is the first clinical report of salvage of an ischemic limb by this approach.


Molecular analysis of the (CGG)n expansion in the FMR-1 gene in 59 Spanish fragile X syndrome families.
The fragile X mental retardation syndrome is caused by an expansion of a trinucleotide repeat (CGG)n in the FMR-1 gene. Molecular genetic study of fragile X provides accurate diagnosis and facilitates genetic counseling in families with affected members. We present here the molecular study of 59 Spanish fragile X syndrome families using probe StB 12.3 and the polymerase chain reaction (PCR) of the (CGG)n repeat sequence of the FMR-1 gene. The results obtained have allowed us to characterize 455 individuals, including eight prenatal diagnoses. The clinical diagnosis of fragile X in 89 affected males was confirmed, 137 female carriers were identified (48 of whom were mentally retarded), 176 individuals "at risk" were found not to have the expansion, and 12 cases of normal transmitting males (NTM) were detected. In the sample studied, no de novo mutations were detected, nor any mutation different from that described for the (CGG)n expansion. One nonmentally retarded male was detected as having an unmethylated CpG island for the FMR-1 gene, but with more than 200 CGG repeats (high functioning male). The analysis of the (CGG)n repeat in 208 normal chromosomes gave an allele distribution similar to that in other Caucasoid population groups, with alleles of 29 and 30 CGG repeats accounting for 46% of the chromosomes. The combination of Southern analysis and PCR of the (CGG)n repeat is highly efficient for diagnosis, compared with cytogenetic techniques, especially in the detection of female carriers, NTMs, and prenatal diagnosis, enabling accurate genetic counseling to be provided in all cases.


Level IIb lymph nodes metastasis in elective supraomohyoid neck dissection for oral cavity squamous cell carcinoma: a molecular-based study.
To identify the incidence of level IIb lymph nodes metastasis in elective supraomohyoid neck dissection (SOHND) as a treatment for patients with squamous cell carcinoma (SCC) of the oral cavity. Prospective analysis of a case series. Forty-eight patients with SCC of the oral cavity and with no palpable lymph nodes at the neck who underwent an elective SOHND were prospectively studied. The incidence of micrometastasis to level IIb lymph nodes after performing elective SOHND was evaluated by pathologic examination and molecular analysis. Of the 48 patients, 15 (31%) by pathologic analysis and 22 (46%) by molecular analysis had lymph nodes positive for metastatic SCC. By molecular analysis, 5 (10%) of the 48 patients had involvement of level IIb lymph nodes. All patients with metastasis to level IIb lymph nodes have their primary lesions in the tongue and constituted 22% of patients with tongue lesions. There was no instance of isolated metastasis to level IIb lymph nodes without involvement of other nodes in the SOHND specimens. In this study, level IIb lymph node metastasis was only found in association with tongue carcinoma. Although this region may be preserved in elective SOHND in patients with SCC of the oral cavity, it should be included whenever the tongue is the primary site.


Strengths of Latinas in Spain: A Challenge for a Resilient Social Work Practice.
This article aims to break with two social stereotypes often held about Latinas in Spain. Authors analyze Latinas' main strengths from a resilient and intersectional approach, to consider them holistically within social work interventions. Rather than focusing on Latinas' difficulties, authors point to their multiple strengths and the ability to move forward. The study took place in the province of Tarragona, Catalonia (Spain). A qualitative approach was used. Participants included Latinas living in Tarragona and social workers from the Tarragona social services. The techniques used were nine life stories and 59 semi-open questionnaires with Latinas, and 14 interviews with social workers. The authors identified a fighting attitude and an entrepreneurial and creative spirit as both individual and collective strengths, especially within Latinas' social networks. Latinas did not recognize themselves as victims, nor did they claim to assume that identity. The social workers' interventions are implemented in a weak welfare system based on a model characterized by a paternalistic and victim-based viewpoint. Adopting approaches such as intersectionality and resilience would allow for the creation of fairer policies, programs, and projects targeted for Latinas, not just in Spain, but in other countries, too.


Implicit evaluation of familiar and novel concepts presented at low levels of conscious detectability.
In 2 experiments, implicit evaluation of novel and familiar concepts was assessed using a sequential priming procedure that enabled estimates of evaluative priming effects at low levels of detectability. In Experiment 1, the novel concepts referenced common names, and in Experiment 2 they referenced nonsense words. Whereas familiar concepts yielded priming effects at low levels of detectability in both experiments, novel concepts did not elicit any priming effect. Implicit evaluation of novel concepts has been documented in related research but under conditions that differ from those investigated here. The present results identify important limiting conditions associated with the implicit evaluation effect.


Artificial intelligence for prediction of biological activities and generation of molecular hits using stereochemical information.
In this work, we develop a method for generating targeted hit compounds by applying deep reinforcement learning and attention mechanisms to predict binding affinity against a biological target while considering stereochemical information. The novelty of this work is a deep model Predictor that can establish the relationship between chemical structures and their corresponding [Formula: see text] values. We thoroughly study the effect of different molecular descriptors such as ECFP4, ECFP6, SMILES and RDKFingerprint. Also, we demonstrated the importance of attention mechanisms to capture long-range dependencies in molecular sequences. Due to the importance of stereochemical information for the binding mechanism, this information was employed both in the prediction and generation processes. To identify the most promising hits, we apply the self-adaptive multi-objective optimization strategy. Moreover, to ensure the existence of stereochemical information, we consider all the possible enumerated stereoisomers to provide the most appropriate 3D structures. We evaluated this approach against the Ubiquitin-Specific Protease 7 (USP7) by generating putative inhibitors for this target. The predictor with SMILES notations as descriptor plus bidirectional recurrent neural network using attention mechanism has the best performance. Additionally, our methodology identify the regions of the generated molecules that are important for the interaction with the receptor's active site. Also, the obtained results demonstrate that it is possible to discover synthesizable molecules with high biological affinity for the target, containing the indication of their optimal stereochemical conformation.


Hazardous drinking, alcohol use disorders, and need for treatment among Pacific Islander young adults.
Pacific Islander (PI) young adults are suspected to bear heavy risk for hazardous drinking, alcohol use disorders (AUD), and alcohol-related harms. Yet, PIs remain among the most understudied racial groups in the United States-creating a lack of empirical data documenting their alcohol use problems and treatment needs. The present study presents the first known data on PI young adults' hazardous drinking, possible AUDs, alcohol-related harms, and treatment needs. Survey data were collected from 156 community-dwelling PI young adults (40% women, age 18-30 years) in 2 large PI communities: Los Angeles County and Northwest Arkansas. We screened participants for alcohol, cigarette, and marijuana use, hazardous drinking, possible AUD, alcohol-related harms, and past-year need for mental health and substance use disorder (SUD) treatment. Logistic regressions examined whether experiencing possible AUD and alcohol-related harms were associated with past-year need for treatment. PI young adults reported 78% lifetime rate of alcohol use with 56% screening positive for hazardous drinking, 49% for any possible AUD, and 40% experiencing significant alcohol-related harm (e.g., health, finances). Yet, just 25% of participants reported past-year need for SUD treatment. Although having possible AUD was not associated with perceived SUD treatment need, experiencing any alcohol-related harm associated with 4.7-13.2 times greater adjusted odds for needing treatment. Therefore, despite having low self-perceived treatment need, PI young adults experience excessive burden of hazardous drinking and alcohol-related harms. Given the profound negative social and health effects of AUDs, culturally grounded interventions should be designed to reduce PI young adults' elevated rates of hazardous drinking and alcohol-related harms. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


The tubulin mutation database: A resource for the cytoskeleton community.
Over the last 40 years, the phenotypic consequences of point mutations to tubulin genes have been described in a wide variety of eukaryotes. A publicly available web-based catalog of all published point mutations to tubulin was assembled. Each entry records a specific substitution to a discrete tubulin, the species where the mutation was described, the associated phenotype, and provides hyperlinks to the parental amino acid sequence and citation(s) for the original research. The data is represented in individual tables for the universal tubulin families (α-, β-, and γ-tubulins) with the smaller datasets for point mutations to δ-, ε-, and ζ-tubulins individually appended to the γ-tubulin mutation table. Because tubulins are highly conserved proteins, the benefit of organizing the database tables in order of amino acid position is that comparison between equivalent residues in different isotypes or species is straightforward. For example, it was shown that seven substitutions which are associated with human brain malformations known as tubulinopathies were previously identified in other contexts that suggest that they influence microtubule stability. It was anticipated that this resource will simplify evaluation of the role of specific amino acids or domains in microtubule function.


Mononuclear cells in exudative malignant pleural effusions. Characterization of pleural phagocytic cells.
The aims of this study were to develop a methodology for the isolation of highly enriched mononuclear phagocyte populations from exudative malignant pleural effusions (EMPE) and to characterize the phenotype and functional properties of these cells. Pleural effusion mononuclear cells (PEMC) were isolated by Ficoll centrifugation of EMPE and transudative pleural effusions and allowed to adhere to plastic for 1 h to obtain a pleural effusion mononuclear adherent cell (PEMAC) fraction. Only 66.0 +/- 4.2 percent of PEMAC ingested latex particles, indicating that a significant proportion of PEMAC were not phagocytic cells. Latex-positive PEMAC had the morphologic appearance of macrophages and stained positive (97.3 +/- 4.3 percent) with the anti-CD68 monoclonal antibody (MoAb), specific for macrophages. Conversely, latex-negative PEMAC (34.0 +/- 4.1 percent of PEMAC) did not react with the anti-CD68 MoAb and stained with anti-CD3 (34.7 +/- 10.7 percent) and anticytokeratin (50.5 +/- 16.4 percent) MoAbs, indicating that T cells and mesothelial cells were present in the PEMAC fraction. To improve the purification of pleural macrophages, PEMAC were cultured for an additional 18 h and the cells that remained adherent after this period constituted the firmly adherent mononuclear cell (FAMC) fraction. Nearly 90 percent of FAMC ingested latex particles and were CD68-positive. Virtually all FAMC were CD3-negative and cytokeratin-negative. Similar percentages of FAMC from EMPE and transudative effusions expressed the monocyte-lineage markers CD11b and CD14, suggesting that the proportion of monocyte-like mononuclear phagocytes in the pleural space is not increased during local tumor-associated inflammatory responses. The FAMC from EMPE (1) expressed HLA-DR antigens, (2) released interleukin 1 (IL-1) beta and tumor necrosis factor (TNF) alpha, and (3) stimulated allogeneic T-lymphocyte proliferation. The results of this study suggest that pleural mononuclear phagocytes may be involved in tumor-associated inflammatory reactions in the pleural compartment by stimulating the proliferation of other inflammatory cells and by releasing inflammatory cytokines.


Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.
Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.


Surveillance of some infectious diseases among aircrew personnel in Southeast Asia.
A 2-year analysis of specimens among aircrew personnel in Southeast Asia is reported. Stool specimens were examined for intestinal parasites and enteric bacteria, blood smears for blood parasites, and sera tested for transaminases (SGOT) and antibodies to Entamoeba histolytica, Toxoplasma gondii, Chikungunya and Japanese encephalitis viruses, Rickettsia tsutsugamushi, Leptospira sp. and Pseudomonas pseudomallei. One to four specimens each were obtained from 537 adult males and 20 females. There were 56 subjects with intestinal parasites as follows: Giardia lamblia (3.8%), Endolimax nana (2.6%), Entamoeba histolytica (1.4%), Entamoeba hartmanni (0.9%), Entamoeba coli (0.7%), Trichiuris trichiura (1.7%), Ascaris lumbricoides (1.4%), hookworm (0.9%), and Clonorchis sinensis (1.2%). Two individuals had malaria, Plasmodium vivax (0.6%). Pathogenic enteric bacteria were isolated from seven stool specimens; Shigella groups B and D (0.9%), Salmonella paratyphi (0.3%), and Arizona group (0.9%). Significantly elevated SGOT levels were found in 0.9% and antibodies to Japanese encephalitis virus in 1.5%, to Rickettsia tsutsugamushi in 1.2%, to Pseudomonas pseudomallei in 0.3%, to Entamoeba histolytica in 0.9% and to Toxoplasma gondii in 10.1%. No antibodies were found to Chikungunya virus or Leptospira sp.


Initial characterization of PMMA as a discriminative stimulus.
The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2-aminopropane, a structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been previously shown to unexpectedly lack amphetamine-like or hallucinogen-like stimulus properties in animals. For example, in tests of stimulus generalization, neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It has also been shown, however, that stimulus generalization does occur in animals trained to discriminate the designer drug MDMA ("Ecstasy" or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane) from vehicle. In order to further characterize this unique agent, we trained a group of six Sprague-Dawley rats to discriminate 1.25 mg/kg of PMMA (ED50 = 0.44 mg/kg) from saline vehicle. The PMMA stimulus failed to generalize to the phenylisopropylamine stimulant (+)amphetamine, or to the phenylisopropylamine hallucinogen DOM. Stimulus generalization occurred to (+/-)MDMA (ED50 = 1.32 mg/kg) and S(+)MDMA (ED50 = 0.48 mg/kg). Partial generalization occurred with R(+)MDMA, PMA, 3.4-DMA, and fenfluramine. The PMMA stimulus also generalized to the alpha-ethyl homolog of PMMA (EH/PMMA, ED50 = 1.29 mg/kg). Taken together, the results of these studies suggest that PMMA is an MDMA-like agent that lacks the amphetamine-like stimulant character of MDMA. These findings support our previous suggestion that PMMA be considered the structural parent of the MDMA-like family of designer drugs.


The Association Between Anticholinergic Medication Burden and Health Related Outcomes in the 'Oldest Old': A Systematic Review of the Literature.
Increased exposure to anticholinergic medication is problematic, particularly in those aged 80 years and older. The aim of this systematic review was to identify tools used to quantify anticholinergic medication burden and determine the most appropriate tool for use in longitudinal research, conducted in those aged 80 years and older. A systematic literature search was conducted across six electronic databases to identify existing tools. Data extraction was conducted independently by two researchers; studies describing the development of each tool were also retrieved and relevant data extracted. An assessment of quality was completed for all studies. Tools were assessed in terms of their measurement of the association between anticholinergic medication burden and a defined set of clinical outcomes, their development and their suitability for use in longitudinal research; the latter was evaluated on the basis of criteria defined as the key attributes of an ideal anticholinergic risk tool. In total, 807 papers were retrieved, 13 studies were eligible for inclusion and eight tools were identified. Included studies were classed as 'very good' or 'good' following the quality assessment analysis; one study was unclassified. Anticholinergic medication burden as measured in studies was associated with impaired cognitive and physical function, as well as an increased frequency of falls. The Drug Burden Index (DBI) exhibited most of the key attributes of an ideal anticholinergic risk tool. This review identified the DBI as the most appropriate tool for use in longitudinal research focused on older people and their exposure to anticholinergic medication burden.


Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: a systematic in-depth review.
High-density lipoprotein (HDL) particles exhibit multiple antiatherogenic effects. They are key players in the reverse cholesterol transport which shuttles cholesterol from peripheral cells (e.g. macrophages) to the liver or other tissues. This complex process is thought to represent the basis for the antiatherogenic properties of HDL particles. The amount of cholesterol transported in HDL particles is measured as HDL cholesterol (HDLC) and is inversely correlated with the risk for coronary artery disease: an increase of 1mg/dL of HDLC levels is associated with a 2% and 3% decrease of the risk for coronary artery disease in men and women, respectively. Genetically determined conditions with high HDLC levels (e.g. familial hyperalphalipoproteinemia) often coexist with longevity, and higher HDLC levels were found among healthy elderly individuals. HDLC levels are under considerable genetic control with heritability estimates of up to 80%. The identification and characterization of genetic variants associated with HDLC concentrations can provide new insights into the background of longevity. This review provides an extended overview on the current genetic-epidemiological evidence from association studies on genes involved in HDLC metabolism. It provides a path through the jungle of association studies which are sometimes confusing due to the varying and sometimes erroneous names of genetic variants, positions and directions of associations. Furthermore, it reviews the recent findings from genome-wide association studies which have identified new genes influencing HDLC levels. The yet identified genes together explain only a small amount of less than 10% of the HDLC variance, which leaves an enormous room for further yet to be identified genetic variants. This might be accomplished by large population-based genome-wide meta-analyses and by deep-sequencing approaches on the identified genes. The resulting findings will probably result in a re-drawing and extension of the involved metabolic pathways of HDLC metabolism.


[Growth inhibition effection of perlecan anti-sense cDNA on human laryngeal carcinoma xnograft in nude mice].
To observe growth inhibition effect of perlecan anti-sense cDNA (pAP) on human laryngeal carcinoma xnografted in nude mice. To vertify its antitumor effect and mechanism in vivo, and it may be useful as a biomarker in carcinoma of larynx cancer. Created the model of human laryngeal carcinoma xnograft in nude mice. To observe growth of those xnografts in nude mice and draw growth curve of xnografted. The expression of perlecan mRNA and portein in xnografts were examined by RT-PCR and immunohistochemistry. Volume of xnografts in the group transfected by the plasmids of pAP were significant small as compared with other two groups made by the wild type cells and phpApr-neol cells (P < 0.05). It was showed that the expression of perlecan mRNA and protein were significantly reduced in the tumor of pAP transfected Hep-2 cells as compared with the tumors transfected by the wild type cells and phβApr-neol cells (P < 0.01). These data raise the possibility that pAP many play key roles in the growth of those xnografts in nude mice.