The role of molecular methods in evaluating biological treatment processes.
Methods derived from molecular biology provide powerful new tools to analyze biological treatment processes. Because molecular methods can be used to directly interrogate genetic information about the microbial community, they can provide the fine detail that is impossible with the blunt, nondiscriminating information usually obtained from more traditional measures such as biochemical oxygen demand and volatile suspended solids. Molecular methods allow tracking of critical groups of microorganisms, such as ammonia oxidizers, that comprise a small fraction of the total biomass. Molecular methods also allow tracking of specific metabolic reactions or other functions that are key to the satisfactory performance of a system. Despite their power, molecular methods do not provide sufficient information when used alone. Aggregated measures and quantitative modeling remain necessary to establish mass balances, quantify the function of the microbial community, and connect the results of molecular assays to practice. Several examples involving nitrifying bacteria in activated sludge illustrate the fine detail available with molecular methods and how they can be linked to traditional and quantitative analyses. Other manuscripts in this special issue also provide examples of the value of using molecular tools in combination with traditional methods.


Natural product drug discovery and development: new perspectives on international collaboration.
Until recently, the prevailing attitude in developed nations regarded the world's genetic resources, which are mainly concentrated in the developing world, as a common resource of humankind, to be exploited freely irrespective of national origin. With the devastation being wreaked in the tropical rainforests and the resurgence in interest in recent years in the discovery of novel drugs from natural sources, particularly plants and marine organisms, the international scientific community has realized that the conservation of these global genetic resources and the indigenous knowledge associated with their use are of primary importance if their potential is to be fully explored. With this realization has come a recognition that these goals must be achieved through collaboration with, and fair and equitable compensation of, the scientists and communities of the genetically rich source countries. The signing of the United Nations Convention on Biological Diversity by nearly all of the World's nations has emphasized the need for the implementation of such policies. In this review, the articles of the Convention of relevance to the activities and practices of the natural products scientific community are briefly discussed. This discussion is followed by a summary of policies for international collaboration and compensation being implemented by several developed country organizations, and the perspectives on the current developments given by representatives of some of the source countries located in the regions of greatest biodiversity.


Reductive dechlorination of beta-hexachlorocyclohexane (beta-HCH) by a Dehalobacter species in coculture with a Sedimentibacter sp.
An anaerobic coculture was enriched from a hexachlorocyclohexane (HCH) polluted soil. The coculture reductively dechlorinates the beta-HCH isomer to benzene and chlorobenzene in a ratio of 0.5-2 depending on the amount of beta-HCH degraded. The culture grows with H(2) as electron donor and beta-HCH as electron acceptor, indicating that dechlorination is a respiratory process. Phylogenetic analysis indicated that the coculture consists of two bacteria that are both related to gram-positive bacteria with a low G + C content of the DNA. One bacterium was identified as a Dehalobacter sp. This bacterium is responsible for the dechlorination. The other bacterium was isolated and characterized as being a Sedimentibacter sp. This strain is not able to dechlorinate beta-HCH. The Dehalobacter sp. requires the presence of Sedimentibacter for growth and dechlorination, but the function of the latter bacterium is not clear. This is the first report on the metabolic dechlorination of beta-HCH by a defined anaerobic bacterial culture.


Long-term follow-up of hip subluxation in cerebral palsy patients.
Spastic subluxation of 64 hips in 45 patients with cerebral palsy (CP) was reviewed in a 19-year follow-up. Varus osteotomy prevented dislocation in all patients. All nine hips that later dislocated were in quadriplegic patients who had not received treatment or who had had muscle releases. Dislocated hips had the most degenerative arthritis, pain, and the least movement. Subluxated hips also had more degenerative arthritis but approximately the same level of pain as reduced hips.


Personalized HLA typing leads to the discovery of novel HLA alleles and tumor-specific HLA variants.
Accurate and full-length typing of the HLA region is important in many clinical and research settings. With the advent of next generation sequencing (NGS), several HLA typing algorithms have been developed, including many that are applicable to whole exome sequencing (WES). However, most of these solutions operate by providing the closest-matched HLA allele among the known alleles in IPD-IMGT/HLA Database. These database-matching approaches have demonstrated very high performance when typing well characterized HLA alleles. However, as they rely on the completeness of the HLA database, they are not optimal for detecting novel or less well characterized alleles. Furthermore, the database-matching approaches are also not adequate in the context of cancer, where a comprehensive characterization of somatic HLA variation and expression patterns of a tumor's HLA locus may guide therapy and clinical outcome, because of the pivotal role HLA alleles play in tumor antigen recognition and immune escape. Here, we describe a personalized HLA typing approach applied to WES data that leverages the strengths of database-matching approaches while simultaneously allowing for the discovery of novel HLA alleles and tumor-specific HLA variants, through the systematic integration of germline and somatic variant calling. We applied this approach on WES from 10 metastatic melanoma patients and validated the HLA typing results using HLA targeted NGS sequencing from patients where at least one HLA germline candidate was detected on Class I HLA. Targeted NGS sequencing confirmed 100% performance for the 1st and 2nd fields. In total, five out of the six detected HLA germline variants were because of Class I ambiguities at the third or fourth fields, and their detection recovered the correct HLA allele genotype. The sixth germline variant let to the formal discovery of a novel Class I allele. Finally, we demonstrated a substantially improved somatic variant detection accuracy in HLA alleles with a 91% of success rate in simulated experiments. The approach described here may allow the field to genotype more accurately using WES data, leading to the discovery of novel HLA alleles and help characterize the relationship between somatic variation in the HLA region and immunosurveillance.


The right of patients in mental hospitals to refuse drug treatment.
The use of antipsychotic drugs has caused conflicts between the medical decision concerning what is in a patient's best interests and the legal decision as to what treatment constitutes a violation of the mental patient's right to due process. The medical profession has a duty to treat patients; patients have a right to refuse medical treatment. With legislation leading to the release of mental patients into the community, the focus has turned away from treatment of a disease and toward prevention through changes in social policy. The law has recognized that the state has an interest in compelling treatment and that the patient has a right to refuse medical treatment. The rights of the state and the patient are not absolute and must be balanced by the judiciary. The result is that a mental patient's right to refuse antipsychotic drugs mut be determined on a case by case basis. The authors propose that states pass legislation covering the rights of mental patients. A model bill is proposed at the end of the article. It establishes a procedural system which addresses the issues of informed consent, competency, emergencies, medical review, and judicial review.


Analysis of genotype 2 and 3 hepatitis C virus variants in patients treated with telaprevir demonstrates a consistent resistance profile across genotypes.
Study C209 evaluated the activity of telaprevir in treatment-naïve patients with genotypes 2 or 3 (G2, G3) hepatitis C virus (HCV) infection. Telaprevir monotherapy showed potent activity against HCV G2, but limited activity against G3. This analysis was performed to characterize HCV viral variants emerging during telaprevir-based treatment of G2/G3 HCV-infected patients. Patients were randomized to receive 2 weeks of treatment with telaprevir (telaprevir monotherapy), telaprevir plus peginterferon alfa-2a and ribavirin (triple therapy), or placebo plus peginterferon alfa-2a and ribavirin (control), followed by 22-24 weeks of peginterferon/ribavirin alone. Viral breakthrough was defined as an increase >1 log10 in HCV RNA from nadir, or HCV RNA >100 IU/mL in patients previously reaching <25 IU/mL. Twenty-three patients (47%) had G2 and 26 (53%) had G3 HCV. Viral breakthrough occurred during the initial 2-week treatment phase in six G2 patients (66.7%; subtypes 2, 2a and 2b) and three G3 patients (37.5%; all subtype 3a), all in the telaprevir monotherapy arm. Four breakthrough patients (three G2, one G3) subsequently achieved sustained virologic response (SVR). In all patients with breakthrough and available sequence data, mutations associated with reduced susceptibility to telaprevir in genotype 1 (G1) HCV were observed. No novel G2/G3-specific mutations were associated with telaprevir resistance. The telaprevir resistance profile appeared consistent across HCV genotypes 1, 2 and 3. Although viral breakthrough with resistance occurred in patients receiving telaprevir monotherapy, half of these patients achieved an SVR upon addition of peginterferon/ribavirin highlighting the importance of combination therapy.


Transition path times reveal memory effects and anomalous diffusion in the dynamics of protein folding.
Recent single-molecule experiments probed transition paths of biomolecular folding and, in particular, measured the time biomolecules spend while crossing their free energy barriers. A surprising finding from these studies is that the transition barriers crossed by transition paths, as inferred from experimentally observed transition path times, are often lower than the independently determined free energy barriers. Here we explore memory effects leading to anomalous diffusion as a possible origin of this discrepancy. Our analysis of several molecular dynamics trajectories shows that the dynamics of common reaction coordinates used to describe protein folding is subdiffusive, at least at sufficiently short times. We capture this effect using a one-dimensional fractional Brownian motion (FBM) model, in which the system undergoes a subdiffusive process in the presence of a potential of mean force, and show that this model yields much broader distributions of transition path times with stretched exponential long-time tails. Without any adjustable parameters, these distributions agree well with the transition path times computed directly from protein trajectories. We further discuss how the FBM model can be tested experimentally.


Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis.
An activation of T-cells that is restricted to the lung has been demonstrated in pulmonary sarcoidosis. The role of blood monocytes (MO) and alveolar macrophages (AM) in this concept of compartmentalized inflammation has not yet been evaluated. In order to elucidate this question, we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by peripheral blood mononuclear cells (PBMNC) and AM in 43 patients with sarcoidosis (32 with active, 11 with inactive disease) without therapy and correlated the spontaneous monokine release to parameters of the T-cell alveolitis and the course of the disease. TNF alpha as well as IL-1 were spontaneously released by AM of the active group, i.e., 2,385 +/- 735 pg/ml/10(8) cells/24 h and 7/12 (IL-1+/total), respectively. Autologous PBMNC were quiescent, releasing only baseline levels of any monokine. AM were not activated in the inactive group, releasing 500 +/- 212 pg/ml/10(6) cells/24 h TNF alpha, whereas 1/5 were IL-1-positive (p less than 0.05 in both comparisons), which is within the range of the control group. Kinetic experiments revealed that the TNF alpha gene of AM is activated in vivo, resulting in TNF alpha mRNA-positive, TNF alpha-releasing cells that, cultured in vitro, regulate the TNF alpha gene transcription down and cease to release TNF alpha. Interestingly, there is no stringent correlation between the spontaneous release of TNF alpha by AM and signs of T-cell activation as soluble interleukin-2 (IL-2) receptor serum concentration, release of IL-2, and expression of IL-2 receptor by alveolar T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Screening for non-alcoholic fatty liver disease in children and adolescents with type 1 diabetes mellitus: a cross-sectional analysis.
The liver is intensely involved in glucose metabolism and is thereby closely related to diabetes pathophysiology. Adult patients with type 1 diabetes mellitus (DM) are at an increased risk for non-alcoholic fatty liver disease (NAFLD). Here, we studied the prevalence of NAFLD in a cohort of children and adolescents with type 1 DM in a tertiary care paediatric diabetes centre in Germany. We screened 93 children and adolescents with type 1 DM using ultrasound, laboratory investigations, and liver stiffness measurements (Fibroscan® [FS] and acoustic radiation force imaging [ARFI]). Of these, 82 (88.1%) had completely normal results in all examined aspects. Only one patient (1.1%) fulfilled the criteria as potential NAFLD with ALT > twice the upper limit of normal. Ten of the 93 patients (10.8%) showed any mild abnormality in at least one examined category including ALT, conventional ultrasounds and liver stiffness measurements. However, none of these ten fulfilled the NAFLD case definition criteria. Therefore, these slightly abnormal results were judged to be unspecific or at least of unknown significance in terms of NAFLD indication. Compared to data from the general population, our results do not indicate a significantly increased prevalence of NAFLD in this cohort, and advocate against the systematic screening for NAFLD in paediatric type 1 DM. What is Known: • Non-alcoholic fatty liver disease (NAFLD) is common in adults with type 1 DM, and paediatric patients with type 1 DM in Egypt and Saudi Arabia. What is New: • Our results do not indicate a significantly increased prevalence of NAFLD in a cohort of children and adolescents with type 1 DM from Germany compared to prevalence data from the general population. • This finding advocates against the systematic screening for NAFLD in paediatric type 1 DM in western countries.


Atom Probe Tomography Analysis of Ag Doping in 2D Layered Material (PbSe)5(Bi2Se3)3.
Impurity doping in two-dimensional (2D) materials can provide a route to tuning electronic properties, so it is important to be able to determine the distribution of dopant atoms within and between layers. Here we report the tomographic mapping of dopants in layered 2D materials with atomic sensitivity and subnanometer spatial resolution using atom probe tomography (APT). APT analysis shows that Ag dopes both Bi2Se3 and PbSe layers in (PbSe)5(Bi2Se3)3, and correlations in the position of Ag atoms suggest a pairing across neighboring Bi2Se3 and PbSe layers. Density functional theory (DFT) calculations confirm the favorability of substitutional doping for both Pb and Bi and provide insights into the observed spatial correlations in dopant locations.


Diagnosis and Management of an Inferior ST-elevation Myocardial Infarction: A Simulation Scenario.
Immediate diagnosis and management of ST-elevation myocardial infarction (STEMI), a condition resulting from the complete occlusion of a coronary artery, is critical to achieving optimal patient outcomes. This report outlines an acute inferior STEMI simulation which can be used for teaching different levels of learner including novice, intermediate and advanced. It focuses on the presentation, diagnosis, and management of inferior myocardial infarctions. Additionally, it incorporates the advanced cardiovascular life support (ACLS) protocol for more advanced learners and uses the CanMEDS collaborator/communicator role as an adjunct objective for all learners.


[Effect of posture on pharyngeal area measured by acoustic reflection technique].
Patients with obstructive sleep apnea (OSA) have a smaller pharyngeal area (PA) and higher compliance than normal subjects. The apnea-hypopnea index (AHI) in OSA patients determined by polysomnographic study was greater in the supine than lateral position. Recently there have been reports of reduction in the PA by the acoustic reflection technique (ART) in the supine position. However, there has been no report on the PA measured by ART in the lateral position which is important in the treatment of OSA. To evaluate differences in the PA with posture changes, we measured the PA in 41 normal subjects (11 males and 30 females) in the sitting, lateral and supine positions by ART. The average PA in the sitting position in the males and females was 3.8 +/- 0.6 cm2, and 3.3 +/- 0.5 cm2, respectively. The average PA in the lateral position in the males and females was 3.5 +/- 0.6 cm2, and 3.1 +/- 0.5 cm2, respectively. The average PA in the supine position in the males and females was 2.9 +/- 0.5 cm2, and 2.7 +/- 0.4 cm2, respectively. PA in the sitting position correlated well with body surface area (BSA). The average PA in both the males and females was significantly smaller in the supine than in the sitting position. The average PA in the lateral position in both males and females was significantly smaller than that in the sitting position and was significantly larger than that in the supine position. Decrease in PA with posture (from sitting to lateral) in the males (9.2 +/- 5.5%) was similar to that in the female (5.7 +/- 5.4%). Decrease in PA with posture (from sitting to supine) was significantly larger in male (24.4 +/- 9.5%) than in female (16.6 +/- 6.8%). We conclude that the decrease of PA in the supine position is ameliorated in the lateral position in normal subjects. Lateral position may be the preferred sleeping position in snoring or OSA patients.


Bcl-2 expression correlates with favourable outcome in head and neck cancer treated by accelerated radiotherapy.
The aim of this study was to investigate bcl-2 expression in head and neck cancer patients and to investigate its correlation with biological and clinical characteristics and outcome of accelerated radiotherapy. A series of 93 patients with squamous cell carcinoma of the head and neck who had been uniformly treated with continuous hyperfractionated accelerated radiation treatment (CHART) were investigated. These patients had also been injected with bromodeoxyuridine (BrdUrd) to measure cell kinetic parameters using flow cytometry (FCM) and their p53 protein status had also previously been described. Bcl-2 expression was assessed using immunohistochemistry. Sixteen of the 93 (17.2%) patients stained positively for bcl-2 proto-oncogene. The percentage of positive tumour cells within the specimens was highly variable, ranging from a few percent to complete positivity. Bcl-2 positivity was correlated with improved local control (p > 0.0016) and survival (p > 0.012) in comparison with non-expressing tumours. There was no correlation between bcl-2 expression and histological grade, T stage or site but overexpressors were almost exclusively node negative. The significance of bcl-2 was reduced when node negative tumours were analysed alone. There was no correlation of bcl-2 with p53 expression but there was a trend for overexpression to be associated with diploidy and rapidly proliferating tumours. These data suggest that bcl-2 expression in head and neck cancer is not associated with disease progression.


Managing the infected knee: as good as it gets.
The clinical presentation is a useful guide for selecting the treatment of an infected total knee arthroplasty. Prosthesis retention is indicated in patients with infections that occur within 30 days after arthroplasty and in patients with well-functioning prostheses who develop an acute late hematogenous infection. Débridement attempts should be open and not arthroscopic. When prosthesis removal is required, the preferred approach is a delayed reconstructive technique, the 2-staged reimplantation, rather than a direct-exchange procedure. The use of block spacers or mobile articulating devices to deliver high-dose local antibiotics is recommended between implant removal and delayed revision surgery. The use of antibiotic-loaded acrylic cement for cemented prostheses or antibiotic-soaked bone-graft with cementless prostheses is helpful in the overall cure rate of infection.


[Analysis of zinc concentrations in leukocytes and its application to patients with non-insulin-dependent diabetes mellitus].
Zinc concentrations in leukocytes of healthy subjects and patients with NIDDM were determined by inductively coupled plasma mass spectrometry. Lymphocytes and granulocytes were isolated from whole blood by discontinuous gradients of mono-poly resolving medium and flow cytometry. Flow cytometry was used for isolating lymphocytes and granulocytes from mononuclear and polymorphonuclear leukocytes. The results in healthy subjects and patients with NIDDM were as follows: lymphocytes of healthy male and female subjects were 49.8 +/- 1.0 (mean +/- SE, microgram per 10(10) cells) and 50.0 +/- 1.4, respectively; granulocytes were 46.4 +/- 1.0 in male, 49.3 +/- 1.4 in female. Lymphocytes of male and female patients with NIDDM were 43.3 +/- 0.9 and 43.1 +/- 1.7, respectively; granulocytes, 41.2 +/- 1.4 in male, 43.8 +/- 1.0 in female. There was a significant difference in the zinc concentrations of lymphocytes and granulocytes between healthy subjects and patients with NIDDM. However, there was no significant difference in the zinc concentrations of lymphocytes and granulocytes between male and female. In healthy subjects, zinc concentrations of lymphocytes and granulocytes significantly lowered with aging.


Calcium modulates promoter occupancy by the Entamoeba histolytica Ca2+-binding transcription factor URE3-BP.
The Entamoeba histolytica upstream regulatory element 3-binding protein (URE3-BP) binds to the URE3 sequence of the Gal/GalNAc-inhibitable lectin hgl5 and ferredoxin 1 (fdx) gene promoters. This binding can be inhibited in vitro by addition of calcium. Two EF-hand motifs, which are associated with the ability to bind calcium, are present in the amino acid sequence of URE3-BP. Mutation of the second EF-hand motif in URE3-BP resulted in the loss of calcium inhibition of DNA binding as monitored by electrophoretic mobility shift assay. Chromatin immunoprecipitation assays revealed that URE3-BP was physically bound to the hgl5 and fdx promoters in vivo. Parasite intracellular calcium concentrations were altered by changes in extracellular calcium. Promoter occupancy was lost when intracellular calcium levels were increased by coordinate increases in extracellular calcium. Increased intracellular calcium also resulted in decreased levels of URE3-BP mRNA. Together these results demonstrate that changes in extracellular calcium result in changes in URE3-BP mRNA and in the ability of URE3-BP to bind to URE3-containing promoters. Modulation of URE3-BP by calcium may represent an important mechanism of control of gene expression in E. histolytica.


Prospective cytochrome P450 phenotyping for neuroleptic treatment in dementia.
Older patients have more adverse experiences when treated with psychotropics than younger patients. Age-associated physiological changes, such as reductions in hepatic mass and blood flow, magnify genetic and acquired variations in drug metabolism. Cytochrome P450 2D6 (debrisoquine hydroxylase), which is responsible for the metabolism of several antidepressants and neuroleptics, is constitutionally deficient in up to 10 percent of the population. In this study of 45 elderly patients suffering from dementia and treated with perphenazine, 5 patients who were prospectively identified as poor P450 2D6 metabolizers had significantly greater side effects than the 40 extensive metabolizers.


Hemostasis of the thyroid carcinoma invading the skin and trachea. Conservative treatment.
In most instances, the prognosis of well-differentiated thyroid carcinoma is generally favorable and adequately controlled by surgery alone. In some cases, however, in which the tumor has remained or in recurrent cases, infiltrates surrounding the skin or trachea can result in uncontrollable hemorrhage which cannot be treated with conventional medical or surgical therapy. We present our attempts at hemostatic procedures in such cases. When a thyroid cancer for which radical surgery is not indicated invades the skin with hemorrhage, we remove the ulcerated skin area with as much of underlying cancerous tissue as possible, and cover the defect skin area with a Bakamjian's deltopectoral flap or a musculocutaneous flap. In the 4 cases we have experienced, there had been no ulceration of the flap skin or recurrent. When a thyroid cancer invades the tracheal wall resulting in an intratracheal tumor accompanied by hemoptysis, we attempt to perform bronchoscopic cauterization using Nd-YAG Laser. Cauterization is repeatedly performed weekly, up to five times in one series. In all cases, radioiodine therapy is used before or after treatment. In all 4 cases we have experienced, hemostasis and shrinkage of the tumor was achieved. No complication such as ulcer formation or perforation was noted.


Student nurses' attitudes towards adolescents and their care in hospital.
The aim of this study was to explore nursing students' attitudes towards adolescents and their care in hospital. A questionnaire containing a series of open-ended questions was emailed to a sample of 50 child branch degree-level students in their second, third or fourth year at a West Midlands university; 14 (28 per cent) responded. It was found that the students had a good knowledge of young people and of their needs while in hospital. They did not report strong negative attitudes towards adolescents but suggested that a number of factors affected their attitudes towards nursing young people, including media reports and the attitudes of mentors. Most of the students expressed a preference for working with younger children, partly because the students lacked experience and confidence, and partly because of a lack of age-appropriate resources in ward areas, which made caring for adolescents more challenging. It was concluded that more could be done to improve student exposure to adolescent patients and that inadequate inpatient facilities, rather than staff attitudes and knowledge, may prevent some young people receiving good quality care in hospital.


Electrospinning Nanofibers for Therapeutics Delivery.
The limitations of conventional therapeutic drugs necessitate the importance of developing novel therapeutics to treat diverse diseases. Conventional drugs have poor blood circulation time and are not stable or compatible with the biological system. Nanomaterials, with their exceptional structural properties, have gained significance as promising materials for the development of novel therapeutics. Nanofibers with unique physiochemical and biological properties have gained significant attention in the field of health care and biomedical research. The choice of a wide variety of materials for nanofiber fabrication, along with the release of therapeutic payload in sustained and controlled release patterns, make nanofibers an ideal material for drug delivery research. Electrospinning is the conventional method for fabricating nanofibers with different morphologies and is often used for the mass production of nanofibers. This review highlights the recent advancements in the use of nanofibers for the delivery of therapeutic drugs, nucleic acids and growth factors. A detailed mechanism for fabricating different types of nanofiber produced from electrospinning, and factors influencing nanofiber generation, are discussed. The insights from this review can provide a thorough understanding of the precise selection of materials used for fabricating nanofibers for specific therapeutic applications and also the importance of nanofibers for drug delivery applications.


Linear and Nonlinear Bullets of the Bogoliubov-de Gennes Excitations.
We report on the focalization of Bogoliubov-de Gennes excitations of the nonlinear Schrödinger equation in the defocusing regime (Gross-Pitaevskii equation for repulsive Bose-Einstein condensates) with a spatially modulated periodic potential. Exploiting the modification of the dispersion relation induced by the modulation, we demonstrate the existence of localized structures of the Bogoliubov-de Gennes excitations, in both the linear and nonlinear regimes (linear and nonlinear "bullets"). These traveling Bogoliubov-de Gennes bullets, localized both spatially and temporally in the comoving reference frame, are robust and propagate remaining stable, without spreading or filamentation. The phenomena reported in this Letter could be observed in atomic Bose-Einstein condensates in the presence of a spatially periodic potential induced by an optical lattice.


MnO2/CNT supported Pt and PtRu nanocatalysts for direct methanol fuel cells.
Pt/MnO2/carbon nanotube (CNT) and PtRu/MnO2/CNT nanocomposites were synthesized by successively loading hydrous MnO2 and Pt (or PtRu alloy) nanoparticles on CNTs and were used as anodic catalysts for direct methanol fuel cells (DMFCs). The existence of MnO2 on the surface of CNTs effectively increases the proton conductivity of the catalyst, which then could remarkably improve the performance of the catalyst in methanol electro-oxidation. As a result, Pt/MnO2/CNTs show higher electrochemical active surface area and better methanol electro-oxidation activity, compared with Pt/CNTs. As PtRu alloy nanoparticles were deposited on the surface of MnO2/CNTs instead of Pt, the PtRu/MnO2/CNT catalyst shows not only excellent electro-oxidation activity to methanol with forward anodic peak current density of 901 A/gPt but also good CO oxidation ability with lower preadsorbed CO oxidation onset potential (0.33 V vs Ag/AgCl) and peak potential (0.49 V vs Ag/AgCl) at room temperature.


Lipid Signaling Requires ROS Production to Elicit Actin Cytoskeleton Remodeling during Plant Innate Immunity.
In terrestrial plants a basal innate immune system, pattern-triggered immunity (PTI), has evolved to limit infection by diverse microbes. The remodeling of actin cytoskeletal arrays is now recognized as a key hallmark event during the rapid host cellular responses to pathogen attack. Several actin binding proteins have been demonstrated to fine tune the dynamics of actin filaments during this process. However, the upstream signals that stimulate actin remodeling during PTI signaling remain poorly characterized. Two second messengers, reactive oxygen species (ROS) and phosphatidic acid (PA), are elevated following pathogen perception or microbe-associated molecular pattern (MAMP) treatment, and the timing of signaling fluxes roughly correlates with actin cytoskeletal rearrangements. Here, we combined genetic analysis, chemical complementation experiments, and quantitative live-cell imaging experiments to test the role of these second messengers in actin remodeling and to order the signaling events during plant immunity. We demonstrated that PHOSPHOLIPASE Dβ (PLDβ) isoforms are necessary to elicit actin accumulation in response to flg22-associated PTI. Further, bacterial growth experiments and MAMP-induced apoplastic ROS production measurements revealed that PLDβ-generated PA acts upstream of ROS signaling to trigger actin remodeling through inhibition of CAPPING PROTEIN (CP) activity. Collectively, our results provide compelling evidence that PLDβ/PA functions upstream of RBOHD-mediated ROS production to elicit actin rearrangements during the innate immune response in Arabidopsis.


The potential for prehospital thrombolytic therapy.
Several large trials of thrombolytic therapy have shown that treatment initiated in the first 1 or 2 hours following the onset of symptoms of acute myocardial infarction (AMI) is more effective than therapy started later in the course of illness. From our experience in three thrombolytic trials we concluded it would be difficult to reduce the total time from symptom onset to therapy without a major change in patient management. To accomplish this goal we have initiated MITI (Myocardial Infarction Triage and Intervention Project), a program for the prehospital diagnosis of AMI using specially trained paramedics, a checklist to establish eligibility for and contraindications to thrombolytic therapy, and a portable, battery-powered 12-lead electrocardiography (ECG) cellular telephone system that allows an electrocardiographic diagnosis to be made remotely by an emergency department physician. In the feasibility phase of MITI, 2,472 patients with chest pain of presumed cardiac origin were evaluated; 677 (27%) met the rigorous history and physical exam inclusion and exclusion criteria for potential thrombolytic therapy and had an ECG performed in the field. Of these ECGs, 522 were transmitted successfully by cellular telephone to a base station physician. Of the 522 patients, 107 had ST-segment elevation and met our criteria for initiation of thrombolytic therapy. Of the 2,472 patients with chest pain evaluated by the emergency medical technicians, 453 (18%) were diagnosed with AMI during hospitalization. Of these AMI patients, only 105 (23%) met the clinical examination and ECG criteria for pre-hospital thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cloning and structure analysis of a restriction and modification system, LlaBIII from Lactococcus lactis subsp. cremoris W56].
A 22.4 kb naturally occurring plasmid pJW566, isolated from L. lactis W56, was found to encode an R/M system named LlaBIII. The LlaBIII R/M system was isolated on a chloramphenicol resistant derivative of plasmid pJW566, resulting in a plasmid pJK1. Subcloning analysis showed that the LlaBIII determinant was located on a 5 kb HindIII-Sph I fragment. The fragment was sequenced. It contained a single open reading frame (ORF), corresponding to a protein of 1584 or 1576 aa. In the deduced amino acid sequence seven helicase motifs characteristic of endonuclease type I and type III and a conserved catalysis motif X in the R subunits of type I R/M systems were located in the N-terminus, followed by four conserved motifs found in DNA N6-adenine methyltransferases. The C-terminus of the deduced amino acid sequence showed no homology to known R/M systems. Therefore, this polypeptide encoded by LlaBIII is a multifunctional protein possessing putative DNA recognition, methylation and restriction activities.


Photocontrol of gibberellin metabolism in situ in maize.
Mature maize seeds were labeled with 10 to 100 pg per seed of [(3)H] gibberellins (GA) and [(3)H]GA glucosyl conjugate-like substances by feeding [(3)H]GA(20) of high specific activity (2.3 Curies per millimole) during seed maturation. The dry seeds, which contained 14% [(3)H]GA(20), 7% putative [(3)H]GA(1) and 78% [(3)H]GA glucosyl conjugate-like metabolites, were imbibed and germinated in the dark and under incandescent light. In both light and dark the proportion of [(3)H]GA conjugate-like metabolities declined (relative to that in the mature dry seeds) during imbibition and up to germination at hour 36. This decline was accompanied by increases in the proportions of [(3)H]GA(20) and putative [(3)H]GA(1) thereby indicating hydrolysis, which was greater in the dark than in the light. The proportions of [(3)H]GA conjugate-like substances in light-grown germinants were higher (121 and 141% of dark-grown) at 24 and 48 hour harvests and this statistically significant pattern was sustained up to 120 hours after imbibition. Conversely, the proportions of [(3)H]GA(20) and putative [(3)H]GA(1) were lower in the light-grown seedlings. Thus, during imbibition, hydrolysis (de-conjugation) of [(3)H]GA glucosyl conjugate-like substances apparently occurred, and occurred more rapidly in the dark than in the light. Subsequently, during germination the reformation of [(3)H]GA conjugate-like substances was less rapid in the dark than in the light. The observation that dark-imbibed seeds and dark-grown seedlings have higher proportions of putative free [(3)H]GAs, relative to [(3)H]GA conjugate-like substances, is consistent with the increased shoot elongation (etiolation) that occurs in dark-grown maize seedlings, and may indicate a homeostatic role for GAs and their conjugates in shoot elongation of maize germinants.


[Immediate evaluation of continuous medical education].
To analyse the results of the immediate evaluation of an European teaching session using a questionnaire provided by the French College of anaesthesiologists. Open evaluation. Questionnaires completed after each topic by 50 participants of an European course including 15 lectures were collected. The types of professional exercise and the medical practise reliable to the different topics were pointed out. The evaluation included 4 items noted from 1 to 10: new information for medical practise, definition of pedagogic objectives, quality of means used for teaching, interest for the treated subject. The global mean score for each item and for each speaker was calculated. Results were compared according to the professional mode of exercise, the own medical practise and the project to modify it in the future. Scores affected to items were significantly lower for participants exercising in PSPH compared to general and university hospitals and private clinics (p < 0.001). New information was better found in case of poor or absence of practise, but interest was improved when medical practise was frequent. 2/3 of the participants projected to modify their practise after the session. The analysis of medical evaluation should allow to determine an acceptable zone of quality which may be useful for accreditation. However, distorting results according to the professional mode of exercise and the own medical practise should encourage the development of adapted continuous medical education. Delayed evaluation may be necessary to objective the putative benefits of CME on medical practise.


Humanin Ameliorates Late-onset Hypogonadism in Aged Male Rats.
The potential to reproduce declines with age. Late-onset hypogonadism is characterized by reduced serum testosterone. Humanin is a mitochondrial-derived signaling peptide encoded by short open reading frames within the mitochondrial genome. It may protect against some age-related diseases such as atherosclerosis by its cytoprotective effects. The study aimed to investigate the potential anti-aging effects of humanin on the testicular architecture, oxidative stress, some apoptotic and inflammatory markers in the hypogonadal aged male rats. Forty male albino rats were divided into 4 groups: normal adult controls, aged vehicle- treated group, aged testosterone-treated group, and aged humanin-treated group. Twenty-month- old male rats with declined serum testosterone were selected to be the animal models of lateonset hypogonadism. Testicular weights, serum testosterone, and some sperm parameters were measured. Testicular tissue IL-6 and TNF-α, superoxide dismutase activity, glutathione peroxidase, and malondialdehyde were assessed. The activity of caspase-3, BCL2, PCNA, and the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway were evaluated. Testes were subjected to histopathological and immunohistochemical examination. Statistical analysis was executed using. One Way Analysis of variance (ANOVA) followed by Post hoc (LSD) test to compare means among all studied groups. Humanin treatment significantly improved serum testosterone, sperm characteristics, and antioxidant defenses. It decreased active caspase-3, pro-apoptotic BAX expression, and increased antiapoptotic BCL2 and proliferating cell nuclear antigen (PCNA) possibly via activating the (Nrf2- ARE) pathway. Humanin might be a promising therapeutic modality in late-onset hypogonadism as it ameliorated some age-related testicular and hormonal adverse effects.


Synergistic Effects of Cryptotanshinone and Senkyunolide I in Guanxinning Tablet Against Endogenous Thrombus Formation in Zebrafish.
Thrombosis is a key pathological event in cardiovascular diseases, and is also the most important targeting process for their clinical management. New drug development in thrombosis treatment is still in great demand. According to the traditional Chinese medicine (TCM) theory, thrombosis belongs to the syndrome of blood stasis. Salvia miltiorrhiza Bunge and Ligusticum striatum DC. are two common TCM herbs with long-term documented function in promoting blood circulation and inhibiting thrombosis, especially when used together. Guanxinning Tablet, a modern Chinese drug which contains extracts of the two herbs, also showed strong therapeutic effects in coronary heart disease. However, the pharmacological mechanism is still lacking for the compatibility of the two herbs. Here, through zebrafish-based in vivo fluorescence screening, we demonstrated the synergistic effects between S. miltiorrhiza Bunge and L. striatum DC. in regulating endogenous thrombosis. Moreover, combined with high-resolution mass spectrometry, the main compounds of the botanical drugs were analyzed and screened in our model system. Interestingly, cryptotanshinone and senkyunolide I, two representative compounds, respectively derived from the two herbs, also showed synergistic antithrombotic effects. Further analysis suggested that they may regulate thrombi formation at different levels via multiple signaling pathways, including oxidative stress, platelet activation and coagulation cascade. Taken together, our findings provided solid biological supports toward the drug compatibility theory of TCM, and suggested cryptotanshinone and senkyunolide I as promising drug candidates in thrombosis management.


Blunt traumatic bronchial rupture in patients younger than 18 years.
The aim of this study was to evaluate our results of management of bronchial rupture after blunt chest trauma in young patients. Between January 2000 and December 2007, 34 patients aged 6-18-years old were treated for bronchial rupture; 25 presented early and 9 presented late. The 21 (62%) boys and 13 (38%) girls had a mean age of 11.58 +/- 2.51 years. Radiography, computed tomography, and rigid bronchoscopy were performed in stable acute cases and late-presenting cases, with rapid bronchoscopy followed by thoracotomy in urgent cases. In the patients who presented early, repair was undertaken through a right thoracotomy in 21 (84%) and via a left thoracotomy in 4 (16%). Direct suturing was carried out in all except 3 patients who needed lobectomy. Reimplantation of the main bronchus after debridement of the edges was possible in 4 (44%) of the chronic cases, and pulmonary resection was required in 5 (56%). Four (11.8%) patients died due to perioperative cardiac arrest and cerebral hypoxia with failure of resuscitation. Meticulous collaboration between the surgeon and anesthetist is important to ensure survival.


The role of C3 in mediating binding and ingestion of group B streptococcus serotype III by murine macrophages.
To understand how complement effects phagocytosis of type III group B streptococcus, we assessed the specific role of C3 in mediating binding and ingestion of these bacteria by macrophages. Phagocytosis of bacteria by resident mouse peritoneal macrophages was measured under conditions in which C3 deposition on bacteria was inhibited or after blockade of C3-ligands or of complement receptor type three (CR3) with specific antibodies. C3 depletion, incubation with F(ab')2 fragments of antibody to C3, or blockade of CR3 completely inhibited the binding of bacteria that was seen in the presence of nonimmune serum. Immune serum increased the number of associated organisms 6-fold compared to that seen with nonimmune serum. With this serum, 82% of organisms were ingested. C3 depletion or CR3 blockage had a modest effect, but this interaction could be ablated completely only after Fc receptors were blocked. Using varied concentrations of an IgG2a MAb against type III capsular antigen, it was possible to show that small amounts of antibody incapable of mediating bacterial binding by itself directed an interaction that also depended upon C3. Phagocytosis of group B streptococci by macrophages in the presence of little or no antibody requires complement and C3 opsonization specifically. C3-dependent binding may be important in determining mononuclear phagocyte-dependent clearance of these pathogens from blood, particularly in patients with little or no type-specific serum antibody.


Transition rates between specialization and generalization in phytophagous insects.
Although most species of animals exhibit specialized patterns of resource use, it is unclear whether specialization evolves at a faster rate than generalization. To test this hypothesis, transition rates toward specialization and toward generalization were estimated using phylogenies from 15 groups of phytophagous insects. Among the groups studied, maximum-likelihood analyses showed that the forward transition rate from generalization to specialization was significantly higher than the reverse transition rate from specialization to generalization (mean ratio of forward to reverse transition rate = 1.47 using uniform branch lengths and 1.76 using Grafen branch lengths). Although phylogenetic conservatism of host-plant use is common, the results suggest that the evolution of specialization is a highly dynamic process. For example, higher transitions rates both toward and away from specialization as well as equal transition rates were inferred. Collectively, the results reveal a tendency for directional evolution toward increased specialization but also indicate that specialization does not always represent an evolutionary dead-end that strongly limits further evolution.


A phase I/II trial of recombinant granulocyte-macrophage colony-stimulating factor for children with aplastic anemia.
Nine pediatric patients (median age, 8 years; range, 0.7 to 19 years), eight with refractory aplastic anemia and one with newly diagnosed aplasia, were enrolled in a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered via continuous intravenous infusion. Doses ranged from 8 to 32 micrograms/kg/d. Six of eight evaluable patients responded with a significant rise in neutrophil count (median fourfold increase; range, 2.5- to 31-fold) during the 28-day induction period. Five patients completed 2 further months of therapy (maintenance) with persistent or improved neutrophil responses. Three patients had bone marrow aspirates suggestive of increased erythropoiesis, although only one patient had improvement in peripheral hematocrit and platelet count. In the five patients completing maintenance, three experienced a rapid return to baseline counts after rhGM-CSF was discontinued, one maintained a neutrophil response for 2 months after drug discontinuation, and one has maintained a trilineage response for greater than 1 year off study. Drug therapy was well tolerated. Toxicity was minimal at doses from 8 to 16 micrograms/kg/d. Fever and rash were more commonly seen at 32 micrograms/kg/d. No patient developed an infection during the course of rhGM-CSF administration. These results demonstrate that rhGM-CSF increases peripheral neutrophil counts in children with refractory and newly diagnosed aplastic anemia and may be able to stimulate a multilineage response in a more limited number. Randomized, prospective trials are necessary to determine if rhGM-CSF administration will impact favorably on the morbidity and mortality of severe aplastic anemia.


[Characterization and simultaneous assay of polymers and additives composing multilayer plastic material for pharmaceutical use by FTIR].
Multilayer plastic materials provide useful solutions for primary pharmaceutical formulae (maintaining physical properties, compatibility with contents, protection against exterior agents). Fourier transform infrared spectometry is an ideal method to identify and quantify the different polymers and additives. Each functional group has a characteristic band which can be selected and rapidly identified for routine quality control. The proportional quantities of each polymers in the multilayer system can be determined directly using the characteristic bands for each functional group. The technique was applied to the analysis of heat-formed platelets made of polyvinyl chloride and polyvinylidene chloride.


Molecular packing of nucleic acids in spherical viruses.
Electron microscopy and X-ray scattering show that double-stranded DNA is wound in a regular way in the heads of phage such as P22 and lambda. DNA is "pumped" into such heads, which may simply act as passive containers. In contrast, the protein-coat subunits of tomato bushy stunt virus have a flexibly tethered N-terminal domain that appears to be a major locus of interactions with the compactly folded RNA. Both modes of packaging permit considerable latitude in the detailed arrangement of the nucleic-acid chain, while still ensuring specific and efficient incorporation.


Improving Cancer Data Interoperability: The Promise of the Minimal Common Oncology Data Elements (mCODE) Initiative.
Because of expanding interoperability requirements, structured patient data are increasingly available in electronic health records. Many oncology data elements (eg, staging, biomarkers, documentation of adverse events and cancer outcomes) remain challenging. The Minimal Common Oncology Data Elements (mCODE) project is a consensus data standard created to facilitate transmission of data of patients with cancer. In 2018, mCODE was developed through a work group convened by ASCO, including oncologists, informaticians, researchers, and experts in terminologies and standards. The mCODE specification is organized by 6 high-level domains: patient, laboratory/vital, disease, genomics, treatment, and outcome. In total, 23 mCODE profiles are composed of 90 data elements. A conceptual model was published for public comment in January 2019 and, after additional refinement, the first public version of the mCODE (version 0.9.1) Fast Healthcare Interoperability Resources (FHIR) implementation guide (IG) was presented at the ASCO Annual Meeting in June 2019. The specification was approved for balloting by Health Level 7 International (HL7) in August 2019. mCODE passed the HL7 ballot in September 2019 with 86.5% approval. The mCODE IG authors worked with HL7 reviewers to resolve all negative comments, leading to a modest expansion in the number of data elements and tighter alignment with FHIR and other HL7 conventions. The mCODE version 1.0 FHIR IG Standard for Trial Use was formally published on March 18, 2020. The mCODE project has the potential to offer tremendous benefits to cancer care delivery and research by creating an infrastructure to better share patient data. mCODE is available free from www.mCODEinitiative.org. Pilot implementations are underway, and a robust community of stakeholders has been assembled across the oncology ecosystem.


Antileishmanial Activity of Ezetimibe: Inhibition of Sterol Biosynthesis, In Vitro Synergy with Azoles, and Efficacy in Experimental Cutaneous Leishmaniasis.
Leishmaniasis affects mainly low-income populations in tropical regions. Radical innovation in drug discovery is time-consuming and expensive, imposing severe restrictions on the ability to launch new chemical entities for the treatment of neglected diseases. Drug repositioning is an attractive strategy for addressing a specific demand more easily. In this project, we have evaluated the antileishmanial activities of 30 drugs currently in clinical use for various morbidities. Ezetimibe, clinically used to reduce intestinal cholesterol absorption in dyslipidemic patients, killed Leishmania amazonensis promastigotes with a 50% inhibitory concentration (IC50) of 30 μM. Morphological analysis revealed that ezetimibe caused the parasites to become rounded, with multiple nuclei and flagella. Analysis by gas chromatography (GC)-mass spectrometry (MS) showed that promastigotes treated with ezetimibe had smaller amounts of C-14-demethylated sterols, and accumulated more cholesterol and lanosterol, than untreated promastigotes. We then evaluated the combination of ezetimibe with well-known antileishmanial azoles. The fractional inhibitory concentration index (FICI) indicated synergy when ezetimibe was combined with ketoconazole or miconazole. The activity of ezetimibe against intracellular amastigotes was confirmed, with an IC50 of 20 μM, and ezetimibe reduced the IC90s of ketoconazole and miconazole from 11.3 and 11.5 μM to 4.14 and 8.25 μM, respectively. Subsequently, we confirmed the activity of ezetimibe in vivo, showing that it decreased lesion development and parasite loads in murine cutaneous leishmaniasis. We concluded that ezetimibe has promising antileishmanial activity and should be considered in combination with azoles in further preclinical and clinical studies.


Is Cell Death Primary or Secondary in the Pathophysiology of Idiopathic Parkinson's Disease?
Currently, the pathophysiology of idiopathic Parkinson's disease is explained by a loss of mainly dopaminergic nerve cells that causes a neurotransmitter deficiency. In the final stage of the disease, there is a marked loss of neurons in the substantia nigra. In addition, Lewy bodies can be found in some of the remaining neurons, which serve as the pathological hallmark of the disease. These Lewy bodies are composed mainly of aggregated α-synuclein, a physiological presynaptic protein. Lewy bodies were thought to be the pathophysiologically relevant form of α-synuclein because their appearance coincided with neuron loss in the substantia nigra. In consequence, neuron loss was thought to be the primary step in the neurodegeneration in Parkinson's disease. On the other hand, the clinical syndrome suggests a synaptic disorder. If α-synuclein aggregation was causally linked to the pathophysiology of disease, α-synuclein pathology should be found at the synapse. As recently demonstrated, one to two orders of magnitude more α-synuclein aggregates are present in presynaptic terminals than in Lewy bodies or Lewy neurites. Degeneration of dendritic spines associated with synaptic α-synuclein aggregates has been shown to occur in human disease. In experiments, using transgenic mice or cell cultures, mild (two- to three-fold) overexpression of α-synuclein caused an altered vesicle turnover and led to a reduction in neurotransmitter release. Different approaches linked these alterations to presynaptic aggregation of α-synuclein. These findings may fundamentally change the pathophysiological concept of Parkinson's disease: not nerve cell loss, but the synaptic dysfunction of still existing nerve cells should become the focus of attention. From recent findings, it is quite evident that the death of dopaminergic neurons is a secondary event in the pathophysiology of Parkinson's disease.


Hepatoprotective activity of six polyherbal formulations in CCl4-induced liver toxicity in mice.
To evaluate pretreatment of six polyherbal liquid formulations (PLFs) commercially available in India, on CCl4-induced liver injury, Swiss albino mice were treated for 7 days with distilled water or PLFs (2.6 and 5.2 ml/kg body weight/day, po) followed by single sc injection of 50% (v/v) CCl4 in arachis oil at a dose of 1 ml/kg. The serum biochemical parameters such as alanine transaminases, aspartate transaminases and alkaline phosphatase were estimated. Phenobarbitone-induced sleeping time and liver histopathology were also carried out. CCl4-treated animals showed significant increase in the levels of liver enzymes, phenobarbitone-induced sleeping time and revealed fatty changes and centrizonal necrosis on histological examination of liver indicating hepatic damage. When pretreated with PLFs at a dose of 5.2 ml/kg body weight/day, the CCl4-induced changes were significantly reversed. The pretreatment with PLFs can prevent acute liver damage induced by CCl4 only at a higher dose. Therefore, it is suggested that a dose adjustment of these PLFs may be necessary for their optimal effects in human liver diseases.


Principal signalling complexes in haematopoiesis: structural aspects and mimetic discovery.
Blood production is a highly regulated process involving multiple inhibitory and stimulatory cytokines present in the haematopoietic stem cell niche. Small molecules mimics of these signalling molecules have substantial potential as drugs and in the development of bioreactors to generate blood products. We review the structural biology of the extracellular signalling domains of five of the most important cytokines, analyze their structure-property relationships, and summarize the progress in developing small molecule mimics using the molecular information from structural biology and mutation studies.


Psychoanalytic developmental theory: a contemporary reconsideration.
Psychoanalytic developmental theory has never enjoyed a broad consensus among psychoanalytic thinkers. In today's postmodern era, its relevance and basic premises are even more in question as a legitimate part of psychoanalytic theorizing. Part of the problem has been (1) the serious errors perpetrated historically in the name of psychoanalytic developmental theory and (2) its current state of disarray in the wake of piecemeal efforts to rectify these errors. Nonetheless, its presence is discernible in every psychoanalyst's theory and clinical work, whether or not it is acknowledged or brought into a cohesive theoretical frame. The point of view of "intersubjective ego psychology" (Chodorow 2004), embraced by a growing number of analysts interested in development, offers a more flexible and inclusive paradigm for psychoanalytic developmental thinking in order to preserve its rightful place in contemporary psychoanalysis.


Antagonistic Activities of Lactobacillus rhamnosus JB3 Against Helicobacter pylori Infection Through Lipid Raft Formation.
Helicobacter pylori is a Gram-negative pathogen that can increase the risk of stomach cancer in infected patients. H. pylori exploits lipid rafts to infect host cells. Infection triggers clustering of Lewis x antigen (Lex) and integrins in lipid rafts to facilitate H. pylori adherence to the gastric epithelium. H. pylori infection can be treated with probiotics containing lactic acid bacteria that offer numerous benefits to the host while lacking the side effects associated with antibiotic therapy. Previously, we showed that the cell-free supernatant (CFS) derived from Lactobacillus rhamnosus JB3 (LR-JB3) at a multiplicity of infection (MOI) of 25 attenuated the pathogenicity of H. pylori. In this study, we established a mucin model to simulate the gastric environment and to further understand the influence of mucin on the pathogenesis of H. pylori. Porcine stomach mucin dramatically upregulated H. pylori virulence gene expression, including that of babA, sabA, fucT, vacA, hp0499, cagA, and cagL, as well as the adhesion and invasion ability of H. pylori and induced increased levels of IL-8 in infected-AGS cells. The CFS derived from LR-JB3 at a MOI of 25 reduced the expression of H. pylori sabA, fucT, and hp0499 in mucin, as well as that of the Lex antigen and the α5β1 integrin in AGS cells during co-cultivation. These inhibitory effects of LR-JB3 also suppressed lipid raft clustering and attenuated Lewis antigen-dependent adherence, type IV secretion system-mediated cell contact, and lipid raft-mediated entry of VacA to host cells. In conclusion, LR-JB3 could affect H. pylori infection through mediating lipid raft formation of the host cells. The currently unknown cues secreted from LR-JB3 are valuable not only for treating H. pylori infection, but also for treating diseases that are also mediated by lipid raft signaling, such as cancer and aging-associated and neurodegenerative conditions.


Relationship between serum soluble urokinase plasminogen activator receptor level and steroid responsiveness in FSGS.
Soluble urokinase plasminogen activator receptor (suPAR) was initially proposed as a pathogenic and predictive biomarker of primary FSGS, but the findings were controversial. This study aimed to clarify the clinical implications of suPAR. The study enrolled 109 patients with biopsy-proven primary FSGS who were administered prednisone between January 2011 and May 2013 and followed up for 6-24 months (median duration of follow-up, 12 months). Ninety-six healthy volunteers, 20 patients with minimal-change disease (MCD), and 22 patients with membranous nephropathy (MN) served as controls. Serum suPAR levels were measured using ELISA. suPAR levels in patients with FSGS (median, 3512 [interquartile range (IQR), 2232-4231] pg/ml) were significantly higher than in healthy controls (median, 1823 [IQR, 1563-2212] pg/ml; P<0.001), patients with MCD (median, 1678 [IQR, 1476-2182] pg/ml; P<0.001), and patients with MN (median, 1668 [IQR, 1327-2127] pg/ml; P<0.001). With 3000 pg/ml used as a threshold, suPAR levels were elevated in 48.6% of patients with FSGS, in contrast to 5% of patients with MCD and 4.5% of those with MN. suPAR levels were independently associated with steroid response in patients with FSGS (odds ratio, 85.02; P=0.001). Patients who were sensitive to steroids had significantly higher suPAR levels than nonsensitive patients (median, 3426 [IQR, 2670-5655] pg/ml versus 2523 [IQR, 1977-3460] pg/ml; P=0.001). A suPAR level of 3400 pg/ml was chosen as the optimal cutoff value for steroid response. At the 6-month follow-up in 84 patients with FSGS, suPAR levels were significantly decreased in those with suPAR level ≥ 3400 pg/ml (median, 4553 [IQR, 3771-6120] pg/ml versus 3149 [IQR, 2278-3953]; P=0.002) but were unchanged in patients with suPAR level <3400 pg/ml (median, 2359 [IQR, 2023-2842] pg/ml versus 2490 [IQR, 1916-3623] pg/ml; P=0.09). suPAR is specifically elevated in some patients with FSGS, which differs from the finding in patients with MCD and MN. A suPAR assay may help predict steroid response in patients with primary FSGS.


Microleakage of CEM Cement and ProRoot MTA as Furcal Perforation Repair Materials in Primary Teeth.
Iatrogenic furcal perforation is a procedural accident in endodontic treatments of primary/permanent teeth; prognosis may be favorable if a complete seal with biomaterial is immediately established. The purpose of this in vitro study was to evaluate microleakage of calcium enriched mixture (CEM) cement and ProRoot mineral trioxide aggregate (MTA) for sealing primary molar furcal perforations. This study was conducted on 38 extracted human primary molars. Furcation perforations were created in the pulp chamber floor. The teeth were divided randomly in two experimental groups (n=17) and two positive and negative controls (n=2). Perforations were then repaired with biomaterials. After 72 h, the teeth were submerged in 2% fuchsin dye solution for 24h. The samples were sectioned longitudinally and evaluated for dye leakage. Data analyzed statistically using ANOVA test. The negative and positive controls behaved as expected. Dye microleakage was observed in all experimental samples; however, there was no statistically significant difference between the microleakage of MTA (4.411±2.042 mm) and CEM (3.647±1.040 mm) groups (P>0.05). Based on the findings of this in vitro study, CEM and tooth-colored ProRoot MTA have similar sealing ability for furcal perforation repair of primary molar teeth.


Analysis of alterations in white matter integrity of adult patients with comitant exotropia.
Objective This study was performed to investigate structural abnormalities of the white matter in patients with comitant exotropia using the tract-based spatial statistics (TBSS) method. Methods Diffusion tensor imaging data from magnetic resonance images of the brain were collected from 20 patients with comitant exotropia and 20 age- and sex-matched healthy controls. The FMRIB Software Library was used to compute the diffusion measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). These measures were obtained using voxel-wise statistics with threshold-free cluster enhancement. Results The FA values in the right inferior fronto-occipital fasciculus (IFO) and right inferior longitudinal fasciculus were significantly higher and the RD values in the bilateral IFO, forceps minor, left anterior corona radiata, and left anterior thalamic radiation were significantly lower in the comitant exotropia group than in the healthy controls. No significant differences in the MD or AD values were found between the two groups. Conclusions Alterations in FA and RD values may indicate the underlying neuropathologic mechanism of comitant exotropia. The TBSS method can be a useful tool to investigate neuronal tract participation in patients with this disease.


Ionization of N2O4 in contact with water: mechanism, time scales and atmospheric implications.
Ionization of N(2)O(4) in and on thin water films on surfaces is believed to be a key step in the hydrolysis of NO(2) which generates HONO, a significant precursor to the OH free radical in the lower atmosphere. Molecular dynamics simulations using "on the fly" high-level MP2 potentials are carried out for ONONO(2) x (H(2)O)(n) clusters, n < or = 8, used to mimic the surface reaction, in order to investigate the ionization process and determine its time-scale and mechanism around room temperature. The results are (i) the isolated molecule does not convert to the NO(+)NO(3)(-) ion pair, even for long times; (ii) for ONONO(2) x (H(2)O)(n) with n = 1 and 2, ionization takes place in several picoseconds; (iii) for n > or = 3, ionization is essentially immediate, implying that the neutral species does not have sufficient lifetime to be considered a significant intermediate in the reaction; and (iv) even at ice temperatures, T < or = 250 K, ionization for n > or = 3 is immediate. The implications for hydrolysis of oxides of nitrogen on surfaces in the atmosphere are discussed.


Scent counter-marks: specialized mechanisms of perception and response to individual odors in golden hamsters (Mesocricetus auratus).
Scent counter-marking is a wide-spread phenomenon among mammals that is not well understood. Using a habituation paradigm, it was found that male golden hamsters (Mesocricetus auratus) exposed to partially overlapping scents of 2 females behaved on test trials as if they remembered the top scent but not the bottom scent. If the 2 females' scents did not overlap during exposure trials, males remembered both of them. Thus, if 2 individual scents partially overlap, hamsters (a) perceive which of the 2 scents was deposited most recently and (b) either remember the top scent and forget the bottom scent or attach greater significance to the top scent. These results indicate the existence of specialized perceptual and cognitive or motivational mechanisms that are used for interpretation and response to complex arrays of social odors.


A Point-of-Care Based on Label-Free Interferometric Optical Detection Method to Evaluate Interferon Gamma (IFN-γ): A Correlation with the ELISA Technique.
Interferon-gamma (IFN-γ) is a cytokine associated with inflammatory diseases, virus, infection, etc. The quantification of interferon-gamma concentration levels is studied to relate the immune system response to the progression of disease. In this work, we used a label-free point-of-care device based on the increase relative optical power (IROP) and a biosensor based on photonic transducers called BICELLs (Biophotonic Sensing Cells) to evaluate interferon-gamma concentrations. The BICELLs' sensing surface size used is 100 μm in diameter. The bioreceptor is attached to the surface by streptavidin-biotin affinity. This label-free IROP-based device can work with a low concentration of reagents and a low sample volume for measurements. Furthermore, this new device was compared with an ELISA technique in the same conditions. A good correlation was achieved between both techniques. This device is easy to use, and it is a cost-effective tool for monitoring an analyte in a disease.


Corneal thickness in congenital glaucoma.
Central corneal thickness is very important measurement in glaucoma treatment because it influences the eye pressure measurements. A thinner cornea gives us artifactually lower intraocular pressure and a thicker cornea gives higher intraocular pressure reading, so it has to be corrected in both cases. The aim of this study is to compare central corneal thickness between congenital glaucoma patients and normal subjects. Prospective study included 27 patients with congenital glaucoma and 35 patients in control group. First group was subdivided in two subgroups: A--8 earlier operated patients, B--19 patients treated with topic therapy. Patients had no other corneal disorders, history of trauma, corneal surgery and they were not contact lens wearers. Measurements were performed by specular microscope Tomey EM 3000 on central corneas. This study showed that patients with congenital glaucoma have lower central corneal thickness than normal subjects. Also, the study showed that antiglaucomatous operation doesn't influence central corneal thickness. Central corneal thickness need to be a routine part of examination measurements because of need to correct intraocular pressure according to it, but also the thinner corneas values can suggest congenital glaucoma diagnosis beside the other parameters.


Importance of the quality of metal and ligand basis sets in transition metal species.
Recent development of pseudopotential-based correlation consistent basis sets (cc-pVnZ-PP) by Peterson and Puzzarini [Theor. Chem. Acc. 114, 283 (2005)] has enabled the relative importance of metal versus ligand basis set size to be examined systematically. The impact of basis set choice on geometries and dissociation energies for a series of group 11 transition metal species has been assessed via three series of calculations: (1) systematically increasing the size of the cc-pVnZ-PP basis set on the metal while holding the basis set on the ligand constant, (2) systematically increasing the size of the cc-pVnZ basis set on the ligand while holding the basis set on the metal constant, and (3) systematically increasing the size of the basis set on both the metal and the ligand. Holding the ligand basis set static while systematically increasing the metal basis set results in changes in the equilibrium bond length that are an order of magnitude smaller than for calculations where the metal basis set is held constant and the quality of the ligand basis set is systematically increased. Interestingly, holding the metal basis set static while systematically increasing the basis set size on the ligand results in monotonic convergence of dissociation energies with respect to increasing basis set size, while maintaining the basis set size on the ligand and increasing the size of the basis set on the metal do not result in monotonic convergence. Also, variance of the ligand basis set size has a greater impact on the energetics than variance of the metal basis set size. This suggests that the choice of basis set for the ligands is much more important for accurate chemical description than the choice of the transition metal basis set for these species and properties. In fact, complete basis set limit dissociation energies obtained from increasing the size of the basis set on the ligand while maintaining a constant level basis set on the metal at any level basis set result in similar energies to those obtained utilizing large basis sets on both the metal and the ligand at significant computational cost savings.


Selective inhibition of coagulation factors: advances in antithrombotic therapy.
Heparin and coumarin derivatives have long been used for the prophylaxis and treatment of venous thromboembolism (VTE). Although they have demonstrated efficacy and safety, they act at multiple targets within the coagulation cascade and their efficacy is influenced by many patient variables. Because of the need to improve the benefit-to-risk ratio of antithrombotic drugs, newer agents that target single coagulation factors have been developed. These include selective factor Xa inhibitors, direct thrombin inhibitors (DTIs), and inhibitors of factor IXa and the factor VII-tissue factor complex. Three DTIs-hirudin, bivalirudin, and argatroban-have been approved for clinical use. Fondaparinux, a novel pentasaccharide and the first selective factor Xa inhibitor to be approved by the U.S. Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products, is indicated for the prevention of VTE after major orthopedic surgery. Fondaparinux has predictable pharmacokinetics, is almost 100% bioavailable, and has a half-life that allows once-daily dosing in all indications. In addition, the routine monitoring of standard indicators of hemostasis is not required. The availability of these agents and the continued development of investigational selective coagulation inhibitors have the potential to improve efficacy and decrease adverse events in patients at risk for VTE.


Walsh-Hadamard transform kernel-based feature vector for shot boundary detection.
Video shot boundary detection (SBD) is the first step of video analysis, summarization, indexing, and retrieval. In SBD process, videos are segmented into basic units called shots. In this paper, a new SBD method is proposed using color, edge, texture, and motion strength as vector of features (feature vector). Features are extracted by projecting the frames on selected basis vectors of Walsh-Hadamard transform (WHT) kernel and WHT matrix. After extracting the features, based on the significance of the features, weights are calculated. The weighted features are combined to form a single continuity signal, used as input for Procedure Based shot transition Identification process (PBI). Using the procedure, shot transitions are classified into abrupt and gradual transitions. Experimental results are examined using large-scale test sets provided by the TRECVID 2007, which has evaluated hard cut and gradual transition detection. To evaluate the robustness of the proposed method, the system evaluation is performed. The proposed method yields F1-Score of 97.4% for cut, 78% for gradual, and 96.1% for overall transitions. We have also evaluated the proposed feature vector with support vector machine classifier. The results show that WHT-based features can perform well than the other existing methods. In addition to this, few more video sequences are taken from the Openvideo project and the performance of the proposed method is compared with the recent existing SBD method.


Sedentary Behavior and Atrial Fibrillation in Older Women: The OPACH Study.
Background Sedentary behavior is associated with cardiovascular disease, but its association with incident atrial fibrillation is not well studied. Our aim was to measure the association between objectively measured sedentary behavior and incident atrial fibrillation. Methods and Results Sedentary behavior was measured by a triaxial accelerometer worn on a belt for 1 week. Incident atrial fibrillation was ascertained from Medicare claims. The associations between total sedentary time (or patterns of sedentary behavior) and incident atrial fibrillation were assessed using Cox proportional hazards models adjusted for demographic and clinical covariates. Among 2675 participants (mean age, 78.2 years), there were 268 (10.0%) cases of incident atrial fibrillation at a rate of 31 cases per 1000 person-years. Greater total sedentary time was associated with a higher risk of incident atrial fibrillation after adjustment for age, race and ethnicity, body mass index, education, smoking history, hypertension, diabetes, stroke, heart disease, and other chronic conditions (quartile 4 versus quartile 1: hazard ratio, 1.20, [95% CI, 0.81-1.78]; P for trend=0.05). After adjusting for physical function and self-rated health, this was no longer statistically significant. Both longer mean sedentary bout duration and more continuous sedentary periods (versus frequent breaks in sedentary time) were also associated with higher risks of incident atrial fibrillation, but these associations were also attenuated with serial adjustment. Conclusions Total sedentary time and prolonged patterns of sedentary accumulation were associated with a higher risk of atrial fibrillation in this prospective study of community-dwelling older women, but these associations were attenuated by adjustment for physical function and self-reported health. This suggests that associations between sedentary behavior and atrial fibrillation may be attributable to global measures of overall function and health.


Fatty Acid Amide Hydrolase (FAAH) Inhibition Plays a Key Role in Counteracting Acute Lung Injury.
Acute lung injury (ALI) is a group of lung illnesses characterized by severe inflammation, with no treatment. The fatty acid amide hydrolase (FAAH) enzyme is an integral membrane protein responsible for the hydrolysis of the main endocannabinoids, such as anandamide (AEA). In pre-clinical pain and inflammation models, increasing the endogenous levels of AEA and other bioactive fatty acid amides (FAAs) via genetic deletion or the pharmacological inhibition of FAAH produces many analgesic benefits in several different experimental models. To date, nobody has investigated the role of FAAH inhibition on an ALI mouse model. Mice were subjected to a carrageenan injection and treated orally 1 h after with the FAAH inhibitor URB878 dissolved in a vehicle consisting of 10% PEG-400, 10% Tween-80 and 80% saline at different doses: The inhibition of FAAH activity was able to counteract not only the CAR-induced histological alteration, but also the cascade of related inflammatory events. URB878 clears the way for further studies based on FAAH inhibition in acute lung pathologies.


Plk1-dependent and -independent roles of an ODF2 splice variant, hCenexin1, at the centrosome of somatic cells.
Outer dense fiber 2 (ODF2) was initially identified as a major component of the sperm tail cytoskeleton, and was later suggested to be localized to somatic centrosomes and required for the formation of primary cilia. Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles. Earlier in the cell cycle, hCenexin1, but again not hODF2, also contributed to centrosomal recruitment of ninein and primary cilia formation independent of Plk1 interaction. These findings provide a striking example of how a splice-generated C-terminal extension of a sperm tail-associating protein mediates unanticipated centrosomal events at distinct stages of the somatic cell cycle.


In vivo measurement of anterior tibial translation using continuous passive motion devices.
Early motion protocols following anterior cruciate reconstruction often use continuous passive motion devices. There is concern that these devices may induce undesired anterior translation of the tibia and resulting graft stretching or rupture. This study measured the amount of anterior tibial translation that occurred during one cycle in 10 different brands of continuous passive motion devices. Five patients with ACL deficient knees participated in this study. Anterior translation was recorded by using an electrogoniometer with four degrees of freedom (Knee Signature System). Anterior translation measurements were also recorded for a 20 pound Lachman test in these same five patients using the Knee Signature System. Two of the devices showed anterior translation measurements that approached the recorded 20 pound Lachman values. These two devices had a high calf bar for the primary support of the leg. The results indicate that, when using a continuous passive motion device for early postoperative management of the reconstructed ACL in a patient, use of a calf-supporting type of continuous passive motion could induce an undesired strain of the healing graft.


Evolving connective tissue disease influenced by splenectomy: beneath the sword of Dameshek.
In years past, there was concern that splenectomy could lead to dissemination of occult systemic lupus erythematosus. Clinical studies subsequently effectively refuted that concept. However, there remains uncertainty regarding the role of the spleen in autoimmune diseases and the effect of splenectomy on their course. We present a case of a 56-year-old woman with autoimmune hepatitis and rheumatoid arthritis, without clinical or serologic features of lupus, who developed glomerulonephritis and antiphospholipid syndrome subsequent to an elective splenectomy. Literature review was performed to identify examples of the effect of splenectomy on other autoimmune diseases. Splenectomy has been linked with the development of new autoimmune phenomenon, alterations in the clinical course of patients with prior autoimmune disease, such as in our patient, and in a progressive redistribution of memory B cells that may influence autoimmune disease activity and may have been involved in the alteration in our patient's clinical course.


Vascularized versus nonvascularized island median nerve grafts in the facial nerve regeneration and functional recovery of rats for facial nerve reconstruction study.
Histological and physiological basis of the therapeutic efficacy of the vascularized autologous nerve graft in facial nerve regeneration remains poorly understood because of no established rat model. The left median nerve and median artery/vein of Lewis rats were collectively ligated, and harvested as a vascularized island median nerve, which was transplanted to a 7-mm gap in the left buccal branch of facial nerve. Nerve regeneration was investigated. The numbers of myelinated fibers, axon diameter, and myelin thickness were significantly higher in the vascularized nerve graft group than in the nonvascularized nerve graft group. Compound muscle action potential measurement showed that the parameters of vascularized group were similar to those in the intact control group. A vascularized median nerve graft resulted in better facial nerve regeneration outcomes.


Nonmotor manifestations in Parkinson disease.
Although the diagnosis of Parkinson disease (PD) still relies mainly on the appearance of its classical motor features of resting tremor, rigidity, bradykinesia, and postural instability, nonmotor manifestations in PD are now recognized as an integral component of this multisystem disorder. Nonmotor complications in PD occur commonly. The current understanding of cognitive dysfunction; neuropsychiatric manifestations including psychosis, impulsive control, and compulsive disorders, depression, anxiety and apathy; autonomic complications such as hypotension, erectile dysfunction, and urinary complications; sleep disorders and other nonmotor manifestations are summarized in this review. Nonmotor complications often carry a greater impact than motor features in PD. Therefore, heightened awareness and proper recognition of these features are critical in improving a Parkinson patient's quality of life.


Effects of ascorbic Acid on serum level of unconjugated estriol and its relationship with preterm premature rupture of membrane: a double-blind randomized controlled clinical trial.
Vitamin C is a water-soluble antioxidant that not only stimulates and protects collagen synthesis but also plays an important role in maintaining cellular integrity in a normal pregnancy. This study surveyed the effects of ascorbic acid on the serum level of unconjugated estriol and the relationship between unconjugated estriol and preterm premature rupture of membrane (PPROM). This double-blind, randomized clinical trial recruited 60 patients with predisposing factors to PPROM. The women were randomly divided into two groups of intervention and control and received vitamin C and placebo, respectively. The intervention group received 250 mg vitamin C twice a day and the controls received the placebo only. Unconjugated estriol was measured using the ELISA. All data were extracted and recorded in a checklist and compared using descriptive statistics as well as the x (2), Fisher exact, and t tests. The demographic data showed no difference between the two groups. The mean level of serum unconjugated estriol was significantly lower in the intervention group than in the control group (P=0.044). Also, the frequency of PPROM was lower in the intervention group, but the difference was not significant (P>0.05). Unconjugated estriol levels were not significantly different between the healthy women and the PPROM patients. This study demonstrated that vitamin C administration decreased unconjugated estriol levels in the patients with PPROM. The findings of this study also indicated that administration of ascorbic acid was a safe and effective method to reduce the incidence of PPROM. Alteration in unconjugated estriol is an active mediator for this effect.


Opposite effects of clozapine and sulpiride on the lipopolysaccharide-induced inhibition of the GR-mediated gene transcription in fibroblast cells.
Previously, we have found that some antipsychotic drugs are able to inhibit glucocorticoid receptor (GR)-mediated gene transcription. Since these drugs are known not only to inhibit hypothalamic-pituitary-adrenal (HPA) axis activity, but also to modulate the immunological system, the aim of the present study was to compare the effect of sulpiride and clozapine on GR function under basal culture conditions and during activation by lipopolysaccharide (LPS). The effect of clozapine and sulpiride alone and with LPS, the immune system activator, on glucocorticoid-mediated gene transcription was investigated in fibroblast cells, stably transfected with a mouse mammary tumor virus--chloramphenicol acetyltransferase plasmid (LMCAT cells). Treatment of the cells with clozapine (3-10 microM) for 2 days significantly and in concentration-dependent manner decreased the chloramphenicol acetyltransferase (CAT) activity, while sulpiride (1, 3, 5 and 10 microM) was without any effect. LPS (1 microg/ml) given alone inhibited the corticosterone-induced gene transcription by ca. 35%. Clozapine (3, 5 and 10 microM) inhibited the effect of LPS (1 microM), while sulpiride, which alone had no effect on GR function, enhanced LPS (1 microM) action. The obtained results indicate that inhibition of GR-mediated gene transcription by LPS and clozapine can be a mechanism by which these compounds blocked some effects induced by glucocorticoids. Opposite effect of clozapine and sulpiride on LPS action may result from their distinct effect on activity of some kinases involved in regulation of GR transcriptional function and may determine their utility in the treatment of schizophrenia with or without immune system activation.


Operant conditioning in the newly hatched chicken.
Techniques are described for conditioning key-pecking reinforced with food and for recording cheeping in newly hatched chickens. A mirror in the test box is essential when conditioning isolated chickens up to five or more days old. Conditioning proceeds more rapidly when frequently pecked objects and materials that move when scratched are not present. Stimulus control over key-pecking is present in the three-day-old chicken and multiple fixed-ratio, fixed-interval schedule control develops in succeeding days. In young chickens, pecking and cheeping are inversely related. The newly hatched chicken is useful for pharmacological studies and appears to offer other advantages for behavioral studies.


[Morphological characteristics of mucinous cancer of the breast containing endocrine cells].
It was established that mucus-forming mammary gland carcinoma containing endocrine cells may have a structure of an ordinary colloid mammary gland carcinoma or carcinoid carcinoma with mucus formation. The presence of amyloid in the stroma of colloid carcinoma containing endocrine cells may serve as an additional sign of the endocrine cell differentiation. Simultaneous observation in the tumour cells of both mucous inclusions and endocrine granules may be regarded as a proof of an origin of epithelial and endocrine cells of the mammary gland from a pluripotent stem cell.


The influence of monocular vision on the plantar pressure distribution.
Although the influence of monocular vision to upper limb biomechanics has been well documented, data about lower extremity biomechanics are limited. The objective of the present study was to demonstrate pedobarographic differences between both feet of the individuals with monocular vision in static and dynamic conditions. Pedobarographic analysis of twenty-four participants with monocular vision was performed. Relative static pressure load (%) and dynamic peak plantar pressure (N/cm(2)), force (N) distributions and contact area percentages (%) were recorded under both low vision and normal vision side foot. The results showed that relative static pressure loads did not differ between low vision and normal vision foot. Under midfoot of low vision side, a significant increment was found in peak plantar pressures (2.42 (SD 1.09) N/cm(2)) and forces (136.77 (SD 64.96) N) compared to normal vision side foot (1.87 (SD 0.96) N/cm(2); 106.94 (SD 65.03) N). No difference in contact area percentages was detected. These results indicate that there are differences in plantar pressure measurements between feet of individuals with monocular vision. These pedobarographic differences reported here appear to support the assumption that individuals with monocular vision have adaptive gait strategies such as, decreased walking speed, limited ankle motion and postural compensations.


On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease.
Nitrite and nitrate are frequently used surrogate markers of nitric oxide (NO) production. Using rat models of acute and chronic DSS-induced colitis we examined the applicability of these and other NO-related metabolites, in tissues and blood, for the characterization of inflammatory bowel disease. Global NO dynamics were assessed by simultaneous quantification of nitrite, nitrate, nitroso and nitrosyl species over time in multiple compartments. NO metabolite levels were compared to a composite disease activity index (DAI) and contrasted with measurements of platelet aggregability, ascorbate redox status and the effects of 5-aminosalicylic acid (5-ASA). Nitroso products in the colon and in other organs responded in a manner consistent with the DAI. In contrast, nitrite and nitrate, in both intra- and extravascular compartments, exhibited variations that were not always in step with the DAI. Extravascular nitrite, in particular, demonstrated significant temporal instabilities, ranging from systemic drops to marked increases. The latter was particularly evident after cessation of the inflammatory stimulus and accompanied by profound ascorbate oxidation. Treatment with 5-ASA effectively reversed these fluctuations and the associated oxidative and nitrosative stress. Platelet activation was enhanced in both the acute and chronic model. Our results offer a first glimpse into the systemic nature of DSS-induced inflammation and reveal a greater complexity of NO metabolism than previously envisioned, with a clear dissociation of nitrite from other markers of NO production. The remarkable effectiveness of 5-ASA to abrogate the observed pattern of nitrite instability suggests a hitherto unrecognized role of this molecule in either development or resolution of inflammation. Its possible link to tissue oxygen consumption and the hypoxia that tends to accompany the inflammatory process warrants further investigation.


An Unusually Large Parakeratinised Odontogenic Keratocyst in the Maxilla With Extension Into the Floor of the Maxillary Sinus.
Parakeratinised odontogenic keratocyst is a developmental odontogenic cyst affecting the jaw with aggressive behaviour, rapid growth, extension into adjacent structures, and a high recurrence rate of 4.4% in either jaw. This cyst usually occurs in the molar-ramus region of the mandible. If it occurs in the maxilla, the cyst can traverse through the trabecular bone marrow spaces resulting in expansion more mediolaterally than in the buccolingual direction. Here, we present you a case of peripherally occurring parakeratinised variant of odontogenic keratocyst in a 20-year-old-male in relation to impacted left maxillary cuspid in the maxilla with involvement of the floor of the maxillary sinus, imaged by cone-beam computed tomography systems (CBCT) and treated by surgical enucleation.


Transcription Regulator YgeK Affects the Virulence of Avian Pathogenic Escherichia coli.
Avian pathogenic Escherichia coli (APEC) is the responsible pathogen for colibacillosis in poultry, and is a potential gene source for human extraintestinal pathogenic Escherichia coli. Escherichia coli type III secretion system 2 (ETT2) is widely distributed in human and animal ExPEC isolates, and is crucial for the virulence of ExPEC. Transcriptional regulator YgeK, located in the ETT2 gene cluster, was identified as an important regulator of gene expression in enterohemorrhagic E. coli (EHEC). However, the role of YgeK in APEC has not been reported. In this study, we performed amino acid alignment analysis of YgeK among different E. coli strains and generated ygeK mutant strain AE81ΔygeK from clinical APEC strain AE81. Flagellar formation, bacterial motility, serum sensitivity, adhesion, and virulence were all significantly reduced following the inactivation of YgeK in APEC. Then, we performed transcriptome sequencing to analyze the functional pathways involved in the biological processes. Results suggested that ETT2 transcriptional regulator YgeK plays a crucial role in APEC virulence. These findings thus contribute to our understanding of the function of the ETT2 cluster, and clarify the pathogenic mechanism of APEC.


Social Capital, Technological Empowerment, and Resilience in Rural China.
In the post-pandemic era, the need for resilient and flexible COVID-19 prevention strategies in rural areas has become increasingly prominent. Based on a sample of 2229 rural residents nationwide, the Structural Equation Model was adopted to analyze the influence of social capital and technological empowerment on pandemic resilience in rural areas. The proportion of diversity, adequacy, and effectiveness of pandemic prevention measures taken by communities was about 57%. Social capital (0.667) and technological empowerment (0.325) had a significant positive impact on rural resilience and pandemic prevention. Social capital plays a mediating role between technological empowerment and pandemic resilience in rural areas. The risk of disease in society stimulates the inherent social capital factors in villages, with the individual social network generating strong social support. Technological empowerment can not only provide new methods for the connection of social capital, but also bring new means for rural authorities to improve their governance capabilities. Social trust in social capital plays an important role in rural resilience and pandemic prevention. The indirect effect of technological empowerment through social capital on pandemic resilience is greater than its direct effect. Social capital construction is the key to rural resilience and pandemic prevention.


Primary School Teachers and Parents Perception of Peer Bullying Among Children in Iran: A Qualitative Study.
The present study aimed to recognize bullying behavior in the students in Iran and analyze the perception of school teachers and parents in this regard. Several semi-structured interviews and observations were conducted with four teachers and eight parents of children involved in bully/victim problems and the analysis was interpreted through established comparative evaluation methods. Iranian teachers and the parents perceived bullying mainly as physical and verbal attacks with little understanding of the psychological factors. They emphasized that the underlying influence of religious beliefs should also be considered in the context of bullying among Iranian society due to the strict conformance applied by parents upon their child. Based on the outcomes of the study, it is recommended that the teachers participate in anti-bullying programs orientated to prevent bullying behaviors and develop strong supportive relationship with parents to reduce this behavior through personal contacts and interactive workshops.


[Clinical features and gene mutation analysis in Machado-Joseph disease of spinocerebellar ataxia type 3 in littoral of Zhejiang].
To study the clinical features and gene mutation analysis in Machado-Joseph disease of spinocerebellar ataxia type 3 in littoral of Zhejiang. Clinical manifestation and brain MRI data 18 patients with SCA in family were analyzed. The gene mutations of 18 patients and 10 family numbers without abnormal presentation, and 12 healthy persons of controls. The gene mutations of 18 patients is SCA3/MJD, and 2 asymptomatic SCA3/MJD had been detected in SCA family. Normal alleles of SCA3/MJD have CAG repeats ranging from 14 to 27, patients from 67 to 82, asymptomatic and carrier SCA3/MJD from 28 to 45. The main features of 18 patients included gait ataxia, ambiguity in speech and action clumsiness. Brain MRI showed remarkable atrophy on cerebellum and brain stem. CAG expansions were related to SCA3/MJD. The clinical manifestations are ataxia and dysarthria. The detection of repeated times CAG can provide an effective way for the genetic and asymptomatic diagnosis.