Magel2 knockout mice manifest altered social phenotypes and a deficit in preference for social novelty.
MAGEL2 is one of five protein-coding, maternally imprinted, paternally expressed genes in the Prader-Willi syndrome (PWS)-critical domain on chromosome 15q11-q13. Truncating pathogenic variants of MAGEL2 cause Schaaf-Yang syndrome (SHFYNG) (OMIM #615547), a neurodevelopmental disorder related to PWS. Affected individuals manifest a spectrum of neurocognitive and behavioral phenotypes, including intellectual disability and autism spectrum disorder (ASD). Magel2 knockout mice carrying a maternally inherited, imprinted wild-type (WT) allele and a paternally inherited Magel2-lacZ knock-in allele, which abolishes endogenous Magel2 gene function, exhibit several features reminiscent of the human Prader-Willi phenotypes, including neonatal growth retardation, excessive weight gain after weaning and increased adiposity in adulthood. They were shown to have altered circadian rhythm, reduced motor activity and reduced fertility. An extensive assessment for autism-like behaviors in this mouse model was warranted, because of the high prevalence of ASD in human patients. The behavior of Magel2 knockout mice and their WT littermates were assayed via open field, elevated plus maze, tube, three-chamber and partition tests. Our studies confirm decreased horizontal activity of male and female mice and increased vertical activity of females, in the open field. Both sexes spent more time in the open arm of the elevated plus maze, suggestive of reductions in anxiety. Both sexes displayed a lack of preference for social novelty, via a lack of discrimination between known and novel partners in the partition test. The in-depth investigation of behavioral profiles caused by Magel2 loss-of-function helps to elucidate the etiology of behavioral phenotypes both for SHFYNG and PWS in general.


Zfp335 establishes eTreg lineage and neonatal immune tolerance by targeting Hadha-mediated fatty acid oxidation.
Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset. Mechanistically, Zfp335-deficient Tregs displayed reduced oxidative phosphorylation and dysfunctional mitochondrial activity. Further studies revealed that Zfp335 controlled eTreg differentiation by regulating fatty acid oxidation (FAO) through direct targeting of the FAO enzyme Hadha. Importantly, we demonstrate a positive correlation between ZNF335 and HADHA expression in human eTregs. Our findings reveal that Zfp335 controls FAO-driven eTreg differentiation to establish immune tolerance.


Direct Oral Anticoagulants in Dental Patients Including the Frail Elderly Population.
Direct oral anticoagulants (DOACs) have led to a paradigm shift in the field of anticoagulation, providing safe and convenient anticoagulation without the need for regular blood testing. Currently, there are three major DOACs available-Factor Xa inhibitors (apixaban and rivaroxaban) and direct thrombin inhibitors (dabigatran)-that are available for use in atrial fibrillation and venous thromboembolism. While these agents have been shown to be as effective as warfarin, with a similar or better bleeding profile, there remains some concern of the use of these drugs in vulnerable populations, such as the frail elderly patients; particularly since reversal agents and drug monitoring are not routinely available. We aim to provide a review of the use of DOACs and the impact of DOACs on dental treatment in the elderly population.


A telephone survey of factors affecting willingness to participate in health research surveys.
In recent years, reduced participation has been encountered across all epidemiological study designs, both in terms of non-response as well as refusal. A low response rate may reduce the statistical power but, more importantly, results may not be generalizable to the wider community. In a telephone survey of 1413 randomly selected members of the Australian general population and of 690 participants sourced from previous studies, we examined factors affecting people's stated willingness to participate in health research. The majority of participants (61 %) expressed willingness to participate in health research in general but the percentage increased when provided with more specific information about the research. People were more willing if they have personal experience of the disease under study, and if the study was funded by government or charity rather than pharmaceutical companies. Participants from previous studies, older people and women were the groups most willing to participate. Younger men preferred online surveys, older people a written questionnaire, and few participants in any age and sex groups preferred a telephone questionnaire. Despite a trend toward reduced participation rates, most participants expressed their willingness to participate in health research. However, when seeking participants, researchers should be concrete and specific about the nature of the research they want to carry out. The preferred method of recommended contact varies with the demographic characteristics.


Effect of Age on Transalveolar Sinus Floor Elevation with Simultaneous Placement of Dental Implants: A Retrospective Study.
Purpose: To analyze the effects of age on the sinus graft remodeling of transalveolar sinus floor elevation (SFE) with simultaneous placement of dental implants. Materials and Methods: A retrospective study design was adopted. A total of 222 sites in 216 patients who underwent transalveolar SFE with immediate implant placement were included. The clinical and radiographic data were collected at preoperative, postoperative, and postloading time points. Age was divided into three groups: < 30 years, 30 to 50 years, and > 50 years. The ratio of sinus graft resorption (Ratio) was used to evaluate the outcomes of the surgery and loading. ANOVA was applied to explore the correlation of total elevation height (TEH) with implant loading. The Ridge regression model was used to explore the relationship between Ratio and age and other possible factors. Results: A total of 222 implants in 216 patients were included for implant-based analysis. The TEH averaged 6.983 ± 2.251 mm on the day after surgery (T1), and sinus graft resorption was found during the healing period and after implant loading (P < .01). Age was found to be a reliable correlation with the Ratio (P < .01). A significantly decreased bone formation efficiency was found with aging. Conclusion: According to the results of this retrospective chart review, age was the main factor affecting the outcomes when applying transalveolar SFE with simultaneous implant placement. This finding could be a guide for clinical treatment.


Highly Stable Lyophilized Homogeneous Bead-Based Immunoassays for On-Site Detection of Bio Warfare Agents from Complex Matrices.
This study shows the development of dry, highly stable immunoassays for the detection of bio warfare agents in complex matrices. Thermal stability was achieved by the lyophilization of the complete, homogeneous, bead-based immunoassay in a special stabilizing buffer, resulting in a ready-to-use, simple assay, which exhibited long shelf and high-temperature endurance (up to 1 week at 100 °C). The developed methodology was successfully implemented for the preservation of time-resolved fluorescence, Alexa-fluorophores, and horse radish peroxidase-based bead assays, enabling multiplexed detection. The multiplexed assay was successfully implemented for the detection of Bacillus anthracis, botulinum B, and tularemia in complex matrices.


Soliton synchrotron afterglow in a laser plasma.
Coherent synchrotron radiation can be emitted by relativistic electromagnetic subcycle solitons dwelling in a low-temperature collisionless plasma. Using three-dimensional particle-in-cell simulations we show that solitons, left in a wake of a relativistically intense short circularly polarized laser pulse in the plasma, emit spiral electromagnetic wave, as a result of charge density oscillations in the wall of the soliton cavity. This high-frequency afterglow persists for tens of Langmuir periods.


The micronucleus assay in human lymphocytes after high radiation doses (5-15 Gy).
Individuals can be exposed to high doses (more than 5Gy) during radiation accidents. It is, of course, helpful to the physician to have biological indicators also for such high doses. The problem with most cytogenetic indicators is, that the response levels off at doses starting around 5-7Gy of low LET radiation and that the dose-response curve even declines after doses exceeding about 10Gy. Thus, it may be difficult to decide, whether the dose was, for example, 8 or 14Gy. We studied how the micronucleus assay can be used to give information also in the high dose range. It turned out that micronucleus frequency itself cannot be used for the estimation of doses exceeding about 5-7Gy. There are, however, at least three other endpoints that can be determined in the cytochalasin B assay that can assist the decision in the high dose range: (1) the number of mononucleated cells; (2) the ratio of tri- to tetranucleated cells; (3) the average micronucleus frequency in micronucleus positive binucleated cells.


[Detection of colistin-resistant Acinetobacter baumannii with the mcr-4 gene].
The emergence of plasmid-mediated colistin resistance carried by mcr genes and polymyxin resistance in carbapenem-resistant bacteria poses a threat to antibiotic therapy of bacterial infections. The worldwide spread of colistin resistance carried by mcr genes, particularly in Enterobacteriaceae, points to the possibility of the spread of this type of resistance also in non-fermenting Gram-negative bacteria such as Pseudomonas aeruginosa or Acinetobacter baumannii. This study provides information on the first described occurrence of the mcr-4 gene in A. baumannii isolated from imported turkey liver obtained in the retail market of the Czech Republic.


Field evaluation of an engineering control for respirable crystalline silica exposures during mortar removal.
During mortar removal with a right angle grinder, a building renovation process known as "tuck pointing," worker exposures to respirable crystalline silica can be as high as 5 mg/m(3), 100 times the recommended exposure limit developed by the National Institute for Occupational Safety and Health. To reduce the risk of silicosis among these workers, a vacuum cleaner can be used to exhaust 80 ft(3)/min (2.26 m(3)/min) from a hood mounted on the grinder. Field trials examined the ability of vacuum cleaners to maintain adequate exhaust ventilation rates and measure exposure outcomes when using this engineering control. These field trials involved task-based exposure measurement of respirable dust and crystalline silica exposures during mortar removal. These measurements were compared with published exposure data. Vacuum cleaner airflows were obtained by measuring and digitally logging vacuum cleaner static pressure at the inlet to the vacuum cleaner motor. Static pressures were converted to airflows based on experimentally determined fan curves. In two cases, video exposure monitoring was conducted to study the relationship between worker activities and dust exposure. Worker activities were video taped concurrent with aerosol photometer measurement of dust exposure and vacuum cleaner static pressure as a measure of airflow. During these field trials, respirable crystalline silica exposures for 22 samples had a geometric mean of 0.06 mg/m(3) and a range of less than 0.01 to 0.86 mg/m(3). For three other studies, respirable crystalline silica exposures during mortar removal have a geometric means of 1.1 to 0.35. Although this field study documented noticeably less exposure to crystalline silica, video exposure monitoring found that the local exhaust ventilation provided incomplete dust control due to low exhaust flow rates, certain work practices, and missing mortar. Vacuum cleaner airflow decrease had a range of 3 to 0.4 ft(3)/min (0.08 to 0.01 m(3)/sec(2)) over a range of vacuum cleaners, hose diameters, and hose lengths. To control worker exposure to respirable crystalline silica, local exhaust ventilation needs to be incorporated into a comprehensive silica control program that includes respiratory protection, worker training, and local exhaust ventilation.


A unique pattern of cortical connectivity characterizes patients with attention deficit disorders: a large electroencephalographic coherence study.
Attentional disorders (ADD) feature decreased attention span, impulsivity, and over-activity interfering with successful lives. Childhood onset ADD frequently persists to adulthood. Etiology may be hereditary or disease associated. Prevalence is 5% but recognition may be 'overshadowed' by comorbidities (brain injury, mood disorder) thereby escaping formal recognition. Blinded diagnosis by MRI has failed. ADD may not itself manifest a single anatomical pattern of brain abnormality but may reflect multiple, unique responses to numerous and diverse etiologies. Alternatively, a stable ADD-specific brain pattern may be better detected by brain physiology. EEG coherence, measuring cortical connectivity, is used to explore this possibility. Participants: Ages 2 to 22 years; 347 ADD and 619 neurotypical controls (CON). Following artifact reduction, principal components analysis (PCA) identifies coherence factors with unique loading patterns. Discriminant function analysis (DFA) determines discrimination success differentiating ADD from CON. Split-half and jackknife analyses estimate prospective diagnostic success. Coherence factor loading constitutes an ADD-specific pattern or 'connectome'. RESULTS: PCA identified 40 factors explaining 50% of total variance. DFA on CON versus ADD groups utilizing all factors was highly significant (p≤0.0001). ADD subjects were separated into medication and comorbidity subgroups. DFA (stepping allowed) based on CON versus ADD without comorbidities or medication treatment successfully classified the correspondingly held out ADD subjects in every instance. Ten randomly generated split-half replications of the entire population demonstrated high-average classification success for each of the left out test-sets (overall: CON, 83.65%; ADD, 90.07%). Higher success was obtained with more restricted age sub-samples using jackknifing: 2-8 year olds (CON, 90.0%; ADD, 90.6%); 8-14 year olds (CON, 96.8%; ADD 95.9%); and 14-20 year-olds (CON, 100.0%; ADD, 97.1%). The connectome manifested decreased and increased coherence. Patterns were complex and bi-hemispheric; typically reported front-back and left-right loading patterns were not observed. Subtemporal electrodes (seldom utilized) were prominently involved. CONCLUSIONS: Results demonstrate a stable coherence connectome differentiating ADD from CON subjects including subgroups with and without comorbidities and/or medications. This functional 'connectome', constitutes a diagnostic ADD phenotype. Split-half replications support potential for EEG-based ADD diagnosis, with increased accuracy using limited age ranges. Repeated studies could assist recognition of physiological change from interventions (pharmacological, behavioral).


Identifying diagnostic DNA methylation profiles for facioscapulohumeral muscular dystrophy in blood and saliva using bisulfite sequencing.
Facioscapulohumeral muscular dystrophy (FSHD) is linked to chromatin relaxation due to epigenetic changes at the 4q35 D4Z4 macrosatellite array. Molecular diagnostic criteria for FSHD are complex and involve analysis of high molecular weight (HMW) genomic DNA isolated from lymphocytes, followed by multiple restriction digestions, pulse-field gel electrophoresis (PFGE), and Southern blotting. A subject is genetically diagnosed as FSHD1 if one of the 4q alleles shows a contraction in the D4Z4 array to below 11 repeats, while maintaining at least 1 repeat, and the contraction is in cis with a disease-permissive A-type subtelomere. FSHD2 is contraction-independent and cannot be diagnosed or excluded by this common genetic diagnostic procedure. However, FSHD1 and FSHD2 are linked by epigenetic deregulation, assayed as DNA hypomethylation, of the D4Z4 array on FSHD-permissive alleles. We have developed a PCR-based assay that identifies the epigenetic signature for both types of FSHD, distinguishing FSHD1 from FSHD2, and can be performed on genomic DNA isolated from blood, saliva, or cultured cells. Samples were obtained from healthy controls or patients clinically diagnosed with FSHD, and include both FSHD1 and FSHD2. The genomic DNAs were subjected to bisulfite sequencing analysis for the distal 4q D4Z4 repeat with an A-type subtelomere and the DUX4 5' promoter region. We compared genomic DNA isolated from saliva and blood from the same individuals and found similar epigenetic signatures. DNA hypomethylation was restricted to the contracted 4qA chromosome in FSHD1 patients while healthy control subjects were hypermethylated. Candidates for FSHD2 showed extreme DNA hypomethylation on the 4qA DUX4 gene body as well as all analyzed DUX4 5' sequences. Importantly, our assay does not amplify the D4Z4 arrays with non-permissive B-type subtelomeres and accurately excludes the arrays with non-permissive A-type subtelomeres. We have developed an assay to identify changes in DNA methylation on the pathogenic distal 4q D4Z4 repeat. We show that the DNA methylation profile of saliva reflects FSHD status. This assay can distinguish FSHD from healthy controls, differentiate FSHD1 from FSHD2, does not require HMW genomic DNA or PFGE, and can be performed on either cultured cells, tissue, blood, or saliva samples.


Engineering Planar Transverse Domain Walls in Biaxial Magnetic Nanostrips by Tailoring Transverse Magnetic Fields with Uniform Orientation.
Designing and realizing various magnetization textures in magnetic nanostructures are essential for developing novel magnetic nanodevices in the modern information industry. Among all these textures, planar transverse domain walls (pTDWs) are the simplest and the most basic, which make them popular in device physics. In this work, we report the engineering of pTDWs with arbitrary tilting attitude in biaxial magnetic nanostrips by transverse magnetic field profiles with uniform orientation but tuneable strength distribution. Both statics and axial-field-driven dynamics of these pTDWs are analytically investigated. It turns out that, for statics, these pTDWs are robust against disturbances which are not too abrupt, while for dynamics, it can be tailored to acquire higher velocity than Walker's ansatz predicts. These results should provide inspiration for designing magnetic nanodevices with novel one-dimensional magnetization textures, such as 360 ∘ walls, or even two-dimensional ones, such as vortices and skyrmions.


Presence of the plasma membrane proteolipid (plasmolipin) in myelin.
Plasma membrane proteolipid (plasmolipin), which was originally isolated from kidney membranes, has also been shown to be present in brain. In this study, we examined the distribution of plasmolipin in brain regions, myelin, and oligodendroglial membranes. Immunoblot analysis of different brain regions revealed that plasmolipin levels were higher in regions rich in white matter. Plasmolipin was also detected in myelin, myelin subfractions, and oligodendroglial membranes. Immunocytochemical analysis of the cerebellum revealed that plasmolipin was localized in the myelinated tracts. Plasmolipin levels in myelin were enriched during five successive cycles of myelin purification, similar to the enrichment of myelin proteolipid apoprotein (PLP) and myelin basic protein (MBP). In contrast, levels of Na+,K(+)-ATPase and a 70-kDa protein were decreased. When myelin or white matter was extracted with chloroform/methanol, it contained, in addition to PLP, a significant amount of plasmolipin. Quantitative immunoblot analysis suggested that plasmolipin constitutes in the range of 2.2-4.8% of total myelin protein. Plasmolipin, purified from kidney membranes, was detected by silver stain on gels at 18 kDa and did not show immunological cross-reactivity with either PLP or MBP. Thus, it is concluded that plasmolipin is present in myelin, possibly as a component of the oligodendroglial plasma membrane, but is structurally and immunologically different from the previously characterized myelin proteolipids.


Hybrid composites of mesenchymal stem cell sheets, hydroxyapatite, and platelet-rich fibrin granules for bone regeneration in a rabbit calvarial critical-size defect model.
The reconstruction of large bone defects remains a major clinical challenge, and tissue engineering is a promising technique for resolving this problem. Many attempts have been made to optimize bone tissue engineering protocols. The aim of the present study was to develop a process incorporating mesenchymal stem cell (MSC) sheets with nanoscale hydroxyapatite (nano-HA) and autologous platelet-rich fibrin (PRF) granules for enhanced bone formation within a critical-sized rabbit cranial defect. MSC sheets and PRF were prepared prior to in vivo experiments. The osteogenic differentiation ability of MSCs and the ultrastructure of PRF were also studied. A total of 15 New Zealand white rabbits were used in the current study and critical-size defects (CSDs) were surgically introduced in the cranium (diameter, 15 mm). The surgical defects were treated with MSC/PRF composites, MSC composites or left empty. Animals were euthanized at week 8 post-surgery. Iconography, histological and histomorphometric analysis were performed to assess de novo bone formation. The percentage of new bone in the MSC/PRF group (35.7±5.1%) was significantly higher than that in the MSC (18.3±3.2%; P<0.05) and empty defect groups (4.7±1.5%; P<0.05). The results of the present study suggest that combined application of an MSC sheet with nano-HA and granular PRF enhances bone regeneration in a rabbit calvarial CSD model, and provides a novel insight into bone tissue regeneration for large bone defects.


Rare Cases of Bronchial Aneurysm and Comparison of Interventional Embolization in the Treatment of True Bronchial Aneurysm and Pseudobronchial Aneurysm.
Bronchial artery aneurysm (BAA) is a rare disease. Rupture of BAA can lead to life-threatening hemoptysis, and once diagnosed, treatment is needed regardless of symptoms. Transcatheter artery embolization is the first choice of treatment because it is minimally invasive and effective. This study aimed to retrospectively compare the embolization treatment of a case of true BAA and that of a pseudobranchial aneurysm and explore the choice of embolization method for BAA with short neck or no neck. Embolization treatment and imaging characteristics of one case of true BAA and one case of pseudobronchial aneurysm admitted to our hospital were analyzed retrospectively. Embolization methods and therapeutic effects of two cases of BAAs were compared. Case 1 was that of an intact true BAA inside the mediastinum located at the opening of the bronchial artery. The distal end of the aneurysm was embolized, and tumor cavity was occluded. No recurrence of BAA was found after the operation. Case 2 was that of a ruptured and hemorrhagic pseudobronchial aneurysm of the mediastinum. Coil embolization combined with covered stent graft exclusion of the thoracic aorta were performed, and the left bronchial artery and BAA were almost occluded. Nine months postoperatively, the mediastinal hematoma was almost completely absorbed. Endovascular embolization has become the most commonly used for the treatment of BAA. Different methods should be selected according to the location and nature of the aneurysm.


Solubilization and partial characterization of the intestinal receptor for Escherichia coli heat-stable enterotoxin.
Binding of Escherichia coli strain 431 heat-stable enterotoxin (STa) and activation of intestinal particulate guanylate cyclase by E. coli STa were studied with rat intestinal epithelial cells and brush border membranes (BBMs). The rates of guanylate cyclase stimulation by 431 STa in cells and BBMs were rapid, with maximal levels of cyclic GMP observed within 5 min. Specific binding of 125I-labeled STa from E. coli 431 (431 125I-STa) and activation of guanylate cyclase by unlabeled 431 STa were observed with intestinal BBMs; however, neither was detected with membranes from nonintestinal tissues. The STa receptor was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, a nondenaturing dipolar ionic detergent, in yields of approximately 50%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the detergent-solubilized receptor-431 125I-STa complex, followed by autoradiography, showed that 431 125I-STa bound to a single BBM component with a molecular weight of about 100,000. Binding of 431 STa to its solubilized receptor was saturable, specific, and essentially irreversible. Pretreatment of the soluble receptor with trypsin and pronase but not chymotrypsin decreased binding of 431 125I-STa. The 431 STa-receptor complex was dissociated by boiling in the presence of 1% sodium dodecyl sulfate, incubation with 0.5 M acetic acid, or reduction with dithiothreitol. In contrast to the residual particulate guanylate cyclase activity of detergent-treated membranes, solubilized guanylate cyclase was not stimulated by STa. Membrane structure appears to play an important role in the coordination of STa binding and stimulation of guanylate cyclase activity.


Comparative effect of ZnO NPs, ZnO bulk and ZnSO4 in the antioxidant defences of two plant species growing in two agricultural soils under greenhouse conditions.
The present study has investigated the toxicity of ZnO NPs to bean (Phaseolus vulgaris) and tomato (Solanum lycopersicon) crops grown to maturity under greenhouse conditions using an acidic (soil pH5.4) and a calcareous soil (soil pH8.3). The potentially available Zn in the soils and the Zn accumulation in the leaves from NPs applied to the soil (3, 20 and 225mgZnkg-1) and changes in the chlorophylls, carotenoids and oxidative stress biomarkers were measured at 15, 30, 60 and 90days and compared with those caused by bulk ZnO and ZnSO4. The available Zn in the soil and the leaf Zn content did not differ among the Zn chemical species, except in the acidic soil at the highest concentration of Zn applied as Zn ions, where the highest values of the two variables were found. The ZnO NPs showed comparable Zn toxicity or biostimulation to their bulk counterparts and Zn salts, irrespective of certain significant differences suggesting a higher activity of the Zn ion. The treatments altered the photosynthetic pigment concentration and induced oxidative stress in plants. ROS formation was observed at Zn plant concentrations ranging from 590 to 760mgkg-1, but the effects on the rest of the parameters were highly dependent on the plant species, exposure time and especially soil type. In general, the effects were higher in the acidic soil than in the calcareous soil for the bean and the opposite for the tomato. The similar uptakes and toxicities of the different Zn forms suggest that the Zn ions derived from the ZnO NPs exerted a preferential toxicity in plants. However, several results obtained in soils treated with NPs at 3mgZnkg-1 soil indicated that may exist other underlying mechanisms related to the intrinsic nanoparticle properties, especially at low NP concentrations.


Pollution and Perceptions of Lead in Automobile Repair Shops in Dhaka, Bangladesh.
Lead acid batteries are widely used, dependable, and inexpensive. Lead from these batteries can contaminate the surrounding ecosystem due to improper disposal and contribute to lead poisoning. Lead poisoning is an important public health issue that can cause adverse human health impacts. The present study aimed to assess exposure to lead released from automobile repair shops handling lead acid batteries in the city of Dhaka, Bangladesh, as well as shop owner and worker perceptions of lead pollution. Ten dust samples were collected for atomic absorption spectrophotometer analysis to determine the concentration of lead. In addition, a questionnaire survey (N=75) was conducted to determine the level of knowledge of lead exposure and associated risks. Lead contamination was found in all dust samples, with lead concentrations ranging from 11.40 ppm to greater than 1000 ppm. In addition, 80% of respondents did not have any knowledge about the harmful effects of lead pollution. The present study suggests the importance of defining permissible air lead levels and improving worker education on lead pollution. The study was approved by the Ethics Committee of the Department of Environmental Science, Stamford University, Bangladesh. The authors declare no competing financial interests.


[Anesthesia in a patient with hereditary angioedema].
One of the most serious manifestations of hereditary angioneurotic edema is the occurrence of an acute airway obstruction due to laryngeal edema. The anesthetic technique of choice is a conduction rather than an intubation anesthesia. In the treatment of an acute attack steroids and antihistamines are commonly ineffective. Specific prophylactic and therapeutic measures involving the infusion of fresh-frozen plasma and treatment with Danazol are described.


Folate action in nervous system development and disease.
The vitamin folic acid has been recognized as a crucial environmental factor for nervous system development. From the early fetal stages of the formation of the presumptive spinal cord and brain to the maturation and maintenance of the nervous system during infancy and childhood, folate levels and its supplementation have been considered influential in the clinical outcome of infants and children affected by neurological diseases. Despite the vast epidemiological information recorded on folate function and neural tube defects, neural development and neurodegenerative diseases, the mechanisms of folate action in the developing neural tissue have remained elusive. Here we compiled studies that argue for a unique role for folate in nervous system development and function and its consequences to neural disease and repair. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 391-402, 2018.


Equilibrium studies on the association of the nuclear poly(A) binding protein with poly(A) of different lengths.
The nuclear poly(A) binding protein (PABPN1) binds the growing poly(A) tail during pre-mRNA 3'-end processing, stimulating its elongation and controlling its final length. Here we report binding studies of PABPN1 to poly(A) in solution. Quantitative fluorescence titration was used to determine the stoichiometry, intrinsic affinity, and cooperativity of binding to a series of size-fractionated poly(A). The intrinsic association constant K(i) was about 2 x 10(6) M(-1) for oligo(A) and all size classes of poly(A). The binding of PABPN1 to poly(A) was enhanced by protein-protein interactions which were, however, weak (cooperativity parameter omega < 50). No significant change of cooperativity could be detected with increasing polynucleotide length in the range of 140-450 nucleotides. An average binding site size n of 11-14 was found for all poly(A) lengths, which is close to the minimal site size m found for binding to oligo(A). The data are discussed with respect to the previous observation of two different forms of the poly(A)-PABPN1 complex.


Transanal minimal invasive surgery for rectal lesions: should the defect be closed?
Transanal minimal invasive surgery (TAMIS) of rectal lesions is increasingly being used, but the technique is not yet standardized. The aims of this study were to evaluate peri-operative complications and long-term functional outcome of the technique and to analyse whether or not the rectal defect needs to be closed. Consecutive patients undergoing TAMIS using the SILS port (Covidien) and standard laparoscopic instruments were studied. Seventy-five patients (68% male) of mean age 67 (± 15) years underwent single-port transanal surgery at three different centres for 37 benign lesions and 38 low-risk cancers located at a mean of 6.4 ± 2.3 cm from the anal verge. The median operating time was 77 (25-245) min including a median time for resection of 36 (15-75) min and for closure of the rectal defect of 38 (9-105) min. The defect was closed in 53% using interrupted (75%) or a running suture (25%). Intra-operative complications occurred in six (8%) patients and postoperative morbidity was 19% with only one patient requiring reoperation for Grade IIIb local infection. There was no difference in the incidence of complications whether the rectal defect was closed or left open. Patients were discharged after 3.4 (1-21) days. At a median follow-up of 12.8 (2-29) months, the continence was normal (Vaizey score of 1.5; 0-16). Transanal rectal resection can be safely and efficiently performed by means of a SILS port and standard laparoscopic instruments. The rectal defect may be left open and at 1 year continence is not compromised.


[Characteristics of hemodynamic reactions during various endoscopic surgeries for cholelithiasis in patients with concurrent cardiovascular pathologies].
A prospective study of 170 patients with concurrent cardiac pathology, who had underwent the laparoscopic cholecystectomy under the conditions of a tense carboxyperitomium, led to isolating two groups of patients with high-risk of intra- and postoperative unfavorable cardiac-vascular responses: an original high risk degree (III-IV classes according to ASA), a high value of cardiac risk indices according to Goldman (III-IV classes) and according to Detsky (II-III classes), a hypodynamic blood circulation regimen under rest conditions, and ejection fraction (according to echocardiography) amounting below 50%. Such patients are recommended to be operated on by laparolifting or by low-gas laparoscopy with a local lifting, i.e. by using the surgical techniques free of any negative effects produced on the carboxyperitomium hemodynamics, while all positive features of small-invasion surgery remain intact.


Endothelial activation and inflammation in prepubertal obese Turkish children.
To investigate the degree of endothelial activation and inflammation in prepubertal obese children and to determine the relationship between the markers of endothelial activation, inflammation, and cardiovascular risk factors. In 30 obese and 28 healthy prepubertal children, soluble intercellular adhesion molecule-1 and endothelial leukocyte adhesion molecule-1 (sE-selectin) as markers of endothelial activation and soluble vascular cell adhesion molecule-1 (sVCAM-1) and C-reactive protein (CRP) as markers of endothelial inflammation in addition to cardiovascular risk factors including blood lipids, glucose, insulin, hemoglobin A1c, and systolic and diastolic blood pressure were investigated and compared. The tests were repeated after an oral glucose tolerance test in the obese group. Fasting CRP levels were found to be significantly higher in obese children. Vascular cell adhesion molecule-1 levels were found to be significantly increased in obese children after oral glucose tolerance test. Fasting CRP was positively correlated with body mass index (BMI) and low-density lipoprotein, whereas sE-selectin was positively correlated with total cholesterol. In the obese group, postload levels of soluble sE-selectin was positively correlated with low-density lipoprotein; sVCAM-1 was positively correlated with insulin and homeostasis model assessment values. Postload soluble intercellular adhesion molecule-1, sVCAM-1, and soluble sE-selectin levels were also positively correlated with each other. In the fasting state, BMI was the significant independent risk factor for CRP, and total cholesterol was the significant risk factor for soluble sE-selectin. Insulin resistance was the significant independent risk factor for postload sVCAM-1, and postload low-density lipoprotein stood as the significant independent risk factor for postload soluble sE-selectin. Endothelial inflammation is present in obese prepubertal children and is mainly associated with insulin resistance and lipid levels as well as BMI.


Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study.
To investigate the real-world safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (T2DM). Japanese patients (≥65 years old) who were first prescribed ipragliflozin within 3 months after its launch in April 2014 were registered in this post-marketing surveillance (PMS). Final data collection was in July 2015. Survey items included demographics, treatments, adverse drug reactions (ADRs), vital signs, and laboratory variables. The PMS included 8505 patients (4181 males/4324 females). The mean age and diabetes duration were 72.3 years and 10.6 years, respectively. In 84.3% of patients, ipragliflozin was prescribed at 50 mg/day, which was continued unchanged. Overall, 16.91% of patients experienced 1880 ADRs, and 165 ADRs were classified as serious in 127 patients (1.49%). ADRs of special interest included skin complications, volume depletion, polyuria/pollakiuria, genital infection, urinary tract infection, renal disorders, hypoglycemia, cerebrovascular disease, cardiovascular disease, malignant tumor, fracture, and ketone body-related events. This 1-year PMS revealed probable ADRs in elderly Japanese patients with T2DM prescribed ipragliflozin in real-world settings, with no new safety concerns. The risk factors for ADRs varied but could be rationalized. The results should help physicians to identify possible treatment-emergent ADRs in ipragliflozin-treated patients.


Pharmacokinetics and Pharmacodynamics of the Nitroimidazole DNDI-0690 in Mouse Models of Cutaneous Leishmaniasis.
The nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for the treatment of CL, we investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative Leishmania pathogen. This study evaluates the pharmacokinetics (PK) and pharmacodynamics (PD) of DNDI-0690 in mouse models of CL. Skin microdialysis and Franz diffusion cell permeation studies revealed that DNDI-0690 permeated poorly (<1%) into the skin lesion upon topical drug application (0.063% [wt/vol], 30 μl). In contrast, a single oral dose of 50 mg/kg of body weight resulted in the rapid and nearly complete distribution of protein-unbound DNDI-0690 from the plasma into the infected dermis (ratio of the area under the curve [0 to 6 h] of the free DNDI-0690 concentration in skin tissue to blood [fAUC0-6 h, skin tissue/fAUC0-6 h, blood] is greater than 80%). Based on in vivo bioluminescence imaging, two doses of 50 mg/kg DNDI-0690 were sufficient to reduce the Leishmania mexicana parasite load by 100-fold, while 6 such doses were needed to achieve similar killing of L. major; this was confirmed by quantitative PCR. The combination of rapid accumulation and potent activity in the Leishmania-infected dermis indicates the potential of DNDI-0690 as a novel oral treatment for CL.


The use of biographies and stories in paediatric palliative care education.
Paediatric palliative care has emerged as a distinct specialty over recent years and, as a consequence, robust and innovative educational programmes are required to further develop the exisitng attitudes and skills of practitioners working within this field. Understanding the experiences of children and families is key to providing quality care in this context and a number of teaching and learning activities have been reported in the literature. This article discusses one such learning activity--the use of parent biographies and stories by students undertaking the paediatric palliative care programme at Queen's University Belfast, UK. Feedback from students indicated that this was a positive learning experience that was both interesting and useful from a practice perspective.


Thermophysical properties of trehalose and its concentrated aqueous solutions.
To address the lack of fundamental thermophysical data for trehalose and its aqueous systems by measuring equilibrium and non-equilibrium properties of such systems. Differential scanning calorimetry (DSC) and dynamic mechanical analysis were used to measure glass transition temperatures of trehalose and its solutions. X-ray diffractometry was used to verify the structure of amorphous trehalose. Controlled-stress rheometry was used to measure viscosity of several aqueous trehalose systems at ambient and sub-ambient temperatures. Over this temperature range, the density of these solutions was also measured with a vibrating tube densimeter. The equilibrium phase diagram of aqueous trehalose was determined by measuring the solubility and freezing point depression. Our solubility measurements, which have allowed long times for attainment of chemical equilibrium, are substantially different from those reported earlier that used different techniques. Our measurements of the glass transition temperature of trehalose are higher than reported values. A simple model for the glass transition is presented to describe our experimental observations.


Burial Depth Effect of Crack on the Lcr Wave Acoustoelastic Coefficient for Stress Measurement of Laser Cladding Coating.
In this paper, the influence of burial depth of crack on stress measurement of laser cladding coating with the critical refracted longitudinal wave (Lcr wave) was discussed based on the Lcr wave acoustoelastic effect. The regular rectangular slots with different depths that were used to simulate the burial crack in coating was based on the equivalent theory. The experimental system including an ultrasonic wave generator, digital oscilloscope (2.5 GHz sampling rate), and two Lcr wave transducers (2.5 MHz center frequency) was used to collect the Lcr wave under different tensile loads, and the Lcr wave was denoised by using wavelet analysis technology, then the fracture morphology was observed using SEM. The results show that after the denoising by wavelet analysis technology, the signal-to-noise ratio of Lcr wave becomes bigger and the mean square deviation of Lcr wave becomes smaller. When the tensile load is within the turning point load, the difference in time of flight between Lcr wave increases linearly as the tensile load increases, and the deviation of the experimental results becomes obvious as the tensile load increases. When the tensile load is the same, as the burial depth of the slot increases, the nominal Lcr wave acoustoelastic coefficient decreases and tends to be stable gradually. At last, the experimental results are discussed based on the Lcr wave acoustoelastic effect and deformation theory, and it is analyzed that the uneven deformation caused by the interface in coating, anisotropic microstructure, and the burial crack is considered as the main reason.


Applications of Spatio-temporal Mapping and Particle Analysis Techniques to Quantify Intracellular Ca2+ Signaling In Situ.
Ca2+ imaging of isolated cells or specific types of cells within intact tissues often reveals complex patterns of Ca2+ signaling. This activity requires careful and in-depth analyses and quantification to capture as much information about the underlying events as possible. Spatial, temporal and intensity parameters intrinsic to Ca2+ signals such as frequency, duration, propagation, velocity and amplitude may provide some biological information required for intracellular signalling. High-resolution Ca2+ imaging typically results in the acquisition of large data files that are time consuming to process in terms of translating the imaging information into quantifiable data, and this process can be susceptible to human error and bias. Analysis of Ca2+ signals from cells in situ typically relies on simple intensity measurements from arbitrarily selected regions of interest (ROI) within a field of view (FOV). This approach ignores much of the important signaling information contained in the FOV. Thus, in order to maximize recovery of information from such high-resolution recordings obtained with Ca2+dyes or optogenetic Ca2+ imaging, appropriate spatial and temporal analysis of the Ca2+ signals is required. The protocols outlined in this paper will describe how a high volume of data can be obtained from Ca2+ imaging recordings to facilitate more complete analysis and quantification of Ca2+ signals recorded from cells using a combination of spatiotemporal map (STM)-based analysis and particle-based analysis. The protocols also describe how different patterns of Ca2+ signaling observed in different cell populations in situ can be analyzed appropriately. For illustration, the method will examine Ca2+ signaling in a specialized population of cells in the small intestine, interstitial cells of Cajal (ICC), using GECIs.


Central neurocytoma of thalamic origin.
Central neurocytoma is a rare benign tumour of neuronal origin that has only recently been described. The majority of previously reported cases have originated from the septum pellucidum and the walls of the lateral ventricles. We describe a case of central neurocytoma arising from the thalamus. This site of origin has not been previously described. A review of the literature and discussion of the management follow.


Tumors of the major salivary glands in children.
During the 30-year period 1955-1985, 21 children with neoplasms of the major salivary glands were treated at the Johns Hopkins Hospital. A thorough review of the English literature revealed an additional 472 cases. The cases were studied as to age, sex, site, histopathologic characteristics, mode of treatment, and results. The majority of the patients were between 8 and 20 years of age. There was a female preponderance of 1.42:1. The parotid gland was the site of origin in 85.1%, the submandibular in 11.7%, and the sublingual in 3.2%. An equal incidence of benign (50.1%) and malignant (49.9%) lesions is noted. Pleomorphic adenoma was the most common benign neoplasm and mucoepidermoid carcinoma the most common malignant neoplasm. The final prognosis seems to be similar with superficial or total parotidectomy, provided the tumor has been completely removed at the initial surgery. Re-excision is recommended for tumor recurrence, and the use of radiation therapy should be individually determined in cases of aggressive malignancies.


The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity.
Escherichia coli can ameliorate the toxic effects of alkylating agents either by preventing DNA alkylation or by repairing DNA alkylation damage. The alkylation-sensitive phenotype of E. coli alkB mutants marks the alkB pathway as an extremely effective defense mechanism against the cytotoxic effects of the SN2, but not the SN1, alkylating agents. Although it is clear that AlkB helps cells to better handle alkylated DNA, no DNA alkylation repair function could be assigned to the purified AlkB protein, suggesting that AlkB either acts as part of a complex or acts to regulate the expression of other genes whose products are directly responsible for alkylation resistance. However, here we present evidence that the provision of alkylation resistance is an intrinsic function of the AlkB protein per se. We expressed the E. coli AlkB protein in two human cell lines and found that it confers the same characteristic alkylation-resistant phenotype in this foreign environment as it does in E. coli. AlkB expression rendered human cells extremely resistant to cell killing by the SN2 but not the SN1 alkylating agents but did not affect the ability of dimethyl sulfate (an SN2 agent) to alkylate the genome. We infer that SN2 agents produce a class of DNA damage that is not efficiently produced by SN1 agents and that AlkB somehow prevents this damage from killing the cell.


HSA growth and the associated opportunities/challenges presented by pharmacy benefits.
Consumer-driven health plans (CDHPs) have grown steadily and significantly over the past ten years in terms of covered employees, enrollment and assets under management. The authors explain the reasons for this growth and how CDHPs address health care costs. They discuss how pharmacy benefits present some of the greatest opportunities and challenges for CDHP growth. Challenges center on recent research that revealed decreased utilization and adherence among members of a CDHP population in four out of the five therapeutic categories examined. Although an influx of generic drugs has entered the marketplace, specialty pharmacy drugs will more than offset those savings, increasing the threat of noncompliance. Nonetheless, with appropriate design and implementation, CDHPs can be very effective for both employers and their employees.


Patterns of mental health problems and well-being in children with disabilities in Sweden: A cross-sectional survey and cluster analysis.
Children with disabilities have an increased risk of mental health problems. Patterns of mental health problems and well-being may vary. To identify patterns of mental health problems and well-being in children with disabilities in Sweden, and investigate the influence of parental background (migration, education), and child cognitive level. In this cross-sectional study, cluster analysis was used to analyse parents' ratings of conduct problems, emotional symptoms, and prosocial behaviour on the Strengths and Difficulties Questionnaire (SDQ) in children with disabilities (n = 136). The influence of parental background (migration, education) and child cognitive level on cluster membership was explored through multinomial logistic regression. Five clusters of mental health patterns emerged. Three clusters had mean ratings near or past clinical cut-off for one each of the SDQ-subscales. One cluster had difficulties on all three subscales. Greater child cognitive difficulties increased the likelihood of low prosocial behaviour (OR 2.501, p < .001) and of difficulties on all three subscales (OR 2.155, p = .006). Parental background did not influence cluster membership. Children with disabilities display varying mental health patterns. Awareness of the complexity of mental health patterns among children with disabilities is important. Screening and support for emotional symptoms and prosocial behaviour deficits should be considered for children with conduct problems.


Langerhans cells in S-phase in normal skin detected by simultaneous analysis of cell surface antigen and BrdU incorporation.
We report on a double immunofluorescence staining for the detection of the Langerhans Cell (LC) population in S-phase. After trypsinization, the epidermal cell suspensions were enriched for LC and exposed to 10 microM BrdU for 2 h. Studies of BrdU labeled cells included the determination of their cell surface phenotype. Both membrane labeling and incorporated BrdU as revealed using anti-BrdU demonstrated the BrdU as revealed using anti-BrdU demonstrated the presence of LC in S-phase. We observed 6% of the epidermal LC in S-phase. This is a proof that LC are able to proliferate in the epidermal microenvironment. This technique, besides being rapid and free of radioactivity, allows the cytokinetic study of phenotypically defined LC in heterogeneous epidermal cell populations.


Endoscopic endonasal odontoidectomy with anterior C1 arch preservation in elderly patients affected by rheumatoid arthritis.
Rheumatoid arthritis is the most common inflammatory disease involving the spine with predilection for the craniovertebral segment. Surgery is usually reserved to patients with symptomatic craniovertebral junction (CVJ) instability, basilar invagination, or upper spinal cord compression by rheumatoid pannus. Anterior approaches are indicated in cases of irreducible ventral bulbo-medullary compression. Classically performed through the transoral approach, the exposure of this region can be now achieved by a minimally invasive endonasal endoscopic approach (EEA). The aim of this article is to demonstrate the feasibility of performing an odontoidectomy and a rheumatoid pannus removal by a minimally invasive EEA, preserving the anterior C1 arch continuity and avoiding a posterior fixation procedure. Technical description and cohort report. We report three cases of elderly patients with a long history of rheumatoid arthritis and irreducible anterior bulbo-medullary compression secondary to basilar invagination and/or rheumatoid pannus. Anterior decompression was achieved by an endonasal image-guided fully endoscopic approach. Neurological improvement and adequate bulbo-medullary decompression were obtained in all cases. The anterior C1 arch continuity was preserved, and none of the patients required a subsequent posterior fixation. Anterior decompression by a minimally invasive EEA could represent an innovative option for the treatment of irreducible ventral CVJ lesions in elderly patients with rheumatoid arthritis. This approach permits the preservation of the anterior C1 arch and the avoidance of a posterior fixation, thus preserving the rotational movement at C0-C2 segment and reducing the risk of a subaxial instability development.


Associated Factors of Exclusive Breastfeeding Intention among Pregnant Women in Najran, Saudi Arabia.
The exclusive breastfeeding (EBF) intention conceived by pregnant women is the most important predictor of breastfeeding (BF) initiation, duration, and continuation. This study explores the associated factors of EBF intention among pregnant women. This was a descriptive cross-sectional study conducted from November 2022 to January 2023 with 382 pregnant women who came to the outpatient clinic in the Maternal and Children Hospital (MCH). Four instruments were used for data collection: the Infant Feeding Intention scale, the Gender-Friendly BF Knowledge scale (GFBKS), the Iowa Infant Feeding Attitude scale (IIFAS), and the basic data questionnaire. The study findings indicated that 51.8% and 75.9% of gravida women had adequate knowledge and a positive attitude regarding BF. Furthermore, 56.3% of the participants had a high intention for EBF. Binary logistic regression illustrated that occupational status, antenatal care, plan for the current pregnancy, BF practice, last child delivery mode, medical disorder during the current pregnancy, age, BF knowledge, and attitude are potential predictors. The goodness of fit test revealed that 46.8% of the EBF intention could be anticipated through the positive pre-mentioned factors. The low EBF intention is modifiable by addressing the previously positive predictors. BF educational interventions should be tailored based on EBF intention predictors in order to be effective and lead to behavior change.


[Analysis of risk factors of perioperative blood transfusion in the treatment of femoral intertrochanteric fracture with proximal femoral nail antirotation].
To explore the influencing factors of perioperative blood transfusion in the treatment of elderly femoral intertrochanteric fractures with proximal femoral nail antirotation(PFNA). The clinical data of 109 elderly patients with intertrochanteric fractures who received PFNA treatment from July 2018 to January 2020 were retrospectively analyzed. Both pelvic hip X-rays and CT plain scans were performed before surgery. All patients were diagnosed by X-ray and CT plain scan of pelvis and hip before operation. Through the statistical analysis of the basic data of patients before and during operation, the risk factors of perioperative blood transfusion were explored. Logistic regression analysis showed that age (P=0.013), fracture type (P<0.01), diabetes history (P=0.031) and preoperative hemoglobin (P<0.01) were independent risk factors for perioperative blood transfusion in the treatment of intertrochanteric fractures in elderly patients with 109 patients. Spearman correlation analysis showed that there was a positive correlation between blood transfusion and age of patients (P= 0.017), fracture type (P<0.01), diabetes history (P=0.023), and negatively correlated with preoperative hemoglobin (P<0.01). However, gender (P=0.297), history of hypertension (P=0.318) and operation time(P=0.325) had no significant relationship with perioperative blood transfusion. Age, fracture type, diabetes history, and preoperative hemoglobin are independent risk factors for perioperative blood transfusion in the treatment of elderly intertrochanteric fractures with PFNA. The older the patient, the history of diabetes, the more unstable the fracture, and the lower preoperative hemoglobin, the more likely it is to require a blood transfusion, which may provide a reference for clinical perioperative blood transfusion decisions.


Muscle strength and force development in high- and low-functioning elderly men: Influence of muscular and neural factors.
Aging leads to a loss of muscle strength and functional capacity likely resulting from a combination of neural and muscle alterations. The aim of this study was to identify possible disparities in muscle strength and force development profiles in high- and low-functioning elderly men and to investigate muscular and neurophysiological factors that could explain the differences. Sixty community-dwelling men in good general health were divided in two groups based on a functional capacity (FC) z-score derived from 6 tests of the Short Physical Performance Battery and Senior Fitness Test (Normal and fast 4m-walk tests, normal and fast Timed-up and go, chair and stair tests). Extensor strength of the lower limbs (LL) was obtained for concentric (CLES) contraction and combined with lean masses of LL (LLLM) to yield concentric (CLES/LLLM) index. Similarly, extensor strength of the right Quadriceps Femoris (IKES) was obtained during maximal voluntary isometric contraction (MVC) and combined with right thigh lean mass (rTLM) to produce an isometric strength (IKES/rTLM) index. A muscular profile was obtained from: ascending and descending force slopes during the MVC; Vastus Lateralis (VL) muscle twitches parameters (amplitude, contraction and ½ relaxation times); the knee joint velocity (KV) as well as integrated EMG (iEMG) were determined for a sit-to-stand functional evaluation; muscle phenotype. A neurophysiological profile was established from: the spinal excitability (Hmax/Mmax ratio); motoneuron conduction velocity (CV); the completeness of muscle activation (% of force reserve), median power frequency (MPF) and mean amplitude (MA) of the VL EMG signal during MVC. Coincidently, age did not differ between groups. Strength and force indices, descending force slopes for MVC, KV and iEMG during the sit-to-stand evaluation and FC parameters were all significantly (p<0.05) lower in the LoFC group than in the HiFC group. In contrast, no difference was observed between groups in: LLLM and rTLM, Hmax/Mmax ratio, CV, twitch parameters and muscle phenotype. The lower concentric and isometric strengths found in the LoFC group could not be accounted for by muscular factors. Similarly, peripheral nervous systems alterations could not explain group differences. It can be suggested that modifications within the central nervous system may be responsible for the differences in the functional status of healthy elderly individuals. Finally, more complex and demanding tasks, such as those requiring greater intensity or coordination, may further clarify how healthy elderly individuals with low and high functional capacities differ.


INCIDENCE AND RISK FACTORS FOR HYPOTONY AFTER 25-GAUGE PARS PLANA VITRECTOMY WITH NONEXPANSILE ENDOTAMPONADE.
The purpose of this study was to assess the incidence and risk factors for early postoperative hypotony after 25-gauge pars plana vitrectomy with nonexpansile endotamponade. A retrospective study of consecutive patients who underwent 25-G pars plana vitrectomy. Hypotony was defined as an intraocular pressure of 5 mmHg or less after surgery and ocular hypertension as an intraocular pressure greater than 21 mmHg. Overall, 307 eyes of 307 patients with a mean age of 61.7 ± 14.3 of which 56.7% were males were included. Hypotony was identified in 5.2% of cases (n = 16) at Day 1 and 0.7% (n = 2) at Week 1 with no hypotony-related complications. The hypotony group had a higher number of previous vitreoretinal surgeries (1.5 ± 1.1 vs. 0.4 ± 0.7, P < 0.001) and a higher prevalence of preoperative ocular hypertension (22.2% vs. 4.8%, P = 0.02), pseudophakia (77.8% vs. 48.4%, P = 0.01), silicone oil removal (61.1% vs. 8.3%, P < 0.001), and external diathermy performed (55.6% vs. 20.1%, P = 0.001). In stepwise multivariate analysis, significant parameters were silicone oil removal (R = 16.34%, odds ratio 13.45, P < 0.001), pseudophakia (R = 5.69%, odds ratio 3.65, P = 0.03), and younger age (R = 2.68%, odds ratio 0.96, P = 0.04). Silicone oil removal is a significant risk factor for early postoperative hypotony after 25-G pars plana vitrectomy.


Antifungal activity of D0870 against murine infections and its mechanism of action.
We evaluated the in vivo antifungal activity of D0870, a new triazole agent, in comparison with that of fluconazole in two murine infection models. The therapeutic mechanism of D0870 in these models was also investigated in vitro. In a pulmonary infection with Cryptococcus neoformans in immunosuppressed mice, D0870 at 10-100 mg/kg significantly reduced viable counts in lungs infected with C. neoformans to 1/10-1,000 of the control on day 14, whereas fluconazole, only at 100 mg/kg, showed a significant reduction in the viable counts and was less active than D0870 at 10 mg/kg. D0870 at 3-30 mg/kg also showed excellent therapeutic efficacy against murine vaginal candidiasis and completely eliminated viable yeasts from the vaginal cavity, whereas positive cultures were found in 20% of mice treated with 30 mg fluconazole/kg. At pH 7 and 37 degrees C, D0870 was active against C. neoformans in synthetic amino acid medium, fungal or sabouraud dextrose broth. By reducing the pH of the medium, the in vitro anticryptococcal activity of D0870 was enhanced and found to be fungicidal under all culture conditions at pH 4-5. D0870 also showed a stronger fungistatic activity against Candida albicans at pH 4. These results suggest that D0870 may exhibit a potent activity against these two murine infections by exerting an excellent antifungal activity at the infection sites thought to be acidic environments.


Polychlorinated biphenyls residues in bivalve shellfish from Niger Delta: distribution pattern, tissue burden and food safety assessment.
This study investigated the distribution pattern, tissue burden, and safety of bivalve shellfish for human consumption. Edible species of bivalve shellfish harvested from Niger delta were screened for polychlorinated biphenyl (PCB) contaminants. Instrumental analysis and quantification of PCB congeners were performed using gas chromatography fitted with electron capture detector (GC-ECD). Results indicated an accumulation of PCB concentration of 0.36 ng/g, 0.89 ng/g, 0.98 ng/g, and 1.73 ng/g at Andoni, Iko Town, Ibeno, and Bonny, respectively. The PCB burden showed bloody cockle at Bonny location recorded the highest concentration of PCB congeners (2.37 ng/g), closely followed by mangrove oyster (2.13 ng/g) at Iko Town location, while Donax clam at Ibeno (0.09 ng/g) has the least PCB burden. The results obtained were lower in relation to food regulatory threshold. However, PCB tissue burden of bivalve shellfish harvested at the study locations indicated an environment impacted by anthropogenic activities that could negatively affect human health which depends on these shellfish for food.


Ahaptoglobinaemia in a Nigerian Cohort.
Ahaptoglobinaemia have been indicated in blacks from West Africa. Owing to the clinical and biologicimportance of haptoglobin (hpt), this work explores the situation in a Nigerian cohort since there are no published values ofhaptoglobin levels of individuals in this locality. The study was aimed at determining the amount of haptoglobin in the bloodof normal healthy Nigerians. Haptoglobin was quantitatively estimated in one hundred and fifty-two apparently healthyindividuals using highly sensitive immunoassay technology. Blood grouping and haemoglobin genotype were assayed forall subjects to know if they influence haptoglobin levels. The association between haptoglobin and blood group was alsoestablished. Serum levels of haptoglobin among all subjects analyzed revealed a marked decrease in their haptoglobin levelswhen compared to other reference intervals. A further association between haptoglobin and gender did not reveal a statisticalsignificant relationship (p>0.05). However, there was a significant different when haptoglobin levels of different bloodgroups and haemoglobin genotype when compared. Our data suggest that serum levels of haptoglobin are significantly lowerin healthy Nigerians. The lower limit was remarkably lower than the internationally acceptable Caucasian reference rangesuggesting a clear necessity for establishing reference African values.


Compound(s) secreted by Lactobacillus casei strain Shirota YIT9029 irreversibly and reversibly impair the swimming motility of Helicobacter pylori and Salmonella enterica serovar Typhimurium, respectively.
We conducted experiments in order to examine whether the probiotic Lactobacillus casei strain Shirota YIT9029 (LcS) in vitro and in vivo antagonism of Helicobacter pylori and Salmonella, involves inhibition of the swimming motility of these pathogens. We report the irreversible inhibition of the swimming motility of H. pylori strain 1101 and reversible inhibition of Salmonella enterica serovar Typhimurium (S. Typhimurium) strain SL1344 by compound(s) secreted by LcS. In H. pylori 1101, irreversible inhibition results in the helical cells being progressively replaced by cells with 'c'-shaped and coccoid morphologies, accompanied by a loss of FlaA and FlaB flagellin expression. In S. Typhimurium SL1344, transient inhibition develops after membrane depolarization and without modification of expression of FliC flagellin. The inhibitory activity of strain LcS against both S. Typhimurium and H. pylori swimming motilities is linked with a small sized, heat-sensitive, and partially trypsin-sensitive, secreted compound(s), and needed the cooperation of the secreted membrane permeabilizing lactic acid metabolite. The inhibition of S. Typhimurium SL1344 swimming motility leads to delayed cell entry into human enterocyte-like Caco-2/TC7 cells and a strong decrease of cell entry into human mucus-secreting HT29-MTX cells.


Effect of blood transfusion on iron status in sickle cell anaemia.
The iron status of 31 patients with sickle cell anaemia (Hb SS) and balanced globin chain synthesis was studied. Twelve patients (group I) had never been transfused; 14 had received up to 4 units of blood in the past (group II) and five had been hypertransfused for 6 months to 2 years (group III). The hypertransfused group had significantly higher MCV and MCH than the nontransfused one, and significantly lower total iron binding capacity and higher serum ferritin concentration than either groups I or II. The serum ferritin concentration was lower than normal in eight patients (five in group I and three in group II), and higher than normal in seven patients (four in group III and three in group II). The remaining 16 patients had normal serum ferritin concentrations. Our results indicate that iron overload is uncommon in adults with Hb SS who have not been transfused, and that a proportion of patients have lower than normal serum ferritin concentrations. Transfused patients, even 6 months after the last transfusion, show increased haemoglobin content of red cells, which may have an adverse effect on the frequency and severity of sickle crises.


The double burden of undernutrition and excess body weight in Ecuador.
Ecuador's current nutrition policies have not taken adequate notice of the double burden of malnutrition and continue to focus on stunting and to a lesser extent on overweight, without addressing the simultaneous presence of undernutrition, micronutrient deficiencies, and overweight or obesity (OW/OB). The aim of this article was to describe the prevalence and distribution of undernutrition (stunting, anemia, and zinc deficiency), overweight, and obesity in Ecuador to explore the evolving double burden of malnutrition at the national, household, and individual levels and to discuss whether current public health policies are addressing the double burden. Data from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) was used to estimate the dual burden of malnutrition at the national, household, and individual levels in children <5 y old, school-aged children, and women of reproductive age. In 13.1% of households, mothers with excess body weight coexist with a stunted child <5 y old. Moreover, among households with overweight or obese mothers, 12.6% have an anemic child and 14% have a zinc-deficient child. At the individual levels, the coexistence of OW/OB and stunting, anemia, or zinc deficiency was found in 2.8%, 0.7%, and 8.4% of school-aged children, respectively. In addition, 8.9% and 32.6% of women aged 12-49 y have excess body weight and anemia or zinc deficiency, respectively. This article shows the coexistence of high rates of undernutrition and OW/OB at the individual, household, and national levels in Ecuador. Although integrated approaches to address the emerging double burden are required, public health policies to date have not responded adequately.


Drug treatment of the neuroleptic malignant syndrome.
We performed a case-controlled analysis on the effectiveness of dantrolene and certain dopamine agonists--bromocriptine, amantadine 3,4-dihydroxyphenylalanine, (DOPA)--for the neuroleptic malignant syndrome (NMS). This was based on a review of all known published studies using as controls those cases not treated with these drugs and/or electroconvulsive therapy. In this control group, the NMS-related death rate was 21 percent. Dantrolene alone reduced the death rate to 8.6 percent, bromocriptine alone to 7.8 percent, and amantadine alone to 5.9 percent. We also stratified patients into five levels of severity based on state of consciousness and temperature and showed that the relative reduction in death rate held up at all levels. The dopamine agonists and dantrolene have a therapeutic effect independent of each other.


Biomonitoring of glyphosate and AMPA in the urine of Spanish lactating mothers.
The objectives of this study were to evaluate the urinary levels of Glyphosate (Gly) and its metabolite aminomethylphosphonic acid (AMPA) in Spanish breastfeeding mothers (n = 97), to identify the main predictors of exposure and to perform a risk assessment. Urine samples were analyzed using a method based on solid phase extraction and liquid chromatography tandem mass spectrometry (LC-MS/MS) determination. The developed method showed limits of quantification of 0.1 μg/L for both analytes. The detection frequencies (DFs) were 54% for Gly and 60% for AMPA, with geometric means (GMs) of 0.12 μg/L and 0.14 μg/L, respectively. In the statistical analysis, no relationship was found between the urinary levels of Gly and AMPA. Multiple regression analysis showed a significant relationship between the intake of eggs and fruits and Gly levels in urine. Estimated daily intakes (EDIs), hazard quotients (HQs), and a hazard index (HI) were calculated to analyze the obtained data from a health risk perspective. The GMs of the EDIs were 0.31 and 0.37 μg/kg of body weight (BW)/day for Gly and AMPA, respectively. The HQs were calculated considering 0.5 mg/kg BW/day as an acceptable daily intake (ADI), which EFSA has established as a health-based reference value for both analytes. The values obtained were lower than 1, and thus, low health risk due to Gly and AMPA exposure was expected for the population under study.


[In-house radio-assisted emergency call system in continuous monitoring of microcirculation using laser doppler flowmetry].
Instrumental monitoring is being increasingly employed in the postoperative phase after microsurgery. For this purpose, laser Doppler flowmetry has proven to be very useful. Monitoring of the perfusion of tissue with blood is mainly by clinical examination, which, however, requires the physical presence of the observer, and this is generally not possible on a continuous basis. By connecting up a laser Doppler unit with a computer and telephone modem and making use of the in-house radio system, it proved possible to produce an automatic emergency call system that responds to a worsening of perfusion and alerts the responsible doctor. For this purpose, the software program "call-doc" was developed, which provides the necessary monitoring and control functions. A general perfusion-independent emergency call can also be triggered at the touch of a button.


Acute treatment of migraine headaches.
Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes.


Problem drinking in a general practice population: the construction of an interval scale for severity of problem drinking.
The main aim of this article is to describe the construction of an interval scale measuring the severity of problem drinking among patients of general practitioners. A questionnaire, including the existing screening instruments CAGE, SMAST, a shortened version of the SAAST and some additional items on alcohol-related problems, was given to three categories of patients: those who, according to the general practitioner, were not problem drinkers (Group 1), those who perhaps were (Group 2) and those who were known by the general practitioner to be problem drinkers (Group 3). According to the Classical Test Theory, the three existing screening instruments and the combination of all questions form a reliable scale. Advanced scaling techniques were applied to select the best items for the construction of an interval scale. These analyses showed that 18 of the 28 questions in the complete screening list fitted in a unidimensional Rasch scale. These questions can be used to estimate the severity of problem drinking. For research purposes an interval scale is attractive, since no information is lost by dichotomization. Such a scale enables the level of problem drinking to be specified at which correlations with other factors, whether as a cause or as an effect, can be found. The scale could also be a help to general practitioners for referral decisions. In more specialized settings it can be used to assign patients to various treatments.


Cells in human adipose tissue developing into adipocytes.
Sedimentable cells from human adipose tissue of different origins were cultured under conditions when cell multiplication was prevented but lipid filling optimized (suspension culture). In this way an estimation was obtained of the number of in vivo determined adipose precursor cells (preadipocytes) which were not filled with lipid. Under these conditions no cells from adult, non-obese subjects developed to adipocytes. Cells developing to adipocytes constituted less than 0.02% and 1% of adipocytes in tissues from obese adults and from children, respectively. It was concluded that in vivo determined adipocyte precursor cells (preadipocytes, lipid-free fat cells) are not present in a significant number in human adipose tissue either from adults or from children as tested with the method employed, allowing detection of a large number of such cells in adipose tissue from small rats.


Effect of tryptic digestion of myosin subfragment-1 on its binding to F-actin.
We investigated the effect of tryptic digestion of S-1 (95K) into three segments (27K, 50K, and 20K) on the binding of F-actin with S-1, using an ultracentrifugal separation method and a light-scattering method. The tryptic digestion of S-1 decreased the affinity of S-1 for F-actin both in the absence of nucleotide and the presence of AMPPNP or ATP, suggesting that the peptide cutting impairs the structures participating in the binding of S-1 or S-1-nucleotide complex with F-actin. Although nucleotides markedly weakened the affinity of S-1 for F-actin, the ratios of affinity of digested S-1 for F-actin to that of intact S-1 were all about 1/10 both in the absence and presence of nucleotides. This may be understood if we accept the assumption that two kinds of structure participate in the binding of S-1 with F-actin; one is independent of nucleotides and the other is dependent on them, with only the former being affected by the tryptic digestion of S-1.


The role of estrogens in prostate carcinogenesis: a rationale for chemoprevention.
Estrogens as hormonal therapy, particularly diethylstilbestrol, are effective against androgen-dependent prostate cancer, but paradoxically estrogens might also be involved in the causation of this malignancy. Therefore, antiestrogens have been suggested as both a chemopreventive and chemotherapeutic treatment, thereby inhibiting the development and progression of prostate cancer. This review addresses the role of estrogens in prostate carcinogenesis and prostate cancer progression and examines the rationale for using antiestrogenic agents in chemoprevention of prostate cancer.


Recent studies on 'hyalinized' glomeruli.
Hyalinized glomeruli in tissue sections those isolated from kidneys of subjected with end-stage and diabetic nephropathies and from aged persons (older than 75 years) were studied by histochemical, immunohistochemical, electron microscopic, and chemical methods. Our purposes were as follows: (1) to clarify the pathogenic mechanisms of glomerular hyalinization; (2) to resolve some of the controversies on terminology in the literature. Results showed significant increases in the amounts of collagen (13% to 30%), carbohydrates (30% to 47%), and lipids (58% to 82%), and decreases in the amounts of DNA (40%) and RNA (40% to 50%) in the hyalinized glomeruli of diseases compared with normally sized matched glomeruli. I conclude that glomerular hyalinization is a complex molecular pathogenic process.


The psychosexual and psychosocial profile of male genitourinary medicine patients with a history of sexual abuse/assault or unwanted sexual experiences.
One hundred and forty-one male patients who attended a District General Hospital's department of genitourinary medicine completed a questionnaire including demographic indices, history of sexual abuse/assault, anxiety and depression, and sexual concerns and attitudes. Of these, 52 (36.9%) reported past unwanted sexual experiences (USE). A significantly higher proportion of the USE group consisted of homosexual men than the non-USE majority. The prevalence rate for USE involving other men was 15.6%, which is comparable to previous studies. Hospital Anxiety and Depression scores were significantly greater for patients with a history of USE (t = -2.82, P = 0.006, for anxiety and t = -3.01, P = 0.003 for depression). Patients with a history of USE also scored significantly higher on a measure of sexual concerns. However, there were no significant differences between the USE and non-USE groups on two brief measures of alcohol and drug consumption. Clinicians in sexual health settings need to be sensitive to the fact that a significant proportion of male patients may have an undisclosed history of USE.


Prolonged inhibition of inflammation in osteoarthritis by triamcinolone acetonide released from a polyester amide microsphere platform.
Controlled biomaterial-based corticosteroid release might circumvent multiple injections and the accompanying risks, such as hormone imbalance and muscle weakness, in osteoarthritic (OA) patients. For this purpose, microspheres were prepared from an amino acid-based polyester amide (PEA) platform and loaded with triamcinolone acetonide (TAA). TAA loaded microspheres were shown to release TAA for over 60days in PBS. Furthermore, the bioactivity lasted at least 28days, demonstrated by a 80-95% inhibition of PGE2 production using TNFα-stimulated chondrocyte culture, indicating inhibition of inflammation. Microspheres loaded with the near infrared marker NIR780-iodide injected in healthy rat joints or joints with mild collagenase-induced OA showed retention of the microspheres up till 70days after injection. After intra-articular injection of TAA-loaded microspheres, TAA was detectable in the serum until day seven. Synovial inflammation was significantly lower in OA joints injected with TAA-loaded microspheres based on histological Krenn scores. Injection of TAA-loaded nor empty microspheres had no effect on cartilage integrity as determined by Mankin scoring. In conclusion, the PEA platform shows safety and efficacy upon intra-articular injection, and its extended degradation and release profiles compared to the currently used PLGA platforms may render it a good alternative. Even though further in vivo studies may need to address dosing and readout parameters such as pain, no effect on cartilage pathology was found and inflammation was effectively lowered in OA joints.


[Surgical treatment of patients with micro-cystitis of tuberculous and other etiology].
The urinary bladder was reconstructed by using different segments of the gastrointestinal tract in 45 patients aged 21 to 72 years. The indication for surgery was microcystis of tuberculous and other etiology in 28 (62.2%) and 17 (37.8%) patients, respectively. The overall post-operative mortality was 2.2% (1 patient). Early and late complications were observed in 17.8 and 30.4% patients, respectively. Analysis of the causes of complications has indicated that they are associated with the urine diversion method and with the scope of urinary bladder resection. Seven repeated operations were performed. Augmentation cystoplasty should follow subtotal microcystectomy. For correction of azotemia and for prevention of stricture in the early postoperative period, the neocystis should be continuously irrigated with antiseptic solutions in order to eliminate urine, mucus, and blood clots.


Characterization and expression of a cloned tetracycline resistance determinant from Campylobacter jejuni plasmid pUA466.
A tetracycline resistance (Tcr) determinant previously cloned from the Campylobacter jejuni plasmid pUA466 (D. E. Taylor, J. Bacteriol. 165:1037-1039, 1986) was localized by restriction endonuclease mapping, subcloning, and Tn1000 insertion mutagenesis to a 2-kilobase region consisting of 1.8- and 0.2-kilobase HincII fragments. Tcr encoded by the cloned fragment (pUOA1) was expressed constitutively in Escherichia coli. A protein with an apparent molecular weight of 68,000 encoded by pUOA1 was produced in an in vitro transcription-translation system and in minicells. Tn1000 insertions which resulted in inactivation of Tcr expression also resulted in an alteration in the 68,000-molecular-weight protein. Some mutants specified a truncated protein, whereas others completely lost the ability to specify the protein. The protein which appears to be involved in the expression of Tcr specified by C. jejuni plasmids is of approximately the same molecular weight as the protein specified by the streptococcal class M determinant. This finding is consistent with our previous results which indicate that homology exists between the Tcr determinant from C. jejuni and a 5-kilobase HincII probe derived from the streptococcal class M determinant.


Femtosecond laser nanostructuring in porous glass with sub-50 nm feature sizes.
We report on controllable production of nanostructures embedded in a porous glass by femtosecond laser direct writing. We show that a hollow nanovoid with a lateral size of ~40 nm and an axial size of ~1500 nm can be achieved by manipulating the peak intensity and polarization of the writing laser beam. Our finding enables applications ranging from direct construction of 3D nanofluidics in glass to clean stealth dicing of transparent plates.


Kinetics of charged antibiotic penetration into human intervertebral discs: A numerical study.
Little quantitative information exists on the kinetics of charged antibiotic penetration into human intervertebral discs (IVD). This information is crucial for determining the dosage to use, timing of administration, and duration of treatment for infected IVDs. The objective of this study was to quantitatively analyze the transport of various charged antibiotics into human lumbar IVDs. Penetration of charged and uncharged antibiotics into a human lumbar disc was analyzed using a 3D finite element model. The valence (z) of the electrical charge of antibiotics varied from z=+2 (positively charged) to z=-2 (negatively charged). An uncharged antibiotic (z=0) was used as a control. Cases with intravenous (IV) administrations of different charged antibiotics were simulated. Our results showed that the electrical charge had great effects on kinetics of an antibiotic penetration into the IVD; with higher concentrations and uptakes for positively charged antibiotics than those for negatively charged ones. This study provides quantitative information on selecting antibiotics for treating intervertebral disc infections.


Methoxychlor enhances degranulation of murine mast cells by regulating FcεRI-mediated signal transduction.
Methoxychlor, an organochlorine insecticide developed to replace DDT (dichlorodiphenyltrichloroethane), has been reported to induce mast cell degranulation and to enhance IgE-mediated allergic responses. However, the mechanisms underlying these effects are not clear. To clarify potential mechanisms, the effects of methoxychlor on degranulation of mast cells were examined. Degranulation responses were evaluated using RBL-2H3 cells and mouse bone marrow-derived mast cells with either the antigen-induced or calcium ionophore-induced stimulation. Phosphorylation of enzymes related to signaling events associated with mast cell degranulation was analyzed by immunoblotting. Effects on vascular permeability in the passive cutaneous anaphylaxis reaction were evaluated following oral administration of methoxychlor to BALB/c mice. The results indicated that methoxychlor caused increased mast cell degranulation in the presence of antigen, whereas it had no effect on calcium ionophore-induced degranulation of RBL-2H3 cells. Immunoblot analyses demonstrated that the phosphorylation level of phosphoinositide 3-kinase (which plays a central role in mast cell signaling) was increased by methoxychlor during antigen-induced degranulation. In addition, methoxychlor activated the signaling pathway via the high-affinity IgE receptor by inducing phosphorylation of Syk and PLCγ1/2, which transfer the signal for degranulation downstream. Lastly, oral administration of methoxychlor exhibited a tendency to promote vascular permeability in passive cutaneous anaphylaxis model mice. Taken together, the results here suggested that methoxychlor enhanced degranulation through FcεRI-mediated signaling and promoted allergenic symptoms involved in mast cell degranulation.


Free fatty acid content and release kinetics as manifestations of cerebral lateralization in mouse brain.
Free fatty acid (FFA) content was analyzed in mouse cerebral hemispheres and cerebellum under basal and postdecapitative ischemic conditions. Total FFA content immediately after decapitation (2 s) was about two-fold higher in the left hemisphere than in the right. Marked dissimilarities between hemispheres were also apparent when FFA levels were measured during short periods of ischemia. Whereas in the right side a significant FFA release took place as early as 10 s, no accumulation was detected in the left in the 2-20 s interval. The highest rates of total fatty acid release occurred in the 20-30 s interval in both hemispheres and decreased afterwards (3 min). Individual FFA, especially stearate and arachidonate, differed in their rates of production, the right cerebral hemisphere being more active in releasing arachidonic acid. In cerebellum, FFA levels were lower and accumulation was slower than in cerebrum in both intervals. When subjected to 3 min ischemia, the same difference in FFA levels between right and left hemispheres (50%) was observed in heads kept at 20 or 30 degrees C. The differences between hemispheres are interpreted as manifestations of an inherent lateralization in the regulation of acylation-deacylation reactions of complex lipids.


Voids as alternatives to dark energy and the propagation of γ rays through the universe.
We test the opacity of a void universe to TeV energy γ rays having obtained the extragalactic background light in that universe using a simple model and the observed constraints on the star formation rate history. We find that the void universe has significantly more opacity than a Λ cold dark matter universe, putting it at odds with observations of BL-Lac objects. We argue that while this method of distinguishing between the two cosmologies contains uncertainties, it circumvents any debates over fine-tuning.


Time-course of masked response priming and inhibition in Parkinson's disease.
Parkinson's disease patients have enhanced interference effects arising from the conflict between competing responses, as probed in various 'conflict tasks'. The possibility that this is due to an inhibitory deficit received recent support from a masked response priming task [Seiss, E., & Praamstra, P. (2004). The basal ganglia and inhibitory mechanisms in response selection: Evidence from subliminal priming of motor responses in Parkinson's disease. Brain, 127, 330-339]. The added information from a masked priming task is that the introduction of a delay between presentation of prime and target stimuli reveals an inhibition of the covert response activation induced by the masked prime stimulus. This inhibition results in a reversal of normal priming effects, such that performance is better with incompatible than with compatible prime-target pairs. We previously found that this reversal is attenuated in Parkinson's disease, when tested at a prime-target delay of 100 ms, thus revealing deficient inhibition of covert response activation. The present study was undertaken to investigate the time course of the underlying inhibition process, using five prime-target ISIs between 0 and 200 ms. While we reproduced the attenuation at ISI 100 ms, the time course information revealed that the rate of change of the compatibility effect over ISIs from 0 to 200 ms was identical for patients and controls. This result indicates that the inhibition underlying the reversal of masked priming effects is normal in Parkinson's disease.


Symptom distresses and coping strategies in patients with non-small cell lung cancer.
The purpose of this study is to understand the correlation of symptom distresses and coping strategies of patients with lung cancer. Seventy-three patients with non-small cell lung cancer from the cancer center or ward in the two medical centers located in northern Taiwan participated. The instruments used in this study were the Symptom Distress Scale and Coping Strategies Scale. The results of the study showed that the degree of symptom distress during the therapeutic period was mild to moderate. When patients were confronted with symptom distress, they combined problem- and emotion-focused coping strategies. Participants with higher physical symptom distress had higher psychological distress and emotion-focused coping strategy frequency. It was also found that the distress of tension-anxiety and age explained 39.4% of variance in physical symptom distresses. The physical symptom distresses and the frequency of emotion-focused coping strategy frequency explained 48.8% of variance in the psychologic symptom distresses. Finally, it is recommend that a support group be established to enable sharing of experiences and emotional support among patients.


Suprasternal Doppler estimation of cardiac output: standard versus sequential combined spinal epidural anesthesia for cesarean delivery.
Sequential (Seq) combined spinal epidural (CSE) may provide better cardiovascular stability than standard (Std) CSE for cesarean delivery. We compared the cardiovascular stability of both techniques using suprasternal Doppler. Healthy women (n = 40) scheduled for elective cesarean delivery were randomized into two groups; Std or Seq CSE. Serial measures of cardiac output indices, including minute distance, stroke distance, stroke volume, peak velocity, and corrected flow time, were recorded before and after intravascular fluid administration and after CSE. Women received either hyperbaric bupivacaine 10 mg (Std) or 5 mg (Seq) with intrathecal fentanyl 15 microg. An epidural top-up with bupivacaine 0.5% w/v (5 mL at 20 min in the Std group and 10 mL at 15 min followed by 5 mL at 25 min in the Seq group) was given if predefined sensory targets were not met. Data were collected every 5 min after intrathecal injection. Hypotension was treated with ephedrine. Statistical analyses included repeated measures analysis of variance, analysis of covariance and Student's t-test. P < 0.05 denoted significance. Results showed no difference in cardiac output, minute distance, stroke distance, stroke volume, peak velocity, or corrected flow time between groups over the first 20 min after spinal injection. For whole measurement periods, mean lowest values for these same measures showed no group differences. We therefore found no benefit in terms of cardiovascular stability of Seq to Std CSE for elective cesarean delivery in the healthy pregnant population.


Obstetric care of women with female genital mutilation attending a specialized clinic in a tertiary center.
To study the obstetric outcomes of women attending a specialized clinic for women with female genital mutilation (FGM). The medical charts of women with FGM who consecutively attended a specialized clinic between 2010 and 2012 were reviewed retrospectively. The present study focused on women attending for obstetric reasons. The outcome measures were type of delivery, reason for cesarean delivery or assisted delivery, blood loss, episiotomy, perineal tear, duration of the second stage of labor, postpartum complications, weight of the neonate, and Apgar score. Outcomes were compared between women with FGM type III who underwent defibulation, and patients with FGM type I and II. The clinic was attended by 129 women, 84 perinatally. Obstetric outcomes were similar to average outcomes for women without FGM presenting at the same department and in Switzerland generally. Specifically, 20 women had a cesarean delivery. An assisted delivery was performed for 18 patients; among these, only eight had experienced obstructed labor. No statistically significant differences were found for the outcome measures when women with FGM type III were compared to FGM type I and II. Routine obstetric follow-up combined with specialized care for women with FGM, including defibulation, can avoid inappropriate obstetric practices and reduce obstetric complications known to be associated with FGM.


Thyroid hormone regulates heparan sulfate proteoglycan expression in the growth plate.
Thyroid hormone is essential for normal skeletal development. Hypothyroidism is associated with growth arrest, failure of chondrocyte differentiation, and abnormal matrix synthesis. Thyroid hormone modulates the Indian hedgehog/PTHrP feedback loop and regulates fibroblast growth factor (FGF)/FGF receptor signaling. Because heparan sulfate (HS) proteoglycans (Prgs) (HSPGs) are absolutely required by these signaling pathways, we have investigated whether thyroid status affects HSPG expression within the growth plate. Tibial growth plate sections were obtained from 12-wk-old rats rendered euthyroid, thyrotoxic, or hypothyroid at 6 wk of age, 14-d-old congenitally hypothyroid Pax8-null mice, and TRalpha/TRbeta double-null mice lacking all thyroid hormone receptors. HS and chondroitin sulfate Prg expression was determined by immunohistochemistry using three monoclonal antibodies. There was increased HS staining in growth plates from hypothyroid animals predominantly within the extracellular matrix of reserve and proliferative zones. Cellular HS staining was also increased particularly in prehypertrophic chondrocytes. T3 regulation of HSPG core protein and HS synthetic and modification enzyme expression was studied in ATDC5 cells using semiquantitative RT-PCR. Thyroid hormone negatively regulated expression of the core protein Gpc6, the polymerase Ext1, and the modification enzyme Hs6st2. These studies demonstrate that the expression and distribution of growth plate Prgs are regulated by thyroid hormone, and the regulation of HSPG expression provides an important additional link between FGF and Indian hedgehog signaling and T3. These novel observations suggest that the cartilage matrix and especially HSPGs are critical mediators of the skeletal response to thyroid hormone.