Arthroscopic-assisted reduction and internal fixation for complex tibial plateau fracture: radiographic and clinical outcomes with 2- to 15-year follow-up.
To investigate the radiologic and prognostic outcomes after using arthroscopic-assisted reduction and internal fixation (ARIF) in complex tibial plateau fractures with mid- to long-term follow-up. This retrospective study reviewed complex tibial plateau fractures that underwent ARIF from 1999 to 2019. Radiologic outcomes, including tibial plateau angle (TPA), posterior slope angle (PSA), Kellgren-Lawrence classification and Rasmussen radiologic assessment, were measured and evaluated. The prognosis and complications were assessed by the Rasmussen clinical assessment with a minimum follow-up of 2 years. Ninety-two consecutive patients (mean age: 46.9 years) with a mean follow-up of 74.8 months (24-180) were included in our series. Using AO classification, there were 20 type C1 fractures, 21 type C2 fractures, and 51 type C3 fractures. All the fractures achieved solid union. TPA was maintained well on average at the last follow-up and showed no significant difference compared to postoperatively (p = 0.208). In the sagittal plane, the mean PSA increased from 9.3 ± 2.9° to 9.6 ± 3.1° (p = 0.092). A statistically significant increase in PSA was also noted in the C3 group (p = 0.044). Superficial or deep infection was noted in 4 cases (4.3%), and total knee arthroplasty (TKA) was performed in 2 cases (2.2%) due to grade 4 osteoarthritis (OA). Ninety (97.8%) and 89 (96.7%) patients had good or excellent results in the Rasmussen radiologic assessment and Rasmussen clinical assessment, respectively. The complex tibial plateau fracture could be treated successfully using arthroscopy-assisted reduction and internal fixation. Most patients achieve excellent and good clinical outcomes with low complication rates. In our experience, a higher incidence of increased slope was noted, especially in type C3 fractures. Reduction of the posterior fragment should be done cautiously during the operation. Level III.


December 2001: rapidly progressive motor weakness, starting in pregnancy.
A 25-year-old woman presented with rapidly progressive motor weakness necessitating ventilation 10 months after the onset. Despite immunosuppressive therapy she died 27 months later, without developing significant extramotor features. Autopsy revealed evidence of both upper and lower motor neuron loss with wide-spread motor and extramotor intraneuronal basophilic inclusions, most of which did not show ubiquitin immunoreactivity. Motor neuron disease with basophilic inclusions appears to be a rare, but distinctive pathological subtype, with most reported cases occurring sporadically in young women and having a rapid clinical progression.


Conserved neural dynamics and computations across species in olfaction.
Interpreting chemical information and translating it into ethologically relevant output is a common challenge of olfactory systems across species. Are computations performed by olfactory circuits conserved across species to overcome these common challenges? To understand this, we compared odor responses in the locust antennal lobe (AL) and mouse olfactory bulb (OB). We found that odors activated nearly mutually exclusive neural ensembles during stimulus presentation ('ON response') and after stimulus termination ('OFF response'). Strikingly, ON and OFF responses evoked by a single odor were anticorrelated with each other. 'Inverted' OFF responses enhanced contrast between odors experienced close together in time. Notably, OFF responses persisted long after odor termination in both AL and OB networks, indicating a form of short-term memory. Taken together, our results reveal key neurodynamic features underlying olfactory computations that are conserved across insect and mammalian olfactory systems.


Economic impact of targeted government responses to COVID-19: Evidence from the large-scale clusters in Seoul.
We estimate the economic impact of South Korea's targeted responses to the large-scale COVID-19 clusters in a highly concentrated business area (Guro) and a highly concentrated entertainment area (Itaewon) in Seoul, respectively. We find that foot traffic and retail sales decreased only within a 300 m radius and recovered to their pre-outbreak level after four weeks in the case of the Guro cluster. The reductions appear to be driven by temporary business closures rather than by citizens' risk avoidance behavior. However, the adverse economic impacts measured by foot traffic and retail sales of another outbreak of the COVID-19 cluster in Itaewon were persistent. Our results imply that the effects of less intense but more targeted COVID-19 interventions, such as pinpointed, temporary closures of businesses, can differ by underlying geographical characteristics.


Degradation analysis of polymeric pipe materials used for water supply systems under various disinfectant conditions.
Addition of chlorine dioxide (ClO2) or sodium hypochlorite (NaOCl) as a disinfectant in municipal water distribution systems is a common practice to deactivate micropollutants, but their impact on the pipe material with long-term exposure has not been discussed in detail. In this study, accelerated aging experiments were conducted for evaluating the oxidation of high-density polyethylene (HDPE), low-density polyethylene (LDPE), unplasticized polyvinylidene chloride (UPVC), and high-impact polyvinylidene chloride (Hi-PVC) pipes. The pipes were immersed in deionized (DI) water, ClO2, and NaOCl (2 mg/L, 5 mg/L, and 10 mg/L doses) for 1200 h of aging at 40 °C. The variations in the pipes structural, thermal, and mechanical characteristics were systematically investigated by attenuated total reflectance-Fourier transform infrared radiation (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), and a universal testing machine (UTM). The formation of carbonyl groups due to methylene groups (C-C/C-H) oxidation resulted in an increased carbonyl index (CI) of the material exposed to accelerated aging conditions. Moreover, the XPS and ATR-FTIR results elucidated that the oxidation patterns under the exposure conditions followed from ketone/aldehyde formation to carboxylate groups (carboxylic acid/ester). The pipes were more vulnerable to the ClO2 compared to the DI water and NaOCl solution exposure. The increase in crystallinity and the decrease in oxidation induction time (OIT) of the pipe materials confirmed that the loss of stabilizer and changes in the chain alignment resulted in chain secession, loss of ductility, and lower percent elongation at break. Furthermore, results also elucidated that oxidative stability of the HDPE/UPVC was greater than that of the LDPE/Hi-PVC under disinfectant exposure regardless of the concentration and duration.


Liver organoids as a primary human model to study HBV-mediated Hepatocellular carcinoma. A review.
Hepatitis B Virus (HBV) is the prevailing cause of chronic liver disease, which progresses to Hepatocellular carcinoma (HCC) in 75% of cases. It represents a serious health concern being the fourth leading cause of cancer-related mortality worldwide. Treatments available to date fail to provide a complete cure with high chances of recurrence and related side effects. The lack of reliable, reproducible, and scalable in vitro modeling systems that could recapitulate the viral life cycle and represent virus-host interactions has hindered the development of effective treatments so far. The present review provides insights into the current in-vivo and in-vitro models used for studying HBV and their major limitations. We highlight the use of three-dimensional liver organoids as a novel and suitable platform for modeling HBV infection and HBV-mediated HCC. HBV organoids can be expanded, genetically altered, patient-derived, tested for drug discovery, and biobanked. This review also provides the general guidelines for culturing HBV organoids and highlights their several prospects for HBV drug discovery and screening.


Na+K+ATPase activity and ouabain binding sites in erythrocytes in hyperthyroidism before and after treatment.
Erythrocyte sodium pump is decreased in hyperthyroid patients. We described the effect of untreated hyperthyroidism on Na+K+ATPase activity, ouabain binding sites and intracellular sodium concentration. We found a reduction in Na+K+ATPase activity and in number of ouabain binding sites with a concomitant increase in intracellular sodium. B-blockade therapy failed to restore normal pump activity and sodium concentration, where only thionamide treatment was successful when it was able to decrease free T3.


Effects of microplastics on the properties of different types of sewage sludge and strategies to overcome the inhibition: A review.
Microplastics have been identified as an emerging pollutant. When microplastics enter wastewater treatment plants, the plant traps most of the microplastics in the sludge during sewage treatment. Therefore, the effects of microplastics on sludge removal performance, and on the physical and chemical properties and microbial communities in sludge, have attracted extensive attention. This review mainly describes the presence of microplastics in wastewater treatment plants, and the effects of microplastics on the decontamination efficiency and physicochemical properties of activated sludge, aerobic granular sludge, anaerobic granular sludge and anaerobic ammonium oxidation sludge. Further, the review summarizes the effects of microplastics on microbial activity and microbial community dynamics in various sludges in terms of type, concentration, and contact time. The mechanisms used to strengthen the reduction of microplastics, such as biochar and hydrochar, are also discussed. This review summarizes the mechanism by which microplastics influence the performance of different types of sludge, and proposes effective strategies to mitigate the inhibitive effect of microplastics on sludge and discusses removal technologies of microplastics in sewage. Biochar and hydrochar are one of the effective measures to overcome the inhibition of microplastics on sludge. Meanwhile, constructed wetland may be one of the important choice for the future removal of microplastics from sewage. The goal is to provide theoretical support and insights for ensuring the stable operation of wastewater treatment plants and reducing the impact of microplastics on the environment.


Decreasing intraocular pressure significantly improves retinal vessel density, cytoarchitecture and visual function in rodent oxygen induced retinopathy.
We attempted to explore a noninvasive, easily applicable and economically affordable therapy for retinopathy of prematurity (ROP). Rat pups were raised in 80% oxygen from postnatal day 7 to P12, and returned to room air. Travoprost eye drops were administered twice a day for 7 days, to reduce intraocular pressure (IOP) by about 20%. Immunohistochemical staining was performed to visualize vessel endothelial cells, to analyze retinal neurons and cytoarchitecture. Behavioral experiments were carried out to test visual acuity and contrast sensitivity. At the end of the 7-day treatment, the number of vessels extending to the vitreous body was significantly reduced and retinal vessel density increased. This improvement was maintained to the end of the 12th week. In the central retina of the model group, the horizontal cells were completely wiped out, the outer plexiform layer was undetectable, and the rod bipolar cell dendrites sprouted into the outer nuclear layer. The treatment partially reverted these architectural changes. Most importantly, behavioral experiments revealed significantly improved visual acuity and contrast sensitivity in the treated group. Therefore, reducing IOP could potentially serve as a safe and economical measure to treat ROP.


High-content analysis of cancer genome DNA alterations.
New technologies as well as concerted brute-force approaches have increased the content (number of genes) that can be characterized for genomic DNA alterations. Recent advances include the detection of activating point mutations in key kinase genes (BRAF, EGFR, and PIK3CA) in multiple cancer types: preliminary insight into the entire repertoire of genes that can be mutated in cancer; the discovery of new oncogenes by high-resolution profiling of DNA copy number alterations; and the bioinformatic-driven discovery of oncogenic gene fusions. High-content promoter methylation detection systems have been used to discover additional methylated genes and have provided evidence for a stem cell origin for certain tumors. Some of these advances have had significant impact on the development and clinical testing of new therapeutics.


Tumour suppressor role of microRNA-335-5p in esophageal squamous cell carcinoma by targeting TTK (Mps1).
Esophageal cancer is an aggressive malignancy. miR-335-5p is reported to possess both tumour suppressor and tumour promoter activities in different cancers. We investigated the role of miR-335-5p in esophageal cancer by expression and functional studies. The role of miR-335-5p in ESCC was evaluated using MTT assay, cell cycle analysis, colony formation assay, scratch assay, matrigel invasion, and migration assay. Our expression studies showed a significantly decreased expression of tissue and circulating miR-335-5p in esophageal cancer. Our results herein report a key tumour suppressive role of miR-335-5p in esophageal carcinogenesis by inhibiting proliferation, migration, and invasion in ESCC cells. Using RNA-seq and Insilico analysis we found TTK to be a newly identified direct target and confirmed it by using luciferase assay. Overall, our expression and functional analysis results demonstrated herein point towards the potential role of miR-335-5p in esophageal tumorigenesis. Moreover, this is the first report showing TTK as a downstream target of miR-335-5p.


Effects on age on spinal cord lesion patients' rehabilitation.
The present study was undertaken to focus the age-related characteristics of a population of traumatic and nontraumatic spinal cord patients. to examine demographic, injury and outcome characteristics of older adults with spinal cord lesions as a result of trauma and nontrauma, and to compare these characteristics with those of younger patients in matched cohorts. Spinal Cord Unit, Fondazione Santa Lucia IRCCS, a large rehabilitation hospital of the centre-south of Italy. In total, 284 consecutive newly injured patients with traumatic and nontraumatic spinal cord lesions were retrospectively reviewed and divided according to age into two groups: under 50 years (group 1) and over 50 years (group 2). The following information was collected: onset of lesion to admission; injury variables: aetiology, level, associated injuries, medical complications and surgical intervention; length of stay; American Spinal Injury Association (ASIA) impairment and motor scores; Barthel Index (BI) and Rivermead Mobility Index (RMI) to assess independence in daily living; Walking Index for Spinal Cord Injury to assess ambulation; patients destination at discharge. In a subset of 130 subjects, a block design, matching procedure was used to control for the covariant effects of injury characteristics, time from lesion and aetiology on age effects. In the entire group of 284 patients, older subjects had a higher probability of having incomplete tetraplegia of nontraumatic origin; they also showed a shorter length of stay and a higher rate of complications. In the matched cohorts, younger patients showed better neurologic recovery (intended as ASIA impairment grade improvement and motor scores increase), significantly higher Barthel Index and RMI at discharge, a higher level of independence in spontaneous bladder and bowel management and a higher frequency of independent walking. Older individuals with spinal cord injury and disease do well, but have a less favourable outcome in regard to walking, bladder and bowel independence than younger subjects and have more associated medical problems. Different rehabilitative strategies, therefore, are required for older subjects, which maximises the shorter length of stay and provides the necessary medical care and increased physical assistant resources following discharge.


Studies toward the synthesis of spirolide C: exploration into the formation of the 23-membered all-carbon macrocyclic framework.
The synthesis of two complex subunits en route to spirolide C is described. A key alkyllithium addition to an aldehyde joins the fragments, which are advanced in order to investigate a ring-closing metathesis to form the 23-membered all-carbon macrocyclic framework.


Distally based dorsalis pedis island flap for coverage of the distal portion of the foot.
A distally based dorsalis pedis island flap is described which has been successfully used for reconstructing the distal portion of the foot in two patients with amputation of all 5 toes. The indication for this flap is a wide skin defect of the distal half of the dorsal foot without history of local vascular disorder. The arterial inflow of the flap comes from the posterior tibial artery via the deep plantar branch of the dorsalis pedis artery, while the venous drainage is most likely to be through the venae comitantes of the dorsalis pedis artery to those of the deep branch.


Nigral Pathology Contributes to Microstructural Integrity of Striatal and Frontal Tracts in Parkinson's Disease.
Motor and cognitive impairment in Parkinson's disease (PD) is associated with dopaminergic dysfunction that stems from substantia nigra (SN) degeneration and concomitant α-synuclein accumulation. Diffusion magnetic resonance imaging (MRI) can detect microstructural alterations of the SN and its tracts to (sub)cortical regions, but their pathological sensitivity is still poorly understood. To unravel the pathological substrate(s) underlying microstructural alterations of SN, and its tracts to the dorsal striatum and dorsolateral prefrontal cortex (DLPFC) in PD. Combining post-mortem in situ MRI and histopathology, T1-weighted and diffusion MRI, and neuropathological samples of nine PD, six PD with dementia (PDD), five dementia with Lewy bodies (DLB), and 10 control donors were collected. From diffusion MRI, mean diffusivity (MD) and fractional anisotropy (FA) were derived from the SN, and tracts between the SN and caudate nucleus, putamen, and DLPFC. Phosphorylated-Ser129-α-synuclein and tyrosine hydroxylase immunohistochemistry was included to quantify nigral Lewy pathology and dopaminergic degeneration, respectively. Compared to controls, PD and PDD/DLB showed increased MD of the SN and SN-DLPFC tract, as well as increased FA of the SN-caudate nucleus tract. Both PD and PDD/DLB showed nigral Lewy pathology and dopaminergic loss compared to controls. Increased MD of the SN and FA of SN-caudate nucleus tract were associated with SN dopaminergic loss. Whereas increased MD of the SN-DLPFC tract was associated with increased SN Lewy neurite load. In PD and PDD/DLB, diffusion MRI captures microstructural alterations of the SN and tracts to the dorsal striatum and DLPFC, which differentially associates with SN dopaminergic degeneration and Lewy neurite pathology. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


The link between ADHD-like inattention and obsessions and compulsions during treatment of youth with OCD.
Attention-deficit/hyperactivity disorder (ADHD) has been found to be highly comorbid in children and adolescents with obsessive-compulsive disorder (OCD). Some have proposed, however, that obsessive anxiety may cause inattention and executive dysfunction, leading to inappropriate ADHD diagnoses in those with OCD. If this were the case, these symptoms would be expected to decrease following successful OCD treatment. The present study tested this hypothesis and evaluated whether ADHD symptoms at baseline predicted OCD treatment response. Obsessive-compulsive and ADHD symptoms were assessed in 50 youth enrolled in a randomized controlled trial investigating selective serotonin reuptake inhibitor and cognitive behavioral treatment. Repeated-measures analysis of variance (RMANOVA) revealed that ADHD symptoms at baseline do not significantly predict treatment outcome. A multivariate RMANOVA found that OCD treatment response moderated change in inattention; participants who showed greater reduction in OCD severity experienced greater reduction in ADHD-inattentive symptoms, while those with less substantial reduction in obsessions and compulsions showed less change. These findings suggest that children and adolescents with OCD and inattention may experience meaningful improvements in attention problems following OCD treatment. Thus, in many youth with OCD, inattention may be inherently tied to obsessions and compulsions. Clinicians may consider addressing OCD in treatment before targeting inattentive-type ADHD.


Misclassification of Loss to Care Among Persons with HIV: Improved Capture of Silent Transfers through Surveillance Linkage using Statewide Mandatorily Reported Laboratory Measures.
HIV-positive individuals lost to follow-up from particular clinics may not be lost to care (LTC). After linking Vanderbilt's Comprehensive Care Clinic cohort to Tennessee's statewide HIV surveillance database, LTC decreased from 48.4% to 35.0% at 10 years. Routine surveillance-linkage by domestic HIV clinics would improve LTC and retention measure accuracy.


2-(Dimesitylboryl)phenyl-Substituted [2.2]Paracyclophanes Featuring Intense and Sign-Invertible Circularly Polarized Luminescence.
We have disclosed a new type of [2.2]paracyclophanes that contain a 2-(dimesitylboryl)phenyl and a N,N-disubstituted amino groups at two different phenyl rings. They show intense circularly polarized luminescence combining high fluorescence efficiency (ΦF) and luminescence dissymmetry factor (|glum|), which are up to 0.93 and 1.73 × 10-2, respectively. In addition, the pseudo-meta derivatives display solvent-induced CPL sign inversion owing to the solvent-dependent excited-state dynamics.


Recent progress in sustainable polymers obtained from cyclic terpenes: synthesis, properties, and application potential.
The functionalization and polymerization of biobased monocyclic terpenes and their derivatives for the synthesis of sustainable polymers is described, especially in view of the synthetic routes and properties of the obtained macromolecular architectures. Comparison of these procedures and the obtained materials with "classical" oil-based approaches, and also with alternative biobased routes, gives interesting insights into the potential of these small terpene building-block structures for modern polymer science and technology.


Experimental and clinical experience with iodine 123-labeled iodophenylpentadecanoic acid in cardiology.
Iodine 123-labeled iodophenylpentadecanoic acid (IPPA) has been synthesized for investigating myocardial free fatty acid (FFA) metabolism. The diagnostic application of labeled FFA in heart disease may be important, because FFA is the preferred substrate of cardiac energy metabolism at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation, which is extremely sensitive to oxygen deprivation. This article outlines basic physiologic pathways of cardiac IPPA metabolism in normal, acutely ischemic, and reperfused viable myocardium and summarizes the results of experimental studies in animals, validating the application of IPPA as an 123I-labeled fatty acid analog. In addition, the most important clinical studies indicating the clinical use of IPPA for diagnosis of coronary heart disease and myocardial viability are presented.


Growth or survival: What is the role of calmodulin-like proteins in plant?
Calcium signalling, including pulse, amplitude, and duration, is essential for plant development and response to various stimuli. However, the calcium signalling should be decoded and translated by calcium sensors. In plants, three classes of calcium-binding proteins have been identified as calcium sensors, including calcium-dependent protein kinase (CDPK), calcineurin B-like protein (CBL), and calmodulin (CaM). Calmodulin-like proteins (CMLs), which have several EF-hands, also serve as specific calcium sensors and can sense, bind, and interpret the calcium signal during the plant's growth and defense decision-making processes. In recent decades, the function of CMLs in plant development and response to various stimuli has been systematically reviewed, shedding light on the molecular mechanism of plant CML-mediated networks in calcium signal transduction. Here, by providing an overview of CML expression and biological function in plants, we demonstrate that growth-defense trade-offs occur during calcium sensing, an aspect that has not been well studied in recent years.


Variations in the retinal synapses of the cat superior colliculus revealed using quantitative electron microscope autoradiography.
This study has examined the retinal synapses of the cat superior colliculus using electron microscope autoradiography and morphometric techniques. The depth of each retinal synapse was measured using a computer-based EM plotter. The area, perimeter, and synapse contact density of selected synapses were calculated using a computer-based digitizer. Pale mitochondria were found to be an accurate cytological marker of retinal input to the colliculus. Fifty-eight percent of pale mitochondria terminals were labeled in the colliculus contralateral to eye injections. Ten percent of pale mitochondria terminals were labeled in the ipsilateral colliculus. A few labeled terminals contained dark mitochondria. The labeled retinal terminals in the contralateral colliculus were concentrated in a 60 microns wide dense band at the top of the superficial gray layer. They were also found within the deep superficial gray and upper optic layers. This distribution corresponded exactly to a larger population of pale mitochondria terminals. The cross-sectional area and synaptic contact density of selected pale mitochondria terminals varied with depth. Within the upper superficial gray, the terminals were small (mean area = 1.26 microns squared) and had high contact densities (mean = 0.25 per microns). These small terminals were also found deeper within the colliculus. Below the upper subdivision of the superficial gray, some labeled terminals were much larger and had lower contact densities. These results suggest there may be two subpopulations of retinal terminal in the cat superior colliculus: (1) small terminals with scalloped contours and complex synaptic relationships which may correspond to W-type input; and (2) larger terminals with simpler synaptic relationships which are distributed deeper and may correspond to Y-type input.


Fixation Strategy Does Not Affect Risk of Growth Disturbance After Surgical Treatment of Pediatric Tibial Spine Fracture.
To characterize growth abnormalities after surgical treatment of tibial spine fractures and to investigate risk factors for these abnormalities. A retrospective analysis of children who underwent treatment of tibial spine fractures between January 2000 and January 2019 was performed, drawing from a multicenter cohort among 10 tertiary care children's hospitals. The entire cohort of surgically treated tibial spine fractures was analyzed for incidence and risk factors of growth disturbance. The cohort was stratified into those who were younger than the age of 13 years at the time of treatment in order to evaluate the risk of growth disturbance in those with substantial growth remaining. Patients with growth disturbance in this cohort were further analyzed based on age, sex, surgical repair technique, implant type, and preoperative radiographic measurements with χ2, t-tests, and multivariate logistic regression. Nine patients of 645 (1.4%) were found to have growth disturbance, all of whom were younger than 13 years old. Patients who developed growth disturbance were younger than those without (9.7 years vs 11.9 years, P = .019.) There was no association with demographic factors, fracture characteristics, surgical technique, hardware type, or anatomic placement (i.e., transphyseal vs physeal-sparing fixation) and growth disturbance. In this study, we found an overall low incidence of growth disturbance after surgical treatment of tibial spine fractures. There was no association with surgical technique and risk of growth disturbance. Level III, retrospective comparative study.


Molecular analysis of residual ThinPrep material from thyroid FNAs increases diagnostic sensitivity.
Molecular testing for genetic alterations associated with malignancy is a potential triage approach for thyroid fine-needle aspiration (FNA) samples with indeterminate cytology. Because liquid-based FNA material allows for efficient RNA extraction, the authors analyzed residual material for common point mutations and rearrangements. Thyroid FNAs were classified according to The Bethesda System for Reporting Thyroid Cytopathology after routine ThinPrep slide preparation. Residual samples from malignant and indeterminate cases were submitted for molecular analysis, along with a random cohort of nondiagnostic and benign aspirates. Blinded analysis of BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements was correlated with subsequent follow-up. Adequate results were obtained in 402 of 597 cases (67%). Mutations or rearrangements were detected in 24 of 117 cytologically indeterminate specimens (21%) (17 RAS rearrangements, 6 BRAF rearrangements, and 1 PAX8/PPARγ rearrangement). BRAF mutations were preferentially associated with malignant cytologic diagnoses (22 of 42 cases; 52%), with less frequent detection in the suspicious for malignancy category (4 of 27 cases; 15%) and very low detection in all other categories (1%-4%). Surgical follow-up confirmed malignancy in all 21 BRAF-mutated cases, 42% of RAS-mutated cases (10 of 24 cases), and 37% of cases with no detected mutation (39 of 105 cases). Molecular analysis is feasible on residual ThinPrep material with the advantage of not requiring additional FNA procedures. The majority of BRAF mutations are identified in cases classified cytologically as malignant, and, to a lesser extent, as suspicious for malignancy. The usefulness of BRAF testing is limited by the low rate of BRAF-positive cases in other categories, thereby highlighting the need to identify other genetic drivers of clinically aggressive thyroid cancers.


Effect of Climate Change on Allergenic Airborne Pollen in Japan.
In Japan, the representative allergenic airborne pollen-related allergic diseases include Cupressaceae in early spring, the birch family and grass in spring and mugwort in autumn. As a result of a long- term survey the past 27 to 33 years, an increasing in the amount of conifer airborne pollen and an earlier start dispersal were observed, related climate change. In addition, an increase in the number of patients with Japanese cedar pollinosis and the severity has been observed. Provision of medical pollen information, medication and sublingual immunotherapy have all been enhanced. Recently, pollen-food allergic syndrome has become of increased interest.


Ultrahigh-field magnetic resonance imaging: the clinical potential for anatomy, pathogenesis, diagnosis and treatment planning in neck and spine disease.
An increase of the magnetic field strength to ultrahigh-field yields advantageous as well as disadvantageous changes in physical effects. The beneficial increase in signal/noise ratio can be leveraged into higher spatiotemporal resolution, and an exacerbation of artifacts can impede ultrahigh-field imaging. With the successful introduction of intracranial and musculoskeletal imaging at 7 T, recent advances in coil design have created opportunities for further applications of ultrahigh-field magnetic resonance (MR) imaging in other parts of the body. Initial studies in 7 T neck and spine MR imaging have revealed promising insights and new challenges, demanding further research and methodological optimization.


Development of PCR markers for the Pl5/Pl8 locus for resistance to Plasmopara halstedii in sunflower, Helianthus annuus L. from complete CC-NBS-LRR sequences.
Sunflower downy mildew, caused by Plasmopara halstedii, is one of the major diseases of this crop. Development of elite sunflower lines resistant to different races of this oomycete seems to be the most efficient method to limit downy mildew damage. At least two different gene clusters conferring resistance to different races of P. halstedii have been described. In this work we report the cloning and mapping of two full-length resistance gene analogs (RGA) belonging to the CC-NBC-LRR class of plant resistance genes. The two sequences were then used to develop 14 sequence tagged sites (STS) within the Pl5/Pl8 locus conferring resistance to a wide range of P. halstedii races. These STSs will be useful in marker-assisted selection programs.


Metataxonomic signature of beef burger perishability depends on the meat origin prior grinding.
Spoilage dynamics of two beef burger batches from different beef origins were followed from their shared processing run until the use-by date and beyond. Amplicon based sequencing of bacterial and fungal communities were compared with microbial counts and volatilome profile in order to determine whether and at which extent their perishability was related to the batch origin. Microbiological counts did not differ between batch A and B, whereas Volatile Organic Compounds (VOCs) profiles were only distinguishable after the use-by date. Metataxonomic analysis showed that both batches shared the same initial fungal and bacterial community, which however represented a transient signature of the processing run. Indeed, it was rapidly replaced by batch-autochthonous species of fungi and bacteria. Different temporal succession patterns of psychotropic lactic acid bacteria (LAB) were observed between the batches from the fourth day of vacuum storage. In particular, the sequential dominance of Carnobacterium divergens and Leuconostoc piscium in batch B was correlated with a more heterogeneous volatilome and greater production of VOCs linked to off-odours, such as the acetoin. The metataxonomic survey was able to discriminate between the two batches of hamburgers in relation to their origin and regardless of the initially shared processing-derived contamination.


A genetic model for cloacal exstrophy, the extreme cloacal malformation.
Cloacal exstrophy (CE) or vesicointestinal fissure is an uncommon but well known anomaly that represents the extreme cloacal malformation. It is most often seen as an isolated anomaly, or as part of the OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects). Limb anomalies are also seen with CE. Unlike the OEIS complex, limb anomalies occur as independent malformations. Here, we present two cases of CE with limb anomalies that are consistent with the phenotype seen in Disorganization (Ds), an unusual human malformation syndrome. From reviewing the mouse model, it may be that the Ds gene is a candidate for isolated CE as well.


Bioactive phloroglucinols from Mallotus oppositifolius.
The two new acylphloroglucinol derivatives, methylene-bis-aspidinol AB (1) and mallopposinol (2), together with the nine known compounds, aspidinol B (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of Mallotus oppositifolius. Their structures were elucidated by spectral analysis including MS, 1D and 2D-NMR spectroscopy. In vitro trypanocidal and antileishmanial activities of compounds 1-9 were evaluated. Mallopposinol (2) and aspidinol B (3) displayed weak antileishmanial activities against Leishmania donovani promastigotes, with EC50 values of 21.3 and 38.8μM, respectively. Only the methylene-bis-aspidinol (4) exhibited trypanocidal activity against Trypanosoma brucei brucei trypomastigotes (LC100=0.8μM) similar to the reference drug pentamidine (LC100=0.4μM).


Erratum to: "Rhamnose-Containing Cell Wall Glycopolymers from Rathayibacter toxicus VKM Ac-1600 and "Rathayibacter tanaceti" VKM Ac-2596" [Biochemistry (Moscow), 83, 717 (2018)].
This corrects the article DOI: 10.1134/S0006297918060093.


[Value of pharmacokinetic data during the treatment of psychoses with haloperidol].
Pharmacokinetic data of psychotropic drugs should allow a better understanding of therapeutic results and side effects. The different factors influencing liberation, absorption, protein binding, distribution, metabolism and excretion are reviewed. Then, the principal pharmacokinetic data of haloperidol are exposed with a special emphasis on the lack of information about the correlations between plasma levels and clinical effects. The role of pharmacokinetic informations in the interpretation of responses to treatment is detailed, wishing that the monitoring of haloperidol plasma levels will be more developped in a next future.


Myeloid-Cell-Specific IL-6 Signaling Promotes MicroRNA-223-Enriched Exosome Production to Attenuate NAFLD-Associated Fibrosis.
NAFLD is associated with elevation of many cytokines, particularly IL-6; however, the role of IL-6 in NAFLD remains obscure. The aim of this study was to examine how myeloid-specific IL-6 signaling affects NAFLD by the regulation of antifibrotic microRNA-223 (miR-223) in myeloid cells. Patients with NAFLD or NASH and healthy controls were recruited, and serum IL-6 and soluble IL-6 receptor α (sIL-6Rα) were measured. Compared to controls, serum IL-6 and sIL-6Rα levels were elevated in NAFLD/NASH patients. IL-6 levels correlated positively with the number of circulating leukocytes and monocytes. The role of IL-6 in NAFLD was investigated in Il6 knockout (KO) and Il6 receptor A (Il6ra) conditional KO mice after high-fat diet (HFD) feeding. HFD-fed Il6 KO mice had worse liver injury and fibrosis, but less inflammation, compared to wild-type mice. Hepatocyte-specific Il6ra KO mice had more steatosis and liver injury, whereas myeloid-specific Il6ra KO mice had a lower number of hepatic infiltrating macrophages (IMs) and neutrophils with increased cell death of these cells, but greater liver fibrosis (LF), than WT mice. Mechanistically, the increased LF in HFD-fed, myeloid-specific Il6ra KO mice was attributable to the reduction of antifibrotic miR-223 and subsequent up-regulation of the miR-223 target gene, transcriptional activator with PDZ-binding motif (TAZ), a well-known factor to promote NASH fibrosis. In vitro, IL-6 treatment up-regulated exosome biogenesis-related genes and subsequently promoted macrophages to release miR-223-enriched exosomes that were able to reduce profibrotic TAZ expression in hepatocytes by exosomal transfer. Finally, serum IL-6 and miR-223 levels were elevated and correlated with each other in NAFLD patients. Myeloid-specific IL-6 signaling inhibits LF through exosomal transfer of antifibrotic miR-223 into hepatocytes, providing therapeutic targets for NAFLD therapy.


Fundus autofluorescence after full macular translocation surgery for myopic choroidal neovascularization.
To investigate fundus autofluorescence (FAF) findings in patients who underwent full macular translocation surgery with 360-degree retinotomy (MT360) for myopic choroidal neovascularization (CNV). Observational case series. Thirty-one eyes of 31 patients who underwent MT360 for myopic CNV from February 1999 through September 2005 were included. We measured the best-corrected visual acuity and obtained color fundus photographs, optical coherence tomography (OCT) images, and fluorescein angiography images. FAF imaging by confocal scanning laser ophthalmoscope was obtained postoperatively in all study eyes and preoperatively in two study participants. FAF features at the new macula were qualitatively evaluated and compared with preoperative lesions associated with CNV. The FAF features at the retinal pigment epithelial (RPE) area with preoperative CNV also were evaluated. The mean interval between MT360 and the final FAF examination was 58 months (range, 8-94 months). FAF imaging was almost normal in five eyes (16%), the increased FAF was well defined at the new macula area in 23 eyes (74%), and the FAF was decreased in three eyes (10%). Neither newly developed CNV nor subretinal fluid was seen at the new macular region in any eyes on fluorescein angiography or OCT imaging. The configurations of well-defined increased FAF in 23 eyes corresponded with the preoperative CNV in two eyes (9%) and subretinal hemorrhages in five eyes (22%). Well-defined increased FAF larger than the CNV or subretinal hemorrhage was seen in 16 eyes (69%). The RPE area located at the area of the preoperative CNV had a FAF defect or decreased FAF in 30 eyes (97%) on postoperative FAF imaging; there were no increased FAF changes. Well-defined increased FAF at the new macula after MT360 suggests that FAF reflects not only fluorophores in the RPE but also in the neurosensory retina. These fluorophores may result from interactions between the retina and CNV/pathologic RPE.


Stimulation of V1a receptor increases renal uric acid clearance via urate transporters: insight into pathogenesis of hypouricemia in SIADH.
Hypouricemia is pathognomonic in syndrome of inappropriate secretion of antidiuretic hormone (SIADH) but the underlying mechanism remains unclear. Based on the previous studies, we hypothesized that V1a receptor may play a principal role in inducing hypouricemia in SIADH and examined uric acid metabolism using a rat model. Terlipressin (25 ng/h), a selective V1a agonist, was subcutaneously infused to 7-week-old male Wistar rats (n = 9). Control rats were infused with normal saline (n = 9). The rats were sacrificed to obtain kidney tissues 3 days after treatment. In addition to electrolyte metabolism, changes in expressions of the urate transporters including URAT1 (SLC22A12), GLUT9 (SLC2A9), ABCG2 and NPT1 (SLC17A1) were examined by western blotting and immunohistochemistry. In the terlipressin-treated rats, serum uric acid (UA) significantly decreased and the excretion of urinary UA significantly increased, resulting in marked increase in fractional excretion of UA. Although no change in the expression of URAT1, GLUT9 expression significantly decreased whereas the expressions of ABCG2 and NPT1 significantly increased in the terlipressin group. The results of immunohistochemistry corroborated with those of the western blotting. Aquaporin 2 expression did not change in the medulla, suggesting the independence of V2 receptor stimulation. Stimulation of V1a receptor induces the downregulation of GLUT9, reabsorption urate transporter, together with the upregulation of ABCG2 and NPT1, secretion urate transporters, all changes of which clearly lead to increase in renal UA clearance. Hypouricemia seen in SIADH is attributable to V1a receptor stimulation.


Cognitive and neuropsychological examination of the elderly.
Neuropsychological assessment plays a prominent role in the evaluation and care of patients with neurodegenerative diseases throughout the dynamic course of disease. As a biomarker of disease, neuropsychological measurement can distinguish normal from pathologic aging processes. Further, neuropsychological data can help distinguish and classify underlying pathologies in dementing diseases, augmenting imaging and biofluid markers in this area. Neuropsychological data can predict increased or reduced risk for dementia conferred by multiple factors, and describe disease trajectory in affected individuals. Cognitive evaluation can also estimate and address functional outcomes that are most important to patients and their loved ones and that are clinically relevant to diagnostic staging. In informing intervention and patient care needs, areas of cognitive weakness highlight targets for support/intervention, while areas of cognitive strength can be capitalized upon to modify the clinical course of disease. These functions can be accomplished through the complementary use of brief screening tools and comprehensive test batteries. However, for neuropsychological data to serve these functions, it is critical to understand neuropsychological test properties and nondisease factors that can account for variance in test performance. This chapter concludes with directions for future research.


Shifting ground for big data researchers.
To harness the strength of data sets growing by leaps and bounds every day, cultural norms in biomedical research are under pressure to change with the times.


Divergent effects of oncostatin M on astroglioma cells: influence on cell proliferation, invasion, and expression of matrix metalloproteinases.
Oncostatin M (OSM), a cytokine of the interleukin-6 (IL-6) family, can either promote or inhibit cell growth in various normal and tumor cells. We addressed the effects of exogenous OSM on the proliferation and invasion of human astroglioma cells. In addition, we investigated one of the possible mechanisms involved: modulation of matrix metalloproteinase (MMP) expression and enzymatic activity. We found that OSM inhibited the proliferation of two human astroglioma cell lines (CH235-MG and U87-MG), and that this effect was not due to apoptosis. The inhibitory effect of OSM on proliferation was mediated through the gp130/OSMRbeta receptor complex. To extend these findings, we analyzed the effects of OSM on primary tumor cells from glioblastoma patients. OSM suppressed the proliferation of primary glioblastoma cells, but not that of normal astrocytes. Interestingly, OSM did not suppress astroglioma cell invasion. This may be due to the differential regulation of MMPs by OSM. We found that OSM inhibited the constitutive expression of MMP-2, while MMP-9 expression was enhanced in astroglioma cell lines. We conclude that OSM inhibits proliferation of human astroglioma cells and primary glioblastoma cells via the gp130/OSMRbeta receptor complex. However, OSM does not affect the invasive capacity of the astroglioma cells, which may be due to the divergent effects of OSM on MMP-2 and MMP-9 expression. Collectively, these findings suggest a complex role for OSM in astroglioma biology.


A thematic analysis assessing clinical decision-making in antipsychotic prescribing for schizophrenia.
In recent decades atypical antipsychotics have increased treatment options available for schizophrenia, however there is conflicting evidence concerning the trade-off between clinical efficacy and side effects for the different classes of antipsychotics. There has been a consistent increase in atypical antipsychotic prescribing compared to typical, despite evidence showing that neither class is superior. This leads to the question of whether prescribers are selective in their uptake of research evidence and clinical guidelines and if so, what influences their choice.. This study aims to identify the factors that contribute to the prescribing choice and how these can be used to aid knowledge translation and guideline implementation. A thematic analysis study was conducted using data from 11 semi-structured interviews with clinicians with experience in prescribing for schizophrenia. The analysis identified five themes underpinning prescribing behaviour: (1) ownership and collaboration; (2) compromise; (3) patient involvement; (4) integrating research evidence; and (5) experience. The themes mapped to various degrees onto current models of evidence-based decision making and suggest that there is scope to re-think the guideline implementation frameworks to incorporate recurring themes salient to clinicians who ultimately use the guidelines. This will further translation of future evidence into clinical practice, accelerating clinical progress.


Lipoxin synthesis by arachidonate 5-lipoxygenase purified from porcine leukocytes.
Arachidonate 5-lipoxygenase purified from porcine leukocytes produced several more polar compounds from 5,15-dihydroperoxy-eicosatetraenoic acid added as such or generated from 15-hydroperoxy acid. These polar products with absorption maxima at 301-302 nm and shoulders at 289 nm and 316-317 nm were identified as 5S,6R,15S-11-cis-lipoxin A and its 6-epimer, all-trans-lipoxin A isomers, and all-trans-lipoxin B isomers. Most of these lipoxins were presumably degradation products of a 5,6-epoxy intermediate formed by the catalysis of leukotriene A synthase, an integral part of 5-lipoxygenase. The rate of the enzymatic lipoxin synthesis from 15-hydroperoxy acid was about 6% of arachidonate 5-oxygenation.


Methods for Functional Characterization of the Type IX Secretion System of Porphyromonas gingivalis.
The type IX secretion system (T9SS) is a protein secretion system for gingipain proteases and is found on the cell surface of Porphyromonas gingivalis. Proteins secreted by T9SS contain a signal peptide, functional domains, an immunoglobulin (Ig)-like domain, and a C-terminal domain (CTD). Thirty genes on the P. gingivalis chromosome encode proteins that possess the CTD, which is important for T9SS-mediated translocation to the cell surface across the outer membrane. In T9SS mutant strains, proteins accumulate as precursors in the cell and therefore exhibit a phenotype similar to that of secreted protein-deficient mutants. Black pigment productivity and hemagglutination are phenotypic features of P. gingivalis associated with the activity of gingipains. In P. gingivalis T9SS mutants, unprocessed gingipains with high molecular weights accumulate in the cell, and colony pigmentation and hemagglutination are not observed in the same phenotype as a gingipain null mutant.


Eubacteria have 3 growth modes keyed to nutrient flow. Consequences for the concept of maintenance and maximal growth yield.
Aerobic growth of Escherichia coli and Paracoccus denitrificans has been studied in chemostat, fed batch, and recycling fermentor modes under carbon and energy limitation. Two abrupt drops or discontinuities in molar growth yield, Y, have been found that occur over relatively short ranges in the value of specific growth rate. Before the first discontinuity, Y is constant and maximal. After the first discontinuity, at a doubling time of 33 h, Y becomes constant again and independent of mu until the second discontinuity appears at a doubling time of about 50 h, corresponding to a mu of about 0.014. At this point, Y drops to a lower value that is constant at doubling times longer than 100 h, corresponding to a mu of about 0.007. The second discontinuity is associated in Paracoccus with elevated levels of guanosine tetraphosphate (ppGpp) that impose stringent regulation as has been found previously with Bacillus and Escherichia species. It is thus likely that the stringent response generally occurs in bacteria in vivo at a doubling time of about 50 h. The cause of the first discontinuity is unknown. All experiments indicate that Pirt-type calculations relating mu, Y, and maintenance energy demand are no longer valid. In chemostat experiments, the intercept of the relationship between specific substrate utilization and specific growth rate is defined as maintenance. However, this intercept most probably is caused by stringent regulation at low dilution rates. Three regions of bacterial growth rates are defined by this study, corresponding to doubling times of 0.5 to 15 h, 33 to 50 h, and greater than 100 h. Some growth behavior in each region is unique to that region.


Toxicity assessment of zebrafish following exposure to CdTe QDs.
CdTe quantum dots (QDs) are nanocrystals of unique composition and properties that have found many new commercial applications; therefore, their potential toxicity to aquatic organisms has become a hot research topic. The lab study was performed to determine the developmental and behavioral toxicities to zebrafish under continuous exposure to low concentrations of CdTe QDs (1-400 nM) coated with thioglycolic acid (TGA). The results show: (1) the 120 h LC(50) of 185.9 nM, (2) the lower hatch rate and body length, more malformations, and less heart beat and swimming speed of the exposed zebrafish, (3) the brief burst and a higher basal swimming rate of the exposed zebrafish larvae during a rapid transition from light-to-dark, and (4) the vascular hyperplasia, vascular bifurcation, vascular crossing and turbulence of the exposed FLI-1 transgenic zebrafish larvae.


The assessment of developmental trauma in children and adolescents: A systematic review.
The assessment of children and young people with history of complex developmental trauma presents a significant challenge to services. Traditional diagnostic categories such as post-traumatic stress disorder (PTSD) are argued to be of limited value, and while the proposed 'Developmental Trauma Disorder' definition attempts to address this debate, associated assessment tools have yet to be developed. This review builds on a previous review of assessment measures, undertaken in 2005. To identify trauma assessment tools developed or evaluated since 2004 and determine which are developmentally appropriate for children or adolescents with histories of complex trauma. A systematic search of electronic databases was conducted with explicit inclusion and exclusion criteria. A total of 35 papers were identified evaluating 29 measures assessing general functioning and mental health ( N = 10), PTSD ( N = 7) and trauma symptomatology outside, or in addition to, PTSD ( N = 11). Studies were evaluated on sample quality, trauma/adversity type, as well as demographic and psychometric data. Distinction was made between measures validated for children (0-12 years) and adolescents (12-18 years). Few instruments could be recommended for immediate use as many required further validation. The Assessment Checklist questionnaires, designed with a developmental and attachment focus, were the most promising tools.


Is severe pain immediately after spinal augmentation a predictor of long-term outcomes?
Severe, immediate postprocedural pain and the need for analgesics after vertebroplasty can be a discouraging experience for patients and caregivers. The goal of this study was to investigate whether the presence of severe pain immediately after vertebroplasty predicts short- and long-term pain relief. A chart review was performed to categorize patients regarding pain severity and analgesic usage immediately after vertebroplasty (< 4 h). "Severe" pain was defined as at least 8 of 10 with the 10-point VAS. Outcomes were pain severity and pain medication score and usage at 1 month and 1 year after vertebroplasty. Outcomes and clinical characteristics were compared between groups by using the Wilcoxon signed-rank test and the Fisher exact test. Of the 429 vertebroplasty procedures identified, 69 (16%) were associated with severe pain, and 133 (31%) were associated with analgesic administration immediately after the procedure. The group experiencing severe pain had higher preprocedure median VAS rest pain scores (5 [IQR, 2-7]) and activity pain scores (10 [IQR, 8-10]) compared with patients who did not experience severe pain (3 [IQR, 1-6]; P = .0208, and 8 [IQR, 7-10]; P = .0263, respectively). At 1 month postprocedure, VAS rest and activity pain scores were similar between the severe pain group and the nonsevere pain group (P = .16 and P = .25, respectively) and between the group receiving pain medication and the group not receiving pain medication (P = .25 and P = .67, respectively). This similarity continued for 1 year after the procedure. Analgesic usage was similar among all groups at 1 year postprocedure. Patients with severe pain immediately after vertebroplasty have similar long-term outcomes compared with patients without severe pain.


Effects of amphetamine and nembutal on social exploration in the Mongolian gerbil.
Male Mongolian gerbils were injected intraperitoneally with amphetamine, nembutal, or saline and placed in a preference chamber one side of which contained a female gerbil. Amphetamine significantly decreased amount of time in contact with the females. Although the amphetamine effect held for both novel and familiar females, it was more marked for novel than for familiar females.


Immunomodulatory and anti-SARS activities of Houttuynia cordata.
Severe acute respiratory syndrome (SARS) is a life-threatening form of pneumonia caused by SARS coronavirus (SARS-CoV). From late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in China. Owing to the absence of definitive therapeutic Western medicines, Houttuynia cordata Thunb. (Saururaceae)(HC) was shortlisted by Chinese scientists to tackle SARS problem as it is conventionally used to treat pneumonia. The present study aimed to explore the SARS-preventing mechanisms of HC in the immunological and anti-viral aspects. Results showed that HC water extract could stimulate the proliferation of mouse splenic lymphocytes significantly and dose-dependently. By flow cytometry, it was revealed that HC increased the proportion of CD4(+) and CD8(+) T cells. Moreover, it caused a significant increase in the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In the anti-viral aspect, HC exhibited significant inhibitory effects on SARS-CoV 3C-like protease (3CL(pro)) and RNA-dependent RNA polymerase (RdRp). On the other hand, oral acute toxicity test demonstrated that HC was non-toxic to laboratory animals following oral administration at 16 g/kg. The results of this study provided scientific data to support the efficient and safe use of HC to combat SARS.


Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): primary analysis of a randomised, phase 2 trial.
The introduction of immunomodulatory agents, proteasome inhibitors, and autologous haematopoietic stem-cell transplantation has improved outcomes for patients with multiple myeloma, but patients with high-risk multiple myeloma have a poor long-term prognosis. We aimed to address optimal treatment for these patients. SWOG-1211 is a randomised phase 2 trial comparing eight cycles of lenalidomide (25 mg orally on days 1-14 every 21 days), bortezomib (1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11 every 21 days), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12 every 21 days; RVd) induction followed by dose-attenuated RVd maintenance (bortezomib 1 mg/m2 subcutaneously on days 1, 8, and 15; lenalidomide 15 mg orally on days 1-21; dexamethasone 12 mg orally on days 1, 18, and 15 every 28 days) until disease progression with or without elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, on days 1 and 11 for cycles 3-8, and on days 1 and 15 during maintenance). Patients were randomly assigned (1:1) to either RVd or RVd-elotuzumab. High-risk multiple myeloma was defined by one of the following: gene expression profiling high risk (GEPhi), t(14;16), t(14;20), del(17p) or amp1q21, primary plasma cell leukaemia and elevated serum lactate dehydrogenase (two times the upper limit of normal or more). The primary endpoint was progression-free survival, and all analyses were done on intention-to-treat basis among eligible patients who were evaluable for response. This study is registered with ClinicalTrials.gov, NCT01668719. 100 (RVd n=52, RVd-elotuzumab n=48) patients were enrolled between Oct 27, 2013, and May 15, 2016, across 26 cooperative group institutions in the USA. Median age was 64 years (IQR 57-70, range 36-85). 74 (75%) of 99 had International Staging System stage II or stage III disease, 47 (47%) of 99 had amp1q21, 37 (37%) of 100 had del17p, 11 (11%) of 100 had t(14;16), eight (9%) of 90 were GEPhi, seven (7%) of 100 had primary plasma cell leukaemia, five (5%) of 100 had t(14;20), four (4%) of 100 had elevated serum lactate dehydrogenase, and 17 (17%) had two or more features. With a median follow-up of 53 months (IQR 46-59), no difference in median progression-free survival was observed (RVd 33·64 months [95% CI 19·55-not reached], RVd-elotuzumab 31·47 months [18·56-53·98]; hazard ratio 0·968 [80% CI 0·697-1·344]; one-sided p=0·45]. 37 (71%) of 52 patients in the RVd group and 37 (77%) of 48 in the RVd-elotuzumab group had grade 3 or worse adverse events. No significant differences in the safety profile were observed, although some notable results included grade 3-5 infections (four [8%] of 52 in the RVd group, eight [17%] of 48 in the RVd-elotuzumab group), sensory neuropathy (four [8%] of 52 in the RVd group, six [13%] of 48 in the RVd-elotuzumab group), and motor neuropathy (one [2%] of 52 in the RVd group, four [8%] of 48 in the RVd-elotuzumab group). There were no treatment-related deaths in the RVd group and one death in the RVd-elotuzumab group for which study treatment was listed as possibly contributing by the investigator. In the first randomised study of high-risk multiple myeloma reported to date, the addition of elotuzumab to RVd induction and maintenance did not improve patient outcomes. However, progression-free survival in both study groups exceeded the original statistical assumptions and supports the role for continuous proteasome inhibitors and immunomodulatory drug combination maintenance therapy for this patient population. National Institutes of Health, National Cancer Institute, Bristol Myers Squibb, Celgene, Leukemia and Lymphoma Society.


The prevalence of freezing of gait in Parkinson's disease and in patients with different disease durations and severities.
The prevalence rates of freezing of gait (FOG) in Parkinson's disease (PD) vary widely, ranging from 14.0 to 55.1%. Our aim is to calculate the overall prevalence of FOG in all PD patients with different disease durations and severities. Using Medline/PubMed/Embase, we carried out a systematic literature search for studies reporting the PD and clinically relevant FOG. After primary screening, a total of 35 studies were identified and further analyzed for inclusion into the analysis, and 29 studies fulfilled the quality criteria and included in this meta-analysis. The overall prevalence of FOG in PD was 39.9% (95% CI 35.3-44.5%). The FOG identified by the freezing of gait questionnaire item 3 may be more prevalent (43.8%, 95% CI 38.5-49.1%) than the FOG identified by the Unified Parkinson's Disease Rating Scale item 14 (36.0%, 95% CI 29.0-43.1%). Disease duration and severity are both the clinical features associated with the FOG. The highest FOG prevalence rate in PD patients was seen in patients with disease durations ≥ 10 years, at 70.8%, followed that of PD patients with disease durations ≥ 5 years (53.3%), and PD patients with disease durations < 5 years (22.4%). FOG presented in 28.4% of PD patients with Hoehn and Yahr staging (H&Y) score ≤ 2.5, and in 68.4% of PD patients with H&Y score ≥ 2.5. This meta-analysis confirms that the prevalence of FOG in PD is considerable, and highlights the need for accurate identification of FOG in PD.


Neuropsychiatric sequelae one year after a minor head injury.
To assess neuropsychiatric sequelae 1 year after minor head injury in a cross sectional study using home interviews with patients and their relatives at 1 year after head injury. The study cohort included 148 adults who were admitted to hospital after a minor head injury between 1 July 1994 and 30 June 1995 and showed clinical or radiological evidence of brain injury. Main outcome measures used in the study were the Glasgow outcome scale, Edinburgh rehabilitation status scale, Barthel index, clinical interview schedule-revised, mini mental state examination, and assessment of symptoms of postconcussional syndrome. At one year follow up, four (2.9%) patients had a severe disability, 35 (25.5%) had a moderate disability, and 95 (69.3%) had no disability according to the Glasgow outcome scale. A slightly higher proportion (33.3%, n=45) showed disability according to the Edinburgh rehabilitation status scale. Thirty one patients (23.1%) scored <24 in the mini mental state examination. These were mostly patients over the age of 65. Twenty three patients (17.2%) were diagnosed as psychiatric cases according to the clinical interview schedule-revised scale. Seventy four (55.2%) patients showed one of the symptoms of postconcussional syndrome. The most commonly shown neurobehavioural problems were irritability (30%), sleep disturbance (29%), and impatience (27%). One year after a minor head injury, a substantial proportion of patients showed neuropsychiatric sequelae.


The impact of allogenic blood transfusion on the outcomes of total pancreatectomy with islet autotransplantation.
Allogenic blood transfusion (ABT) may be needed for severe bleeding during total pancreatectomy with autotransplantation (TPIAT), but may induce inflammation. This study investigated the impact of ABT. With a population of 83 patients who underwent TPIAT from 2006 to 2014, this study compared cytokine levels, patient characteristics, islet characteristics, metabolic outcomes, insulin requirements, and hemoglobin A1c for those who received a blood transfusion (BT) versus no blood transfusion (NBT). Initially, proinflammatory cytokines were moderately higher in the BT group than the NBT group. Despite longer procedures and more severe bleeding, the BT group had similar values to the NBT group for insulin requirements, serum C-peptide, hemoglobin A1c, and insulin independence rate. The probability of insulin independence was slightly higher in patients receiving ≥3 units of blood. ABT induced elevation of proinflammatory cytokines during the perioperative period in TPIAT, but these changes did not significantly change posttransplant islet function.


Preparation and characterization of superhydrophobic organic-inorganic hybrid cotton fabrics via γ-radiation-induced graft polymerization.
A new kind of non-fluorine-based organic-inorganic hybrid superhydrophobic cotton fabric was successfully prepared by simultaneous radiation-induced graft polymerization of γ-methacryloxypropyl trimethoxy silane (MAPS) and subsequent end-capping modification with hexamethyldisilazane (HMDS). The chemical structure and surface topography of the pristine and modified cotton fabrics were investigated in detail by ATR-FTIR, XPS, (29)Si NMR, SEM and TGA to confirm that the graft reaction and end-capping modification had taken place. The above results demonstrated that the grafting polymerization and following end-capping reaction were completed, and a grafting layer was immobilized onto the surface of the cotton fabric. Surface wettability measurement and oil-water separation showed that the modified cotton surface not only exhibited the superhydrophobicity with a water contact angle of 165°, but also afforded a high efficiency of oil-water separation (96%). In particular, this modified cotton fabric retains superhydrophobicity even after 30 laundering cycles or 400 cycles of abrasion.


Centrosomal protein DZIP1 regulates Hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis.
The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery. Functionally, both CEP164 and Ninein appendage proteins fail to localize to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary cilia in Dzip1 mutant cells. Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog signaling through a dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.


Mapping of mitochondrial DNA of individual sheep and goats: rapid evolution in the D loop region.
Mitochondrial DNA (mtDNA) from sheep and goat was compared by restriction endonuclease analysis and heteroduplex mapping in the electron microscope. The fragment patterns produced by endonuclease Hae III from three individual sheep and two goat mtDNAs all differed from each other. The three sheep mtDNAs had identical Eco RI and Hind III fragments, but the two goat mtDNA patterns differed from each other as well as from sheep mtDNA. We estimate that each sheep mtDNA differs from each other by 0.5-1% of its nucleotide sequences, the two goat mtDNAs by 1-2%, and there is a 6-11% sequence difference between sheep and goat mtDNAs. We have mapped the Eco RI and Hind III sites of goat and sheep mtDNA and determined the positions of the D loop, which marks the replication origin, relative to the restriction map. The D loops are at homologous positions on the mtDNAs from both species, but the goat D loop is only 75% as long as the sheep D loop. Regions with a high degree of sequence divergence occur at both ends of the D loop. We suggest that a duplication of about 150 base pairs has occurred in the region where the sheep and goat D loops differ in length. We discuss mtDNA evolution in terms of divergence of isolated "mitochondrial DNA clones."


The stepping pattern of myosin X is adapted for processive motility on bundled actin.
Myosin X is a molecular motor that is adapted to select bundled actin filaments over single actin filaments for processive motility. Its unique form of motility suggests that myosin X's stepping mechanism takes advantage of the arrangement of actin filaments and the additional target binding sites found within a bundle. Here we use fluorescence imaging with one-nanometer accuracy to show that myosin X takes steps of ∼18 nm along a fascin-actin bundle. This step-size is well short of the 36-nm step-size observed in myosin V and myosin VI that corresponds to the actin pseudohelical repeat distance. Myosin X is able to walk along bundles with this step-size if it straddles two actin filaments, but would be quickly forced to spiral into the constrained interior of the bundle if it were to use only a single actin filament. We also demonstrate that myosin X takes many sideways steps as it walks along a bundle, suggesting that it can switch actin filament pairs within the bundle as it walks. Sideways steps to the left or the right occur on bundles with equal frequency, suggesting a degree of lateral flexibility such that the motor's working stroke does not bias it to the left or to the right. On single actin filaments, we find a broad mixture of 10-20-nm steps, which again falls short of the 36-nm actin repeat. Moreover, the motor leans to the right as it walks along single filaments, which may require myosin X to adopt strained configurations. As a control, we also tracked myosin V stepping along actin filaments and fascin-actin bundles. We find that myosin V follows a narrower path on both structures, walking primarily along one surface of an actin filament and following a single filament within a bundle while occasionally switching to neighboring filaments. Together, these results delineate some of the structural features of the motor and the track that allow myosin X to recognize actin filament bundles.


Evaluation of rain-shelter cultivation mode effects on microbial diversity during Cabernet Sauvignon (Vitis vinifera L.) maturation in Jingyang, Shaanxi, China.
Rainfall particularly under continental climates with monsoonal tendency impacts the vineyard microbial niches during grapevine growth. With microbial community shifts, vine traits (grape flavor and yield) cultivated/protected under rain-shelter may ultimately be altered. Such cultivation may influence microflora dynamics via meteorological parameter variations, however this is unclear yet. Here, we used Cabernet Sauvignon, a prevalent red cultivar among wine growing regions, to evaluate the effects of the rain-shelter cultivation on the microorganism diversity. We found that average air temperature under rain-shelter conditions was 2-3 °C higher than the non-covered group, while air humidity the maximum reduction was 5.79% (p < 0.05). After grape setting stage, similar trends were observed on soil temperature (increased) and humidity (lowered) under the treatments (p < 0.05). UV and precipitation of rain-shelter treatment were less by a total of 72% and 96%, respectively (p < 0.05). The rain-shelter management presented lower fungal and bacterial OTUs. The fungal alpha diversity on leaves and branches under rain-shelter was lower (p < 0.05) than the control as the grape ripeness, with Ascomycota, Mycosphaerella and Cladosporium as the principal fungi. Our results revealed that the fungal microbiota patterns were differentiated by the cultivations from setting stage to the entire véraison and then tended to be similar at harvesting. Only branch fungal patterns were observed asymmetrically at all stages. Meanwhile, bacterial diversity and distribution varied on colonization locations where Proteobacteria and Actinobacteria were the primary bacteria phyla. Bacterial community structures overlapped at harvest, while the differences were observed between two cultivations at other stages, excluding grape berry. The rain-shelter cultivation reduced the abundance of Alternaria and Colletotrichum that may adversely affect grapevine health. Multivariate statistical analysis suggested that the effect of vineyard microclimate on microbiota distribution and succession were influenced by cultivation modes and grapevine developmental stages. This research provides evidence to address the dynamics of microbial ecology from vineyard to grape under rain-shelter cultivation, and its benefits as a sustainable vineyard management.


A simple, inexpensive technique to permit the half-axial projection in laboratories with single plane cineangiography.
A simple inexpensive modification to permit x-ray beam angulation of a cineradiographic system consisting of a ceiling-suspended image intensifier and an under-the-table x-ray tube is described. This has permitted the incorporation of the half-axial projection into the routine evaluation of the proximal left anterior descending artery (LAD) with a minimum of patient discomfort.


Extensive Hidden Genomic Mosaicism Revealed in Normal Tissue.
Genomic mosaicism arising from post-zygotic mutation has recently been demonstrated to occur in normal tissue of individuals ascertained with varied phenotypes, indicating that detectable mosaicism may be less an exception than a rule in the general population. A challenge to comprehensive cataloging of mosaic mutations and their consequences is the presence of heterogeneous mixtures of cells, rendering low-frequency clones difficult to discern. Here we applied a computational method using estimated haplotypes to characterize mosaic megabase-scale structural mutations in 31,100 GWA study subjects. We provide in silico validation of 293 previously identified somatic mutations and identify an additional 794 novel mutations, most of which exist at lower aberrant cell fractions than have been demonstrated in previous surveys. These mutations occurred across the genome but in a nonrandom manner, and several chromosomes and loci showed unusual levels of mutation. Our analysis supports recent findings about the relationship between clonal mosaicism and old age. Finally, our results, in which we demonstrate a nearly 3-fold higher rate of clonal mosaicism, suggest that SNP-based population surveys of mosaic structural mutations should be conducted with haplotypes for optimal discovery.


Mitochondria-targeted nanozymes eliminate oxidative damage in retinal neovascularization disease.
Retinal neovascularization is typically accompanied by hypoxia-induced oxidative injury in the vascular system. This study developed an ultrasmall (6-8 nm) platinum (Pt) nanozyme loaded mitochondria-targeted liposome (Pt@MitoLipo) to alleviate hypoxia and eliminate excess reactive oxygen species (ROS) for effective retinal neovascularization disease therapy. Pt nanozymes possess superoxide dismutase (SOD) and catalase (CAT) cascade enzyme-like activities, which convert cytotoxic O2•- and H2O2 into nontoxic H2O and O2. Triphenylphosphonium (TPP)-conjugated liposomes were coated on the surface of Pt nanozymes to increase their biocompatibility and help them penetrate the cell membrane, escape from the lysosomal barrier, and target mitochondria, thus achieving precise scavenging of mitochondrial O2•- and relief from hypoxia. Using an oxygen-induced retinopathy (OIR) mouse model, we demonstrated that Pt@MitoLipo nanozymes significantly suppressed hypoxia-induced abnormal neovascularization and facilitated avascular normalization of the retina in vivo without any noticeable toxicity. This study provides a promising way to break through cellular barriers and target scavenging mitochondrial O2•- and illustrates the potential of ROS-scavenging and hypoxia relief in retinal neovascularization disease therapy.


Strategies to improve communication about neurocognitive impacts in pediatric oncology: Quality improvement findings.
Neurocognitive deficits are common among children who receive central nervous system (CNS)-directed therapy for childhood cancer. Parents report that they lack information from and communication with oncology providers about neurocognitive impacts of therapy. Furthermore, oncology providers report they lack training and institutional support to appropriately address the neurocognitive needs of these patients/families. A parent/provider stakeholder informed, quality improvement (QI) project was conducted to educate providers about neurocognitive impacts, increase parent/provider communication, and improve adherence to supportive care guidelines for neuropsychological assessment for children receiving CNS-directed therapy. A 1-h Continuing Medical Education (CME) course was developed to educate providers about neurocognitive impacts and their relation to schooling. A provider-focused electronic medical record (EMR) strategy was used to deliver parent stakeholder-informed return-to-school "roadmaps," with prompts to scaffold parent/provider communication and enhance documentation of findings. Hospital-based CME sessions were attended by 76% (41 out of 54) of providers from our institution. Among the 34 who completed both pretest and posttest, the mean knowledge score improved from 56% at pretest to 74% at posttest. Compliance with the EMR strategy was 80% and there was a 42% increase in neuropsychological assessment referrals. We conclude that this QI project is an example of a successful parent/provider stakeholder collaboration that achieved demonstrable positive change in the areas of provider knowledge, patient/provider communication, and alignment of neuropsychological assessment referrals with existing guidelines. Our results confirm that improving knowledge, communication, and compliance with neuropsychological standards of care is possible with this evidence-based approach.


Staphylococcal alpha toxin--recent advances.
The elucidation of the amino acid sequence of alpha toxin in 1984 has greatly promoted our understanding of the basic biochemistry and interaction of this toxin with membranes. These aspects are discussed and the concept of alpha toxin as a channel forming protein is critically evaluated. The lethal action of alpha toxin has not yet been clarified, but the previously postulated action as a neurotoxin is not supported by recent observations.


Proline residues in the maturation and degradation of peptide hormones and neuropeptides.
The proteases involved in the maturation of regulatory peptides like those of broader specificity normally fail to cleave peptide bonds linked to the cyclic amino acid proline. This generates several mature peptides with N-terminal X-Pro-sequences. However, in certain non-mammalian tissues repetitive pre-sequences of this type are removed by specialized dipeptidyl (amino)peptidases during maturation. In mammals, proline-specific proteases are not involved in the biosynthesis of regulatory peptides, but due to their unique specificity they could play an important role in the degradation of them. Evidence exists that dipeptidyl (amino)peptidase IV at the cell surface of endothelial cells sequesters circulating peptide hormones which are then susceptible to broader aminopeptidase attack. The cleavage of several neuropeptides by prolyl endopeptidase has been demonstrated in vitro, but its role in the brain is questionable since the precise localization of the protease is not clarified.


[Diffraction enhanced imaging of condylar cartilage of osteoarthritic rats].
To observe the images of early lesions of condylar cartilage of osteoarthritic rats in synchrotron radiation diffraction enhanced imaging (DEI). The animal model of temporomandibular joint osteoarthrosis was established in rat following the method of partial resection of the joint disc. The changes of osteoarthritic condylar cartilage in different pathological stages were observed by DEI and compared with those in situ histopathological sections. With DEI, straight and orbicular lines were detected in condylar cartilage 45 to 60 days after discs resection. The lines were confirmed by histopathology to be collagen degradation and tiny fissure formation inside the cartilage. DEI is capable of imaging the early stages of pathological changes of excised condylar cartilage such as collagen degradation and tiny fissure formation, and this technique is of potential value to clinical application.


QMRA and decision-making: are we handling measurement errors associated with pathogen concentration data correctly?
Knowledge of the variability in pathogen or indicator concentrations over time at a particular location (e.g. in drinking water sources) is essential in implementation of concentration-based regulations and in quantitative microbial risk assessment. Microbial enumeration methods, however, are known to yield highly variable counts (even among replicates) and some methods are prone to substantial losses (i.e. only a fraction of the target microorganisms in a sample are observed). Consequently, estimated microorganism concentrations may be biased and only a fraction of the variability that is observed in temporally distributed concentration estimates is due to variability in concentration itself. These issues have often been ignored in the past, and approaches to integrate knowledge about the measurement error associated with enumeration methods into decisions have not been standardized. Here, an existing model that describes variability in microorganism counts as a function of sample volume and the analytical recovery of the enumeration method is expanded to include temporal concentration variability and sample-specific recovery information. This model is used to demonstrate that microorganism counts and analytical recovery are not independent (as has often been assumed), even if the correlation is obscured by other sources of variability in the data. It is also used as an experimental design tool to evaluate strategies that may yield more accurate concentration estimates. Finally, the model is implemented in a Bayesian framework (with a Gibbs sampling algorithm) to quantify temporal concentration variability with appropriate consideration of measurement errors in the data and the analytical recovery of the enumeration method. We demonstrate by simulation that this statistical approach facilitates risk analyses that appropriately model variability in microorganism concentrations given the available data and that it enables decisions based on quantitative measures of uncertainty.


"Propylene spaced" allyl tin reagents: a new class of fluorous tin reagents for allylations under radical and metal-catalyzed conditions.
A new generation of propylene-spaced fluorous allyltin reagents [(Rf(CH2)3)3SnCH2CH = CH2] is described. These succeed in radical allylations where their lower homologs (ethylene-spaced) fail, and they provide improved performance in transition metal catalyzed allylations. The reagents and byproducts are readily separated by simple fluorous-organic liquid-liquid or solid-liquid extractions.


Risk factor analysis of hepatitis C virus seropositivity in Iranian blood donors: a case-control study.
Due to blood screening and blood donor selection, the prevalence of hepatitis C virus (HCV) is expected to be lower among blood donors compared to the general population. The effective control of blood-transmitted infectious diseases should be one of the goals of public health. Thus, this case-control study was conducted to evaluate the risk factors of HCV in a representative sample of blood donors in Iran. A case-control study was conducted on HCV-negative and on serologically confirmed HCV-positive donors across the country from 2009 to 2013. Univariate logistic regression, multiple logistic regression, and subgroup analyses were performed to assess the risk factors in first-time blood donors (FTs) and repeat blood donors (RDs) independently. A total of 970 cases and 1542 controls were selected from the cohort of Iranian blood donors registered in the Iran Blood Transfusion Organization. Intravenous (IV) drug abuse (ORFT , 6.42; 95% CI, 3.34-12.34; and ORRD , 27.62; 95% CI, 12.58-60.62), living with an IV drug abuser (ORFT , 3.47; 95% CI, 1.26-9.55; and ORRD , 6.95; 95% CI, 1.54-31.34), prison history (ORFT , 2.4; 95% CI, 1.48-3.88; and ORRD , 2.42; 95% CI, 1.38-4.27), sharing personal razors (ORFT , 2.00; 95% CI, 1.01-3.96; and ORRD , 5.62; 95% CI, 2.65-11.89), and medical exposure (ORFT , 1.97; 95% CI, 1.15-3.37; and ORRD , 2.19; 95% CI, 1.27-3.76) were significant independent risk factors in both types of blood donation. The findings of this analytic study on HCV exposure in Iranian blood donors conforms to those of international studies. Behavioral and medical factors should be examined in the donor health screening process.


Increased expression of IL-20 is associated with ischemic cardiomyopathy and acute myocardial infarction.
Background: The expression and clinical significance of IL-20 in coronary artery diseases needs to be analyzed. Methods: IL-20 and its receptors were analyzed in coronary artery tissues. In a separate study, plasma IL-20 was also evaluated. Results: IL-20 and its receptors were significantly higher in coronary artery stenosis tissues from ischemic cardiomyopathy patients than that from controls. T lymphocytes and macrophages were the main source of IL-20 and expressed its receptors abundantly. Plasma IL-20 was significantly higher in acute myocardial infarction patients than that in controls. Conclusion: IL-20 was closely associated with the presence of acute myocardial infarction. IL-20 may participate in the progression of coronary artery stenosis and plaque vulnerability via regulating T lymphocytes and macrophages.


Molecular Characterization of Herpesviral Encephalitis in Cetaceans: Correlation with Histopathological and Immunohistochemical Findings.
Herpesviruses are causative agents of meningitis and encephalitis in cetaceans, which are among the main leading known natural causes of death in these species. Brain samples from 103 stranded cetaceans were retrospectively screened for the presence of herpesvirus DNA in the brain. Molecular detection of Cetacean Morbillivirus was performed in HV positive brain cases. Histopathologic evaluation of brain samples included the presence or absence of the following findings (n = 7): meningitis, perivascular cuffings, microgliosis, intranuclear inclusion bodies, malacia, neuronal necrosis and neurophagic nodules, and haemorrhages. Histological evidence of the involvement of other etiological agents led to complementary analysis. We detected the presence of alpha and gamma-HVs in 12 out of 103 (11.6%) brain samples from stranded cetaceans of five different species: one bottlenose dolphin, six striped dolphins, three Atlantic spotted dolphins, one Cuvier's beaked whale, and one common dolphin. Pathogenic factors such as viral strain, age, sex, and the presence of co-infections were analysed and correlated with the brain histopathological findings in each case. Herpesvirus was more prevalent in males, juveniles, and calves and a 41.6% incidence of co-infections in the brain was detected in our study: three with Dolphin Morbillivirus, one with Staphilococcus aureus septicaemia and one with Brucella spp.


Mobile health technology for hypertension management with Hmong and Latino adults: mixed-methods community-based participatory research.
To identify Hmong and Latino adults' perspectives about a mHealth-based care model for hypertension (HTN) management involving blood pressure (BP) self-monitoring, electronic transmission of BP readings, and responsive HTN medication adjustment by a provider team. We conducted a mixed-methods formative study with 25 Hmong and 25 Latino participants with HTN at an urban federally-qualified health center. We used a tool to assess HTN knowledge and conducted open-ended interviews to identify perspectives about mHealth-based care model. While most participants agreed that lowering high blood pressure decreased the risk of strokes, heart attacks, and kidney failure, there were gaps in medical knowledge. Three major themes emerged about the mHealth-based care model: (1) Using mHealth technology could be useful, especially if assistance was available to patients with technological challenges; (2) Knowing blood pressures could be helpful, especially to patients who agreed with doctors' medical diagnosis and prescribed treatment; (3) Transmitting blood pressures to the clinic and their responsive actions could feel empowering, and the sense of increased surveillance could feel entrapping. Some people may feel empowered since it could increase patient-provider communication without burden of clinic visits and could increase involvement in BP control for those who agree with the medical model of HTN. However, some people may feel entrapped as it could breach patient privacy, interfere with patients' lifestyle choices, and curtail patient autonomy. In general, Hmong and Latino adults responded positively to the empowering aspects of the mHealth-based care model, but expressed caution for those who had limited technological knowledge, who did not agree with the medical model and who may feel entrapped. In a shared decision-making approach with patients and possibly their family members, health care systems and clinicians should explore barriers and potential issues of empowerment and entrapment when offering a mHealth care model in practice.


Fatal duodenal hemorrhage complicated after living donor liver transplantation: case report.
Fatal hemorrhage caused by duodenal ulcer is rarely seen after liver transplantation. We report a case with penetrating duodenal ulcer resulting in massive gastrointestinal tract hemorrhage from a ruptured pseudoaneurysm of the hepatic artery. The patient, a 54-year-old man, had undergone living donor liver transplantation with a graft from his son. Massive hematelnesis occurred 7 days after transplantation. Endoscopy revealed a penetrating duodenal ulcer. Repeated episodes of hemorrhage resulted in shock. Angiography showed a ruptured pseudoaneurysm of the proper hepatic artery. Embolization controlled the bleeding; however, the grafted liver became ischemic. The patient subsequently developed ischemic cholangitis, which was treated with percutaneous transhepatic cholangial drainage. Repeat transplantation was performed 30 months later. The patient was doing well at 10-month follow-up.


Investigations of prion and virus safety of a new liquid IVIG product.
A highly purified, liquid, 10% immunoglobulin product stabilized with proline, referred to as IgPro10 has recently been developed. IgG was purified from human plasma by cold ethanol fractionation, octanoic acid precipitation and anion-exchange chromatography. The manufacturing process includes two distinctly different partitioning steps and virus filtration, which were also assessed for the removal of prions. Prion removal studies used different spike preparations (brain homogenate, microsomes, purified PrP(sc)) and three different detection methods (bioassay, Western blot, conformation-dependent immunoassay). All of the investigated production steps were shown to reduce significantly all different spike preparations, resulting in an overall reduction of >10log(10). Moreover, the biochemical assays proved equally effective to the bioassay for the demonstration of prion elimination. Four of the manufacturing steps cover three different mechanisms of virus clearance. These are: i) virus inactivation; ii) virus filtration; and iii) partitioning. These mechanisms were assessed for their virus reduction capacity. Virus validation studies demonstrated overall reduction factors of >18log(10) for enveloped and >7log(10) for non-enveloped model viruses. In conclusion, the IgPro10 manufacturing process has a very high reduction potential for prions and for a wide variety of viruses resulting in a state-of-the-art product concerning safety towards known and emerging pathogens.


Accurate measurement of bromine contents in plastic samples by instrumental neutron activation analysis.
Accurate measurements of bromine contents in plastic samples were made by the direct comparator instrumental neutron activation analysis (INAA). Individual factors affecting the measurements were comprehensively evaluated and compensated, including the volatility loss of bromine from standard comparators, the background bromine level in the filter papers used for preparation of the standard comparators, nuclear interference, γ-ray spectral interference and the variance among replicates of the samples. Uncertainty contributions from those factors were thoroughly evaluated and included in the uncertainty budgeting of the INAA measurement. (81)Br was chosen as the target isotope, and the INAA measurements for bromine were experimentally confirmed to exhibit good linearity within a bromine content range of 10-170 μg. The established method has been applied to the analysis of eight plastic samples: four commercially available certified reference materials (CRMs) of polyethylene and polystyrene and four acrylonitrile butadiene styrene (ABS) samples prepared as the candidate reference materials (KRISS CRM 113-01-012, -013, -014 and -015). The bromine contents of the samples were calculated at three different γ-ray energies and compared, showing good agreement. The results of the four CRMs also showed good consistency with their certified values within the stated uncertainties. Finally, the bromine contents of the ABS samples were determined with expanded uncertainties (at a 95% level of confidence) between 2.5% and 5% in a bromine content range of 25-900 mg kg(-1).


Roles of G protein and beta-arrestin in dopamine D2 receptor-mediated ERK activation.
ERK activation by dopamine D(2) receptor (D(2)R) has been extensively characterized in various cell types including brain tissues. However, the involvement of beta-arrestin in the D(2)R-mediated ERK activation is not clear yet. Three different strategies were employed in this study to determine the roles of G protein or beta-arrestin in D(2)R-mediated ERK activation. The cellular level of beta-arrestins was reduced by RNA interference and pertussis toxin-insensitive Gi proteins were used to identify the G protein involved. Finally point mutations of D(2)R in which coupling with G protein was abolished but the interaction with beta-arrestin was increased, were employed to determine whether the affinity between D(2)R and beta-arrestin is a critical factor for beta-arrestin-mediated ERK activation. Our results show that G(i2) protein is involved in D(2)R-mediated ERK activation but beta-arrestins are either not involved or play minor role.


Interaction of rabbit muscle aldolase with phospholipid liposomes.
The interaction between rabbit muscle fructose diphosphate aldolase and phospholipid model membranes (liposomes) was studied by measurement of the tryptophan fluorescence of the enzyme. Interaction with liposomes decreases intrinsic fluorescence intensity of the enzyme and shifts the emission wavelength maximum to higher values. The effects appear to be strongly dependent on the nature of the phospholipid polar group and on ionic strength. Also, a reversible modification of specific activity of aldolase upon interaction with liposomes was found. It is postulated that aldolase binds to liposomes mainly by electrostatic interactions and that the binding causes a change in the conformation of the enzyme.


Analysis of mutations induced by 4'-hydroxymethyl-4,5',8-trimethylpsoralen and UVA in Escherichia coli lac Z gene and its regulatory region.
The mutagenic consequences of covalent adducts induced in M13mp19 DNA by 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) and UVA have been determined in a forward mutational system capable of detecting all classes of mutagenic events. The photoreaction mediated by HMT has been carried out at a very low molar ratio of HMT to DNA which favours the induction of cross-links between high affinity reaction sites. When damaged M13mp19 DNA is used to transfect competent Escherichia coli K12 JM105 cells, a five-fold increase in mutation frequency is observed at 3.5% survivors when measured as a loss of beta-galactosidase alpha-complementation. The enhanced mutation frequency is largely due to base substitutions, frameshift events and large deletions. The single nucleotide substitutions occur both in the lac Z coding sequence and in its regulatory region. Transversion and transition have been detected with a predominant form consisting of A.T-to-G.C transversion at position +159. Frameshift mutations have been observed at five positions while three large deletions removing either part of the coding sequence or both the coding and the regulatory regions have been detected with a higher frequency. The spectrum of base substitutions detected between the M13 lac Z- phages surviving to the treatment is totally different from those appearing spontaneously whereas several frameshift events or deletions can already be detected between the spontaneous mutations. Despite the presence of these spontaneous hot spots, the spectrum of mutations recovered after HMT photoaddition appears to be unique and a detailed analysis of the different classes of mutations indicates an important role of cross-links in the production of mutations.