High levels of inorganic arsenic in rice in areas where arsenic-contaminated water is used for irrigation and cooking.
Rice is the staple food for the people of arsenic endemic South (S) and South-East (SE) Asian countries. In this region, arsenic contaminated groundwater has been used not only for drinking and cooking purposes but also for rice cultivation during dry season. Irrigation of arsenic-contaminated groundwater for rice cultivation has resulted high deposition of arsenic in topsoil and uptake in rice grain posing a serious threat to the sustainable agriculture in this region. In addition, cooking rice with arsenic-contaminated water also increases arsenic burden in cooked rice. Inorganic arsenic is the main species of S and SE Asian rice (80 to 91% of the total arsenic), and the concentration of this toxic species is increased in cooked rice from inorganic arsenic-rich cooking water. The people of Bangladesh and West Bengal (India), the arsenic hot spots in the world, eat an average of 450g rice a day. Therefore, in addition to drinking water, dietary intake of arsenic from rice is supposed to be another potential source of exposure, and to be a new disaster for the population of S and SE Asian countries. Arsenic speciation in raw and cooked rice, its bioavailability and the possible health hazard of inorganic arsenic in rice for the population of S and SE Asia have been discussed in this review.


Some stereotypic behaviors in rhesus macaques (Macaca mulatta) are correlated with both perseveration and the ability to cope with acute stressors.
The most prevalent sub-group of abnormal repetitive behaviors among captive animals is that of stereotypies. Previous studies have demonstrated some resemblance between stereotypy in captive animals and in humans, including the involvement of neurological malfunctions that lead to the expression of stereotypies. This malfunction can be evaluated through the use of neuropsychological tasks that assess perseveration as implying a failure of the basal ganglia (BG) to operate properly. Other studies, in contrast, have suggested that stereotypies are the product of neurologically intact individuals reacting to the abnormal nature of their surroundings, and are possibly characterized by an adaptive feature that enables the subject to cope with such adversity. Employing neuropsychological tests and also measuring the levels of fecal corticoids in captive rhesus macaques, we tested the hypothesis that stereotypies are related both to brain pathology and to a coping mechanism with stress, resembling accounts by autistic individuals exhibiting basal ganglia malfunction, and who report a sense of relief when performing stereotypies. Self-directed and fine-motor stereotypies exhibited by the monkeys were positively correlated with perseveration, suggesting BG malfunction; while self-directed stereotypies were also negatively correlated with an increase in fecal corticoids following a stress challenge, suggesting a related coping mechanism. We therefore suggest that not all repetitive, unvarying, and apparently functionless behaviors should be regarded as one homogeneous group of stereotypic behaviors; and that, reflecting reports from autistic individuals, self-directed stereotypies in captive rhesus monkeys are related both to brain pathology, and to an adaptive mechanism that allows those that express them to better cope with acute stressors.


Selenium status parameters in patients with polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. To date, no systematic study of interactions between selenium status parameters (SSPs: serum selenium concentration, plasma glutathione peroxidase, GPX3, plasma selenoprotein P, SELENOP), sex hormones, thyroid function parameters, and other laboratory parameters in patients with PCOS has been undertaken. Therefore we aimed to compare such parameters in women with PCOS and in the control groups, and to investigate the multidimensional interactions between various parameters in PCOS patients and in controls. The subjects were diagnosed either with PCOS (n=28, 25.4±5.2 y) or with PCOS+Hashimoto disease (n=13, 27.3±5.6 y). Female patients having normal menses were recruited into the first control group (n=70, 26.8±7.3 y) or to the second control group comprising women only with Hashimoto disease (n=10, 26.2±6.9 y). No apparent differences in SSPs between control subjects and patients with PCOS, also complicated with Hashimoto disease, were identified, though such differences were noticeable for total testosterone (tT), sex hormone binding globulin, free androgen index, dehydroepiandrosterone sulfate (DHEAS), and insulin profile. The correlation between tT and DHEAS was found the strongest. The other group of mutually highly and positively correlated parameters consisted of GPX3, follicle stimulating hormone, free triiodothyronine and free thyroxine. All the latter parameters correlated negatively with vitamin D3. SSPs took part in interactions with thyroid hormones, sex hormones and some other parameters, but only for GPX3 such interactions were statistically significant. The significance of these findings remains open for further investigation, particularly in patients with PCOS and/or Hashimoto disease.


Reliability of Anthropometry-Based Equations Compared to Dual Energy Absorptiometry for Assessing Body Composition in Predialysis Chronic Kidney Disease-A Longitudinal Study.
Skinfold thickness measurements for assessing body composition are reported to have good reproducibility compared to the reference method of dual energy absorptiometry (DXA). In the current study, we compared the level of agreement between body composition measured with DXA and skinfold thickness (SFT) in CKD Stage 3 and 4, at 2 occasions, 6 months apart. Body composition was assessed in 177 Indian patients with CKD Stage 3 and 4 using DXA and anthropometry (SFT). The body fat mass obtained by the 2 methods was compared by paired t-test, intraclass correlation coefficients, regression analysis, and Bland-Altman plots. A linear regression analysis was done to identify the patient-related parameters which would account for the intermethod differences between DXA and SFT. Compared to DXA, SFT underestimated the fat mass at baseline as well as 6 months [DXA vs. SFT at entry: 15.85 kg (95% confidence interval, CI 15.07-16.65) vs. 13.71 kg (95% CI 13.21-14.32), P < .001; at 6 months: 16.13 (95% CI 15.33-16.93) vs. 13.85 (95% CI 13.25-14.45), P < .001]. The intraclass correlation coefficients at entry and 6 months were 0.894 (0.857-0.921) and 0.896 (0.860-0.923), respectively. The intermethod differences between DXA and SFT at baseline and 6 months were comparable: 2.08 kg (95% CI 1.66-2.5) at baseline versus 2.27 kg (95% CI 1.83-2.71) at 6 months, P = 0.200. Gender and body mass index turned out to be the significant predictors of intermethod differences at base line and exit (P < .001). SFT-based measurements show good reproducibility compared to DXA over a period of 6 months. However, SFT systematically underestimates the fat mass by 2 Kg compared to DXA.


Control of exogenous proteinases and their inhibitors at the macrophage cell surface.
The actions and availability of human neutrophil elastase and its protein inhibitor, Eglin, when co-incubated with macrophages were investigated. Eglin did not induce radical production by mouse peritoneal macrophages; nor were specific binding sites for Eglin detected on these cells. Mouse peritoneal macrophages could inactivate both elastase and Eglin extensively, when these targets were used at concentrations appropriate to the extravascular fluids. Two methods were used for assessing such inactivation: one, as in previous literature, only took account of molecules remaining in the supernatant after interaction with the cells; the other (lacking from most previous studies) took into account all target molecules, including those associated with the cells. From an analysis of both types of experiment, it was shown that the cell-derived inactivators were stable products, whose quantity was not significantly influenced by the induction of a macrophage oxidative burst and its associated free radicals. They were probably mainly proteinases and proteinase inhibitors. Thus, mouse peritoneal macrophages restrict the activity of proteinases and inhibitors by means of stable molecules, such as proteins. Other mononuclear phagocytes may use free radicals and oxidants more extensively in this respect.


Quantitative assessment of cerebral autoregulation from transcranial Doppler pulsatility: a computer simulation study.
Transcranial Doppler (TCD) ultrasonography is largely used today to achieve non-invasive assessment of cerebral autoregulation and cerebrovascular reactivity in neurosurgical patients. Recent experimental and clinical studies suggest that not only the pattern of mean velocity, but also velocity pulse amplitude alterations during changes in cerebral perfusion pressure (CPP) contain information on autoregulation status. The aim of this work is to investigate the relationship between cerebral autoregulation and TCD pulsatility by means of a comprehensive mathematical model of intracranial dynamics and cerebrovascular regulation. Simulation results, performed using different values of the most important clinical parameters of the model (autoregulation strength, cerebrospinal fluid (CSF) outflow resistance and intracranial elastance coefficient) show that velocity pulse amplitude increases with a reduction in CPP in patients with intact autoregulation, whereas changes in velocity pulsatility are modest in patients with weak autoregulation. Finally, velocity pulse amplitude decreases during a CPP reduction in patients with impaired autoregulation. Moreover, the relationship between the velocity pulse amplitude changes and autoregulation strength is almost linear in a wide range of CPP values, and is scarcely affected by changes in CSF circulation and intracranial elasticity. Starting from these results, we suggest a new quantitative index to assess autoregulation strength, i.e. G(aut)% = (s-b)/a, where G(aut)% is autoregulation strength (100% means intact autoregulation, 0% means impaired autoregulation), a approximately -0.03; b approximately 1.5 and s is the slope of the relationship ' percentage changes of velocity pulse amplitude to arterial pressure pulse amplitude vs. CPP changes'.


Effects of dopamine D4 receptor-selective antagonists on motor hyperactivity in rats with neonatal 6-hydroxydopamine lesions.
Dopamine D4 receptor gene polymorphism has been repeatedly associated with attention deficit hyperactivity disorder (ADHD) and related personality traits. We recently reported that motor hyperactivity in an animal model of ADHD was dose-dependently reversed by CP-293,019, a D4 receptor-selective antagonist. However, behavioral effects of this agent may not be attributed exclusively to D4 receptor blockade, since it interacts with other sites including serotonin receptors. To test further the hypothesis that D4 receptor blockade can reduce motor hyperactivity, behavioral effects of three chemically and pharmacologically dissimilar D4 antagonists were compared to that of ketanserin, a serotonin 5-HT(2A/2C) antagonist. Selective dopamine lesions were made in male rats at postnatal day (PD) 5 with intracisternal 6-hydroxydopamine (100 microg) after desipramine pretreatment (25 mg/kg, SC) to protect noradrenergic neurons. Effects of D4 receptor-selective antagonists and ketanserin on lesion-induced motor hyperactivity were examined during the periadolescent period (postnatal days 23-26) with an infrared photobeam activity system. The D4 antagonists L-745,870 and U-101,958 dose-dependently inhibited motor hyperactivity in rats with neonatal lesions, whereas S-18126 lacked this effect at doses up to 30 mg/kg. None of these drugs affected motor behavior in sham control rats. In contrast, ketanserin produced apparent sedative effects in both lesioned and intact control rats without normalizing hyperactivity. Motor hyperactivity in this ADHD model was selectively antagonized by three of four dopamine D4 receptor antagonists evaluated, encouraging clinical assessment of D4 antagonists in patients with ADHD.


The first total synthesis of (+/-)-arisugacin A, a potent, orally bioavailable inhibitor of acetylcholinesterase.
The first convergent total synthesis of (+/-)-arisugacin A was accomplished by stereoselective construction of the arisugacin skeleton via a Knoevenagel-type reaction of an alpha,beta-unsaturated aldehyde with a 4-hydroxy 2-pyrone and stereoselective dihydroxylation followed by deoxygenation.


Microbiological mechanism for "production while remediating" in Cd-contaminated paddy fields: A field experiment.
Security utilization measures (SUMs) for "production while remediating" in moderate and mild Cd-polluted paddy fields had been widely used. To investigate how SUMs drove rhizosphere soil microbial communities and reduced soil Cd bioavailability, a field experiment was conducted using soil biochemical analysis and 16S rRNA high-throughput sequencing. Results showed that SUMs improved rice yield by increasing the number of effective panicles and filled grains, while also inhibiting soil acidification and enhancing disease resistance by improving soil enzyme activities. SUMs also reduced the accumulation of harmful Cd in rice grains and transformed it into FeMn oxidized Cd, organic-bound Cd, and residual Cd in rhizosphere soil. This was partly due to the higher degree of soil DOM aromatization, which helped complex the Cd with DOM. Additionally, the study also found that microbial activity was the primary source of soil DOM, and that SUMs increased the diversity of soil microbes and recruited many beneficial microbes (Arthrobacter, Candidatus_Solibacter, Bryobacter, Bradyrhizobium, and Flavisolibacter) associated with organic matter decomposition, plant growth promotion, and pathogen inhibition. Besides, special taxa (Bradyyrhizobium and Thermodesulfovibrio) involved in sulfate/sulfur ion generation and nitrate/nitrite reduction pathway were observably enriched, which effectively reduced the soil Cd bioavailability through adsorption and co-precipitation. Therefore, SUMs not only changed the soil physicochemical properties (e.g., pH), but also drove rhizosphere microbes to participate in the chemical species transformation of soil Cd, thus reducing Cd accumulation in rice grains.


Stepping Down and Stepping In: Youth's Perspectives on Making the Transition from Residential Treatment to Treatment Foster Care.
Older youth preparing to emancipate from the foster care system are often served in residential treatment settings where they have limited opportunities to practice skills for independent living in a community setting. Stepping these youth down to less restrictive environments such as treatment foster care is a growing trend, especially for youth with mental health issues. Yet, few studies have explored the youth's perspective on making this transition. This study utilized qualitative interviews with youths who were participating in a treatment foster care intervention study (n=8) to gain their perspectives on the process of transitioning from residential care. Youths were interviewed right before they exited residential care and two months after placement in the new foster home. Youths reported hopes for gaining family in the new home as well as fears of placement disruption. Findings point to the need to enlist youths in discussion and problem solving about difficulties they anticipate in the new home and expectations for their relationship with the new foster parents. In addition, the struggles described after two months in the home point to the need for youths to build specific skills to better manage ongoing relationships with foster parents and for foster parent training on how to help build these skills.


Shared epigenetic alterations between oral cancer and periodontitis: A preliminary study.
We recently developed a non-invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease (PD) and the methylation status using our 13-gene panel. Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut-off value. Positive results were found for 23/23 OSCC patients, 3/15 PD patients, and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups. Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193). This study may help to identify potential links between the two diseases and serve as a starting point for the future research focused on pathogenesis.


Bactericidal effects and stability of LL-37 and CAMA in the presence of human lung epithelial cells.
Cationic antimicrobial peptides (CAMPs) are important actors in host innate immunity and represent a promising alternative to combat antibiotic resistance. Here, the bactericidal activity of two CAMPs (LL-37 and CAMA) was evaluated against Pseudomonas aeruginosa (PA) in the presence of IB3-1 cells, a cell line derived from patients with cystic fibrosis. The two CAMPs exerted different effects on PA survival depending on the timing of their administration. We observed a greater bactericidal effect when IB3-1 cells were pretreated with sub-minimum bactericidal concentrations (Sub-MBCs) of the CAMPs prior to infection. These findings suggest that CAMPs induce the production of factors by IB3-1 cells that improve their bactericidal action. However, we observed no bactericidal effect when supra-minimum bactericidal concentrations (Supra-MBCs) of the CAMPs were added to IB3-1 cells at the same time or after infection. Western-blot analysis showed a large decrease in LL-37 levels in supernatants of infected IB3-1 cells and an increase in LL-37 binding to these cells after LL-37 administration. LL-37 induced a weak inflammatory response in the cells without being toxic. In conclusion, our findings suggest a potential prophylactic action of CAMPs. The bactericidal effects were low when the CAMPs were added after cell infection, likely due to degradation of CAMPs by bacterial or epithelial cell proteases and/or due to adherence of CAMPs to cells becoming less available for direct bacterial killing.


Foliar application of biosynthetic nano-selenium alleviates the toxicity of Cd, Pb, and Hg in Brassica chinensis by inhibiting heavy metal adsorption and improving antioxidant system in plant.
Biosynthetic nano-selenium (bio-SeNP), as a plant growth regulator, has better bioavailability and lower toxicity than selenite and selenate. This study investigated the beneficial role of bio-SeNP in mitigating the adverse effects of multiple heavy metals (HMs, e.g., Cd, Pb, and Hg) on growth and yield of pak choi (Brassica chinensis) grown in slightly or heavily polluted (SP or HP) soil by regulating metabolic and antioxidant systems. The results revealed that foliar application of bio-SeNP (5, 10, 20 mg L-1 Se) at the 6-leaf stage greatly reduced the levels of Cd, Pb, and Hg in shoots and roots of pak choi. Application of 5 mg L-1 bio-SeNP significantly (p < 0.05) decreased the translocation factor (TF) of Cd, Pb, and Hg from root to shoot by 9.83%, 44.21%, and 46.99% for SP soil, 24.17%, 56.00%, and 39.36% for HP soil, respectively. Meanwhile, all bio-SeNP treatments led to a significant improvement in plants growth by enhancing the antioxidant defense system (e.g., AsA-GSH) and promoting chlorophyll synthesis as well as suppressed the lipid peroxidation products contents (MDA) in shoots. Moreover, the enhanced levels of mineral nutrient elements (e.g., Ca, Mg, Fe, or Zn) and organic selenium (e.g., selenocystine, Se-methylselenocysteine, and selenomethionine) in the edible shoots of bio-SeNP-treated pak choi plant under multiple HMs stress indicated the positive impacts of bio-SeNP on the improvement of shoot quality and nutritional values. Collectively, our results indicated that bio-SeNP play an important role in the management of multiple HMs-induced adverse effects on pak choi. Foliar application of bio-SeNP at appropriate concentration (≤ 5 mg L-1 Se) can be considered as a promising agronomic measure for safety leafy vegetable production in multiple HMs polluted soils when bio-SeNP application.


Skin and eye irritancy assessment of six lactic acid bacteria strains.
Here we investigate the suitability of in vitro models to assess the skin and eye irritation potential of six microbial strains. Acute skin irritation was tested according to the unmodified and modified OECD test guideline (OECD TG) 439, while acute eye irritation was examined using the OECD TG 491 and 492. The OECD TG 439 guideline, modified to introduce 8-10 μg/mL of streptomycin during the recovery phase and use of test items containing 100% microbial product instead of finished formulae, was found to be suitable for skin irritation evaluation. On the other hand, the OECD TG 491 procedure was the most appropriate for evaluating eye irritation. None of the six microbial strains, namely, Lactiplantibacillus plantarum (IMI 507026, IMI 507027, IMI 507028), Lacticaseibacillus rhamnosus (IMI 507023), and Pediococcus pentosaceus (IMI 507024, IMI 507025), tested in this study caused skin or eye irritation under the study condition.


[Chronic low back pain and functional restoring program: applicability of the Patient Acceptable Symptom State].
To search for predictors of reduced low back pain under the patient acceptable symptom state (PASS) at the end of a functional restoration program (FRP) in chronic low back pain, and then to compare the effectiveness of FRP depending on the rate of people returning to work, the acceptability threshold of pain has been reached or not at the end of the program. Open prospective study on 303 patients with chronic low back pain included in a FRP. An assessment of the deficiencies (finger-tip-to-floor (cm) and Schöber tests (cm), VO2max (l/min), Shirado and Sorensen tests (seconds), lumbar and radicular VAS (0-100), the functional disability (Wadell and Quebec scales (0-9 and 0-100), and the psychological status (Beck and Hamilton scale (0-35 and 0-30), HAD scale (0-21), FABQ (0-42 and 0-24)) was conducted at the beginning and end of the program. Data on the work were also collected (arduous physical labor, work-related accident or not, sick leaves or not and length, return to work at the end of the program). The variables associated with a PASS at the end of the FRP and a correlation between the level of pain and the return to work were sought. The parameters were significantly improved: finger-tip-to-floor test (-17.5+/-16.2), Schöber test (-0.5+/-5.4), lumbar VAS(-6.3+/-23.6), VO2max (0.14+/-0.4), Wadell (-1.3+/-2.4), Quebec (-10.5+/-17), Beck D (-3.1+/-4.5), Beck A (-2.5+/-4.3), HAD D (-2.4+/-4.7), HAD A (-1.3+/-3.8) et FABQ1 (-5.7+/-11.6), FABQ2 (-3.9+/-9.6) scores, endurance of the flexor (35+/-63.83) and extensor (44.8+/-112) spine. Patients reaching the PASS for pain level return significantly more to work (73% versus 52%). Five parameters indicative of a reduction of back pain under the PASS were identified : lumbar VAS and endurance of the flexor spine at the beginning, changes in finger-tip-to-floor test, radicular VAS and Beck score for anxiety. The PASS appears to be a relevant concept associated with a successful return to work for patients with chronic low back pain and severe disability after a program of FRP.


Arthroscopic evaluation of the injured athlete's knee.
In summary, arthroscopic evaluation of the athlete's knee joint provides a highly accurate means of diagnosing intra-articular lesions. It provides valuable information regarding treatment and prognosis. In addition, if arthroscopic surgical treatment is possible, even greater benefits in regard to more rapid return to full athletic activity will be possible.


Identification of covalently bound fatty acids on acylated proteins immobilized on nitrocellulose paper.
A general method for identification of fatty acids covalently bound to acylated proteins following their electrophoretic transfer onto nitrocellulose paper is described. As demonstrated for [3H]palmitoylated RAS1 protein of Saccharomyces cerevisiae and the acylated acyl carrier protein of Spirodela oligorrhiza, this procedure alleviates the need for elution of proteins from polyacrylamide gel slices. Fatty acid ligands of such proteins are hydrolyzed directly from their immobilized state on the nitrocellulose paper, then derivatized with p-nitrophenacyl bromide, and finally resolved by reversed-phase high-performance liquid chromatography. The amount of acylated protein required for identification of acyl groups is minimized compared to that required for more conventional approaches by coupling a radioactive flow detector with the HPLC system.


Parkinsonism and severe hypothyroidism in an elderly patient: a case of lithium toxicity due to pharmacological interactions.
Hypothyroidism is a common clinical side effect of lithium treatment, whereas parkinsonism is a very rare adverse event. A number of case series of clinical signs of reversible and permanent parkinsonism due to lithium toxicity have been previously published, but never in association with hypothyroidism. We describe a rare clinical case of concurrent reversible parkinsonism and severe hypothyroidism due to lithium toxicity. The patient was a 74-year-old woman chronically treated with carbonate lithium (300 mg, twice daily) and clomipramine (75 mg, once daily); she also received valsartan (160 mg) plus hydrochlorothiazide (12·5 mg), once daily. The patient was visited after a 1-week history of progressively worsening and disabling parkinsonism. Laboratory tests showed elevated values of lithium and thyroid stimulating hormone (TSH) serum concentrations as well as reduced circulating thyroid hormone serum concentrations. Lithium treatment was discontinued; treatment with levothyroxine and saline solution i.v. was readily performed, and valsartan plus hydrochlorothiazide were replaced with amlodipine (5 mg, once daily). Within a few days, the patient showed a rapid improvement in overall clinical condition, but complete resolution of neurologic symptoms occurred only after about 5 months. Lithium toxicity may present with concurrent hypothyroidism and parkinsonism. In the present case, interaction with valsartan and hydrochlorothiazide most likely played an important role. In patients who receive chronic therapy with lithium, prescribers should monitor lithium serum concentration both periodically and immediately at the onset of signs and symptoms, potentially related to lithium toxicity.


The Hitchhiker's Guide across a Waddington's landscape of melanoma.
Melanoma evolution may recapitulate the embryonic development of its progenitor tissue, neural crest (NC), but the exact process is unclear. In a recent issue of Nature, Karras et al. (2022) demonstrate that melanoma expansion mirrors the hierarchic process of NC differentiation, generating cell subpopulations, each with distinct function, including growth and metastasis.


In memory of G. N. Papanicolaou in the centennial of his birth.
The author recalls the most important events in the life of George N. Papanicolaou, "the father of modern cytology", underlining the social message arising out of his scientific achievement and moral personality.


Hydroxycoumarins and some Flavonoids from Pistacia atlantica Desf. as Multi-targets Inhibitors for Alzheimer's Disease: Molecular Docking and ADMET Studies.
The present study aimed to identify new selective inhibitors for acetylcholinesterase, butyrylcholinesterase, monoacylglycerol lipase, beta-secretase, and Asparagine endopeptidase, the targets enzymes in Alzheimer's disease. The inhibitory effect of P. atlantica Desf. methanol extracts against AChE were determined using Ellman's method. The molecular docking study is achieved using Autodock Vina. The structures of the molecules 3-methoxycarpachromene, masticadienonic acid, 7-ethoxycoumarin, 3',5,7- trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol-3-O-rutinoside and the five enzymes were obtained from the PubChem database and Protein databank. ADMET parameters were checked to confirm their pharmacokinetics using swiss-ADME and ADMET-SAR servers. P. atlantica Desf. methanol extracts showed a notable inhibitory effect against AChE (IC50 = 0.26 ± 0.004 mg/ml). The molecular docking results of 3-methoxycarpachromene, masticadienonic acid, 7-ethoxycoumarin, 3',5,7-trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol-3-Orutinoside with the five enzymes show significant affinities of these molecules towards Alzheimer disease targets, where they could form several interactions, such as hydrogen bonds and hydrophobic interactions with the studied enzymes. The shortest hydrogen bond is 1.7 A° between masticadienonic acid and Arg128 of the active site of BACE, while the lowest free energy is -11.2 of the complex 5,6,7,4'-tetrahydroxyflavonol-3-O-rutinoside -HuBchE. To the best of our knowledge, these molecules' potential anti-Alzheimer disease effect is studied in this paper for the first time. The docking studies of this work show that 3-methoxycarpachromene and masticadienonic acid, 7-ethoxycoumarin, 3',5,7-Trihydroxy-4'-methoxyflavanone and 5,6,7,4'-tetrahydroxyflavonol- 3-O-rutinoside have good affinities towards the enzymes involved in Alzheimer pathology, which confirm the ability of these molecules to inhibit the studied enzymes namely: HuAChE, HuBChE, BACE, MAGL, and AEP. These molecules might become drug candidates to prevent Alzheimer's disease.


[Enzymes and metabolic products in the cerebrospinal fluid in acute craniocerebral trauma].
A study of the activity of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, lactate and pyruvate in the CSF of patients with head injuries in the acute period revealed a high activity of the above enzymes and increased content of lactate as compared with a control group of patients. The activity of alanine aminotransferase and aspartate aminotransferase as well as the content of lactate showed a tendency to rise in patients with an unfavourable outcome of the disease.


Seasonal changes in vitamin D status and bone turnover in healthy Irish postmenopausal women.
To examine the effect of season on biochemical markers of bone turnover in 51-to 75-year-old Irish women and to investigate whether such changes are related to vitamin D status. Longitudinal observational study. Cork, Ireland (52 degrees N). 76 apparently healthy, free-living postmenopausal women (aged 51-75 years), not taking any medication and free from any condition likely to affect vitamin D status or calcium/bone metabolism. Serum 25-hydroxyvitamin D [S-25(OH)D] showed a clear seasonal variation with significantly higher (p < 0.001) values during late summer than late winter. Both urinary pyridinoline (Ur-Pyr) (p < 0.01) and deoxypyridinoline (Ur-Dpyr) (p < 0.001), but not serum parathyroid hormone or osteocalcin, showed a marked seasonal variation with lowest values during late-summer. Stratifying women into those with S-25(OH)D levels > or = or <50 nmol/L (vitamin D adequate and inadequate, respectively) during late-winter, showed that Ur-Pyr and Ur-Dpyr in both groups were significantly (p < 0.05) lower during late summer, and the magnitude of the reduction from winter to summer was similar in both groups. Seasonal changes in bone resorption markers appeared to be linked to seasonal changes in vitamin D status. Further research is needed to investigate the impact of these changes on risk of bone loss and fracture.


Effect of habitual physical activity on regulation of insulin-stimulated glucose disposal in older males.
The goal of this study was to evaluate the effect of differences in habitual level of physical activity on insulin action in healthy males between 60 and 75 years of age. The study population consisted of 20 non-obese individuals with normal glucose tolerance: 13 older subjects (68 +/- 4 years) not exercising regularly and 7 older subjects (66 +/- 3 years) who exercised regularly. Measurements were made of body mass index (BMI), percentage body fat by underwater weighing, maximal O2 consumption by bicycle ergometry (VO2max), and insulin-stimulated glucose disposal by the insulin clamp technique. The results demonstrated that insulin-stimulated glucose disposal was significantly increased (P less than 0.001) in the normal older subjects who exercised regularly. Furthermore, a direct relationship (r = 0.74, P less than 0.001) existed between maximal aerobic capacity and in vivo insulin action, which was independent of either BMI or percentage body fat. These data are consistent with the view that the extensive variation previously noted in in vivo insulin-stimulated glucose disposal of older subjects is related to differences in habitual physical activity.


Sex-related Anthropometrics in a Lower-Body Mobility Assessment Among Professional Soccer Athletes.
The functional movement screen (FMS™) and Y-balance test (YBT) are commonly used to evaluate mobility in athletes. The primary aim of this investigation was to determine the relationship between demographic and anthropometric factors such as sex, body composition, and skeletal dimension and scoring on YBT and FMS™ in male and female professional soccer athletes. Cross Sectional. During pre-season assessments, athletes from two professional soccer clubs were recruited and underwent body composition and skeletal dimension analysis via dual-energy X-ray absorptiometry (DEXA) scans. Balance and mobility were assessed using the YBT and FMS™. A two-tailed t-test was used to compare YBT between sexes. Chi-square was used for sex comparisons of FMS™ scores. Correlation analysis was used to determine if body composition and/or skeletal dimensions correlated with YBT or FMS™ measures. Type-I error; α=0.05. 40 Participants were successfully recruited: (24 males: 27±5yr, 79±9kg; |16 females: 25±3yr, 63±4kg). YBT: Correlations were found between anterior reach and height (r=-0.36), total lean mass (LM)(r=-0.39), and trunk LM(r=-0.39) as well as between posterolateral reach and pelvic width (PW)(r=0.42), femur length (r=0.44), and tibia length (r=0.51)(all p<0.05). FMS™: The deep squat score was correlated with height(r=-0.40), PW(r=0.40), LM(r=-0.43), and trunk LM (r =-0.40)(p<0.05). Inline lunge scores were correlated with height(r=-0.63), PW(r=0.60), LM(r=-0.77), trunk LM(r=-0.73), and leg LM(r=0.70)(all p<0.05). Straight leg raise scores were correlated with PW (r=0.45, p<0.05). Females scored higher for the three lower body FMS™ measures where correlations were observed (p<0.05). Lower body FMS™ scores differ between male and female professional soccer athletes and are related to anthropometric factors that may influence screening and outcomes for the FMS™ and YBT, respectively. Thus, these anatomical factors likely need to be taken into account when assessing baseline performance and risk of injury to improve screening efficacy. Level 3b.


A multifaceted program for improving quality of care in intensive care units: IATROREF study.
To test the effects of three multifaceted safety programs designed to decrease insulin administration errors, anticoagulant prescription and administration errors, and errors leading to accidental removal of endotracheal tubes and central venous catheters, respectively. Medical errors and adverse events are associated with increased mortality in intensive care patients, indicating an urgent need for prevention programs. Multicenter cluster-randomized study. One medical intensive care unit in a university hospital and two medical-surgical intensive care units in community hospitals belonging to the Outcomerea Study Group. Consecutive patients >18 yrs admitted from January 2007 to January 2008 to the intensive care units. We tested three multifaceted safety programs vs. standard care in random order, each over 2.5 months, after a 1.5-month observation period. Incidence rates of medical errors/1000 patient-days in the multifaceted safety program and standard-care groups were compared using adjusted hierarchical models. In 2117 patients with 15,014 patient-days, 8520 medical errors (567.5/1000 patient-days) were reported, including 1438 adverse events (16.9%, 95.8/1000 patient-days). The insulin multifaceted safety program significantly decreased errors during implementation (risk ratio 0.65; 95% confidence interval [CI] 0.52-0.82; p = .0003) and after implementation (risk ratio 0.51; 95% CI 0.35-0.73; p = .0004). A significant Hawthorne effect was found. The accidental tube/catheter removal multifaceted safety program decreased errors significantly during implementation (odds ratio [OR] 0.34; 95% CI 0.15-0.81; p = .01]) and nonsignificantly after implementation (OR 1.65; 95% CI 0.78-3.48). The anticoagulation multifaceted safety program was not significantly effective (OR 0.64; 95% CI 0.26-1.59) but produced a significant Hawthorne effect. A multifaceted program was effective in preventing insulin errors and accidental tube/catheter removal. Significant Hawthorne effects occurred, emphasizing the need for appropriately designed studies before definitively implementing strategies. clinicaltrials.gov Identifier: NCT00461461.


Identification of long non-coding RNA using single nucleotide epimutation analysis: a novel gene discovery approach.
Long non-coding RNAs (lncRNAs) are involved in a variety of mechanisms related to tumorigenesis by functioning as oncogenes or tumor-suppressors or even harboring oncogenic and tumor-suppressing effects; representing a new class of cancer biomarkers and therapeutic targets. It is predicted that more than 35,000 ncRNA especially lncRNA are positioned at the intergenic regions of the human genome. Emerging research indicates that one of the key pathways controlling lncRNA expression and tissue specificity is epigenetic regulation. In the current article, a novel approach for lncRNA discovery based on the intergenic position of most lncRNAs and a single CpG site methylation level representing epigenetic characteristics has been suggested. Using this method, a novel antisense lncRNA named LINC02892 presenting three transcripts without the capacity of coding a protein was found exhibiting nuclear, cytoplasmic, and exosome distributions. The current discovery strategy could be applied to identify novel non-coding RNAs influenced by methylation aberrations.


Increased access to liver transplantation for patients with acute on chronic liver failure after implementation of Share 35 Rule: An analysis from the UNOS database.
Acute on chronic liver failure (ACLF), leads to high mortality. These patients are at risk of being delisted for liver transplantation (LT). Emerging data shows 1y post-transplant survival of 80-92%. The Share 35 (S35) policy was implemented to prioritize patients with MELD ≥35 on the LT waitlist. Our aim was to compare the LT outcomes of ACLF patients as a result of S35. Data from the UNOS scientific registry were used to classify ACLF patients using the NACSELD criteria. For the analyses, data were divided into two eras; 2 years before S35 (Era 1) and 2 years after S35 (Era 2). Waitlist status was classified into categories: Transplanted, Death or Too Sick to Transplant and Still Waiting/Other. LT cumulative incidence between the populations in the eras was calculated using Fine and Gray's method. A proportional hazards model was used to investigate the era effect on cumulative incidence of LT. 46,861 patients were reviewed, of which 817 had ACLF. 366 patients (mean MELD: 37.1) were identified in Era 1 and 451 patients (mean MELD: 37.3) in Era 2. We found that ACLF patients were more likely to receive a liver transplant in Era 2 (p=0.0074). In both eras, transplanted patients had a significantly higher survival than those who were not transplanted (p<0.0001). Our study shows that S35 improved LT rate for ACLF suggesting that there should be broader recognition of ACLF and early transplantation should be pursued.


The Association of Joint Power Kinetic Variables with Running Injuries: A Case-Control Study.
There is conflicting data on which kinetic variables are important to consider with running injuries. Furthermore, less is understood regarding differences in these variables when considering demographics such as age, sex, weight, and running speed. The primary question was what joint power kinetic variables were different between non-injured and injured runners. The purpose of this study was to identify if there were differences in joint power kinetic variables between non-injured runners and injured runners. Case-Control Study. Kinetic data were collected on 122 runners (26 non-injured and 96 injured) over three years with a Bertec force plated treadmill and Qualisys 3D motion capture. The subjects were considered eligible if they self-identified themselves as runners or had running as a key component of their activity. The subjects ran at a comfortable, self-selected pace while two 10-second trials of recordings were used to calculate the means of peak power generated at the hips, knees, and ankles of each gait cycle. Foot strike was categorized by kinematic data. Two sample T-tests were used to compare peak power variables at the hips, knees, and ankles between non-injured and injured runners. Logistic regression analyses examined how a combination of demographics and peak power variables were associated with injuries. No peak power variable at the hip, knee, or ankle was significantly different between injured and non-injured runners (p=0.07-0.87). However, higher hip power absorbed was found to be protective against injuries (odds ratio, .16; 95% CI .025-.88) when considering demographics using a logistic regression model including sex, foot strike, BMI, speed, age, and power variables from the hip, knee, and ankle. The area under the ROC curve was .74, which is acceptable discrimination. When controlling for age, sex, BMI, foot strike, and speed; higher hip power absorbed was found to be protective against injury. This could be due to the hip muscles' unique role in absorbing force during early stance phase. 3b©The Author(s).


Constraints to implementing guidelines for the identification, assessment, and management of childhood obesity in the clinical care setting: Prevention and treatment framework.
The "Pathway for the Identification, Assessment and Management of Overweight and Obese Children & Youth" was developed to support healthcare providers in identifying and treating childhood obesity in British Columbia (Canada). The study aimed to determine the feasibility and effectiveness of using the Pathway in clinical settings. 13 healthcare providers (7 family physicians, 2 pediatricians, 2 registered dietitians, and 2 nurse practitioners) assessed the Pathway and participated in semi-structured interviews in 2015. A direct constant comparative analysis guided the coding of the interviews in the NVivo 9 software. The interviews uncovered the complexity of factors that influenced practices of healthcare providers. Three broad issues were identified as required if the "Pathway" were to be used and fully implemented in practices. First, the "Pathway" needs to be modified in terms of how it is presented and explained and be supplemented with appropriate documentation and resources for its implementation, Second, the constraints that limit implementation need to be addressed and should include a focus on both individual (i.e., the healthcare providers themselves) and environmental (i.e., factors within and outside of providers' organizations) factors. Lastly, there is a need to establish processes and/or infrastructure for adapting the "Pathway" to the local context as resources and supports vary by organizations and regions. Healthcare providers should be involved in screening and managing childhood obesity. Addressing the challenges found in this study will enable healthcare providers to take a more active role in addressing childhood obesity in their day to day practices.


Co-exposure of chronic stress and alumina nanoparticles aggravates hippocampal microglia pyroptosis by activating cathepsin B/NLRP3 signaling pathway.
Combined exposure of chronic stress and alumina nanoparticles (AlNPs) aggravates hippocampal injury, but the pathogenesis is unevaluated. This study aimed to investigate the effect and mechanism of co-exposure to chronic stress and AlNPs on hippocampal microglia pyroptosis. In this study, chronic restraint stress (CRS) alone caused NLRP3-mediated hippocampal microglia pyroptosis, but AlNPs did not. Moreover, co-exposure to CRS and AlNPs exacerbated hippocampal microglia pyroptosis, resulting in more severe hippocampal damage and behavioral deficits in rats. Protein-protein interaction network predicted that cathepsin B was a potential regulatory protein of NLRP3. CRS up-regulated cathepsin B expression which had a more pronounced increase in co-exposure group. Whereas, caspase-1 inhibitor VX-765 alleviated hippocampal microglia pyroptosis and behavioral deficits in rats. Consistent with in vivo results, co-exposure of corticosterone and AlNPs aggravated NLRP3-mediated pyroptosis and cathepsin B expression in HAPI cells. Nevertheless, the pyroptosis of HAPI cells was inhibited by cathepsin B inhibitor CA-074Me and NLRP3 knockout, respectively. NLRP3 agonist nigericin failed to promote the pyroptosis of HAPI cells in the presence of cathepsin B inhibition. These results demonstrated that co-exposure to chronic stress and AlNPs could aggravate hippocampal microglia pyroptosis by activating cathepsin B/NLRP3 signaling pathway, resulting in hippocampal damage and behavioral deficits.


Polyurethane from biosource as a new material for fabrication of microfluidic devices by rapid prototyping.
This paper presents the use of elastomeric polyurethane (PU), derived from castor oil (CO) biosource, as a new material for fabrication of microfluidic devices by rapid prototyping. Including the irreversible sealing step, PU microchips were fabricated in less than 1h by casting PU resin directly on the positive high-relief molds fabricated by standard photolithography and nickel electrodeposition. Physical characterization of microchannels was performed by scanning electron microscopy (SEM) and profilometry. Polymer surface was characterized using contact angle measurements and the results showed that the hydrophilicity of the PU surface increases after oxygen plasma treatment. The polymer surface demonstrated the capability of generating an electroosmotic flow (EOF) of 2.6 x 10(-4)cm(2)V(-1)s(-1) at pH 7 in the cathode direction, which was characterized by current monitoring method at different pH values. The compatibility of PU with a wide range of solvents and electrolytes was tested by determining its degree of swelling over a 24h period of contact. The performance of microfluidic systems fabricated using this new material was evaluated by fabricating miniaturized capillary electrophoresis systems. Epinephrine and l-DOPA, as model analytes, were separated in aqueous solutions and detected with end-channel amperometric detection.


A new endothelin C-terminal analogue IBDP 064 antagonizes endothelin-3-induced cell proliferation.
A series of C-terminal linear endothelin analogues were prepared and their activities in C6 rat glioma cell line were tested. Among the synthetic analogues, IBDP 064, Fmoc-Leu-Asp-Ile-Ile-Trp-OH, was the most potent and selective inhibitor of endothelin-3-induced cell proliferation. Its action was comparable with that of the previously described peptide IRL 1038, [Cys11-Cys15]-ET-1(11-21), an ETB specific inhibitor.


Needle biopsy for muscle diagnosis and research: an Italian experience.
We report our experience of needle biopsy over the past two and a half, viz. 395 cases. We find that the technique meets the needs of diagnosis and research very satisfactorily. We describe its advantages over open biopsy and recommend it in preference to the latter, provided that the necessary technical skill for processing the sample is available.


Controlling the D-band for improved oxygen evolution performance in Ni modulated ultrafine Co nanoparticles embedded in Nitrogen-doped carbon microspheres.
Despite the challenges on tuning the d-band structure of transition metals, the d-band is of great importance for promoting the interaction between catalytic and intermediates during the oxygen evolution reaction (OER) process. Herein, ultrafine Co nanoparticles embedded in the surface layer of nitrogen-doped carbon microspheres are prepared through an in-situ co-coordination strategy, and its d-band is modulated by introducing different Ni amounts. The introduction of Ni in the Co crystal lattice can tune the d-band center and unpaired electrons, which collectively result in an enhancement of OER activity and kinetics. By investigating the catalysts with Ni content from 0% to 75%, it is concluded that the catalyst with 25% Ni shows optimal OER activity, lower overpotential (285 mV at 10 mA cm-2) and higher current densities (73.75 mA cm-2 at 1.63 V). Moreover, the good stability is also demonstrated with the negligible decrease on current densities after 3000 CV cycles or 100 h of continuous test in alkaline media. This concept of modulating the d-band structure by introducing a transition metal with different contents in another transition metal crystal lattice could present an alternative pathway to the development of highly active catalytic materials for OER and beyond.


Synthesis of BiOI@NH2-MIL125(Ti)/Zeolite as a novel MOF and advanced hybrid oxidation process application in benzene removal from polluted air stream.
One of the popular process in volatile organic compounds removal in gas phase is advanced oxidation process. We in this research, synthesized BiOI@NH2-MIL125(Ti)/Zeolite nanocomposite as a novel nanocomposite to degradation of benzene in hybrid advanced oxidation process. The nanocomposite synthesized via solvothermal method. The effect of airflow, ozone gas concentration, hydrogen peroxide concentration, relative humidity and initial benzene concentration are the main parameters in the UV/O3/H2O2/ nanocomposite hybrid process that were studied. The characterization by XRD, FT-IR, FESEM, EDS element mapping, TEM, BET, and UV-vis spectra indicated that nanocomposite were well synthesized. Optimal operating conditions of the process were determined at air flow of 0.1 l/min, ozone concentration of 0.3 mg/min, hydrogen peroxide concentration of 150 ppm, relative humidity of 45 ± 3% and benzene concentration of 50 ppmv. Under these conditions, more than 99% of benzene was degraded. The synergistic effect coefficient of the mechanisms is 1.53. The nanocomposite had good stability in the hybrid process and remained above 99% efficiency up to 5 times. The ozone concentration residual the system was reported to be negligible (0.013 mg/min). The CO and CO2 emissions in the hybrid process was higher than other processes, which indicates better mineralization in the hybrid process. Formaldehyde, octane, noonan, phenol, decanoic acid were reported as the main by-products. The results indicated that UV/O3/H2O2/ nanocomposite hybrid process has fantastic efficiency in the degradation of benzene as one of the indicators of VOCs.


A case of multicentric Castleman's disease associated with advanced systemic amyloidosis treated with chemotherapy and anti-CD20 monoclonal antibody.
Multicentric Castleman's disease (MCD) is a rare systemic lymphoproliferative disorder with too few patient series reported in the literature to have a clear idea about the etiology, outcome and the best treatment available. Systemic reactive amyloidosis is a very rare complication of MCD and its presence worsens the prognosis. We report a case of a 28-year-old patient with plasma-cell type, human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative MCD who responded to treatment with chemotherapy and the anti-CD20 monoclonal antibody, rituximab. Anti-CD20 therapy could be an interesting adjunctive treatment in MCD.


Additional benefit of laparoscopy for nonpalpable testes: finding a contralateral patent processus.
To determine the incidence of contralateral patent processus vaginalis discovered at laparoscopy in patients presenting with a unilateral nonpalpable testis. From August 1997 through February 2006, 159 boys underwent laparoscopic exploration for a unilateral nonpalpable testis. The data were retrospectively reviewed to determine the incidence of contralateral patency, and the results were analyzed with respect to age at repair and side and size of the unilateral nonpalpable testis. The median age of the patients was 1.2 years (range 2 months to 16 years). The nonpalpable testis was on the left side in 100 patients (63%) and on the right side in 59 (37%). The testis was absent in 13 patients (8%), atrophic in 78 (49%), and of normal size in 68 (42%). The overall incidence of a contralateral patent processus vaginalis was 19% (30 of 159). A contralateral patent processus vaginalis was seen in 21% of the boys younger than 2 years old, 19% of boys 2 to 5 years old, and 12% of boys older than 5 years. The incidence of a contralateral patent processus vaginalis was no different for patients with right (20%) versus left (18%) nonpalpable testes. Patients with normal-size testes (34%) had a much greater rate of a contralateral patent processus vaginalis than did those with an atrophic/absent testis (8%) (P <0.001). Our data suggest that the incidence of a contralateral patent processus vaginalis is considerable in patients presenting with a unilateral nonpalpable testis. This is another benefit of laparoscopy in patients with nonpalpable testes.


A prospective randomized trial of the effect of a soluble adhesive on the ease of dressing removal following hypospadias repair.
To determine whether the use of a novel dressing removal technique resulted in shorter removal times, reduced the child's experience of pain and/or reduced parental anxiety when compared to a standard approach. This prospective unblinded randomized controlled trial of 53 consecutive boys undergoing primary hypospadias repair was powered using data from a prior feasibility study. Children were randomized to a standard control dressing (A) or standard dressing plus Cavilontrade mark (B) group. Removal was by (A) soaking the child and dressing in the bath or (B) application of an adhesive remover to the dressing. The primary outcome measure was dressing removal time. Secondary measures were: child pain scores on a visual analogue scale measured by the parent and nurse, and parental anxiety using the self-evaluative state anxiety measure. Data are expressed as median (range); P<0.05 is significant. Dressing B was significantly quicker to remove than A: B 30 min (5-86 min) vs A 40 min (17-105 min), P=0.01, Mann-Whitney. No differences in parent/nurse pain scores between the two groups were seen. There was a strong correlation between parent and nurse reporting of pain scores at the time of dressing removal (Spearman 0.79, P<0.000). No significant differences in pre- and post-dressing removal parental anxiety scores were seen (P=0.159, Mann-Whitney). Several parents had high anxiety levels at both times. The novel dressing removal approach (B) was significantly shorter than the standard one (A). There were no significant differences in child's pain or parental anxiety score between the two approaches.


Manifestation and occurrence of selective adult-type lactose malabsorption in Finnish teenagers. A follow-up study.
In 1969--1970, a simple random sample of 129 Finnish school-aged children was examined to study selective adult-type lactose malabsorption (SLM) in this age category. SLM was found in 8 children. All subjects were reexamined 5 years later. SLM was reconfirmed in these 8 persons and found in 3 additional subjects who had normal lactose absorption in the first examination. The prevalence of SLM was 9.3%, being 8.5% in the age category 12--15 years and 9.9% in that 16--20 years. Low rise of blood glucose in the lactose tolerance test of the first examination, very low milk consumption, milk intolerance, and history of gastrointestinal symptoms were found to be of low predictive value as indicators of SLM. It was also concluded that information about dietetic sources of lactose is important to persons with SLM, but categorical exclusion of lactose from the diet is not necessary, at least in the Finnish population.


Induction of peripheral tolerance to experimental autoimmune myasthenia gravis by acetylcholine receptor-pulsed dendritic cells.
Dendritic cells (DC) are usually regarded as antigen-presenting cells involved in T cell activation, but DC also directly and indirectly affect B cell activation, antibody synthesis, and isotype switch. In the present study, bone marrow (BM)-derived DC from healthy rats were pulsed in vitro with acetylcholine receptor (AChR) and injected subcutaneously into healthy Lewis rats. No clinical signs of the first phase of experimental autoimmune myasthenia gravis (EAMG) were observed during 3 weeks of observation. Upon immunization with AChR and complete Freund's adjuvant, the rats that had received AChR-pulsed DC did not develop clinical EAMG. This tolerance of rats injected with AChR-pulsed DC was associated with reduced expression of B cell-activating factor (BAFF) and by reduced numbers of B cells among splenic mononuclear cells (MNC) compared to rats injected with medium or unpulsed DC. Anti-AChR IgG antibody-secreting cells were decreased, while the ratio of IgG1:IgG2b isotypes was enhanced in rats treated with AChR-pulsed DC compared to control EAMG rats. These results demonstrate that AChR-pulsed DC induce peripheral tolerance to EAMG by possibly inhibiting the expression of BAFF and production of anti-AChR antibodies, providing a possible potential for immunotherapy of antibody-mediated autoimmune diseases.


Stocking and over-the-counter sale of misoprostol for medical abortion in Ghana's community pharmacies: comparison of questionnaire and mystery client survey.
In many sub-Saharan African countries with restricted safe abortion services, community pharmacies are important sources of abortifacients. However, data on stocking and over-the-counter sale of abortifacients in community pharmacies are often limited. The main objective of this study was to compare stocking and over-the-counter sale of misoprostol at community pharmacies using questionnaire and mystery client surveys in Ghana. A cross-sectional questionnaire-based survey, complemented with a mystery client survey, was conducted at 165 randomly selected community pharmacies in Accra, Ghana. Structured questionnaires were administered to pharmacists/pharmacy workers. A mystery client survey to each of these pharmacies was also undertaken. Descriptive statistical techniques (frequencies and proportions) were used to estimate and compare stocking and over-the-counter sale of misoprostol at community pharmacies from the two data collection methods. Some 50.3% (83) of community pharmacists/pharmacy workers reported stocking misoprostol and selling it over-the-counter for medical abortion in the questionnaire-based survey. However, in the mystery client survey, 122 (74%) pharmacists/pharmacy workers reported stocking misoprostol and actually selling it over-the-counter to the mystery clients. Thus approximately 39 (24%) more pharmacies stocked misoprostol and sold it over-the-counter even though they originally denied stocking the drug in the questionnaire survey. Also, the drug was often sold without a prescription, and many did so without asking for a confirmatory pregnancy test or gestational age. In contexts where access to safe abortion services is restricted, mystery client surveys, rather than conventional questionnaire-based survey techniques, may better illuminate stocking and over-the-counter sale of abortifacients at community pharmacies.


The effect of canine disimpaction performed with temporary anchorage devices (TADs) before comprehensive orthodontic treatment to avoid root resorption of adjacent teeth.
The aim of this study was to evaluate the movement of impacted canines away from the roots of neighboring teeth before full-mouth bracket placement, performed by means of TADs to decrease undesired side effects on adjacent teeth. The study sample consisted of 34 palatally impacted canines, being 19 in the experimental group and 15 in the control group. In the experimental group, before placement of brackets, the impacted canine was erupted by means of miniscrews. In the control group, after initiation of comprehensive orthodontics, canine disimpaction was performed by means of a cantilever spring soldered to a palatal bar. At the end of treatment, volume of lateral incisors and canine root resorption were measured and compared by means of a CBCT-derived tridimensional model. Visual Analogue Scale (VAS) score, bleeding on probing (BOP) and gingival index (GI) were recorded. Clinical success rate was also calculated. The volume of root resorption of lateral teeth in the control group was significantly greater than in the experimental group (p < 0.001). At the end of treatment, VAS score, GI and BOP were not significantly different between the two groups. Based on our results, it seems that disimpaction of canines and moving them to the arch can be done successfully carried out with minimal side effects by means of skeletal anchorage.


Differentiation of functional endothelial cells from human induced pluripotent stem cells: A novel, highly efficient and cost effective method.
Endothelial cells derived from human induced pluripotent stem cells (hiPSC- EC) are of significant value for research on human vascular development, in vitro disease models and drug screening. Here we report an alternative, highly efficient and cost-effective simple three step method (mesoderm induction, endothelial cell differentiation and endothelial cell expansion) to differentiate hiPSC directly into endothelial cells. We demonstrate that efficiency of described method to derive CD31+ and VE-Cadherin+ double positive cells is higher than 80% in 12 days. Most notably we established that hiPSC-EC differentiation efficacy depends on optimization of both mesoderm differentiation and endothelial cell differentiation steps.


Skin necrosis in giant cell (temporal) arteritis: report of three cases.
Three elderly, female patients presented with scalp ulceration. One developed sudden blindness before the ulceration of the scalp. Biopsy from the ulcerated area in this patient did not show evidence of giant cell arteritis, but the two other patients had histological evidence of giant cell arteritis and one of these also became blind.


Experimental Evolution Reveals a Genetic Basis for Membrane-Associated Virus Release.
Many animal viruses replicate and are released from cells in close association to membranes. However, whether this is a passive process or is controlled by the virus remains poorly understood. Importantly, the genetic basis and evolvability of membrane-associated viral shedding have not been investigated. To address this, we performed a directed evolution experiment using coxsackievirus B3, a model enterovirus, in which we repeatedly selected the free-virion or the fast-sedimenting membrane-associated viral subpopulations. The virus responded to this selection regime by reproducibly fixing a series of mutations that altered the extent of membrane-associated viral shedding, as revealed by full-genome ultra-deep sequencing. Specifically, using site-directed mutagenesis, we showed that substitution N63H in the viral capsid protein VP3 reduced the ratio of membrane-associated to free viral particles by 2 orders of magnitude. These findings open new avenues for understanding the mechanisms and implications of membrane-associated viral transmission.


A case with diffuse sclerosing variant of papillary carcinoma of the thyroid: characteristic features on ultrasonography.
We describe the case of a patient who had a diffuse sclerosing variant of papillary carcinoma of the thyroid with characteristic features on ultrasonography. Most papillary thyroid carcinomas can be easily recognized and diagnosed by ultrasonography. The thyroid carcinoma in this patient, however, showed diffuse enlargement of the thyroid without formation of any masses, and it had hypoechoic and heterogeneous internal echoes, which contained fine and multiple high-echo spots. Multiple lymph nodes were found to be swollen in the bilateral jugular chains on B-mode ultrasonography. It is very important that this type of papillary carcinoma with characteristic clinical features be detected by careful examination.


Hypnotic efficacy of a modified triazolodiazepine, brotizolam.
Fifty-nine outpatients with insomnia were treated in a 3-week study to assess the safety and efficacy of a new triazolothienodiazepine with a short t1/2, brotizolam. Therapy was initiated with 0.25 mg at night, but by the end of the study all subjects who were receiving brotizolam were taking 0.50 mg. Results indicate brotizolam efficacy as measured by daily subject and weekly physician questionnaires in essentially all sleep parameters, including global subject and physician evaluation of treatment efficacy, sleep latency and sleep maintenance, and quality of sleep. Tolerance to the hypnotic action of brotizolam was not observed after 21 days of daily dosing.


Identification and characterization of apoptosis-related gene serine/threonine kinase 17A (STK17A) from Japanese flounder Paralichthys olivaceus.
Apoptosis plays important roles in regulation of the immune response and has a direct impact on disease resistance in teleost. Death associated protein kinase (DAPK)-related Serine/Threonine kinase 17A (STK17A) is a positive apoptosis regulator. However, the expression and function of STK17A in fish still remains uninvestigated. In this study, we identified and characterized a STK17A gene (termed PoSTK17A) from Japanese flounder Paralichthys olivaceus. We also investigated the pro-apoptotic role of PoSTK17A in fish. Real-time quantitative PCR analysis revealed that PoSTK17A is widely present in various Japanese flounder tissues, and dominantly expressed in liver. Immune challenge experiments showed that PoSTK17A expression was upregulated by inflammatory challenge, Edwardsiella tarda infection and DNA-damaging agent cisplatin treatment as well. Immunofluorescence microscopy revealed that the recombinant PoSTK17A proteins are mainly located in the nucleus of Japanese flounder FG-9307 cells, and human Hela and MCF7 cells. However, PoSTK17A was translocated from the nucleus to cytoplasm following cisplatin treatment. Overexpression of PoSTK17A significantly increased the apoptosis in human MCF7 cells through both cisplatin-dependent and independent manners. Importantly, PoSTK17A also promotes the ATP-gated P2X7 receptor-mediated apoptosis in Japanese flounder FG-9307 cells. Collectively, we characterized an inducible STK17A gene (PoSTK17A) that may play a conserved pro-apoptotic role in fish.


Childhood behavior problems and adolescent sexual risk behavior: familial confounding in the child and adolescent twin study in Sweden (CATSS).
Previous studies have found associations between childhood behavior problems and adolescent sexual risk behavior. Using a quasi-experimental approach, we examined the extent to which this association may be due to between-family differences (i.e., unmeasured familial confounds) not adequately explored in prior research. We used data from a longitudinal, population-based cohort of young twins in Sweden (first assessment: age 9 or 12 years; second assessment: age 15; n = 2,388). We explored the nature of the association between symptom scores for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) at age 9 or 12 and the likelihood of having had sexual intercourse and number of sexual partners by age 15. Two-level mixed-effects models were used to estimate the effect of symptom score on each outcome after controlling for potential unmeasured familial confounds. Higher ADHD, ODD, and CD scores were associated with significantly increased likelihood of sexual intercourse by age 15. Higher ADHD and ODD scores were also associated with increased number of sexual partners. After controlling for unmeasured familial confounds, however, behavior problems were no longer significantly associated with either outcome. The association between childhood behavior problems and sexual risk behaviors may be due to characteristics shared within families. Hence, prevention strategies aimed at reducing these behaviors might need to address broader risk factors that contribute to both behavior problems and a greater likelihood of sexual risk behavior.


Competition in an Indo-Pacific hermit crab community.
This article uses a method developed previously (Abrams 1980) to estimate the relative intensities of inter- and intra-specific competition between pairs of species in a highdiversity intertidal hermit crab community in the tropical Indo-Pacific. The community could be separated into two sub-communities, with relatively weak interactions between members of different sub-communities. The average amount of inter-specific competition experienced by the members of this community was greater than that for the species in a less diverse community in Panama (1980). Average competition ratios for the species in the Indo-Pacific community were still less than competition coefficients calculated from overlap data for other taxa of animal.


Guanidinium and aminoimidazolinium derivatives of N-(4-piperidyl)propanamides as potential ligands for mu opioid and I2-imidazoline receptors: synthesis and pharmacological screening.
Derivatives of N-(1-phenethyl-4-piperidyl)propanamides incorporating guanidinium and 2-aminoimidazolinium groups have been prepared by a synthetic approach involving first introduction of a spacer between the piperidine and the functional group by reductive amination of piperidinone. The formation of each of these functional groups was carried out using N-N'-di(tert-butoxycarbonyl)thiourea and 2-methylthioimidazolinium iodide, respectively. These structures have been designed to incorporate two pharmacologic goals into one entity. Radioligand binding assays have been used to study their affinity for opioid (mu, delta and kappa) and I2-imidazoline receptors. Two of them, 10 and 16, showed high affinity for mu opioid receptors and functionally they had moderate analgesic properties in the hot plate and writhing tests. The in vitro studies on guinea pig ileum (GPI) indicated that both compounds are mu opioid agonists. In what concerns I2-imidazoline receptor activity, these derivatives showed low affinity around 6 to 7 times less than idazoxan.


Emergency ultrasound of the gall bladder: comparison of a concentrated elective experience vs. longitudinal exposure during residency.
It is unknown how an intensive emergency ultrasound (EUS) experience compares with comparable exposure done over the course of residency training. Our objective was to compare the accuracy of EUS of the gall bladder done by physicians after a 2-week EUS elective with similarly numbered examinations done by physicians longitudinally over several years of residency training. This was a secondary analysis of a previously reported prospective study of EUS for biliary disease. The 21(st)-40(th) examinations were compared between those who participated in an EUS elective and those who did not. The gold standard was ultrasound done by the Department of Radiology. Mean time to complete 40 EUS examinations for biliary disease was 14 months for those participating in an EUS elective compared with 29 months for those who did not. One hundred and ninety-one examinations (49%) were done by 19 operators who did not participate in an EUS elective and 202 examinations (51%) were done by 23 operators who completed an EUS elective. There was no statistical difference between the two groups with regard to detecting the presence of gall stones, gall bladder wall thickening, pericholecystic free fluid, ductal dilation, or sludge. Physicians who participated in a 2-week, semi-structured EUS elective demonstrated EUS accuracy for biliary disease that was comparable with those who performed the same number of examinations over a longer period of time.


Effects of vacuuming on dye penetration patterns in root canals and glass tubes.
This study compared the dye leakage pattern of prepared root canals with that of glass tubes, with and without vacuuming. The apical 12 mm of 40 calcified root canals were prepared to tubes with a diameter of 0.5 mm. The coronal end of these canals and 40 glass tubes with similar diameters (12 mm x 0.5 mm) were closed with 2 mm of Cavit. Twenty samples from each group were left empty, and the rest (20) were filled with gutta-percha without sealer. Half of the samples of filled (10) and unfilled (10) specimens were then placed horizontally in 2% methylene blue dye. The other half (10) of the samples from each group were placed in a vacuum (25 mm Hg) and submerged in the dye. Leakage was then measured in millimeters and statistically analyzed using analysis of variance. The 20 empty glass tubes with or without vacuum leaked 17% or less of their lengths. The 20 glass tubes filled with gutta-percha averaged 70.5% leakage. Of those, the 10 glass tubes that were vacuumed had 100% leakage. Empty root canals exhibited mean leakage of 74% without vacuum and 91% of their length with vacuum. Canals filled with gutta-percha leaked a mean of 95.5% of their entire lengths without vacuum and 100% with vacuum (no significant difference). The results showed that filled and unfilled, prepared root canals leaked significantly more than their glass tube counterparts (p < 0.001), and vacuuming may not be necessary for dye leakage studies in filled root canals.


The prediction of ovulation: a comparison of the basal body temperature graph, cervical mucus score, and real-time pelvic ultrasonography.
Ninety-five menstrual cycles were studied in 20 women undergoing donor artificial insemination (AID). In 49 cycles basal body temperature (BBT) changes were charted daily and both daily cervical mucus scoring (modified Insler score) and daily realtime ultrasonography (USS) were performed from day 11 to ovulation. AID was performed only on the day of follicular rupture. A control group, not subjected to USS, were inseminated two to three times per cycle over 46 cycles in the periovulatory period. The Insler score was found to be a reliable indicator of follicular development and rupture. The BBT was found to be less reliable than the Insler score or USS. While USS may be used to confirm follicular development, the Insler score is reliable and less costly.


Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair.
A new intravenous (i.v.) formulation of paracetamol and propacetamol (prodrug of paracetamol) were compared to determine tolerance and relative analgesic efficacy during the first 6 h after inguinal hernia repair performed under general anesthesia combined with ilioinguinal block in children. A total of 183 ASA I or II in-patients, aged 1-12 years, admitted for unilateral inguinal hernia repair were randomized to receive in a double-blind design either i.v. paracetamol 15 mg.kg(-1) (n = 95) or propacetamol 30 mg.kg(-1) (n = 88) for postoperative pain relief as soon as pain intensity was greater than 30 on a 100 mm visual analog scale. All patients were evaluated for efficacy and tolerance. Efficacy was evaluated between 15 min and 6 h after the start of the 15 min infusion. The most frequently reported adverse event was injection site pain, which was significantly reduced in the new formulation group (i.v. paracetamol 14.7% vs propacetamol 33.0% of children, P = 0.005). No significant difference was obtained between treatments on pain relief (PR), pain intensity difference (PAID) from baseline, and objective pain scale intensity difference (OPSD). Also, treatment effects did not differ significantly for maximum values and weighted sums of PR, PAID (investigator and child rated), OPSD, time to first request for rescue medication, proportion of children requesting rescue medication, and investigators' global treatment satisfaction. A single infusion of i.v. paracetamol 15 mg.kg(-1) produced analgesia similar to a single infusion of propacetamol 30 mg.kg(-1) following inguinal hernia repair in children. Paracetamol i.v. 15 mg.kg(-1) was better tolerated at the injection site than propacetamol.


BaselinTc99-MIBI scanning predicts survival in multiple myeloma and helps to differentiate this disease from monoclonal gammopathy of unknown significance.
We performed baselineTc(99)-MIBI scanning in 43 patients with multiple myeloma (MM) and in 31 with monoclonal gammopathy of unknown significance (MGUS) patients. We identified two groups of MM patients whose actuarial survival correlated with low or high MIBI scores. MGUS patients had normal or very low scores.


Immunological regulation of Angiostrongylus cantonensis infections in rats: modulation of population density and enhanced parasite growth following one or two superimposed infections.
Rats acquired a degree of protective immunity to reinfection with Angiostrongylus cantonensis after a single infection with 50 infective larvae. Infected rats resisted the establishment of most challenging larvae and protective immunity increased with subsequent reinfections. Part of the primary infection was lost after a superimposed second and also following a superimposed third infection, but the total size of the concurrent adult worm populations remained the same as that from a primary infection. Worms surviving from the primary infection showed enhanced growth after each reinfection but their fecundity was impaired.


Plasma steroids in benign prostatic hypertrophy and carcinoma of the prostate.
Cortisol, 17-hydroxyprogesterone (17-OH-P), progesterone, testosterone, 5 alpha-dihydrotestosterone (DHT), estrone (E1) and estradiol (E2) were determined by RIA after chromatographic separation of steroids on Sephadex LH-20 columns, in 54 hospitalized patients with benign prostatic hyperplasia (BPH) and in 32 hospitalized patients with prostatic carcinoma (PCA) (T34, N01, M01). The patients' values were compared with those of 63 age-matched controls. Increased cortisol and DHT levels, subnormal estrogen and 17-OH-P values and normal progesterone level were found in both benign and malignant groups. Higher mean values for testosterone, and T/DHT ratio and lower mean values for E2/T ratio were found in PCA, as compared with those in BPH. An age invariance of cortisol, testosterone, T/DHT ratio and estradiol was found in both BPH and PCA, instead of the age dependence found in normal subjects. The normal relations between testosterone and its precursor (17-OH-P) and its peripheral metabolite (E2), respectively, and the normal relation between estrone and 17-OH-P were not evident in either BPH or PCA group. The normal direct relation between testosterone and DHT has been found in both patient groups.


Effects of phosphorus concentration on the growth and enzyme production of Phanerochaete chrysosporium.
The effects of different phosphorus concentrations in culture media on the growth and enzyme production of Phanerochaete chrysosporium was investigated at a glucose concentration of 10 g L(-1). The results showed that the optimal KH(2)PO(4) concentration was 2.0 g L(-1). Optimal phosphorus content not only supported robust growth of P. chrysosporium, but also helped produce higher yields of manganese-dependent peroxidase (MnP) (324.9 U L(-1)). In addition, the results revealed that a relationship between the consumption of total phosphorus (TP) and fungal growth and enzyme production existed in P. chrysosporium cultures. Over a range of 0-0.5 g L(-1) KH(2)PO(4) concentration in the medium, the biomass and MnP activity increased in proportion to phosphorus concentration. When the KH(2)PO(4) concentration reached 0.5 g L(-1), it was generally found that the increase in biomass gradually slowed down, while MnP production decreased greatly with an increase in phosphorus concentration.


Lactobacillus plantarum vaccine vector expressing hemagglutinin provides protection against H9N2 challenge infection.
Hemagglutinin (HA) has been demonstrated as an effective candidate vaccine antigen against AIVs. Dendritic cell-targeting peptide (DCpep) can enhance the robustness of immune responses. The purpose of this study was to evaluate whether DCpep could enhance the immune response against H9N2 AIV when utilizing Lactobacillus plantarum NC8 (NC8) to present HA-DCpep in mouse and chicken models. To accomplish this, a mucosal vaccine of a recombinant NC8 strain expressing HA and DCpep that was constructed in a previous study was employed. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. These results revealed that recombinant L. plantarum NC8-pSIP409-HA-DCpep is an effective vaccine candidate against H9N2 AIVs.


Distribution of the GC (group-specific component) subtypes in cord bloods and blood donors.
The common allele, GC/1, was subtyped into GC*IF and GC*IS by isoelectric focusing, increasing the proportion of heterozygotes from 0.42 to 0.58. In a series of 200 blood donors and 200 cord bloods the allele frequencies were found to be: GC*IS = 0.59, GC*IF = 0.11, GC*2 = 0.30; and GC*IS = 0.54, GC*IF = 0.16, GC*2 = 0.30, respectively. These values were similar to frequencies obtained in studies of other Caucasian populations. The average probability of detecting non-paternity for this population is increased from 17% to 30% after subtyping GC 1.


A comparison of mtDNA restriction sites vs. control region sequences in phylogeographic assessment of the musk turtle (Sternotherus minor).
A total of nearly 800 base pairs of mitochondrial DNA sequence was assayed in each of 52 musk turtles (Sternotherus minor) collected across the species' range in the south-eastern USA. About one-half of the sequence information in effect was accessed by conventional recognition-site assays of the entire mtDNA molecule; the remainder came from direct sequence assays of a normally hypervariable 5' section of the noncoding control region. The two assay methods produced essentially nonoverlapping sets of variable character states that were compared with respect to magnitudes and phylogeographic patterns of mtDNA variation. The two assay procedures yielded nearly identical outcomes with regard to: (a) total levels of species-wide mtDNA genetic variation; (b) mean levels of within-locale variation; (c) extremely high population genetic structure; (d) a phylogenetically significant separation of samples from the north-western half of the species' range vs. those in the south-eastern segment; and (e) considerably lower genetic variability within the north-western clade. The micro- and macro-phylogeographic mtDNA patterns in the musk turtle are consistent with a low-dispersal natural history, and with a suspected longer-term biogeographic history of the species, respectively.


Anti-inflammatory and immunoregulatory effects of flax-seed oil and Lactobacillus plantarum - Biocenol™ LP96 in gnotobiotic pigs challenged with enterotoxigenic Escherichia coli.
The aim of this study was to determine the immune response after preventive administration of flax-seed oil (rich in n-3 PUFAs) or probiotic strain Lactobacillus plantarum - Biocenol™ LP96 or their combination in the jejunum of ETEC-challenged gnotobiotic pigs. Subsequently, gene expression of selected cytokines, phagocytic activity of leukocytes from peripheral blood and percentage of CD2(+), CD4(+), CD8(+) and CD4(+)CD25(+) lymphocytes in jejunal mucosa were evaluated. Our results showed that combined treatment down-regulates IL-1α and IL-8 gene expression, up-regulates IFN-γ and tends to regulate inflammation induced by ETEC through cytokine IL-10. In general, changes in cytokine gene expression correlated with the proportions of immune cells isolated from the same part of the jejunal mucosa. Results indicate that probiotic L. plantarum in combination with flax-seed oil rich in n-3 PUFAs has anti-inflammatory properties, stimulates Th1-mediated cell immunity and phagocytosis, and tends to regulate the inflammatory response induced by ETEC.


BRD7 suppresses tumor chemosensitivity to CHK1 inhibitors by inhibiting USP1-mediated deubiquitination of CHK1.
Checkpoint kinase 1 (CHK1), a key effector in the cellular response to DNA lesions, is a crucial component of all cell cycle checkpoints. Recent reports have revealed that CHK1 is highly expressed in numerous cancer types in the clinical settings. However, the mechanisms underlying the regulation of CHK1 expression in tumor cells remain unclear. Here, we report that CHK1 is negatively regulated by the bromodomain-containing protein 7 (BRD7). Specifically, BRD7 silencing increased CHK1 (but not CHK2) expression at both mRNA and protein levels, in a p53-independent manner in multiple tumor cell lines. Furthermore, BRD7 silencing stabilized CHK1 via reducing its ubiquitination. Mechanistically, BRD7 knockdown not only increased the levels of USP1, a deubiquitinase for CHK1, but also promoted the interaction between CHK1 and USP1, subsequently enhancing the de-ubiquitination of CHK1. USP1 knockdown abrogated BRD7 silencing-induced CHK1 induction. Biologically, the increased expression of CHK1 in tumor cells caused by BRD7 silencing significantly increased cell sensitivity to CHK1 inhibitors by enhancing tumor cell apoptosis, and this effect was reversed by the simultaneous knockdown of CHK1 or USP1. Taken together, our findings suggest that BRD7 is a potential genetic or drug target that may help to improve the efficacy of chemotherapeutic drugs targeting CHK1 in combinatorial therapy.


[Screening for sepsis, the central role of the nurse].
In 2016, the International Consensus Conference 'Sepsis-3' highlighted the value of Sequential Organ Failure Assessment (SOFA) and Quick Sequential Organ Failure Assessment (qSOFA) scores in addition to medical and paramedical clinical reasoning to assess severity and the risk of mortality. The option of using qSOFA scores in healthcare services underlines the important role of nurses in the early detection of sepsis with a risk of unfavourable outcome, raising hopes of reducing the associated mortality.


Hip fracture incidence in the canton of Vaud, Switzerland, 1986-1991.
The objective of this study was to estimate the incidence of hip fracture in the canton of Vaud, Switzerland (total population 584,000), for the period 1986-1991 using routine hospital discharge data collected by the Cantonal Service of Statistical Research and Information (SCRIS). For the survey period, the estimated average annual crude incidence rate of hip fractures was 167 per 100,000 persons aged 20 or older (241 for women and 84 for men). For the population aged 50 years or older, the crude incidence rate was 388 per 100,000 persons (546 for women and 185 for men). The average annual age-specific rates rose exponentially by successive 5-year age groups. The median age of patients at the time of the fracture was 82 years in women and 74 years in men. There was no significant difference between the total number of cervical and trochanteric fractures. Between the ages of 20 and 84 years, the cumulative risk for a woman to be admitted to hospital with a hip fracture was twice that of a man (15.8% vs 7.8%). From 1986 to 1991, the age- and sex-adjusted incidence, like the ratio of cervical to trochanteric fractures, did not show any significant trend, although it was consistent with an increase in men (p = 0.09). However, the annual number of fractures rose from 644 to 776, particularly among very aged men. The mean length of stay in the acute care hospital fell from 38 days in 1986 to 25 days in 1991.(ABSTRACT TRUNCATED AT 250 WORDS)


Home-based interventions for black patients with uncontrolled hypertension: a cluster randomized controlled trial.
Assess the comparative effectiveness of two blood pressure (BP) control interventions for black patients with uncontrolled hypertension. A total of 845 patients were enrolled in a three-arm cluster randomized trial. On admission of an eligible patient, field nurses were randomized to usual care, a basic or augmented intervention. Across study arms there were no significant 12 months differences in BP control rates (primary outcome) (25% usual care, 26% basic intervention, 22% augmented intervention); systolic BP (143.8 millimeters of mercury [mmHg], 146.9 mmHG, 143.9 mmHG, respectively); medication intensification (47, 43, 54%, respectively); or self-management score (18.7, 18.7, 17.9, respectively). Adjusted systolic BP dropped more than 10 mmHg from baseline to 12 months (155.5-145.4 mmHg) among all study participants. Neither the augmented nor basic intervention was more effective than usual care in improving BP control, systolic BP, medication intensification or patient self-management. Usual home care yielded substantial improvements, creating a high comparative effectiveness threshold. NCT00139490.


Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study.
The present study was performed to evaluate the significance of biologic subtype and 21-gene recurrence score relative to local recurrence and local-regional recurrence after breast conservation treatment with radiation. Eastern Cooperative Oncology Group E2197 was a prospective randomized clinical trial that compared two adjuvant systemic chemotherapy regimens for patients with operable breast carcinoma with 1-3 positive lymph nodes or negative lymph nodes with tumor size >1.0 cm. The study population was a subset of 388 patients with known 21-gene recurrence score and treated with breast conservation surgery, systemic chemotherapy, and definitive radiation treatment. Median follow-up was 9.7 years (range = 3.7-11.6 years). The 10-year rates of local recurrence and local-regional recurrence were 5.4 % and 6.6 %, respectively. Neither biologic subtype nor 21-gene Recurrence Score was associated with local recurrence or local-regional recurrence on univariate or multivariate analyses (all P ≥ 0.12). The 10-year rates of local recurrence were 4.9 % for hormone receptor positive, HER2-negative tumors, 6.0 % for triple negative tumors, and 6.4 % for HER2-positive tumors (P = 0.76), and the 10-year rates of local-regional recurrence were 6.3, 6.9, and 7.2 %, respectively (P = 0.79). For hormone receptor-positive tumors, the 10-year rates of local recurrence were 3.2, 2.9, and 10.1 % for low, intermediate, and high 21-gene recurrence score, respectively (P = 0.17), and the 10-year rates of local-regional recurrence were 3.8, 5.1, and 12.0 %, respectively (P = 0.12). For hormone receptor-positive tumors, the 21-gene recurrence score evaluated as a continuous variable was significant for local-regional recurrence (hazard ratio 2.66; P = 0.03). The 10-year rates of local recurrence and local-regional recurrence were reasonably low in all subsets of patients. Neither biologic subtype nor 21-gene recurrence score should preclude breast conservation treatment with radiation.


Computer system for quantitative evaluation of an electrotactile vocoder for artificial hearing.
A computer-controlled experimental electrotactile vocoder system is designed to evaluate quantitatively the transmission of speech information and to test various design options for tactual vocoders. The system is composed of a digital speech synthesizer, a digital vocoder, a computer-driven electrotactile display, and an adaptive controller for psychophysical experimentation. Samples of continua representing speech contrast types occurring in natural languages are synthesized by systematically manipulating selected subphonemic features. The synthesized speech stimuli are processed using a programmable vocoder and presented to the skin with an electrotactile display belt worn on the abdomen. Transmission of significant speech parameters is quantitatively evaluated using adaptive psychophysical techniques and labeling tests. The system is used to assess the potential of speech transmission through the skin and to evaluate different vocoder configurations and processing techniques for tactual vocoders to be used as artificial hearing devices by the deaf.


Effects of preeclampsia on the amplitude integrated electroencephalography activity in preterm infants.
Preeclampsia leads to chronic intrauterine hypoxia by interfering with placental blood supply. The aim of this study was to investigate whether preeclampsia exposure has an influence on the central nervous system of infants, as monitored by amplitude integrated electroencephalography (aEEG). We recruited 52 infants with gestational age between 30 and 34 weeks. Twenty-seven infants were born to preeclamptic mothers, and 25 gestational age-matched infants whose mothers were healthy were enrolled as a control group. aEEG recordings were performed between 24 and 48 h of life using a cerebral function monitor (CFM) (Olympic Brainz monitor). Along with aEEG, middle cerebral artery (MCA) blood flow velocities (BFV) were measured using Doppler ultrasound. The duration of quiet sleep was significantly shorter (P=0.001), and Burdjalov score was lower (P=0.04) in the preeclampsia group. However, there was no change in MCA BFV in this group. Preeclampsia altered cerebral electrical activity of premature infants born to preeclamptic mothers.


Novel porous gold-palladium nanoalloy network-supported graphene as an advanced catalyst for non-enzymatic hydrogen peroxide sensing.
In an effort to develop electrocatalysts associated with effective design, testing, and fabrication, novel porous gold-palladium nanoalloy network-supported graphene (AuPd@GR) nanohybrids were successfully synthesized via electroless deposition followed by a chemical vapor deposition (CVD) method for the first time. The AuPd@GR nanohybrids were obtained as a continuous, porous, transparent, bendable, and ultrathin film with good assembly of the AuPd nanoalloy particles (<10nm) within the GR. The AuPd@GR nanohybrids exhibited excellent catalytic activity towards H2O2 detection with a wide detection range (5μM-11.5mM), high sensitivity (186.86μAmM(-1)cm(-2)), low limit of detection (1μM), fast response (3s), and long-term working stability (2500s). Furthermore, the AuPd@GR nanohybrids demonstrated outstanding durability, along with negligible interference from ascorbic acid, dopamine, uric acid, urea, potassium ions, chloride ions, and glucose. These findings open a new pathway to fabricate electrocatalysts for application in high performance electrochemical sensors and bioelectronics.


Recent developments in the detailed characterization of polymers by multidimensional chromatography.
Synthetic polymers as well as biopolymers reveal complex structures, such as variations in functionality, chain length and architecture. Therefore, combinations of different chromatographic techniques are a prerequisite for a detailed characterization. One possible approach is the combination of high performance liquid chromatography at critical conditions (LCCC) and size-exclusion chromatography, also named as two-dimensional chromatography, which allows the separation of the polymers according to different properties, like molar mass, chemical composition or functionality. In addition, LCCC hyphenated with different mass spectrometry techniques, e.g. MALDI-TOF or ESI-TOF, leads to additional information about molecular details of the polymeric structure. We summarize in this article the recent developments in two-dimensional chromatography of synthetic polymers and biopolymers since 2005.