Significant Multi Tesla Fields Within a Solenoid Encircled by Nanostructure Windings.
This theoretical investigation develops analytical concepts on how to realize magnetic fields for the Multi to Mega Tesla realm within the range from milli to nano volumes and periods. The fields are anticipated to be realized using solenoids with multi-walled carbon (MWCNT) nanostructure composite metal windings. The study presented here opens up the issue of the miniaturization of large magnetic field systems. Concern has been raised that for such large magnetic fields and associated energies that the solenoidal structure may be highly reconfigured. Consequently, an investigation is undertaken of the tensile strength resulting from the azimuthal current. Also, the azimuthal power per turn will be addressed along with its limitations in generating the magnetic field. Further, the study finds the allowable eigenvalue frequencies of the electric field. Tables are provided for given values of Bz0(0) from 2T to 2(10)6T for a number of important parameters for consideration in designing solenoidal systems.


[Viability assay on animal cells with ethidium bromide by fluorescence microscopy (author's transl)].
The present paper reports on a viability assay on animal cells with the fluorochrome ethidium bromide and its combined use with fluorescein diacetate. The fluorescence microscopic investigations were quantified by pulse cytophotometry, slide preparation, and counting chamber.


The on-line characterization of a radium slurry by gamma-ray spectrometry.
We have developed an in-line monitor to directly measure the (226)Ra concentration in a nuclear waste stream using quantitative gamma-ray spectrometry applied to the 186keV emission. The waste stream is in the form of a slurry composed of the solid waste material mixed with water. The concentration measurement includes a self-attenuation correction factor determined from a transmission measurement using the 122keV gamma from (57)Co. Presented here is the model for the measurement system and results from some initial tests.


Cell surface exposure of the outer membrane cytochromes of Shewanella oneidensis MR-1.
To determine if the outer membrane (OM) cytochromes of the metal-reducing bacterium Shewanella oneidensis MR-1 are exposed on the cell surface. MR-1 cells were incubated with proteinase K or buffer and the resulting degradation of the OM cytochromes was examined by Western blotting. The periplasmic fumarate reductase (control) was not degraded. The OM cytochromes OmcA and OmcB were significantly degraded by proteinase K (71 and 31%, respectively). Immunofluorescence confirmed a prominent cell surface exposure of OmcA and a partial exposure of OmcB and the noncytochrome OM protein MtrB. The cytochromes OmcA and OmcB are exposed on the outer face of the OM. The cell surface exposure of these cytochromes could allow them to directly contact extracellular insoluble electron acceptors (e.g. manganese oxides) and is consistent with their in vivo role.


Astaxanthin ameliorates lung fibrosis in vivo and in vitro by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells.
Astaxanthin, a member of the carotenoid family, is the only known ketocarotenoid transported into the brain by transcytosis through the blood-brain barrier. However, whether astaxanthin has antifibrotic functions is unknown. In this study, we investigated the effects of astaxanthin on transforming growth factor β1-mediated and bleomycin-induced pulmonary fibrosis in vitro and in vivo. The results showed that astaxanthin significantly improved the structure of the alveoli and alleviated collagen deposition in vivo. Compared with the control group, the astaxanthin-treated groups exhibited downregulated protein expressions of α-smooth muscle actin, vimentin, hydroxyproline, and B cell lymphoma/leukemia-2 as well as upregulated protein expressions of E-cadherin and p53 in vitro and in vivo. Astaxanthin also inhibited the proliferation of activated A549 and MRC-5 cells at median inhibitory concentrations of 40 and 30 μM, respectively. In conclusion, astaxanthin could relieve the symptoms and halt the progression of pulmonary fibrosis, partly by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells.


Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark.
Natural antisense transcripts (NATs), which are transcribed from opposite strands of DNA with partial or complete overlap, affect multiple stages of gene expression, from epigenetic to post-translational modifications. NATs are dysregulated in various types of cancer, and an increasing number of studies focusing on NATs as pivotal regulators of the hallmarks of cancer and as promising candidates for cancer therapy are just beginning to unravel the mystery. Here, we summarize the existing knowledge on NATs to highlight their underlying mechanisms of functions in cancer biology, discuss their potential roles in therapeutic application, and explore future research directions.


Clinicopathologic Correlation of Anti-Vascular Endothelial Growth Factor-Treated Type 3 Neovascularization in Age-Related Macular Degeneration.
To correlate histologic results with previously recorded multimodal imaging results from a patient with type 3 neovascularization secondary to age-related macular degeneration (AMD). Case study, clinical imaging, laboratory imaging, and eye-tracked clinicopathologic correlation. An 86-year-old white woman with type 3 neovascularization secondary to AMD treated with 6 intravitreal injections of bevacizumab. Multimodal retinal imaging at each clinic visit was correlated with ex vivo and high-resolution histologic images of the preserved donor eye. Clinical imaging included serial near-infrared reflectance and eye-tracked spectral-domain OCT. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding to clinical OCT signatures. Histologic correlates for clinical OCT signatures were sought, including reflectivity of the vascular complex, intraretinal hyperreflective foci and intraretinal cellularity, analysis of the topography of pathologic features, and evaluation of the sub-retinal pigment epithelium (RPE) plus basal lamina (BL) space. Clinical imaging showed a deep neovascular lesion in close relationship with a mixed serous and drusenoid pigment epithelium detachment (PED), characteristic of type 3 neovascularization. Antiangiogenic therapy achieved a complete resolution of exudation. The PED progressively flattened with each treatment, leaving a persistent triangular hyperreflectivity in the outer retina. This persistent deep lesion histologically correlated with a vascular complex implanted into sub-RPE basal laminar deposit. No connection between the choriocapillaris and the sub-RPE plus BL space was observed. Both RPE-derived and lipid-filled cells were correlated with clinical intraretinal hyperreflective foci. The sub-RPE plus BL space contained macrophages, lymphocytes, Müller cell processes, and subducted RPE. Clinicopathologic correlation of type 3 neovascularization showed vascular elements of retinal origin accompanied by collagenous material and Müller cell processes implanting into thick sub-RPE basal laminar deposit, which may simulate the appearance of chorioretinal anastomosis. Surrounding RPE-derived and lipid-filled cells thought to be microglia correlated with clinical intraretinal hyperreflective foci.


USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.
Thioredoxin reductase 1 (TXNRD1) is one of the major redox regulators in mammalian cells, which has been reported to be involved in tumorigenesis. However, its roles and regulatory mechanism underlying the progression of HCC remains poorly understood. In this study, we demonstrated that TXNRD1 was significantly upregulated in HCC tumor tissues and correlated with poor survival in HCC patients. Functional studies indicated TXNRD1 knockdown substantially suppressed HCC cell proliferation and metastasis both in vitro and in vivo, and its overexpression showed opposite effects. Mechanistically, TXNRD1 attenuated the interaction between Trx1 and PTEN which resulting in acceleration of PTEN degradation, thereby activated Akt/mTOR signaling and its target genes which conferred to elevated HCC cell mobility and metastasis. Moreover, USF2 was identified as a transcriptional suppressor of TXNRD1, which directly interacted with two E-box sites in TXNRD1 promoter. USF2 functioned as tumor suppressor through the downstream repression of TXNRD1. Further clinical data revealed negative co-expression correlations between USF2 and TXNRD1. In conclusion, our findings reveal that USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.


Metal bioavailable contamination engages richness decline, species turnover but unchanged functional diversity of stream macroinvertebrates at the scale of a French region.
Freshwater ecosystems are the main source of water for sustaining life on earth, and the biodiversity they support is the main source of valuable goods and services for human populations. Despite growing recognition of the impairment of freshwater ecosystems by micropollutant contamination, different conceptual and methodological considerations can newly be addressed to improve our understanding of the ecological impact into these ecosystems. Here, we originally combined in situ ecotoxicology and community ecology concepts to unveil the mechanisms structuring macroinvertebrate communities along a regional contamination gradient. The novelty of our study lies in the use of an innovative biomonitoring approach (measurement of metal contents in caged crustaceans) allowing to quantify and compare on a regional scale the levels of bioavailable metal contamination to which stream communities are exposed. We were hence able to identify 23 streams presenting a significant gradient of bioavailable metal contamination within the same catchment area in the South West of France, from which we also obtained data on the composition of resident macroinvertebrate communities. Analyses of structural and functional integrity of communities revealed an unexpected decoupling between taxonomic and functional diversity of communities in response to bioavailable metal contamination. We show that despite the negative impact of bioavailable metal contamination exposure on taxonomic diversity (with an average species loss of 17% in contaminated streams), functional diversity is maintained through a process of non-random species replacement by functional redundant species at the regional scale. Such unanticipated findings call for a deeper characterization of metal-tolerant communities' ability to cope with environmental variability in multi-stressed ecosystems.


Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism.
Recent work has demonstrated the impact of dysfunction of the GABAergic signaling system in brain and the resultant behavioral pathologies in subjects with autism. In animal models, altered expression of Fragile X mental retardation protein (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the autistic phenotype is also observed in individuals with Fragile X syndrome. This study was undertaken to test previous theories relating abnormalities in levels of FMRP to GABA(A) receptor underexpression. We observed a significant reduction in levels of FMRP in the vermis of adults with autism. Additionally, we found that levels of metabotropic glutamate receptor 5 (mGluR5) protein were significantly increased in vermis of children with autism versus age and postmortem interval matched controls. There was also a significant decrease in level of GABA(A) receptor beta 3 (GABRβ3) protein in vermis of adult subjects with autism. Finally, we found significant increases in glial fibrillary acidic protein in vermis of both children and adults with autism when compared with controls. Taken together, our results provide further evidence that altered FMRP expression and increased mGluR5 protein production potentially lead to altered expression of GABA(A) receptors.


Second trimester amniotic fluid myo-inositol concentrations in women later developing gestational diabetes mellitus or pregnancy-induced hypertension.
To evaluate myo-inositol concentrations in amniotic fluid in women later developing gestational diabetes and hypertension. A retrospective study was carried out with three groups of amniotic fluid samples (15-18 gestational weeks): 30 gestational hypertension pregnancies, 30 gestational diabetes pregnancies, and 30 normal pregnancy. A significant difference was observed in myo-inositol concentrations between the median gestational diabetes values (124.0 µmol/L, IQR 90.0-162.5) and the control group values (79.0 µmol/L, IQR 62.0-107.5), but also with gestational hypertension median values (79.0 µmol/L, IQR 67.75-92.0) (p < 0.001). This study has shown that myo-inositol concentrations in amniotic fluid increased significantly in women later developing gestational diabetes compared to the control group.


Hypersensitivity to histamine in the guinea-pig brain: microiontophoretic and biochemical studies.
Electrolytic lesions of the medial forebrain bundle induce a fall in histidine decarboxylase activity (the specific synthetic enzyme of brain histamine) in the ipsilateral cerebral cortex and hippocampus of the guinea pig brain; these results suggest the presence of an ascending histaminergic pathway in the guinea pig brain similar to that described in the rat. Possible alterations in the sensitivity of histaminergic receptors present in the target areas were studied following this type of lesion by combining electrophysiological and biochemical approaches. Microiontophoretic applications of histamine or noradrenaline reveal a hypersensitivity (lower ejecting currents for threshold and maximal responses) in cortical neurons ipsilateral but not contralateral to the lesion, whereas responses to iontophoretically applied GABA are not modified. In contrast the responsiveness of histamine-sensitive cyclic AMP generating systems is not modified, neither in the cerebral cortex nor in the hippocampus after this type of lesion. Similar conclusions are reached from the data obtained with specific agonists of the two classes of histaminergic receptors and measurements in the presence of a phosphodiesterase inhibitor. Several hypotheses are discussed in order to reconcile the finding of a denervation hypersensitivity revealed by iontophoresis contrasting with an unaltered responsiveness of the histaminergic receptors linked to the adenylate cyclase.


Effect of preexposure to dietary benzo[a]pyrene (BP) on the first-pass metabolism of BP by the intestine of toadfish (Opsanus tau): in vivo studies using portal vein-catheterized fish.
The effect of preexposure of fish to dietary benzo[a]pyrene (BP) on the intestinal metabolism of BP was examined in toadfish (Opsanus tau). The portal veins of toadfish were cannulated following administration of radiolabeled BP to the intestinal lumen. Because these fish lack a lymphatic vessel system, the portal vein is the sole route by which BP and its metabolites enter the circulation. In fish preexposed to dietary BP (10 mg BP/kg food), the radioactivity entering the portal vein was almost entirely (ca. 90%) BP metabolites. In fish fed a laboratory control diet, a smaller percentage (ca. 60%) of the radioactivity entering the portal vein was in the form of BP metabolites. The enhanced efficiency of the intestines of preexposed fish in metabolizing BP appears to be a result of induction of intestinal aryl hydrocarbon hydroxylase (AHH) activity. Intestinal microsomal AHH activities in control and preexposed fish were 0.033 +/- 0.032 and 0.320 +/- 0.060 nmol.min-1.mg-1, respectively. Gel filtration of portal vein plasma indicated differences in the roles of plasma proteins in transporting BP and BP metabolites. Native BP was associated primarily with the high density lipoproteins, whereas organic-soluble BP metabolites were associated primarily with serum albumin fractions. A large percentage of BP metabolites was recovered as water-soluble conjugates. These studies indicate that in fish, the intestine can be an important organ involved in dietary BP metabolism.


Psychoeducation and Problem-Solving Therapy as an Integrative Model of Mutual-Help Groups for People with Severe Mental Disorders: A Report from Brazil.
This case study describes the "Entrelaços" Peer Support Program, a psychoeducational program of a psychiatric institution in the city of Rio de Janeiro that admitted, between 2011 and 2019, 246 people comprising family members and patients to participate in eight educational seminars followed by multifamily problem-solving groups in cycles that were 18 months in duration. Ninety percent of the participants who completed the program decided to create 7 mutual-help groups in the community independent of technicians and the institution. Community groups have already served spontaneously more than 214 families. They have organized scientific, social and anti-stigma events, expanded their social support network and demonstrated empowerment by switching from service users to peer providers to receive new families. This work is based on a pioneering model in Brazil that integrates psychoeducation with problem-solving therapy, spreading the benefits of education and peer-support with lower cost and greater representativeness.


Red cell glucose-6-phosphate dehydrogenase deficiency and haemoglobin variants among ten endogamous groups of Maharshtra and West Bengal.
Over 900 individuals from ten endogamous groups in the Indian states of Maharashtra and West Bengal were studied for G-6-PD deficiency and haemoglobin variants. The incidence of G-6-PD varied from nil to 17.3%, while that of Hb-S varied from nil to 22.3%. In general, the tribal populations of Maharashtra are characterized by the presence of a high incidence of both Hb-S and G-6-PD deficiency. The caste Hindus showed an absence of Hb-S and rather low G-6-PD deficiency. Immigrant Parsis possessed the highest incidence of G-6-PD deficiency (17.3%).


Graphene oxide wrapped with gold nanorods as a tag in a SERS based immunoassay for the hepatitis B surface antigen.
A composite consisting of graphene oxide and gold nanorods (GO-GNRs) was designed for the trace determination of hepatitis B surface antigen (HBsAg) using surface enhanced Raman spectroscopy (SERS). GO contains numerous carboxy and hydroxy groups on its surface and therefore can serve as the substrate for decoration with GNRs and for immobilizing antibody against HBsAg. The GNRs (carrying the SERS probe 2-mercaptopyridine) exhibit high SERS activity, and this improves the sensitivity of the biosensor. The antibody on the GO-GNRs binds HBsAg with high specificity, and it results in excellent selectivity. The SERS signal (measured at 1002 cm-1) increases in the 1-1000 pg·mL-1 HBsAg concentrations range, and the limit of detection is 0.05 pg·mL-1 (at an S/N ratio of 3). The immunoassay achieves the sensitive and selective determination of HBsAg in serum and expands the potential application of GO-GNR based SERS tag in clinical research. Graphical abstract A novel graphene oxide-gold nanorod (GO-GNRs) based surface-enhanced Raman scattering (SERS) tag for immunoassay was designed. It allows for sensitive and selective determination of HBsAg in serum. The method is expected to expand the potential application in the environment, in medicine and in food analysis.


[Systemic treatment of melanoma. Current clinical trials].
Malignant melanoma is one of the most common cancers accounting for 4-5% of all human malignancies and steadily increasing in incidence. The medical management of melanoma patients in Germany can be regarded as largely standardized based upon interdisciplinary guide lines. The results of adjuvant and especially palliative treatment of melanoma are unsatisfactory. Thus there is an urgent need for controlled clinical trials in order to optimize standard treatment approaches and to evaluate new drugs. The treatment of patients affected with high risk or metastatic melanoma within those clinical trials should be standard of care. This overview delineates the most important clinical trials currently conducted or planned in the adjuvant and palliative setting of melanoma treatment.


Migration and emission behavior of arsenic and selenium in a circulating fluidized bed power plant burning arsenic/selenium-enriched coal.
Arsenic (As) and selenium (Se) pollution caused by coal combustion is receiving increasing concerns. The environmental impacts of As/Se are determined not only by stack emission but also by leaching process from combustion byproducts. For a better control of As/Se emission from As/Se-enriched coal combustion, this study investigated the migration and emission behavior of As/Se in a circulating fluidized bed (CFB) power plant equipped with fabric filter (FF) and wet flue gas desulfurization (WFGD) system. The results demonstrated that arsenic was both enriched in bottom ash (41.4-47.6%) and fly ash (52.4-58.6%), while selenium was mainly captured by fly ash (73.9-83.4%). Limestone injection into furnace promoted As/Se retention in ash residues. Arsenic was mainly converted into arsenate in high-temperature regions and partly trapped in bottom ash as arsenite. In contrast, selenium capture mainly occurred in low-temperature flue gas by the formation of selenite, because of the poor thermal stability of most selenite. Triplet-tank method can totally remove arsenic in WFGD wastewater. And 18.4-58.7% of selenium was removed, resulting from the precipitation of Se4+ anions with highly soluble Se6+ anions remaining in wastewater. The concentrations of As and Se in the stack emission were 0.25-1.02 and 0.96-2.24 μg/m3, receptively. The CFB boiler equipped with FF + WFGD was shown to provide good control of the As/Se emission into the atmosphere. Leaching tests suggested that more attention should be paid to As leachability from fly ash/gypsum, and Se leachability from gypsum/sludge.


Searching MEDLINE via PubMed.
As the volume of biomedical literature has increased, so have the number and complexity of databases that index it. Learning to conduct an efficient literature search in an online database is an essential skill for today's clinical laboratory scientist. This article describes basic and advanced strategies for searching PubMed and the use of specialized features including MyNCBI.


Untangling Complexities of Glial-Neuronal Communications: Astroglial Metabolic Cascades Orchestrate Tonic Inhibition in the Thalamus.
In this issue of Neuron, Kwak et al. describe novel astroglial pathway for synthesis of GABA, which is subsequently released through plasmalemmal Best1 channels to control neuronal excitability and tactile acuity through tonic inhibition of thalamic neurons.


Long-Term Outcome of Low Scrotal Approach Orchiopexy without Ligation of the Processus Vaginalis.
We performed low scrotal approach orchiopexy in patients with prescrotal cryptorchidism. The processus vaginalis was not ligated if it was not widely patent. We retrospectively evaluated the long-term outcomes of low scrotal approach orchiopexy without processus vaginalis ligation. A total of 137 patients (227 testes) were diagnosed with prescrotal cryptorchidism between October 2009 and April 2014. All patients underwent low scrotal approach orchiopexy. Mean age at surgery was 34.9 months. The processus vaginalis was deemed to be not widely patent when a sound could not be passed into the abdominal cavity through the internal inguinal ring, and the processus vaginalis was not ligated in such cases. Intraoperative findings revealed that the processus vaginalis was widely patent in 10 testes and was not widely patent in 217. A widely patent processus vaginalis was closed via scrotal approach in 5 testes, while an inguinal approach was necessary in 5. Median followup was 44 months (range 20 to 73). Postoperative complications included reascending testis in 1 case where an inguinal approach was necessary. No patient manifested testicular atrophy or inguinal hernia. Low scrotal approach orchiopexy is a useful and safe procedure for treating patients with prescrotal cryptorchidism. Ligation is unnecessary when the processus vaginalis is not widely patent.


Induction and Detection of Mitophagy.
Mitophagy, a process of selective elimination of mitochondria by autophagy, is a mechanism of mitochondrial quality control that maintains mitochondrial network functionality. The elimination of damaged mitochondria through autophagy requires two steps: induction of general autophagy and priming of damaged mitochondria for selective autophagic recognition. Mitophagy impairment is linked to various pathologies; thus, removal of malfunctioning or even harmful mitochondria is vital to cellular physiology. Here, we describe methods that can be applied to the investigation of mitophagy.


Data Augmentation and Pretraining for Template-Based Retrosynthetic Prediction in Computer-Aided Synthesis Planning.
This work presents efforts to augment the performance of data-driven machine learning algorithms for reaction template recommendation used in computer-aided synthesis planning software. Often, machine learning models designed to perform the task of prioritizing reaction templates or molecular transformations are focused on reporting high-accuracy metrics for the one-to-one mapping of product molecules in reaction databases to the template extracted from the recorded reaction. The available templates that get selected for inclusion in these machine learning models have been previously limited to those that appear frequently in the reaction databases and exclude potentially useful transformations. By augmenting open-access data sets of organic reactions with explicitly calculated template applicability and pretraining a template-relevance neural network on this augmented applicability data set, we report an increase in the template applicability recall and an increase in the diversity of predicted precursors. The augmentation and pretraining effectively teaches the neural network an increased set of templates that could theoretically lead to successful reactions for a given target. Even on a small data set of well-curated reactions, the data augmentation and pretraining methods resulted in an increase in top-1 accuracy, especially for rare templates, indicating that these strategies can be very useful for small data sets.


Effect of educational intervention on nurses' perception and practice of antimicrobial stewardship programs.
Nurse involvement in antimicrobial stewardship programs is insufficient, which limits the programs' effectiveness. To evaluate the effect of the training programs on nurses' perception and practice of antimicrobial stewardship to embed it in practice. A quasi-experimental study without a control group was conducted on 115 nurses. A specifically validated and designed instrument was utilized to evaluate perception and practice before, after, and 2 months follow-up the training sessions. The difference between the pre, post, and 2 months follow-up tests was highly significant for the dimensions of knowledge, perception, and practice (P < .01). Also, nurses reported a lack of knowledge, lack of training, high workload as barriers of AMS. Nurses suggested ways to overcome barriers such as physician and manager support, in-service training every 6 months, and saving time for training and education. An educational intervention improved perception and practice among nurses related to antimicrobial stewardship and easily embedded it in practice.


Comparison of high-frequency lung ventilation with conventional mechanical lung ventilation. Prospective trial in patients who have undergone cardiac operations.
High-frequency lung ventilation was compared with conventional mechanical lung ventilation following elective cardiac operation. The results indicate that this high-frequency ventilator works as well as conventional mechanical ventilators and that it accomplishes the desired gas exchange at lower peak airway pressures. We conclude that routine use of high-frequency ventilation in the postoperative period is possible and that it may be indicated if lower peak airway pressures are desired.


Assessing the causal role of hypertension on left atrial and left ventricular structure and function: A two-sample Mendelian randomization study.
The aim of this study was to investigate whether hypertension may be causally linked to left atrial (LA) and left ventricular (LV) structure and function. We performed a two-Mendelian randomization (MR) analysis implementing the results from the FinnGen large-scale, genome-wide association study for hypertension (N = 218,754), and LV (N = 16,923) and LA studies (N = 35,648) by the UK Biobank to identify genetic instruments. The MR analysis was implemented using an inverse-variance weighted (IVW) approach. We identified a positive potential causal relationship between hypertension and indices for the LA maximum (LAmax with causal estimates of 0.126 [95% CI, (0.093 to 0.160)]); LA minimum (LAmin with causal estimates of 0.122 [95% CI, (0.089 to 0.156)]); LV function (causal estimates are LV end-diastolic volume (LVEDV), 0.078 [95% CI, (0.003 to 0.153)]; LV end-systolic volume (LVESV), 0.102 [95% CI, (0.030 to 0.173)]; LV mass (LVM), 0.171 [95% CI, (0.108 to 0.233)]; and LV mass to end-diastolic volume ratio (LVMVR at 0.098 [95% CI, (0.048 to 0.149)], respectively), which was directionally concordant with other robust MR methods. Other than this, we observed a significantly negative causal relationship between hypertension and the LA active emptying fraction (LAAEF), the LA passive emptying fraction (LAPEF), and the LA total emptying fraction (LATEF). Our genetic analyses demonstrated a potential causal relationship between hypertension and the left atrium and left ventricle's structures and functions.


Accuracy, reproducibility, and repeatability of forensic footwear examiner decisions.
The interpretation of footwear evidence relies on the expertise of forensic footwear examiners. Here we report on the largest study to date of the accuracy, reproducibility (inter-examiner variation), and repeatability (intra-examiner variation) of footwear examiners' decisions. In this study, 84 practicing footwear examiners each conducted up to 100 comparisons between questioned footwear impressions (provided as photographs and digital images) and known footwear (provided as photographs, transparent test impressions, and digital images), resulting in a total of 6610 comparisons. The quality and characteristics of the impressions were selected to be broadly representative of those encountered in casework. A multilevel conclusion scale was used: 40% of responses were definitive conclusions (identification or exclusion), 14% probable conclusions (high degree of association or indications of non-association), 40% class associations (association of class characteristics or limited association of class characteristics), and 6% neutral conclusions (inconclusive or not suitable). On nonmated comparisons, 0.2% of conclusions were erroneous identifications (false positives), and 1.4% were incorrect responses of "high degree of association." The majority of erroneous identifications were made by a single participant. On mated comparisons, 6.0% of conclusions were erroneous exclusions (false negatives), and 1.8% were incorrect responses of "indications of non-association." Erroneous conclusions were sometimes reproduced by different examiners, but rarely repeated by the same examiner-1.1% of erroneous identifications were reproduced (none were repeated) and 19.9% of erroneous exclusions were reproduced (just one was repeated). Examiners' assessments of whether a questioned impression was suitable for comparison were notably inconsistent and may benefit from standardization. Rates of correct definitive conclusions are directly associated with the quality of the questioned impression and the extent of class similarities/differences between the questioned impression and known footwear.


The Al61.49Mn11.35Ni4 phase in the Al-Mn-Ni system.
An inter-metallic phase in the Al-Mn-Ni system crystallizing in space group Cmcm (No. 63) and refined formula Al61.49Mn11.35Ni4 (called the R' phase) has been synthesized by high-temperature sinter-ing of a mixture with initial chemical composition Al60Mn7Ni3. In comparison with the structure model of the previously reported R phase with composition Al60Mn11Ni4 [Robinson (1954 ▸). Acta Cryst. 7, 494-497], there are two mutually exchanged Mn and Ni sites together with one positionally disordered Al site [occupancy ratio 0.811 (8):0.121 (7)] and one partially occupied Mn site [s.o.f. 0.677 (5)] in the current structure model of the R' phase.


Constancy of convexity air block on pneumoencephalography.
Twenty-two patients with dementia were examined by pneumoencephalography using special technic with the aim of filling the subarachnoid convexity space. Seven had no obvious hydrocephalus. All patients had convexity blocks which were more or less extensive. Ten had bilateral air block in the frontal, parietal and occipital regions. It was concluded that convexity air block is not a technical artifact and consequently seems to have an organic background.


Nanocrystalline anatase TiO2: a new anode material for rechargeable sodium ion batteries.
Anatase TiO2 nanocrystals were successfully employed as anodes for rechargeable Na-ion batteries for the first time. The mesoporous electrodes exhibited a highly stable reversible charge storage capacity of ~150 mA h g(-1) over 100 cycles, and were able to withstand high rate cycling, fully recovering this capacity after being cycled at rates as high as 2 A g(-1).


Treatment of multiple-risk patients: using combination therapy to treat beyond LDL lowering.
During the past 25 years, the role of traditional "risk factors" in the genesis of atherosclerotic vascular disease has been convincingly validated. The impact of elevated low-density lipoprotein cholesterol, hypertension, type II diabetes, and metabolic syndrome are now well accepted. However, until recently, there was guilt by association without a clear understanding of the manner in which the crime was committed. It is now acknowledged that the presence of multiple risk factors can increase the likelihood of an ischemic event. This has become a great concern, given the very high prevalence of patients who fall into this category. In light of this information, the mandate for appropriate guideline-driven therapy has become even stronger, and we must consider the use of multiple medications to effectively neutralize this risk.


Intracranial hemorrhage complicating anticoagulant prophylactic therapy in three hospitalized COVID-19 patients.
SARS-CoV2 has led to a global pandemic affecting almost 3 million people in almost over 3 months. Various clinical presentations have been reported so far and no definite therapy is established. Anticoagulation is recommended by several experts to address the potential prothrombotic complications from COVID-19, but its safety and regimen need further clinical trials and safety and efficacy profile. Here, we present three cases of intracranial hemorrhage in three critically ill patients with COVID-19 and discuss their course in relation to various regimens of anticoagulation used.


Patellar stabilization surgeries in cases of recurrent patellar instability: a retrospective clinical and radiological audit.
Patellar instability is a disabling condition that limits the functional ability and physical aspirations of patients. There are multiple anatomical structures which stabilize the patella and surgical treatment is tailored to repair the underlying aetiology. To evaluate the clinical and radiological outcome of patellar stabilization procedures in patients with recurrent patellar instability. We analysed 34 patients (36 knees) (mean age, 26.6) with recurrent patellar instability who underwent patellar stabilization surgery from June 2009 to September 2014. Type of procedure was dependent on the concomitant aetiological factors; tibial tuberosity osteotomy (61.76%), medial patellofemoral ligament reconstruction (67.64%), lateral release (5.88%) and trochleoplasty (2.94%). Mean follow-up was 3 years (range 9 months-6 years). At follow-up, 77% of patients were satisfied with the overall outcome of the procedure. The mean IKDC was 66.7, Lysholm 74.9. Mean patellar height decreased significantly (P < .05) to anatomical values. Pre-operatively, the mean tibial tuberosity-trochlear groove distance was 14.66 mm (55.6% at borderline/abnormal level) and 81% showed evidence of trochlear dysplasia. Complications were found in 3 patients (8.33%), 2 of which had further episodes of instability. Patellar stabilization surgery is an effective method of treating patellar instability, resulting in stability of the knee in 94.4%. Despite this, patient dissatisfaction rates are quite high suggesting that this patient group, whilst mostly stable, remains significantly symptomatic from their knee. These positive results which are reflected in the recent literature represent a strong case for consideration of primary surgical stabilization in cases of patellar instability.


The use of site-directed mutagenesis and time-resolved fluorescence spectroscopy to assign the fluorescence contributions of individual tryptophan residues in Bacillus stearothermophilus lactate dehydrogenase.
Site-directed mutagenesis has been used to generate two mutant Bacillus stearothermophilus lactate dehydrogenases: in one, Trp-150 has been replaced with a tyrosine residue and, in the other, both Trp-150 and -80 are replaced with tyrosines. Both enzymes are fully catalytically active and their affinities for substrates and coenzymes, and thermal stabilities are very similar to those of the native enzyme. Time-resolved fluorescence measurements using a synchrotron source have shown that all three tryptophans in the native enzyme fluoresce. By comparing the mutant and native enzymes it was possible, for the first time, to assign, unambiguously, lifetimes to the individual tryptophans: Trp-203 (7.4 ns), Trp-80 (2.35 ns) and Trp-150 (less than 0.3 ns). Trp-203 is responsible for 75-80% of the steady-state fluorescence emission, Trp-80 for 20%, and Trp-150 for less than 2%.


Present trend in the primary treatment of aggressive malignant glioma: glioblastoma multiforme.
The standard treatment for glioblastoma multiforme is surgery, radiation, and chemotherapy. Yet this aggressive therapy has only a modest effect on survival with most patients surviving less than 1 year after diagnosis. This poor prognosis has lead scientists to seek alternative molecular approaches for the treatment of glioblastoma multiforme. Among these, gene therapy, vaccine therapy, and immunotherapy are all approaches that are currently being investigated. While these molecular approaches may not herald an immediate change in the prognosis of these aggressive tumors, combining them with existing approaches may bring some progress in the standard of care. This paper reviews current treatments and several newer therapies in preclinical and early clinical studies.


Histopathological changes of the dural myeloid cells and lymphatic vessels in a mouse model of sepsis-associated encephalopathy.
As a common diffuse encephalopathy caused by sepsis, sepsis-associated encephalopathy (SAE) is closely associated with increased mortality, severe cognition dysfunction and increased cost of health care in patients of sepsis. Accumulating evidence suggests that the dura mater, the outermost meninges of the central nervous system (CNS), plays an important role in CNS immunity, especially with the discovery of meningeal lymphatic vessels (mLVs), as well as a plentiful array of resident or infiltrating immune cells harbored in the dura. Although these findings have significantly enhanced our understanding of the immune function of dura under both steady-state and pathological condition of CNS, whether and how the immune cells and mLVs within dura response to SAE still remains largely unexplored. Here, we established lipopolysaccharide (LPS) intraperitoneal injection-induced SAE model and examined the dural resident immune cells and mLVs. We analysed the histological change in dura by performing hematoxylin and eosin (H&E) and immunofluorescence staining. Results showed that systemic exposure to LPS induced neutrophils recruitment, exudation and gathering around the dural blood vessels. Moreover, resident macrophage altered its shape as well as location, and downregulated major histocompatibility (MHC) class II expression following LPS injection. We also found that LPS exposure induced dorsal meningeal lymphangiogenesis. Together, these findings collectively demonstrated that LPS-induced SAE can stimulate immune cells and mLVs within dura and provided more information about the immune response of the dura in sepsis.


Emergency ambulatory outpatient management of immune-mediated hypophysitis.
Immune-mediated hypophysitis is an important toxicity related to immune checkpoint inhibitors (ICI). Optimal management is associated with improved outcomes. It represents a wide spectrum of clinical presentations, and a proportion may be suitable for emergency ambulatory management. Emergency ambulatory management of patients presenting with clinical features and findings consistent with ICI-induced hypophysitis was considered at a tertiary cancer/endocrinology hospital. Suitable patients were initially investigated and treated in accordance with the UK emergency management guidelines for ICI induced hypophysitis. After an initial observation period of 4 h, patients were discharged with oral hydrocortisone (20, 10, 10 mg). An initial cohort of 4 patients with emergency presentations of ICI-induced hypophysitis has been managed in an ambulatory fashion in the first 3 months. There were no 30-day readmissions. Carefully selected emergency presentations with immune-mediated hypophysitis may be suitable for ambulatory management.


Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial.
The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients. We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively. There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively. This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia.


Radioactive and stable isotopes reveal variations in nearshore submarine groundwater discharge composition and magnitude across low inflow northwestern Gulf of Mexico estuaries.
To determine how submarine groundwater discharge (SGD) magnitudes and composition (fresh or saline/recirculated) vary in nearshore low inflow estuaries across ⁓125 km of a semiarid coastline, this study assessed three south Texas estuaries, using radon [222Rn], radium [226Ra and 224Ra], and water isotopes [δ18O and δD]. Mass balance models of time-series 222Rn, found to be representative of total SGD in this study, revealed much higher SGD inputs to the Nueces Estuary (average [x̅] Nueces, Corpus Christi and Oso Bays: 120, 83, and 44 cm·d-1, respectively), attributed to anthropogenically-disturbed substrates and potentially surfacing growth-faults. The lowest 222Rn-derived SGD occurred in the Upper Laguna Madre Estuary (x̅: Upper Laguna Madre and Baffin Bay: 21 and 18 cm·d-1, respectively), explained by the drier climate, lower anthropogenic disturbance, and neighboring groundwater cone of depression. Aransas Bay in the Mission Aransas Estuary received greater average annual precipitation but exhibited low total SGD rates (x̅: 23 cm·d-1). Seasonally, average 222Rn-derived SGD rates increased following Hurricane Harvey (43 cm·d-1 in spring to 64 cm·d-1 in summer). In the Nueces Estuary, the overall 222Rn-derived SGDs were substantially higher than SGDs from 224Ra and 226Ra. The closer agreement between 224Ra and 222Rn-derived SGD and larger 224Ra rates in the Upper Laguna Madre Estuary, Aransas Bay and Oso Bay indicate that saline/recirculated SGD contributions were significant. Values of δ18O and δD confirm these types of inputs, with effects of evaporation/salinization more pronounced where recirculation was predominant and the opposite where terrestrial/222Rn-derived SGD inputs dominate. 226Ra-derived SGDs were lower than the 224Ra due to different behavior of the two isotopes while released into water following transport through saline and fine-grained estuarine sediments or due to wind-driven disturbances.


Interplay between TRP channels and the cytoskeleton in health and disease.
Transient receptor potential (TRP) channels are a family of cation channels that play a key role in ion homeostasis and cell volume regulation. In addition, TRP channels are considered universal integrators of sensory information required for taste, vision, hearing, touch, temperature, and the detection of mechanical force. Seminal investigations exploring the molecular mechanisms of phototransduction in Drosophila have demonstrated that TRP channels operate within macromolecular complexes closely associated with the cytoskeleton. More recent evidence shows that mammalian TRP channels similarly connect to the cytoskeleton to affect cytoskeletal organization and cell adhesion via ion-transport-dependent and -independent mechanisms. In this review, we discuss new insights into the interplay between TRP channels and the cytoskeleton and provide recent examples of such interactions in different physiological systems.


Seminal 'priming' for protection from pre-eclampsia-a unifying hypothesis.
Conventional belief holds that an immune response to ejaculate antigens should interfere with fertilisation and establishment of pregnancy. However, emerging evidence now supports the opposing view-that insemination acts to activate maternal immune mechanisms exerting a positive effect on reproductive events. In a response well documented in rodents, semen triggers an influx of antigen-presenting cells into the female reproductive tract which process and present paternal ejaculate antigens to elicit activation of lymphocytes in the adaptive immune compartment. Transforming growth factor beta (TGFbeta), a cytokine present in abundance in seminal plasma, initiates this inflammatory response by stimulating the synthesis of pro-inflammatory cytokines and chemokines in uterine tissues. Lymphocyte activation is evident in lymph nodes draining the uterus and leads to hypo-responsiveness in T-cells reactive with paternal alloantigens. TGFbeta has potent immune-deviating effects and is likely to be the key agent in skewing the immune response against a Type-1 bias. Prior exposure to semen in the context of TGFbeta can be shown to be associated with enhanced fetal-placental development late in gestation. In this paper, we review the experimental basis for these claims and propose the hypothesis that, in women, the partner-specific protective effect of insemination in pre-eclampsia might be explained by induction of immunological hypo-responsiveness conferring tolerance to histocompatibility antigens present in the ejaculate and shared by the conceptus.


Human papillomavirus sequences are not detectable by Southern blotting or general primer-mediated polymerase chain reaction in transitional cell tumours of the bladder.
A large series of transitional cell tumours has been screened for the presence of human papillomavirus (HPV) sequences using Southern blotting and general primer-mediated polymerase chain reaction (GP-PCR). The latter technique allows the detection of a broad spectrum of both sequenced and unsequenced HPV types using two primer pairs located in the highly conserved L1 and E1 regions of the HPV genome. No evidence for HPV infection was found in 100 transitional cell tumours, 6 cases of carcinoma in situ, 2 adenocarcinomas and a squamous carcinoma of the bladder and 3 cases of cystitis. Similarly, 12 bladder tumour cell lines were HPV-negative in these assays. Cervical carcinoma cell lines containing from 1-3 to 600 copies of the HPV genome were used as positive controls and were scored positive in all assays by both Southern blotting and GP-PCR. It is concluded that despite the close proximity of the urothelium to the genital mucosa and the resemblance of some bladder tumours to known HPV-induced lesions in other tissues, HPV infection is absent or very uncommon in bladder tumours.


Monocular pattern-shift visual evoked potentials in hemispheric strokes.
Monocular pattern-shift visual evoked potentials were obtained in (i) 33 patients with unilateral non-hemorrhagic hemispheric infarction (age 50-79 years; 23 males, 10 females), (ii) 21 age- and sex-matched patient controls (control group or CGI) with no remote or recent stroke, normal neurological examination and similar incidence of diabetes mellitus, hypertension and heart disease, and (iii) 21 age- and sex-matched healthy elderly community volunteers (CGII). Subjects with history of glaucoma, cataracts, other media opacities or symptomatic retinal lesions were not considered or included in any of the 3 study groups. In addition, all subjects in each of the 3 groups had a normal ocular and fundoscopic examination. The mean interocular P100 latency difference in the stroke group was significantly greater than that in CGI or II (P less than 0.01). The mean interocular P100 amplitude ratio (small P100/large P100) in the stroke subjects was significantly different from that of CGI or II (P less than 0.02). The mean P100 latency on ocular stimulation ipsilateral to the side of infarction was significantly longer than that of either left or right ocular stimulation in CGI or II (P less than 0.01). The mean P100 latency on ocular stimulation contralateral to the side of infarction was similarly but less significantly longer than that on left or right ocular stimulation in CGI or II (P less than 0.05). Evidence of anterior visual pathway dysfunction was thus elicited in the stroke population using the technique.


Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway.
To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule (EtAc-LME) in MKN-74, NUGC gastric cancer cells and non cancerous gastric mucous cells (GES-1), and to explore the mechanism of EtAc-LME induced apoptosis. The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases, PARP cleavage, expression of cytochrome-c (Cyt-c) was determined by western blotting, mRNA expression of Bcl-2, Bax by RT-PCR, loss of mitochondrial potential using DiOC6 dye, annexin binding assay and its influence on cell cycle arrest by flow cytometry. The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells (NUGC and MKN-74) compared to normal gastric cells (GES-1), suggesting more specific cytotoxicity to the malignant cells. Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway. The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.


Plasmodium malariae: distribution of circumsporozoite protein in midgut oocysts and salivary gland sporozoites.
The distribution of the circumsporozoite protein within developing Plasmodium malariae oocysts and salivary gland sporozoites was examined by immunoelectron microscopy using protein A-gold and a monoclonal antibody specific for the CS protein of P. malariae. Gold particles were found along the capsule of immature oocysts but rarely within the cytoplasm. Gold label was detected on the inner surface of peripheral vacuoles during oocyst maturation and the plasma membrane of the sporoblast. Salivary gland sporozoites and budding sporozoites in mature oocysts were labeled uniformly on the outer surface of their plasma membranes. The surface of sporozoites that ruptured into midgut epithelial cells were entirely covered with gold particles. No label was seen on the surface of sporozoites which ruptured into the midgut lumen. In addition, a rabbit polyclonal antibody against repeat a region of P. brasilianum CS protein reacted with P. malariae sporozoites.


Cold processed oil-in-water emulsions for dermatological purpose: formulation design and structure analysis.
The aim of this work is to develop, optimize and characterize cold process emulsions that are stable at acidic pH. The main surfactant was selected according to the hydrophilic lipophilic balance (HLB) concept and surface tension, whereas polymers were selected by viscoelastic measurements and analytical centrifugation. It was showed that the inclusion of methyl vinyl ether/maleic anhydride copolymer crosslinked with decadiene (PVM/MA) increased the storage modulus (G') of the gels (23.9-42.1 Pa) two-fold and the droplet migration decreased from 3.66% to 0.95%/h. Cetrimide was selected as a preservative based on its microbiological results and additional contribution to the stability of the emulsions. Four emulsions were developed that differed by the co-emulsifier used (PEG-20 glyceril laurate and polyglyceryl-4-isostearate) and the glycol (2-methyl-2,4-pentanediol and ethoxydiglycol). Viscoelastic measurements and droplet size/microscopic analysis showed that the structure of PEG-20 glyceril laurate emulsion (η' = 76.0 Pa.s at 0.01 Hz and 32.9 ± 3.7 µm, respectively) was stronger compared to polyglyceryl-4-isostearate (η' = 37.4 Pa.s at 0.01 Hz and 37.8 ± 15.7 µm, respectively). Differential scanning calorimetry (DSC) results were in accordance with the latter and showed that PEG-20 glyceril laurate with 2-methyl-2,4-pentanediol corresponded to the strongest structure (|224.4| W °C g(-1)). This cold process allowed a total production savings of more than 17% when compared to the traditional hot process.


Treatment with an elevated dose of the GnRH analogue dephereline in the early luteal phase improves pregnancy rates in repeat-breeder dairy cows.
This study sought to establish whether treatment with the GnRH analog dephereline in the early luteal phase could be useful to improve fertility in repeat-breeder cows (>3 inseminations). Dephereline was given 5-7 days after insemination, and effects of both a single and elevated (2.5 times) dephereline dose on pregnancy and subsequent embryo survival determined in repeat-breeder lactating dairy cows. The study population comprised 810 cows: 399 repeat-breeder cows and 411 non repeat breeders. To determine the effects of treatment on the pregnancy rate, three study groups were established: Control, no treatment (n = 269), DEPH, single dephereline dose (100 μg) (n = 270), or 2.5DEPH, 2.5 dephereline doses (250 μg) (n = 271). Recorded pregnancy rates in these groups were 28.6% (77/269), 31.9% (86/270) and 39.1% (106/271), respectively. Binary logistic regression analysis revealed a significant effect of the interaction treatment x repeat breeder on the pregnancy rate. This meant that the single dose and control treatments led to a pregnancy likelihood of repeat-breeder cows reduced by factors of 0.47 and 0.34, respectively, when compared to the 2.5 dose treatment as reference. Treatment had no effects on non repeat breeders. Based on odds ratios, treatment given either as a single or 2.5 dose increased the probability of an additional corpus luteum (more corpora lutea than embryos) in pregnant cows by factors of 5 or 5.4, respectively. Treatment had no effect on embryo survival. Our findings support the hypothesis that dephereline treatment in the early luteal phase after AI improves fertility in repeat-breeder cows. A dephereline dose 2.5 times higher than normal led to improved pregnancy rates, thus overcoming the impacts of repeat-breeder syndrome. Importantly, both the single and 2.5 dephereline doses increased the chances of pregnant cows having an additional corpus luteum, likely favoring embryo survival.


The feasibility of characterizing the spatial distribution of cartilage T(2) using texture analysis.
The purpose of this study was (1) to characterize the spatial distribution of cartilage T(2) in postmenopausal osteoarthritis (OA) patients and age-matched healthy subjects using second order texture measures at baseline, and (2) to analyze changes in the texture of cartilage T(2) after 9 months. 3.0T-MRI of the knee was performed in 8 mild OA patients and 10 age-matched controls at baseline and after 9 months. Cartilage T(2), volume, and average thickness were calculated in all patients. Texture analysis, based on the gray level co-occurrence matrix, was performed on the cartilage T(2) maps. Texture parameters, including entropy and angular second moment, were calculated at 0 degrees (corresponding to the anterior-posterior axis) and at 90 degrees (corresponding to the superior-inferior axis), with pixel offsets ranging from 1 to 3 pixels. Least square means analysis showed that mean T(2) values, their standard deviation (SD), and their entropy were greater (P<0.05) in OA patients than in controls. Over 9 months, the SD and entropy of cartilage T(2) significantly (P<0.05) decreased in OA patients, while no significant changes were evident in cartilage thickness or volume. The mean cartilage T(2) values, their SD, and their entropy were greater in OA patients than in controls, indicating that the T(2) values in osteoarthritic cartilage are not only elevated, but also more heterogeneous than those in healthy cartilage. The longitudinal results demonstrate that changes in texture parameters of cartilage T(2) may precede morphological changes in thickness and volume in the progression of OA.


Elevated LDL-cholesterol level predicts diabetes in centrally obese women but not men: relative roles of insulin resistance and central obesity.
The aim was to investigate the sex-specific effect of hypercholesterolemia interacting with abdominal obesity (AO) in predicting Type 2 diabetes mellitus (DM). The 3,048 participants (aged > or =28 years) were free of DM at baseline, a representative sample of Turkish adults and were evaluated prospectively. As cut-off points for AO were used > or =95 cm in men and > or =91 cm in women, and for hypercholesterolemia > or =5.2 mmol/L. Diabetes was diagnosed using criteria of the American Diabetes Association. Four groups were formed at baseline: Group I subjects had neither AO nor hypercholesterolemia (33.3%), Group II subjects had AO only (27.6%), Group III subjects had hypercholesterolemia only (17.8%), and Group IV subjects had AO combined with hypercholesterolemia (21.3%). Over a mean of 5.9 years, DM developed in 103 women and 116 men. An age-adjusted relative risk (RR) by logistic regression for DM in the 4 groups, using AO as a reference group, disclosed an RR of 1.88 (95% confidence interval 1.14; 3.09) in women and an insignificant RR 1.29 in men (women were predicted to be 1.46 times more likely to develop DM). Hypercholesterolemia alone did not differ significantly from Group I in its ability to predict diabetes. An elevated level of low-density lipoprotein (LDL)-cholesterol (C) (> or =3.4 mmol/L) was delineated as the element associated with diabetes in hypercholesterolemia by multiple logistic regression. The identification of 48 participants with familial-combined hyperlipidemia phenotypes alone could not account for most of the centrally obese and hypercholesterolemic women developing DM. It was suggested that a diminished effectiveness of insulin resistance in centrally obese Turkish women (but not men) might predispose them to an elevation in LDL concentrations, while other features of visceral adiposity still predispose them to DM. In summary, an elevated LDL-C level interacts with AO in Turkish women to enhance the development of diabetes.


Effect of water on the glass transition of a potassium-magnesium carbonate melt.
Calorimetric measurements of the glass transition temperatures (Tg) of hydrous carbonate melts are reported on a near-eutectic composition of 55 mol% K2CO3 - 45 mol% MgCO3 with up to 42 mol% bulk H2O dissolved in the carbonate melt. Hydrous melts were quenched from 750°C to transparent and crystal-free glasses and were subsequently analysed for water content before and after measuring Tg by high-sensitivity differential scanning calorimetry. The glass transition and limited fictive temperatures as a function of the water content were determined at 10 K/min cooling/heating rates resulting in Tg ranging from 245°C at nominally anhydrous conditions to 83°C in the presence of 42 mol% H2O in the glass. Through a generalized Gordon-Taylor analysis, the factors k (7.27), k0 (3.2) and the interaction parameter Ax (0.49) were derived. The limited fictive temperature of a hypothetically, zero water containing 55 mol% K2CO3 - 45 mol% MgCO3 glass is 232 ± 5°C (505 K). The high value of the interaction parameter A indicates strong specific molecular interactions between water and the carbonates in the glassy state and a large decrease in the excess enthalpy of mixing during the conversion of the glassy into the liquid state at the glass transition. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.


Enantiomeric resolution of some 2-arylpropionic acids using L-(-)-serine-impregnated silica as stationary phase by thin layer chromatography.
The enantiomeric resolution of certain 2-arylpropionic acids was achieved on thin silica gel plates impregnated with optically pure L-(-)-serine as chiral selector. The mobile phase enabling successful resolution of (+/-)-ibuproxam and (+/-)-ketoprofen was acetonitrile-methanol-water (16:4:0.5, v/v/v) and (16:3:0.5, v/v/v) for (+/-)-tiaprofenic acid. The spots were detected with iodine vapors and the detection limits were found to be different for each of the 2-arylpropionic acid, ranging between 0.25 and 0.50 microg/ml. The effect of concentration of the impregnating chiral selector, temperature and pH on resolution has been studied. The procedure was applied successfully to resolve commercial ampoules of ketoprofen dosage formulation.


Counter aggression and reconciliation in Assamese macaques (Macaca assamensis).
Patterns of aggressive and affiliative behavior, such as counter aggression and reconciliation, are said to covary in the genus Macaca; this is referred to as the systematic variation hypothesis. These behavior patterns constitute a species dominance style. Van Schaik's [1989] socioecological model explains dominance style in macaques in terms of within- and between-group contest competition. Dominance style is also said to correlate with phylogeny in macaques. The present study was undertaken to examine phylogenetic and socioecological explanations of dominance style, as well as the systematic variation hypothesis. We collected data on counter aggression and reconciliation from a habituated group of Assamese macaques (Macaca assamensis) at the Tukeswari Temple in Assam, India. The proportion of agonistic episodes that involved counter aggression was relatively low. Counter aggression, however, occurred more often among males than among females, and it was most common when females initiated aggression against males. The conciliatory tendency for this group of Assamese macaques was 11.2%. The frequency of reconciliation was low for fights among males and for fights among females, but reconciliation was particularly rare for opposite-sexed opponents. Female social relationships were consistent with the systematic variation hypothesis, and suggest a despotic dominance style. A despotic dominance style in Assamese macaques weakens the correlation between dominance style and phylogeny in macaques, but it is not inconsistent with the socioecological model. Male-female relationships were not well explained by the despotic-egalitarian framework, and males may well have more tolerant social relationships than do females. Sex differences need to be considered when categorizing species according to dominance style.


Predictors of Mortality in Elderly and Very Elderly Emergency Patients with Sepsis: A Retrospective Study.
Elderly patients are at increased risk of developing sepsis and its adverse outcomes. Diagnosing and prognosing sepsis is particularly challenging in older patients, especially early at emergency department (ED) arrival. We aimed to study and compare the characteristics of elderly and very elderly ED patients with sepsis and determine baseline factors associated with in-hospital mortality. We also compared prognostic accuracy of the criteria for systemic inflammatory response syndrome, quick sequential organ failure assessment (qSOFA), and the National Early Warning Score in predicting mortality. We conducted a retrospective study at the ED of Siriraj Hospital Mahidol University in Bangkok, Thailand. Patients over 18 years old who were diagnosed and treated for sepsis in the ED between August 2018-July 2019 were included. We categorized patients into non-elderly (aged <65 years), elderly (aged 65-79 years), and the very elderly (aged >80 years) groups. The primary outcome was in-hospital mortality. Baseline demographics, comorbidities, source and etiology of sepsis, including physiologic variables, were compared and analyzed to identify predictors of mortality. We calculated and compared the area under the receiver operator characteristics curves (AUROC) of early warning scores. Of 1616 ED patients with sepsis, 668 (41.3%) were very elderly, 512 (31.7%) were elderly, and 436 (27.0%) were non-elderly. The mortality rate was highest in the very elderly, followed by the elderly and the non-elderly groups (32.3%, 25.8%, and 24.8%, respectively). Factors associated with mortality in the very elderly included the following: age; do-not-resuscitate (DNR) status; history of recent admission <3 months; respiratory tract infection; systolic blood pressure <100 millimeters mercury (SBP<100); oxygen saturation; and Glasgow Coma Scale (GCS) score. Factors associated with mortality in the elderly were DNR status, body temperature, and GCS score. qSOFA had the highest AUROC in predicting in-hospital mortality in both very elderly and elderly patients (AUROC 0.60 [95% confidence interval {CI}, 0.55-0.65] and 0.55 [95% CI, 0.49-0.61, respectively]). The mortality rate in the very elderly was higher than in the younger populations. Age, DNR status, recent admission, respiratory tract infection, SBP<100, oxygen saturation. and GCS score independently predicted hospital mortality in very elderly patients. The qSOFA score had better but only moderate accuracy in predicting mortality in elderly and very elderly sepsis patients.


Heat shock phenomena in Aspergillus nidulans. I. The effect of heat on mycelial protein synthesis.
Heat shock was found to induce characteristic changes in the pattern of protein synthesis in Aspergillus nidulans as analysed by SDS-polyacrylamide gel electrophoresis. Six to seven new bands were found to show increased incorporation to 35S-methionine at 43 degrees C compared to 37 degrees C, the standard temperature for this organism. The heat shock response of five different strains of A. nidulans was examined. This comparative study showed that these strains (haploids and diploids) show exactly the same set of heat shock proteins.


Biological characterization of an English granulovirus from the summer fruit tortrix moth, Adoxophyes orana.
Adoxophyes orana granulovirus (AdorGV) was isolated from overwintering larvae in an orchard in Kent, in the UK. The developmental time of each A. orana instar was determined by measuring the size of the head capsule. The susceptibility of the larvae to the English isolate of AdorGV was evaluated in laboratory bioassays using inoculation by microdroplet feeding and applied dose assays. A series of bioassays were performed to determine LD(50) and ST(50) values for first, fourth and fifth instar larvae. The median lethal doses ranged from 30 occlusion bodies in first instar to 1.36 x 10(6) in fifth instar. The median survival time decreased the later the larvae were infected and ranged from 37 days in first instar to 24 days in fifth instar. Approximately half of the infected larvae released a discharge rich in occlusion bodies from their posterior end prior to death. Approximately 85% of larvae attempted pupation and died as larva-pupa intermediates.


Trans IL-6 signaling does not appear to play a role in renal scarring after urinary tract infection.
While inflammation is an important innate defense mechanism against infection, it can also lead to local tissue damage. The trans signaling pathway of interleukin (IL)-6 is a known mediator of inflammation. We hypothesized that the trans IL-6 signaling pathway is associated with the development of post febrile urinary tract infection (UTI) renal scarring. To compare soluble regulators of trans IL-6 signaling between patients with a history of febrile UTI who do or do not have renal scarring. After IRB-approval, we collected urine samples in pediatric patients with a history of febrile (≥38 °C) UTI (urine culture >50 K uropathogen) with documented presence or absence of renal scarring on imaging. Samples were collected at a time when patients were not actively infected. Enzyme-linked immunosorbent assays were performed on samples for markers of trans IL-6 signaling: IL-6, soluble (s) IL-6 receptor (R), and soluble (s)gp130, a buffer in trans IL-6 signaling. Values were normalized to urine creatinine. Results were analyzed by t-test or Mann-Whitney U. Spearman rank correlation was used. A p-value of <0.05 was considered significant. A total of 50 urines from patients with a history of febrile UTI were collected: 23 with and 27 without scarring. There was no difference between groups regarding age or gender. There was no significant difference in urine IL-6, sIL-6R, or sgp130 between those with and without scarring (Figure). While IL-6 values significantly correlated with sIL-6R and sgp130 in those without renal scarring, IL-6 did not correlate with sgp130 in those with scarring. Ratios of IL-6 to sgp130 and sIL-6R to sgp130 were not different between groups. The inflammatory response generated in response to infection is believed to be largely responsible for the development of renal scarring after UTI. IL-6 is a cytokine known to be induced during UTI with a pro-inflammatory pathway, known as trans signaling. This study investigated for differences in markers of trans IL-6 signaling between patients with a history of febrile UTI with and without renal scarring. There was no significant difference between the absolute values or ratio of these markers between groups. Markers of trans IL-6 signaling are not different between individuals with a history of febrile UTI with and without renal scarring in the non-acute setting.


Physiological and behavioral responses to routine procedures in captive common marmosets (Callithrix jacchus).
The effect of routine captive procedures on the welfare of species used as experimental models in biomedical research is of great interest, since stress may alter the generalization and interpretation of results. This study investigated behavioral and endocrine (fecal cortisol) reactivity patterns in common marmoset (Callithrix jacchus) adult males (N = 10) and females (N = 9) subjected to three types of routine procedures in captivity: (1) moving to a same-sized cage (P1), to a smaller cage (P2), and (2) first-time pair formation (P3). Sexually dimorphic cortisol responses were detected in animals submitted to a physical environmental stressor (cage change). Females showed an increased response throughout P1, in relation to baseline (BP) cortisol, and a trend during P2. Males increased cortisol only during P2. On the other hand, males and females showed a similar endocrine response when management involved social challenge (pair formation), with both sexes increasing cortisol levels, but females exhibited a more intense and longer-lasting cortisol increase. Males and females exhibited similar behavioral responses to cage change, except for autogrooming, with males decreasing this behavior in P1. Only females demonstrated a significantly higher increase in piloerection frequency than that of males during the pair formation phase. These endocrine and behavioral changes must be taken into account when interpreting research data that involve these types of procedures. Further studies on the impacts of routine colony management are required to devise and include protocols in official husbandry guidelines.


Mixed Reality Interaction and Presentation Techniques for Medical Visualisations.
Mixed, Augmented and Virtual reality technologies are burgeoning with new applications and use cases appearing rapidly. This chapter provides a brief overview of the fundamental display presentation methods; head-worn, hand-held and projector-based displays. We present a summary of visualisation methods that employ these technologies in the medical domain with a diverse range of examples presented including diagnostic and exploration, intervention and clinical, interaction and gestures, and education.


Poly(ADP-ribosyl)ation is required for p53-dependent signal transduction induced by radiation.
p53 and poly(ADP-ribose) polymerase (PARP) are both DNA damage recognition proteins and can be functionally activated by DNA strand breaks. To understand the functional interaction between these two proteins, the effects of a PARP inhibitor, 3-aminobenzamide (3AB), on the p53 pathway were investigated in human glioblastoma cells with different p53 status. Consistent with previous studies, irradiation with gamma-rays induced both p53 and WAF1 accumulation in A-172 cells (wtp53) but not in T98G cells (mp53). However, the presence of 3AB but not its analog suppressed radiation-induced accumulation of wtp53 and the expression of WAF1 and MDM2. Similar results were also obtained from U87MG, another human glioblastoma cell line with wtp53 status. Northern blotting analysis showed that 3AB inhibited the gamma-ray-induced WAF1 gene expression. Moreover, 3AB but not its analog inhibited irradiation-induced activation of sequence-specific DNA binding of wtp53 as detected using 32P-labeled or biotin-labeled p53 consensus sequence (p53CON). However, immunoblotting with an anti-poly(ADP-ribose) antibody showed that p53 proteins of the p53CON-bound fraction did not contain poly(ADP-ribose) (PAR). These findings suggested that poly(ADP-ribosyl)ation is required for rapid accumulation of p53, activation of p53 sequence-specific DNA binding and its transcriptional activity after DNA damage.


Solution- and solid-phase synthesis of 4-hydroxy-4,5-dihydroisoxazole derivatives from enantiomerically pure N-tosyl-2,3-aziridine alcohols.
[reaction: see text] Enantiomerically pure N-tosyl-2,3-aziridine alcohols are directly converted into 4-hydroxy-4,5-dihydroisoxazole 2-oxides through oxidation to the corresponding aldehydes followed by in situ tandem nitroaldol-intramolecular cyclization. This study was concerned with (i) the selection of a suitable aziridine activation, (ii) the preparation of the target 4-hydroxy-4,5-dihydroisoxazole derivatives in solution, and (iii) the elaboration of a solid-phase process using hydroxy Merrifield-supported nitroacetic acid ester.


Synthesis of Green/Blue Light Emitting Quinolines by Aza-D-A Reaction Using InCl3 Catalyst.
An efficient InCl3-catalyzed sequential reaction of aromatic amines, aromatic aldehydes and functionalized alkynes leading to the formation of new quinoline derivatives exhibiting significant fluorescence activities is described. The photophysical investigations of quinolines were carried out by absorption and photoluminescence measurements. One particular compound 4 h having maximum intensity, emitting green colour (Φ = 0.78) with average life time of 6.20 ns was the best amongst the tested compounds. The presence of the amino group at the 4-aryl substituent of the quinoline backbone played an important role in executing the Povarov cyclization successfully and enhancing the flourescence properties of the newly synthesized quinolines.


[Planned reoperation following perforation of peptic ulcer with a simple suture. A differentiated treatment concept].
Even after perforation of chronic peptic ulcer with simple closure, patients continue to be in danger for additional complications of the ulcer ailment. Postoperative conditions of patients with perforated ulcer were analysed for a period of ten years. Classical indications for re-operation were recorded from 60 per cent. A differentiated concept for treatment of ulcer perforation is presented in this paper.


Response of Human Osteoblast to n-HA/PEEK--Quantitative Proteomic Study of Bio-effects of Nano-Hydroxyapatite Composite.
Nano-sized hydroxyapatite (n-HA) is considered as a bio-active material, which is often mixed into bone implant material, polyetheretherketone (PEEK). To reveal the global protein expression modulations of osteoblast in response to direct contact with the PEEK composite containing high level (40%) nano-sized hydroxyapatite (n-HA/PEEK) and explain its comprehensive bio-effects, quantitative proteomic analysis was conducted on human osteoblast-like cells MG-63 cultured on n-HA/PEEK in comparison with pure PEEK. Results from quantitative proteomic analysis showed that the most enriched categories in the up-regulated proteins were related to calcium ion processes and associated functions while the most enriched categories in the down-regulated proteins were related to RNA process. This enhanced our understanding to the molecular mechanism of the promotion of the cell adhesion and differentiation with the inhibition of the cell proliferation on n-HA/PEEK composite. It also exhibited that although the calcium ion level of incubate environment hadn't increased, merely the calcium fixed on the surface of material had influence to intracellular calcium related processes, which was also reflect by the higher intracellular Ca(2+) concentration of n-HA/PEEK. This study could lead to more comprehensive cognition to the versatile biocompatibility of composite materials. It further proves that proteomics is useful in new bio-effect discovery.


Correlating metal poisoning with zeolite deactivation in an individual catalyst particle by chemical and phase-sensitive X-ray microscopy.
Fluid catalytic cracking (FCC) is the main conversion process used in oil refineries. An X-ray microscopy method is used to show that metal poisoning and related structural changes in the zeolite active material lead to a non-uniform core–shell deactivation of FCC catalyst particles. The study links the detrimental effect of V and Ni poisoning with zeolite destruction and dealumination in a spatial manner within a single FCC catalyst particle.


Aryl hydrocarbon hydroxylase activity in chemically induced and toremifene-treated mammary tumors in rats.
Aryl hydrocarbon hydroxylase (AHH) and NADPH-cytochrome P450 reductase (NCR) activity of microsomes from liver, lungs, uterus and mammary tumors in dimethylbenzanthracene-induced and toremifene-treated female Sprague-Dawley rats were studied. AHH and NCR activity in tumors and uteri was low compared with that in livers and lungs. The distribution of AHH in tumors was wide and skewed. It varied in different tumors of the same animal as widely as between different animals. The enzyme activity in tumors did not correlate with that in the liver, lungs or uterus of the same animal. Toremifene had no effect on AHH or NCR in tumor or liver, but it decreased them in lungs. Tumor AHH activity correlated with its overall growth rate and development stage. The results suggest that malignant transformation leading to the defect in growth regulation also confuses the complex regulatory system of AHH activity.


Novel BTEX-degrading strains from subsurface soil: Isolation, identification and growth evaluation.
Monoaromatic hydrocarbons such as benzene, toluene, ethylbenzene, and o, m, and p-xylenes (BTEX) are high-risk pollutants because of their mutagenic and carcinogenic nature. These pollutants are found with elevated levels in groundwater and soil in Canada at several contaminated sites. The intrinsic microbes present in the subsurface have the potential to degrade pollutants by their metabolic pathways and convert them to non-toxic products. However, the low subsurface temperature (5-10 °C) limits their growth and degradation ability. This study examined the feasibility of subsurface heat augmentation using geothermal heating for BTEX bioremediation. Novel potent BTEX-degrading bacterial strains were isolated from soil at 3.0, 42.6, and 73.2 m depths collected from a geothermal borehole during installation and screened using an enrichment technique. The selected strains were identified with Sanger sequencing and phylogenetic tree analysis, revealing that all the strains except Bacillus subtilis are novel with respective to BTEX degradation. The isolates, Microbacterium esteraromaticum and Bacillus infantis showed the highest degradation with 67.98 and 65.2% for benzene, 72.8 and 71.02% for toluene, 77.52 and 76.44% for ethylbenzene, and 74.58 and 74.04% for xylenes respectively. Further, temperature influence at 15 ± 1 °C, 28 ± 1 °C and 40 ± 1 °C was observed, which showed increased growth by two-fold and on average 35-49% more biodegradation at higher temperatures. Results showed that temperature is a positive stimulant for bioremediation, hence geothermal heating could also be a stimulant for in-situ bioremediation.


Enhancing computing studies in high schools: A systematic literature review & UAE case study.
Open source software (OSS) is increasingly being integrated into educational institutions, and many countries require the use of OSS in government departments. However, not much focus is placed on integrating it into the educational sector in a strategic and productive manner. This paper examines the existing literature on the use of OSS in terms of the potential enhancements it can provide for computer science studies in high schools in general, and those in the UAE more specifically. It also details a survey conducted among 400 high school teachers after teaching them about multiple types of OSS that might enhance their teaching experience. After examining more than 69 different research papers and taking the survey findings into account, we drafted a roadmap that can be used by any educational institute-especially high schools-to strategically integrate OSS into the educational system.


Adults with attention deficit hyperactivity disorder: an investigation of age-related differences in behavioural symptoms, neuropsychological function and co-morbidity.
The outcomes of attention deficit hyperactivity disorder (ADHD) have been studied extensively in the first decades of life, but less is known about ADHD in adulthood. Hence we investigated cross-sectional age-related differences in behavioural symptoms, neuropsychological function and severity of co-morbid disorders within a clinically referred adult ADHD population. We subdivided 439 referrals of individuals with ADHD (aged 16-50 years) into four groups based on decade of life and matched for childhood ADHD severity. We compared the groups on measures of self- and informant-rated current behavioural ADHD symptoms, neuropsychological performance, and self-rated co-morbid mood and anxiety symptoms. There was a significant age-related reduction in the severity of all ADHD symptoms based on informant-ratings. In contrast, according to self-ratings, inattentive symptoms increased with age. Neuropsychological function improved across age groups on measures of selective attention and response inhibition. There was a mild correlation between the severity of depression symptoms and increasing age. This observational study suggests that, in adulthood, ADHD symptoms as measured using informant-ratings and neuropsychological measures continue to improve with increasing age. However the subjective experience of people with ADHD is that their symptoms worsen. This dichotomy may be partially explained by the presence of co-morbid affective symptoms. The main limitation of the study is that it is cross-sectional rather than longitudinal, and the latter design would provide more conclusive evidence regarding age-related changes in an adult ADHD population.


Depletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment.
Immunosuppressive cells residing in the tumor microenvironment, especially tumor associated macrophages (TAMs), hinder the infiltration and activation of T cells, limiting the anti-cancer outcomes of immune checkpoint blockade. Here, we report a biocompatible alginate-based hydrogel loaded with Pexidartinib (PLX)-encapsulated nanoparticles that gradually release PLX at the tumor site to block colony-stimulating factor 1 receptors (CSF1R) for depleting TAMs. The controlled TAM depletion creates a favorable milieu for facilitating local and systemic delivery of anti-programmed cell death protein 1 (aPD-1) antibody-conjugated platelets to inhibit post-surgery tumor recurrence. The tumor immunosuppressive microenvironment is also reprogrammed by TAM elimination, further promoting the infiltration of T cells into tumor tissues. Moreover, the inflammatory environment after surgery could trigger the activation of platelets to facilitate the release of aPD-1 accompanied with platelet-derived microparticles binding to PD-1 receptors for re-activating T cells. All these results collectively indicate that the immunotherapeutic efficacy against tumor recurrence of both local and systemic administration of aPD-1 antibody-conjugated platelets could be strengthened by local depletion of TAMs through the hydrogel reservoir.


Effect of a low concentration of angiotensin II on vascular smooth muscle tone.
We have previously found that long-term blockade of angiotensin II (AII) formation by captopril suppresses the "leakiness" of vascular smooth muscle membrane from spontaneously hypertensive rats. The present study was undertaken to examine whether a subpressor concentration of AII alters the membrane permeability and the tension of vascular smooth muscle of rats. The isometric tensions of rat aortic strips were recorded and the cellular Na contents in the muscles were measured by the "cold Li-exchange method." Lowering external K+ concentration to 0 or 0.5 mM produced slowly developing contractions in the muscles. These contractions were significantly enhanced by 4 h of pretreatment with 3 X 10(-10) M AII, whereas there were no contractions in normal Tyrode solution. Increase in cellular Na during incubation in K+-free solution was greater in AII-pretreated muscles and the cellular Na in these muscles leaked out more rapidly into cold Li solution than it did in untreated muscles. These findings suggest that the subpressor concentration of AII increases the passive permeability of vascular smooth muscles to Na and, if the Na pump activity is partially impaired, elevates the vascular tone.


Traditional Chinese medicine Zhiqiao-Houpu herb-pair induce bidirectional effects on gastric motility in rats.
Zhiqiao-Houpu herb-pair (ZQHPHP), composed of Fructus Aurantii (Zhiqiao [ZQ] in Chinese) and Magnolia officinalis (Houpu [HP] in Chinese), is a traditional herbal formula that has been extensively used for treating gastrointestinal motor dysfunction. The aim of the study was to evaluate the effect and possible mechanism of ZQHPHP on gastric emptying (GE) and gastric antral smooth muscle contractility (GASMC). This study includes four parts: (a) study of ZQHPHP's effect on GE; (b) study of ZQHPHP's effect on gastric antral smooth muscle contractility (GASMC); (c) comparing the effects of ZQHPHP, ZQ and HP on GASMC; (d) study of antagonists or agonists on ZQHPHP-induced GASMC. A test meal of Evans blue was adopted to estimate GE in rats. A polygraph was used to measure GASMC in rats. The in vivo experiments demonstrated that, at the doses of 10mg/kg bw and 20mg/kg bw, ZQHPHP could promote GE. While, at the higher dose of 30 mg/kg bw, ZQHPHP delayed the GE. From the in vitro experiments we found that ZQHPHP (3-10 μg/ml) concentration-dependently increased the mean amplitude of contractions in the antral circular strip compared to untreated controls. While, in the concentration of 30 μg/ml, ZQHPHP prohibited GASMC. Besides, atropine blocked the stimulatory effect of ZQHPHP on GASMC and norepinephrine partly prohibited the stimulatory effect of ZQHPHP on GASMC, whereas isoproterenol showed no effect. From the in vitro experiment, we also found that ZQ and HP used together can synergistically increase gut motor. The experiment indicated that ZQHPHP could induce bidirectional regulation on gastric motility. ZQ and HP used together can synergistically increase gut motor at a certain dosage. Lower dosage of ZQHPHP increases gastric motility, while higher dosage produces inhibition. In addition, the improvement of gastric motility by ZQHPHP is predominantly involved with muscarinic receptors and secondarily with alpha-receptors.


Sumo wrestling in ants: major workers fight over male production in Acanthomyrmex ferox.
In the myrmicine ant Acanthomyrmex ferox, major workers have the same number of ovarioles as queens, thrice that of minor workers, making them well suited for egg-laying. In the queen's presence, infrequent aggression allows ranking of majors but they lay only unviable trophic eggs. Major workers engage each other, but not the minors, in antennal boxing and spectacular shaking contests, a novel interaction in ants. The absence of reversals allows a clear ranking of major workers. After queen removal, aggression becomes very frequent, but previous ranking is maintained. All majors start laying reproductive eggs although they show a skew in ovary development according to ranking. The dominant major, however, actively patrols the egg-pile and cannibalises eggs laid by subordinates.


Interleukin-17 Promotes the Infiltration of CD8+ T Cells into the Brain in a Mouse Model for Alzheimer's Disease.
Interleukin-17 (IL-17) family cytokines play critical roles in inflammation and pathogen resistance. Inflammation in the central nervous system, denoted as neuroinflammation, promotes the onset and progression of Alzheimer's disease (AD). Previous studies showed that IL-17A neutralizing antibody treatment alleviated Amyloid β (Aβ) burden in rodent models of AD, while overexpression of IL-17A in mouse lateral ventricles rescued part of the AD pathology. However, the involvement of IL-17 in AD and its mechanism of action remain largely unknown. To investigate the role of IL-17 in AD, we crossed mice lacking the common receptor of IL-17 signaling (IL-17RA knockout mice) to the APP/PS1 mouse model of AD. We then analyzed the composition of immune cells and cytokines/chemokines during different phases of AD pathology, and interrogated the underlying mechanism by which IL-17 may regulate immune cell infiltration into AD brains. Ablation of IL-17RA in APP/PS1 mice decreased infiltration of CD8+ T cells and myeloid cells to mouse brain. IL-17 was able to promote the production of myeloid- and T cell-attracting chemokines CXCL1 and CXCL9/10 in primary glial cells. We also observed that IL-17 is upregulated in the late stage of AD development, and ectopic expression of IL-17 via adenoviral infection to the cortex trended towards worsened cognition in APP/PS1 mice, suggesting a pathogenic role of excessive IL-17 in AD. Our data show that IL-17 signaling promotes neuroinflammation in AD by accelerating the infiltration of CD8+ T lymphocytes and Gr1+ CD11b+ myeloid cells.


Freeze fracture analysis of apical membranes in cochlear cultures: differences between basal and apical-coil outer hair cells and effects of neomycin.
Previous studies have shown that exposure of cochlear cultures to the ototoxic aminoglycoside antibiotic neomycin leads to the rapid formation of numerous membrane filled protrusions on the apical surface of the hair cells but not on the surrounding supporting cells, and that hair cells in basal-coil cultures are more sensitive to these effects of neomycin than those in the distal end of apical-coil cultures. Freeze-fracture has been used to examine and compare the apical surfaces of hair cells and supporting cells in basal and apical-coil cultures in order to look for features that may explain the differential sensitivity of the various cell types to neomycin, and to characterize the membrane type that forms in response to neomycin and compare it with the normal apical membrane of the hair cell. The apical surface of the highly responsive basal-coil outer hair cells differs significantly from the apical surfaces of apical-coil outer hair cells and supporting cells in both regions of the cochlea in both surface area and the number and density of endocytotic vesicles associated with this surface. Basal-coil hair cells have an average of 120 +/- 39 vesicles per cell surface and a density of 3.5 +/- 0.89 vesicles per microns 2, whereas apical-coil hair cells have 14.8 +/- 15.8 vesicles/cell surface and density of 0.73 +/- 0.72 vesicles per microns 2. There are no significant differences in intramembrane particle (IMP) density on the apical surfaces of all the cell types examined, and qualitative observations of filipin-treated specimens indicate that cholesterol densities are also similar. The membrane that accumulates in response to neomycin treatment at the apical pole of the hair cell is IMP free, does not respond to filipin, and fractures in a manner that is indicative of a high content of unsaturated phospholipid in a fluid phase, and is therefore different in several respects from the normal apical surface of the hair cell. The results of this study suggest that apical surface associated endocytotic vesicle numbers may determine the differential sensitivity of apical and basal-coil hair cells to neomycin, and that neomycin may interfere with some aspect of phospholipid metabolism or membrane turnover in sensory hair cells.


Companies under stress: the impact of shocks on the production network.
In this paper we analyze the effect of shocks in production networks. Our work is based on a rich dataset that contains information about companies from Slovenia right after the financial crisis of 2008. The processed data spans for 8 years and covers the transaction history as well as performance indicators and various metadata of the companies. We define sales shocks at different levels, and identify companies impacted by them. Next we investigate stress, the potential immediate upstream and downstream impact of a shock within the production network. We base our main findings on a matched pairs analysis of stressed companies. We find that both shock and stress are associated with reporting bankruptcy in the future and that stress foremost impacts the future sales of customers. Furthermore, we find evidence that stress not only results in performance losses but the reconfiguration of the production network as well. We show that stressed companies actively seek for new trading partners, and that these new links often share the industry of the shocked company. These results suggest that both stressed customers and suppliers react quickly to stress and adjust their trading relationships.