Global hypomethylation pattern in systemic sclerosis: An application for absolute quantification of epigenetic DNA modification products by 2D-UPLC-MS/MS.
Systemic sclerosis (SSc) is a rare autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Besides genetics risk factors, understanding the epigenetic modifications in SSc has been gaining acceleration in recent years. Epigenetic modifications are reversible and defined as druggable targets. In this context, it is highly important to present a systemic perspective to epigenetic modifications of SSc in terms of both pathogenesis and clinical utility. DNA samples from the whole blood specimens of the 41 SSc patients and 27 healthy controls (HCs) were obtained. Absolute quantification of 5-mC, 5-hmdC, 5-cadC, 5-fdC, and 5-hmdU as the DNA methylation and demethylation products were performed using 2D-UPLC-MS/MS. Demographic data and clinical scores were recorded in detail. 5-hmdU was significantly higher in SSc patients while 5-hmdC was lower compared to the HCs (p < 0.01, p = 0.012 respectively). 5-cadC and 5-fdC had upward trend in SSc (p = 0.064; p = 0.066). These results support that SSc patients tend to have a global hypomethylation pattern. Clinical analyzes revealed that lung, gastrointestinal, joint, and vascular involvement of SSc is also associated with increased demethylation or decreased methylation profile. We performed absolute quantification of epigenetic DNA modification products in SSc for the first time. We demonstrated an upward trend in global hypomethylation in SSc. Furthermore, as a result of detailed clinical analyzes, the relationship between lung, GIS, and vascular involvement with epigenetic changes was shown. We believe that absolute quantification of DNA methylation and demethylation products with novel technologies can provide a deep understanding of disease pathogenesis and has the potential to mark an era for developing new therapeutic strategies.


Sunlight-Coordinated High-Performance Moisture Power in Natural Conditions.
It is a challenge to spontaneously harvest multiple clean sources from the environment for upgraded energy-converting systems. The ubiquitous moisture and sunlight in nature are attractive for sustainable power generation especially. A high-performance light-coordinated "moist-electric generator" (LMEG) based on the rational combination of a polyelectrolyte and a phytochrome is herein developed. By spontaneous adsorption of gaseous water molecules and simultaneous exposure to sunlight, a piece of 1 cm2 composite film offers an open-circuit voltage of 0.92 V and a considerable short-circuit current density of up to 1.55 mA cm-2 . This record-high current density is about two orders of magnitude improvement over that of most conventional moisture-enabled systems, which is caused by moisture-induced charge separation accompanied with photoexcited carrier migration, as confirmed by a dynamic Monte Carlo device simulation. Flexible devices with customizable size are available for large-scale integration to effectively work under a wide range of relative humidity (about 20-100%), temperature (10-80 °C), and light intensity (30-200 mW cm-2 ). The wearable and portable LMEGs provide ample power supply in natural conditions for indoor and outdoor electricity-consuming systems. This work opens a novel avenue to develop sustainable power generation through collecting multiple types of natural energy by a single hybrid harvester.


Ex Situ Limb Perfusion System to Extend Vascularized Composite Tissue Allograft Survival in Swine.
Organ perfusion systems have successfully been applied in solid organ transplantations. Their use in limb transplantation and replantation has not been widely investigated. In this study, we tested the potential for ex situ perfusion system to prolong limb allograft viability in a swine forelimb amputation/replantation model. Fourteen swine were used. In group 1 (n = 4), we perfused 4 amputated limbs for 12 hours using warm (27 °C-32 °C) autologous blood. Group 2 (n = 3) served as a cold preservation control group, preserving limbs for 6 hours at 4 °C. All limbs were transplanted into healthy swine (n = 7) and observed for another 12 hours. Hemodynamic variables of circulation, as well as perfusate gases and electrolytes (pH, pCO2, pO2, O2 saturation, Na(+), K(+), Cl(-), Ca(2+), HCO3(-), glucose, lactate) were measured. Muscle samples were used to measure single-muscle fiber contractility. In the control group, no microcirculation was observed after 6 hours of cold storage. In the pump perfusion group, all limbs displayed a gradual increase in lactate levels (P < 0.05) during ex situ perfusion that returned to normal after transplantation and reperfusion (P = 0.05). The pH and potassium remained stable throughout the experiment. Single-muscle fiber contractility testing showed near normal contractility at the end of the reperfusion period (P > 0.05). Limb weight did not increase significantly between the end of pump perfusion and reperfusion (P > 0.05). We demonstrated the potential to preserve limb allograft using ex vivo circulation. This approach promises to extend the narrow time frame for revascularization of procured extremities in limb transplantation.


Wheat endonuclease WEN1 dependent on S-adenosyl-L-methionine and sensitive to DNA methylation status.
Ca(2+)-, Mg(2+)-dependent wheat endonuclease WEN1 with molecular mass of about 27 kDa was isolated from coleoptyles. Methylated DNA of lambda phage grown on E. coli dam(+), dcm(+) cells was hydrolyzed by WEN1 more effectively than DNA of phage grown on dam(-), dcm(-) cells. Two pH activity maxima (pH 6.5-7.5 and 9.0-10.5) were observed when double-stranded DNA was hydrolyzed. WEN1 is stable at elevated temperatures (65 degrees C ) and in wide range of pH values. WEN1 is activated by S-adenosyl-L-methionine, S-adenosyl-L-homocysteine and S-isobutyladenosine. It is a first case to show that higher eukaryote endonuclease discriminates between DNA of various methylation status and is modulated by S-AdoMet and its analogs.


Patient safety and sense of security when telemonitoring chronic conditions at home: the views of patients and healthcare professionals - a qualitative study.
Chronic diseases are increasing worldwide, and the complexity of disease management is putting new demands on safe healthcare. Telemonitoring technology has the potential to improve self-care management with the support of healthcare professionals for people with chronic diseases living at home. Patient safety threats related to telemonitoring and how they may affect patients' and healthcare professionals' sense of security need attention. This study aimed to explore patients' and healthcare professionals' experiences of safety and sense of security when using telemonitoring of chronic conditions at home. Semi-structured interviews were conducted with twenty patients and nine healthcare professionals (nurses and physicians), recruited from four primary healthcare centers and one medical department in a region in southern Sweden using telemonitoring service for chronic conditions in home healthcare. The main theme was that experiences of safety and a sense of security were intertwined and relied on patients´ and healthcare professionals´ mutual engagement in telemonitoring and managing symptoms together. Telemonitoring was perceived to increase symptom awareness and promote early detection of deterioration promoting patient safety. A sense of security emerged through having someone keeping track of symptoms and comprised aspects of availability, shared responsibility, technical confidence, and empowering patients in self-management. The meeting with technology changed healthcare professionals' work processes, and patients' daily routines, creating patient safety risks if combined with low health- and digital literacy and a naïve reliance on technology. Empowering patients' self-management ability and improving shared understanding of the patient's health status and symptom management were prerequisites for safe care and the patient´s sense of security. Telemonitoring chronic conditions in the homecare context can promote a sense of security when care is co-created in a mutual understanding and responsibility. Attentiveness to the patient's health literacy, symptom management, and health-related safety behavior when using eHealth technology may enlighten and mitigate latent patient safety risks. A systems approach indicates that patient safety risks related to telemonitoring are not only associated with the patient's and healthcare professionals functioning and behavior or the human-technology interaction. Mitigating patient safety risks are likely also dependent on the complex management of home health and social care service.


[Results of school inspections in the county of Karl-Marx-Stadt (author's transl)].
Within the Health Protection in Childhood and Adolescence Research Project a hygienic inspection questionnaire was designed for schools. To test this questionnaire, 248 schools in 11 districts of the county of Karl-Marx-Stadt were inspected. From the ascertainments made, several instances are cited to point out the priorities of school hygiene.


Unintended consequences of curtailment cap policies on power system decarbonization.
As countries pursue power system decarbonization, a well-intentioned strategy being pursued in jurisdictions like China is the strict integration target, often in the form of a curtailment cap. The effects of these curtailment caps have not been systematically studied. Here, we evaluate the effects of these caps on the decarbonization of one provincial power system using a capacity expansion model. Results reveal that curtailment caps yield deleterious effects that do not align with the stated goals of these policies. Capping curtailment significantly increases storage capacity (+43% with a 5% curtailment cap) and reduces renewable capacity (-17%). Even with the increase in flexible storage capacity, the policy still jeopardizes power system reliability by increasing occurrences of over or under generation. It also suppresses power generation from hydropower and reduces energy storage utilization while increasing fossil fuel utilization. Capping curtailment increases economic costs (+6% with a 5% curtailment cap) and CO2 emissions (+7%).


Removal of potentially toxic elements from contaminated soil and water using bone char compared to plant- and bone-derived biochars: A review.
Conversion of hazardous waste materials to value-added products is of great interest from both agro-environmental and economic points of view. Bone char (BC) has been used for the removal of potentially toxic elements (PTEs) from contaminated water, however, its potential BC for the immobilization of PTEs in contaminated water and soil compared to bone (BBC)- and plant (PBC)-derived biochars has not been reviewed yet. This review presents an elaboration for the potentials of BC for the remediation of PTEs-contaminated water and soil in comparison with PBC and BBC. This work critically reviews the preparation and characterization of BC, BBC, and PBC and their PTEs removal efficiency from water and soils. The mechanisms of PTE removal by BC, BBC, and PBC are also discussed in relation to their physicochemical characteristics. The review demonstrates the key opportunities for using bone waste as feedstock for producing BC and BBC as promising low-cost and effective materials for the remediation of PTEs-contaminated water and soils and also elucidates the possible combinations of BC and BBC aiming to effectively immobilize PTEs in water and soils.


Usefulness of [68Ga]FAPI-04 and [18F]FDG PET/CT for the detection of primary tumour and metastatic lesions in gastrointestinal carcinoma: a comparative study.
To assess and compare the diagnostic performance of gallium-68-labelled fibroblast activation protein inhibitor ([68Ga]FAPI-04) and fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in gastrointestinal cancer. Fifty-one patients who underwent both [18F]FDG and [68Ga]FAPI-04 PET/CT for initial staging or restaging were enrolled. Histopathological findings, typical radiological appearances, and clinical imaging follow-up were used as the reference standard. The diagnostic performance of the two tracers was calculated and compared. The maximum standardised uptake value (SUVmax), mean SUV (SUVmean), tumour-to-mediastinal blood pool ratio (TBR), and tumour-to-liver ratio (TLR) of primary and metastatic lesions were measured and compared between two imaging modalities. In patient-based analysis, [68Ga]FAPI-04 showed much better diagnostic sensitivity than [18F]FDG in detecting primary tumour (94.44% [17/18] vs. 61.11% [11/18]), postoperative recurrence and metastases (95.65% [22/23] vs. 69.57% [16/23]), and peritoneal carcinomatosis (100% [28/28] vs. 60.71% [17/28]) (all p < 0.05). In lesion-based analysis, [68Ga]FAPI-04 showed higher sensitivity than [18F]FDG for detecting lymph node metastases. In peritoneal carcinomatosis, the median SUVmax (12.12 vs. 7.18) and SUVmean (6.84 vs. 4.11) with [68Ga]FAPI-04 were significantly higher than those with [18F]FDG (all p < 0.005). The TBR and TLR of [68Ga]FAPI-04 were significantly higher than those of [18F]FDG for detecting primary tumour, lymph node, liver, and peritoneal metastases (all p < 0.005). Therapeutic management changed in 13 patients according to [68Ga]FAPI-04 PET/CT compared with conventional imaging. [68Ga]FAPI-04 is superior to [18F]FDG PET/CT for detecting primary tumour, postoperative recurrence and metastasis, and peritoneal carcinomatosis in gastrointestinal cancer. • [68Ga]FAPI-04 PET/CT showed significantly higher sensitivity than [18F]FDG PET/CT in the detection of primary tumour and postoperative recurrence and metastasis in patients with gastrointestinal carcinoma. • [68Ga]FAPI-04 PET/CT had obvious advantages over [18F]FDG PET/CT in the detection of peritoneal carcinomatosis from gastrointestinal carcinoma with a much higher FAPI uptake value, TBR, and TLR. • Although the median SUVmax and SUVmean of [68Ga]FAPI-04 were similar to those of [18F]FDG for the primary tumour, lymph node metastases, and liver metastases in gastrointestinal carcinoma, the TBR and TLR of the SUVmax and SUVmean were significantly higher on [68Ga]FAPI-04 PET/CT, causing the lesions to be displayed more clearly.


Dilemma after termination of pregnancy due to urogenital fetal anomalies: Discrepancy between prenatal ultrasonographic diagnosis and autopsy.
To evaluate the agreement and disagreement between prenatal ultrasound and fetal autopsy findings in pregnancy terminations due to urogenital anomalies. Of 453 pregnancy terminations performed due to fetal anomalies, 82 cases with urogenital anomalies on either prenatal ultrasound or fetal autopsy were included in this retrospective study. The discrepancy between prenatal ultrasound and fetal autopsy findings on urogenital anomaly findings was evaluated. Complete agreement between prenatal ultrasound and fetal autopsy findings was noted in 33 (40.2%) cases (particularly for megacystis, bilateral renal agenesis, and infantile polycystic kidney), whereas partial agreement (anal atresia and horseshoe kidney as additional minor findings) and altered diagnosis were noted in 12 (14.6%) and 8 (9.8%) cases, respectively. Disagreement was noted in 29 (35.4%) cases including anomaly only on autopsy in 20 (24.3%) cases (renal agenesis, horseshoe kidney and multicystic dysplastic kidney in particular) and anomaly only on ultrasound in 9 (10.9%) cases. Accordingly, our findings indicate fetal autopsy to be a method of vital importance in complementing prenatal diagnosis; it may add valuable information that may improve future pregnancy management and counseling of parents, and hence prenatal ultrasound and fetal autopsy should be regarded as complementary techniques.


Reducing racial and social-class inequalities in health: the need for a new approach.
It is well known that people in racial and ethnic minority groups and in lower social-class positions have higher morbidity and mortality rates from virtually every disease. To effectively deal with the problem, we will need to adopt a more appropriate conceptual model that focuses on the fundamental determinants of health, we will need to understand how important this is for all Americans as a society, and we will need to better deal with the issues people care about: their children, homes, jobs, safety, education, families, retirement, and future prospects.


Evidence for the spontaneous formation of disulfide crosslinked aggregates of tubulin during nondenaturing electrophoresis.
Phosphocellulose-purified tubulin has been shown to form a characteristic "ladder" of nonmicrotubular aggregates during nondenaturing gel electrophoresis (J. J. Correia and R. C. Williams, Jr. (1985) Arch. Biochem. Biophys. 239, 120-129). In this paper we describe evidence that the intersubunit bonds responsible for formation of these oligomeric particles are disulfides. Two-dimensional nondenaturing-denaturing gel electrophoresis demonstrates that each aggregate zone is composed of alpha- and beta-subunits of tubulin. Omission of beta-mercaptoethanol during the sodium dodecyl sulfate (SDS)-electrophoresis step causes a pattern of aggregates to appear and implicates disulfide linkages in their stabilization. Molecular weights, estimated from mobilities in the second (SDS) dimension of two-dimensional gels, suggest that the aggregates are crosslinked in units of monomers, not heterodimers. Consistent with this conclusion, alpha- or beta-subunits alone (isolated by isoelectric focusing) will form the same ladder of aggregates. The disulfide crosslinking of tubulin is also achievable in solution. It is favored by high concentrations of alcohol, the presence of oxidizing agents, high pH, and high temperature, conditions that denature tubulin and cause rapid noncovalent aggregation or precipitation. When aggregate formation was monitored as a function of time by SDS-gel electrophoresis in the absence of beta-mercaptoethanol and by quantitative sulfhydryl and disulfide titrations, the most effective conditions for the crosslinking reaction included greater than 75% alcohol, excess H2O2, or excess iodine. These results suggest that proximity of a hydrophobic gel matrix, high pH, the presence of oxidizing agents, high protein concentration, tubulin's propensity to aggregate nonspecifically, and the availability of as many as 20 sulfhydryls in alpha beta-tubulin contribute, during nondenaturing gel electrophoresis, to the spontaneous formation of disulfide-crosslinked tubulin aggregates.


Delayed vasculogenesis and impaired angiogenesis due to altered Ang-2 and VE-cadherin levels in the chick embryo model following exposure to cadmium.
Cadmium (Cd) causes chick embryo malformation and abnormal extra-embryonic vasculature. This study investigates the effect of Cd on vasculogenesis, quantifies extra-embryonic vascular development following exposure to cadmium acetate (CdAc). After 48 or 60 h incubation, chicks were explanted and treated with 50 µl of 50 µM CdAc or equimolar sodium acetate. Embryos were again incubated then re-examined 4, 8, 24 and 48 h later. Gross morphological and histological manifestations were noted. Vasculogenesis was assessed by the development of omphalomesenteric vessels from blood islands. Sinus terminalis (ST), area vasculosa (AV), vessel density and embryo crown-rump length (CRL) were measured. Ang-2 and VE-cadherin mRNA expression was analysed by RT-PCR. Vasculogenesis was delayed on gross and histological examination. ST length, AV area, vessel density and CRL were significantly reduced in the Cd group. Ang-2 was increased 4 h after exposure to Cd, whereas VE-cadherin was reduced. Cd exposure inhibits normal development of extra-embryonic vasculature in line with growth retardation of the chick embryo in association with altered expression of Ang-2 and VE-cadherin.


Dwelling on potential threat cues: an eye movement marker for combat-related PTSD.
Although several studies have documented an attentional bias toward threat in posttraumatic stress disorder (PTSD), the nature of this bias has not been clearly delineated. The present study utilized eye tracking technology to delineate the time course and components of attentional bias for threat cues in combat-related PTSD. Veterans with PTSD (n = 21), combat-exposed veterans without PTSD (n = 16), and nonveteran controls (n = 21) viewed emotional expressions (fearful, disgusted, happy) paired with neutral expressions for 3 s presentations. Veterans with PTSD maintained attention longer on the fearful and disgusted expressions relative to the happy expression. This negativity bias was sustained over the course of the 3 s trials, and robustly distinguished veterans with PTSD from both veterans without PTSD and nonveteran controls. Dwelling on potential threat cues may reflect current PTSD symptoms, or it could reflect a cognitive vulnerability factor for PTSD.


Modulation of intravariceal pressure with pentoxifylline: a possible new approach in the treatment of portal hypertension.
In this study the effect of the hemorheological agent pentoxifylline on the pressure of esophageal varices was investigated in portal hypertensive cirrhotic patients. Intravariceal pressure was measured endoscopically using the direct puncture technique in 20 patients. Measurements were obtained under baseline conditions and 30 min after double-blind administration of pentoxifylline (1.4 mg/kg BW, n = 10 patients) or an identical volume of NaCl 0.9% solution (n = 10 patients). Under baseline conditions, intravariceal pressure was similar in pentoxifylline and placebo groups (17.3+/-5.5 mm Hg vs 18.8+/-4.6 mm Hg, respectively; p = N.S.). Placebo administration had no significant effect on intravariceal pressure (18.8+/-4.6 mm Hg vs 18.3+/-4.1 mm Hg; p = N.S.). In contrast, pentoxifylline caused a highly significant reduction of intravariceal pressure, (from 17.3+/-5.5 mm Hg to 11.4+/-5.9 mm Hg; p = 0.0001), the overall mean reduction being 36.1+/-14.1% mm Hg. We concluded that pentoxifylline, by reducing blood flow viscosity, caused a significant decrease in variceal pressure in patients suffering from portal hypertension.


Development of an absolute gas-counting capability for low to medium activities.
Pacific Northwest National Laboratory (PNNL) is developing a capability to measure the absolute activity concentration of gaseous radionuclides using length-compensated proportional-counting. This capability will enable the validation of low-level calibration standards for use in PNNL's new shallow underground laboratory. Two sets of unequal length proportional counters have been fabricated; one set has been fabricated using ultra-low background (ULB) electroformed copper and a second set fabricated from Oxygen-Free High-Conductivity Copper (OFHC).


Comparison of the retinal microvasculature between compressive and glaucomatous optic neuropathy.
To compare the patterns of retinal microvasculature change in the peripapillary and macular region between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to assess the ability of optical coherence tomography angiography (OCTA) in differentiating the two conditions. This cross-sectional study included 108 participants (108 eyes), 36 with CON, 36 with GON, and 36 healthy controls. The CON and GON eyes were matched by the average peripapillary retinal nerve fiber layer (pRNFL) thickness (1:1). Optical coherence tomography (OCT) and OCTA were performed to compare the structural and vascular change of the peripapillary and macular region between groups. Both CON and GON eyes showed more severe structural and vascular damage than the control eyes. The CON eyes had lower pRNFL thickness than the GON eyes in the temporal and nasal quadrants, and thicker pRNFL thickness in the inferior quadrant. The average GCC thickness did not differ between the two groups. The peripapillary vessel density of the CON group was significantly higher in the inferior sectors than that of the GON group. In the macular region, the CON group had significantly higher vessel density in the whole image, the temporal sector in parafovea region, and the temporal, superior, and inferior sectors in perifovea region. To a similar degree of structural damage, CON had less retinal vascular impairment than GON, especially in the macular region, and the significance of the finding needs further evaluation.


Using decision analysis to assess the quality of quality assurance.
Quality assurance is rapidly encroaching on the fields of epidemiology and infection control. If we are to lead this most recent revolution in medical care, we must ensure that our approach is structured, that we reassess our goals and methods regularly and that we achieve the maximal benefit from the resources we consume. According to Colloton, "Unless refined or replaced, the unsophisticated methodologies now emerging on several fronts will be used, with or without our endorsement, to assess the quality of care rendered within all of medical practice."


The role of interleukin-15 in the development and treatment of hematological malignancies.
Cytokines are a vital component of the immune system that controls the activation and growth of blood cells. However, chronic overexpression of cytokines can trigger cellular events leading to malignant transformation. The cytokine interleukin-15 (IL-15) is of particular interest, which has been shown to contribute to the development and progression of various hematological malignancies. This review will provide an overview of the impact of the immunopathogenic function of IL-15 by studying its role in cell survival, proliferation, inflammation, and treatment resistance. We will also review therapeutic approaches for inhibiting IL-15 in blood cancers.


A ribonucleopeptide module for effective conversion of an RNA aptamer to a fluorescent sensor.
Ribonucleopeptide (RNP) is a new class of scaffold for modular fluorescent sensors. We report here a short RNA motif that induces an efficient communication between the structural changes associated with the ligand-binding event of RNA aptamer and an optical response of a fluorescent RNP module. An optimized short RNA motif was used as a communication module for the rational design of modular RNP sensors. A modular combination of a GTP-binding RNA aptamer, the short RNA motif and the fluorophore-labeled RNP module afforded a fluorescent GTP sensor that retain the ligand-binding affinity of the parent aptamer.


Two new pregnanes from Aglaia perviridis Hiern.
Two new pregnanes, 2alpha,3alpha,20-trihydroxy-16beta-acetoxy-20(R)-pregnane (1) and 2alpha,3alpha,15beta-trihydroxy-16beta-acetoxy-pregnane-20(R)-methacrylate (2), along with five known compounds, were isolated from the ethanolic extract of the twigs of Aglaia perviridis Hiern using chromatographic methods. The structures of 1 and 2 were elucidated on the basis of spectral data.


Carboxymethyl cellulose nanocomposite beads as super-efficient catalyst for the reduction of organic and inorganic pollutants.
Carboxymethyl cellulose/copper oxide-nickel oxide (CMC/CuO-NiO) nanocomposite beads were prepared by facile, simple and environmentally friendly method. Initially, CuO-NiO was prepared and applied for the catalytic reduction of 4-nitrophenol (4-NP). The results showed that CuO-NiO demonstrate high catalytic activity toward the reduction of 4-NP to 4-aminophenol (4-AP) with a rate constant of 2.97 × 10-2 s-1. Further, CuO-NiO were well-dispersed in the polymeric matrix of carboxymethyl cellulose to prepare CMC/CuO-NiO beads. CMC/CuO-NiO nanocomposite beads were also applied to catalyze the reduction of potassium ferrocyanide (K3Fe (CN)6), 4-NP, Congo red (CR) and Eosin yellow (EY) in the presence of sodium borohydride. Experimental data indicated that CMC/CuO-NiO nanocomposite has higher catalytic activity and high rate constant compared to CuO-NiO. The rate constant found to be 6.88 × 10-2, 6.27 × 10-2, 1.89 × 10-2 and 2.43 × 10-2 for K3Fe(CN)6, 4-NP, CR and EY, respectively, using 5 mg CMC/CuO-NiO beads. FE-SEM, EDX, FTER, XRD and XPS were used to characterize the nanocomposites. CMC/CuO-NiO beads catalytically reduced up to 95-99% of K3Fe(CN)6, 4-NP, CR and EY within 40, 60, 120 and 120 s. CMC/CuO-NiO beads were found more selective for the reduction of 4-NP. The catalytic reduction performance of CMC/CuO-NiO beads was optimized by studying the influence of different parameters on the catalytic reduction of 4-NP. Hence, the effective and super catalytic performance toward the reduction of different organic and inorganic pollutants makes CMC/CuO-NiO beads a smart material and suitable for numerous scientific and industrial applications and may be used as an alternative to high-cost commercial catalysts.


Principal component analysis suggests subtle changes in glutamate receptor subunit expression in the rat hippocampus following bilateral vestibular deafferentation.
Previous studies have shown that lesions of the peripheral vestibular system result in electrophysiological dysfunction in the hippocampus. Given the importance of glutamate as a neurotransmitter in the hippocampus, it was predicted that bilateral vestibular deafferentation (BVD) would alter the expression of NMDA and AMPA receptors in this area of the brain. However, the results of studies conducted to date are inconsistent. In this study, we performed principal component analysis (PCA) on the expression of the NR1, NR2B, GluR1, GluR2 and GluR3 glutamate receptor subunits, as well as calmodulin kinase IIα (CaMKIIα) and phosphorylated CaMKIIα (pCaMKIIα), in the rat CA1, CA2/3 and dentate gyrus (DG) subregions of the hippocampus, at 6 months following BVD, using western blotting. The expressions of the different glutamate receptor subunits, in terms of NMDA versus AMPA receptor subunits, as well as CaMKIIα and pCaMKIIα, were tightly correlated, and this was shown again the loading plots. However, the pattern of the contributions of each protein to the first 2 principal components appeared to be inverted for the BVD group compared to the sham group.


Pathway-based integration of multi-omics data reveals lipidomics alterations validated in an Alzheimer's disease mouse model and risk loci carriers.
Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder. Despite increasing evidence of the importance of metabolic dysregulation in AD, the underlying metabolic changes that may impact amyloid plaque formation are not understood, particularly for late-onset AD. This study analyzed genome-wide association studies (GWAS), transcriptomics, and proteomics data obtained from several data repositories to obtain differentially expressed (DE) multi-omics elements in mouse models of AD. We characterized the metabolic modulation in these data sets using gene ontology, transcription factor, pathway, and cell-type enrichment analyses. A predicted lipid signature was extracted from genome-scale metabolic networks (GSMN) and subsequently validated in a lipidomic data set derived from cortical tissue of ABCA-7 null mice, a mouse model of one of the genes associated with late-onset AD. Moreover, a metabolome-wide association study (MWAS) was performed to further characterize the association between dysregulated lipid metabolism in human blood serum and genes associated with AD risk. We found 203 DE transcripts, 164 DE proteins, and 58 DE GWAS-derived mouse orthologs associated with significantly enriched metabolic biological processes. Lipid and bioenergetic metabolic pathways were significantly over-represented across the AD multi-omics data sets. Microglia and astrocytes were significantly enriched in the lipid-predominant AD-metabolic transcriptome. We also extracted a predicted lipid signature that was validated and robustly modeled class separation in the ABCA7 mice cortical lipidome, with 11 of these lipid species exhibiting statistically significant modulations. MWAS revealed 298 AD single nucleotide polymorphisms-metabolite associations, of which 70% corresponded to lipid classes. These results support the importance of lipid metabolism dysregulation in AD and highlight the suitability of mapping AD multi-omics data into GSMNs to identify metabolic alterations.


The forest behind the bar charts: bridging quantitative and qualitative research on Roma/Tigani in contemporary Romania.
Rughiniş discusses three controversial issues with regard to surveys of the Romani population: ethnonym use, self-identification versus hetero-attribution of Romani ethnicity, and the use of variables in reference to Romani settlements. She uses data sets from ten surveys of Romanian Roma between 2000 and 2008 as well as the 2002 Romanian Census to compare two types of samples, and to explore the consequences of several research choices for the quality of the data. In addition to specific methodological issues, Rughiniş addresses the relevance to such surveys of qualitative research in Romani communities.


Proscillaridin activity in portal and peripheral venous blood after oral administration to man.
The absorption of proscillaridin A was studied in four patients undergoing catheterization of the portal vein for diagnostic purposes. Proscillaridin 1.5 mg was given as a single oral dose and plasma glycoside activity was analyzed by the 86Rb-uptake inhibition technique. Proscillaridin appeared rapidly in the portal blood, peak activity being found after 15 min in three and after 30 min in one patient. In peripheral blood the peak activity occurred after approximately 35 min. Despite rapid passage across the gut wall, porto-peripheral differences in glycoside activity were small; they were zero after 4h. The mean amount absorbed as active porscillaridin during the first 4h after the dose was calculated to be only 7.1% of the given amount. Late porto-peripheral differences, probably due to enterohepatic recycling, appeared after 6h in three patients; The results suggest that proscillaridin undergoes first pass inactivation in the gut wall. Enterohepatic recirculation may contribute to the amounts of active glycoside that reach the systemic circulation.


The Law Commission's proposals for the reform of the defences of insanity and automatism.
The article offers an overview of the Law Commission's project on Insanity and Automatism and the provisional conclusions reached in its Discussion Paper in 2013.


Production of functionalized polyhydroxyalkanoates by genetically modified Methylobacterium extorquens strains.
Methylotrophic (methanol-utilizing) bacteria offer great potential as cell factories in the production of numerous products from biomass-derived methanol. Bio-methanol is essentially a non-food substrate, an advantage over sugar-utilizing cell factories. Low-value products as well as fine chemicals and advanced materials are envisageable from methanol. For example, several methylotrophic bacteria, including Methylobacterium extorquens, can produce large quantities of the biodegradable polyester polyhydroxybutyric acid (PHB), the best known polyhydroxyalkanoate (PHA). With the purpose of producing second-generation PHAs with increased value, we have explored the feasibility of using M. extorquens for producing functionalized PHAs containing C-C double bonds, thus, making them amenable to future chemical/biochemical modifications for high value applications. Our proprietary M. extorquens ATCC 55366 was found unable to yield functionalized PHAs when fed methanol and selected unsaturated carboxylic acids as secondary substrates. However, cloning of either the phaC1 or the phaC2 gene from P. fluorescens GK13, using an inducible and regulated expression system based on cumate as inducer (the cumate switch), yielded recombinant M. extorquens strains capable of incorporating modest quantities of C-C double bonds into PHA, starting from either C6= and/or C8=. The two recombinant strains gave poor results with C11=. The strain containing the phaC2 gene was better at using C8= and at incorporating C-C double bonds into PHA. Solvent fractioning indicated that the produced polymers were PHA blends that consequently originated from independent actions of the native and the recombinant PHA synthases. This work constitutes an example of metabolic engineering applied to the construction of a methanol-utilizing bacterium capable of producing functionalized PHAs containing C-C double bonds. In this regard, the PhaC2 synthase appeared superior to the PhaC1 synthase at utilizing C8= as source of C-C double bonds and at incorporating C-C double bonds into PHA from either C6= or C8=. The M. ex-phaC2 strain is, therefore, a promising biocatalyst for generating advanced (functionalized) PHAs for future high value applications in various fields.


Modifying effects of pH and temperature on (14C)erythromycin uptake into Staphylococcus aureus--relation to antimicrobial activity.
The uptake of (14C)erythromycin into Staphylococcus aureus was investigated by use of a rapid centrifugation method. Erythromycin uptake was saturable with time and with increasing erythromycin concentrations (apparent uptake constant Km = 6.0 x 10(-7) moles/l). Inhibitors of glycolysis, respiration and oxidative phosphorylation did not influence the uptake process but uptake was decreased by reducing temperature. Increases of erythromycin uptake, decreases of half life times of the uptake reaction and a log dose linked to enhancement of antimicrobial activity were seen with alkaline pH levels of the incubation medium. The experimental data conform well with the concept of non ionic diffusion. The high affinity of erythromycin to the intracellular ribosomal target site probably generates the driving force of uptake and the unionized antibiotic obviously represents the antimicrobially active molecular form.


Risk of Coronary Obstruction Due to Sinus Sequestration in Redo Transcatheter Aortic Valve Replacement.
The aim of this study was to evaluate the risk of coronary obstruction due to sinus sequestration in redo transcatheter aortic valve replacement (TAVR) using post-TAVR computed tomography (CT). Little information is available regarding the risk of coronary obstruction due to sinus sequestration in redo TAVR inside a previously implanted TAV. Post-TAVR CT of 66 patients who received an Evolut R or Evolut PRO and 345 patients who received a SAPIEN 3 were analyzed. Redo TAVR was considered at risk of coronary obstruction due to sinus sequestration if: 1) the prior TAV commissure level was above sinotubular junction (STJ); and 2) the distance between TAV and STJ was <2.0 mm in each coronary sinus. In total, 45.5% in the Evolut R/Evolut PRO group and 2.0% in the SAPIEN 3 group had CT-identified risk of sinus sequestration at 1 or both coronary arteries (p < 0.001). CT-identified risk of sinus sequestration was observed in 39.4% for the left coronary artery and 24.2% for the right coronary artery in the Evolut R/Evolut PRO group, while those percentages were 2.0% for the left coronary artery and 0.6% for the right coronary artery in the SAPIEN 3 group. In a coronary-level analysis, overlaps between the first TAV commissural posts and coronary ostium were observed in 45.2% in the Evolut R/Evolut PRO group and 11.1% in in the SAPIEN 3 group among coronary arteries at CT-identified risk of sinus sequestration. The risk of sinus sequestration in redo TAVR should be carefully screened by CT, especially in patients with low STJ height. TAV with low commissure height that was designed to achieve commissure-to-commissure alignment with the native aortic valves may be preferable to avoid the risk of coronary obstruction due to sinus sequestration and allow for a preventive leaflet laceration procedure in future redo TAVR. (Assessment of TRanscathetEr and Surgical Aortic BiOprosthetic Valve Thrombosis and Its TrEatment With Anticoagulation [RESOLVE]; NCT02318342).


The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T lymphocyte response to potent antiretroviral therapy.
To study the long-term immunological recovery in HIV-1-infected individuals receiving potent antiretroviral therapy (ART). Prospective, observational study. Plasma HIV-1 RNA, CD4 and CD8 T lymphocyte counts were determined at 3-6 monthly intervals in 95 HIV-1-infected subjects receiving ART who suppressed plasma HIV-1 RNA to levels below 400 copies/ml during a median observation period of 45 months. The median CD4 cell count rose from 325 to 624 cells/microl at 48 months, increasing by 22.6 cells/microl per month in the first 3 months, 8.1 cells/microl per month from months 3 to 12, 6.8 cells/microl per month in the second year, 3.3 cells/microl per month in the third, and 1.7 cells/microl per month in the fourth year. At 48 months, 98% of subjects reached CD4 cell counts > 200 cells/microl, 86% > 350 cells/microl, and 74% > 500 cells/microl. A higher nadir CD4 cell count and younger age were independently associated with greater increases in CD4 cell counts, and higher absolute CD4 cell counts at 48 months. Poor immunological responders who did not reach 500 CD4 lymphocytes/microl at 48 months showed lower nadir and baseline CD4 cell counts than good responders (99 versus 300 cells/microl and 160 versus 373 cells/microl, respectively). The recovery of CD4 T lymphocytes occurs mainly in the first 2 years after the initiation of ART, and is associated with age and the pre-existing degree of HIV-1-related immunodeficiency, suggesting that the long-term exposure to HIV-1 infection has caused damage to the immune system that is difficult to correct.


Impairment of the ubiquitin-proteasome system associated with extracellular transthyretin aggregates in familial amyloidotic polyneuropathy.
The ubiquitin-proteasome system (UPS) has been associated with neurodegenerative disorders of intracellular protein aggregation. We have studied the UPS in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder caused by extracellular deposition of mutant transthyretin (TTR). The studies were conducted in TTR-synthesizing and non-synthesizing tissues from affected individuals, in transgenic mouse models for FAP, and in neuronal or Schwannoma cell lines cultured with TTR aggregates. In human FAP tissues presenting extracellular TTR aggregates, ubiquitin-protein conjugates were up-regulated, the proteasome levels were decreased and parkin and alpha-synuclein expression were both decreased. A similar response was detected in mouse models for TTR V30M or L55P. On the other hand, the liver, which normally synthesizes variant TTR V30M, did not show this response. Furthermore, transgenic mice immunized to decrease TTR deposition showed a significant reduction in ubiquitin levels and an increase in parkin and alpha-synuclein levels in comparison to control mice. Studies performed in cell lines with aggregates in the medium resulted in increased ubiquitin and decreased parkin levels. The overall results are indicative of TTR deposition as an external stimulus to an intracellular UPS response in FAP.


Quantitative Analysis of the Cerebral Vasculature on Magnetic Resonance Angiography.
The arterial connections in the Circle of Willis are a central source of collateral blood flow and play an important role in pathologies such as stroke and mental illness. Analysis of the Circle of Willis and its variants can shed light on optimal methods of diagnosis, treatment planning, surgery, and quantification of outcomes. We developed an automated, standardized, objective, and high-throughput approach for categorizing and quantifying the Circle of Willis vascular anatomy using magnetic resonance angiography images. This automated algorithm for processing of MRA images isolates and automatically identifies key features of the cerebral vasculature such as branching of the internal intracranial internal carotid artery and the basilar artery. Subsequently, physical features of the segments of the anterior cerebral artery were acquired on a sample and intra-patient comparisons were made. We demonstrate the feasibility of using our approach to automatically classify important structures of the Circle of Willis and extract biomarkers from cerebrovasculature. Automated image analysis can provide clinically-relevant vascular features such as aplastic arteries, stenosis, aneurysms, and vessel caliper for endovascular procedures. The developed algorithm could facilitate clinical studies by supporting high-throughput automated analysis of the cerebral vasculature.


Pneumococcal vaccine efficacy for mucosal pneumococcal infections depends on Fcgamma receptor IIa polymorphism.
IgG2 antibodies are the main antibody subclass produced after pneumococcal polysaccharide vaccination. For these antibodies to be effective, interaction with FcgammaIIa receptors on phagocytic cells is necessary. FcgammaRIIa displays a functional polymorphism with either a histidine (H) or arginine (R) at position 131. Interaction of IgG2 antibodies depends on the H131 allele, whereas this interaction is low to absent with the R131 allele. We tested the clinical efficacy of combined pneumococcal conjugate and pneumococcal polysaccharide vaccination according to FcgammaIIa-H/R131 genotype in a randomized double blind placebo controlled vaccination trial in children with a history of acute otitis media. We found a decisive role for the FcgammaIIa-H/R131 polymorphism on the clinical vaccine efficacy of combined pneumococcal conjugate and polysaccharide vaccinations. RR homozygotes showed a significant increase in recurrence of acute otitis media after pneumococcal vaccinations. This cannot be explained by differences in the pneumococcal specific antibody response or differences in nasopharyngeal pneumococcal carriage, but may be explained by less efficient interaction of FcgammaRIIa with polysaccharide-induced IgG2 anti-pneumococcal antibodies in RR homozygotes. Our data show that the genetic make-up of individuals or populations under study should be considered while evaluating vaccine efficacy trials.


Optisol-GS Storage of Cultured Human Limbal Epithelial Cells at Ambient Temperature Is Superior to Hypothermic Storage.
To investigate the feasibility of using Optisol-GS as a convenient, xenogeneic-free alternative for storage of cultured human limbal epithelial cells (HLECS) for use in treatment of limbal stem cell deficiency (LSCD). In the present study, we compared storage of cultured HLEC using the conventional hypothermic Optisol-GS storage method at 4°C versus storage at 23°C (room temperature). HLECs were cultured for three weeks on amniotic membrane (AM), transferred to polypropylene containers and stored in Optisol-GS for 4 days at 23°C and 4°C. A calcein-acetoxymethyl ester/ethidium homodimer-1 assay was used to assess viability. Morphology and phenotype were analyzed by light microscopy and immunohistochemistry, respectively. Expression of stem cell and proliferation markers p63, ∆Np63α, ABCG2, K19, K3, Cx43, Ki67, and PCNA was maintained at pre-storage control levels during storage at 23°C. ABCG2 and PCNA expression were both significantly altered during storage at 4°C. HLEC cell sheet viability also significantly declined following storage at 4°C. HLEC sheets stored at 4°C demonstrated extensive detachment of basal cells from the AM in sharp contrast to storage at 23°C, where attachment to the AM was maintained throughout the storage period. The present study demonstrates the feasibility of short-term storage of cultured HLECs in Optisol-GS, which offers a convenient standardized xenogeneic-free storage method. Storage temperature highly affected the results. Maintenance of cell viability, morphology and undifferentiated proliferative phenotype of cultured HLEC sheets favored storage at 23°C.


Characterization of arginine preventive effect on heat-induced aggregation of insulin.
Aggregation of proteins can affect their efficacy, and is especially important concerning therapeutic proteins such as insulin. Use of additives such as amino acids can counteract this deleterious process. Heat-induced aggregate formation of human insulin was kinetically studied with the use of various concentrations of the protein, at different temperatures, and in the presence of EDTA by UV-visible spectrophotometry. Effect of arginine, lysine, and histidine was then tested on the process at pH 4.8 and 45 °C. Kinetic parameters of the obtained growth curves (parameters t* and t0.5 characterizing the rate of the nucleation stage and the rate of the stage of aggregate growth respectively) were computed in all these conditions, and structure of aggregates was characterized by spectrofluorimetry, and transmission electron microscopy (TEM). Presence of high concentrations of the chelator EDTA increased aggregation. Among used additives, L-arginine (50 mM) most efficiently suppresses the heat-induced amorphous aggregation of insulin, affecting parameters t0.5 and t* presumably by preserving the protein's structure, as observed by the protein intrinsic fluorescence and CD spectra, and smaller formed aggregates in TEM images and dynamic light scattering. Docking experiment and subsequent molecular dynamics simulation indicated possible sites of interaction for arginine with the B-chain of insulin.


Butyrate esterase (4-methylumbelliferyl butyrate) spot test, a simple method for immediate identification of Moraxella (Branhamella) catarrhalis [corrected].
A total of 47 Moraxella (Branhamella) catarrhalis strains, 89 strains of Neisseria spp., and 82 strains of miscellaneous bacteria and yeasts were studied by using a fluorogenic spot method which detects butyrate esterase. A positive butyrate esterase spot test correctly differentiated M. catarrhalis from Neisseria spp., which had a negative butyrate esterase spot test reaction. The test is rapid, simple, and easy to perform. The butyrate esterase spot test was useful for direct identification of M. catarrhalis from primary cultures. However, false-positive reactions may occur with mixed cultures.


Splenic lymphangiomatosis: a rare cause of splenomegaly.
A case of lymphangiomatosis of the spleen and adrenal in a 10-year-old girl is described. The patient had multiple recurrent lymphangiomata excised from her neck during the first 4 years of life. She presented with a recurrent cystic hygroma of the neck and was found to have an enlarged spleen. This increased in size during 5 months of observation, causing left upper quadrant discomfort, and was excised. The diagnosis, management, and prognosis of this rare disorder are discussed.


Anticoagulation for Stroke Prevention in Atrial Fibrillation.
Cardioembolic stroke from atrial fibrillation causes substantial death and disability in the United States. Treatment with oral anticoagulants provides safe and effective stroke prevention for high-risk patients. This article reviews strategies for the use of anticoagulation and highlights the nurse's role in patient education.


Neurosurgical patients admitted via the emergency department initiating comfort care measures: a prospective cohort analysis.
Given the serious nature of many neurosurgical pathologies, it is common for hospitalized patients to elect comfort care (CC) over aggressive treatment. Few studies have evaluated the incidence and risk factors of CC trends in patients admitted for neurosurgical emergencies. To analyze all neurosurgical patients admitted to a tertiary care academic referral center via the emergency department (ED) to determine incidence and characteristics of those who initiated CC measures during their initial hospital admission. We performed a prospective, cohort analysis of all consecutive adult patients admitted to the neurosurgical service via the ED between October 2018 and May 2019. The primary outcome was the initiation of CC measures during the patient's hospital admission. CC was defined as cessation of life-sustaining measures and a shift in focus to maintaining the comfort and dignity of the patient. Of the 428 patients admitted during the 7-month period, 29 (6.8%) initiated CC measures within 4.0 ± 4.0 days of admission. Patients who entered CC were significantly more likely to have a medical history of cerebrovascular disease (58.6% vs. 33.3%, p = 0.006), dementia (17.2% vs. 1.5%, p = 0.0004), or cancer with metastatic disease (24.1% vs. 7.0%, p = 0.001). Patients with a presenting pathology associated with cerebrovascular disease were significantly more likely to initiate CC (62.1% vs. 35.3, p = 0.04). Patients who underwent emergent surgery were significantly more likely to enter CC compared with those who had elective surgery (80.0% vs. 42.7%, p = 0.02). Only 10 of the 29 (34.5%) patients who initiated CC underwent a neurosurgical operation (p = 0.002). Twenty of the 29 (69.0%) patients died within 0.8 ± 0.8 days after the initiation of CC measures. CC measures were initiated in 6.8% of patients admitted to the neurosurgical service via the ED, with the majority of patients entering CC before an operation and presenting with a cerebrovascular pathology.


Comparison of patient-reported need of psycho-oncologic support and the doctor's perspective: how do they relate to disease severity in melanoma patients?
Psycho-neuro-immune research suggests an association between cancer outcomes and psychosocial distress. Objective criteria to determine patients' levels of distress are important to establish potential links to disease outcomes. We compared three patient-reported with one doctor-reported measures of psycho-oncologic distress frequently used in routine cancer care and investigated associations with standard disease severity parameters in melanoma patients. We enrolled n = 361 patients, successively seen at two outpatient university clinics in Germany. In the naturalistic study, n = 222 patients had been diagnosed <180 days and were seen for the first time (Group I); n = 139 had been diagnosed >180 days and were in after-care (Group II). Across groups, only moderate associations were seen between patient- reported and doctor-reported measures. Regarding clinical variables, disease severity and perceived need of psycho-oncologic support reported by patients or doctors showed hardly any association. After subgroup stratification, in patients of Group II, patient-reported and doctor-reported instruments showed some small associations with disease parameters commonly linked to more rapid cancer progression in patients who are in cancer after-care. Overall, the few and low associations suggest that need of psycho-oncologic support and clinical variables were largely independent of each other and doctors' perception may not reflect the patient's view. Therefore, the assessment of the patient perspective is indispensable to ensure that melanoma patients receive appropriate support, as such need cannot be derived from other disease parameters or proxy report. More research is needed applying psychometrically robust instruments that are ideally combined with sensitive biomarkers to disentangle psycho-neuro-immune implications in melanoma patients. Copyright © 2015 John Wiley & Sons, Ltd.


Glutamate and aspartate mimic the afferent transmitter in the cochlea.
Glutamate (50 mM) and aspartate (50 mM) applied intracochlearly increase the spontaneous activity of ganglion cells of the auditory nerve. This activity may account for the decreased magnitude of the compound action potential observed with these substances in previous studies, and also may be additional evidence that these substances have a role in synaptic transmission between the hair cells and primary auditory afferent nerve cells.


Bilateral pallidal stimulation for cervical dystonia. An optimal paradigm from our experiences.
We sought to identify optimal paradigms of bilateral globus pallidus internus (GPi) stimulation in 3 subsequent patients with severe cervical dystonia. At low frequency stimulation (50-60 Hz) with wide pulse width (500 micros) and high amplitude (4.5-8.0 V), we observed immediate and consistent improvement of dystonia and dystonia-associated pain. Stimulation of the posteroventral portion of the GPi led to pronounced alleviation of dystonia; stimulation of the anterodorsal portion or at the dorsal border of the GPi resulted in significant worsening of symptoms. The therapeutic benefit obtained by using the optimal stimulation parameters continues and has lasted for at least 1 year in each patient.


Physical Performance and Mobility Tests Using Telehealth: A Feasibility Study With Athletes.
Physical performance tests (PPTs) and mobility tests have been widely used in sports rehabilitation. However, the feasibility of PPTs and mobility tests via telehealth is unknown. To verify the feasibility of PPTs and mobility tests to assess athletes via telehealth. This is a feasibility study. Athletes enrolled in a sports team or club for at least 2 years and with previous enrollment in a competitive league were recruited through advertisements on social media. The athletes included in this study (mean age = 25.9 y, from different sports) performed a battery of PPTs and mobility tests for the lower-extremity or upper-extremity and trunk, according to their sport modality. The feasibility was assessed with recruitment, success, and dropout rates. In addition, athletes' perceptions of easiness, satisfaction, and safety during the lower-extremity or upper-extremity and trunk PPTs and mobility tests were assessed. Seventy-three athletes were included, between January and April 2021: 41 were allocated to the lower-extremity and 32 to the upper-extremity and trunk PPTs and mobility test, according to their sports modality. The overall dropout rate was 20.55%; >89% of the athletes agreed that the PPTs and mobility tests via telehealth were easy to perform, >78% were satisfied, and >75% felt safe during the assessments. This study indicated that these 2 batteries of performance and mobility tests via telehealth are feasible to assess the lower and upper-extremities, and the trunk of athletes, considering the adherence, athletes' perception of easiness, satisfaction, and safety.


[Immunohistochemistry for pituitary hormones and Ki-67 in growth hormone producing pituitary adenomas].
Growth hormone (GH) producing adenomas, frequently express several hormones. This condition could confer them a higher proliferative capacity. Ki-67 is a nuclear protein antigen that is a marker for proliferative activity. To measure the immunohistochemical hormone expression in pituitary adenomas, excised from patients with acromegaly. To determine if the plurihormonal condition of these adenomas is associated with a higher proliferative capacity, assessed through the expression of Ki-67. Forty one paraffin embedded surgical samples of pituitary adenomas from patients with acromegalia were studied. Immunohistochemistry for GH, prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH) and for the expression of Ki-67 was carried out. All samples were positive for GH. Twenty seven had positive staining for PRL, 12 had positive staining for glycoproteic hormones and 11 for PRL and one or more glycoproteic hormones. Mean staining for Ki-67 was Z.6+/-3.3%. There were no differences in the expression of this marker between mono or plurihormonal tumors. The expression was neither associated with extrasellar extension. Half of GH producing pituitary adenomas are plurihormonal. There are no differences in the expression of Ki-67 between mono and plurihormonal adenomas.


History of echocardiography in the Netherlands: 30 years of education and clinical applications.
The development of ultrasound has created great opportunities for diagnostic cardiac imaging. For more than 30 years, echocardiography has been the most important and cost-effective diagnostic imaging modality in clinical cardiology. Many developments originated in the Netherlands, including the very first practical real-time crosssectional imaging of the moving heart with a linear array. Milestones include the first portable echo apparatus, early versions of echo catheters and transoesophageal echocardiography probes as well as many clinical 'firsts' with reference to the more than 100 Dutch dissertations related to echocardiography. The future of echocardiography promises to be as productive and exciting as it has been in the previous three decades, including threedimensional echocardiography, myocardial perfusion echocardiography, tissue Doppler imaging and speckle tracking. New potential therapeutic applications are upcoming. In this article, the advances of echocardiography in the Netherlands are described, in the past and during 30 years of education, as was recently presented by three Dutch pioneers during the 'Echomiddagen 2006-2007' organised by the CVOI. (Neth Heart J 2008;16:16-20.).


The combination of a nylon and traditional partial removable dental prosthesis for improved esthetics: a clinical report.
A benefit of a nylon partial removable dental prosthesis (PRDP) is the absence of a metal framework, providing improved esthetics. Unfortunately, the lack of a traditional framework reduces rigidity and the support of occlusal rests. This clinical report describes a combination of a nylon PRDP (polyamide denture base resin) and a traditional PRDP (framework/resin) for a Kennedy Class II, Modification 1, partially edentulous mandible.


Is folklore use of Euphorbia helioscopia devoid of toxic effects?
To evaluate acute toxic effects of Euphorbia helioscopia in order to assure the safety and usefulness of herbal remedy. The Organization for Economic Cooperation and Development (OECD) for chemical testing guidelines No. 425 for acute oral toxicity testing were followed in this study. Mice were divided into three groups (n = 5). Group I served as control. Groups II and III were administered methanol extract of E. helioscopia leaves and latex orally at dose of 2000 mg/kg, respectively. Then, all the animals were observed for two weeks. Blood sampling was done by cardiac puncture after 14 days from each group for biochemical analysis. Histopathology was performed to find out any microscopic lesion in vital organs. LD50 was found greater than 2000 mg/kg. There was decrease in cholesterol, triglycerides, LDL and VLDL levels of latex and leaves with methanol extract-treated animals, with respect to control indicating plant's hypolipidemic effect. On macroscopic examination, no lesions were found on vital organs, such as liver, heart and kidney; and normal architecture was observed on microscopic examination. On the basis of results, it was concluded that methanol extract of E. helioscopia leaves and latex were devoid of toxic effects in acute toxicity study.


Will the real author please stand up!
This is a Guest editorial on the ethics of authorship in scientific publications. The editorial analyzes the qualification and roles of an author. It also discusses controversial issues and the relevance of the order of authorship in bio-medical journal publications.


Elucidating the intercalation mechanism of zinc ions into α-MnO2 for rechargeable zinc batteries.
The intercalation mechanism of zinc ions into 2 × 2 tunnels of an α-MnO2 cathode for rechargeable zinc batteries was revealed. It involves a series of single and two-phase reaction steps and produces buserite, a layered compound with an interlayer spacing of 11 Å as a discharge product.


Novel phthalide derivatives: Synthesis and anti-inflammatory activity in vitro and in vivo.
Phthalide is a promising chemical scaffold and has been proved to show potent anti-inflammatory efficacy. In this study, three series, total of 31 novel phthalide derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. The anti-inflammatory activity of all the compounds were screened on LPS induced NO production to evaluating their inhibitory effects. Structure-activity relationship has been concluded, and finally 3-((4-((4-fluorobenzyl)oxy)phenyl)(hydroxy)methyl)-5,7-dimethoxyisobenzofuran-1 (3H)-one (compound 9o) was found to be the active one with low toxicity, which showed 95.23% inhibitory rate at 10 μM with IC50 value of 0.76 μM against LPS-induced NO over expression. Preliminary mechanism studies indicated that compound 9o activated Nrf2/HO-1 signaling pathway via accumulation ROS and blocks the NF-κB/MAPK signaling pathway. The in vivo anti-inflammatory activity shown that compound 9o had obvious therapeutic effect against the adjuvant-induced rat arthritis model.


Oxytocin promotes attention to social cues regardless of group membership.
The social saliency account proposes that oxytocin (OT) plays a major role in modulating attentional shifts toward social cues at early stages of processing. We investigated how OT promotes early attention toward nonsocial and social stimuli and explored differences between in-group- and out-group-related social cues. After participants intranasally self-administered OT or placebo, they were eye-tracked while observing a nonsocial and social cues that were assigned to the in- or out-group by a minimal group paradigm. Participants under placebo did not differ in their fixation durations between stimuli, whereas participants administered OT increased gaze durations toward social but not nonsocial stimuli. In this early stage of processing, no in-group bias occurred: in-group- and out-group-related social cues were fixated equally long. These findings support that OT works by a simple illumination of social cues that seem to be processed regardless of social identity aspects at early stages of attention.


Involvement of Matrix Metalloproteinase 9 in Vertebral Arterial Dissection With Posterior Circulation Ischemic Stroke.
Background Spontaneous vertebral arterial dissection (VAD) is an important cause of posterior circulation ischemic stroke (PCS), but its pathogenesis remains elusive. Matrix metalloproteinase 9 (MMP-9) is a gelatinase involved in inflammation process and several vascular diseases, such as aorta dissection, but its role in VBD is unclear yet. The present study aimed to determine the association between serum MMP-9 level and VAD-related PCS. Methods and Results We recruited 149 patients with PCS, of which 30 were VAD and 119 had other determined etiologies (non-VAD), and 219 non-stroke individuals. Serum MMP-9 was measured within 14 days from stroke onset. The age of VAD group was 59.6±15.0 years, which is similar to non-stroke group (P=0.510) but significantly younger than non-VAD group (69.9±14.0 years, P<0.001). Males and vascular risk factors were significantly more prevalent in VAD and non-VAD groups than non-stroke group (P<0.001). Multivariate logistic regression analysis adjusting potential confounders revealed that every 100 ng/mL of serum MMP-9 level increment significantly predicted VAD (versus non-stroke group: odds ratio (OR), 4.572; 95% CI, 2.240-9.333, P<0.001; versus non-VAD group: OR, 1.819; 95% CI, 1.034-3.200, P=0.038). Conclusions Patients with VAD-related PCS had higher levels of serum MMP-9 at the acute stage of stroke compared with non-stroke individuals and PCS of other causes, supporting the potential involvement of extracellular matrix-degrading protease in the mechanism of VAD, which leads to ischemic events.


Early reproduction and increased reproductive allocation in metal-adapted populations of the terrestrial isopod Porcellio scaber.
Organisms inhabiting metal-contaminated areas can be stressed by metal exposure and are possibly subject to selection, resulting in increased metal tolerance and changes in growth and/or reproduction characteristics. In a previous study it was found that in the terrestrial isopod Porcellio scaber, sampled from the vicinity of a zine smelter, the body size was small and the brood size was large compared to isopods from a reference area. To assess whether these differences were due to genetic differentiation between strains, isopods collected from a reference wood, a zinc smelter area and a lead mine were cultured on non-polluted food, while growth, reproduction and metal concentrations were studied in first and second laboratory generations. The isopods from the three populations differed in age and weight at first reproduction, although there were hardly any differences in growth. The females of the mine and the smelter population started to reproduce earlier, at a lower weight, which resulted in fewer young per female. However, reproductive allocation (=wight of young relative to the weight of the mother) was higher in mine and smelter isopods. We conclude that the isopods at the metal-contaminated sites have been selected for early reproduction and increased reproductive allocation. The results indicate that populations inhabiting metal-polluted sites have probably undergone evolutionary changes. This study showed that growth and reproduction characteristics of different populations under laboratory conditions may provide information on selection processes in the field.


Noninvasive monitoring of hormones in bird droppings: physiological validation, sampling, extraction, sex differences, and the influence of diet on hormone metabolite levels.
During the past several years, the noninvasive measurement of steroid metabolites from mammalian feces and bird droppings has become more and more popular. With an increasing acceptance of the method, investigators may become less aware of the need to validate their assays. It is shown why such validations are essential for each new species investigated and various ways to physiologically validate such noninvasive methods are described. Using the European stonechat (Saxicola torquata rubicola) as a model, it is explained why a validated method to measure androgen metabolites in males does not necessarily work in females. In addition the difficulties that may be neglected owing to the superficial ease of sampling and processing of excreta are investigated. Various issues that may arise during sampling, storage, and extraction of excreta are addressed. Finally, results suggesting that experimental manipulations of the diet may affect hormone metabolite levels in European stonechats are presented. So far, only a few studies have investigated the impact of diet on hormone metabolite levels, and these are the first data to report such an impact in birds. More studies are urgently needed to learn more about differences between the sexes, individuals, and populations and the impact of diet and energy metabolism on hormone metabolites.


A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.
The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.


Can wind farms change the phenology of grassland in China?
Wind energy has attracted worldwide attention as a clean energy source and wind farms are rapidly increasing in number. However, operation of wind farms can affect the local climate and, consequently, local vegetation phenology. Hence, the influence of wind farms on phenology needs to be understood. In this paper, we use remote sensing MOD09GQ data to calculate phenological indexes of vegetation near a large wind farm in a semi-arid grassland area of Inner Mongolia, China. The vegetation phenology before and wind farm construction is compared, with a control area used to account for long-term climate change. The results show that the wind farm extended the growing season of vegetation in areas upwind and downwind of the wind farm. In the prevailing wind direction, the growing season was extended by 11.7 days within 4 km of the wind farm in the upwind area, by 10.0 days within the wind farm, and by 5.5 days within 4 km of the wind farm in the downwind area. The extension of the growing season is due to an earlier start of the growing season, which was mainly influenced by increases in local land surface temperatures. And such an extension will increase the evaporation from vegetation transpiration in study area, which is very likely to bring about decreases in soil moisture here. Such effects should be considered when assessing the ecological impacts of planned wind farms.


Physicochemical characteristics of the Dombrovska pit lake (Ukraine) formed in an opencast potassium salt mine and the genome response of Chironomus salinarius Kieffer (Chironomidae, Diptera) to these conditions.
This study focuses on the Dombrovska pit lake, near the city of Kalush in Ukraine, which is a former potassium salt mine filled with brine and freshwater. The water level is still increasing and as a result the salinity is decreasing. We analyzed the benthic fauna communities and the genome instability by assessing the rearrangements in the polytene chromosomes of Chironomus salinarius and the physicochemical parameters of the near-bottom water (pH, conductivity, mineralization, major ions, NO3-, NH4+, metals Cd, Pb, Cu, Mn, and Fe) and sediment (pH, organic matter and metals Cd, Pb, Cu, Zn, Mn, and Fe) at four sites. The water mineralization ranged from 17.3 to 26.2 g dm-3 which are classified as mesohaline and polyhaline waters, respectively. The biodiversity of the benthic fauna was low, and the dominant species was C. salinarius. The density of C. salinarius varied spatially and changed from 637 ind./m2 at a depth of 5 m to 8167 ind./m2 at a depth of 2.5 m. The genome instability was analyzed by examining the structural and functional changes in the salivary gland chromosomes of C. salinarius. The exposure of C. salinarius damaged the chromosomes and the activities of key structures, such as the Balbiani ring and nucleolar organizer, were partially or completely suppressed.


Association between polymorphism of SMAD3 gene and risk of sporadic intracranial arterial aneurysms in the Chinese Han population.
Intracranial arterial aneurysms (IAAs) are locally abnormal dilations of the cerebral arteries and often result in subarachnoid hemorrhages (SAH). Genetic, molecular and cellular mechanisms of sporadic IAAs forms are poorly understood. In this study, we investigate the association between mothers against decapentaplegic homolog 3 (SMAD3) genotypes and the risk of sporadic intracranial arterial aneurysms among the Chinese Han population. A case-control study was conducted examining 330 IAA patients and 313 controls. There were eight single nucleotide polymorphisms of SMAD3 selected and genotyped using the polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Our results indicated that SMAD3 rs1065080 polymorphism was associated with a risk of IAAs in a codominant model (GA vs GG, OR=1.433; 95% CI 1.030-1.994; P=0.032). In summary, we observed that SMAD3 rs1065080 single nucleotide gene polymorphisms were significantly associated with patient susceptibility to IAAs.


Managemental influences on the selective proliferation of two strains of haemolytic Escherichia coli in weaned pigs.
In an experimental study on a piggery it was found that haemolytic Escherichia coli of O-serotypes 138 or 139 proliferated in the intestinal tracts of pigs following weaning, with E. coli of the O-138 type also being occasionally recovered from unweaned pigs, and once from a sow. Organisms of the O-138 type produced heat labile enterotoxin and their presence in weaned pigs was associated with the development of severe post-weaning diarrhoea. E. coli of O-139 type produced a vero cell cytotoxin and were associated with a milder diarrhoea in weaned pigs. Under various managemental circumstances the O-138 type E. coli almost invariably proliferated after weaning. The O-139 strain of E. coli did however proliferate rather than the O-138 strain following the movement of weaned pigs to new accommodation, after weaned pigs were returned to their sow and then weaning again 5 days later, and very occasionally in pigs weaned at 5 weeks of age. In all these cases earlier proliferation of the O-138 E. coli had been detected, suggesting that this may be a prerequisite for proliferation of the O-139 strain.


[Chronic bilateral orbital tumors in IgG4-related disease].
The IgG4-related disease describes a new multisystem disorder, which can also be manifested in the orbit. This syndrome is characterized by a multifocal chronic fibroinflammation with high levels of plasma cells expressing IgG4. This article reports the case of a patient with advanced bilateral tumors of the upper eyelid and orbit. The diagnosis of IgG4-related disease was only revealed after many years and after many biopsies of the tumors had been carried out. The initiation of a systemic steroid therapy led to a rapid reduction of the tumors and an improvement in the general condition of the patient.


A call to readjust the Israeli school feeding program.
The COVID-19 pandemic challenged the food and nutrition security status of thousands of children in Israel. This commentary argues that policymakers should urgently readjust the Israeli school feeding program based on experts' advice. Children should have the right to select food items, grow the items, prepare the meals, and clean and care for the waste together. They should eat as a community in suitable school dining rooms. Access to the school feeding program should also be ensured during emergencies, school closures, isolation and quarantine, treatment, and rehabilitation of children. The food provided through the program should be integrated into the food baskets of their families, aimed at improving their households' food and nutrition security. It is important to activate a universal school feeding program that does not differentiate, separate, and stigmatize children, their households, their communities, and their schools. The United States National School Lunch Program is briefly reviewed, highlighting the importance of the program's routine monitoring, evaluation, and improvement. Engaging the children in planning the meals and in the production, preparedness, provision, and waste management processes are key to improving their involvement, health literacy and promotion, and their families' resilience. Implementing a holistic Food System Approach, including school gardening and "Farm to School," is suggested. It is recommended to urgently formulate a modern, universal, and comprehensive Israeli Food and Nutrition Security Plan, with a dedicated chapter for the upgraded School Feeding Programe with a section on its implementation in emergency preparedness, response, and Resilience. It should be anchored in the Food Systems framework and the One Health Approach.


On the mechanism of stimulation of H+ transport in gastric mucosa by Ca++ ionophore A23187. II. Ca++-cyclic AMP interactions.
The possibility of interactions between calcium and cyclic AMP (cAMP) in the mechanism of stimulation of H+ transport by A23187 was studied in the isolated gastric mucosa of the toad Bufo marinus. A23187 stimulated H+ secretion and histamine release. The amount of histamine released by A23187 did not explain the degree of stimulation. Metiamide partially inhibited the response to A23187. Ca++ ionophore produced an overstimulation of secretion after H+ transport had been induced by supramaximal effective concentrations of histamine (10-4 M). In the presence of metiamide, IMX potentiated the response to A23187. Also, in the same condition (metiamide treated) the effects of db-cAMP and A23187 were additive. The results are consistent with an interaction between Ca++ and ionophore-released histamine at the oxyntic cell in the stimulation by A23187. The stimulatory response may be the result of a potentiation between calcium and cAMP at the intracellular level.


Differences in phosphorylation of phosphoglucomutase 1 in beef steaks from the longissimus dorsi with high or low star probe values.
The objective of this study was to use proteomics to identify alterations of proteins that are related to tenderness. The longissimus dorsi (LD) were removed from ten beef carcasses at 24 h postmortem, and the two with the highest (HSP; average kg of force=6.57) and lowest star probe values (LSP; average kg of force=3.75) at 14 days postmortem were identified. Two-dimensional PAGE was used to compare the sarcoplasmic fraction of the LD from HSP and LSP steaks. A series of spots identified as phosphoglucomutase 1 (PGM1) were identified. Only the most alkaline isoform was identified as being unphosphorylated. The least phosphorylated isoform (isoform 5) had a greater density of the total protein (P<0.05) and phosphorylated protein (P<0.05) in the samples from HSP steaks compared to the samples from LSP steaks. This study illustrates the importance of identifying posttranslational modifications of proteins in the search for biomarkers.


Mortalization of human promyelocytic leukemia HL-60 cells to be more susceptible to sodium butyrate-induced apoptosis and inhibition of telomerase activity by down-regulation of nucleophosmin/B23.
Vanadate (10 microM), a potent inhibitor of tyrosine phosphatase, added simultaneously potentiated BuONa-induced (1 mM) apoptosis. The steady-state level of nucleophosmin/B23 mRNA and the total cellular nucleophosmin/B23 protein decreased during the BuONa/vanadate-induced apoptosis. Stabilization and promotor transcriptional activity assays indicate that the decrease in nucleophosmin/B23 mRNA in BuONa/vanadate-treated HL-60 cells was transcriptionally regulated. A decline in telomerase activity was observed in HL-60 cells treated with BuONa/vanadate for 24-96 h. There was virtually no decline of nucleophosmin/B23 mRNA nor the telomerase activities during the growth arrest by serum-starvation. The decrease in nucleophosmin/B23 mRNA expression and telomerase activity in HL-60 cells subsequent to BuONa/vanadate treatment can thus be attributed to cellular apoptosis rather than the growth arrest induced by BuONa/vanadate. Nucleophosmin/B23 antisense oligomer treatment significantly potentiated BuONa-induced apoptosis and inhibition of telomerase activity. Results of this study suggest that nucleophosmin/B23 is one of the key elements in the down-regulation of nucleolar function for cellular apoptosis and mortalization.


Evidence for therapeutic intervention in the prevention of cerebral palsy: hope from animal model research.
Knowledge translation, as defined by the Canadian Institute of Health Research, is defined as the exchange, synthesis, and ethically sound application of knowledge--within a complex system of interactions among researchers and users--to accelerate the capture of the benefits of research through improved health, more effective services and products, and a strengthened healthcare system. The requirement for this to occur lies in the ability to continue to determine mechanistic actions at the molecular level, to understand how they fit at the in vitro and in vivo levels, and for disease states, to determine their safety, efficacy, and long-term potential at the preclinical animal model level. In this regard, particularly as it relates to long-term disabilities such as cerebral palsy that begin in utero, but only express their full effect in adulthood, animal models must be used to understand and rapidly evaluate mechanisms of injury and therapeutic interventions. In this review, we hope to provide the reader with a background of animal data upon which therapeutic interventions for the prevention and treatment of cerebral palsy, benefit this community, and increasingly do so in the future.


Sailing the Seven Seas: A Multinational Comparison of ChatGPT's Performance on Medical Licensing Examinations.
The use of AI-powered technology, particularly OpenAI's ChatGPT, holds significant potential to reshape healthcare and medical education. Despite existing studies on the performance of ChatGPT in medical licensing examinations across different nations, a comprehensive, multinational analysis using rigorous methodology is currently lacking. Our study sought to address this gap by evaluating the performance of ChatGPT on six different national medical licensing exams and investigating the relationship between test question length and ChatGPT's accuracy. We manually inputted a total of 1,800 test questions (300 each from US, Italian, French, Spanish, UK, and Indian medical licensing examination) into ChatGPT, and recorded the accuracy of its responses. We found significant variance in ChatGPT's test accuracy across different countries, with the highest accuracy seen in the Italian examination (73% correct answers) and the lowest in the French examination (22% correct answers). Interestingly, question length correlated with ChatGPT's performance in the Italian and French state examinations only. In addition, the study revealed that questions requiring multiple correct answers, as seen in the French examination, posed a greater challenge to ChatGPT. Our findings underscore the need for future research to further delineate ChatGPT's strengths and limitations in medical test-taking across additional countries and to develop guidelines to prevent AI-assisted cheating in medical examinations.


Nurse mentored, student research in undergraduate nursing education to support evidence-based practice: A pilot study.
The aim was to investigate if an extracurricular research skills development program builds the knowledge, attitudes, and skills (KAS) to support evidence-based practice (EBP). Twenty nursing students and six mentors in four teams completed small, student-led research projects over 1 year. Using a mixed-methods design, the knowledge, attitudes, and practice (KAP) survey was administered at three-time points, followed by qualitative interviews. A linear mixed-effects regression model was used to analyze survey data and thematic analysis for qualitative data. The change from the KAP survey from the first to the third time point showed a statistically significant difference following engagement in the program. Qualitative data indicated benefits and challenges to participation for both students and mentors. Mentorship provided students with improved relationships, collaboration, and leadership skills. Students believed the program enhanced their understanding of research and reported increased confidence in using EBP. Offering students innovative first-hand experiences with research develops research KAS to support EBP.


[Treatment of patients with malignant tumors of organs in the pancreaticobiliary zone complicated by the development of emergency situations].
The results of surgical treatment of patients with cancer of the gallbladder (23), extrahepatic bile ducts (16), pancreas (28), major duodenal papilla (10), with tumour metastases in the liver (10), who developed, as a consequence of the tumour process progression, acute abdominal conditions--inflammatory syndrome, increasing jaundice, high ileus and hemorrhage are analysed. Emergency operative interventions were directed at solving the urgent situations and had, mainly, the palliative character. After the operation, 16 (21%) patients died.


Systematic review and meta-analysis of the effect of bipolar electrocoagulation during laparoscopic ovarian endometrioma stripping on ovarian reserve.
Laparoscopic stripping is the gold-standard treatment for ovarian endometriosis. The choice of hemostasis method might affect ovarian reserve. To determine whether bipolar electrocoagulation is more detrimental to ovarian reserve than non-thermal hemostasis methods. Entry terms associated with the MeSH terms "endometrioma," "laparoscopy," and "ovarian reserve" were used to search databases for articles published up to April 3, 2017, in English, Spanish, Portuguese, French, and Italian. Randomized controlled trials comparing the 3-month postoperative serum anti-Müllerian hormone (AMH) level in premenopausal women undergoing laparoscopic stripping with bipolar hemostasis or non-thermal hemostasis methods were selected. Data were extracted by two independent reviewers and a meta-analysis was performed. Three studies met the inclusion criteria; overall, 105 patients underwent surgery with bipolar electrocoagulation and 105 patients underwent surgery with an alternative hemostasis method. The AMH level 3 months after surgery was decreased in the bipolar electrocoagulation group (mean difference -0.79 ng/mL, 95% confidence interval -1.19 to -0.39). Bipolar electrocoagulation negatively impacts ovarian reserve and should be avoided, especially for patients with reproductive goals.


Adherence to an Injury Prevention Warm-Up Program in Children's Soccer-A Secondary Analysis of a Randomized Controlled Trial.
This study examined the impact of high adherence to a neuromuscular training (NMT) warm-up on the risk of lower extremity (LE) injuries in children's soccer. Twenty U11-U14 youth clubs (n = 92 teams, 1409 players) were randomized into intervention (n = 44 teams) and control (n = 48 teams) groups. The intervention group was advised to perform an NMT warm-up 2 to 3 times a week for 20 weeks. Team adherence, injuries, and exposure were registered throughout the follow-up. Primary outcomes were the incidence of soccer-related acute LE injuries and the prevalence of overuse LE injuries. Intervention teams conducted mean 1.7 (SD 1.0) NMT warm-ups weekly through follow-up. The seasonal trend for adherence declined significantly by -1.9% (95% CI -0.8% to -3.1%) a week. There was no difference in the incidence of acute injuries nor the prevalence of overuse LE injuries in high team adherence group (n = 17 teams) compared to controls. However, the risk for acute noncontact LE injuries was 31% lower in the high team adherence group compared to controls (IRR 0.69, 95% CI 0.49 to 0.97). In an efficacy analysis (n = 7 teams), there was a significant reduction of 47% in the rate of noncontact LE injuries (IRR 0.53, 95% CI 0.29 to 0.97). In conclusion, teams conducted NMT warm-up sessions regularly, but with a declining trend. A greater protective effect was seen in teams with the highest adherence to the NMT warm-up.


Remarkable promotion effect of trace sulfation on OMS-2 nanorod catalysts for the catalytic combustion of ethanol.
OMS-2 nanorod catalysts were synthesized by a hydrothermal redox reaction method using MnSO4 (OMS-2-SO4) and Mn(CH3COO)2 (OMS-2-AC) as precursors. SO4(2-)-doped OMS-2-AC catalysts with different SO4(2-) concentrations were prepared next by adding (NH4)2SO4 solution into OMS-2-AC samples to investigate the effect of the anion SO4(2-) on the OMS-2-AC catalyst. All catalysts were then tested for the catalytic oxidation of ethanol. The OMS-2-SO4 catalyst synthesized demonstrated much better activity than OMS-2-AC. The SO4(2-) doping greatly influenced the activity of the OMS-2-AC catalyst, with a dramatic promotion of activity for suitable concentration of SO4(2-) (SO4/catalyst=0.5% W/W). The samples were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), inductively coupled plasma optical emission spectroscopy (ICP-OES), NH3-TPD and H2-TPR techniques. The results showed that the presence of a suitable amount of SO4(2-) species in the OMS-2-AC catalyst could decrease the Mn-O bond strength and also enhance the lattice oxygen and acid site concentrations, which then effectively promoted the catalytic activity of OMS-2-AC toward ethanol oxidation. Thus it was confirmed that the better catalytic performance of OMS-2-SO4 compared to OMS-2-AC is due to the presence of some residual SO4(2-) species in OMS-2-SO4 samples.


Association between flexibility activity and blood-pressure change among older adults in Japan: A 5-year longitudinal study.
This longitudinal study examined the relationship between flexibility-activity and blood-pressure (BP) change among older adults in Japan. Our study included 452 older adults who took part in our survey in both 2012/2013 and 2017/2018. The seated systolic blood pressure (SBP) and diastolic BP (DBP) were measured both at baseline and at the 5 years follow-up. The frequencies of the different physical activities at baseline were assessed using a questionnaire. A generalized linear mixed model was used to estimate the non-standardized coefficient (B) of BP change associated with flexibility activity, after adjustments for sex, age, body mass index, smoking status, alcohol consumption, antihypertensive medication use, history of heart disease, walking time, and muscle-strengthening activity as a fixed-effect, and area of residence as a random-effect. Higher flexibility-activity frequency was significantly associated with reduced SBP (B = -0.77 [95% confidence intervals = -1.36, -0.18], p for linear trend = 0.01, p for quadratic trend = 0.85) and DBP (-0.33 [-0.71, 0.05], p for linear trend = 0.09, p for quadratic trend = 0.04). Engaging in flexibility activity for 3 days per week was significantly associated with a reduction in DBP (B = -4.16, 95% CI [-7.53, -0.79], p = 0.02) compared with that in the reference group (0 days per week). Interaction tests were not significant between basic variables (sex, age, BMI, and antihypertensive medication) and flexibility. In conclusion, higher flexibility activity frequency was associated with a reduction in BP in older adults. Future longitudinal and interventional studies should examine the effects of flexibility activity on cardiovascular disease prevention.


Management of sustained arrhythmias for patients with cardiogenic shock in intensive cardiac care units.
Cardiac arrhythmias that occur in patients referred to intensive care units worsen symptoms and outcomes and need urgent correction, especially in patients admitted for refractory heart failure. Electrical storm is a frequent reason for referral to an intensive care unit. Specific, efficient and rapid management of patients presenting with various arrhythmias is therefore mandatory and procedures should be known by any physician involved in an intensive care unit. This article reviews the current knowledge on the management of supraventricular and ventricular arrhythmias in this setting, from medications and sedation to ablation and more exceptional therapy. It also covers the occasional indications of resynchronization in refractory heart failure and the interest for haemodynamic assistance when specific therapy fails.


Butorphanol.
Butorphanol (Stadol) is a synthetic agonist-antagonist analgesic from the 14-hydroxymorphinan series. Animal studies display analgesia, antitussive effects, low gastrointestinal activity, limited respiratory depression, some cardiovascular and skeletal muscle actions, diuresis, slight miosis and opiate antagonism. Butorphanol is metabolized in the liver with renal excretion, yielding a half-life of 3-4 h. Pain relief is good to excellent with parenteral administration in 90% of patients with moderate to severe pain. Surgical anesthetic indications involve preoperative and preinduction supplementation, balanced anesthesia and postoperative pain. Side effects are sedation, nausea, elevated pulmonary vascular pressures and rarely CNS excitation. Limited respiratory depression exists. Butorphanol is a potent analgesic agent with a favorable side effect profile.


Assessment of neuroprotection in the retina with DARC.
Currently, assessment of new drug efficacy in glaucoma relies on conventional perimetry to monitor visual field changes. However, visual field defects cannot be detected until 20-40% of retinal ganglion cells (RGCs), the key cells implicated in the development of irreversible blindness in glaucoma, have been lost. We have recently developed a new, noninvasive real-time imaging technology, which is named DARC (detection of apoptosing retinal cells), to visualize single RGC undergoing apoptosis, the earliest sign of glaucoma. Utilizing fluorescently labeled annexin 5 and confocal laser scanning ophthalmoscopy, DARC enables evaluation of treatment effectiveness by monitoring RGC apoptosis in the same living eye over time. Using DARC, we have assessed different neuroprotective therapies in glaucoma-related animal models and demonstrated DARC to be a useful tool in screening neuroprotective strategies. DARC will potentially provide a meaningful clinical end point that is based on the direct assessment of the RGC death process, not only being useful in assessing treatment efficacy, but also leading to the early identification of patients with glaucoma. Clinical trials of DARC in glaucoma patients are due to start in 2008.


Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium.
Six new coumarins, schinicoumarin, acetoxyaurapten, epoxycollinin, schininallylol, schinilenol and schinindiol, along with seven known coumarins, aurapten, collinin, epoxyaurapten, hydrangetin, umbelliferone, acetoxycollinin and aesculetin dimethyl ether, three known alkaloids, norchelerythrine, dictamnine and skimmianine, and two triterpenoids, beta-amyrin and friedelin, were isolated and characterized from the chloroform-soluble part of the bark of Zanthoxylum schinifolium. The structures of these compounds were elucidated by spectral analyses. Separation accompanied by bioassay-guided fractionation resulted in the isolation of seven compounds with strong inhibitory activity on platelet aggregation in vitro. These are schinicoumarin, acetoxyaurapten, schininallylol, aurapten, collinin, (-)-acetoxycollinin and dictamnine.