Motor and mechanical bases of the courtship call of the male treehopper Umbonia crassicornis.
This study is a physiological, anatomical and biophysical analysis of how plant-borne vibrational signals are produced by the treehopper Umbonia crassicornis During courtship, males and females engage in a vibrational duet, with each producing a characteristic call. For males, this consists of a frequency-modulated tonal signal which is accompanied by rhythmic broad-band clicks. Although previous studies have described these complex signals in detail, little is known about how they are produced. By combining video recordings, electromyograms, dissections and mechanical modeling, we describe the mechanism by which the male produces his courtship signal. High-speed videos show that the tonal portion of the call is produced by periodic dorso-ventral movements of the abdomen, with a relatively large amplitude oscillation alternating with a smaller oscillation. Electromyograms from the muscles we identified that produce this motion reveal that they fire at half the frequency of the abdominal oscillation, throughout the frequency modulation of the tonal signal. Adding weight to the abdomen of a calling male reduces the frequency of motion, demonstrating that the abdominal motion is strongly influenced by its mechanical resonance. A mathematical model accounting for this resonance provides excellent qualitative agreement with measurements of both the muscle firing rate recorded electrophysiologically and the oscillatory motion of the abdomen as recorded in the high-speed video. The model, electromyograms and analysis of video recordings further suggest that the frequency modulation of the abdominal response is due to a simultaneous modulation in the muscle firing rate and a fluctuation in stiffness of the abdominal attachment.


17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells.
Mutations in the proto-oncogene c-kit cause constitutive kinase activity of its product, KIT protein, and are associated with human mastocytosis and gastrointestinal stromal tumors (GISTs). Although currently available tyrosine kinase inhibitors are effective in the treatment of GISTs, there has been limited success in the treatment of mastocytosis. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin antibiotic, which binds to heat shock protein 90 (hsp90) causes destabilization of various hsp90-dependent kinases important in oncogenesis. Treatment with 17-AAG of the mast cell line HMC-1.2, harboring the Asp816Val and Val560Gly KIT mutations, and the cell line HMC-1.1, harboring a single Val560Gly mutation, causes both the level and activity of KIT and downstream signaling molecules AKT and STAT3 to be down-regulated following drug exposure. These data were validated using Cos-7 cells transfected with wild-type and mutated KIT. 17-AAG promotes cell death of both HMC mast cell lines. In addition, neoplastic mast cells isolated from patients with mastocytosis, incubated with 17-AAG ex vivo, are selectively sensitive to the drug compared to the mononuclear fraction. These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer.


Effects of Reiki on the Perception of Quality of Life Determined by the Questionnaire WHOQOL-BREF.
Reiki is a philosophy and healing technique that directs the use of vital energy (ki) for energy rebalance, as well as healing, in a holistic sense, of physical, emotional, mental, and spiritual processes. The practice is part of the integrative and complementary practices recognized by the World Health Organization. This study aimed to evaluate the Reiki effects on people's life quality perception, by using the World Health Organization Quality of Life-BREF (WHOQOL-BREF). We analyzed the answers of 144 individuals, and the data were categorized in quartiles according to the number of Reiki sessions attended. The results of each question and dimension of the questionnaire were analyzed by Student's t test (individual questions) and analysis of variance (dimensions). We observed significant improvement in the perception of physical pain, need for medical treatment, meaning of life, physical environment, availability of money, availability of information, locomotion, work capacity, access to health, place of residence, and transportation facilities. Reiki sessions have improved people's quality of life perception in many aspects, proving its therapeutic efficacy in a broader approach to health promotion.


Lack of association of angiotensin I-converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians.
Eighty-five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early-onset MI was found in this population group. Other gene components of the renin-angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.


Variability in Cumulative Habitual Sleep Duration Predicts Waking Functional Connectivity.
We examined whether interindividual differences in habitual sleep patterns, quantified as the cumulative habitual total sleep time (cTST) over a 2-w period, were reflected in waking measurements of intranetwork and internetwork functional connectivity (FC) between major nodes of three intrinsically connected networks (ICNs): default mode network (DMN), salience network (SN), and central executive network (CEN). Resting state functional magnetic resonance imaging (fMRI) study using seed-based FC analysis combined with 14-d wrist actigraphy, sleep diaries, and subjective questionnaires (N = 33 healthy adults, mean age 34.3, standard deviation ± 11.6 y). Data were statistically analyzed using multiple linear regression. Fourteen consecutive days of wrist actigraphy in participant's home environment and fMRI scanning on day 14 at the Birmingham University Imaging Centre. Seed-based FC analysis on ICNs from resting-state fMRI data and multiple linear regression analysis performed for each ICN seed and target. cTST was used to predict FC (controlling for age). cTST was specific predictor of intranetwork FC when the mesial prefrontal cortex (MPFC) region of the DMN was used as a seed for FC, with a positive correlation between FC and cTST observed. No significant relationship between FC and cTST was seen for any pair of nodes not including the MPFC. Internetwork FC between the DMN (MPFC) and SN (right anterior insula) was also predicted by cTST, with a negative correlation observed between FC and cTST. This study improves understanding of the relationship between intranetwork and internetwork functional connectivity of intrinsically connected networks (ICNs) in relation to habitual sleep quality and duration. The cumulative amount of sleep that participants achieved over a 14-d period was significantly predictive of intranetwork and inter-network functional connectivity of ICNs, an observation that may underlie the link between sleep status and cognitive performance.


[A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION THAT DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY FOR MYASTHENIA GRAVIS WITH RECURRENT THYMOMA].
A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases.


MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4.
Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. miR-20a-5p negatively regulated Smad4 by directly targeting its 3'UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients' clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan-Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.


Precipitation increases the abundance of fungal plant pathogens in Eucalyptus phyllosphere.
Understanding the current and future distributions of plant pathogens is critical to predict the plant performance and related economic benefits in the changing environment. Yet, little is known about the roles of environmental drivers in shaping the profiles of fungal plant pathogens in phyllosphere, an important habitat of microbiomes on Earth. Here, using a large-scale investigation of Eucalyptus phyllospheric microbiomes in Australia and the multiple linear regression model, we show that precipitation is the most important predictor of fungal taxonomic diversity and abundance. The abundance of fungal plant pathogens in phyllosphere exhibited a positive linear relationship with precipitation. With this empirical dataset, we constructed current and future atlases of phyllosphere plant pathogens to estimate their spatial distributions under different climate change scenarios. Our atlases indicate that the abundance of fungal plant pathogens would increase especially in the coastal regions with up to 100-fold increase compared with the current abundance. These findings advance our understanding of the distributions of fungal plant pathogens in phyllospheric microbiomes under the climate change, which can improve our ability to predict and mitigate their impacts on plant productivity and economic losses.


Era of Molecular Diagnostics Techniques before and after the COVID-19 Pandemic.
Despite the growth of molecular diagnosis from the era of Hippocrates, the emergence of COVID-19 is still remarkable. The previously used molecular techniques were not rapid enough to screen a vast population at home, in offices, and in hospitals. Additionally, these techniques were only available in advanced clinical laboratories.The pandemic outbreak enhanced the urgency of researchers and research and development companies to invent more rapid, robust, and portable devices and instruments to screen a vast community in a cost-effective and short time. There has been noteworthy progress in molecular diagnosing tools before and after the pandemic. This review focuses on the advancements in molecular diagnostic techniques before and after the emergence of COVID-19 and how the pandemic accelerated the implantation of molecular diagnostic techniques in most clinical laboratories towardbecoming routine tests.


A generalized model for the interaction of microwave radiation with bound water in biological material.
Calculations have been performed concerning the deposition of microwave energy in bound water surrounding a biological macromolecule immersed in a continuum consisting of free water and dissolved ions. In particular a previous model of a hydrated macromolecule has been generalised to one where the relaxation frequency of the bound water varies across the layer, and the calculations have been carried out for three combinations of values of ionic conductivity of the bound water and the continuum. When these conductivities are equal, but low, the average energy deposition per unit volume in the bound water is greater, sometimes by at least an order of magnitude, than that in the continuum at frequencies in the region of hundreds of MHz to a few GHz. As the ionic conductivity increases this effect decreases and at conductivities equal to that of physiological saline the specific energy deposition in the bound water is not more than around twice that in the surrounding electrolyte continuum over this frequency range. Therefore, for tissues of high bound water content exposed to microwaves of a given power density the biological effect produced is enhanced. For a biological tissue of high ionic conductivity with 20% of its water in the bound state the overall energy absorption would be 25% greater at certain frequencies than if all the water were in the free state. For materials of low ionic conductivity the increase would be more than one order of magnitude.


THE DETERMINATION OF NEUTRON FLUENCE TO ABSORBED DOSE CONVERSION COEFFICIENTS AND RELATIVE BIOLOGICAL EFFECT BASED ON MICRODOSIMETRY MEASUREMENTS.
A tissue-equivalent proportional counter (TEPC) is a reference detector to measure microdosimetric quantities. A conventional spherical TEPC and a novel TEPC based on a ceramic thick gas electron multiplier (THGEM) foil were developed to carry out microdosimetric measurements of lineal energy spectra in monoenergetic and 252Cf/241Am-Be neutron radiation fields, and the absorbed dose values had been derived. In order to go further in radiobiology and therapy, the fluence to absorbed dose conversion coefficients in neutron fields were also determined. According to the dose distribution in lineal energy, the neutron relative biological effect (RBE) values were also calculated using an empirical procedure applying biological weighting functions.


[Comprehensive measurement and quantification of bio-mechanical properties of the temporomandibular joint disc].
Objective: To comprehensively investigate the biomechanical properties of the temporomandibular joint (TMJ) disc and to perfect the mechanical testing system of the TMJ disc by conducting tests of compression, tension, cyclic compression, cyclic tension, creep and friction. Methods: Fifteen fresh goat heads (weighing 2.5-3.0 kg) were purchased from the market. They were all ordinary goats (9-12 months old, body weighing 18-21 kg) regardless of gender. Bilateral articular discs (a total of 30) were dissected within 30 minutes after execution. According to the national standard for mechanical testing of viscoelastic materials, fresh TMJ disc specimens of goat were prepared and tests were carried out in physiological conditions. The universal mechanical testing machine was utilized to test biomechanical properties of TMJ discs. Results: The compressive modulus of TMJ discs was (8.41±2.12) MPa and the tensile modulus was (9.54±3.26) MPa. The mechanical characteristics would be irreversibly altered once the load exceeded the physiological range. In addition, it underwent apparent creep relaxation under continuous strain (0.5 MPa or 3.0 MPa) and the surface friction coefficient of the TMJ discs (0.015+0.011) was much lower than that of general viscoelastic materials. Conclusions: The TMJ disc was a bio-viscoelastic structure with excellent tensile and compressive properties and its surface was extremely smooth in wet conditions.


The perils of Grandma's medication: colchicine toxicity causing pneumomediastinum.
A 19 year old male presented with a deliberate overdose of colchicine (50mg). He had no other significant medical history. 36 hours following admission he developed widespread surgical emphysema. An urgent CT scan of his chest and abdomen demonstrated mediastinal gas of lung origin. He also developed bone marrow suppression and disseminated intravascular coagulopathy. He was treated supportively with intravenous fluids, high flow oxygen and intravenous antibiotics and made a full recovery. Colchicine toxicity is a rare, but important presentation with high levels of morbidity and mortality. Pneumomediastinum is a potentially important complication. It may be appropriate to monitor patients in the later stages of the condition through an ambulatory setting.


Comparative PCR-based restriction fragment length polymorphism analysis of the plasmid gene orf3 of Chlamydia trachomatis and Chlamydia psittaci.
The BfaI digestion of PCR-based restriction fragment length polymorphism analysis of the plasmid orf3 of Chlamydia trachomatis and Chlamydia psittaci provided evidence for two distinct restriction patterns, respectively. The nucleotide sequences of orf3 genes confirmed these differences. Serum antibodies against recombinant C. psittaci protein (pgp3) encoded by orf3 were detected both in pigeons with C. psittaci infection and in a human patient with psittacosis.


Diversity of Anopheles species and trophic behavior of putative malaria vectors in two malaria endemic areas of northwestern Thailand.
We determined the species diversity, blood-feeding behavior, and host preference of Anopheles mosquitoes in two malaria endemic areas of Tak (Mae Sot District) and Mae Hong Son (Sop Moei District) Provinces, located along the Thai border with Myanmar, during a consecutive two-year period. Anopheline mosquitoes were collected using indoor and outdoor human-landing captures and outdoor cow-baited collections. Mosquitoes were initially identified using morphological characters, followed by the appropriate multiplex AS-PCR assay for the identification of sibling species within Anopheles (Cellia) complexes and groups present. Real-time PCR was performed for parasite-specific detection in mosquitoes (Plasmodium spp. and Wuchereria bancrofti). A total of 7,129 Anopheles females were captured, 3,939 from Mae Sot and 3,190 from Sop Moei, with 58.6% and 37% of all anophelines identified as An. minimus, respectively. All three malaria vector complexes were detected in both areas. One species within the Minimus Complex (An. minimus) was present along with two related species in the Funestus Group, (An. aconitus, An. varuna), two species within the Dirus Complex (An. dirus, An. baimaii), and four species within the Maculatus Group (An. maculatus, An. sawadwongporni, An. pseudowillmori, and An. dravidicus). The trophic behavior of An. minimus, An. dirus, An. baimaii, An. maculatus, and An. sawadwongporni are described herein. The highest An. minimus densities were detected from February through April of both years. One specimen of An. minimus from Mae Sot was found positive for Plasmodium vivax.


Meta-analysis examining the efficacy and safety of almotriptan in the acute treatment of migraine.
To evaluate the comparative efficacy and safety of oral almotriptan in treating acute migraine attacks. Almotriptan is an oral selective sertonin(1B/1D) receptor agonist (triptan) with a high bioavailability and short half-life, developed for the treatment of migraine. In recent years, a number of randomized controlled trials have been published examining the efficacy and safety of almotriptan in the acute treatment of migraine. Systematic review and meta-analysis of randomized controlled trials (RCTs) using a random-effects model to estimate the pooled rate ratios (RRs) and 95% confidence intervals (95%CI) for the proportions of patients achieving headache relief and pain-free responses at 1 or 2 hours post-dose, sustained pain-free response at 2-24 hours post-dose, and safety outcomes (proportions of patients experiencing any adverse events, dizziness, somnolence, asthenia, and chest tightness) comparing almotriptan against placebo, other triptans, and different dosages of almotriptan. Absolute rate differences (ARDs) for 2-hour headache relief, pain free, and sustained pain free responses between almotriptan and placebo were also calculated. Eight RCTs involving 4995 patients were included in the analysis. Almotriptan 12.5 mg was significantly more effective than placebo for all efficacy outcomes (RRs ranged from 1.47 to 2.15; ARDs ranged from 0.01 to 0.28) and there were no significant differences in any of the safety outcomes. There were also no significant differences in efficacy outcomes comparing almotriptan 12.5 mg against sumatriptan 100 mg and zolmitriptan 2.5 mg, but almotriptan 12.5 mg was associated with significantly fewer adverse events than sumatriptan 100 mg (RR: 0.39, 95%CI: 0.23, 0.67). However, there was no significant difference between almotriptan and sumatriptan in terms of clinically important adverse effects, such as dizziness, somnolence, asthenia, and chest tightness. Almotriptan 12.5 mg was significantly less effective than almotriptan 25 mg for 1-hour pain-free response (RR: 0.45, 95%CI: 0.21, 0.95), but associated with significantly fewer patients experiencing adverse events (RR: 0.61, 95%CI: 0.41, 0.91) than almotriptan 25 mg. Almotriptan 12.5 mg is an effective treatment for acute attacks of migraine, in particular, it has been found to be as effective as sumatriptan 100 mg and zolmitriptan 2.5 mg. The risk of adverse events associated with almotriptan 12.5 mg was similar to placebo and significantly lower than sumatriptan 100 mg. Further research is required to assess the comparative efficacy of almotriptan against other triptans.


Transformation of a human mixed GH-PRL adenoma cell population in response to long-term bromocriptine treatment.
A child was operated 3 times because of a recurrent growth hormone- and prolactin-producing pituitary adenoma. Between the operations she was treated for five years with bromocriptine. The characteristics of the tumour cell population collected after the last operation was now examined by electron microscopy, immunocytochemistry, and in tissue culture and compared to those of the primary tumour cells reported earlier. A prominent change was the reversal of the proportion of the densely and sparsely granulated cells in favour of the GH-type, densely granulated cells. These cells, some of them coexpressing PRL, did not essentially change their characteristics either in vivo or in culture. On the other hand, pleomorphous cells with smaller cytoplasmic area and prominent lysosomal structures represented the sparsely granulated population containing PRL or both PRL and GH. The morphological alteration of the PRL-type cells was also reflected in vitro. Hence, while GH-type cells prevail, at least a sub-population of PRL-type cells survives long-term bromocriptine administration. A shift in the incidence of the two cell types in favour of the GH-type cells explains the change in the endocrine status of the patient.


[Selection of reference genes for quantitative real-time PCR in six oil-tea camellia based on RNA].
qRT-PCR is becoming a routine tool in molecular biology to study gene expression. It is nec- essary to find stable reference genes when performing qRT-PCR. The expression of genes cloned in oil-tea camellia currently can't be accurately analyzed because of a lack of suitable reference genes. We collected different tissues (including roots, stems, leaves, flowers and seeds) from six oil-tea camellia species to determine stable reference genes. Five novel and ten traditional reference gene sequences were selected from the RNA-seq database of Camellia oleifera C. Abel seeds and specific PCR primers were designed for each. Cycle threshold (Ct) data were obtained from each reaction for all samples. Three different software tools, geNorm, NormFinder and BestKeeper were applied to calculate the expression stability of the candidate reference genes according to the Ct values. The results were similar between analyzed by the three software packages, and indicated that the traditional gene TUBa-3, AC17a and the novel gene CESA were relatively stable in all species and tissues. However, no genes were sufficiently stable across all species and tissues, thus the optimal number of reference genes required for accurate normalization varied from two to six. Finally, the relative expression ofsqualene synthase (SQS) and squalene epoxidase (SQE) genes related to important ingredients squalene and tea saponin in oil-tea camellia seeds were compared by using stable to less stable reference genes. The comparison results validated the selection of reference genes in the current study. In summary, different optimal numbers of suitable reference genes were found for the different tissues of six oil-tea camellia species.


Change in relaxation scenario at the order-disorder transition of a colloidal fluid of hard spheres seen from the Gaussian limit of the self-intermediate scattering function.
Self-intermediate scattering functions (ISFs) are measured by dynamic light scattering for the colloidal fluid of hard spheres for both equilibrium and nonequilibrium (undercooled) conditions, i.e., for volume fractions below and above the known freezing transition of the hard-sphere system. The delay time tau(m) where the mean-squared displacement, or the low wave-vector limit of the ISF, exhibits its maximum stretching is identified as a characteristic of the non-Markovian process(es) and is used to separate the ISF into fast (tau < tau(m)) and slow (tau > tau(m)) contributions. Each of these contributions exposes qualitative differences in the dynamics of the particles between the equilibrium and nonequilibrium colloidal fluids. These changes in the relaxation scenario signal the colloidal fluid's awareness of its traversal of the freezing volume fraction.


Outcomes of Hemospray therapy in the treatment of intraprocedural upper gastrointestinal bleeding post-endoscopic therapy.
With increasing advances in minimally invasive endoscopic therapies and endoscopic resection techniques for luminal disease, there is an increased risk of post-procedure bleeding. This can contribute to significant burden on patient's quality of life and health resources when reintervention is required. Hemospray (Cook Medical, North Carolina, USA) is a novel haemostatic powder licensed for gastrointestinal bleeding. The aim of this single-arm, prospective, non-randomised multicentre international study is to look at outcomes in patients with upper gastrointestinal bleeds following elective endoscopic therapy treated with Hemospray to achieve haemostasis. Data was prospectively collected on the use of Hemospray from 16 centres (January 2016-November 2019). Hemospray was used during the presence of progressive intraprocedural bleeding post-endoscopic therapy as a monotherapy, dual therapy with standard haemostatic techniques or rescue therapy once standard methods had failed. Haemostasis was defined as the cessation of bleeding within 5 min of the application of Hemospray. Re-bleeding was defined as a sustained drop in haemoglobin (>2 g/l), haematemesis or melaena with haemodynamic instability after the index endoscopy. A total of 73 patients were analysed with bleeding post-endoscopic therapy. The median Blatchford score at baseline was five (interquartile range 0-9). The median Rockall score was six (interquartile range 5-7). Immediate haemostasis following the application of Hemospray was achieved in 73/73 (100%) of patients. Two out of 57 (4%) had a re-bleed post-Hemospray, one was following oesophageal endoscopic mucosal resection and the other post-duodenal endoscopic mucosal resection. Both patients had a repeat endoscopy and therapy within 24 h. Re-bleeding data was missing for 16 patients, and mortality data was missing for 14 patients. There were no adverse events recorded in association with the use of Hemospray. Hemospray is safe and effective in achieving immediate haemostasis following uncontrolled and progressive intraprocedural blood loss post-endoscopic therapy, with a low re-bleed rate.


Physical activity as a determinant of mortality in women.
There is substantial evidence that higher levels of activity reduce the risk of mortality, but several research questions remain about the protective effect of physical activity. We aimed to quantify the effect of physical activity on overall mortality in younger women and to assess the effect of past versus current activity. During 1991-1992, we enrolled 99,099 women, age 30-49 years, from the entire country of Norway and one Swedish region, in a population-based cohort study. The women provided information on physical activity level at age 14 and 30 years and at enrollment, as well as information on other personal characteristics at enrollment. We achieved complete follow-up into 2003 using record linkages to nationwide registers. We used Cox proportional hazard models to calculate multivariate relative risks (RRs) of dying from any cause. During an average 11.4 years of follow-up, 1,313 women died. Risk of death decreased with increasing physical activity at enrollment (5 categories; P for trend<0.0001) and was reduced by half in the highest compared with the lowest category (RR=0.46; 95% confidence intervals=0.33-0.65). This protective effect was consistent across strata of age at entry, smoking, country, and education. After adjustment for physical activity at enrollment, activity at age 14 and 30 was not associated with mortality. Current physical activity substantially reduces mortality among women. This association is observed even with low levels of physical activity and is accentuated with increased physical activity.


Localization of chromogranin A-immunoreactivity in bovine gastrointestinal endocrine cells with special reference to Grimelius silver stain.
Immunohistochemical studies of the gastrointestinal tract were carried out to characterize the cells exhibiting immunoreactivity for chromogranin A (CGA), a glycosylated protein primarily found in secretory granules of the adrenal medulla. Double immunostaining for gastrointestinal hormones and CGA revealed that in the bovine gastrointestinal tract CGA immunoreactivity occurs in mucosal epithelial cells containing gastrin, glucagon, substance P or motilin, but not in those containing somatostatin. Combined staining with anti-CGA serum and Grimelius' silver demonstrated frequent association of the two stains in a variety of endocrine cells. However, intracellular distribution of the two stains was different: CGA-immunoreactivity was detected in both supra- and infranuclear cytoplasm, whereas Grimelius' silver was mostly localized in the infranuclear region. These results suggest that CGA is the target of Grimelius' silver, as postulated recently (Rindi et al., 1986), but that some subcellular structure-related modification of molecules such as sialation is necessary for the positive Grimelius reaction.


Spectral measurements of runaway electrons by a scanning probe in the TEXTOR tokamak.
Energy spectral measurements of runaway electrons were performed by a scanning probe with high spatial and temporal resolution in the TEXTOR tokamak. The probe consists of ten YSO (Y(2)SiO(5):Ce) crystals, which are shielded by tungsten filters. The probe can resolve electrons with different energies between 4 and 30 MeV. An insertion of the probe to the plasma boundary several times during the discharge allowed spectral measurements of runaway electrons at different minor radial positions at the plasma edge as well as the study of runaway production in time. The high temporal resolution of the probe, 0.05 ms, enabled measurements of runaway electrons not only during low density discharges, but also during plasma disruptions.


English Language Medical Schools in China: An Analysis of International Medical Graduates Practicing in the UK.
From 2006, the Ministry of Education in China has approved universities to provide undergraduate medical training in English, targeting fee-paying international students. Students on these courses can face challenges in their clinical training, particularly in the domains of communication and professionalism. This study examines the proportion of doctors qualified from such medical schools who are currently listed on the UK medical register. The UK General Medical Council register of medical practitioners was searched to identify doctors qualified from 33 Chinese medical schools who provide education in the English language. As of February 2022, 502 doctors whose primary medical qualification is from a university offering English language education in China were registered on the UK medical register. Four hundred twenty-five (84.7%) of these doctors were aged 39 and under, approximately double the proportion of doctors in this age bracket overall. Three hundred forty nine (69.5%) were staff grade and associate specialist doctors, 109 (21.7%) were doctors in training, 36 (7.2%) were on the General Practitioner (GP) register, and 20 (4.0%) were on the specialist register. Among doctors in training, the most common specialty areas were in general practice and psychiatry that are both facing recruitment shortages in the UK at present. A small but significant number of graduates whose medical training was in the English language in China are practicing medicine in the UK. These doctors are in younger age groups than the overall medical workforce, and are less likely to be in training, and specialist or GP posts. Among those in training, a high proportion are in GP and psychiatry training and could contribute to alleviating UK medical workforce shortages. Policymakers and educators should be mindful of the growing numbers of doctors qualified from these schools, and the additional support they may require considering the unique training environments they have encountered.


[Epidemiological study on disability caused by injury in the Chinese population].
To describe and analyze the prevalence and epidemiological features of people with disability caused by injury in the Chinese population, and to provide scientific basis for developing the prevention and control programs on injuries. Statistics and intervention measures were used to analyze the data from the Second China National Sample Survey on injury-caused Disability. Cluster analysis was used to analyze the differences in regions. The overall prevalence of disability caused by injury was 99.68/10 000 which occupied 15.59% of all the disability, with multiple disability excluded. Physical disability and hearing disability accounted for 65.59% and 23.35% of all the injury-caused disability respectively, while those ranked Grade IV and III making up the majority (55.14% and 25.83%) of the disability, respectively. There were significant differences in the distribution of injury-caused disability among different age groups (χ(2) = 23 106.14, P < 0.001) and gender (χ(2) = 2161.74, P < 0.001). Ageing and being males having a higher risk on injury-caused disability. Five clusters were identified by cluster analysis, in which injury-caused disability were severe in the fifth (Sichuan province) and the fourth clusters (Hunan, Chongqing, Guizhou, Ningxia province). Problems discovered by injury-caused disability in the Chinese population should not be ignored. Both physical and hearing disabilities appeared to be the two main types of disability while age, gender and region were related to injury-caused disability. Targeted strategies should be developed to decrease the injury-caused disability in China.


Benign prostatic hyperplasia and growth factors.
A great deal of work has been accomplished in the attempt to determine the cause of benign prostatic hyperplasia (BPH). Early work by morphologists suggests that BPH starts as a stromal disease and that the hyperplastic stroma secretes a substance that stimulates the growth of epithelial cells. The quantitative morphometric data also suggest that BPH is primarily a stromal disease. Experimental embryology data have shown that the basic fibroblast growth factor, bFGF, is involved in early embryogenesis and is the primary inducer of mesodermal tissue. Work in mouse embryos has shown that a powerful inducer for prostatic epithelial growth is elaborated by the urogenital mesenchyme. Both of these findings fit the hypothesis that stromal hyperplasia may be initiated by a growth factor and that a second growth factor stimulates epithelial growth. Work in our laboratory has established that bFGF is the primary growth factor present in human BPH. We have also found that bFGF is synthesized by prostate fibroblasts and bFGF may be in higher concentration in the periurethral tissues of BPH. At this time, no definite link between growth factors and hyperplastic growth of the prostate has been established. However, circumstantial evidence has lead us to formulate several hypothesis regarding the role of growth factors in BPH. Hopefully, these hypothesis will be of some assistance in guiding future work on growth factors and BPH.


Treatment strategies of intermediate-stage hepatocellular carcinomas in Japan (Barcelona Clinic Liver Cancer stage B).
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and it shows increasing incidence worldwide. The Barcelona Clinic Liver Cancer (BCLC) staging system has become widely accepted in clinical practice, but in Japan, two clinical practice guidelines have been used for HCC: the Evidence-Based Clinical Practice Guidelines and the Consensus-Based Clinical Practice Guidelines. Although, in Japan, chemoembolization is the first-line treatment of intermediate-stage (stage B) HCC patients in the BCLC staging system, along with chemoembolization, locoregional treatments, such as resection and radiofrequency ablation, and hepatic arterial infusion chemotherapy are incorporated into the treatment algorithm based on the tumor number and size as well as on the liver profile.


Hypertension and adrenal disorders.
Abnormalities of adrenal cortical and medullary function are important causes of hypertension in adults. Mineralocorticoid hypertension, characterized by spontaneous hypokalemia with excessive kaliuresis and low plasma renin activity, is most commonly caused by aldosterone-producing adenoma or, less frequently, by nonadenomatous adrenal hyperplasia. However, recent evidence indicates that this classification oversimplifies the pathophysiologic diversity of this syndrome. Advances in steroid biochemistry and molecular biology have improved our ability to identify patients with various forms of mineralocorticoid hypertension and also provide evidence that they are underdiagnosed. Pheochromocytomas are most commonly located in the adrenal medulla, where they may overproduce norepinephrine or epinephrine. Appropriate screening of norepinephrine, epinephrine, and their metabolites is essential because tumors that secrete epinephrine exclusively may not present with hypertension and, thus, can be overlooked. Extra-adrenal pheochromocytomas are more prevalent than previously considered and pose special problems because they may be multicentric, difficult to locate, and more likely to be malignant than are adrenal pheochromocytomas.


The starting point of eating disorders: role of genetics.
Eating disorders are perplexing diseases of which the etiology is still unknown. Recent research has focused on the possibility that genetics plays a role in vulnerability to these pathologies. This study gives an overview of the available literature focusing on family, twin and molecular genetic studies of eating disorders.


Recent otological evaluation of aminoglycoside antibiotics.
A survey is made of comparative studies of ototoxicity of different aminoglycoside antibiotics. Animal studies show clearly lower netilmicin ototoxicity compared with that of other aminoglycoside antibiotics. Clinical controlled comparative trials are few. Most studies have few patients in each group. The significance of auditory threshold shifts in single frequencies as criteria of ototoxicity is uncertain. An analysis of clinical and animal studies together indicates, however, that netilmicin has a higher ratio of efficacy to ototoxicity than other aminoglycoside antibiotics.


The impact of violence on development in low- to middle-income countries.
Along with the numerous trauma-related impacts of violence and its effects on other health outcomes, the social toll of violence is further exacerbated by economic costs that represent formidable threats to fiscal growth and development. A companion piece to a review of the scientific literature describing the nature, magnitude and impact of violence on health (Matzopoulos, Bowman, Butchart & Mercy, 2008) in this issue, this paper reviews the current knowledge base on violence and development with a specific focus on low- to middle-income countries. It describes how violence impacts on all eight goals of the Millennium Development Plan and exerts a considerable economic burden on already stressed state systems and social spending. Violence will become an increasingly important threat to development and is receiving growing recognition among the global health community and within health ministries. The near absence of violence prevention within the global development agenda is, however, cause for concern. There is an urgent need to mobilise the international development community to provide financial and technical support for intersectoral collaboration, multilateral research cooperation and the development of research capacity towards addressing violence as a significant threat to development.


Bisacenaphthopyrazinoquinoxaline derivatives: synthesis, physical properties and applications as semiconductors for n-channel field effect transistors.
Several bisacenaphthopyrazinoquinoxaline (BAPQ) based derivatives 1-3 were synthesized by condensation between the acenaphthenequinones and 1,2,4,5-tetraaminobenzene tetrahydrochloride. Their optical, electrochemical and self-assembling properties are tuned by different substituents. Among them, compound 3 possesses a homogeneously distributed low-lying LUMO due to the peripheral substitution with four cyano groups. The corresponding n-channel field effect transistors showed a field effect electron mobility of 5 × 10(-3) cm(2) V(-1) s(-1).


Monoclonal antibody against microtubule associated protein-1 produces immunofluorescent spots in the nucleus and centrosome of cultured mammalian cells.
A monoclonal antibody was raised against the highest molecular weight protein associated with microtubules (MAP-1). Its specific binding to MAP-1 was determined by immunoblotting of the gel electrophoretogram of microtubule proteins prepared from porcine brain. The antibody reacted only with MAP-1, not with MAP-2, tau or tubulin. Indirect immunofluorescent staining by this antibody showed bright intranuclear spots, the centrosome and the faint meshwork of the cytoplasm in several types of cultured mammalian cells; HeLa, PtK2, human skin fibroblasts, mouse melanoma cells, Chinese hamster ovary cells. The nuclear spots in the interphase cells, were replaced by diffuse enhanced fluorescence throughout the cell except for chromosomes during mitosis. They reappeared in late telophase, first in the cytoplasm, late in the nucleus. The punctate pattern of nuclear immunofluorescence was not affected by microtubule-depolymerizing agents. The result that it persisted on residual cell structures after extraction with a high salt concentration buffer containing Triton X-100 followed by digestion with DNase I and RNase A suggests that the antigen is associated with the nuclear skeleton.


Oxytocin as a biomarker of the formation of therapeutic alliance in psychotherapy and counseling psychology.
The therapeutic alliance is one of the most consistent predictors of therapeutic change, including symptom reduction and improvement in wellbeing and quality of life, across a variety of mental health interventions. Yet, little is known about its biological mechanisms. Oxytocin (OT) has been suggested as a biological mechanism by which bonds are formed and strengthened across species. This article is intended to demonstrate the potential of OT as a biomarker of therapeutic change in psychotherapy and counseling psychology, especially of the therapeutic alliance. We delineate three main potential paths of investigation based on the most recent research on OT in parent-child and romantic partner dyads. For each path, we provide a detailed explanation for whom, when, and how OT should be measured. Each path is illustrated using data collected in a randomized controlled trial of psychotherapy for major depressive disorder. These illustrations demonstrate the great potential of OT as a biomarker of (a) trait-like characteristics of the patients and the therapists, (b) the processes of therapeutic change, and (c) the dyadic synchrony between patients and their therapists. The potential clinical contribution of OT as a biomarker for each of these three paths is further demonstrated using a case study. Practical suggestions and directions for future research are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Low-dose streptokinase in the treatment of arterial graft occlusions.
During the past 24 months, 19 infrainguinal bypass graft occlusions occurring in 17 patients were treated with local infusions of streptokinase. The treated grafts included three venous femorocrural grafts and four venous and 13 Goretex femoropopliteal grafts. Infusion managed to restore flow completely in 10 grafts. Partial clot lysis occurred in three and no lysis in six grafts. All successful recanalisations occurred within 120 hours of the initiation of thrombolytic therapy. Despite three major complications and the development of two minor haematomas, with an overall success rate of 55% our results support the use of streptokinase in the management of occluded bypass grafts.


Calculation of effective VV interval facilitates optimization of AV delay and VV interval in cardiac resynchronization therapy.
In hearts with left bundle branch block (LBBB), both atrioventricular (AV) delay and interventricular (VV) interval determine left ventricular (LV) pump function in cardiac resynchronization therapy (CRT). The optimal combination of AV delay and VV interval currently is determined by extensive hemodynamic testing. The purpose of this study was to investigate whether the effective VV interval (VV(eff)) can be used to optimize AV delay and VV interval. In eight canine hearts with chronic LBBB, LV pacing was performed at various AV delays as well as biventricular pacing at multiple AV delays and VV intervals. LV pump function was assessed from LVdP/dt(max) and stroke volume (conductance catheter). Interventricular asynchrony was calculated from the timing difference between upslope of LV and RV pressure curves. VV(eff) was defined as the time delay between activation of the RV apex and LV lateral wall, irrespective of the source of RV activation (RV pacing or intrinsic conduction). VV(eff) was determined from pacemaker settings and surface ECGs recorded during biventricular pacing at various AV delays (positive values denote LV preexcitation). For all animals, the relationship between VV(eff) and LVdP/dt(max) as well as LV stroke work was parabolic. Maximal improvement in LVdP/dt(max) was similar during LV pacing, simultaneous biventricular pacing, and sequential biventricular pacing and was obtained at similar values of VV(eff). VV(eff) was strongly correlated with interventricular asynchrony (R = 0.97 +/- 0.03). Optimum LVdP/dt(max) occurred at VV(eff) ranging from -24 to 12 ms (mean -6 +/- 13 ms). For each experiment, the optimal VV(eff) was virtually equal to the value halfway between its minimum (during LV pacing at short AV delay) and maximum (during LBBB) value (R = 0.91). Use of VV(eff) facilitates determination of the best combination of AV delay and VV interval during biventricular pacing. For each individual heart, VV(eff), resulting in optimum LV pump function, can be estimated using surface ECGs recorded during biventricular pacing.


NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma.
There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations.


[Educational practices in accordance with the "Ten steps to successful breastfeeding" in a Human Milk Bank].
This article sought to evaluate educational practices in line with the "Ten Steps to Successful Breastfeeding" in a Human Milk Bank. It involved a retrospective study using sociodemographic data about the pregnancy and the baby, obtained from a nursing mothers care protocol (2009-2012). These data were associated to steps related to educational practices from the "Ten Steps." Descriptive analysis, chi-square test and Poisson regression were performed. 12,283 mothers, with a median of 29 (12-54) years old, were evaluated. The guidelines about breastfeeding received during prenatal care (step 3) prevailed among mothers aged 30-39 years and the skin to skin contact (step 4) prevailed among oriented mothers. Breastfeeding training (step 5) predominated among those who breastfed exclusively. Higher prevalence of exclusive breastfeeding (step 6), breastfeeding on demand (step 8) and use of artificial nipples (step 9) were noted among infants whose mothers were oriented. These findings indicate the important role of health professionals on mother/child training about breastfeeding, on encouragement of the skin/skin contact, exclusive breastfeeding and breastfeeding on demand. The guidelines indicated the need to improve in order to reduce the use of artificial nipples and enhance exclusive breastfeeding.


Flunarizine, a calcium channel antagonist, is partially prophylactically neuroprotective in hypoxic-ischemic encephalopathy in the fetal sheep.
Calcium antagonist therapy has been reported to reduce neuronal death after hypoxia-ischemia; however, its potential use in prenatal hypoxic-ischemic events has received little attention. We examined the effect of pretreatment with flunarizine in chronically instrumented late gestation fetal sheep subjected to 30 min of cerebral ischemia. Eight fetuses were given 0.11 mmol (45 mg) of flunarizine over 2 h preischemia (high dose), 10 were given 0.07 mmol (30 mg) over 3 h preischemia (low dose), 17 were given nothing (ischemia controls), and 5 received neither the ischemic insult nor any treatment (sham controls). The fetal electrocorticogram was monitored for 3 d postinsult. Histologic outcome was quantified after 72 h. Low-dose, but not high-dose, flunarizine therapy was associated with an overall reduction in cerebral damage (p < 0.01), a greater final electrocorticogram intensity, and a reduction in the incidence of seizures (p < 0.02) compared with ischemia controls. High-dose, but not low-dose, flunarizine was associated with a significant acute mortality and a decrease in fetal blood pressure (p < 0.05) at the time of occlusion, although there was no effect on the initial hypertensive response to occlusion. These observations suggest that flunarizine is partially neuroprotective when given before severe global ischemia in utero, but that its hypotensive effects make it unsuitable for prophylactic administration in utero.


Preliminary Evidence That High-Dose Vitamin C has a Vascular Disrupting Action in Mice.
High intravenous doses of vitamin C (ascorbic acid) have been reported to benefit cancer patients, but the data are controversial and there is incomplete knowledge of what physiological mechanisms might be involved in any response. Vitamin C is taken up efficiently by cells expressing SVCT2 transporters and since vascular endothelial cells express SVCT2, we explored the hypothesis that administration of high-dose vitamin C (up to 5 g/kg) to mice might affect vascular endothelial function. A single administration of vitamin C to mice induced time- and dose-dependent increases in plasma concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), a marker for vascular disrupting effects. Responses were comparable to those for the tumor vascular disrupting agents, vadimezan and fosbretabulin. High-dose vitamin C administration decreased tumor serotonin concentrations, consistent with the release of serotonin from platelets and its metabolism to 5-HIAA. High-dose vitamin C also significantly increased the degree of hemorrhagic necrosis in tumors removed after 24 h, and significantly decreased tumor volume after 2 days. However, the effect on tumor growth was temporary. The results support the concept that vitamin C at high dose increases endothelial permeability, allowing platelets to escape and release serotonin. Plasma 5-HIAA concentrations could provide a pharmacodynamic biomarker for vitamin C effects in clinical studies.


Comparative Study of TiO2, ZnO, and Nb2O5 Photoanodes for Nitro-Substituted Naphthoquinone Photosensitizer-Based Solar Cells.
This research focuses on the first demonstration of NO2Lw (2-hydroxy-3-nitronaphthalene-1,4-dione) as a photosensitizer and TiO2, ZnO, and Nb2O5 as photoanode materials for dye-sensitized solar cells (DSSCs). The metal-free organic photosensitizer (i.e., nitro-group-substituted naphthoquinone, NO2Lw) was synthesized for this purpose. As a photoanode material, metal oxides, such as TiO2, ZnO, and Nb2O5, were selected. The synthesized NO2Lw contains an electron-withdrawing group (-NO2) and anchoring groups (-OH) that exhibit absorption in the visible range. The UV-visible absorbance spectrum of NO2Lw demonstrates the absorption ascribed to ultraviolet and visible region charge transfer. The NO2Lw interacts with the TiO2, ZnO, and Nb2O5 photoanode, as shown by bathochromic shifts in wavelengths in the photosensitizer-loaded TiO2, ZnO, and Nb2O5 photoanodes. FT-IR analysis also studied the bonding interaction between NO2Lw and TiO2, ZnO, and Nb2O5 photoanode material. The TiO2, ZnO, and Nb2O5 photoanodes loaded with NO2Lw exhibit a shift in the wavenumber of the functional groups, indicating that these groups were involved in loading the NO2Lw photosensitizer. The amount of photosensitizer loading was calculated, showing that TiO2 has higher loading than ZnO and Nb2O5 photoanodes; this factor may constitute an increased JSC value of the TiO2 photoanode. The device performance is compared using photocurrent-voltage (J-V) curves; electrochemical impedance spectroscopy (EIS) measurement examines the device's charge transport. The TiO2 photoanode showed higher performance than the ZnO and Nb2O5 photoanodes in terms of photoelectrochemical properties. When compared to ZnO and Nb2O5 photoanodes-based DSSCs, the TiO2 photoanode Bode plot shows a signature frequency peak corresponding to electron recombination rate toward the low-frequency region, showing that TiO2 has a greater electron lifetime than ZnO and Nb2O5 photoanodes based DSSCs.


Combined inhibition of IL1, CXCR1/2, and TGFβ signaling pathways modulates in-vivo resistance to anti-VEGF treatment.
Resistance of tumors to antiangiogenic therapies is becoming increasingly relevant. We recently identified interleukin-1 (IL1), CXC receptors (CXCR)1/2 ligands, and transforming growth factor β (TGFβ) among the proinflammatory factors that were expressed at higher levels in murine models resistant to the antivascular endothelial growth factor (anti-VEGF) antibody bevacizumab. Here, we hypothesized that the combined inhibition of these proinflammatory signaling pathways might reverse this anti-VEGF resistance. Bevacizumab-resistant FGBR pancreatic cancer cells were treated in vitro with bevacizumab, the recombinant human IL1 receptor antagonist anakinra, the monoclonal antibody against TGFβ receptor type II TR1, and a novel recombinant antibody binding CXCR1/2 ligands. The FGBR cells treated with these agents in combination had significantly higher levels of E-cadherin and lower levels of vimentin, IL6, phosphorylated p65, and SMAD2, and showed significantly lower migration rates than did their controls treated with the same agents without bevacizumab or with a single agent bevacizumab as a control. Consistently, the combination of these agents with bevacizumab reduced the FGBR tumor burden and significantly prolonged mice survival compared with bevacizumab in monotherapy. Tumors from mice receiving the combination treatment showed significantly lower expression of IL6 and phosphorylated SMAD2, higher expression of E-cadherin and lower levels of vimentin, and a significantly lower infiltration by CD11b cells compared with bevacizumab-treated controls. This study suggests that inhibition of IL1, CXCR1/2, and TGFβ signaling pathways is a potential therapeutic approach to modulate the acquired resistance to anti-VEGF treatment by reversing epithelial-mesenchymal transition and inhibiting CD11b proangiogenic myeloid cells' tumor infiltration.


Women at the top: powerful leaders define success as work + family in a culture of gender.
How do women rise to the top of their professions when they also have significant family care responsibilities? This critical question has not been addressed by existing models of leadership. In a review of recent research, we explore an alternative model to the usual notion of a Western male as the prototypical leader. The model includes (a) relationship-oriented leadership traits, (b) the importance of teamwork and consensus building, and (c) an effective work-family interface that women with family care responsibilities create and use to break through the glass ceiling. We adopted a cross-cultural perspective to highlight the importance of relational orientation and work-family integration in collectivistic cultures, which supplements models of leadership based on Western men. Our expanded model of leadership operates in the context of a "culture of gender" that defines expectations for women and men as leaders. This complex model includes women in diverse global contexts and enriches our understanding of the interplay among personal attributes, processes, and environments in leadership.


Nuclear medicine in diagnosis, staging and follow-up of thyroid cancer.
Diagnostic strategy in thyroid cancer is conditioned by epidemiological, pathophysiological, cost-effective issues changing with age and countries. Nuclear medicine has a role mainly in differentiated carcinomas, i.e. in the large majority of thyroid cancers. In diagnosis of thyroid nodule (99m)Tc-perthecnetate is indicated in patients with low TSH levels, multinodular goiter, solid nodules at US negative at FNA. Radiolabeled somatostatin analogs or Metaiodobenzylguanidine (MIBG) can be used in suspicion of medullary carcinoma. There is no role in staging. WBS with 131I has a role after surgical resection of the thyroid gland and it is no more suggested before ablative therapy, because of the possible stunning effect. In the follow-up thyroglobulin (Tg) test is mandatory both after therapy withdrawal or after rhTSH administration. Some authors already suggest to use this test alone, as 1st step, in patients with differentiated carcinoma at low risk of recurrence, but this approach is not yet generally accepted and it has not yet been validated in tumors at intermediate/high risk. WBS with 131I is ever indicated when autoantibodies can affect reliability of Tg values and in presence of high Tg levels to better define a radiometabolic therapy. In case of negative WBS, PET-FDG can be proposed. In WBS, 123I can be an alternative to 131I, but it is not yet generally accepted mainly because of its higher costs. The clinical use of rhTSH to increase accuracy both of Tg and WBS can be already accepted in patients at high risk following hypothyroidism, with a worst prognosis or a low pituitary response.


Insulin-like growth factor-I induces arginase activity in Leishmania amazonensis amastigote-infected macrophages through a cytokine-independent mechanism.
Leishmania (Leishmania) amazonensis exhibits peculiarities in its interactions with hosts. Because amastigotes are the primary form associated with the progression of infection, we studied the effect of insulin-like growth factor (IGF)-I on interactions between L. (L.) amazonensis amastigotes and macrophages. Upon stimulation of infected macrophages with IGF-I, we observed decreased nitric oxide production but increased arginase expression and activity, which lead to increased parasitism. However, stimulation of amastigote-infected macrophages with IGF-I did not result in altered cytokine levels compared to unstimulated controls. Because IGF-I is present in tissue fluids and also within macrophages, we examined the possible effect of this factor on phosphatidylserine (PS) exposure on amastigotes, seen previously in tissue-derived amastigotes leading to increased parasitism. Stimulation with IGF-I induced PS exposure on amastigotes but not on promastigotes. Using a PS-liposome instead of amastigotes, we observed that the PS-liposome but not the control phosphatidylcholine-liposome led to increased arginase activity in macrophages, and this process was not blocked by anti-TGF-β antibodies. Our results suggest that in L. (L.) amazonensis amastigote-infected macrophages, IGF-I induces arginase activity directly in amastigotes and in macrophages through the induction of PS exposure on amastigotes in the latter, which could lead to the alternative activation of macrophages through cytokine-independent mechanisms.


Ototoxic potential of JP-8 and a Fischer-Tropsch synthetic jet fuel following subacute inhalation exposure in rats.
This study was undertaken to identify the ototoxic potential of two jet fuels presented alone and in combination with noise. Rats were exposed via a subacute inhalation paradigm to JP-8 jet fuel, a kerosene-based fuel refined from petroleum, and a synthetic fuel produced by the Fischer-Tropsch (FT) process. Although JP-8 contains small ( approximately 5%) concentrations of aromatic hydrocarbons some of which known to be ototoxic, the synthetic fuel does not. The objectives of this study were to identify a lowest observed adverse effect level and a no observed adverse effect level for each jet fuel and to provide some preliminary, but admittedly, indirect evidence concerning the possible role of the aromatic hydrocarbon component of petroleum-based jet fuel on hearing. Rats (n = 5-19) received inhalation exposure to JP-8 or to FT fuel for 4 h/day on five consecutive days at doses of 500, 1000, and 2000 mg/m(3). Additional groups were exposed to various fuel concentrations followed by 1 h of an octave band of noise, noise alone, or no exposure to fuel or noise. Significant dose-related impairment in the distortion product otoacoustic emissions (DPOAE) was seen in subjects exposed to combined JP-8 plus noise exposure when JP-8 levels of at least 1000 mg/m(3) were presented. No noticeable impairment was observed at JP-8 levels of 500 mg/m(3) + noise. In contrast to the effects of JP-8 on noise-induced hearing loss, FT exposure had no effect by itself or in combination with noise exposure even at the highest exposure level tested. Despite an observed loss in DPOAE amplitude seen only when JP-8 and noise were combined, there was no loss in auditory threshold or increase in hair cell loss in any exposure group.


Thyrotropin-secreting pituitary adenoma responsive to bromocriptine therapy.
To describe a case of a thyrotropin-secreting pituitary adenoma that responded to bromocriptine therapy by suppression of thyrotropin and tumor shrinkage. We present the clinical course, laboratory data, and radiographic findings in a 32-year-old woman with a thyrotropin-secreting pituitary adenoma before and after treatment with bromocriptine. The patient's pituitary tumor was detected after she had been treated with radioactive iodine for thyrotoxicosis presumed to be due to Graves' disease. After thyroid ablation, the thyrotropin levels could not be brought into the normal range, even while the patient was receiving supraphysiologic doses of orally administered levothyroxine. Magnetic resonance imaging of the pituitary, along with hormonal workup, confirmed the diagnosis of a thyrotropin-secreting pituitary adenoma. Because the tumor was not threatening vital structures and was considered incurable by operation, medical therapy was elected. A trial of bromocriptine was initiated at 15 mg/day and increased to 30 mg/day in three divided doses. Follow-up hormonal studies showed that thyrotropin levels declined into the suppressed range, and repeated magnetic resonance imaging scans showed substantial shrinkage of the pituitary lesion. Thyrotropin-secreting tumors may respond hormonally and structurally to bromocriptine therapy. In patients with such tumors, a trial of dopamine agonists at high dose may be considered before initiation of more invasive medical treatment.


[Natural rewarding and drug rewarding].
In the brain of animals and humans there is a rewarding mechanism to encourage the behavior that is beneficial for the living of the individual and for the prolongation of the generation. However, when this system is being abused by drugs of addiction, chronic adaptive changes may occur that would cause serious damage to the organism. The neural substrate of the rewarding system is mainly based on the dopaminergic pathway, starting from the ventral tegmental area of the midbrain and ended in the nucleus accumbens of the limbic brain. This pathway serves both natural rewarding such as food and sex as well as drug rewarding such as heroin and cocaine. This paper is aimed to discuss the similarities and differences between the natural and drug-induced rewarding in an attempt to block the latter without affecting the former.


Accurately Shaping Supercontinuum Spectrum via Cascaded PCF.
Shaping is very necessary in order to obtain a wide and flat supercontinuum (SC). Via numerical simulations, we accurately demonstrated shaping the SC using the fiber cascading method to significantly increase the width as well as the flatness of the spectrum in silica photonic crystal fiber (PCF). The cascaded PCF contains two segments, each of which has dual zero-dispersion frequencies (ZDFs). The spectral range of the SC can be expanded tremendously by tuning the spacing between the two ZDFs of the first segmented cascaded PCF. Increasing the pump power generates more solitons at the red edge, which accelerates solitons trapping and improves the spectral flatness of the blue edge. Furthermore, cascading the second segmented PCF by choosing appropriate fiber parameters ensures the flatness of the red end of SC. Therefore, a cost-effective alternative method for broad and flat supercontinuum generation in the near-infrared range is proposed here, which can be implemented easily in any photonics laboratory, where dual ZDFs PCFs are commonly found.


[ORP in the Main Anoxic Stage as the Control Parameter for Nitrogen and Phosphorus Removal in the Single Sludge System with a Continuous Flow].
To optimize the performance of nitrogen and phosphorus removal, based on test results and mass balance, the feasibility of control for nitrogen and phosphorus removal in the single sludge system with a continuous flow using ORP in the main anoxic stage (ORPm) was investigated, meanwhile, the objective laws of conversion for nitrogen and phosphorus under different ORPm were expounded. During the experiments, nitration liquid internal circulation flow rate was controlled as the variable. The OPRm was controlled by PLC automatically, and the other operation parameters remained unchanged. The experiments tested six different ORPs in main anoxic stage affecting nitrogen and phosphorus removal, i.e., -143, -123, -105, -95, -72, and -57 mV. The ammonia concentration changed a little in effluent under the condition of different ORP.s, however, the TN and TP concentrations changed obviously. When the ORPm was controlled as -95 mV, the active sludge reached the maximal nitrogen and phosphorus removal with the continuous flow. According to mass balance calculation, when ORPm increased from -143 mV to -57 mV, (1) In the main anoxic stage, nitrate nitrogen reaction rates were 214. 40, 235. 16, 241. 16, 244. 02, 240. 90 and 233. 65 mg.h-1, respectively; the amount of total nitrogen conversions were 244. 92, 255. 85, 328. 04, 347. 45, 336. 42 and 320. 60 mg.h-1, respectively; both reaction rates reached the peak at the ORPm of -95 mV; (2)Phosphorus release rates in anaerobic stage were -214. 12, -228. 64, -259. 26, -264.54, -256.92 and -252.84 mg.h-1, respectively; total phosphorus absorption rates were 252. 15, 275.85, 332. 25, 338. 10, 336. 15 and 324. 30 mg.h-1, respectively, and phosphorus absorption rates were 30. 27, 62. 14, 124. 58, 154. 41, 150. 41 and 138. 30 mg.h-1, respectively, in the main anoxic stage; phosphorus absorption rates reached the peak when ORPm was -95 mV. The experiments revealed that ORPm could be used as the control parameter of nitrogen and phosphorus removal in single sludge system with a continuous flow.


p16 promoter hypermethylation is associated with increased risk of nasopharyngeal carcinoma.
The present study aimed to investigate the effects of p16 hypermethylation on the risk of nasopharyngeal carcinoma (NPC) quantitatively, through a meta-analysis of available case-control studies including malignant and normal NPC tissue samples. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between p16 hypermethylation and NPC risk. A total of 9 studies, including 406 NPC and 376 control cases, were identified for meta-analysis. Statistically significant ORs of p16 hypermethylation were obtained from the NPC and control groups (OR=19.53; 95% CI: 9.54-39.97; P=0.685). The meta-analysis indicated that p16 hypermethylation significantly increases NPC risk.


Hierarchically Porous N-Doped Carbon Nanotubes/Reduced Graphene Oxide Composite for Promoting Flavin-Based Interfacial Electron Transfer in Microbial Fuel Cells.
Interfacial electron transfer between an electroactive biofilm and an electrode is a crucial step for microbial fuel cells (MFCs) and other bio-electrochemical systems. Here, a hierarchically porous nitrogen-doped carbon nanotubes (CNTs)/reduced graphene oxide (rGO) composite with polyaniline as the nitrogen source has been developed for the MFC anode. This composite possesses a nitrogen atom-doped surface for improved flavin redox reaction and a three-dimensional hierarchically porous structure for rich bacterial biofilm growth. The maximum power density achieved with the N-CNTs/rGO anode in S. putrefaciens CN32 MFCs is 1137 mW m-2, which is 8.9 times compared with that of the carbon cloth anode and also higher than those of N-CNTs (731.17 mW m-2), N-rGO (442.26 mW m-2), and the CNTs/rGO (779.9 mW m-2) composite without nitrogen doping. The greatly improved bio-electrocatalysis could be attributed to the enhanced adsorption of flavins on the N-doped surface and the high density of biofilm adhesion for fast interfacial electron transfer. This work reveals a synergistic effect from pore structure tailoring and surface chemistry designing to boost both the bio- and electrocatalysis in MFCs, which also provide insights for the bioelectrode design in other bio-electrochemical systems.


[Intracranial atherosclerosis].
Until recently, intracranial atheromatosis was a probably underdiagnosed clinicopathological entity that was rarely studied in depth. In the last years the advance and expansion in the use of non-invasive diagnostic tools have led intracranial atheromatosis to the front page among the most prevalent causes of stroke worldwide. Important efforts have been accomplished with the aim of identifying markers of poor outcome, which, besides the underlying mechanisms of cerebral ischemia in these patients, are the most important factors on which clinical and therapeutic decisions should be based. To date, the therapeutic armamentarium is scarce and far from optimun, regarding medical and endovascular measures. In this review we address the most important aspects of the natural history and cure treatment of intracranial atheromatosis.


Neurobehavioral effects of antihypertensive medications.
Although millions of hypertensive individuals receive chronic treatment with antihypertensive medication, the effect on the central nervous system by these drugs is poorly understood. Such treatment, while generally well tolerated, frequently produces symptoms of drowsiness, weakness, altered memory and impaired concentration. In addition to subjective evidence derived from patient reports, a large number of investigations have now been published which attempt to objectively assess the influence of antihypertensive medication on behavioral or cognitive performance. This paper summarizes and critically evaluates experimental studies of the effect of antihypertensive medication on subjects' performance of neuropsychological tasks and reviews the pharmacologic mechanisms by which these drugs may affect behavior. The literature is incomplete in its assessment of all domains of neuropsychological performance and all drug classes, and methodologic deficiencies are common. Nonetheless, the consensus of all studies and the findings of well-designed studies in particular do not identify any notable areas of performance impairment in patients receiving antihypertensive medication. Moreover, results suggest that, in certain instances, drug treatment may even enhance performance. In light of the limitations of the literature, however, an adequate understanding of the effects of antihypertensive therapy on behavioral functioning awaits completion of large, well-designed investigations including all major drug classes and thorough neurobehavioral assessments.


Increased risks of venous thromboembolism in patients with psoriasis. A Nationwide Cohort Study.
Systemic inflammation and hypercoagulability in psoriasis are related to cardiovascular morbidity. The aim of the study was to investigate the incidence and risk of venous thromboembolism (VTE) in patients with psoriasis in Taiwan. We identified inpatients aged ≥ 18 years with a diagnosis of psoriasis and controls at a 1: 1 ratio of frequency matched by sex, age, frequency of medical visits, length of stay, and comorbidities between 2000 and 2010 in the Taiwan National Health Insurance Research Database. Each patient was traced to the date of VTE occurrence, loss to follow-up, death, or the December 31, 2011, whichever occurred first. We analysed 8945 patients with psoriasis and 8945 controls. The patients with psoriasis exhibited a greater incidence rate of VTE (19.2 vs 9.88 per 10 000 person-years) than did the controls. After adjustment for covariates, the patients with psoriasis presented a 2.02-fold risk of VTE (adjusted hazard ratio [aHR] = 2.02, 95 % confidence interval [CI] = 1.42-2.88) compared with that in the control cohort. The aHR of VTE was significantly higher in the first year of follow-up (aHR = 3.30, 95 % CI = 1.45-7.55) than after one year (aHR = 1.68, 95 % CI = 1.13-2.49).


Oxidative stress in heart failure: what are we missing?
Over the past several decades, investigations in humans and animal models of heart failure (HF) have provided substantial evidence that oxidative stress is increased in HF and contributes to disease progression. The high metabolic activity of cardiac myocytes makes these cells active sources of reactive oxygen species. Work in cell and animal models clearly demonstrates that oxidative stress activates processes such as changes in gene expression and cell death that are now accepted components of myocardial remodeling and HF. Antioxidants prevent progressive remodeling and even improve cardiac function in animal models of HF. It is therefore disappointing that to date no antioxidant strategy has translated to a therapeutic in the HF clinic. Possible explanations, including inadequate appreciation of the critical disease-modifying sources of reactive oxygen species, the choice of the wrong antioxidant strategy, or incomplete understanding of individual variability in human antioxidant defenses in this brief review.


[Construction and analysis of gene expression profiles in the testes of patients with unilateral cryptorchidism using cDNA gene chips].
To analyze the differentially expressed genes in the testicular tissues of men with unilateral cryptorchidism using cDNA gene chips. Probes were prepared with the mRNA extracted from the testes of 6 patients with unilateral cryptorchidism and 3 normal fertile men. Then the differential gene expression profiles of the two groups were detected with cDNA gene chips containing 45 034 genes. The differentially expressed genes were analyzed with Pathway and GO in the MAS system. Based on the ratio of > 3.0 or < 0.33, 346 differentially expressed genes were detected in the testis tissues of the patients with unilateral cryptorchidism, among which 60 were up-regulated and 286 down-regulated. The up-regulated genes were distributed mainly on chromosomes 1, 15, 5 and 19, associated with cell cycles, sperm motility, flagellar movement, DNA replication, and chromatin modification, while the down-regulated genes, mainly on chromosomes 1, 19, 16 and 11, related with spermatogenesis and anti-apoptosis. Unilateral cryptorchidism involves the variation of the expressions of multifunctional genes. The establishment of gene expression profiles of unilateral cryptorchidism in human testes may provide a new theoretical basis for analyzing the genetic factors of unilateral cryptorchidism and investigating the etiology of spermatogenic failure.


Determination of Ultralow Level 135Cs and 135Cs/137Cs Ratio in Environmental Samples by Chemical Separation and Triple Quadrupole ICP-MS.
An analytical method was developed for the determination of ultralow level 135Cs in environmental samples by chromatographic separation of cesium with AMP-PAN and AG50W-X8 columns and sensitive measurement of cesium isotopes with triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS/MS). Cesium was simply released by acid leaching using aqua regia from environmental solid samples and preconcentrated on AMP-PAN column. The cesium adsorbed on the column was effectively eluted with NH4Cl solution without dissolving the AMP. The excessive amount of NH4Cl in the eluate was removed by sublimation in the presence of small amount of LiCl. The remaining barium and other interfering elements such as Mo, Sn, Sb, and Li were efficiently removed using cation exchange chromatography (AG50W-X8). The decontamination factors of this procedure are above 4 × 107 for barium and 4 × 105 for molybdenum; the chemical yields of cesium are more than 85% for samples of less than 10 g. This method enables to separate cesium from large size of samples for the determination of ultralow level 135Cs, avoiding the problem of removal of a huge amount of Mo in the dissolved AMP. Intrinsic 137Cs in the environmental samples measured by gamma spectrometry before and after separation was used as internal isotope dilution standard for quantitative determination of 135Cs without complete release and recover of radiocesium. The interference of barium (135Ba and 137Ba) to the ICP-MS measurement of 135Cs and 137Cs was further suppressed to 8 × 10-5 by using N2O as the reaction gas in ICP-MS/MS at a flow rate of 0.7 mL/min, so a total suppression of 2 × 10-12 for Ba was achieved, making the isobaric interference of Ba isotopes to the measurement of 135Cs and 137Cs in environmental samples negligible. A detection limit of 9.1 × 10-17 g/g for 135Cs and 137Cs was achieved for 60 g samples. The developed method was validated by analysis of standard reference materials (IAEA-375, IAEA-330, and IAEA-385) and successfully applied for the determination of 135Cs concentrations and 135Cs/137Cs ratios in soil samples collected from Denmark, Sweden, and Ukraine. The 135Cs/137Cs isotopic ratios in Danish soil (2.08-2.68) were significantly higher than that from Sweden and Ukraine (0.65-0.71), indicating different sources of radiocesium. This work demonstrated the application of 135Cs/137Cs as a unique fingerprint for discriminating the sources of radioactive contamination and estimating their contribution to the total inventory, which will be useful for nuclear forensics and environmental tracer studies.


Mammalian GADD34, an apoptosis- and DNA damage-inducible gene.
The mammalian cellular response to genotoxic stress is a complex process involving many known and probably many as yet unknown genes. Induction of the human DNA damage- and growth arrest-inducible gene, GADD34, by ionizing radiation was only seen in certain cell lines and correlated with apoptosis following ionizing radiation. In addition, the kinetics and dose response of GADD34 to ionizing radiation closely paralleled that of the apoptosis inhibitor, BAX. However, unlike BAX, the GADD34 response was independent of cellular p53 status. The carboxyl terminus of GADD34 has homology with the carboxyl termini of two viral proteins, one of which is known to prevent apoptosis of virus infected cells. The association of GADD34 expression with certain types of apoptosis and its homology with a known apoptosis regulator suggests that GADD34 may play a role in apoptosis as well.


Design and Fabrication of a Sandwichlike Zn/Cu/Al-Zr Coating for Superior Anticorrosive Protection Performance of ZM5 Mg Alloy.
A new three-layered film was fabricated on magnesium (Mg) alloy via electroplating to guard against corrosion in a chloride aqueous environment, which consisted of an underlying double-layered zinc/copper (Zn/Cu) and a top aluminum-zirconium (Al-Zr) layer. The Zn/Cu underlayers not only impeded the galvanic corrosion between the Al-Zr coating and Mg alloy but also improved the adhesive ability between the substrate and the upper Al-Zr layer. Herein, we discussed the nucleus sizes of Al-Zr coatings at the stage of nucleation carried out with different contents of ZrCl4 in AlCl3-1-butyl-3-methylimidazolium chloride ionic liquid. The sandwichlike three-layered Zn/Cu/Al-Zr coatings were systematically investigated by surface morphology, phase structure, hardness, anticorrosion performances, and first-principles calculations. The corrosion current density declined from 1.461 × 10-3 A·cm-2 of bare Mg to 4.140 × 10-7 A·cm-2 of the Zn/Cu/Al-Zr3 sample. Neutral salt spray testing demonstrated that the Zn/Cu/Al-Zr3 sample showed no evident signs of corrosion after 6 days of exposure. The enhancement of the corrosion protection property was related to the fact that the application of the Cu layer changed the corrosion direction from initial longitudinal corrosion to extended lateral corrosion and the top Al-Zr coating hindered the transmission of aggressive ions. In addition, upon increasing the Zr content in the alloy films, the Fermi energy reduced initially and then increased. The Al-Zr3 alloy with 8.3 atom % Zr showed the lowest Fermi energy (-3.0823 eV), which exhibited the most efficient corrosion protection. These results showed that the prepared three-layered coating provided reliable corrosion protection to Mg alloy and may thus promote its practical applications.


Nickel(II) cyclidenes with appended ethylpyridine receptor centers as molecular tweezers for dicarboxylic acids.
A series of 14-, 15-, and 16-membered nickel(II) cyclidene macrocycles appended with 2-aminoethyl(2-pyridine) receptors I-III, respectively, were prepared and characterized by X-ray crystallography and NMR techniques. The 14- and 15-membered macrocycles I and II exist in a planar or extended Z-configuration, whereas the 16-membered macrocycle III was saddle shaped and had two asymmetric configurations in the unit cell (IIIa in a "capped" configuration and IIIb in an "open" configuration). Variable-temperature (1)H NMR studies of III in CD(3)CN were conducted (25-65 degrees C), and at room temperature, the interconversion between capping and uncapping is slow on the NMR time scale, resulting in a broad spectrum, whereas at 65 degrees C, interconversion was fast. (1)H NMR binding studies indicated I-III bind unsaturated dicarboxylic acids in a 1:1 stoichiometry with binding constants approaching 400 M(-)(1) in CD(3)CN, and the binding strength was dependent on the shape of the macrocyclic cyclidene platforms, whereas monocarboxylic acids were not bound. Generally, the planar 14-membered cyclidene I bound diacids the weakest and the 16-membered cyclidene III bound diacids the strongest. The presence of nuclear Overhauser effect spectrometry cross peaks in a 20 mM solution of 1:1 II-maleic acid indicates that the binding mode is ditopic with the guest being encapsulated by the aminoethylpyridine arms above the macrocyclic framework.


Empirical Equations to Predict the Characteristics of Hyporheic Exchange in a Pool-Riffle Sequence.
The hyporheic zone is the saturated interstitial space surrounding a stream. Water actively moves into, through, and out of the hyporheic zone, resulting in hyporheic exchange (HE), which is crucial to the physicochemical and biological processes in these systems. The HE in pool-riffle sequences is one of the most common forms of HE and has received a vast amount of attention. This study aimed to derive empirical equations to predict the scale, median residence time (RT), and flux of HE in a single pool-riffle sequence by considering stream discharge, bedform geometry, streambed hydraulic conductivity, and groundwater flow. The resulting equations, which were derived using previously published data, allow quick approximations of the mean depth, median RT, and flux of HE in a single pool-riffle sequence. Therefore, these equations can be used to conveniently and efficiently generate insights into the physicochemical and biological processes, facilitating the prediction of water quality and the restoration of HE in stream rehabilitation. The overall framework of the derived equations is also generally applicable to considering HE with additional influential factors (e.g., stream width, sinuosity, bed slope, alluvial depth) and cases with more available data.


Extranodal anaplastic large cell lymphoma mimicking sarcoma: A report of an interesting case.
Lymphomas are malignancies of the lymphoid tissues involving cells of the immune system. Primary systemic anaplastic large cell lymphoma (ALCL) represents an aggressive lymphoma characterized by neoplastic proliferation of lymphoid cells with an anaplastic appearance. Large pleomorphic cells are "hallmark" cells with horseshoe-shaped or kidney-shaped nuclei and a constant expression of the CD30 molecule on all neoplastic cells. There is a vast morphological spectrum posing a challenge to pathologists in the diagnosis of ALCL.


Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia.
Barrett's oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett's oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett's oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett's metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett's metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett's metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett's metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett's metaplasia.


Group I metabotropic glutamate receptors bind to protein phosphatase 1C. Mapping and modeling of interacting sequences.
The modulation of neurotransmitter receptors by kinases and phosphatases represents a key mechanism in controlling synaptic signal transduction. However, molecular determinants involved in the specific targeting and interactions of these enzymes are largely unknown. Here, we identified both catalytic gamma-isoforms of protein phosphatase 1C (PP1gamma1 and PP1gamma2) as binding partners of the group I metabotropic glutamate receptors type 1a, 5a, and 5b in yeast cells and pull-down assays, using recombinant and native protein preparations. The tissue distribution of interacting proteins was compared, and protein phosphatase 1C was detected in dendrites of retinal bipolar cells expressing the respective interacting glutamate receptors. We mapped interacting domains within binding partners and identified five amino acids in the intracellular C termini of the metabotropic glutamate receptors type 1a, 5a, 5b, and 7b being both necessary and sufficient to bind protein phosphatase 1C. Furthermore, we show a dose-dependent competition of these C termini in binding the enzyme. Based on our data, we investigated the structure of the identified amino acids bound to protein phosphatase 1C by homology-based molecular modeling. In summary, these results provide a molecular description of the interaction between protein phosphatase 1C and metabotropic glutamate receptors and thereby increase our understanding of glutamatergic signal transduction.


Does external pleural suction reduce prolonged air leak after lung resection? Results from the AirINTrial after 500 randomized cases.
External pleural suction is used after lung resection to promote lung expansion and minimize air leak duration. Published randomized trials failed to prove this advantage but they are limited in number and underpowered in many cases. The aim of the AirINTrial study was to test the hypothesis that external pleural suction may reduce the rate of prolonged air leak in a large, randomized cohort. All candidates for lung resection (with the exception of pneumonectomy) were considered eligible for this single-center study. At the end of operation, patients were stratified by the type of resection (anatomic versus nonanatomic) and randomly allocated into the external suction arm (-15 cmH2O, group A) or into the no external suction arm (control arm, group B) in a 1:1 ratio. Chest drains were maintained for 3 days and then they were either removed or connected to an Heimlich valve, when an air leak was present. The main endpoint was to compare groups in terms of prolonged air leak (defined as the rate of patients having a chest drain still in place by postoperative day 7). Starting on February 2011, 500 patients were randomized over a 21-month period, 250 in group A and 250 in group B. Twenty-one patients in group B (8.4%) required pleural suction owing to large pneumothorax or diffuse subcutaneous emphysema. On postoperative day 7, the chest drain was still in place in 25 patients in group A and in 34 patients in group B (10% and 14%, respectively; p = 0.2). Subgroup analysis showed that external pleural suction reduced the prolonged air leak rate in the subgroup of patients who underwent anatomic resection (n = 296, 9.6% in group A and 16.8% in group B; p = 0.05). Results from the AirINTrial showed that the routine use of external suction reduces the rate of prolonged air leak after anatomic lung resection. More accurate strategies of pleural suction based on the amount of air flow and the degree of lung expansion should be probably established to improve its effectiveness.


[Polycystic ovarian syndrome and diabetes].
Polycystic ovary syndrome is the most common endocrine condition in women of fertile age. The syndrome is associated with insulin resistance, hyperinsulinaemia and diabetes. This paper reviews the association between polycystic ovary syndrome and diabetes; implications for clinical practice are suggested. The review is based on Medline searches, our own studies, and clinical experience. Polycystic ovary syndrome is present in one third of women with type 1 diabetes and in almost half of all women with type 2 diabetes. In women with polycystic ovary syndrome, the prevalence of type 2 diabetes is considerably increased and gestational diabetes may occur in as many as 40%. In women with previous gestational diabetes, the risk of type 2 diabetes as well as polycystic ovarian syndrome is increased. Women with polycystic ovary syndrome are at increased risk of developing type 2 diabetes and gestational diabetes and should be followed up accordingly. Pregnant women with polycystic ovary syndrome should have an oral glucose tolerance test as soon as the pregnancy has been confirmed. The procedure should be repeated at gestational weeks 20 and 32. Treatment with metformin should be initiated in women with type 2 diabetes who want to conceive. For the same reason metformin may also be initiated in women with type 1 diabetes.


Part of purified human plasma kallikrein removed together with a remaining IgG fraction--immunoblot experiments and functional tests.
In the present study it is shown that a preparation of highly purified plasma kallikrein (specific activity 81 S-2302 U/mg) still contained small amounts of an IgG fraction. Amidase assays of the fresh enzyme with four peptide substrates (S-2302, Bz-Pro-Phe-Arg-pNA, S-2366, S-2222) did not reveal any inhomogeneity, and immunoblot experiments with antibodies against prekallikrein yielded only an 85 kD double band. After a storage period (2 years at -70 degrees C), S-2366 and S-2222 amidase activities not reflecting the initial kallikrein appeared. Immunoblot studies with Fc-specific antibodies against IgG showed a 170 kD band, and immunoblots with a monoclonal antibody against prekallikrein demonstrated that, in addition to the 85 kD band, a band with a mol weight of about 152 kD could also be detected. Immunoblots showed that only 85 kD kallikrein was recovered in the eluate from Protein G columns, and amidase assays based on S-2302 and Bz-Pro-Phe-Arg-pNA showed a recovery of about 70%. The other part of the kallikrein (30%) was removed along with the additional S-2366 and S-2222 activities and the IgG3 fraction present. The theory is advanced that the additional activity reflects a kallikrein fraction with a mol weight of about 152 kD, and is present in the fresh enzyme preparation in inactive complex with IgG. Storage of the kallikrein preparation led to some weakening of this complex and the appearance of functional activities of the kallikrein fraction involved.