Novel Effects of Traditional Wooden Toothbrush on Bowel Motility Symptoms in Spinal Cord Injury Patients; Findings from a Pilot Quasi-experimental Study.
The aim of this study was to investigate the therapeutic effect of traditional wooden toothbrush usage on most severe constipation, which usually occurs in spinal cord injury (SCI) patients. In a quasi-experimental study, 61 SCI patients were selected who had injuries in different spinal levels (cervical, thoracic, and lumbar), and severe constipation from one defection in a few days to 3 weeks. They were recommended to use traditional wooden toothbrush for 5 min twice a day, after breakfast and dinner, over a 6 weeks period. Two proper standard scales, called neurogenic bowel dysfunction (NBD), and "Constipation Assessment Scale (CAS)," were used for evaluating the changes in patients' gastrointestinal (GI) habits during the period of using the wooden toothbrush. Through these scales (NBD and CAS), the therapeutic effects of traditional wooden toothbrush usage on the severity of constipation before and after intervention were measured. The mean of NBD and CAS scores were reduced significantly, from 8.95 ± 0.78 and 3.34 ± 0.28; respectively, to 3.03 ± 0.57 and 1.74 ± 0.25, after 6 weeks using traditional wooden toothbrush (P < 0.0001). There was a significant difference in terms of NBD scores in patients with different levels of injury (P < 0.01), particularly in patients with thoracic injury, before (10.52 ± 0.88) and after (3.13 ± 0.78) treatment, respectively (P < 0.0001). Eventually, all symptoms of bowel problems improved significantly after the intervention (P < 0.05). The use of traditional wooden toothbrush lead to the improvement of bowel and defecation problems in SCI patients. Yet more studies, particularly randomized control clinical trials are needed to investigate the effect of using wooden toothbrush on other GI reflexes. In addition, if some clinical trials are devised to study the effects of wooden toothbrush on both conscious and unconscious patients in ICU, best results are expected to be found on keeping their mouth and teeth hygiene, as well as, getting rid of their constipations.


Identification of the porcine sialoadhesin gene promoter region and its cell-specific expression in porcine alveolar macrophage cells.
Porcine reproductive and respiratory syndrome (PRRS), which is caused by the PRRS virus (PRRSV), is a communicable disease. PRRS caused huge economic losses to swine breeding. The porcine alveolar macrophage (PAM) cell is the main target cell of PRRSV; therefore, it is very important to identify the specific gene promoter that controls expression in PAM cells so that the anti-PRRSV exogenous gene can be efficiently and specifically expressed in PAM cells to improve porcine resistance to PRRSV. In this study, the transcription initiation site for sialoadhesin (Siglec-1), which is a porcine alveolar macrophage-specific gene, was determined by 5' rapid amplification of cDNA end, and 88 bp of the 5'-untranslated region was cloned. Siglec-1 promoter activity was detected by a dual-luciferase reporter assay, which showed that the fragment from -173 to +81 bp had the strongest promoter activity. Additionally, the cell-specific expression of the promoter fragments was tested in a PAM cell line (CRL-2844 cells), porcine kidney 15 cell line (PK-15 cells), porcine fetal fibroblast (PEF) cells, and porcine preadipocytes. These results also showed that the fragment from -173 to +81 bp had the strongest cell-specific expression in PAM cells.


Unity-order magnetochiral effects exhibited by a single metamolecule.
A numerical study predicts that a single metamolecule with magnetism and chirality has giant magnetochiral (MCh) effects at microwave frequencies. The magnetism is provided by the ferromagnetic resonance of ferrite under dc bias magnetic fields, while the chirality is provided by the spiral arrangement of dielectric cubes with Mie resonance. The dielectric and magnetic resonances interfere in the metamolecule, resulting in a two-order of magnitude enhancement of the MCh effect compared with that reported in previous studies. This prediction is verified experimentally. A unity-order directional difference in the refractive index caused by the MCh effect is also demonstrated. This study is a significant milestone in the practical use of the MCh effect.


Down-regulated PAR-2 is associated in part with interrupted melanosome transfer in pigmented basal cell epithelioma.
In pigmented basal cell epithelioma (BCE), there seems to be an abnormal transfer of melanized melanosomes from proliferating melanocytes to basaloid tumor cells. In this study, the interruption of that melanosome transfer was studied with special respect to the altered function of a phagocytic receptor, protease-activated receptor (PAR)-2 in the basaloid tumor cells. We used electron microscopy to clarify the disrupted transfer at the ultrastructural level and then performed immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to examine the regulation of a phagocytic receptor, PAR-2, expressed on basaloid tumor cells. Electron microscopic analysis revealed that basaloid tumor cells of pigmented BCE have a significantly lower population of melanosomes ( approximately 16.4%) than do normal keratinocytes located in the perilesional normal epidermis ( approximately 91.0%). In contrast, in pigmented seborrheic keratosis (SK), a similarly pigmented epidermal tumor, the distribution of melanin granules does not differ between the lesional ( approximately 93.9%) and the perilesional normal epidermis ( approximately 92.2 %), indicating that interrupted melanosome transfer occurs in BCE but not in all pigmented epithelial tumors. RT-PCR analysis demonstrated that the expression of PAR-2 mRNA transcripts in basaloid cells is significantly decreased in pigmented BCE compared with the perilesional normal epidermis. In contrast, in pigmented SK, where melanosome transfer to basaloid tumor cells is not interrupted, the expression of PAR-2 mRNA transcripts is comparable between the basaloid tumor cells and the perilesional normal epidermis. Immunohistochemistry demonstrated that basaloid cells in pigmented BCE have less immunostaining for PAR-2 than do keratinocytes in the perilesional normal epidermis whereas in pigmented SK, there is no difference in immunostaining for PAR-2 between the basaloid tumor and the perilesional normal epidermis. These findings suggest that the decreased expression of PAR-2 in the basaloid cells is associated in part with the observed interruption of melanosome transfer in pigmented BCE.


Ensuring content integrity when using commercial support.
Preventing continuing education program bias when commercial support is used can be challenging. Standards have been developed by health care professional accreditation organizations that focus on independence, conflict of interest, appropriate management of commercial funds, content integrity, and disclosure to learners. Implementation of these standards can significantly reduce the risk of bias and improve dissemination of balanced clinical information.


Heritability and genetic association analysis of neuroimaging measures in the Diabetes Heart Study.
Patients with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Neuroimaging measures such as white matter lesion volume, brain volume, and fractional anisotropy may reflect the pathogenesis of these cognitive declines, and genetic factors may contribute to variability in these measures. This study examined multiple neuroimaging measures in 465 participants from 238 families with extensive genotype data in the type 2 diabetes enriched Diabetes Heart Study-Mind cohort. Heritability of these phenotypes and their association with candidate single-nucleotide polymorphisms (SNPs), and SNP data from genome- and exome-wide arrays were explored. All neuroimaging measures analyzed were significantly heritable (ĥ(2) = 0.55-0.99 in unadjusted models). Seventeen candidate SNPs (from 16 genes/regions) associated with neuroimaging phenotypes in prior studies showed no significant evidence of association. A missense variant (rs150706952, A432V) in PLEKHG4B from the exome-wide array was significantly associated with white matter mean diffusivity (p = 3.66 × 10(-7)) and gray matter mean diffusivity (p = 2.14 × 10(-7)). This analysis suggests genetic factors contribute to variation in neuroimaging measures in a population enriched for metabolic disease and other associated comorbidities.


A new method for constructing linker scanning mutants.
A new procedure for the construction of linker scanning mutants is described. A plasmid containing the target DNA is randomly linearized and slightly shortened by a novel combination of established methods. After partial apurination with formic acid a specific nick or small gap is introduced at the apurinic site by exonuclease III, followed by nuclease S1 cleavage of the strand opposite the nick/gap. Synthetic linkers are ligated to the ends and plasmids having the linker inserted in the target DNA are enriched. Putative linker scanning mutants are identified by their topoisomer patterns after relaxation with topoisomerase I. This technique allows the distinction of plasmids differing in length by a single basepair. We have used this rapid and efficient strategy to generate a set of 32 linker scanning mutants covering the chicken lysozyme promoter from -208 to +15.


Pancreatic carcinoma recurrence in the remnant pancreas after a pancreaticoduodenectomy.
We report a rare case of a repeated pancreatic resection in the remnant distal pancreas 18 months after a Whipple R0 procedure. In September 2003, a 63-year-old man underwent a Whipple procedure with an extended lymphadenectomy, portal vein resection and direct reconstruction for pancreatic cancer. In September 2004, the tumor marker level increased and MR revealed a tumor in the remnant pancreas. There were no findings of invasion into the surrounding tissue or distant metastasis. After three months of systemic chemotherapy and a radiological reevaluation (PET and CT) in March 2005, we removed the remnant pancreas. Histopathologically, the tumor was classified as a ductal adenocarcinoma like the tumor which had been removed during the first operation, with infiltration of peripancreatic adipose tissue and a segmentary tract of the transverse mesocolon, without lymph node metastasis. There are very few reports of pancreatic carcinoma recurrence in the remnant pancreas after a pancreaticoduodenectomy in the literature. In most of these cases, it is difficult to assess whether the remnant pancreatic cancer is a recurrence or a second primary cancer. In our patient, the first hypothesis seems to be more realistic due to the brief recurrence-free survival period. Otherwise the high rate of multicentricity in pancreatic cancer may also explain the development of a secondary cancer in the remnant pancreas, even though the interval was relatively brief.


Sterols in infant formulas: validation of a gas chromatographic method.
Sterols are components present in the fat fraction of infant formulas (IFs). Their characterization is therefore of interest, though there are no official reference methods for their analysis in these matrices. To validate a gas chromatographic method with flame ionization detection for the determination of animal (cholesterol and desmosterol) and plant sterols (brassicasterol, campesterol, stigmasterol, β-sitosterol and sitostanol) found in IFs. All correlation coefficients obtained for the calibration curves of sterols studied were >0.99. Limits of detection (<1 μg/100 mL) and quantification (<4 μg/100 mL) are suitable for sterols determination in IFs. The within-assay precision ranged from 1.6% to 8.8%, while the between-assay precision was <10% for most of sterols. Accuracy was satisfactory and was calculated by recovery assays (ranging 93-108%). The analytical parameters obtained showed the suitability of the proposed method for the determination of sterols in IFs.


Structure and development of viruses as observed in the electron microscope. I. Herpes simplex virus.
Herpes simplex virus was visualized by the electron microscope in sections of infected chorioallantoic membrane of chicken embryos. Removal of the embedding methacrylate from relatively thick sections permitted large numbers of viral particles to be seen but caused extensive alteration of cellular components as well as variable distortion of viral structure. This distortion was characterized by disruption of particles and loss of central bodies, resulting in ring or empty shell forms. An inner structure of the virus was revealed in ultrathin sections from which the embedding plastic was not removed. The nuclei of infected cells contained small, dense, primary bodies (30 to 40 mmicro in diameter) as well as slightly larger and less dense particles (40 to 50 mmicro in diameter) surrounded by a single membrane (70 to 100 mmicro in diameter). In the cytoplasm most of the particles possessed a double outer membrane (120 to 130 mmicro in diameter). It is suggested that the initial site of viral development is restricted to the nucleus where primary bodies form and become enclosed by a single outer membrane. Upon release into the cytoplasm these particles appear to acquire a second outer membrane and presumably represent the mature virus.


Physiologic changes associated with endotracheal intubation in preterm infants.
Physiologic changes associated with endotracheal intubation were examined in 10 preterm infants. Laryngoscopy was associated with apnea and minor abnormalities in cardiac rhythm in 2 infants. Three infants had nasal airflow recordings which demonstrated obstructed breaths during laryngoscopy. Systolic blood pressure (BP) increased 47% when the trachea was intubated, whereas heart rate and transcutaneous oxygen tension (PtcO2) decreased. Because endotracheal intubation is a physiologically stressful procedure, personnel who intubate preterm infants must be skilled and experienced to minimize the duration of laryngoscopy and the number of intubation attempts.


Fabrication of CuO (p)-ZnO (n) Core-Shell Nanowires and Their H2-Sensing Properties.
Unlike the conventional one-dimensional (1D) core-shell nanowires (NWs) composed of p-type shells and n-type cores, in this work, an inverse design is proposed by depositing n-type ZnO (shell) layers on the surface of p-type CuO (core) NWs, to have a comprehensive understanding of their conductometric gas-sensing kinetics. The surface morphologies of bare and core-shell NWs were investigated by field emission scanning electron microscope (FE-SEM). The ZnO shell layer was presented by overlay images taken by electron dispersive X-ray spectroscopy (EDX) and high-resolution transmission electron microscopy (HRTEM). The pronounced crystalline plane peaks of ZnO were recorded in the compared glancing incident X-ray diffraction (GI-XRD) spectra of CuO and CuO-ZnO core-shell NWs. The ZnO shell layers broaden the absorption curve of CuO NWs in the UV-vis absorption spectra. As a result of the heterostructure formation, the intrinsic p-type sensing behavior of CuO NWs towards 250 and 500 ppm of hydrogen (H2) switched to n-type due to the deposition of ZnO shell layers, at 400 °C in dry airflow.


Dynamic Event-Driven Finite-Horizon Optimal Consensus Control for Constrained Multiagent Systems.
This article investigates the event-driven finite-horizon optimal consensus control problem for multiagent systems with symmetric or asymmetric input constraints. Initially, in order to overcome the difficulty that the Hamilton-Jacobi-Bellman equation is time-varying in finite-horizon optimal control, a single critic neural network (NN) with time-varying activation function is applied to obtain the approximate optimal control. Meanwhile, for minimizing the terminal error to satisfy the terminal constraint of the value function, an augmented error vector containing the Bellman residual and the terminal error is constructed to update the weight of the NN. Furthermore, an improved learning law is proposed, which relaxes the tricky persistence excitation condition and eliminates the requirement of initial stability control. Moreover, a specific algorithm is designed to update the historical dataset, which can effectively accelerate the convergence rate of network weight. In addition, to improve the utilization rate of the communication resource, an effective dynamic event-triggering mechanism (DETM) composed of dynamic threshold parameters (DTPs) and auxiliary dynamic variables (ADVs) is designed, which is more flexible compared with the ADV-based DETM or DTP-based DETM. Finally, to support the effectiveness of the proposed method and the superiority of the designed DETM, a simulation example is provided.


The refurbished pulse generator.
With the advent of long-life lithium pulse generators, normally functioning pulse generators with a potential life of more than five years have been removed from patients and become available for re-implantation. Although pulse generator refurbishing is widely employed, the practice has not been accepted in the United States. At The Royal Melbourne Hospital, all lithium pulse generators removed because of patient death or other causes were washed in a quaternary ammonium compound and soaked in formaldehyde. Pulse generators were than electronically tested and, if within specification, were made available for re-implantation. Pulse generators were then washed under sterile conditions in distilled water and gas-sterilized with ethylene oxide. Between 1975 and 1978 (48 months), 600 pulse generators were implanted and 93 pulse generators removed. There were 56 deaths, 22 cases of pre-erosion, erosion, or infection and 15 elective removals either due to lead problems or impending power source depletion. Eight-three (89%) pulse generators were refurbished (14% of total implants). This included 12 pulse generators refurbished on two occasions. Ten pulse generators were returned to manufacturers, seven because of impending power source depletion, two with suspected electronic faults, and one with a damaged case. Two complications occurred in patients with refurbished pulse generators. An infective process present with the previous pulse generator spread to a new pocket. The other pulse generator was removed 35 months post second implantation because of impending power source depletion. Primary infection or unusual tissue reactions did not occur. Pulse generator refurbishing as described was found to be a safe and economic procedure.


Assessment of Visual and Chromatic Functions in a Rodent Model of Retinal Degeneration.
We evaluated the photoreceptor response of pigmented P23H and normal pigmented Long Evans (LE) rats over time using functional tests in variable lighting conditions. Pigmented P23H rats were studied by optomotor testing and electroretinogram (ERG) recordings at P30, P150, and P240. Pigmented LE rats were used as a normal wild-type control. Stimuli were modified with colored filters. Neutral density filters were used to reduce luminance. Age-related decreases in visual acuity (VA) and contrast sensitivity (CS) were observed in P23H rats. Good correlations in measurements without filter and with green filter were observed between LE and P23H P30 rat values. Differences between groups were smaller with red and purple filters. A strong relationship with luminance was observed in LE rats (VA and CS) and with P23H P30 rats (CS). A decline in the ERG responses of P23H rats was consistent with the gradual loss of photoreceptors. Differences in a- and b-wave amplitudes with different colored filters were negligible with the exception of the red filter, which resulted in smaller responses. Visual function parameters decreased with age in pigmented P23H rats. Irrespective of luminance, color filter, and retinal degeneration, minimum thresholds of VA and CS were found. Smaller differences than expected were found using color filters. Responses to functional tests at long wavelengths were observed, where there is very low photoreceptor spectral sensitivity. The use of filters with functional testing could minimize light-induced retinal damage in rats.


A Comparative Evaluation of Ramosetron with Ondansetron for the Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Urological Procedures.
Postoperative nausea and vomiting (PONV) is a common problem causing distress to patients in the postoperative period. Younger age, gynecological surgeries, laparoscopic surgeries, female gender, volatile anesthetics, increased duration of anesthesia, and postoperative opioid use are associated with increased incidence of PONV. The present study was conducted to study the efficacy of ramosetron and its comparison with ondansetron in the prevention of PONV in patients undergoing pyelolithotomy, pyeloplasty, and upper ureterolithotomy. One hundred patients with physical status American Society of Anesthesiologists I and II, aged 20-60 years were enrolled in the study. Patients were randomly distributed to receive either injection ramosetron 0.3 mg intravenously (IV) or injection ondansetron 6 mg IV just before extubation. There was no significant difference between the groups in age, gender, weight, duration of anesthesia, and duration of surgery. In the patients, who received ramosetron, it was observed that incidence of the episodes of nausea and vomiting increased with time after surgery. Each patient had an episode of nausea and an episode of vomiting during the 6-12 h interval. Similarly, two patients had episodes of nausea and two patients had episodes of vomiting at 18-24 h. This necessitated the increased need for rescue antiemetics with a total of four patients needing rescue antiemetics at 18-24 h. In patients receiving ondansetron, the episodes of nausea were more in number when compared with the ramosetron group. Twelve patients complained of nausea and thirteen patients had episodes of vomiting with the needfor rescue antiemetic in 14 patients. Both genders had a comparable incidence of nausea and vomiting. A single dose of IV ramosetron (0.3 mg) is more effective when compared with a single dose IV ondansetron (6 mg) in the prevention of PONV. We observed that the benefit was more in the later stages of the postoperative period (12-24 h).


The WISC-V in children and adolescents with epilepsy.
Despite its popularity in the neuropsychological evaluation of children, the utility of the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) has not yet been investigated in children with epilepsy. Eighty clinically referred children and adolescents with epilepsy were administered the WISC-V as part of a comprehensive assessment and scores were compared to matched controls from the WISC-V standardization sample. T tests compared WISC-V indices and subtests between patients and controls and Chi-square analyses compared the rates of low scores. Correlational analyses assessed the relationships between epilepsy severity variables (e.g., age of onset, duration of epilepsy, number of antiepileptic drugs, seizure frequency). All WISC-V composites and subtests were significantly lower in patients versus controls and the rate of low scores was higher in patients than controls for all composites and subtests with the exception of Figure Weights. The Working Memory Index and Processing Speed Index were most sensitive to impairment, while the Verbal Comprehension Index and Fluid Reasoning Index were least sensitive. Of the epilepsy severity variables, age of seizure onset and number of antiepileptic drugs were strong predictors of deficits, whereas seizure frequency was the weakest predictor. Importantly, no significant differences were seen in children with right hemisphere epilepsy versus left on the five WISC-V composites, though a trend was seen towards a lower Visual-Spatial Index in those with right-sided focal seizures.


ATM gene mutations are not involved in medulloblastoma in children.
Primitive neuroectodermal tumors (PNET)-medulloblastomas account for approximately 20% of all brain tumors in children. Ataxia-telangiectasia is an autosomal recessive neurological disorder with predisposition to cancer. The most common neoplasms are lymphoid malignancies and solid tumors, including central nervous system tumors, astrocytomas, and medulloblastomas. To investigate the potential role of the ATM gene in the pathogenesis of medulloblastoma, 13 tumors were screened for ATM mutations and 9 for loss of heterozygosity (LOH) of the ATM locus and flanking regions. In none of the tumors were mutations identified. In five of them, the well-known polymorphisms D1853N and F858L were identified and in all 22 tumors, the wild-type allele was preserved. The frequency of the polymorphisms was similar to that reported in our and other normal populations. The LOH of the 11q region (including the ATM gene), detected in 25% of informative cases, is consistent with the molecular and cytogenetic reports of deletion of chromosome 11 in 13%-41% of medulloblastomas. These results indicate that mutations in the ATM gene do not play a role in the pathogenesis of medulloblastoma in children. The LOH in the 11q region may suggest hidden unidentified tumor suppressor genes that may be involved in the malignant transformation.


Transgenic overexpression of ephrin b1 in bone cells promotes bone formation and an anabolic response to mechanical loading in mice.
To test if ephrin B1 overexpression enhances bone mass, we generated transgenic mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1 promoter (Col3.6-Tg (efnb1) ). Col3.6-Tg (efnb1) mice express 6-, 12- and 14-fold greater levels of full-length ephrin B1 protein in bone marrow stromal cells, calvarial osteoblasts, and osteoclasts, respectively. The long bones of both genders of Col3.6-Tg (efnb1) mice have increased trabecular bone volume, trabecular number, and trabecular thickness and decreased trabecular separation. Enhanced bone formation and decreased bone resorption contributed to this increase in trabecular bone mass in Col3.6-Tg (efnb1) mice. Consistent with these findings, our in vitro studies showed that overexpression of ephrin B1 increased osteoblast differentiation and mineralization, osterix and collagen 1A1 expression in bone marrow stromal cells. Interaction of ephrin B1 with soluble clustered EphB2-Fc decreased osteoclast precursor differentiation into multinucleated cells. Furthermore, we demonstrated that the mechanical loading-induced increase in EphB2 expression and newly formed bone were significantly greater in the Col3.6-Tg (efnb1) mice than in WT littermate controls. Our findings that overexpression of ephrin B1 in bone cells enhances bone mass and promotes a skeletal anabolic response to mechanical loading suggest that manipulation of ephrin B1 actions in bone may provide a means to sensitize the skeleton to mechanical strain to stimulate new bone formation.


HutT functions as the major L-histidine transporter in Pseudomonas putida KT2440.
Histidine is an important carbon and nitrogen source of γ-proteobacteria and can affect bacteria-host interactions. The mechanisms of histidine uptake are only partly understood. Here, we analyze functional properties of the putative histidine transporter HutT of the soil bacterium Pseudomonas putida. The hutT gene is part of the histidine utilization operon, and the gene product belongs to the amino acid-polyamine-organocation (APC) family of secondary transporters. Deletion of hutT severely impairs growth of P. putida on histidine, suggesting that the encoded transporter is the major histidine uptake system of P. putida. Transport experiments with cells and purified and reconstituted protein indicate that HutT functions as a high-affinity histidine : proton symporter with high specificity for the amino acid. Substitution analyses identified amino acids crucial for HutT function.


Cytosolic prion protein toxicity is independent of cellular prion protein expression and prion propagation.
Prion diseases are transmissible neurodegenerative diseases caused by a conformational isoform of the prion protein (PrP), a host-encoded cell surface sialoglycoprotein. Recent evidence suggests a cytosolic fraction of PrP (cyPrP) functions either as an initiating factor or toxic element of prion disease. When expressed in cultured cells, cyPrP acquires properties of the infectious conformation of PrP (PrP(Sc)), including insolubility, protease resistance, aggregation, and toxicity. Transgenic mice (2D1 and 1D4 lines) that coexpress cyPrP and PrP(C) exhibit focal cerebellar atrophy, scratching behavior, and gait abnormalities suggestive of prion disease, although they lack protease-resistant PrP. To determine if the coexpression of PrP(C) is necessary or inhibitory to the phenotype of these mice, we crossed Tg1D4(Prnp(+/+)) mice with PrP-ablated mice (TgPrnp(o/o)) to generate Tg1D4(Prnp(o/o)) mice and followed the development of disease and pathological phenotype. We found no difference in the onset of symptoms or the clinical or pathological phenotype of disease between Tg1D4(Prnp(+/+)) and Tg1D4(Prnp(o/o)) mice, suggesting that cyPrP and PrP(C) function independently in the disease state. Additionally, Tg1D4(Prnp(o/o)) mice were resistant to challenge with mouse-adapted scrapie (RML), suggesting cyPrP is inaccessible to PrP(Sc). We conclude that disease phenotype and cellular toxicity associated with the expression of cyPrP are independent of PrP(C) and the generation of typical prion disease.


MicroRNA-122 influences the development of sperm abnormalities from human induced pluripotent stem cells by regulating TNP2 expression.
Sperm abnormalities are one of the main factors responsible for male infertility; however, their pathogenesis remains unclear. The role of microRNAs in the development of sperm abnormalities in infertile men has not yet been investigated. Here, we used human induced pluripotent stem cells to investigate the influence of miR-122 expression on the differentiation of these cells into spermatozoa-like cells in vitro. After induction, mutant miR-122-transfected cells formed spermatozoa-like cells. Flow cytometry of DNA content revealed a significant increase in the haploid cell population in spermatozoa-like cells derived from mutant miR-122-transfected cells as compared to those derived from miR-122-transfected cells. During induction, TNP2 and protamine mRNA and protein levels were significantly higher in mutant miR-122-transfected cells than in miR-122-transfected cells. High-throughput isobaric tags for relative and absolute quantification were used to identify and quantify the different protein expression levels in miR-122- and mutant miR-122-transfected cells. Among all the proteins analyzed, the expression of lipoproteins, for example, APOB and APOA1, showed the most significant difference between the two groups. This study illustrates that miR-122 expression is associated with abnormal sperm development. MiR-122 may influence spermatozoa-like cells by suppressing TNP2 expression and inhibiting the expression of proteins associated with sperm development.


COVID-19 and Nigeria: putting the realities in context.
Coronavirus disease 2019 (COVID-19), which was previously known as 2019-novel coronavirus (2019-nCoV), was first reported in Wuhan, China in December 2019. The disease evolved into a serious global emergency, leading to its declaration as a pandemic. On the African continent, Nigeria is just experiencing the direct effects of this pandemic, having recorded her index case in February 2020, with an increasing number of cases every day and a current case fatality ratio of 0.03 as at 13 April 2020. Although the recorded cases may seem low, it has been forecast that Africa will have some of the worst effects of this disease by the end of the pandemic. Generally, African countries have fragile health systems and this remains a source of concern, especially in the event of increased outbreaks. Nigeria's current national health systems cannot effectively respond to the growing needs of already infected patients requiring admission into intensive care units for acute respiratory diseases and severe acute respiratory syndrome (SARS COV-2) pneumonia. This has grim implications for Nigeria, especially as increased cases loom that may require critical care. Provision of quarantine or isolation facilities and availability of rapid diagnostic kits for fast and reliable testing and diagnosis of the disease can also be a challenge in Africa. There is an urgent need to put into perspective these realities peculiar to Africa including Nigeria and explore available collective measures and interventions to address the COVID-19 pandemic.


Tracheal necrosis following tracheal intubation in a dog.
Tracheal rupture and stenosis are well-reported problems in human beings and cats following endotracheal intubation. However, this problem has been rarely reported in dogs. This case report describes a case of tracheal necrosis 5 days following endotracheal intubation in a dog associated with overinflation of the endotracheal tube cuff and multiple changes in position.


Quality of life and sexual functioning in cervical cancer survivors.
To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy. Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer. One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures. Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.


[Tim-3: a novel biomarker and therapeutic target in oncology].
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis. Tim-3 recently appeared as a potential biomarker of anti-PD-1 resistance. Combined blockade of PD-1 and Tim-3 axis demonstrated potent clinical efficacy in preclinical models and reinforced the rationale of using an anti-Tim-3 to override tumor resistance.


Rapid detection of oxacillin-resistant Staphylococcus aureus in blood cultures by an impedance method.
The feasibility of using an impedance method for direct detection of oxacillin-resistant Staphylococcus aureus (ORSA) in blood cultures was evaluated. An aliquot (0.1 ml) of the positive blood culture, which showed growth of gram-positive cocci and demonstrated thermonuclease activity, was inoculated into the module well of a Bactometer incubator (bioMerieux Vitek, Hazelwood, Mo.) containing 0.6 ml of Mueller-Hinton agar supplemented with oxacillin (2 microg/ml). The modules were incubated at 37 degrees C, and the change in impedance in each well was continuously monitored by the instrument at 6-min intervals for 24 h. ORSA strains from blood cultures could multiply in the oxacillin-containing medium, and a time point (detection time [DT]) at which an accelerating change of impedance occurred in the medium was obtained, with an average of 5.5 h. The growth of oxacillin-sensitive S. aureus (OSSA) strains was largely inhibited, and no DT was obtained for these strains within an incubation period of 24 h. For 96 positive blood cultures (38 ORSA and 58 OSSA) tested, 36 and 57 were found to be oxacillin resistant and oxacillin sensitive, respectively, by the impedance method. The impedance method had a sensitivity and specificity of 94.7 and 98.3%, respectively, for the detection of ORSA and had an agreement of 96.9% with the disc diffusion method. Comparable results were obtained by the testing of 235 clinical stock cultures of S. aureus (149 ORSA and 86 OSSA). The impedance test is simple for detecting ORSA in blood cultures and may allow proper antimicrobial treatment almost 36 h before the results of the conventional culture methods are available.


[A case of interferon-alpha-resistant renal cell carcinoma responding to interleukin-2 therapy].
A 71-year-old woman was admitted with fever up and weight loss. Abdominal computed tomography (CT) revealed right renal tumor 7 cm in diameter and inferior vena caval thrombus and multiple lymph node metastases and lung metastases. Transabdominal right nephrectomy and thrombectomy was performed and pathological examination was renal cell carcinoma (clear cell carcinoma, G3, INFbeta, v (+), pT3b, pN2) with adrenal invasion and lymph node metastases. She received 600 x 10(4) IU/day of interferon alpha (IFN-alpha) intramuscularly 3 times a week for 16 weeks from the 20th post-operative day. The disease showed progression and liver metastases 5 cm in diameter appeared. Then she received 140 x 10(4) JRU/day of IL-2 (div) 5 times a week for 4 weeks. CT showed a complete response on lung metastases and lymph node metastases and marked decrease of liver metastases after the first course of IL-2. After the second course, the liver mass remained 2 cm in diameter and then radiofrequency ablation (RFA) under CT was performed. CT after RFA showed a low density area at the liver tumor without enhancement. About five years after the operation, she is alive without evidence of disease.


Differential assessment of vascular survival ability and tumor angiogenic activity in colorectal cancer.
The process of new vessel formation during neoplastic transformation and growth (neoangiogenesis) comprises proliferation, sprouting, and migration of endothelial cells within normal tissues adjacent to the tumor. These new vessels are directed toward the tumor invading edge and provide the bed for the subsequent growth of new tumor layers. We previously showed various degrees of decreasing vascular density in tumor layers once these lose contact with the normal tissue. This suggests that, apart from angiogenic factors, vascular survival factors contribute equally to the structure of the tumoral vasculature. This "vascular survival" potential can be assessed by comparatively examining the vascular density in peripheral and inner tumor areas. Using immunohistochemistry with the anti-CD31 monoclonal antibody, we assessed the tumor angiogenic activity (TAA) and vascular survival ability (VSA) in a sample of 242 patients with Dukes' stage A (90 patients), B (73 patients), and C (79 patients) colorectal cancer treated with surgery alone. Overall, High TAA and VSA were significantly related with poor prognosis (P = 0.03; hazard ratio, 1.9 and P = 0.001; hazard ratio, 2.7, respectively). In multivariate analysis, VSA was revealed as the most potent and independent prognostic factor (P = 0.0001; t ratio, 4.5), followed by vascular invasion (P = 0.0001; t ratio, 4.4) and stage (P = 0.01; t ratio, 2.5). Tumors with high TAA and high VSA had a significantly higher risk to develop liver metastasis (P = 0.0003). Assessment of VSA in addition to TAA provides additional important prognostic information in patients with colorectal cancer and can be a useful tool in the recruitment of patients who would benefit from angiostatic versus angiotoxic therapies.


Production of IL-12, IL-18 and TNF-alpha by alveolar macrophages in hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is characterized by a macrophage-lymphocyte alveolitis and granuloma formation. A wide range of cytokines have been implicated in the pathophysiology and development of granulomas in HP, but there is no information about the production of interleukin-12 (IL-12) and IL-18 by alveolar macrophages (AM) in human HP. We evaluated whether the production of IL-12, IL-18 and tumor necrosis factor-alpha (TNF-alpha) is locally increased in HP, and whether there is a correlation between these cytokines, as well as with the cellular profile of bronchoalveolar lavage (BAL) fluid in HP. AM from 11 patients with HP and 10 control subjects were cultured for 24h in 10% RPMI medium alone, or with RPMI medium and lipopolysaccharide (LPS) (100 ng/ml). Cytokines in the culture supernatants were assayed by ELISA. The production of IL-18 and TNFalpha was increased in patients with HP in either absence or presence of LPS compared with controls. Although the spontaneous production of IL-12 was low, with LPS stimulation it was significantly elevated in HP. The concentration of the LPS-stimulated IL-12 production positively correlated with the percentage of lymphocytes (r = 0.72, p = 0.011), and negatively correlated with the percentage of macrophages (r = -0.88, p < 0.001). These observations suggest that IL-12, IL-18 and TNFalpha may be involved in the pathogenesis of HP.


Prevalence of neurosyphilis at Government Rajaji Hospital, Madurai, India.
Forty patients (34 males and 6 females) with neurological complaints/manifestations and with a past history of multiple sexual partners attending the Government Rajaji Hospital, Madurai, India between April 1992 and October 1992 were investigated for neurosyphilis. Metabolic disorders, hypertension, ischaemic heart disease, arrhythmias and trauma were excluded. Seven males (17.5%) were found to have neurosyphilis. The youngest was 26 years old and the oldest was 47. All were married and of low socioeconomic background. Meningovascular syphilis was the predominant presentation (6:1). Associated cardiovascular involvement was noticed in one of the cases. There was no associated HIV infection in these cases. The incidence is higher than previous reports from this centre.


Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction.
Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD.


Distinct Packings of Supramolecular Building Blocks in Metal-Organic Frameworks Based on Imidazoledicarboxylic Acid.
When the supramolecular building block packings (face-centered, body-centered, and primitive cubic) with different interactions (hydrogen and coordination bonding) were controlled, four new structures based on octahedral M(II) (M = Zn, Ni, Mn) and imidazoledicarboxylate were constructed. The interaction modes between the supramolecular building blocks affect the water stability of the structures. Furthermore, with uncoordinated carboxylate O atoms in the structures, these compounds demonstrate a strong capability of capturing metal ions in the solution.


Experimental studies of the effects of extrinsic factors on conduction in normal and demyelinated nerve. 1. Temperature.
Previous studies in experimentally demyelinated mammalian nerves have demonstrated that a reversible conduction block occurs with small increases of temperature within the animal's normal body temperature range. This phenomenon is believed to be the mechanism for clinical temperature effects in multiple sclerosis. This study examines some quantitative thermal relationships in demyelinated nerves of guinea pigs with experimental allergic neuritis. The observed results in normal and experimental animals are in good agreement with previous theoretical calculations based on the effects of temperature on the voltage and time-dependent behavior of the ionic permeabilities of the nodes of Ranvier. Guinea pigs with increasing motor dysfunction generally exhibited corresponding increases in the overall latency of the conducted action potential, as well as decreases in amplitude. In addition, the lower the initial velocity increment per degree of temperature elevation, the lower was the temperature at which conduction block began to occur. Except for a few cases in which the recorded action potential was bimodal, with response at both normal and prolonged latency, the results tended to indicate a remarkedly uniform involvement of the sciatic nerve within the region of temperature control.


Nursing management, religion and spirituality: a bibliometric review, a research agenda and implications for practice.
This article aims to contribute to the growing field of spirituality and nursing management by analysing bibliographic data on peer-reviewed research in the field. Articles on spirituality and nursing management often claim that these fields have grown over the past two decades. This article gathers empirical evidence to test these claims. Bibliometric data on peer-reviewed research articles on nursing, nursing management, spirituality and religion in the Social Sciences Citation Index were analysed to ascertain general trends in publication and citation. The data support claims that research activity and interest in both spirituality and religion in the field of nursing have grown steeply over recent years, and continue to accelerate. The research identified spirituality as a beneficial variable in management, training and/or care scenarios. Critical studies of nursing management spiritual initiatives could add considerably to the growing body of research and theory in this field. It is essential that nurse managers be equipped to foster not only a broader understanding of the variety of faith traditions found in a multi-cultural society, but also to develop an understanding of the ways in which individuals engage in spiritual practice outside traditional religious settings.


The "complex" RNA post-transcriptional element of a "simple" retrovirus.
Replication of retroviruses and transposition of endogenous retroelements exploits a unique mechanism of post-transcriptional regulation as a means of exporting their incompletely-spliced mRNAs (which serve as both the genomic RNA and the template for protein synthesis). Following discovery of the Rev response element (RRE) that mediates nucleocytoplasmic export of the full-length and singly-spliced human immunodeficiency virus type 1 (HIV-1) genome, equivalent cis-acting regulatory elements have been characterized for both complex and simple retroviruses and retroelements, together with the obligate viral and host proteins with which they interact. The exception to this is the gammaretrovirus family of simple retroviruses, exemplified by reticuloendotheliosis virus (REV), murine leukemia virus (MLV) and xenotropic MLV-related retrovirus (XMRV). In this commentary, we discuss our recent data that reported structural and functional data on the MLV/XMRV post-transcriptional regulatory element (designated the PTE). The PTE was characterized by a highly-structured region of multiple stem-loops (SL1 - SL7) overlapping the pro and 5' portion of the pol open reading frames, comprising a bipartite export signal whose structures are separated by ∼1400 nt. In addition, structural probing suggested that SL3 nucleotides were involved in pseudoknot formation. These data, when compared with RNA transport elements of complex retroviruses (HIV) and simple murine retrotransposons (musD), collectively present an emerging picture that long-range tertiary interactions are critical mediators of their biological function.


Relationship between ventilatory response and body temperature during prolonged submaximal exercise.
We examined whether an increase in skin temperature or the rate of increase in core body temperature influences the relationship between minute ventilation (Ve) and core temperature during prolonged exercise in the heat. Thirteen subjects exercised for 60 min on a cycle ergometer at 50% of peak oxygen uptake while wearing a suit perfused with water at 10 degrees C (T10), 35 degrees C (T35), or 45 degrees C (T45). During the exercise, esophageal temperature (Tes), skin temperature, heart rate (HR), Ve, tidal volume, respiratory frequency (f), respiratory gases, blood pressure (BP), and blood lactate were all measured. We found that oxygen uptake, carbon dioxide output, BP, and blood lactate did not differ among the sessions. Tes, HR, Ve, and f remained nearly constant from minute 10 onward in the T10 session, but all of these parameters progressively increased in the T35 and T45 sessions, and significantly higher levels were seen in the T45 than the T35 session. For all but two subjects in the T35 and T45 sessions, plotting Ve as a function of Tes revealed no threshold for hyperventilation; instead, increases in Ve were linearly related to Tes, and there were no significant differences in the slopes or intercepts between the T35 and T45 sessions. Thus, during prolonged submaximal exercise in the heat, Ve increases with core temperature, and the influences of skin temperature and the rate of increase in Tes on the relationship between Ve and Tes are apparently small.


Effect of vaccination with mutant KRAS peptides on rat colon carcinogenesis induced by azoxymethane.
Rat colon carcinogenesis induced by 2 x 15 mg/kg body weight of azoxymethane (AOM) is a standard model, widely used to evaluate the role of nutritional components and chemopreventive agents at various stages of tumorigenesis. In this model, KRAS mutations have been frequently observed in aberrant crypt foci (ACF), putative preneoplastic lesions, as well as in tumours. Therefore we used this model and vaccinated F344 rats with a mixture of synthetic mutant KRAS peptides (MT KRAS) corresponding to frequent KRAS exon 1 mutations before AOM treatment in order to study the role of KRAS mutations in the development of ACF and subsequently tumours. The controls were sham-vaccinated with KRAS exon 1 wild-type KRAS peptides (WT KRAS). MT KRAS vaccination suppressed the number of ACF by 42% at week 13 (p=0.001). The subpopulation of ACF suppressed by MT KRAS vaccination had higher focal crypt multiplicity than the control ACF population (p=0.001). At week 26, vaccination reduced the KRAS mutation frequency in ACF from 50% in the MT KRAS group to 13% in the WT KRAS (p=0.038). However, at this phase of carcinogenesis, vaccination did not have significant effects on the ACF number and focal crypt multiplicity. Surprisingly, the KRAS mutation frequency was only 5% in the colonic tumours of the controls (1 out of 20 tumours). Although there were no tumours with KRAS mutations in the MT KRAS group, the possible effect of vaccination could not be evaluated. These data indicate that KRAS mutations play a minor role in colonic tumorigenesis and that ACF with KRAS mutations could hardly be the precursors of the AOM-induced tumours in rats. Hence, the cancer protective potential of a KRAS vaccine in the early phase of AOM-induced colon carcinogenesis in the rat appeared minuscule. Additional studies in a model with a high outcome of KRAS mutations in colonic tumours are needed to evaluate the effects of a KRAS vaccine at later stages of tumorigenesis.


Pressure induced topological and structural phase transitions in 1T-TiSe2: a Raman study.
High pressure Raman spectroscopy studies on 1T-TiSe2 were carried out up to ~20.5 GPa. Based on the anomalies in phonon linewidth (lifetime) and phonon frequency of A 1g mode, we observe three transitions at ~2.5 GPa, ~6.0 GPa and ~15 GPa. The transitions at ~2.5 and ~6.0 GPa are the two topological phase transitions consistent with the theoretical prediction by Zhu et al in 1T-TiSe2 under pressure, namely, a topological trivial to non-trivial transition (Z 2 = 1) and topological non-trivial to trivial transition (Z 2 = 0). The trigonal (1T) phase of TiSe2 is stable up to ~15 GPa beyond which it undergoes structural transition as seen from the appearance of new Raman modes. There is a coexistence of the 1T and the new high-pressure phase up to ~19 GPa. The structural transition is completely reversible as seen from the appearance of 1T phase Raman spectra upon release of the pressure.


Myringotomy and ventilation tube insertion: a ten-year follow-up.
Eighty children who had myringotomy performed for otitis media with effusion in 1984 were reviewed in 1994. This had involved surgery on 158 ears. Three aspects of ear condition were studied: hearing loss, tympanic membrane perforation, and tympanosclerosis. Hearing losses were present in 13 ears (8.2 per cent), involving 10 children (12.5 per cent), although losses were under 20 dB in seven of these ears (five patients). Of the six ears with losses more than 20 dB (3.8 per cent), in five patients bilateral losses of 30 dB were due to a recurrence of effusions, a large dry posterior perforation was the cause of a 30 dB loss, an infected anterior perforation had caused a 30 dB loss, an ear which had a cholesteatoma, and had a mastoidectomy and ossiculoplasty in 1987, had a 30-40 dB loss, and one ear which had a Type 1 tympanoplasty in 1994 had a 50 dB loss. Therefore in only three ears (1.9 per cent) could hearing loss be associated directly with myringotomy and ventilation tube insertion. Perforations had persisted unilaterally in seven patients, three having had tympanoplasties. Of the remaining perforated tympanic membranes, two were free of symptoms, one had only a slight hearing loss, and one had a more significant loss with recurrent infection. Tympanosclerosis was only found in those ears which had ventilation tubes inserted (and not those which had myringotomy only), occurring in 48 ears (31 per cent, of 39 per cent of those which had a ventilation tube inserted). There was no link between tympanosclerosis and hearing loss. The site of tympanosclerosis was not restricted to the site of myringotomy, and in many cases was present only in other areas of the tympanic membrane. There was a tendency for more extensive tympanosclerosis to occur in those ears which had more ventilation tube insertions. The risk of perforation in particular lends support to a policy of 'watchful waiting'.


Highly Conductive Polypropylene-Graphene Nonwoven Composite via Interface Engineering.
Here we report a highly conductive polypropylene-graphene nonwoven composite via direct coating of melt blown polypropylene (PP) nonwoven fabrics with graphene oxide (GO) dispersions in N,N-dimethylformamide (DMF), followed by the chemical reduction of GO with hydroiodic acid (HI). GO as an amphiphilic macromolecule can be dispersed in DMF homogeneously at a concentration of 5 mg/mL, which has much lower surface tension (37.5 mN/m) than that of GO in water (72.9 mN/m, at 5 mg/mL). The hydrophobic PP nonwoven has a surface energy of 30.1 mN/m, close to the surface tension of GO in DMF. Therefore, the PP nonwoven can be easily wetted by the GO/DMF dispersion without any pretreatment. Soaking PP nonwoven in a GO/DMF dispersion leads to uniform coatings of GO on PP-fiber surfaces. After chemical reduction of GO to graphene, the resulting PP/graphene nonwoven composite offers an electrical conductivity of 35.6 S m-1 at graphene loading of 5.2 wt %, the highest among the existing conductive PP systems reported, indicating that surface tension of coating baths has significant impact on the coating uniformity and affinity. The conductivity of our PP/graphene nonwoven is also stable against stirring washing test. In addition, here we demonstrate a monolithic supercapacitor derived from the PP-GO nonwoven composite by using a direct laser-patterning process. The resulted sandwich supercapacitor shows a high areal capacitance of 4.18 mF/cm2 in PVA-H2SO4 gel electrolyte. The resulting highly conductive or capacitive PP/graphene nonwoven carries great promise to be used as electronic textiles.


Physician Experience in Technical Success of Achieving NPVR ≥ 80% of High-Intensity Focused Ultrasound Ablation for Uterine Fibroids: A Multicenter Study.
To evaluate the experience of the physician of the technical success in high-intensity focused ultrasound (HIFU) ablation of uterine fibroids with a nonperfused volume ratio (NPVR) of at least 80%. Patients from a 20-center prospective study were enrolled in this study. In this study, among the 20 clinical centers, five centers had physician with >3 years of HIFU experience, and the other 15 centers initiated HIFU therapy <3 years, were defined as the experienced group and the inexperienced group, respectively. Technical success was defined as achieving NPVR ≥ 80% of uterine fibroids with no major complications and it was defined as the successful group; otherwise, it was defined as the unsuccessful group. A total of 1,352 patients were included at the age of 41.32 ± 5.08 years. The mean NPVR (87.48 ± 14.91%) was obtained in the inexperienced group (86.50 ± 15.76%) and in the experienced group (89.21 ± 13.12%), respectively. The multivariate analysis showed that the volume of uterus, location of fibroids, and physician experience were significantly correlated with technical success (p < 0.05). In the experienced group, 82.20% of uterine fibroids obtained NPVR ≥ 80%, compared with 75.32% in the inexperienced group, and the difference was significant (p = 0.003). The technical success rate of the experienced group was 82.00% which was higher than 75.20% of the inexperienced group (p = 0.004). In technical success of achieving NPVR ≥ 80%, experience of the physician was positively correlated with technical success; NPVR and major complications for the inexperienced group were comparable to those of the experienced group from a clinical perspective; inexperienced physicians could reach NPVR ≥ 80% of sufficient ablation and were trustworthy in efficacy. Smaller uterus and fibroids of anterior wall were correlated with better technical success; experienced physicians still have better technical success when choosing patients with larger uterus, contributing to clinical decision-making and patient referral.


Oxygen and life on earth: an anesthesiologist's views on oxygen evolution, discovery, sensing, and utilization.
The advent of oxygenic photosynthesis and the accumulation of oxygen in our atmosphere opened up new possibilities for the development of life on Earth. The availability of oxygen, the most capable electron acceptor on our planet, allowed the development of highly efficient energy production from oxidative phosphorylation, which shaped the evolutionary development of aerobic life forms from the first multicellular organisms to the vertebrates.


The nose shape as a predictor of maxillary central and lateral incisor width.
One of the primary aspects of complete denture prosthodontics is determining the correct proportion for the maxillary central incisor width to the lateral incisor width. It has been suggested that the anatomy of the patient's nose is a reliable guide for deciding this ratio. The aim of this study was to test the hypothesis about the relationship between the shape of the nose and the proportion of the central incisor width (CIW) to the lateral incisor width (LIW). The CIW and LIW from a total of 138 subjects (73 males, 65 females) were measured intraorally. The interalar width (IAW) and the width of the root of the nose (WRN) were measured on standard photographs of the subjects. Spearman's rho test was used to analyze the correlation between the proportions of the CIW to the LIW and the IAW to the WRN. The Mann-Whitney Utest was applied to test for any possible gender differences. The IAW, the WRN, and the nose angle (NA) were statistically significantly wider in male subjects than in female subjects. The correlation between IAW/WRN, NA, and CIW/LIW was statistically significant only in female subjects. In the general population, the only statistically significant relationship was between CIW/LIW on the left side and IAW/WRN. Within the results of the IAW, WRN, and NA measurements, we suggest that males have wider, more triangular-shaped noses than females. The proportion of IAW to WRN seems to be a reliable guide for deciding the proportion of the maxillary central incisor width to the lateral incisor.


Incidents reporting: barriers and strategies to promote safety culture.
The purpose was to identify the barriers of underreporting, the factors that promote motivation of health professionals to report, and strategies to enhance incidents reporting. Group conversations were carried out within a hospital multidisciplinary team. A mediator stimulated reflection among the subjects about the theme. Sixty-five health professionals were enrolled. Complacency and ambition were barriers exceeded. Lack of responsibility about culture of reporting was the new barrier observed. There is a belief only nurses should report incidents. The strategies related to motivation reported were: feedback; educational intervention with hospital staff; and simplified tools for reporting (electronic or manual), which allow filling critical information and traceability of management risk team to improve the quality of report. Ordinary and practical strategies should be developed to optimize incidents reporting, to make people aware about their responsibilities about the culture of reporting and to improve the risk communication and the quality of healthcare and patient safety.


In Vitro Nanobody Library Construction by Using Gene Designated-Region Pan-Editing Technology.
Camelid single-domain antibody fragments (nanobodies) are an emerging force in therapeutic biopharmaceuticals and clinical diagnostic reagents in recent years. Nearly all nanobodies available to date have been obtained by animal immunization, a bottleneck restricting the large-scale application of nanobodies. In this study, we developed three kinds of gene designated-region pan-editing (GDP) technologies to introduce multiple mutations in complementarity-determining regions (CDRs) of nanobodies in vitro. Including the integration of G-quadruplex fragments in CDRs, which induces the spontaneous multiple mutations in CDRs; however, these mutant sequences are highly similar, resulting in a lack of sequences diversity in the CDRs. We also used CDR-targeting traditional gRNA-guided base-editors, which effectively diversify the CDRs. And most importantly, we developed the self-assembling gRNAs, which are generated by reprogrammed tracrRNA hijacking of endogenous mRNAs as crRNAs. Using base-editors guided by self-assembling gRNAs, we can realize the iteratively diversify the CDRs. And we believe the last GDP technology is highly promising in immunization-free nanobody library construction, and the full development of this novel nanobody discovery platform can realize the synthetic evolution of nanobodies in vitro.


Prehospital intubation in severe thoracic trauma without respiratory insufficiency: a matched-pair analysis based on the Trauma Registry of the German Trauma Society.
On the basis of the data of a multicenter study, the impact of prehospital intubation and ventilation in the therapy of severe thoracic trauma without manifest respiratory insufficiency was analyzed. Data were collected prospectively in the Trauma Registry of the German Trauma Society. In a matched-pair analysis, patients with severe thoracic trauma (Abbreviated Injury Scale score of 4) with and without prehospital intubation were compared. Patients were paired with respect to age, injury severity, and prognosis (according to the TRISS method). From a total of 3,814 patients, two groups (with/without prehospital intubation) of 44 matched patients each with comparable average age (36 vs. 36 years), Injury Severity Score (29 vs. 29), and TRISS (95.2 vs. 95.3) were identified. No patient was unconscious at the scene (all Glasgow Coma Scale scores > or = 8) or presented with severe respiratory insufficiency (all > or = 10 breaths/min). Time between injury and hospital admission was significantly longer (73 minutes; p < 0.05) in the group with prehospital intubation compared with the nonintubated group (47 minutes). Furthermore, fluid requirements in the prehospital period were significantly higher in the intubated patients (3,000 mL vs. 1,000 mL). In the prehospital intubation group, the number of patients with mass transfusion (9 vs. 4) as well as with emergency operations (10 vs. 4) were not significantly different from the nonintubated group. The prehospital intubation group showed a similar incidence of lung failure (17 vs. 14), kidney failure (6 vs. 2), and circulation failure (13 vs. 5). Except for two of the primarily nonintubated patients, all were intubated during their stay in the emergency room or on the intensive care unit. Days of ventilation (median, 7 days) as well as the length of stay on the ICU (median, 11 days) were comparable in both groups. Mortality in the prehospital intubation group was not significantly different between groups (six vs. two deceased). Prognosis with respect to organ failure, treatment time, and mortality is not adversely affected in the German trauma system, if patients with severe thoracic trauma without manifest respiratory insufficiency and without other indications for intubation are not treated with prehospital intubation.


Severe pain at the end of life: a population-level observational study.
Pain is a prevalent symptom at the end of life and negatively impacts quality of life. Despite this, little population level data exist that describe pain frequency and associated factors at the end of life. The purpose of this study was to explore the prevalence of clinically significant pain at the end of life and identify predictors of increased pain. Retrospective population-level cohort study of all decedents in Ontario, Canada, from April 1, 2011 to March 31, 2015 who received a home care assessment in the last 30 days of life (n = 20,349). Severe daily pain in the last 30 days of life using linked Ontario health administrative databases. Severe pain is defined using a validated pain scale combining pain frequency and intensity: daily pain of severe intensity. Severe daily pain was reported in 17.2% of 20,349 decedents. Increased risk of severe daily pain was observed in decedents who were female, younger and functionally impaired. Those who were cognitively impaired had a lower risk of reporting pain. Disease trajectory impacted pain; those who died of a terminal illness (i.e. cancer) were more likely to experience pain than those with frailty (odds ratio 1.66). Pain is a common fear of those contemplating end of life, but severe pain is reported in less than 1 in 5 of our population in the last month of life. Certain subpopulations may be more likely to report severe pain at the end of life and may benefit from earlier palliative care referral and intervention.


Ionic covalent organic framework for selective detection and adsorption of TcO4-/ReO4.
Herein, a novel fluorescent ionic covalent organic framework (BTTA-BDNP) based on a linked carbazole unit was constructed for the synchronous monitoring and capture of TcO4-/ReO4-. BTTA-BDNP has a fast fluorescence response time with a low detection limit (66.7 nM) for ReO4- (a non-radioactive substitute for TcO4-). Meanwhile, the high charge density and hydrophobic skeleton of BTTA-BDNP enable it to exhibit rapid and selective trapping of ReO4- in complex environments.


Essix appliances. Provisional anterior prosthesis for pre and post implant patients.
Missing anterior teeth are being replaced by implant-supported restorations quite frequently in modern dentistry. Providing the patient with a temporary prosthesis prior to or following implant fixture placement must satisfy established esthetic and functional criteria. When orthodontic treatment is included as part of the overall treatment effort, additional considerations include the retention and stabilization of newly established tooth positions. This article describes the fabrication, use and advantages of a provisional anterior prosthesis that replaces missing teeth prior to or following implant placement.


Synthesis and Assembly of Laccase-Polymer Giant Amphiphiles by Self-Catalyzed CuAAC Click Chemistry.
Covalent coupling of hydrophobic polymers to the exterior of hydrophilic proteins would mediate unique macroscopic assembly of bioconjugates to generate amphiphilic superstructures as novel nanoreactors or biocompatible drug delivery systems. The main objective of this study was to develop a novel strategy for the synthesis of protein-polymer giant amphiphiles by the combination of copper-mediated living radical polymerization and azide-alkyne cycloaddition reaction (CuAAC). Azide-functionalized succinimidyl ester was first synthesized for the facile introduction of azide groups to proteins such as albumin from bovine serum (BSA) and laccase from Trametes versicolor. Alkyne-terminal polymers with varied hydrophobicity were synthesized by using commercial copper wire as the activators from a trimethylsilyl protected alkyne-functionalized initiator in DMSO under ambient temperature. The conjugation of alkyne-functionalized polymers to the azide-functionalized laccase could be conducted even without additional copper catalyst, which indicated a successful self-catalyzed CuAAC reaction. The synthesized amphiphiles were found to aggregate into spherical nanoparticles in water and showed strong relevance to the hydrophobicity of coupled polymers. The giant amphiphiles showed decreased enzyme activity yet better stability during storage after chemical modification and self-assembly. These findings will deepen our understanding on protein folding, macroscopic self-assembly, and support potential applications in bionanoreactor, enzyme immobilization, and water purification.


Visuomotor Map Determines How Visually Guided Reaching Movements are Corrected Within and Across Trials.
When a visually guided reaching movement is unexpectedly perturbed, it is implicitly corrected in two ways: immediately after the perturbation by feedback control (online correction) and in the next movement by adjusting feedforward motor commands (offline correction or motor adaptation). Although recent studies have revealed a close relationship between feedback and feedforward controls, the nature of this relationship is not yet fully understood. Here, we show that both implicit online and offline movement corrections utilize the same visuomotor map for feedforward movement control that transforms the spatial location of visual objects into appropriate motor commands. First, we artificially distorted the visuomotor map by applying opposite visual rotations to the cursor representing the hand position while human participants reached for two different targets. This procedure implicitly altered the visuomotor map so that changes in the movement direction to the target location were more insensitive or more sensitive. Then, we examined how such visuomotor map distortion influenced online movement correction by suddenly changing the target location. The magnitude of online movement correction was altered according to the shape of the visuomotor map. We also examined offline movement correction; the aftereffect induced by visual rotation in the previous trial was modulated according to the shape of the visuomotor map. These results highlighted the importance of the visuomotor map as a foundation for implicit motor control mechanisms and the intimate relationship between feedforward control, feedback control, and motor adaptation.


Universality in quasi-two-dimensional granular shock fronts above an intruder.
We experimentally study quasi-two-dimensional dilute granular flow around intruders whose shape, size, and relative impact speed are systematically varied. Direct measurement of the flow field reveals that three in-principle independent measurements of the nonuniformity of the flow field are in fact all linearly related: (1) granular temperature, (2) flow-field divergence, and (3) shear-strain rate. The shock front is defined as the local maxima in each of these measurements. The shape of the shock front is well described by an inverted catenary and is driven by the formation of a dynamic arch during steady flow. We find universality in the functional form of the shock front within the range of experimental values probed. Changing the intruder size, concavity, and impact speed only results in a scaling and shifting of the shock front. We independently measure the horizontal lift force on the intruder and find that it can be understood as a result of the interplay between the shock profile and the intruder shape.


Effects of Aerobic Exercise on Postprandial Carbohydrate and Lipoprotein Metabolism Following Cookie Ingestion in Healthy Young Women.
We examined the acute effects of postprandial aerobic exercise on glucose and lipid metabolism following cookie ingestion. Fifteen healthy young women with a sedentary lifestyle, normal weight and apolipoprotein E3/3 participated. After a 12-h overnight fast, each subject ingested a cookie (1.53 g/kg, Meal Test C) and then performed two trials, one with postprandial exercise (E trial) and one without exercise (C trial), in a randomized crossover design. A single 30-min bout of walking exercise was performed 20 min after the cookie intake. Venous blood samples were drawn before (0 h) and 20 min and 1, 2, 4, and 6 h after cookie ingestion. The Δglucose concentration was not significantly different between the two trials, but the Δinsulin concentration at 1 h and the incremental area under the curve (IAUC) (0-2 h)-insulin in the E trial were significantly lower than in the C trial. The ratio of glucose/insulin at 1 h was significantly higher in the E trial than in the C trial. The ΔTG, ΔRLP-TG, ΔapoB48 and ΔRemL-C concentrations at 1 h in the E trial were significantly higher than in the C trial. The IAUC (0-2 h)-apoB48 in the E trial was significantly larger than in the C trial. Postprandial exercise showed an insulin-sparing effect following the cookie ingestion by increasing insulin sensitivity. However, postprandial exercise transiently stimulated the secretion of exogenous apoB48-containing lipoprotein during the early period, and no further effects were observed. These results suggest that postprandial aerobic exercise is effective for the promotion of postprandial carbohydrate metabolism, but not lipidemia.


Caffeine as a probe for CYP1A2 activity: potential influence of renal factors on urinary phenotypic trait measurements.
Two established caffeine-based urinary methods for measuring CYP1A2 activity were compared with each other, and also with the systemic clearance of caffeine which served as a standard of reference for such activity. Following a standardized dose, caffeine (137X) and its metabolites were measured in urine and plasma of 39 healthy subjects. The measurements allowed determinations of: (1) systemic caffeine clearance (CL(caff)); (2) the caffeine metabolite ratio (AFMU + 1X + 1U)/17U determined in an overnight-urine specimen and referred to as CMR, and (3) the ratio (17X + 17U)/137X measured in urine collected between 4 and 5 h after caffeine intake and referred to as PCUR for 'paraxanthine-caffeine urinary ratio'. The PCUR showed a bimodal distribution and a relatively wide variation, CL(caff) and CMR were both normally distributed. The correlation between CL(caff) and CMR was r = 0.77 (p < 0.001), between CLcaff and PCUR r = 0.46 (p < 0.01), and between CMR and PCUR r = 0.40 (p < 0.02). The difference between the correlation coefficients 0.77 and 0.46 was statistically significant (z-test; p < 0.05). The well established decrease of caffeine metabolism by oral contraceptive use was observed with both CL(caff) and CMR but not with PCUR. Examination of possible explanations for the differences between PCUR and CMR led to the finding of a correlation between PCUR and the renal clearance of caffeine (CLr) with r = -0.47 (p < 0.01). Further scrutiny demonstrated that a bimodal or non-normal frequency distribution as shown by PCUR was also shown by CLr and by urine flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis and opioid activity of 7-oxygenated 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolin-9-ols.
3-(Cyclopropylmethyl)-9-hydroxy-7-oxo-2,3,4,4a alpha,5,6,7,7a alpha- octahydro-1H-benzofuro[3,2-e]isoquinoline (4b) containing the ACNO ring system of morphine and a 7-keto function on ring C has been synthesized and found to possess potent PQW (ED50 = 0.15 mg/kg sc) and anti-Straub tail (ED50 = 0.02 mg/kg sc) activity. As compared to its 7-deoxy analog 1b, introduction of the 7-keto group did not significantly affect binding to any of the three opioid receptors (mu, kappa, and delta), but caused a 34-fold reduction in sigma-binding, suggesting reduced propensity to induce psychotomimetic effects. The C/D cis isomer of 4b (4c) was much less potent at the three opioid receptors, while displaying a slight increase in sigma affinity. Both 7-hydroxy derivatives 4e and 4f were active in anti-Straub tail assay (ED50 < or = 0.8 mg/kg sc), but only the alpha-isomer 4e demonstrated analgesic activity (PQW ED50 = 0.37 mg/kg sc) in the dose range tested. In guinea pig ileum preparations, 4e was characterized as a selective full agonist at the kappa opioid receptor (IC50 = 2.8 nM); while its beta-isomer 4f was a partial agonist (78% at 1 microM), with antagonist activity observed at both mu- and kappa-opioid receptors.


The role of platelet membrane potential in the initiation of platelet aggregation.
The membrane potential of human platelets, and the role of this potential in platelet aggregation, was assessed using the noncovalent, fluorescent probe DiS-C3-5. High K+ and Gramicidin depolarised the cells, whereas valinomycin in standard (4 mMK+) solution produced a hyperpolarisation. Very small changes in potential were observed when choline Cl replaced NaCl. These findings indicate that platelets possess a relatively K+-perm-selective membrane. The resting potential calculated from the "valinomycin null point" (the K+ concentration gradient at which valinomycin did not change the potential) was approximately -60 mV. Other factors that contribute to the platelet membrane potential include a significant Cl- permeability, demonstrated by replacing Cl- with methylsulphate, and an electrogenic Na+ pump, demonstrated using strophanthidin. Little or no change in potential was observed upon addition of ADP, collagen, U44069 or thrombin. Neither strong depolarisation with high K+ or gramicidin nor hyperpolarisation with valinomycin induced platelet aggregation or altered platelet responses to agonists. It is concluded that the information transduction mechanisms involved in platelet activation do not include changes in platelet membrane potential.


[Guillain-Barré syndrome with high titers of anti-GM2 and anti-GalNAc-GD1a antibody following cytomegalovirus hepatitis].
A 28-year-old housewife developed motor and sensory neuropathy in both limbs with facial nerve paralysis and decreased taste sensation, two weeks after cough and sore throat with slight fever. On laboratory examination, mild increase of transaminases was found. Enzyme-linked immunosorbent assay showed that the serum had markedly high titers of IgG antibodies to GM2 (1:3,200) and Ga1NAc-GD1a (1:1,600). Serum IgM-EIA index and CF titer of cytomegalovirus were markedly high. In cerebrospinal fluid examination, protein was increased (110 mg/dl). Blink reflex indicated involvement of bilateral facial nerves. In limb motor and sensory nerves, conduction studies revealed the presence of both axonal degeneration and segmental demyelination. The diagnosis of Guillain-Barré syndrome (GBS) with facial nerve paralysis, relatively unique to CMV infection, was made. In the fourth week following the initial neurologic symptom, weakness in facial and limb muscles and sensory disturbances in both limbs were gradually improved. In about three months, conduction studies of limb nerves and CSF protein were normalized. During the clinical course above, the titers of antibodies to GM2 and Ga1NAc-GD1a, IgM-EIA index and the titer of CF of CMV were significantly decreased. Anti-GM2 antibody was reported to be found in the sera from the patient of GBS associated with CMV infection. However, there is no report of GBS patient with CMV infection whose serum showed the presence of both anti-GM2 and anti-Ga1NAc-GD1a antibodies. In this patient, antibodies to CMV, GM2 and Ga1NAc-GD1a epitopes and other unexamined or/and unknown epitopes may be related to the neuropathy. The studies of the specific antibody to react with facial nerve in the serum from GBS patients with facial nerve paralysis and the molecular mimicry between the specific ganglioside and the structure of CMV are warranted in future.


Hesitance towards voluntary medical male circumcision in Lesotho: reconfiguring global health governance.
Drawing on work examining HIV prevention initiatives in Lesotho, this paper considers the hesitation of national state actors towards the new strategy for HIV prevention - voluntary medical male circumcision (VMMC). Lesotho offers a representative case study on global health governance, given the country's high HIV burden and heavy dependence on foreign donor nations to implement local HIV prevention initiatives. In this paper, I use the case of VMMC opposition in Lesotho to examine how the new era of 'partnerships' has shifted the architecture of contemporary global health, specifically considering how global agreements are translated or negotiated into local practice. I argue that Lesotho's domestic policy-makers, in employing national statistics to assess if VMMC is an effective approach to addressing the local epidemic, are asserting a claim of expertise. In doing so, they challenge the traditional structures of global health politics, which have largely been managed by experts and funders from and in the global North. I explore the development of global VMMC policy, what drives Lesotho's resistance to comply, and consider the impact renegotiation efforts may have on future global health architecture.


Intrabilary obstruction by colorectal metastases.
Intrabiliary colorectal metastases are rare. We present a case of an 84-year-old man who developed obstructive jaundice secondary to intrabiliary growth of colorectal metastases. The patient presented with three weeks of jaundice and significant weight loss in the preceding months. The patient's background included metastatic colorectal carcinoma, with a previous right hemicolectomy and left hepatectomy for liver metastases. A MRCP showed an obstruction of the biliary tract transitioning at the ampulla. Histology confirmed a malignant adenocarcinoma. When compared to the patient's previous resected colorectal liver metastases, morphology and immunohistochemistry was consistent with colorectal metastases. This case highlights the importance of differentiating a new intraductal papillary neoplasm from a colorectal metastasis. Correctly identifying these lesions requires the use of MRCP and ERCP, as well as immunohistochemistry. This is a priority for clinicians to ensure appropriate therapy.


Proximal femoral epiphysiolysis in the neonate.
Seven neonates with eight proximal femoral epiphysiolyses were reviewed. Pain elicited by leg motion was the common diagnostic finding in all. Radiography showed lateralization of the shaft similar to congenital hip dysplasia. However, the acetabular index was normal in all but one child. Arthrography confirmed the diagnosis, showing a located proximal femoral epiphysis and a laterally displaced, externally rotated proximal metaphysis. Treatment usually consisted of traction followed by abduction splinting. The long-term results were excellent in six fractures. Growth complications included angular deformation (bowing) in one patient and coxa vara due to localized premature epiphysiodesis in one patient. Duplication of the lesion in stillborn cadavers showed that the fracture was usually a type 1 physeal injury traversing the entire physis beneath both the capital femur and the greater trochanter. The periosteal sleeve was intact posteriorly and still attached to the proximal physis. However, in two instances there was comminution (rather than crushing) of the epiphysis, physis, and metaphysis medially, which might explain the residual varus deformation and premature growth arrest seen infrequently as complications of this particular proximal femoral injury. An experimental animal model also duplicated these morphologic observations.


A multiplexed transcription activator-like effector system for detecting specific DNA sequences.
Transcription activator-like effectors (TALEs), originating from the Xanthomonas genus of bacteria, bind to specific DNA sequences based on amino acid sequence in the repeat-variable diresidue (RVD) positions of the protein. By altering these RVDs, it has been shown that a TALE protein can be engineered to bind virtually any DNA sequence of interest. The possibility of multiplexing TALEs for the purposes of identifying specific DNA sequences has yet to be explored. Here, we demonstrate a system in which a TALE protein bound to a nitrocellulose strip has been utilized to capture purified DNA, which is then detected using the binding of a second distinct TALE protein conjugated to a protein tag that is then detected by a dot blot. This system provides a signal only when both TALEs bind to their respective sequences, further demonstrating the specificity of the TALE binding.


Changing brains, changing perspectives: the neurocognitive development of reciprocity.
Adolescence is characterized by the emergence of advanced forms of social perspective taking and significant changes in social behavior. Yet little is known about how changes in social cognition are related to changes in brain function during adolescence. In this study, we investigated the neural correlates of social behavior during three phases of adolescence, carrying out functional magnetic resonance imaging of participants' brains while they were Player 2 in the Trust Game. We found that with age, adolescents were increasingly sensitive to the perspective of the other player, as indicated by their reciprocal behavior. These advanced forms of social perspective-taking behavior were associated with increased involvement of the left temporo-parietal junction and the right dorsolateral prefrontal cortex. In contrast, young adolescents showed more activity in the anterior medial prefrontal cortex, a region previously associated with self-oriented processing and mentalizing. These findings suggest that the asynchronous development of these neural systems may underlie the shift from thinking about self to thinking about the other.


Task instructions influence the cognitive strategies involved in line bisection judgements: evidence from modulated neural mechanisms revealed by fMRI.
Manual line bisection and a perceptual variant thereof (the Landmark test) are widely used to assess visuospatial neglect in neurological patients, but little is known about the cognitive strategies involved. In the Landmark test, one could explicitly compare the lengths of the left and right line segments; alternatively, one could compute the centre of mass of the display. We here investigate with functional MRI if these cognitive strategies modulate the neural mechanisms underlying judgements whether pre-transected horizontal lines are correctly bisected (the Landmark test) in normal volunteers. Functional neuroimaging (fMRI) was carried out in 12 healthy volunteers who judged: (a) whether the line segments on either side of the transection mark were of equal length, and (b) whether the transection mark was in the centre of the line. Line centre judgements were made significantly faster than line length comparisons. Increased neural activity common to both strategies was observed in inferior parietal lobes bilaterally and right temporooccipital cortex. Further activations, most likely reflecting general task demands like response selection and motor control, were found in the precentral gyrus bilaterally, supplementary motor area bilaterally, right anterior cingulate, right dorsolateral prefrontal cortex, cerebellar vermis, and right thalamus and right putamen. Explicit length comparisons (relative to line centre judgements) differentially activated left superior posterior parietal cortex, with a tendency toward activation of the equivalent area on the right, while the reverse comparison revealed differential activation in the lingual gyrus bilaterally and anterior cingulate cortex. The activations observed in inferior parietal cortex during task performance using either strategy are consistent with the results of lesion studies. The differential activation of superior posterior parietal cortex following length instructions suggests that explicit comparisons of spatial extent were implicated. The differential activation of bilateral occipital cortex following centre judgements suggests that the centre of a line is extracted at an early stage of visual processing.


Nrf2 expression in pancreatic stellate cells promotes progression of cancer.
It was previously identified that systemic Nrf2 deletion attenuates pancreatic cancer progression in a mutant K-ras/p53-expressing mouse model (KPC mouse). In this study, the type of cell that is responsible for the retarded cancer progression was elucidated. Human pancreatic cancers were first examined, and elevated expression of NRF2-target gene products in α-smooth muscle actin-positive cells was found, suggesting that pancreatic stellate cells (PSCs) are involved in this process. Closer examination of primary cultured PSCs from Nrf2-deleted mice revealed that the cells were less proliferative and retained a lower migration capacity. The conditioned medium of Nrf2-deleted PSCs exhibited reduced growth-stimulating effects in pancreatic cancer cells. KPC mouse-derived pancreatic cancer cells coinjected with wild-type PSCs developed significantly larger subcutaneous tumors in immunodeficient mice than those coinjected with Nrf2-deleted PSCs. These results demonstrate that Nrf2 actively contributes to the function of PSCs to sustain KPC cancer progression, thus, suggesting that Nrf2 inhibition in PSCs may be therapeutically important in pancreatic cancer.NEW & NOTEWORTHY This study identified that Nrf2 contributes to PSC activation. Nrf2 deletion in PSCs resulted in attenuation of cancer-promoting role. Nrf2 in PSCs could be an attractive therapeutic target in pancreatic cancer.


Prolonged irritative voiding symptoms due to Enterobius vermicularis bladder infestation in an adult patient.
Enterobius vermicularis (pinworm) is one of the most prevalent intestinal parasites in the world. The urinary tract is rarely affected and few cases have been reported. We report a case of bladder infestation by mature female worms of E. vermicularis in a woman presenting with irritative voiding symptoms.


Nerve growth factor-mediated vascular endothelial growth factor expression of astrocyte in retinal vascular development.
The angiogenic aspect of neurotrophins and their receptors rather than the neuroscientific aspect has been focused. However, their role in retinal vascular development is underdiscovered. The purpose of this study is to understand the role of neurotrophin receptors in retinal vascular development and the mechanisms of their action. To identify the expression of tropomyosin receptor kinase receptor (Trk) in developing retina, tissues of 4, 8, 12, 16 and 26 day-old mice were prepared for experiments. Immunohistochemistry and immunofluorescence double staining against glial fibrillary acidic protein and type IV collagen were performed. TrkA was expressed mainly along the vessel structure in inner part of retina, especially in retinal astrocyte. In cultured primary astrocyte, recombinant nerve growth factor (NGF) was used to activate TrkA. NGF induced the phosphorylation of TrkA, and it also enhanced the level of activated Akt and vascular endothelial growth factor (VEGF) mRNA. Inhibition of phosphoinositide 3-kinase (PI3K) reversed the NGF-induced activation of these two molecules. This study demonstrated that TrkA activation on NGF leads to VEGF elevation by PI3K-Akt pathway and therefore suggested that TrkA could be a stimulator of retinal vascular development.


Imaging cryosurgery with EIT: tracking the ice front and post-thaw tissue viability.
Cryosurgery employs freezing for targeted destruction of undesirable tissues such as cancer. Ice front imaging has made controlled treatment of deep body tumors possible. One promising method, recently explored for this task, is EIT, which recovers images of electrical impedance from measurements made at boundary electrodes. However, since frozen tissue near the ice front survives, ice front imaging is insufficient. Monitoring treatment effect would enable iterative cryosurgery, where extents of ablation and need for further treatment are assessed upon thawing. Since lipid bilayers are strong barriers to low frequency electrical current and cell destruction implies impaired membranes, EIT should be able to detect the desired effect of cryosurgery: cell death. Previous work has tested EIT for ice front imaging with tank studies while others have simulated EIT in detecting cryoablation, but in vivo tests have not been reported in either case. To address this, we report 3D images of differential conductivity throughout the freeze-thaw cycle in a rat liver model in vivo with histological validation, first testing our system for ice front imaging in a gel and for viability imaging post-thaw in a raw potato slice.


Cluster-based photography and modeling integrated method for an efficient measurement of cassava leaf area.
Leaf area (LA) and biomass are important agronomic indicators of the growth and health of plants. Conventional methods for measuring the LA can be challenging, time-consuming, costly, and laborious, especially for a large-scale study. A hybrid approach of cluster-based photography and modeling was, thus, developed herein to improve practicality. To this end, data on cassava palmate leaves were collected under various conditions to cover a spectrum of viable leaf shapes and sizes. A total of 1,899 leaves from 3 cassava genotypes and 5 cultivation conditions were first assigned into clusters by size, based on their length (L) and width (W). Next, 111 representative leaves from all clusters were photographed, and data from image-processing were subsequently used for model development. The model based on the product of L and W outperformed the rest (R2 = 0.9566, RMSE = 20.00). The hybrid model was successfully used to estimate the LA of greenhouse-grown cassava as validation. This represents a breakthrough in the search for efficient, practical phenotyping tools for LA estimation, especially for large-scale experiments or remote fields with limited machinery.


Co-oxidation of diethylstilbestrol and structural analogs by prostaglandin synthase.
Structural analogs of diethylstilbestrol (DES) with at least one phenolic hydroxyl group are metabolized by prostaglandin H synthase (PHS) from ram seminal vesicle microsomes (RSVM) in vitro in the presence of arachidonic acid (20:4). U.v. spectroscopy revealed the formation of p-quinoid intermediates in incubations of DES, tetrafluoro-DES and dimethylstilbestrol, and tautomerization of the quinones to the respective dien-compounds which were characterized by h.p.l.c. and GC/MS. Indomethacin inhibits the formation of these metabolites which are identical to the major metabolites formed in incubations with horseradish peroxidase/hydrogen peroxide. Covalent binding to protein was observed in incubations of PHS co-substrates. Notably, formation of reactive intermediates which bind to protein is not limited to DES-analogs which form quinone intermediates: radiolabeled hexestrol and E,E-dienestrol yield protein-bound radioactive products upon incubation with RSVM and 20:4, probably via one electron-oxidation to a phenoxy radical. PHS-catalyzed metabolism of structural analogs of DES is accompanied by a concentration-dependent increase in cyclo-oxygenase activity. The measurement of the 20:4-dependent oxygen uptake rates in vitro can serve as a convenient assay for estrogenic compounds which undergo co-oxidation. At high concentrations, however, DES structural analogs can inhibit rather than stimulate PHS. The PHS-catalyzed formation of reactive intermediates from DES structural analogs and their effect on PHS may be of importance for their biological activity in estrogen target tissues with low mono-oxygenase activity.