Do health systems respond to the quality of their competitors?
Some large employers and healthcare analysts have advocated for retail competition that relies on providers competing on performance metrics to improve care quality. Using publicly available performance measures, we determined whether health systems increased the quality of diabetes care provided by their clinics based on performance relative to competitors. Our analysis examined publicly reported performance measures of diabetes care from 2006 to 2013 for clinics in Minnesota health systems. We obtained data for 654 clinics, of which 572 publicly reported diabetes care performance. Because some clinics did not report performance, we estimated a Heckman selection model. First, we predicted whether or not clinics reported performance. Second, we estimated the effect of relative performance (a clinic's performance minus the mean performance of clinics in competing health systems) on clinic performance using the results of the reporting model to control for selection into the sample of reporting clinics. Although diabetes care performance improved during our study, health systems did not differentially improve the diabetes care performance of their clinics performing worse than clinics in competing systems. This result indicates divergence between high-performing and low-performing clinics. This result does not appear to be due to risk selection. Publicly reporting quality information did not incentivize health systems to increase the performance of their clinics with lower performance than competitors, as would be expected under retail competition. Our results do not support strategies that rely on competition on publicly reported performance measures to improve quality in diabetes care management.


Participation of co-ligands in electronic transitions of platinum(II) diazabutadiene complexes.
The low-lying electronic transitions and photochemical reactions of a series of [((i)Pr-DAB)Pt(R)(2)] (where the co-ligand R = CH(3), CD(3), adme, neop, neoSi, C(triple bond)C(t)Bu, C(triple bond)CPh, Ph, Mes) compounds were studied using both experimental (electronic absorption and resonance Raman spectroscopy) and theoretical (density functional theory, DFT) techniques. The high-lying filled orbitals were revealed to have a significant co-ligand contribution in the case of alkyl complexes, while this contribution is predominant for the complexes with unsaturated co-ligands. Because the electronic transition removes electron density from the sigma(Pt-C) bond in the former complexes, it is best described as a metal-to-ligand charge transfer transition (MLCT) with partial sigma-bond-to-ligand charge transfer (SBLCT) character. Because the sigma(Pt-C) orbital is not involved in the HOMOs of the latter complexes, the low-lying transitions were characterized as mixed MLCT/L'LCT, where L'LCT stands for ligand-to-ligand charge transfer from the pi system of the unsaturated co-ligand to the pi((i)Pr-DAB) orbital. The alkyl complexes are photoreactive on visible light irradiation with Pt-C bond homolysis as the primary step. The efficiency of the photoreaction increases with increasing sigma donor strength of the alkyl ligand. The absolute quantum yield is quite low. The other complexes are virtually photostable, except when irradiated at relatively high energies.


Effects of interscapular brown adipose tissue denervation on body weight and energy metabolism in ovariectomized and estradiol-treated rats.
Ovariectomy-induced increases and estradiol-induced decreased in body weight cannot be fully accounted for by changes in energy intake and appear to reflect alterations in thermogenesis. Because changes in energy expenditure have been linked to altered sympathetic nervous system (SNS) activity in brown adipose tissue (BAT), the role of estradiol in thermogenesis and body weight, as mediated by the SNS innervation of interscapular BAT (IBAT), was examined. The IBAT of ovariectomized rats was bilaterally or unilaterally surgically denervated. The chow-fed, bilaterally denervated group gained more weight than the unilaterally denervated or sham-operated group, an effect that was exaggerated by sucrose feeding. Food intake did not differ among the groups within each dietary condition. Estradiol benzoate (EB) injections decreased body weight in all groups. Bilateral, and to a lesser extent, unilateral IBAT denervation blocked the EB-induced increase in thermogenesis. Treatment with EB increased IBAT wet weight regardless of surgical treatment. Because IBAT denervation markedly decreased lipoprotein lipase activity and fatty acid synthesis/uptake, the estradiol-induced increase in denervated IBAT wet weight is most likely due to decreased lipolysis produced by the surgical sympathectomy. These results are discussed in terms of the role of the SNS and IBAT in the mediation of estradiol-induced changes in body weight and energy metabolism.


Loss of protein kinase D activity demonstrates redundancy in cardiac glucose metabolism and preserves cardiac function in obesity.
Protein kinase D (PKD) signaling has been implicated in stress-induced cardiac remodeling and function as well as metabolic processes including contraction-mediated cardiac glucose uptake. PKD has recently emerged as a nutrient-sensing kinase that is activated in high-lipid environments, such as in obesity. However, the role of PKD signaling in cardiac glucose metabolism and cardiac function in both normal and obese conditions remains unknown. A cardiac-specific and inducible dominant negative (DN) PKD mouse model was developed. Echocardiography was used to assess cardiac function, while metabolic phenotyping was performed, including stable isotope metabolomics on cardiac tissue in mice fed either regular chow or a high-fat diet (43% calories from fat). Cardiac PKD activity declined by ∼90% following DN PKD induction in adult mice. The mice had diminished basal cardiac glucose clearance, suggesting impaired contraction-mediated glucose uptake, but normal cardiac function. In obesity studies, systolic function indices were reduced in control mice, but not in cardiac DN PKD mice. Using targeted stable isotope metabolomic analyses, no differences in glucose flux through glycolysis or the TCA cycle were observed between groups. The data show that PKD contributes to cardiac dysfunction in obesity and highlight the redundancy in cardiac glucose metabolism that maintains cardiac glucose flux in vivo. The data suggest that impairments in contraction-mediated glucose uptake are unlikely to drive cardiac dysfunction in both normal and metabolic disease states.


[Update on recent progress in vitamin D research. Development of novel Vitamin D Derivatives.]
Vitamin D3 plays important roles in many physiological processes, including calcium and phosphate homeostasis, bone metabolism, and immune regulation. An active form of vitamin D3, 1α,25(OH)2D3, binds to vitamin D nuclear receptor(VDR, vitamin D receptor), and regulates expression of specific target genes. Thousands of vitamin D3 analogs have been synthesized, and the structure-activity relationships of secosteroidal compounds have been examined in detail. On the other hand, development of non-secosteroidal VDR ligands remains limited, and only a few non-secosteroidal VDR ligands with potent activity have been reported so far. Development of novel structures with unique biological profiles would enable the new clinical application of vitamin D function.


Much higher risk of premalignant and malignant cervical diseases in younger women positive for HPV16 than in older women positive for HPV16.
Human papillomavirus (HPV), particularly HPV16, is strongly associated with premalignant lesions of the uterine cervix and cervical cancer. However, HPV infection is a common sexually transmitted disease and only a few women develop cervical cancer. Although the presence of HPV and abnormal cytology are independent risk factors for cervical diseases, implementing both tests on every woman is argued not to be recommended mainly in terms of cost-effectiveness. During a 20-month period between October, 1994, and May, 1996, cervical swabs from 207 women who were referred for colposcopy because of cervical dyskaryosis (Papanicolaou class IIIa or higher) were examined by PCR for the presence of HPV16. When these women were divided into two groups; i.e., group A consisting of women who were 44 years old or younger (n = 111), and group B consisting of women who were 45 years old or older (n = 96), the risk of having premalignant and malignant cervical diseases upon infection with HPV16 was approximately 8 times higher in group A than in group B. Thus, we conclude that HPV-testing should be implemented on every young woman with an abnormal Papanicolaou smear test.


Voltage-controlled enzyme-catalyzed glucose-gluconolactone conversion using a field-effect enzymatic detector.
The field-effect enzymatic detection (FEED) technique was used to control the kinetics of the enzymatic conversion of glucose to gluconolactone. The glucose-gluconolactone conversion occurring at an enzyme-immobilized electrode, a well-studied process, was confirmed using mass spectrometry. Electrochemical studies showed that the glucose oxidation current depends on the gating voltage VG and the ion concentration of the sample solution. Additionally, the depletion of glucose in the sample also showed a dependence on VG. FEED was used to detect H2O2 on the zepto-molar level in order to show the ultrasensitive detection capability of the technique. These results, while providing evidence for the proposed mechanism of FEED, indicate that VG controls the conversion process. The effect of VG on the glucose-gluconolactone conversion was demonstrated by the observed VG-dependent kinetic parameters of the conversion process.


A comparison of CO2 laser ignition of the Xomed, plastic, and rubber endotracheal tubes.
The combustibility of Xomed LaserShield endotracheal tubes was compared to that of polyvinylchloride (PVC) and rubber endotracheal tubes at 15, 17, and 20 watts (W) of power from a CO2 laser. Oxygen, 5.0 L/min, flowed through the tubes during the investigation. The laser was aimed perpendicularly at the shaft of the endotracheal tube under study and actuated until an intraluminal fire occurred. The times to blow torch combustion of the PVC tubes were 1.7, 1.8, and 1.5 s at 15, 17, and 20 W, respectively. For the Xomed tube, the times to combustion were 85.9, 42.5, and 20.3 s at 15, 17, and 20 W, respectively. Intraluminal (blow torch) fires of the rubber endotracheal tubes occurred after 24.5, 25.4, and 21.9 s at 15, 17, and 20 W. The times to combustion of the PVC and Xomed tubes were significantly different at 15 and 17 W. The times to intraluminal combustion of the rubber tubes were significantly different from those of the Xomed tubes only at 15 W. We conclude that the Xomed tube does not offer consistently better resistance to laser-induced combustion than the PVC or rubber endotracheal tubes tested.


Quinone analogues: a drug of choice for the control of filariasis.
Human filariasis is caused by Wuchereria bancrofti, Brugia malayi and B. timori. Of the several recommended model filarial parasites by WHO, Setaria digitata a bovine one has characteristics such as cyanide insensitivity, lack of detectable cytochromes, presence of two quinones Q8 and Q6. Of the two quinones Q8 seems to have a predominant role in energy production. In vitro inhibitory studies using quinone analogues, coenzyme Q0 and menadione have shown that these compounds paralyse the worms in very low concentrations compared to diethyl carbamazine, the drug of choice for filariasis. The mitochondrial energy production associated with electron transfer is intercepted by quinone analogues. Hence for the treatment of filariasis, this study paves a chemotherapeutic target for the design of drugs which can control the parasites by interacting at the subcellular level by energy depletion.


[Immunological markers of disease activity in the course of 2-CDA treatment of multiple sclerosis].
52 clinically definite multiple sclerosis (MS) patients were treated with subcutaneous injection of 5 mg 2-CDA in 5 consecutive days. The injection courses were repeated 6 times in one month interval. The MRI pattern and immunological markers were studied in serum and CSF before and after 6 months of treatment. The obtained results suggest that treatment with 2-CDA has not any significant effect on humoral immunological events in multiple sclerosis, what is in contrast to some normalization of cellular immunopathological processes.


Bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and subcutaneous emphysema after thoracoscopic anterior fracture stabilization.
Case report and clinical discussion. A rare case of air passage into multiple body compartments after thoracoscopic minimally invasive spine surgery is described. In recent years, there is growing interest in thoracoscopic minimally invasive spine surgery for the treatment of thoracic and lumbar spine fractures. Severe complications due to the operative procedure are rare. We present a case of a 73-year-old woman who developed bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and subcutaneous emphysema after thoracoscopic anterior stabilization of a Th12 fracture. The operative procedure was completed without any obvious intraoperative complications. Routine made postoperative radiograph of the chest revealed a pneumothorax on the right side, bilateral subphrenic free air, and bilateral supraclavicular air. Subsequently, a CT scan showed bilateral pneumothoraces, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum and a supraclavicular subcutaneous emphysema. Bronchoscopy, esophagogastroduodenoscopy, and laryngoscopy showed no hollow organ injury or any other pathologic changes. Intraabdominal free air and pneumothoraces could not be detected on thoracic radiographs after 2 days. The patient remained cardiopulmonary stable throughout the hospital course. This report documents a rare case of air passage into multiple body compartments after thoracoscopic-assisted treatment of a spinal fracture, which has not yet been described previously. After exclusion of a tracheo-bronchial and hollow organ injury the process was self-limiting. To avoid this complication, special care should be taken to evacuate all intrathoracal air at the end of the endoscopic procedure.


External heavy-atom effect on the prompt and delayed fluorescence of [70]fullerenes.
The influence of the external heavy-atom effect (HAE) on the fluorescence properties of C(70) and a C(70) methano monoadduct is determined. For this purpose the photophysics of these [70]fullerenes is studied in polystyrene (PS) and in a related heavy-atom polymer, poly(4-bromostyrene) (PBS). In the absence of HAE (PS matrix) both fullerenes display a strong thermally activated delayed fluorescence (DF) that is more pronounced in the case of C(70). In the presence of HAE (PBS matrix) both prompt (PF) and DF intensities decrease significantly, the same happening to the delayed fluorescence lifetimes. The relative fluorescence intensities (DF intensity/PF intensity) for each fullerene are on the other hand surprisingly similar to the respective ones in PS for the full experimental temperature range. The HAE is responsible for a significant increase of the S(1)→T(1) and S(1)←T(1) intersystem crossing (ISC) rates, and of the T(1)→S(0) radiative rate. In particular, the HAE on a S(1)←T(1) ISC rate is reported here for the first time. The overall substantial insensitivity of relative fluorescence intensities to HAE is explained by a compensation effect: As the S(1)→T(1) and S(1)←T(1) ISC rates on the one hand, and the T(1)→S(0) radiative rate on the other hand work in opposition with respect to DF, a near cancellation of effects occurs.


Action of Halowax 1051 on Enzymes of Phase I (CYP1A1) and Phase II (SULT1A and COMT) Metabolism in the Pig Ovary.
Polychlorinated naphthalenes (PCNs) are a group of organochlorinated compounds exhibiting dioxin-like properties. Previously published data showed the direct action of PCN-rich Halowax 1051 on ovarian follicular steroidogenesis. Taking into consideration that the observed biological effects of PCNs may be frequently side effects of metabolites generated by their detoxification, the aim of this study was to determine the activity and expression of enzymes involved in phase I (cytochrome P450, family 1 (CYP1A1)) and phase II (sulfotransferase (SULT1A) and catechol-O-methyltransferase (COMT)) detoxification metabolism. Cocultures of granulosa and theca interna cells collected from sexually mature pigs were exposed to 1 pg/mL to 10 ng/mL of Halowax 1051 for 1 to 48 hours, after which levels and activities of CYP1A1, SULT1A, and COMT were measured. Dose-dependent increases of CYP1A1 activity and expression were observed. High doses of Halowax 1051 were inhibitory to COMT and SULT1A activity and reduced their protein levels. In conclusion, fast activation of phase I enzymes with simultaneous inhibition of phase II enzymes indicates that the previously observed effect of Halowax 1051 on follicular steroidogenesis may partially result from metabolite action occurring locally in ovarian follicles.


Ascending aortic dilatation rate after transcatheter aortic valve replacement in patients with bicuspid and tricuspid aortic stenosis: A multidetector computed tomography follow-up study.
Current data is lacking about the progression of ascending aortic dilatation after transcatheter aortic valve replacement (TAVR) in aortic stenosis (AS) patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). This study aims to assess the ascending aortic dilatation rate (mm/year) after TAVR in patients with BAV versus TAV using a multidetector computed tomography (MDCT) follow-up and to determine the predictors of ascending aortic dilatation rate. Severe AS patients undergoing TAVR from March 2013 to March 2018 at our center with MDCT follow-ups were included. BAV and TAV were identified using baseline MDCT. Baseline and follow-up MDCT images were analyzed, and the diameters of ascending aorta were measured. Study end point is ascending aortic dilatation rate (mm/year). Furthermore, factors predicting ascending aortic dilatation rate were also investigated. Two hundred and eight patients were included, comprised of 86 BAV and 122 TAV patients. Five, 4, 3, 2, and 1-year MDCT follow-ups were achieved in 7, 9, 30, 46, and 116 patients. The ascending aortic diameter was significantly increased after TAVR in both BAV group (43.7±4.4 mm vs. 44.0±4.5 mm; P<0.001) and TAV group (39.1±4.8 mm vs. 39.7±5.1 mm; P<0.001). However, no difference of ascending aortic dilatation rate was found between BAV and TAV group (0.2±0.8 mm/year vs. 0.3±0.8 mm/year, P=0.592). Multivariate linear regression revealed paravalvular leakage (PVL) grade was independently associated with ascending aortic dilatation rate in the whole population and BAV group, but not TAV group. No aortic events occurred during follow-ups. Ascending aortic size continues to grow after TAVR in BAV patients, but the dilatation rate is mild and comparable to that of TAV patients. PVL grade is associated with ascending aortic dilatation rate in BAV patients post-TAVR.


Cloning and expression of aminopeptidase P gene from Escherichia coli HB101 and characterization of expressed enzyme.
The aminopeptidase P gene in Escherichia coli HB101 was cloned into the plasmid pBR322. Introduction of the hybrid plasmid, pAPP01, into the E. coli DH1 resulted in an 8-fold increase of aminopeptidase P activity as compared with that of the host. The enzyme was purified by series of chromatographies on DEAE-Sephadex, QAE-Sephadex, and hydroxyapatite. The purified enzyme was homogeneous as judged by disc-gel and SDS-gel electrophoreses. the enzyme was inhibited strongly by EDTA and slightly by p-chloromercuribenzoate, but was not affected by diisopropyl phosphorofluoridate, E-64, or iodoacetic acid. The optimum pH of the enzyme was 8.5. The enzyme was stable at pH 8 to 9. After incubation for 30 min at pH 8.0, 50% remaining activity was observed at 50 degrees C. The enzyme was activated 3-fold by the addition of 5 microM Mn2+. The molecular weight of the enzyme was estimated to be 50,000 and 200,000 by SDS-PAGE and gel filtration, respectively. The amino terminal amino acid was identified to be serine by Edman degradation, indicating that the enzyme is composed of a homo-tetramer. The enzyme hydrolyzed X-Pro bonds (X = amino acid) of peptides. These characteristics suggest that cloned aminopeptidase P is identical to APP-II reported by Yoshimoto et al. (Agric. Biol. Chem. 52(8), in press (1988].


Positional identification of hypertension susceptibility genes on chromosome 2.
Chromosome 2 has been consistently identified as a genomic region with genetic linkage evidence suggesting that one or more loci contributes to blood pressure and hypertension status. As with all complex disease traits, following-up linkage evidence to identify the underlying susceptibility gene(s) is an arduous yet biologically and clinically important task. Using combined positional candidate gene methods, the Family Blood Pressure Program (FBPP) has concentrated efforts in narrowing a large region of chromosome 2, demonstrating evidence for linkage in several populations, and identifying underlying candidate hypertension susceptibility gene(s). Initial informatics efforts identified the boundaries of the region and the known genes within it. A total of 82 polymorphic sites in 8 genes were genotyped in a large hypothesis-generating sample consisting of 1640 African Americans, 1339 whites, and 1616 Mexican Americans. After resampling-based false discovery adjustment, SLC4A5, a sodium bicarbonate transporter, was identified as a primary candidate gene for hypertension. Polymorphisms in SLC4A5 were subsequently genotyped and analyzed for validation in two other subcomponents of the FBPP, each contributing African Americans (N=461; N=778) and whites (N=550; N=967). Again, single nucleotide polymorphisms within this gene were significantly associated with blood pressure levels and hypertension status. Although not identifying a single causal gene variant that is significantly associated with blood pressure levels and hypertension status across all samples, the results further implicate SLC4A5 as a candidate hypertension susceptibility gene. Moreover, the present study validates previous evidence for one or more genes on chromosome 2 that influence hypertension-related phenotypes in the population-at-large.


A randomized, observer-blinded immunogenicity trial of Cervarix(®) and Gardasil(®) Human Papillomavirus vaccines in 12-15 year old girls.
The current generation of Human Papillomavirus (HPV) vaccines, Cervarix® and Gardasil®, exhibit a high degree of efficacy in clinical trials against the two high-risk (HR) genotypes represented in the vaccines (HPV16 and HPV18). High levels of neutralizing antibodies are elicited against the vaccine types, consistent with preclinical data showing that neutralizing antibodies can mediate type-specific protection in the absence of other immune effectors. The vaccines also confer protection against some closely related non-vaccine HR HPV types, although the vaccines appear to differ in their degree of cross-protection. The mechanism of vaccine-induced cross-protection is unknown. This study sought to compare the breadth and magnitudes of neutralizing antibodies against non-vaccine types elicited by both vaccines and establish whether such antibodies could be detected in the genital secretions of vaccinated individuals. Serum and genital samples were collected from 12-15 year old girls following vaccination with either Cervarix® (n = 96) or Gardasil® (n = 102) HPV vaccine. Serum-neutralizing antibody responses against non-vaccine HPV types were broader and of higher magnitude in the Cervarix®, compared to the Gardasil®, vaccinated individuals. Levels of neutralizing and binding antibodies in genital secretions were closely associated with those found in the serum (r = 0.869), with Cervarix® having a median 2.5 (inter-quartile range, 1.7-3.5) fold higher geometric mean HPV-specific IgG ratio in serum and genital samples than Gardasil® (p = 0.0047). There was a strong positive association between cross-neutralizing antibody seropositivity and available HPV vaccine trial efficacy data against non-vaccine types. These data demonstrate for the first time that cross-neutralizing antibodies can be detected at the genital site of infection and support the possibility that cross-neutralizing antibodies play a role in the cross-protection against HPV infection and disease that has been reported for the current HPV vaccines. ClinicalTrials.gov NCT00956553.


JMATING: a software for the analysis of sexual selection and sexual isolation effects from mating frequency data.
Many different sexual isolation and sexual selection statistics have been proposed in the past. However, there is no available software that implements all these statistical estimators and their corresponding tests for the study of mating behaviour. JMATING is an easy-to-use program developed in Java for the analysis of mating frequency data to study sexual selection and sexual isolation effects from laboratory experiments as well as descriptive studies accomplished in the wild. The software allows the re-organization of the data previous to the analysis, the estimation of the most important estimators, and a battery of complementary statistical tests. JMATING is the first complete and versatile software for the analyses of mating frequency data. It is available at http://www.uvigo.es/webs/c03/webc03/XENETICA/XB2/JMsoft.htm and requires the Java runtime environment.


Abolishment of Specific Toxicity of Host-Specific Toxin of Helminthosporium carbonum by Electrolytic Reduction.
The host-specific toxin produced by the plant pathogen, Helminthosporium carbonum Ullstrup is normally about 300 times as toxic for corn plants susceptible to the disease as it is for disease-resistant plants. Electrolytic reduction of the toxin destroys this specificity, rendering the material no more toxic for disease susceptible plants than for disease resistant ones.


Selection of RNA aptamers that are specific and high-affinity ligands of the hepatitis C virus RNA-dependent RNA polymerase.
In order to find small RNA molecules that are specific and high-affinity ligands of nonstructural 5B (NS5B) polymerase, we screened by SELEX (systematic evolution of ligands by exponential amplification) a structurally constrained RNA library with an NS5BDeltaC55 enzyme carrying a C-terminal biotinylation sequence. Among the selected clones, two aptamers appeared to be high-affinity ligands of NS5B, with apparent dissociation constants in the low nanomolar range. They share a sequence that can assume a stem-loop structure. By mutation analysis, this structure has been shown to correspond to the RNA motif responsible for the tight interaction with NS5B. The aptamers appeared to be highly specific for the hepatitis C virus (HCV) polymerase since interaction with the GB virus B (GBV-B) NS5B protein cannot be observed. This is consistent with the observation that the activity of the HCV NS5B polymerase is efficiently inhibited by the selected aptamers, while neither GBV-B nor poliovirus 3D polymerases are affected. The mechanism of inhibition of the NS5B activity turned out to be noncompetitive with respect to template RNA, suggesting that aptamers and template RNA do not bind to the same site. As a matter of fact, mutations introduced in a basic exposed surface of the thumb domain severely impaired both the binding of and activity inhibition by the RNA aptamers.


Development of a PCR Kit for Detection of Coxiella burnetii in Ukraine.
Coxiella burnetii is an obligate intracellular pathogen and the causative agent of Q fever. In Ukraine, 28 human cases of Q fever were reported between 1997 and 2006; however, there are no state-approved, standardized molecular diagnostic assays that can be used systematically to investigate C. burnetii transmission to humans and its distribution throughout Ukraine. To address this deficiency, we followed the recommendation of the World Organization for Animal Health (OIE) and developed a confirmatory PCR for C. burnetii for veterinary diagnosis in Ukraine. The PCR assay targeted the outer membrane-associated gene com1 in C. burnetii. Oligonucleotide primers were selected that amplify a 689-bp DNA fragment of the com1 gene (primers: CoxF2 = 5'-ACYGCAGGCGTGGCGATAG-3' and CoxR4 = 5'-TGAAGGTTTTGTTGTGAGGTGGC-3'). The assay proved highly sensitive and specific to C. burnetii DNA detection (LOD = 0.37 pg/μL). Reproducibility of the test was verified by comparing the PCR results with those of a different PCR protocol and qPCR. Using the CoxF2/CoxR4 primer set and reaction conditions described here, the PCR Diagnostic Kit C. burnetii-PCR-TEST was developed and officially registered for use in Ukraine by the State Scientific Control Institute of Biotechnology and Strains (Kyiv, Ukraine) for diagnostic purposes.


β-Arrestin 2 mediates arginine vasopressin-induced IL-6 induction via the ERK1/2-NF-κB signal pathway in murine hearts.
Evidence to date suggests that β-arrestins act beyond their role as adapter proteins. Arginine vasopressin (AVP) may be a factor in inflammation and fibrosis in the pathogenesis of heart failure. In the present study we investigated the effect of AVP on inflammatory cytokine IL-6 production in murine hearts and the impact of β-arrestin 2-dependent signaling on AVP-induced IL-6 production. We found that administration of AVP (0.5 U/kg, iv) markedly increased the levels of IL-6 mRNA in rat hearts with the maximum level occurred at 6 h. In β-arrestin 2 KO mouse hearts, deletion of β-arrestin 2 decreased AVP-induced IL-6 mRNA expression. We then performed in vitro experiments in adult rat cardiac fibroblasts (ARCFs). We found that AVP (10-9-10-6 M) dose-dependently increased the expression of IL-6 mRNA and protein, activation of NF-κB signaling and ERK1/2 phosphorylation, whereas knockdown of β-arrestin 2 blocked AVP-induced IL-6 increase, NF-κB activation and ERK1/2 phosphorylation. Pharmacological blockade of ERK1/2 using PD98059 diminished AVP-induced NF-κB activation and IL-6 production. The selective V1A receptor antagonist SR49059 effectively blocked AVP-induced NF-κB phosphorylation and activation as well as IL-6 expression in ARCFs. In AVP-treated mice, pre-injection of SR49059 (2 mg/kg, iv) abolished AVP-induced NF-κB activation and IL-6 production in hearts. The above results suggest that AVP induces IL-6 induction in murine hearts via the V1A receptor-mediated β-arrestin2/ERK1/2/NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V1A/β-arrestin 2/ERK1/2/NF-κB signaling pathway.


Transthoracic echocardiography for imaging of the different coronary artery segments: a feasibility study.
Transthoracic echocardiography (TTE) may be used for direct inspection of various parts of the main coronary arteries for detection of coronary stenoses and occlusions. We aimed to assess the feasibility of TTE to visualise the complete segments of the left main (LM), left descending (LAD), circumflex (Cx) and right (RCA) coronary arteries. One hundred and eleven patients scheduled for diagnostic coronary angiography because of chest pain or acute coronary syndrome had a TTE study to map the passage of the main coronary arteries. LAD, Cx and RCA were each divided into proximal, middle and distal segments. If any part of the individual segment of a coronary artery with antegrade blood flow was not visualised, the segment was labeled as not satisfactorily seen. Complete imaging of the LM was achieved in 98% of the patients. With antegrade directed coronary artery flow, the proximal, middle and distal segments of LAD were completely seen in 96%, 95% and 91% of patients, respectively. Adding the completely seen segments with antegrade coronary flow and segments with retrograde coronary flow, the proximal, middle and distal segments of LAD were adequately visualised in 96%, 96% and 93% of patients, respectively. With antegrade directed coronary artery flow, the proximal, middle and distal segments of Cx were completely seen in 88%, 61% and 3% and in RCA in 40%, 28% and 54% of patients. Retrograde coronary artery flow was correctly identified as verified by coronary angiography in seven coronary segments, mainly in the posterior descending artery (labeled as the distal segment of RCA) and distal LAD. TTE is a feasible method for complete demonstration of coronary flow in the LM, the proximal Cx and the different segments of LAD, but less suitable for the RCA and mid and distal segments of the Cx. (ClinicalTrials.gov number NTC00281346.).


Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type 1 is more pronounced in the duodenal mucosa than in the peripheral blood. Berlin Diarrhea/Wasting Syndrome Study Group.
Although changes in T lymphocyte subset distribution in the peripheral blood of patients infected with human immunodeficiency virus (HIV) are well defined it is not known whether these changes reflect changes in lymphoid compartments clearly involved in HIV related disease like the intestinal mucosa. This study analysed lymphocytes isolated simultaneously from the peripheral blood and duodenal biopsy specimens by three colour flow cytometry in eight asymptomatic HIV infected patients, 26 AIDS patients, and 23 controls. The proportion of CD4, CD8, CD4-CD8-, or gamma delta T cells did not correlate between circulating and duodenal T cells. CD4 T cells were reduced in the peripheral blood (7.5% (25th-75th percentile, 2-16%) v 52% (41-63%), p < 0.0005) and even more reduced in the duodenum (1% (1-2%) v 36% (23-57%), p < 0.0005) of AIDS patients compared with controls. Patients with asymptomatic HIV infection had intermediate CD4 T cells in the peripheral blood (24% (22-35%); p < 0.002 v controls; p < 0.01 v AIDS) but like AIDS patients very low CD4 T cells in the duodenum (3% (1-6%); p < 0.002 v controls). The ratio of duodenal to circulating CD4+ T cells was significantly reduced to 0.2 (0-1) in AIDS patients (p < 0.001) and even to 0.1 (0.04-0.5) in asymptomatic HIV infected patients (p < 0.002) compared with 0.72 (0.44-0.95) in controls. These findings show an early and preferential loss of duodenal CD4 T cells in HIV infection. Immunological abnormalities in HIV infection are distinct between lymphoid compartments, and profound immunodeficiency may occur in the intestinal immune system although circulating T cells are largely preserved.


Asf1 mediates histone eviction and deposition during elongation by RNA polymerase II.
Histones are rapidly evicted and deposited during transcription by RNA polymerase (Pol) II, but a factor that mediates histone eviction in vivo has not yet been identified. Here, we show that the histone chaperone Asf1 associates with promoters and coding regions of transcriptionally active genes. Asf1 mediates histone H3, but not H2B, eviction and deposition during Pol II elongation, suggesting that nucleosome assembly and disassembly occur in a stepwise fashion. Lastly, Asf1 inhibits internal initiation from cryptic promoters within coding regions. These results strongly suggest that Asf1 functions as an elongation factor to disassemble and reassemble histones during Pol II elongation.


Testicular metastasis from hepatocellular carcinoma.
We document a case of testicular metastasis from hepatocellular carcinoma. The patient suffered from bilateral testicular painful swelling for 6 months. Scrotal ultrasonography showed bilateral testicular tumors and the whole abdominal computed tomography revealed a huge tumor in the left lobe of the liver. Bilateral orchiectomy and postoperative ultrasound-guided liver biopsy were done. Pathological examination revealed metastatic hepatocellular carcinoma. Hepatocellular carcinoma with testicular metastases is a very rare disease.


[Characteristics of particle size structure of plankton community in turbidity zone of near-shore waters, Liaoning Province of Northeast China].
Estuary and nearshore waters have complicated environment, where plankton community has a frequent feedback regulation and a very unstable particle size structure. In this paper, an investigation was made on the particle size structure of plankton in the turbidity zone of nearshore and port area waters in Liaoning Province of Northeast China. In the waters with high concentration inorganic nitrogen, phytoplankton biomass was mainly of small particle sizes, with the equivalent sphere diameter (ESD) being primarily 20-100 micro m, while in low nutrient waters, the phytoplankton biomass was mainly of larger size particles, with the ESD>100 micro m, indicating that the phytoplankton feedback regulation caused the phytoplankton community to be comprised of small sized organisms as part of the biological responses to high concentration suspended solids, which reduced the individual number of larger organisms such as Coscinodiscus. sp. and other species, and in turn, directly affected the fisheries resources, including a variety of fish and shrimp larvae fed on phytoplankton. A normalized biomass size spectrum with the characteristics of nearshore shallow aquatic oceanic ecosystems exhibiting eutrophication was constructed. The spectrum slope indicated that the plankton community biomass would gradually increase in size. The feasibility of using dinoflagellates and cladocerans as the bio-indicators for eutrophication was discussed.


Employing standardized risk assessment in pretrial release decisions: Association with criminal justice outcomes and racial equity.
We examined efforts by a Mississippi court to base pretrial release decisions on risk assessment rather than primarily on bond. (a) Pretrial detention will be shorter than that associated with prevailing bond practices in the same counties. (b) Rearrest rates will be lower than a similar pretrial population in a nearby southern state. (c) False positive rates for predicting rearrests will be higher for African American than Caucasian participants. (d) Pretrial detention will be longer for African American participants because of higher risk scores or assessment overrides. Pretrial defendants (N = 521) completed the Risk and Needs Triage (RANT) within 2 weeks of arrest, and outcomes examined included the length of pretrial detention, index case dispositions, and rearrest rates. (a) Pretrial detention averaged approximately 60 days compared with prevailing detentions averaging approximately 90 and 180 days in the same counties. (b) Pretrial rearrest rates were 17 percentage points higher than a similar pretrial population; however, representative comparison data are unavailable to confidently measure recidivism impacts. (c) Positive predictive power did not differ by race in predicting pretrial rearrests, SE = .04, 95% CI [.11, -.06], z = .61, p = .54, d = .08. (d) Despite comparable risk scores, African American participants were detained significantly longer than Caucasian participants (M = 60.92 vs. 45.58 days), p = .038, d = .18, 95% CI [.01, .36], and were less likely to receive a diversion opportunity (11% vs. 23%), p = .009, V = .17. The observational design precludes causal conclusions; however, risk assessment was associated with shorter pretrial detention than prevailing bond practices with no racial disparities in risk prediction. Greater attention to risk assessment may reduce racial inequities in pretrial conditions. Representative comparison data are needed to measure the recidivism impacts of pretrial reform initiatives. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Technical aspects of perichondrial grafting in the rabbit.
A screening process to determine the most appropriate model for the study of cartilage growth from perichondrium obtained from the rabbit's left tenth costal cartilage has resulted in the following observations: (1) best growth is achieved when fixation of the graft is secure and conformity to the recipient bed is complete; (2) immobilization enhances fixation, but permits fibrous tissue growth onto the graft, and (3) diminishing periods of immobilization enhance perichondrial growth, but have a deleterious effect on fixation.


The Co-occurrence of Pediatric Chronic Pain and Anxiety: A Theoretical Review of a Developmentally Informed Shared Vulnerability Model.
The development and maintenance of pediatric chronic pain and anxiety are complex, underscoring the need to better understand the interactive forces contributing to their co-occurrence. The shared vulnerability model (SVM) was developed to explain the co-occurrence of chronic pain and posttraumatic stress disorder in adults. Although many core tenets have been well supported by pediatric research, the SVM has yet to be extended to pediatric pain populations. We propose a developmentally informed pediatric SVM for advancing our understanding of the co-occurrence of pediatric chronic pain and anxiety disorders. The proposed SVM postulates that youth at increased risk for the development of chronic pain and/or anxiety share predisposing vulnerabilities, including anxiety sensitivity, and that these shared vulnerabilities give rise to negative emotional responses (child and parent) in the context of stressful events. Consequences of fear and anxiety, including avoidance behavior, further contribute to the development of chronic pain, anxiety, and their co-occurrence. The parental, school, and peer contexts in which these problems develop and are maintained in youth are pertinent to integrate into a SVM, as pediatric chronic pain and anxiety disorders share several social-contextual risk and maintenance factors. We also highlight new areas of inquiry.


The influence of experience on knee mechanics during side-step cutting in females.
It is thought that female athletes with limited experience in a sport perform athletic maneuvers differently than their more experienced counterparts, and that they do so in a manner that places them at greater risk for injury. The purpose of this study was to evaluate the influence of athletic experience on knee mechanics during the execution of a side-step cutting maneuver in young female athletes. Three-dimensional kinematics, ground reaction forces and electromyographic activity (surface electrodes) were recorded during the early deceleration phase of side-step cutting in 30 high school females (15 experienced, 15 novice). Group differences in knee joint kinematics, peak moments, net joint moment impulse and average muscle activation were evaluated. No significant group differences were found in knee kinematics. When compared to experienced females, novice females demonstrated significantly smaller flexor, adductor, and internal rotator peak moments and smaller net joint moment impulse in all three planes at the knee. No group differences were found for average EMG; however, novice athletes had significantly greater co-contraction at the knee. The finding of smaller knee moments and greater muscle co-contraction in the novice group suggests that these athletes may adopt a protective strategy in response to a relatively unfamiliar task. In addition, these results suggest that increased moments at the knee emerge with experience, indicating that more skilled athletes may be at greater risk for anterior cruciate ligament (ACL) injury.


Biomechanical comparison of anatomic humeral head resurfacing and hemiarthroplasty in functional glenohumeral positions.
Resurfacing of the humeral head has gained interest as an alternative to traditional hemiarthroplasty because it preserves bone stock and respects the native geometry of the glenohumeral articulation. The purpose of this study was to compare the biomechanics of the intact glenohumeral joint with those following humeral head resurfacing and following hemiarthroplasty. Seven fresh-frozen cadaveric shoulders were tested with the rotator cuff, pectoralis major, and latissimus dorsi musculature loaded with 20 N and the deltoid muscle loaded with 40 N in a custom shoulder testing system. Each specimen was tested in 20°, 40°, 60°, and 80° of vertical abduction. The articular surfaces of the humeral head and the glenoid were digitized to calculate the positions of the geometric center and apex of the humeral head relative to the geometric center of the glenoid at each testing position. The contact area and contact pressures were also measured with use of a Tekscan pressure sensor. The geometric center of the humeral head shifted by a mean (and standard error) of 2.2 ± 0.3 mm following humeral resurfacing and 4.7 ± 0.3 mm following hemiarthroplasty (p < 0.0002). The apex of the humeral head was shifted superiorly at all abduction angles following hemiarthroplasty (p < 0.03). Both humeral resurfacing and hemiarthroplasty decreased the glenohumeral contact area and increased the peak pressure. Resurfacing more closely restored the geometric center of the humeral head than hemiarthroplasty did, with less eccentric loading of the glenoid. Compared with hemiarthroplasty, humeral resurfacing may limit eccentric glenoid wear and permit better function because the glenohumeral joint biomechanics and the moment arms of the rotator cuff and the deltoid muscle are restored more closely to those of the intact condition.


The Simon effect in action: planning and/or on-line control effects?
Choice reaction tasks are performed faster when stimulus location corresponds to response location (Simon effect). This spatial stimulus-response compatibility effect affects performance at the level of action planning and execution. However, when response selection is completed before movement initiation, the Simon effect arises only at the planning level. The aim of this study was to ascertain whether when a precocious response selection is requested, the Simon effect can be detected on the kinematics characterizing the online control phase of a non-ballistic movement. Participants were presented with red or green colored squares, which could appear on the right, left, above, or below a central cross. Depending on the square's color, participants had to release one of two buttons (right/left), then reach toward and press a corresponding lateral pad. We found evidence of the Simon effect on both action planning and on-line control. Moreover, the investigation of response conflict at the level of previous trials (i.e., n-1), a factor that might determine interference at the level of the current response, revealed a conflict adaptation process across trials. Results are discussed in terms of current theories concerned with the Simon effect and the distinction between action planning and control.


Checklist of the ants (Hymenoptera, Formicidae) of the Solomon Islands and a new survey of Makira Island.
The intent of this paper is to facilitate future research of the Solomon Islands ant fauna by providing the first comprehensively researched species inventory in over 75 years. The species list presented here includes the names of all ant species recorded from the islands that are available in the literature together with specimen records from several museum collections and new records from our 2008 Makira field expedition. All the names of described species presented are valid in accordance with the most recent Formicidae classification. In total, the checklist is composed of 237 species and subspecies (including 30 morphospecies) in 59 genera representing nine subfamilies. We report that the recent field expedition added 67 new species records to Makira and 28 new species records to the Solomon Islands. Our research recovered species occurrence records for 32 individual islands and five island groups. The five islands with the highest number of recorded species are: Makira (142 spp.), Guadalcanal (107 spp.), Malaita (70 spp.), Santa Isabel (68 spp.), and Rennell (66 spp.). Based on our results, we discuss the taxonomic composition of the archipelago's ant fauna, which islands are most in need of additional sampling, and the importance of establishing biodiversity baselines before environmental threats such as the invasive ant Wasmannia auropunctata cause irrevocable harm to the native biodiversity.


Sex and intrauterine growth restriction modify brain neurotransmitters profile of newborn piglets.
The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets. The results showed, firstly, significant effects of sex on the NBW newborns, with females having higher dopamine (DA) concentrations than males. The IUGR processes affected DA metabolism, with LBW piglets having lower concentrations of noradrenaline at the hippocampus and higher concentrations of the DA metabolites, homovanillic acid (HVA), at both the hippocampus and the amygdala than NBW neonates. The effects of IUGR were modulated by sex; there were no significant differences between LBW and NBW females, but LBW males had higher HVA concentration at the amygdala and higher concentration of 5-hydroxyindoleacetic acid, the serotonin metabolite, at the hippocampus than NBW males. In conclusion, the present study shows that IUGR is mainly related to changes, modulated by sex, in the concentrations of catecholamine neurotransmitters, which are related to adaptation to physical activity and to essential cognitive functions such as learning, memory, reward-motivated behavior and stress.


Distinct evolution process among type I interferon in mammals.
Interferon (IFN) is thought to play an important role in the vertebrate immune system, but systemic knowledge of IFN evolution has yet to be elucidated. To evaluate the phylogenic distribution and evolutionary history of type I IFNs, 13genomes were searched using BLASTn program, and a phylogenetic tree of vertebrate type I IFNs was constructed. In the present study, an IFNδ-like gene in the human genome was identified, refuting the concept that humans have no IFNδ genes, and other mammalian IFN genes were also identified. In the phylogenetic tree, the mammalian IFNβ, IFNɛ, and IFNκ formed a clade separate from the other mammalian type I IFNs, while piscine and avian IFNs formed distinct clades. Based on this phylogenetic analysis and the various characteristics of type I IFNs, the evolutionary history of type I IFNs was further evaluated. Our data indicate that an ancestral IFNα-like gene forms a core from which new IFNs divided during vertebrate evolution. In addition, the data suggest how the other type I IFNs evolved from IFNα and shaped the complex type I IFN system. The promoters of type I IFNs were conserved among different mammals, as well as their genic regions. However, the intergenic regions of type I IFN clusters were not conserved among different mammals, demonstrating a high selection pressure upon type I IFNs during their evolution.


Infection control: do we all have a role to play?
Infection control became a recognised discipline in 1970. Its principles, however, had been in existence for some time. In the middle of the nineteenth century, Semelweiss showed the importance of hand washing in coping with the transmission of infections. Better acceptance of Semelweiss's idea came after Pasteur, Lister and Koch related asepsis to the prevention of the spread of infection. Florence Nightingale, on the other hand, at about the same time, made a remarkable contribution to sanitation and isolation practices.


Rotational echo double resonance without proton decoupling under fast spinning condition.
We show that rotational echo double resonance (REDOR) experiments can be carried out without proton decoupling under the conditions of fast spinning and strong rf field. Numerical simulations on a five-spin systems show that no significant attenuation of the reference signal (S(0)) is observed at a spin rate of 25 kHz, provided that the rf power is larger than 100 kHz. This approach has been validated by (31)P{(13)C} REDOR measurements on isotopically labeled glyphosate. The obtained van Vleck's second moment is in favorable agreement with the value calculated based on the crystal structure.


[Large-vessel granulomatous vasculitis during the course of sarcoidosis: Takayasu's arteritis?].
Vascular involvement in sarcoidosis is very rare and is characterized by preferential involvement of large vessels similar to that observed in Takayasu's disease. Distinguishing between these two diseases is often difficult and constitutes a diagnostic pitfall. The association between sarcoidosis and Takayasu's arteritis is not coincidental and a common physiopathological factor may exist; it suggests a possible aetiopathogenetic relationship between sarcoidosis and Takayasu's arteritis and casts doubt on whether this form of vasculitis is a disease in its own right or simply a syndrome caused by other diseases. We report the case of a man with a 10-year history of cutaneous and pulmonary sarcoidosis who developed ischaemia of the right upper limb evocative of Takayasu's arteritis. The patient was successfully treated with oral steroids and methotrexate. This case prompts discussion about the relationship between Takayasu's disease and sarcoidosis. Physicians should be aware of the possible occurrence of granulomatous arteritis during the course of sarcoidosis which requires a special work-up.


Spa2p functions as a scaffold-like protein to recruit the Mpk1p MAP kinase module to sites of polarized growth.
Scaffold proteins play a major role in regulating MAP kinase pathways. In yeast, the Mpk1p-MAP kinase pathway functions to maintain the integrity of the cytoskeleton and the cell wall. In this module, the MEKK Bck1p functions upstream of the MEKs Mkk1p and Mkk2p, which in turn activate the MAP kinase Mpk1p. Mpk1p regulates several nuclear targets, including the transcription factors Rlm1p and SBF, and the two HMG1-like proteins NHP6A and NHP6B. Here we show that Mpk1p constitutively shuttles between the nucleus and the cytoplasm, and both Mpk1p and Mkk1p localize to sites of polarized growth in a Spa2p-dependent manner. Spa2p belongs to a group of proteins that includes Bni1p, Bud6p, and Pea2p, which are involved in the dynamic organization of the actin cytoskeleton during polarized growth. FRAP analysis shows that Spa2p-GFP is stably anchored at bud tips, whereas Mpk1p binds transiently. Spa2p interacts with Mkk1p and Mpk1p, and membrane bound Spa2p is sufficient to recruit Mkk1p and Mpk1p but not other MAP kinases to the cell cortex. Taken together, these results suggest that Spa2p functions as a scaffold-like protein for the cell wall integrity pathway during polarized growth.


Comparison of N2O Emissions and Gene Abundances between Wastewater Nitrogen Removal Systems.
Biological nitrogen removal (BNR) systems are increasingly used in the United States in both centralized wastewater treatment plants (WWTPs) and decentralized advanced onsite wastewater treatment systems (OWTS) to reduce N discharged in wastewater effluent. However, the potential for BNR systems to be sources of nitrous oxide (NO), a potent greenhouse gas, needs to be evaluated to assess their environmental impact. We quantified and compared NO emissions from BNR systems at a WWTP (Field's Point, Providence, RI) and three types of advanced OWTS (Orenco Advantex AX 20, SeptiTech Series D, and Bio-Microbics MicroFAST) in nine Rhode Island residences ( = 3 per type) using cavity ring-down spectroscopy. We also used quantitative polymerase chain reaction to determine the abundance of genes from nitrifying () and denitrifying () microorganisms that may be producing NO in these systems. Nitrous oxide fluxes ranged from -4 × 10 to 3 × 10 µmol NO m s and in general followed the order: centralized WWTP > Advantex > SeptiTech > FAST. In contrast, when NO emissions were normalized by population served and area of treatment tanks, all systems had overlapping ranges. In general, the emissions of NO accounted for a small fraction (<1%) of N removed. There was no significant relationship between the abundance of or genes and NO emissions. This preliminary analysis highlights the need to evaluate NO emissions from wastewater systems as a wider range of technologies are adopted. A better understanding of the mechanisms of NO emissions will also allow us to better manage systems to minimize emissions.


Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants - Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) - a molecular docking study.
COVID-19 (Coronavirus disease 2019) is a transmissible disease initiated and propagated through a new virus strain SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) since 31st December 2019 in Wuhan city of China and the infection has outspread globally influencing millions of people. Here, an attempt was made to recognize natural phytochemicals from medicinal plants, in order to reutilize them against COVID-19 by the virtue of molecular docking and molecular dynamics (MD) simulation study. Molecular docking study showed six probable inhibitors against SARS-CoV-2 Mpro (Main protease), two from Withania somnifera (Ashwagandha) (Withanoside V [10.32 kcal/mol] and Somniferine [9.62 kcal/mol]), one from Tinospora cordifolia (Giloy) (Tinocordiside [8.10 kcal/mol]) and three from Ocimum sanctum (Tulsi) (Vicenin [8.97 kcal/mol], Isorientin 4'-O-glucoside 2″-O-p-hydroxybenzoagte [8.55 kcal/mol] and Ursolic acid [8.52 kcal/mol]). ADMET profile prediction showed that the best docked phytochemicals from present work were safe and possesses drug-like properties. Further MD simulation study was performed to assess the constancy of docked complexes and found stable. Hence from present study it could be suggested that active phytochemicals from medicinal plants could potentially inhibit Mpro of SARS-CoV-2 and further equip the management strategy against COVID-19-a global contagion. HighlightsHolistic approach of Ayurvedic medicinal plants to avenge against COVID-19 pandemic.Active phytoconstituents of Ayurvedic medicinal plants Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) predicted to significantly hinder main protease (Mpro or 3Clpro) of SARS-CoV-2.Through molecular docking and molecular dynamic simulation study, Withanoside V, Somniferine, Tinocordiside, Vicenin, Ursolic acid and Isorientin 4'-O-glucoside 2″-O-p-hydroxybenzoagte were anticipated to impede the activity of SARS-CoV-2 Mpro.Drug-likeness and ADMET profile prediction of best docked compounds from present study were predicted to be safe, drug-like compounds with no toxicity.Communicated by Ramaswamy H. Sarma.


Prevalence of attention deficit/hyperactivity disorder in pediatric allergic rhinitis: a nationwide population-based study.
Allergic rhinitis (AR) is the most common chronic condition in pediatric populations. Characteristic symptoms in AR may bother daily activities and disturb sleep, leading to daytime inattention, irritability, and hyperactivity, which are also components of attention deficit/hyperactivity disorder (ADHD). Conflicting data exist in the literature regarding the relationship between ADHD and AR. The aim of this nationwide population-based study was to examine the prevalence and risk of ADHD among AR patients in a pediatric group. Data from a total of 226,550 pediatric patients <18 years old were collected from Taiwan's National Health Insurance Research Database from January 1 to December 31, 2005 and analyzed. We calculated the prevalence of allergic diseases based on various demographic variables, as well as in ADHD patients. We also used multivariable logistic regression to analyze the risk factors of ADHD. In 2005, the period prevalence rates of atopy and ADHD in patients <18 years of age were 15.35 and 0.6%, respectively. Pediatric patients with AR had a substantially increased rate of ADHD (p < 0.001) in terms of period prevalence and odds ratio. This significance existed across various demographic groups regardless of age, gender, area, or degree of urbanization. Neither comorbidity of atopic dermatitis nor bronchial asthma carried high risk for ADHD in AR patients. The present study revealed an increased rate of ADHD among AR patients. Therefore, evaluation of ADHD is advised for treatment of AR children.


[[Mortality estimation using proportional mortality indicators for developing countries]].
The author extends a technique for the indirect estimation of mortality originally developed by Courbage and Fargues. The technique is applied to national data from 35 developing countries for the year 1975. "Nine families of model life tables constructed by Coale and Demeny and the United Nations were applied to each of the object populations, and the level of mortality corresponding to the value of PMI (proportional mortality indicator: percentage of deaths at the ages 50 years and over) obtained from death registration data, was determined for each family." The author notes that the technique does not require assumptions regarding features of the population in question and is applicable to a non-stable population or an open population without any adjustment. (SUMMARY IN ENG)


On the fate of centrally administered somatostatin in the rat: massive hypersomatostatinemia resulting from leakage into the peripheral circulation has effects on growth hormone secretion and glucoregulation.
We examined the effects of intracerebroventricular (icv) administration of the somatostatin peptides, S-14 and S-28, and an analog, [D-Trp22]S-28, on spontaneous GH and glucose secretion in freely moving rats bearing chronic icv and intraatrial cannulae. Normal saline icv-treated control rats exhibited the typical pulsatile pattern of GH secretion. Central injection of S-14, S-28, and [D-Trp22]S-28 (each at two different doses, 5 and 10 micrograms) caused an early significant suppression of plasma GH levels which was of longer duration after S-28 or [D-Trp22]S-28 than after S-14 injection. The icv administration of S-28 and [D-Trp22]S-28 (but not S-14) also resulted in significant hyperglycemia, which persisted for periods up to 1 h. In a second study designed to determine whether somatostatin administered via the brain ventricle can reach the peripheral circulation, we measured plasma levels of S-14-like immunoreactivity (S-14 LI) and S-28-(15-28) LI at frequent time intervals after icv injection of S-14 (5 micrograms) and S-28 (10 micrograms). Plasma S-14 LI rose from a basal value of 0.16 +/- 0.02 (+/- SE) ng/ml to a peak of 3.0 +/- 1.0 ng/ml at 1 min, and S-28 icv resulted in a 150-fold increase in plasma S-28-(15-28) LI 1 min after injection. Sephadex G-50 gel chromatography revealed that the plasma immunoreactivity consisted of a single molecular species (either S-14 or S-28) corresponding to the centrally administered counterpart. These results demonstrate that after icv administration at high doses, both forms of somatostatin cause an acute inhibition of spontaneous GH secretion and that the larger form also causes hyperglycemia. We correlate these events with massive hypersomatostatinemia resulting from leakage of the somatostatin peptides from the cerebrospinal fluid into the systemic circulation. The findings indicate that icv injected hypothalamic hormones can reach the peripheral circulation and exert significant biological actions on distant target organs; thus, they have important implications for the design and interpretation of experiments in which peptides are administered via the cerebral ventricles.


Clinical outcome in a series of 173 cases of foreign body granuloma: improved outcomes with a novel surgical technique.
Soft-tissue filler injections have become popular, and injections of even illegal materials are widespread. Complications such as foreign body granuloma often occur in such cases, and appropriate treatment is mandatory but no optimal treatment has been established. We treated 173 patients who underwent surgical excision of foreign body granulomas via direct approach to the lesion (n = 121) or injection therapies (n = 52) at Kangbuk Samsung Hospital over a period of 7 years from April 2004 to February 2011. A retrospective chart review found that 104 patients had a history of treatment failure at other hospitals. Among these 104 patients, 83 had a history of prior injection therapy and 21 patients had a history of prior surgical therapy. Patient satisfaction was evaluated at our hospital on a scale of 1-5 using an in-house questionnaire. Comparisons between patients receiving injection therapy and patients receiving surgical therapy were made using the Mann-Whitney test. Patients who underwent surgical therapy via direct approach to the lesion reported statistically higher satisfaction scores 4(3-4) than those who underwent injection therapy 3(2-3) (p < 0.001). Our novel surgical technique results in better outcomes and patient satisfaction in cases of severe foreign body granuloma.


An empirical model for independent dose verification of the Gamma Knife treatment planning.
A formalism for an independent dose verification of the Gamma Knife treatment planning is developed. It is based on the approximation that isodose distribution for a single shot is in the shape of an ellipsoid in three-dimensional space. The dose profiles for a phantom along each of the three major axes are fitted to a function which contains the terms that represent the contributions from a point source, an extrafocal scattering, and a flat background. The fitting parameters are extracted for all four helmet collimators, at various shot locations, and with different skull shapes. The 33 parameters of a patient's skull shape obtained from the Skull Scaling Instrument measurements are modeled for individual patients. The relative doses for a treatment volume in the form of 31 x 31 x 31 matrix of points are extracted from the treatment planning system, the Leksell Gamma-Plan (LGP). Our model evaluates the relative doses using the same input parameters as in the LGP, which are skull measurement data, shot location, weight, gamma-angle of the head frame, and helmet collimator size. For 29 single-shot cases, the discrepancy of dose at the focus point between the calculation and the LGP is found to be within -1% to 2%. For multi-shot cases, the value and the coordinate of the maximum dose point from the calculation agree within +/-7% and +/-3 mm with the LGP results. In general, the calculated doses agree with the LGP calculations within +/-10% for the off-center locations. Results of calculation with this method for the dimension and location of the 50% isodose line are in good agreement with results from Leksell GammaPlan. Therefore, this method can be served as a useful tool for secondary quality assurance of Gamma Knife treatment plans.


Cerebrospinal fluid investigations in tuberculous meningitis.
The results of conventional cerebrospinal fluid (CSF) investigations (CSF cell count, protein and glucose concentrations and Pandy's test for CSF globulin) obtained on admission and sequentially from weekly follow-up lumbar punctures for 4 weeks were evaluated in 99 children (median age 28 months) with stage II (50 children) and stage III (49 children) tuberculous meningitis. On admission, six children (6%) had a CSF cell count greater than 500 x 10(6)/l and nine (9%) a polymorphonuclear predominance. A CSF protein less than 0.8 g/l was found in 17 children (18%) of 97 in whom CSF protein was evaluated. Globulin was either absent or present as a trace only in 26 children (27%). CSF glucose was less than 2.2 mmol/l in 58 cases (60%) and less than 2.5 mmol/l in 67 (69%). In 63 children weekly CSF specimens obtained for the 1st 4 weeks of therapy showed an uninterrupted decline in cell count in 23 (37%), a fluctuating downward trend in 27 (43%) and a fluctuating upward trend in 13 (21%). Sequential CSF protein values in 57 children showed an uninterrupted rise in three (5%), a fluctuating upward course in 19 (33%), an uninterrupted downward trend in seven (12%), and a fluctuating downward course in 28 (49%). Of the 61 children in whom sequential CSF glucose concentrations were available, 11 (18%) experienced fluctuating concentrations, values falling to less than 2.2 mmol/l after being greater than 2.2 mmol/l on admission or after having risen to greater than 2.2 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)


Non-Hermitian surface hopping.
We present a generalized non-Hermitian equation of motion (nH-EOM) to go beyond standard trajectory surface hopping dynamics. The derivation is based on the Born-Huang expansion of the total wave function and the polar representation of the nuclear factor. The nH-EOM contains two additional terms, a skew symmetry term iΓ with dissipation operator Γ to account for decoherence, and a kinetic-energy renormalization term to account for phase shifts, without destroying the invariance to the choice of representation. Numerically, the nH-EOM can still be solved efficiently using a semiclassical approximation in the framework of Tully's fewest-switches surface hopping (FSSH) algorithm. Applications to model Hamiltonians demonstrate improved performance over the standard FSSH approach, through comparison to exact quantum results.


Evolution of coarctation of the aorta in intrauterine life.
The echocardiographic appearances in a case of coarctation of the aorta, first suspected at 21 weeks of intrauterine life, changed progressively during this time. Early right ventricular hypertrophy and increasing aortic arch hypoplasia were evident and suggest the possible sequence of evolution of the coarctation in this case.


Comparison of ghosting effects for three commercial a-Si EPIDs.
Many studies have reported dosimetric characteristics of amorphous silicon electronic portal imaging devices (EPIDs). Some studies ascribed a non-linear signal to gain ghosting and image lag. Other reports, however, state the effect is negligible. This study compares the signal-to-monitor unit (MU) ratio for three different brands of EPID systems. The signal was measured for a wide range of monitor units (5-1000), dose-rates, and beam energies. All EPIDs exhibited a relative under-response for beams of few MUs; giving 4 to 10% lower signal-to-MU ratios relative to that of 1000 MUs. This under-response is consistent with ghosting effects due to charge trapping.


Organogenic responses of Pinus pinea cotyledons to hormonal treatments: BA metabolism and cytokinin content.
Isolated cotyledons from mature Pinus pinea L. embryos were cultured in vitro in a factorial combination of 4.4, 10 and 44.4 microM N6-benzyladenine (BA) for 2, 4, 8, 16 and 35 days to optimize shoot regeneration. Incubation of explants in 44.4 microM BA for 4 days, in place of the standard incubation in 4.4 microM BA for 35 days, reduced the entire culture period to 4 weeks. Shortening the culture period had no significant effect on the caulogenic response or the number of buds formed per cotyledon. To establish the relationship between key moments in the caulogenic process induced by 4.4 microM BA and the endogenous concentrations of the active forms of BA and other isoprenoid-type cytokinins (CKs), we examined uptake, metabolism and amount of BA, as well as the amounts of zeatin, dihydrozeatin and their ribosides in P. pinea cotyledons after 1, 2, 6, 12 and 24 h, and 2, 4, 8, 16 and 35 days of exposure to 8-[14C]BA. Uptake and release of BA were associated with water movement between explants and the medium during the first 8 days of culture. The interconvertible forms of BA were the main metabolites formed in the tissues. Inactivation of BA as a result of conjugation or oxidation was insignificant. The endogenous concentration of BA + N6-benzyladenosine was 20-fold higher than the exogenously applied BA during the competence acquisition phase (Days 0-3). The concentration of isoprenoid-type CKs also increased 16-fold and then decreased during this time. Induction of shoot buds (Days 4-8) was characterized by a second peak of BA uptake by explants that triggered the synthesis of N6-benzyladenosine-5 -monophosphate and by the maintenance of isoprenoid-type CKs. Reestablishment of CK homeostasis marked the shift from the induction phase to the shoot development phase in this organogenic process (Days 8-12).


Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy.
Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S-antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from Sierra Leone, West Africa using a two-step migration-inhibition factor assay. Patients were subdivided into three groups: (1) without ocular involvement (n = 10), (2) with ocular onchocerciasis limited to the anterior segment (n = 19), and (3) with onchocercal chorioretinopathy (n = 21). A group of endemic controls (n = 25) from Sierra Leone were also studied. The cellular immune response to concanavalin A (Con A) was measured to assess the general capacity of lymphocytes to respond to a mitogen. Four of 50 (8%) patients with onchocerciasis and four of 25 (16%) endemic controls reacted with at least one retinal antigen. From the patients with onchocercal chorioretinopathy two of 21 (10%) showed a positive cellular response. The general mitogen response tested with Con A was positive in all these individuals. A role for an antiretinal autoimmune mechanism in the pathogenesis of onchocercal chorioretinopathy, as studied with human S-antigen, IRBP, or crude retinal extract, could not be shown because the cellular response to these antigens did not differ in patients with or without onchocercal chorioretinopathy or in endemic controls.


Molecular characterization of a unique retrovirus associated with a fish tumor.
The walleye dermal sarcoma is a mesenchymal tumor which seasonally affects up to 27% of adult walleye fish (Stizostedion vitreum). It arises multicentrically in the dermis, in which its development remains restricted. We report the molecular cloning of a type C retrovirus from this tumor. The genome of this virus (13.2 kb) is larger than that of all retroviruses and in that respect is approximated only by the recently characterized spumaviruses. In tumors, the predominantly unintegrated linear viral DNA has a single-stranded gap region which is similar to the structure found in some lentiviruses and all spumaviruses. The presence of at least four viral transcripts suggests that this virus has the capacity to encode accessory functions and is reminiscent of the transcriptional complexity of lentiviruses and spumaviruses.


The validation of patient-rated global assessments of treatment benefit, satisfaction, and willingness to continue--the BSW.
This study evaluated the validity of three single-item, patient-rated, interviewer-administered, global assessments of treatment benefit, satisfaction with treatment and willingness to continue treatment, collectively referred to as the BSW. The BSW, micturition diaries, the Overactive Bladder Questionnaire (OAB-q) and the King's Health Questionnaire (KHQ) were included in part or in total in three OAB clinical trials. Discriminant validity for full and dichotomized responses was assessed with anovas models and correlations were used to evaluate construct validity. The BSW demonstrated significant differences among the majority of the response levels on all measures of micturitions in all studies. The BSW also demonstrated discriminant validity with the OAB-q and the KHQ. BSW measures demonstrated significant differences among the change scores for all subscales of the OAB-q and the majority of the KHQ domains with both full and dichotomized responses. Patients who were dissatisfied with treatment and those unwilling to continue treatment also reported significantly worse OAB-q and KHQ scores compared with those who were satisfied with treatment or willing to continue treatment. BSW measures were moderately correlated with the micturition variables, moderate to strongly correlated with the OAB-q and weak to moderately with the KHQ, providing support for the construct validity of the BSW measures. The BSW is a useful tool to capture patients' global impressions of three key elements of treatment outcome: a perceived benefit, satisfaction with treatment, and the willingness to continue treatment, and can facilitate patient-physician communication as well as be informative to researchers.


Controversy of free radical hypothesis: reactive oxygen species--cause or consequence of tissue injury?
For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species (ROS), due to their potentially harmful effect towards cellular constituents, is one of the most frequently cited in biomedical sciences. In fact, the ROS-mediated alterations of biomacromolecules are considered to be essential events in the etiopathogenesis of those diseases where involvement of ROS has been indicated. ROS easily react in vitro with most biological molecules, causing their degradation and destruction. This may implicitly suggest that, when excessively produced in vivo, ROS are deleterious to integral components of the cell and cause their dysfunctions. Some experimental data indicate that ROS-mediated lipid peroxidation, protein oxidation and oxidative alterations to nucleic acids are crucial events of unfavorable actions of ROS. Yet the most convincing evidence, i.e. unambiguous inhibition of tissue injury by pretreatment with antioxidants, has not been provided. On the contrary, there are quite a few papers reporting failure in applying antioxidants to heal those pathologies where the causal role of ROS was supposed. Other papers reported serious complications arising from antioxidant therapy, which is quite in contradiction to its expected effect. On the other hand, an increasing number of recent findings have provided evidence of a key role of ROS in both intracellular signaling and intercellular communication, processes involved in maintaining homeostasis. Hence, some investigators consider excessive production of ROS to be rather a "smoke after the fire" than "a deleterious fire" itself, suggesting the occurrence of overproduced ROS as being the consequence of some primary damage. The present paper aims at summarizing some pros and cons of various opinions with an attempt to help better understand the involvement of ROS in tissue injury.


Head-to-head comparison of Enzyme Linked Immunosorbent Assay (ELISA) and Enhanced Chemiluminescence Immunoassay (ECLIA) for the detection of Transfusion Transmitted Disease (TTD) Markers; HIV, HCV and HBV in blood donors, in India.
Safe blood transfusion being the cornerstone of any Blood Transfusion Services requires meticulous testing for Transfusion Transmitted Disease (TTD) markers in donated blood. We performed head-to-head comparison of ELISA and ECLIA for detection of TTD markers for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) in 10,164 Indian blood donors. All concordant reactive, discordant reactive and concordant non-reactive samples were re-confirmed using Individual Donor-Nucleic Acid Amplification Test (ID-NAT) as the 'gold standard' test. 223 samples were found reactive; out of which 93 (four HIV, 34 HCV and 55 HBV) samples were concordant reactive and tested positive by both methods while 130 discordant reactive samples were reactive either by ELISA or ECLIA. Out of 130 discordant reactive samples ELISA-reactive and ECLIA-non-reactive samples for HIV, HCV and HBV were 15, eight, and 29 respectively while ECLIA-reactive ELISA-non-reactive samples for HIV, HCV and HBV were 39, 36 and three respectively. Sensitivity of ECLIA and ELISA was 100 % for all three TTD markers, while specificity was 99.62 % and 99.85 % for HIV; 99.64 % and 99.84 % for HCV and 99.97 % and 99.70 % for HBV respectively. Strength of agreement and Kappa Statistics for ECLIA and ELISA compared to the gold standard test was poor and fair for HIV (k = 0.169 and 0.347), moderate and good for HCV (k = 0.539 and 0.763), and very good and good for HBV (k = 0.973 and 0.783). According to this study, it can be concluded both the testing techniques; ELISA and ECLIA have 100 % sensitivity for the detection for HBV, HCV and HIV in blood donors and therefore, either can be used for TTD screening in blood banks in India.


[Early diagnosis of myelopathy hand improves efficacies of surgical treatment of cervical spondylotic myelopathy].
To evaluate the value of early diagnosis of myelopathy hand in improving the efficacies of surgical treatment of cervical spondylotic myelopathy. Analyses were conducted for 118 cases of cervical spondylotic myelopathy at Department of Orthopedics, Changzheng Hospital and Zhabei Campus from January 2009 to November 2012. They were diagnosed with myelopathy hand and classified by finger escape sign, 10-second grip and release test of fist along with electromyography of ill limb to evaluate the movement function of hands . They were divided into early diagnosis group with myelopathy hand (A, n = 62) and routine diagnosis group without myelopathy hand (B, n = 56) . All patients with cervical spondylotic myelopathy underwent anterior corpectomy decompression and fusion. The average follow-up period was up to 4. 1 years. Modified Japanese Orthopedic Association (JOA) score was used to evaluate neurological function preoperation and 48 months postoperation respectively. T-test of SPSS statistical software 13. 0 was used to analyze the inter-group difference of JOA scores before and after surgery. There were no inter-group significant differences in age, gender or smoking ratio. The JOA scores of groups A and B were 10. 1 ± 2. 3, 14. 9 ± 2. 0; 9. 8 ± 3. 1, 12. 1 ± 2. 3 before surgery and 48 months postoperation and the increase of JOA scores were 4. 8 ± 0. 9, 2. 3 ± 0. 6. The inter-group differences between JOA scores before and after surgery were statistically significant (P = 0. 00). And the inter-group differences between the increase of JOA scores at 48 months postoperation were statistically significant (P = 0. 00). Neurological function improves more for patients with cervical spondylotic myelopathy diagnosed with myelopathy hand in early stage than those diagnosed conventionally without myclopathy hand. And an early diagnosis of this sign may boost the surgical efficacies for cervical spondylotic myelopathy.


Effects of increased and deregulated expression of cell division genes on the morphology and on antibiotic production of streptomycetes.
This paper describes the effects of increased expression of the cell division genes ftsZ, ftsQ, and ssgA on the development of both solid- and liquid-grown mycelium of Streptomyces coelicolor and Streptomyces lividans. Over-expression of ftsZ in S. coelicolor M145 inhibited aerial mycelium formation and blocked sporulation. Such deficient sporulation was also observed for the ftsZ mutant. Over-expression of ftsZ also inhibited morphological differentiation in S. lividans 1326, although aerial mycelium formation was less reduced. Furthermore, antibiotic production was increased in both strains, and in particular the otherwise dormant actinorhodin biosynthesis cluster of S. lividans was activated in liquid- and solid-grown cultures. No significant alterations were observed when the gene dosage of ftsQ was increased. Analysis by transmission electron microscopy of an S. coelicolor strain overexpressing ssgA showed that septum formation had strongly increased in comparison to wild-type S. coelicolor, showing that SsgA clearly influences Streptomyces cell division. The morphology of the hyphae was affected such that irregular septa were produced with a significantly wider diameter, thereby forming spore-like compartments. This suggests that ssgA can induce a process similar to submerged sporulation in Streptomyces strains that otherwise fail to do so. A working model is proposed for the regulation of septum formation and of submerged sporulation.


[Surgical treatment for tumors in the superior sulcus].
Surgical challenge for tumors arising posterior-apical lung well known as Pancoast tumor and those of the apical lung involving anterior thoracic outlet structures (mainly subclavian vessels) have been continued with seeking the pathway of the proper approaches and the strategy combined modalities as radiotherapy or chemoradiotherapy followed by surgery for these 50 years, and operative outcome have been improved these decades. As complete resection of the tumors is the main factor for operative results, the preoperative evaluation on involved structures and the choice among the different approaches is important. We present our experience for Pancoast tumors with posterior approaches and for cervico-thoracic tumors resected with anterior approaches.


Annotation: the therapeutic alliance--a significant but neglected variable in child mental health treatment studies.
There has been relatively little research into therapeutic alliance in child and adolescent mental health and virtually no incorporation of alliance measures as a variable in treatment trials in Child and Adolescent Mental Health Services (CAMHS). A selective literature review on studies in therapeutic alliance in adulthood and childhood along with a theoretical formulation of possible mechanisms of alliance. Therapeutic alliance is reliably measurable both by observation and questionnaire methods at all points in the treatment cycle. In both adult and child studies it shows a consistent, albeit modest, association with treatment outcome. In specific adult studies it has shown a high predictive validity in relation to outcome compared to other variables. In child studies alliance is particularly salient in externalising disorder and predicts outcome of inpatient treatment. Child alliance and parental alliance are independent factors. Theoretical models of alliance outlined in this paper suggest testable hypotheses regarding predictors for positive and negative alliance. Therapeutic alliance in CAMHS is measurable and worth measuring. It is likely to be an important variable for treatment outcome studies and should be included in future trial designs.


Miniaturization: the clue to clinical application of the artificial placenta.
The artificial placenta as a fascinating treatment alternative for neonatal lung failure has been the subject of clinical research for over 50 years. Pumpless systems have been in use since 1986. However, inappropriate dimensioning of commercially available oxygenators has wasted some of the theoretical advantages of this concept. Disproportional shunt fractions can cause congestive heart failure. Blood priming of large oxygenators and circuits dilutes fetal hemoglobin (as the superior oxygen carrier), is potentially infectious, and causes inflammatory reactions. Flow demands of large extracorporeal circuits require cannula sizes that are not appropriate for use in preterm infants. NeonatOx, a tailored low-volume oxygenator for this purpose, has proven the feasibility of this principle before. We now report the advances in biological performance of a refined version of this specialized oxygenator.


SUPPORTING THE PROFESSIONAL DEVELOPMENT OF FACULTY TEACHERS.
I and my colleagues designed and implemented a longitudinal faculty development program to improve humanistic teaching and role modeling at 30 medical schools involving more than 1,000 faculty members and 50 local facilitators. Evaluation demonstrated that participating faculty members who completed our program were superior humanistic teachers compared to controls as rated by their learners on a validated questionnaire. Participants were also sufficiently engaged to attend 80% or more of the curricular sessions with few dropouts, indicating the feasibility and generalizability of the program. Preliminary analysis of participants' personal narratives at the beginning compared to the end of our program suggested advancement in professional identity formation. I provide examples of the narratives and discuss future studies addressing this topic.


Effective Separation of High-Ash Fine Coal Using Water Containing Positively Charged Nanobubbles and Polyaluminum Chloride.
The coal industry is facing the challenge of treating high-ash fine coal. In this study, we proposed an effective method to handle high-ash fine coal using water containing positively charged nanobubbles (PCNBs) and polyaluminum chloride (PAC). For comparison, normal nanobubble (NB) water was tested in parallel. Flotation results of a modeled high-ash fine coal showed that compared to the use of NBs alone, an enhanced combustible recovery with a simultaneous reduction in ash recovery was obtained when using water containing PCNBs and PAC. Particle size distribution together with particle video microscopy (PVM) and the degree of entrainment analysis were conducted to understand the underpinning mechanism. It was found that the presence of PCNBs intensified the aggregation of fine coal particles, which accounted for the boosted combustible recovery. It was interesting that PAC could disrupt coal flocs induced by NBs, leading to the release of trapped kaolinite particles with alleviated clay recovery by entrapment.


The corticosteroid synthesis inhibitors metyrapone and aminoglutethimide impair long-term memory for a passive avoidance task in day-old chicks.
Long-term memory for a passive avoidance task in day-old chicks has proved to depend upon an action of the adrenal steroid corticosterone through specific receptors in a brain region, the intermediate medial hyperstriatum ventrale (IMHV), involved in learning the task. In this study, we questioned whether pretraining peripheral administration of drugs described to inhibit either basal levels of corticosterone - aminoglutethimide - or treatment-induced stimulated corticosterone secretion - metyrapone - might interfere with retention for the task at 24 h post-training. The results showed a dose-dependent effect of the inhibitors, with the highest doses tested for both drugs (10 and 50 mg/kg for metyrapone, and 50 mg/kg for aminoglutethimide) being amnestic for the task. Additional experiments, in which we studied possible effects of the inhibitors on concomitant aspects of learning (i.e., reactivity to novelty, and pecking pattern), show that the drugs did not affect general behavioural reactivity. The present results thus support the idea that training-induced corticosterone release plays a key role in the neurobiological processes that determine the establishment of a persistent memory for the aversively motivated avoidance response. In addition, they point to corticosteroid inhibitor drugs as potential tools for the study of the interactions between steroid hormones and cognition-enhancing compounds in this learning task.


Why aggregated learning follows the power law of practice when individual learning does not: comment on Rickard (1997, 1999), Delaney et al. (1998), and Palmeri (1999).
The power law of practice is often considered a benchmark test for theories of cognitive skill acquisition. Recently, P. F. Delaney, L. M. Reder, J. J. Staszewski, and F. E. Ritter (1998), T. J. Palmeri (1999), and T. C. Rickard (1997, 1999) have challenged its validity by showing that empirical data can systematically deviate from power-function fits. The main purpose of the present article is to extend their explanations in two ways. First, the authors empirically show that abrupt changes in performance are not necessarily based on a shift from algorithm to memory-based processing, but rather and more generally, that they occur whenever a more efficient task strategy is generated. Second, the authors show mathematically and per simulation that power functions can perfectly fit aggregated learning curves even when all underlying individual curves are discontinuous. Therefore, the authors question conclusions drawn from fits to aggregated data.


Identifying disruptors of male germ cell development by small molecule screening in ex vivo gonad cultures.
Germ cell development involves formation of the spermatogenic or oogenic lineages from the bipotential primordial germ cells. Signaling mechanisms in the fetal testis and ovary determine whether germ cells enter the male or female developmental pathway, respectively. These signaling processes underpin an important phase of germ cell development, disruption of which can lead to failed germ cell function resulting in infertility or the formation of germ cell tumours. In this study we have developed a small molecule screening protocol combined with flow cytometry to identify signaling pathways that direct male-specific development of germ cells. Here we provide a detailed method for this screening protocol, which we have used to identify signaling pathways important for male germ cell development. This method will be of particular use in screening inhibitors of signaling pathways, endocrine disruptors or other chemicals for their ability to disrupt testis and germ cell development, thereby providing insight into testicular dysgenesis and factors underlying poor male reproductive health.


Pituitary adenylate cyclase-activating polypeptide specifically increases cytosolic calcium ion concentration in rat gonadotropes and somatotropes.
The hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), is a potent stimulator of cAMP accumulation in the anterior pituitary gland, though its physiological function has yet to be defined. To establish the target cells of PACAP action we have measured PACAP-induced changes in cytosolic free calcium ion concentration ([Ca2+]i) in single identified anterior pituitary cells. This was achieved by combining fura-2 videomicroscopy, to measure [Ca2+]i, and reverse hemolytic plaque assays, to identify the secreted hormone. PACAP (100 nM) increased [Ca2+]i in 32% of all pituitary cells. These responses were predominantly seen in identified gonadotropes and somatotropes, but rarely in corticotropes or lactotropes. PACAP induced two forms of Ca2+ response in gonadotropes; a "Ca2+ spike" (independent of extracellular Ca2+) in 72% of responding gonadotropes, and an extracellular Ca(2+)-dependent "Ca2+ plateau" (28% of cells). In somatotropes, PACAP stimulated either Ca2+ plateau responses (58% of responding somatotropes) or repetitive "Ca2+ transients" (42% of cells), both of which were dependent upon extracellular Ca2+. PACAP, therefore, produces distinct changes in [Ca2+]i in gonadotropes and somatotropes, which may be related to distinct intracellular messenger pathways. The identification of these cell types as targets of PACAP action suggests a role in the regulation of reproduction and growth.


Controlling stomatal aperture in semi-arid regions-The dilemma of saving water or being cool?
Stomatal regulation of leaf gas exchange with the atmosphere is a key process in plant adaptation to the environment, particularly in semi-arid regions with high atmospheric evaporative demand. Development of stomata, integrating internal signaling and environmental cues sets the limit for maximum diffusive capacity of stomata, through size and density and is under a complex genetic control, thus providing multiple levels of regulation. Operational stomatal conductance to water vapor and CO2 results from feed-back and/or feed-forward mechanisms and is the end-result of a plethora of signals originated in leaves and/or in roots at each moment. CO2 assimilation versus water vapor loss, proposed to be the subject of optimal regulation, is species dependent and defines the water use efficiency (WUE). WUE has been a topic of intense research involving areas from genetics to physiology. In crop plants, especially in semi-arid regions, the question that arises is how the compromise of reducing transpiration to save water will impact on plant performance through leaf temperature. Indeed, plant transpiration by providing evaporative cooling, is a major component of the leaf energy balance. In this paper we discuss the dilemma of 'saving water or being cool' bringing about recent findings from molecular genetics, to development and physiology of stomata. The question of 'how relevant is screening for high/low WUE in crops for semi-arid regions, where drought and heat co-occur' is discussed.


Qualitative and quantitative effects of treatment for dental fear and avoidance.
In a Swedish community-based program for the treatment of dental phobic patients, a clinical trial was performed among 99 severely phobic individuals with long-standing avoidance of dental treatment. The modes of treatment compared were dentistry under general anesthesia and a broad-based psychophysiological therapy both followed by conventional dental treatment. Psychometric as well as overt behavioral measures were used to elucidate initial state and changes in patients' dental fear and behaviors. Quantitative and qualitative data are presented of initial and long-term (two years) treatment effects. The results indicate a significantly better effect for the psychophysiological therapy.


Recovery of Functional Proteins from Pig Brain Using pH-Shift Processes.
The goal of this work is to explore if pH-shift processing could be used as a cold refinery technique to manufacture pig brain protein isolate (PI). Pig brain protein had the highest solubility at pH 2 (acid method) and pH 12 (alkaline method). As the protein solution's zeta-potential was near 0 with the lowest solubility, pH 5.0 was chosen as the precipitation pH. Alkaline process produced a 32% dry matter yield with phospholipid content of 35 mg/100 g. The alkaline-made PI was better at forming soft gels and had good emulsifying and foaming capabilities. Although the acid-made PI included less residual lipid and total haem protein and was whiter in colour, it could not be gelled. Acid-made PI was more prone to lipid oxidation with a poorer ability to function as an emulsifier and foaming agent. Thus, functional proteins from pig brain may be isolated using the alkaline pH-shift technique.