Correlates of soy food consumption in women at increased risk for breast cancer.
The objectives of the present study were to examine sociodemographic correlates of soy food consumption among women at increased risk of breast cancer, describe factors influencing soy food consumption or nonconsumption, and identify women's sources of information about soy foods. A cross-sectional, self-report survey was used to assess frequency of and factors influencing soy food consumption. Soy food intake was reported for the past year. Participants were 452 women with family histories of breast cancer who were enrolled in a cancer risk assessment program. Comparisons between consumers and nonconsumers of soy foods were performed using multivariate logistic regression and chi(2) analyses. Thirty-two percent reported soy food consumption. Commonly consumed soy foods were vegetable burgers, tofu, and soymilk. Consumers of soy foods were more likely to have higher levels of education and report eating five or more daily servings of fruits and vegetables. The primary reason for consumption of soy foods was eating a healthful diet, whereas insufficient knowledge about soy food preparation was the primary reason stated for nonconsumption. Both consumers and nonconsumers reported obtaining information about soy foods from magazines, friends, and newspapers. Consumers also indicated using the Internet to seek information. These findings contribute to our understanding of the level of soy intake among women at increased risk for breast cancer and highlight potential factors that may influence women's decisions regarding soy food consumption. Women, particularly in this vulnerable population, would benefit from clear messages regarding the health effects of soy.


The reduced neuropil hypothesis: a circuit based model of schizophrenia.
In recent years, quantitative studies of the neuropathology of schizophrenia have reignited interest in the cerebral cortex and focused attention on the cellular and subcellular constituents that may be altered in this disease. Findings have ranged from compromised circuitry in prefrontal areas to outright neuronal loss in temporal and cingulate cortices. Herein, we propose that a reduction in interneuronal neuropil in the prefrontal cortex is a prominent feature of cortical pathology in schizophrenia and review the growing evidence for this view from reports of altered neuronal density and immunohistochemical markers in various cortical regions. The emerging picture of neuropathology in schizophrenia is one of subtle changes in cellular architecture and brain circuity that nonetheless have a devastating impact on cortical function.


Neuroscience: Intelligence in the Honeybee Mushroom Body.
Intelligence, in most people's conception, involves combining pieces of evidence to reach non-obvious conclusions. A recent theoretical study shows that intelligence-like brain functions can emerge from simple neural circuits, in this case the honeybee mushroom body.


Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia.
Iron deficiency anemia (IDA) is a major public health problem especially in underdeveloped and developing countries. Zinc is the co-factor of several enzymes and plays a role in iron metabolism, so zinc deficiency is associated with IDA. In this study, it was aimed to investigate the relationship of symptoms of IDA and zinc deficiency in adult IDA patients. The study included 43 IDA patients and 43 healthy control subjects. All patients were asked to provide a detailed history and were subjected to a physical examination. The hematological parameters evaluated included hemoglobin (Hb); hematocrit (Ht); red blood cell (erythrocyte) count (RBC); and red cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (МСН), mean corpuscular hemoglobin concentration (МСНС), and red cell distribution width (RDW). Anemia was defined according to the criteria defined by the World Health Organization (WHO). Serum zinc levels were measured in the flame unit of atomic absorption spectrophotometer. Symptoms attributed to iron deficiency or depletion, defined as fatigue, cardiopulmonary symptoms, mental manifestations, epithelial manifestations, and neuromuscular symptoms, were also recorded and categorized. Serum zinc levels were lower in anemic patients (103.51 ± 34.64 μ/dL) than in the control subjects (256.92 ± 88.54 μ/dL; <0.001). Patients with zinc level <99 μ/dL had significantly more frequent mental manifestations (p < 0.001), cardiopulmonary symptoms (p = 0.004), restless leg syndrome (p = 0.016), and epithelial manifestations (p < 0.001) than patients with zinc level > 100 μ/dL. When the serum zinc level was compared with pica, no statistically significant correlation was found (p = 0.742). Zinc is a trace element that functions in several processes in the body, and zinc deficiency aggravates IDA symptoms. Measurement of zinc levels and supplementation if necessary should be considered for IDA patients.


Effects of temperature and CO2 enrichment on kinetic properties of phospho-enol-pyruvate carboxylase in two ecotypes of Echinochloa crus-galli (L.) Beauv., a C4 weed grass species.
Two populations of Echinochloa crus-galli (Québec, Mississippi) were grown at the Duke University Phytotron under 2 thermoperiods (28°/22°C, 21°/15°C day/night) and 2 CO2 regimes (350 and 675 μl l-1). Thermostability, energy of activation (E a ),K m (PEP), K m (Mg++), and specific activity of phospho-enol-pyruvate carboxylase (PEPc) were analyzed in partially purified enzyme preparations of plants grown for 5 weeks. Thermostability of PEPc from extracts (in vitro) and leaves (in situ) was significantly higher in Mississippi plants. In vitro denaturation was not appreciably modified by thermal acclimation but CO2 enrichment elicited higher thermostability of PEPc. In situ thermostability was significantly higher than that of in vitro assays and was higher in Mississippi plants acclimated at 28°/22°C and in plants of the two ecotypes grown at 675 μl l-1 CO2. E a (Q 10 30°/20°C) for PEPc was significantly lower in Québec plants as compared to Mississippi and no acclimatory shifts were observed. Significantly higher K m's (PEP) in 20°C assays were obtained for Mississippi as compared to Québec plants but values were similar at 30°C and 40°C assays. K m (Mg++) decreased at higher assay temperatures and were significantly lower for PEPc of the Québec ecotype. No significant changes in K m (Mg++) values were associated with modifications in temperature on CO2 regimes. PEPc activity measured at 30°C was significantly higher for Québec plants when measured on a leaf fresh weight, leaf area or protein basis but not on a chlorophyll basis. Significantly higher PEPc activity for both genotypes was observed for plants acclimated at 21°/15°C or grown at 675 μl l-1 CO2. Net photosynthesis (Ps) and net assimilation rates (NAR) were higher in Québec plants and were enhanced by CO2 enrichment. NAR was higher in plants acclimated at low temperature, while an opposite trend was observed for Ps. PEPc activities were always in excess of the amounts required to support observed rates of CO2 assimilation.


Use of social audits to examine unofficial payments in government health services: experience in South Asia, Africa, and Europe.
Unofficial payments in health services around the world are widespread and as varied as the health systems in which they occur. We reviewed the main lessons from social audits of petty corruption in health services in South Asia (Bangladesh, Pakistan), Africa (Uganda and South Africa) and Europe (Baltic States). The social audits varied in purpose and scope. All covered representative sample communities and involved household interviews, focus group discussions, institutional reviews of health facilities, interviews with service providers and discussions with health authorities. Most audits questioned households about views on health services, perceived corruption in the services, and use of government and other health services. Questions to service users asked about making official and unofficial payments, amounts paid, service delivery indicators, and satisfaction with the service. Contextual differences between the countries affected the forms of petty corruption and factors related to it. Most households in all countries held negative views about government health services and many perceived these services as corrupt. There was little evidence that better off service users were more likely to make an unofficial payment, or that making such a payment was associated with better or quicker service; those who paid unofficially to health care workers were not more satisfied with the service. In South Asia, where we conducted repeated social audits, only a minority of households chose to use government health services and their use declined over time in favour of other providers. Focus groups indicated that reasons for avoiding government health services included the need to pay for supposedly free services and the non-availability of medicines in facilities, often perceived as due to diversion of the supplied medicines. Unofficial expenses for medical care represent a disproportionate cost for vulnerable families; the very people who need to make use of supposedly free government services, and are a barrier to the use of these services. Patient dissatisfaction due to petty corruption may contribute to abandonment of government health services. The social audits informed plans for tackling corruption in health services.


Polyquaternium-1-Preserved Travoprost 0.003% or Benzalkonium Chloride-Preserved Travoprost 0.004% for Glaucoma and Ocular Hypertension.
To demonstrate equivalence of polyquaternium-1-preserved travoprost 0.003% with benzalkonium chloride-preserved travoprost 0.004% in patients with open-angle glaucoma or ocular hypertension. Double-masked, randomized, 2-treatment, equivalence clinical trial. setting: Multicenter clinical trial conducted in 60 centers in the United States and Europe. Adult patients with open-angle glaucoma or ocular hypertension. One eye per patient was analyzed. Patients were randomized 1:1 to receive polyquaternium-1-preserved travoprost 0.003% (n = 442) or benzalkonium chloride-preserved travoprost 0.004% (n = 422) once daily for 3 months. Mean intraocular pressure (IOP) was assessed at 8 AM, 10 AM, and 4 PM at week 2, week 6, and month 3. Supportive outcomes were mean and percent IOP change, percentage of patients achieving IOP <18 mm Hg or ≥30% IOP reduction, and adverse events. Mean IOP was similar between groups at all study visits (travoprost 0.003% range, 17.5-18.9 mm Hg; travoprost 0.004% range, 17.4-19.0 mm Hg). Mean change (least squares mean differences, -0.1 to 0.3 mm Hg; 95% confidence interval, -0.5 to 0.7 mm Hg) and percentage change (travoprost 0.003%, 28.4%-30.7%; travoprost 0.004%, 28.5%-31.0%) from baseline were comparable. The percentages of patients with IOP <18 mm Hg and ≥30% reduction of IOP were also similar. Hyperemia was the most frequent treatment-related adverse event with both formulations (travoprost 0.003%, 11.8%; travoprost 0.004%, 14.5%). In patients with open-angle glaucoma or ocular hypertension, polyquaternium-1-preserved travoprost 0.003% solution provided equivalent IOP-lowering efficacy to that of benzalkonium chloride-preserved travoprost 0.004%.


Increased risk of phosphorus and metal leaching from paddy soils after excessive manure application: Insights from a mesocosm study.
Livestock manure has gradually become an alternative fertilizer for maintaining soil fertility, whereas excessive application of manure leads to the release of phosphorus (P) and toxic metals that may cause complex environmental risks. To investigate the accumulation and migration of P within soil profiles, a mesocosm experiment was conducted to analyze the content and leaching of soil P, metals, and dissolved organic carbon after different fertilization treatments, including control (no fertilizer, CK), chemical fertilizer (CF), chemical fertilizer combined low (CF + LPM) and high (CF + HPM) rate of manure application. Results showed that a high rate of manure application significantly enhanced the accumulation of total soil P (by ~14%) and P availability (easily-available P, by ~24%; Olsen-P, by ~20%) in topsoil, and also increased the content of easily-available organic P (EA-Po) in both topsoil and subsoil compared to the CK treatment. The migration of dissolved inorganic and organic P (DIP and DOP) in leachate within soil profiles was strengthened by manure application. Moreover, significant positive correlations between P, metals, and dissolved organic carbon (DOC) in leachate indicated that downward co-migration occurred within the soil profiles, and also suggested that excessive manure application can intensify the risk of P loss by increasing the migration of manure-derived DOC. Overall, our findings provide insights into P accumulation and migration within soil profiles after excessive manure application, which is useful for predicting the potential risk of P and metal leaching from paddy soils.


Serpin-type serine protease inhibitor mediates coelomocyte apoptosis in Apostichopus japonicus.
Serine protease inhibitors (SPIs, serpins) are a protein superfamily involved in almost all physiological processes in all organisms. In this study, a novel serpin was identified from Apostichopus japonicus (Ajserpin) by using high-throughput sequencing and RACE approaches. The full-length cDNA of Ajserpin was 1893 bp with a 5'-untranslated region (UTR) of 130 bp, a 3'-UTR of 587 bp, and an open reading frame of 1176 bp encoding a polypeptide of 391 amino acids with a deduced molecular weight of 43.8 kDa. Ajserpin shares the standard structure of SPI, including three β-sheets and eight α-helices. The deduced amino acid sequences of Ajserpin had no nuclear location signal and signal peptide structure. The phylogenetic tree and immunofluorescence showed that Ajserpin belonged to the clade B subfamily and was mainly located in the cytoplasm and nucleus. Sequence comparison and protein inhibition experiments showed that the active site (P1-P1' site) of Ajserpin was Arginine and Serine, which displayed inhibitory activity toward trypsin in a dose-dependent manner. Tissue distribution analysis showed that Ajserpin transcripts were constitutively expressed in all examined tissues with the peak in the body wall. Ajserpin mRNA transcripts could be induced in Vibrio splendidus-challenged sea cucumber or lipopolysaccharide-exposed coelomocytes. Furthermore, Ajserpin knockdown by small interfering RNAs could inhibit coelomocytes apoptosis. All our results revealed that Ajserpin might serve as an immune regulator in sea cucumber.


Analysis of LIN28A in early human ovary development and as a candidate gene for primary ovarian insufficiency.
Lin28 proteins are emerging as important regulators of microRNAs in endocrine systems. Lin28a regulates primordial germ cell development and puberty timing in mice, whereas the related protein LIN28B is associated with age at menarche in genome-wide association studies in humans. Here, we studied expression of LIN28A and LIN28B in early human gonad development. LIN28A increased in the developing ovary between 6 and 9weeks post conception, but not in the developing testis. Immunohistochemistry demonstrated LIN28A in peripheral germ cells. LIN28B was expressed at lower levels in both tissues and did not increase with time. As disruption of Lin28a affects germ cell development in mice, LIN28A was considered a candidate gene for primary ovarian insufficiency (POI) in humans. However, no significant changes were found in 50 women studied. These findings show LIN28A is strongly expressed in germ cells during early human ovary development, but disruption of LIN28A is not a common cause of POI.


Cardiovascular responses and lateral hypothalamic self-stimulation: anatomical differentiation and functional significance.
Heart rate was telemetrically recorded from rats self-stimulating in a two-day shuttle-box. Blood pressure changes to intracranial stimulation (ICS) were determined in acute studies with the same subjects. Stimulus-bound heart rate decreases were found only at sites in the anterodorsal aspect of the lateral hypothalamus, whereas no changes in heart rate were observed at ventral or posterior sites. In the acute experiments, stimulation of the anterodorsal sites produced either decreases or no change in blood pressure. Stimulus-bound blood pressure increases were observed only in the ventrolateral hypothalamus. The differential topographical distribution of the electrode sites producing the heart rate and blood pressure changes suggests that these two aspects of cardiovascular function are subserved by separate neural systems in the hypothalamus and that the bradycardia during self-stimulation is a primary response to ICS and is not a reflex elicited by blood pressure increases. Blockade of the bradycardia with the peripheral cholinergic blocker methyl-hyoscine HBr had no effect on the initiation of or escape from ICS indicating that peripheral parasympathetic activity is not causally related to either the rewarding or aversive components of hypothalamic ICS.


The validity of the static-charge-sensitive bed in the detection of fentanyl-induced respiratory depression.
Only a few methods for the measurement of breathing are non-invasive and do not interfere with measured parameters. The static-charge-sensitive bed (SCSB) could be such a monitor. The aim of this study was to evaluate the validity of the SCSB compared with the respiratory inductive plethysmograph (RIP) using a fentanyl-induced respiratory depression model. Eight healthy male volunteers were infused with intravenous (i.v.) fentanyl (15 microg/kg/h) until a decrease in SpO2 below 90% for 1 min emerged. Breathing was continuously and simultaneously measured with SCSB and RIP. Oxygenation, hemodynamics, arterial blood gas analysis, and subjective opioid-related effects were monitored. Fentanyl concentration was measured from an arterial blood sample. The respiratory rate data of the SCSB (automated analysis and manual calculation) were compared with the corresponding RIP data, using analysis of variance for repeated measures. The validity of the SCSB compared with RIP was evaluated using an intra-class correlation coefficient. Mean fentanyl dose was 629 microg. A statistically significant association was found between the RIP and SCSB data in the manual SCSB analysis (P < 0.0001), but not in the automated SCSB analysis (P = 0.91). After adjusting for the effect of time and the SCSB method, an intra-class correlation coefficient between the manually calculated SCSB values and the RIP values was 0.66. Clinically significant changes in respiratory rate were detected with the SCSB, but the results had to be analyzed manually. The SCSB best suits situations, where comprehensive data are needed. It is not suitable for on-line respiratory monitoring, as the automated analysis did not calculate the respiratory rate correctly.


Purification, conformational analysis and cytotoxic activities of host-defense peptides from the Tungara frog Engystomops pustulosus (Leptodactylidae; Leiuperinae).
The amphibian family Leptodactylidae is divided into three sub-families: Leiuperinae, Leptodactylinae, and Paratelmatobiinae. Host-defense peptides (HDPs) present in the skins of frogs belonging to the Leptodactylinae have been studied extensively, but information is limited regarding peptides from Leiuperinae species. Peptidomic analysis of norepinephrine-stimulated skin secretions from the Tungara frog Engystomops pustulosus (Leiuperinae) collected in Trinidad led to the isolation and structural characterization of previously undescribed pustulosin-1 (FWKADVKEIG KKLAAKLAEELAKKLGEQ), [Q28E] pustulosin-1 (pustulosin-2), and pustulosin-3 (DWKETAKELLKKIGAKVAQVISDKLNPAPQ). The primary structures of these peptides do not resemble those of previously described frog skin HDPs. In addition, the secretions contained tigerinin-1EP (GCKTYLIEPPVCT) with structural similarity to the tigerinins previously identified in skin secretions from frogs from the family Dicroglossidae. Pustulosin-1 and -3 adopted extended α-helical conformations in 25% trifluoroethanol-water and in the presence of cell membrane models (sodium dodecylsulfate and dodecylphosphocholine micelles). Pustulosin-1 and -3 displayed cytotoxic activity against a range of human tumor-derived cell lines (A549, MDA-MB-231, and HT29), but their therapeutic potential for development into anti-cancer agents is limited by their comparable cytotoxic activity against non-neoplastic human umbilical vein endothelial cells. The peptides also displayed weak antimicrobial activity against Escherichia coli (MIC = 125 µM) but were inactive against Staphylococcus aureus. Tigerinin-1EP was inactive against both the tumor-derived cells and bacteria.


Left ventricular performance during psychological stress.
Left ventricular ejection fraction, systolic blood pressure and plasma norepinephrine were measured in six normotensive and six mildly hypertensive subjects during rest and psychological stress. Compared with rest, 8 of the 12 subjects developed significant (P less than 0.05) changes in ejection fraction (increase in 6, decrease in 2); 10 of 12 subjects developed significant elevations of plasma norepinephrine; and all developed significant increases in systolic blood pressure. When the stress effects were examined for the total group, as opposed to within subjects, there were significant increases in plasma norepinephrine (P less than 0.001) and systolic blood pressure (P less than 0.001) but, interestingly, mean ejection fraction and stroke volume remained unchanged, implying stress led to increased left ventricular contractility.


Relaxation-compensated CEST (chemical exchange saturation transfer) imaging in breast cancer diagnostics at 7T.
To investigate whether fat-corrected and relaxation-compensated amide proton transfer (APT) and guanidyl CEST-MRI enables the detection of signal intensity differences between breast tumors and normal-appearing fibroglandular tissue in patients with newly-diagnosed breast cancer. Ten patients with newly-diagnosed breast cancer and seven healthy volunteers were included in this prospective IRB-approved study. CEST-MRI was performed on a 7 T-whole-body scanner followed by a multi-Lorentzian fit analysis. APT and guanidyl CEST signal intensities were quantified in the tumor and in healthy fibroglandular tissue after correction of B0/B1-field inhomogeneities, fat signal contribution, T1- and T2-relaxation; signal intensity differences of APT and guanidyl resonances were compared using Mann-Whitney-U-tests. Pearson correlations between tumor CEST signal intensities and the proliferation index Ki-67 were performed. APT CEST signal in tumor tissue (6.70 ± 1.38%Hz) was increased compared to normal-appearing fibroglandular tissue of patients (3.56 ± 0.54%Hz, p = 0.001) and healthy volunteers (3.70 ± 0.68%Hz, p = 0.001). Further, a moderate positive correlation was found between the APT signal and the proliferation index Ki-67 (R2 = 0.367, r = 0.606, p = 0.11). Guanidyl CEST signal was also increased in tumor tissue (5.24 ± 1.85%Hz) compared to patients' (2.42 ± 0.45%Hz, p = 0.006) and volunteers' (2.36 ± 0.54%Hz, p < 0.001) normal-appearing fibroglandular tissue and a positive correlation with the Ki-67 level was observed (R2 = 0.365, r = 0.604, p = 0.11). APT and guanidyl CEST signal in normal-appearing fibroglandular tissue was not different between patients and healthy volunteers (p = 0.88; p = 0.93). Relaxation-compensated and fat-corrected CEST-MRI allowed a non-invasive differentiation of breast cancer and normal-appearing breast tissue. Thus, this approach represents a contrast agent-free method that may help to increase diagnostic accuracy in MR-mammography.


Hyperferritinaemia: An Iron Sword of Autoimmunity.
Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response. Different electronic databases were searched in a non-systematic way to find out the literature of interest. The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still's diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm. This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.


Chromatographic study on the specificity of bis-p-nitrophenylphosphate in vivo. Identification of labelled proteins of rat liver after intravenous injection of bis-p-nitro[14C]phenylphosphate as carboxylesterases and amidases.
The procedure established to isolate the carboxylesterases E1, E2 and EA from rat liver (Arndt, R. and Krisch, K. (1972) Hoppe-Seyler's Z. Physiol. Chem. 353, 589-598) was applied to characterize in vivo bis-p-nitro[14C]-phenyl-P-labelled proteins. The peaks of radioactivity and of residual enzyme activities (hydrolysing methylbutyrate, p-nitrophenylacetate and acetanilide) were found in the same peaks after column chromatography and could be related to the well-defined esterases E1, E2 and EA. There is no indication of a nonspecific binding of bis-p-nitrophenyl-P or of one of its metabolites. The relative quantitative amounts of E1, E2 and EA were calculated to represent 40, 14 and 46%, respectively, of the total carboxylesterase content of rat liver. The relative amount of bound (not dialysable) radioactivity in rat liver depended on the survival time. During purification, the yield of enzyme activities corresponded to that of bound radioactivity, confirming the specificity of bis-p-nitrophenyl-P in vivo. Hence the radioactive metabolites of the inhibitor obviously do not possess binding affinities of quantitative importance to the rat liver proteins.


Warfarin: metabolism and mode of action.
The various stages involved in the transport, pharmacological action and elimination of warfarin involve the specific binding of warfarin to a chiral macromolecular complex. However, it seems that the degree of stereoselectivity is variable, which presumably reflects the importance of the side-chain in binding to each type of macromolecule. It would appear that there is greater stereoselective control in the interaction of warfarin with cytochrome P-450 enzymes than that observed for interaction with the receptor, vitamin K1 epoxide reductase. Indeed, warfarin has been developed as a powerful stereochemical probe for in vitro studies of the terminal enzyme in the mixed-function oxidase system, cytochrome P-450. Warfarin undergoes hydroxylation in the 6, 7 and 8-positions of the aromatic ring which must interact with the active (haemoprotein) portion of the molecule, leaving the side-chain, which contains the chiral centre, free for recognition by the substrate binding site. In vitro studies indicate that the interaction of warfarin at its receptor, vitamin K1 epoxide reductase, is completely non-stereoselective. This suggests that only the 4-hydroxycoumarin ring portion of the drug binds to the enzyme. Consistent with this hypothesis, salicylate, which can mimic part of the 4-hydroxycoumarin ring system, produces hypothrombinaemia by inhibition of vitamin K1 epoxide reductase. These findings suggest that the coumarin ring system is largely responsible for the pharmacodynamic properties of warfarin, whereas the side-chain dictates the disposition and metabolism of the drug.


Engaging young people within a collaborative knowledge mobilization network: Development and evaluation.
It is critical that mental health systems place a focus on prevention and early intervention focused on young people while integrating youth voice to guide priority directions. This study was designed to better understand how youth advisories can be utilized to influence strategic directions within integrated knowledge mobilization networks operating within the youth mental health system. To support this objective, we reviewed the detailed stages of development in establishing a youth advisory within a national network designed to support the integration of youth services. We also engaged the advisory in a participatory evaluation process that examined the extent to which the network had created processes to include youth voice in decision-making. Results from the surveys identified moderate to high levels of individual engagement as well as strong development of processes and procedures that support the inclusion of youth voice across the network. Major successes and challenges are presented and discussed with respect to the development of the advisory. The findings are useful for youth advocates and adult allies working to support youth engagement (YE) in knowledge mobilization to enhance the mental health services system. This study also contributes to research and evaluation efforts examining YE and represents an exemplar methodology for evaluating YE efforts at the system level. Young people as mental health service users and youth mental health advocates were involved in the design, data collection, analysis and interpretation of the data as well as the preparation of this manuscript.


Vowel processing by a model of the auditory periphery: a comparison to eighth-nerve responses.
A model of peripheral auditory processing that incorporates processing steps describing the conversion from the acoustic pressure-wave signal at the eardrum to the time course activity in auditory neurons has been developed. It can process arbitrary time domain waveforms and yield the probability of neural firing. The model consists of a concatenation of modules, one for each anatomical section of the periphery. All modules are based on published algorithms and current experimental data, except that the basilar membrane is assumed to be linear. The responses of this model to vowels alone and vowels in noise are compared to neural population responses, as determined by the temporal and average rate response measures of Sachs and Young [J. Acoust. Soc. Am. 66, 470-479, (1979)] and Young and Sachs [J. Acoust. Soc. Am. 66, 1381-1403, (1979)]. Despite the exclusion of nonlinear membrane mechanics, the model accurately predicts the vowel formant representations in the average localized synchronized rate (ALSR) responses and the saturating characteristics of the normalized average rate responses in quiet. When vowels are presented in background noise, the modeled ALSR responses are less robust than the neural data.


Elucidation of cellular targets responsible for tetrachlorodibenzo-p-dioxin (TCDD)-induced suppression of antibody responses: I. The role of the B lymphocyte.
The objective of these studies was to identify the primary cellular target(s) responsible for TCDD (tetrachlorodibenzo-p-dioxin)-induced suppression of antibody production. Responses to T-independent and T-dependent antigens (administered in vivo or directly to splenic culture) were suppressed in a dose-related fashion in female B6C3F1 mice dosed for 5 consecutive days with 0.1, 1.0 and 10.0 micrograms/kg of 2,3,7,8-TCDD. When nonadherent (B and T) and adherent (macrophage) cells from vehicle- and TCDD-treated mice were combined in various combinations and immunized with either DNP-Ficoll (T-independent) or sRBCs (T-dependent), it was demonstrated that nonadherent cells, but not adherent cells, were functionally affected by TCDD. Similarly, as various combinations of B + macrophage and T + macrophage populations were immunized with sRBCs, the B cell was shown to be the primary target. Using LPS as the stimulus, an inhibition of the antibody response with no effect on the mitogenic response further indicated that the primary target of the TCDD-induced suppression of IgM antibody production is the B lymphocyte at the level of cell differentiation.


Cooperative interactions between replication origin-bound molecules of herpes simplex virus origin-binding protein are mediated via the amino terminus of the protein.
The virally encoded origin binding protein (OBP) of herpes simplex virus (HSV) is required for viral DNA synthesis. OBP binds at the replication origin to initimultienzyme replication complex (Challberg, M. D., and Kelly, T. J. (1989) Annu Rev. Biochem. 58, 671-717), OBP binds to two sites at the replication origin. The sequence-specific interaction of OBP with each binding site is localized to the major groove, and in both HSV origins the two interaction surfaces are in phase, aligned on the same face of the helix (Hazuda, D. J., Perry, H. C., Naylor, A. M., and McClements, W. L. (1991) J. Biol. Chem. 261, 24621-24625). Using native gel electrophoresis, we now demonstrate that OBP binding to the origin is highly cooperative and that cooperativity requires the putative NH2-terminal leucine zipper. Neither the phase nor orientation of the binding sites affect cooperativity, suggesting that the interaction promotes wrapping of origin DNA around the OBP multimer. A comparison of OBP DNase I footprints with the DNase I footprints of a truncated protein defective in cooperativity demonstrates that the interaction between OBPs bound at sites I and II affects the conformation of the intervening DNA, particularly when the phase or orientation of the two sites is different from wild type. OBP may elicit a unique nucleoprotein structure which facilitates unwinding of the origin and/or assembly of the replication complex. We also demonstrate that OBP can exchange binding sites, forming interduplex complexes. This property may be important for reinitiation of DNA replication.


Drosophila melanogaster Zelda and Single-minded collaborate to regulate an evolutionarily dynamic CNS midline cell enhancer.
The Drosophila Zelda transcription factor plays an important role in regulating transcription at the embryonic maternal-to-zygotic transition. However, expression of zelda continues throughout embryogenesis in cells including the developing CNS and trachea, but little is known about its post-blastoderm functions. In this paper, it is shown that zelda directly controls CNS midline and tracheal expression of the link (CG13333) gene, as well as link blastoderm expression. The link gene contains a 5' enhancer with multiple Zelda TAGteam binding sites that in vivo mutational studies show are required for link transcription. The link enhancer also has a binding site for the Single-minded:Tango and Trachealess:Tango bHLH-PAS proteins that also influences link midline and tracheal expression. These results provide an example of how a transcription factor (Single-minded or Trachealess) can interact with distinct co-regulatory proteins (Zelda or Sox/POU-homeodomain proteins) to control a similar pattern of expression of different target genes in a mechanistically different manner. While zelda and single-minded midline expression is well-conserved in Drosophila, midline expression of link is not well-conserved. Phylogenetic analysis of link expression suggests that ~60 million years ago, midline expression was nearly or completely absent, and first appeared in the melanogaster group (including D. melanogaster, D. yakuba, and D. erecta) >13 million years ago. The differences in expression are due, in part, to sequence polymorphisms in the link enhancer and likely due to altered binding of multiple transcription factors. Less than 6 million years ago, a second change occurred that resulted in high levels of expression in D. melanogaster. This change may be due to alterations in a putative Zelda binding site. Within the CNS, the zelda gene is alternatively spliced beginning at mid-embryogenesis into transcripts that encode a Zelda isoform missing three zinc fingers from the DNA binding domain. This may result in a protein with altered, possibly non-functional, DNA-binding properties. In summary, Zelda collaborates with bHLH-PAS proteins to directly regulate midline and tracheal expression of an evolutionary dynamic enhancer in the post-blastoderm embryo.


Spatial distribution of polychlorinated biphenyls in High Tatras lake sediments.
The objective of the present study was to gain insight on the spatial distribution of seven polychlorinated biphenyl (PCB) congeners in the High Tatras mountain range in Eastern Europe. Twenty high mountain lakes were sampled on their top-core sediment. Despite the relative uniform composition of PCB congeners among the lakes, there are important differences in the observed concentrations. Moderate top-core sediment concentrations of PCB congeners were observed (1.9 to 38 ng/g dw for ∑PCB) in comparison to other high mountain or Arctic areas. The variation in PCB concentrations can partly be explained by a possible altitudinal effect, resulting in higher PCB concentrations at higher (colder) altitudes. Part of this enhanced accumulation of PCBs could be caused by external factors (topography and meteorology) and internal lake factors (sediment dynamics). Many of these factors were not quantified for all individual lakes and their influence could, therefore, only be studied for some.


Higher Order Architecture of Designer Peptides Forms Bioinspired 10 nm siRNA Delivery System.
The higher-order architecture observed in biological systems, like viruses, is very effective in nucleic acid transport. The replications of this system has been attempted with both synthetic and naturally occurring polymers with mixed results. Here we describe a peptide/siRNA quaternary complex that functions as an siRNA delivery system. The rational design of a peptide assembly is inspired by the viral capsids, but not derived from them. We selected the collagen peptide (COL) to provide the structural stability and the folding framework, and hybridize it with the cell penetrating peptide (CPP) that allows for effective penetration of biological barriers. The peptide/siRNA quaternary complex forms stoichiometric, 10 nm nanoparticles, that show fast cellular uptake (<30 min), effective siRNA release, and gene silencing. The complex provides capsid-like protection for siRNA against nucleases without being immunostimulatory, or cytotoxic. Our data suggests that delivery vehicles based on synthetic quaternary structures that exhibit higher-order architecture may be effective in improving delivery and release of nucleic acid cargo.


Reliability of body composition assessment using A-mode ultrasound in a heterogeneous sample.
Several studies have addressed the validity of ultrasound (US) for body composition assessment, but few have evaluated its reliability. This study aimed to determine the reliability of percent body fat (%BF) estimates using A-mode US in a heterogeneous sample. A group of 144 healthy adults (81 men and 63 women), 30.4 (10.1) years (mean (SD)), BMI 24.6 (4.7) kg/m2, completed 6 consecutive measurements of the subcutaneous fat layer thickness at 8 anatomical sites. The measurements were done, alternatively, by two testers, using a BodyMetrix™ instrument. To compute %BF, 4 formulas from the BodyView™ software were applied: 7-sites Jackson and Pollock, 3-sites Jackson and Pollock, 3-sites Pollock, and 1-point biceps. The formula with the most anatomic sites provided the best reliability quantified by the following measures: intraclass correlation coefficient (ICC) = 0.979 for Tester 1 (T1) and 0.985 for T2, technical error of measurement (TEM) = 1.07% BF for T1 and 0.89% BF for T2, and minimal detectable change (MDC) = 2.95% BF for T1, and 2.47% BF for T2. The intertester bias was -0.5% BF, whereas the intertester ICC was 0.972. The intertester MDC was 3.43% BF for the entire sample, 3.24% BF for men, and 3.65% BF for women. A-mode US is highly reliable for %BF assessments, but it is more precise for men than for women. Examiner performance is a source of variability that needs to be mitigated to further improve the precision of this technique.


Transplantation analysis of B cell destruction in (NOD x CBA)F1 mouse bone marrow chimeras.
F1 hybrids produced by outcross of non-obese diabetic (NOD) mice with diabetes resistant strains are also diabetes resistant. This resistance is abrogated if F1 hybrids are lethally irradiated and then haematopoietically reconstituted with NOD bone marrow. This model was employed to determine whether T lymphocyte recognition and elimination of pancreatic B cells in NOD mice is restricted by the MHC haplotype of the target B cell. Diabetes resistant (NOD/Lt x CBA/J)F1 hybrids were lethally irradiated and reconstituted with NOD/Lt bone marrow. Following haematopoietic reconstitution, donor matched NOD/Lt or CBA/J pancreatic islet and anterior pituitary grafts were grafted under a renal capsule to determine whether effector cells derived from NOD/Lt marrow progenitors would reject islet grafts in a MHC restricted fashion. The H-2k haplotype expressed by CBA/J mice differs from all known loci of the unique H-2 haplotype of NOD; therefore, if NOD/Lt T lymphocytes eliminate pancreatic B cells in a MHC restricted fashion. NOD islet grafts would be eliminated in these chimeras while CBA islet grafts would be retained. Overt diabetes developed in 80% of the female and 40% of the male F1 hybrids following reconstitution with NOD/Lt marrow, while no hybrids reconstituted with CBA/J marrow became diabetic through a year of age. The retention of CBA/J skin and pituitary grafts in NOD/Lt marrow reconstituted F1 hybrids confirmed that the F1 thymic environment imparted tolerance to CBA/J alloantigens. Nonetheless, responses to a T cell dependent model antigen were restricted to the unique MHC haplotype of NOD. This was associated in the hyperglycaemic chimeras with rejection (8-21 days post-implantation) of both CBA/J and NOD/Lt islet grafts.(ABSTRACT TRUNCATED AT 250 WORDS)


MRI-based radiomics analysis of bladder cancer: prediction of pathological grade and histological variant.
To develop magnetic resonance imaging (MRI)-based radiomics models for the prediction of the pathological grade and histological variant of bladder cancer. A total of 227 patients who underwent bladder MRI and had histopathologically confirmed grades and variants were included retrospectively from January 2017 to March 2022. They were assigned to a training set (n=131) and a testing set (n=96) based on the MRI system. MRI-based radiomics features were extracted from manually segmented volumes of interest from high-b-value DWI images and ADC maps. The radiomics models were trained with all possible pipelines in the training set. One optimal model was selected using the fivefold cross-validation method and verified by the testing set according to the pathological results. Univariate and multivariate analyses were performed to identify the significant clinical and imaging factors for developing clinical-radiomics models. The radiomics model for grade prediction had area under the curve (AUC) values of 0.784, 0.786, and 0.733 in the training, cross-validation, and testing sets, respectively. The radiomics model for variant prediction had AUC values of 0.748, 0.757, and 0.789 in the training, cross-validation, and testing sets, respectively. The performance of the clinical-radiomics model was significantly improved compared with the radiomics models alone for the total dataset (AUC for grade: 0.846 versus 0.756; AUC for variant: 0.810 versus 0.757, p<0.05). MRI-based radiomics models could be used to predict the pathological grade and histological variants of bladder cancer with relatively good performance.


Improving the sense of city belonging among migrant elderly following family from an elderly service perspective: a cross-sectional study.
The migrant elderly following family (MEFF), who migrates to new community to reunite with families, may face challenges of city integration and belonging. This study aims to explore from an elderly service perspective how to improve the sense of city belonging for MEFFs with and without hypertension/diabetes conditions. Data were derived from the 2017 China Migrants Dynamic Survey and China National Statistical Yearbooks in 2017. The study included 882 MEFFs with hypertension or diabetes and 1266 MEFFs without hypertension and diabetes. Hierarchical linear modeling was applied to analyze the effects of individual and provincial elderly services on sense of city belonging among the MEFF with and without hypertension/diabetes. The MEFFs with hypertension or diabetes exhibited a greater sense of city belonging when they were familiar with a wider range of health education topics (γ = 0.05, p = 0.033) and were in those provinces with a greater number of licensed doctors (γ = 0.39, p < 0.001) and hospitals (p = 0.042). For those MEFFs without hypertension or diabetes, social security cards (γ = 0.57, p < 0.001) and awareness of a wider range of health education topics (γ = 0.07, p = 0.018) may help to improve their sense of city belonging. This study calls for strengthening the accessibility in inclusive elderly services, and minimizing or even eliminating the inequality in elderly services at the individual and provincial levels to increase sense of city belonging among the MEFFs. For the MEFFs with hypertension or diabetes, health managers should focus on improving health information dissemination and increasing the number of doctors per 1000 people as well as and the number of hospitals to enhance the sense of city belonging. Moreover, the government should strengthen social security and health education to facilitate the adaptation and integration of MEFFs without hypertension and diabetes into the host city.


Variation in Treatment of Children Hospitalized With New-Onset Systemic Juvenile Idiopathic Arthritis in the US.
Increasing evidence supports the conclusion that early initiation of biologics may dramatically improve disease course and reduce glucocorticoid exposure for children with systemic juvenile idiopathic arthritis (JIA). The present study was undertaken to characterize variation in the use of first-line biologic and glucocorticoid therapy and to identify drivers of variation in children hospitalized with new-onset systemic JIA. We conducted a retrospective cohort study of children hospitalized with new-onset systemic JIA from 2008 to 2019 utilizing a comparative pediatric database from 52 tertiary care children's hospitals. Subjects and treatment receipt were identified using International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 discharge diagnosis codes, pharmacy billing data, and clinical transaction classification codes. Mixed-effects logistic regression was used to identify patient- and hospital-level factors associated with receipt of glucocorticoids and biologics. In total, 534 children with new-onset systemic JIA hospitalized during the study period met inclusion criteria. Twenty-nine percent received biologics, and 58% received glucocorticoids. Biologic use increased over time (P < 0.001), methotrexate use decreased (P < 0.01), and glucocorticoid use remained unchanged. Biologics and glucocorticoid use varied significantly between hospitals. High annual hospital volume, intensive care unit stay, and later discharge year were significantly associated with biologic exposure. Medium-high and high annual hospital volume were significantly associated with less glucocorticoid exposure. Despite increasing evidence demonstrating improved outcomes with first-line treatment with biologics, we found significant treatment variation across hospitals with many children not receiving biologics and a persistent high rate of glucocorticoid exposure. These results underscore the need for comparative efficacy studies and improved treatment standardization.


Macrolide-resistant Mycoplasma pneumoniae in humans, Ontario, Canada, 2010-2011.
Antimicrobial drug resistance rates for Mycoplasma pneumoniae was determined in clinical specimens and isolates obtained during 2011-2012 in Ontario, Canada. Of 91 M. pneumoniae drug-resistant specimens, 11 (12.1%) carried nucleotide mutations associated with macrolide resistance in the 23S rRNA gene. None of the M. pneumoniae specimens were resistant to fluoroquinolones or tetracyclines.


Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells.
Human cervical cancer is the fourth most common malignancy among women worldwide, and it is expected to result in 460,000 deaths per year by 2040. Moreover, patients with cervical cancer often display drug resistance and severe side effects; therefore, the development of effective novel chemotherapeutic agents is important. In the present study, the effects of metformin, a first‑line therapeutic drug for type 2 diabetes mellitus, were evaluated in cervical cancer. Compared with the control group, metformin significantly inhibited cell viability and migration, and induced apoptosis and cell cycle arrest in human cervical cancer cell lines (CaSki and HeLa). Following metformin treatment, the protein expression levels of p‑AMP‑activated protein kinase (p‑AMPK), which promotes cell death, and the tumor suppressor protein p‑p53 were remarkably upregulated in CaSki and C33A cells compared with the control group. Furthermore, compared with the control group, metformin significantly suppressed the PI3K/AKT signaling pathway in CaSki, C33A and HeLa cells. Compound C (an AMPK inhibitor) significantly reversed the effects of metformin on CaSki, C33A and HeLa cell viability, and AMPK and p53 phosphorylation. The results of the present study suggested that metformin induced AMPK‑mediated apoptosis, thus metformin may serve as a chemotherapeutic agent for human cervical cancer.


A polymeric device for delivery of anti-microbial and anti-fungal drugs in the oral environment: effect of temperature and medium on the rate of drug release.
The use of drug delivery systems in dentistry is a relatively new area of research with the exception of fluoride ion release from polyalkenoate cements and their predecessor silicate cements. The present study is based on the use of a bio-compatible material ethylene vinyl acetate copolymer (EVA) that enables constant release of drugs of therapeutic levels over extended periods of time at doses suitable for the treatment of oral conditions. Polymer casting solutions were made by dissolving EVA and the drug in the ratio of 40:1 in 70 ml of dichloromethane at 38 degrees C for 6 h. Thin square films of 3 x 3 cm2 with a thickness of 1 mm were cut from the dry sheet obtained by solvent evaporation technique. Drug loaded samples were extracted for a minimum of 14 days in 10 ml medium (double distilled water or water/ethanol (4:1)) which was replaced daily. Spectral measurements were made to follow changes in optical densities (OD) during release kinetics. Effect of temperature (24 and 37 degrees C) on the rate of drug release was studied and the energies of activation (DeltaE not equal ) were calculated using Arrehenius equation for the diffusion (translocation) of molecules of tetracycline hydrochloride (TTH), doxycycline hydrochloride (DOH), and chlorhexidine diacetate (CDA) in water as extracting medium. Effect of extracting medium (water and water/ethanol (4:1)) was also investigated on the rate of drug release measurements at 24 degrees C. Analysis of variance of the data revealed that significantly enhanced rates were observed at the higher temperature (37 degrees C) and when extracting medium was changed to water/ethanol (4:1) for TTH, DOH and CDA (p<0.0015). The enhanced rate values seem to be due to the formation of channels in the polymer. The largest activation energy (21.83 kcal mol(-1)) observed for CDA was interpreted as due to the highest average molecular weight (626) compared to TTH (481) and DOH (481).Significance. These in vitro rate of drug release measurements will provide a basis for establishing a novel approach (treatment modality) for sustained intra-oral drug delivery over extended time periods using laboratory methods and materials that are readily available to dentists.


Insights into nucleic acid-based self-assembling nanocarriers for targeted drug delivery and controlled drug release.
Over the past few decades, rapid advances of nucleic acid nanotechnology always drive the development of nanoassemblies with programmable design, powerful functionality, excellent biocompatibility and outstanding biosafety. Nowadays, nucleic acid-based self-assembling nanocarriers (NASNs) play an increasingly greater role in the research and development in biomedical studies, particularly in drug delivery, release and targeting. In this review, NASNs are systematically summarized the strategies cooperated with their broad applications in drug delivery. We first discuss the self-assembling methods of nanocarriers comprised of DNA, RNA and composite materials, and summarize various categories of targeting media, including aptamers, small molecule ligands and proteins. Furthermore, drug release strategies by smart-responding multiple kinds of stimuli are explained, and various applications of NASNs in drug delivery are discussed, including protein drugs, nucleic acid drugs, small molecule drugs and nanodrugs. Lastly, we propose limitations and potential of NASNs in the future development, and expect that NASNs enable facilitate the development of new-generation drug vectors to assist in solving the growing demands on disease diagnosis and therapy or other biomedicine-related applications in the real world.


Perichondrial arthroplasty in the hand: a case report.
A two-stage arthroplasty technique was used to treat an isolated fibrous ankylosis that developed in the index metacarpophalangeal joint of a 14-year-old boy after a rattlesnake bite. The first stage consisted of a minimal joint resection combined with rib perichondrial grafts to resurface the joint. The second stage, performed 5 months later, consisted of a capsulotomy and removal of a silicone membrane left within the joint to separate the grafts. Biopsy of the joint surfaces revealed the presence of hyaline-like cartilage. Nearly normal pain-free motion was restored. Follow-up now exceeds 30 months.


Multidisciplinary Care Pathway Improves Outcomes in Geriatric Trauma Patients.
According to this study: Implementation of a multidisciplinary geriatric clinical pathway for people who have traumatic injury led to substantial improvement in delirium and other clinical outcomes.


A putative GTP binding protein homologous to interferon-inducible Mx proteins performs an essential function in yeast protein sorting.
Members of the Mx protein family promote interferon-inducible resistance to viral infection in mammals and act by unknown mechanisms. We identified an Mx-like protein in yeast and present genetic evidence for its cellular function. This protein, the VPS1 product, is essential for vacuolar protein sorting, normal organization of intracellular membranes, and growth at high temperature, implying that Mx-like proteins are engaged in fundamental cellular processes in eukaryotes. Vps1p contains a tripartite GTP binding motif, which suggests that binding to GTP is essential to its role in protein sorting. Vps1p-specific antibody labels punctate cytoplasmic structures that condense to larger structures in a Golgi-accumulating sec7 mutant; thus, Vps1p may associate with an intermediate organelle of the secretory pathway.


Novel method utilizing microbial treatment for cleaner production of diosgenin from Dioscorea zingiberensis C.H. Wright (DZW).
A novel method utilizing microbial treatment for cleaner production of diosgenin from Dioscorea zingiberensis C.H. Wright (DZW) was presented. A new Bacillus pumilus HR19, which has the great ability to secrete pectinase, was screened and applied in the microbial treatment. Low-pressure steam expansion pretreatment (LSEP) was employed in advance to assist microbial treatment efficiently in releasing saponins, which are the precursors of diosgenin. Compared with the traditional process of acid hydrolysis, this novel process reduced the consumptions of water, acid and organic solvent by more than 92.5%, 97.0%, 97.0%, respectively, while simultaneously increasing the diosgenin yield by 6.21%. In addition, the microbial treatment was more efficient than enzymatic treatment, which arised from that microorganisms could be induced to secrete related enzymes by the compositions of DZW and relieve product inhibition by utilizing enzyme hydrolysates.


Detection of contagious ovine ecthyma (orf) and risk factors for infection in small ruminants in Iran.
The primary cause of contagious ecthyma is the orf virus, the parapoxvirus prototype. It is a viral problem observed in goat and sheep flocks in Iran, causing economic loss. Orf is a zoonosis with little epidemiological investigation present in Iran. The current research aims at determining the status of this virus, and a PCR was used as a confirmatory instrument. We sampled 668 goats and sheep and various breeding systems. Besides, the orf prevalence was studied, and vaccination efficacy was determined. Moreover, the potential risk factors surveyed for infection with ecthyma were identified. Samples were taken from goat and sheep flocks in the present cross-sectional research, and PCR was used for testing orf DNA. A checklist including animals' general information was completed. Data were analyzed using univariate tests (chi-square and t-tests) and multivariable binary logistic regression analysis. Three hundred one (45%) goats and sheep detected orf DNA. The age of 70% of positive cases was below one month. Ecthyma infection was significantly higher in imported breeds (87.3%) than indigenous (39.3%). Ninety-six percent of infected goats and sheep in the present work were not vaccinated against ecthyma. The high prevalence of the orf virus was confirmed among goat and sheep flocks in Iran. It is necessary to train ranchers regarding sanitary actions, quarantine, and application of orf vaccination plans.


Bloodless surgery of acute type A aortic dissection in a Jehovah's Witness patient.
We report successful surgery for acute type A aortic dissection in a Jehovah's Witness patient without the use of any transfusion of allogeneic blood or blood products. We combined the normothermic cross-clamping technique with a blood conservation strategy.


[An automated procedure for the determination of the malignancy of tumorous tissue changes].
The accuracy of the "Histomat", an apparatus for automated histophotometric determination of malignant or benign tissues, was used on samples from 235 breast tumours (94 malignant and 141 benign tumours). Analysis of the measured data, using the schema developed by the manufacturer (Hytec), showed that in tumours of the breast this type of histophotometric analysis cannot distinguish between benign and malignant tissue changes. Its diagnostic use is therefore not justified.


Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study.
The effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population. A total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06-0.45). The association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.


BRL 13776: a novel antihypertensive agent with interesting monoamine depleting properties.
1. Oral doses of 10-100 mg/kg of BRL 13776 lowered the blood pressure of both deoxycorticosterone acetate (DOCA)/NaCl-treated hypertensive rats and untreated normotensive rats. 2. BRL 13776 (100 mg/kg, orally) also reduced the blood pressure of renal hypertensive cats (cellophane perinephritis model). 3. No tolerance developed to the blood-pressure lowering action of BRL 13776 when an oral daily dose of 100 mg/kg was administered repeatedly for up to 15 days to hypertensive rats and cats. 4. The fall in blood pressure to BRL 13776 in rats was associated with a reduction of tissue catecholamines. 5. The catecholamine depletion occurred in all the peripheral tissues examined but in the brain was restricted to certain regions, these being the hind-brain on single dosing and the hind-brain, hypothalamus and mid-brain on repeated dosing. Catecholamine levels in the cerebral hemispheres were not affected by either single or repeated doses of BRL 13776. 6. BRL 13776 caused some reduction of the 5-hydroxytryptamine content of the heart but not of whole brain or any brain region. 7. Neither single doses (up to 900 mg/kg orally) nor repeated doses (100-300 mg/kg orally) of BRL 13776 produced any significant behavioural effects in animals. 8. BRL 13776 is a new type of agent to display both antihypertensive and monoamine-depleting properties. The reduction of noradrenaline in certain brain regions may be a cause of the antihypertensive response but depletion in the periphery could contribute in a major or minor way. The differential action on noradrenaline in the brain together with the lack of effect on 5-hydroxytryptamine might also explain the apparent absence of behavioural effects.


Chromosome engineering allows the efficient isolation of vertebrate neocentromeres.
Centromeres are specified by sequence-independent epigenetic mechanisms in most organisms. Rarely, centromere repositioning results in neocentromere formation at ectopic sites. However, the mechanisms governing how and where neocentromeres form are unknown. Here, we established a chromosome-engineering system in chicken DT40 cells that allowed us to efficiently isolate neocentromere-containing chromosomes. Neocentromeres appear to be structurally and functionally equivalent to native centromeres. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis with 18 neocentromeres revealed that the centromere-specific histone H3 variant CENP-A occupies an ∼40 kb region at each neocentromere, which has no preference for specific DNA sequence motifs. Furthermore, we found that neocentromeres were not associated with histone modifications H3K9me3, H3K4me2, and H3K36me3 or with early replication timing. Importantly, low but significant levels of CENP-A are detected around endogenous centromeres, which are capable of seeding neocentromere assembly if the centromere core is removed. In summary, our experimental system provides valuable insights for understanding how neocentromeres form.


Discovery of novel feruloyl esterase activity of BioH in Escherichia coli BL21(DE3).
To characterize a novel feruloyl esterase from Escherichia coli BL21 DE3. The gene encoding BioH was cloned and overexpressed in E. coli. The protein was purified and its catalytic activity was assessed. BioH exhibited feruloyl esterase activity toward a broad range of substrates, and the corresponding kinetic constants for the methyl ferulate, ethyl ferulate, and methyl p-coumarate substrates were: K m values of 0.48, 6.3, and 1.9 mM, respectively, and k cat /K m values of 9.3, 3.8, and 3.8 mM(-1) s(-1), respectively. Feruloyl esterase from E. coli was expressed for the first time. BioH was confirmed to be a feruloyl esterase.


First Molecular Confirmed Outbreak of Malignant Ovine Theileriosis in Sheep from North India.
Malignant ovine theileriosis is a tick-borne disease of sheep and goats, caused by protozoan Theileria lestoquardi. The disease has serious economic implications for small ruminant production around the world. An outbreak of malignant ovine theileriosis in a sheep flock was investigated from Hisar district of Haryana, India, in March 2022. The etiological agent was identified using polymerase chain reaction assay with genus specific primers targeting 18S rRNA gene and subsequently confirmed by sequencing. The morbidity, mortality and case fatality rate reported in the outbreak were 22.2, 18.8 and 85%, respectively. The phylogenetic analysis clustered the present study T. lestoquardi isolate in the same clade with T. lestoquardi from Iraq, Iran and Pakistan with maximum nucleotide identity of 99.37% with strains from Iraq. The tick vector Hyalomma anatolicum recovered from dead animals was implicated in the disease's transmission. Malignant ovine theileriosis resulted in high case fatality rate. This study presents the first molecularly confirmed outbreak of malignant ovine theileriosis outbreak in the North Indian region, with characteristic post-mortem findings.


Induction of preterm labor in the rat by antiprogesterone.
The validity of a new concept, predicting that preterm labor can be induced without oxytocic stimulation by a regulatory imbalance, generated by antiprogesterone (A-P)-provoked P withdrawal (Pw), has been examined in the rat model. At day 19 of pregnancy a single oral dose of the steroidal A-O isoxazol, which inhibits P synthesis, significantly reduced uterine P levels, increased uterine estradiol and prostaglandin F levels, and induced preterm labor. This precocious regulatory imbalance and preterm labor were prevented, by blocking the A-P-induced Pw with P treatment. The regulatory imbalance which triggered the onset of spontaneous labor in the control animals was similar, but it occurred at term rather than before term. The potential of this method in improving the management of medically indicated induction of preterm labor is discussed.


Synthetic studies on the mycolactone core.
Two approaches are presented for the synthesis of the macrolide core of the mycolactone polyketides. The first intertwines ring closing metathesis (RCM) within a two-step Julia olefination protocol, while the second intercepts the optimized routes of Kishi, thereby providing formal access to the mycolactones.


Altered interleukin-2 (IL-2) production and responsiveness after hyposensitization to house dust.
Interleukin-2 (IL-2 or T cell growth factor, TCGF) is a lymphokine absolutely required for clonal expansion of activated T-lymphocytes with specific cytotoxic, helper, and suppressor functions. The capability of production of and responsiveness to IL-2 in 15 normal children, 28 newly diagnosed, and 22 hyposensitized (greater than 1 yr) children with asthma was studied. The results demonstrated (1) The lymphocytes from newly diagnosed patients produced a much greater amount of IL-2 when they were stimulated with specific allergen (house dust) but not with phytohemagglutinin (PHA) than did those from both hyposensitized patients and normal subjects. (2) The responsiveness to IL-2 of activated lymphocytes from hyposensitized patients was much more vigorous than those from both new patients and normal subjects, whether the responder lymphocytes were pretreated with PHA or house dust. Thus, hyposensitization is able to modulate the immunobiologic functions of T cells with respect to production of and responsiveness to IL-2, and such alterations may contribute to the immunologic changes occurring in patients receiving long-term hyposensitization.


Comparative assessment for hyperaccumulatory and phytoremediation capability of three wild weeds.
The composition and the organization of soil are changing rapidly by the diverged mankind activities, leading to the contamination of environment. Several methods are employed to clean up the environment from these kinds of contaminants, but most of them are costly and ineffective to yield optimum results. Phytoremediation is a natural green technology, which is eco-friendly for the removal of toxic metals from the polluted environment. Phytoremediation is a cost-effective technique through which the cleanup of contaminated soil laced with heavy metals is performed by wild weeds and small herbal plants. The phytoremediation technique provides a promising tool for hyperaccumulation of heavy metals; arsenic, lead, mercury, copper, chromium, and nickel, etc., by the wild weeds and that has been discussed here in detail in case of Cannabissativa, Solanum nigrum and Rorippa globosa. In general, weeds that have the intrinsic capacity to accumulate metals into their shoots and roots, have the ability to form phytochelates and formation of stable compound with ions. This behavior of accumulation along with chelate and stable compound formation is utilized as a tool for phytoremediation activity.


Effects of early standardized management on the growth trajectory of offspring with gestational diabetes mellitus at 0-5 years old: a preliminary longitudinal study.
To explore the application value of early standardized management in the delivery of neonates of pregnant women with gestational diabetes mellitus (GDM). Parturient diagnosed with GDM and their offspring were selected in our hospital from January 1, 2015 to December 31, 2017 to underwent early standardized management. Non-GDM pregnant women and their offspring were selected as the control group. The growth and development of children aged 0-5 years in the two groups were longitudinally followed up, and the mixed linear model was used to evaluate and compare the growth trajectories. There was no significant difference in height and weight between the two groups at 1 year old (P > 0.05), but the BMI of the GDM group was significantly higher than that in the control group. After 1 year of age, both groups of offspring were similar in height, weight, and BMI, and these similarities persisted at 2, 3, 4, and 5 years of age. After controlling for covariates, the weight, length/height of the two groups of children were slightly different in the growth trajectories between 0-1 years old, 1-2 years old, 2-3 years old, 3-4 years old, and 4-5 years old with no statistical significance (P > 0.05). Although growth differences between the two groups of children were detected within 1 year of age, there were no significant differences in growth trajectories from 1 to 5 years between two groups, which proved that early standardized management has positive significance.


Iatrogenic Atrial Septal Defects Following Transcatheter Mitral Valve Repair and Implications of Interventional Closure.
The authors investigated whether iatrogenic atrial septal defect (iASD) closure post-transcatheter mitral valve edge-to-edge repair (TMVR) is superior to conservative therapy (CT) and whether outcomes (death/heart failure [HF] hospitalization) differ between patients with and without an iASD post-TMVR. Transseptal access for TMVR can create an iASD, which is associated with impaired outcomes. Controversially, the creation of an iASD in HF has been linked to improved hemodynamics. 80 patients with an iASD and relevant left-to-right shunting (Qp:Qs ≥1.3) 30 days following TMVR were randomized to CT or interventional closure of the iASD (MITHRAS [Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair] cohort), and 235 patients without an iASD served as a comparative cohort. All patients of the MITHRAS cohort (mean age 77 ± 9 years, 39% women) received their allocated treatment, and follow-up was completed for all MITHRAS and comparative cohort (mean age 77 ± 8 years, 47% women) patients. Twelve months post-TMVR, there was no significant difference in the combined endpoint of death or HF hospitalization within the MITHRAS cohort (iASD closure: 35% vs CT 50%; P = 0.26). The combined endpoint was more frequent among patients within the MITHRAS cohort as opposed to the comparative cohort (43% vs 17%; P < 0.0001), primarily driven by a higher rate of HF hospitalization (34% vs 8%; P = 0.004). In this randomized controlled trial, interventional closure of a relevant iASD 1 month after TMVR did not result in improved clinical outcomes at 12 months post-TMVR. Patients with an iASD are at higher risk for HF hospitalization independent of iASD management and warrant close follow-up. (Closure of Iatrogenic Atrial Septal Defect Following Transcatheter Mitral Valve Repair [MITHRAS]; NCT03024268).


Comparative performance of head ultrasound and MRI in detecting preterm brain injury and predicting outcomes: A systematic review.
To systematically review the literature to compare the performance of head ultrasound (HUS) and magnetic resonance imaging (MRI) in their ability to detect brain injury and their predictive value for neurodevelopmental outcomes. This was a systematic review based on literature search in three electronic databases (MEDLINE, EMBASE, Cochrane Library) and additional sources for studies on routine brain injury screening in preterm neonates published during 2000-May 2020. Studies were included if they reported on the comparative performance of HUS and MRI in detecting preterm brain injury and/or their predictive value for neurodevelopmental outcomes. Findings from the included studies underwent narrative synthesis. Forty-six studies were included. In comparison with HUS, MRI detected more anomalies and provided more details on the severity and the extent of preterm brain injury, particularly for white matter injury and cerebellar haemorrhage. Neonatal neuroimaging predicted outcomes with high negative predictive value but relatively low positive predictive value. The prognostic value of neonatal neuroimaging varied according to several factors including modality and timing of imaging, and tools used for grading brain injury. Compared with HUS, MRI offers a better characterisation of preterm brain injury and may enhance the ability to predict neurodevelopmental outcomes.


Partial characterization of a unique growth factor secreted by human Sertoli cells.
Human Sertoli cells were grown in a serum-free environment, and the Sertoli cell conditioned medium (hSCCM) was tested for mitogenic activity. The presence of a potent growth factor(s), termed Sertoli cell secreted growth factor (SCSGF), in hSCCM was confirmed and supports previous observations based on experiments using rat SCCM. Mitogenicity of hSCSGF was demonstrated in cell proliferation assays with the A431 (human epidermoid carcinoma) cell line and in [methyl-3H]-thymidine incorporation (DNA synthesis) assays with the Swiss 3T3 (mouse embryo fibroblast) cell line. In a dose-dependent manner, hSCSGF stimulated A431 cell growth up to 4-fold over control values (P less than 0.0001) and stimulated thymidine incorporation up to 4.5-fold over control values (P less than 0.0002). Importantly, SCSGF stimulated A431 proliferation 2-fold over control values (P less than 0.0002) in the presence of 5% serum. With the exception of rat SCSGF, human SCSGF is the only growth factor known to stimulate A431 cells. SCSGF also demonstrated epidermal growth factor (EGF)-like activity based upon displacement of EGF from its receptor in a radioreceptor assay. However, SCSGF is not EGF since it is a potent stimulator of A431 cells, whereas EGF is inhibitory. The growth factor was stable to heat, freeze-thaw, acid (pH 3), and trypsin treatment. Furthermore, it did not bind heparin agarose and is thus distinct from the endothelial cell growth factor family. High-pressure liquid chromatography on size exclusion (TSK G2000 SW) columns revealed an approximate size of 8000 daltons. Human SCSGF is a unique growth factor and may play a key role in the regulation of normal spermatogenesis.


Quantitative analysis of retinal and choroid capillary ischaemia using optical coherence tomography angiography in type 2 diabetes.
To perform a quantitative analysis of retinal and choroid capillary ischaemia in diabetic patients by using optical coherence tomography angiography (OCTA). A total of 97 type 2 diabetic patients and 48 controls were included in this cross-sectional study. Diabetic patients without diabetic retinopathy (DR) were categorized as no DR (NDR) group; DR was classified into mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR and proliferative diabetic retinopathy (PDR). Quantitative parameters included foveal and parafoveal vascular density (VD) in superficial, deep and choroid capillary plexus (SCP, DCP and CCP), and foveal flow area in CCP. Stepwise comparisons between groups were performed in the adjacent stages. Diabetic patients had significantly lower flow area in CCP and VD in all three layers compared with controls. In NDR group, foveal flow area in CCP significantly decreased compared with controls. In mild NPDR, parafoveal VD significantly decreased in all three layers compared with NDR, especially in temporal and nasal areas. In moderate NPDR, VD reduction extended to the inferior area in SCP and DCP compared with mild NPDR. In severe NPDR, progressive losses of VD were presented in all layers compared with moderate NDPR. In PDR, the superior VD in SCP significantly increased compared with severe NPDR. In diabetic patients, the microvascular ischaemia originated in choroid layer and extended inward affecting the deep and superficial layer. OCTA can serve as a reliable method for early detection and to monitor progressions in diabetic retinopathy.


Obtaining a Proportional Allocation by Deleting Items.
We consider the following control problem on fair allocation of indivisible goods. Given a set I of items and a set of agents, each having strict linear preferences over the items, we ask for a minimum subset of the items whose deletion guarantees the existence of a proportional allocation in the remaining instance; we call this problem Proportionality by Item Deletion (PID). Our main result is a polynomial-time algorithm that solves PID for three agents. By contrast, we prove that PID is computationally intractable when the number of agents is unbounded, even if the number k of item deletions allowed is small-we show that the problem is W [ 3 ] -hard with respect to the parameter k. Additionally, we provide some tight lower and upper bounds on the complexity of PID when regarded as a function of |I| and k. Considering the possibilities for approximation, we prove a strong inapproximability result for PID. Finally, we also study a variant of the problem where we are given an allocation π in advance as part of the input, and our aim is to delete a minimum number of items such that π is proportional in the remainder; this variant turns out to be N P -hard for six agents, but polynomial-time solvable for two agents, and we show that it is W [ 2 ] -hard when parameterized by the number k of.


An individual with gastric schwannoma with pathologically malignant potential surviving two years after laparoscopy-assisted partial gastrectomy.
Schwannomas are a kind of neurogenic tumor. They are generally benign and originate primarily from the central and peripheral nerve. They rarely develop in the gastrointestinal tract: gastric schwannomas make up 0.2% of gastric neoplasms. A malignant gastric schwannoma is a comparatively rare tumor, a few cases have been reported until now. We present the case of a 34-year-old male patient diagnosed during medical examination. The patient was treated with surgical resection, and 2 years passed without recurrence.


Adherence with an Acute Agitation Algorithm and Subsequent Restraint Use.
Timely use of pharmacological interventions to treat acute agitation has the potential to decrease physical restraint use. The aim of this study is to determine if adherence to standardized pharmacological recommendations for the treatment of acutely agitated pediatric patients decreases physical restraint use. Additionally, this study aims to identify predictors of physical restraint use and describe treatment related adverse events. This is a retrospective chart review of patient visits between September 1, 2016 and August 31, 2017. Patient visits were included if the patient presented to the pediatric emergency department, met ICD-10 codes, and received pharmacologic management or physical restraint to treat acute agitation. The differences in rate of physical restraint was assessed between patients treated according to the standardized pharmacological recommendations and patients who were not. 447 patients were included with a mean age of 13 years. No significant difference in physical restraint use was found when standardized pharmacological recommendations were followed compared to when they were not (P = 0.16). Only presentation on day shift when compared to evening shift resulted in increased odds of being restrained (OR 2.03; 95% CI 1.18, 3.50). Nine adverse events possibly related to medications were identified with none considered to be of significant clinical concern. Standardized pharmacological treatment recommendations was not associated with a decrease in physical restraint use for agitated patients presenting to the pediatric emergency department. The pharmacologic strategies utilized were generally safe and well tolerated in this patient population.


Use of a removable endobronchial valve for the treatment of bronchopleural fistula.
We report the case of a patient with a prolonged bronchopleural fistula and empyema that were successfully treated by the placement of a removable, unidirectional endobronchial valve. This is the first report of the use of such a device for this indication.


A practical guide to handling competing events in etiologic time-to-event studies.
Competing events are events that preclude the occurrence of the primary outcome. Much has been written on mainly the statistics behind competing events analyses. However, many of these publications and tutorials have a strong statistical tone and might fall short in providing a practical guide to clinician researchers as to when to use a competing event analysis and more importantly which method to use and why. Here we discuss the different target effects in the Fine-Gray and cause-specific methods using simple causal diagrams and provide strengths and limitations of both approaches for addressing etiologic questions. We argue why the Fine-Gray method might not be the best approach for handling competing events in etiological time-to-event studies.


Current practice and barriers in the implementation of ultrasound-based assessment of muscle mass in Japan: A nationwide, web-based cross-sectional study.
Muscle mass is an important factor for surviving an illness. Ultrasound has gained increased attention as a muscle mass assessment method because of its noninvasiveness and portability. However, data on the frequency of ultrasound-based muscle mass assessment are limited, and there are some barriers to its implementation. Hence, a web-based cross-sectional survey was conducted on healthcare providers in Japan, which comprised four parts: 1) participant characteristics; 2) general muscle mass assessment; 3) ultrasound-based muscle mass assessment; and 4) the necessity of, interest in, and barriers to its implementation. Necessity and interest were assessed using an 11-point Likert scale, whereas barriers were assessed using a 5-point Likert scale, in which "Strongly agree" and "Agree" were counted for the analysis. Of the 1,058 responders, 1,026 participants, comprising 282 physicians, 489 physical therapists, 84 occupational therapists, 120 nurses, and 51 dieticians, were included in the analysis. In total, 93% of the participants were familiar with general muscle mass assessment, and 64% had conducted it. Ultrasound-based muscle mass assessment was performed by 21% of the participants. Necessity and interest scored 7 (6-8) and 8 (7-10), respectively for ultrasound-based muscle mass assessment. The barriers to its implementation included lack of relevant education (84%), limited staff (61%), and absence of fixed protocol (61%). Regardless of the necessity of and interest in ultrasound-based muscle mass assessment, it was only conducted by one-fifth of the healthcare providers, and the most important barrier to its implementation was lack of education.


Retinopretectal and accessory optic projections of normal mice and the OKN-defective mutant mice beige, beige-J, and pearl.
Retinal projections to the pretectal and terminal accessory optic nuclei were studied in normal wild-type mice and mutant mice with abnormal optokinetic nystagmus (OKN, Mangini, Vanable, Williams, and Pinto: J. Comp. Neurol. 241:191-209, '85). The mutants used were pearl, which exhibits an inverted OKN in response to stimulation of only the temporal retina, and beige and beige-J, which show inverted OKN in response to stimulation of only the temporal retina and, in addition, exhibit eye movements with a vertical component in response to horizontally moving, full-field stimuli. These projections were studied following intraocular injections of 3H-proline or horseradish peroxidase (HRP) with, respectively, light microscopic autoradiography or HRP histochemistry. In wild-type mice, strong contralateral retinal projections covered the entire nucleus of the optic tract, the anterior and posterior divisions of the olivary pretectal nucleus, and the posterior pretectal nucleus. Similar heavy contralateral projections were distributed over the dorsal and medial terminal nuclei of the accessory optic system. Also, terminals sparsely covered the entire neuropil of the contralateral lateral terminal nucleus in some but not all wild-type mice. The most prominent accessory optic input was to the medial terminal nucleus and was provided by the inferior fasciculus of the accessory optic tract. A typical mammalian superior fasciculus of the accessory optic system with anterior, middle, and posterior components was present. Ipsilateral label was found in anterior and posterior olivary pretectal nuclei in all of the wild-type animals, but was found inconsistently in the ipsilateral terminal accessory optic nuclei. The pattern of contralateral retinal projection to the nucleus of the optic tract and posterior pretectal nucleus in mutants was indistinguishable from that seen in the normal wild-type mice. However, retinal inputs to the ipsilateral anterior and posterior olivary pretectal nuclei were significantly reduced in pearl mutants and were exceedingly sparse in the beige and beige-J mutant mice, while the contralateral inputs to these nuclei were increased in a complementary fashion in the mutants. The labeling of the accessory optic input to the contralateral dorsal terminal nucleus appeared to be substantially reduced in all of the mutant mice. The size of the principal accessory optic fascicle, the inferior fasciculus, was significantly smaller in beige, beige-J, and pearl mice; this reduction was greater in the beige and beige-J than in the pearl mice.(ABSTRACT TRUNCATED AT 400 WORDS)


Carboxymethyl cellulose-hydrogel embedded with modified magnetite nanoparticles and porous carbon: Effective environmental adsorbent.
Adsorption is the most efficient technique for the removal of metal ions and organic dyes from water. This stimulates demand for the preparation of eco-friendly adsorbents. In this study, magnetic hydrogels based on a crosslinked carboxymethyl cellulose grafted acrylamide (CMC-g-AM) embedded with porous carbon (PC) and citric acid-modified magnetite were prepared. PC was synthesized via single-step oxidation of bagasse under muffled atmosphere condition. The magnetite (Fe3O4) nanoparticles were synthesized using the co-precipitation method (Fe2+/Fe3+) and citric acid modification (CFe). Functionality and parameters of adsorbent were characterized by infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray. The magnetic hydrogels have a highly effective performance for Pb-ions and methylene blue dye (MB) removal from water due to the unique role of crosslinked CMC matrix in supporting synergy between embedded PC and CFe. Adsorption testing using time intervals (5-120 min) and Pb-ions and MB concentrations (5-500 mg/L) indicate that CMC-g-AM containing equal content of PC and CFe has substantially higher removal efficiency; 70.8 and 96.1 % against 47.8 and 30.2 % (without PC and CFe) for Pb-ions and MB adsorption respectively for CMC-g-AM. The equilibrium time and the maximum sorption capacity (qm) from the adsorption studies were found to be 60 and 30 min and 294.1 and 222.2 mg/g for Pb-ions and MB respectively. The kinetics and isotherms were studied to highlight the adsorption rate and mechanism of the adsorption process.


Improving rapid response systems: progress, issues, and future directions.
"Detect the emergency and respond to it right at the patient's bedside" sums up the focus of the recent Third International Conference on Rapid Response Systems.


A short guide for molecular dynamics simulations of RNA systems.
As a result of important methodological advances and of the rapid growth of experimental data, the number of molecular dynamics (MD) simulations related to RNA systems has significantly increased. However, such MD simulations are not straightforward and great care has to be exerted during the setup stage in order to choose the appropriate MD package, force fields and ionic conditions. Furthermore, the choice and a correct evaluation of the main characteristics of the starting structure are primordial for the generation of informative and reliable MD trajectories since experimental structures are not void of inaccuracies and errors. The aim of this review is to provide, through numerous examples, practical guidelines for the setup of MD simulations, the choice of ionic conditions and the detection and correction of experimental inaccuracies in order to start MD simulations of nucleic acid systems under the best auspices.


Localization of central noradrenergic mechanisms in cardiovascular regulation in rats.
1. Various drugs were injected stereotactically into the brain of anaesthetized rats. 2. Noradrenaline injected into the area of the nucleus of the tractus solitarius in the lower brain stem or into the far anterior hypothalamus/pre-optic region induced a fall in blood pressure and heart rate related to the administered dose. 3. When injected into the anterior hypothalamus/pre-optic region, clonidine and alpha-methylnoradrenaline induced a long-lasting decrease in blood pressure and heart rate.


[Role of grafts in the treatment of resistant ulcers].
Despite a correction as complete as possible of the venous stasis, certain ulcers prove resistant to treatment. In these cases, grafts, whose active mechanism is still not well known in many respects, can turn out to be effective.


Anticipating, measuring, and minimizing MEMS mirror scan error to improve laser scanning microscopy's speed and accuracy.
We describe a method to speed up microelectromechanical system (MEMS) mirror scanning by > 20x, while also improving scan accuracy. We use Landweber deconvolution to determine an input voltage which would produce a desired output, based on the measured MEMS impulse response. Since the MEMS is weakly nonlinear, the observed behavior deviates from expectations, and we iteratively improve our input to minimize this deviation. This allows customizable MEMS angle vs. time with <1% deviation from the desired scan pattern. We demonstrate our technique by optimizing a point scanning microscope's raster patterns to image mammal submandibular gland and pollen at ~10 frames/s.


Comparison of minute distribution frequency for anesthesia start and end times from an anesthesia information management system and paper records.
Use of an anesthesia information management system (AIMS) has been reported to improve accuracy of recorded information. We tested the hypothesis that analyzing the distribution of times charted on paper and computerized records could reveal possible rounding errors, and that this effect could be modulated by differences in the user interface for documenting certain event times with an AIMS. We compared the frequency distribution of start and end times for anesthesia cases completed with paper records and an AIMS. Paper anesthesia records had significantly more times ending with "0" and "5" compared to those from the AIMS (p < 0.001). For case start times, AIMS still exhibited end-digit preference, with times whose last digits had significantly higher frequencies of "0" and "5" than other integers. This effect, however, was attenuated compared to that for paper anesthesia records. For case end times, the distribution of minutes recorded with AIMS was almost evenly distributed, unlike those from paper records that still showed significant end-digit preference. The accuracy of anesthesia case start times and case end times, as inferred by statistical analysis of the distribution of the times, is enhanced with the use of an AIMS. Furthermore, the differences in AIMS user interface for documenting case start and case end times likely affects the degree of end-digit preference, and likely accuracy, of those times.


The β-lactam clavulanic acid mediates glutamate transport-sensitive pain relief in a rat model of neuropathic pain.
Following nerve injury, down-regulation of astroglial glutamate transporters (GluTs) with subsequent extracellular glutamate accumulation is a key factor contributing to hyperexcitability within the spinal dorsal horn. Some β-lactam antibiotics can up-regulate GluTs, one of which, ceftriaxone, displays analgesic effects in rodent chronic pain models. Here, the antinociceptive actions of another β-lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)-induced neuropathic pain. In addition, the protein expression of glutamate transporter-1 (GLT1), its splice variant GLT1b and glutamate-aspartate transporter (GLAST) was measured in the spinal cord of CCI rats. Finally, protein expression of the same GluTs was evaluated in cultured astrocytes obtained from rodents and humans. Repeated injection of ceftriaxone or clavulanic acid over 10 days alleviated CCI-induced mechanical hypersensitivity, whilst clavulanic acid was additionally able to affect the thermal hypersensitivity. In addition, clavulanic acid up-regulated expression of GLT1b within the spinal cord of CCI rats, whereas ceftriaxone failed to modulate expression of any GluTs in this model. However, both clavulanic acid and ceftriaxone up-regulated GLT1 expression in rat cortical and human spinal astrocyte cultures. Furthermore, clavulanic acid increased expression of GLT1b and GLAST in rat astrocytes in a dose-dependent manner. Thus, clavulanic acid up-regulates GluTs in cultured rodent- and human astroglia and alleviates CCI-induced hypersensitivity, most likely through up-regulation of GLT1b in spinal dorsal horn. Chronic dosing of clavulanic acid alleviates neuropathic pain in rats and up-regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up-regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel β-lactam-based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain.


Organizations in science and medicine must hold each other accountable for discriminatory practices.
Many organizations persist in working with others that engage in known, remediable structural discrimination. We name this practice interorganizational structural discrimination (ISD) and argue it is a pivotal contributor to inequities in science and medicine. We urge organizations to leverage their relationships and demand progress from collaborators.


Pronator quadratus repair after volar plating of distal radius fractures or not? Results of a prospective randomized trial.
The purpose of the present study was to investigate the influence of the pronator quadratus (PQ) muscle repair following volar plate fixation of distal radius fractures with special regards to the forearm pronation strength. During the early recovery period of 3 months, an improvement of pronation strength and functional scorings was hypothesized for the PQ repair when compared to no repair. The inclusion criteria were (1) men or women between 18 and 80 years, (2) isolated, closed fractures of the distal radius, (3) A2 to B2 types of fracture according to the AO fracture classification system, (4) primary volar locking plate osteosynthesis. Patients were randomized to group A = PQ repair and group B = no repair. Follow-up examinations after 6 and 12 weeks included bilateral isometric pronation strength measurement, range of motion, the QuickDASH and the Mayo-Wrist-Score, and a visual analog scale (VAS). 60 patients (n = 31 in group A and n = 29 in group B) with an average age of 54 years (range 22-77 years) returned for both follow-up visits. The pronation strength measurements showed no significant differences between groups (PQ repair vs. no repair) neither at 6 weeks nor at 12 weeks. Additionally, no statistical significant differences were noted for ROM, QuickDASH-Score or Mayo-Wrist-Score. The VAS scoring revealed a significant decreased pain level after PQ repair at 6 weeks postoperatively (p = 0.017). An improved pronation strength after PQ repair in the early rehabilitation period could not be confirmed. However, the PQ repair might reduce pain in the early postoperative period. NCT02595229 (ClinicalTrials.gov, registered 02 November 2015).