Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I.
Cell death is an important target for imaging the early response of tumors to treatment. We describe here the validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of synaptotagmin-I. Methods: The capability of near-infrared fluorophore-labeled and 99mTc- and 111In-labeled derivatives of C2Am for imaging tumor cell death, using planar near-infrared fluorescence imaging and SPECT, respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft. Results: The fluorophore-labeled C2Am derivative showed predominantly renal clearance and high specificity and sensitivity for detecting low levels of tumor cell death (2%-5%). There was a significant correlation (R > 0.9, P < 0.05) between fluorescently labeled C2Am binding and histologic markers of cell death, including cleaved caspase-3, whereas there was no such correlation with a site-directed mutant of C2Am (iC2Am) that does not bind phosphatidylserine. 99mTc-C2Am and 111In-C2Am also showed favorable biodistribution profiles, with predominantly renal clearance and low nonspecific retention in the liver and spleen at 24 h after probe administration. 99mTc-C2Am and 111In-C2Am generated tumor-to-muscle ratios in drug-treated tumors of 4.3× and 2.2×, respectively, at 2 h and 7.3× and 4.1×, respectively, at 24 h after administration. Conclusion: Given the favorable biodistribution profile of 99mTc- and 111In-labeled C2Am, and their ability to produce rapid and cell death-specific image contrast, these agents have potential for clinical translation.


Long progression-free survival by pemetrexed continuation maintenance therapy following cisplatin-based chemotherapy in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. The combination of cisplatin and pemetrexed has been established as a standard chemotherapy that confers a survival benefit. Because the regimen is sometimes hampered by the renal toxicity of cisplatin and no second-line chemotherapy has yet been established, the strategy of administering a higher total dose of pemetrexed to optimize the regimen could be promising. We herein describe the case of a 69-year-old man with MPM who underwent five cycles of cisplatin plus pemetrexed and exhibited a partial response. Because his serum creatinine increased, pemetrexed maintenance therapy (PMT) was adopted, and 18 cycles were successfully delivered and the patient achieved a complete response. This case suggests that PMT could thus be useful for treating MPM.


Protein Stabilization by Alginate Binding and Suppression of Thermal Aggregation.
Polymers designed to stabilize proteins exploit direct interactions or crowding, but mechanisms underlying increased stability or reduced aggregation are rarely established. Alginate is widely used to encapsulate proteins for drug delivery and tissue regeneration despite limited knowledge of its impact on protein stability. Here, we present evidence that alginate can both increase protein folding stability and suppress the aggregation of unfolded protein through direct interactions without crowding. We used a fluorescence-based conformational reporter of two proteins, the metabolic protein phosphoglycerate kinase (PGK) and the hPin1 WW domain to monitor protein stability and aggregation as a function of temperature and the weight percent of alginate in solution. Alginate stabilizes PGK by up to 14.5 °C, but stabilization is highly protein-dependent, and the much smaller WW domain is stabilized by only 3.5 °C against thermal denaturation. Stabilization is greatest at low alginate weight percent and decreases at higher alginate concentrations. This trend cannot be explained by crowding, and ionic screening suggests that alginate stabilizes proteins through direct interactions with a significant electrostatic component. Alginate also strongly suppresses aggregation at high temperature by irreversibly associating with unfolded proteins and preventing refolding. Both the beneficial and negative impacts of alginate on protein stability and aggregation have important implications for practical applications.


The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of follicular lymphoma: an evidence-based review.
Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of follicular non-Hodgkin lymphoma in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations reached unanimously by a panel of follicular lymphoma experts are: (1) autologous SCT is recommended as salvage therapy based on pre-rituximab data, with a significant improvement in overall survival (OS) and progression-free (PFS) survival; (2) autologous SCT is not recommended as first-line treatment for most patients because of no significant improvement in OS; (3) autologous SCT is recommended for transformed follicular lymphoma patients; (4) reduced intensity conditioning before allogeneic SCT appears to be an acceptable alternative to myeloablative regimens; (5) an HLA-matched unrelated donor appears to be as effective an HLA-matched related donor for reduced intensity conditioning allogeneic SCT. There are insufficient data to make a recommendation on the use of autologous SCT after rituximab-based salvage therapy. Eleven areas of needed research in the treatment of follicular lymphoma with SCT were identified and are presented in the review.


Discovery of an Inhibitor of the Proteasome Subunit Rpn11.
The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Additionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have been validated in the treatment of multiple myeloma, with several FDA-approved therapeutics. Rpn11 is a Zn2+-dependent metalloisopeptidase that hydrolyzes ubiquitin from tagged proteins that are trafficked to the proteasome for degradation. A fragment-based drug discovery (FBDD) approach was utilized to identify fragments with activity against Rpn11. Screening of a library of metal-binding pharmacophores (MBPs) revealed that 8-thioquinoline (8TQ, IC50 value ∼2.5 μM) displayed strong inhibition of Rpn11. Further synthetic elaboration of 8TQ yielded a small molecule compound (35, IC50 value ∼400 nM) that is a potent and selective inhibitor of Rpn11 that blocks proliferation of tumor cells in culture.


Sensitization to the behavioural effects of cocaine: alterations in tyrosine hydroxylase or endogenous opioid mRNAs are not necessarily involved.
After repeated administration of cocaine at intervals, sensitization phenomena can be observed, so that its behavioural effects are enhanced. Since this phenomenon is long-lasting, it was of interest to study which persistent alterations in the activity of dopaminergic neurones or of endogenous opioid systems downstream of dopaminergic synapses in the basal ganglia are involved in the sensitization. Cocaine (10 mg/kg i.p.) was administered to rats on days 1, 3, 5 and 7 and saline on days 2, 4 and 6 ("repeated cocaine"), or saline was injected on days 1-6 and cocaine on day 7 ("acute cocaine"), or saline was injected on days 1-7 ("saline group"). The "repeated cocaine" schedule led to a significant sensitization to the locomotor activation produced by cocaine on day 7 or on day 17, 10 days after the end of sensitization protocol. Microdialysis in the nucleus accumbens which was performed after administration of cocaine (10 mg/kg i.p.) on day 7, or after an administration of the same dose 10 days after the last administration of cocaine, respectively, revealed significant acute increases of extracellular dopamine to about 200% of basal values. These increases were similar in "acute cocaine" and in "repeated cocaine" animals both after 7 days and after 17 days. For in situ hybridization studies, rats were sacrificed on day 7, 4.5 h after the last cocaine or saline administration. The mRNA for tyrosine hydroxylase (TH) in substantia nigra + ventral tegmental area was significantly elevated to about 140% of saline controls both in the "repeated cocaine" and the "acute cocaine" group as compared with the "saline group". In contrast, there were no differences between the three groups in the mRNAs of preprodynorphin or preproenkephalin levels measured in the nucleus accumbens (core and shell). These results suggest that sensitization phenomena to cocaine are not necessarily connected with alterations in the dopaminergic activity in the mesolimbic system or in the transcription of precursors of endogenous opioid peptides which are located downstream of the dopaminergic synapses.


Energy source and ionophore supplementation effects on lamb growth, carcass characteristics, visceral organ mass, diet digestibility, and nitrogen metabolism.
In Exp. 1, 72 Targhee lambs (initial BW 22.1+/-.3 kg) were used to determine the effects of energy source (alfalfa pasture vs limit-fed, all-concentrate) and ionophore addition on performance, visceral organ mass, and carcass characteristics. There were no differences (P > . 10) in ADG or gain/ feed due to ionophore supplementation. Lambs that grazed alfalfa had greater (P < .05) liver, omasum, abomasum, small intestine, cecum, and large intestine weights than did lambs fed the concentrate diet. Lambs fed the concentrate diet had greater (P < .01) hot carcass weights, larger (P < .01) loin eye areas, and greater (P < .001) dressing percentages than lambs that grazed alfalfa. In Exp. 2, lambs offered the concentrate diet had greater (P < .001) DM and OM digestibilities than lambs offered alfalfa (89.5 and 91.1 vs 72.4 and 74.2%, respectively). Apparent and true N digestibilities were greater (P < .001) for the concentrate diet than for alfalfa (90.9 and 101.7 vs 77.7 and 91.9%, respectively). Likewise, grams of N retained per day were twice as great (P < .001) with the concentrate diet than with alfalfa (14.9 vs 6.0 g/ d). The greater visceral organ mass and resulting increases in energy and protein requirements in lambs that grazed alfalfa were probably responsible for the lesser hot carcass weight and dressing percentage compared with lambs fed 100% concentrate.


Membrane uptake kinetics of jet fuel aromatic hydrocarbons from aqueous solutions studied by a membrane-coated fiber technique.
The absorption of aromatic hydrocarbons from aqueous media is a critical step involved in many biological processes after occupational and environmental exposures to jet fuel. A membrane-coated fiber (MCF) technique was used to study the uptake kinetics. A flow-through system was used to provide a constant concentration for the prolonged permeation experiments. Polydimethylsiloxane (PDMS) and polyacrylate (PA) MCFs were used to study the differential absorptivity of the aromatic compounds between the two membrane materials. The equilibrium absorption amount and a kinetic parameter describing the absorption kinetics were obtained by the regression of the permeation profiles of the aromatic compounds with a mathematical model. The partition coefficients, uptake, and elimination rate constants were determined for six benzene and three naphthalene derivatives. The PDMS/water partition coefficients of the benzene and naphthalene derivatives were linearly correlated with their logK(o/w) (LogK(pdms/w) = 0.871LogK(o/w) - 0.241, R(2) = 0.995). The PA/water partition coefficients of the benzene derivatives and the naphthalene derivatives were correlated differently with their logK(o/w). The correlation equations for benzene and naphthalene derivatives were LogK(pa/w) = 0.865LogK(o/w) + 0.0045, R(2) = 0.997 and LogK(pa/w) = 0.763LogK(o/w) + 0.911, R(2) = 1.00, respectively. These results suggest that the MCF technique can detect subtle differences in molecular interactions of the two group derivatives between the two membrane/water systems and may be used to study the absorption and permeation properties of closely related compounds. Finally, the regression method is a particularly useful tool to determine partition coefficients of very lipophilic compounds.


Gene silencing in androgen-responsive prostate cancer cells from the tissue-specific prostate-specific antigen promoter.
The success of gene therapy using a RNA interference approach relies on small interfering RNA (siRNA) expression from a highly tissue-specific RNA polymerase II promoter rather than from ubiquitous RNA polymerase III. Accordingly, we have developed a prostate-specific vector that expresses siRNAs from the human prostate-specific antigen promoter, a RNA polymerase II promoter. Our data demonstrate androgen-dependent and tissue-specific siRNA-mediated gene silencing in the androgen-responsive prostate cancer cell line, LNCaP. The biological significance was evidenced by altered apoptotic activity through the inhibition of the apoptosis-related regulatory gene. These results demonstrate that siRNA-mediated gene silencing from a tissue-specific RNA polymerase II promoter could be a potential tool for tissue-specific gene therapy.


Mechanisms of the Complex Thermo-Mechanical Behavior of Polymer Glass Across a Wide Range of Temperature Variations.
This paper aims to explore the mechanisms of the complex thermo-mechanical behavior of polymer glass across a wide range of temperature variations. To this end, the free vibration frequency spectrum of simply supported poly(methyl methacrylate) (PMMA) beams was thoroughly investigated with the aid of the impulse excitation technique. It was found that the amplitude ratio of the multiple peaks in the frequency spectrum is a strongly dependent on temperature, and that the peaks correspond to the multiple vibrational modes of the molecular network of PMMA. At a low temperature, the vibration is dominated by the overall microstructure of PMMA. With increasing the temperature, however, the contribution of the sub-microstructures is retarded by β relaxation. Above 80 °C, the vibration is fully dominated by the microstructure after relaxation. The relaxation time at the transition temperature is of the same order of the vibration period, confirming the contribution of β relaxation. These findings provide a precise method for establishing reliable physical-based constitutive models of polymer glass.


Fourier Transform Spectroscopy of the BaI Molecule: Simultaneous Analysis of Seven Electronic States Including the D(2)Sigma(+) and the G(2)Sigma(+) States.
In this work, the BaI D(2)Sigma(+) and G(2)Sigma(+) electronic states were investigated using laser-induced fluorescence (LIF) and Fourier transform spectroscopy (FTS). The LIF visible spectra were obtained by using the second harmonic of the Ti:sapphire single-mode laser and the Ar(+) and Kr(+) multimode lasers as excitation sources. Previously recorded data, taken from C. A. Leach, A. A. Tsekouras, and R. N. Zare (1992, J. Mol. Spectrosc. 153, 59-72) and from R. F. Gutterres, J. Vergès, and C. Amiot (1999, J. Mol. Spectrosc. 196, 29-44; 2000, J. Mol. Spectrosc. 200, 253-260; and 2000, J. Mol. Spectrosc. 201, 326-327) were combined with the present data. Accurate and improved molecular constants for the X(2)Sigma(+), B(2)Sigma(+), A('2)Delta, A(2)Pi, C(2)Pi, and D(2)Sigma(+) states and 16 term values of the G(2)Sigma(+) state were derived from a simultaneous treatment of the whole data set (12 684 transitions) with a standard deviation of 3.26x10(-3) cm(-1). Copyright 2001 Academic Press.


Salt tolerance enhancement Of wheat (Triticum Asativium L) genotypes by selected plant growth promoting bacteria.
The study was conducted at green house and laboratories of Agriculture Botany Department, Faculty of Agriculture, Suez Canal University, Ismailia governorate, Egypt during 2018/2019 to test rhizosphere growth promoting bacteria as known strategy to increase salinity tolerance of six genotypes of wheat namely; Line 404, Line 356, Line 420, Line432, Sakha 93 and Line 380 were grown under 3000 ppm and 5000 ppm of salinity. Four bacterial strains were used namely; Pseudomonas fluorescens NBRC 14160, Serratia liquefaciens ATCC 27592, Bacillus subtilis SBMP4 and Bacillus megaterium NBRC 15308. All the strains could be able to tolerate salinity levels up to 3% NaCl and produced indole acetic acid (IAA). The both strains Pseudomonas fluorescens NBRC 14160 and Bacillus megaterium NBRC 15308 were grow on NA media supplemented with 6% NaCl, and showed 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity and Pseudomonas fluorescens NBRC 14160 strain also fixed nitrogen. PCR results confirmed the previous results for both strains. Pseudomonas fluorescens NBRC 14160 and Bacillus megaterium NBRC 15308 were selected to study their reflection in vivo on wheat plants growth at different levels of salinity. The selected strains were able to improve plants growth under salinity stress conditions when compared with non-inoculated plants for all wheat genotypes especially sakha93 showed the highest mean values over rest genotypes under saline and non-saline conditions. Results of genetic parameters for studied traits showed that values of PCV were higher than GCV values for most studied traits. Germination percentage, shoot length and potassium content had high values of heritability and genetic advance, so these traits might use in selection of plant breeding programs for salinity tolerance.


Insertion reactions of beta-diketiminate-stabilised calcium amides with 1,3-dialkylcarbodiimides.
A series of heteroleptic beta-diketiminate-stabilised calcium amides of the form [{ArNC(Me)CHC(Me)NAr}Ca{NR1R2}(THF)] (Ar = 2,6-diisopropylphenyl; R1 = H, R2 = Ar; R1 = H, R2 = CH2CH2OMe; R1 = R2 = Ph) react with 1,3-dialkylcarbodiimides, R3NCNR3 (R3 = Cy, iPr), to yield the corresponding insertion products [{ArNC(Me)CHC(Me)NAr}Ca{(R3N)2CNR1R2}(THF)] at room temperature in hydrocarbon solutions. These latter compounds contain both beta-diketiminate and guanidinate ligands bound to calcium. Solid-state data are consistent with the guanidinate ligands adopting a number of binding modes including 2 through 3 coordination, with varying degrees of delocalisation of the non-bound guanidinate nitrogen lone-pair across the -framework of the ligand. DFT computational studies have been conducted to address these variations in coordination behaviour.


Biochar pyrolyzed at two temperatures affects Escherichia coli transport through a sandy soil.
The incorporation of biochar into soils has been proposed as a means to sequester carbon from the atmosphere. An added environmental benefit is that biochar has also been shown to increase soil retention of nutrients, heavy metals, and pesticides. The goal of this study was to evaluate whether biochar amendments affect the transport of Escherichia coli through a water-saturated soil. We looked at the transport of three E. coli isolates through 10-cm columns packed with a fine sandy soil amended with 2 or 10% (w/w) poultry litter biochar pyrolyzed at 350 or 700°C. For all three isolates, mixing the high-temperature biochar at a rate of 2% into the soil had no impact on transport behavior. When added at a rate of 10%, a reduction of five orders of magnitude in the amount of E. coli transported through the soil was observed for two of the isolates, and a 60% reduction was observed for the third isolate. Mixing the low-temperature biochar into the soil resulted in enhanced transport through the soil for two of the isolates, whereas no significant differences in transport behavior were observed between the low-temperature and high-temperature biochar amendments for one isolate. Our results show that the addition of biochar can affect the retention and transport behavior of E. coli and that biochar application rate, biochar pyrolysis temperature, and bacterial surface characteristics were important factors determining the transport of E. coli through our test soil.


[Vascular dementia: clinical and radiological characteristics in 26 cases].
Twenty six patients with vascular dementia were studied. Five of them only, were referred for a cognitive decline and all the others because of focal neurological symptoms or a stroke. Twelve patients had a previous history of stroke and 21 an history of high blood pressure. Twenty three patients had gait disturbances. CT scanner and MRI showed a large proportion (23 patients) of lacunar or small sub-cortical strokes. Leuko-araiosis was present in 21 patients and cortical stroke only in 6. Finally, the lack of information concerning the onset and the course of the cognitive decline in 12 patients explain the difficulties to fulfill the criteria in some diagnostic evaluation scores particularly those of the DSM III R.


[Effectiveness of primary and postsurgical hydrotubation (author's transl)].
Hydrotubation is a conservative method to cope with complete or partial tubal occlusion. Hydrotubation was applied postsurgically to 60 women and as primary treatment to another 72 women, all patients suffering from primary and secondary sterility. - Minor complications, including abdominal pain, were recorded from 15 patients. Pregnancy occurred to 13, among them eleven who had received postsurgical hydrotubation.


Mortality attributable to carbapenem-resistant nosocomial Acinetobacter baumannii infections in a Turkish university hospital.
This study was performed to compare the mortality associated with carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-sensitive A. baumannii (CSAB) infections, to identify potential risk factors for CRAB infections, and to investigate the effects of potential risk factors on mortality in CRAB and CSAB patients. This retrospective case-control study was conducted in a university hospital between January 1, 2005 and December 30, 2006. One hundred and ten patients with CRAB and 55 patients with CSAB infection were identified during the study period. The mortality rate was 61.8% and 52.7% in CRAB and CSAB cases, respectively (P = 0.341). In CRAB cases, the risk factors for mortality were identified as intubation (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.0-10.1; P = 0.042) and high APACHE II score (OR, 1.2; 95% CI, 1.1-1.3; P = 0.000), by multivariate analysis. Previous use of carbapenem (OR, 6.1; 95% CI, 2.2-17.1; P = 0.001) or aminopenicillin (OR, 2.5; 95% CI, 1.2-5.1; P = 0.013) were independently associated with carbapenem resistance. Although the mortality rate was higher among patients with CRAB infections, this difference was not found to be statistically significant. Previous use of carbapenem and aminopenicillin were found to be independent risk factors for infections with CRAB.


Trends in Pediatric Thyroid Cancer Incidence, Treatment, and Clinical Course in Korea During 2004-2016: A Nationwide Population-Based Study.
Background: The incidence of thyroid cancer has increased worldwide. We investigated nationwide trends in the incidence and treatment course of pediatric thyroid cancer in South Korea. Methods: Using the National Health Information Database, we analyzed 1580 patients (324 males) <20 years of age diagnosed with thyroid cancer during 2004-2016 in South Korea. The annual percentage change (APC) in the age-standardized incidence rate (ASR) was calculated by joinpoint regression analysis. The initial treatment modality was categorized as either surgery only or surgery with radioactive-iodine treatment (surgery+RAIT), and we defined new treatment events as reoperations or additional RAITs among 1464 patients followed up for ≥12 months. Results: During 2004-2016, the mean ASR per 100,000 person-years increased from 0.6 [confidence interval; CI 0.5-0.8] to 0.9 [CI 0.8-1.1], with a mean APC of 4.0% [CI 1.8-6.2]. The ASRs (APCs) among 0-9-, 10-14-, 15-17-, and 18-19-year olds were 0.07 (9.9% [CI 0.08-20.7]), 0.6 (4.6% [CI 0.2-9.2]), 2.2 (3.9 [CI 1.7-6.0]), and 4.2 (3.5% [CI 0.9-6.2]), respectively. The lobectomy and lymph-node-dissection rates increased (from 18.5% to 33.6%, p = 0.0014; and from 29.6% to 84.5%, p < 0.001; respectively), but the RAIT rate decreased (67.9-39.7%, p < 0.001) during the study period. During a median 6.3-year follow-up, two patients died. New treatment events occurred in 56 (10.7%) of patients in the initial surgery-only group (n = 523). In the initial surgery+RAIT group (n = 941), 316 patients received two or more RAITs within 2 years, and 80 (12.8%) of the remaining 625 patients underwent new treatment events. In the surgery+RAIT subgroup, the event-free survival rate was lower in 0-14-year olds than in 18-19-year olds (hazard ratio 2.5 [CI 1.4-4.4]). Conclusions: The pediatric thyroid cancer incidence increased from 2004 to 2012 in South Korea. The lobectomy and lymph-node-dissection rates increased, but the RAIT rate decreased. The higher risk for new treatment events in patients younger than 15 years requiring initial RAIT may be linked to advanced stage at diagnosis, and it needs to be further evaluated.


Plasminogen activator inhibitor 1 and vitronectin protect against stenosis in a murine carotid artery ligation model.
We previously reported that plasminogen activator inhibitor 1 (PAI-1), in the presence of vitronectin (VN), inhibits thrombin activity in vitro. Furthermore, we demonstrated in human atherosclerotic plaques the colocalization of thrombin, PAI-1, and VN, as well as activity of thrombin and PAI-1. Here, we show that PAI-1 is a local thrombin inhibitor in vivo. We used the murine carotid artery ligation model to assess the role of PAI-1 and VN in stenosis by using PAI-1-deficient (PAI-1(-/-)) and VN(-/-) mice. Ligation resulted in a smooth muscle cell (SMC)-rich intima without infiltrating cells. We show that PAI-1(-/-) and VN(-/-) mice generate a larger intima than wild-type mice as the result of more extensive SMC proliferation, as evidenced by cell counting and staining for proliferating cell-nuclear antigen. In PAI-1(-/-) mice, excessive intima formation is prevented by the thrombin-specific inhibitor hirudin. Finally, immunohistochemical analysis revealed PAI-1, VN, and (pro)thrombin antigen in intimal lesions. Our observations are compatible with inhibition of thrombin-mediated SMC proliferation by PAI-1/VN complexes.


Atomistic Modelling of Confined Polypropylene Chains between Ferric Oxide Substrates at Melt Temperature.
The interactions and conformational characteristics of confined molten polypropylene (PP) chains between ferric oxide (Fe₂O₃) substrates were investigated by molecular dynamics (MD) simulations. A comparative analysis of the adsorbed amount shows strong adsorption of the chains on the high-energy surface of Fe₂O₃. Local structures formed in the polymer film were studied utilizing density profiles, orientation of bonds, and end-to-end distance of chains. At interfacial regions, the backbone carbon-carbon bonds of the chains preferably orient in the direction parallel to the surface while the carbon-carbon bonds with the side groups show a slight tendency to orient normal to the surface. Based on the conformation tensor data, the chains are compressed in the normal direction to the substrates in the interfacial regions while they tend to flatten in parallel planes with respect to the surfaces. The orientation of the bonds as well as the overall flattening of the chains in planes parallel to the solid surfaces are almost identical to that of the unconfined PP chains. Also, the local pressure tensor is anisotropic closer to the solid surfaces of Fe₂O₃ indicating the influence of the confinement on the buildup imbalance of normal and tangential pressures.


Nuclear receptor coregulator SNP discovery and impact on breast cancer risk.
Coregulator proteins are "master regulators", directing transcriptional and posttranscriptional regulation of many target genes, and are critical in many normal physiological processes, but also in hormone driven diseases, such as breast cancer. Little is known on how genetic changes in these genes impact disease development and progression. Thus, we set out to identify novel single nucleotide polymorphisms (SNPs) within SRC-1 (NCoA1), SRC-3 (NCoA3, AIB1), NCoR (NCoR1), and SMRT (NCoR2), and test the most promising SNPs for associations with breast cancer risk. The identification of novel SNPs was accomplished by sequencing the coding regions of these genes in 96 apparently normal individuals (48 Caucasian Americans, 48 African Americans). To assess their association with breast cancer risk, five SNPs were genotyped in 1218 familial BRCA1/2-mutation negative breast cancer cases and 1509 controls (rs1804645, rs6094752, rs2230782, rs2076546, rs2229840). Through our resequencing effort, we identified 74 novel SNPs (30 in NCoR, 32 in SMRT, 10 in SRC-3, and 2 in SRC-1). Of these, 8 were found with minor allele frequency (MAF) >5% illustrating the large amount of genetic diversity yet to be discovered. The previously shown protective effect of rs2230782 in SRC-3 was strengthened (OR = 0.45 [0.21-0.98], p = 0.04). No significant associations were found with the other SNPs genotyped. This data illustrates the importance of coregulators, especially SRC-3, in breast cancer development and suggests that more focused studies, including functional analyses, should be conducted.


Effect of age and lordotic angle on the level of lumbar disc herniation.
It has been previously suggested in the literature that with aging, degenerative changes as well as disc herniation start at the lower lumbar segments, with higher disc involvement observed in an ascending fashion in older age groups. We conducted a study to investigate this correlation between age and level of disc herniation, and to associate it with the magnitude of the Lumbar Lordotic Angle (LLA), as measured by Cobb's method. We followed retrospectively lumbosacral spine MRI's of 1419 patients with symptomatic disc herniation. Pearson's correlation was used in order to investigate the relationship between LLA, age, and level of disc herniation. Student's t-test was applied to assess gender differences. Young patients were found to have higher LLA (R = 0.44, P < 0.0001) and lower levels of disc herniation (R = 0.302, P < 0.0001), whereas older patients had higher level herniation in lower LLA group (mean LLA 28.6° and 25.4°) and lower level herniation in high LLA group (mean LLA 33.2°). We concluded that Lumbar lordotic Cobb's angle and age can be predictors of the level of lumbar disc herniation. This did not differ among men and women (R = 0.341, P < 0.0001).


Cervical thymic cyst in childhood: a case report.
Cervical thymic cysts are rare cervical masses which usually present in the first decade of life accounting for 0.3% - 1% of all congenital neck masses. Due to its rarity thymic cysts are seldom included in the differential diagnosis of cystic cervical mass and are often mistaken for more common conditions such as branchial cleft cyst or cystic hygroma. Herein we present a case of a 6-year-old girl with a right lateral cervical cystic mass with multiple septae extended from mandibular angle along the neurovascular bundle of the neck which revealed to be a thymic cyst at histopathology.


[[Clodronate therapy of hypercalcemia caused by hyperparathyroidism].
The diphosphonates, powerful agents which inhibit osteolysis, have been used parenterally with success to treat malignant hypercalcemia. 4 cases of anatomically confirmed primary hyperparathyroidism (age of patients 58-78 years) were admitted with a serum calcium of over 4 mmol/l in one case, over 3,5 mmol/l in a second case and over 3 mmol/l in the other two. The patients received an infusion of isotonic saline and dichloromethylene-diphosphonate (clodronate) parenterally in a dose of 500 mg a day. Serum calcium began to fall in all four patients 48 hours after the treatment was started. Intravenous clodronate therefore appears to be the treatment of choice for parathyroid crises and allows surgery of the adenomas in better metabolic conditions.


Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report.
We report the case of a 3-(1/2)-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzymes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.


Parkin: much more than a simple ubiquitin ligase.
Parkin is mainly a cytosolic protein involved in a subset of Parkinson's disease (PD) cases referred to as autosomal juvenile recessive forms of PD. Most studies have established as a dogma that parkin function could be resumed as an ubiquitin ligase activity. Accordingly, several cellular functions ascribed to parkin derive from its ability to ubiquitinate a series of proteins, thereby rendering them prone to proteasomal degradation. Several lines of data indicated that parkin could display antiapoptotic properties and we demonstrated that indeed, parkin could downregulate the p53-dependent pathway. However, we showed that such function remained independent of parkin's ability to act as an ubiquitin ligase. Thus, we established that parkin repressed p53 transcription by physically interacting with its promoter. Here, we describe this novel parkin-associated transcription factor function and we speculate on putative additional transcriptional targets.


Boston type 1 keratoprosthesis: the university of california davis experience.
To compare the University of California Davis experience using the Boston keratoprosthesis with the Boston Keratoprosthesis Study Group's initial report. Retrospective chart review. We analyzed 30 eyes of 28 patients who previously underwent Boston type 1 keratoprosthesis surgery at our institution between 2004 and 2008. Preoperative, intraoperative, and postoperative parameters were collected and analyzed. Visual acuity and keratoprosthesis stability. Preoperative diagnoses were failed graft (26 eyes, 87%), chemical injury (3 eyes, 10%), and Stevens-Johnson syndrome (1 eye, 3%). Twenty eyes (66%) had preoperative glaucoma. Preoperative best-corrected visual acuity ranged from 20/150 to light perception and was <20/200 in 83% of eyes. At an average follow-up of 19 months (range, 1-48; SD, 13.8; and median, 13), postoperative vision improved to >or=20/200 in 77% of eyes. Among eyes at least 1 year after the operation (16 eyes), vision was >or=20/200 in 75% of eyes and >or=20/40 in 25% of eyes. At an average follow-up of 19 months, retention of the initial keratoprosthesis was 83.3%. The Boston type 1 keratoprosthesis is a viable option after multiple keratoplasty failures or in conditions with a poor prognosis for primary keratoplasty. Patients with autoimmune disease are at higher risk for complications. The University of California Davis experience seems equivalent to the initial report of the Boston Keratoprosthesis Study Group. With longer follow-up, additional surgical procedures may be required but good anatomic and functional outcomes can be maintained.


mHealth apps delivering early intervention to support parents of children with autism: a scoping review protocol.
This review aims to identify the mhealth apps delivering early intervention to support parents of children with autism spectrum disorders (ASD). We aim to explore the concept, context and methodology of implementation that is, theoretical framework, feasibility, quality of evidence, for such apps. To improve outcomes for children with autism, early intervention has been found to be promising. Parental training, parent psychoeducation and parent-mediated intervention are regarded as the gold standard, to achieve early childhood development goals. Digital health technologies like tele-health, web-based services, have been used to deliver this at a reduced cost. There is little evidence about their use and efficacy in empowering parents of children with ASD. The studies reporting the use of mhealth apps to support parents of children with ASD, in community settings, school settings, special schools, clinics, hospitals or child development centres. There will be no exclusion based on region, gender or sociocultural factors. The types of studies included will be quantitative, qualitative, mixed-methods study designs, case reports, grey literature, systematic reviews, clinical trials and studies reporting feasibility of digital mhealth applications. Using the NICE Healthcare Databases Advanced Search, we will search the following databases: MEDLINE, PUBMED, CINAHL, EMBASE, PsycINFO, Cochrane Library, EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect. Furthermore, grey literature will be searched through Google Scholar, ShodhGanga, JSTOR, CORE, EBSCO, DOAJ, BASE. The searches will be limited to the age range of children between 2 and 6 years with ASD, and the date range is from the inception of the database to the current date. The terms for the ASD will be combined with terms for parent, early intervention and digital mhealth to identify eligible studies.


tRNAHis-guanylyltransferase establishes tRNAHis identity.
Histidine transfer RNA (tRNA) is unique among tRNA species as it carries an additional nucleotide at its 5' terminus. This unusual G(-1) residue is the major tRNA(His) identity element, and essential for recognition by the cognate histidyl-tRNA synthetase to allow efficient His-tRNA(His) formation. In many organisms G(-1) is added post-transcriptionally as part of the tRNA maturation process. tRNA(His) guanylyltransferase (Thg1) specifically adds the guanylyate residue by recognizing the tRNA(His) anticodon. Thg1 homologs from all three domains of life have been the subject of exciting research that gave rise to a detailed biochemical, structural and phylogenetic enzyme characterization. Thg1 homologs are phylogenetically classified into eukaryal- and archaeal-type enzymes differing characteristically in their cofactor requirements and specificity. Yeast Thg1 displays a unique but limited ability to add 2-3 G or C residues to mutant tRNA substrates, thus catalyzing a 3' → 5' RNA polymerization. Archaeal-type Thg1, which has been horizontally transferred to certain bacteria and few eukarya, displays a more relaxed substrate range and may play additional roles in tRNA editing and repair. The crystal structure of human Thg1 revealed a fascinating structural similarity to 5' → 3' polymerases, indicating that Thg1 derives from classical polymerases and evolved to assume its specific function in tRNA(His) processing.


[Role of preoperative nutritional status on postoperative morbidity].
Correlations between preoperative nutritional status on the one hand and postoperative morbidity and mortality on the other hand were reviewed in articles from literature. The inclusion criteria for analysis were the following: large series, well defined nutritional status, major surgery, objective evaluation of postoperative complications and relevant statistical analysis. This study considered factors supposed to alter this correlation, namely the type of primary disease, intensity of denutrition, obesity, site and grade of cancer and age. There was a highly significant correlation between preoperative denutrition and postoperative morbidity and mortality. This correlation was existing whether operation was performed on the gastrointestinal tract or not, whether the primary disease was a cancer or not. The more important the denutrition, the more frequent the postoperative complications and deaths. Morbidity and mortality rates were linearly correlated to denutrition. After head and neck surgery for malignant diseases, malnourished elderly patients had poor prognosis. Obesity had the same prognostic value as denutrition.


Ingestion of corrosive substances by adults.
Compared with the ingestion of corrosive substances in children, this problem tends to be more serious, in adults, because its intent is often suicidal, rather than accidental. The severity and extent of damage produced to the gastrointestinal tract depends on the morphological form of the caustic agent. In the acute stage, perforation and necrosis may occur. Long-term complications include esophageal stricture, antral stenosis, and the development of esophageal carcinoma. X-rays of the abdomen and chest should be done initially to detect any evidence of perforation. Endoscopy should be performed as soon as possible in all cases to evaluate the extent and severity of damage, unless there is evidence of perforation. A complete examination is feasible in most cases. Stricture formation is more common in patients with second- and third-degree burns. Measures to prevent stricture formation, including the use of steroids, have not been successful. Esophageal carcinoma usually occurs 40 yr after the time of injury.


RNA folding with hard and soft constraints.
A large class of RNA secondary structure prediction programs uses an elaborate energy model grounded in extensive thermodynamic measurements and exact dynamic programming algorithms. External experimental evidence can be in principle be incorporated by means of hard constraints that restrict the search space or by means of soft constraints that distort the energy model. In particular recent advances in coupling chemical and enzymatic probing with sequencing techniques but also comparative approaches provide an increasing amount of experimental data to be combined with secondary structure prediction. Responding to the increasing needs for a versatile and user-friendly inclusion of external evidence into diverse flavors of RNA secondary structure prediction tools we implemented a generic layer of constraint handling into the ViennaRNA Package. It makes explicit use of the conceptual separation of the "folding grammar" defining the search space and the actual energy evaluation, which allows constraints to be interleaved in a natural way between recursion steps and evaluation of the standard energy function. The extension of the ViennaRNA Package provides a generic way to include diverse types of constraints into RNA folding algorithms. The computational overhead incurred is negligible in practice. A wide variety of application scenarios can be accommodated by the new framework, including the incorporation of structure probing data, non-standard base pairs and chemical modifications, as well as structure-dependent ligand binding.


Recommendations for cellular and molecular pathology input into clinical trials: a systematic review and meta-aggregation.
The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological components in clinical trial protocols. However, these standards do not include guidance specific to pathology input in clinical trials. This systematic review aims to synthesise existing recommendations specific to pathology practice in clinical trials for implementation in trial protocol design. Articles were identified from database searches and deemed eligible for inclusion if they contained: (1) guidance and/or a checklist, which was (2) pathology-related, with (3) content relevant to clinical trial protocols or could influence a clinical trial protocol design from a pathology perspective and (4) were published in 1996 or later. The quality of individual papers was assessed using the AGREE-GRS (Appraisal of Guidelines for REsearch & Evaluation - Global Rating Scale) tool, and the confidence in cumulative evidence was evaluated using the GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative research) approach. Extracted recommendations were synthesised using the best fit framework method, which includes thematic analysis followed by a meta-aggregative approach to synthesis within the framework. Of the 10 184 records screened and 199 full-text articles reviewed, only 40 guidance resources met the eligibility criteria for inclusion. Recommendations extracted from 22 guidance documents were generalisable enough for data synthesis. Seven recommendation statements were synthesised as follows: (1) multidisciplinary collaboration in trial design with early involvement of pathologists, particularly with respect to the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology-related parameters; (2) funding and training for personnel undertaking trial work; (3) selection of an accredited laboratory with suitable facilities to undertake scheduled work; (4) quality assurance of pathology-related parameters; (5) transparent reporting of pathology-related parameters; (6) policies regarding informatics and tracking biospecimens across trial sites; and (7) informed consent for specimen collection and retention for future research.


Manpower problems in a capital-rich country: the case of Saudi Arabia.
"In order to provide an insight into the possible problems that face Saudi Arabia in its Fourth Five-Year Plan (1985-1990), this paper assesses several aspects of the manpower problems encountered in the Third Five-Year Plan (1980-1985). In general, it appears that the country's abundance of fixed capital, or at least the means to acquire it, only emphasizes the scarcity of other resources in the Kingdom, notably the shortage of indigenous labour and the absence of the skills required to run new industries.... The paper argues that it is apparent from the performance of the Third Plan that the Government will probably use the size of the foreign labour force as a safety valve to ensure the attainment of its priorities."


Energetic coupling between plastids and mitochondria drives CO2 assimilation in diatoms.
Diatoms are one of the most ecologically successful classes of photosynthetic marine eukaryotes in the contemporary oceans. Over the past 30 million years, they have helped to moderate Earth's climate by absorbing carbon dioxide from the atmosphere, sequestering it via the biological carbon pump and ultimately burying organic carbon in the lithosphere. The proportion of planetary primary production by diatoms in the modern oceans is roughly equivalent to that of terrestrial rainforests. In photosynthesis, the efficient conversion of carbon dioxide into organic matter requires a tight control of the ATP/NADPH ratio which, in other photosynthetic organisms, relies principally on a range of plastid-localized ATP generating processes. Here we show that diatoms regulate ATP/NADPH through extensive energetic exchanges between plastids and mitochondria. This interaction comprises the re-routing of reducing power generated in the plastid towards mitochondria and the import of mitochondrial ATP into the plastid, and is mandatory for optimized carbon fixation and growth. We propose that the process may have contributed to the ecological success of diatoms in the ocean.


Comparative study of the Fränkel (FR-2) and bionator appliances in the treatment of Class II malocclusion.
The purpose of this investigation was to compare the dentoalveolar and skeletal cephalometric changes produced by the Fränkel (FR-2) and bionator appliances in persons with Class II malocclusion. Lateral cephalograms were available for 66 patients of both sexes, who were divided into 3 groups of 22. The control group included untreated Class II children, with an initial mean age of 8 years 7 months; they were followed without treatment for 13 months. The FR-2 appliance group had an initial mean age of 9 years; those children were treated for a mean period of 17 months. The bionator group initially had a mean age of 10 years 8 months; on average, they were treated for 16 months. The results demonstrated no significant changes in maxillary growth during the evaluation period. Both appliances showed statistically significant increases in mandibular growth and mandibular protrusion, with greater increases in patients treated in the bionator group. Both experimental groups showed an improvement in the maxillomandibular relationship. There were no significant changes in growth direction, while the bionator group had a greater increase in posterior facial height. Both appliances produced similar labial tipping and protrusion of the lower incisors, lingual inclination, retrusion of the upper incisors, and a significant increase in mandibular posterior dentoalveolar height. The major treatment effects of bionator and FR-2 appliances were dentoalveolar, with a smaller, but significant, skeletal effect.


Trauma-hemorrhage causes prolonged depression in cellular immunity.
A number of clinical studies have shown that multiple and severe trauma causes immunosuppression and increases the susceptibility to sepsis. However, because there is a close temporal relationship between trauma and hemorrhage in humans, it is difficult to dissociate the effects of tissue trauma versus hemorrhage on immunity in the clinical setting. Studies in mice have shown that simple hemorrhage per se as well as laparotomy alone produces a marked depression in cellular immunity and no difference was seen in the extent of depression at 2 h if these two insults were combined. Nonetheless, it remains unknown whether the combined model of trauma-hemorrhage produces a more protracted depression in immune function. To study this, 5 days after either sham operation, laparotomy (i.e. trauma), hemorrhage alone (35 mmHg for 1 h, followed by resuscitation), or the combination of laparotomy and hemorrhage, mice (C3H/HeN) were sacrificed, after which splenocyte and peritoneal macrophage cultures were established. The proliferative capacity of the splenocytes, as well as their ability to release IL-2 and IL-3, was markedly decreased in the trauma-hemorrhage animals but was normal in the other groups. Furthermore, the release of IL-6 by peritoneal macrophages from animals that underwent trauma-hemorrhage was also significantly depressed. These results support the concept that traumatic injury in the form of a midline laparotomy combined with hemorrhage produces a more protracted impairment in cell-mediated immunity than laparotomy or hemorrhage alone.


Effect of TV food advertising restriction on food environment for children in South Korea.
This study attempted to determine the effects of restrictions on television (TV) food advertising on children's food environments in South Korea. It examined changes that occurred in the marketing mix of food companies following enactment of those restrictions. An on-line survey was conducted with marketers or R&D managers of 108 food companies. A questionnaire was used to inquire about changes that occurred in Product, Place, Price and Promotion as a result of the restrictions placed on TV food advertising. Analysis was performed on the data collected from the responding 63 food companies (58.3%). The results of their answers showed that among the four marketing mix components the restrictions exerted relatively stronger effects on Product. Effects were stronger on companies that produced foods within the product categories of Energy-Dense and Nutrient-Poor foods (EDNP companies) in comparison with companies that did not (non-EDNP companies). The restrictions exerted positive effects on EDNP companies with respect to compliance with labeling requirements and reinforcement of nutritional contents examination, as well as changes to products such as reducing unhealthy ingredients and fortifying nutrients. Overall, the results revealed the possibility that restrictions on TV food advertising could improve children's food environments by encouraging EDNP companies to make favorable product changes. On the one hand, the results also found that some food companies attempted to bypass the regulations by changing marketing channels from TV to others and by reducing product serving sizes. Thus, future measures should be implemented to prevent food companies from bypassing regulations and to control children's exposure to marketing channels other than TV.


A framework and standardized methodology for developing minimum clinical datasets.
The concept of the minimum dataset (MDS) is taking on an increasingly important role in healthcare. In the current environment of health information exchange and universal implementation of electronic health records, work related to the development of one specific type of MDS, the minimum clinical dataset (MCDS), is beginning to permeate the literature. While there is currently no unified definition of either an MDS or an MCDS, an MDS is generally agreed to be a coherent set of explicitly defined data elements. Despite the growing body of literature on MCDSs, very little empirical evidence exists in the literature related to best methods for developing them. The primary objective of the current study is to fill this gap. By presenting a streamlined approach to the development of MCDSs the current study attempts to provide individuals and organizations with a coherent methodology and framework for developing a high quality MCDS.


Observation of Coulomb-Assisted Nuclear Bound State of Ξ^{-}-^{14}N System.
In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.


Resolution and quality enhancement in terahertz in-line holography by sub-pixel sampling with double-distance reconstruction.
We demonstrate the enhancement of resolution and image quality in terahertz (THz) lens-free in-line digital holography by sub-pixel sampling with double-distance reconstruction. Multiple sub-pixel shifted low-resolution (LR) holograms recorded by a pyroelectric array detector (100 μm × 100 μm pixel pitch, 124 × 124 pixels) are aligned precisely to synthesize a high-resolution (HR) hologram. By this method, the lateral resolution is no more limited by the pixel pitch, and lateral resolution of 150 μm is obtained, which corresponds to 1.26λ with respect to the illuminating wavelength of 118.8 μm (2.52 THz). Compared with other published works, to date, this is the highest resolution in THz digital holography when considering the illuminating wavelength. In addition, to suppress the twin-image and zero-order artifacts, the complex amplitude distributions of both object and illuminaing background wave fields are reconstructed simultaneously. This is achieved by iterative phase retrieval between the double HR holograms and background images at two recording planes, which does not require any constraints on object plane or a priori knowledge of the sample.


From radical mastectomy to breast-conserving therapy and oncoplastic breast surgery: a narrative review comparing oncological result, cosmetic outcome, quality of life, and health economy.
Surgical management of breast cancer has evolved considerably over the last two decades. There has been a major shift toward less-invasive local treatments, from radical mastectomy to breast-conserving therapy (BCT) and oncoplastic breast surgery (OBS). In order to investigate the efficacy of each of the three abovementioned methods, a literature review was conducted for measurable outcomes including local recurrence, survival, cosmetic outcome, quality of life (QOL), and health economy. From the point of view of oncological result, there is no difference between mastectomy and BCT in local recurrence rate and survival. Long-term results for OBS are not available. The items assessed in the QOL sound a better score for OBS in comparison with mastectomy or BCT. OBS is also associated with a better cosmetic outcome. Although having low income seems to be associated with lower BCT and OBS utilization, prognosis of breast cancer is worse in these women as well. Thus, health economy is the matter that should be studied seriously. OBS is an innovative, progressive, and complicated subspeciality that lacks published randomized clinical trials comparing surgical techniques and objective measures of outcome, especially from oncologic and health economy points of view.


The pharmacophylogenetic relationships of two edible medicinal plants in the genus Artemisia.
Artemisia argyi and Artemisia indica are edible medicinal plants belonging to the genus Artemisia in the Asteraceae. There are many similarities in their morphology, traditional curative effect, and modern pharmacological treatment. In this study, we built distribution maps of A. argyi and A. indica in China and a phylogenetic tree of common medicinal plants in Asteraceae. Then, we verified the chemical composition changes of A. argyi and A. indica via their metabolome. Traditional efficacy and modern pharmacological action were verified by network pharmacology and in vitro using RAW264.7 cells. The results showed that A. argyi and A. indica are widely distributed in China, and they shared pharmaphylogeny, which provides theoretical support for the mixed use of A. argyi and A. indica in most regions of China. Furthermore, there were both similarities and differences in volatile oil and flavonoid composition between A. argyi and A. indica. The network pharmacology results showed that A. argyi and A. indica had 23 common active compounds and that both had pharmacological effects on chronic gastritis (CG). Molecular docking analyses showed that quercetin, luteolin, and kaempferol have strong binding affinities with the target proteins JUN, TP53, AKT1, MAPK3, TNF, MAPK, and IL6. The cell experiment results further demonstrated that A. argyi and A. indica treat CG via the NOD-like receptor pathway. Based on the theory of pharmaphylogeny, this study explored the pharmaphylogeny between A. argyi and A. indica from various perspectives to provide a basis for the substitution of A. argyi and A. indica.


Intraprocedural bowel cleansing with the JetPrep cleansing system improves adenoma detection.
To investigate the impact of JetPrep cleansing on adenoma detection rates. In this prospective, randomized, crossover trial, patients were blindly randomized to an intervention arm or a control arm. In accordance with the risk profile for the development of colorectal carcinoma, the study participants were divided into high-risk and low-risk groups. Individuals with just one criterion (age > 70 years, adenoma in medical history, and first-degree relative with colorectal cancer) were regarded as high-risk patients. Bowel preparation was performed in a standardized manner one day before the procedure. Participants in the intervention arm underwent an initial colonoscopy with standard bowel cleansing using a 250-mL syringe followed by a second colonoscopy that included irrigation by the use of the JetPrep cleansing system. The reverse sequence was used in the control arm. The study participants were divided into a high-risk group and a low-risk group according to their respective risk profiles for the development of colorectal carcinoma. A total of 64 patients (34 men and 30 women) were included in the study; 22 were included in the high-risk group. After randomization, 30 patients were assigned to the control group (group A) and 34 to the intervention group (group B). The average Boston Bowel Preparation Scale score was 5.15 ± 2.04. The withdrawal time needed for the first step was significantly longer in group A using the JetPrep system (9.41 ± 3.34 min) compared to group B (7.5 ± 1.92 min). A total of 163 polyps were discovered in 64 study participants who underwent both investigation steps. In group A, 49.4% of the polyps were detected during the step of standard bowel cleansing while the miss rate constituted 50.7%. Group B underwent cleansing with the JetPrep system during the first examination step, and as many as 73.9% of polyps were identified during this step. Thus, the miss rate in group B was a mere 26.1% (P < 0.001). When considering only the right side of the colon, the miss rate in group A during the first examination was 60.6%, in contrast to a miss rate of 26.4% in group B (P < 0.001). JetPrep is recommended for use during colonoscopy because a better prepared bowel enables a better adenoma detection, particularly in the proximal colon.


Channeling of substrates and intermediates in enzyme-catalyzed reactions.
The three-dimensional structures of tryptophan synthase, carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, and asparagine synthetase have revealed the relative locations of multiple active sites within these proteins. In all of these polyfunctional enzymes, a product formed from the catalytic reaction at one active site is a substrate for an enzymatic reaction at a distal active site. Reaction intermediates are translocated from one active site to the next through the participation of an intermolecular tunnel. The tunnel in tryptophan synthase is approximately 25 A in length, whereas the tunnel in carbamoyl phosphate synthetase is nearly 100 A long. Kinetic studies have demonstrated that the individual reactions are coordinated through allosteric coupling of one active site with another. The participation of these molecular tunnels is thought to protect reactive intermediates from coming in contact with the external medium.


Identification of novel oxidized levuglandin D2 in marine red alga and mouse tissue.
In animals, the product of cyclooxygenase reacting with arachidonic acid, prostaglandin(PG)H(2), can undergo spontaneous rearrangement and nonenzymatic ring cleavage to form levuglandin(LG)E(2) and LGD(2). These LGs and their isomers are highly reactive γ-ketoaldehydes that form covalent adducts with proteins, DNA, and phosphatidylethanolamine in cells. Here, we isolated a novel oxidized LGD(2) (ox-LGD(2)) from the red alga Gracilaria edulis and determined its planar structure. Additionally, ox-LGD(2) was identified in some tissues of mice and in the lysate of phorbol-12-myristate-13-acetate (PMA)-treated THP-1 cells incubated with arachidonic acid using LC-MS/MS. These results suggest that ox-LGD(2) is a common oxidized metabolite of LGD(2). In the planar structure of ox-LGD(2), H8 and H12 of LGD(2) were dehydrogenated and the C9 aldehyde was oxidized to a carboxylic acid, which formed a lactone ring with the hydrated ketone at C11. These structural differences imply that ox-LGD(2) is less reactive with amines than LGs. Therefore, ox-LGD(2) might be considered a detoxification metabolite of LGD(2).


High sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, and vascular cell adhesion molecule-1 levels in Asian Indians with metabolic syndrome and insulin resistance (CURES-105).
The aim of this study was to assess levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and without MS and among MS subjects with and without insulin resistance (IR). From the population-based Chennai Urban Rural Epidemiology Study, 334 subjects with MS and 342 subjects without MS were selected. Metabolic syndrome was diagnosed based on modified National Cholesterol Education Program criteria. High-sensitivity C-reactive protein, TNF-α, IL-6, and VCAM-1 were measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR) using the following formula: fasting insulin (µIU/ml) × fasting glucose (mmol/liter)/22.5. Subjects with MS had significantly higher levels of all four inflammatory markers compared to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) (p < .05), TNF-α (4.47 vs 3.89 pg/ml) (p < .05), IL-6 (16.22 vs 10.96 pg/ml) (p < .05), and VCAM-1 (13.8 vs 7.94 pg/ml) (p < .05). In the total study subjects, hs-CRP (r = 0.089, p = .047), TNF-α (r = 0.113, p = .040), IL-6 (r = 0.176, p = .042), and VCAM-1 (r = 0.230, p = .06) were significantly correlated with MS. With increasing quartiles of IR, mean levels of hs-CRP (p for trend <.001) and TNF-α (p for trend <.05) increased linearly. MS subjects with IR had higher levels of hs-CRP (p < .001) and TNF-α (p < .05) compared to MS subjects without IR. In Asian Indians, inflammatory cytokines hs-CRP, TNF-α, IL-6, and VCAM-1 are elevated in subjects with MS while hs-CRP and TNF-α are further elevated in those with MS and IR.


Lineage specification of neuronal precursors in the mouse spinal cord.
We have investigated the differentiation potential of precursor cells within the developing spinal cord of mice and have shown that spinal cord cells from embryonic day 10 specifically give rise to neurons when plated onto an astrocytic monolayer, Ast-1. These neurons had the morphology of motor neurons and > 83% expressed the motor neuron markers choline acetyltransferase, peripherin, calcitonin gene-related peptide, and L-14. By comparison, < 10% of the neurons arising on monolayers of other neural cell lines or 3T3 fibroblasts had motor neuron characteristics. Cells derived from dorsal, intermediate, and ventral regions of the spinal cord all behaved similarly and gave rise to motor neuron-like cells when plated onto Ast-1. By using cells that expressed the lacZ reporter gene, it was shown that > 93% of cells present on the Ast-1 monolayers were motor neuron-like. Time-lapse analysis revealed that the precursors on the Ast-1 monolayers gave rise to neurons either directly or following a single cell division. Together, these results indicate that precursors in the murine spinal cord can be induced to differentiate into the motor neuron phenotype by factors produced by Ast-1 cells, suggesting that a similar factor(s) produced by cells akin to Ast-1 may regulate motor neuron differentiation in vivo.


Alterations in cerebral and cardiac mitochondrial function in a porcine model of acute carbon monoxide poisoning.
The purpose of this study is the development of a porcine model of carbon monoxide (CO) poisoning to investigate alterations in brain and heart mitochondrial function. Two group large animal model of CO poisoning. Laboratory. Ten swine were divided into two groups: Control (n = 4) and CO (n = 6). Administration of a low dose of CO at 200 ppm to the CO group over 90 min followed by 30 min of re-oxygenation at room air. The Control group received room air for 120 min. Non-invasive optical monitoring was used to measure cerebral blood flow and oxygenation. Cerebral microdialysis was performed to obtain semi real time measurements of cerebral metabolic status. At the end of the exposure, both fresh brain (cortical and hippocampal tissue) and heart (apical tissue) were immediately harvested to measure mitochondrial respiration and reactive oxygen species (ROS) generation and blood was collected to assess plasma cytokine concentrations. Animals in the CO group showed significantly decreased Complex IV-linked mitochondrial respiration in hippocampal and apical heart tissue but not cortical tissue. There also was a significant increase in mitochondrial ROS generation across all measured tissue types. The CO group showed a significantly higher cerebral lactate-to-pyruvate ratio. Both IL-8 and TNFα were significantly increased in the CO group compared with the Control group obtained from plasma. While not significant there was a trend to an increase in optically measured cerebral blood flow and hemoglobin concentration in the CO group. Low-dose CO poisoning is associated with early mitochondrial disruption prior to an observable phenotype highlighting the important role of mitochondrial function in the pathology of CO poisoning. This may represent an important intervenable pathway for therapy and intervention.


Individual and Institutional Corruption in European and US Healthcare: Overview and Link of Various Corruption Typologies.
In recent years, the fight against healthcare corruption has intensified. Estimates from the European Healthcare Fraud and Corruption Network calculate an approximate €56 billion annual loss to Europe as a result of corruption. To promote understanding of the complexity and interconnection of corrupt activities, we aim to present healthcare-related corruption typologies of the European Union and European Healthcare Fraud and Corruption Network. We subsequently link them to the typology of individual and institutional corruption introduced by Dennis Thompson in the context of investigating misconduct of US Congressional members. According to Thompson, individual corruption is the personal gain of individuals performing duties within an institution in exchange for nurturing private interests, while institutional corruption pertains to the failure of the institution in directing the individual's behaviour towards the achievement of the institution's primary purpose because the institutional design promotes the pursuit of individual goals. Effective anti-corruption activities not only require the enactment of anti-corruption laws but also the monitoring and, where appropriate, revision of institutional frameworks to prevent the undermining of the primary purposes of health systems or institutions. To gain further understanding of the similarities and differences of the three typologies, prime examples of corrupt activities in the health sector in the European Union and USA (along with their potential remedies) are provided. Linking corruption cases to Thompson's typology revealed that many corrupt activities may show elements of both individual and institutional corruption because they are intertwined, partly overlap and may occur jointly. Hence, sanctioning individual actors only does not target the problem.


Probenecid Reduces Alcohol Drinking in Rodents. Is Pannexin1 a Novel Therapeutic Target for Alcohol Use Disorder?
The development of novel and more effective medications for alcohol use disorder (AUD) is an important unmet medical need. Drug repositioning or repurposing is an appealing strategy to bring new therapies to the clinic because it greatly reduces the overall costs of drug development and expedites the availability of treatments to those who need them. Probenecid, p-(di-n-propylsulfamyl)-benzoic acid, is a drug used clinically to treat hyperuricemia and gout due to its activity as an inhibitor of the kidneys' organic anion transporter that reclaims uric acid from urine. Probenecid also inhibits pannexin1 channels that are involved in purinergic neurotransmission and inflammation, which have been implicated in alcohol's effects and motivation for alcohol. Therefore, we tested the effects of probenecid on alcohol intake in rodents. We tested the effects of probenecid on operant oral alcohol self-administration in alcohol-dependent rats during acute withdrawal as well as in nondependent rats and in the drinking-in-the-dark (DID) paradigm of binge-like drinking in mice. Probenecid reduced alcohol intake in both dependent and nondependent rats and in the DID paradigm in mice without affecting water or saccharin intake, indicating that probenecid's effect was selective for alcohol and not the result of a general reduction in reward. These results raise the possibility that pannexin1 is a novel therapeutic target for the treatment of AUD. The clinical use of probenecid has been found to be generally safe, suggesting that it can be a candidate for drug repositioning for the treatment of AUD.


The "Phillips" Ileostomy Correction Technique for Prolapsed Stoma.
Stoma prolapse is a common complication associated with ostomy creation, causing leakage, obstruction, and sometimes incarceration. Sometimes ileostomy prolapse cannot be treated with resection and alternative methods must be applied. We propose a new surgical revisional technique for ileostomy prolapse. Under general anesthesia, the prolapsed stoma is dissected and freed from the fascia and skin. The bowel is everted to create a nipple of 2-3 cm and subsequently fixed with a 3-row linear stapler, creating a "Phillips ileostomy." The ileostomy is then sutured to the skin with 3-0 full thickness stitches. In our center, 3 patients were treated in a day surgery setting, and no complication occurred. One patient reported a prolapse recurrence after 6 months and was successfully treated with the same technique with no recurrence at 1 year. The 3-row stapler fixation of prolapsed ileostomy is simple to perform, preserves the bowel, and can be performed in the day surgery setting.


Treatment of severe infections due to metallo-β-lactamases-producing Gram-negative bacteria.
In the last decades, there was an important paucity of agents for adequately treating infections due to metallo-β-lactamases-producing Gram-negative bacteria (MBL-GNB). Cefiderocol, a novel siderophore cephalosporin showing in vitro activity against MBL-GNB, has been recently marketed, and a combination of aztreonam and ceftazidime/avibactam has shown a possible favorable effect on survival of patients with severe MBL-GNB infections in observational studies. Other agents showing in vitro activity against MBL-GNB are currently in clinical development (e.g., cefepime/taniborbactam, LYS228, cefepime/zidebactam) that could be an important addition to our future armamentarium for severe MBL-GNB infections. Nonetheless, we should not discontinue our efforts to optimize the use of non-β-lactams agents, since they could remain an essential last-resort or alternative option in selected cases.


Therapeutic controversies in hypertension management: angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers for diabetic nephropathy? A case for ACE inhibitors.
Diabetic nephropathy is the number one cause of endstage renal disease in the United States. Blockade of the renin angiotensin system (RAS) is important in the treatment of diabetic nephropathy. With the reports of recently completed trials examining the role of angiotensin receptor blockers (ARBs) in type 2 diabetic nephropathy, the question has arisen as to which agents are best to block the RAS in type 2 diabetes. ACE inhibitors have been to preserve renal function in type 1 diabetics with nephropathy in large, randomized, placebo controlled trials, but such data is lacking in type 2 diabetes. Neverthelesss, ACE inhibitors have been recommended for use in type 2 diabetic nephropathy for some time. In type 2 diabetics, ACE inhibitors may have a role in preventing development of nephropathy, and, importantly, ACE inhibitors have been shown to reduce cardiovascular disease in diabetics with and without nephropathy. In addition, ACE inhibitors have beneficial effects on other diabetic complications such as retinopathy and neuropathy. Until better comparative data between ACE inhibitors and ARBs on nephropathy and cardiovascular outcomes is available, ACE inhibitors should remain an important consideration for treatment of diabetic nephropathy.


Knee-spine syndrome: correlation between sacral inclination and patellofemoral joint pain.
Low back pain is an enormous clinical and public health problem. When we use spinal instrumentation, measurements of spinal and leg alignment in the standing position are thought to be important. Knee joint pain has also become an enormous clinical problem in the increasing elderly population. However, the correlation between spinal alignment, particularly sacral inclination, and knee joint pain is not clear. We examined the correlation between lumbar lordosis, sacral inclination, and patellofemoral joint pain in elderly subjects. Three hundred and ninety-nine people aged 50-85 years were examined. Clinical findings and physical status were determined. Measurements and determination of total lordosis from L1 to S1 and sacral inclination were made from standing radiographs. The knee joints were evaluated by using the standing knee flexion angle, radiographs, and the patellofemoral (PF) joint grinding test. Thirty-nine percent of subjects were excluded because they had definite osteo-arthritis at the femorotibial joints. Fifty-eight percent of the subjects had felt low back pain within the previous 3 months, and 16% of the subjects complained of PF joint grinding pain. Sixteen percent of the subjects showed knee flexion when standing. There was a significant difference in sacral inclination between the groups with and without PF joint grinding pain ( P < 0.01). Sacral inclination was approximately 5 degrees less in the knee flexion group. A correlation between sacral inclination and PF joint pain is defined, and its prevalence in the elderly is reported. We speculate that this phenomenon is caused by changing of lumbar alignment. In addition, we think this is a new pathological concept that we call the knee-spine syndrome.


Association of exclusive breastfeeding duration and fibrinogen levels in childhood and adolescence: the European Youth Heart Study.
To examine the association of exclusive breastfeeding (BF) duration on serum fibrinogen levels of children and adolescents from Estonia and Sweden, controlling for other potential confounding factors that could mediate in this relationship. Cross-sectional study. Estonia and Sweden. A total of 704 children (mean [SD] age, 9.5 [0.4] years) and 665 adolescents (15.5 [0.5] years). Exclusive BF duration was reported by the mother and categorized in the following 5 categories: never, less than 1 month, 1 to 3 months, more than 3 to 6 months, and more than 6 months. Fasting fibrinogen level. Age, sex, pubertal status, country, adiposity (sum of 5 skin-fold thicknesses), total cholesterol and triglyceride levels, blood pressure, physical activity (accelerometry), birth weight, maternal education, body mass index, and age were considered confounders in the analyses. Longer duration of exclusive BF was associated with lower fibrinogen levels regardless of confounders (P < .001). Mean (SD) fibrinogen levels were lower in youth who were breastfed for more than 3 months (after adjusting for all confounders, P < .01) in children (2.55 [0.04] vs 2.77 [0.03] g/L), adolescents (2.59 [0.06] vs 2.72 [0.03] g/L), boys (2.47 [0.04] vs 2.73 [0.04] g/L), and girls (2.60 [0.03] vs 2.75 [0.02] g/L), compared with groups who were not breastfed. The results did not change substantially after further adjustment for birth weight and maternal educational level. Exclusive BF is associated with less low-grade inflammation, as estimated by serum fibrinogen levels, in healthy children and adolescents. These findings give further support to the notion that early feeding patterns could program cardiovascular disease risk factors later in life.


Multistep process of squamous differentiation of tracheobronchial epithelial cells: role of retinoids.
The objective of our research is to elucidate the molecular mechanisms that regulate the proliferation and differentiation of tracheobronchial epithelial cells. A clear insight into the basic mechanisms of these processes is required in order to understand the mechanisms involved in tumor development and other pathological conditions. To study the regulation of differentiation of the tracheobronchial epithelium, an in vitro cell culture model was developed using rabbit tracheal epithelial cells. Our studies were directed towards answering the following questions: (1) What is the differentiation capacity of these cells? (2) Does differentiation occur as a multistep process? (3) What factors control differentiation and by what mechanism? (4) What are the biochemical markers for the various differentiated phenotypes and at what level are they controlled? (5) Is there a link between control of cell growth and control of cell differentiation?


Superoxide dismutase mimetic m40401 reduces ischemia-reperfusion injury and graft coronary artery disease in rodent cardiac allografts.
The oxidative stress associated with ischemia-reperfusion (I/R) of cardiac allografts leads to production of injurious cytokines and expression of proinflammatory adhesion molecules. This is one of the most important alloantigen-independent factors associated with graft coronary artery disease (GCAD). M40401 is a newly developed cell permeable superoxide dismutase mimetic, which has been shown to scavenge superoxide anion with highly specific and enhanced catalytic activity. We hypothesized that M40401 would exert a protective effect in I/R injury of cardiac allografts and ameliorate the progression of GCAD. Recipient ACI rats were pretreated with M40401 or vehicle control. PVG donor hearts were heterotopically transplanted into the abdomen of ACI recipients. Cardiac allografts were analyzed for adhesion molecule mRNA expression and tumor necrosis factor-alpha expression after 4 hr of reperfusion. Neutrophil infiltration was detected by myeloperoxidase activity. Intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1 mRNA were detected by reverse-transcriptase polymerase chain reaction. Immunohistochemical analysis of adhesion molecule expression was also performed. Additional grafts were procured 90 days after transplantation and assessed for the development of GCAD by computer-assisted image analysis. In the M40401-treated group, adhesion molecule expression was significantly less than in the vehicle control group. Treated grafts also had lower myeloperoxidase activity and tumor necrosis factor-alpha concentration compared with controls. Neointimal proliferation and intima to media ratios in M40401-treated allografts were significantly decreased compared with controls. Selective removal of superoxide anion by M40401 results in inhibition of I/R injury. Furthermore, M40401 treatment decreases the development of oxidative stress-associated GCAD. This treatment strategy may have broad cardioprotective applications for all cardiac operations in addition to cardiac transplantation.


Copper/zinc superoxide dismutase overexpression promotes survival of cortical neurons exposed to neurotoxins in vitro.
Oxidative stress and excitotoxicity have been implicated as triggering factors in various neurodegenerative diseases or acute neurological insults. Cu/Zn superoxide dismutase (SOD1), a potent free radical scavenging factor, may prevent the progression of such diseases. In the present study, we show that SOD1 overexpression promoted the survival of cortical neuronal cultures originating from mice carrying the human SOD1 transgene. SOD1 overexpression significantly protected against the deleterious effect of reactive oxygen species, ceramide, or N-methyl-D-aspartate (NMDA). It also preserved cortical neurons against apoptosis induced by NMDA or ceramide, as revealed by a smaller increase in caspase 3 activity. SOD1 overexpression was correlated with higher SOD1 activity, and neurotoxins induced an increase in SOD1 activity in cultures from both mice. Moreover, the ratio of increase of SOD1 in cultures from nontransgenic vs. transgenic mice was similar in control cultures or following neurotoxins administration. The highest amount of neurotoxin-induced SOD1 activity was generated by NMDA. Moreover, following exposure to hydrogen peroxide, the cytoskeletal organization was altered, as evidenced by modifications of beta-tubulin or MAP2 labelling. The fact that increased superoxide dismutase activity protected neurons suggests that appropriate control of SOD1 activity is required for neuronal survival under stressful conditions.


Early discharge after thoracoscopic anatomical pulmonary resection for non-small-cell lung cancer.
Although video-assisted thoracic surgery (VATS) has shortened hospitalization duration for non-small-cell lung cancer (NSCLC) patients, the factors associated with early discharge remain unclear. This study aimed to identify patients eligible for a 72-h stay after VATS anatomical resection. Monocentric retrospective study including all consecutive patients undergoing VATS anatomical resection for NSCLC between February 2010 and December 2019. Two groups were defined according to the discharge: 'early discharge' (within 72 postoperative hours) and 'routine discharge' (at >72 postoperative hours). A total of 660 patients with a median age of 66.5 years (interquartile range 60-73 years) (female/male: 321/339) underwent VATS anatomical pulmonary resection for NSCLC [segmentectomy in 169 (25.6%), lobectomy in 481 (72.9%), bilobectomy in 8 (1.2%) and pneumonectomy in 2 (0.3%) patients]. The cardiopulmonary and Clavien-Dindo III-IV postoperative complication rates were 32.6% and 7.7%, respectively. The median postoperative length of stay was 6 days (interquartile range 4-10 days). In total, 119 patients (18%) could be discharged within 72 h of surgery. On multivariable analysis, the factors significantly associated with an increased likelihood of early discharge were: body mass index >20 kg/m2 [odds ratio (OR) 2.37], absence of prior cardiopathy (OR 2), diffusing capacity of the lung for carbon monoxide >60% (OR 1.82), inclusion in an enhanced recovery after surgery protocol (OR 2.23), use of a single chest tube (OR 5.73) and postoperative transfer to the ward (OR 4.84). Factors significantly associated with a decreased likelihood of early discharge were: age >60 years (OR 0.53), American Society of Anaesthesiologists score >2 (OR 0.46) and use of an epidural catheter (OR 0.41). Readmission rates were not statistically different between both groups (5.9% vs 3.1%; P = 0.17). Age, pulmonary functions and comorbidities may influence discharge after VATS anatomical resection. The early discharge does not increase readmission rates.


The Acute Respiratory Infection Quality Dashboard: a performance measurement reporting tool in an electronic health record.
Quality reporting tools, integrated with electronic health records, can help clinicians understand performance, manage populations, and improve quality. The Acute Respiratory Infection Quality Dashboard (ARI QD) for LMR users is a secure web report for performance measurement of an acute condition delivered through a central data warehouse and custom-built reporting tool. Pilot evaluation of the ARI QD indicates that clinicians prefer a quality report that combines not only structured data regarding diagnosis and antibiotic prescribing rates entered into EHRs but one that also shows billing data. The ARI QD has the potential to reduce inappropriate antibiotic prescribing for ARIs.


Evaluation of AOAC microbial diffusion procedure for analysis of chlortetracycline in high mineral feeds.
The performance of the AOAC microbial diffusion assay procedure for the analysis of chlortetracycline was evaluated in mixed feeds and premixes as well as laboratory-prepared feeds, all with various mineral contents. In 100 mixed feeds with a calcium content ranging from less than 1 to greater than 22%, no relationship was shown between calcium content and incidence of chlortetracycline deficiency. In 106 premixes, a relationship was shown between chlortetracycline content and adherence to guarantee: below 10 g/lb, the incidence of deficiency was high; in premixes containing 20 g chlortetracycline and above, the incidences of deficiency were less than 5%. In laboratory-prepared feeds containing 12-15% calcium, grinding and storage at both 4 degrees C and at room temperature (20 degrees C) caused no decrease in the chlortetracycline concentration. Only storage of the ground feed at 37 degrees C caused a distinct loss of activity. The temperature-related loss was attributed to the epimerization of chlortetracycline.


Neurocardiogenic injury in subarachnoid hemorrhage: A wide spectrum of catecholamin-mediated brain-heart interactions.
The purpose of this review was to summarize the up-to-date knowledge on clinical presentation and management of neurocardiogenic injury and to deliver the evidence of common pathophysiology of this broad spectrum of disorders. Medline and EmBase databases were searched to obtain original research articles and review papers using the following key words: neurocardiogenic injury, stress cardiomyopathy,tako-tsubo, subarachnoid hemorrhage, ECG abnormalities, catecholamine toxicity, neuropulmonary edema. Various forms of cerebral pathology, most importantly subarachnoid hemorrhage (SAH), are accompanied by transient cardiac dysfunction with ST-segment elevation and QT interval prolongation and T wave inversion with simultaneous release of cardiac troponin. In the past 20 years a great deal of data emerged concerning stress cardiomyopathy ('tako-tsubo') presenting as a rare transient apical ballooning syndrome following stressful life events with symptoms and signs resembling acute myocardial infarction (AMI), yet without significant coronary artery stenosis. Both forms of cardiac dysfunction are mediated by catecholamine toxicity, triggered by physical and psychological distress, leading to a specific type of neurogenic myocardial stunning reflected by histopathological image of contraction band necrosis. Neurocardiogenic injury should be carefully differentiated from AMI. Cardiac dysfunction in SAH heralds increased mortality. The criteria for the diagnosis of stress cardiomyopathy should be revised to comprise the diversity of its clinical symptomatology and to include cardiac dysfunction accompanying cerebral pathology.


Illness centrality, disclosure, and well-being in younger and middle-aged adult cancer survivors.
Cancer survivorship is often linked with identity reconstruction, and the extent to which individuals identify with their cancer experience may be an important aspect of their adjustment to longer-term cancer survivorship. However, little is known about the extent to which cancer is central to one's identity or the relations of centrality of cancer to identity with well-being. Further, the impact of cancer identity centrality might be moderated by the extent to which survivors openly disclose their survivorship status. The present study examined centrality of cancer and well-being along with the potential moderation effect of disclosure. Using a cross-sectional design, 167 participants (cancer survivors aged 18-55, diagnosed 1-3 years prior) completed measures of demographics, centrality of cancer identity, openness/disclosure, and well-being (including health-related quality of life [HRQOL], positive and negative affect, intrusive thoughts, life satisfaction, and post-traumatic growth). Cancer identity centrality was fairly low while disclosure/openness was fairly high. In regression analyses, centrality was adversely related to most measures of well-being, except unrelated to physical HRQOL and post-traumatic growth. Openness/disclosure about cancer survivorship status was positively related to most measures of well-being but did not moderate relationships between centrality and well-being. These findings support the notion that both cancer identity centrality and openness/disclosure are important aspects of the cancer survivorship experience that may impact well-being and warrant further research.


"Got to build that trust": the perspectives and experiences of Aboriginal health staff on maternal oral health.
In Australia, models of care have been developed to train antenatal care providers to promote oral health among pregnant women. However, these models are underpinned by Western values of maternity care that do not consider the cultural needs of Aboriginal and Torres Strait Islander women. This study aimed to explore the perceptions and experiences of Aboriginal health staff towards oral health care during pregnancy. It is part of a larger program of research to develop a new, culturally safe model of oral health care for Aboriginal women during pregnancy. A descriptive qualitative methodology informed the study. Focus groups were convened to yarn with Aboriginal Health Workers, Family Partnership Workers and Aboriginal management staff at two antenatal health services in Sydney, Australia. A total of 14 people participated in the focus groups. There were four themes that were constructed. These focused on Aboriginal Health Workers and Family Partnership Workers identifying their role in promoting maternal oral health, where adequate training is provided and where trust has been developed with clients. Yet, because the Aboriginal health staff work in a system fundamentally driven by the legacy of colonisation, it has significantly contributed to the systemic barriers Aboriginal pregnant women continue to face in accessing health services, including dental care. The participants recommended that a priority dental referral pathway, that supported continuity of care, could provide increased accessibility to dental care. The Aboriginal health staff identified the potential role of Aboriginal Health Workers and Family Partnership Workers promoting oral health among Aboriginal pregnant women. To develop an effective oral health model of care among Aboriginal women during pregnancy, there is the need for training of Aboriginal Health Workers and Family Partnership Workers in oral health. Including Aboriginal staff at every stage of a dental referral pathway could reduce the fear of accessing mainstream health institutions and also promote continuity of care. Although broader oral health policies still need to be changed, this model could mitigate some of the barriers between Aboriginal women and both dental care providers and healthcare systems.


Effect of holding at room temperature on initial chromatin configuration and in vitro maturation rate of equine oocytes.
The relationship of holding time in media at room temperature (approximately 22 degrees C) to initial chromatin configuration and rate of in vitro maturation (IVM) of equine oocytes was determined. Only oocytes having a complete, compact cumulus were used in this study. Oocytes were removed from ovaries 3.5-8 h after slaughter and were put into one of four treatment groups: (1) immediate/fix (IF) = immediate fixation following removal from the ovary; (2) delay/fix (DF) = fixation after oocytes were held 1-4 h in medium at room temperature; (3) immediate/mature (IM) = immediate placement into maturation medium at 5% CO2 at 38.2 degrees C; and (4) delay/mature (DM) = placement into maturation medium at 5% CO2 at 38.2 degrees C after oocytes were held 1-4 h in medium at room temperature. Chromatin configurations in fixed oocytes were classified as fluorescent nucleus (FN), condensed chromatin (CC), fibrillar, intermediate, or fibrous germinal vesicle (GV). Other classifications were Metaphase I, II, or degenerating/abnormal. Oocytes held at room temperature before fixation (DF) had a lower proportion of oocytes in the fibrous GV, fibrillar and intermediate configurations than did oocytes fixed immediately (IF; 1/54, 2% versus 15/51, 30%, respectively, P < 0.001). Oocytes held before fixation tended to have a higher percentage of both the CC and FN configurations than did oocytes fixed immediately (CC: 22/40, 55% versus 11/36, 31%, respectively, P = 0.056; FN: 17/40, 43% versus 10/36, 28%, respectively, P = 0.066). Holding of oocytes did not affect the rate of resumption of meiosis or the rate of degeneration in culture; however, of oocytes resuming meiosis, more oocytes in the delayed than in the immediate maturation group had reached MII by 24h culture (14/15, 93% versus 8/15, 53%, respectively, P = 0.018).


Evaluation of an adjustment group for people with multiple sclerosis: a pilot randomized controlled trial.
The aim was to evaluate a group treatment for people with multiple sclerosis and low mood. Randomized controlled trial. Community. Patients with multiple sclerosis and low mood, scoring >7 on the Hospital Anxiety and Depression Scales or >2 on the General Health Questionnaire 12. Participants either attended an adjustment group for six, 2-hour group treatment sessions or were on a waiting list to attend the group. Hospital Anxiety and Depression Scale, General Health Questionnaire 12, Multiple Sclerosis Self Efficacy Scale, Multiple Sclerosis Impact Scale and Short Form 36 administered 3 and 6 months after random allocation. Of the 219 patients identified, 100 (46%) reported depressive symptoms and 126 (58%) anxiety symptoms. Forty participants were recruited, aged 25-68 (mean 47.7 SD 9.7) and eight were men. Patients allocated to the group intervention reported fewer depressive symptoms than those in the control group (U 109.5, P<0.05) but there were no significant differences in anxiety symptoms, self-efficacy or quality of life. Depressive symptoms were reduced following group intervention, which suggests this may be an effective psychological treatment and warrants further evaluation.


A CMOS micromachined capacitive tactile sensor with integrated readout circuits and compensation of process variations.
This paper presents a capacitive tactile sensor fabricated in a standard CMOS process. Both of the sensor and readout circuits are integrated on a single chip by a TSMC 0.35 μm CMOS MEMS technology. In order to improve the sensitivity, a T-shaped protrusion is proposed and implemented. This sensor comprises the metal layer and the dielectric layer without extra thin film deposition, and can be completed with few post-processing steps. By a nano-indenter, the measured spring constant of the T-shaped structure is 2.19 kNewton/m. Fully differential correlated double sampling capacitor-to-voltage converter (CDS-CVC) and reference capacitor correction are utilized to compensate process variations and improve the accuracy of the readout circuits. The measured displacement-to-voltage transductance is 7.15 mV/nm, and the sensitivity is 3.26 mV/μNewton. The overall power dissipation is 132.8 μW.