Parenting Stress Plays a Mediating Role in the Prediction of Early Child Development from Both Parents' Perinatal Depressive Symptoms.
Maternal postnatal depression has been associated with a broad range of developmental risk among children. However, there has been less focus on disentangling the effects of pre- and postnatal depressive symptoms, as well as examining the symptoms of both parents. This study aims to investigate the separate effects of pre- and postnatal depressive symptoms in mothers and fathers, and parents' differential effects on child social-emotional, cognitive, and language development at 18 months of age. Further, we investigate whether effects of depressive symptomatology on child outcomes are particularly strong when both parents evinced high symptom loads and whether parenting stress mediates associations between perinatal depressive symptoms and child developmental outcomes. The study used data from 1036 families participating in a community-based study from mid-pregnancy until 18 months postpartum. Depressive symptoms were assessed at seven time points (four prenatally). Within a structural equation framework, we found that parental perinatal depressive symptoms predicted child social-emotional functioning, specifically externalizing, internalizing, and dysregulation problems, as well as language developmental delay at 18 months. Controlling for postnatal symptoms we found no independent effect of prenatal depressive symptoms on any child outcomes. A differential effect was evident, linking maternal symptoms to social-emotional outcomes, and paternal symptoms to language outcomes. There was no evidence of stronger associations between depressive symptoms and child outcomes when both parents showed high symptom loads. However, parenting stress mediated most relations between parental depressive symptoms and child outcomes. Findings demonstrate the importance of including paternal depressive symptoms in both clinical and research contexts.


Clinical usefulness of second-generation antipsychotics in treating children and adolescents diagnosed with bipolar or schizophrenic disorders.
The onset of severe, chronic or recurrent psychiatric illnesses, such as schizophrenia-spectrum and bipolar disorders, is a dramatic clinical event often detectable during adolescence and even in childhood. At any age, pharmacotherapy, along with enhancement of social skills and family support, is the mainstay for the management of such disorders. The aim of this review is to critically analyze findings from randomized controlled trials (RCTs) that have investigated the clinical utility of second-generation antipsychotics (SGAs) for the treatment of early-onset schizophrenia and bipolar disorders. Eighteen studies were considered, all of which were unfortunately impaired by methodologic limitations, such as the paucity of long-term data and lack of a three-arm comparison (SGA vs SGA vs placebo). Nevertheless, the results of this review allow us to suggest the effectiveness of three SGAs (aripiprazole, olanzapine, and risperidone) in the short-term treatment of both early-onset schizophrenia and bipolar mania, although such agents show different safety profiles. The use of clozapine should be strictly limited to patients with non-affective, psychotic symptoms who do not respond to any of these three SGAs. In contrast, the use of quetiapine and ziprasidone in young patients with either affective or non-affective psychosis is not yet supported by evidence-based information. Given our findings, further studies are urgently required to identify the best treatment option(s) for pediatric bipolar disorder (especially the depressive phase) and the long-term management of early-onset schizophrenia.


Evidence in court: witness preparation and cross-examination style effects on adult witness accuracy.
Witnesses play a clear and pivotal role in the criminal justice system and there is an obvious public interest in identifying procedures that both undermine and maximize the quality of evidence received by the criminal courts. This paper reports an investigation into the effects of witness familiarization and cross-examination type on adult witness accuracy that situates outcomes in both legal and psychological context. 60 mock witnesses observed a crime event and each witness was then cross-examined by a practising barrister in a moot courtroom according to two conditions - either via a scripted complex version of cross-examination or by a simpler but equivalent scripted examination. Mock witnesses were also allocated to two further conditions - half the participants received a guidance booklet on cross-examination and the other half received no familiarization to the process. Study outcomes showed that familiarization of witnesses to cross-examination processes increased accurate responses and reduced errors. The guidance seemingly allowed accessibility to cognitive information that enabled witnesses to process information more effectively. On this basis, advance written information about the nature of the cross-examination and potentially misleading tactics used by advocates could help to immunize against negative lawyerly influence.


Ockham's razor cuts to the root: Simplicity in causal explanation.
When evaluating causal explanations, simpler explanations are widely regarded as better explanations. However, little is known about how people assess simplicity in causal explanations or what the consequences of such a preference are. We contrast 2 candidate metrics for simplicity in causal explanations: node simplicity (the number of causes invoked in an explanation) and root simplicity (the number of unexplained causes invoked in an explanation). Across 4 experiments, we find that explanatory preferences track root simplicity, not node simplicity; that a preference for root simplicity is tempered (but not eliminated) by probabilistic evidence favoring a more complex explanation; that committing to a less likely but simpler explanation distorts memory for past observations; and that a preference for root simplicity is greater when the root cause is strongly linked to its effects. We suggest that a preference for root-simpler explanations follows from the role of explanations in highlighting and efficiently representing and communicating information that supports future predictions and interventions. (PsycINFO Database Record


Longitudinal modeling of human neuronal aging identifies RCAN1-TFEB pathway contributing to neurodegeneration of Huntington's disease.
Aging is a common risk factor in neurodegenerative disorders and the ability to investigate aging of neurons in an isogenic background would facilitate discovering the interplay between neuronal aging and onset of neurodegeneration. Here, we perform direct neuronal reprogramming of longitudinally collected human fibroblasts to reveal genetic pathways altered at different ages. Comparative transcriptome analysis of longitudinally aged striatal medium spiny neurons (MSNs), a primary neuronal subtype affected in Huntington's disease (HD), identified pathways associated with RCAN1, a negative regulator of calcineurin. Notably, RCAN1 undergoes age-dependent increase at the protein level detected in reprogrammed MSNs as well as in human postmortem striatum. In patient-derived MSNs of adult-onset HD (HD-MSNs), counteracting RCAN1 by gene knockdown (KD) rescued HD-MSNs from degeneration. The protective effect of RCAN1 KD was associated with enhanced chromatin accessibility of genes involved in longevity and autophagy, mediated through enhanced calcineurin activity, which in turn dephosphorylates and promotes nuclear localization of TFEB transcription factor. Furthermore, we reveal that G2-115 compound, an analog of glibenclamide with autophagy-enhancing activities, reduces the RCAN1-Calcineurin interaction, phenocopying the effect of RCAN1 KD. Our results demonstrate that RCAN1 is a potential genetic or pharmacological target whose reduction-of-function increases neuronal resilience to neurodegeneration in HD through chromatin reconfiguration.


Longitudinal twin study of borderline personality disorder traits and substance use in adolescence: developmental change, reciprocal effects, and genetic and environmental influences.
Although the comorbidity between borderline personality disorder (BPD) and substance abuse is well established, there are few longitudinal studies that have examined its developmental origins or whether the comorbidity is due to common genetic or environmental risk factors. To fill this gap, we used a large sample of female adolescent twins (N = 1,280) to examine the developmental course, reciprocal influences, and the genetic and environmental factors underlying the co-occurrence of BPD traits and substance use from age 14 to 18. Rank-order stability was moderate to high for both BPD traits (r = .58) and substance use (r = .51), whereas mean levels of substance use increased substantially from age 14 to 18 (d = 0.77) and BPD traits showed a small decline (d = -0.21). BPD traits and substance use exhibited concurrent and prospective associations; however, the longitudinal associations dropped to nonsignificance after accounting for the temporal stability of each trait. Twin analyses revealed that shared environmental factors accounted for the association between BPD traits and substance use at age 14, but genetic factors accounted for the association at age 18. These results indicate that, at least in adolescence, the comorbidity between BPD traits and substance use is a consequence of common risk factors rather than due to one being a casual antecedent of the other.


Platelet-rich plasma and bone healing: a histologic study in titanium bone chambers.
The potential benefits of platelet-rich plasma in the healing of isolated defects are unclear. The purpose of this study was to evaluate the effects of PRP on bone healing in titanium bone chambers, which represented isolated defects. PRP was prepared from blood collected from six adult female albino New Zealand rabbits. Titanium bone chambers with a 4-mm inner diameter were implanted into the tibiae of each animal at baseline and 2 weeks later; chambers healed for 6 or 8 weeks, either with PRP (test) or without PRP (control). Bone chambers were harvested from each animal and processed for histologic evaluation. Bone formation in 8-week test samples was not significantly different from that of the 6-week test samples. In control samples, more bone formation was seen at 8 weeks than at 6 weeks. The fibrous tissue content in control samples was higher than that of the test group in superficial sections, revealing that the tissue differentiation rate was higher in the test chambers. Time-dependent bone tissue differentiation in bone chambers augmented with PRP is higher than in normal wound healing, and PRP seems to increase the rate of tissue differentiation in early healing.


Modified Organosilica Core-Shell Nanoparticles for Stable pH Sensing in Biological Solutions.
Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core-shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties. The ratio of the fluorescence intensities at specific wavelengths was found to be highly sensitive to pH over a physiologically relevant range (4.5-8) with a response time of <100 ms, significantly faster than that of previously reported response times using silica-based particles. Particles produced stable, pH-specific signals when stored at room temperature for more than 80 days. Finally, we demonstrated that the nanosensors successfully monitored the pH of a bacterial culture over 15 h and that pH changes in the skin of mouse cadavers could also be observed via in vivo fluorescence imaging following subcutaneous injection. The understanding gained from linking sensor characteristics and material properties will inform the next generation of optical nanosensors for continuous-monitoring applications.


Blood lead concentrations of children and dogs from 83 Illinois families.
In comparison of blood lead concentrations (BLC) of 119 children and 94 dogs from 83 low-income suburban Illinois families, the mean BLC in the children was 8.9 mug/100 ml greater than that in the dogs. Demonstration of a BLC of diagnostic significance in a family dog increased the probability sixfold of finding a child in the same family with a BLC similarly increased. A history of pica in a family dog also increased the likelihood of finding pica in the family's children. It was concluded that family dogs may be useful sentinels of lead poisoning in children, and that veterinarians seeing dogs in clinical situations may have public health responsibilities with regard to lead poisoning.


In situ Tissue Regeneration in the Cornea from Bench to Bedside.
Corneal blindness accounts for 5.1% of visual deficiency and is the fourth leading cause of blindness globally. An additional 1.5-2 million people develop corneal blindness each year, including many children born with or who later develop corneal infections. Over 90% of corneal blind people globally live in low- and middle-income regions (LMIRs), where corneal ulcers are approximately 10-fold higher compared to high-income countries. While corneal transplantation is an effective option for patients in high-income countries, there is a considerable global shortage of corneal graft tissue and limited corneal transplant programs in many LMIRs. In situ tissue regeneration aims to restore diseases or damaged tissues by inducing organ regeneration. This can be achieved in the cornea using biomaterials based on extracellular matrix (ECM) components like collagen, hyaluronic acid, and silk. Solid corneal implants based on recombinant human collagen type III were successfully implanted into patients resulting in regeneration of the corneal epithelium, stroma, and sub-basal nerve plexus. As ECM crosslinking and manufacturing methods improve, the focus of biomaterial development has shifted to injectable, in situ gelling formulations. Collagen, collagen-mimetic, and gelatin-based in situ gelling formulas have shown the ability to repair corneal wounds, surgical incisions, and perforations in in-vivo models. Biomaterial approaches may not be sufficient to treat inflammatory conditions, so other cell-free therapies such as treatment with tolerogenic exosomes and extracellular vesicles may improve treatment outcomes. Overall, many of the technologies described here show promise as future medical devices or combination products with cell or drug-based therapies. In situ tissue regeneration, particularly with liquid formulas, offers the ability to triage and treat corneal injuries and disease with a single regenerative solution, providing alternatives to organ transplantation and improving patient outcomes.


Graphene-Assisted Growth of Patterned Perovskite Films for Sensitive Light Detector and Optical Image Sensor Application.
Controlled growth of high-quality patterned perovskite films on a large scale is essentially required for the application of this class of materials in functional integrated devices and systems. Herein, graphene-assisted hydrophilic-hydrophobic surface-induced growth of Cs-doped FAPbI3 perovskite films with well-patterned shapes by a one-step spin-coating process is developed. Such a facile fabrication technique is compatible with a range of spin-coated perovskite materials, perovskite manufacturing processes, and substrates. By employing this growing method, controllable perovskite photodetector arrays are realized, which have not only prominent photoresponse properties with a responsivity and specific detectivity of 4.8 AW-1 and 4.2 × 1012 Jones, respectively, but also relatively small pixel-to-pixel variation. Moreover, the photodetectors array can function as an effective visible light image sensor with a decent spatial resolution. Holding the above merits, the proposed technique provides a convenient and effective pathway for large-scale preparation of patterned perovskite films for multifunctional application purposes.


Afferent sympathetic unmyelinated fibres with left ventricular endings in cats.
1. We recorded the electrical impulse activity of thirty-three single afferent fibres with left ventricular endings from the third and fourth left thoracic sympathetic rami communicantes of anaesthetized cats. Their conduction velocity ranged from 0.23 to 0.98 m/sec (group C). 2. The endings of each fibre were localized to the left ventricle by mechanical probing performed at the end of the experiment on the non-beating heart. No fibre had multiple sensory fields. 3. The impulse activity (0.95 +/- 0.2 impulses/sec) was spontaneous but most often a fixed temporal correlation between impulses and ventricular dynamics was not detectable. It was increased during occlusion of the thoracic aorta, I.V. administration of isoprenaline or infusion of saline. It was unaffected by asphyxia, haemorrhage and I.V. administration of acetylcholine. It was decreased during occlusion of inferior vena cava. Therefore these ventricular receptors appeared to be mainly sensitive to mechanical events. 4. The fibres were excited during the occlusion of the left main coronary artery, after a latency of 14.5 +/- 1.3 sec. They were also excited during ventricular fibrillation, exhibiting the highest values of impulse activity (2.51 +/- 0.4 impulses/sec). The increase in impulse activity during ventricular fibrillation was sometimes immediate and extreme, with peak frequencies of about 50 impulses/sec. 5. These spontaneously active ventricular receptors with unmyelinated nerve fibres participate in the transmission of the continuous impulse activity which from the cardiovascular system reaches the spinal cord through the sympathetic nerves and which is likely to contribute to the neural control of circulation. Thus the unmyelinated cardiac sympathetic afferents should not be considered as purely nociceptive in function.


Challenges and Special Aspects of Pulmonary Hypertension in Middle- to Low-Income Regions: JACC State-of-the-Art Review.
Challenges and special aspects related to the management and prognosis of pulmonary hypertension (PH) in middle- to low-income regions (MLIRs) range from late presentation to comorbidities, lack of resources and expertise, cost, and rare options of lung transplantation. Expert consensus recommendations addressing the specific challenges for prevention and therapy of PH in MLIRs with limited resources have been lacking. To date, 6 MLIR-PH registries containing mostly adult patients with PH exist. Importantly, the global prevalence of PH is much higher in MLIRs compared with high-income regions: group 2 PH (left heart disease), pulmonary arterial hypertension associated with unrepaired congenital heart disease, human immunodeficiency virus, or schistosomiasis are highly prevalent. This consensus statement provides selective, tailored modifications to the current PH guidelines to address the specific challenges faced in MLIRs, resulting in the first pragmatic and cost-effective consensus recommendations for PH care providers, patients, and their families.


A New LBP Variant: Corner Rhombus Shape LBP (CRSLBP).
The local binary model is a straightforward, dependable, and effective method for extracting relevant local information from images. However, because it only uses sign information in the local region, the local binary pattern (LBP) is ineffective at capturing discriminating characteristics. Furthermore, most LBP variants select a region with one specific center pixel to fill all neighborhoods. In this paper, a new variant of a LBP is proposed for texture classification, known as corner rhombus-shape LBP (CRSLBP). In the CRSLBP approach, we first use three methods to threshold the pixel's neighbors and center to obtain four center pixels by using sign and magnitude information with respect to a chosen region of an even block. This helps determine not just the relationship between neighbors and the pixel center but also between the center and the neighbor pixels of neighborhood center pixels. We evaluated the performance of our descriptors using four challenging texture databases: Outex (TC10,TC12), Brodatz, KTH-TIPSb2, and UMD. Various extensive experiments were performed that demonstrated the effectiveness and robustness of our descriptor in comparison with the available state of the art (SOTA).


Absence of M100 source asymmetry in autism associated with language functioning.
Various clinical populations display atypical volume asymmetry of language structures and also the auditory M100 source. Although such atypical volume asymmetries have also been observed in autism, M100 source asymmetries have not yet been investigated. We examined M100 asymmetry in autism and its relationship with language functioning. Evoked neural activity to a 1 kHz tone was recorded using whole-cortex 151-channel magnetoencephalography in three groups of individuals. A single-dipole model identified the M100 generator in auditory cortex in each hemisphere. Healthy adults and control children displayed the expected right-sided M100 anteriority, whereas children with autism showed no such asymmetry. An association was found between language functioning and the degree of asymmetry across the two groups of children, suggesting a possible relationship between functional-structural asymmetry and language ability.


Parental style. Mothers' and fathers' and perceptions of their relations with twin children.
Mothers and fathers rated their interaction with twin children on the Parent's Report (PR) questionnaire containing two scales-how the parent actually relates and how the ideal parent would relate. Mothers and fathers differed in parental style. Mothers perceived themselves as being profoundly more child-centered; fathers perceived themselves as using more control through arousal of guilt and anxiety. Parents asserted more control through temper and detachment with same-sex children. Boys and girls and monozygotic (MZ) and dizygotic (DZ) twins did not receive distinctly different parenting. Parents described MZ children as much more similar than DZ children but acted similarly with children in both types of twinships. Parental knowledge of zygosity did not affect the way the parents treated children. These findings suggest the relative importance of genetic contributions to behavioral similarity in MZ twins.


Maternal Larp6 controls oocyte development, chorion formation and elevation.
La-related protein 6 (Larp6) is a conserved RNA-binding protein found across eukaryotes that has been suggested to regulate collagen biogenesis, muscle development, ciliogenesis, and various aspects of cell proliferation and migration. Zebrafish have two Larp6 family genes: larp6a and larp6b Viable and fertile single and double homozygous larp6a and larp6b zygotic mutants revealed no defects in muscle structure, and were indistinguishable from heterozygous or wild-type siblings. However, larp6a mutant females produced eggs with chorions that failed to elevate fully and were fragile. Eggs from larp6b single mutant females showed minor chorion defects, but chorions from eggs laid by larp6a;larp6b double mutant females were more defective than those from larp6a single mutants. Electron microscopy revealed defective chorionogenesis during oocyte development. Despite this, maternal zygotic single and double mutants were viable and fertile. Mass spectrometry analysis provided a description of chorion protein composition and revealed significant reductions in a subset of zona pellucida and lectin-type proteins between wild-type and mutant chorions that paralleled the severity of the phenotype. We conclude that Larp6 proteins are required for normal oocyte development, chorion formation and egg activation.


Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats.
Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions. Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms. The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect.


The Effect of Orthographic Transparency on Auditory Word Recognition Across the Development of Reading Proficiency.
A question under debate in psycholinguistics is the nature of the relationship between spoken and written languages. Although it has been extensively shown that orthographic transparency, which varies across writing systems, strongly affects reading performance, its role in speech processing is much less investigated. The present study addressed this issue in Persian, whose writing system provides a possibility to assess the impact of orthographic transparency on spoken word recognition in young children at different stages of reading acquisition. In Persian, the long vowels are systematically present in the script, whereas the spelling correspondence of short vowels is progressively omitted from the script in the course of reading acquisition, thus, turning transparent into opaque spelling. Based on this unique characteristic, we tested 144 monolingual Persian-speaking nonreaders (i.e., preschoolers) and readers (second graders to fifth graders and young adults) in an auditory lexical decision task using transparent and opaque words. Overall, the results showed that, in accordance with the fact that the diacritics of short vowels are progressively omitted during the second year of schooling, the stimuli containing short vowels (opaque words) were recognized more slowly than transparent ones in third graders. Interestingly, there is a hint that the emergence of the transparency effect in the third graders was associated with an overall slower recognition speed in this group compared to their younger peers. These findings indicate that learning opaque spelling-sound correspondence might not only generate interference between the two language codes but also induce a general processing cost in the entire spoken language system.


Study of KAP with regard to taking folic acid supplements and factors affecting the recommendation and prescription of those supplements among obstetricians and specialists in women's health in six provinces of Northern China, 2009.
Taking folic acid (FA) supplements reduces the risks of neural tube defects (NTDs) in early pregnancy. Obstetricians and specialists in women's health play important roles in promoting FA intake. However, surveys on their knowledge of, attitudes toward, and behavior regarding giving FA to pregnant women are limited. A cross-sectional study was conducted with 5,860 obstetricians and specialists in women's health using a self-administered questionnaire to collect information on participants' demographic characteristics and their knowledge of and attitudes toward and practices related to taking FA supplements. Chi-square analysis was used for rate comparison while logistic regression analysis was performed to predict influencing factors. For items on knowledge about FA and taking FA supplements the overall correct response rate was 60.3% (24,235/40,173). Questions about related practices and attitudes were correctly answered for the most part (more than 90%), but participants were less likely to follow the practice of prescribing FA tablets to women planning a pregnancy while working (77.2%). Statistical analysis indicated that the "Level of facility where the participant works" and "Rate of correct responses on a test of knowledge" were the main factors affecting participants' recommendation to take FA while "Job title", "Amount of professional work experience", and "Rate of correct responses on a test of knowledge" were the main factors affecting participants' prescription of FA. In conclusion, participants had a good deal of knowledge about NTDs and FA but the lack of some knowledge possibly led to the relatively low rate of correct behaviors. Therefore, educating obstetricians and specialists in women's health in this regard is crucial.


gamma-Aminobutyrate, alpha-carboxy-2-nitrobenzyl ester selectively blocks inhibitory synaptic transmission in rat dentate gyrus.
gamma-Aminobutyrate, alpha-carboxy-2-nitrobenzyl ester (cGABA) is a stable photoactivatable probe used to study gamma-aminobutyrate (GABA) receptors. GABA is released from this compound when it is exposed to ultraviolet light, but little is known about the electrophysiological effects of the compound itself. Whole cell patch clamp recordings on rat hippocampal slices demonstrated that cGABA blocked polysynaptic inhibitory postsynaptic currents (IPSCs) evoked in dentate granule cells by antidromic stimulation of the mossy fibers. It also reduced monosynaptically evoked IPSCs with an IC(50) of 28 microM. In contrast, cGABA had no effect on excitatory postsynaptic currents (EPSCs) evoked by perforant path stimulation. The effect of cGABA was not mediated by depression of GABA release through activation of presynaptic GABA(B) receptors. cGABA inhibited muscimol-evoked currents by only 15% at a concentration of 40 microM. At this same concentration, it reduced the mean frequency of miniature inhibitory postsynaptic potentials by 71%, their mean peak amplitude by 44%, their mean decay time constant by 26% and the mean charge transfer per event by 52%. These effects may be explained by a phenothiazine-like modification of GABA(A) receptor kinetics and/or a selective block of somatic GABA synapses.


Site-specific ribosomal DNA insertion elements in Anopheles gambiae and A. arabiensis: nucleotide sequence of gene-element boundaries.
The nucleotide sequence of the junctions between the 28S ribosomal gene and site-specific insertion elements from two sibling mosquito species, Anopheles gambiae and A. arabiensis, is reported. In both species, elements insert at the same point within the 28S gene, but this site is 634 basepairs (bp) 3' of the R1 (Type I) insertion site in Drosophila melanogaster. The two mosquito elements each have poly A tails and a polyadenylation signal, but the extreme 3' and 5' ends show no other similarity to each other or to any other insertion element. In both mosquito species, identical target site duplications of 17 bp are generated. The sequence TNTCCCTNT found in this duplication is also found in the 14 bp target site duplications that flank R1 elements in D. melanogaster. Another sequence in this duplication, GGGATAACT, is very similar to the sequence GGGAGTAACT found in the 24 base sequence required by the Bombyx mori R2 endonuclease.


[Contamination of respirators in long-term ventilation].
The role of artificial ventilation as an exogenous source of nosocomial pneumonia in long-term ventilated patients is well established. Hence, decontamination of respirators after use is inevitable, although this procedure is costly and time-consuming. The purpose of the study was to prove the efficacy of bacterial filters (Ultipor BB 50, Pall Ltd., Dreieich) in preventing microbial contamination of respirators during long-term ventilation. We investigated the impact of the patient tracheal flora on different parts of the ventilation system. A total of 30 patients included 9 patients treated with an aminoglycoside intratracheally and whose ventilators were equipped with breathing system filters, 10 patients treated with the aminoglycoside intratracheally and without filters, and finally 11 patients without antibiotic prophylaxis and without filters. 1495 samples were taken from different parts of the ventilation circuit. The data obtained suggest that there is no significant influence on the contamination rate of the ventilators by application of bacterial filters or intratracheal aminoglycoside. The use of the breathing system filters to protect the ventilator from microbial contamination, therefore, seems to be unnecessary.


Reorientation of Suspended Ceramic Particles in Robocasted Green Filaments during Drying.
This work considers the fabrication of ceramic parts with the help of an additive manufacturing process, robocasting, in which a paste with suspended particles is robotically extruded. Within the final part, the material properties depend on the orientation of the particles. A prediction of the particle orientation is challenging as the part usually undergoes multiple processing steps with varying contributions to the orientation. As the main contribution to the final particle orientation arises from the extrusion process, many corresponding prediction models have been suggested. Robocasting involves, however, further processing steps that are less studied as they have a smaller influence on the orientation. One of the processing steps is drying by natural convection, which follows directly after the extrusion process. A quantification of the reorientation that occurs during drying is mostly unknown and usually neglected in the models. Therefore, we studied the amount of reorientation of suspended particles in robocasted green filaments during drying in detail. For our study, we applied the discrete element method, as it meets various requirements: The exact particle geometry can be resolved precisely; particle-particle interactions can be described; the paste composition is reproduced exactly; the initial particle orientation can be set in accordance with the prediction from the analytical models for the extrusion part; macroscopic force laws exist to represent capillary forces due to the remaining fluid phase that remains during drying. From our study, we concluded that the magnitude of particle reorientation during drying is small compared to the orientation occurring during the extrusion process itself. Consequently, reorientation during drying might further be neglected within analytical orientation prediction models.


[Immunologic behavior in 50 patients with acute anterior uveitis].
A prospective study that included 50 patients with acute anterior uveitis was done. The aim was to describe their immunological behavior. According to the results, patients with an allergic basis are predisposed and have more severe disease. However, immunoallergic tests are positives in patients with acute anterior uveitis where associated pathologies modify the tests, even if allergic etiology may or may not be possible. We recommend further studies in patients with allergic antecedents, in order to pay more attention to them.


The immune escape in melanoma: role of the impaired dendritic cell function.
Melanoma is an immunogenic cancer that overcomes the control of the immune system through the production of tolerogenic cytokines and growth factors in the microenvironment. In melanoma, dendritic cells (DC) show severe alterations in maturation, cross-priming and antigenic presentation, while other accessory cells infiltrating the tumor milieu also suppress DCs through the activation of the STAT pathway by IL-10 and IL-6. Novel immunotherapy strategies blocking cytotoxic T-lymphocyte antigen (CTLA-4) are successful in advanced disease, while melanoma cells carrying the BRAF(V600E) mutation further reinforce the immune suppression by activating MAPKs. Here, we review the major mechanisms involved in the cross-talk between melanoma cells and the immune system as well as the issue of defects in DCs in relation to novel studies aimed at restoring their anti-tumor activity.


Chronotype and stability of spontaneous locomotor activity rhythm in BMAL1-deficient mice.
Behavior, physiological functions and cognitive performance change over the time of the day. These daily rhythms are either externally driven by rhythmic environmental cues such as the light/dark cycle (masking) or controlled by an internal circadian clock, the suprachiasmatic nucleus (SCN), which can be entrained to the light/dark cycle. Within a given species, there is genetically determined variability in the temporal preference for the onset of the active phase, the chronotype. The chronotype is the phase of entrainment between external and internal time and is largely regulated by the circadian clock. Genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population. However, little is known about the determination of the chronotype, the stability of the locomotor rhythm and the re-synchronization capacity to jet lag in an animal without a functional endogenous clock. Therefore, we analyzed the chronotype of BMAL1-deficient mice (BMAL1-/-) as well as the effects of repeated experimental jet lag on locomotor activity rhythms. Moreover, light-induced period expression in the retina was analyzed to assess the responsiveness of the circadian light input system. In contrast to wild-type mice, BMAL1-/- showed a significantly later chronotype, adapted more rapidly to both phase advance and delay but showed reduced robustness of rhythmic locomotor activity after repeated phase shifts. However, photic induction of Period in the retina was not different between the two genotypes. Our findings suggest that a disturbed clockwork is associated with a late chronotype, reduced rhythm stability and higher vulnerability to repeated external desynchronization.


Effect of the deposition potential on the voltammetric determination of complexing ligand concentrations in sea-water.
The effect of the deposition potential on the determination of complexing ligand concentrations in natural waters was investigated by titration with Cu from sea-water samples originating from the North Sea and monitoring the labile Cu concentration after deposition at two potentials, viz., -0.05 and -0.7 V. The amount of deposited metal was measured by cathodic stripping voltammetry with ligand competition, using tropolone as the added ligand. It was found that the complexing ligand concentration detected decreased by more than 60% when the more negative deposition potential was applied. The data indicate that a significant fraction of the organic complexes of Cu in natural waters is electrochemically labile at negative deposition potentials and is not determined by anodic stripping voltammetry. The concentrations and conditional stability constants of the complexing ligands in the North Sea are similar to those detected previously in the Irish Sea.


3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors.
A new class of selective FXIIIa inhibitors with a bicyclic [1,2,4]-thiadiazole pharmacophore is described. At 160 muM, compound 8 caused 50% reduction in fibrin gamma-chain cross-linking and suppressed the polymerization of alpha chains in platelet-depleted human plasma clots. Fibrinolysis rates in response to tissue plasminogen activator were directly proportional to the concentration of 8 in plasma at the time of clotting.


Sodium tungstate decreases sucrase and Na+/D-glucose cotransporter in the jejunum of diabetic rats.
Sodium tungstate reduces glycemia and reverts the diabetic phenotype in several induced and genetic animal models of diabetes. Oral administration of this compound has recently emerged as an effective treatment for diabetes. Here we examined the effects of 30 days of oral administration of tungstate on disaccharidase and Na+/D-glucose cotransporter (SGLT1) activity in the jejunum of control and streptozotocin-induced diabetic rats. Diabetes increased sucrase-specific activity in the jejunal mucosa but did not affect the activity of lactase, maltase, or trehalase. The abundance and the maximal rate of transport of SGLT1 in isolated brush-border membrane vesicles also increased. Tungstate decreased sucrase activity and normalized SGLT1 expression and activity in the jejunum of diabetic rats. Furthermore, tungstate did not change the affinity of SGLT1 for d-glucose and had no effect on the diffusional component. In control animals, tungstate had no effect on disaccharidases or SGLT1 expression. Northern blot analysis showed that the amount of specific SGLT1 mRNA was the same in the jejunum from all experimental groups, thereby indicating that changes in SGLT1 abundance are due to posttranscriptional mechanisms. We conclude that the antidiabetic effect of tungstate is partly due to normalization of the activity of sucrase and SGLT1 in the brush-border membrane of enterocytes.


Perioperative redox changes in patients undergoing hepato-pancreatico-biliary cancer surgery.
Tissue injury induces inflammation and the surgical stress response, which are thought to be central to the orchestration of recovery or deterioration after surgery. Enhanced formation of reactive oxygen and nitrogen species accompanies the inflammatory response and triggers separate but integrated reduction/oxidation (redox) pathways that lead to oxidative and/or nitrosative stress (ONS). Quantitative information on ONS in the perioperative period is scarce. This single-centre exploratory study investigated the effects of major surgery on ONS and systemic redox status and their potential associations with postoperative morbidity. Blood was collected from 56 patients at baseline, end of surgery (EoS) and the first postoperative day (day-1). Postoperative morbidity was recorded using the Clavien-Dindo classification and further categorised into minor, moderate and severe. Plasma/serum measures included markers of lipid oxidation (thiobarbituric acid-reactive substances; TBARS, 4-hydroxynonenal; 4-HNE, 8-iso-prostaglandin F2⍺; 8-isoprostanes). Total reducing capacity was measured using total free thiols (TFTs) and ferric-reducing ability of plasma (FRAP). Nitric oxide (NO) formation/metabolism was measured using cyclic guanosine monophosphate (cGMP), nitrite, nitrate and total nitroso-species (RxNO). Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-⍺) were measured to evaluate inflammation. Both oxidative stress (TBARS) and nitrosative stress (total nitroso-species) increased from baseline to EoS (+14%, P = 0.003 and +138%, P < 0.001, respectively), along with an increase in overall reducing capacity (+9%, P = 0.03) at EoS and protein-adjusted total free thiols (+12%, P = 0.001) at day-1 after surgery. Nitrite, nitrate and cGMP concentrations declined concomitantly from baseline to day-1. Baseline nitrate was 60% higher in the minor morbidity group compared to severe (P = 0.003). The increase in intraoperative TBARS was greater in severe compared to minor morbidity (P = 0.01). The decline in intraoperative nitrate was more marked in the minor morbidity group compared to severe (P < 0.001), whereas the cGMP decline was greatest in the severe morbidity group (P = 0.006). In patients undergoing major HPB surgery, intraoperative oxidative and nitrosative stress increased, with a concomitant increase in reductive capacity. Baseline nitrate was inversely associated with postoperative morbidity, and the hallmarks of poor postoperative outcome include changes in both oxidative stress and NO metabolism.


In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases.
The potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genus Alphavirus), dengue virus (DENV, genus Flavivirus), and zika virus (ZIKV, genus Flavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection. The results described in our study demonstrate the inhibitory potential of two flavonoids derived from citrus plants: Hesperetin (HST) against NS2B/NS3pro of ZIKV and nsP2pro of CHIKV and, Hesperidin (HSD) against nsP2pro of CHIKV. The flavonoids are noncompetitive inhibitors and the determined IC50 values are in low µM range for HST against ZIKV NS2B/NS3pro (12.6 ± 1.3 µM) and against CHIKV nsP2pro (2.5 ± 0.4 µM). The IC50 for HSD against CHIKV nsP2pro was 7.1 ± 1.1 µM. The calculated ligand efficiencies for HST were > 0.3, which reflect its potential to be used as a lead compound. Docking and molecular dynamics simulations display the effect of HST and HSD on the protease 3D models of CHIKV and ZIKV. Conformational changes after ligand binding and their effect on the substrate-binding pocket of the proteases were investigated. Additionally, MTT assays demonstrated a very low cytotoxicity of both the molecules. Based on our results, we assume that HST comprise a chemical structure that serves as a starting point molecule to develop a potent inhibitor to combat CHIKV and ZIKV co-infections by inhibiting the virus proteases.


Mycorrhizae increase arsenic uptake by the hyperaccumulator Chinese brake fern (Pteris vittata L.).
Chinese brake fern (Pteris vittata L.) is a hyperaccumulator of arsenic (As) that grows naturally on soils in the southern United States. It is reasonable to expect that mycorrhizal symbiosis may be involved in As uptake by this fern. This is because arbuscular mycorrhizal (AM) fungi have a well-documented role in increasing plant phosphorus (P) uptake, P and As have similar chemical properties, and ferns are known to be colonized by AM fungi. We conducted a factorial greenhouse experiment with three levels of As (0, 50, and 100 mg kg(-1)) and P (0, 25, and 50 mg kg(-1)) and with and without Chinese brake fern colonized by a community of AM fungi from an As-contaminated site. We found that the AM fungi not only tolerated As amendment, but their presence increased frond dry mass at the highest As application rate. Furthermore, the AM fungi increased As uptake across a range of P levels, while P uptake was generally increased only when there was no As amendment. These data indicate that AM fungi have an important role in arsenic accumulation by Chinese brake fern. Therefore, to effectively phytoremediate As-contaminated soils, the mycorrhizal status of ferns needs to be taken into account.


The heterogeneity-diversity-system performance nexus.
Ever-growing human population and nutritional demands, supply chain disruptions, and advancing climate change have led to the realization that changes in diversity and system performance are intimately linked. Moreover, diversity and system performance depend on heterogeneity. Mitigating changes in system performance and promoting sustainable living conditions requires transformative decisions. Here, we introduce the heterogeneity-diversity-system performance (HDP) nexus as the conceptual basis upon which to formulate transformative decisions. We suggest that managing the heterogeneity of systems will best allow diversity to provide multiple benefits to people. Based on ecological theory, we pose that the HDP nexus is broadly applicable across systems, disciplines, and sectors, and should thus be considered in future decision making as a way to have a more sustainable global future.


Self-Assembling ELR-Based Nanoparticles as Smart Drug-Delivery Systems Modulating Cellular Growth via Akt.
This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug-delivery system based on elastin-like block recombinamers. The DNA recombinant techniques allowed us to create this smart complex polymer containing bioactive sequences for internalization, lysosome activation under acidic pH, and blockage of cellular growth by a small peptide inhibitor. The recombinant polymer reversibly self-assembled when the temperature was increased above 15 °C into nanoparticles with a diameter of 72 nm and negative surface charge. Furthermore, smart nanoparticles were shown to enter in the cells via clathrin-dependent endocytosis and properly blocked phosphorylation and consequent activation of Akt kinase. This system provoked apoptosis-mediated cell death in breast and colorectal cancer cells, which possess higher expression levels of Akt, whereas noncancerous cells, such as endothelial cells, fibroblasts, and mesenchymal stem cells, were not affected. Hence, we conclude that the conformational complexity of this smart elastin-like recombinamer leads to achieving successful drug delivery in targeted cells and could be a promising approach as nanocarriers with bioactive peptides to modulate multiple cellular processes involved in different diseases.


Persistent postmolar gestational trophoblastic disease: use of transvaginal sonography and colour flow Doppler.
Invasive moles have been difficult to diagnose except at hysterectomy. Many patients with persistent gestational trophoblastic disease (GTD) have been treated without ever demonstrating the site of the persistent trophoblastic focus. High resolution transvaginal sonography (TVS) has provided a technique of demonstrating very small uterine lesions, previously unsuspected by transabdominal sonography. The addition of colour flow Doppler further increased diagnostic sensitivity and provides another means of monitoring response to therapy. Three patients with persistent GTD, scanned by TVS and CFD (colour flow Doppler) performed as part of their metastatic work-up are presented. The only abnormalities detected were foci demonstrated within the myometrium that demonstrated increased flow on CFD. Single agent chemotherapy was commenced and the patients were monitored periodically through their course with repeat ultrasonography. After an initial lag period, the lesions decreased in size as the beta-HCG titres fell. An unsuspected adnexal mass was diagnosed on 1 patient, later proving to be a mature ovarian teratoma.


[Activity of specific and natural killer cells in experimental tuberculosis and vaccination].
The dynamics of activity of specific and natural killers was studied in 125 Balb/c mice by reproducing the BCG vaccinal process and primary and secondary tuberculosis. The activity of specific killers rose after vaccination and infection. Their level reached maximum in secondary tuberculosis reproduction. In tuberculosis development cellular killer activity declined. The vaccinal and tuberculous processes are attended by phase variations of natural killer lymphocyte activity which at first rises and subsequently declines. It is suggested that natural killers might play a role in the self-limitation of the immune response and elimination of the mutant cells formed during lymphocyte reproduction in the course of immune response to antigen.


Psychiatric Disorders and Genotoxicity Following Primary Metal on Polyethylene Total Hip Arthroplasty and Their Correlation to Cobalt/Chromium Levels.
Hip arthroplasty (HA) using implantable metal components is among the commonest orthopedic interventions. However, it can be followed by several complications following corrosion and the release of metal ions. Several studies proved that damaged genomic DNA may contribute to the pathophysiology of mental disorders. The current work aims to evaluate the psychiatric disorders in metal on polyethylene hip arthroplasty (MOP-HA) patients and its correlation to cobalt/chromium (Co/Cr) levels and genotoxicity. The work was a longitudinal follow-up study including 34 adults with unilateral primary MOP-HA meeting the inclusion and exclusion criteria. Preoperatively, 6, 12-months-postoperatively, patients were examined for cognitive impairment using mini-mental-state-examination (MMSE), depression using major-depressive-inventory (MDI), and blood samples were collected for estimation of Co/Cr, detection of genotoxicity by single-cell-gel-electrophoresis (comet assay) and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). Cognitive impairment was reported in 18.5% and 14.8% at 6-months, and 12-months postoperative, respectively. Depressive disorder was recorded in 22.2% at 6-months and 14.8% at 12-months postoperative. The marginal homogeneity tests proved a non-significant difference. There was a non-significant difference in preoperative, 6-months, 12-months postoperative MMSE, and MDI scores. There were significantly increased Co/Cr levels at 6-months postoperative. The levels decreased at 12-months postoperative, however, still significantly higher than preoperative values. There was a significant increase in serum 8-OHdG and the levels were positively correlated to cobalt levels at both 6 and 12-months-postoperative. There was a non-significant difference among preoperative, 6-months, and 12-months postoperative comet assay measurements. From previous findings, we can conclude that will-functioning MOP hip arthroplasty can induce increased ion levels and positively correlated increase in biochemical markers of genotoxicity (8-OHdG).


Human fetal hepatocyte line, L-02, exhibits good liver function in vitro and in an acute liver failure model.
A great many patients awaiting liver transplantation die because of the inavailability of donor livers. Liver support systems such as the bioartificial liver have been effective alternatives to ease the shortage. However, the problem with these systems is the difficulty to obtain sufficient amounts of hepatocytes with good liver function. This study explored the possibility of employing a human fetal hepatocyte cell line L-02 for a liver support system. To confirm the hepatocytic functions of L-02 cells and their potential as a novel cell source to treat acute liver failure (ALF) in a liver support system. Hepatocyte markers were detected by Western blotting and laser confocal microscopy; their gene expression of hepatic markers was examined by polymerase chain reaction (PCR). An in vivo ALF model was established by 90% partial hepatectomy. Ten rats undergoing hepatectomy received 5 × 10(7) L-02 cells intrasplenically and 15 served as controls. Survival and liver functions were assessed in both groups. In vitro, Western blotting and laser confocal microscopy showed L-02 to express liver function markers: Albumin (ALB), uridine diphosphate glucuronosyltransferase, and cytochrome P450 3A4. PCR showed the expression of liver-specific genes, such as ALB, human glutathione S transferase, and human factor-X. In vivo, rats transplanted with L-02 cells showed significantly improved survival of 70% versus 0% in controls (P < .01). Liver function in the L-02 group was significantly improved versus controls: ALB, 30.2143 ± 2.68665 versus 25.3 ± 7.27942 g/L; alanine transaminase, 1611.333 ± 342.0078 versus 2831.333 ± 110.437 U/L; aspartate aminotransferase, 2210.667 ± 97.57732 versus 3149.333 ± 71.98842 U/L; serum ammonia, 360.4667 ± 74.94656 versus 660.62 ± 63.41681 μmol/L; alkaline phosphates, 408.6667 ± 48.00347 versus 698.5 ± 17.67769 U/L; total bilirubin, 29.8 ± 6.19785 versus 44.6 ± 9.73858 μmol/L; and direct bilirubin, 25.4333 ± 6.60631 versus 32.5 ± 7.07107 μmol/L (P < .05). L-02 cells, expressing the main molecules of human hepatocytes, improved liver functions and survival of ALF rats, suggesting them to be a feasible source for liver support systems.


Scale invariant dynamics of surface growth.
We describe in detail and extend a recently introduced nonperturbative renormalization group (RG) method for surface growth. The scale invariant dynamics which is the key ingredient of the calculation is obtained as the fixed point of a RG transformation relating the representation of the microscopic process at two different coarse-grained scales. We review the RG calculation for systems in the Kardar-Parisi-Zhang (KPZ) universality class and compute the roughness exponent for the strong coupling phase in dimensions from 1 to 9. Discussions of the approximations involved and possible improvements are also presented. Moreover, very strong evidence of the absence of a finite upper critical dimension for KPZ growth is presented. Finally, we apply the method to the linear Edwards-Wilkinson dynamics where we reproduce the known exact results, proving the ability of the method to capture qualitatively different behaviors.


Particle swarm optimization-based approach for optical finite impulse response filter design.
This study presents what is to our knowledge a new and efficient method for the design of an optical finite impulse response (FIR) filter by employing a particle swarm optimization technique. With the method proposed, the design of an optical FIR filter, which is able to provide an arbitrary spectrum output based on crystal birefringence, could be implemented with good performance and high efficiency. The design procedure is discussed. A typical example of a green/magenta filter used in a liquid crystal on silicon projection display is included to demonstrate the feasibility and efficiency of this method in this design process as compared with simulated annealing.


Differential distribution of the adenovirus E1A proteins and colocalization of E1A with the 70-kilodalton cellular heat shock protein in infected cells.
Five distinct localization patterns were observed for the adenovirus E1A proteins in the nuclei of infected HeLa cells: diffuse, reticular, nucleolar, punctate, and peripheral. The variable distribution of E1A was correlated with the time postinfection and the cell cycle stage of the host cell at the time of infection. All staining patterns, with the exception of peripheral E1A localization, were associated with the early phase of infection since only the diffuse, reticular, nucleolar, and punctate staining patterns were observed in the presence of hydroxyurea. Because the E1A proteins (12S and 13S) stimulate the expression of the cellular heat shock 70-kilodalton protein (hsp70), we examined the intracellular distribution of hsp70 in the adenovirus-infected cells. Whereas hsp70 was predominantly cytoplasmic in the cells before infection, after adenovirus infection most of the protein was now found within the nucleus. Specifically, hsp70 was found within the nucleoli as well as exhibiting reticular, diffuse, and punctate nuclear staining patterns, analogous to those observed for the E1A proteins. Double-label indirect immunofluorescence of E1A and hsp70 in infected cells demonstrated a colocalization of these proteins in the nucleus. Translocation of hsp70 to the nucleus was dependent upon both adenovirus infection and expression of the E1A proteins. The localization of hsp70 was unaltered by infection with an E1A 9S cDNA virus which does not synthesize a functional E1A gene product. Moreover, the discrete nuclear localization patterns of E1A and the colocalization of E1A with hsp70 were not observed in adenovirus-transformed 293 cells which constitutively express E1A and E1B. E1A displayed exclusively diffuse nuclear staining in 293 cells; however, localization of E1A into the discrete nuclear patterns occurred after adenovirus infection of 293 cells. Immunoprecipitation of labeled infected-cell extracts with a monoclonal antibody directed against the E1A proteins resulted in precipitation of small amounts of hsp70 along with E1A. These data indicate that the adenovirus E1A proteins colocalize with, and possibly form a physical complex with, cellular hsp70 in infected cells. The relevance of this association, with respect to the function of these proteins during infection and the association of other oncoproteins with hsp70, is discussed.


'Rounding' for better patient care: an evaluation of an improvement intervention implementation.
'Rounding' is reported to be an effective intervention to enhance patient-centred care; nurses make frequent calls on their patients to ensure their needs are met and reassure them they are the focus of their care. In our hospital, two clinical units implemented rounding as improvement projects and asked the research unit to evaluate the effectiveness of implementation. A qualitative descriptive study using focus groups and in-depth interviews revealed that although the idea of rounding was well intended, it was not as effectively implemented as it might have been. Consequently, lessons have been learnt about the difficulties of changing clinician behaviour and will inform a new attempt at implementation.


Characteristics of Plantar Loads During Walking in Patients with Knee Osteoarthritis.
BACKGROUND Knee osteoarthritis (KOA) is a common disease that can change the load on lower limbs during walking. Plantar loads in patients with KOA may provide a basis for clinical decisions regarding footwear and foot orthoses. This study aimed to compare plantar loads in females with and without KOA during gait. MATERIAL AND METHODS Plantar pressure during walking was recorded in 23 females with KOA and 23 females without KOA. Maximum force (MF), contact area (CA), and peak pressure (PP) were measured at 7 different regions underneath the foot, named heel (M1), midfoot (M2), first metatarsophalangeal joint (MPJ) (M3), second MPJ (M4), third to fifth MPJ (M5), hallux (M6), and lesser toes (M7). RESULTS PPs for M2 and (M3) in females with KOA were higher than those in females without KOA. High PPs were also found in females with KOA for M2, M3, and M4. CONCLUSIONS Increased plantar loading in females with KOA may lead to foot pronation and gait changes during walking. Plantar loading may be offered to patients with KOA when considering footwear and foot orthoses.


Fragility fractures and the osteoporosis care gap: an international phenomenon.
To describe practice patterns in the management of osteoporosis after fragility fracture. Systematic review of articles in MEDLINE, EMBASE, Cochrane, and CINAHL databases (1996 to February 2005). Diagnostic outcomes included clinical osteoporosis diagnoses, laboratory tests, and bone density scans. Treatment outcomes included initiation of calcium, vitamin D, hormone replacement therapy, bisphosphonates, calcitonin, raloxifene and falls assessments. Thirty-five studies met our inclusion criteria and demonstrated that adults who experience fragility fracture are not receiving osteoporosis management. An osteoporosis diagnosis was reported in 1 to 45% of patients with fractures; laboratory tests were ordered for 1 to 49% and 1 to 32% of patients had bone density scans. Calcium/vitamin D and pharmacological therapy was reported in 2 to 62% and 1 to 65% of patients, respectively. Osteoporosis treatment was recommended more often in women than men, and more often in patients with vertebral fractures than in patients with nonvertebral fractures. Older patients were more likely to be diagnosed with osteoporosis, but treatment was more likely in younger patients. A history of prior fracture was reported in 7 to 67% of patients. Between 1 and 22% of patients had a subsequent fracture during follow-up periods of 6 months to 5 years. Falls assessments were not often reported; when they were, they were infrequently performed. A greater proportion of patients were diagnosed/treated during follow-up studies than in studies evaluating diagnosis/treatment on discharge from acute care. The majority of individuals who sustain fragility fractures are not receiving adequate osteoporosis management. Future research should address barriers to appropriate management and the efficacy of implementation strategies designed to close the osteoporosis care gap. This article is of particular importance to health care professionals who provide care for patients with fragility fracture.


Sperm activation by heat shock protein 70 supports the migration of sperm released from sperm storage tubules in Japanese quail (Coturnix japonica).
Systems for maintaining the viability of ejaculated sperm in the female reproductive tract are widespread among vertebrates and invertebrates. In birds, this sperm storage function is performed by specialized simple tubular invaginations called sperm storage tubules (SSTs) in the uterovaginal junction (UVJ) of the oviduct. Although the incidence and physiological reasons for sperm storage in birds have been reported extensively, the mechanisms of sperm uptake by the SSTs, sperm maintenance within the SSTs, and control of sperm release from the SSTs are poorly understood. In this study, we demonstrated that the highly conserved heat shock protein 70 (HSP70) stimulates sperm motility in vitro and also that HSP70 expressed in the UVJ may facilitate the migration of sperm released from the SSTs. Quantitative RT-PCR analysis demonstrated that the expression of HSP70 mRNA in the UVJ increases before ovulation/oviposition. Gene-specific in situ hybridization and immunohistochemical analysis with a specific antibody to HSP70 demonstrated that HSP70 is localized in the surface epithelium of the UVJ. Furthermore, injection of anti-HSP70 antibody into the vagina significantly inhibited fertilization in vivo. In addition, we found that recombinant HSP70 activates flagellar movement in the sperm and that the binding of recombinant HSP70 to the sperm surface is mediated through an interaction with voltage-dependent anion channel protein 2 (VDAC2). Our results suggest that HSP70 binds to the sperm surface by interacting with VDAC2 and activating sperm motility. This binding appears to play an important role in sperm migration within the oviduct.


Movement and Persistence of 1,2-dibromo-3-chloropropane in a Soil with a Plow-pan.
Movement and persistence of 1,2-dibrotno-3-chloropropane (DBCP) in a Coastal Plain soil containing a sandy plow-pan were enhanced in each of 2 years by subsoiling, increased depth of application, and increased rate of application. DBCP was extracted from the soil with hexane and analyzed by gas chromatography. Subsoiling at a 35-cm depth gave the greatest increase in lateral movement and downward penetration of DBCP in 1975 (a wet year), but bad less effect in 1976 (a dry year). An increased application rate (10 kg/ha vs. 13.5) improved coverage moderately in 1975 by increasing lateral movement, but had little effect in 1976. Increased application depth (18 vs. 35 cm) improved coverage in both years though more in 1976. Deep placement extended DBCP retention time. Rainfall in 1975 probably decreased the number and size of air-filled pores, slowing loss of DBCP to the atmosphere. Because of reduced porosity, the plow-pan was impervious to the passage of DBCP unless disrupted by subsoiling.


Mechanism of arachidonic acid transport across rabbit distal colonic mucosa.
The initial rate of [1-14C]arachidonic acid (AA) entry in the serosal side of rabbit distal colonic mucosa mounted in Ussing-type chambers is linear and independent of intracellular metabolism. When the maximal AA uptake was plotted as a function of medium AA concentration in ranges between 50 and 500 nM, saturation of the AA uptake with increasing concentrations was observed. The time course of the uptake of oleic acid and palmitic acid was similar to that observed with AA, and their separate addition to incubation medium strongly reduced the AA uptake. The influx of arachidonate was largely inhibited by ouabain and by incubation with mucosal sodium-free solution and amiloride, while it was increased when colonic mucosa was exposed to luminal amphotericin B. However, voltage-clamp studies showed that the AA entry rate appeared to be linearly related (r = 0.99) to transepithelial potential difference (PD) and suggested that the sodium dependence of AA translocation is an indirect effect of the changes in transepithelial PD induced by sodium transport shifts. These features provide evidence that there is a common entry pathway for AA and other long-chain free fatty acids mediated by a mechanism of facilitated diffusion driven by transmembrane PD.


Prenatal exposure to valproate induces sex-, age-, and tissue-dependent alterations of cholesterol metabolism: Potential implications on autism.
Here, we investigated the protein network regulating cholesterol metabolism in the liver and brain of adolescent and adult male and female rats prenatally exposed to valproate (VPA), a well validated experimental model of autism spectrum disorders (ASD). We were aimed at studying whether prenatal VPA exposure affected the proteins involved in cholesterol homeostasis in a sex-dependent manner. To this aim the protein network of cholesterol metabolism, in term of synthesis and plasma membrane trafficking, was analyzed by western blot in the liver and different brain areas (amygdala, cerebellum, cortex, hippocampus, nucleus accumbens, and dorsal striatum) of adolescent and adult male and female rats prenatally exposed to VPA. Our results show that physiological sex-dependent differences are present both in the liver and in brain of rats. Interestingly, VPA affects specifically the brain in an age- and region-specific manner; indeed, cerebellum, cortex, hippocampus and nucleus accumbens are affected in a sex-dependent way, while this does not occur in amygdala and dorsal striatum. Overall, we demonstrate that each brain area responds differently to the same external stimulus and males and females respond in a different way, suggesting that this could be related to the diverse incidences, between the sexes, of some neurodevelopmental pathologies such as autism, which displays a 3:1 male to female ratio.


Functionally distinct communities of ammonia-oxidizing bacteria along an estuarine salinity gradient.
The relationship between ammonia-oxidizing bacteria (AOB) and potential nitrification rates was examined along a salinity gradient in a New England estuary in spring and late summer over 3 years. Ammonia-oxidizing bacteria abundance was estimated by measuring gene copies of the ammonia monooxygenase catalytic subunit (amoA) using real-time polymerase chain reaction. Ammonia-oxidizing bacteria abundance ranged from below detection to 6.0 x 10(7)amoA copies (gdw sediment)(-1). Mean potential nitrification rates ranged from 0.5 to 186.5 nmol N (gdw sediment)(-1) day(-1). Both AOB abundance and potential rates were significantly higher in spring than late summer. Correlations between rates and abundance varied significantly among sites, but showed site-specific ammonia oxidation kinetics related to AOB community structure. The effect of salinity on potential nitrification rates was evaluated by incubating sediment from each site under four salinity conditions (0, 5, 10 and 30 psu). At all sites, rates were generally highest in the intermediate salinity treatments, but rates at the upstream site were inhibited at high salinity, while rates at the two downstream sites were inhibited at the lowest salinity. Although salinity appears to be an important factor in determining AOB distribution, it may not be the primary factor as AOB exhibited a broad range of salinity tolerance in our experiments. Our results indicate that there are significant differences in abundance and community composition of AOB along the salinity gradient, and the differences are reflected in community function.


Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice.
To identify biomarkers associated with the development of hepatocellular carcinoma (HCC) in CuZn superoxide dismutase (CuZnSOD, Sod1) deficient mice, 2-DE followed by MS analysis was carried out with liver samples obtained from 18-month-old Sod1-/- and +/+ mice. The intracellular Ca binding protein, regucalcin (RGN), showed a divergent alteration in Sod1-/- samples. Whereas elevated RGN levels were observed in -/- samples with no obvious neoplastic changes, marked reduction in RGN was observed in -/- samples with fully developed HCC. GST mu1 (GSTM1), on the other hand, showed a significant increase only in the neoplastic regions obtained from Sod1-/- livers. No change in GSTM1 was observed in the surrounding normal tissues. Marked reduction was observed in two intracellular lipid transporters, fatty acid binding protein 1 (FABP1) and major urinary protein 11 and 8 (MUP 11&8), in Sod1-/- samples. Analysis of additional samples at 18-22 months of age showed a three-fold increase in enolase activities in Sod1-/- livers. Consistent with previous findings, carbonic anhydrase 3 (CAIII) levels were significantly reduced in Sod1-/- samples, and immunohistochemical analysis revealed that the reduction was not homogenous throughout the lobular structure in the liver.


The impact of pretransplantation serum albumin levels on long-term renal graft outcomes.
The association between pretransplantation serum albumin concentrations and renal graft outcomes is unclear. Hypoalbuminemia is a strong predictor of cardiovascular and all-cause mortality in chronic renal disease. Protein-energy wasting in dialysis patients is associated with irreversible damage and an increased risk of adverse outcomes. In this retrospective study, we investigated the association between preoperative albumin levels and short-term as well as long-term renal graft outcomes. We included 375 renal transplant recipients in our center between 1991 to 2011, who were grouped according to their preoperative serum albumin levels: group I (<3.5 g/dL), group II (3.5-3.9 g/dL), group III (4.0-4.4 g/dL), and group IV (≥ 4.5 g/dL). We measured the frequencies of delayed graft function (DGF), acute rejection episodes, and viral infections as well as the long-term graft outcomes. DGF affected 12.8%, 6.8%, 7.7%, and 9.3% of patients in groups I-IV, respectively. Acute rejection occurred in 27.7%, 27.2%, 31.6%, and 24.1%, while cytomegalovirus (CMV) and fungal infection occurred in 12.8% (6.4%), 23.3% (5.8%), 16.2% (2.6%), and 11.1% (5.6%) of patients, respectively. Serum creatinine levels at 12 months were not significantly different among the groups. Long-term graft survival was poorest in group I and best in group IV (P = .039). A Cox proportional hazards model showed group IV compared with group displayed the lowest relative risk of graft failure (hazard ratio [HR] = .536; P = .029). Low pretransplantation serum albumin levels were associated with poor long-term graft outcomes and with more post-transplantation complications. It may be necessary to focus on improving patients' nutritional status prior to transplantation to ensure long-term renal graft survival.


Natural genetic variation in cuticular hydrocarbon expression in male and female Drosophila melanogaster.
Cuticular hydrocarbons (CHCs) act as contact pheromones in Drosophila melanogaster and are an important component of several ecological traits. Segregating genetic variation in the expression of CHCs at the population level in D. melanogaster is likely to be important for mate choice and climatic adaptation; however, this variation has never been characterized. Using a panel of recombinant inbred lines (RILs) derived from a natural population, we found significant between-line variation for nearly all CHCs in both sexes. We identified 25 QTL in females and 15 QTL in males that pleiotropically influence CHC expression. There was no evidence of colocalization of QTL for homologous traits across the sexes, indicating that sexual dimorphism and low intersex genetic correlations between homologous CHCs are a consequence of largely independent genetic control. This is consistent with a pattern of divergent sexual and natural selection between the sexes.


Comparative Experimental Study of a High-Temperature Raman-Based Distributed Optical Fiber Sensor with Different Special Fibers.
An experimental study of a high temperature distributed optical fiber sensor based on Raman Optical-Time-Domain-Reflectometry (ROTDR) (up to 450 °C) and optical fibers with different coatings (polyimide/carbon, copper, aluminum and gold) is presented. Analysis of the distributed temperature sensor (DTS) measurements determined the most appropriate optical fiber to be used in high temperature industrial environment over long periods of time. To demonstrate the feasibility of this DTS for an industrial application, an optical cable was designed with the appropriate optical fiber and it was hermetically sealed to provide the required mechanical resistance and isolate the fiber from environmental degradations. This cable was used to measure temperature up to 360 °C of an industrial furnace during 7 days.


Enantiomeric composition of N'-nitrosonornicotine and N'-nitrosoanatabine in tobacco.
The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and N'-nitrosoanatabine (NAT) are found in substantial quantities in unburned tobacco. Although this has been documented in many previous studies, no data are available on the enantiomeric composition of these nitrosamines, which both have a chiral center at their 2'-positions. We used chiral stationary phase gas chromatography with nitrosamine-selective detection to determine the enantiomeric composition of NNN and NAT in moist snuff, chewing tobacco, and cigarette tobacco. (S)-NNN comprised 75.0 +/- 8.83% (SD) (n = 12) of total NNN while (S)-NAT comprised 82.6 +/- 1.44% (n = 12) of total NAT. Levels of the (S)-enantiomers of NNN and NAT were generally similar to those of the corresponding secondary amines, nornicotine and anatabine, suggesting a precursor to product relationship. Nitrosation of (S)-nicotine at pH 7.0 produced >99% (S)-NNN. These results suggest that nornicotine is a significant precursor of NNN in tobacco. The results of this study provide new insights into the structures and precursors of tobacco-specific nitrosamines in tobacco products.


Humor Styles Are Related to Loneliness Across 15 Countries.
The relationships between self-report loneliness and the four humor styles of affiliative, aggressive, self-defeating, and self-enhancing were investigated in 15 countries (N = 4,701). Because loneliness has been suggested to be both commonly experienced and detrimental, we examine if there are similar patterns between humor styles, gender, and age with loneliness in samples of individuals from diverse backgrounds. Across the country samples, affiliative and self-enhancing humor styles negatively correlated with loneliness, self-defeating was positively correlated, and the aggressive humor style was not significantly related. In predicting loneliness, 40.5% of the variance could be accounted. Younger females with lower affiliative, lower self-enhancing, and higher self-defeating humor style scores had higher loneliness scores. The results suggest that although national mean differences may be present, the pattern of relationships between humor styles and loneliness is consistent across these diverse samples, providing some suggestions for mental health promotion among lonely individuals.


c-MYC, RB-1, TP53, and centromere 8 and 17 copy number in B-cell non-Hodgkin's lymphomas assessed by dual-color fluorescence in situ hybridization.
Dual-color interphase FISH was performed to B-cell Non-Hodgkin's lymphomas to detect numerical genetic alterations in c-MYC, RB-1, TP53 and centromere 8 and 17. The probe combinations c-MYC/centromere 8, RB-1/centromere 8 and TP53/centromere 17 were applied, and the hybridization signals scored in a correlated fashion. Copy number aberrations was found in 24 of 45 lymphomas examined (53%). Nine tumors (20%) had increased c-MYC gene copy number (three to 8 copies). Seven of these nine had increase in c-MYC copies relative to centromere 8 copy number. Allelic loss of RB-1 was found in 9 tumors (20%), one tumor lacked both alleles. Nine cases (20%) showed hemizygous TP53 deletion. TP53 deletion was significantly associated with high-grade histology (P = 0.02). Numerical alterations in c-MYC and RB-1 were not associated with prognosis. Patients with hemizygous TP53 deletion had shorter survival (relative risk = 6.1, P<0.001) than the ones with two or more alleles.


Structural and electronic properties of V2O5 and their tuning by doping with 3d elements - modelling using the DFT+U method and dispersion correction.
New electrode materials for alkaline-ion batteries are a timely topic. Among many promising candidates, V2O5 is one of the most interesting cathode materials. While having very high theoretical capacity, in practice, its performance is hindered by its low stability and poor conductivity. As regards the theoretical descriptions of V2O5, common DFT-GGA calculations fail to reproduce both the electronic and crystal structures. While the band gap is underestimated, the interlayer spacing is overestimated as weak dispersion interactions are not properly described within GGA. Here we show that the combination of the DFT+U method and semi-empirical D2 correction can compensate for the drawbacks of the GGA when it comes to the modelling of V2O5. When compared to common PBE calculations, with a modest increase in the computational cost, PBE+U+D2 fully reproduced the experimental band gap of V2O5, while the errors in the lattice parameters are only a few percent. Using the proposed PBE+U+D2 methodology we studied the doping of V2O5 with 3d elements (from Sc to Zn). We show that both the structural and electronic parameters are affected by doping. Most importantly, a significant increase in conductivity is expected upon doping, which is of great importance for the application of V2O5 in metal-ion batteries.


Morphological variations in ulnar supinator crests and fossae as identifying markers of occupational stress.
Recent morphometric studies of ulnae of prehistoric skeletal remains from populations known to have used spears, atlatls, and similar projectile weapons for hunting and warfare reveal a high incidence of hypertrophy of the ulnar crest, to which the supinator muscle is attached, along with pronounced depth of the adjacent supinator fossa, especially in the upper extremities of males. Similar features occur in the right ulnae of living persons of both sexes who are habitually engaged in certain occupational and athletic activities involving angular displacement of the forearm as a result of medial rotation of the arm at the shoulder, shoulder and arm rapid extension, and abrupt shifts from forearm supination to pronation. Aside from its forensic science implications in determination of right- or left-handedness as a trait peculiar to the individual, observation of these markers of stress on the proximal end of the ulna are significant in identification of skeletal remains of persons known to have engaged in specific brachial activities during life. The biomechanics of these movement patterns and activities in which they occur, when properly interpreted, are relevant to forensic science problems of individual identification and paleoanthropological studies of occupational stress factors in extinct populations for which a skeletal record is available.


"Eat more protein, build more muscle": A grounded theory study of muscle-building behaviors among Canadian adolescents and young adults.
Unique risk factors for the development of muscle dissatisfaction and engagement in muscle-building behaviors have been described by theoretical frameworks and supported by empirical research. What remains unknown are the unique processes, including catalysts and facilitators, which underpin engagement in muscle-building behaviors. Therefore, this study used a grounded theory methodology to elucidate the process of engagement in muscle-building behaviors. Thirty-three individual semi-structured interviews with Canadian adolescents and young adults ages 16-30 years were conducted. Transcripts were analyzed using initial and focused coding to identify themes that explained the grounded theory. The core theme underpinning the grounded theory was balancing aesthetic, health, and functional goals in relation to participants' engagement in muscle-building behaviors. Participants described experiences that encompassed several unique phases of muscle-building engagement, including the initiation phase, beginner phase, preservation phase, and intensification phase. Participants also described unique methods of gathering information on muscle-building behaviors, and their own analysis and decision-making processes driving their behaviors. Findings from this study extend prior theory and research by conceptualizing a novel process theory of engagement in muscle-building behaviors among adolescent and young adults, resulting in important implications for research and practice.


Reactive oxygen species and antioxidant defense mechanisms in the oral cavity: a literature review.
Through dental procedures and environment, periodontal tissues are exposed to many types of reactive oxygen species (ROS). Recently, various forms of antioxidants have been introduced as an approach to fight dental diseases and improve general gingival health. This article focuses on the classification of antioxidants and the link between oxidative stress and periodontal disease. The protective mechanisms of antioxidants and how routine dental procedures may increase ROS is discussed. The final section reviews the effect of tobacco products on gingival health and disease.


[A rare splenic involvement by Echinococcus multilocularis - case report].
In the present case an 81-year-old patient was operated upon for a suspected atraumatic spleen rupture. During the operation a spleen abscess was found. Histological examination of the removed spleen revealed an Echinococcus multilocularis infection. There was no sign of further organ involvement: surprisingly the liver was not affected. Case history, clinical outcome and the prescribed treatment are described. A short overview of the Echinococchus multilocularis syndrome is presented.


Frequency of NSAID induced peptic ulcer disease.
To determine the frequency of peptic ulcer disease in patients on nonsteroidal anti-inflammatory drugs (NSAID). Record of eight hundred and twenty consecutive patients undergoing upper gastrointestinal (GI) endoscopy; from January 1998 to December 2000 were reviewed. The endoscopic diagnosis varied from gastritis, peptic ulcer to duodenitis. The use of NSAID was documented by reviewing medical records of patients with peptic ulcer. Peptic ulcers were found in 43% (353/820) patients. NSAID associated peptic ulcers were identified in 14.7% (52/353) patients. Diclofenac and aspirin were most common NSAIDs associated with peptic ulcers in 32.7% (17/52) and 30.7% (16/52) patients, respectively. Duodenal ulcer was more common than gastric ulcer 65.3% (34/52) and 42.3% (22/52), respectively. H. pylori infection was present in 46% (24/52) of the cases. NSAIDs treatment and / or H. pylori infection compared to non NSAIDs and non H. pylori infected peptic ulcer disease were significantly associated with gastric ulcer (p = 0.004) and duodenal ulcer (p = 0.009) respectively. NSAID-associated peptic ulcer disease is common in Pakistan and most frequently associated with gastric and duodenal ulcer. H. pylori infection is common in association with NSAID related peptic ulcers.


Injected nuclei in frog oocytes: fate, enlargement, and chromatin dispersal.
A method is described by which nuclei associated with some cytoplasm can be rapidly prepared from a suspension of cells. The method involves the use of lysolecithin and bovine serum albumin. Oocytes of Xenopus laevis were injected with about 200 nuclei perpared from human HeLa cells by this method. Nuclei were deposited in oocyte cytoplasm, in the oocyte nucleus, or in the dispersed contents of a ruptured oocyte nucleus. Injected HeLa nuclei enlarge up to several hundred times in volume in the course of a few days. Their enlargement is associated with chromatin dispersion, increased binding of an acidic dye, and with the reduction in size, and eventual disappearance, of nucleoli. The amount of HeLa nucleus enlargement is much greater when the oocyte nucleus is ruptured. The fate of injected nuclei was followed by the use of HeLa nuclei whose DNA had been previously labelled with [3H]thymidine. Labelled DNA does not pass from injected HeLa nuclei into the oocyte nucleus. Injected nuclei appear not to fuse with each other or with the oocyte nucleus. Nuclei prepared by the above method look morphologically healthy in oocytes cultured in vitro for up to one month after nuclear injection. Nuclei prepared by other methods, such as those involving the use of detergents, undergo deterioration within a few days after injection into oocytes.


Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus.
The human and rat hippocampus is highly susceptible to iron deficiency (ID) during the late fetal, early neonatal time period which is a peak time of regulated brain iron uptake and utilization. ID during this period alters cognitive development and is characterized by distinctive, long-term changes in hippocampal cellular growth and function. The fundamental processes underlying these changes are not entirely understood. In this study, ID-induced changes in expression of 25 genes implicated in iron metabolism, including cell growth and energy metabolism, dendrite morphogenesis, and synaptic connectivity were assessed from postnatal day (P) 7 to P65 in hippocampus. All 25 genes showed altered expression during the period of ID (P7, 15, and 30); 10 had changes on P65 after iron repletion. ID caused long-term diminished protein levels of four factors critical for hippocampal neuron differentiation and plasticity, including CamKII alpha, Fkbp1a (Fkbp12), Dlgh4 (PSD-95), and Vamp1 (Synaptobrevin-1). ID altered gene expression in the mammalian target of rapamycin (mTOR) pathway and in a gene network implicated in Alzheimer disease etiology. ID during late fetal and early postnatal life alters the levels and timing of expression of critical genes involved in hippocampal development and function. The study provides targets for future studies in elucidating molecular mechanisms underpinning iron's role in cognitive development and function.


[Interrelation of delta-aminolevulinic acid and brain myelin proteins as affected by benzene and lead].
An experimental model of subacute lead and benzene intoxication was induced in rabbits. It increased significantly delta-aminolevulinic acid (14C-ALA) incorporation into CNS myelin. ALA stably fixes on myelin proteins, especially Wolfgram proteins. In spite of this about one half of ALA incorporated into myelin linked with its basic proteins. Lead and benzene intoxication cause changes in the proportion of the basic fractions of myelin proteins. The amount of basic proteins increases, while the amount of proteolipid and Wolfgram proteins decreases. Lead and especially benzene intoxication decreases exogenous ALA insertion into basic proteins and proteolipid proteins, with ALA fixation on Wolfgram proteins remaining unchanged.


Environmental epidemiology of non-Hodgkin's lymphoma in eastern Nebraska.
The incidence of non-Hodgkin's lymphoma (NHL) is increased in many counties in eastern Nebraska. Histologic analysis has revealed a twofold increase in the clinically aggressive, diffuse large cell subtype of NHL. To investigate the possible association between NHL and agricultural exposures, a population-based case-control study was conducted in eastern Nebraska in 1985. Telephone interviews were conducted with 201 men having histologically confirmed NHL and 725 controls. Among men, the use of the herbicide 2,4-D was associated with a 50% increased risk of NHL (OR 1.5, 95% CI 0.9, 2.4). Personal exposure to 2,4-D more than 20 days per year increased the risk threefold (OR 3.3, 95% CI 0.5, 22.1). Several classes of insecticides were also associated with increased risk: organophosphates (OR 1.9, 95% CI 1.1, 3.1), carbamates (OR 1.8, 95% CI 1.0, 3.2), and chlorinated hydrocarbons (OR 1.4, 95% CI 0.8, 2.3). As a result of intense agrichemical use, extensive contamination of shallow groundwater by nitrate and atrazine has also occurred in eastern Nebraska. A twofold increased incidence of NHL is present in counties with greater than 20% of the wells contaminated by nitrate (greater than 10 ppm) and in counties with intense fertilizer use. These findings suggest that NHL in eastern Nebraska may be related to the use of pesticides and nitrogen fertilizers.


Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis.
Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams. This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis.


Normal Physiologic Birth Continuing Professional Development: From a National Health Priority to Expanded Capacity.
The Republic of Liberia has experienced many barriers to maintaining the quality of its healthcare workforce. The Resilient and Responsive Health Systems (RRHS) Initiative supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has responded to Liberian identified health priorities. Liberia's maternal morbidity and mortality rates continue to rank among the highest in the world. Recent country regulations have put forth required continuing professional development (CPD) for all licensed healthcare workers for re-licensure. The Model for Improvement was the guiding framework for this CPD to improve midwifery and nursing competencies in assisting birthing women. Two novel activities were used in the CPD. We tested the formal CPD application and approval process as this is a recent regulatory body policy. We also included the use of simulation and its processes as a pedagogical method. Over a two-year period, we developed a two-day CPD module, using didactic training and clinical simulation, for Liberian midwives. We then piloted the module in Liberia, training a group of 21 participants, including midwives and nurses, including pre- and post-test surveys as well as observational evaluation of participant skills. There were no significant changes in knowledge acquisition noted in the post-test. Small tests of change were implemented during the program, supporting the stages of the Model of Improvement. Observation of skill acquisition was done; however, using a formal observation checklist, such as an Observed Structured Clinical Evaluation (OSCE), would add more robust findings. The CPD and follow-up activity highlighted the need for human and financial support to maintain the simulation kits and to create sustainability for future trainings. Videotaping the didactic and simulation two-day continuing professional development train-the-trainer workshop expands the sustainability beyond newly prepared trainers. Simultaneous with this CPD, the Liberian Board for Nursing and Midwifery (LBNM) worked with a partner to create a CPD portal. The CPD partners created modules from the videos and have uploaded these modules to the LBNM's new CPD portal. Using a quality improvement model as a framework for developing and implementing CPDs provides a clear structure and supports the dynamic interactions in learning and clinical care. It is too soon to determine measurable health outcomes resulting from this project. Anecdotal feedback from clinicians and leaders was not directly related to the content of the CPD; however, it does demonstrate an increased awareness of examining changes in practice to support expanded health outcomes. Further research to examine methods and processes to determine the quality and safety outcomes of CPD trainings is necessary.