Endoscopic palliation of esophageal cancer.
Endoscopic palliation is the most suitable approach to improve quality of life in patients with esophageal cancer since diagnosis is often made at an advanced stage, when radical treatment is unfeasible. Endoscopy offers several techniques to palliate dysphagia either by stenting the stenosis or by reducing the tumor mass with thermoablation. A small number of randomized controlled trials is available to compare the efficacy of different techniques and the ideal palliation has not been defined as yet. Recently, the development of self-expandable covered metal stents has rapidly gained ground in the endoscopy units throughout the world as a simple, single step procedure for palliation of dysphagia.


A new chromogenic amylase method compared with two established methods.
We tested a new amylase reagent involving chromogenic substrates (Pantrak, Calbiochem-Behring) for precision, dynamic range, and susceptibility to potential interferences. Two p-nitrophenyl-alpha-maltaosides are used as substrates, which amylase cleaves to shorter-chain p-nitrophenyl maltaosides, the latter then yielding p-nitrophenol from the activity of alpha-glucosidase. A series of 100 specimens were tested by Pantrak and two established methodologies. In both cases, correlation was excellent. Precision was good for all methods; CVs for Pantrak were 3.0 to 4.5%. The dynamic range of Pantrak extended to 800 U/L. Above-normal quantities of triglyceride, hemoglobin, or bilirubin did not cause spurious results, but anticoagulants that bind divalent cations should not be used. The Pantrak method has desirable analytical features and is easy to use.


Total synthesis of the alkaloids martinelline and martinellic acid via a hetero Diels-Alder multicomponent coupling reaction.
[reaction: see text] A concise synthesis of the guanidine alkaloids, (+/-)-martinelline and (+/-)-martinellic acid, using a protic acid catalyzed 2:1 hetero Diels-Alder coupling reaction between N-Cbz 2-pyrroline and methyl 4-aminobenzoate, is described. Protic acid catalysis, rather than Lewis acid catalysis, was necessary to achieve the desired sense of diastereocontrol in the coupling reaction.


Vector competence of two Indian populations of Culex quinquefasciatus (Diptera: Culicidae) mosquitoes to three West Nile virus strains.
Culex quinquefasciatus is one of the principal vectors of West Nile virus (WNV). The mosquito also acts as a bridge vector as it feeds on both birds and humans. In the background of the recent reports of WNV activity in Kerala and Assam with fatalities, a study was initiated to determine the growth kinetics and transmission mechanisms of three strains of WNV in two populations of Cx. quinquefasciatus. Mosquitoes were infected by oral feeding and growth on different post-infection days was determined with the three strains. Horizontal transmission was determined by confirming sickness and mortality in infant mice after infected mosquito bite. F1 generation eggs, larvae, pupae and adults of experimentally infected mosquitoes were screened for WNV to determine vertical (transovarial) transmission. Trans-stadial transmission was determined by detecting WNV in adult mosquitoes emerged from infected larvae. Both the mosquito populations replicated and maintained WNV for a prolonged period with high titers (≥ 5log10 PFU/ml). WNV could be detected in saliva from Days 2 to 32 post-infection. Horizontal transmission by both the populations could be established but no vertical transmission was observed. However, parenterally infected larvae transmitted WNV to adults. WNV has been isolated from >10 mosquito species from India, however, vector competence of none of the species has been studied. The present study demonstrates efficient transmission of WNV by Cx. quinquefasciatus mosquitoes. With its country wide prevalence and high vector competence, the mosquitoes could create grave consequences especially when virulent strains with potential to cause acute flaccid paralysis and death are circulating.


The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters (223)Ra, (188)Re, and (99m)Tc.
DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by (223)Ra compared to (188)Re and (99m)Tc modulated by the radical scavenger dimethyl sulfoxide (DMSO). Radioactive solutions of (223)Ra, (188)Re, or (99m)Tc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay. Exposure to 120 Gy of (223)Ra, (188)Re, or (99m)Tc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy (223)Ra and 500 Gy (188)Re or (99m)Tc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the α-emitter (223)Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with (223)Ra, (188)Re, and (99m)Tc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 ± 0.04, 1.20 ± 0.19, and 1.34 ± 0.05 for (223)Ra, (188)Re, and (99m)Tc, respectively. For (223)Ra, as well as for (188)Re and (99m)Tc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the α-particle induced DNA damage.


[So-called nephrogenic adenoma (adenomatous metaplasia). A rare tumorous adenopapillary lesion of the urothelium in the urinary bladder in a 6-year-old boy following injury].
A 6-year-old boy developed an extensive adenopapillary proliferation of the urothelium of the urinary bladder--a nephrogenic adenoma (adenomatous metaplasia)--2 years after he had been injured in an accident, which was followed by operation and medical treatment. Histologically this lesion is characteristic. Like other epithelial tumors of the urinary tract, it is very rarely found in children. A dysontogenetic or metaplastic pathogenesis has been suggested. Once more is known about them, adenomas may be diagnosed more often. The clinical picture and therapy are briefly discussed and a review of the literature is given.


Important agronomic characteristics of yielding ability in common buckwheat; ecotype and ecological differentiation, preharvest sprouting resistance, shattering resistance, and lodging resistance.
Common buckwheat is recognized as a healthy food because its seed contains large amounts of protein, minerals, and rutin. However, the yielding ability of common buckwheat is lower than that of other major crops. The short growing period, moisture injury, occurrence of sterile seeds due to lack of flower-visiting insects, and yield loss due to lodging and shattering cause low and unstable grain yield. Therefore, many common buckwheat breeders have tried to increase yielding ability by improving various characteristics. Recently, new breeding objectives for improving yielding ability by increasing preharvest sprouting resistance; reducing shattering loss; introducing self-compatibility; the ecotype, and semidwarf have been reported. In this review, we introduce the research on the important agronomic characteristics, preharvest sprouting resistance, ecotype and ecological differentiation, shattering resistance, and lodging resistance in common buckwheat.


CXCL5 Plays a Promoting Role in Osteosarcoma Cell Migration and Invasion in Autocrine- and Paracrine-Dependent Manners.
CXCL5, a CXC-type chemokine, is an important attractant for granulocytic immune cells by binding to its receptor CXCR2. Recently, CXCL5/CXCR2 has been found to play an oncogenic role in many human cancers. However, the exact role of CXCL5 in osteosarcoma cell migration and invasion has not been revealed. Here we found that the protein expression of CXCL5 was significantly increased in osteosarcoma tissues compared with that in matched adjacent nontumor tissues. Moreover, the expression of CXCL5 was significantly associated with advanced clinical stage and metastasis. Further investigation showed that the CXCL5 expression levels were also significantly increased in osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared with those in normal osteoblast hFoB1.19 cells. U2OS cells were further transfected with CXCL5-specific siRNA or overexpression plasmid. Knockdown of CXCL5 significantly suppressed U2OS cell migration and invasion. On the contrary, overexpression of CXLC5 remarkably promoted the migration and invasion of U2OS cells. Interestingly, both exogenous CXCL5 treatment and the conditioned medium of CXCL5-overexpressing hFoB1.19 cells could also enhance the migration and invasion of U2OS cells, suggesting that the promoting role of CXCL5 in U2OS cell migration and invasion is also in a paracrine-dependent manner. According to these data, our study demonstrates that CXCL5 is upregulated in osteosarcoma and may play an oncogenic role in osteosarcoma metastasis. Therefore, CXCL5 may become a potential therapeutic target for osteosarcoma treatment.


Exogenous growth hormone inhibits growth hormone-releasing factor-induced growth hormone secretion in normal men.
Previous studies from this laboratory and by others in rats, monkeys, and humans support the concept that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism. With the availability of human growth hormone-releasing factor (GRF), the possible existence of such a mechanism was reexplored by examining the effect of exogenous GH on the GH response induced by GRF-44-NH2 in six normal men (mean age, 32.4 yr). In all subjects the plasma GH response evoked by GRF-44-NH2 (1 microgram/kg i.v. bolus) was studied before and after 5 d of placebo (1 ml normal saline i.m. every 12 h), and then before and 12 h after 5 d of biosynthetic methionyl human GH (5 U i.m. every 12 h). The GH response to GRF (maximal increment over time 0 value) was significantly inhibited after GH treatment (0-1.3 vs. 2.3-11.2 ng/ml before treatment, P = 0.05), but was not significantly affected by placebo. This impaired pituitary response to GRF persisted for at least 24 h following exogenous GH treatment in two subjects who underwent further study. Serum somatomedin-C concentrations were significantly increased after 5 d of GH treatment (2.66-5.00 vs. 0.92-1.91 U/ml before treatment, P = less than 0.01). The impaired pituitary response to GRF may be mediated indirectly through somatomedin, somatostatin, by a direct effect of GH on the pituitary somatotropes, or by all of these mechanisms. These data suggest that after GH treatment, the blunted GH response to synthetic GRF is not solely a consequence of the inhibition of hypothalamic GRF secretion.


Running and Osteoarthritis: Does Recreational or Competitive Running Increase the Risk?
Exercise, like running, is good for overall health and, specifically, our hearts, lungs, muscles, bones, and brains. However, some people are concerned about the impact of running on longterm joint health. Does running lead to higher rates of arthritis in knees and hips? While many researchers find that running protects bone health, others are concerned that this exercise poses a high risk for age-related changes to hips and knees. A study published in the June 2017 issue of JOSPT suggests that the difference in these outcomes depends on the frequency and intensity of running. J Orthop Sports Phys Ther 2017;47(6):391. doi:10.2519/jospt.2017.0505.


Patterns of Herbivory in Neotropical Forest Katydids as Revealed by DNA Barcoding of Digestive Tract Contents.
Many well-studied animal species use conspicuous, repetitive signals that attract both mates and predators. Orthopterans (crickets, katydids, and grasshoppers) are renowned for their acoustic signals. In Neotropical forests, however, many katydid species produce extremely short signals, totaling only a few seconds of sound per night, likely in response to predation by acoustically orienting predators. The rare signals of these katydid species raises the question of how they find conspecific mates in a structurally complex rainforest. While acoustic mechanisms, such as duetting, likely facilitate mate finding, we test the hypothesis that mate finding is further facilitated by colocalization on particular host plant species. DNA barcoding allows us to identify recently consumed plants from katydid stomach contents. We use DNA barcoding to test the prediction that katydids of the same species will have closely related plant species in their stomach. We do not find evidence for dietary specialization. Instead, katydids consumed a wide mix of plants within and across the flowering plants (27 species in 22 genera, 16 families, and 12 orders) with particular representation in the orders Fabales and Laurales. Some evidence indicates that katydids may gather on plants during a narrow window of rapid leaf out, but additional investigations are required to determine whether katydid mate finding is facilitated by gathering at transient food resources.


Compressor/nebulizers differences in the nebulization of corticosteroids. The CODE study (Corticosteroids and Devices Efficiency).
Nebulization is a common method of medical aerosol generation and it is largely used by adults and children all over the world, both for emergency treatment of acute illness and for long-term home treatment of lung diseases. The aim of this study was to determine the differences in nebulization of inhaled corticosteroids among four representative types of compressor/nebulizers. Twelve compressor/jet nebulizers from four commercial sources were studied (three for each type): Clenny (MEDEL), Turbo Boy/LC Plus (PARI), Nebula Nuovo/MB5 (MARKOS MEFAR) and Maxaer (ARTSANA) compressor/Sidestream (Medic-Aid Ltd.) nebulizer. We compared the required time for the treatment (nebulization time), output/minutes, compressor pressures, and aerosol characteristics of inhaled corticosteroids: Beclomethasone dipropionate, Flunisolide, Fluticasone propionate and Budesonide. Nebulization Times showed a significant difference between nebulizer and inhaled corticosteroids for Clenny, Turbo Boy, and Maxaer. A considerable difference in the output of nebulized drugs was observed through the compressors/nebulizers. MMAD of all inhaled corticosteroids was significantly different among the four nebulizers. The percentage of particles <5 microm (respirable range) was high for all devices with beclomethasone and budesonide (> 90%), whereas with flunisolide was good only for Clenny (98.8%) and Maxaer (96.3%), and with fluticasone only for Clenny (98%), Turbo Boy (99.1%), and Maxaer (86%). Also percentage of particles <2 microm showed significant variability among the devices. Our results clearly demonstrate that compressor/nebulizer unit plays a key role in the effectiveness of the treatment during inhaled corticosteroid therapy, and that several differences exist in the performance of the different nebulizers studied. Therefore, the device has the same importance of the compound to reach the best clinical response in the inflammatory diseases of the lower airways.


[Dystrophin and utrophin expression in muscle tissues of DMD mouse model after transplantation treatment by bone marrow mesenchymal stem cells].
To observe dystrophin and utrophin expression in muscle tissues of Duchenne muscular dystrophy (DMD) mouse model (dko mouse) after having been treated with bone marrow mesenchymal stem cells (MSC) transplantation. The fifth generation of MSCs, cultured in vitro, was transplanted into dko mice by tail vein. The fluorescent expression of dystrophin and utrophin in gastrocnemius muscle tissue of dko mouse was detected and the average optical density of positive fibers was calculated. MSCs that had been cultured for three generations had good homogeneousness and the immunological reaction after vein transplantation was low. There was an increasing tendency of dystrophin and utrophin fluorescent expression in sarcolemma of dko mouse within 5-20 weeks. Significant difference existed in fluorescent average optical density of positive fibers fifteen weeks before and after cell transplantation. MSC has strong plasticity both in vitro and in vivo. MSC has a trend to reach the injured muscle tissues and turn into muscle fibers, which express dystrophin and utrophin. There is some plerosis function for myatrophy of dko mouse by MSC transplantation.


A randomized Phase III trial of weekly or 3-weekly doses of nab-paclitaxel versus weekly doses of Cremophor-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE Trial).
Paclitaxel is an agent widely used in second-line chemotherapy for advanced gastric cancer. The aim of this trial is to evaluate the efficacy and safety of 3-weekly or weekly doses of nanoparticle albumin-bound-paclitaxel compared with weekly doses of Cremophor-based paclitaxel in patients with unresectable or recurrent gastric cancer refractory to first-line chemotherapy comprising fluoropyrimidines. A total of 730 patients will be enrolled from 72 institutions. The primary endpoint is the overall survival, and the secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, quality of life (by using the EQ-5D system) and safety.


Long-range critical wetting: observation of a critical end point.
Alkanes deposited on aqueous substrates exhibit two different types of wetting behavior: alternatively to the usual first-order wetting transition, a sequential-wetting scenario of a long-range critical wetting transition preceded by a first-order thin-thick transition may be observed. Here, we present the first successful experimental attempt to locate the transition point between the standard first-order wetting and the long-range critical wetting: a critical end point, observed in a mixture of pentane and hexane which is deposited on an aqueous solution of glucose. Furthermore, we present the first direct measurement of the contact angle in the intermediate wetting state (frustrated-complete wetting) in the sequential-wetting scenario of hexane on brine and compare to theoretical predictions.


Expression of adenylyl cyclase type I in cochlear inner hair cells.
Expression of calcium/calmodulin-activated adenylyl cyclase type I (ACI) mRNA has been determined in the cochlea and in an organ-of-Corti subdissected tissue fraction by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Amplification products of predicted size were obtained from the mouse cochlea and rat organ of Corti with nucleotide sequences corresponding to respective ACI brain transcripts. In addition, ACI template was detected in a rat inner hair cell cDNA library by PCR. Immunoreactivity to ACI has been localized within the organ of Corti to the inner hair cell, with diaminobenzidine staining found in both the cell body and in the stereocilia. Evidence, thus, has been obtained that both ACI transcript and protein are expressed in the inner hair cell, the primary mechanosensory receptor cell of the cochlea. We hypothesize that ACI is activated by calcium influx through a calcium/calmodulin interaction and that this adenytyl cyclase isoform may have a role in modulation of receptoneural afferent transmission and/or mechanosensory transduction in the cochlea.


[Urinary cytodiagnostic abnormality in a patient with malignant lymphoma].
A 69-year-old man was admitted due to chronic subdural hematoma. He had lymphadenopathies in the neck. The diagnosis of non-Hodgkin lymphoma (diffuse, large, B cell type) was made by a cervical lymph node biopsy. The renal failure by obstruction of the urinary tract developed gradually, and the tumor cells were found by urinary cytodiagnosis. He was treated immediately with chemotherapy. After the treatment, the urine volume increased and the general conditions improved. It was indicated from this case that the urinary cytodiagnosis is useful for the detection of urinary tract infiltration by lymphoma cell. The urinary cytodiagnostic abnormalities in patients with non-Hodgkin lymphomas were discussed from the literature, including this case.


Green Process for Industrial Waste Transformation into Super-Oxidizing Materials Named Alkali Metal Ferrates (VI).
The investigation presented here features the design of a cleaner and greener chemical process for the conversion of industrial wastes into super-oxidizing materials. The waste of interest is the iron sulfate heptahydrate (FeSO4·7H2O) mainly generated through the sulfate route used for titanium dioxide industrial production. The products of this transformation process are alkali ferrates (A2FeO4, A = Na, K) containing iron in its hexavalent state and considered as powerful oxidants characterized by properties useful for cleaning waters, wastewaters, and industrial effluents. The proposed process includes two steps: (i) The first step consisting of the pre-mixing of two solids (AOH with FeSO4·xH2O) in a rotary reactor allowing the coating of iron sulfate in the alkali hydroxides through solid-solid reactions; and (ii) the second step involves the synthesis of alkali ferrates in a fluidized bed by oxidation of the single solid obtained in the first step in diluted chlorine. The chemical synthesis of alkali ferrates can be carried out within a timeframe of a few minutes. The usage of a fluidized bed enhanced the energy and mass transfer allowing a quasi-complete control of the ferrate synthesis process. The alkali ferrate synthesis process described here possesses many characteristics aligned with the principles of the "green chemistry".


Clinical significance of a positive serology for mimivirus in patients presenting a suspicion of ventilator-associated pneumonia.
A seroconversion to mimivirus has been observed in patients with community-acquired or nosocomial pneumonia. The aim of this study was to determine whether a positive serology for mimivirus was associated with increased morbidity and mortality in patients with a suspicion of ventilator-associated pneumonia (VAP). Prospective matched-cohort study. A 12-bed medical intensive care unit (ICU) in a teaching hospital. Patients ventilated for at least 2 days presenting with a suspicion of VAP. Patients with a positive serology for mimivirus were matched to seronegative patients. None. Matching criteria were: 1) the same main diagnosis on ICU admission, 2) the same age (+/- 10 yrs), 3) the same Simplified Acute Physiology II score (+/-10 points), 4) the same McCabe and Jackson comorbidity score, 5) admission within 1 year, and 6) diagnosis of at least one bacterial VAP during the ICU stay or not. A total of 55 pairs were submitted for analysis. The effectiveness of matching was 94.8%. Patients with a positive serology for mimivirus had longer duration of mechanical ventilation and ICU stay with median excesses of 7 days and 10 days, respectively. There was no difference in ICU mortality. The duration of mechanical ventilation before bronchoalveolar lavage (adjusted odds ratios [OR]1.08, p = 0.02), viral identification other than mimivirus during ICU stay (adjusted OR 0.32, p = 0.05), and enteral nutrition (adjusted OR 0.13, p = 0.01) were associated with positive serology for mimivirus. A positive serology for mimivirus is associated with a poorer outcome in mechanically ventilated ICU patients.


The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17beta-estradiol and hydroxytamoxifen in endometrial cancer cells.
The growth of both normal and transformed epithelial cells of the female reproductive system is stimulated by estrogens, mainly through the activation of estrogen receptor alpha (ERalpha), which is a ligand-regulated transcription factor. The selective ER modulator tamoxifen (TAM) has been widely used as an ER antagonist in breast tumor; however, long-term treatment is associated with an increased risk of endometrial cancer. To provide new insights into the potential mechanisms involved in the agonistic activity exerted by TAM in the uterus, we evaluated the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, to transactivate wild-type ERalpha and its splice variant expressed in Ishikawa and HEC1A endometrial tumor cells, respectively. OHT was able to antagonize only the activation of ERalpha by 17beta-estradiol (E2) in Ishikawa cells, whereas it up-regulated c-fos expression in a rapid manner similar to E2 and independently of ERalpha in both cell lines. This stimulation occurred through the G protein-coupled receptor named GPR30 and required Src-related and epidermal growth factor receptor tyrosine kinase activities, along with the activation of both ERK1/2 and phosphatidylinositol 3-kinase/AKT pathways. Most importantly, OHT, like E2, stimulated the proliferation of Ishikawa as well as HEC1A cells. Transfecting a GPR30 antisense expression vector in both endometrial cancer cell lines, OHT was no longer able to induce growth effects, whereas the proliferative response to E2 was completely abrogated only in HEC1A cells. Furthermore, in the presence of the inhibitors of MAPK and phosphatidylinositol 3-kinase pathways, PD 98059 and wortmannin, respectively, E2 and OHT did not elicit growth stimulation. Our data demonstrate a new mode of action of E2 and OHT in endometrial cancer cells, contributing to a better understanding of the molecular mechanisms involved in their uterine agonistic activity.


Achieving desirable charge transport by porous frame engineering for superior 3D printed rechargeable Ni-Zn alkaline batteries.
Rechargeable 3D printed batteries with extraordinary electrochemical potential are typical contenders as one of the promising energy storage systems. Low-cost, high-safety, and excellent rechargeable aqueous alkaline batteries have drawn extensive interest. But their practical applications are severely hampered by poor charge carrier transfer and limited electrochemical activity at high loading. Herein, we report a unique structure-based engineering strategy in 3D porous frames using a feasible 3D printing technique and achieve 3D printed full battery devices with outstanding electrochemical performance. By offering a 3D porous network to provide prominently stereoscopic support and optimize the pore structure of electrodes, the overall charge carrier transport of engineered 3D printed Ni-Zn alkaline batteries (E3DP-NZABs) is greatly enhanced, which is directly demonstrated through a single-wired characterization platform. The obtained E3DP-NZABs deliver a high areal capacity of 0.34 mA h cm-2 at 1.2 mA cm-2, and an outstanding capacity retention of 96.2% after 1500 cycles is also exhibited with an optimal electrode design. Particularly, parameter changes such as a decrease in pore sizes and an increase in 3D network thickness are favorable to resultant electrochemical performance. This work may represent a vital step to promote the practical application progress of alkaline batteries.


Purification of isocitrate lyase from Escherichia coli and watermelon using fast protein liquid chromatography.
The enzyme isocitrate lyase has been purified to gel electrophoretic homogeneity from Escherichia coli and watermelon. From cotyledons of the latter source, the enzyme is obtained in less than 8 hours after precipitation with (NH4)2 SO4 followed by fractionation on cationic Mono S microbeads and anionic Mono Q microbeads using Fast Protein Liquid Chromatography (FPLC). From a genetically engineered E. coli strain, in which high-level expression of isocitrate lyase occurs, the enzyme has been purified in one step from the high-speed supernatant using a Mono Q column with FPLC. These purifications, both of which give satisfactory yields, potentiate rapid access to isocitrate lyase from both prokaryotic and eukaryotic sources.


Listen to the heart or mind first? Examining sequential coping mechanisms among Indians during the COVID-19 pandemic.
The present study examines the mediating role of emotion-focused and problem-focused coping between stress and psychological well-being during the COVID-19 pandemic. The sample comprised 501 (312 women and 184 men aged between 18 and 42) Indians who experienced the first-ever continued lockdown in India during the COVID-19 pandemic. The results of this study confirmed the presence of perceived stress due to the lockdown and pandemic among participants. Furthermore, perceived stress, coping including emotion-focused and problem-focused, and psychological well-being were found to be interrelated. The serial mediation analysis revealed that participants dealt with stress by choosing emotion-focused coping first as an immediate resort. After a reappraisal of stress-inducing situations, they used problem-focused coping, and this sequence of constant coping mechanisms helped maintain their psychological well-being. The findings of this study can be applied to develop strategies for people's mental health by public health organizations and health professionals.


Dietary zinc treatment for chronic copper intoxication in palm kernel cake (PKC) fed sheep.
Thirty, 4 month-old male Maim x Polled Dorset crossbred sheep were allocated into 6 groups of 5 animals each. Four groups of animals were stall-fed with basal diet of 90% palm kernel cake (PKC) and 10% grass (G) for 16 weeks. One group of the animal was slaughtered at the end of the 16 weeks feeding trial (PKC group), whilst the other three groups were further fed with either the same diet (PKC+PKC group) or fed with a new diet consisting of 30% corn and 10% fish meals (CF) and grass (60%) either with (PKC+CF+Zn group) or without (PKC+CF group) zinc supplementation (500 mg/g Zn as zinc sulfate) for another 16 weeks and were slaughtered at the end of the feeding trial, The other two groups which act as controls were fed with corn (30%) and fish meals (10%) and grass (60%), and were slaughtered at weeks 16 (CF group) and 32 (CF+CF group) of the trial. The blood, right and left liver, renal cortex and medulla, pancreas, bile and urine of all animals were analysed for copper and zinc contents using an atomic absorption spectrophotometer. The liver and kidney were also fixed in 10% buffered formalin for histopathological examination. The study showed that neither clinical signs nor gross lesions of copper or zinc toxicity were observed throughout the trial. However, the copper concentration in both the right and left liver of PKC fed sheep at weeks 16 and 32 rose to about 3 times that of the controls and remained high in both the PKC+CF and PKC+CF+Zn groups. A similar pattern of copper concentration was observed in the blood. The copper and zinc contents in the renal cortex and medulla, pancreas, bile and urine remained low in all groups. The zinc content in the liver of PKC+CF+Zn group was significantly increased. Histologically, moderate hepatic lesions were observed in the PKC fed sheep at week 32. The lesions were milder in the other groups especially in the PKC+CF+Zn group. No significant renal lesions was recorded in all groups. It was concluded that the usage of dietary zinc supplementation (500 mg/g) in the treatment of PKC toxicity in sheep was unsatisfactory. The ability of Malin x Polled Dorset crossbred sheep to tolerate the high copper content in PKC at least during the first 16 weeks of the feeding trial may provide more avenue in the utilization of PKC as a major feed ingredient in sheep.


On the microscopic anatomy of periadventitial tissue of Cisterna chyli and Ductus thoracicus of the cat (Felix domestica).
Anatomical and histological techniques were adopted to study the structure of periadventitial tissue of Cisterna chyli and Ductus thoracicus of the cat. Basically this tissue is represented by a loose connective tissue, presenting a relatively large amount of unilocular adipocytes. Inside the periadventitial tissue there is a predominantly collagenous membrane and it seems to link the cisterna chyli and the ductus thoracicus to the adventitia of the Aorta.


Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells.
Different phenotypes of macrophages (M0, M1 and M2 Mφs) have been demonstrated to play distinct roles in regulating mesenchymal stem cells in various in vitro and in vivo systems. Our previous study also found that cell-conditioned medium (CM) derived from M1 Mφs supported the proliferation and adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), whereas CM derived from either M0 or M2 Mφs showed an enhanced effect on cell osteogenic differentiation. However, the underlying mechanism remains incompletely elucidated. Exosomes, as key components of Mφ-derived CM, have received increasing attention. Therefore, it is possible that exosomes may modulate the effect of Mφ-derived CM on the property of BMMSCs. This hypothesis was tested in the present study. In this study, RAW264.7 cells were induced toward M1 or M2 polarization with different cytokines, and exosomes were isolated from the unpolarized (M0) and polarized (M1 and M2) Mφs. Mouse BMMSCs were then cultured with normal complete medium or inductive medium supplemented with M0-Exos, M1-Exos or M2-Exos. Finally, the proliferation ability and the osteogenic, adipogenic and chondrogenic differentiation capacity of the BMMSCs were measured and analyzed. We found that only the medium containing M1-Exos, rather than M0-Exos or M2-Exos, supported cell proliferation and osteogenic and adipogenic differentiation. This was inconsistent with CM-based incubation. In addition, all three types of exosomes had a suppressive effect on chondrogenic differentiation. Although our data demonstrated that exosomes and CM derived from the same phenotype of Mφs didn't exert exactly the same cellular influences on the cocultured stem cells, it still confirmed the hypothesis that exosomes are key regulators during the modulation effect of Mφ-derived CM on BMMSC property.


Morphine in the treatment of acute pulmonary oedema--Why?
Morphine has for a long time, been used in patients with acute pulmonary oedema due to its anticipated anxiolytic and vasodilatory properties, however a discussion about the benefits and risks has been raised recently. A literature search in Medline and Embase using the keywords "pulmonary oedema" OR "lung oedema" OR "acute heart failure" AND "morphine" was performed. A certain vasodilation has been described after morphine administration, but the evidence for this mechanism is relatively poor and morphine-induced anxiolysis may possibly be the most important factor of morphine in pulmonary oedema and therefore some authors have suggested benzodiazepines as an alternative treatment. Respiratory depression seems to be a less relevant clinical problem according to the literature, whereas vomiting is common, which may cause aspiration. In the largest outcome study, based on the ADHERE registry, morphine given in acute decompensated heart failure was an independent predictor of increased hospital mortality, with an odds ratio of 4.8 (95% CI: 4.52-5.18, p<0.001). Other, smaller studies have shown a significant association between morphine administration and mortality, which was lost after adjusting for confounding factors. Morphine is still used for pulmonary oedema in spite of poor scientific background data. A randomised, controlled study is necessary in order to determine the effect--and especially the risk--when using morphine for pulmonary oedema. Since the positive effects are not sufficiently documented, and since the risk for increased mortality cannot be ruled out, one can advocate that the use should be avoided.


Providing feedback to users on unacceptable practice in the delivery of a hospital transfusion service--a pilot study.
The Serious Hazards of Transfusion Scheme's (SHOT) annual report continues to emphasize the importance of investigating serious transfusion errors. It is now recognized that lessons can also be learnt from near-miss events as these occur more frequently than serious errors in transfusion. One of the key features in developing a culture that can promote safety in relation to transfusion is providing feedback to staff on what is acceptable and unacceptable practice. We have developed a scoring system based on the number of serious errors and near misses that occur in the transfusion service to provide feedback to staff on their performance in relation to the administration of blood components and blood products. This was developed as part of an ongoing error logging system that we have previously described. The implementation of this feedback has resulted in an increased awareness within our organization of safety issues in relation to transfusion, and has highlighted the importance of the detection and correction of less serious errors.


Basal ganglia and autism - a translational perspective.
The basal ganglia are a collection of nuclei below the cortical surface that are involved in both motor and non-motor functions, including higher order cognition, social interactions, speech, and repetitive behaviors. Motor development milestones that are delayed in autism such as gross motor, fine motor and walking can aid in early diagnosis of autism. Neuropathology and neuroimaging findings in autism cases revealed volumetric changes and altered cell density in select basal ganglia nuclei. Interestingly, in autism, both the basal ganglia and the cerebellum are impacted both in their motor and non-motor domains and recently, found to be connected via the pons through a short disynaptic pathway. In typically developing individuals, the basal ganglia plays an important role in: eye movement, movement coordination, sensory modulation and processing, eye-hand coordination, action chaining, and inhibition control. Genetic models have proved to be useful toward understanding cellular and molecular changes at the synaptic level in the basal ganglia that may in part contribute to these autism-related behaviors. In autism, basal ganglia functions in motor skill acquisition and development are altered, thus disrupting the normal flow of feedback to the cortex. Taken together, there is an abundance of emerging evidence that the basal ganglia likely plays critical roles in maintaining an inhibitory balance between cortical and subcortical structures, critical for normal motor actions and cognitive functions. In autism, this inhibitory balance is disturbed thus impacting key pathways that affect normal cortical network activity. Autism Res 2017, 10: 1751-1775. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Habit learning, action selection and performance are modulated by the basal ganglia, a collection of groups of neurons located below the cerebral cortex in the brain. In autism, there is emerging evidence that parts of the basal ganglia are structurally and functionally altered disrupting normal information flow. The basal ganglia through its interconnected circuits with the cerebral cortex and the cerebellum can potentially impact various motor and cognitive functions in the autism brain.


Temporal and physiological influence of the absorption of nutrients and toxic elements by Eichhornia crassipes.
Aquatic macrophytes are a very important subject of study due to their capacity to restore polluted aquatic environments as they need high nutrient concentrations to develop. The present study aims to determine their temporal and physiological influence on the amount of total nitrogen, gross protein, P, Cu, Ni, Co, Cd, Pb and Cr absorbed by Eichhornia crassipes (water hyacinth) in the River Apodi/Mossoró, RN, Brazil, identifying viable possibilities for the use of cultivated biomass. Results obtained from the parameters analyzed show that these substances are impacted by the temporality and physiology of Eichhornia crassipes. Leaves showed higher crude protein and macronutrients, while the content of micronutrients and toxic elements was higher in roots. It could, therefore, be utilized to improve water quality in the River Apodi/Mossoró.


[The Stimulation Program Health Research. X. Evaluation of the program section 'Psychogeriatrics'].
In the programme section 'Psychogeriatrics' of the SGO Health Research Promotion Programme a longitudinal study was carried out in Amsterdam from 1989 until 1994, concerning the course of mild cognitive decline in elderly people (the AMSTEL project). The scientific aims were the development of diagnostical instruments for the early diagnosis of dementia, the development of criteria which predict the course of mild cognitive impairment and the expansion of knowledge on the relationship between somatic and psychiatric pathology and dementia. The programme also had aims regarding medical education and patient care. The results include the following: in order to diagnose dementia in general practice questions regarding orientation and short-term memory are helpful. Risk factors for cognitive deterioration in elderly people include hippocampal atrophy on the MRI scan, a low level of education and subjective complaints regarding memory. Subjective complaints regarding memory are not primarily caused by a depressive mood, as is often thought, but are important as correct self-observations of cognitive deterioration, and go with an increased risk of developing dementia. Besides the AMSTEL project a feasibility study was carried out concerning a psychogeriatric case register in Amsterdam.


Diversity of Bartonella genotypes in Richardson's ground squirrel populations.
The diversity and dynamics of Bartonella genotypes found in wild Richardson's ground squirrels (RGS), Spermophilus richardsonii were monitored at multiple sites in Saskatchewan, Canada from 2002 to 2004. Based on sequence analysis of a portion of the Bartonella citrate synthase (gltA) gene, four different genotypes were detected in 233 isolates from 176 animals. The majority (87%) of sequences were identified as genotype H, with genotypes I, J, and K accounting for 8%, 4%, and 1% of sequences, respectively. Only one animal was concurrently infected with multiple Bartonella genotypes. Of 23 animals sampled four times or more, 26% were never infected with Bartonella. Of 32 RGS infected with Bartonella at first capture and then sampled again the following month, 50% were infected with the same Bartonella genotype, 41% were no longer infected, and 9% were infected with a different Bartonella genotype in the subsequent sample. The diversity of Bartonella genotypes varied among sites. At one site almost all RGS were infected with genotype H in September, and up to 60% of the same population was infected with genotype I the following spring. We compare our results with previous studies of Bartonella infections in rodents and discuss possible explanations for the observed differences.


Propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR/p70S6K signaling pathway in melanoma cells.
Propofol is an intravenous anesthetic, which is widely used in clinical anesthesia induction and maintenance and is critical in the sedation of patients. However, the functions and mechanisms of propofol on apoptosis of melanoma cells remain unclear. The present study investigated whether propofol promotes cell apoptosis and suppresses the HOX transcript antisense RNA (HOTAIR)-mediated mechanistic target of rapamycin (mTOR) pathway in melanoma cells. B16F10 cells were cultured with different concentrations (0-10 µM) of propofol for 24 or 48 h. Proliferation and apoptosis of B16F10 cells were detected using MTT assay and flow cytometry. The pcDNA 3.1(-)-HOTAIR and pcDNA 3.1(-)-control plasmids were transfected into B16F10 cells using Lipofectamine 2000. In the present study, treatment with propofol significantly reduced viability, and induced apoptosis and caspase-3 activity in melanoma cells. Propofol treatment significantly inhibited HOTAIR expression and the expression of phosphorylated (p)-mTOR and p- p70S6K protein in melanoma cells. Overexpression of HOTAIR significantly increased viability of melanoma cells, and increased HOTAIR, p-mTOR and p-p70S6K protein expression in melanoma cells. These results indicated that propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR signaling pathway in melanoma cells.


[Molecular approach for development of new medicaments for chronic infections treatment].
Owing to the progress in cellular microbiology it has been evidently proved that inflammation induced by infectious agents forms the basis of many chronic conditions. Therefore a microbial infection can be considered as a triggering factor of such widespread and significant diseases as infertility, arthritis, atherosclerosis, asthma, gastritis, stomach ulcer and cancer, neurological syndromes and some oncological formations. Practically all pathogenic and conditionally pathogenic bacteria can induce chronic infections of different organs and tissues. It has been revealed that in spite of differences of clinical syndromes and participation of different bacteria in their induction the several general mechanisms of chronic infections are detected. Failure in chronic infections therapy is due to the absence of medicaments to eradicate persistent forms of pathogens. The development of new medicaments for chronic infections treatment should be based on the selection of new specific targets, influence on which would to inhibit the mechanism of chronic infections induction.


Novel conditionally replicating adenovirus-mediated efficient detection of circulating tumor cells in lung cancer patients.
Circulating tumor cells (CTCs) are present in the blood of cancer patients from the early stage of cancer development, and their presence has been correlated with patient prognosis and treatment responses. Accordingly, CTCs have been attracting attention as a novel biomarker for early detection of cancer and monitoring of treatment responses. However, since patients typically have only a few CTCs per milliliter of blood, development of an accurate and highly sensitive CTC detection method is crucial. We previously developed a CTC detection method using a novel conditionally replicating adenovirus (Ad) that expresses green fluorescence protein (GFP) in a tumor cell-specific manner by expressing the E1 gene using a tumor-specific human telomerase reverse transcriptase (hTERT) promoter (rAdF35-142T-GFP). CTCs were efficiently detected using rAdF35-142T-GFP, but GFP expression levels in the CTCs and production efficiencies of rAdF35-142T-GFP were relatively low. In this study, in order to overcome these problems, we developed four types of novel GFP-expressing conditionally replicating Ads and examined their ability to visualize CTCs in the blood samples of lung cancer patients. Among the four types of novel recombinant Ads, the novel conditionally replicating Ad containing the 2A peptide and the GFP gene downstream of the E1A gene and the adenovirus death protein (ADP) gene in the E3 region (rAdF35-E1-2A-GFP-ADP) mediated the highest number of GFP-positive cells in the human cultured tumor cell lines. Titers of rAdF35-E1-2A-GFP-ADP were significantly higher (about 4-fold) than those of rAdF35-142T-GFP. rAdF35-E1-2A-GFP-ADP and rAdF35-142T-GFP efficiently detected CTCs in the blood of lung cancer patients at similar levels. GFP+/CD45- cells (CTCs) were found in 10 of 17 patients (58.8%) for both types of recombinant Ads.


UTX promotes hormonally responsive breast carcinogenesis through feed-forward transcription regulation with estrogen receptor.
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis. We demonstrated that UTX promotes the proliferation and migration of ER+ breast cancer cells. Interestingly, UTX itself is transactivated by ER, forming a feed-forward loop in the regulation of hormone response. Indeed, UTX is upregulated during ER+ breast cancer progression, and the expression level of UTX is positively correlated with that of CXCR4 and negatively correlated with the overall survival of ER+ breast cancer patients. Our study identified a feed-forward loop between UTX and ER in the regulation of hormonally responsive breast carcinogenesis, supporting the pursuit of UTX as an emerging therapeutic target for the intervention of certain ER+ breast cancer with specific epigenetic vulnerability.


Soluble Axl is generated by ADAM10-dependent cleavage and associates with Gas6 in mouse serum.
Axl receptor tyrosine kinase exists as a transmembrane protein and as a soluble molecule. We show that constitutive and phorbol 12-myristate 13-acetate-induced generation of soluble Axl (sAxl) involves the activity of disintegrin-like metalloproteinase 10 (ADAM10). Spontaneous and inducible Axl cleavage was inhibited by the broad-spectrum metalloproteinase inhibitor GM6001 and by hydroxamate GW280264X, which is capable of blocking ADAM10 and ADAM17. Furthermore, murine fibroblasts deficient in ADAM10 expression exhibited a significant reduction in constitutive and inducible Axl shedding, whereas reconstitution of ADAM10 restored sAxl production, suggesting that ADAM10-mediated proteolysis constitutes a major mechanism for sAxl generation in mice. Partially overlapping 14-amino-acid stretch deletions in the membrane-proximal region of Axl dramatically affected sAxl generation, indicating that these regions are involved in regulating the access of the protease to the cleavage site. Importantly, relatively high circulating levels of sAxl are present in mouse sera in a heterocomplex with Axl ligand Gas6. Conversely, two other family members, Tyro3 and Mer, were not detected in mouse sera and conditioned medium. sAxl is constitutively released by murine primary cells such as dendritic and transformed cell lines. Upon immobilization, sAxl promoted cell migration and induced the phosphorylation of Axl and phosphatidylinositol 3-kinase. Thus, ADAM10-mediated generation of sAxl might play an important role in diverse biological processes.


Is there an association between zinc and COVID-19-associated mucormycosis? Results of an experimental and clinical study.
The enormous increase in COVID-19-associated mucormycosis (CAM) in India lacks an explanation. Zinc supplementation during COVID-19 management is speculated as a contributor to mucormycosis. We conducted an experimental and clinical study to explore the association of zinc and mucormycosis. We inoculated pure isolates of Rhizopus arrhizus obtained from subjects with CAM on dichloran rose Bengal chloramphenicol (DRBC) agar enriched with (three different concentrations) and without zinc. At 24 h, we counted the viable colonies and measured the dry weight of colonies at 24, 48 and 72 h. We also compared the clinical features and serum zinc levels in 29 CAM cases and 28 COVID-19 subjects without mucormycosis (controls). We tested eight isolates of R arrhizus and noted a visible increase in growth in zinc-enriched media. A viable count percentage showed a significantly increased growth in four of the eight isolates in zinc-augmented DRBC agar. A time- and concentration-dependent increase in the mean fungal biomass with zinc was observed in all three isolates tested. We enrolled 29 cases of CAM and 28 controls. The mean serum zinc concentration was below the reference range in all the subjects and was not significantly different between the cases and controls. Half of the R arrhizus isolates grew better with zinc enrichment in vitro. However, our study does not conclusively support the hypothesis that zinc supplementation contributed to the pathogenesis of mucormycosis. More data, both in vitro and in vivo, may resolve the role of zinc in the pathogenesis of CAM.


CDNs-STING Interaction Mechanism Investigations and Instructions on Design of CDN-Derivatives.
Cyclic dinucleotides (CDNs) present thousand-fold differences of dissociation constants to STING, a pivotal protein in cytosolic dsDNA immunity. To understand how subtle chemical changes in CDNs lead to these substantial variances, a precise ranking of binding affinity is needed. However, the large size and flexibility of CDNs elevate the entropic effect and pose a challenge for this precise prediction. Therefore, in this paper, we developed a new protocol, a combination of selective-integrated tempering sampling of ligands and molecular docking, to take into account the entropic effects originating from extensive ligand configurational space and solvation on binding affinity evaluations. The calculated ranking orders of CDNs and CDN-derivatives to wild type STING and R232H mutant are in agreement with experimental measurements. Further molecular dynamics analysis revealed that the interaction between phosphonate groups and 232R differentiates the binding affinities. The 2'-5' linked phosphonate groups have a larger tendency to form hydrogen bonds with 232R than those with 3'-5' linkages. Moreover, the new protocol identified structural features that enhanced CDNs-STING binding, such as anti-glycosidic bonds and large pro-R distances, which explains the high binding affinity of dithio-RpRp-2'3'-CDA to STING and is expected to provide valuable guidance in the lead-drug optimization.


Growth of Scenedesmus obliquus on anaerobic soybean wastewater using different wasted organics for high biomass production and nutrients recycling.
The microalgae culture in mixing sewage with different characteristics may significantly improve biomass production and nutrients recycling efficiency. In this study, three waste organic wastewater including molasses, alcohol and glycerol wastewater were mixed with anaerobic soybean wastewater as mediums for microalgae culture. The optimal mixture of molasses, alcohol and glycerol wastewater was at an initial carbon-nitrogen ratio of 7:1, 5:1 and 10:1, improving biomass production by 60.4%, 31.3% and 68.7%, respectively. The removal efficiencies of organics, ammonia nitrogen and phosphorus at optimal mixture were 54.8-62.4%, 79.5-99.1% and 49.3-61.5%, and the removal rates increased by 340-630%, 27.5-66.3% and 36.3-70.2% compared to the blank culture. In addition, the culture in mixed wastewater increased lipids contrast by 0.7-1.3 times, while achieving higher saturation in fatty acids. The results suggested that microalgae culture using mixed wastewater was a strategy for high biomass production and nutrients recycling efficiency.


Repeatability of Cone Spacing Measures in Eyes With Inherited Retinal Degenerations.
To determine short-term variability of adaptive optics scanning laser ophthalmoscopy (AOSLO)-derived cone spacing measures in eyes with inherited retinal degenerations (IRD) and in normal eyes. Twenty IRD patients and 10 visually normal subjects underwent AOSLO imaging at two visits separated by no more than 1 month (NCT00254605). Cone spacing was measured in multiple macular regions in each image by three independent graders. Variability of cone spacing measures between visits, between graders, and between eyes was determined and correlated with standard clinical measures. Cone spacing was measured in 2905 regions. Interobserver agreement was high both in normal eyes and eyes with IRD (mean intraclass correlation coefficient [ICC] = 0.838 for normal and 0.892 for eyes with IRD). Cone spacing measures were closely correlated between visits (ICC > 0.869 for both study groups). Mean relative intervisit spacing difference (absolute difference in measures divided by the mean at each region) was 4.0% for normal eyes and 4.9% for eyes with IRD. Cone spacing measures from fellow eyes of the same subject showed strong agreement for all subjects (ICC > 0.85 for both study groups). Adaptive optics scanning laser ophthalmoscopy-derived macular cone spacing measures were correlated between observers, visits, and fellow eyes of the same subject in normal eyes and in eyes with IRD. This information may help establish the role of cone spacing measures derived from images of the cone mosaic obtained with AOSLO as a sensitive biomarker for longitudinal tracking of photoreceptor loss during disease progression and in response to treatment. (ClinicalTrials.gov number, NCT00254605.).


The Rater Applied Performance Scale: development and reliability.
Previous studies of rater performance and interrater reliability have used passive scoring tasks such as rating patients from a videotaped interview. Little is known, however, about how well raters conduct assessments on real patients or how reliably they apply scoring criteria during actual assessment sessions. With growing recognition of the importance of monitoring and review of actual evaluation sessions, there is need for a systematic approach to quantify raters' applied performance. The Rater Applied Performance Scale (RAPS) measures six dimensions of rater performance (adherence, follow-up, clarification, neutrality, rapport, and accuracy) based on reviews of audiotaped or videotaped assessment sessions or on live monitoring of assessment sessions. We tested this new scale by having two reviewers rate 20 Hamilton Depression Scale rating sessions ascertained from a multi-site depression trial. We found good internal consistency for the RAPS. Interrater (i.e. inter-reviewer) reliability was satisfactory for RAPS total score ratings. In addition, RAPS ratings correlated with quantitative measures of scoring accuracy based on independent expert ratings. Preliminary psychometric data suggest that the RAPS may be a valuable tool for quantifying the performance of clinical raters. Potential applications of the RAPS are considered.


Isolation and characterization of cDNA clones encoding the human carcinoembryonic antigen reveal a highly conserved repeating structure.
For the isolation of cDNA clones encoding the carcinoembryonic antigen (CEA), we have constructed a cDNA library from human colon tumor mRNA. The library was screened with various oligonucleotides whose sequence had been deduced from partial amino acid sequence data for CEA. Positive candidate clones were hybridized with a probe for repetitive DNA, because CEA mRNA contains an Alu repetitive element, and with a fragment of a genomic clone of nonspecific cross-reacting antigen, an antigen closely related to CEA. Here we report the nucleotide sequence of the two overlapping CEA cDNA clones comprising 1422 nucleotides of CEA mRNA. This sequence encodes the 372 COOH-terminal amino acids of CEA followed by 305 nucleotides of 3' untranslated sequence containing a truncated Alu repeat. The predicted protein sequence is composed of two repeats comprising 178 amino acids, each with an exceptionally high homology of 67%. Each repeat unit contains four conserved cysteine residues and six to nine putative N-glycosylation sites. CEA mRNA is most strongly expressed in primary colon tumors and, to a lesser extent, in normal colonic tissue. No CEA mRNA is found in HeLa cells and normal human fibroblasts.


[Atypical chronic myeloid leukemia with polymorphism of the BCR gene].
The region of greatest rupture of the gene BCR (M-bcr) was analysed with the restriction enzyme Bgl II plus a molecular probe containing the 5' end of M-bcr in a woman with atypical, Ph'-negative chronic myelogenous leukaemia. An abnormal DNA fragment of 5.0 kb and an extra band were found, suggesting rearrangement. Nevertheless, the use of several restriction enzymes and the addition of a different probe showed the existence of polymorphism with the enzyme Bgl II, which is an unusual finding. These findings stress the usefulness of using different restriction enzymes and molecular probes in the molecular study of chronic myelogenous leukaemia.


18F-fluorodeoxyglucose positron emission tomography is useful for the diagnosis of intraocular sarcoidosis in patients with a normal CT scan.
To assess the usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and the predictive factors for the diagnosis of sarcoidosis in patients with uveitis who have normal thoracic tomography. We retrospectively reviewed 67 consecutive patients with uveitis of unknown aetiology or a suspected sarcoidosis. All patients with normal thoracic tomography underwent an 18F-FDG PET/CT, which was blindly reinterpreted. We then assessed the proportion of positive 18F-FDG PET/CT and the impact on the final aetiology, using Abad's criteria for the diagnosis of intraocular sarcoidosis. 19 of the 67 patients (28.4%) had mediastinal hypermetabolic foci on their 18F-FDG PET/CT consistent with sarcoidosis. It identified a biopsy site in two cases, which were consistent with sarcoidosis. At the end of the study, six patients (10%) had a proven sarcoidosis, six patients (9%) were considered as having a presumed sarcoidosis and 18 patients (26.9%) as having indeterminate sarcoidosis. 18F-FDG PET/CT enabled the diagnosis of presumed sarcoidosis in these six patients. An older age at diagnosis (p=0.004) and the presence of synechiae (p=0.02) were significantly related to an abnormal 18F-FDG PET/CT, with a trend for an elevated ACE (p=0.0993). We established a nomogram to estimate the probability of having positive findings on the 18F-FDG PET/CT according to different predictive factors. 18F-FDG PET/CT enabled the diagnosis of intraocular sarcoidosis even in patients with a normal CT scan. Older age at diagnosis, presence of synechiae and elevated ACE are associated with positive findings on 18F-FDG PET/CT consistent with sarcoidosis.


Postoperative acute kidney injury in high-risk patients undergoing major abdominal surgery.
Acute kidney injury (AKI) is a frequent complication in high-risk patients undergoing major surgery and is associated with longer hospital stay, increased risk for nosocomial infection and significantly higher costs. A prospective observational study exploring the incidence of AKI (AKIN classification at any stage) in high-risk patients within 48 hours after major abdominal surgery was conducted. Patients' preoperative characteristics, intraoperative management, and outcome were evaluated for associations with AKI using a logistic regression model. Data from 258 patients were analyzed. Thirty-one patients (12%) developed AKI, reaching the AKIN stage 1. No patient reached an AKIN stage higher than 1. AKI patients were older (75.2 vs 70.2 years; P = 0.0113) and had a higher body mass index (26.5 vs 25.1 kg/m(2)). In addition, AKI patients had a significantly longer ICU length of stay (3.4 vs 2.4 days; P= .0017). Creatinine levels of AKI patients increased significantly compared to the preoperative levels at 24 (P= .0486), 48 (P= .0011) and 72 hours (P= .0055), while after 72 hours it showed a downwards trend. At ICU discharge, 28 out of 31 patients (90.3%) recovered preoperative levels. Multivariate analysis identified age (OR 1.088; P= .002) and BMI (OR 1.124; P= .022) as risk factors for AKI development. Moreover, AKI development was an independent risk factor for ICU stays longer than 48 hours (OR 2.561; P= .019). Mild AKI is a not rare complication in high-risk patients undergoing major abdominal surgery. Although in almost the totality of cases, the indicators of renal function recovered to preoperative levels, post-operative AKI represents a primary risk factor for a prolonged ICU stay.


Bile Salt Enterolith: An Unusual Etiology Mimicking Gallstone Ileus.
Primary enterolithiasis is a relatively uncommon but important cause of small bowel obstruction. We present a case of a 69-year-old male with a history of laparoscopic Roux-en-Y gastric bypass and asymptomatic duodenal diverticulum diagnosed with small bowel obstruction. CT imaging showed an obstruction distal to the jejunojejunostomy, and surgical intervention was warranted. A 4.5 cm enterolith removed from the distal jejunum was found to contain 100% bile salts, consistent with a primary enterolith. Clinicians should retain a high index of suspicion for enteroliths as a cause of small bowel obstruction, especially if multiple risk factors for enterolith formation are present.


Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up.
Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance. Single-arm Interventional Human Study. 23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years). Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects' daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month. While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ± 146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the end of the follow-up. Urinary acetoacetate levels were higher during the IF period suggesting a constant lipid catabolism. Our results suggest that, CR affects metabolic parameters positively which will help especially pre-diabetic and insulin resistant patients without any pharmacological approach. In addition IF without calorie restriction can enhance health and cellular resistance to disease without losing weight and those effects may be attributed to different signalling pathways and circulating ketones during IF. Changes observed during IF are probably due to the changes in eating and sleeping pattern and thus changes in metabolic rhythm.


[Priapism in sickle cell anaemia in Senegal: prevalence, attitudes and knowledge].
We interviewed 108 sickle cell anaemia patients aged 5 years older on priapism, and 113 healthy subjects in a control group. They were recruited in the out-patient consultation of the two sickle cell anemia care units of the Fann teaching hospital in Dakar. Ten cases of priapism were identified, all in the group of sickle cell patients (the difference is significant, p = 0.004). Prevalence of priapism was 9.3%. Actuarial probability of having priapism was 8.3% by 10 years of age, and 38.9% +/- 5.7 by 20 years of age. Before the interview, only 10.2% of the sickle cell patients and 8% in the control group knew about priapism, and most of them were unaware of its association with sickle cell disease (75% of sickle cell anaemia patients and 80% of control subjects). This lack of information should be improved by an educational program.


MiR-301a-5p/SCIN promotes gastric cancer progression via regulating STAT3 and NF-κB signaling.
Objective: Gastric cancer (GC) is a type of highly malignant cancer. Although the diagnostic and therapeutic methods are innovating, the outcome of GC patients is still poor. Therefore, our research was carried out to explore potential molecular mechanism in the diagnosis of GC. Materials and methods: Bioinformatics analyses were used to obtain microRNA and target mRNA of interest. The expression level of miR-301a-5p and Scinderin (SCIN) mRNA were detected by quantitative real-time PCR (qRT-PCR). Western blot assay was used to investigate SCIN protein level. Cell Counting Kit-8 assay (CCK-8) and colony formation assay were used to investigate cell proliferation ability. Transwell assay was employed to examine cell motility. The interaction between miR-301a-5p and SCIN mRNA was verified by dual-luciferase reporter assay. Results: The qRT-PCR analysis revealed that the expression of miR-301a-5p was higher in gastric cancer tissues than para-cancer tissues (P<0.05). Cox regression analysis showed upregulated miR-301a-5p was associated with larger tumor size (P=0.036) and more advanced TNM stage (P=0.048). The Kaplan-Meier analysis showed a correlation between increased miR-301a-5p expression and shorter overall survival (OS)(P=0.018). By using bioinformatic analysis, SCIN was predicted as one of the targets of miR-301a-5p. Overexpressing miR-301a-5p promoted proliferation and motility of GC cells while knockdown of SCIN exhibited the same performance. Further, we verified the alteration of miR-301a-5p and SCIN expression level could affect the epithelial-mesenchymal transition (EMT) progression on GC cells via STAT3 and NF-κB signaling. Conclusion: Highly expressed miR-301a-5p was associated with aggressiveness of GC. Upregulation of miR-301a-5p promoted malignant phenotype of GC by targeting SCIN. The present results indicated miR-301a-5p might be a promising molecule in the prognosis of GC.


Experimental evaluation of leaky least-mean-square algorithms for active noise reduction in communication headsets.
An adaptive leaky normalized least-mean-square (NLMS) algorithm has been developed to optimize stability and performance of active noise cancellation systems. The research addresses LMS filter performance issues related to insufficient excitation, nonstationary noise fields, and time-varying signal-to-noise ratio. The adaptive leaky NLMS algorithm is based on a Lyapunov tuning approach in which three candidate algorithms, each of which is a function of the instantaneous measured reference input, measurement noise variance, and filter length, are shown to provide varying degrees of tradeoff between stability and noise reduction performance. Each algorithm is evaluated experimentally for reduction of low frequency noise in communication headsets, and stability and noise reduction performance are compared with that of traditional NLMS and fixed-leakage NLMS algorithms. Acoustic measurements are made in a specially designed acoustic test cell which is based on the original work of Ryan et al. ["Enclosure for low frequency assessment of active noise reducing circumaural headsets and hearing protection," Can. Acoust. 21, 19-20 (1993)] and which provides a highly controlled and uniform acoustic environment. The stability and performance of the active noise reduction system, including a prototype communication headset, are investigated for a variety of noise sources ranging from stationary tonal noise to highly nonstationary measured F-16 aircraft noise over a 20 dB dynamic range. Results demonstrate significant improvements in stability of Lyapunov-tuned LMS algorithms over traditional leaky or nonleaky normalized algorithms, while providing noise reduction performance equivalent to that of the NLMS algorithm for idealized noise fields.


Preliminary Study on Determining the Sequence of Intersecting Lines by Fluorescence Technique.
The determination of the sequence of intersecting lines is an important part of questioned document examinations. A fluorescence technique was used to determine the sequence of heterogeneous intersecting lines produced using inkpad ink, stamp-pad ink, ballpoint pens, gel pens, fountain pens, colorants of carbon paper, photocopiers, laser printers, and inkjet printers. A SteREO Discovery.V20 equipped with the ZEN Blue Lite software was chosen to perform the tests.As the results obtained from the study were positive under most conditions, the fluorescence technique was found to be very successful in determining the sequence of intersecting lines from ballpoint pen, gel pen, fountain pen, photocopier, laser and inkjet printers, and inkpad inks. The method was also successful in determining the sequence of intersecting lines from ballpoint pen, photocopier, laser printer, and stamp-pad inks under most conditions. The technique was not successful in determining the order of crossing lines blending together.


A high molecular weight component of the human tumor necrosis factor receptor is associated with cytotoxicity.
We compared the molecular structure of the receptor to human recombinant tumor necrosis factor (HurTNF) on cells of different tissue origin that differ in their response to one of the known activities of TNF. We studied tumor cell lines that respond to the cytotoxic action of TNF and resistant variants that bind TNF, normal cell lines that are stimulated to proliferate by TNF and those that are not affected by TNF, and peripheral blood granulocytes whose activation is also augmented by TNF. Using 125I-labeled HurTNF, we found that it bound mainly to four cellular polypeptides (138, 90, 75, and 54 kDa), three of which were found in every cell type examined and one (138 kDa) that was observed only in a human breast carcinoma cell line (MCF-7) that is highly responsive to the cytotoxic action of TNF. The 138-kDa polypeptide was not found in resistant variants of MCF-7 that bind TNF. In contrast to the other polypeptides, the 138-kDa protein was detected 30 min after incubation at 4 degrees C, as compared to 5 min. Scatchard analysis and cross-linking data suggest a model for the TNF receptor structure whereby the receptor is composed of noncovalently linked membrane-bound polypeptides that bind TNF with high affinity (Kd, 0.05-0.8 X 10(-9) M) with the 138-kDa protein being the least abundant and/or even absent in most cells.


Matrix effects in analysis of β-agonists with LC-MS/MS: influence of analyte concentration, sample source, and SPE type.
The synergistic influences of analyte concentration, sample source, and solid-phase extraction (SPE) type on matrix effects in the multiresidue analyses of eight β-agonists with LC-ESI-MS/MS were evaluated. Porcine muscle and liver extracts and urine from diverse sources were purified by strong or mixed-mode cation exchange and molecularly imprinted polymer SPE cartridges, respectively. Three spiked concentrations (2, 10, and 20 ng/mL) of eight β-agonists in the purified matrices and the different sample sources were analyzed. The results show that for most β-agonists there are significant differences in matrix effects between analyte concentrations or sample sources (P < 0.05), whereas there is no significant difference in matrix effects between different SPE cartridges (P > 0.05). Results from main effects testing indicated that analyte concentration was the main effector.


Aberrant elastin remodeling in the lungs of O₂-exposed newborn mice; primarily results from perturbed interaction between integrins and elastin.
Excessive localization of elastin from septal tips to alveolar walls is a key feature of bronchopulmonary dysplasia (BPD). The abnormal accumulation of lung elastin, involving the structural and functional interaction of a series of proteins, remains poorly understood. To further investigate the mechanisms accounting for the abnormal accumulation of elastin in the lungs of newborn mice with BPD, we evaluate elastin distribution and its interaction with proteins involved in its aberrant localization, such as integrin αv, fibulin-5 and transforming growth factor β1 (TGF-β1), in lungs of newborn mice exposed to 60% O2 for 21 days. Lung histology revealed aberrant elastin production and impaired lung septation in O2-exposed lungs, while tropoelastin, integrin αv, fibulin-1, fibulin-2 and fibulin-4 gene expression were elevated. Dual staining image analysis of lung sections revealed that co-localization of integrin αv and elastin increased following O2 exposure with elastin distributed throughout the walls of air spaces rather than at septal tips. Furthermore, integrin αv appeared to be induced initially. Concurrently, increased fibulin-5 and TGF-β1 (which may regulate elastic fiber assembly) expression was detected, which may explain the altered lung elastin deposition and defective septation that are observed during BPD. These data support the hypothesis that excessive and aberrant αv integrin expression was initially induced by hyperoxia; αv integrin then interacted with and recruited elastin. These alterations were accompanied by fibulin-5 deposition and TGF-β1 activation, which may impede normal matrix remodeling, thereby contributing to the pathological pulmonary features of BPD.


Actions of gamma-aminobutyric acid on neurones of guinea-pig myenteric plexus.
The effects of gamma-aminobutyric acid (GABA) applied by ionophoresis, pressure ejection and superfusion to myenteric neurones of the guinea-pig ileum were investigated by intracellular recording techniques. Ionophoretic or pressure application of GABA (10 pC-30 nC) caused membrane depolarizations of AH neurones but not S neurones. This depolarization was associated with a conductance increase. It reversed polarity at a membrane potential of -18 mV when intracellular electrodes contained KCl, and -39 mV when electrodes contained K acetate, citrate or sulphate. The ionophoretic depolarization was antagonized by bicuculline (1-30 microM) in an apparently competitive manner. During prolonged or repeated ionophoretic application of GABA, both the depolarization and conductance increase desensitized. Superfusion of GABA (1-100 microM) caused a membrane depolarization in AH neurones, associated with an increase in membrane conductance. The increase in conductance was always smaller than that evoked by ionophoresis of GABA. Bicuculline only partially depressed the depolarization induced by superfusion of GABA, particularly slowing its rising phase. beta-p-Chlorophenyl GABA (baclofen) (10 microM) caused a depolarization similar to that observed with GABA in the presence of bicuculline. The depolarization induced by baclofen and GABA (in presence of bicuculline) superfusion did not decline during prolonged applications; superfusion of GABA but not baclofen reversibly reduced or eliminated the effects of GABA ionophoresis. It is concluded that GABA has two effects on the membrane of myenteric neurones. The first is a bicuculline-sensitive, rapidly desensitizing chloride activation: the second is a bicuculline-insensitive, non-desensitizing depolarization.


Volume transport and generalized hydrodynamic equations for monatomic fluids.
In this paper, the effects of volume transport on the generalized hydrodynamic equations for a pure simple fluid are examined from the standpoint of statistical mechanics and, in particular, kinetic theory of fluids. First, we derive the generalized hydrodynamic equations, namely, the constitutive equations for the stress tensor and heat flux for a single-component monatomic fluid, from the generalized Boltzmann equation in the presence of volume transport. Then their linear steady-state solutions are derived and examined with regard to the effects of volume transport on them. The generalized hydrodynamic equations and linear constitutive relations obtained for nonconserved variables make it possible to assess Brenner's proposition [Physica A 349, 11 (2005); Physica A 349, 60 (2005)] for volume transport and attendant mass and volume velocities as well as the effects of volume transport on the Newtonian law of viscosity, compression/dilatation (bulk viscosity) phenomena, and Fourier's law of heat conduction. On the basis of study made, it is concluded that the notion of volume transport is sufficiently significant to retain in irreversible thermodynamics of fluids and fluid mechanics.


Pharmacotherapy for Insomnia in Primary Care.
Pharmacotherapy for insomnia in primary care settings can be challenging. Frequently, there are multiple coexisting medical and psychiatric conditions, drug interactions, concern regarding use of habit-forming sleep aids, and paucity of time in office visits to discuss management of sleep difficulties. This article reports the results of a literature search related to pharmacotherapy for insomnia and presents 4 clinical vignettes with corresponding treatment options.


Headaches in older people. How are they different in this age-group?
The cause of headaches in older people is more likely to be disease than in younger people. Therefore, a high index of suspicion and a willingness to investigate new headaches in the elderly are essential. Benign dysfunctional headaches (eg, migraine, tension-type headaches) that have carried over from youth are found most often. However, several diseases with increased prevalence in the elderly can cause headaches, including giant cell arteritis, intracranial mass lesions, ischemic cerebrovascular disease, and chronic obstructive lung disease with hypercapnia. Unfortunately, many prescription and over-the-counter drugs being taken for medical diseases commonly found in aging patients can cause headaches. Hypnic headaches are an unusual but easily recognized and treated problem found only in the elderly.


Determining risk factors of bleeding in patients on warfarin treatment.
Background. Warfarin is a commonly used oral anticoagulant agent. The most common adverse effects of warfarin are bleeding complications. Methods. We performed a 1-year retrospective chart review of emergency department patients using warfarin. A total of 65 patients with bleeding disorder (study group) and 63 patients without bleeding (control group) were included, making up a total of 128 subjects. Demographic data, frequency of international normalized ratio (INR) checks, and routine blood results were extracted. Logistic regression analysis was used to determine which factors were most closely associated with bleeding complications. Results. Median age was 62.0 ± 14.4 and 61.9 ± 14.5 for study group and control group, respectively. Educational status and frequency of INR checks were similar in both groups (P = 0.101 and P = 0.483, resp.). INR levels were higher in the study group (5.45 ± 3.98 versus 2.63 ± 1.71, P < 0.001). Creatinine levels were also higher in the study group (1.14 ± 0.57 mg/dL versus 0.94 ± 0.38 mg/dL, P = 0.042). Acetylsalicylic acid use was more frequent in the study group and was associated with a 9-fold increase in bleeding complications (P < 0.001). Conclusions. High INR levels, high creatinine levels, and acetylsalicylic acid use were associated with bleeding complications in ED patients using warfarin.


Magnesium content of the hair in alopecia areata atopica.
The magnesium content of hair from alopecia areata atopica patients, from nonatopic dermatological patients and from normal controls has been studied using atomic absorption spectroscopy. The two groups of patients had lower means and ranges than did the normal subjects, but the overlap was considerable. It is suggested that the lower levels found in the patients may be due to the nonspecific 'metabolic cost' of the skin diseases.


Factors affecting the amplitude of the τ angle in proteins: a revisitation.
The protein folded state is the result of the fine balance of a variety of different forces. Even minor structural perturbations may have a significant impact on the stability of these macromolecules. Studies carried out in recent decades have led to the convergent view that proteins are endowed with a flexible spine. One of the open issues related to protein local backbone geometry is the identification of the factors that influence the amplitude of the τ (N-Cα-C) angle. Here, statistical analyses performed on an updated ensemble of X-ray protein structures by dissecting the contribution of the major factors that can potentially influence the local backbone geometry of proteins are reported. The data clearly indicate that the local backbone conformation has a prominent impact on the modulation of the τ angle. Therefore, a proper assessment of the impact of the other potential factors can only be appropriately evaluated when small (ϕ, ψ) regions are considered. Here, it is shown that when the contribution of the backbone conformation is removed by considering small (ϕ, ψ) areas, an impact of secondary structure, as defined by DSSP, and/or the residue type on τ is still detectable, although to a limited extent. Indeed, distinct τ-value distributions are detected for Pro/Gly and β-branched (Ile/Val) residues. The key role of the local backbone conformation highlighted here supports the use of variable local backbone geometry in protein refinement protocols.


Hand dermatitis among university hospital nursing staff with or without atopic eczema: assessment of risk factors.
Nurses are prone to develop hand dermatitis. Although an atopic constitution has been identified as a genetic risk factor, the behavioural risk factors associated with hand dermatitis in wet work conditions have not been fully explored. This study aimed to clarify the impact of atopic eczema (fulfilling the diagnostic criteria during the past 1 year) on the occurrence of hand dermatitis and to identify the behavioural risk factors among non-atopic nurses with hand dermatitis. From August 2007 to July 2009, nurses from Kaohsiung Medical University Hospital were recruited. The associations between different risk factors and hand dermatitis were documented. In addition, the behavioural risk factors among non-atopic nurses were evaluated via observational study. One thousand one hundred and thirty-two nurses participated in the first part of the study, which revealed that individuals with atopic eczema had a 3.76-fold increased risk for hand dermatitis. However, among 248 nurses with hand dermatitis, only 43 had atopic eczema. The observational study performed on 140 non-atopic nurses identified frequency of hand washing as the behavioural risk factor associated with hand dermatitis. Although atopic eczema is the major risk factor for hand dermatitis, those with atopic eczema constitute only 17% of nurses with hand dermatitis. Decreasing hand washing frequency is the most effective strategy to reduce the occurrence of hand dermatitis among non-atopic nurses.


Fish sounds and boat noise are prominent soundscape contributors in an urban European estuary.
Passive acoustic monitoring is a valuable tool for non-intrusive monitoring of marine environments, also allowing the assessment of underwater noise that can negatively affect marine organisms. Here we provide for the first time, an assessment of noise levels and temporal soundscape patterns for a European estuary. We used several eco-acoustics methodologies to characterize the data collected over six weeks within May 2016 - July 2017 from Tagus estuary. Biophony was the major contributor dominated by fish vocalizations and the main driver for seasonal patterns. Maritime traffic was the major source of anthropogenic noise, with daily patterns monitored using 1584 Hz third-octave band level. This indicator avoided biophony and geophony, unlike other indicators proposed for the EU Marine Strategy Framework Directive. Furthermore, the frequency overlap between anthropophony and biophony demands precautionary actions and calls for further research. This study provides an assessment that will be useful for future monitoring and management strategies.


Eliminating Gender-Based Bias in Academic Medicine: More Than Naming the "Elephant in the Room".
Gender-based discrimination and bias are widespread in professional settings, including academic medicine. Overt manifestations such as sexual harassment have long been identified but attention is only more recently turning towards subtler forms of bias, including inequity in promotion and compensation. Barriers to progress vary across institutions and include lack of awareness, inadequate training, poor informational transparency, and challenging power dynamics. We propose five solutions that the academic medical community can adopt to not only name, but also address, gender-based bias as the proverbial elephant in the room: definitively identify the systemic nature of the problem, prompt those with influence and power to advance a culture of equity, broadly incorporate evidence-based explicit anti-sexist training, increase transparency of information related to professional development and compensation, and use robust research methods to study the drivers and potential solutions of gender inequity within academic medicine. While implementing these proposals is no small task, doing so is an important step in helping the academic medical community become more just.


[Enterotoxigenic Escherichia in patients with acute intestinal infection].
Out of 4,082 Escherichia strains isolated from 989 hospitalized patients with acute enteric infections 2,979 strains belonged to 139 O-groups and the remaining strains could not by typed with O-sera (O1-O164) or were in the serological R-form. 19.3% of the strains isolated from 354 patients showed a positive reaction for thermolabile enterotoxin (TLET) determined in the radioimmunoassay. Escherichia with pronounced reaction for TLET were isolated from 5.5% of the patients. The serological picture of Escherichia with a positive reaction for TLET comprised 78 O-groups, showed practically no variations in children of different age and adult patients and was related to the intensity of reaction for TLET. The number of enterotoxigenic Escherichia greatly varied within individual O-groups: from 3.1 +/- 3.63% (O11) to 100 +/- 9.81% (O114) of the total number of known strains in these O-groups. In most O-groups the number of enterotoxigenic strains varied from 10% to 50%. The most widely spread serovars of etiologically important enterotoxigenic Escherichia belonged to 24 O-groups and were often isolated as monocultures. The capacity for producing TLET (and, probably, some other antigenically related substances) in widely spread among Escherichia; still, the determination of enterotoxicity is a necessary, but not sufficient criterion of their etiological importance in acute enteric infections.


Understanding the links between vestibular and limbic systems regulating emotions.
Vestibular system, which consists of structures in the inner ear and brainstem, plays a vital role is body balance and patient well-being. In recent years, modulating this system by vestibular stimulation techniques are reported to be effective in stress relief and possibly patient's emotional well-being. Emotions refer to an aroused state involving intense feeling, autonomic activation, and related change in behavior, which accompany many of our conscious experiences. The limbic system is primarily involved in the regulation of emotions. Considering the extensive networks between vestibular and limbic system, it is likely that vestibular stimulation techniques may be useful in influencing emotions. Hence, we review here, the possible mechanisms through which vestibular system can influence emotions and highlight the necessary knowledge gaps, which warrants further research to develop vestibular stimulation techniques as a means to treat health conditions associated with emotional disturbances.


Dietary fat intake and risk of stroke in male US healthcare professionals: 14 year prospective cohort study.
To examine the association between intake of total fat, specific types of fat, and cholesterol and risk of stroke in men. Design and setting Health professional follow up study with 14 year follow up. 43 732 men aged 40-75 years who were free from cardiovascular diseases and diabetes in 1986. Relative risk of ischaemic and haemorrhagic stroke according to intake of total fat, cholesterol, and specific types of fat. During the 14 year follow up 725 cases of stroke occurred, including 455 ischaemic strokes, 125 haemorrhagic stokes, and 145 strokes of unknown type. After adjustment for age, smoking, and other potential confounders, no evidence was found that the amount or type of dietary fat affects the risk of developing ischaemic or haemorrhagic stroke. Comparing the highest fifth of intake with the lowest fifth, the multivariate relative risk of ischaemic stroke was 0.91 (95% confidence interval 0.65 to 1.28; P for trend = 0.77) for total fat, 1.20 (0.84 to 1.70; P = 0.47) for animal fat, 1.07 (0.77 to 1.47; P = 0.66) for vegetable fat, 1.16 (0.81 to 1.65; P = 0.59) for saturated fat, 0.91 (0.65 to 1.28; P = 0.83) for monounsaturated fat, 0.88 (0.64 to 1.21; P = 0.25) for polyunsaturated fat, 0.87 (0.62 to 1.22; P = 0.42) for trans unsaturated fat, and 1.02 (0.75 to 1.39; P = 0.99) for dietary cholesterol. Intakes of red meats, high fat dairy products, nuts, and eggs were also not appreciably related to risk of stroke. These findings do not support associations between intake of total fat, cholesterol, or specific types of fat and risk of stroke in men.


The attenuation of ultrasound in biological fluids.
We have measured the ultrasonic attenuation parameters alpha o and n of several biological fluids in vitro in the frequency range 2.8-6.8 MHz, using frequency shift and/or a sinc (.) sidelobe ratio technique. The parameters alpha 0 and n describe the frequency-dependent attenuation via a power-law model, i.e., alpha(f) = alpha 0 fn, where f is frequency. The samples investigated were blood, pus, cyst fluid, bile, and infected hematoma. It was found that the values of alpha o span approximately the range between 0.03-0.3 dB cm-1 MHz-n, and values of n range from about 1.1-1.3.


Effects of the downregulation of SnoN expression on HepG2 cell proliferation and apoptosis.
Ski‑novel protein (SnoN) is a proto‑oncogene that belongs to the Ski protein family and is involved in regulating processes such as cell proliferation and apoptosis. To investigate the role of SnoN in the proliferation and apoptosis of HepG2 cells, we downregulated its expression by the use of small interfering RNA (siRNA). Three fragments predicted to have RNAi capacity were designed and synthesized as the target siRNAs (siRNA‑A, ‑B and ‑C). Following transfection, inhibition efficiency was detected by reverse transcription PCR (RT‑PCR) and western blot analysis. The siRNA with the optimal inhibition efficiency was used for the cell proliferation and apoptosis analysis. Cell proliferation was analyzed by the Cell Counting Kit‑8 (CCK‑8) and cell apoptosis was investigated by flow cytometry. In our study, all three siRNAs efficiently inhibited SnoN expression, and siRNA‑C demonstrated the optimal inhibition efficiency. We found that following downregulation of SnoN expression, HepG2 cell proliferation was significantly inhibited (P<0.05), while HepG2 cell apoptosis was significantly increased (P<0.05). SnoN‑specific siRNA is capable of effectively inhibiting the expression of SnoN in human HepG2 cells, and the downregulation of SnoN expression induces growth inhibition and apoptosis.


The Haglund painful heel syndrome. Experimental investigation of cause and therapeutic implications.
Haglund syndrome, a common cause of pain in the posterior heel, consists of a painful swelling of the local soft tissues (the so-called pump bump) and prominence of the calcaneal bursal projection. The condition is caused by compression of the distal Achilles tendon and surrounding soft tissue between the os calcis and the posterior shoe counter. Osseous plantar projections appear to be a critical etiologic factor in Haglund syndrome. With an experimental model, it has been demonstrated that osseous projections on the plantar surface of the calcaneus adversely influence the bone-soft tissue relation of the posterior heel. Shoe heel elevation has been shown to be clinically effective in alleviating symptoms. It is demonstrated with an experimental model that elevation of the shoe heel decreases the pitch angle. This diminishes the prominence of the bursal projection and allows the foot to slip forward, displacing the posterior calcaneus away from the shoe counter.