Ergonomics related to seating arrangements in the classroom: worst in South East Asia? The situation in Sri Lankan school children.
Sri Lanka is a resource-poor country in the South-East Asian region with good health indices. Ergonomics of children in educational environments is still novel in the region. An exploration into such issues and dissemination of the scientific evidence will stimulate policy makers in both education and health sector. An important ergonomic issue of the classroom is the seating arrangement. Essential aspects of seating include location of the chair and desk in relation to the blackboard and features of the chair and desk. Musculoskeletal pain is considered to be the most important negative effect due to mismatched ergonomics. A school-based descriptive cross sectional study was carried out in a district of Sri Lanka to ascertain the distribution of selected ergonomic factors related to seating arrangements in the classroom of school-going early adolescents and to assess their relationship to musculoskeletal pain. A sample of 1607 school children of Grade 6,7 and 8 were selected using stratified multi-stage cluster sampling method. There were 52.1% (N=838) females and 47.9% (N=769) males. Many ergonomic aspects related to classroom seating arrangements are not conducive for children. Children were seated with a mean distance of 398.04 cm (SD=132.09) to the blackboard. Nearly 23% of children had to turn more than 45~degrees to see the blackboard. A prevalence of > 80% mismatch was found between body dimensions of children and measurements of furniture. Musculoskeletal pain may have resulted from efforts to maintain stability while seated in incompatible furniture. Nearly 36% children complained of recurrent musculoskeletal pain. Musculoskeletal pain may have resulted from efforts to maintain stability while seated in incompatible furniture. Mismatched seat depth - buttock-popliteal length posed 1.59 times risk recurrent musculoskeletal pain. Despite, children perceived a good chair comfort. Use of backrest lowered the risk of recurrent pain. Results shows that programme planners can utilize such evidence to provide simple ergonomic solutions at national and school level.


Pathogenesis of infections due to coagulase-negative staphylococci.
As a group, the coagulase-negative staphylococci (CoNS) are among the most frequently isolated bacteria in the clinical microbiology laboratory and are becoming increasingly important, especially as causes of hospital-acquired infections. These bacteria are normal inhabitants of human skin and mucous membranes and, therefore, one of the major challenges of daily diagnostic work is to distinguish clinically significant CoNS from contaminant strains. This overview addresses current knowledge of the pathogenesis of infections due to CoNS and particularly focuses on virulence factors of the species Staphylococcus epidermidis. S epidermidis has been identified as a major cause of nosocomial infections, especially in patients with predisposing factors such as indwelling or implanted foreign polymer bodies. Most important in the pathogenesis of foreign-body-associated infections is the ability of these bacteria to colonise the polymer surface by the formation of a thick, multilayered biofilm. Biofilm formation takes place in two phases. The first phase involves the attachment of the bacteria to polymer surfaces that may be either unmodified or coated with host extracellular matrix proteins. In the second phase, the bacteria proliferate and accumulate into multilayered cell clusters that are embedded in an extracellular material. The bacterial factors involved in both phases of biofilm formation are discussed in this review. In addition, the most important aspects of the pathogenic potential of S saprophyticus, S lugdunensis, and S schleiferi are described, although, compared with S epidermidis, much less is known in these species concerning their virulence factors.


Association of pre-kidney transplant markers of mineral and bone disorder with post-transplant outcomes.
Mineral and bone disorders (MBDs) are common in long-term dialysis patients and are risk factors for unfavorable outcomes. The associations between pretransplant levels of MBD surrogates and outcomes after kidney transplantation are not clear. Data from the Scientific Registry of Transplant Recipients up to June 2007 were linked to the 5-year (July 2001-June 2006) cohort of a large dialysis organization in the United States. All dialysis patients who received a kidney transplant during this period were identified and divided into groups according to increments of pretransplant MBD markers. Unadjusted and multivariate adjusted predictors of transplant outcomes were examined. The 11,776 patients were aged 47 ± 14 years and 39% were women. Compared with recipients with pretransplant time-averaged serum alkaline phosphatase of 80-120 U/L, recipients with pretransplant serum alkaline phosphatase of 120-160 and ≥160 U/L had 49% and 64% higher graft failure censored all-cause mortality in multivariable adjusted models. There was no significant association between time-averaged serum alkaline phosphatase categories and risk of death censored graft failure, delayed graft function (DGF), or acute rejection (AR). Compared with recipients with pretransplant time-averaged serum parathyroid hormone (PTH) levels of 150-300 pg/ml, there was no significant association with graft censored death among recipients with pretransplant serum PTH ≥800 pg/ml. In addition, the risk of graft failure, DGF, and AR did not show any association with time-averaged serum intact PTH level. There was no significant association between time-averaged serum calcium categories and risk of graft failure censored death, DGF, and AR. In this cohort, hemodialysis patients with pretransplant serum alkaline phosphatase >120 U/L have unfavorable post-transplant mortality, whereas there was no association between serum PTH and serum calcium levels and post-transplant outcomes.


Learning Disabilities in Primary School. How to Diagnose and Remediate the Difficulties with a Team Approach: The First Results.
An important problem of our day is the significant increase in the number of learning-disabled pupils all over the world. This has led to the emergence of a new branch of neuropsychology!- "school neuropsychology" or the "Neuropsychology of learning." This paper analyzes the role and functions of a neuropsychologist in primary schools and the possibilities of his/her collaboration with other specialists in diagnosing children's problems and organizing remediation for problematic kids. We established four steps for launching neuropsychological work at primary schools: 1) setting up a screening group for neuropsychological assessment of all children entering the first year of school; 2) a comprehensive neuropsychological assessment of the children who showed poor results in the first step of the study; 3)ateam remediation program; and 4) evaluation of the remediation results by a new neuropsychological assessment at the end of the remediation program. The results of the first step of our study showed a very high percentage of children with cognitive problems- 37% of 202 6-8 year-old schoolchildren entering the first year of school. They formed a group at risk for future learning disabilities and maladjustment at school. Age and gender differences, and the structure of cognitive underdevelopment, were discussed in the second step of our study. In the third step, a team of school specialists, including a neuropsychologist, a teacher, a school psychologist, and a school social worker, implemented a remediation program which was created and supervised by a neuropsychologist. A comprehensive neuropsychological assessment of the pupils revealed a complex structure of cognitive disturbances which interfere with pupils' learning abilities in primary school. The team approach can efficiently prevent learning disabilities and help children with cognitive underdevelopment and risks of future unsuccess at school, when this collaboration of school specialists has a common theoretical approach and is based upon comprehensive neuropsychological assessment.


Antiviral drug resistance in human cytomegalovirus.
Drug-resistant cytomegalovirus (CMV) should be considered when viral shedding persists after several weeks of therapy. The problem is most likely to arise in the setting of a severely immunosuppressed host with continuing or relapsing disease. Not all treatment failure can be attributed to drug resistance. The testing of CMV isolates for drug resistance in cell culture is time-consuming and labor-intensive, but recent advances in understanding of the genetics of resistance have resulted in rapid genotypic assays for specific mutations in the viral UL97 phosphotransferase or UL54 DNA polymerase genes that can predict resistance and cross-resistance to specific drugs. This information may help in the selection of alternative therapy.


Thermostability of bacterial luciferase expressed in different microbes.
Bacterial luciferase was used to investigate the relationship between the thermostability of a cytoplasmic reporter molecule and cellular heat resistance. The luciferase activity of Vibrio fischeri was expressed in strains of Escherichia coli, Salmonella typhimurium, Listeria monocytogenes and Brochothrix thermosphacta following transformation with plasmid pSP13 carrying the luxAB genes. The thermostability of intracellular luciferase varied depending on the organism in which it was expressed, but was not related to the cellular heat resistance of the different organisms. Addition of xylitol to the heating medium protected against loss of viability and inactivation of intracellular luciferase. Glycerol also protected against loss of viability but was less effective at preventing thermal denaturation of luciferase.


Using Fundamental Spectroscopy to Elucidate Kinetic and Energetic Mechanisms within Environmentally Relevant Inductively Coupled Plasma Systems.
Understanding energy distributions and kinetic processes in NxOy plasma systems is vital to realizing their potential in a range of applications, including pollution abatement. Energy partitioning between degrees of freedom and multiple molecules formed within NxOy plasma systems (N2, N2O, N2/O2) was investigated using both optical emission and broadband absorption spectroscopies. Specifically, we determined electron temperatures (Te) as well as rotational (TR) and vibrational (TV) temperatures for various N2 (B3Πg and C3Πu) and NO (X2Π and A2Σ+) states. TR and TV for both molecules (regardless of state) show a strong positive correlation with applied plasma power, as well as a negative correlation with system pressure. In all cases, TV values are significantly higher than TR for both species, suggesting vibrational modes are preferentially excited over rotational degrees of freedom. Time-resolved optical emission spectroscopy was utilized to determine rate constants, providing mechanistic insight and establishing the relationships between system parameters and plasma chemistry. Ultimately, the combination of these data allows us to glean information regarding both the kinetics and energetics of N2 and NO molecules formed within nitrogen- and oxygen-containing plasma systems for potential applications in gas remediation of pollutants.


The effect of anger management by nursing staff on violence rate against them in the emergency unit.
Violence at work is considered as part of the occupational hazards which can affect medical staff and have undesirable effects on quality of patients care. Anger management training causes increases the ability of individuals to change behavior and also can increase the ability of the individual in controlling the excitation in the undesirable conditions. This study aimed to determine the effect of anger management training program by nursing staff on violence rate against them. This was a two-group, two-phase, semi-experimental study. Sixty six qualified nurses employed in emergency unit of Al-Zahra Hospital were divided into test and control groups. In this study, the modified questionnaire of World Health Organization was used with adequate validity and reliability to measure the violence rate and anger control. Thereafter, the test group received anger management training for four 60-minute sessions. The results of the study showed that there was no significant difference between the two groups in terms of demographic characteristics except marital status. In addition, there was a significant difference between the two groups in frequency distribution of psychological violence against nurses after the intervention, but there was no significant difference between the two groups in frequency distribution of physical violence against nurses. The results of this study corroborated the findings of the previous studies. Therefore, increase in self-control and communication skills and problem solving skills at the time of dealing with the patients and their relatives is a step in reducing one of the factors of violence at workplace.


The plant organelles database (PODB): a collection of visualized plant organelles and protocols for plant organelle research.
The plant organelles database (PODB; http://podb.nibb.ac.jp/Organellome) was built to promote a comprehensive understanding of organelle dynamics, including organelle function, biogenesis, differentiation, movement and interactions with other organelles. This database consists of three individual parts, the organellome database, the functional analysis database and external links to other databases and homepages. The organellome database provides images of various plant organelles that were visualized with fluorescent and nonfluorescent probes in various tissues of several plant species at different developmental stages. The functional analysis database is a collection of protocols for plant organelle research. External links give access primarily to other databases and Web pages with information on transcriptomes and proteomes. All the data and protocols in the organellome database and the functional analysis database are populated by direct submission of experimentally determined data from plant researchers and can be freely downloaded. Our database promotes the exchange of information between plant organelle researchers for the comprehensive study of the organelle dynamics that support integrated functions in higher plants. We would also appreciate contributions of data and protocols from all plant researchers to maximize the usefulness of the database.


Simultaneous detection of four pesticides in agricultural products by a modified QuEChERS method and LC-MS/MS.
A modified QuEChERS pretreatment method and LC-MS/MS technique were performed to simultaneously determine four pesticide (Hexachlorophene, Dinex, Dinosam, Dinoterb) residues in agricultural products. Through the optimization of LC-MS/MS detection parameters in SIM mode, the optimal instrument conditions are obtained. The modified QuEChERS method was used to pretreat the samples. Solid phase extractants PSA, C18 and GCB were used for sample purification. The research results showed that the correlation coefficients of the four pesticides were all greater than 0.991, which had a good linear relationship. The limits of quantitation (LOQ) of the four pesticides were 0.05-0.56 μg/kg. The recoveries were 70.51-113.20% with relative standard deviations (RSDS) of 1.6-11.2%. The developed method can provide reliable data support for the subsequent simultaneous detection of these four pesticides.


Caregivers' inability to identify childhood adiposity: a cross-sectional survey of rural children and their caregivers' attitudes.
To determine the prevalence of overweight and obese children in north-western New South Wales and to assess caregivers' ability to detect adiposity in their children. A cross-sectional survey using a standardised caregiver questionnaire and anthropometric measurements of school children attending 10 primary schools selected by stratified random sampling. A total of 598 eligible school children aged between five and eight years. Body mass index for children; caregivers' assessment of their children's dietary intake, physical activity and adiposity by questionnaire. A total of 348 caregivers responded to the survey, yielding a response rate of 58.2%. Significantly more caregivers of boys (200) than girls (144) chose to participate (chi2 = 8.3, d.f. = 1, P < 0.01). The vast majority of caregivers (87%) consented to their children being measured. Body mass index measurements revealed the following: more than three quarters of boys (82%) and girls (77%) were of normal weight. Of boys and girls 13% were overweight. Twice as many girls (6%) than boys (3%) were obese. In total, 31% of caregivers underestimated the weight of their children. This proportion of caregivers underestimating the correct weight category of their children almost doubled to 56% of caregivers of overweight children. Proportionately more caregivers of overweight boys underestimated their children's weight than caregivers of girls (67% compared with 44%). Health promotional activities need to address, as a matter of priority, caregivers' ability to accurately assess the correct weight category of their children.


Calls for concerted barcoding drive.
With the NHS in England spending some pound 6 billion annually on hospital supplies, but (says the Department of Health) some English hospitals paying nearly three times as much for the same items as their counterparts, Health Minister, Simon Burns, has called on suppliers to significantly extend use of standardised GS1 barcodes in an attempt to improve "transparency" for procurement staff. The Minister argues that individually barcoding many more hospital-bound items would give procurement teams a clearer, more accurate picture of what they were buying, enable fairer price comparison, and radically improve stock control in many NHS hospitals, potentially reducing NHS procurement costs by millions of pounds. Other anticipated benefits include fewer medication errors, lower risk of wrong-site surgery, and the ability to track and trace everything from surgical instruments to patient beds. HEJ editor Jonathan Baillie reports.


Introduction of continuous regional analgesia via wound catheters in a peripheral hospital.
To review the effectiveness of continuous regional analgesia (CRA) via wound catheters after abdominal surgery in a district general hospital (Wanganui, New Zealand). Retrospective review of postoperative analgesia after CRA via wound catheters was introduced (April 2008 to December 2008). Pain scores, HDU stay, opiate use and complications were recorded. Fifty-four patients' notes have been reviewed after elective and emergency laparotomies. Twenty-seven had WC (± patient controlled analgesia [PCA]), 15 had PCA only, 12 had epidural (± PCA). Resting pain scores were nil or zero in 18/27 (66.7%) wound catheter, 9/15 (60%) PCA and 5/12 (41.7%) epidural patients. Moderate/severe pain on movement was scored in patients 5/27 (18.5%) with wound catheter, 6/15 (40%) with PCA, 5/12 (41.7%) with epidural catheters. A single PCA syringe lasted over 24 hours in 18/27 (66.7%) wound catheter, 6/15 (40%) PCA, and 5/8 (63%) epidural + PCA patients. Eight adverse effects were seen; 4 wound infections (2 wound catheter, 1 PCA, 1 epidural patient) and 4 blockages of epidural catheters in epidural group. No adverse effect was found directly related to the WC. Continuous regional analgesia via wound catheters provides effective and safe postoperative analgesia for surgical patients in a small district general hospital. Used as part of a multimodal approach it allows easy step-down from HDU to surgical wards. This technique has been readily accepted over the year by theatre, HDU, ward, and anaesthetics colleagues.


The Online Use of the Newest Vital Sign in Adolescents.
Seventy percent of premature adult deaths are caused by adolescent behaviors. Data suggests that health literacy may influence adolescent behaviors. However, adolescent health literacy research is scarce; and, timely, more robust data is imperative. Nonetheless, many potential study samples are currently inaccessible due to the pandemic. Thus, there is an immediate need to evaluate online adolescent health literacy research modalities to further the science. The purpose of this study is to explore the psychometric properties of online administration of the Newest Vital Sign (NVS) health literacy instrument in adolescents. A total of 105 adolescents completed the study via Qualtrics. Internal consistency reliability of the online NVS was good (α = .77). There was, however, no significant correlation between online and in-person comparison scores (r = .05, p = .59). This study yields clinically significant results showing insight into the online NVS for adolescents, providing a foundation for future adolescent health literacy research.


Synthesis of pyrimidine derivatives possessing an antioxidative property and their inhibitory effects on picryl chloride-induced contact hypersensitivity reaction.
We conducted a preliminary structure-activity relationship (SAR) study of some barbituric acid and uracil derivatives against the picryl chloride-induced contact hypersensitivity reaction. The introduction of an antioxidative moiety to the side chain of the C(6)-position of uracil was effective against this model. The introduction of dimethoxyphenol (8b) or dimethylphenol (8c) instead of di-t-butylphenol (8a) as an antioxidative moiety gave diminished activities, so, the reactive oxygen would contribute to the inflammation of this model, and an antioxidative activity was required for exhibiting the inhibitory activity. The inhibitory activity was significantly affected by the substituent at the N(1)-phenyl moiety.


Optimizing principal component models for representing interfraction variation in lung cancer radiotherapy.
To optimize modeling of interfractional anatomical variation during active breath-hold radiotherapy in lung cancer using principal component analysis (PCA). In 12 patients analyzed, weekly CT sessions consisting of three repeat intrafraction scans were acquired with active breathing control at the end of normal inspiration. The gross tumor volume (GTV) and lungs were delineated and reviewed on the first week image by physicians and propagated to all other images using deformable image registration. PCA was used to model the target and lung variability during treatment. Four PCA models were generated for each specific patient: (1) Individual models for the GTV and each lung from one image per week (week to week, W2W); (2) a W2W composite model of all structures; (3) individual models using all images (weekly plus repeat intrafraction images, allscans); and (4) composite model with all images. Models were reconstructed retrospectively (using all available images acquired) and prospectively (using only data acquired up to a time point during treatment). Dominant modes representing at least 95% of the total variability were used to reconstruct the observed anatomy. Residual reconstruction error between the model-reconstructed and observed anatomy was calculated to compare the accuracy of the models. An average of 3.4 and 4.9 modes was required for the allscans models, for the GTV and composite models, respectively. The W2W model required one less mode in 40% of the patients. For the retrospective composite W2W model, the average reconstruction error was 0.7 +/- 0.2 mm, which increased to 1.1 +/- 0.5 mm when the allscans model was used. Individual and composite models did not have significantly different errors (p = 0.15, paired t-test). The average reconstruction error for the prospective models of the GTV stabilized after four measurements at 1.2 +/- 0.5 mm and for the composite model after five measurements at 0.8 +/- 0.4 mm. Retrospective PCA models were capable of reconstructing original GTV and lung shapes and positions within several millimeters with three to four dominant modes, on average. Prospective models achieved similar accuracy after four to five measurements.


Sulfur- and Selenium-Containing Compounds Potentially Exhibiting Al Ion Conductivity.
We have created a set of crystalline model structures exhibiting straight lines of Al3+ connected to chalcogenides (O2- , S2- , and Se2- ) connected to metal cations of varying valence (Sr2+ , Y3+ , Zr4+ , Nb5+ , and Mo6+ ). They were relaxed with density functional theory computations and analysed by Bader partitioning. As Al3+ ions are supposed to strongly interact with their atomic environment, we studied the electron density topology induced by higher-valent cations in the extended chemical neighbourhood of Al. In fact, we found a general decrease of ionic charges and an increasing displacement of the chalcogenides towards higher-valent ions for the heavier chalcogens. Therefore, we comprehensively screened S- and Se-containing compounds for candidates theoretically exhibiting low migration barriers for Al3+ ions by using Voronoi-Dirichlet partitioning and bond valence site energy calculations. The basis for this search is the Inorganic Crystal Structure Database. Indeed, we could extract six promising candidates with low Al3+ migration barriers. which are even lower than the barriers for any other element inside of these materials. This will encourage efforts towards preparing suitable Al3+ conductors.


A prospective comparison of urinary tract infections in patients treated with either clean intermittent catheterization or urinary diversion.
Clean intermittent catheterization (CIC) has replaced urinary diversion as the treatment of choice for patients with neurogenic bladder. Yet, no well controlled studies are available assessing the efficacy of CIC over ileal loop diversion (ILD). Consequently, a one-year pospective study was carried out comparing short-term patient morbidity, infection rates, and bacterial organisms in 33 children with meningomyelocele. Twenty-four of the children were treated with CIC whereas nine children had an ILD. A minimum of four cultures per year were obtained on each patient. Patients maintained on CIC had 36.8% of their cultures positive for bacteriuria whereas children with ILD had 61.8% of their cultures positive (P less than .001). The incidence of bacteriuria associated with clinical signs and symptoms was similar in both groups. Four of 24 children treated with CIC had sterile urine whereas none of the children with ILD were persistently free from bacteriuria. Only five of 24 children receiving CIC had 50% or more of their cultures positive as contrasted with seven of nine children with an ILD (P less than .01). Escherichia coli accounted for approximately one third of organisms recovered from infected urine in both groups. Although the short-term morbidity associated with both treatment modalities is similar, the incidence of asymptomatic bacteriuria in children maintained on CIC is significantly less than in children with ILD. Whether this factor plays a role in determining long-term morbidity is a subject for further study.


Reconstruction of penetrated nasal defects with nasolabial skin flap pedicled on the infraorbital vessels.
Penetrated nasal defects involve complicated problems of reconstruction because they require a relatively larger volume of flaps and grafts as well as aesthetic needs. The nasolabial skin flap pedicled on infraorbital vessels was evaluated in this research. Sixteen patients underwent nasal defect reconstruction with nasolabial skin flap pedicled on the infraorbital vessels through the subcutaneous tunnel. All of the 16 flaps were viable, with a maximum area of 5.0 x 2.5 cm. The color and texture of the flaps were similar to those of surrounding skin of the recipient site. Thermal and tactile sensation of the flap proved satisfactory in all the patients. The scar of donor site was occulted, and the contour of the nose did not change after the operation. The nasolabial skin flap pedicled on the infraorbital vessels had many distinct advantages and was recommended for defect reconstruction as an adjacent axial flap.


Zeptosecond precision pulse shaping.
We investigate the temporal precision in the generation of ultrashort laser pulse pairs by pulse shaping techniques. To this end, we combine a femtosecond polarization pulse shaper with a polarizer and employ two linear spectral phase masks to mimic an ultrastable common-path interferometer. In an all-optical experiment we study the interference signal resulting from two temporally delayed pulses. Our results show a 2σ-precision of 300 zs = 300 × 10(-21) s in pulse-to-pulse delay. The standard deviation of the mean is 11 zs. The obtained precision corresponds to a variation of the arm's length in conventional delay stage based interferometers of 0.45 Å. We apply these precisely generated pulse pairs to a strong-field quantum control experiment. Coherent control of ultrafast electron dynamics via photon locking by temporal phase discontinuities on a few attosecond timescale is demonstrated.


Focal neuronal gigantism and cerebral cortical thickening after therapeutic irradiation of the central nervous system.
An exceptional type of cortical dysplasia is described in the brain of a 32-year-old woman who had received radiation therapy for a large pituitary adenoma 6 years before death. Markedly thickened gyri of the left inferior frontal, insular, and temporal cortex were found grossly. Microscopically, these gyri showed laminar disorganization and many unusually large and abnormally shaped ganglion cells. These neurons were heavily impregnated with silver preparations; were strongly reactive for neuron-specific enolase, synaptophysin, and neuronal cytoskeletal proteins (68- and 200-kd subunits of neurofilament protein, microtubule-associated protein 2, and tau); and ultrastructurally contained numerous perikaryal neurofilaments. Collectively, these findings suggest that the abnormally large, misshapen neurons contained excessive accumulations of cytoskeletal intermediate filaments. The present case and a similar one described in 1964 are the only two documented instances of neuronal gigantism apparently related to therapeutic irradiation of the brain.


Genome-wide analysis of CRISPR perturbations indicates that enhancers act multiplicatively and without epistatic-like interactions.
A single gene may be regulated by multiple enhancers, but how they work in concert to regulate transcription is poorly understood. Prior studies have mostly examined enhancers at single loci and have reached inconsistent conclusions about whether epistatic-like interactions exist between them. To analyze enhancer interactions throughout the genome, we developed a statistical framework for CRISPR regulatory screens that utilizes negative binomial generalized linear models that account for variable guide RNA (gRNA) efficiency. We reanalyzed a single-cell CRISPR interference experiment that delivered random combinations of enhancer-targeting gRNAs to each cell and interrogated interactions between 3,808 enhancer pairs. We found that enhancers act multiplicatively with one another to control gene expression, but our analysis provides no evidence for interaction effects between pairs of enhancers regulating the same gene. Our findings illuminate the regulatory behavior of multiple enhancers and our statistical framework provides utility for future analyses studying interactions between enhancers.


Renal neoplasia in the hyperparathyroidism-jaw tumor syndrome.
Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a familial multi-tumor syndrome resulting from mutations in the HRPT2 tumor suppressor gene, which encodes a protein product named parafibromin. We review current knowledge of the renal manifestations of the HPT-JT syndrome, and examine recent advances in understanding the biological function of parafibromin.


Development and pharmaceutical evaluation of the anticancer Anthrafuran/Cavitron complex, a prototypic parenteral drug formulation.
To improve the water solubility of the anticancer drug candidate LCTA-2034 (A1), we investigated the formation of complexes of this anthrax[2,3-b]furan congener with the solubilizing 2-hydroxypropyl derivative of β-cyclodextrin HP-βCD (Cavitron®). The interaction of A1 with HP-βCD resulted in the inclusion complex A1/HP-βCD in 1:1 stoichiometry. The A1/HP-βCD complex was used to develop a prototype of a lyophilised drug formulation with enhanced (>10-fold) aqueous solubility than A1 and a long-term stability. The use of HP-βCD decreased the acute toxicity of A1 by >30%. The A1/HP-βCD drug formulation as well as A1 in equal doses (5×30mg/kg) to increase the lifespan by up to 140% for mice with i.p. transplanted P388 leukaemia. Furthermore, the A1/HP-βCD formulation demonstrated a significant and reliable antitumor efficacy in a Р388/ADR drug resistant leukaemia and B16/F10 melanoma, proving a perspective of investigations of toxicology, biodistribution and pharmacokinetics.


Faunistic analyses of fruit fly species (Diptera: Tephritidae) in orchards surrounded by Atlantic Forest fragments in the metropolitan region of Curitiba, Paraná state, Brazil.
The objective of this trial was to characterize the assemblage structure of fruit flies (Diptera: Tephritidae) by determining the diversity and faunal indices. Fruit flies were collected for ten years between 2003 and 2015 in six municipalities of the Metropolitan Region of Curitiba, Paraná. The orchards were divided into three crop protection strategies: organic, conventional, and integrated pest management. The characteristic of each community was determined using the Shannon-Wiener, Margalef, and Pielou's indexes. The frequency, constancy, and dominance indexes were also determined. Biological material was analyzed using the explanatory variables: site, crop, plant protection strategy, and susceptibility period. A total of 8,089 fruit flies were collected, of which 4,681 were females. The species Anastrepha daciformis Bezzi, A. dissimilis Stone, A. distincta Greene and A. pickeli Lima were recorded for the first time in Paraná State, the occurrence of three other species was recorded for the first time in the Metropolitan Region of Curitiba (A. montei Lima, A. obliqua Macquart, and A. sororcula Zucchi), in addition A. fraterculus (Wiedemann), A. grandis (Macquart) and Ceratitis capitata (Wiedemann). A. fraterculus accounted for 98.5% of the collected species. Only A. fraterculus and A. sororcula were found in fruits. Fruit flies occurred predominantly in peach trees cultivated under organic conditions. The Shannon index indicated that the municipality of Cerro Azul had the highest diversity and richness whereas apple orchards had the lowest diversity. Crops cultivated under organic conditions exhibited the highest diversity whereas those cultivated under conventional conditions had the highest evenness index. The largest specimens number was collected during the period of crop susceptibility.


Plk1 controls the Nek2A-PP1γ antagonism in centrosome disjunction.
In human cells, separation of the centrosomes and formation of a bipolar spindle are essential for correct chromosome segregation [1]. During interphase, centrosomes are joined together by the linker proteins C-Nap1 and rootletin [2-4]. At the onset of mitosis, these linker proteins are phosphorylated and displaced from centrosomes by the Nek2A kinase, which is regulated by two Hippo pathway components, Mst2 kinase and the scaffold protein hSav1. The kinesin-5 motor protein Eg5 promotes centrosome separation in a parallel pathway to Nek2A [5]. Here, we report that Polo-like kinase 1 (Plk1) functions upstream of the Mst2-Nek2A kinase module in centrosome disjunction as well as being important for Eg5 localization at centrosomes. Plk1 regulates Mst2-Nek2A-induced centrosome disjunction by phosphorylating Mst2. The absence of Plk1 phosphorylation of Mst2 promotes assembly of Nek2A-PP1γ-Mst2 complexes, in which PP1γ counteracts Nek2A kinase activity. In contrast, Plk1 phosphorylation of Mst2 prevents PP1γ binding to Mst2-Nek2A, allowing Nek2A activity to promote centrosome disjunction. We propose that centrosome disjunction is regulated by Plk1, providing a well-balanced control between the counteracting Nek2A and PP1γ activities on the centrosome linker.


A Parent-focused Child Sexual Abuse Prevention Program: Development, Acceptability, and Feasibility.
Child sexual abuse (CSA) affects nearly 60,000 children in the U.S. annually. Although prevention efforts targeting adults in the community and school-aged children have been somewhat successful, there is a clear gap in the current prevention efforts: parents. Generalized parent-education (PE) programs have effectively reduced the rates of physical abuse and neglect; however, currently no PE program targets risk factors for CSA specifically. We sought to develop a brief module to be added onto existing PE programs thereby leveraging the skills and implementation infrastructure to ensure sustainability. In three phases, we developed the curriculum, refined content and presentation while simultaneously developing and psychometrically evaluating a measurement tool, and conducted an acceptability and feasibility pilot. These phases are described in detail such that intervention scientists wishing to develop a module to be added onto existing programs can follow our procedures. The results of each phase are described so that the reader can see how information gleaned in one part of a phase informed subsequent phases of research. This was an iterative process of development, refinement, and piloting. The resultant module is designed to be added onto extant evidence-based PE programs. The module, and the additive approach of the intervention, will be evaluated in a future randomized controlled trial.


Application of the SCCmec element in the molecular typing of methicillin-resistant Staphylococcus aureus.
Acquisition of the staphylococcal chromosome cassette mec (SCCmec) is one of the key reasons for the resistance of methicillin-resistant Staphylococcus aureus (MRSA). SCCmec is composed of a mec gene complex encoding the PBP2a determinant that is responsible for the β-lactam resistance of MRSA, and a ccr gene complex encoding recombinases that mediate the integration of SCCmec into and its excision from the recipient chromosome, and so-called three junkyard (J) regions of different sizes. The SCCmec elements carried by MRSA from different geographic locations are diverse, and each type contains characteristic DNA fragments in size. These characteristics of SCCmec element may facilitate the usage of SCCmec in the molecular typing of MRSA strains. In this review, we summarize the structure and function of SCCmec elecments, and discuss the application of SCCmec elements in the molecular typing of MRSA.


Encoding seasonal information in a two-oscillator model of the multi-oscillator circadian clock.
The suprachiasmatic nucleus (SCN) is a collection of about 10 000 neurons, each of which functions as a circadian clock with slightly different periods and phases, that work in concert with form and maintain the master circadian clock for the organism. The diversity among neurons confers on the SCN the ability to robustly encode both the 24-h light pattern as well as the seasonal time. Cluster synchronization brings the different neurons into line and reduces the large population to essentially two oscillators, coordinated by a macroscopic network motif of asymmetric repulsive-attractive coupling. We recount the steps leading to this simplification and rigorously examine the two-oscillator case by seeking an analytical solution. Through these steps, we identify physiologically relevant parameters that shape the behaviour of the SCN network and delineate its ability to store past details of seasonal variation in photoperiod.


Factors predicting malnutrition in hemodialysis patients.
Signs of protein-energy malnutrition are common in maintenance hemodialyis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 37 HD patients treated with thrice weekly sessions for at least two weeks. Global nutritional status was evaluated by the dual-energy X-ray absorptiometry (DEXA) scan. Body weight and several laboratory values, including serum albumin (Salb), serum prealbumin, bicarbonate, cholesterol, serum C-reactive protein (SCRP), and hemoglobin, were recorded. Dose of dialysis was evaluated by urea kinetic modeling. The patients were subdivided into two groups based on body mass index: group I, normal nutritional status (71%) and group II, malnutrition (29%). The clinical factors associated with malnutrition included advanced age and cardio-vascular diseases (CVD), decreased fat mass (FM) measured by DEXA, low Salb and prealbumin, and severe anemia. The Salb level was not only a predictor of nutritional status, but also was independently influenced by age and SCRP, which was more common in malnourished patients than in patients with normal nutritional status. Both low Kt/V and less weekly dialysis time were associated with malnutrition. The FM and lean body mass (LBM) calculated by DEXA correlated with CVD and other markers of malnutrition (Salb, total cholesterol).


[Genetic and clinical characteristics of 22q11.2 deletion syndrome].
In a group of 140 patients with typical phenotype, the 22q11.2 microdeletion was detected in 43 patients (32%) using FISH and MLPA methods. There were no deletions of other chromosomal loci leading to phenotypes similar to the 22q11.2 deletion syndrome (22q11.2DS). Sequencing of the TBX1 gene did not detect any mutations, except for some common neutral polymorphisms. For the first time in the Russian Federation, the diagnostic efficiency of 22q11.2DS appeared to be 32%, as a result of the application of a combination of genetic approaches for a large group of patients with suspected 22q11.2DS.


Cell dynamics and expression of tumor necrosis factor (TNF)-alpha, interleukin-6, and TNF receptors in angioimmunoblastic lymphadenopathy-type T cell lymphoma.
Angioimmunoblastic lymphadenopathy (AILD)-type T cell lymphoma is histologically characterized by a mixed infiltrate of atypical T cells and B cells including B immunoblasts and plasma cells as well as eosinophils accompanied by proliferation of high endothelial venules. These morphological peculiarities are widely believed to reflect an abnormal pattern of cytokine expression. To clarify the cell dynamics and cytokine expression pattern in the lymph nodes of AILD-type T cell lymphoma, the frequency of proliferating/apoptotic cells and localization of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 producing cells were determined. Double staining was performed for (1) cell markers and Ki-67 antigen, (2) cell markers and the terminal deoxytransferase-mediated dUTP nick end labeling (TUNEL) method, or (3) cell markers and cytokines. The proliferating cell ratio in atypical T cells of AILD-type T cell lymphoma determined by Ki-67 labeling was 20.2+/-5.0%, while other peripheral T cell lymphomas (PTL) exhibited a ratio of 32.9+/-2.5%. TUNEL-positive apoptotic cells were 0.8+/-0.1% of total cells in AILD-type T cell lymphoma. They were dominantly atypical cells with positive T cell markers. In contrast, lymphoma cells in other types of PTL or paracortical cells in reactive follicular hyperplasia had only 0.3+/-0.1 or 0.4+/-0.1% TUNEL-positive cells, respectively. Thus, lymphoma cells in AILD-type T cell lymphoma demonstrated suppressed proliferating activity and enhanced apoptosis when compared to other types of PTL. TNF-alpha-producing cells were observed in all of the lymph nodes from AILD-type T cell lymphoma cases (15/15) and positive staining was obtained in the majority of atypical T cells and scattered macrophages. In contrast, IL-6 was localized to clusters of atypical T cells in some of the cases (9/15). Further, the expression of TNF-alpha, IL-6, and TNF receptors I and II (TNFRI and TNFRII) was examined by RT-PCR. The TNF-alpha message (2/2) and IL-6 message (2/2) was present in the lymph nodes of AILD-type T cell lymphoma by examination using RT-PCR, while both messages were negative in control cases (0/7). As far as an expression of mRNA for TNF receptors in AILD-type T cell lymphoma cases, mRNA for TNFRI was definitely expressed in both of the cases (2/2) while TNFRII mRNA was weakly expressed in one case (1/2). Overexpression of TNF-alpha as well as TNFRI may play a role in controlling T cell proliferation through an autocrine (T cell-T cell interaction) and paracrine (macrophage-T cell interaction) fashion. IL-6, which was also expressed by part of lymphoma cells of AILD-type T cell lymphoma, facilitates the proliferation of B cells, plasma cells, and T cells or endothelial cells in the lymph nodes of AILD-type T cell lymphoma.


Nanoindentation study of optically patterned surface relief grating of azobenzene polymers.
We present the light-controlled hierarchical mechanical properties of optically patterned azobenzene thin films through a nanoindentation study. In this study, we inscribed holographic surface relief grating (SRG) of azopolymers by two-beam coupling-based light interference lithography. The resultant morphological profile of azopolymers was monitored by atomic force microscope (AFM), followed by the nanoindentation study. From the load-displacement curve of the indentation procedure, photomechanical changes of the azopolymers along grating patterns were evaluated in terms of hardness and modulus at the crest and trough of the SRG, respectively. The results revealed that the surface height as well as the mechanical properties was modulated according to the light interference pattern.


[Treatment of peptic ulcer of the gastroduodenal area with the antioxidant dibunol and the change in antioxidant activity of erythrocyte lipids in patients during treatment].
Variation in the AOA of red cell lipids in peptic ulcer of the gastroduodenal zone was studied before and after treatment. Dibunol was administered by local applications of a 20% oily solution in a dose of 5 ml every other day with the aid of a fibroscope. The AOA was measured in experimental oxidation of methyl oleate in 20 normal subjects. In 25 patients, it was measured before treatment and 14 days after instituting local therapy. Twenty-five patients with peptic ulcer received treatment. In 96% of the patients, the ulcers healed. In the majority of the patients, the healing took place at early times. The healing occurred according to the "mucosal" type. In all the patients, the AOA was considerably less than normal before treatment. During dibunol treatment, the patients were divided into 2 groups according to the changes in the AOA. The first group (15 patients) manifested an increase in lipid AOA, rapid cicatrization of the ulcerous defect, favourable long-term results. The 2nd group (10 patients) showed a lowering of lipid AOA as compared with the initial level, which correlated with more prolonged times of ulcer cicatrization and a greater number of relapse at early times, though the results of dibunol treatment in the 2nd group patients were also considerably better than those obtained with conventional therapy.


Health-related mobility, health inequalities and gradient constraint. Discussion and results from a Norwegian study.
Recent studies have argued that health-related mobility does not widen social class health differentials, but rather moderates them. This is termed gradient constraint. This paper examines gradient constraint from a theoretical and empirical angle. How health-related mobility influences social class health differentials is discussed using hypothetical models. In a Norwegian survey with data on intergenerational mobility (N = 1,853 males aged 30-69 years), mean health and height values for different subsections of the sample were analysed. When initial social class health differences are large and mobility widespread, health-related mobility may lead to smaller differentials, but the result depends on how closely mobility varies with health. This empirical study found non-significant increases in height and health differentials from class of origin to class of destination. The interpretation has to consider effects of both social mobility and social causation. Health is measured in the post-mobility situation and the effects of social mobility and social causation are difficult to separate from each other for most of the health indicators analysed. However, this limitation does not apply to height which is not influenced by social causation during adulthood. In these data mobility did not reduce the height differential. Health-related mobility can either lead to smaller or larger social class health differentials. The specific effects of social mobility cannot be determined without knowing how social causation has interfered. The intergenerational mobility process analysed in this paper does not show gradient constraint as regards the height differential between the worker and higher occupational categories.


[The electronystagmography in neurology (author's transl)].
The electronystagmogram has its place in clinical neurological diagnosis as a recording method for the investigation of nystagmus with different conditions (spontaneous nystagmus, testing of eye-following movements, optokinetic nystagmus and rotational excitability). It must be used in all patients with complaints of dizziness, with clinically demonstrable nystagmus phenomena, in patients being examined for expert opinion after cranial traumata and in searching for vestibular involvement in certain diseases, e.g. vestibular disinhibition or dishabituation in multiple sclerosis.


A longitudinal study of the development of low back pain in an industrial population.
This is a longitudinal study in which industrial workers without chronic low back pain (LBP) were initially assessed with a comprehensive test battery and surveyed every 6 months thereafter for 2 years. To determine factors that may predispose industrial workers who lift over 5000 kg per shift to LBP. Prospective studies are small in number and often limited in breadth or depth of the test battery, methodologic issues, or investigator expertise. There are no prospective studies that focus on a homogeneous work sample of industrial employees. Production workers (n = 149) who volunteered for the 2-year study were assessed using physical measures (e.g., muscular strength, endurance, and flexibility), lifting kinematics (a sagittal plane box lift), and health, lifestyle, and work environment data (paper questionnaires). Follow-up questionnaires were distributed every 6 months for 2 years. Using self-report of LBP as the main outcome measure, eight variables predicted LBP in this sample with a 75% correct prediction rate. Predictor variables included age, thoracic acceleration during the trunk velocity test, median frequency intercept of electromyography of the right L3 erector spinae, quadriceps strength, quadriceps endurance, self-assessment of fitness, having a confidante, and number of medications currently taken. Results confirmed the multifactorial nature of low back pain and suggest that personal fitness is an important defense against low back pain, even in manual handling lifting tasks.


Rheumatoid factor, complement, and mixed cryoglobulinemia.
Low serum level of complement component 4 (C4) that occurs in mixed cryoglobulinemia (MC) may be due to in vivo or ex vivo activation of complement by the classical pathway. Potential activators include monoclonal IgM rheumatoid factor (RF), IgG antibodies, and the complexing of the two in the cold, perhaps modulated by the rheology and stoichiometry of cryocomplexes in specific microcirculations. There is also the potential for activation of complement by the alternative and lectin pathways, particularly in the setting of chronic infection and immune stimulation caused by hepatitis C virus (HCV). Engagement of C1q and interaction with specific cell surface receptors serve to localize immune complexes (ICs) to the sites of pathology, notably the cutaneous and glomerular microcirculations. Defective or saturated clearance of ICs by CR1and/or Fc receptors may explain persistence in the circulation. The phlogistic potential of cryoprecipitable ICs depends upon the cleavage of complement components to generate fragments with anaphylatoxin or leukocyte mobilizing activity, and the assembly of the membrane attack complex (C5b-9) on cell surfaces. A research agenda would include further characterization of the effector arm of complement activation in MC, and elucidation of activation mechanisms due to virus and viral antigens in HCV infection.


Prominent periventricular fiber system related to ganglionic eminence and striatum in the human fetal cerebrum.
Periventricular pathway (PVP) system of the developing human cerebrum is situated medial to the intermediate zone in the close proximity to proliferative cell compartments. In order to elucidate chemical properties and developing trajectories of the PVP we used DTI in combination with acetylcholinesterase histochemistry, SNAP-25 immunocytochemistry and axonal cytoskeletal markers (SMI312, MAP1b) immunocytochemistry on postmortem paraformaldehyde-fixed brains of 30 human fetuses ranging in age from 10 to 38 postconceptional weeks (PCW), 2 infants (age 1-3 months) and 1 adult brain. The PVP appears in the early fetal period (10-13 PCW) as two defined fibre bundles: the corpus callosum (CC) and the fetal fronto-occipital fascicle (FOF). In the midfetal period (15-18 PCW), all four components of the PVP can be identified: (1) the CC, which at rostral levels forms a voluminous callosal plate; (2) the FOF, with SNAP-25-positive fibers; (3) the fronto-pontine pathway (FPP) which for a short distance runs within the PVP; and (4) the subcallosal fascicle of Muratoff (SFM) which contains cortico-caudate projections. The PVPs are situated medial to the internal capsule at the level of the cortico-striatal junction; they remain prominent during the late fetal and early preterm period (19-28 PCW) and represent a portion of the wider periventricular crossroad of growing associative, callosal and projection pathways. In the perinatal period, the PVPs change their topographical relationships, decrease in size and the FOF looses its SNAP-25-reactivity. In conclusion, the hitherto undescribed PVP of the human fetal cerebrum contains forerunners of adult associative and projection pathways. Its transient chemical properties and relative exuberance suggest that the PVP may exert influence on the development of cortical connectivity (intermediate targeting) and other neurogenetic events such as neuronal proliferation. The PVP's topographical position also indicates that it is a major site of vulnerability in hypoxic-ischaemic perinatal brain injury.


Pharmacoeconomics applied to chronic hepatitis C.
Life expectancy has increased over the last century as it had never been before. This is the result of a combination of many favorable variables such as level of education, improved socio-economic environment and development of medicine. However, new improvements demand heavy investment. Thus, the incorporation of medical technology became a health and economic issue. The pharmacoeconomic knowledge field is being developed to help in the analysis of medical costs and patient needs. The applies to hepatitic C, a common and chronic worldwide disease. In this article, the authors describe the rational behind this type of health economic analysis and review a hepatitis C model. Overall, in a non-Brazilian scenario, it was demonstrated that peginterferon alfa-2a (40KD) is cost effective in the treatment of HCV disease.


Management of Intravenous Leiomyomatosis of Uterus with Extension to Heart.
Leiomyoma is a benign smooth muscle tumor. Intra-venous extensions of these tumors occur due to tumor growth within uterine vein or lymphatic vessels. In rare cases, intracaval and intracardiac extension can also be seen. Clinical suspicion of this disease should become certain by use of imaging techniques. While the treatment is complete resection of the tumor, one or two-stage surgery can be planned for patient depending on tumor extension and patient's condition. In this report, a 52-year-old woman with a rare presentation of uterine leiomyoma will be discussed. While the tumor was extended toward right atrium, the patient had nonspecific symptoms. By use of two-stage surgery, separated laparotomy and cardiopulmonary bypass, the tumor was completely removed.


Phase II clinical trials in oncology: strengths and limitations of two-stage designs.
Two-stage designs are used widely in Phase II oncology clinical trials to reduce the number of patients placed on ineffective experimental therapies. They provide clear-cut rules for stopping early in the event that treatment is not succeeding as hoped and are relatively simple to implement. Such designs, however, can lead to situations in which patient accrual is continued in the face of a clearly inferior treatment. In situations where patients' response can be determined for many or most subjects before additional patients are enrolled, analyses using Bayesian methodology can lead to earlier termination of studies of ineffective treatments and better align the statistical assessment of treatment effect with the therapeutic objectives of study. These points are discussed in context of the role of Phase II clinical trials in the development of new treatments for cancer.


Batch, fed-batch, and microcarrier cultures with CHO cell lines in a pressure-cycle driven miniaturized bioreactor.
Miniaturized bioreactors for suspension cultures of animal cells, such as Chinese Hamster Ovary (CHO) cells, could improve bioprocess development through the ability to cheaply explore a wide range of bioprocess operating conditions. A miniaturized pressure-cycled bioreactor for animal cell cultures, described previously (Diao et al., 2008), was tested with a suspension CHO cell line producing commercially relevant quantities of human IgG. Results from the suspended CHO cell line showed that the cell growth was comparable to conventional flask controls and the target protein production was enhanced in the minibioreactor, which may be due to the relatively high oxygen transfer rate and the moderate shear stress, measured and simulated previously. Microcarrier culture using an anchorage-dependent CHO cell line and Cytodex 3 also showed a similar result: comparable growth and enhanced production of a model protein (secreted alkaline phosphatase or SEAP). Various fed-batch schemes were applied to the CHO cells producing human IgG, yielding cell numbers (1.1 × 10(7) /mL) at day 8 and titers of human IgG (2.3 g/L) at day 14 that are typical industrial values for CHO cell fed-batch cultures. The alteration of the volumetric oxygen transfer coefficient is a key parameter for viability of the CHO cell line producing human IgG. We conclude that the minibioreactor can provide favorable cell culture environments; oxygen transfer coefficient and mixing time can be altered to mimic values in a larger scale system allowing for potential prediction of response during scale-up.


Tri-ortho-cresyl phosphate induces autophagy of mouse ovarian granulosa cells.
Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners and flame-retardants in industry and reported to have male reproductive toxicology. However, it is still unknown whether TOCP affects the female reproductive system and its underlying mechanism. In the present study, we found that TOCP exposure significantly decreased ovarian coefficient, caused disintegration and depletion of the granulosa cells in the ovary tissue and significantly inhibited the level of serum estradiol (E2). TOCP markedly increased both LC3-II and the ratio of LC3-II/LC3-I as well as autophagy proteins ATG5 and Beclin1 in the ovary tissue, implying that TOCP could induce autophagy in the ovary tissue. To further investigate the potential mechanism, primary ovarian granulosa cells were isolated in vitro and treated with 0-0.5 mM TOCP for 48 h. We showed that TOCP decreased the number of viable mouse granulosa cells without affecting cell cycle and apoptosis of the cells. Intriguingly, TOCP treatment markedly increased both LC3-II and the ratio of LC3-II/LC3-I as well as ATG5 and Beclin1. Furthermore, transmission electron microscopy (TEM) showed that autophagic vesicles in the cytoplasm increased significantly in the TOCP-treated cells, indicating that TOCP could induce autophagy in the cells. Taken together, TOCP reduces the number of viable cells and induces autophagy in mouse ovarian granulosa cells without affecting cell cycle and apoptosis.


The Care Dependency Scale: an assessment instrument for elderly patients in German hospitals.
The purpose of the study was to examine aspects of reliability and validity of the German version of the Care Dependency Scale (CDS), a Dutch assessment instrument originally developed for demented and mentally handicapped patients. Data of 1806 patients, 60 years or older from a larger sample, collected in 11 hospitals in Germany, were analyzed. Reliability was determined by Cronbach's alpha, showing a very good result with a value of.98. Criterion related validity was examined by comparing the data of the CDS with the German nursing personal regulation. The scores of the CDS correlate to the scores of the personal regulation. The study shows further that most elders are fairly independent and care dependency increases with age.


The stereo-microstructure of ZnO affects the lithium storage capacity of Li2ZnTi3O8 anode materials.
ZnO materials with multidimensional stereoscopic morphologies were synthesized via a one-step solvothermal process with water, ethanol and acetone as solvents. In this work, well-prepared ZnO was used as a Zn source for preparing pristine Li2ZnTi3O8 anode materials for the first time by a facile solid-state method. The resulting Li2ZnTi3O8 electrode material with rice-shaped ZnO as the zinc source (LZTO-E) possessed a smaller particle size and larger specific surface area, which were conducive to increase the electrochemical reaction area. Impressively, the LZTO-E electrode showed an excellent electrochemical performance with large discharge capacity (253.4 mA h g-1 at 100 mA g-1) and good cycling stability (175 mA h g-1, 133.4 mA h g-1, and 115.0 mA h g-1 at 1000 mA g-1, 2000 mA g-1, and 5000 mA g-1 after 500 cycles, respectively). This superior electrochemical performance of the as-synthesized Li2ZnTi3O8 was attributed to the specific microtopography of ZnO.


Reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods: an open clinical trial.
To test the hypothesis that maternal restriction of polyphenol-rich foods (PRF), which, like non-steroidal anti-inflammatory drugs (NSAID), inhibit prostaglandin synthesis in the third trimester, reverse fetal ductal constriction (DC). An open clinical trial of 51 third trimester fetuses with DC with no history of NSAID intake was designed. All mothers were submitted to a food frequency questionnaire and were oriented to withdrawl PRF, being reassessed after 3 weeks. Doppler parameters were assessed before and after discontinuation of these substances. A control group of 26 third trimester normal fetuses, with no ductus arteriosus (DA) constriction, in which no dietary intervention was offered, was reviewed after 3 weeks. Student's t-test and Wilcoxon's test were used. Mean gestational age was 32±3 weeks (28 to 37 weeks). After discontinuation of PRF (≥3 weeks), 48/51 fetuses (96%) showed complete reversal of DC, with decrease in mean ductal systolic velocity (1.74±0.20 m s(-1) to 1.31±0.34 m s(-1), P<0.001), mean diastolic velocity (0.33±0.09 m s(-1) to 0.21±0.07 m s(-1), P<0.001) and mean right to left ventricular dimension ratio (1.37±0.26 to 1.12±0.17, P<0.001) and increase in mean ductal pulsatility index (PI) (1.98±0.36 to 2.46±0.23, P<0.001). Median daily maternal consumption of PRF was 286 mg per day and decreased after orientation to 0 mg per day, P<0.001. In the control group, with GA of 32±4 w (29-37 w), there was no significant differences in median daily maternal consumption of PRF, mean ductal systolic velocitiy, diastolic velocity, PI and right ventricular to left ventricular diameter ratio (RV/LV) ratio. Reduction of maternal PRF intake during pregnancy, especially in the third trimester, is followed by complete reversal of DC (wide open DA), which may influence maternal dietary habits in late pregnancy.


Subarachnoid catheter placement after wet tap for analgesia in labor: influence on the risk of headache in obstetric patients.
The incidence of postdural puncture headache (PDPH) after epidural wet tap for obstetric patients may be as high as 75%. We have studied how subsequent placement of a subarachnoid catheter immediately after confirmation of a wet tap, and leaving the catheter in place for 24 hours affects the incidence of PDPH. Over a 5-year interval, 115 consecutive patients who had unintentional dural puncture were divided into 3 groups by consecutive assignment. Group A had an epidural catheter placed at another interspace. Group B had a subarachnoid catheter placed for labor analgesia that was removed immediately after delivery. Group C had a subarachnoid catheter that was left in place for 24 hours after delivery. Data were collected retrospectively. The incidence of PDPH and blood patch was compared between groups. The overall incidence of PDPH was 46.9% and need for blood patch 36.5%, significantly less in both subarachnoid catheter groups, 31% in B and 3% in group C, compared with group A (PDPH 81%) (P <.001). Subarachnoid catheter placement after wet tap in obstetric patients reduces the PDPH rate and does so to a greater extent if left in place for 24 hours after delivery.


Diversity in dermatology: Roadmap for improvement.
The American Academy of Dermatology has taken an active stance in addressing the lack of racial and ethnic diversity in the specialty. At the American Academy of Dermatology President's Conference on Diversity in Dermatology, which was held on August 5, 2017, key action items to increase the number of practicing board-certified dermatologists who are under-represented in medicine (UIM) were identified in 3 main areas. The action items include increasing the pipeline of UIM students applying to medical school, increasing UIM medical students' exposure to the field of dermatology and their level of interest in it, and increasing the number of UIM students recruited into dermatology residency programs.


Small alarmones (p)ppGpp regulate virulence associated traits and pathogenesis of Salmonella enterica serovar Typhi.
How Salmonella enterica serovar Typhi (S. Typhi), an important human pathogen, survives the stressful microenvironments inside the gastrointestinal tract and within macrophages remains poorly understood. We report here that S. Typhi has a bonafide stringent response (SR) system, which is mediated by (p)ppGpp and regulates multiple virulence-associated traits and the pathogenicity of the S. Typhi Ty2 strain. In an iron overload mouse model of S. Typhi infection, the (p)ppGpp0 (Ty2ΔRelAΔSpoT) strain showed minimal systemic spread and no mortality, as opposed to 100% death of the mice challenged with the isogenic wild-type strain. Ty2ΔRelAΔSpoT had markedly elongated morphology with incomplete septa formation and demonstrated severely attenuated motility and chemotaxis due to the loss of flagella. Absence of the Vi-polysaccharide capsule rendered the mutant strain highly susceptible to complement-mediated lysis. The phenotypes of Ty2ΔRelAΔSpoT was contributed by transcriptional repression of several genes, including fliC, tviA, and ftsZ, as found by reverse transcriptase quantitative polymerase chain reaction and gene complementation studies. Finally, Ty2ΔRelAΔSpoT had markedly reduced invasion into intestinal epithelial cells and significantly attenuated survival within macrophages. To the best of our knowledge, this was the first study that addressed SR in S. Typhi and showed that (p)ppGpp was essential for optimal pathogenic fitness of the organism.


Disruption of the nitrogen cycle in acidified lakes.
Experimental acidification of two small soft-water lakes caused nitrification to cease at pH values of 5.4 to 5.7. The resulting blockage of the nitrogen cycle caused a progressive accumulation of amnonium. When the epermental acidification of one of the lakes was ended and the pH was raised to 5.4, nitrification resumed after a time lag of 1 year.


Effect of peripapillary chorioretinal atrophy on GDx parametersin patients with degenerative myopia.
To determine the effect of peripapillary chorioretinal atrophy in degenerative myopia on the retinal nerve fibre layer (RNFL) thickness measurements performed by scanning laser polarimetry. Polarimetric RNFL analysis was done in 41 degenerative myopic eyes of 25 patients with spherical refractive errors between -7.50 and -22.00 D (mean -12.50 D;SD 3.5). Analysis was also performed on 46 eyes of 24 age-matched healthy subjects with spherical refractive errors between -1.00 and +1.00 D (mean -0.25 D; SD 0.50) with GDx Nerve Fiber Analyzer (Version 1.0.12). All of the myopic patients had clinically evident peripapillary chorioretinal atrophy in their fundus examination. In myopic patients most of the GDx parameters were statistically different from the control group (P < 0.05). Although average thickness, ellipse average, number, inferior maximum and inferior average were found to be higher than the healthy subjects,the modulation parameters and the ratio-based parameters were significantly decreased in degenerative myopic patients (P < 0.05). The TSNIT (temporal, superior, nasal, inferior, temporal) graph showed irregular high spikes with loss of the regular double hump pattern, especially in quadrants with large chorioretinal atrophy and visible sclera. Peripapillary chorioretinal atrophy increased retardation values, which might be explained by the high reflectivity of the bare sclera in these areas.


Use of intraluminal stents in multiple intestinal atresia.
Multiple intestinal atresia presents a difficult technical problem because of extreme loss of intestinal length, disparity of residual bowel wall size, and discontinuity of multiple short intestinal segments. The authors report on a 3,000-g infant with gastroschisis complicated by intrauterine volvulus and multiple intestinal atresias who was treated successfully with intraluminal stenting and sutureless anastomoses. A total of 25 cm of small bowel was salvaged including 13 segments each measuring 1 to 8 cm in length. Subsequent radiographic studies showed spontaneous anastomosis with a compartmental configuration of the residual bowel and decreased transit time. Five months postoperatively, the patient was weaned off total parenteral nutrition completely and one year later is growing and gaining weight with 4 to 6 bowel movements per day.


Human breath odors and their use in diagnosis.
Humans emit a complex array of volatile and nonvolatile molecules that are influenced by an individual's genetics, health, diet, and stress. Olfaction is the most ancient of our distal senses and may be used to evaluate food and environmental toxins as well as recognize kin and potential predators. Many body odors evolved to be olfactory messengers, which convey information between individuals. Consequently, those practicing the healing arts have used olfaction to aid in their diagnosis of disease since the dawn of medical practice. Studies using modern instrumental analyses have focused upon analysis of breath volatiles for biomarkers of internal diseases. In these studies, a subject's oral health status appears to seldom be considered. However, saliva and properly collected alveolar air samples must pass over or come in contact with the posterior dorsal surface of the tongue, a site of bacterial plaque development and source of halitosis-related volatiles. Because of our basic research into the nature of human body odors, our lab has received referrals of people with idiopathic malodor production, from either the oral cavity or body. We developed a protocol to help differentiate individuals with chronic halitosis from those with the genetic, odor-producing metabolic disorder trimethylaminuria (TMAU). In our referred population, TMAU is the largest cause of undiagnosed body odor. Many TMAU-positive individuals present with oral symptoms of dysguesia and halitosis as well as body odor. We present data regarding the presentation of our referred subjects as well as the analytical results from a small number of these subjects regarding their oral levels of halitosis-related malodorants and trimethylamine.


Lipoprotein metabolism and atherosclerosis susceptibility in transgenic mice.
Lipoprotein transport genes have been used to make either transgenic or knockout mice with altered lipoprotein levels and metabolism. Either singly or in combination, these mice have provided new animal models of lipoprotein disorders and atherosclerosis.


Case of diabetic scleredema: diagnostic value of magnetic resonance imaging.
We report the case of a patient with a 20-year history of diabetes mellitus type 2 who developed sclerotic skin lesions on his neck and upper back. Physical and histological findings were compatible with diabetic scleredema. T(2)-weighted magnetic resonance imaging (MRI) revealed diffuse thickening of the dermis and subcutaneous tissue, with hyperintense signals. The MRI findings in the dermis corresponded with the accumulation of collagen tissue with deposition of glycosaminoglycans.


Improving attribution of extreme heat deaths through interagency cooperation.
Attributing individual deaths to extreme heat events (EHE) in Canada and elsewhere is important for understanding the risk factors, protective interventions, and burden of mortality associated with climate change. However, there is currently no single mechanism for identifying individual deaths due to EHE and different agencies have taken different approaches, including (1) vital statistics coding based on medical certificates of death, (2) probabilistic methods, and (3) enhanced surveillance. The 2018 EHE in Montréal provides an excellent case study to compare EHE deaths identified by these different approaches. There were 353 deaths recorded in the vital statistics data over an 8-day period, of which 102 were potentially attributed to the EHE by at least one approach and 251 were not attributed by any approach. Only nine of the 102 deaths were attributed to the EHE by all three approaches, 23 were attributed by two approaches, and 70 were attributed by only one approach. Given that there were approximately 50 excess deaths during the EHE, it remains unclear exactly which of the total 353 deaths should be attributed to the extreme temperatures. These results highlight the need for a more systematic and cooperative approach to EHE mortality in Canada, which will continue to increase as the climate changes.


[Prostatic middle lobe hyperplasia correlates with bladder outflow obstruction: analysis of 131 cases].
To analyze the correlation between the size of prostatic middle lobe hyperplasia and the degree of bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). This study included 131 BPH patients who presented with dysuria between May 2008 and June 2010. The prostate volume and intravesical prostatic protrusion (IPP) were measured by transabdominal ultrasound, Qmax and detrusor pressure at Qmax (P(det@ Qmax)) detected by urodynamic examination, the obstruction degree and detrusor contractility judged using the LinPURR Figure, and the AG value calculated (AG = P(det@ Qmax) -2Qmax). The degrees of BOO were compared between different groups of IPP by variance analysis, and the prostate volume, IPP and AG values underwent Bivariate correlation analysis. IPP was highly positively correlated with BOO when it was > 10 mm (r = 0.821, P < 0.01), while PV and BOO had a lower correlation (r = 0.475, P < 0.01). There was also a high positive correlation between IPP and P(det@ Qmax) (r = 0.865, P < 0.01). A close correlation exists between prostatic middle lobe hyperplasia and BOO, and evaluating IPP by ultrasound is a reliable method to determine the degree of BOO.


16,16 Dimethyl prostaglandin E2 decreases the formation of collagen in fibrotic rat liver slices.
The effect of 16,16 dimethyl prostaglandin E2 (DMPG) on fibrogenesis was studied in slices from normal and fibrotic rat liver. Rats received a cirrhogenic diet for seven months; supplemented controls received a diet with the deficient nutrients restored. Slices from fibrotic livers incorporated more 14C-proline and produced more 14C-hydroxyproline in TCA precipitable proteins than slices from control livers. DMPG (10(-10) M) decreased the incorporation of labeled proline and the synthesis of labeled hydroxyproline in slices from fibrotic livers to the same extent, suggesting that DMPG did not affect the hydroxylation of proline per se. The magnitude of the DMPG induced decrease in labeled proline incorporation correlated with the hydroxyproline content in the liver (i.e. with increasing fibrosis there was a greater effect of DMPG: while in control rat liver slices, DMPG had no effect). DMPG did not change the size of the proline pool, its specific activity, or the activity of proline oxidase. We conclude that under these conditions of enhanced fibrogenesis, DMPG decreases the formation of collagen in vitro, possibly by lowering the incorporation of proline into collagen precursors. This may explain, at least in part, the inhibition of fibrogenesis by DMPG in vivo.


Risk factors and stratification for recurrence of patients with differentiated thyroid cancer, elevated thyroglobulin and negative I-131 whole-body scan, by restaging 18F-FDG PET/CT.
In nearly 20%-30% of patients with differentiated thyroid carcinoma (DTC) relapse and 7% of them die during the next 10 years after initial diagnosis. In 10%-30% of patients with DTC after ablation therapy during the follow-up show a negative iodine-131 (131I) whole-body screening test (131I WBS) and increased serum thyroglobulin (Tg) level. Loss of ability of DTC metastatic lesions to trap 131I is associated with pure survival and often aggressive disease. Several studies have shown that in DTC cases non trapping 131I, fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can detect recurrence or metastases with high sensitivity (80%-90%). The purpose of this study was to investigate the clinicopathologic features and other related risk factors of patients with DTC having elevated Tg levels and negative 131I WBS in which recurrence was detected by 18F-FDG PET/CT. We tried to study and stratify patients in this grey zone who could benefit from 18F-FDG PET/CT for the detection of metastases/recurrence according to predefined risk factors not investigated by other researchers. We studied retrospectively 165 DTC patients with elevated Tg levels and a negative 131I WBS during their follow-up between 2004-2015. Metastases/recurrence was found in 49% of the patients on restaging with 18F-FDG PET/CT and were compared with nonmetastatic group according to predefined risk factors. These factors were also evaluated in true positive and false negative cases. The sensitivity and specificity of 18F-FDG PET/CT for detecting recurrent/metastatic disease were 90% and 98.5%, respectively. No apparent predefined risk factor impacting a false negative 18F-FDG PET/CT was found. Findings in follicular carcinoma, Hürtle cell carcinoma and papillary carcinoma were not different from positive PET findings. The variants of papillary carcinoma also had no statistically difference with regard to 18F-FDG results. The most important factors affecting a true positive 18F-FDG PET/CT study were: ETE, high total 131I dose and the SUVmax values over 4.5.


Patient-Reported Quality of Life versus Physical Examination in Treating Temporomandibular Disorders with Intra-Articular Platelet-Rich Plasma Injections: An Open-Label Clinical Trial.
Temporomandibular disorders, often manifested by articular pain, limitation of the mouth opening range, and unpleasant acoustic symptoms originating from inside the joint, have been associated with reduced quality of life. These symptoms, among others, can be treated with intra-articular injections of various substances, including repeated platelet-rich plasma (PRP) administration. The reported study was designed as an uncontrolled open-label clinical trial of consecutive cases. The participants completed a Fonseca questionnaire and evaluated acoustic symptoms, and spontaneous and provoked pain on VAS, and were subjected to a physical examination before, during, and after PRP therapy. The total Fonseca questionnaire results were statistically significantly (p < 0.05) correlated with 340 out of 348 (98%) other variables. The fully subjective assessment of the presence and intensity of acoustic symptoms coming from the temporomandibular joints was correlated with the physical examination results (0.45-0.63) and the maximum mouth opening with the maximum pain-free mouth opening (0.73-0.87). There were no correlations observed between the patient's and the physician's assessment of mandibular mobility. The Fonseca questionnaire seems to cover the entire spectrum of temporomandibular disorders, making it a balanced tool for assessing the quality of life in TMDs. However, it is worth considering extending the standard 3-point response scale to an 11-point one. The patient is somewhat able to perform a self-diagnosis with regard to the acoustic symptoms, but it is not possible for them to determine without measurement whether the range of mandibular mobility is appropriate..


Catheter ablation of anteroseptal accessory pathway in the non-coronary aortic sinus.
We report a patient with atrioventricular reentrant tachycardia (AVRT) with bidirectional conduction over an anteroseptal accessory pathway (AP) who underwent successful ablation in the non-coronary aortic sinus (AS). In three previous attempts, the intracardiac recordings showed an anteroseptal AP with antegrade and retrograde conduction that failed to be ablated in spite of radiofrequency (RF) applications from the right and left anteroseptal regions. During the study, the earliest atrial activation during tachycardia was recorded in the non-coronary AS preceding the atrial activation at the His bundle (HB) region by 24 ms, and the anteroseptal AP was successfully blocked by one single ablation in the non-coronary AS. These data strongly suggest that careful mapping of an anteroseptal AP in the non-coronary AS may provide an alternative ablation approach in patients with previously failed ablation.


Etiology of Bronchopulmonary Dysplasia: Before Birth.
Bronchopulmonary dysplasia affects thousands of infants annually with high attendant morbidity, mortality, and healthcare costs. Respiratory outcomes for preterm infants may be widely disparate even within the same medical center for infants of similar gestational ages. Given the high estimates for the heritability for bronchopulmonary dysplasia as measured at 36 weeks of postmenstrual age, the course of disease for a particular infant is likely heavily influenced by factors that operate prenatally or in the early postnatal period. In this review we discuss the etiologies of lung disease in the premature infant, including in utero, genetic, and epigenetic factors that may influence pulmonary outcomes.


[The effect of bacterial endotoxin on the activity of liver mitochondria monoamine oxidase].
An increase of lipid peroxidation and a decrease of the monoamine oxidase (EC 184.108.40.206) activity were found in mice liver mitochondria within 9 hrs of intoxication developed after administration of bacterial endotoxin at a dose corresponding to its LD50. The decrease in the monoamine oxidase activity appears to occur due to some alteration of the enzyme substrate specificity as well as to its partial liberation from mitochondrial membrane.


NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD.
Dysregulated innate immune responses play an important role in inflammatory bowel disease (IBD). NKG2D innate immunity receptor is a major sensor of tissue damage that, by recognizing multiple stress-induced, cell-associated ligands (MIC-A/B and ULBP1-5), potentiates the effector functions of "innate-like" (γ/δ TcR+, and natural killer receptor+ [NKR+]) T-cell populations. We analyzed the representivity, NKG2D/ligand expression pattern, and functional ability of the major innate immunity cell populations in pediatric IBD patients. We analyzed 41 Crohn's disease (CD) patients, 33 ulcerative colitis (UC) patients, and 51 age-matched non-IBD controls. The expression of NKG2D and its ligands, interferon-gamma (IFN-γ) production, and cytotoxic granule release were assessed by immunostaining and multiparameter cytofluorimetric analysis on circulating and mucosal mononuclear subsets; the inflammatory infiltrate was also characterized by immunohistochemistry. The expression pattern of NKG2D receptor and its ligands on mucosal and circulating innate immunity populations is severely disturbed in IBD; NKG2D and ligands are upregulated on immune infiltrate in both CD and UC active lesions; receptor/ligand upregulation also occurs on circulating leukocyte populations, where it depends on both disease activity and type (UC vs. CD). Finally, the frequency and effector capability of peripheral blood "innate-like" T-cell populations are also altered in IBD patients. The circulating and mucosal innate immunity compartment is phenotypically and functionally altered in pediatric IBD; some alterations may represent a distinctive feature of the pediatric disease condition. The disturbance of NKG2D/ligand pathway may play a role in sustaining immune activation which leads to chronic inflammatory tissue damage.


Regulation of Toll-like receptor 2 interaction with Ecgp96 controls Escherichia coli K1 invasion of brain endothelial cells.
The interaction of outer membrane protein A (OmpA) with its receptor, Ecgp96 (a homologue of Hsp90β), is critical for the pathogenesis of Escherichia coli K1 meningitis. Since Hsp90 chaperones Toll-like receptors (TLRs), we examined the role of TLRs in E. coli K1 infection. Herein, we show that newborn TLR2(-/-) mice are resistant to E. coli K1 meningitis, while TLR4(-/-) mice succumb to infection sooner. In vitro, OmpA+ E. coli infection selectively upregulates Ecgp96 and TLR2 in human brain microvascular endothelial cells (HBMEC), whereas OmpA- E. coli upregulates TLR4 in these cells. Furthermore, infection with OmpA+ E. coli causes Ecgp96 and TLR2 translocate to the plasma membrane of HBMEC as a complex. Immunoprecipitation studies of the plasma membrane fractions from infected HBMEC reveal that the C termini of Ecgp96 and TLR2 are critical for OmpA+ E. coli invasion. Knockdown of TLR2 using siRNA results in inefficient membrane translocation of Ecgp96 and significantly reduces invasion. In addition, the interaction of Ecgp96 andTLR2 induces a bipartite signal, one from Ecgp96 through PKC-α while the other from TLR2 through MyD88, ERK1/2 and NF-κB. This bipartite signal ultimately culminates in the efficient production of NO, which in turn promotes E. coli K1 invasion of HBMEC.


Effect of positional isomerism on the excited state charge transfer dynamics of anthracene-based D-π-A systems.
Understanding the dynamics of the back electron transfer (BET) rate of ion pairs from the electronically excited state of donor-acceptor systems is crucial for developing materials for organic electronics. The structure-property relationships in the organic molecular architectures play a key role in controlling the BET rate and have been utilized as a criterion to design systems with a reduced BET rate. Here, we examine the influence of isomerism on the BET rate in anthracene based systems, viz., (E)-2-(2-(anthracen-9-yl)vinyl)benzonitrile (ortho-CN) and (E)-3-(2-(anthracen-9-yl)vinyl)benzonitrile (meta-CN) with N,N-diethylaniline (DEA) in methylcyclohexane using time-resolved spectroscopy. The radical cation (DEA˙+) and the radical anion (ortho-CN˙- or meta-CN˙-) generated after photoexcitation show synchronous decay kinetics, and the rate constant of back electron transfer (kBET) for the DEA/ortho-CN pair was 6.6 × 104 s-1, which is ca. 2 orders of magnitude lower compared with the DEA/meta-CN pair. The role of isomerism in providing resonance stabilization for the organic radicals is expected to have implications for strategies that retard charge recombination in photovoltaics. The role of the molecular structural features that dictate the kinetics for charge recombination has been further identified using quantum calculations.


Cloning and characterization of Xenopus Id4 reveals differing roles for Id genes.
We have identified Xenopus Id4, a member of the Id (inhibitor of differentiation/DNA binding) class of helix-loop-helix proteins. Id factors dimerize with general bHLH factors, preventing their interaction with tissue-specific bHLH factors, to inhibit premature differentiation. The presence of several Id proteins could reflect simple redundancy in function, or more interestingly, might suggest different activities for these proteins. During embryonic development, Xenopus Id4 is expressed in a number of neural tissues, including Rohon-Beard neurons, olfactory placode, eye primordia, and the trigeminal ganglia. It is also expressed in other organs, such as the pronephros and liver primordium. As embryogenesis progresses, it is expressed in the migrating melanocytes and lateral line structures. We compare the expression of Id4 mRNA with that of Id2 and Id3 and find that the Id genes are expressed in complementary patterns during neurogenesis, myogenesis, kidney development, in the tailbud, and in the migrating neural crest. To examine the regulation of Id gene expression during Xenopus neural development, we show that expression of Id3 and Id4 can be induced by overexpression of BMP4 in the whole embryo and in ectodermal explants. Expression of Id2, Id3, and Id4 in these explants is unaffected by the expression of FGF-8 or a dominant-negative Ras (N17ras), suggesting that Id genes are not regulated by the FGF signaling pathway in naive ectoderm. We also show that Notch signaling can activate Id2 and Id3 expression in the whole embryo. In contrast, Id4 expression in the Rohon-Beard cells is inhibited by activated Notch and increased by a dominant-negative Delta. This may reflect an increase in Rohon-Beard cells in response to inhibition of Notch signaling rather than transcriptional regulation of Id4. Finally, to compare the activities of Id2, Id3, and Id4, we use animal cap explants and in vivo overexpression to show that Id proteins can differentially inhibit the activities of neurogenin and neuroD, both neurogenic bHLH molecules and MyoD, a myogenic bHLH protein. Id4 is able to inhibit the activity all these bHLH molecules, Id2 inhibits MyoD and neuroD, while Id3 blocks only neuroD activity in our assays.


[Studies of the Chinese crude drug "Fangji" (1) herbological studies of name].
The Japanese Pharmacopoeia standardizes a Chinese crude drug "Bou-i" as the woody stem of Sinomenium acutum Rherder et Wilson of the family Menispermaceae. The Chinese Pharmacopoeia writes about the same drug under the name of "Fang-ji". The present herbological studies resulted in learning that the original written character for this drug is in China. The ancient Japanese misread it as "--" because of confusion between "--" and "--" in old Chinese herbals. The reason for changing "--" to "--" in China is presumed to be because the pronunciation of these characters changed in the Yuan dynasty, to "--" from "zi" to "si", and to "--" from "ki" to "tsi." That is, the original name "Fang-ji," written in today's Chinese phonetic symbols, can be used without big changes by switching the character from "--" to "--".


A potential noninvasive neurobiological test for Alzheimer's disease.
Currently Alzheimer's disease, which affects more than 20 million people worldwide, can only be definitely diagnosed by histological examination of brain tissue obtained at autopsy or biopsy. There is a great need for an early, noninvasive, sensitive, and easily administered diagnostic test of Alzheimer's disease. Here it is reported that patients diagnosed with probable Alzheimer's disease by standard clinical criteria exhibited a marked hypersensitivity in their pupil dilation response to a cholinergic antagonist, tropicamide, placed in their eyes. It was possible to distinguish 18 of 19 individuals (95%) either clinically diagnosed with Alzheimer's disease or classified as suspect Alzheimer's individuals by neuropsychological screening from 30 of 32 normal elderly controls (94%).


Gene expression analysis of the hedgehog signaling cascade in the chick midbrain and spinal cord.
The signaling molecule Sonic Hedgehog (SHH) plays a critical role in patterning the ventral midbrain of vertebrates. Our recent studies have established that the requirement for Hedgehog (HH) signaling in the chick midbrain is modulated spatially and temporally in a complex manner across the midbrain anlage. Unfortunately, the patterns of expression of downstream regulators that might modulate the HH signal in the midbrain are not currently known. To fill this gap, we have examined across time, the expression pattern of 14 genes that function in the HH signaling cascade in the midbrain and spinal cord. Our results suggest that SHH expression in the axial mesendoderm begins before the expression of known HH receptors/HH-binding proteins (e.g., PTC1, PTC2, HHIP, BOC, MEGALIN). In the midbrain, PTC and GLI genes are expressed and then eliminated very early from the ventral midline. However, they exhibit high and persistent expression in the midbrain region circumscribing the SHH source. Intriguingly, multiple HH-binding proteins (BOC, MEGALIN) and HH effectors (GLI1-3, SMO, SUFU, DZIP) are expressed in the dorsal midbrain and the midbrain-hindbrain boundary. Finally, we report for the first time that IHH is expressed in intermediate regions of the spinal cord, where its expression does not overlap with that of SHH.


Comparative study of high-linoleic acid vegetable oils for the production of conjugated linoleic acid.
Conjugated linoleic acid (CLA) is found in small quantities in dairy and beef products. Obtaining optimum dietary CLA levels from these sources requires an increased intake of saturated fat. A 20% CLA soy oil was produced by UV photoisomerization of soy oil linoleic acid (LA), which is naturally low in saturated fat, but no other high-LA vegetable oils have been studied for their potential as CLA-rich oils. The objectives of this research were to (1) compare flax, sunflower, corn, soy, and high-LA safflower oils as sources of CLA-rich vegetable oils using laboratory-scale equipment, (2) compare CLA yields obtained by laboratory-scale and pilot-scale equipment, and (3) compare the oxidative stabilities of laboratory-scale processed oils. High-LA safflower oil produced the most CLA; soy oil produced slightly less, followed by corn, with flax producing very little and sunflower none at all. Minor oil components and turbidity reduced CLA yields, suggesting that oils should be highly refined before CLA production. The pilot-scale system was more effective than the laboratory-scale system due to greater light exposure and larger surface area to volume ratio of the oil samples. The oxidative stabilities of high-LA safflower oil and soy oil were similar before or after irradiation, indicating that these oils are the most suitable for high-CLA production.


Quantitative variation of four morphological traits in Drosophila melanogaster under larval crowding.
Effects of three different larval densities (low, intermediate and high) on phenotypic and genetic variation of four morphological traits (thorax and wing length, sternopleural and abdominal bristle number) were studied in Drosophila melanogaster using the isofemale line technique. Phenotypic variation was found to increase at high larval density in all traits examined. Environmental variance for three traits (exception was sternopleural bristle number) and fluctuating asymmetry for both bilateral traits were also increased under high density conditions. For estimates of genetic variability (among isofemale lines variance, heritability and evolvability), no statistically significant differences among density regimes were detected. However, the trends in changes of these estimates across densities indicated a possibility for enhanced genetic variation under larval crowding for all traits except abdominal bristle number. For the latter trait, genetic variation seemed not to be dependent on density regime. Generally, two metric traits (thorax and wing length) were more affected by larval crowding than two meristic ones (sternopleural and abdominal bristle number). The Results are in complete agreement with those previously obtained for D. melanogaster using extreme temperatures as stress-factors.


[Effect of exposure to tobacco smoke and selected socioeconomic factors in occurrence of low birth weight].
The aim in this survey was analysis of contribution of exposure to tobacco smoke and selected socioeconomic factors in occurrence of low birth weight. The research was done on the group of 1528 pregnant women. Smoking habit was declared by 18.2% of women and passive exposure to tobacco smoke was stated by 31% of respondents. Significant association between active and passive smoking and socioeconomic status of respondents was observed. Cigarette smoking during pregnancy was the main cause of lower birth weight of newborns. The newborns of actively smoking mothers were lighter of about 332 g according to those ones of mothers who did not smoke and were not exposed to passive smoking, and were lighter than newborns of mothers who were not exposed to passive smoking of about 342 g.