Genome-wide association study of economically important traits in Charolais and Limousin beef cows.
Genomic selection has proven effective for advancing genetic gain for key profit traits in dairy cattle production systems. However, its impact to-date on genetic improvement programs for beef cattle has been less effective. Despite this, the technology is thought to be particularly useful for low heritability traits such as those associated with reproductive efficiency. The objective of this study was to identify genetic variants associated with key determinants of reproductive and overall productive efficiency in beef cows. The analysis employed a large dataset derived from the national genetic evaluation program in Ireland for two of the most predominant beef breeds, viz. Charolais (n = 5 244 cows) and Limousin (n = 7 304 cows). Single nucleotide polymorphisms (SNPs) were identified as being statistically significantly associated (adj. P < 0.05) with both reproductive and productive traits for both breed types. However, there was little across breed commonality, with only two SNPs (rs110240246 and rs110344317; adj. P < 0.05) located within the genomic regions of the LCORL and MSTN genes respectively, identified in both Charolais and Limousin populations, associated with traits including carcass weight, cull-cow weight and live-weight. Significant SNPs within the MSTN gene were also associated with both reproduction and production related traits within each breed. Finally, traits including calving difficulty, calf mortality and calving interval were associated with SNPs within genomic regions comprising genes involved in cellular growth and lipid metabolism. Genetic variants identified as associated with both important reproductive efficiency and production related traits from this study warrant further analyses for their potential incorporation into breeding programmes to support the sustainability of beef cattle production.


Arterial wave reflections and ventricular-vascular interaction in patients with left ventricular systolic dysfunction.
Central aortic pressure waveform (AoPW) is the summation of a forward-traveling wave generated by the left ventricle and a backward-traveling wave caused by the reflection of the forward wave. The aim of this study was to evaluate the effect of ventricular-vascular coupling on the morphology of AoPW in chronic heart failure patients with different degrees of left ventricular systolic dysfunction (LVSD) using pulse wave analysis (PWA). PWA of AoPW and left ventricular (LV) function were evaluated by applanation tonometry in 26 control subjects, in 12 patients with left ventricular ejection fraction (LVEF) ≤ 30%, and in 14 patients with LVEF > 30%. Augmentation pressure, augmentation index, wasted energy, and ejection duration were lower in patients with LVEF ≤ 30% than in those with LVEF > 30% and in control subjects. Furthermore, augmentation index showed an inverse correlation with Doppler mitral E-wave amplitude (r = -0.40; P = 0.04) and E/A ratio (r = -0.42; P = 0.03) and a direct correlation with deceleration time of mitral E-waves (r = 0.39; P = 0.04). In patients with severe LVSD (LVEF ≤ 30%), aortic wave reflections negatively interfere with LV function and induce a shortening of ejection duration. In contrast, AoPW is similar in patients with moderate LVSD (LVEF > 30%) and in control subjects.


Initial non-responders to ranibizumab in the treatment of age-related macular degeneration (AMD).
Patients with exudative age-related macular degeneration (AMD) who did not respond to ranibizumab at the induction phase were assessed and referred to as initial non-responders. We retrospectively reviewed the medical records of 215 patients (218 eyes) with exudative AMD. For the initial treatments, patients received three intravitreal injections of ranibizumab (IVR) every 4 weeks. Minimum follow-up period was 12 months. We defined patients with no improvement of best corrected logMAR visual acuity (BCVA), and with no decrease of central retinal thickness (CRT) at the end of the initial treatment, as initial non-responders. Patients who had previous treatment history prior to this investigation were included, but patients who had photodynamic therapy (PDT) with IVR were excluded. Twenty-two eyes (10.1%) were identified as initial non-responders. The mean BCVA of initial non-responders before IVR and after induction phase were 0.39 and 0.36, respectively. There was no significant difference between these values, however the mean BCVA decreased significantly to 0.55 at 12 months after the beginning of the induction phase (P = 0.021). The mean greatest linear dimension (GLD) of the lesion before IVR of initial non-responders was 4,121 μm. We found 16 eyes with typical AMD, and six eyes with polypoidal choroidal vasculopathy. One eye had predominantly classic choroidal neovascularization (CNV), and others had occult CNV of typical AMD. As additional treatments, twelve eyes received PDT, and in three of the eyes exudation remained after PDT. Initial non-responders were more prevalent in patients with occult CNV than in patients with other CNV types. Some of the initial non-responders did not respond to PDT. This study suggested possible involvement of other factors, in addition to vascular endothelial growth factor, in the occurrence of CNV in initial non-responder patients.


Characterization and Valorization of the Agricultural Waste Obtained from Lavandula Steam Distillation for Its Reuse in the Food and Pharmaceutical Fields.
The main focus of the current research was the characterization of the by-products from the steam distillation of Lavandula angustifolia Mill. (LA) and Lavandula x intermedia Emeric ex Loisel (LI) aerial parts, as they are important sources of bioactive compounds suitable for several applications in the food, cosmetic, and pharmaceutical industries. The oil-exhausted biomasses were extracted and the total polyphenol and flavonoid contents were, respectively, 19.22 ± 4.16 and 1.56 ± 0.21 mg/g for LA extract and 17.06 ± 3.31 and 1.41 ± 0.10 mg/g for LI extract. The qualitative analysis by liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS) revealed that both the extracts were rich in phenolic acids and glycosylated flavonoids. The extracts exhibited radical scavenging, chelating, reducing activities, and inhibitory capacities on acetylcholinesterase and tyrosinase. The IC50 values against acetylcholinesterase and tyrosinase were, respectively, 5.35 ± 0.47 and 5.26 ± 0.02 mg/mL for LA, and 6.67 ± 0.12 and 6.56 ± 0.16 mg/mL for LI extracts. In conclusion, the oil-exhausted biomasses demonstrated to represent important sources of bioactive compounds, suitable for several applications in the food, cosmetic, and pharmaceutical industries.


Low prevalence of apolipoprotein E epsilon 4 allele in the neurofibrillary tangle predominant form of senile dementia.
Apolipoprotein E (apoE) genotypes were analyzed in a subset of demented very old patients who share a uniform neuropathological picture consisting of various numbers of neurofibrillary tangles (NFT) in allocortical areas of the inferomedial temporal lobe without significant numbers of either diffuse amyloid or neuritic plaques. Among 18 patients with this condition referred to as NFT-predominant senile dementia (average age at death 87 +/- 4.7 years), we found allele frequencies of 0.11 epsilon 2, 0.86 epsilon 3 and 0.03 epsilon 4, which are significantly different from allele frequencies reported in Alzheimer's disease (0.04 epsilon 2, 0.59 epsilon 3 and 0.38 epsilon 4). The low prevalence of the apoE epsilon 4 allele in this subset of patients is striking and suggests that NFT-predominant senile dementia is a dementing neurodegenerative disease in which the deposition of A beta-amyloid did not occur, possibly due to protective effects of epsilon 2 and/or epsilon 3 alleles or lack of a promoting effect of apoE epsilon 4 on amyloidogenesis. We propose that NFT-predominant dementia is a variant of Alzheimer's disease occurring in the very old.


Immunohistochemical characterization of 53 monoclonal antibodies to prostate-specific antigen.
Fifty-three antibodies submitted to the ISOBM TD-3 Workshop on the prostate specific antigen (PSA) were evaluated for their reactivity in frozen and formalin fixed tissue from benign hyperplastic prostate and salivary gland tissue. Only 13/53 antibodies showed clear reactivity in both frozen and paraffin sections, while some antibodies appeared to react only in formalin-fixed paraffin sections. Many antibodies showed extensive nonspecific reactivity in tissue sections. These results highlight the fact that the number of monoclonal antibodies suitable for immunohistochemical detection of PSA is still relatively limited.


De-implementing low-value care in cancer care delivery: a systematic review.
Accumulating evidence suggests that interventions to de-implement low-value services are urgently needed. While medical societies and educational campaigns such as Choosing Wisely have developed several guidelines and recommendations pertaining to low-value care, little is known about interventions that exist to de-implement low-value care in oncology settings. We conducted this review to summarize the literature on interventions to de-implement low-value care in oncology settings. We systematically reviewed the published literature in PubMed, Embase, CINAHL Plus, and Scopus from 1 January 1990 to 4 March 2021. We screened the retrieved abstracts for eligibility against inclusion criteria and conducted a full-text review of all eligible studies on de-implementation interventions in cancer care delivery. We used the framework analysis approach to summarize included studies' key characteristics including design, type of cancer, outcome(s), objective(s), de-implementation interventions description, and determinants of the de-implementation interventions. To extract the data, pairs of authors placed text from included articles into the appropriate cells within our framework. We analyzed extracted data from each cell to describe the studies and findings of de-implementation interventions aiming to reduce low-value cancer care. Out of 2794 studies, 12 met our inclusion criteria. The studies covered several cancer types, including prostate cancer (n = 5), gastrointestinal cancer (n = 3), lung cancer (n = 2), breast cancer (n = 2), and hematologic cancers (n = 1). Most of the interventions (n = 10) were multifaceted. Auditing and providing feedback, having a clinical champion, educating clinicians through developing and disseminating new guidelines, and developing a decision support tool are the common components of the de-implementation interventions. Six of the de-implementation interventions were effective in reducing low-value care, five studies reported mixed results, and one study showed no difference across intervention arms. Eleven studies aimed to de-implement low-value care by changing providers' behavior, and 1 de-implementation intervention focused on changing the patients' behavior. Three studies had little risk of bias, five had moderate, and four had a high risk of bias. This review demonstrated a paucity of evidence in many areas of the de-implementation of low-value care including lack of studies in active de-implementation (i.e., healthcare organizations initiating de-implementation interventions purposefully aimed at reducing low-value care).


Effects of synthetic silymarin-PLGA nanoparticles on M2 polarization and inflammatory cytokines in LPS-treated murine peritoneal macrophages.
Silymarin (SM) is a natural antioxidant compound with good anti-inflammatory effects, but its poor water solubility restricts its usage. Today, nanomaterial compounds (such as PLGA Poly D, L-lactic-co-glycolic acid) can provide a proper drug delivery system and help improve the accessibility of bioactive compounds to cells and tissues. In this study, PLGA nanoparticles (NPs) containing SM (SM-PLGA) were synthesized and characterized and their biological effects were evaluated on M2 macrophage polarization to regulate inflammation. SM-PLGA NPs were fabricated by the oil in water emulsion (O/W) method. Macrophages (MQs) were isolated from mouse peritoneum by the cold RPMI lavage protocol. Primary mouse MQ cells were treated by SM and SM-PLGA NPs and then stimulated with lipopolysaccharide (LPS). M2 polarization was evaluated by measurements of cytokine secretion levels (TNF-α, IL1-β, and IL-10), flow cytometry markers (F4/80, CD11b, CD38, and CD206), and the expression of specific proteins (M2 Ym1 and Fizz1). SM-PLGA characterization showed that NPs were fabricated in the desired form. SM and SM-PLGA decreased pro-inflammatory cytokines (TNF-α and IL1-β) and increased IL10 as an anti-inflammatory cytokine. On the other hand, the M2-associated markers and proteins increased following treatment with SM and SM-PLGA. Post-hoc analysis indicated that these changes were more pronounced in the SM-PLGA group. This study revealed that SM-PLGA could markedly promote M2 polarization, thereby providing a valuable medical approach against sepsis and septic shock.


A multi-institutional comparison of dosimetric data for a 0.35 T MR-linac.
Objective.A comparison of percent depth dose (PDD) curves, lateral beam profiles, output factors (OFs), multileaf collimator (MLC) leakage, and couch transmission factors was performed between ten institutes for a commercial 0.35 T MR-linac.Approach.The measured data was collected during acceptance testing of the MR-linac. The PDD curves were measured for the 3.32 × 3.32 cm2, 9.96 × 9.96 cm2, and 27.20 × 24.07 cm2field sizes. The lateral beam profiles were acquired for a 27.20 × 24.07 cm2field size using an ion chamber array and penumbra was defined as the distance between 80% of the maximum dose and 20% of the maximum dose after normalizing the profiles to the dose at the inflection points. The OFs were measured using solid-state dosimeters, whereas radiochromic films were utilized to measure radiation leakage through the MLC stacks. The relative couch transmission factors were measured for various gantry angles. The variation in the multi-institutional data was quantified using the percent standard deviation metric.Main results.Minimal variations (<1%) were found between the PDD data, except for the build-up region and the deeper regions of the PDD curve. The in-field region of the lateral beam profiles varied <1.5% between different institutions and a small variation (<0.7 mm) in penumbra was observed. A variation of <1% was observed in the OF data for field sizes above 1.66 × 1.66 cm2, whereas large variations were shown for small-field sizes. The average and maximum MLC leakage was calculated to be <0.3% and <0.6%, which was well below the international electrotechnical commission (IEC) leakage thresholds. The couch transmission was smallest for oblique beams and ranged from 0.83 to 0.87.Significance.The variation in the data was found to be relatively small and the different 0.35 T MR-linacs were concluded to have similar dosimetric characteristics.


Simplified Postoperative Care After Spring-assisted Strip Craniotomy for Sagittal Synostosis: A Prospective Before-and-After Study.
Since the development of spring-assisted techniques for corrective craniofacial surgery, routine postoperative admission to intensive care units (ICUs) has been questioned. However, close monitoring is necessary if the continuous infusion of morphine is used as recommended for better pain relief. In this study, the authors evaluated a simplified postoperative protocol without continuous morphine infusion and no indwelling urinary catheter following spring-assisted surgery (SAS) for sagittal synostosis. Ten children were cared for according to a standard protocol with postoperative intravenous (i.v.) infusion of morphine and an indwelling urinary catheter, and 11 consecutive children were treated according to a simplified protocol with pain relief based on intermittent injections of morphine and clonidine [according to Face, Legs, Activity, Cry, Consolability (FLACC) scores >4] without the indwelling catheter. A Mann-Whitney U test was used for comparison of distributions between the two groups. The results revealed no differences between groups regarding the proportion of FLACC scores >4, total amount of administered i.v. morphine and clonidine, total volume of buffered glucose infused, time to first feeding on breast milk or substitute, or the length of stay. Despite the inherent limitations of our small observational study, the authors concluded that at our institution, it was possible to exclude a standard continuous i.v. infusion of morphine and an indwelling urinary catheter from our postoperative care protocol without decreasing the quality of pain relief in children submitted to SAS for sagittal synostosis. This finding supports downgrading the level of care from the ICU to a regular ward after limited immediate postoperative observation.


A specific autistic trait that modulates visuospatial illusion susceptibility.
Although several accounts of autism have predicted that the disorder should be associated with a decreased susceptibility to visual illusions, previous experimental results have been mixed. This study examined whether a link between autism and illusion susceptibility can be more convincingly demonstrated by assessing the relationships between susceptibility and the extent to which several individual autistic traits are exhibited as a continuum in a population of college students. A significant relationship was observed between the systemizing trait and susceptibility to a subset of the tested illusions (the rod-and-frame, Roelofs, Ponzo and Poggendorff illusions). These results provide support for the idea that autism involves an imbalance between the processing of local and global cues, more heavily weighted toward local features than in the typically developed individual.


Triplane fracture associated with a proximal third fibula fracture.
The case of a Maisonneuve fracture occurring in association with a triplane fracture in an adolescent wrestler is presented. In this combination of injuries, the deltoid ligament may be ruptured, and/or the medial malleolus fractured. If the proximal fibula fracture is not discovered, and the syndesmosis rupture is not treated, the resulting chronic talocrural instability may lead to chronic ankle pain and degenerative arthritis. The orthopedist should be aware of the possibility of a Maisonneuve fracture occurring in association with a triplane fracture, and should treat both injuries appropriately.


3D numerical simulations of negative hydrogen ion extraction using realistic plasma parameters, geometry of the extraction aperture and full 3D magnetic field map.
Decreasing the co-extracted electron current while simultaneously keeping negative ion (NI) current sufficiently high is a crucial issue on the development plasma source system for ITER Neutral Beam Injector. To support finding the best extraction conditions the 3D Particle-in-Cell Monte Carlo Collision electrostatic code ONIX (Orsay Negative Ion eXtraction) has been developed. Close collaboration with experiments and other numerical models allows performing realistic simulations with relevant input parameters: plasma properties, geometry of the extraction aperture, full 3D magnetic field map, etc. For the first time ONIX has been benchmarked with commercial positive ions tracing code KOBRA3D. A very good agreement in terms of the meniscus position and depth has been found. Simulation of NI extraction with different e/NI ratio in bulk plasma shows high relevance of the direct negative ion extraction from the surface produced NI in order to obtain extracted NI current as in the experimental results from BATMAN testbed.


Adopting Western Retinopathy of Prematurity Screening Programs in Eastern Countries, are we Screening Properly?
To describe retinopathy of prematurity (ROP) among Jordanian preterm infants and evaluate the efficacy of applying current Western screening guidelines for Jordanian preterms. In this retrospective, descriptive hospital-based study, we collected data on preterm infants who were referred by their neonatologist for ROP screening at King Abdullah University Hospital between July 2006 and June 2007. Guidelines suggested by the American Academy of Pediatrics were followed. Additionally, older preterms considered at risk for ROP by the neonatal intensive care unit were screened. Any neonate with stage 1 ROP or higher in either eye was considered a positive case of ROP. Ninety-one preterms were included in the study. The median birth weight was 1390 gm (range,730-1980 gms) and the gestational age ranged from 26 to 35 weeks with 64.8% of preterms ≤ 32 weeks. ROP occurred in 28.6% of all patients, in 20% of infants with birth weight greater than 1500 gms and in 9.4% of preterms with gestational age ≥ 32 weeks. Six patients (6.6%) required laser treatment, two with low birth weight greater than 1250 gm and one was 33 weeks of age. Consanguinity was identified in 19.2% of infants with ROP while consanguinity in infants who did not develop ROP was 1.9%. This difference was statistically significant (P<0.05). ROP occurs in premature infants in Jordan with gestational age above 32 weeks and birth weight above 1250 gm. Future guidelines for screening should incorporate the current study outcomes. A prospective, population-based is required to set national guidelines for ROP screening in the Jordanian population and similarly for different populations worldwide. Consanguinity may play a role in ROP development and further genetic studies may aid in elucidating the pathogenesis of ROP.


Application of modular control analysis to inhibition of the adenine nucleotide translocator by palmitoyl-CoA.
Modular kinetic analysis was used to characterize inhibition of adenine nucleotide translocation by palmitoyl-CoA in isolated rat-liver mitochondria. To this purpose, oxidative phosphorylation has been divided into two modules with the fraction of matrix ATP as linking intermediate. The adenine nucleotide translocator is the matrix ATP-consuming module and the remainder of oxidative phosphorylation (ATP synthesis, respiratory chain and transport of phosphates and respiratory substrate) is the matrix ATP-producing module. We found that palmitoyl-CoA inhibits ATP-consuming module (ANT) and has no effect on ATP-producing module. There were no significant differences between kinetic curves obtained with oligomycin and myxothiazol, inhibitors that have opposite effect on membrane potential, suggesting that the use of the fraction of matrix ATP as the only intermediate is a good approximation. A new method has been used to determine the fraction of ATP in the mitochondrial matrix.


Prediction and Elucidation of Triglycerides Levels Using a Machine Learning and Linear Fuzzy Modelling Approach.
Triglycerides are lipids composed of fatty acids that provide energy to the cell. These compounds are delivered to the body's cells via lipoproteins found in the bloodstream. Increased blood triglyceride levels have been associated with high-fat or high-carbohydrate diets. Generally, increased triglyceride levels occur in conjunction with other symptoms that are difficult to notice and recognize. The study's goal was to develop and predict the model that could be used to explain the relationship between triglycerides and waist circumference, high-density lipoprotein (HDL), and hypertension status by determining the relationship between triglycerides and waist circumference, HDL, and hypertension status. This model was developed using qualitative predictor variables and incorporated data bootstrapping multilayer perceptron neural networks and fuzzy linear regression. Materials and procedures. This was a public health study that combined retrospective data analysis with methodology development. The medical records of patients who attended outpatient clinics at Hospital Universiti Sains Malaysia (USM) were collected and analyzed. This was to provide a more extensive illustration of the methods developed. Screening and selection of patient data were necessary following the inclusion and exclusion criteria. The patient's medical record was used to obtain triglycerides, high-density lipoprotein (HDL), waist circumference, and hypertension status. Due to the critical nature of the variable, it was chosen to aid the clinical expert. The R-Studio software was used to develop the associated syntax for the hybrid model, which would define the association between the examined variables. The purpose of this study is to create a technique for the clinical trial design that utilizes bootstrapping, Qualitative Predictor Variables (QPV), Multiple Linear Regression (MLR), Artificial Neural Networks (ANNs), and Fuzzy Regression (FR). All analyses were performed using the newly introduced R syntax. The research developed a fuzzy linear model that increased modelling performance by incorporating clinically significant factors and validated variables via Multilayer Perceptron (MLP). The proposed technique for modelling and prediction appeared to be the ideal combination of bootstrap, Multilayer Feed Forward (MLFF) neural network, and fuzzy linear regression. The created syntax is currently being evaluated and validated clinically. For modelling and prediction, the proposed technique looked to be the best, as it incorporated bootstrap, MLFF neural network, and fuzzy linear regression. The established syntax is now being utilized in the clinic to evaluate and validate the outcome. In terms of variable selection, modelling, and model validation, this strategy was superior to earlier approaches for fuzzy regression modelling.


Multimodal microscale mechanical mapping of cancer cells in complex microenvironments.
The mechanical phenotype of the cell is critical for survival following deformations due to confinement and fluid flow. One idea is that cancer cells are plastic and adopt different mechanical phenotypes under different geometries that aid in their survival. Thus, an attractive goal is to disrupt cancer cells' ability to adopt multiple mechanical states. To begin to address this question, we aimed to quantify the diversity of these mechanical states using in vitro biomimetics to mimic in vivo two-dimensional (2D) and 3D extracellular matrix environments. Here, we used two modalities Brillouin microscopy (∼GHz) and broadband frequency (7-15 kHz) optical tweezer microrheology to measure microscale cell mechanics. We measured the response of intracellular mechanics of cancer cells cultured in 2D and 3D environments where we modified substrate stiffness, dimensionality (2D versus 3D), and presence of fibrillar topography. We determined that there was good agreement between two modalities despite the difference in timescale of the two measurements. These findings on cell mechanical phenotype in different environments confirm a correlation between modalities that employ different mechanisms at different temporal scales (Hz-kHz versus GHz). We also determined that observed heterogeneity in cell shape is more closely linked to the cells' mechanical state. Moreover, individual cells in multicellular spheroids exhibit a lower degree of mechanical heterogeneity when compared with single cells cultured in monodisperse 3D cultures. The observed decreased heterogeneity among cells in spheroids suggested that there is mechanical cooperativity between cells that make up a single spheroid.


Mild congenital primary hypothyroidism in a Turkish family caused by a homozygous missense thyrotropin receptor (TSHR) gene mutation (A593 V).
Congenital primary hypothyroidism (CH) occurs in 1 of 4000 births. The majority of the cases are due to agenesis or dysgenesis of the thyroid gland, which can be caused by mutations in genes encoding for transcriptional factors that are responsible for the development of the thyroid gland. It is also known that the thyrotropin receptor (TSHR), a G-protein coupled receptor, is involved in late stages of thyroid organogenesis. Thus, mutations in the TSHR gene can cause congenital hypothyroidism. However, the clinical spectrum of thyroid abnormalities due to mutant TSHRs is wide and ranges from severe hypoplasia to an almost normal sized and structured thyroid gland. So far, 23 distinct loss-of-function mutations in the TSHR gene have been reported, occurring in families of different ethnic backgrounds and geographical areas. Here we report on a Turkish kindred in which two children were diagnosed to have very mild congenital primary hypothyroidism and one child had subclinical hypothyroidism. A novel homozygous missense mutation in codon 593 (A593 V) of the TSHR gene was identified in the affected individuals as the underlying molecular defect. This mutation substitutes a non-polar amino acid (alanine) with a non-polar amino acid (valine), so that only a minimal impairment of the TSHR function is expected. Indeed, the molecular finding is in agreement with the observed mild phenotype of the affected individuals. Our conclusion is that in mild primary hypothyroidism or subclinical hypothyroidism, mutations in the TSHR gene have to be considered as the molecular cause, especially in patients who have no detectable thyroid autoantibodies and have thyroid glands of normal size and in normal location.


Viral strain dependent differences in experimental Argentine hemorrhagic fever (Junin virus) infection of guinea pigs.
Guinea pigs infected with low-passage Junin virus of human origin showed viral strain dependent differences in mortality, LD50, time to death, and in viral spread and distribution. Different Junin strains appeared to cause at least two broad patterns of Argentine hemorrhagic fever in guinea pigs. A number of strains of Junin virus caused a viscerotropic type of illness in which virus replicated predominantly in lymph nodes, spleen, and bone marrow. With the most severe visceral forms of Argentine hemorrhagic fever, the guinea pigs became viremic, developed necrosis of spleen, lymph nodes, and bone marrow, showed gastric hemorrhages, and all animals died within 13-15 days. Other Junin strains induced a neurological type of illness with transient viral replication in and lymphocyte depletion of spleen and lymph nodes, with no detectable viremia or viral replication in bone marrow. Subsequently, virus was found in the brain with varying severities of polioencephalitis, and the guinea pigs frequently showed rear leg paralysis before death occurred 28-34 days after inoculation. Not all animals infected with a neurotropic strain developed all these signs. One viral strain induced some signs characteristic of both patterns of illness. Although the disease forms in the guinea pig model did not strictly correlate with those observed in the humans from which these strains were obtained, the different strains of Junin virus consistently caused very different patterns of illness in infected guinea pigs.


High-Frequency EEG Variations in Children with Autism Spectrum Disorder during Human Faces Visualization.
Autism spectrum disorder (ASD) is a neuropsychiatric disorder characterized by the impairment in the social reciprocity, interaction/language, and behavior, with stereotypes and signs of sensory function deficits. Electroencephalography (EEG) is a well-established and noninvasive tool for neurophysiological characterization and monitoring of the brain electrical activity, able to identify abnormalities related to frequency range, connectivity, and lateralization of brain functions. This research aims to evidence quantitative differences in the frequency spectrum pattern between EEG signals of children with and without ASD during visualization of human faces in three different expressions: neutral, happy, and angry. Quantitative clinical evaluations, neuropsychological evaluation, and EEG of children with and without ASD were analyzed paired by age and gender. The results showed stronger activation in higher frequencies (above 30 Hz) in frontal, central, parietal, and occipital regions in the ASD group. This pattern of activation may correlate with developmental characteristics in the children with ASD.


Measurement of long-range repulsive forces between charged particles at an oil-water interface.
Using a laser tweezers method, we have determined the long-range repulsive force as a function of separation between two charged, spherical polystyrene particles (2.7 microm diameter) present at a nonpolar oil-water interface. At large separations (6 to 12 microm between particle centers) the force is found to decay with distance to the power -4 and is insensitive to the ionic strength of the aqueous phase. The results are consistent with a model in which the repulsion arises primarily from the presence of a very small residual electric charge at the particle-oil interface. This charge corresponds to a fractional dissociation of the total ionizable (sulfate) groups present at the particle-oil surface of approximately 3 x 10(-4).


Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats.
Intrathecal (IT) morphine given after a short interval of aortic occlusion in a rodent model induced transient spastic paraparesis via opioid receptor-predicted actions in spinal cord. To determine the role(s) of spinal opioid receptor subtypes we investigated whether IT administration of various selective opioid receptor agonists can induce paraparesis following a short period of spinal cord ischaemia in rats. In Sprague-Dawley rats implanted with an IT catheter, spinal cord ischaemia was induced for 6 min using an intraaortic balloon. Mu ([D-Ala2, N-Me Phe4, Gly-ol5] enkephalin), kappa (U50488H) or delta ([D-Pen(2,5)] enkephalin) selective agonists were injected intrathecally 30 min after reperfusion. A separate group of animals was used to investigate the dose-response effect on this motor dysfunction. For this purpose, three doses of mu, kappa, or delta agonists were injected intrathecally after ischaemia. After IT injection, recovery of motor function was assessed periodically using the motor deficit index (0=complete recovery; 6=complete paraplegia). IT administration of mu and delta but not kappa agonists produced dose-dependent effects in the induction of spastic paraparesis. In addition, this spasticity induced by IT mu and delta agonists was reversed completely by IT naloxone and naltrindole, respectively. These results suggest that the effect of various opioids on motor function after a short period of spinal cord ischaemia depends upon individual opioid receptor subtypes.


[Achromic ungual melanoma. Apropos of a case].
A 55-year-old woman presented with suppurative paronychia that became chronic. In fact, this was an exceptional case of amelanotic subungual melanoma. This case is compared with a general review of subungual melanomas. Diagnosis is often delayed, due to the difficulty caused by the misleading clinical symptoms.


Frequency and structure of precautionary behavior in the domains of hazard preparedness, crime prevention, vehicular safety, and health maintenance.
A sample of 831 adults were interviewed by researchers using a 72-item inventory about their precautionary behaviors and attitudes. Exploratory and confirmatory factor analyses conducted on random halves of the sample provided evidence of consistency and structure in precautionary behavior both within and across domains of concern. Hazard preparedness activities clustered into having basic supplies on hand, advance planning, and hazard alertness. Crime prevention acts organized according to person protection, neighborly cooperation, and professional guidance. Vehicular safety factored into auto care, responsible driving, and seat belt use. Health maintenance activities entailed healthy habits (diet and exercise), risk monitoring, and avoiding tobacco and alcohol. Higher order factor analyses evidenced intra-individual consistency in the use of Disciplined, Vigilant, and Proactive Behaviors across precautionary domains. At all levels, perceptions of the usefulness of precautionary measures were related strongly to the frequency of self-protective acts.


Utilization of neonatal medication error prevention strategies: a clinical practice survey of Australian and New Zealand neonatal units.
Medication errors are common in neonatal care and can lead to significant harm. We sought to explore utilization of various medication error prevention strategies across Australian and New Zealand neonatal units (NNUs) through a clinical practice survey. An electronic survey was distributed in October 2016 to relevant staff at each of the 29 level III NNUs identified as members of the Australian and New Zealand Neonatal Network (ANZNN). The survey contained questions relating to a range of medication error prevention strategies identified from a previous systematic review on the topic. The evaluated interventions targeted different aspects of the medication-use process including prescribing, evaluation/checking of orders by clinical pharmacists, transmission, preparation and dispensing of orders, storage of medications, and medication administration. From the 20 respondents, the evidence-based strategies most commonly utilized were use of smart pumps (n = 18; 90%), and ward-based clinical pharmacists (n = 17; 85%). Interventions least commonly utilized included barcode scanning with medication administration (n = 0; 0%), electronic prescribing and clinical decision support (n = 1; 5%), and dedicated medication administration nurse (n = 2; 10%). The total number of evidence-based medication error prevention strategies utilized in each NNU ranged from 2 to 10 (median = 7), 10 of 16 strategies were utilized by less than 50% of NNUs. While evidence supports utilization of a number of medication error prevention strategies, these appear inconsistently utilized across current practice settings.


Vascular injuries and closed extremity fractures in children.
The association of a major vascular injury with a closed extremity fracture in the pediatric patient is uncommon. The present study of seven such patients includes five fractures treated by open reduction and internal fixation (ORIF) prior to vascular reconstruction. Two were treated in skeletal traction without vascular reconstruction. Most vascular injuries were not diagnosed initially, consequently delaying repair. Early follow-up examination revealed the following complications: wound infections, below-knee amputation, deep vein thrombosis (DVT), and motor and sensory deficits. All of the fractures healed. Late follow-up examinations revealed two cases of overgrowth and one of limb undergrowth. Minor motor and sensory deficits were present, but overall function was good. Arteriography should be performed prior to surgical repair. Because of problems with growth disturbance that require long-term follow-up evaluation, all major vascular injuries should be repaired despite adequate collateral circulation to keep the limb viable. Prompt, accurate diagnosis followed by surgical repair will improve the long-term results.


Disconjugate adaptation of saccades: contribution of binocular and monocular mechanisms.
We studied the effects of prism-induced disparity on static and intrasaccadic alignment in six normal human subjects. A ten diopter base-out prism, calling for convergence, was placed in front of the central field of the right eye, so that at the center the eye viewed through the prism; at left and right, outside the prism. During 15 min of training, subjects made repetitive saccades solely in the right field of vision (C-R-C sequence). This paradigm required relative divergence for centrifugal (C-R) saccades and relative convergence for centripetal (R-C) saccades, as well as increase of the amplitude for all saccades made by the right eye. We found that during training, all subjects incorporated the necessary change in alignment into the saccades. After training the resultant intrasaccadic disconjugacy persisted when tested during monocular viewing, indicating that motor learning had occurred. Subjects demonstrated increased divergence for C-R and increased convergence for R-C saccades, in accordance with the change acquired during adaptation to the prism. In addition, five subjects developed increased divergence for C-L saccades, for which they did not train. Smaller and less consistent divergence was also observed for L-C saccades. Changes in intrasaccadic alignment were accompanied by changes in the relative velocities of the two eyes' saccades and slowing of the peak velocities in both eyes during training. Static alignment showed a general tendency toward convergence that did not parallel the changes in the intrasaccadic alignment, suggesting that saccade adaptation is system-specific. The pattern of transfer of the intrasaccadic disconjugacy to saccades in the untrained field and the changes in the relative speeds of the two eyes cannot be explained by monocular adjustment of the saccades. Our results indicate that both a binocular mechanism--saccade-vergence interaction--and monocular adaptation contribute to disconjugate adaptation of saccades.


Negative symptoms in schizophrenia, assessed by the brief negative symptom scale, self-evaluation of negative symptom scale, and social cognition: a gender effect.
Negative symptoms of schizophrenia can be related to social cognition. The aim was to measure a relationship between the results on the new scales for the assessment of negative symptoms such as the Brief Negative Symptom Scale (BNSS) and Self-evaluation of Negative Symptoms (SNS), and the measures of social cognition. The study included 80 patients (40 men, 40 women) with schizophrenia, aged 19-63 (mean 38 years), during the improvement period. They were assessed using the BNSS, SNS, Personal and Social Performance (PSP) scales, and the tests for social cognition such as the Facial Emotion Identification Test, Reading the Mind in Eyes Test, Strange Stories and Faux Pas Test. Male patients obtained higher scores than females when assessed by the BNSS. No gender differences were observed for the SNS scale. Female patients scored better in the PSP and both parts of the Faux Pas test and obtained a significant correlation between the results of the SNS scale, BNSS, PSP, and the affective part of the Faux-Pas test what was not the case in males. Gender differences were found in the assessment of negative symptoms by a clinical scale and the relationship between negative symptoms and social cognition.KEY POINTSFemale patients scored better in the BNSS, PSP and both parts of the Faux-Pas testGender differences were present in the assessment of negative symptoms by clinical (BNSS) but not the self-assessment (SNS) scale.Female patients obtained a significant correlation between the results of the SNS scale, BNSS, PSP, and the affective part of the Faux-Pas test what was not the case in male subjects.


A Chinese family with congenital Dysfibrinogenemia carries a heterozygous missense mutation in FGA: Concerning the genetic abnormality and clinical treatment.
Congenital dysfibrinogenemia is a rare hereditary disease characterized by normal antigen level but lower function level of fibrinogen. Patients with congenital dysfibrinogenemia usually present as bleeding and/or thrombotic events. In this study, we explored the genetic abnormality and clinical treatment of a Chinese family with dysfibrinogenemia. This study was conducted in Jan 2015 to Jan 2016 in the Second Medical College (Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong Province, P.R. China. Coagulation function test were used to screen patients in this family. For all family members, DNA from peripheral blood was isolated. Whole-genome exon sequencing was carried out to screen possible mutations. And sanger sequencing was employed to further confirm the mutation in patients. The proband is a woman who had anemia and increased menstruation. Hypofibrinogenemia was found after admission. However, a pulmonary embolism occurred after the fibrinogen replacement treatment. Whole exon sequencing was conducted afterward. A candidate mutation in FGA gene (c.103C>A) was identified and validated in the woman and in two siblings. From this case, we learned that1) point mutation of c.103C>A is the pathogenesis for congenital dysfibrinogemia in this family; 2) thromboprophylaxis should always be in consideration when fibrinogen replacement is conducted. Prospective studies are needed to determine the best fibrinogen replacement strategy in order to achieve adequate hemostasis while minimize risk of thrombosis.


Gene expression assay for hazard assessment of chemicals.
Recent progress in our knowledge of gene expression systems provides evidence that many industrial chemicals affect the transcriptional machineries directly or indirectly, and gene expression is now recognized as one of the main targets of many chemicals. In view of the increasing number of man-made chemicals, it is therefore necessary to establish a reliable gene expression assay with rapidity and high sensitivity. Among various gene expression assays, the so-called reporter assay is now accepted as a suitable tool to assess hazardous effects of chemicals on gene expression. This article focuses on the principle and applications of the reporter assay in research on endocrine disrupters.


Generative models in pathology: synthesis of diagnostic quality pathology images†.
Within artificial intelligence and machine learning, a generative model is a powerful tool for learning any kind of data distribution. With the advent of deep learning and its success in image recognition, the field of deep generative models has clearly emerged as one of the promising fields for medical imaging. In a recent issue of The Journal of Pathology, Levine, Peng et al demonstrate the ability of generative models to synthesize high-quality pathology images. They suggested that generative models can serve as an unlimited source of images either for educating freshman pathologists or training machine learning models for diverse image analysis tasks, especially in scarce cases, while resolving patients' privacy and confidentiality concerns. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Frequency dependence of local cerebral blood flow induced by somatosensory hind paw stimulation in rat under normo- and hypercapnia.
We measured the field potential and the changes in local cerebral blood flow (LCBF) response during somatosensory activation (evoked LCBF) in alpha-chloralose--anesthetized rats by laser-Doppler flowmetry under normocapnia (PaCO(2)=34.3+/-3.8 mmHg) and hypercapnia (PaCO(2)=70.1+/-9.8 mmHg). Somatosensory activation was induced by electrical stimulation (0.2, 1, and 5 Hz with 1.5 mA for 5 s) of the hind paw. The neuronal activity of the somatosensory area of the hind paw was linear to the stimulus frequency, and there was no significant difference in the neuronal activity between hypercapnia and normocapnia. The baseline level of LCBF under hypercapnia was about 72.2% higher than that under normocapnia (p<0.01). The absolute response magnitude under hypercapnia was greater than that under normocapnia (p<0.05). The evoked LCBF under both conditions showed a frequency-dependent increase in the 0.2 to 5 Hz range, and the difference in the absolute response magnitude at the same stimulus frequency between normocapnia and hypercapnia became large with increasing stimulus frequency (p<0.05). On the other hand, after normalization to each baseline level there was no significant difference in the response magnitude of the normalized evoked LCBF between normocapnia and hypercapnia, indicating that the normalized evoked LCBF reflects neuronal activity even when the baseline LCBF was changed by the PaCO(2) level. The peak time and termination time of LCBF response curves with respect to the graded neuronal activity at 1 and 5 Hz stimulation increased significantly under hypercapnia, compared with those under normocapnia (p<0.05), although the rise time of 0.5 s was nearly constant. In conclusion, the results suggest a synergistic effect of the combined application of graded neuronal stimuli and hypercapnia on the LCBF response.


Neuronal correlates of extinction learning are modulated by sex hormones.
In emotional learning tasks, sex differences, stress effects and an interaction of these two moderators have often been observed. The sex hormones estradiol (E2) and progesterone (P4) vary over the menstrual cycle. We tested groups with different sex hormone status: 39 men, 30 women in the luteal phase (LU, high E2+P4) and 29 women taking oral contraceptives (OC, low E2+P4). They received either 30 mg cortisol or placebo prior to instructed differential fear conditioning consisting of neutral conditioned stimuli (CS) and an electrical stimulation (unconditioned stimulus; UCS). One figure (CS+) was paired with the UCS, the other figure (CS-) never. During extinction, no electrical stimulation was administered. Regarding fear acquisition, results showed higher skin conductance and higher brain responses to the CS+ compared to the CS- in several structures that were not modulated by cortisol or sex hormones. However, OC women exhibited higher CS+/CS- differentiations than men and LU women in the amygdala, thalamus, anterior cingulate and ventromedial prefrontal cortex during extinction. The suppression of endogenous sex hormones by OC seems to alter neuronal correlates of extinction. The observation that extinction is influenced by the current sex hormone availability is relevant for future studies and might also be clinically important.


Blood leukocyte responses in rats vaccinated with cDNA encoding glutathioinie-S-transferase of Fasciola hepatica.
Changes in blood leucocyte levels were investigated in Spraque-Dowley rats vaccinated with cDNA or protein of glutathione S-transferase (GST) of F. hepatica and subsequently challenged with metacercariae of the liver fluke. The analysis of the leucocyte responses measured in vaccinated rats suggests that the form of antigen used for vaccination influenced dynamics of white blood cell response to the fluke infection. The most clear differences were observed in neutrophil and eosinophil levels. The weakest reaction of these cells to the challenge infection was observed in rats vaccinated twice with cDNA. In contrast, in rats which received the first antigen dose as cDNA and the second vaccination with GST protein, both neutrophil and eosinophil responses were much higher, especially at 5 and 9 WAI.


New minimally invasive technique for cystoscopic laser treatment of fetal ureterocele.
Prenatal ultrasound detection of fetal ureterocele with bilateral hydroureteronephrosis, obstruction of the bladder outlet and progressive amniotic fluid reduction have been associated with a significant risk of end-stage chronic renal disease after birth. Fetal cystoscopic laser incision of the ureterocele, using standard 3.5-mm fetoscopic access to the amniotic cavity and the fetal bladder with the aim of relieving the bladder outflow obstruction to preserve renal function, has been reported previously in a case with a favorable outcome. We report on two additional cases of fetal ureterocele treated by cystoscopic laser decompression. In the first case, a standard 3.3-mm uterine entry was used. In the second case, a new approach was adopted using an 'all-seeing needle' 1.6-mm endoscope. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Evolution of "On-Barcode" Luminescence Oxygen Channeling Immunoassay by Exploring the Barcode Structure and the Assay System.
The multiplexed luminescence oxygen channeling immunoassay (multi-LOCI) platform we developed recently that combines conventional LOCI and suspension array technology is capable of realizing facile "mix-and-measure" multiplexed assays without tedious washing steps. However, previous work lacks comprehensive studies of the structure-performance relationship of the host-guest-structured barcode, which may obstruct the evolution and further translation of this exciting new technology to practical applications. Accordingly, this work revealed that polyelectrolyte interlayers played a crucial role in tuning the packing density of guest acceptor beads (ABs). More interestingly, we noticed that "sparse" barcodes (barcodes with low ABs packing density) exhibited comparable assay performance with "compact" ones (barcodes with high ABs packing density). The high robustness of barcodes allows for multi-LOCI to be a more universal and flexible assay platform. Furthermore, through optimization of the assay system including the laser power, as well as the concentrations of donor beads and biotinylated detection antibodies, the multi-LOCI platform showed a significant improvement in sensitivity compared with our previous work, with the limit of detection decreasing to as low as ca. 1 pg/mL. Impressively, multi-LOCI that enabled simultaneous detection of multiple analytes exhibited comparable sensitivity with the classical single-plexed LOCI, due to the ingenious structural design of the multi-LOCI barcode and the unique "on-barcode" assay format.


Instrumented Functional Test for Objective Outcome Evaluation of Balance Rehabilitation in Elderly Fallers: A Clinical Study.
Observational tests, e.g., the Berg Balance Scale (BBS) are widely used for balance evaluation in the elderly fallers. However, they do not allow objective outcome evaluation of rehabilitative interventions. This study aimed to investigate, in a clinical setting, the use of inertial measurement units (IMUs) integrated into the BBS test for objective outcome evaluation of balance rehabilitation in elderly fallers compared to conventional BBS scores. Thirty-six elderly fallers were recruited from the in-patient population of a geriatrics Clinic. Participants performed the BBS test while wearing 3 IMUs placed on the sternum, sacrum, and tibia of the dominant leg following admission to the clinic. Subsequently, they completed a rehabilitation program for 2-4 weeks. They performed a similar test before their discharge. The physical therapist recorded the BBS scores at both sessions, and the sensor data of the 2-min quiet standing task (BBS task 2) were extracted for objective balance evaluation. Moreover, eleven young adults were recruited to perform a 2-min quiet standing test while wearing the same IMUs. Center-of-pressure (COP) and segmental center-of-mass (COM) accelerations were calculated to estimate time-domain, frequency-domain, and intersegment coordination biomarkers of balance. COP time- and frequency-domain measures, COM acceleration time-domain measures, and intersegment coordination measures could identify age-related changes in balance of seniors compared to young adults (p < 0.05). Moreover, balance biomarkers of senior adults exhibited a reduced sway acceleration and jerkiness in the medial-lateral direction post-rehabilitation (p < 0.05). Although the total BBS scores increased post-rehabilitation, sway displacement and velocity did not significantly improve. We observed a significant association between pelvis-leg coordination at high sway oscillations and the total BBS scores pre- and post-rehabilitation. IMUs enable not only the characterization of underlying causes of impaired balance but also the identification of improved and yet impaired aspects of balance post-rehabilitation. Hence, IMUs allow us to characterize risk factors post-rehabilitation in elderly fallers, whereas the BBS scores only show changes in overall balance. It is crucial to objectively evaluate the effectiveness of such interventions to reduce future falls and their adverse consequences. Therefore, instrumented balance assessment is recommended since it can provide quantitative and objective measures for clinical outcome evaluations.


Investigating in Vivo and in Vitro Effects of Ethanolic and Aqueous Extracts of Myrtle (Myrtus communis) on Leishmania major.
The extract of myrtle plant contains polyphenolic compounds that show antibacterial, antiviral, and anti-parasitic properties. We aimed to investigate the therapeutic effect of aqueous and ethanolic myrtle extract against leishmaniasis caused by L. major in vivo and in vitro conditions. This study was carried out in Tarbiat Modares University, Tehran, Iran in 2018. Aqueous and ethanolic extract of myrtle plant at 6.25 to 400 mg/ml concentrations were tested on Leishmania major promastigotes, non-infected macrophages, and macrophages infected with amastigotes in vitro using counting, MTT and flow cytometry techniques. Then, BALB/c mice were treated with ethanolic, aqueous and a mixture of both extracts of myrtle plant. The treatment was carried out for four weeks. Then, the effectiveness of the herbal medicine was assessed by measuring wounds diameters, mice weights and their mortality rate on weekly basis. The IC50 values of aqueous and ethanolic extracts for promastigotes were 7.86 and 11.66 μg/mL respectively. The IC50 values of the aqueous and ethanolic extracts for amastigotes were 12.5 and 47.2 μg/mL respectively. Flow cytometry indicates 62.88% and 60.16% apoptosis induced by ethanolic and aqueous extract of myrtle plant respectively. The lowest parasitic load was seen in the group treated with ethanolic extract. The lesion sizes for treated groups with extracts were similar to those treated with glucantime. Oral administration instead of injection is another advantage of myrtle plant over glucantime, which makes the herb easy and more practical.


Pneumothorax necessitans in a patient with trapped lung and rheumatoid arthritis.
The authors report the case of a patient with a background of trapped lung following thoracocentesis who developed an anterolateral intercostal pneumothoracocele resulting in a pneumothorax necessitans (PN). Our purpose is to highlight the pathophysiology and interesting radiological features associated with PN in trapped lung. Our case is particularly unique due to the subacute nature of its presentation in a patient with rheumatoid arthritis and unusual pre-existing lung pathology.


[In vitro activity of tigecycline against multiple resistant Acinetobacter baumannii and carbapenem resistant Klebsiella pneumoniae isolates].
In order to detect the in vitro activity of tigecycline against multiple resistant gram-negative bacilli isolated in our hospital, tigecycline susceptibilities of clinical isolates of multiple and/or panresistant 100 Acinetobacter baumannii isolates, and 38 carbapenem resistant Klebsiella pneumoniae (17 of which were panresistant), obtained between January 2005 and August 2007, were evaluated by using E-test (AB Biodisc, Sweden). Carbapenem resistance rate was found to be 59% for A.baumannii, using Vitek2 Compact System (Bio-Merieux, France) which is present in our laboratory for routine use. Minimal inhibitory concentration (MIC) levels for tigecycline were < or =2 mcg/ml in 93% of the isolates while the MIC level was 3 mcg/ml for 7% of the isolates. Tigecycline MIC50 and MIC 90 values were 1.5 and 2 mcg/ml, respectively. Among K. pneumoniae the least resistance was detected against amikacin (52.6% resistant) while tigecycline MIC levels were between 0.13 mcg/ml and 2 mcg/ml. All of the K.pneumoniae strains were susceptible to tigecycline, and the MIC50 ve MIC90 values of these isolates were 1 mcg/ml and 1.5 mcg/ml, respectively. The in vitro susceptibility rates of tigecycline against multiple and/or panresistant A. baumannii and K. pneumoniae isolates are found to be promising for use in therapy.


Malignant rhabdoid tumor of the uterine corpus.
Malignant rhabdoid tumor (MRT) was first described as a variant of Wilms' tumor but was subsequently found to be a highly malignant tumor composed of primitive cells that resemble rhabdomyoblasts. In the past decade, extrarenal MRTs were reported in different locations and organs throughout the body including the female genital tract. We here report an MRT that arose in the corpus uteri, the second such case reported.


Weight Status and Weight Perception in Relation to Mental Distress and Psychosocial Protective Factors Among Adolescents.
To measure how weight status and weight perception relate to mental distress and psychosocial protective factors in adolescents. Adolescents in 8th, 9th, and 11th grade participating in the 2013 Minnesota Student Survey (N = 122,180) were classified on the basis of weight perception (overweight or not overweight) and weight status (not overweight, overweight, obese). Bivariate tests were used to assess the relationship of weight status and weight perception with internal mental distress, and generalized linear models were used to measure the association between weight status and weight perception with psychosocial protective factors including parent, school, and friend connectedness, social competency, and positive identity. Logistic regressions measured the relationship between psychosocial protective factors and internal mental distress. Prevalence of internal mental distress ranged from 14.5% for overweight boys who perceived themselves as not overweight to 55.0% for girls who were not overweight but self-perceived as overweight. Across all weight-status categories, adolescents who perceived themselves as overweight, compared to those who did not, had higher internal mental distress and lower mean levels of psychosocial protective factors. All psychosocial protective factors were related to lower odds of internal mental distress, with significant small differences by weight status and weight perception. Weight status and weight perception affected both mental distress and psychosocial protective factors. Those who perceived themselves as overweight, regardless of weight status, had the highest prevalence of mental distress and the lowest levels of psychosocial protective factors. Health care providers should consider screening for weight perception to provide a tailored approach to adolescent care.


Patient Preferences in Office-Based Orthopedic Care: A Prospective Evaluation.
Patient satisfaction has become a topic of interest within orthopedics as the landscape of provider reimbursement continues to evolve to reward value of care. Online internet physician rating sites are becoming increasingly popular ways for patients to subjectively express their provider experience. Understanding what patients value during their episode of care is important in the modern healthcare environment. The purpose of this study is to determine what preferences, if any, patients have when selecting their physician and how they experience care in an outpatient orthopedic setting. A prospective survey was electronically administered to 212 patients in an adult reconstruction clinic. One hundred ninety-six patients (92.5%) completed the survey. Demographic questions regarding age, sex, ethnicity, and prior adult reconstruction surgical history were obtained. When patients were asked how much time they would like the doctor to spend with them on a routine visit, the most common answer was 10 to 15 minutes (41.3%), with only 10.2% patients desiring >20 minutes. The majority of patients (83.1%) believe ≥30 minutes is too long to wait to see their surgeon. Less than half of patients (41.8%) stated that they would feel as though they were receiving below average care if seen only by a nurse practitioner or physician's assistant at a postoperative visit. Patients reported no significant age, gender, or ethnicity preferences for their physician. Recommendations from friends or other physicians was the most common (66.4%) way for patients to find their physicians, while 12.2% utilized online rating sites during their search. Optimizing patient experiences in the office may include keeping wait times to <30 minutes and educating patients on the roles of physician extenders. More work needs to be done to further elucidate variables influencing the subjective patient experience with their orthopedic care.


Signal transduction mechanisms for leukotriene B4 induced hyperadhesiveness of endothelial cells for neutrophils.
We have previously demonstrated that leukotriene B4 (LTB4) induces in vitro a transient state of hyperadhesiveness in cultured human umbilical vein endothelial cells (HUVEC) for neutrophils (PMN). The magnitude of this response is intermediate of that conferred by thrombin and by platelet-activating factor (PAF). This report shows that the LTB4 response was neither related to HUVEC expression of PAF (because it could not be blocked by the PAF receptor antagonist WEB-2086), nor to access to LTB4 receptors on neutrophils (as shown by LTB4 receptor desensitization experiments). However, it could be partly blocked by treating HUVEC with an LTB4 receptor antagonist (SC-41930). LTB4 evoked a rise of intracellular calcium concentrations, [Ca2+]i, in the HUVEC, and the hyperadhesive HUVEC response to LTB4 was abrogated by buffering of [Ca2+]i by Quin-2. The response was not inhibited by treating HUVEC with pertussis toxin before LTB4. Neutrophils showed no signs of activation when adhering to LTB4-treated HUVEC because they did not i) release lactoferrin, or ii) react with an increase of [Ca2+]i, and iii) they bound equally well to the stimulated endothelial cells after having been treated with pertussis toxin so that up-regulation of PMN adhesion to LTB4 was abolished. LTB4-treated HUVEC did not shed factors that modulated neutrophil adherence or chemotaxis. Thus, LTB4 promotes HUVEC hyperadhesiveness for PMN, and the transduction mechanism involves calcium ions, may depend on a surface receptor for LTB4, but does not involve pertussis toxin-sensitive G proteins or PMN activation.


[Clinical evaluations of neoadjuvant chemotherapy with DN and FP regimens for patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma].
To explore the efficacies and side effects of neoadjuvant chemotherapy with DN (docetaxel plus cisplatin) and FP (nedaplatin plus cisplatin) regimens for patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma. From January 2008 to January 2012, a total of 124 patients with upper or middle thoracic locally advanced esophageal squamous cell carcinoma were randomized into DN group (n = 64) and FP group (n = 60). Both groups received neoadjuvant chemotherapy. The treatment schedule was recycled every 3 weeks. After 2 cycles, those with potential surgical resection underwent surgery. The 2-year overall, locoregional relapse-free and distant metastasis-free survival rates in DN and FP groups were 71.1% and 66.7%, 65.0% and 63.0%, 78.3% and 74.3% respectively (P > 0.05). The incidence of leucopenia was higher in DN group than that in FP group (P < 0.05). And the occurrence rates of gastrointestinal toxicity and mucositis were significantly higher in FP group than those in DN group. No perioperative mortality occurred with a low incidence of postoperative complications. The rates of overall response, resection, postoperative complications and pathological complete rates response were similar in two groups. And the rates of downstage and R0 resection were significantly higher in DN group than those in FP group (P < 0.05). For patients with middle or lower thoracic locally advanced esophageal squamous cell carcinoma, neoadjuvant chemotherapies of docetaxel and nedaplatin may achieve excellent outcomes in clinical response and 2-year survival rate. And the side effects are clinically acceptable.


Nucleolar association and transcriptional inhibition through 5S rDNA in mammals.
Changes in the spatial positioning of genes within the mammalian nucleus have been associated with transcriptional differences and thus have been hypothesized as a mode of regulation. In particular, the localization of genes to the nuclear and nucleolar peripheries is associated with transcriptional repression. However, the mechanistic basis, including the pertinent cis- elements, for such associations remains largely unknown. Here, we provide evidence that demonstrates a 119 bp 5S rDNA can influence nucleolar association in mammals. We found that integration of transgenes with 5S rDNA significantly increases the association of the host region with the nucleolus, and their degree of association correlates strongly with repression of a linked reporter gene. We further show that this mechanism may be functional in endogenous contexts: pseudogenes derived from 5S rDNA show biased conservation of their internal transcription factor binding sites and, in some cases, are frequently associated with the nucleolus. These results demonstrate that 5S rDNA sequence can significantly contribute to the positioning of a locus and suggest a novel, endogenous mechanism for nuclear organization in mammals.


Alpha3, a transposable element that promotes host sexual reproduction.
Theoretical models predict that selfish DNA elements require host sex to persist in a population. Therefore, a transposon that induces sex would strongly favor its own spread. We demonstrate that a protein homologous to transposases, called alpha3, was essential for mating type switch in Kluyveromyces lactis. Mutational analysis showed that amino acids conserved among transposases were essential for its function. During switching, sequences in the 5' and 3' flanking regions of the alpha3 gene were joined, forming a DNA circle, showing that alpha3 mobilized from the genome. The sequences encompassing the alpha3 gene circle junctions in the mating type alpha (MATalpha) locus were essential for switching from MATalpha to MATa, suggesting that alpha3 mobilization was a coupled event. Switching also required a DNA-binding protein, Mating type switch 1 (Mts1), whose binding sites in MATalpha were important. Expression of Mts1 was repressed in MATa/MATalpha diploids and by nutrients, limiting switching to haploids in low-nutrient conditions. A hairpin-capped DNA double-strand break (DSB) was observed in the MATa locus in mre11 mutant strains, indicating that mating type switch was induced by MAT-specific DSBs. This study provides empirical evidence for selfish DNA promoting host sexual reproduction by mediating mating type switch.


Revealing the Surface Effect on Gas Transport and Mechanical Properties in Nonporous Polymeric Membranes in Terms of Surface Free Energy.
The contribution of surface roughness of nonporous polymeric membranes to their gas separation and mechanical properties was studied in terms of surface free energy. The membranes samples were prepared based on glassy polymers with different chain rigidity, namely polysulfone (PSU), cellulose triacetate (CTA), and poly(vinyl alcohol) (PVA). The results were obtained by atomic force and scanning electron microscopy (AFM and SEM) with individual gas permeation, wettability, and mechanical testing. The specific surface free energy (as well as its polar and dispersive components) for the polymers was calculated by the Owens-Wendt method. It was proven that the surface roughness of the polymer membranes affects both energy components; however, the degree of this influence depends on the chemical nature of the corresponding polymer. Moreover, it was assumed that the dispersive energy component is inversely correlated with any gases' total permeability. In contrast, the polar one is inversely correlated with the permeability by gases with the ability for site-specific interactions. The gas separation results confirmed this assumption. It was also shown that the mechanical properties of the polymer membranes are also influenced by the surface energy, namely, its dispersive component.


[Pancreatic pseudocysts. Our experience with 21 cases treated surgically].
Twenty-one consecutive patients with pancreatic pseudocyst have been reviewed. Nine cases have been treated with internal drainage, 9 with external drainage, while 3 patients have undergone distal pancreatectomy. No mortality was associated to the surgical treatment, while morbidity was of 9.5% due to pancreatic fistulas. Based on their own experience and literature review the Authors describe clinical, diagnostic and therapeutic features of the disease and point out the good results of cistojejunostomy with Roux-en-Y loop.


Members of a family of proteins (the RD family) detected by a U1 70K monoclonal antibody are present in spliceosomal complexes.
We have characterized a monoclonal antibody (mAb) to the U1 snRNP component U1 70K. We find that this antibody recognizes several proteins, in addition to U1 70K, in purified spliceosomal complexes and in total HeLa cell nuclear extract preparations. The novel mAb U1 70K antigens can also be specifically immunoprecipitated by the antibody. Similarly to U1 70K, many of the mAb U1 70K antigens can be phosphorylated by a co-purifying kinase activity. The epitope recognized by mAb U1 70K was previously shown to be a repeating arginine/aspartate (RD) dipeptide. Thus we have designated the novel mAb U1 70K antigens the RD family. Comparison of mAb U1 70K with a recently characterized antibody, mAb 16H3, whose epitope is a repeating R/D or R/E motif, showed that a large subset of the antigens are common. In contrast, most of the mAb U1 70K antigens are distinct from the proteins detected by mAb 104, an antibody to the SR family of splicing factors.


Anticoagulant induced leukoagglutination.
Low leukocyte count secondary to leukocyte aggregation caused by an ethylene diamine tetra acetic acid (EDTA) occur in both benign and malignant disorders. We report a 71-year-old male patient who was admitted to the hospital with acute chest infection. Complete blood count (CBC) collected in EDTA tube and analyzed by sysmex instrument SE/9500 revealed low hemoglobin level of 9.4g/dl, white blood cell (WBC) count of 8.2x109/L and neutrophils of 4.8x109/L. Peripheral blood smear review shows multiple leukocytes aggregation one clump in each field. When we ask for another blood sample in citrate anticoagulant, the CBC showed WBC count of 11.8x109/L and neutrophils of 6.26 x 109/L. This is a case of low leukocyte count secondary to leukocyte aggregation induced by EDTA.


Estimation of the benchmark dose of urinary cadmium as the reference level for renal dysfunction: a large sample study in five cadmium polluted areas in China.
Itai-itai disease primarily results from cadmium (Cd) exposure and is known as one of the four major pollution diseases in Japan. Cd pollution is more serious in several areas of China than in Japan. However, there is still a lack of information regarding the threshold level of Cd exposure for the adverse health effects in the general Chinese population. This study aims to evaluate the reference value of urinary Cd (UCd) for renal dysfunction in a Chinese population as the benchmark dose lower confidence limit (BMDL) based on a large sample survey. A total of 6103 participants who lived in five Cd polluted areas of China participated in this study. We analyzed UCd levels as a biomarker of exposure and urinary β2-microglobulin (Uβ2-MG) levels as a renal tubular effect biomarker. The BMD studies were performed using BMD software. The benchmark response (BMR) was defined as a 10% additional risk above the background. There was a positive correlation between the UCd levels and the prevalence of Uβ2-MG. The BMD of UCd for Uβ2-MG was estimated for each province. The findings showed that the BMD levels were related to the participants' geographic region, which may be partially due to the large differences in Cd exposure level, ethnic group, lifestyle and diet of the sample population in these study areas. The reference level of UCd for the renal effects was further evaluated by combining the five sets of data from all 6103 subjects. The overall BMDLs of UCd for Uβ2-MG with an excess risk of 10% were 2.00 μg/g creatinine (μg/g cr) in males and 1.69 μg/g cr in females, which were significantly lower than the World Health Organization (WHO) threshold level of 5 μg/g cr for Cd-related renal effects. The selection of the sample population and geographic region affected the BMDL evaluation. Based on the findings of this survey of a large sample population, the UCd BMDLs for Uβ2-MG in males with BMRs at 10% were 2.00 μg/g cr. The BMD was slightly lower in females, which indicated that females may be relatively more sensitive to Cd exposure than males.


Recombinant hemagglutinin glycoproteins provide insight into binding to host cells by H5 influenza viruses in wild and domestic birds.
Clade 126.96.36.199, H5 subtype highly pathogenic avian influenza viruses (HPAIVs) have caused devastating effects across wild and domestic bird populations. We investigated differences in the intensity and distribution of the hemagglutinin (HA) glycoprotein binding of a clade 188.8.131.52 H5 HPAIV compared to a H5 low pathogenic avian influenza virus (LPAIV). Recombinant HA from gene sequences from a HPAIV, A/Northern pintail/Washington/40964/2014(H5N2) and a LPAIV, A/mallard/MN/410/2000(H5N2) were generated and, via protein histochemistry, HA binding in respiratory, intestinal and cloacal bursal tissue was quantified as median area of binding (MAB). Poultry species, shorebirds, ducks and terrestrial birds were used. Differences in MAB were observed between the HPAIV and LPAIV H5 HAs. We demonstrate that clade 220.127.116.11 HPAIV H5 HA has a broader host cell binding across a variety of bird species compared to the LPAIV H5 HA. These findings support published results from experimental trials, and outcomes of natural disease outbreaks with these viruses.


Oxygen Inhibition of Photosynthesis: II. Kinetic Characteristics as Affected by Temperature.
The response of whole leaf photosynthesis of wheat (Triticum aestivum L.) in relation to soluble CO(2) available to the mesophyll cells, under low (1.5%) O(2) at 25, 30, and 35 C, followed Michaelis-Menten kinetics up to saturating CO(2) but deviated at high CO(2) levels where the experimental V(max) is considerably less than the calculated V(max). The affinity of the leaves for CO(2) during photosynthesis was similar from 25 to 35 C with Km (CO(2)) values of approximately 3.5 to 5 muM.In considering the effect of O(2) on photosynthesis at 25, 30, and 35 C where O(2) and CO(2) are expressed on a solubility basis: (a) the effect of O(2) on carboxylation efficiency was similar at the three temperature; (b) increasing temperature caused only a slight increase in kinetic constants Ki(O(2)) and Km(CO(2)), while the ratio of Ki(O(2))/Km(CO(2)) was similar at the three temperatures; and (c) the reciprocal plots of apparent rate of photosynthesis versus (CO(2) - Gamma) at various O(2) levels showed O(2) to be a competitive inhibitor of photosynthesis.A model for separating O(2) inhibition of photosynthesis into two components, direct competitive inhibition and inhibition due to photorespiration, was presented from both simulated and experimental data of photosynthetic response curves to varying CO(2) concentrations at low O(2)versus 21% O(2). The photorespiratory part of O(2) inhibition is considered as a major component at Gamma and increases with increasing temperature and with increase in O(2)/CO(2) solubility ratio. The competitive component of O(2) inhibition is considered as a major component of O(2) inhibition under atmospheric CO(2) levels and is relatively independent of temperature at a given O(2)/CO(2) ratio.


Demand and control in human service work in relation to self-rated oral health.
The objective of this study was to investigate the relationships between oral health and job demands (emotional and quantitative), job control (skill discretion and decision authority), and social support, in a human service work context. In April 1997, a questionnaire with items about work conditions and oral health was sent to a sample of employees in the social insurance organisation in Sweden. Response rate was 76% (n = 3,173). The questionnaire contained four questions related to oral health. Emotional demands showed a negative relation to oral health, while there was no relation between quantitative demands, skill discretion, decision authority or social support and oral health. Psychosocial climate, an aspect of support, was significantly related to oral health. The results were controlled in separate models for the index components, with minor changes in the overall picture. Work related stress situations can be hazardous for oral as well as other aspects of health. In the context of human services, attention should be directed towards emotional as well as other demands.


MP3 player listening habits of 17 to 23 year old university students.
This study evaluated the potential risk to hearing associated with the use of portable digital audio players. Twenty-eight university students (12 males, 16 females; aged 17-23) completed a 49-item questionnaire assessing user listening habits and subjective measures of hearing health. Sound level measurements of participants' self-identified typical and 'worst case' volume levels were taken in different classrooms with background sound levels between 43 and 52 dBA. The median frequency and duration of use was 2 h per day, 6.5 days a week. The median sound levels and interquartile ranges (IQR) at typical and 'worst case' volume settings were 71 dBA (IQR=12) and 79 dBA (IQR=9), respectively. When typical sound levels were considered with self-reported duration of daily use, none of the participants surpassed Leq(8) 85 dBA. On the questionnaire, 19 students reported experiencing at least one symptom of possible noise-induced hearing loss. Significant differences in MP3 user listening patterns were found between respondents who had experienced tinnitus and those who had not. The findings add to a growing body of literature that collectively supports a need for further research investigating MP3 player user listening habits in order to assess their potential risk to hearing health.


High activity of monoamine oxidase A is associated with externalizing behaviour in maltreated and nonmaltreated adoptees.
Individual differences in a functional polymorphism of the promoter of the Monoamine oxidase A (MAO-A) gene might partly explain the increased vulnerability of maltreated children for externalizing behaviour. A sample of 239 internationally adopted boys was studied. Adoptive parents provided the information about abuse and neglect before the adoption and rated externalizing behaviour of their adopted children, using the Child Behaviour Checklist. MAO-A alleles were classified in high and low activity. We found that individuals with high MAO-A activity had more externalizing behaviour than those with low MAO-A activity. No modifying effect of MAO-A on the relationship between early maltreatment on externalizing behaviour was observed. Our results suggest that in severely maltreated children, high MAO-A activity may not protect against the effects of maltreatment but may convey an increased risk for externalizing behaviour.


Pharmacokinetics of cefoperazone and sulbactam in liver transplant patients.
The authors evaluated the pharmacokinetics of cefoperazone and sulbactam in 9 liver transplant patients. Cefoperazone and sulbactam were administered as an intravenous infusion over 30 minutes every 12 hours for six doses, and multiple blood samples were collected immediately after the first dose (administered during the surgery) and after the last dose. The concentrations of cefoperazone and sulbactam in serum and, when possible, in urine and bile collected over one dosing interval were measured by high-pressure liquid chromatography. The concentration of cefaperazone ranged from 436 to 4118 microg/ml, and sulbactam ranged from 3.3 to 8.7 microg/ml in the bile samples. The intraoperative clearance of cefoperazone (0.53+/-0.18 ml/min/kg) was significantly higher than the postoperative clearance (0.21+/-0.23 ml/min/kg). The half-life of cefaperazone, although not statistically significantly different, was prolonged in all patients during the postoperative period. The clearance of sulbactam (1.51+/-0.51 ml/min/kg) was lower than what is reported in patients with normal renal function but was comparable to what has been reported in patients with renal impairment and in critically ill patients. There were no significant differences in any of the pharmacokinetic parameters of sulbactam during and after surgery. The pharmacokinetic parameters of cefoperazone and sulbactam were significantly altered in liver transplant patients compared to what has been reported in normal subjects but were similar to what has been reported in patients with liver and renal impairment. There was a significant impairment in the biliary excretion of cefoperazone during the postoperative period in liver transplant patients. Although the percentage of the dose of cefoperazone excreted in the bile was drastically reduced, the biliary concentrations were generally high and above the MIC for most organisms. Given that both renal and hepatic elimination of cefoperazone is decreased, leading to a lower clearance and longer half-life in liver transplant patients, lower doses (1-2 g per day) of cefoperazone may be sufficient in liver transplant patients during the immediate postoperative period.


Chitosan-based nanoparticles as a sustained protein release carrier for tissue engineering applications.
Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of Chi crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly(lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo.


Factors Related to Bone Metabolism in Kidney Transplant Recipients.
This study is aimed at establishing the prevalence of osteoporosis and osteopenia in kidney transplant recipients (KTRs) and determining the risk factors for bone mass loss. We invited KTRs who were under regular follow-up at Jiangxi Provincial People's Hospital Affiliated with Nanchang University to attend an assessment of osteoporotic risk assessed by questionnaire, biochemical profile, and dual-energy X-ray absorptiometry (DXA) scanning of the lumbar spine, total hip, and femoral neck. Binary logistic regression models were used to investigate the relationship between the different variables and bone mass density (BMD). A total of 216 patients satisfied the inclusion criteria. The group consisted of 156 men (72.22%) and 60 women (27.78%), and the mean age was 41.50 ± 9.98 years. There were 81 patients with normal bone mass (37.50%) and 135 patients with bone mass loss (62.50%). Logistic regression analysis showed that a higher phosphorus value and higher alkaline phosphatase concentration and a longer use of glucocorticoids were risk factors for bone mass loss in KTRs, and maintaining an appropriate weight and exercising an appropriate number of times per week helped to maintain bone mass.


Low concentration of serum total cholesterol is associated with multifocal signal loss lesions on gradient-echo magnetic resonance imaging: analysis of risk factors for multifocal signal loss lesions.
Multifocal signal loss lesions (MSLLs) on T2*-weighted gradient-echo (GE) MRI are believed to be microbleeds histopathologically. Previous epidemiological studies suggested that low serum cholesterol is associated with the increased risk of intracerebral hemorrhage. We investigated risk factors of MSLLs and the relationship between lipid profiles and MSLLs on GE-MRI. We included consecutively 172 patients who underwent brain MRI. MSLLs on GE-MRI were counted by 2 neurologists separately and graded by consensus. The concentrations of lipid profiles were categorized as quartiles, and the MSLLs were graded as absent (total count, 0), mild (1 to 2), moderate (3 to 10), and severe (>10). The mean concentrations of total cholesterol and low-density lipoprotein cholesterol were significantly lower in patients with a severe degree of MSLLs than in those without MSLL (P<0.05). By multivariate analysis, MSLLs were significantly correlated with hypertension (odds ratio [OR], 3.42; 95% CI, 1.17 to 9.97), leukoaraiosis (OR, 4.62; 95% CI, 2.87 to 7.41), the lowest quartile of serum total cholesterol (<4.27 mmol/L; OR, 10.91; 95% CI, 3.98 to 25.57), and the highest quartile of high-density lipoprotein (>1.47 mmol/L; OR, 3.5; 95% CI, 1.45 to 8.29). Our results suggest that both the lipid profile levels and the severity of hypertension may be closely associated with MSLLs on GE-MRI.


Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice.
The role of plasminogen system components in focal cerebral ischemic infarction (FCI) was studied in mice deficient in plasminogen (Plg-/-), in tissue or urokinase plasminogen activator (tPA-/- or uPA-/-), or in plasminogen activator inhibitor-1 or alpha2-antiplasmin (PAI-1(-/-) or alpha2-AP-/-). FCI was produced by ligation of the left middle cerebral artery and measured after 24 hours by planimetry of stained brain slices. In control (wild-type) mice, infarct size was 7.6+/-1.1 mm3 (mean+/-SEM), uPA-/- mice had similar infarcts (7.8+/-1.0 mm3, P=NS), tPA-/- mice smaller (2.6+/-0.80 mm3, P<0.0001), PAI-1(-/-) mice larger (16+/-0.52 mm3, P<0.0001), and Plg-/- mice larger (12+/-1.2 mm3, P=0.037) infarcts. alpha2-AP-/- mice had smaller infarcts (2. 2+/-1.1 mm3, P<0.0001 versus wild-type), which increased to 13+/-2.5 mm3 (P<0.005 versus alpha2-AP-/-) after intravenous injection of human alpha2-AP. Injection into alpha2-AP-/- mice of Fab fragments of affinospecific rabbit IgG against human alpha2-AP, after injection of 200 microg human alpha2-AP, reduced FCI from 11+/-1.5 to 5.1+/-1.1 mm3 (P=0.004). Plg system components affect FCI at 2 different levels: (1) reduction of tPA activity (tPA gene inactivation) reduces whereas its augmentation (PAI-1 gene inactivation) increases infarct size, and (2) reduction of Plg activity (Plg gene inactivation or alpha2-AP injection) increases whereas its augmentation (alpha2-AP gene inactivation or alpha2-AP neutralization) reduces infarct size. Inhibition of alpha2-AP may constitute a potential avenue to treatment of FCI.


Targeting of cardiac muscle titin fragments to the Z-bands and dense bodies of living muscle and non-muscle cells.
A 6.5-kb N-terminal region of embryonic chick cardiac titin, including the region previously reported as part of the protein zeugmatin, has been sequenced, further demonstrating that zeugmatin is part of the N-terminal region of titin, and not a separate Z-band protein. This Z-band region of cardiac titin, from both 7- and 19-day embryos as well as from adult animals, was found to contain six different small motifs, termed z-repeats [Gautel et al., 1996: J. Cell Sci. 109:2747-2754], of approximately 45 amino acids each sandwiched between flanking regions containing Ig domains. Fragments of Z-band titin, linked to GFP, were expressed in cultured cardiomyocytes to determine which regions were responsible for Z-band targeting. Transfections of primary cultures of embryonic chick cardiomyocytes demonstrated that the z-repeats play the major role in targeting titin fragments to the Z-band. Similar transfections of skeletal myotubes and non-muscle cells lead to the localization of these cardiac z-repeats in the Z-bands of the myofibrils and the dense bodies of the stress fibers. Over-expression of these z-repeat constructs in either muscle or non-muscle cells lead to the loss of the myofibrils or stress fibers, respectively. The transfection experiments also indicated that small domains of a protein, 40 to 50 amino acids, can be studied for their localization properties in living cells if a suitable linker is placed between these small domains and the much larger 28 kDa GFP protein.


PTSD in children and adolescents: toward an empirically based algorithma.
In considering potential revisions for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), describing developmental influences on symptomatic expression is a high priority. This review presents a number of options and preliminary recommendations to be considered for DSM-V. Research conducted in the past 15 years is reviewed that pertains to expressions of posttraumatic stress disorder (PTSD) symptoms in preschool and school age children and in adolescents. This research has attempted to determine the usefulness of the DSM-IV criteria for PTSD in children and adolescents. Based on the studies of preschool children, evidence supports two sets of suggestions: first, we suggest that developmental manifestations are warranted in A-D criteria of PTSD; and second, we suggest that a developmental preschool PTSD subtype is warranted that lowers the C threshold from three to one symptom. For school-age children and young adolescents, the evidence is more limited. Nevertheless, there is also evidence suggesting that modifications in PTSD criteria A-D, including fewer Cluster C symptoms, may facilitate accurate diagnosis in this age group.


Clinical application of laser treatment for cardiovascular surgery.
Recently, several kinds of lasers have been widely employed in the field of medicine and surgery. However, laser applications are very rare in the field of cardiovascular surgery throughout the world. So, we have experimentally tried to use lasers in the field of cardiovascular surgery. There were three categories: 1) Transmyocardial laser revascularization (TMLR), 2) Laser vascular anastomosis, and 3) Laser angioplasty in the peripheral arterial diseases. By the way, surgery for ischemic heart disease has been widely performed in Japan. Especially coronary artery bypass grafting (CABG) for these patients has been done as a popular surgical method. Among these patients there are a few cases for whom CABG and percutaneous coronary intervention (PCI) could not be carried out, because of diffuse stenosis and small caliber of coronary arteries. Materials and methods of TMLR: A new method of tranasmyocardial revascularization by CO2 laser (output 100 W, irradiation time 0.2 sec) was experimentally performed to save severely ill patients. In this study, a feasibility of transmyocardial laser revascularization from left ventricular cavity through artificially created channels by laser was precisely evaluated. In trials on dogs laser holes 0.2mm in diameter have been shown microscopically to be patent even 3 years after their creation, thus this procedure could be used as a new method of transmyocardial laser revascularization. Clinical application of TMLR: Subsequently, transmyocardial laser revascularization was employed in a 55-year-old male patient with severe angina pectoris who had undergone pericardiectomy 7 years before. He was completely recovered from severe chest pain. Conclusions of TMLR: This patient was the first successful case in the world with TMLR alone. This method might be done for the patients who percutaneous coronary intervention and coronary artery bypass grafting could be carried out. Laser vascular anastomosis: At present time, in vascular surgery there are some problems to keep long-term patency after anastomosis of the conventional suture method, especially for small-caliber vessels. Materials and methods of Laser vascular anastomosis: From these standpoints, a low energy CO2 laser was employed experimentally in vascular anastomosis for small-caliber vessels. Resullts of Laser vascular anastomosis: From preliminary experiments it could be concluded that the optimal laser output was 20-40 mW and irradiation time was 6-12 sec/mm for vascular anastomosis of small-caliber vessels in the extremities. And then, histologic findings and intensity of the laser anastomotic sites were investigated thereafter. Subseqently, good enough intensity and good healing of laser anastomotic sites as well as the conventional suture method could be observed. There were no statistic differences between laser and suture methods. A feasibility of laser anastomosis could be considered and clinical application could be recognized. Clinical applications of Laser vascular anastomosis: On February 21, 1985, arterio-venous laser anastomosis for the patient with renal failure was smoothly done and she could accept hemodialysis. Conclusions of Laser vascular anastomosis: This patient was the first clinical successful case in the world. Thereafter, Laser vascular anastomosis were in 111 patients with intermittent claudication, refractory crural ulcer, and coronary disorders. Thereafter, they are going well. Laser angioplasty: Laser angioplasty for peripheral arterial diseases. There are many methods to treat peripheral arterial diseases such as balloon method, atherectomy, laser technique and stenting graft in the field of endovascular treatment. Recent years, minimal invasive treatment should be employed even in the surgical treatment. However, there are different images between these methods. Materials and methods of Laser angioplasty: We have chosen to use laser for endovascular treatment for peripheral arterial diseases. We have tried to check between laser energy and vessel wall. Results of Laser angioplasty: Subsequently, it could be concluded that optimal conditions for laser angioplasty were 6 W in output and irradiation time was 5 sec. And with another method of feedback control system, temperature of metal tip probe was 200°C and irradiation time was 5 sec for each shot. And histological study and feasibility of angioscopic guidance could be done and clinical application was started. Until now, 115 patients were successfully treated with their life longevity. Conclusions of Laser angioplasty: Thus, laser applications were useful methods to treat a lot of patients with some ischemic problems.