Prostaglandin E2 promotes the survival of bone marrow-derived dendritic cells.
Since dendritic cells (DC) participate in both innate and adaptive immunity, their survival and expansion is tightly controlled. Little is known about the mechanisms of DC apoptosis. PGE(2), an arachidonic acid metabolite, plays an essential role in DC migration. We propose a novel function for PGE(2) as a DC survival factor. Our studies demonstrate that PGE(2) protects DC in vitro against apoptosis induced by withdrawal of growth factors or ceramide. DC matured in conditions that inhibit endogenous PGE(2) release are highly susceptible to apoptosis and exogenous PGE(2) re-establishes the more resistant phenotype. The antiapoptotic effect is mediated through EP-2/EP-4 receptors and involves the PI3K --> Akt pathway. PGE(2) leads to increased phosphorylation of Akt, protection against mitochondrial membrane compromise, and decreased caspase 3 activity. Macroarray data indicate that PGE(2) leads to the down-regulation of a number of proapoptotic molecules, i.e., BAD, several caspases, and granzyme B. In vivo, higher numbers of immature and Ag-loaded CFSE-labeled DC are present in the draining lymph nodes of mice inoculated with PGE(2) receptor agonists, compared with animals treated with ibuprofen or controls injected with PBS. This suggests that PGE(2) acts as an endogenous antiapoptotic factor for DC and raises the possibility of using PGE(2) agonists to increase the survival of Ag-loaded DC following in vivo administration.


Effect of presence or absence of corpora lutea on milk production in East Friesian dairy ewes.
The potential luteal effects on milk production were examined in dairy ewes that were not superovulated in contrast to studies using superovulated ewes. Lactating East Friesian crossbred ewes (n = 24) were synchronized using intravaginal progesterone (controlled intravaginal drug-releasing device), PGF2alpha, and gonadotropins. After ovulation, corpora lutea (CL) were counted via laparoscopy on d 4 and 11. On d 5, ewes received either saline (CLYES, n = 12) or PGF2alpha (CLNO, n = 12) to allow CL persistence (2.4 +/- 0.3 CL on d 11) or regression (0 CL on d 11), respectively. Each ewe received two CIDR d 5 to 18 to maintain high concentrations of plasma progesterone (P4) and to suppress estradiol (E2). Each ewe received PGF2alpha on d 18. Data were collected during three periods (pretreatment: d 0 to 5; treatment: d 6 to 18; posttreatment: d 19 to 25). Milk yield and milking time were recorded daily, milk samples were obtained for analyses of fat and protein, and blood samples were collected for P4 and E2 immunoassay. During treatment, CLYES ewes had higher milk yield (1.56 vs. 1.44 +/- 0.01 kg/d), milk fat (92.2 vs. 81.1 +/- 1.3 g/d), and milk protein (83.7 vs. 77.5 +/- 0.8 g/d) compared with CLNO ewes, respectively. Differences were maintained posttreatment, despite luteolysis in CLYES ewes. Estradiol concentrations did not differ between treatments and were low after d 5. Milk production was increased in East Friesian ewes in the presence of an average of 2.4 corpora lutea, an effect independent of estradiol.


Pediatric reference intervals for hematology parameters in healthy infants and young children in Iran.
Defining accurate age- and sex-specific reference intervals (RIs) for hematology parameters, especially for the pediatric population, is important for making an appropriate clinical diagnosis. To address gaps, we established age-specific RIs for 11 hematologic parameters in Iranian children younger than 30 months for the first time. Fresh whole blood samples collected from a total of 344 participants (males: 158 and females: 186) ages 3 days to 30 months, with a mean age of 12.91 ± 7.15 months, were recruited from healthcare centers in Mashhad, Iran. Hematologic parameters, including complete blood count (CBC), were analyzed on the Sysmex auto-analyzer system (KX-21 N). RIs were calculated with 90% confidence intervals using the direct method based on CLSI Ep28-A3 and C28-A3 guidelines. None of the CBC parameters required sex partitioning. Of 11 CBC parameters, six required age partitions of 3 days-<4 months, 4-<10, 10-<15, and 4-<30 months. Five parameters (i.e., white blood cell count, mean corpuscular hemoglobin concentration, mean platelet volume, red cell distribution width, and platelet distribution width) did not demonstrate age-specific changes. RIs of red blood cell count and hematocrit, as well as hemoglobin, increased with age, while mean corpuscular volume, mean corpuscular hemoglobin, and platelet count, decreased with age. In this study, we established RIs for 11 hematology parameters in young children. Age partitioning was required for six parameters demonstrating marked changes during the early period of growth and development and necessitating the use of pediatric-specific reference standards.


Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury.
Disruption of the alveolar septal barrier leads to acute lung injury, patchy alveolar flooding, and hypoxemia. Although calcium entry into endothelial cells is critical for loss of barrier integrity, the cation channels involved in this process have not been identified. We hypothesized that activation of the vanilloid transient receptor potential channel TRPV4 disrupts the alveolar septal barrier. Expression of TRPV4 was confirmed via immunohistochemistry in the alveolar septal wall in human, rat, and mouse lung. In isolated rat lung, the TRPV4 activators 4alpha-phorbol-12,13-didecanoate and 5,6- or 14,15-epoxyeicosatrienoic acid, as well as thapsigargin, a known activator of calcium entry via store-operated channels, all increased lung endothelial permeability as assessed by measurement of the filtration coefficient, in a dose- and calcium-entry dependent manner. The TRPV antagonist ruthenium red blocked the permeability response to the TRPV4 agonists, but not to thapsigargin. Light and electron microscopy of rat and mouse lung revealed that TRPV4 agonists preferentially produced blebs or breaks in the endothelial and epithelial layers of the alveolar septal wall, whereas thapsigargin disrupted interendothelial junctions in extraalveolar vessels. The permeability response to 4alpha-phorbol-12,13-didecanoate was absent in TRPV4(-/-) mice, whereas the response to thapsigargin remained unchanged. Collectively, these findings implicate TRPV4 in disruption of the alveolar septal barrier and suggest its participation in the pathogenesis of acute lung injury.


Family involvement in the intensive care unit in four Nordic countries.
Relevance to clinical practice The findings from the study highlighting family involvement, high-quality communication and flexible visiting policy as central aspects of family care may inspire clinicians to identify aspects of everyday family care in their ICUs calling for further improvement. To describe family involvement, communication practices and visiting policies in adult ICUs. A cross-sectional survey. A questionnaire consisting of 11 sections was developed, pilot tested and e-mailed to 196 ICUs. The participants were intensive care nurses in adult ICUs in four Nordic countries. The survey was conducted in October to December 2019. The response rate was 81% (158/196) of the invited ICUs. Most of the units had fewer than 11 beds. Family participation in patient care, including involvement in ward rounds and presence during cardiopulmonary resuscitation, varied between the countries, whereas most families in all countries were involved in decision-making. Family conferences were generally initiated by staff or family members. Children under 18 did not always receive information directly from the staff, and parents were not advised about how to inform their children. Although most respondents described open visiting, restrictions were also mentioned in free-text comments. The level of family care in ICUs in the four Nordic countries is generally based on nurses' discretion. Although most Nordic ICUs report having an open or flexible visiting policy, a wide range of potential restrictions still exists. Children and young relatives are not routinely followed up. Family members are included in communication and decision-making, whereas family involvement in daily care, ward rounds and family-witnessed resuscitation seem to be areas with a potential for improvement.


[Early trans-sphenoid decompression in indirect traumatic optic neuropathy].
Indirect traumatic optic neuropathy represents a severe, potential vision-threatening disease process that requires close interdisciplinary cooperation for treatment. In general, any therapy has been discussed controversially in the literature. Based upon experiences with spinal cord trauma, high-dose steroid therapy is recommended initially to minimize secondary consequences following orbital trauma. The usefulness of surgical decompression of the optic nerve has been confirmed in several studies but is still not recommended in principle. In nine consecutive patients with known indirect traumatic optic neuropathy and marked losses of vision, transsphenoidal optic decompressions were carried out with simultaneous systemic megadose steroid therapy. A postoperative increase in visual acuity from 1/35 to 10/20 occurred in five patients, while no improvement in visual acuity could be achieved in the other four patients. Previous reports have indicated that some authors will not recommend surgical decompressions if a loss of sight or no light perception occurs directly after an accident. This situation was seen in seven of our patients. The visual acuity of four patients remained no light perception in spite of surgical treatment. In three other patients, an increase in visual acuity from amaurosis improved to 1/35, 4/20 and 8/20, respectively, following early decompression combined with steroids. This experience together with the positive results of other studies supports carrying out decompressions of the optic nerve, even when an amaurosis occurs directly after trauma.


Deleterious mutations and the evolution of sexual reproduction.
The origin and maintenance of sexual reproduction continues to be an important problem in evolutionary biology. If the deleterious mutation rate per genome per generation is greater than 1, then the greater efficiency of selection against these mutations in sexual populations may be responsible for the evolution of sex and related phenomena. In modern human populations detrimental mutations with small individual effects are probably accumulating faster than they are being eliminated by selection.


Synthesis and structural characterization of group 4 metal carboxylates for nanowire production.
The synthesis and characterization of a series of group 4 carboxylate derivatives ([M(ORc)4] where M = Ti, Zr, Hf) was undertaken for potential utility as precursors to ceramic nanowires. The attempted syntheses of the [M(ORc)4] precursors were undertaken from the reaction of [M(OBu(t))4] with a select set of carboxylic acids (H-ORc where ORc = OPc (O2CCH(CH3)2), OBc (O2CC(CH3)3), ONc (O2CCH2C(CH3)3)). The products were identified by single-crystal X-ray diffraction studies as [Ti(η(2)-OBc)3(OBu(t))] (1), [Zr2(μ3-O)(μ-OPc)4(μ,η(2)-OPc)(η(2)-OPc)]2 (2), [H]2[Zr(η(2)-OBc)2(OBc)2(OBc)2] (3), [Zr(μ-ONc)2(η(2)-ONc)2]2 (4), or [Hf(μ-ORc)2(η(2)-ORc)2]2 [ORc = OPc (5), OBc (6, shown), ONc (7)]. The majority of compounds (4-7) were isolated as dinuclear species with a dodecahedral-like (CN-8) bonding mode around the metals due to chelation and bridging of the ORc ligand. The two monomers (1 and 3) were found to adopt a capped trigonal prismatic and CN-8 geometry, respectively, due to chelating ORc and terminal ORc or OBu(t) ligands. The metals of the oxo-species 2 were isolated in octahedral and CN-8 arrangements. These compounds were then processed by electrospinning methods (applied voltage 10 kV, flow rate 30-60 μL/min, electric field 0.5 kV/cm), and wire-like morphologies were isolated using compounds 4, 6 (shown), and 7.


Role of personality and expectations for itch and scratching induced by audiovisual itch stimuli.
Itch is an unpleasant, bodily sensation, which--similar to pain--evokes behavioral reactions. As a response to itch, people start scratching. There are different ways to provoke itch and subsequent scratching in experimental settings. A non-invasive method to induce itch and scratching is the presentation of itch-related (audio-) visual stimulus material, like slide-supported lectures on skin diseases or crawling insects. Also, watching videos showing other people scratching provokes itch and the desire to scratch. In this review, we focus on psychological factors, which were shown to be associated with itch and scratching provoked by (audio-) visual itch stimuli. First, we summarize the findings on the relationship between personality characteristics and (audio-) visually induced itch. Agreeableness and self-consciousness were shown to be associated with induced itch and scratching in patients with chronic skin diseases, while neuroticism was linked to induced itch in healthy subjects. Second, we present results of a recent study, in which we altered the expectations towards audio-visually induced itch and scratching by changing the information given on upcoming itch stimuli. It was shown that subjects being informed about itch stimuli in a neutral way displayed a shorter scratch duration in itch inducing situations than subjects having catastrophizing expectations. Also, the increase in scratch duration and in the number of scratch movements induced by audiovisual itch stimuli was higher when the patients were not informed about itch induction. Thus, in itch patients neither catastrophizing nor trivializing symptoms seems to be helpful.


Current report on the interferon program at Roswell Park Memorial Institute.
An overview of the interferon program at Roswell Park Memorial Institute (RPMI), is presented. This program encompasses three interrelated areas of research and new drug development: (a) basic research on purification and characterization of animal and human interferons (leukocyte, fibroblast, and immune); (b) large scale manufacture and preclinical testing of human fibroblast interferon (HFIF); and (c) clinical trials with HFIF to determine its safety of administration as well as antiviral, antitumor, and immunomodulatory activities in patients with neoplastic or viral disease. The antitumor effect of HFIF produced at RPMI as assessed by intralesional injection of various metastatic nodules resulted in an overall 71% local response. Phase I studies in 13 patients demonstrated that HFIF can be administered safely by the subcutaneous, intramuscular, and intravenous routes in doses up to 25 million units per day without any serious untoward effects. Intrathecal administration of HFIF into patients with CNS leukemia was also well tolerated. Pharmacokinetic studies indicated significant levels of HFIF in serum and cerebrospinal fluid after intravenous and intrathecal administration, respectively. Coincidental with the HFIF systemic administration during the Phase I trials, favorable responses in several laboratory, immune, and clinical parameters were observed. These results provide the rationale for conducting phase II and phase III clinical trials with HFIF produced at RPMI.


Antidepressant reversal of interferon-alpha-induced anhedonia.
Interferon-alpha(IFN-alpha) is used clinically in the treatment of several pathologies such as hepatitis C and various cancers. The positive therapeutic potential is however often limited by negative secondary effects which include major depression, one of the cardinal symptoms of which is anhedonia which has been operationalized as a decreased sensitivity to rewards (inability to experience pleasure). Previous studies have demonstrated the existence of anhedonia in rats following an acute injection of IFN-alpha at doses corresponding to those used in clinical applications. If this previously demonstrated anhedonia is indeed part of a depression syndrome in rats, this behavioural symptom should be reversible by the administration of antidepressants. The objective of the present experiment was to determine whether two commonly used antidepressants (desipramine and fluoxetine) were effective in ameliorating IFN-alpha-induced anhedonia in rats. The experiment consisted of two phases. In the first, the effects of daily systemic injections of 104 units/kg of IFN-alpha (or vehicle) were evaluated with the three-bottle (1%, 8%, and 32%) sucrose-consumption test. In the second phase of the experiment, in addition to continued injections of IFN-, different groups received daily injections of desipramine (7.5 mg/kg ip), fluoxetine (7.5 mg/kg ip), or vehicle. The IFN-alpha injections during Phase 1 resulted in clear anhedonia, as expressed by increased consumption of the 32% solution and decreased consumption of 1% over the 33 days of this phase. After 15 days of antidepressant treatments, 32% sucrose consumption returned to baseline values. We have therefore confirmed that IFN-alpha-induced anhedonia is susceptible to reversal following chronic antidepressant treatment and thus it may appear timely to consider the prophylactic use of such in particular patients prescribed IFN in the clinic.


Should We Check the Routine Postoperative MRI for Hematoma in Spinal Decompression Surgery?
A postoperative magnetic resonance imaging (MRI) is performed as a routine to assess decompression of the spinal cord as well as to evaluate postoperative complications. The purpose of this study is to analyze the efficacy of postoperative MRI for hematoma in spinal decompression surgery. Between January 1, 2008 and January 31, 2015, 185 patients who underwent postoperative MRI after spinal decompression surgery were included in this study. We checked the history of the use of an anticoagulant or antiplatelet agent, withdrawal period, blood platelet count, and prothrombin time (international normalized ratio [INR]). We measured the total amount of suction drainage and duration until removal. We retrospectively reviewed the presence of hematoma and thecal sac compression. Postoperative prognosis was evaluated by a visual analog scale (VAS) and the Oswestry Disability Index (ODI). Hematomas were found on postoperative MRI scans in 97 out of 185 patients (52.4%). Thirty patients had a thecal sac compressing hematoma: 7 in the cervical spine, 1 in the thoracic spine, and 22 in the lumbar spine. The occurrence of hematoma did not show significant difference according to the use of an anticoagulant (p = 0.157). The blood platelet count, prothrombin time (INR), and suction drainage duration did not have a statistically significant correlation with the occurrence of hematoma (p = 0.562, p = 0.506, and p = 0.429, respectively). The total amount of suction drainage was significantly different according to the presence of hematoma (p = 0.022). The total 185 patients had a significant decrease in the postoperative VAS score (p < 0.001), and the diminution of VAS score was not significantly different according to the occurrence of hematoma (p = 0.243). Even in the cases of thecal sac compressing hematoma, the reduction of VAS score was not significantly different (p = 0.689). Postoperative MRI for hematoma in spinal decompression surgery has little effect on prognosis or management. Therefore, indiscriminate postoperative MRI should be avoided and MRI should be performed depending on the patient's status.


A statistical model for predicting protein folding rates from amino acid sequence with structural class information.
Prediction of protein folding rates from amino acid sequences is one of the most important challenges in molecular biology. In this work, I have related the protein folding rates with physical-chemical, energetic and conformational properties of amino acid residues. I found that the classification of proteins into different structural classes shows an excellent correlation between amino acid properties and folding rates of two- and three-state proteins, indicating the importance of native state topology in determining the protein folding rates. I have formulated a simple linear regression model for predicting the protein folding rates from amino acid sequences along with structural class information and obtained an excellent agreement between predicted and experimentally observed folding rates of proteins; the correlation coefficients are 0.99, 0.96 and 0.95, respectively, for all-alpha, all-beta and mixed class proteins. This is the first available method, which is capable of predicting the protein folding rates just from the amino acid sequence with the aid of generic amino acid properties and structural class information.


Malaria in HIV-infected patients in a nonendemic setting.
The impact of HIV infection on malaria is unclear in nonendemic areas. In endemic territories, HIV has been reported to be a risk factor for higher morbidity. Nowadays, as HIV-infected patients travel more, it is important to assess the impact of HIV at the individual level on imported malaria. This retrospective case-control study collected data on HIV-infected patients diagnosed with malaria (2000-2017) and matched them with two controls based on age, sex and ethnicity. Clinical and biological parameters were collected and compared. We identified 47 cases and matched them with 94 controls. Comparing each of the WHO 2014 severity criteria, hyperparasitemia above 10% (P = 0.006; 12.8 versus 1.1%), icterus (P = 0.042; 14.9 versus 4.3%), acute renal failure (P = 0.022; 25.5 versus 9.6%) and bacteraemia (P = 0.014; 6.4 versus 0%) were significantly more present in HIV-infected patients with a trend to more cerebral malaria (12.8 versus 6.4%). HIV- infected patients were hospitalized more frequently and for longer periods. We observed a higher number of severity criteria when CD4 T-cell count was lower, especially below 200 cells/μl. The difference in occurrence of severe malaria disappeared when patients with CD4 T-cell count more than 500 cells/μl and undetectable viral load (n = 9) were compared with controls. De-novo HIV diagnosis was made during the malaria episode in 17% of cases. HIV infection has an impact on the imported malaria profile, although it is unclear whether well controlled HIV-infected patients have a higher risk of severe malaria. HIV-infected patients should be particularly targeted for pretravel advice.


Structural phase transitions and photoluminescence properties of Eu(3+) doped Ca(2-x)BaxLaNbO6 phosphors.
Crystal structures of the series of double perovskites Ca(2-x)BaxLaNbO6:Eu(3+) phosphors have been examined by powder X-ray diffraction and Rietveld refinements. Ca2LaNbO6 has a monoclinic (P21/n) and Ba2LaNbO6 has a monoclinic (C2/m) structure. The structural phases of Ca(2-x)BaxLaNbO6:Eu(3+) samples are divided into three sections depending on different Ca/Ba ratios: (1) monoclinic phase (P21/n) as Ca2LaNbO6 in the range of x = 0-0.1, (2) mixed phases containing Ca2LaNbO6 and Ba2LaNbO6 between 0.15 and 1.2, and (3) monoclinic phase (C2/m) as Ba2LaNbO6 for x = 1.4-2. Eu(3+) ions act as the structural probes to study the structural phase transitions, and the evolution of the photoluminescence properties and thermal stability behaviours has been also comparatively investigated depending on different structural symmetries from Ca2LaNbO6 to Ba2LaNbO6 phase. The strong red emission from (5)D0-(7)F2 peaking at 618 nm can be found in Ca2LaNbO6:Eu(3+) phosphors, which is attributed to the low crystal field effect of the activator ions located in the highly distorted [LaO8] polyhedra sites. The composition-optimized phosphors can find applications in white light emitting diodes (LEDs).


[Primary carcinoma of the gallbladder: report of 41 cases (author's transl)].
The Authors described their experience in 41 patients operated on because of gallbladder cancer. The overall mortality was 20%. Four cases suitables for a "radical" wide resection showed an average survival of 8 months, while 2 on 3 patients with in "situ" carcinoma treated by simple cholecystectomy are still alive at more than 3 years, the other dying after five years because of disease not related to the gallbladder cancer. The bad general prognosis of the disease is mainly related to the delayed diagnosis together with the anatomical relations of the gallbladder as demonstrated by the discouraging survival in the "radically" widely resected patients. It must be considered consequently categorical to realize an early cholecystectomy, the only possible preventive procedure, in the height risk patients.


[Effect of Lp(a) on human mesangial cell proliferation, adhesion and migration].
The renal disease is commonly associated with hyperlipidemia and correlates with glomerular accumulation of atherogenic lipoproteins and mesangial hypercellularity. Therefore, in this study, the authors investigated a possible growth stimulatory effect and mode of action of lipoprotein(a) [Lp(a)] in human mesangial cells HMC, and the effect of Lp(a) on adhesion and migration in human mesangial cells. The DNA synthesis of HMC was measured by (3)H-thymidine incorporation. The cell adhesion was detected by the expression of vinculin by means of indirect immunofluorescence. The cell migration was observed under the microscope. The incubation of HMC with Lp(a) for 24 hours induced a significant dose-dependent proliferation of HMC [Lp(a): 5 microg, 10 microg, 25 microg, 50 microg/ml vs. control 0 microg/ml; (3)H-TdR incorporation (x 10(3)cpm): 1.69 +/- 0.48, 3.59 +/- 0.68, 4.14 +/- 0.78, 4.05 +/- 0.55 vs. 1.64 +/- 0.31, P < 0.01]. The vinculin staining by indirect immunofluorescence showed positive result when HMC was incubated with 10 microg/ml Lp(a) for 24 hours, while vinculin was negative when HMC was incubated with 0 microg/ml Lp(a) as the control of the study. The incubation of HMC with 10 microg/ml Lp(a) for 72 hours demonstrated significant cell migration effect compared to the control of 0 microg/ml. (16.2/LP vs. 2.4/LP, P < 0.01). Lp(a) could stimulate a proliferation, adhesion and migration effect on human mesangial cells.


Validation of a PCR-based method for detection of food-borne thermotolerant campylobacters in a multicenter collaborative trial.
A PCR-based method for rapid detection of food-borne thermotolerant campylobacters was evaluated through a collaborative trial with 12 laboratories testing spiked carcass rinse samples. The method showed an interlaboratory diagnostic sensitivity of 96.7% and a diagnostic specificity of 100% for chicken samples, while these values were 94.2 and 83.3%, respectively, for pig samples.


CFD-aerosol modeling of the effects of wall composition and inlet conditions on carbon nanotube catalyst particle activity.
The evolution of iron catalyst particles during aerosol (floating catalyst) Chemical Vapor Deposition (CVD) synthesis of Carbon Nanotubes (CNTs) from CO is computed using a multi species Computational Fluid Dynamics (CFD) model incorporating a lognormal aerosol method of moments (MOM) to describe their dynamics and a combined chemical kinetics and equilibrium model for catalytic production of CO2. The influence of the presence of iron at the reactor walls, the fed particle size, number concentration and polydispersity and the effect of the catalytic production of CO2 at the reactor wall are studied in terms of particle size, concentration and polydispersity and reagent concentration during CNT synthesis. It is found that iron catalyst particle dynamics are essentially insensitive to wall iron concentrations and, for a wide range of particle sizes and concentrations, it is found that the catalyst particles are stable up to a critical CNT window in which CNT nucleation and growth occurs. Concentrations of catalyst particles significantly above 1 x 10(14) #/m3, however, lead to poor control over catalyst particle size and polydispersity at the CNT nucleation front which, in turn, leads to poor control over CNT diameter. The location of the growth window is shown to be directly associated with the availability of catalytically produced CO2 diffusing from the reactor walls to the reactor core. These results help to explain the large variations in CNT diameter and chirality and the inefficient use of catalyst material in other floating catalyst CNT processes based on in-situ catalyst particle synthesis.


Simultaneous determination and method validation of difenoconazole, propiconazole and pyraclostrobin in pepper and soil by LC-MS/MS in field trial samples from three provinces, China.
A liquid chromatography-electrospray ionization tandem mass spectrometry method was developed for simple and accurate detection of the fungicides difenoconazole, propiconazole and pyraclostrobin in peppers and soil. Three fungicides residues were extracted from samples by acetonitrile and cleaned up by dispersive solid-phase extraction before instrumental analysis. The accuracy and precision of the method were evaluated by conducting an intra- and inter-day recovery experiment. The limits of quantification and detection of difenoconazole, propiconazole and pyraclostrobin in pepper and soil were 0.005 and 0.0015 mg/kg, respectively. The recoveries were investigated by spiking pepper and soil at three levels, and were found to be in the ranges 79.62-103.15% for difenoconazole, 85.94-103.35% for propiconazole and 80.14-97.69% for pyraclostrobin, with relative standard deviations <6.5%. Field experiments were conducted in three locations in China. The half-lives of difenoconazole, propiconazole and pyraclostrobin were 5.3-11.5 days in peppers and 6.1-32.5 days in soil. At harvest, pepper samples were found to contain difenoconazole, propiconazole and pyraclostrobin well below the maximum residue limits of European Union at the interval of 21 days after last application following the recommended dosage.


Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma: A case report and review of the literature.
Although primary hepatic neuroendocrine carcinomas, whose prognostic mechanisms remain unclear, are rare, coexistence of neuroendocrine carcinomas and other tumors is rarer. In this report, we describe a unique case of coexistence between primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma in the pancreas. A 64-year-old woman with a history of diabetes, but none of hepatitis, was admitted to hospital because of intermittent epigastric distension and pain discomfort for more than 1 month aggravated 1 day. A contrast-enhanced computed tomography (CT) scan of the upper abdomen and abdominal magnetic resonance imaging (MRI) revealed a thickening of the bile duct wall in the middle and lower segment of common bile duct and the corresponding lumen is narrow and low-density tumors with ring enhancement (1.83 cm × 1.9 cm) in lobi hepatis dexte. Primary neuroendocrine carcinoma of the liver was diagnosed to be coexisting with a distal cholangiocarcinoma, which had invaded the pancreas. Immunohistochemical examination revealed that the neoplastic cells strongly expressed chromogranin A, synaptophysin, and CD56 proteins. The tumor cells did not express HepPar-1, glypican-3, S-100, CK7, and CK19 in the liver tumor. A distal bile duct in pancreatic tissues shows the characteristics of typical bile duct carcinoma, as an invasion of carcinoma is also seen in the pancreatic tissues. Gastrointestinal endoscopy, chest and abdominal CT, abdominal MRI, and positron emission tomography (PET)-CT were used to exclude metastatic neuroendocrine tumors of the liver. Resection of the pancreas-duodenum, the right anterior lobe of the liver, and regional lymph nodes was performed in patients. The patient had survived for 5 months after the operation. A unique case of a coexistence of primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma, which had invaded the pancreas. No treatment guidelines are established for the treatment of the unique case.


Long-distance stone transport and pigment use in the earliest Middle Stone Age.
Previous research suggests that the complex symbolic, technological, and socioeconomic behaviors that typify Homo sapiens had roots in the middle Pleistocene <200,000 years ago, but data bearing on human behavioral origins are limited. We present a series of excavated Middle Stone Age sites from the Olorgesailie basin, southern Kenya, dating from ≥295,000 to ~320,000 years ago by argon-40/argon-39 and uranium-series methods. Hominins at these sites made prepared cores and points, exploited iron-rich rocks to obtain red pigment, and procured stone tool materials from ≥25- to 50-kilometer distances. Associated fauna suggests a broad resource strategy that included large and small prey. These practices imply notable changes in how individuals and groups related to the landscape and to one another and provide documentation relevant to human social and cognitive evolution.


The role of left supplementary motor area in grip force scaling.
Skilled tool use and object manipulation critically relies on the ability to scale anticipatorily the grip force (GF) in relation to object dynamics. This predictive behaviour entails that the nervous system is able to store, and then select, the appropriate internal representation of common object dynamics, allowing GF to be applied in parallel with the arm motor commands. Although psychophysical studies have provided strong evidence supporting the existence of internal representations of object dynamics, known as "internal models", their neural correlates are still debated. Because functional neuroimaging studies have repeatedly designated the supplementary motor area (SMA) as a possible candidate involved in internal model implementation, we used repetitive transcranial magnetic stimulation (rTMS) to interfere with the normal functioning of left or right SMA in healthy participants performing a grip-lift task with either hand. TMS applied over the left, but not right, SMA yielded an increase in both GF and GF rate, irrespective of the hand used to perform the task, and only when TMS was delivered 130-180 ms before the fingers contacted the object. We also found that both left and right SMA rTMS led to a decrease in preload phase durations for contralateral hand movements. The present study suggests that left SMA is a crucial node in the network processing the internal representation of object dynamics although further experiments are required to rule out that TMS does not affect the GF gain. The present finding also further substantiates the left hemisphere dominance in scaling GF.


Vaccines for preventing hepatitis B in health-care workers.
Hepatitis B virus (HBV) causes acute and chronic liver diseases. Hepatitis B vaccination is recommended for health-care workers. To assess the beneficial and harmful effects of hepatitis B vaccination in health-care workers. We searched the trial registers of The Cochrane Hepato-Biliary Group, The Cochrane Library, MEDLINE, and EMBASE to February 2003. Randomised trials comparing any dose, injection route, injection site, or schedule of hepatitis B plasma-derived vaccines (PDV) or recombinant vaccines (RV) versus placebo, no intervention, or another hepatitis B vaccine in health-care workers. Two reviewers extracted the data independently. The reviewers assessed the methodological quality of the trials regarding generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The results were presented as relative risk (RR) with 95% confidence intervals (CI). We identified 21 randomised trials, all with one or more methodological weaknesses. Four trials demonstrated that PDV versus placebo significantly decreased hepatitis B events at maximum follow-up (RR 0.51, 95% CI 0.35 to 0.73). RV did not differ significantly from PDV in eliciting a protective hepatitis B surface antibody (anti-HBs) level in two trials. Both vaccines were well tolerated. Low-dose vaccine (1 or 2 microg) by the intradermal route resulted in significantly more participants without protective anti-HBs level compared with high-dose (10 or 20 microg) by the intramuscular route (RR 1.41, 95% CI 1.13 to 1.76). The intradermal route caused significantly more local adverse events, while the intramuscular route caused significantly more systemic adverse events. The gluteal injection produced significantly more participants without protective anti-HBs level than the deltoid injection. The prevalence of anti-HBs seroconversion by rapid vaccination (0, 1, and 2 months) was significantly lower than that by standard vaccination (0, 1, and 6 months). Booster vaccinations with different RV doses (2.5, 5, 10, 20, or 40 microg) produced similar prevalence of anti-HBs seroconversion in three trials assessing participants who did not respond to previous HBV vaccination. PDV significantly prevents hepatitis B events. RV seems to be able to elicit similar protective anti-HBs levels. The intramuscular route with 20 microg RV was significantly more effective compared with the intradermal route with 2 microg RV as was the standard schedule compared with a rapid schedule and deltoid intramuscular injection compared with the gluteal intramuscular injection. It is unclear if booster vaccination of non-responders offers higher anti-HBs seroconversion and hepatitis B vaccine prevents the infection of hepatitis B mutants in health-care workers.


A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium.
Pulmonary neuroendocrine cells (PNEC) are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1) undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5), sensory nerves (calcitonin gene related peptide, CGRP), and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP). The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP) was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.


Stage-III and -IV endometrial cancer: A single oncology centre review of 104 cases.
The objective of this study was to evaluate the clinicopathological characteristics, treatment and prognosis of advanced endometrial cancer (EC). Patients who underwent surgery for advanced EC between January 1995 and December 2012 were retrospectively reviewed. Patients with missing data, concurrent cancers or uterine sarcomas and those who did not undergo surgery were excluded. The effects of clinicopathological factors on progression-free survival (PFS) and overall survival (OS) were analyzed. A total of 104 patients were included. Most presented with endometrioid histology (74%) and stage-III disease (87.5%), and 76.9% underwent optimal cytoreduction. A multivariate analysis confirmed that lymphovascular space invasion (LVSI) is an independent poor prognostic factor for PFS [odds ratio (OR): 21.37, p = 0.005] and OS [OR: 8.09, p = 0.044]. Suboptimal cytoreduction is another independent poor prognostic factor for PFS [OR: 5.68, p < 0.001]. Our study demonstrated that LVSI and optimal cytoreduction are the most significant factors affecting the survival of advanced EC patients.


A morphological investigation of Culicoides spp. biting midges (Diptera: Ceratopogonidae) from the Caribbean.
Features of the antennae, maxillary palps, and mouthparts of the females of seven species of Culicoides spp. biting midges collected from a montane rainforest site in Trinidad, West Indies, were studied by light and scanning electron microscopy. Comparisons were made with two British species, Culicoides impunctatus and Culicoides nubeculosus. Species-specific differences were demonstrated in the camber and pitch of mandibular teeth, the size and shape of the subapical labral sensilla, the size and depth of the palpal sensory pit, and the number and shape of heads of the palpal sensilla. Counts of sensilla coeloconica and palpal sensilla were suggested as being contributory features for the prediction of host preference, indicating that Culicoides darlingtonae, Culicoides glabellus, Culicoides insinuatus, Culicoides paraensis, and Culicoides pseudodiabolicus were probably mammalophilic species. The host preferences of Culicoides heliconiae and Culicoides flavivenula could not be determined accurately.


Shift work and risk factors for coronary heart disease in Japanese blue-collar workers: serum lipids and anthropometric characteristics.
This study was conducted to determine if there is an association between shift work and risk factors for coronary heart disease (CHD) in Japanese male blue-collar shift workers. Health check-up data on serum lipid concentration and anthropometric indices of 33 three-shift workers and 27 two-shift workers were compared with those of day workers. The average years in age of the shift workers and day workers were 34.5 (SD = 7.1) and 32.7 (SD = 7.6), respectively. Serum total cholesterol levels of three-shift, two-shift and day workers were 5.70 (SD = 1.19) mmol/l, 4.81 (SD = 1.01) mmol/l, 4.98 (SD = 0.95) mmol/l, respectively, and the cholesterol levels of three-shift workers were significantly higher than the other workers (p < 0.05). In addition, the abdominal to hip circumference ratios were 0.905 (SD = 0.060) for three-shift workers and 0.877 (SD = 0.054) for day workers, with a significant difference (p < 0.05). In the present Japanese population, three-shift workers had higher risks of CHD than day workers, which was characterized by higher levels of serum total cholesterol and tendency to central obesity. These findings held when lifestyle factors were taken into account.


Potential amyloid plaque-specific peptides for the diagnosis of Alzheimer's disease.
Amyloid plaques (AP) represent one of the main molecular hallmarks of Alzheimer's disease (AD). In order to develop new AP-specific contrast agents for AD molecular imaging, the phage display technology was used to identify peptides specific to amyloid-beta (A beta(42)). A random disulfide constrained heptapeptide phage display library was screened against A beta(42). After biopanning, 72 phage clones were isolated and their binding affinity to A beta(42) was evaluated by enzyme-linked immunosorbent assay (ELISA). The final library was enriched in two peptide sequences. The K(d) of candidate phage clones for binding to A beta(42) are in the picomolar range. The binding affinity for A beta(42) of two selected peptides was confirmed by ELISA, and the specific interaction with AP was validated by immunohistochemistry on brain sections. The preliminary MRI in vivo study, which was performed with a peptide functionalized contrast agent on AD transgenic mouse, showed encouraging results. To conclude, low molecular weight peptides presenting a specific affinity for A beta(42) were identified by phage display. As specific carriers, they have a real potential for molecular imaging of AD thanks to AP binding.


Cerebral Arterial Stiffness as A New Marker of Early Stage Atherosclerosis of The Cerebral Large Artery in Acute Stroke.
Carotid-cerebral pulse wave velocity (ccPWV) reflects the segment (C-M segment) stiffness between the common carotid artery and ipsilateral middle cerebral artery. C-M segment atherosclerosis (CMSA) is regarded the most frequent cause of anterior circulation ischemic stroke. We aimed to evaluate the association of ccPWV with early stage CMSA in this study. Eighty-one acute ischemic stroke (AIS) patients with 154 C-M segments who were successfully evaluated with digital subtraction angiography, ccPWV, carotid intima-media thickness (cIMT), and brachial-ankle pulse wave velocity were enrolled into this study. Patient demographics and clinical data were retrieved from our AIS databases. Multivariate analyses showed that CMSA was independently associated with higher systolic BP, ccPWV, and cIMT. ccPWV and cIMT presented good diagnostic values for evaluating early stage CMSA in the receiver operating characteristic curve analyses. The areas under the curve (AUCs) of ccPWV were significantly higher than that of cIMT (Z=2.204, P=0.007). The AUC, sensitivity, specificity, Youden index, and cutoff of ccPWV for detecting early stage CMSA were 0.815 (P<0.001), 86%, 70.7%, 0.567, and 5.4 m/s, respectively. Furthermore, ccPWV was significantly correlated with the stenosis of CMSA at the early stage in Spearman's correlation analyses (r=0.877, P<0.001) and fractional polynomial plot with 95% confidence intervals. Cerebral arterial stiffness has the potential to be a new marker of early stage atherosclerosis of the cerebral large artery. This finding may help us prevent the occurrence of stroke and decrease the burden of society from stroke patients.


Transaortic valve implantation via occluded saphenous vein grafts--a novel access route for transcatheter aortic valve delivery.
Transaortic valve implantation via direct aortic puncture has been shown to be useful alternative to more traditional access routes. In patients with previously placed ascending aorta saphenous vein grafts, access to the aortic valve may be limited. We therefore sought to detail the utility of a new approach for accessing the ascending aorta during transcatheter aortic valve implantation via the hood of previously placed saphenous vein grafts.


Antioxidant effects of melatonin in rats during chronic exposure to hyperbaric oxygen.
In addition to its beneficial effects, hyperbaric oxygen (HBO) exposure causes some detrimental effects via oxidative stress. Previous experimental studies showed that melatonin is a useful agent to block single session HBO-induced oxidative stress. In the present study, we investigated the antioxidant effect of exogenously administered as well as endogenously produced melatonin in lung and brain tissues of rats exposed to long term HBO. The HBO procedure was set as daily exposures to 2.5 ATA of oxygen for 1 hr and a total of 10 sessions. Twenty-eight male Sprague-Dawley rats were divided into four groups as follows: control, daytime HBO, daytime HBO plus melatonin (5 mg/kg), nighttime HBO. Tissue oxidative/antioxidant status was examined by determining the protein carbonyl content as a criteria for oxidative stress and the activities of the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). HBO exposure for 10 days caused significant increases in protein carbonyl content and SOD levels of lung and brain, but GSH-Px activities remained unaffected. The increases in protein carbonyls were blocked by exogenously administered melatonin and in part by nighttime exposure to darkness whereas the increase of SOD activity was only impeded by endogenously produced melatonin in brain tissue. Lung SOD activity was augmented by endogenous melatonin. In conclusion, melatonin blocks long-term HBO-induced cumulative oxidative stress as indicated changes in protein carbonyls. Both exogenously injected and physiologically secreted melatonin has this potential. The effects of HBO-exposure and melatonin on the activities of the antioxidative enzymes are less clear.


SEM observations of resected root canal ends following apicoectomy.
The purpose of this study was to examine the apical foramen of root apices extracted during apicotomies. A total of 25 teeth extracted from 25 patients admitted to the Department of Conservative Dentistry at Tokyo Dental College's Chiba Hospital were used for the study. All patients were between 22 to 56 years of age at the time of the study, and each of the 25 cases was determined clinically on radiographs to be chronic apical suppurative periodontitis. Microsurgery was performed on all cases, and the extracted root apices were then observed using SEM. The results demonstrated a wide opening, greater than 350 microns as measured along the major axis, of the apical foramen in 80% of the cases. Various characteristics indicative of resorption were observed around the apical foramen. These features included those believed to have been caused by overinstrumentation during root canal treatment as well as irregularly shaped areas presumed to be apical lesions that had enlarged and eroded. We observed a high frequency of manifestations of cementum resorption surrounding the root apices of teeth with apical lesions. Furthermore, we concluded that in the majority of cases in the present study, due to the fact that the apical foramen exceeded normal opening dimensions as a result of overinstrumentation during root canal treatment or resorption around the root apex, prolongation of the lesions had occurred in response to direct contact of microbial infectious matter and tissues surrounding the root apex over a large area. The above finding suggested that, in cases in which the apical foramen is destroyed through overinstrumentation larger than #35 or in which the apical foramen opens up to dimensions greater than 350 microns due to pathologic resorption, surgical intervention may be indicated. On the other hand, in 64% of the cases, an accessory canal was observed in the root apical lesion. Based on this observation, the presence of an accessory canal in the root apex may contribute to some degree to the prolongation of the lesion.


The epidemiology of chemical eye injuries.
To describe the epidemiology and identify categories of agents involved in chemical eye injuries. Retrospective case series of consecutive cases of chemical eye injury presenting to the emergency department (ED) at a large eye hospital. Six-hundred and thirty-three patients presented to the ED between January 1, 2006 and December 31, 2009 for treatment of 640 chemical eye injuries. Information was collected via medical record review and chemical agents were classified into logical categories based on the patient-reported intended use of the product. Demographic measures, month of service, work-related status, and visual acuity at presentation were described overall and by chemical agent category. Males were more often observed than females (58.4% vs. 41.6%). The mean age across all categories was 33.6 years. More injuries were observed in warmer months. The mean visual acuity for all available injured eyes was 0.17 logarithm of the minimum angle of resolution (20/30 Snellen). The most common categories of chemical agents were cleaning agents, personal care products, and automotive chemicals. Thirty-nine cases were observed as having misidentified a product which led to injury. Patterns of eye trauma resulting from chemicals differ by gender, across age groups, and during different months of the year. In most cases, chemical eye injuries do not threaten sight. Improvements in product labeling and design could represent an avenue to prevent some chemical eye injuries.


'There's no straight line…' a consumer-informed intervention for FTD family care partners: the STELLA-FTD pilot study.
Behavioral symptoms and communication challenges are particularly apparent in frontotemporal degenerative (FTD) dementias. There is a paucity of psychoeducation programming specifically tailored to the needs of families with FTD. We revised an existing intervention to meet the needs of these families. We used a quasi-experimental approach. In Phase 1, we sought consumer input about an existing intervention. In Phase 2, we modified the intervention based on the qualitative findings from Phase 1 and tested the revised intervention (STELLA-FTD) for feasibility, acceptability and early-stage efficacy. Outcome for Phase 2 included feasibility data and care partner reactivity to upsetting behaviors. Secondary outcomes included data from unobtrusive sleep monitoring. An inductive analysis of transcripts from the Phase 2 STELLA-FTD focus group provides guidance for future revisions. Fifteen family care partners participated in the Phase 1 focus groups; sixteen care partners enrolled in Phase 2. Testing in Phase 2 revealed that the care partners found our consumer-informed revised intervention both feasible and acceptable. The post-intervention findings suggest STELLA-FTD has the potential to reduce care partner reactivity to upsetting behaviors and to decrease care partner burden. Sleep did not change over the 8-week intervention. The revised STELLA-FTD intervention was found to be feasible and acceptable, and has potential to improve care partner burden for families living with FTD. Providing the intervention via telehealth maximized access and engaged rehabilitation specialists in providing disease management content. Future revisions will include examination of efficacy and mechanism of action (OHSU IRB # 00022721, ClinicalTrials.gov NCT05338710).


Brazilian medicinal plant acts on prostaglandin level and Helicobacter pylori.
Among the current treatment strategies for the peptic ulcer patient with Helicobacter pylori infection, the method of choice is triple therapy based on the concurrent use of proton inhibitors and two antibiotics. Alchornea triplinervia is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. In the present work we proposed therapy based on this medicinal plant that presents effective gastroprotective action with antibiotic effects. Oral pretreatment with methanolic extract (ME) of A. triplinervia in rats and mice decreased the gastric injuries induced by ethanol and HCl/ethanol. Increasing the dose reduced the gastroprotective effects of ME on the gastric lesions induced by nonsteroidal anti-inflammatory drug. After pylorus ligature of mice, oral administration of ME induced a decrease not only in total acid but also in the ulcer index. We also observed that ME displayed antibacterial activity against H. pylori. Liquid-liquid separation of ME indicated that active constituents responsible for the gastroprotective action are concentrated in the ethyl acetate fraction (EAF) (50% protection) rather than in the aqueous fraction, which did not induce significant gastroprotection at the same dose (100 mg/kg). EAF induced an increase of gastric mucosa prostaglandin (PG) E(2) levels, which remained high even after previous administration of indomethacin. The phytochemical profile of ME revealed that EAF contains mainly flavonoids. In conclusion, all these results suggest that ME did not show acute toxicity, but exhibited an antisecretory property, anti-H. pylori effect, and gastroprotective action. The observed effect did not involve the participation of nitric oxide or endogenous sulfhydryl groups. However, EAF showed a more efficient gastroprotective effect than ME at a lower dose and protected the gastric mucosa by increasing PGE(2).


Cloning and sequence analysis of additional splice variants encoding human N-methyl-D-aspartate receptor (hNR1) subunits.
Two cDNA clones representing previously unidentified human N-methyl-D-aspartate receptor (hNR1) subunit polypeptides were isolated and sequenced. Clone hNR1-4 was isolated from a human hippocampus cDNA library and was presumably generated by alternative RNA splicing in the 3' amino acid (aa) coding regions. The hNR1-4 cDNA demonstrated an 85.7% nucleotide (nt) identity to the corresponding rat NR1 (rNR1) cDNA. The nt sequence of hNR1-4 would encode a protein that has a 99.8% identity with the corresponding rNR1 subunit. Clone hNR1N was isolated by polymerase chain reaction (PCR)-mediated amplification of a 0.6-kb DNA fragment from human cerebellum cDNA. The nt sequence of this DNA fragment was identical to previously isolated hNR1 cDNA clones, except for the presence of a 63-bp DNA insertion that would encode an additional 21 aa. This DNA insertion occurs in the 5' aa coding regions of hNR1 and presumably represents an exon that is subject to alternative splicing. The nt and aa sequences of this exon are identical between human and rat.


Effect of UVC-induced damage to DNA on the intercalation of thiazole orange: a convenient reporter for DNA damage.
We report a novel method of identifying damage to DNA leading to the loss of intercalation sites. Thiazole orange (TO), an intercalating cyanine dye, fluoresces strongly when intercalated in DNA, but not free in solution. Upon UVC-induced damage to DNA, the change in TO fluorescence is greater than the change in any of the other spectral or biochemical indicators (absorbance, circular dichroism and agarose gel electrophoresis), thus providing a fast screening method to identify damage to DNA. The method is geared toward high levels of damage, such as those that may result during radiation treatment of food products.


Evaluation of excess significance bias in animal studies of neurological diseases.
Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found nominally (p≤0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10⁻⁹). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature.


Spontaneous shape transition of thin films into ZnO nanowires with high structural and optical quality.
ZnO nanowires are usually formed by physical and chemical deposition techniques following the bottom-up approach consisting in supplying the reactants on a nucleation surface heated at a given temperature. We demonstrate an original alternative approach for the formation of ZnO nanowire arrays with high structural and optical quality, which is based on the spontaneous transformation of a ZnO thin film deposited by sol-gel process following a simple annealing. The development of these ZnO nanowires occurs through successive shape transitions, including the intermediate formation of pyramid-shaped islands. Their nucleation under near-equilibrium conditions is expected to be governed by thermodynamic considerations via the total free energy minimization related to the nanowire shape. It is further strongly assisted by the drastic reordering of the matter and by recrystallization phenomena through the massive transport of zinc and oxygen atoms towards the localized growth areas. The spontaneous shape transition process thus combines the easiness and low-cost of sol-gel process and simple annealing with the assets of the vapor phase deposition techniques. These findings cast a light on the fundamental mechanisms driving the spontaneous formation of ZnO nanowires and, importantly, reveal the great technological potential of the spontaneous shape transition process as a promising alternative approach to the more usual bottom-up approach.


Expression of C5 protein, the protein component of Escherichia coli RNase P, from the tac promoter.
The accurate function of C5 protein, the protein component of Escherichia coli RNase P, is uncertain in vivo. A controllable expression system for C5 protein was constructed which can be used to investigate effects of C5 protein on various cellular functions including biosynthesis of RNase P in vivo. The semisynthetic rnpA gene encoding C5 protein was fused to the tac promoter of the pKK223-3 expression vector. This tac promoter expression system produced a high level of C5 protein upon induction with isopropyl-beta-D-thiogalacto-pyranoside. When the overexpressed C5 protein was purified and used for reconstitution of RNase P, the reconstituted enzyme was active. The N-terminal amino acid of the overexpressed C5 protein was leucine specified by the second codon of the rnpA gene. The more controllable expression system was constructed by introducing the lacIq gene into the vector sequence itself.


Organ procurement in experimental pancreas transplantation with minimal microcirculatory impairment.
Ischemia-reperfusion injury has been shown to deteriorate microcirculation in experimental pancreas transplantation. However, minor concern was taken on the impact of organ procurement in this condition. We examined the impact of a standardized technique of organ procurement on microcirculation and apoptosis in experimental pancreas transplantation. Male Lewis rats were divided into three groups: sham-operated animals without dissection of the pancreas served as controls (n = 5); animals undergoing nearly total process of organ procurement with the pancreas pedunculated on the aorta and the hepatoduodenal ligament (n = 7), and animals receiving pancreaticoduodenal transplantation. Pancreatic grafts were preserved for 6 h in cold University of Wisconsin solution (n = 7). At 1 and 2 h reperfusion and in time-matched controls, microcirculation was assessed by means of intravital fluorescence microscopy. Tissue samples were obtained after 2 h measurement and DNA breaks of acinar cells were detected by in situ nick end-labeling (TUNEL assay). The apoptotic index (apoptotic cells per high- power fields; hpf) was quantified by microscopic counting of at least 50 hpf. Assessment of functional capillary density (FCD) in animals undergoing subtotal process of organ procurement revealed a slight non-significant decrease at 1 and 2 h compared with controls. In addition, leukocyte sticking to postcapillary venules (LAV) as well as the apoptotic index were found slightly increased after organ procurement compared with controls (p > 0.05). However, after pancreas transplantation the apoptotic index and the LAV were significantly increased and the FCD significantly decreased compared with both groups of non-transplanted animals (p < 0.01). Our validated technique of organ procurement does not negatively impact microcirculation and apoptosis in experimental pancreas transplantation.


Animal Experiments in Biomedical Research: A Historical Perspective.
The use of non-human animals in biomedical research has given important contributions to the medical progress achieved in our day, but it has also been a cause of heated public, scientific and philosophical discussion for hundreds of years. This review, with a mainly European outlook, addresses the history of animal use in biomedical research, some of its main protagonists and antagonists, and its effect on society from Antiquity to the present day, while providing a historical context with which to understand how we have arrived at the current paradigm regarding the ethical treatment of animals in research.


Pattern of psychotropic drug use among older adults having a depression or an anxiety disorder: results from the longitudinal ESA study.
To document the use of psychotropic drugs in Quebec older adult population with a depressive or anxiety disorder. Data from the Enquête sur la Santé des Aînés (ESA) study conducted between 2005 and 2008 using a representative sample (n = 1869) of community-dwelling adults aged 65 years and older were used to examine the use of psychotropic drugs in the Quebec older adult population. Our results indicate that only 46.9% of the older adults with a diagnosis of depression or anxiety during the 24-month period studied according to the Régie de l'assurance maladie du Quebec (RAMQ) register used antidepressants (AD) for 400 days (12.9 months) on average during this period. Also, 59% of the RAMQ's mental health disorder patients used a mean daily dose of 5 mg of a diazepam equivalent for 338 days (10.9 months) on average during the same period. However, 10.0% of the older adults without any symptoms (ESA) at T1 and at T2 and any RAMQ depression and anxiety diagnosis between T0 and T2 were AD users during the 24-month period studied. They represent 26.2% of the AD users and consumed them for 494 days (15.9 months) on average during the 24-month period studied. Finally, the number of days of AD and benzodiazepine use was not associated with partial or total remission. This result questions the population effectiveness of these drugs in this population.


Arteriovenous malformation of the mandible presented as massive upper gastrointestinal bleeding: report of one case.
Arteriovenous malformation is an uncommon cause of upper gastrointestinal bleeding in children. It should be taken into consideration when a child has upper gastrointestinal bleeding because without proper management, it might be fatal. We report a 10-year-old boy whose initial presentation was massive hematemesis and impending shock. After angiography, arteriovenous malformation (AVM) of the mandible was found and treated with embolization. This 10-year-old boy also had chicken pox during admission. Case reports regarding AVM of dental arches in literature are reviewed and the proposed managements are summarized. Embolization combined with surgical excision might be the optimal way to manage AVM of dental arches.


Some heavy metals in the muscle of Capoeta trutta: risk assessment for the consumers.
This study was carried out to detect the concentrations of some heavy metals (copper, iron, zinc, cadmium and chromium) in the muscle of Capoeta trutta (Heckel, 1843) and in their surrounding water in order to study the potential human risk of consumption. The relationship between the heavy metal load of fish and some of their biological aspects (weight, length and sex) was also examined. In addition, the accumulation factors of heavy metals in this species were determined. The concentrations of Cu, Fe, Zn, Cd and Cr in water and muscle samples were analysed using ICP. Cu, Zn and Fe were detected in all samples, but Cd and Cr were not found in detectable levels. The results showed that heavy metals accumulation in muscle of fish was higher than that in the water. It was found that the level of heavy metals in the muscle of fish showed differences according to weight, length and sex of fish.


An analysis of extended survival in patients with amyotrophic lateral sclerosis treated with riluzole.
In an attempt to better understand and define the progression of amyotrophic lateral sclerosis (ALS), we developed a classification of 5 discrete health states that reflect patients' activities of daily living. These health states were used to determine whether patients with ALS who are treated with riluzole differed from those treated with placebo. Clinics for patients with ALS. Placebo-controlled trial of riluzole treatment in 959 patients with ALS. Treatment with riluzole or placebo. MAIN DEPENDENT MEASURES: A Cox model was used to assess whether, from the initial randomization to the end of an 18-month follow-up, there was a difference in the times of transition into subsequent health states between patients treated with riluzole and those treated with placebo. Our analysis showed a significant difference in the time to transit between the riluzole and the placebo groups in less severely affected cases, ie, state 2 and state A (the milder states) of ALS. Patients receiving riluzole remained in the milder health states longer (P<.05).


Breastfeeding up to two years of age or beyond and its influence on child growth and development: a systematic review.
A systematic review was undertaken to identify studies describing the global prevalence of breastfeeding up to two years of age or beyond and its effects on child growth and development. The MEDLINE and LILACS databases were searched without any language or date restrictions, retrieving 3,561 titles. All retrieved titles, 453 abstracts and 49 full-text articles were read. Articles with maximum breastfeeding duration of over two years were included. An analysis was carried out of 19 articles that met the inclusion criteria resulting in a combined prevalence of breastfeeding at two years of age of 33 % (95%CI: 0.23; 0.42). Increasing trends towards breastfeeding up to two years of age or beyond were observed in the past decades in South Asia. The six studies analyzing the effects of breastfeeding up to two years of age or beyond on child growth showed contradictory results. No association was found with child development. It is concluded that evidence on the medium-term effects of breastfeeding up to two years of age or beyond is scarce and contradictory. Hence, further research is needed regarding this practice.


[Chronic idiopathic anal pain syndrome].
The study was undertaken to analyse whether intra-anal ultrasound examination, anorectal physiological evaluation, and histopathological examination of patients suffering from chronic idiopathic anal pain presented any common features and to analyse the results of various treatments. Eighteen patients who met the criteria for chronic idiopathic anal pain were studied. Treatment included 0.2% glyceryl nitrate ointment, ultrasound guided injection of botulinum toxin in the intrasphincteric space, analgesics, and colostomy. Anal physiological examinations were normal in all but one patient. Intra-anal ultrasonography demonstrated abnormalities in 12 patients. Defecography showed in one patient a small distal invagination but was otherwise normal. Glyceryl nitrate ointment had an effect in one of four patients, and botulinum toxin in four of nine. Two patients needed a colostomy for definitive pain relief, and in 12 of the 18 patients the final treatment was analgesics. The methods used in this study did not contribute to the understanding of the pathogenesis of chronic anal pain. The treatment is experimental, but injection of botulinum toxin may be tried on the hypothesis that dystonia in the anal sphincter may play a pathogenetic role.


Identifying Language Disorder Within a Migration Context: Development and Performance of a Pre-school Screening Tool for Children With German as a Second Language.
There is a lack of accurate and practicable instruments for identifying language disorders in multilingual children in pre-school settings. To develop a language screening instrument for pre-school children who are growing up with German as their second language. After the development and initial validation of a language screening tool, the new instrument (LOGiK-S) was administered to three cohorts of children (2014, 2015, 2017) with a non-German first language attending a variety of public pre-schools in Upper Austria. The screening instrument measures expressive and receptive grammatical skills in German. The final validation study included the results for 270 children for the screening measure and reference tests. A combination of a standardized comprehensive language test of grammatical skills developed for children acquiring German as a second language and a test of expressive vocabulary with the use of specific cutoffs for second language learners was applied as the gold standard for identifying language disorders. The LOGiK-S screening of expressive grammar demonstrated excellent accuracy (AUC.953). The screening subscale of receptive grammar did not improve the prediction of language disorders. Using an optimized cutoff yielded a fail rate of 17%, excellent sensitivity (0.940), and specificity (0.936). Time economy and acceptance of the screening by children and screeners were mostly rated as high. The LOGiK-S language screening instrument assessing expressive German grammar development using bilingual norms is a valid and feasible instrument for the identification of language disorders in second language learners of German at the pre-school age.


Symptom Assessment of Patients with Allergic Rhinitis Using an Allergen Exposure Chamber.
Allergen exposure chambers (AECs) are clinical facilities that allow the exposure of participants to allergenic and non-allergenic airborne particles. They provide stable particle concentrations under controlled environmental conditions. This is of great importance both for diagnostic purposes and for the monitoring of treatment effects. Here, a protocol and the technical prerequisites for performing a safe and effective allergen challenge in subjects sensitized to airborne allergens (i.e., house dust mite [HDM]) in the ALL-MED AEC are presented. With this method, triggering allergic symptoms corresponds to natural exposure. This can be used for an allergy diagnosis or as a plausible endpoint in clinical trials, particularly for allergen immunotherapy (AIT). A controlled environment (temperature, humidity, and carbon dioxide [CO2]) in the chamber must be maintained. Allergen particles must be dispersed evenly within the AEC at stable levels throughout the challenge. For this presentation, allergic rhinitis (AR) patients sensitive to HDM allergens were enrolled. AR symptoms were assessed by the following parameters: total nasal symptom score (TNSS), acoustic rhinometry (ARM), peak nasal inspiratory flow (PNIF), and nasal secretion weight. The safety of the procedure was assessed by the peak expiratory flow rate (PEFR) and the forced expiratory volume in the first second (FEV1). The allergic subjects developed symptoms within 120 min of the trial. On average, the most intense symptoms appeared after 60-90 min and, after reaching a plateau, remained stable until the end of the trial.


Carboxyhemoglobinemia due to peritoneal smoke absorption from laser tissue combustion at laparoscopy.
The carbon monoxide (CO) smoke component from tissue pyrolysis was evaluated for peritoneal absorption in patients undergoing laparoscopy to determine its effects and ability to be detected in peripheral blood. Previous studies have demonstrated changes in peripheral methemoglobin levels as a result of peritoneal absorption of laser smoke. Fifty patients had preoperative, intraoperative, and postoperative levels of carboxyhemoglobin (COHb) and pulse oximetry evaluated. The control group (25) had no laser or cautery used and the study group (25) had carbon dioxide laser used during the laparoscopic procedures. The control group showed no change in COHb, or intra-abdominal CO levels, before, during, and after the procedures, and no change in blood CO or pulse oximetry reading. The laser smoke group showed a statistically significantly elevated (p < .05) peripheral blood COHb levels, a significant increase in intra-abdominal CO concentration, and a lack of correlation of pulse oximetry and blood oxygen saturation experiments. CO is created in extremely large quantities during laser use at laparoscopy and is absorbed through the peritoneal cavity. Symptoms of smoke poisoning can be seen with these elevations. Continuous or intermittent removal of smoke produced from laser use is recommended.


Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.
When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response.SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the contacted limb and opposite homologous limb help maintain balance and forward progression. Here, we investigated reflexes during quadrupedal locomotion in the cat by electrically stimulating cutaneous nerves in each of the four limbs. Functionally, responses appear to modify the trajectory or stabilize the movement of the stimulated limb while modifying the support phase of the other limbs. Reflexes between limbs are mediated by fast-conducting pathways that involve excitatory and inhibitory circuits controlling each limb. The comparatively stronger descending pathways from cervical to lumbar circuits controlling the forelimbs and hindlimbs, respectively, could serve a protective function.


Enzymatic adaptation in ligaments during immobilization.
Ligaments are a composite of fibroblasts and collagen in a proteoglycan matrix. Seventy-five percent of the organic solid is collagen and 23% is proteoglycan. Fibroblasts are responsible for the overall composition of the ligament, that is the synthesis and the degradation of macromolecular components. Like muscle and bone, ligaments are dynamic, undergoing hypertrophy with exercise and atrophy with immobilization. This paper reviews the structure and composition of ligaments and discusses the cellular events responsible for atrophy of ligaments with immobilization. As an experimental model, one knee of New Zealand White rabbits was immobilized with a pin. After 2, 4, and 8 weeks of immobility, the medial collateral ligaments were isolated and enzyme analysis was performed. Gross and microscopic changes were apparent after 2 weeks. As for enzyme changes, lactic dehydrogenase and malic dehydrogenase decreased in activity. The lysosomal hydrolases responsible for glycosaminoglycan degradation increased in activity, suggesting that enzymatic adaptations mediate the physical and chemical changes in the ligament. The cells switch from an anabolic synthetic state to a catabolic, degradative state during immobility. It would seem from the biochemical viewpoint that, whenever possible, cast-bracing and functional splints may be preferable to rigid plasters in many sports-related ligamentous injuries.


Evaluation of root canal configuration of maxillary and mandibular anterior teeth using cone beam computed tomography: An in-vivo study.
Several studies demonstrate variability of root canal morphology of anterior teeth. This in-vivo study was designed to analyze and characterize root canal morphology of maxillary and mandibular anterior teeth using three-dimensional imaging. Patients who required CBCT radiographic examinations as part of their routine examination, diagnosis, and treatment planning were enrolled on the study. A total of 1,200 healthy, untreated, fully developed maxillary and mandibular incisors and canines were included. The following observations were recorded: (i) number of roots and their morphology; (ii) number of canals per root; and (iii) primary variations in the morphology of the root canal systems. Root canal morphology of maxillary teeth was consistent with a single canal extending from the pulp chamber to the apex in 98% of the cases. In contrast, in mandibular central and lateral incisors, the presence of a single canal represented 64.5% and 60.5% respectively. The second most common morphology was the presence of one canal leaving the pulp chamber, which divided into two within the root, and then merged to exit as one canal in 18% and 25.5% respectively. The presence of one canal leaving the pulp chamber and dividing short of the apex into two separate and distinct canals with separate apical foramina (variant 5) was recorded in 14.5% and 12% respectively. There was a low incidence of anatomical variation in maxillary anterior teeth. In contrast, mandibular anterior teeth presented with a high prevalence of two canals, especially central and lateral incisors. The reported data may help clinicians understand the variations in root canal morphology of anterior teeth in order to overcome problems associated with shaping and cleaning procedures.


Clinical significance of nucleostemin and proliferating cell nuclear antigen protein expression in non-small cell lung cancer.
To investigate the expression and significance of the expression of nucleostemin (NS) and proliferating cell nuclear antigen (PCNA) protein in non-small cell lung cancer (NSCLC). Immunohistochemistry (streptavidin-peroxidase method) was used to detect NS and PCNA expression in 53 NSCLC samples and 15 normal lung samples. NS protein expression was detected in 54.7% (29/53) of the NSCLC samples and 0% (0/15) of the normal lung samples (p<0.01). Furthermore, the positive expression rate of PCNA was 6.67% (1/15) in normal lung samples and 71.7% (38/53) in NSCLC samples (p<0.05). Also, the NS protein expression rate was 65.2% (15/23) in adenocarcinoma tissue samples, significantly higher than that in squamous tissues, where the NS expression rate was 46.7% (14/30) (p<0.05). In addition, the NS expression rate of 42.9% (15/35) in well or moderately differentiated tumor tissues was lower than the rate of 77.8% (14/18) in poorly differentiated tumor tissues (p<0.05). The grade of differentiation had no correlation with tumor-node-metastasis (TNM) stage and lymph node metastasis (p>0.05). Also, the positive expression rate of PCNA was significantly higher in NSCLC samples than in normal lung samples (p<0.05). In addition, a positive correlation was found between NS and PCNA expression in NSCLC (p<0.05). The highly valuable tumor molecular markers, NS and PCNA, had higher expression levels in NSCLC samples. Combined detection of NS and PCNA may be important for the early diagnosis of lung cancer and individualized therapy, having also an important role in predicting tumor prognosis.


Multi-Objective Optimal Trajectory Planning for Robotic Arms Using Deep Reinforcement Learning.
This study investigated the trajectory-planning problem of a six-axis robotic arm based on deep reinforcement learning. Taking into account several characteristics of robot motion, a multi-objective optimization approach is proposed, which was based on the motivations of deep reinforcement learning and optimal planning. The optimal trajectory was considered with respect to multiple objectives, aiming to minimize factors such as accuracy, energy consumption, and smoothness. The multiple objectives were integrated into the reinforcement learning environment to achieve the desired trajectory. Based on forward and inverse kinematics, the joint angles and Cartesian coordinates were used as the input parameters, while the joint angle estimation served as the output. To enable the environment to rapidly find more-efficient solutions, the decaying episode mechanism was employed throughout the training process. The distribution of the trajectory points was improved in terms of uniformity and smoothness, which greatly contributed to the optimization of the robotic arm's trajectory. The proposed method demonstrated its effectiveness in comparison with the RRT algorithm, as evidenced by the simulations and physical experiments.


Brain tumor delineation enhanced by moxifloxacin-based two-photon/CARS combined microscopy.
Delineating brain tumor margin is critical for maximizing tumor removal while sparing adjacent normal tissue for better clinical outcome. We describe the use of moxifloxacin-based two-photon (TP)/coherent anti-Stokes Raman scattering (CARS) combined microscopy for differentiating normal mouse brain tissue from metastatic brain tumor tissue based on histoarchitectural and biochemical differences. Moxifloxacin, an FDA-approved compound, was used to label cells in the brain, and moxifloxacin-based two-photon microscopy (TPM) revealed tumor lesions with significantly high cellular density and invading edges in a metastatic brain tumor model. Besides, label-free CARS microscopy showed diminishing of lipid signal due to the destruction of myelin at the tumor site compared to a normal brain tissue site resulting in a complementary contrast for tumor detection. This study demonstrates that moxifloxacin-based TP/CARS combined microscopy might be advantageous for tumor margin identification in the brain that has been a long-standing challenge in the operating room.


Light-front interpretation of proton generalized polarizabilities.
We extend the recently developed formalism to extract light-front quark charge densities from nucleon form factor data to the deformations of these quark charge densities when applying an external electric field. We show that the resulting induced polarizations can be extracted from proton generalized polarizabilities. The available data for the generalized electric polarizability of the proton yield a pronounced structure in its induced polarization at large transverse distances, which will be pinned down by forthcoming high precision virtual Compton scattering experiments.


Costs and Outcomes in the Care of Bi-ventricular Support as a Bridge to Cardiac Transplant.
Bi-ventricular (Bi-V) mechanical circulatory support is commonly used as a bridge to cardiac transplant. However, the optimal strategy is unknown. We examined the outcomes, as well as the costs in the use of Bi-V support as a bridge to cardiac transplant. From 2001 to 2014, three different Bi-V support strategies were utilized: 1) Para-corporeal ventricular assist device (PVAD-2001-2006), 2) Heartmate II left ventricular assist device in conjunction with a temporary CentriMag right ventricular assist device (HMII + CMAG-2006-2012), and the total artificial heart (TAH-2012-2014). Total costs were derived from the hospitalization at implant, and postimplant costs defined as equipment and re-hospitalizations before transplantation. Sixty-five (34 PVADs, 20 HMII + CMAG, and 11 TAHs) devices were used as a bridge for transplant. There were no differences in implant variables including age, INTERMACS score, or implant length of stay. Although the wait list mortality was not different between groups (PVAD-32%, HMII + CMAG-45%, TAH-54%; p = 0.3), the percentage of patients transplanted were highest in the PVAD group: (PVAD-55.8%, HMII + CMAG-30.0%, TAH-18.2%; p = 0.01). Total costs were not significantly different between groups (PVAD-$306,166 ± 247,839, HMII + CMAG-$278,958 ± 135,324, TAH-$321,387 ± 21,2477; p = 0.5). Despite variations in therapy, outcomes and costs for patients requiring Bi-V support as a bridge to cardiac transplant have remained constant.


Prediction of RNA secondary structure, including pseudoknotting, by computer simulation.
A computer program is presented which determines the secondary structure of linear RNA molecules by simulating a hypothetical process of folding. This process implies the concept of 'nucleation centres', regions in RNA which locally trigger the folding. During the simulation, the RNA is allowed to fold into pseudoknotted structures, unlike all other programs predicting RNA secondary structure. The simulation uses published, experimentally determined free energy values for nearest neighbour base pair stackings and loop regions, except for new extrapolated values for loops larger than seven nucleotides. The free energy value for a loop arising from pseudoknot formation is set to a single, estimated value of 4.2 kcal/mole. Especially in the case of long RNA sequences, our program appears superior to other secondary structure predicting programs described so far, as tests on tRNAs, the LSU intron of Tetrahymena thermophila and a number of plant viral RNAs show. In addition, pseudoknotted structures are often predicted successfully. The program is written in mainframe APL and is adapted to run on IBM compatible PCs, Atari ST and Macintosh personal computers. On an 8 MHz 8088 standard PC without coprocessor, using STSC APL, it folds a sequence of 700 nucleotides in one and a half hour.


An economic analysis of high-dose imatinib, dasatinib, and nilotinib for imatinib-resistant chronic phase chronic myeloid leukemia in China: A CHEERS-compliant article.
The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP). A Markov model combined with clinical effectiveness, utility, and cost data was used. The sensitivity analyses were conducted to determine the robustness of the model outcomes. The impact of patient assistance programs (PAPs) was assessed. Treatment with dasatinib is expected to produce 3.65, 0.59, and 0.15 more quality-adjusted life years (QALYs) in comparison with high-dose imatinib (600 and 800 mg) and nilotinib, respectively. When a PAP was available, dasatinib yielded an incremental cost of $16,417 per QALY compared to imatinib (600 mg) and was cost-saving compared to imatinib (800 mg) and nilotinib. When PAP is available in the Chinese setting, dasatinib is likely to be a cost-effective strategy for patients with CML-CP standard-dose imatinib resistance. The results should be carefully explained due to the assumptions and limitations used in the study.


Multisite accelerometry for sleep and wake classification in children.
Actigraphy is a useful alternative to the gold standard polysomnogram for non-invasively measuring sleep and wakefulness. However, it is unable to accurately assess sleep fragmentation due to its inability to differentiate restless sleep from wakefulness and quiet wake from sleep. This presents significant limitations in the assessment of sleep-related breathing disorders where sleep fragmentation is a common symptom. We propose that this limitation may be caused by hardware constraints and movement representation techniques. Our objective was to determine if multisite tri-axial accelerometry improves sleep and wake classification. Twenty-four patients aged 6-15 years (median: 8 years, 16 male) underwent a diagnostic polysomnogram while simultaneously recording motion from the left wrist and index fingertip, upper thorax and left ankle and great toe using a custom accelerometry system. Movement was quantified using several features and two feature selection techniques were employed to select optimal features for restricted feature set sizes. A heuristic was also applied to identify movements during restless sleep. The sleep and wake classification performance was then assessed and validated against the manually scored polysomnogram using discriminant analysis. Tri-axial accelerometry measured at the wrist significantly improved the wake detection when compared to uni-axial accelerometry (specificity at 85% sensitivity: 71.3(14.2)% versus 55.2(24.7)%, p < 0.01). Multisite accelerometry significantly improved the performance when compared to the single wrist placement (specificity at 85% sensitivity: 82.1(12.5)% versus 71.3(14.2)%, p < 0.05). Our results indicate that multisite accelerometry offers a significant performance benefit which could be further improved by analysing movement in raw multisite accelerometry data.


[Factor analysis of sexual behavior in migratory adolescent and choice of contraceptive measures].
To comprehend the young migrants' sexual behavior and contraceptive status, and to provide the scientific basis for the health education regarding sex and reproduction for the young migrants in cities. An anonymous self-designed structured questionnaire was used to survey 4 389 young migrants in Beijing, Guangzhou and Ji'nan. In the study, 33.4%(1 453/4 354) of the migrant adolescents reported had sexual activity, with the unmarried sex rate of 27.5%(1 066/3 880), and the males accounting for 37.8%(579/1 533) and the females 20.7%(487/2 347); contraception was 44.8%(642/1 432); condoms were the preferred contraceptive measures for floating adolescents; but 31.1%(322/1 034) of the unmarried persons reported experienced pregnancy, and 29.7%(307/1 034) of the unmarried people reported had a history of abortion. Education backgrounds (OR=1.555), marital status (OR=0.432), sex partner number (OR=0.683), knowledge of venereal disease prevention (OR=1.758) were the influence factors. Higher sexual and lower birth control utilization rates have triggered young migrants' reproductive health problems. We should promote the floating people' s reproductive health education and make better choices for effective contraceptive measures.


The holistic assessment of the patient in pain.
Holistic pain assessment involves the recognition of pain, an understanding of the context in which it is experienced and knowledge of the resources available to deal with it. Psychosocial and functional approaches to assessment are key to helping the patient cope with pain.


Three new Lycopodium alkaloids from Lycopodium japonicum.
Three new Lycopodium alkaloids (1-3), together with 15 known alkaloids, were isolated from club moss Lycopodium japonicum. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR spectra. Compound 1 has an unusual β-oriented methyl group substituted at C-15 and an α-hydroxy cyclopentenone moiety. All new alkaloids were evaluated for the inhibition of T-type calcium channel.


Theoretical limitations of the AOFAS scoring systems: an analysis using Monte Carlo modeling.
The AOFAS foot scores are four related outcome instruments based on the use of quantitative interval data and have seen increasing use in the literature. The mathematical construction of the scales is particularly notable for a very small number of intervals available to answer each component item and for quantitatively unequal intervals for some items. Monte Carlo computer modeling techniques were used to simulate the responses to each item for a variety of idealized patient populations with several different means, standard deviations, and levels of interaction between items. The continuous data describing each patient's responses were categorized into the finite number of available intervals in the AOFAS Hindfoot score. The resultant distributions of net scores often demonstrated bizarre, skewed behavior that bore little resemblance to the original distributions of continuous data. The effects were magnified as the ends of the scale were approached and when strong correlations between the items measuring pain and function were present. The distributions did not become distorted when the original continuous data were not rounded off into intervals but were simply weighted by their relative contribution to the AOFAS score and summed. The AOFAS scores, therefore, have inherently limited precision which is entirely due to the small number of response intervals available to answer each component item of the scale. Minor changes in a patient's response to a series of correlated questions can potentially make a drastic difference in their total score. Because the population distributions may be badly skewed, the use of parametric statistics with the AOFAS scores should be regarded with genuine suspicion, and appropriate refinements of the scales should be sought.