Kinetics of C-photosynthate uptake by developing soybean fruit.
By pulse-labeling field-grown soybean leaves for 60 seconds at midday with (14)CO(2) and then sequentially harvesting, dissecting, and extracting the radioactive fruit tissues (of pod and seeds), the route, uptake kinetics, and metabolic fate of (14)C-photosynthate as it was imported by 35- to 40-day-old pods were determined. As the [(14)C]sucrose pulse entered the pods, the seeds became radioactive immediately but a lag of nearly 30 minutes occurred before label could be detected in the pod wall pericarp.Import of the (14)C-pulse by the seeds was exclusively via the seed coats, where rapid unloading occurred. Maximum accumulation of label in the seed coat occurred in about 60 minutes at which time 59% of the total radioactivity in the fruit was in the three seed coats, whereas only 7% was in the cotyledons they enclosed. The photosynthate remained as [(14)C]sucrose as it passed through the seed coat, but appeared to be hydrolyzed relatively soon after uptake by the cotyledons. By 2.5 hours, 60% of the (14)C-photosynthate pulse had passed into the cotyledons with only 27% remaining in the seed coats. Inasmuch as there is no vascular connection between maternal seed coat and the developing embryo, cotyledonary uptake of sucrose released from the inner seed coat surface may require specialized transport mechanisms.


Mechanical declotting of thrombosed dialysis grafts: experience in 86 cases.
To evaluate the efficacy, safety, and primary patency of percutaneous mechanical declotting of thrombosed dialysis grafts using latex balloons. Fifty-nine patients with 86 episodes of dialysis graft thrombosis underwent percutaneous mechanical declotting with balloons using crossing catheter or transjugular technique. Vital signs, peripheral oxygenation, technical success, procedure time, and complications were recorded prospectively. Technical success was defined as a patent graft at the completion of the procedure. Clinical success, defined as successful dialysis for 1 week, and primary patency were obtained retrospectively from review of the dialysis records. Technical success was achieved in 74 of 86 procedures (86%). Median procedure time was 115 minutes, including failed cases. Ten of the 12 technical failures were due to resistant vascular stenoses precluding graft patency, despite removal of thrombus. There were no immediate complications. One patient died of sepsis 4 days after declotting. Clinical success was achieved after 65 of 86 procedures (76%); nine grafts thrombosed within 1 week of a technically successful declotting procedure. Primary patency (including technical failures) was 37% at 3 months, 31% at 6 months, and 17% at 12 months. Mechanical declotting is an effective means of restoring patency to thrombosed dialysis grafts.


Dental endosseous implants: an update. ADA Council on Scientific Affairs.
This report, based on the ADA Acceptance Program for Endosseous Implants and accepted by the ADA Council on Scientific Affairs, provides an update of fully accepted and provisionally accepted dental endosseous implant products.


A convenient and adjustable surface-modified complex containing poly-L-glutamic acid conjugates as a vector for gene delivery.
In order to quantify the amount of ligands or poly(ethylene glycol) (PEG) on each vector, here we developed a system in which poly-L-glutamic acid (PLG) was used as surface modification loading backbone, to which one PEG (MW 5000, 10000, 20000) or epidermal growth factor (EGF) was linked. The PLG conjugates can electro-statically adsorb upon DNA/ polycation complex with positive charge, and, the amount of EGF or PEG on the surface of complexes could be varied. We have made a series of complexes containing the various PLG conjugates and examined their physicochemical properties, and made a comparison of properties and transfection efficiency between these complexes. EGF- and PEG-modified complexes showed 10-25-folds higher cell transfection efficiency than unmodified complexes in medium with or without serum.


Epihyoid bone fracture associated with tongue deviation in an adult dog.
An 8-month-old male Rhodesian ridgeback dog was evaluated for right lingual deviation, mild dysphagia, and inability to retract the tongue. Transverse and three-dimensional computed tomography reconstruction images revealed a transverse fracture of the left epihyoid bone. After 4 months of conservative management, that included assisted feeding of a semi-liquid diet or small volumes of food and analgesics, the dog recovered.


The intersection of socioeconomic variables, oral health, and systemic disease: all health care is cultural.
In the last decade, there has been an increase in the proportion of the American population that lacks health insurance. Additionally, long-term disparities in health access and status for populations of color have continued to exist without major change. A review of the literature in periodontia shows a statistical relationship between the risk of periodontal disease and a range of sociodemographic characteristics (race, income, social class). However, the factors giving rise to this increased risk or how to reduce it are unclear. Cultural competence, an elaboration of biopsychosocial theory, hypothesizes a relationship between the culture of a group and its risk of disease and the kind and quality of services obtained. Four areas of a culturally competent approach are cited as a minimum base of standards for providing services to people of color.


Effect of Rapamycin on the Radio-Sensitivity of Cultured Tumor Cells Following Boron Neutron Capture Reaction.
Mammalian target of rapamycin (mTOR) signaling pathway has been implicated in multiple mechanisms of resistance to anticancer drugs and poor treatment outcomes in various human cancers. Meanwhile, clinical boron neutron capture therapy (BNCT) has been carried out for patients with malignant gliomas, melanomas, inoperable head and neck tumors and oral cancers. This study aimed to evaluate the effect of mTOR inhibition on radio-sensitivity of cultured tumor cells in BNCT, employing p-boronophenylalanine-10B (BPA) as a 10B-carrier. Cultured SAS cells had been incubated for 48 h at RPMI medium with mTOR inhibitor, rapamycin at the dose of 1 µM, and then continuously incubated for 2 more hours at RPMI medium containing both BPA at the 10B concentration of 10 ppm and rapamycin (1 µM). Subsequently, the SAS cells received reactor neutron beams, and then surviving fraction and micronucleus frequency were determined. SAS cells incubated with rapamycin showed resistance to γ-rays compared with no treatment with rapamycin. The efficiency of delivery of 10B from BPA into cultured SAS cells was reduced through combining with rapamycin, leading to reduced sensitivity following boron neutron capture reaction. Since many tumors are characterized by deregulated PI3K/AKT/mTOR pathway, rapamycin is thought to inhibit the pathway and tumor growth. However, it was revealed that rapamycin can also inhibit the transport of 10B for BNCT into tumor cells. When BNCT is combined with mTOR inhibitor, the efficiency as cancer treatment can be reduced by repression of distributing 10B in tumor cells, warranting precaution when the two strategies are combined.


Transfusion of RhD-incompatible blood components in RhD-negative blood marrow transplant recipients.
Transfusion-dependent bone marrow transplant recipients are routinely transfused with ABO group and RhD-compatible blood components. However, because of the scarcity of RhD-negative blood components, particularly platelets, a policy was developed to transfuse RhD-positive blood components to RhD-negative patients during periods of shortage. We reviewed the records of 78 RhD-negative patients with hematologic malignancies who received RhD-negative bone marrow and/or peripheral blood stem cells, from June 1995 to August 2000. The patients transfused with RhD-incompatible blood components were screened periodically for evidence of the development of red blood cell (RBC) alloimmunization. Three of 78 patients (4%) developed anti-D antibodies after receiving RhD-incompatible platelet transfusions. One of the patients developed evidence of anti-RhD antibodies after receiving 42 units of RhD-positive random donor platelets; the second patient developed such evidence after receiving 6 apheresis platelets and 2 infusions of intravenous immunoglobulin G (positive for anti-RhD). The third patient received 206 RhD-positive random donor platelets and 5 apheresis units. All patients were discharged from the hospital. The overall immunization rate was 4%. Six patients received Rh-incompatible packed RBCs and showed no evidence of neither anti-RhD nor any other anti-RBC antibodies. All 78 patients had received RhD-incompatible platelets throughout their engraftment period. Transfusion of RhD-positive blood components to Rh-negative patients with hematologic cancers, who have received RhD-negative bone marrow and/or peripheral blood stem cells, are at low risk of developing RhD antibodies. These findings allow for a flexible strategy of blood component therapy support for this special patient population during periods of shortage.


Labour productivity effects of prescribed medicines for chronically ill workers.
Previous work on the labour productivity effects of chronic illness has not separated the effects of chronic illnesses from the effects of prescription medications taken to alleviate these conditions. Using nationally representative observational data, this study estimates the pure effect of chronic illness, and the marginal effect of prescription medicines, on labour productivity. As Americans continue to scrutinize health care expenditures, such estimates will play an increasing role in determining the allocation of resources for medical treatments. Estimates are presented of the costs and benefits to employers of covering prescription medications for workers aged 18-64 years afflicted with specific chronic illnesses. The effects of prescription medicines on hourly wages and days lost from work are examined for four major chronic illnesses: hypertension, heart disease, non-insulin dependent (type II) diabetes and depression. The net benefits to employers from having workers take prescription medicines for their chronic illnesses are substantial. Assuming average compliance rates are achieved, net benefits to employers in 1987 amounted to $286 per hypertensive employee, $633 per employee with heart disease; $822 per depressed employee, and $1475 per type II diabetic employee under medication from a physician. These estimated benefits accrue because prescription medications substantially lower absenteeism among chronically ill workers.


Incidence and risk factors for nerve injuries in mandibular third molar surgery.
The inferioralveolar (IAN), lingual (LN) and long buccal nerves (LBN)are the three terminal branches of the trigeminal nerve which are susceptible to injury during surgical extraction of impacted mandibular third molars. While it is not always possible to accurately predict the patients that will be affected with these complications, understanding and identifying the risk factors may allow the adoption of appropriate technique and expertise for specific cases. We embarked on this study to document the incidence and duration of injury to the inferior alveolar nerve (IAN), lingual nerve (LN) and long buccal nerve (LBN) following the operative removal of impacted mandibular third molars and to identify the associated radiographic and operative risk factors. Pre- and postoperative neurosensory tests were performed for seventy nine patients who had surgical extraction of unilateral impacted mandibular third molars to determine the incidence and duration of complicating nerve injuries. The risk factors for nerve injury were determined among the radiographic variables and documented operative events. The incidence reported were 6.6% for IAN, 2.6% for LN and 4.0% for LBN; all but one of the nerve injuries resolved within 2 weeks. Depth of impaction (Pell & Gregory Level C) and linguo-version were the significant risk factors for IAN and LN injuries respectively while no risk factors was detected for LBN injury. Some significant operative events were associated with nerve injuries. Nerve injury in third molar surgery can be predicted based on some radiographic risk factors and some unforeseen intraoperative events. Most of the injuries are transitory in nature.


The role of vascular surgery in chronic leg ulcers: report from a specialized ulcer clinic.
Experience gained from cooperation between dermatologists and vascular surgeons in 177 patients evaluated at a joint leg ulcer clinic is reported. Patients were divided into two subgroups: (i) 86 patients with healed ulcers and (ii) 91 patients with ongoing therapy-resistant ulcers. Venous insufficiency was the most common etiology in both subgroups (87% and 55%, respectively). Of previous therapy-resistant ulcers, 71% were healed after the combined effort. The pattern of venous incompetence differed between the two subgroups; patients with isolated superficial disease constituting 68% and 26% of patients, respectively. In patients with therapy-resistant ulcers, those with isolated superficial venous insufficiency were found to have a better prognosis than those with deep venous insufficiency. Cooperation between the dermatologist and vascular surgeon is a mainstay in order to take advantage of the possibilities offered by modern vascular surgery.


[Diagnosis and treatment of rheumatoid arthritis].
The paper describes the typical clinical features of rheumatoid arthritis and principles of its treatment. It includes an overview of the universally accepted diagnostic criteria and discusses the diagnostic value of laboratory and instrumental investigations. The significance of correct diagnosis in an early stage of the disease is emphasized with regard to the difficulties related to differential diagnosis. Appropriate evaluation of the inflammatory activity of rheumatoid arthritis and of the functional state of the patient is discussed. Contemporary principles of complex and individual treatment of rheumatoid arthritis, depending on the course of disease are presented, placing special emphasis on the importance of disease--modifying treatment. Possible side effects of NSAIDs and glucocorticosteroids and methods of their prevention are discussed, as well as indications for new biological medications.


Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population.
Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components, and several candidate genes have been reported to be linked to atopy in Caucasian populations. We conducted a study of linkage between asthma and markers on chromosomes 5q31-q33 and 11q13 in 68 Japanese families (306 members) by affected sib-pair analysis. Families for the linkage study were ascertained through asthmatic children visiting the allergy clinic. The results provide supportive evidence for linkage between asthma and gene markers in or near the interleukin-4 (IL-4) gene, the IL-9 gene, and D5S393 on chromosome 5q31-q33 (p = 0.0013, p = 0.018, and p = 0.0077, respectively). Linkage between atopic phenotype and these genetic markers was also suggested (p = 0.006, p = 0.01, and p < 0.0001 for atopy, respectively). However, we failed to find evidence for linkage of asthma or atopy to the IgE high-affinity receptor gene on 11q13 (p > 0.1). These findings indicate that beyond ethnicity, there are specific loci that contribute to susceptibility to atopy on chromosome 5q31-q33. In addition, our findings suggest that loci on chromosome 5q31-q33 are linked to the development of asthma in childhood.


Real-Time Analysis of Hand Gesture Recognition with Temporal Convolutional Networks.
In recent years, the successful application of Deep Learning methods to classification problems has had a huge impact in many domains. (1) Background: In biomedical engineering, the problem of gesture recognition based on electromyography is often addressed as an image classification problem using Convolutional Neural Networks. Recently, a specific class of these models called Temporal Convolutional Networks (TCNs) has been successfully applied to this task. (2) Methods: In this paper, we approach electromyography-based hand gesture recognition as a sequence classification problem using TCNs. Specifically, we investigate the real-time behavior of our previous TCN model by performing a simulation experiment on a recorded sEMG dataset. (3) Results: The proposed network trained with data augmentation yields a small improvement in accuracy compared to our existing model. However, the classification accuracy is decreased in the real-time evaluation, showing that the proposed TCN architecture is not suitable for such applications. (4) Conclusions: The real-time analysis helps in understanding the limitations of the model and exploring new ways to improve its performance.


Novel Design and Finite Element Analysis of Diamond-like Porous Implants with Low Stiffness.
The purpose of this study was to design porous implants with low stiffness and evaluate their biomechanical behavior. Thus, two types of porous implants were designed (Type I: a combined structure of diamond-like porous scaffold and traditional tapered thread. Type II: a cylindrical porous scaffold filled by arrayed basic diamond-like pore units). Three implant-supported prosthesis models were constructed from Type I, Type II and commercial implants (control group) and were evaluated by finite element analysis (FEA). The stress distribution pattern of the porous implants were assessed and compared with the control group. In addition, the stiffness of the cylindrical specimens simplified from three types of implants was calculated. The Type I implant exhibited better stress distribution than the Type II implant. The maximum stress between the cortical bone-Type I implant interface was 12.9 and 19.0% lower than the other two groups. The peak stress at the cancellous bone-Type I implant interface was also reduced by 16.8 and 38.7%. Compared with the solid cylinder, the stiffness of diamond-like pore cylinders simplified from the two porous implants geometry was reduced by 61.5 to 76.1%. This construction method of porous implant can effectively lower its stiffness and optimize the stress distribution at the implant-bone interface.


Gene editing in tomatoes.
Tomato is an effective model plant species because it possesses the qualities necessary for genetic and functional studies, but is also a food crop making what is learned more translatable for crop improvement when compared with other non-food crop models. The availability of genome sequences for many genotypes and amenability to transformation methodologies (Agrobacterium-mediated, direct DNA uptake via protoplasts, biolistics) make tomato the perfect platform to study the application of gene-editing technologies. This review includes information related to tomato transformation methodology, one of the necessary requirements for gene editing, along with the status of site-directed mutagenesis by TALENs (transcription activator-like effector nucleases) and CRISPR/Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated Proteins). In addition to the reports on proof-of-concept experiments to demonstrate the feasibility of gene editing in tomato, there are many reports that show the power of these technologies for modification of traits, such as fruit characteristics (ripening, size, and parthenocarpy), pathogen susceptibility, architecture (plant and inflorescence), and metabolic engineering. Also highlighted in this review are reports on the application of a recent CRISPR technology called base editing that allows the modification of one base pair in a gene sequence and a strategy that takes advantage of a geminivirus replicon for delivery of DNA repair template.


Expression, Purification and Characterization of Three Overlapping Immunodominant Recombinant Fragments from Bordetella pertussis Filamentous Hemagglutinin.
Filamentous hemagglutinin (FHA) is one of the most important immunoprotective antigens of Bordetella pertussis (B. pertussis) and a major component of the acellular pertussis vaccine. In the present study, three overlapping recombinant fragments from the immunodominant region of FHA were produced and their immunogenicity was investigated. Three overlapping coding sequences of FHA antigen were amplified from B. pertussis genomic DNA by PCR. Amplified fragments were expressed in Escherichia coli (E. coli) BL21(DE3) strain and purified through His-tag using Nickel-based chromatography. Purified fragments were characterized by SDS-PAGE and Western blotting techniques. In vitro peripheral blood mononuclear cells (PBMC) proliferation and IFN-γ production were assessed in a limited number of healthy adults vaccinated with a commercial acellular pertussis vaccine in response to all purified FHA fragments by H3-Thymidine incorporation and ELISA, respectively. Recombinant FHA segments were successfully cloned and produced at high levels in E. coli BL21(DE3). SDS-PAGE and Western blot analyses confirmed their purity and reactivity. All three recombinant fragments together with a commercial native FHA were able to induce in vitro PBMC proliferation and IFN-γ production. Our preliminary results suggest that these overlapping recombinant FHA fragments are immunogenic and may prove to be immuno-protective.


Development of neurons on micropatterns reveals that growth cone responds to a sharp change of concentration of laminin.
In this report we fabricated laminin (LN) stripes on a background of poly-L-lysine as substrates for the growth of rat hippocampal neurons, and found that a sharp change of the concentration of LN guides the growth of neurites by leading the growth cones in a time- and space-dependent manner. The percentage of neurites that grow along the edge of LN stripes (where there is a sharp change of concentration) decreases as a function of the concentration of LN under a threshold value. The actin cytoskeleton plays an important role in the process of growth cone's response to the sharp change of concentration of LN on micropatterns. We believe that the findings here are useful for not only fundamental studies in neuroscience, but also helpful for the design of devices or chips for nervous prosthesis.


Type II diacylglycerol acyltransferase from Claviceps purpurea with ricinoleic acid, a hydroxyl fatty acid of industrial importance, as preferred substrate.
Claviceps purpurea, the fungal pathogen that causes the cereal disease ergot, produces glycerides that contain high levels of ricinoleic acid [(R)-12-hydroxyoctadec-cis-9-enoic acid] in its sclerotia. Recently, a fatty acid hydroxylase (C. purpurea FAH [CpFAH]) involved in the biosynthesis of ricinoleic acid was identified from this fungus (D. Meesapyodsuk and X. Qiu, Plant Physiol. 147:1325-1333, 2008). Here, we describe the cloning and biochemical characterization of a C. purpurea type II diacylglycerol acyltransferase (CpDGAT2) involved in the assembly of ricinoleic acid into triglycerides. The CpDGAT2 gene was cloned by degenerate RT-PCR (reverse transcription-PCR). The expression of this gene restored the in vivo synthesis of triacylglycerol (TAG) in the quadruple mutant strain Saccharomyces cerevisiae H1246, in which all four TAG biosynthesis genes (DGA1, LRO1, ARE1, and ARE2) are disrupted. In vitro enzymatic assays using microsomal preparations from the transformed yeast strain indicated that CpDGAT2 prefers ricinoleic acid as an acyl donor over linoleic acid, oleic acid, or linolenic acid, and it prefers 1,2-dioleoyl-sn-glycerol over 1,2-dipalmitoyl-sn-glycerol as an acyl acceptor. The coexpression of CpFAH with CpDGAT2 in yeast resulted in an increased accumulation of ricinoleic acid compared to the coexpression of CpFAH with the native yeast DGAT2 (S. cerevisiae DGA1 [ScDGA1]) or the expression of CpFAH alone. Northern blot analysis indicated that CpFAH is expressed solely in sclerotium cells, with no transcripts of this gene being detected in mycelium or conidial cells. CpDGAT2 was more widely expressed among the cell types examined, although expression was low in conidiospores. The high expression of CpDGAT2 and CpFAH in sclerotium cells, where high levels of ricinoleate glycerides accumulate, provided further evidence supporting the roles of CpDGAT2 and CpFAH as key enzymes for the synthesis and assembly of ricinoleic acid in C. purpurea.


Antinuclear antibodies and mortality in the National Health and Nutrition Examination Survey (1999-2004).
Recent studies suggest antinuclear antibodies (ANA) may be related to mortality risk, but evidence is sparse and inconclusive. Thus, we investigated ANA associations with all-cause and cause-specific mortality in U.S. adults. Our sample included 3357 adults (ages ≥20 years) from the 1999-2004 National Health and Nutrition Examination Survey with ANA measurements (1:80 dilution) and mortality data through 2011 (median follow-up: 9.4 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) via weighted Cox regression to assess ANA associations with mortality from all causes, cardiovascular disease (CVD), and cancer. Models adjusted for age, sex, race/ethnicity, education, and obesity. Analyses examined mortality in the full sample and in subgroups based on self-reported histories of CVD and cancer, both overall and stratified by sex and age at enrollment. Overall, ANA were not strongly associated with death from all causes (HR: 1.13; CI: 0.79, 1.60), from CVD (HR: 1.60; CI: 0.80, 3.20), or from cancer (HR: 1.58; CI: 0.75, 3.33), though all three HR estimates exceeded 1. In the subgroup with a history of cancer, ANA were associated with elevated all-cause mortality in men (HR: 2.28; CI: 1.01, 5.14) and in participants who enrolled at age ≥75 years (HR: 1.99; CI: 1.04, 3.80). These findings suggest that ANA are not strongly associated with mortality in the general population. Longitudinal studies with repeated assessments are needed to understand the temporal relationship between ANA, aging-associated diseases, and mortality.


Fatty acid profile as affected by fat depot and the sex category of Polish Holstein-Friesian × Limousin fattening cattle fed silage ad libitum.
This study was designed to compare the fatty acid profiles of four types of fat depots from bulls, steers, and heifers. All animals were Polish Holstein-Friesian and Limousin crossbreds fattened semi-intensively-silage at libitum and concentrate in the amount corresponding to 30% of their net energy requirements. The fatty acid profile in intramuscular, intermuscular, and external and internal fat was determined. The intramuscular fat of bulls was most abundant in total PUFAs and n-6 PUFAs, and functional fatty acids C 18:2, C 20:4, and C 22:5 in comparison with steers and heifers. Regardless of sex category, intramuscular and external fat were characterized by higher levels of UFAs and a more desirable MUFA/SFA ratio than the remaining fat types. It should also be noted that external fat was more abundant in CLA than other fat types, and that the highest CLA content was found in bull fat, compared with the remaining sex categories of cattle.


Knowledge, attitude, and barriers towards the use of evidence based practice among senior dental and medical students in western Saudi Arabia.
To investigate the knowledge, attitude, and barriers using evidence based practice (EBP) by future Saudi dentists and physicians. A questionnaire adapted from an EBP questionnaire was distributed to dental and medical final year students and new graduates at King Abdulaziz University, Jeddah, Saudi Arabia during the 2012 to 2013 academic year. The questionnaire consisted of 14 multiple-choice questions, and 2 open ended questions and was divided into 5 sections assessing different categories. Data were grouped as dental (DS) and medical (MS) students. Descriptive and group comparison statistics were conducted. Out of 400, 297 students responded (DS=207, MS=90) with a 74% response rate. The students' knowledge and attitude were low with no significant difference between the 2 groups. Students` knowledge and attitudes towards EBP were assessed: EBP course attendance (DS=40.1%, MS=13.3%; p=0.000), reading journals (DS=6.3%, MS=3.3%; p=0.313), awareness of EBP components (DS=7.7%, MS=0%; p=0.332), and awareness towards the strongest evidence for EBP (DS=58.9%, MS=53.3%; p=0.370). More than half of the students in both groups did not use EBP in their treatment (DS=85%, MS=84.4%; p=0.842). The greatest reported barriers were; EBP is difficult to understand (DS=88.9%, MS=72.2%; p=0.000), and no time (DS=54.6%, MS=46.7%; p=0.210). The reported knowledge and attitudes among the junior health care physicians is considered below the required competency standards. These findings highlight the urgent need for changes in the current educational strategies to assure successful implementation of EBP in Saudi Arabia.


Cloning, expression and purification of the complete domain of the η-carbonic anhydrase from Plasmodium falciparum.
The antimalarial drugs are of fundamental importance in the control of malaria, especially for the lack of efficient treatments and acquired resistance to the existing drugs. For this reason, there is a continuous work in identifying novel, less toxic and effective chemotherapies as well as new therapeutic targets against the causative agents of malaria. In this context, a superfamily of metalloenzymes named carbonic anhydrases (CAs, EC 126.96.36.199) has aroused a great interest as druggable enzymes to limit the development of Plasmodium falciparum gametocytes. CAs catalyze a common reaction in all life domains, the carbon dioxide hydration to bicarbonate and protons (CO2 + H2O ⇔ HCO3- + H+). P. falciparum synthesizes pyrimidines de novo starting from HCO3-, which is generated from CO2 through the action of the η-CA identified in the genome of the protozoan. Here, we propose a procedure for the preparation of a wider portion of the protozoan η-CA, named PfCAdom (358 amino acid residues), with respect to the truncated form prepared by Krungkrai et al. (PfCA1, 235 amino acid residues). The results evidenced that the recombinant PfCAdom, produced as a His-tag fusion protein, was 2.7 times more active with respect the truncated form PfCA1.


Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications.
DNA nanotechnology has been extensively explored to assemble various functional nanostructures for versatile applications. Mediated by Watson-Crick base-pairing, these DNA nanostructures have been conventionally assembled through hybridization of many short DNA building blocks. Here we report the noncanonical self-assembly of multifunctional DNA nanostructures, termed as nanoflowers (NFs), and the versatile biomedical applications. These NFs were assembled from long DNA building blocks generated via rolling circle replication (RCR) of a designer template. NF assembly was driven by liquid crystallization and dense packaging of building blocks, without relying on Watson-Crick base-pairing between DNA strands, thereby avoiding the otherwise conventional complicated DNA sequence design. NF sizes were readily tunable in a wide range, by simply adjusting such parameters as assembly time and template sequences. NFs were exceptionally resistant to nuclease degradation, denaturation, or dissociation at extremely low concentration, presumably resulting from the dense DNA packaging in NFs. The exceptional biostability is critical for biomedical applications. By rational design, NFs can be readily incorporated with myriad functional moieties. All these properties make NFs promising for versatile applications. As a proof-of-principle demonstration, in this study, NFs were integrated with aptamers, bioimaging agents, and drug loading sites, and the resultant multifunctional NFs were demonstrated for selective cancer cell recognition, bioimaging, and targeted anticancer drug delivery.


Glutaraldehyde affects biocompatibility of bioprosthetic heart valves.
A marked release of glutaraldehyde from commercially available pericardial bioprosthetic heart valve (BHV) material in washing solutions was found by high performance liquid chromatography (up to 1.8 ppm of glutaraldehyde per gram of dry tissue). In vitro endothelial cell proliferation rate was impaired dose-dependently in the presence of increasing glutaraldehyde concentrations of the cultivation medium (r = 0.9; p less than 0.05). Cultivation of endothelial cells was impossible on the surface of commercially available BHV material, but successful and uninhibited when toxic glutaraldehyde ligands of the BHV material were antagonized by treatment with L-glutamic acid.


Exploring the contributions of the supplementary eye field to subliminal inhibition using double-pulse transcranial magnetic stimulation.
It is widely accepted that the supplementary eye fields (SEF) are involved in the control of voluntary eye movements. However, recent evidence suggests that SEF may also be important for unconscious and involuntary motor processes. Indeed, Sumner et al. ([2007]: Neuron 54:697-711) showed that patients with micro-lesions of the SEF demonstrated an absence of subliminal inhibition as evoked by masked-prime stimuli. Here, we used double-pulse transcranial magnetic stimulation (TMS) in healthy volunteers to investigate the role of SEF in subliminal priming. We applied double-pulse TMS at two time windows in a masked-prime task: the first during an early phase, 20-70 ms after the onset of the mask but before target presentation, during which subliminal inhibition is present; and the second during a late phase, 20-70 ms after target onset, during which the saccade is being prepared. We found no effect of TMS with the early time window of stimulation, whereas a reduction in the benefit of an incompatible subliminal prime stimulus was found when SEF TMS was applied at the late time window. These findings suggest that there is a role for SEF related to the effects of subliminal primes on eye movements, but the results do not support a role in inhibiting the primed tendency. Hum Brain Mapp 38:339-351, 2017. © 2016 Wiley Periodicals, Inc.


Structure of the Resource Theory of Quantum Coherence.
Quantum coherence is an essential feature of quantum mechanics which is responsible for the departure between the classical and quantum world. The recently established resource theory of quantum coherence studies possible quantum technological applications of quantum coherence, and limitations that arise if one is lacking the ability to establish superpositions. An important open problem in this context is a simple characterization for incoherent operations, constituted by all possible transformations allowed within the resource theory of coherence. In this Letter, we contribute to such a characterization by proving several upper bounds on the maximum number of incoherent Kraus operators in a general incoherent operation. For a single qubit, we show that the number of incoherent Kraus operators is not more than 5, and it remains an open question if this number can be reduced to 4. The presented results are also relevant for quantum thermodynamics, as we demonstrate by introducing the class of Gibbs-preserving strictly incoherent operations, and solving the corresponding mixed-state conversion problem for a single qubit.


Numerical investigation of blood flow and red blood cell rheology: the magnetic field effect.
In this study, the motion and deformation of a red blood cell in a Poiseuille flow through microvessels under the effect of a uniform transverse magnetic field is comprehensively investigated to get a better insight into blood hemorheology. The rheology of the RBC and the surrounding blood flow are examined numerically in two dimensions using a Finite Element Method. It is essential to know that the flow patterns of blood change in the presence of an RBC. The simulation results demonstrate that the magnetic field has significant influence on the flow stream and the behavior of the RBC, including the motion and the cells deformation.


Analysis of free MEDLINE on the WWW.
In the paper, a survey of free MEDLINE access on the WWW is given. We compared five different vendors that provide free unlimited access to MEDLINE. The comparison of different search parameters was made: number of search statements, number of search fields, ability to combine search statements, number of search limits. The possibilities of using MESH thesaurus during the search are also explored. At last, we compared and evaluated the results of two search queries, obtained with searching MEDLINE, provided by five vendors mentioned above.


Rotational Spectra of Unsaturated Carbon Chains Produced by Pyrolysis: The Case of Propadienone, Cyanovinylacetylene, and Allenylacetylene.
Several interstellar molecules are highly reactive unsaturated carbon chains, which are unstable under terrestrial conditions. Laboratory studies in support of their detection in space thus face the issue of how to produce these species and how to correctly model their rotational energy levels. In this work, we introduce a general approach for producing and investigating unsaturated carbon chains by means of selected test cases. We report a comprehensive theoretical/experimental spectroscopic characterization of three species, namely, propadienone, cyanovinylacetylene, and allenylacetylene, all of them being produced by means of flash vacuum pyrolysis of a suitable precursor. For each species, quantum-chemical calculations have been carried out with the aim of obtaining accurate predictions of the missing spectroscopic information required to guide spectral analysis and assignment. Rotational spectra of the title molecules have been investigated up to 400 GHz by using a frequency-modulation millimeter-/submillimeter-wave spectrometer, thus significantly extending spectral predictions over a wide range of frequency and quantum numbers. A comparison between our results and those available in the literature points out the clear need of the reported laboratory measurements at higher frequencies for setting up accurate line catalogs for astronomical searches.


The Prevalence and Predictors of Dietary Supplement Use in the Australian Population.
Current dietary supplement use in Australia is not well described. We investigated the prevalence and predictors of supplement use in the Australian population (n = 19,257) using data from the 2014-2015 National Health Survey. We reported the prevalence of supplement use by sex and age group and investigated the independent predictors of supplement use in adults, adolescents, and children using multiple logistic regression models. A total of 43.2% of adults (34.9% of males, 50.3% of females), 20.1% of adolescents (19.7% of males, 20.6% of females), and 23.5% of children (24.4% of males, 22.5% of females) used at least one dietary supplement in the previous two weeks. The most commonly used supplements were multivitamins and/or multiminerals and fish oil preparations. In adults, independent predictors of supplement use included being female, increasing age, being born outside Australia and other main English-speaking countries, having a higher education level, having a healthy BMI compared to those who were obese, being physically active, and being a non-smoker. To our knowledge, this is the first detailed investigation of dietary supplement use in a nationally-representative sample of the Australian population. Future studies investigating the contribution of supplements to overall dietary intakes of vitamins, minerals, and omega-3 fatty acids are warranted.


Biomarker discovery using protein microarray technology platforms: antibody-antigen complex profiling.
Protein microarrays represent an important new tool in proteomic systems biology. This review focuses on the contributions of protein microarrays to the discovery of novel disease biomarkers through antibody-based assays. Of particular interest is the use of protein microarrays for immune response profiling, through which a disease-specific antibody repertoire may be defined. The antigens and antibodies revealed by these studies are useful for clinical assay development, with enormous potential to aid in diagnosis, prognosis, disease staging and treatment selection. The discovery and characterization of novel biomarkers specifically tailored to disease type and stage are expected to enable personalized medicine by facilitating preventative medicine, predictive diagnostics and individualized curative therapies.


Morphological and morphometrical study of human lens in senile cataract.
Histological changes were studied in 34 senile cataractous lenses removed surgically from patients aged 50 to 78 years. Sixty-eight percent had nuclear sclerosis, 44% swollen cells and morgagnian globular changes, 23% calcium deposition, 15% migration of epithelial cells beneath posterior capsule and villous projection in posterior in 7%. Several cases had more than one histological abnormality. There was significant reduction in the diameter of epithelial cells of the cataract and insignificant change in capsular thickness.


Antimicrobial activity and main chemical composition of two smoke condensates from Peganum harmala seeds.
The smoke of Peganum harmala seeds is traditionally used in Iran as a disinfectant agent. The aim of this study was to determine the antimicrobial activity of two smoke condensates from Peganum harmala seeds. Furthermore the composition of smoke preparations was studied using gas chromatography and mass spectroscopy analysis. The most prevalent compound detected in a dichloromethane extract was harmine. Standard harmine as well as the dichloromethane extract showed antimicrobial activity against all test strains. Harmine was not detected in an n-hexane extract and we did not observe antimicrobial activity from this smoke preparation at the tested concentrations.


Quercetin inhibits virulence properties of Porphyromas gingivalis in periodontal disease.
Porphyromonas gingivalis is a causative agent in the onset and progression of periodontal disease. This study aims to investigate the effects of quercetin, a natural plant product, on P. gingivalis virulence properties including gingipain, haemagglutinin and biofilm formation. Antimicrobial effects and morphological changes of quercetin on P. gingivalis were detected. The effects of quercetin on gingipains activities and hemolytic, hemagglutination activities were evaluated using chromogenic peptides and sheep erythrocytes. The biofilm biomass and metabolism with different concentrations of quercetin were assessed by the crystal violet and MTT assay. The structures and thickness of the biofilms were observed by confocal laser scanning microscopy. Bacterial cell surface properties including cell surface hydrophobicity and aggregation were also evaluated. The mRNA expression of virulence and iron/heme utilization was assessed using real time-PCR. Quercetin exhibited antimicrobial effects and damaged the cell structure. Quercetin can inhibit gingipains, hemolytic, hemagglutination activities and biofilm formation at sub-MIC concentrations. Molecular docking analysis further indicated that quercetin can interact with gingipains. The biofilm became sparser and thinner after quercetin treatment. Quercetin also modulate cell surface hydrophobicity and aggregation. Expression of the genes tested was down-regulated in the presence of quercetin. In conclusion, our study demonstrated that quercetin inhibited various virulence factors of P. gingivalis.


Living conditions of young families in Poland (1991-1992).
"The article presents the results of a survey carried out by [Poland's] Institute of Social Economy in the last quarter of 1991. It included 1,716 women and their families.... The research gathered much information about the functioning of young Polish families at the end of 1991 and at the beginning of 1992; about their material situation as well as their living problems and needs."


[Symptomless amniotic infection related to pregnancy outcome].
Placental histology in 984 pregnancies (758 term and 226 preterm) occurring during the years 1995 to 1998 was investigated and amniotic cavity cultures were taken during 918 cesarean sections. Histology revealed placental infection in 20.3% of placentas. Chorioamnionitis was confirmed in 119 out of 758 term pregnancies (15.7%) while in 81 out of 226 preterm pregnancies (35.8%); the difference is highly significant (chi 2 = 26.6, p < 0.01). Bacteriological culture resulted in bacterial growth in 19.7% of all cases (181/918), its frequency was significant higher in premature births (54/133, 40.3% chi 2 = 25.2, p < 0.01) as compared with pregnancies carried to term. Recovery of any organism from the amniotic cavity was strongly associated with chorioamnionitis confirmed by histology. Comparison of the rates of indicating placental infection found in this study and a study performed between 1981 and 1983, showed that the program aiming at detection and treatment of silent intrauterine infection has only partially been successful.


Cytomegalovirus pneumonia and pulmonary haemorrhage in a patient with polyarteritis nodosa.
Cytomegaloviruses are opportunistic pathogens that cause lung infection in immunocompromised individuals. A 24-year-old male was admitted to the hospital with complaints of cough, fever and dyspnoea. He was receiving immunosuppressive therapy for polyarteritis nodosa. A chest X-ray showed heterogeneous right-sided opacity in the middle and lower lung zones. The diagnosis of cytomegalovirus pneumonia was confirmed by positive testfor serum cytomegalovirus IgM antibodies.Oneday after admission, haemoptysis developed and patient with hemoptysis who had shortness of breath was intubated. Computed tomography (CT) showed bilateral alveolar opacity.


The Effect of Outdoor and Indoor Group Exercise Classes on Psychological Stress in College Students: A Pilot Study with Randomization.
Emerging evidence suggests that outdoor group exercise may reduce stress more than indoor group exercise because the outdoor environment provides unique mental health benefits. Stress leads to illnesses and diseases, but exercise mitigates harmful impacts. This study explored differences in perceived stress and outdoor physical activity participation among college students in an indoor or outdoor group exercise class. Data were collected pre-, mid- (after four sessions), and post-intervention (after eight sessions). Seventeen participants indicated an interest in the study, but 13 signed up. Participants completed a four-week group exercise intervention that met twice weekly in outdoor and indoor conditions. Mixed ANOVAs with Tukey post hoc tests determined between-group differences in perceived stress and outdoor physical activity levels. Partial eta-squared (η2p) estimated effect sizes. Significant differences in perceived stress scores existed across time for the whole sample [f(2, 12) = 48.359, p < 0.001, η2p = 0.890] and for the interaction between time and condition [f(2, 12) = 10.051, p = 0.003, η2p = 0.626]. Post hoc analysis revealed that the outdoor group's perceived stress (p < 0.001) was reduced more than the indoor group post-intervention (p = 0.028).


The relationship of sperm DNA fragmentation index with the outcomes of in-vitro fertilisation-embryo transfer and intracytoplasmic sperm injection.
This study was conducted to investigate the relationship between sperm DNA fragmentation index (DFI) and the outcomes of in-vitro fertilisation-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). Sperm DFI in 116 patients for IVF and 63 patients for ICSI were detected with acridine orange test (AOT), and all the cases were divided into DFI ≤ 30% group and DFI > 30% group according to the DFI value; then, the relationship of DFI with the outcomes of IVF/ICSI were analysed. Both in IVF and ICSI cycles, good embryo rate and spontaneous abortion rate in DFI > 30% group were significantly different from that in DFI ≤ 30% group, meanwhile, the fertilisation rate and cleavage rate were similar in two groups. In ICSI cycles, there was a significantly negative correlation between the DFI value and the rates of embryo implantation and pregnancy; the couples with DFI > 30% had significantly lower embryo implantation rate and pregnancy rate than the ones with DFI ≤ 30%. The receiver operating characteristics curve analysis demonstrated that the DFI value were statistically significant predictors of pregnancy. It is concluded that DNA-damaged sperm could have a potential adverse effect on embryo quality and progression of pregnancy as well as the outcomes of ICSI.


Implicit Theories versus the Social Construal of Ability in Self-Regulation and Performance on a Complex Task.
The present experiment examined the relative impacts of implicit theories and the social construal of ability as either a fixed entity or an incremental skill on self-efficacy, affective reactions, self-set goals, and performance on a complex group-management task. It was also a novel task for participants. Participants who had an implicit theory that group-management ability is an incremental skill that can be acquired with experience developed stronger self-efficacy, maintained more positive affect, and set themselves more challenging goals across multiple trials. They also outperformed participants with a fixed-entity theory of group-management ability. Some of the motivational benefits of an incremental-skill conception were lost when the social construal of managerial ability emphasized a fixed-entity conception. However, the negative motivational effects of a fixed-entity theory of ability were not ameliorated by the social construal of managerial ability as an incremental skill. The effects of conceptions of ability were fully mediated by the self-regulatory responses of participants. The hypothesis that self-efficacy moderates the impact of ability conceptions on self-set goal challenges was not supported. Copyright 1999 Academic Press.


Mutations in hepatitis C virus p7 reduce both the egress and infectivity of assembled particles via impaired proton channel function.
Hepatitis C virus (HCV) p7 protein is critical for the efficient production of infectious virions in culture. p7 undergoes genotype-specific protein-protein interactions as well as displaying channel-forming activity, making it unclear whether the phenotypes of deleterious p7 mutations result from the disruption of one or both of these functions. Here, we showed that proton channel activity alone, provided in trans by either influenza virus M2 or genotype 1b HCV p7, was both necessary and sufficient to restore infectious particle production to genotype 2a HCV (JFH-1 isolate) carrying deleterious p7 alanine substitutions within the p7 dibasic loop (R33A, R35A), and the N-terminal trans-membrane region (N15 : C16 : H17/AAA). Both mutations markedly reduced mature p7 abundance, with those in the dibasic loop also significantly reducing levels of mature E2 and NS2. Interestingly, whilst M2 and genotype 1b p7 restored the same level of intracellular infectivity as JFH-1 p7, supplementing with the isogenic protein led to a further increase in secreted infectivity, suggesting a late-acting role for genotype-specific p7 protein interactions. Finally, cells infected by viruses carrying p7 mutations contained non-infectious core-containing particles with densities equivalent to WT HCV, indicating a requirement for p7 proton channel activity in conferring an infectious phenotype to virions.


Vascular endothelial growth factor ‑634G/C polymorphism is associated with increased breast cancer risk and aggressiveness.
Polymorphisms in the promoter and 5' untranslated region of vascular endothelial growth factor (VEGF) have been associated with VEGF levels. To investigate the role of VEGF polymorphisms in breast cancer, the VEGF ‑2578C/A, ‑1498C/T, ‑1154G/A and ‑634G/C polymorphisms were genotyped in 483 breast cancer patients and 524 healthy controls. VEGF mRNA levels in breast cancer tissue were determined using semi‑quantitative RT‑PCR. The genotypes, ‑634G/C and ‑634C/C, were associated with an increased risk for breast cancer when compared with the ‑634G/G genotype. The VEGF ‑634G/C genotype was associated with tumor size >20 mm, perineural invasion and stage II‑IV. Individuals with ‑634C/C had lower disease‑free survival. Patients with the VEGF ‑634C/C genotype exhibited the highest VEGF mRNA levels. High VEGF mRNA expression correlated with tumor size >20 mm, presence of lymphovascular invasion and axillary nodal metastasis. These observations suggested that VEGF ‑634G/C polymorphisms have a significant role in breast cancer susceptibility and aggressiveness.


[Double-blind randomized comparative study of nicergoline naftidrofuryl on the quality of life in chronic obliterative arteriopathy of lower limbs with intermittent claudication].
The functional limitation of patients with obliterative arterial disease, and with intermittent claudication, damages their quality of life. The purpose of this trial was to compare the effects of nicergoline and naftidrofuryl on the quality of life and the functional discomfort of the 131 patients with claudication. It was a multicentre, randomised, double-blind trial with parallel groups. The patients were asked to complete a quality of life questionnaire and a Visual Analogue Scale, and to evaluate the number of steps on flat ground before the pain began. After 6 months of treatment, we observed, for all treatments combined, a significant improvement (p = 0.0001) in the quality of life and in the functional discomfort. Three variables favoured nicergoline: the estimated time before the onset of the pain (p = 0.003), the functional discomfort quantified by the Visual Analogue Scale (p < 0.05), the distance covered on flat ground (p = 0.013). The other variables, and especially the total score on the self-questionnaire, confirmed this impression, without reaching significance (p = 0.136). The data suggest that in terms of quality of life nicergoline is superior. The clinical tolerance is good and comparable between the two treatments.


Role of compartmentation in promoting toxicity of leukocyte-generated strong oxidants.
A rigorous mathematical model is developed to describe the distribution of respiration-generated oxidants among reactive sites within the phagolysosomes of leukocytic cells. Reaction parameters include the diffusion coefficient of the oxidant, the intrinsic rate constants for its reaction with the phagosomal membrane and the cell envelopes of entrapped bacteria, the overall rate constant for its reaction with solution components of the phagosomal fluid, and the phagosomal dimensions. The model is used to describe the dynamics of randomly generated .OH and HCO3. radicals within the phagosome. These radicals were chosen because the necessary rate parameters either have been measured or could be reasonably estimated. The calculations show that .OH radical cannot be an effective bactericide unless generated in the immediate vicinity of the bacterial surface because its extreme reactivity precludes any significant diffusion. The HCO3. radical, however, is predicted to be a very effective toxin, even when relatively high concentrations of oxidant scavengers are present in the phagosomal fluid. In the absence of complicating features, the reactivity patterns of other less reactive oxidants (e.g., metal oxo or peroxo complex ions) are predicted to be very similar, although quantitative analysis is precluded by the lack of relevant rate data. For these oxidants, the predicted intraphagosomal toxicities differ markedly from toxicities measured in dilute bacterial suspensions because differences in mean diffusion lengths of the oxidants are unimportant in environments with the dimensions of phagosomes, but very important under in vitro conditions. The model is general and can be applied to other reactions occurring in similar microheterogeneous cellular and subcellular environments.


Pubertal development in south-Hungarian boys and girls.
Data on pubertal development in 1392 boys and 1494 girls from the cross-sectional Pécs Growth Study are reported. Genital, breast and pubic-hair development were rated according to Tanner (1962). The initiation of pubic-hair development in boys was 11.8 years and that of genital development was 12.0 years. Stage 2 of pubic-hair development (PH2) in boys occurred 1.7 years later than in girls. The mean time of different stages of pubertal development in boys was in the same range as in Eveleth and Tanner's study (1991). Stages 2, 3 and 4 for pubic-hair and breast development in Pécs girls occurred earlier than in Eveleth and Tanner's subjects (1991), while the mean time of stage 5 for both sexual characteristics occurred at a later age than reported in Eveleth and Tanner (1991). The age of menarche was 12.9 years in Pécs girls, which seems later by 0.1-0.6 years than in Western-European countries and earlier by 0.1-0.3 years than in South-European countries.


All-dielectric hollow nanodisk for tailoring magnetic dipole emission.
We propose a silicon hollow nanodisk for enhancing magnetic dipole (MD) emission. The Purcell factor can be more than 300, which is one order of magnitude larger than the silicon nanosphere case. It is demonstrated that the silicon hollow nanodisk resembles the function of an azimuthally polarized beam for tailoring the magnetic and electric dipole (ED) emission. It is shown that MD emission can be significantly enhanced, while ED emission will be suppressed when emitters are located in the hollow of the nanodisk. The dependence of the Purcell factor on the geometry parameters is also studied. Our results might facilitate the on-chip engineering of magnetic light emission.


Effects of bridge exercise on trunk core muscle activity with respect to sling height and hip joint abduction and adduction.
[Purpose] This study evaluated the effects of bridge exercise on trunk core muscle activity with respect to sling height and hip joint abduction and adduction. [Subjects] Fifteen healthy adult males participated. [Methods] In the bridge exercise, the height of the sling was set low or high during hip joint abduction and adduction. Electromyography was used to compare the differences between the muscle activities of the transverse abdominis, rectus abdominis, and erector spinae muscles. [Results] The muscle activities of the transverse abdominis, rectus abdominis, and erector spinae were significantly higher in the high sling position. Furthermore, the activities of the transverse abdominis and erector spinae were significantly higher during hip joint adduction than abduction regardless of sling height. [Conclusion] A high sling height is the most effective intervention for increasing the muscle activities of the transverse abdominis and erector spinae muscles during hip joint adduction in a bridge exercise.


Urethroplasty for posterior urethral strictures.
To assess the long-term results and complications of urethroplasty for patients with pelvic fracture injuries of the posterior urethra and to determine which type of of procedure is most appropriate. Eighty-two patients were followed prospectively after undergoing transperineal bulboprostatic anastomotic urethroplasty (AU). The results and complications in these patients were compared with 59 patients who had a 'patch' urethroplasty (PU) for a short stricture which in other circumstances might have been amenable to AU. The 1-, 5- and 10-year re-stricture rates were 7, 12 and 12%, respectively, for AU and 12, 20 and 31% for PU. Four of the 10 patients who re-strictured during the 5-year follow-up after AU were > 55 years of age and four of the seven patients who had an AU and who were > 55 years old re-strictured. All the patients who re-strictured were impotent. The commonest complications after AU were principally a consequence of the original injury rather than the surgery, whereas the complications after PU were principally related to the surgery. Impotence sometimes occurred after both types of urethroplasty. Anastomotic urethroplasty is the best available procedure for traumatic proximal urethral strictures but was not tolerated well in the elderly and caused impotence in a small but significant proportion. The results of PU were less satisfactory and the difference became progressively more marked with a longer follow-up.


Phosphatidic Acid Stimulates Myoblast Proliferation through Interaction with LPA1 and LPA2 Receptors.
Phosphatidic acid (PA) is a bioactive phospholipid capable of regulating key biological functions, including neutrophil respiratory burst, chemotaxis, or cell growth and differentiation. However, the mechanisms whereby PA exerts these actions are not completely understood. In this work, we show that PA stimulates myoblast proliferation, as determined by measuring the incorporation of [3H]thymidine into DNA and by staining the cells with crystal violet. PA induced the rapid phosphorylation of Akt and ERK1/2, and pretreatment of the cells with specific small interferin RNA (siRNA) to silence the genes encoding these kinases, or with selective pharmacologic inhibitors, blocked PA-stimulated myoblast proliferation. The mitogenic effects of PA were abolished by the preincubation of the myoblasts with pertussis toxin, a Gi protein inhibitor, suggesting the implication of Gi protein-coupled receptors in this action. Although some of the effects of PA have been associated with its possible conversion to lysoPA (LPA), treatment of the myoblasts with PA for up to 60 min did not produce any significant amount of LPA in these cells. Of interest, pharmacological blockade of the LPA receptors 1 and 2, or specific siRNA to silence the genes encoding these receptors, abolished PA-stimulated myoblast proliferation. Moreover, PA was able to compete with LPA for binding to LPA receptors, suggesting that PA can act as a ligand of LPA receptors. It can be concluded that PA stimulates myoblast proliferation through interaction with LPA1 and LPA2 receptors and the subsequent activation of the PI3K/Akt and MEK/ERK1-2 pathways, independently of LPA formation.


Caspase-cleaved tau expression induces mitochondrial dysfunction in immortalized cortical neurons: implications for the pathogenesis of Alzheimer disease.
In Alzheimer disease (AD) mitochondrial abnormalities occur early in the pathogenic process and likely play a significant role in disease progression. Tau is a microtubule-associated protein that is abnormally processed in AD, and a connection between tau pathology and mitochondrial impairment has been proposed. However, few studies have examined the relationship between pathological forms of tau and mitochondrial dysfunction. We recently demonstrated that inducible expression of tau truncated at Asp-421 to mimic caspase cleavage (T4C3) was toxic to immortalized cortical neurons compared with a full-length tau isoform (T4). In this study we investigated the effects of T4C3 on mitochondrial function. Expression of T4C3 induced mitochondrial fragmentation and elevated oxidative stress levels in comparison with T4-expressing cells. Thapsigargin treatment of T4 or T4C3 cells, which causes an increase in intracellular calcium levels, resulted in a significant decrease in mitochondrial potential and loss of mitochondrial membrane integrity in T4C3 cells when compared with cells expressing T4. The mitochondrial fragmentation and mitochondrial membrane damage were ameliorated in T4C3 cells by pretreatment with cyclosporine A or FK506, implicating the calcium-dependent phosphatase calcineurin in these pathogenic events. Increased calcineurin activity has been reported in AD brain, and thus, inhibition of this phosphatase may provide a therapeutic target for the treatment of AD.


HOX11 interacts with CTF1 and mediates hematopoietic precursor cell immortalization.
HOX11 is a homeodomain-containing oncogenic transcription factor that immortalizes hematopoietic precursor cells. The mechanism by which HOX11 facilitates this initial step of leukemogenesis is, however, not well understood. We have used a DNA binding site selection assay to investigate cooperative DNA binding by HOX11 with other transcription factors. A consensus sequence was derived and identified as the binding site for the CCAAT-box-binding transcription factors (CTF). HOX11 was shown to interact in vitro and in vivo with CTF1. Retrovirus-mediated transduction of an antisense CTF1 cDNA dramatically reduced the proliferative capacity of HOX11-immortalized hematopoietic precursor cells. CTF1 is, therefore, the first HOX11 protein partner identified that plays an important role in hematopoietic precursor cell immortalization.


Tensile stress stimulates the expression of osteogenic cytokines/growth factors and matricellular proteins in the mouse cranial suture at the site of osteoblast differentiation.
Mechanical stress promotes osteoblast proliferation and differentiation from mesenchymal stem cells (MSCs). Although numerous growth factors and cytokines are known to regulate this process, information regarding the differentiation of mechanically stimulated osteoblasts from MSCs in in vivo microenvironment is limited. To determine the significant factors involved in this process, we performed a global analysis of differentially expressed genes, in response to tensile stress, in the mouse cranial suture wherein osteoblasts differentiate from MSCs. We found that the gene expression levels of several components involved in bone morphogenetic protein, Wnt, and epithelial growth factor signalings were elevated with tensile stress. Moreover gene expression of some extracellular matrices (ECMs), such as cysteine rich protein 61 (Cyr61)/CCN1 and galectin-9, were upregulated. These ECMs have the ability to modulate the activities of cytokines and are known as matricellular proteins. Cyr61/CCN1 expression was prominently increased in the fibroblastic cells and preosteoblasts in the suture. Thus, for the first time we demonstrated the mechanical stimulation of Cyr61/CCN1 expression in osteogenic cells in an ex vivo system. These results suggest the importance of matricellular proteins along with the cytokine-mediated signaling for the mechanical regulation of MSC proliferation and differentiation into osteoblastic cell lineage in vivo.


Mental health service users' and practitioners' experiences of engagement in assertive outreach: a qualitative study.
Assertive outreach services have been central to community mental health policy within the UK. These multidisciplinary teams were established to engage with service users who have severe and enduring mental health problems and have found traditional community services unable to meet their needs. Mental health nurses have a pivotal role in these multidisciplinary teams, yet the nature of these relationships from the perspective of those who work in and receive care is poorly understood. This study set out to explore the nature and meaning of engagement for practitioners and service users within assertive outreach services. A qualitative approach, informed by philosophical hermeneutics, underpinned the study. Participants were recruited from a single assertive outreach team in the UK. To be eligible for the study, mental health practitioners needed to be employed within the assertive outreach team. All service users residing in the community and receiving care from the team were also eligible for inclusion. In total 14 interviews were conducted with mental health practitioners and 13 with service users. Data analysis was informed by Turner's method. Four themes emerged from the data; contact, dialogue, transformation and shared understanding. Meaningful engagement was found to manifest itself through experiences such as providing and receiving practical assistance, having a genuine two-way conversation and valuing the experiences and personal attributes of the other person. The findings indicate that engagement is an active, dynamic and skilled process, which leads practitioners and service users to transform together to create a new relationship.


Successful in-vitro fertilization pregnancy with spermatozoa from a patient with Kartagener's syndrome: case report.
This paper reports on the successful treatment by in-vitro fertilization (IVF) of a couple in whom the male partner had Kartagener's syndrome. His spermatozoa were severely asthenozoospermic with deficient dynein arms and disordered microtubular configuration. On computer-assisted sperm analysis (CASA) motile spermatozoa displayed straight non-progressive motility with minimal amplitude of lateral head displacement and none were hyperactivated. This is the first case report in which spermatozoa with axonemal disruption in a man with immotile cilia syndrome (ICS) have been shown to be able to penetrate the zona pellucida and fertilize oocytes. IVF may be a suitable treatment for certain variants of ICS.


The current role of laparoscopic surgery in gynecological oncology.
Transabdominal laparotomy is currently the standard approach to the surgical diagnosis and treatment of gynecological malignancies. Despite the fact that laparoscopy has been widely embraced by our gynecological/infertility colleagues for many years, it has only sporadically been utilized by gynecological oncologists. With the advent of video laparoscopy, novel instrumentation, and new techniques, a reevaluation of the applicability of this procedure is certainly in order. To date, laparoscopy has been employed for the performance of a multitude of intra-abdominal procedures. However, universal applicability may not be feasible or in the best interest of all patients with gynecological malignancies. As instrumentation and techniques evolve, it is possible that procedures currently nonamenable to the laparoscopic approach may become so. However, it is wise to approach these new procedures with healthy skepticism, and within the context of proper scientific study. This article summarizes the status of laparoscopic surgery in gynecological oncology.


Prevalence and pattern of psychiatric morbidity in children.
Present study was carried out at child guidance clinic of Guru Teg Bahadur Hospital, Delhi. Sample consisted of 300 children (175 boys and 125 girls of aged 2-12 years) from November, 1994 to October, 1996. Diagnoses were made by using ICD-10 criteria. The major diagnoses were mental retardation (20.6%), epilepsy (20%), hysterical conversion reaction (6.3%), ADHD (5%) and childhood depression (6%).


Effect of fiber insertion depth on antibacterial efficacy of photodynamic therapy against Enterococcus faecalis in rootcanals.
This in vitro study evaluated the effect of fiber insertion depth on antimicrobial efficacy of antimicrobial photodynamic therapy (aPDT) using a photosensitizer (PS; toluidine blue) and a red light-emitting diode (LED) in root canals infected with Enterococcus faecalis. Single-rooted extracted teeth were prepared with nickel-titanium-instruments, sterilized, contaminated with E. faecalis, and incubated for 72 h. Roots were randomly divided into four experimental groups: PS only, LED only, aPDT with LED in the apical third, aPDT with LED in the coronal third, as well as into infection and sterile controls (each n = 10). Samples were taken by collecting standardized dentine shavings from the root canal walls. After serial dilution and culturing on blood agar, colony-forming units (CFU) were counted. Both aPDT groups showed a CFU reduction of 1-2 log10 steps compared with the infection control, whereas the effect of fiber insertion depth was negligible (<0.5 log10 steps). CFU reduction of approximately 0.5 log10 steps for PS alone was detected compared with the infection control, but PS alone was less effective than both aPDT groups. No antibacterial effect was detected for LED alone. aPDT reduced E. faecalis within the root canal, whereas fiber insertion depth had a negligible influence on antimicrobial effectiveness of aPDT. The insertion depth of the light-emitting diode may not influence the antibacterial efficacy of photodynamic therapy against E. faecalis in straight root canals.


[Reliability of ultrasound ileus diagnosis].
We investigated in this study if we would be able to find the correct indication for laparotomy earlier by sonographical examination than by clinical and radiological findings. In 48 of 594 patients with unknown abdominal diseases we found an intestinal obstruction by laparotomy. The indication based on clinical and radiological findings in 37 patients (sensitivity: 77.1%). In comparison the indication for laparotomy was predetermined correctly only after sonographical examination in 45 patients (sensitivity: 89.6%). According to the number of sonographical findings the reliability of the indication for laparotomy increased. The examination by sonography is a valuable tool in the diagnosis of intestinal obstruction.


Airway obstruction requiring tracheal intubation after fine-needle aspiration of the thyroid gland: a case report.
There have been no reports of tracheal intubation for airway obstruction after acute thyroid swelling following fine-needle aspiration (FNA) of the thyroid gland. A 58-year-old woman with a 22 mm × 13 mm right hypervascular thyroid nodule underwent FNA once with a 22G needle under ultrasonographic guidance. Shortly after the aspiration, ultrasound revealed hypoechoic swelling with a crack-like pattern. The patient was observed under bed rest in the Fowler position and received intravenous steroids. A computed tomography (CT) scan showed swelling not only of the thyroid but also of the retropharyngeal space, and the patient complained of difficulty swallowing saliva. Laryngeal fiberscopy revealed protrusion of the posterior pharyngeal wall, edematous changes in the mucosa of the pharynx and epiglottis, and retention of saliva. The patient was intubated awake and hydrocortisone was administered every 8 h. She was extubated 3 days after FNA and discharged without any complications. When neck swelling is noticed after FNA, ultrasonographic findings are especially important to assess potential causes. If airway obstruction is suspected, CT findings and fiberscope observation of the pharynx provide particularly useful information.


Open channel block and open channel destabilization: contrasting effects of phenol, TEA+ and local anaesthetics on Kv1.1 K+ channels.
(1) Voltage-gated K+ channels are inhibited by a variety of clinical and experimental drugs. (2) Complex changes in channel gating suggest mechanisms in which drug affinity depends on channel state. (3) Here, we use the effects of external TEA+, two local anaesthetics (lidocaine and bupivacaine), and phenol on rat brain Kv1.1 K+ channels expressed in Xenopus oocytes to illustrate three mechanisms. (4) The open state has the highest affinity in the local anaesthetic model but the lowest in the phenol model, and while local anaesthetics simply block the open channel, phenol can produce a conducting but destabilized open state. (5) All states have equal affinity for external TEA+.


Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton's jelly as sources of cell immunomodulatory therapy.
To characterize different tissue MSCs as sources of cell immunomodulatory therapy. Examined the effects of IFN-γ on WJ-MSC and their immunomodulatory function characteristics. We compared human fetal bone marrow (F-BM), adipose tissue (AT), and Warton's Jelly-derived MSCs (WJ-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, gene expression, and whether IFN-γ affected WJ-MSC gene expression, as determined by real time quantitative PCR. Fifteen geneswere examined. We further assess WJ-MSCs-mediated immunomodulatory on peripheral blood mononuclear, stimulated by PHA, IL-2 and CD3Ab after 5 days of co-cultured in a 5:1 ratio (PBMC:MSCs). Examined the effect of WJ-MSCs on the Th1, Th2, Th17 cytokines production and Treg augument. MSCs from different tissues have similar levels of cell surface antigen expression and differentiation ability, while F-BM-MSCs and WJ-MSC had higher rates of cell proliferation and clonality than AD-MSCs. All 15 genes were expressed at similar levels in WJ-MSCs and AD-MSCs (P > 0.05). 9 genes were upregulated in WJ-MSCFor F-MSC, including IL-6, CXCL9, CXCL10, CXCL11, ICAM-1, IDO1, HLA-G5, SDF1A, and NOTCH were down expression, but VCAM-1 was lower expressionin WJ-MSCS. After IFN-γ treatment, 7 genes were upregulated in WJ-MSC, including chemokine ligands CXCL9, CXCL10 and CXCL11, and the adhesion protein VCAM1and ICAM1. Additionally, immunosuppressive factors, such as HLA-G and IDO were both increased. When cocultured with peripheral blood mononuclear, WJ-MSCs showed an immunosuppressive function by inhibit the proliferative response of Th1 and Th17 but augment Th2 and Treg. Primed WJ-MSCs by IFNγ caused a greater reduction in IFNγ and TNFα than untreated WJ-MSCs, also the effect on augument in Treg and inhibit Th17 (P < 0.01). Our results demonstrate that primitive F-BM-MSCs and WJ-MSCs have biological advantages as compared to adult cells, WJ-MSCs have a gene expression pattern similar to AT-MSCs but not F-BM MSCs, and that inflammatory stimuli regulate gene expression in WJ-MSCs. WJ-MSC showed the immunosuppressive function in co-cultured system with PBMC, and IFNγ can promoted the immunosuppressive function.


Atorvastatin reduces sympathetic activity in patients with chronic kidney disease.
Hypertensive chronic kidney disease (CKD) patients often have sympathetic hyperactivity, which appears to contribute to the pathogenesis of hypertension and cardiovascular organ damage. Experimental studies and some clinical studies have shown that statin therapy can reduce central sympathetic activity. Blockade of the renin-angiotensin system (RAS), which is standard treatment for CKD, is known to lower sympathetic activity. We hypothesized that adding a statin for 6 weeks to RAS blockade would further lower sympathetic activity in hypertensive stage 2-4 CKD patients. In 10 stable CKD patients (eight men, aged 45 ± 11 years, estimated glomerular filtration rate 56 ± 22 ml/min per 1.73 m2), who were on chronic treatment with aliskiren 300 mg, blood pressure and sympathetic activity (quantified by assessment of muscle sympathetic nerve activity, MSNA) were assessed at baseline and 6 weeks after atorvastatin 20 mg/day was added. Ten other CKD patients served as time control and were studied twice with an interval of 6 weeks without any change in medication, to quantify within participant reproducibility. Mean arterial blood pressure remained stable throughout the study (93 ± 5 versus 94 ± 5 mmHg). MSNA was reduced from 28 ± 8 to 20 ± 6 bursts/min (P = 0.01), while heart rate remained stable during the study. In the control CKD group, MSNA did not change: 26 ± 5 to 25 ± 6 bursts/min. Atorvastatin reduced total and low-density lipoprotein cholesterol. Atorvastatin has a further sympatholytic effect in CKD patients, who are on chronic aliskiren, which is independent of blood pressure and heart rate.


Preparing synthetic Aβ in different aggregation states.
This chapter outlines protocols that produce homogenous preparations of oligomeric and fibrillar amyloid-β peptide (Aβ). While there are several isoforms of this peptide, the 42 amino acid form is the focus because of its genetic and pathological link to Alzheimer's disease (AD). Past decades of AD research highlight the dependence of Aβ42 function on its structural assembly state. Biochemical, cellular and in vivo studies of Aβ42 usually begin with purified peptide obtained by chemical synthesis or recombinant expression. The initial steps to solubilize and prepare these purified dry peptide stocks are critical to controlling the structural assembly of Aβ. To develop homogenous Aβ42 assemblies, we initially monomerize the peptide, erasing any "structural history" that could seed aggregation, by using a strong solvent. It is this starting material that has allowed us to define and optimize conditions that consistently produce homogenous solutions of soluble oligomeric and fibrillar Aβ42 assemblies. These preparations have been developed and characterized by using atomic force microscopy (AFM) to identify the structurally discrete species formed by Aβ42 under specific solution conditions. These preparations have been used extensively to demonstrate a variety of functional differences between oligomeric and fibrillar Aβ42. We also present a protocol for fluorescently labeling oligomeric Aβ42 that does not affect structure, as measured by AFM, or function, as measured by a cellular uptake assay. These reagents are critical experimental tools that allow for defining specific structure/function connections.


Comparison of multistate Markov modeling with contemporary outcomes in a reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial.
Historically, ordinal measures of functional outcome have been dichotomized for the primary analysis in acute stroke therapy trials. A number of alternative methods to analyze the ordinal scales have been proposed, with an emphasis on maintaining the ordinal structure as much as possible. In addition, despite the availability of longitudinal outcome data in many trials, the primary analysis consists of a single endpoint. Inclusion of information about the course of disease progression allows for a more complete understanding of the treatment effect. Multistate Markov modeling, which allows for the full ordinal scale to be analyzed longitudinally, is compared with previously suggested analytic techniques for the ordinal modified Rankin Scale (dichotomous-logistic regression; continuous-linear regression; ordinal- shift analysis, proportional odds model, partial proportional odds model, adjacent categories logit model; sliding dichotomy; utility weights; repeated measures). In addition, a multistate Markov model utilizing an estimate of the unobservable baseline outcome derived from principal component analysis is compared Each of the methods is used to re-analyze the National Institute of Neurological Diseases and Stroke tissue plasminogen activator study which showed a consistently significant effect of tissue plasminogen activator using a global test of four dichotomized outcomes in the analysis of the primary outcome at 90 days post-stroke in the primary analysis. All methods detected a statistically significant treatment effect except the multistate Markov model without predicted baseline (p = 0.053). This provides support for the use of the estimated baseline in the multistate Markov model since the treatment effect is able to be detected with its inclusion. Multistate Markov modeling allows for a more refined examination of treatment effect and describes the movement between modified Rankin Scale states over time which may provide more clinical insight into the treatment effect. Multistate Markov models are feasible and desirable in describing treatment effect in acute stroke therapy trials.


Inhibition of vesicular stomatitis virus infection in epithelial cells by alpha interferon-induced soluble secreted proteins.
Interferons (IFNs) are potent antiviral cytokines that inhibit infection by a wide spectrum of viruses by activating the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. Several IFN-induced antiviral proteins including 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and Mx play a critical role in conferring the antiviral properties of IFN. However, studies have shown that additional antiviral factors are involved in addition to these proteins during IFN-mediated antiviral action. In an effort to characterize these novel antiviral factors, the antiviral mechanism of alpha IFN (IFN-alpha) against vesicular stomatitis virus (VSV) was investigated in human lung epithelial A549 cells. These studies demonstrated that soluble secreted antiviral proteins as the constituents of conditioned medium prepared from IFN-alpha-treated cells reduced VSV infectivity by more than 2 logs, compared with a 4 log inhibition observed following treatment of cells with IFN-alpha. The antiviral mechanism of these secreted proteins appeared to act at the level of cellular entry of VSV. Interestingly, the IFN-alpha-induced antiviral proteins were secreted independently of STAT1 (an essential component of the JAK/STAT pathway), demonstrating that the release of such extracellular soluble antiviral proteins from cells may represent an alternative mechanism of the antiviral defence strategy of IFN towards VSV infection.


Characterization of the membranous denitrification enzymes nitrite reductase (cytochrome cd1) and copper-containing nitrous oxide reductase from Thiobacillus denitrificans.
Cytochrome cd1-nitrite reductase and nitrous oxide reductase of Thiobacillus denitrificans were purified and characterized by biochemical and immunochemical methods. In contrast to the generally soluble nature of the denitrification enzymes, these two enzymes were isolated from the membrane fraction of T. denitrificans and remained active after solubilization with Triton X-100. The properties of the membrane-derived enzymes were similar to those of their soluble counterparts from the same organism. Nitrous oxide reductase activity was inhibited by acetylene. Nitrite reductase and nitrous oxide reductase cross-reacted with antisera raised against the soluble enzymes from Pseudomonas stutzeri. The nirS, norBC, and nosZ genes encoding the cytochrome cd1-nitrite reductase, nitric oxide reductase, and nitrous oxide reductase, respectively, from P. stutzeri hybridized with genomic DNA from T. denitrificans. Cross-reactivity and similar N-terminal amino acid and gene sequences suggest that the primary structures of the Thiobacillus enzymes are homologous to the soluble proteins from P. stutzeri.


Viewing distance variation and related ophthalmological changes in office activities with and without VDUs.
This experimental study was conducted on 14 volunteer female clerks to measure viewing distance variation and related ophthalmological changes in office activities with (session 1) and without (session 2) VDU. A video camera connected to an electronic elaborator was used to determine eye-screen distance of the VDU operators during the task. Before and after each of the two work sessions far refraction, far phorias, near point of accommodation (APP), and fusional convergence were measured. Blinking rate of each subject was measured by a transducer only during the "VDU session'. The objective measurements of the eye-screen distance, whose range was between 48.42 and 65.33 cm, allowed a precise quantification of the occupational visual load during session 1. The accommodation was about 1.5-2D on average and the fusional convergence 10-13 delta on average. The symptomatology shows a number of disturbances in session 1 (71.4%) clearly higher than in session 2 (35.7%). The study of refraction before and after the task has shown a slight excess of accommodation compared to the theoretical value in both sessions, more marked in session 1. The APP shows no statistical significative variation. A tendency to exophoria was registered at the beginning and at the end of the trial and the fusional convergence clearly decreased, especially in the first session.


Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling.
Phagocytes such as neutrophils and macrophages produce reactive oxygen species (ROS) during phagocytosis or stimulation with a wide variety of agents through activation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase that is assembled at the plasma membrane from resident plasma membrane and cytosolic protein components. One of the subunits of the phagocyte NADPH oxidase is now recognized as a member of a family of NADPH oxidases, or NOX, present in cells other than phagocytes. Physiologic generation of ROS has been implicated in a variety of physiologic responses from transcriptional activation to cell proliferation and apoptosis. The increase in superoxide and hydrogen peroxide (H2O2) that results from stimulation of the NADPH oxidase is transient, in part due to the presence of the antioxidant enzymes, which return their concentrations to the prestimulation steady state level. Thus, the antioxidant enzymes may function in the "turn-off" phase of signal transduction by ROS. During its transient elevation, H2O2 may act as a modifier of key signaling enzymes through reversible oxidation of critical thiols. The rapid reaction of thiols with H2O2 when in their unprotonated state would provide a potential mechanism for the specificity that is necessary for physiologic cell signaling.


Effects of countdown timers on driver behavior after the yellow onset at Chinese intersections.
Few studies have focused on the effect of countdown timers at signalized intersections in China, where such timers are widely deployed for their perceived benefits of increased safety and capacity. This study examines the effect of countdown timers on driver behavior during the yellow interval. Signal phasing and traffic operations were videotaped at 4 comparable signalized intersections under normal conditions. Microscopic details were extracted manually at 25 Hz to yield 24 h of data on onset time of the yellow, onset time of the red, driver location and actions after the onset of the yellow, red light-running violations, etc. For comparable intersections with and without countdown timers, driver behavior measured by driver decision (stop or go) and vehicle entry time (when the vehicle crosses the stop line) were analyzed using binary logistical regression (BLR) and a nonparametric test, respectively. The results suggest that countdown timers can indeed influence driver behaviors, in terms of decisions to stop or cross the intersection as well as the distribution of vehicle entry times. There was a strong correlation between the presence of countdown timers and an increase in red light violations. Countdown timers may lead to increased entrance into the intersection during the later portions of the yellow and even the red. This alarming finding calls for further research as well as for serious consideration before the field deployment of countdown timers.


[Primary diffuse leptomeningeal gliomatosis. Presentation of one case].
A twenty-four-year-old woman presented with asthenia, anorexia and weight los associated with headache, neck ache, lumbo-sacral pain, flaccid quadriparous, bilaterally diminished vision and sphincter disorders. On computerized axial tomography of the skull, only slight signs of ventricular dilatation were seen. Cytochemical study of the cerebro-spinal fluid showed a marked increase in protein and there was a raised erythrocyte sedimentation rate. The patient was treated with steroids in view of the possibility of vasculitis or a demyelinating disorder. However the disease worsened and she died four months after onset of the disorder. Neuro-pathological study showed tumour infiltration of the leptomeninges of the base of both cerebral hemispheres, cerebellum and spinal medulla. The optic nerves, chiasma and spinal nerve roots were also infiltrated with neoplastic cells. No intraparenchymatous tumour was found. The neuropathological findings were compatible with primary diffuse leptomeningeal gliomatosis.


Mucosal human papillomavirus detection and TP53 immunohistochemical expression in non-melanoma skin cancer in Tunisian patients.
Several studies have reported the oncogenic role of human papillomavirus (HPV) in non-melanoma skin cancer (NMSC) carcinogenesis. Considering that HPV could affect tumor protein 53 (TP53) degradation via E6 oncoprotein, we evaluated the expression of TP53 according to HPV infection and E6 expression. Biopsy specimens from 79 NMSCs (28 squamous cell carcinomas, 21 keratoacanthomas and 30 basal cell carcinomas) were enrolled. Nested PCR was used to detect mucosal HPV (mHPV) DNA. Genotyping was performed by reverse line hybridization. Expression of TP53 and E6 was evaluated by immunohistochemistry. mHPVs were detected in 34.2% (27/79) of NMSC, with 92.6% (25/27) of high-risk HPV (HR-HPV) types. HPV16-E6-positive expression was observed in all HPV16-positive samples. TP53 high expression was found in 51.4% (37/72) of specimens. In this group, 78.4% were HPV-negative (P = 0.014). TP53 expression was negative in 8/10 of HPV E6-positive specimens. Multivariate analysis showed that TP53 was associated with HPV infection independently of histopathologic type (P = 0.005). This study showed a high prevalence of mHPV in NMSC. Active infections assessed by E6 expression are associated with loss of p53 function, highlighting the involvement of mHPV in NMSC carcinogenesis.


A new case of NSAID-induced infertility.
A 38-year-old woman on piroxicam for hip osteoarthritis secondary to hip dysplasia developed secondary sterility. Ova collected for in vitro fertilization were immature and failed to fertilize. A further attempt done after piroxicam discontinuation produced seven mature ova that fertilized, allowing embryo implantation. Nonsteroidal antiinflammatory drugs may induce infertility by reducing the production of prostaglandins, most notably via inhibition of the enzyme cyclooxygenase 2. The impact of nonsteroidal antiinflammatory drug therapy on reproductive function needs to be evaluated.


Pulmonary function in a hospital population of asthmatic children.
Traditionally, assessment of control of pediatric asthma has relied on symptoms reported by the child and his or her family, and on clinical examination at office visits. A survey of the pulmonary function of 100 clinically stable asthmatic children, recruited from the outpatient clinics of the Royal Children's Hospital, Melbourne, Australia for a clinical drug trial was performed. Correlation of baseline pulmonary function with symptom scores recorded at home and home monitoring of peak expiratory flow variability (PEFV) found that a third of these clinically stable asthmatic children had an abnormal FEV1 and half had an abnormal FEF25-75; however, there was no correlation between symptom scores and FEV1 or PEFV. Objective measurements of pulmonary function are needed to ensure good asthma control. Home monitoring of peak expiratory flow can provide a valuable aid for the management of pediatric asthma.


Copper regulation disturbance linked to oxidative stress and cell death during Zika virus infection in human astrocytes.
The Zika virus (ZIKV) caused neurological abnormalities in more than 3500 Brazilian newborns between 2015 and 2020. Data have pointed to oxidative stress in astrocytes as well as to dysregulations in neural cell proliferation and cell cycle as important events accounting for the cell death and neurological complications observed in Congenital Zika Syndrome. Copper imbalance has been shown to induce similar alterations in other pathologies, and disturbances in copper homeostasis have already been described in viral infections. Here, we investigated copper homeostasis imbalance as a factor that could contribute to the cytotoxic effects of ZIKV infection in astrocytes. Human induced pluripotent stem cell-derived astrocytes were infected with ZIKV; changes in the gene expression of copper homeostasis proteins were analyzed. The effect of the administration of CuCl2 or a copper chelator on oxidative stress, cell viability and percentage of infection were also studied. ZIKV infection leads to a downregulation of one of the transporters mediating copper release, ATP7B protein. We also observed the activation of mechanisms that counteract high copper levels, including the synthesis of copper chaperones and the reduction of the copper importer protein CTR1. Finally, we show that chelator-mediated copper sequestration in ZIKV-infected astrocytes reduces the levels of reactive oxygen species and improves cell viability, but does not change the overall percentage of infected cells. In summary, our results show that copper homeostasis imbalance plays a role in the pathology of ZIKV in astrocytes, indicating that it may also be a factor accounting for the developmental abnormalities in the central nervous system following viral infection. Evaluating micronutrient levels and the use of copper chelators in pregnant women susceptible to ZIKV infection may be promising strategies to manage novel cases of congenital ZIKV syndrome.


Reproducibility of optic disk evaluation in supine subjects with a Heidelberg Retina Tomograph II laser tomographic scanner.
The aim of this study was to determine the reproducibility and reliability of optic disk evaluation in supine subjects with a Heidelberg Retina Tomograph II (HRT II). One eye was randomly selected for evaluation by HRT II in each of eleven healthy subjects. Five images were obtained by each of two experienced operators at two separate visits with the subjects in both sitting and supine positions. A stand was constructed to allow stable, handheld operation of the HRT II head for imaging of the supine subjects. Measurements of optic disk parameters obtained in the supine position were compared with those obtained in the sitting position. The reliability of measurements in the supine position was evaluated by calculating both the coefficients of variation for measurements made by one observer on the first visit and the interobserver and intervisit intraclass correlation coefficients (ICCs); the values obtained were compared with those obtained for the sitting position. Measurements of all parameters made in the supine position were highly similar to those made in the sitting position. The coefficients of variation obtained for each parameter in the sitting and supine positions ranged from 5.67% to 14.16% and from 2.18% to 16.08%, respectively. The interobserver ICC values in the sitting and supine positions were ≥0.978 and ≥0.989, respectively. The intervisit ICC values in the sitting and supine positions were ≥0.958 and ≥0.983, respectively. Handheld operation of the HRT II in a custom-designed stand is feasible for optic disk evaluation in the supine subjects who were not able to maintain the sitting position.