Differential effects of inflammation models on rat T-kininogen and rat angiotensinogen.
The effect of different experimental models of inflammation on plasma concentrations of T-kininogen and angiotensinogen was examined in the rat. T-kininogen, a major phase protein which inhibits cysteine proteinase is increased in all cases of induced inflammation: administration of lipopolysaccharide and turpentine, bilateral nephrectomy or sham-operation and intraperitoneal injection of peanut oil. Angiotensinogen, the renin-substrate, is increased by lipopolysaccharide but is decreased by turpentine. Sham-operation or peanut oil injection have no effect on angiotensinogen whereas, bilateral nephrectomy and dexamethasone increase its concentration. Therefore, angiotensinogen is regulated differently than T-kininogen during inflammation.


In vitro effect of light-emitting diode light polymerization on the color stability of three resin-based restorative materials.
To investigate the color stability of resin-based restorative materials when polymerized with light-emitting diode (LED) curing light in the constant or exponential mode. Eight specimens of Admira (AD), Compoglass F (CO), and Tetric EvoCeram (TE) constantly cured or exponentially cured with a high-powered LED curing light for 10, 20, or 60 s. The CIE-Lab values (L*, a*, b*) were measured prior to and after performing the water storage or color stability test according to EN ISO 7491 (Suntest). Statistical analysis showed significant changes in the color values after each of the aging processes, as well as between DeltaL, Deltaa, Deltab, and DeltaE of the materials, which were dependent on curing time, mode, and aging condition (p<0.05). CO performed very well during water storage, but AD and TE exceeded the clinically relevant limit DeltaE=1. After the Suntest and 180 d additional water storage, TE showed the highest mean (SD) DeltaE=4.4 (1.1) to 5.4 (1.9). Although AD and CO performed best in the constant mode, they exceeded DeltaE=1. All materials shifted to more red. The extent of discoloration depended on (a) the curing mode, (b) the curing time, and (c) the aging condition. Not all materials performed clinically acceptably in all tests; TE even showed unacceptable DeltaE>3.3. The optimal curing time was 20 s for both curing modes and all tested materials.


Removal of dye by carboxymethyl cellulose, acrylamide and graphene oxide via a free radical polymerization process.
Carboxymethyl cellulose has been used for the design of novel engineered hydrogels in order to obtain effective three-dimensional structures for industrial applications. In this work, dye removal carboxymethyl cellulose-acrylamide-graphene oxide (CMC-AM-GO) hydrogels were prepared by a free-radical polymerization method. The GO was developed by the modified Hummers method. The CMC-AM-GO and GO were characterized by FTIR, XRD and SEM. The swelling and swelling kinetics were calculated using gravimetric process. The kinetic parameter, swelling exponent values [n=0.59-0.7507] explained the fact that the CMC-AM-GO hydrogles have super Case II diffusion transport mechanism. CMCx-AM-GO (x=1-4) and CMC-AM hydrogels were used for removal of Acid Blue-133. The result explains that composite hydrogels significantly removed the acid blue when compared to the neat hydrogel. The maximum AB absorption (185.45mg/g) capacity was found in the case of CMC2-AM-GO hydrogel. Therefore, cellulose-based GO hydrogels can be termed as smart systems for the abstraction of dye in water purification applications.


Synthesis, single crystal and antitumor activities of benzimidazole-quinazoline hybrids.
A series of novel regioisomeric hybrids of quinazoline/benzimidazole viz. (3-allyl-2-methyl-3H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine and (1-allyl-2-methyl-1H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine of biological interest were synthesized. All the synthesized compounds were well characterized by (1)H and (13)C NMR as well as mass spectroscopy. The newly synthesized compounds were screened for in vitro antitumor activities against 60 tumor cell lines panel assay. A significant inhibition for cancer cells were observed with compound 9 and also more active against known drug 5-fluorouracil (5-FU) in some tumor cell lines. Compound 9 displayed appreciable anticancer activity against leukemia, colon, melanoma, renal and breast cancer cell lines.


Lyophilized royal jelly preparation in nanoscale and evaluation of its physicochemical properties and bactericidal activity.
Royal jelly, due to its unique bioactive components, has special biological activities, but a great extent of its nutritional value is lost during processing and storage. Lyophilization, an effective preservation technique, can feasibly preserve the main bioactive compounds present in royal jelly. In this study, fresh royal jelly was subjected to the freeze-drying process at a pressure and temperature of 100 Pa and - 70°C, respectively, for 40 h. The results obtained indicated that the pH, turbidity, total phenol content, and antioxidant activity of the royal jelly powder (RJP), during 3 months of storage at ambient temperature (30°C), were constant with values of 4.30, 1.634 (%A.U.), 0.617 (g/L), and 28.7 (%), respectively. Moisture content of the prepared RJP was less than 1%, while that of the fresh royal jelly was 70%. Furthermore, for the fresh royal jelly, the mentioned parameters were significantly (p < .05) decreased after 2 months of storage at freezer temperature (-20°C). GC-MS analysis indicated that the amount of 10-hydroxy-2-decanoic acid (10H2DA) in RJP was 3.85 times more than that of fresh royal jelly. The obtained results also indicated that prepared RJP had a high bactericidal effect toward Escherichia coli and Staphylococcus aureus, with clear zone diameters of 12 and 15 mm, respectively. The present study provides a foundation for research on the potential application of prepared RJP and the development of dietary supplements and functional foods.


In Vitro Susceptibility Profiles of Eight Antifungal Drugs against Clinical and Environmental Strains of Phaeoacremonium.
In vitro susceptibilities of a worldwide collection of molecularly identified Phaeoacremonium strains (n = 43) belonging to seven species and originating from human and environmental sources were determined for eight antifungal drugs. Voriconazole had the lowest geometric mean MIC (0.35 μg/ml), followed by posaconazole (0.37 μg/ml), amphotericin B (0.4 μg/ml), and isavuconazole (1.16 μg/ml). Caspofungin, anidulafungin, fluconazole, and itraconazole had no activity.


Retracted: A Novel CircRNA Circ_0095424 Regulates Proliferation, Metastasis, and Apoptosis of Osteosarcoma Cells Via the PI3K/AKT Signaling Pathway Through Targeting the miR-1238/HMGB1 Axis.
Cancer Biotherapy and Radiopharmaceuticals is officially retracting the article entitled, A Novel CircRNA Circ_0095424 Regulates Proliferation, Metastasis, and Apoptosis of Osteosarcoma Cells Via the PI3K/AKT Signaling Pathway Through Targeting the miR-1238/HMGB1 Axis by Zhang et al., (Cancer Biother Radiopharm epub 19 Aug 2020; DOI: 10.1089/cbr.2020.3563), due to manipulated images appearing in the published paper. The Editor of the journal received an email on August 31, 2020 from the corresponding author of the article, Dr. Chuan Qin, indicating that, ''due to our negligence in organizing the pictures, the protein pictures are repeatedly placed in Figure 7G PI3K. For this, we express our sincerest apologies. We need to [issue] an [erratum] on this issue. We have replaced the protein picture of Figure 7G with the correct picture.'' However, one of the attachments submitted with the request appeared to be the original version of Figure 7 from the accepted manuscript. A second attachment appeared to be the data from three replicates to be used (by the journal) to construct a revised version of Figure 7. The Editor, in turn, informed the authors that it was not at the journal's discretion to create a new image for them, and asked the authors to create the revised figure and supply it to the publisher. Below is the response from Dr. Qin, dated September 2, 2020. "In fact, our team's Western blot experiment commissioned a third-party company for testing. At present, some peers have found that the company has forged experimental reports. We believe that the authenticity of the data provided by the company is problematic. After contacting the company, they were unable to provide the original images. In view of the problems in this manuscript, all the authors discussed and agreed to withdraw the manuscript." As the entirety of the situation is unacceptable, the Editor officially retracts the article based on the "forged experimental reports" and the questionable validity of the data provided. The Editor and Publisher of Cancer Biotherapy and Radiopharmaceuticals is dedicated to preserving the integrity of the scientific literature and the community it serves.


Effects of n-3 and n-6 feeding sources on the quality and lipid oxidation of meat from feedlot-finished Bos indicus steers.
This study was conducted to evaluate the fatty acid profile, sensory properties and lipid oxidation of meat on retail display (RD) from Nellore steers (n = 96) fed diets containing soybean (SOY), sunflower (SUN), or linseed (LIN) oil or a control diet (CON). After slaughtering, samples of the Longissimus muscle were collected for sensory properties (1 day), fatty acid composition (1 day) and oxidation stability (3 days under RDC) evaluations. No differences in total lipids, cholesterol, TBARS, and total SFAs, MUFAs, PUFAs, and PUFA/SFA were observed. However, meat from animals fed vegetable oil had more CLA than that of the CON samples. The flavour, juiciness and overall acceptability were affected by the treatments (P < 0.05), but no consistent effect of a specific oil source was observed. Meat colour was not affected by diets or days under RD, and 7-ketocholesterol was not detected in any sample. The oil sources used in this work were not effective in consistently changing meat properties.


Images, image quality and observer performance: new horizons in radiology lecture.
Technical and diagnostic image quality are distinguished and the limitations of three methods currently used for assessing diagnostic image quality are discussed. They are evaluations based on individual clinical experience, measurement of diagnostic performance, and physical measurements made on images or imaging systems. Finally, a psychophysical approach to image quality evaluation is presented and its potential value discussed.


[Expression of VP1 gene and ELISA detection of antibodies against duck hepatitis virus].
We developed an indirect enzyme-linked immunosorbent assay (ELISA) by the recombinant VP1 protein of duck hepatitis virus (DHV) expressed in Escherichia coli to detect antibodies against DHV. The VP1 gene of DHV was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into pMD18-T and pET-32a vectors to get a prokaryotic expression vector pET-32a-VP1. DHV VP1 gene was expressed and analyzed. A method of enzyme-linked immunosorbent assay (ELISA) was developed and studied. We obtained the recombinant plasmid pET-32a-VP1 with correct sequence and orientation. DHV VP1 gene was expressed in E. coli BL21 (DE3) at a high level and had good immunoreactivity by SDS-PAGE and western blot. The optimum working concentration of antigen was 5.0 microg in 100 microL per well, the working concentration of serum samples was 1 : 100 dilution and the critical value was OD450 > or = 0.302 for the ELISA assay. The rate of coincidence of ELISA and virus neutralization test (VN) was 97.5% by detecting 80 serum samples. The method was specific, sensitive and could be applied for antibody detection of maternal antibody and the rule of antibody growth and decline in immunizing ducklings. The ELISA method developed by the purified recombinant protein could be used to detect antibodies against DHV.


Fractionated radiation therapy in the treatment of intracranial meningiomas: local control, functional efficacy, and tolerance in 91 patients.
To evaluate efficacy and tolerance of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. From January 1981 to September 1993, 91 patients with intracranial meningiomas were treated with fractionated RT. Indications were as follows: (a) incomplete surgical resection, 29 patients; (b) tumor recurrences without considering the amount of the second resection, if performed, 14 patients; (c) completely excised angioblastic, aggressive benign, and anaplastic tumors, 8 patients; (d) medically inoperable and basilar tumors where operation would involve considerable danger or permanent neurological damage, 44 patients. Most patients were irradiated with 6 to 9 MV photon beams. A three- to four-field technique with coned-down portals was used. Doses were calculated on the 95% isodose and were given 5 days a week for a median total dose of 52 Gy (1.80 Gy/fraction). Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent, but there were six late delayed injuries. Tumor recurrences occurred in six cases. Six patients died from their tumor or RT complications, 19 from nontumoral reasons. Three, 5- and 10-year survival rates were 82, 71, and 40%, respectively. The most significant prognostic factor was age: 5-year survival rate was 86% for patients less than 65 years and 37% for patients more than 65. However, there were no differences in recurrence-free survival rates between patients younger than 65 and the oldest ones. Of 60 symptomatic patients with neurological deficits, 43 had neurological improvement (72%), beginning in some cases within 15 to 20 days after starting RT. These results reassess the role of fractionated RT in the treatment of meningiomas, and stress on its efficacy, especially on cranial nerves palsies, without severe toxicity in most cases.


Regulation of AMPA receptor subunit GluA1 surface expression by PAK3 phosphorylation.
AMPA receptors (AMPARs) are the major excitatory receptors of the brain and are fundamental to synaptic plasticity, memory, and cognition. Dynamic recycling of AMPARs in neurons is regulated through several types of posttranslational modification, including phosphorylation. Here, we identify a previously unidentified signal transduction cascade that modulates phosphorylation of serine residue 863 (S863) in the GluA1 AMPAR subunit and controls surface trafficking of GluA1 in neurons. Activation of the EphR-Ephrin signal transduction pathway enhances S863 phosphorylation. Further, EphB2 can interact with Zizimin1, a guanine-nucleotide exchange factor that activates Cdc42 and stimulates S863 phosphorylation in neurons. Among the numerous targets downstream of Cdc42, we determined that the p21-activated kinase-3 (PAK3) phosphorylates S863 in vitro. Moreover, specific loss of PAK3 expression and pharmacological inhibition of PAK both disrupt activity-dependent phosphorylation of S863 in cortical neurons. EphB2, Cdc42, and PAKs are broadly capable of controlling dendritic spine formation and synaptic plasticity and are implicated in multiple cognitive disorders. Collectively, these data delineate a novel signal cascade regulating AMPAR trafficking that may contribute to the molecular mechanisms that govern learning and cognition.


Development of solid-phase microextraction fibers based on multi-walled carbon nanotubes for pre-concentration and analysis of alkanes in human breath.
In this work, a laboratory preparation method based on sol-gel technology was proposed to develop a new kind of SPME (solid phase microextraction) fibers. Multi-walled carbon nanotubes (MWCNT) were selected as sol-gel active organic component. Stainless steel wires were used as the substrate of the fibers. Instead of traditional modification methods, microwave induced plasma was used to modify the stainless steel wire surface, resulting in a significant improvement in chemical adhesion of the fiber substrate and coating. The MWCNT coating exhibited several good properties. Acceptable fiber-to-fiber reproducibility (RSD≤13%) and repeatability (RSD<7%) were obtained. End-tidal breath of 10 normal humans were collected by Bio-VOC(®) sampler and assayed by the optimized SPME-GC-MS method. The calibration curves were all linear (R(2)≥0.994) in the range from 0.03 to 403.3ppbv for five alkanes. Detection limits (down to 0.001ppbv) were about one order of magnitude better than those of commercial PDMS fibers. The recovery of the spiked alkanes in real breath sample at 1ppbv ranged from 89.71 to 101.08% and the relative standard deviations were less than 8%. These results demonstrated the feasibility and practicality of the proposed preparation procedure. Applications of the in-house fabricated fibers for human breath analysis were successfully verified.


Endocrine late effects from multi-modality treatment of neuroblastoma.
Thyroid dysfunction has been reported after 131I-MIBG-treatment for neuroblastoma. In this study, we have evaluated all endocrine functions from patients who were given multi-modality treatment including 131I-MIBG. Twenty-five neuroblastoma survivors who were off therapy for a median period of 6.0 years (range 1.3-11.1) were evaluated and their median age was 8.1 years (range 2.2-14.7). All patients had received 131I-MIBG, 16 chemotherapy, and 16 surgery. Fourteen patients (56%) had permanently elevated thyrotropin levels and 9 received thyroxine. Two patients had a small thyroid volume while 6 had thyroid nodules or cysts. Two boys showed hypergonadotropic hypogonadism. Growth was retarded in 39% of children. Mean Target Height Standard Deviation Score of patients with thyrotropin elevation was lower than those without (P=0.019). Children treated for neuroblastoma with 131I-MIBG, chemotherapy and surgery were seen to be at risk from developing irreversible thyroid function loss, thyroid nodules, hypergonadotropic hypogonadism, and growth retardation. We recommend that during follow-up of neuroblastoma children, special attention should be paid to their endocrine state.


Circulating IgG antibody to protamine in patients treated with protamine-insulins.
Sera from patients with different types of protamine-insulin were assayed for IgG antibody to protamine. A high prevalence of circulating antibody was found in patients treated with either bovine isophane insulin (26 out of 28 patients; 26 of whom also had antibodies to insulin), or bovine protamine zinc insulin (27 out of 30 patients; all 30 had antibodies to insulin). In sera from 24 patients treated with highly purified porcine isophane insulin, protamine antibody was detected in nine; circulating insulin-antibody was detected in 12 patients, eight of whom had protamine-antibody; in the 12 patients with no detectable antibody to insulin, antibody to protamine was detected in only one (x2 = 8.7, p less than 0.01). This relationship between insulin and protamine antigenicity is of interest as it suggests that the protamine-insulin complex is itself immunogenic.


Amphetamine-induced increase in rat cerebral blood flow: apparent lack of catecholamine involvement.
The influence of D,L-amphetamine (5 mg/kg i.p.) on regional cerebral blood flow (CBF) in rats has been studied after surgically or pharmacologically induced depletion of brain catecholamines. (1) Bilateral removal of the superior cervical ganglion (one week before the experiment) did not prevent the amphetamine-induced augmentation of CBF present in intact animals to 2--4 times above the control value. Maximal changes occurred in the frontal and parietal cortex. (2) Destruction of the ascending noradrenergic pathways by uni- or bilateral injections of 6-hydroxydopamine, which decreased the noradrenaline (NA) level in the frontal cortex by 89%, was ineffective in abolishing the increase in CBF caused by the drug in the frontal cortex. (3) The involvement of other catecholaminergic systems was excluded by pretreatment of the rats with reserpine plus a-methyl-p-tyrosine which reduced the levels of NA, dopamine and adrenaline in the frontal cortex with 92, 97 and 99% respectively. Such treatment did not alter the effect of amphetamine on CBF in the frontal cortex. The results support the hypothesis that the action of amphetamine on CBF is not mainly mediated by catecholamines.


Novel Human Placenta-Based Extract for Vascularization Strategies in Tissue Engineering.
There is critical unmet need for new vascularized tissues to support or replace injured tissues and organs. Various synthetic and natural materials were already established for use of two-dimensional (2D) and three-dimensional (3D) in vitro neovascularization assays, however, they still cannot mimic the complex functions of the sum of the extracellular matrix (ECM) in native intact tissue. Currently, this issue is only addressed by artificial products such as Matrigel™, which comprises a complex mixture of ECM proteins, extracted from animal tumor tissue. Despite its outstanding bioactivity, the isolation from tumor tissue hinders its translation into clinical applications. Since nonhuman ECM proteins may cause immune reactions, as are frequently observed in clinical trials, human ECM proteins represent the best option when aiming for clinical applications. Here, we describe an effective method of isolating a human placenta substrate (hpS) that induces the spontaneous formation of an interconnected network of green fluorescence-labeled human umbilical vein endothelial cells (gfpHUVECs) in vitro. The substrate was biochemically characterized by using a combination of bicinchoninic acid (BCA) assay, DNA, and glycosaminoglycan (GAG) content assays, sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis and Western blot, angiogenesis arrays, chromatographic thrombin detection, high performance liquid chromatography (HPLC)-based amino acid quantification analysis, and assessment of antimicrobial properties. 2D in vitro cell culture experiments have been performed to determine the vasculogenic potential of hpS, which demonstrated that cell networks developed on hpS show a significantly higher degree of complexity (number of tubules/junctions; total/mean tube length) when compared with Matrigel. As 3D cell culture techniques represent a more accurate representation of the in vivo condition, the substrate was 3D solidified using various natural polymers. 3D in vitro vasculogenesis assays have been performed by seeding gfpHUVECs in an hpS-fibrinogen clot. In conclusion, hpS provides a potent human/material-based alternative to xenogenic-material-based biomaterials for vascularization strategies in tissue engineering.


Influence of smoking and esophageal intubation on esophageal pH-metry.
The effect of cigarette smoking on gastroesophageal reflux and the effect of the pH electrode on salivary secretion and swallowing frequency were studied in 30 healthy volunteers (15 habitual smokers, 15 non-smokers) and in 10 smoking patients with proven gastroesophageal reflux disease. Twenty-four-hour pH profiles were measured while the subjects were ambulatory using a combined glass electrode connected to a portable recorder. In 8 of the smoking volunteers, swallowing frequency and salivary secretion were measured, both when smoking and when not. Smokers had more reflux episodes than nonsmokers [median per hour 2.8 (range 0.4-7.1) for the upright body position and 0.5 (range 0.0-1.7) for the supine body position vs. 1.4 (range 0.0-2.1) upright and 0.0 (range 0.0-0.7) supine, p less than 0.01], but the total time of exposure of the esophageal mucosa to acid was affected neither by the status of being a smoker nor by actual smoking. Nasopharyngeal intubation with the pH electrode did not affect the swallowing frequency, but it increased salivary secretion two-to threefold for a period of 4 h. Six hours after introduction of the pH electrode and later, salivary flow was similar to baseline. It is concluded that smoking and nasopharyngeal intubation does not adversely affect the results of 24-h pH-metry.


Volume of reaction, energetics, and kinetics of tetrahydrothiophene displacement of solvent from Mo(CO)5(alkane).
Laser-induced optoacoustic spectroscopy (LIOAS) was used to determine the enthalpies and volumes of reactions for each step in ligand substitution of molybdenum hexacarbonyl with tetrahydrothiophene (THT). The enthalpy for substitution of CO on Mo(CO)6 by an alkane and of coordinated alkane on Mo(CO)5(alkane) by THT are 114 and -99 kJ mol(-1), respectively. Likewise, the volumes of reaction are 13 and -16 ml mol(-1). These results allow the calculation of the bond energies for Mo-alkane (56 kJ mol(-1)) and Mo-THT (155 kJ mol(-1)). Furthers studies should reveal that, for certain cases, the volume of reaction can be neglected in the determination of enthalpies of ligand substitution by LIOAS.


Ex vivo multi-electrode analysis reveals spatiotemporal dynamics of ictal behavior at the infiltrated margin of glioma.
The purpose of this study is to develop a platform in which the cellular and molecular underpinnings of chronic focal neocortical lesional epilepsy can be explored and use it to characterize seizure-like events (SLEs) in an ex vivo model of infiltrating high-grade glioma. Microelectrode arrays were used to study electrophysiologic changes in ex vivo acute brain slices from a PTEN/p53 deleted, PDGF-B driven mouse model of high-grade glioma. Electrode locations were co-registered to the underlying histology to ascertain the influence of the varying histologic landscape on the observed electrophysiologic changes. Peritumoral, infiltrated, and tumor sites were sampled in tumor-bearing slices. Following the addition of zero Mg2+ solution, all three histologic regions in tumor-bearing slices showed significantly greater increases in firing rates when compared to the control sites. Tumor-bearing slices demonstrated increased proclivity for SLEs, with 40 events in tumor-bearing slices and 5 events in control slices (p-value = .0105). Observed SLEs were characterized by either low voltage fast (LVF) onset patterns or short bursts of repetitive widespread, high amplitude low frequency discharges. Seizure foci comprised areas from all three histologic regions. The onset electrode was found to be at the infiltrated margin in 50% of cases and in the peritumoral region in 36.9% of cases. These findings reveal a landscape of histopathologic and electrophysiologic alterations associated with ictogenesis and spread of tumor-associated seizures.


Solanum nigrum produces nitric oxide via nuclear factor-kappaB activation in mouse peritoneal macrophages.
Nitric oxide (NO) is an antitumour molecule produced in activated macrophages and Solanum nigrum is a plant used in oriental medicine to treat tumours. In this study using mouse peritoneal macrophages, we have examined the mechanism by which Solanum nigrum regulates NO production. When Solanum nigrum was used in combination with 20 U/ml of recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production. The increase in NO synthesis was reflected as an increased amount of inducible NO synthase (iNOS) protein. The production of NO from rIFN-gamma plus Solanum nigrum-stimulated peritoneal macrophages was decreased by treatment with N-monomethyl-L-arginine or N-tosyl-Phe chloromethyl ketone, an iNOS inhibitor. Additionally, the increased production of NO from rIFN-gamma plus Solanum nigrum-stimulated cells was almost completely inhibited by pretreatment with 100 micromol/l of pyrrolidine dithiocarbamate, an inhibitor of nuclear factor kappaB (NF-kappaB). Furthermore, Solanum nigrum increased activation of NF-kappaB. These findings suggest that Solanum nigrum increases the production of NO by rIFN-gamma-primed macrophages and NF-kappaB plays a critical role in mediating these effects.


[Patient preference in the choice of dry powder inhalers].
To investigate a group of patients' preferences among 3 dry powder inhalers--Accuhaler, Easyhaler, and Turbuhaler--and to analyze the features that were most important for motivating choices. The study enrolled 30 patients with stable asthma with a mean (SD) age of 40 (13) and who habitually used inhaled corticosteroids. The patients were shown in detail how to use each of the devices and were randomized to begin using them in different orders. After using each inhaler for a week, the patients assessed 9 different features on a scale of 0 to 10 with an independent observer. The patients were asked to put the inhalers in order of preference, and finally to demonstrate they could use them correctly. All patients correctly performed the inhalation maneuver at the beginning and the end of the study. The mean final scores out of 90 of the 9 features evaluated were 75 (13) for the Easyhaler, 67 (12) for the Accuhaler, and 65 (14) for the Turbuhaler. Differences were statistically significant between the first and the second device (P=0.02) and the first and the third (P=.001) but not between the Accuhaler and the Turbuhaler (P=.376). Mean rating scores were 8.6 (1.4) for the Easyhaler, 7.3 (1.9) for the Turbuhaler, and 7.1 (1.6) for the Accuhaler. The Easyhaler was the first choice for 53% of patients, the Turbuhaler for 27%, and the Accuhaler for 20%. The Easyhaler was rated the highest by the patients in the study. The scores were a long way from the maximum score, so research into developing an ideal inhaler must continue.


Trajectories of Liver Fibrosis and Gene Expression Profiles in Nonalcoholic Fatty Liver Disease Associated With Diabetes.
Understanding the mechanisms linking steatosis to fibrosis is needed to establish a promising therapy against nonalcoholic fatty liver disease (NAFLD). The aim of this study was to clarify clinical features and hepatic gene expression signatures that predict and contribute to liver fibrosis development during the long-term real-world histological course of NAFLD in subjects with and without diabetes. A pathologist scored 342 serial liver biopsy samples from 118 subjects clinically diagnosed with NAFLD during a 3.8-year (SD 3.45 years, maximum 15 years) course of clinical treatment. At the initial biopsy, 26 subjects had simple fatty liver, and 92 had nonalcoholic steatohepatitis (NASH). In the trend analysis, the fibrosis-4 index (P < 0.001) and its components at baseline predicted the future fibrosis progression. In the generalized linear mixed model, an increase in HbA1c, but not BMI, was significantly associated with fibrosis progression (standardized coefficient 0.17 [95% CI 0.009-0.326]; P = 0.038) for subjects with NAFLD and diabetes. In gene set enrichment analyses, the pathways involved in zone 3 hepatocytes, central liver sinusoidal endothelial cells (LSECs), stellate cells, and plasma cells were coordinately altered in association with fibrosis progression and HbA1c elevation. Therefore, in subjects with NAFLD and diabetes, HbA1c elevation was significantly associated with liver fibrosis progression, independent of weight gain, which may be a valuable therapeutic target to prevent the pathological progression of NASH. Gene expression profiles suggest that diabetes-induced hypoxia and oxidative stress injure LSECs in zone 3 hepatocytes, which may mediate inflammation and stellate cell activation, leading to liver fibrosis. It remains uncertain how diabetes and obesity contribute to histological courses of nonalcoholic fatty liver disease (NAFLD). Clinical features and gene expression signatures that predict or are associated with future liver fibrosis development were assessed in a serial liver biopsy study of subjects with NAFLD. An increase in HbA1c, but not BMI, was associated with liver fibrosis progression in the generalized linear mixed model. Considering hepatic gene set enrichment analyses, diabetes may enhance liver fibrosis via injuring central liver sinusoidal endothelial cells that mediate inflammation and stellate cell activation during NAFLD development.


Possible roles of human mast cells in the formation of xanthelasma palpebrarum.
Cutaneous xanthoma consist of foam cells that originate from monocytes or macrophages and accumulate in perivascular areas of the skin. The main component of these cells is oxidized low-density lipoprotein (oxLDL). In this study, we show that mast cells surround the accumulated foam cells, suggesting their involvement in xanthoma formation. Coculture of THP-1 or U937 monocytes with the human mast cell line LUVA upregulated their uptake of oxLDL. Positive staining for intracellular cell adhesion molecule-1 (ICAM-1) at the borders between mast cells and foam cells was seen in pathological specimens of the most common cutaneous xanthoma, xanthelasma palpebrarum, and in cocultures. In the latter, ICAM1 messenger RNA levels were upregulated. The administration of anti-ICAM-1 blocking antibody inhibited the increase in oxLDL uptake by THP-1 or U937 monocytes cocultured with LUVA. Taken together, these results suggest a role for mast cells in the formation of xanthelasma palpebrarum and the involvement of ICAM-1 in this process.


Current status, key challenges and its solutions in the design and development of graphene based ORR catalysts for the microbial fuel cell applications.
Microbial fuel cells (MFC) are considered as the futuristic energy device that generates electricity from the catalytic degradation of biodegradable organic wastes using microbes, which exist in waste water. In MFCs, oxygen serves as a cathodic electron acceptor and oxygen reduction kinetics played a significant role in the determination of overall efficiency. A wide range of strategies have been developed for the preparation and substantial modification of oxygen reduction reaction (ORR) catalysts to improve the maximum volumetric power density of MFCs, in which the efforts on graphene based ORR catalysts are highly imperative. Although numerous research endeavors have been achieved in relation with the graphene based ORR catalysts applicable for MFCs, still their collective summary has not been developed, which hinders the acquirement of adequate knowledge on tuning the specific properties of said catalysts. The intension of this review is to outline the significant role of ORR catalysts, factors influencing the ORR activity, strategies behind the modifications of ORR catalysts and update the research efforts devoted on graphene based ORR catalysts. This review can be considered as a pertinent guide to understand the design and developmental strategies of competent graphene based ORR catalysts, which are not only applicable for MFCs but also for number of electrochemical applications.


Relationship between sleep duration and the metabolic syndrome: Korean National Health and Nutrition Survey 2001.
Previous studies have revealed that both short and long sleep durations are linked to obesity, hyperglycemia and hypertension. We evaluate the relationship between sleep duration and the metabolic syndrome using representative national survey data from the Korean population. We analyzed data from the 2001 Korean National Health and Nutrition Survey. The average amount of sleep per night was categorized as: <or=5, 6, 7, 8 and >or=9 h. Those reporting 7 h per night served as a reference group. In this cross-sectional study, the data of 4222 participants were finally analyzed. A majority of the components of the metabolic syndrome demonstrated U-shaped patterns based on sleep duration. Although the prevalences of abdominal obesity and hypertension were highest in subjects who slept <or=5 h per night, those of hyperglycemia and high triglyceridemia were highest in subjects who slept >or=9 h per night. Prevalence of the metabolic syndrome also exhibited U-shape pattern based on sleep duration. More components of the metabolic syndrome were highly associated with sleep duration in subjects under the age of 60 compared to those over the age of 60. Subjects who slept <or=5 h per night demonstrated the highest risk for the metabolic syndrome (OR 1.74, 95% CI 1.33-2.26, P<0.001). Subjects who slept >or=9 h per night exhibited increased risk for the metabolic syndrome even after adjustment of other risk variables (OR 1.69, 95% CI 1.17-2.45, P=0.006). Both short and long sleep durations are related to increased risk of the metabolic syndrome and its components in the Korean population, although adjustment for risk factors attenuates their relationship. Subjects reporting sleep duration of 7 h demonstrated the lowest prevalence of the metabolic syndrome.


Characterization of microbial diversity in hypersaline environments by melting profiles and reassociation kinetics in combination with terminal restriction fragment length polymorphism (T-RFLP).
The diversity of prokaryotes inhabiting solar saltern ponds was determined by thermal melting and reassociation of community DNA. These measurements were compared with fingerprinting techniques such as terminal restriction fragment length polymorphisms (T-RFLP) analysis, denaturant gradient gel electrophoresis (DGGE), and cloning and sequencing approaches. Three ponds with salinities of 22, 32, and 37% (NaCl saturation) were studied. The combination of independent molecular techniques to estimate the total genetic diversity provided a realistic assessment to reveal the microbial diversity in these environments. The changes in the prokaryotic communities at different salinity (22, 32, and 37% salt) were significant and revealed that the total genetic diversity increased from 22% to 32% salinity. At 37% salinity the diversity was reduced again to nearly half that at 22% salinity. Our results revealed that the community "genome" had a DNA complexity that was 7 (in 22% salinity pond), 13 (in 32% salinity pond), and 4 (in 37% salinity pond) times the complexity of an Escherichia coli genome. The base composition profiles showed two abundant populations, which changed in relative amount between the three ponds. They indicated an uneven taxon distribution at 22% and 37% salinity and a more even distribution at 32% salinity. The results indicated a large predominating population at 37% salinity, which might correspond to the abundance of square archaea (SPhT) observed by transmission electron microscopy (TEM) and also indicated by the same T-RFLP fragment as the SPhT. The SPhT phylotype has also been reported to be the most frequently retrieved phylotype from this environment by culture independent techniques. In addition, two different operational taxonomic units (OTU) were detected at 37% salinity based on PCR with bacterial specific primers and T-RFLP. One of these predominant phylotypes is the extreme halophilic bacterium belonging to the bacteroidetes group, Salinibacter ruber.


Characterization and surface-enhanced Raman spectral probing of silver hydrosols prepared by two-wavelength laser ablation and fragmentation.
A four step Ag foil laser ablation-Ag nanoparticle fragmentation procedure in ultrapure water was carried out both under argon and in air. Pulses of a high power Nd/YAG laser were used for laser ablation (1064 nm) and for the three step Ag hydrosol treatment in the absence of Ag foil in the sequence 1064-532-1064 nm. Transmission electron microscopy (TEM) and surface plasmon (SP) extinction spectra provide evidence of Ag nanoparticle fragmentation in the second and third step of the procedure carried out under argon. While polydispersity of Ag hydrosol increases in the second step, both the polydispersity and the mean size of the nanoparticles are reduced in the third step. Qualitative and quantitative surface-enhanced Raman scattering (SERS)/surface-enhanced resonance Raman scattering (SERRS) spectral probing of systems with Ag hydrosols and the selected adsorbates at 514.5 nm excitation shows that Ag hydrosols obtained in the second step of the preparation procedure carried out in air are the most suitable substrates for SERS/SERRS experiments performed at this excitation wavelength.


DNA cleaving activities of 9-membered masked enediyne analogues possessing DNA intercalator and sugar moieties.
The DNA cleaving properties of various enediyne analogues possessing sugar moieties and DNA-intercalators were investigated. The DNA cleaving experiments show that these hybrids analogues induced sequence-selective DNA cleavage and the simple sugars in the enediyne serve as a DNA recognition element for DNA cleavage.


The medical itineraries of Blaise Cendrars. Neuropsychiatry marks life and literature.
Neuropsychiatry had a profound impact on the life and work of one of the most influential French writers of the 20th century, Frédéric Sauser, better known by his pen name Blaise Cendrars (1887-1961). Cendrars, whose right writing hand was amputated after a battlefield wound in 1915, described with acuity his stump pain and phantom limb syndrome. He became a left-handed writer. Between 1956 and his death in 1961, he also suffered two strokes that progressively paralyzed his left side and greatly diminished his ability to speak. Cendrars had started medical school in his youth and found that his ideas about the genesis of mental disorders conflicted with the generally accepted psychiatric conceptions of hysteria or psychoanalysis. His theories were greatly enriched by his observations of fellow World War I soldiers, victims of neuropsychiatric disorders. In his novels, many of his characters had borderline conditions, including two spectacularly mad serial killers, Moravagine and Fébronio. The case of Moravagine, fashioned after a patient with a brain tumor, allowed Cendrars to examine the nebulous frontier between neurological and psychiatric diseases.


Cardiac Amyloidosis in Patients Undergoing TAVR: Why We Need to Think About It.
Systemic amyloidosis encompasses a variety of diseases characterized by extracellular deposition of protein-derived fibrils in different tissues and organs. Immunoglobulin light-chain (AL) and transthyretin (ATTR) amyloid are the two types that more commonly affect the heart and in both subtypes cardiac involvement is the main determinant of prognosis. Recently, several studies have suggested that Cardiac Amyloidosis (CA) and Aortic Stenosis (AS) can coexist more frequently than previously suspected with prevalence ranging from 5,6% to 16% in different cohorts. The unexpected high prevalence of CA in AS and the availability of potentially effective treatment in CA should push us to carefully investigate elderly patients with aortic valve stenosis in order to identify those with coexistent amyloidosis. While the motivation to exclude amyloidosis was in the past their exclusion from active treatment of the valve disease, judged as futile because of their poor unavoidable prognosis, the improved therapeutic options available challenges this conservative approach. Aim of this review is to identify the triggers to investigate AS patients at risk of having concomitant ATTR-CA, to propose a diagnostic path to reach diagnosis and to discuss the changes in the therapeutic strategy caused by this discovery in the era of TAVR and active pharmacological treatments to slow down disease progression.


Knowing the entire story - a focus group study on patient experiences with chronic Lyme-associated symptoms (chronic Lyme disease).
Healthcare providers frequently struggle to provide effective care to patients with chronic Lyme-associated symptoms (chronic Lyme disease, CLD), potentially causing these patients to feel misunderstood or neglected by the healthcare system. This study is the first to use a combined medical and communication science approach, and aims to assess patients' experiences with CLD & CLD-related care, identify themes and repertories in these patients' narrations, and provide potential ways to improve communication with them. Informed by the principles of 'clean language', we conducted focus groups with self-identified CLD patients (N = 15). We asked participants about their experiences with CLD and CLD-related healthcare. We performed thematic analyses using a bottom-up approach based in discourse analysis. We also sought to identify specific types of verbalizations (repertoires) across themes. Participants thematised a heterogeneous set of CLD-associated symptoms, which they frequently labelled as 'invisible' to others. Their illness significantly affected their daily lives, impacting their work, social activities, relationships with loved ones, hobbies and other means of participating in society. Negative experiences with healthcare providers were near-universal, also in patients with short-lived CLD-associated symptoms. Verbalizations were notable for frequent use of communicative modes that implicitly create common ground between participants and that give a certain validity to personal experiences (impersonal 'you' and other forms of presupposition). Central themes found in CLD patients' communication are 1. the experience of significant symptoms, 2. for which adequate relief is only rarely found from conventional medical practitioners, and 3. that are largely invisible to the outside world. Verbalizing these themes, patients use various repertoires for their shared experiences, such as a feeling of abandonment or not being heard by the medical system, feelings of loss with respect to their previous health, and the idea that they might have been better off had they been diagnosed sooner. Working with these repertoires will enable healthcare providers to establish a shared perspective with their CLD patients, thus engaging in more fruitful doctor-patient communication. We hypothesize that these findings are not unique to CLD, but may also be applicable to other conditions with an uncertain aetiology, such as Long COVID.


Severe and selective deficiency of interferon-gamma-producing invariant natural killer T cells in patients with myelodysplastic syndromes.
Here we show that patients with myelodysplastic syndromes (MDS) have a severe deficiency of glycolipid reactive Valpha24+/Vbeta11+ natural killer T (NKT) cells, but not NK cells or CD4+ or CD8+ T cells. Neither the blood nor marrow of MDS patients had detectable interferon-gamma-producing NKT cells in response to the NKT ligand, alpha-galactosyl ceramide, although influenza-virus-specific effector T-cell function was preserved. This severe and selective deficiency of an important immune regulatory cell may contribute to the pathogenesis of MDS.


Searching the half-full glass of COVID-19 pandemic: basic hygienic measures positively impact on postoperative infections after major elective urological surgery: a single-center matched pair analysis.
Since before the COVID-19 pandemic, hospital-acquired infections (HAIs) represented a global healthcare crisis. Few studies suggested that COVID-19-related basic hygiene measures (BHM) could lower HAIs rates, reaching inconclusive results. The aim of this study was to investigate the hypothetical benefit on HAIs rate of COVID-19-enhanced BHM systematic introduction after major elective urological surgery. Since the pandemic began, our hospital has implemented BHM to limit the spread of COVID-19. We compared patients operated in the pre-COVID-19 era (no-BHM period) with those operated after the pandemic started (BHM period). Outcomes were the incidence of HAIs and postoperative complications, and the length of hospital stay (LOS). Two balanced groups were generated by propensity score 1:1 matching. Of 1053 major urological interventions, 604 were performed in the no-BHM period, and 449 in the BHM period. After matched analysis, the comparison groups consisted of 310 patients each. Of 107 recorded HAIs, 43 occurred during the BHM period (13.9%), and 64 during the no-BHM period (20.7%), with a statistically significant difference in multivariable analysis (OR 0.5 [95% CI 0.3-0.8], P=0.004). Postoperative complications rate was significantly lower in the BHM period than in the no-BHM period (29.0% versus 36.5%, OR 0.6 [95% CI 0.4-0.9], P=0.01). The LOS differed significantly between BHM and no-BHM periods: a median of 5 (5-8) days versus 6 (5-8), respectively (P<0.001). The risk of infections, postoperative complications, and prolonged LOS after major urological surgery was significantly reduced with the systematic introduction of COVID-19-related BHM, their application could, therefore, be prolonged with lasting benefits.


Similarities and differences between D-ALA2 MET5 enkephalin amide and morphine in the induction of tolerance to their effects on catalepsy and on dopamine metabolism in the rat brain.
Rats were made tolerant to morphine or to DALA, a synthetic analogue of met-enkephalin, by prolonged exposure to these compounds. Tolerance was assessed by evaluating the resistance of the treated rats to present catalepsy after an acute dose of the opiates. Both morphine and DALA induced tolerance and cross-tolerance to the cataleptic effect. Acute administration of morphine and DALA increased the concentration of DOPAC in striatum, limbic area and s.nigra of control rats. This increase was not present when morphine was given acutely to chronically morphine-treated rats, indicating that these animals were tolerant to this effect. Chronically morphine-treated rats given DALA presented partial tolerance to the biochemical effect of the peptide in limbic area and in s.nigra but not in striatum, indicating that only in certain areas was cross-tolerance produced by chronic morphine. When DALA was administered at different doses to chronically DALA treated rats, the peptide induced rise in DA catabolite was similar to that produced in control animals, so clearly there was no tolerance to this biochemical effect. In these animals cross tolerance to morphine's effect on DA metabolism was present in s.nigra but not in the other two areas, indicating that s.nigra is particularly sensitive to opiate-induced tolerance on DA metabolism.


Emerging Issues in Cannabis Law: Big Business and Equity Challenges.
The cannabis industry continues to evolve at a dizzying pace. Across the United States, states and cities shape and reshape their cannabis policies and regulations, cannabis businesses jockey for position and profit, and consumers sift through a marketplace brimming with cannabis products. It is difficult for many stakeholders to make sense of these rapid changes, and by the time they do, the landscape will likely shift again. This article identifies and explores some emerging legal challenges facing the cannabis industry and its stakeholders. It begins with a breakdown of the state of legalization initiatives in the United States as well as the less than ironclad nature of federal prohibition. Next, the article explores the business of cannabis, considering the size of the industry, the interplay between regulated and unregulated markets, and the regulatory challenges facing cannabis businesses today. Finally, the article explores notions of justice and equity as they relate to the cannabis industry and the role governments can play to right the wrongs of the war on drugs while spreading the benefits of legalization equitably.


A fine structural study of the calcareous opercular plate and associated cells of a polychaete annelid.
The structure of the organic material and inorganic elements of the opercular plate and associated cells in the serpulid annelid, Pomatoceros lamarckii Quatrefages, have been described by transmission and scanning electron microscopy. After decalcification the organic material of the opercular plate was found to consist of three major structurally different components, an outer, thin, electron-dense layer, parallel rows of rectangular profiles partitioned into large units by cross-walls, and layers of orthogonally arranged fibres. The inorganic aragonite components were found, in contrast, to consist of two structurally different elements namely, highly ordered crystals with a prismatic-like morphology and smaller needle-like crystallites. Two morphologically distinct cell types, columnar opercular rim and cuboidal opercular plate cells, are responsible for the formation of the opercular rim and cuboidal opercular plate cells, are responsible for the formation of the opercular plate. Both possess membrane-bound bodies containing filamentous material. However, in addition, membrane-bound bodies, containing calcium carbonate crystals, are found in some cells. Such bodies are seen to be closely related to the Golgi system. Based on the cytoarchitecture of the cells, the mechanisms involved in the formation and calcification of the opercular plate are discussed.


Etanercept treatment-related c-ANCA-associated large vessel vasculitis.
Anti-tumor necrosis factor (TNF) agents have become central players in the management of autoimmune and rheumatic disease. With the wide use of anti-TNF agents today, we have become aware of rare autoimmune complications as systemic lupus erythematosus and psoriasis, yet rarely has large vessels vasculitis been described. We herein describe a case of cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) (with myeloperoxidase (MPO) antibodies)-associated large vessel vasculitis (aortitis) that developed during anti-TNF treatment for ankylosing spondylitis. Awareness of this rare, but serious, adverse event of these commonly used agents in rheumatic diseases is of importance.


Cardiac myonecrosis in hypertensive crisis associated with monoamine oxidase inhibitor therapy.
A young woman taking tranylcypromine for depression was hospitalized with severe chest pain and hypertension after eating cheese. Electrocardiography initially showed arrhythmias and precordial ST segment depression. Myocardial creatine kinase values were elevated, and echocardiography showed regional ventricular dysfunction, suggestive of focal cardiac myonecrosis. The cardiovascular pathophysiology of tyramine hypertensive crisis and related catecholamine excess states, including pheochromocytoma and clonidine withdrawal, is reviewed. Cardiac myonecrosis is a potential adverse effect of the hypertensive crisis associated with monoamine oxidase inhibitor use. Psychiatric indications for monoamine oxidase inhibitors may be expanding, but clinicians should continue to exercise caution in the use of these agents.


Validation of the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4) Among Patients with Schizophrenia.
The main goal of psychiatric care is not to be focused only on reducing psychopathological symptoms, but on improvement of the patient's quality of life. To examine validation and reliability SQLS-R4 among patients with schizophrenia. The sample consisted of 61 outpatients with schizophrenia attending the Psychiatry Hospital "Skopje". nclusion criteria for subject selection were: 1) age more than 18 years, 2) clinically stable (not acutely ill or has not been recently hospitalized at least for the past 3 months). They completed SQLS-R4 and SF36 questioners. The internal consistency reliability was satisfactory for both the psychosocial and vitality domains (Cronbach's α = 0.928, 0.83). Most of the items were significantly correlated with own scale score (from 0.189 to 0.687). The average of the score for the psychosocial quality life was 39.9 ± 8.6 (sometimes), for the cognition and vitality was 26.5 ± 6.1 (sometimes) (SQLS-R4). There was moderate correlation between SF 36-energy with SQOLS - motivation and energy; SF 36-mental health correlation with SQOLS-psychosocial. SQLS-R4 appears to offer excellent potential as an easily administered and patient acceptable assessment and monitoring measure of quality of life (QoL). However, a principle psychometric criterion crucial to the use and validity of the instrument concerns the underlying factor structure.


A high-throughput fully automatic biosensing platform for efficient COVID-19 detection.
We propose a label-free biosensor based on a porous silicon resonant microcavity and localized surface plasmon resonance. The biosensor detects SARS-CoV-2 antigen based on engineered trimeric angiotensin converting enzyme-2 binding protein, which is conserved across different variants. Robotic arms run the detection process including sample loading, incubation, sensor surface rinsing, and optical measurements using a portable spectrometer. Both the biosensor and the optical measurement system are readily scalable to accommodate testing a wide range of sample numbers. The limit of detection is 100 TCID50/ml. The detection time is 5 min, and the throughput of one single robotic site is up to 384 specimens in 30 min. The measurement interface requires little training, has standard operation, and therefore is suitable for widespread use in rapid and onsite COVID-19 screening or surveillance.


Inhibition of insulin/IGF-1 receptor signaling enhances bile acid toxicity in primary hepatocytes.
Modulation of ERBB and insulin-like growth factor 1 (IGF-1) receptor function is recognized as a potential mechanism to inhibit tumor growth. We and others have shown that inhibition of ERBB1 can enhance bile acid toxicity. Herein, we extend our analyses to examine the impact of insulin/IGF-1 receptor inhibition on primary hepatocyte survival when exposed to the secondary bile acid deoxycholic acid (DCA) and compare the impact inhibition of this receptor has on bile acid toxicity effects to that of ERBB1/MEK1/2 inhibition. The insulin/IGF-1 receptor inhibitor NVP-ADW742 at concentrations which inhibit both the insulin and IGF-1 receptors had a modest negative impact on hepatocyte viability, and strongly potentiated DCA-induced apoptotic cell death. Identical data were obtained expressing a dominant negative IGF-1 receptor in hepatocytes; a receptor which acts to inhibit both the IGF-1 receptor and the insulin receptor in trans. Inhibition of ERBB1 function using Iressa (gefitinib) or the tyrphostin AG1478 had more modest effects at enhancing DCA lethality than inhibition of the insulin/IGF-1 receptor function. In contrast, over-expression of a dominant negative ERBB1 protein had pleiotropic effects on multiple signaling pathways in an apparently non-specific manner. These findings suggest that novel therapeutic kinase inhibitors, targeted against growth factor receptors, have the potential to promote bile acid toxicity in hepatocyte when bile flow may be impaired.


Biphasic activation of cytosolic free calcium and LH responses by gonadotropin-releasing hormone.
Gonadotropin-releasing hormone (GnRH) stimulates rapid peak increases in [Ca2+]i and LH release, followed by lower but sustained elevations of both [Ca2+]i and hormone secretion. Omission of extracellular Ca2+ only slightly decreased the peak of [Ca2+]i, but reduced the peak LH response by 40% and prevented the prolonged increases in [Ca2+]i and LH release. Dihydropyridine calcium antagonists did not affect the peak [Ca2+]i and LH responses, but reduced the sustained increases by up to 50%. Whereas GnRH-induced mobilization of intracellular calcium initiates the LH peak, and Ca2+ entry through dihydropyridine-insensitive channels contributes to the peak and plateau phases of LH release, dihydropyridine-sensitive L-type Ca2+ channels participate only in the sustained phase of gonadotropin secretion.


Characterization of the Ste20-like kinase Krs1 of Dictyostelium discoideum.
Ste20-like kinases constitute a ubiquitous and expanding group of serine/threonine kinases, homologous to Ste20 in Saccharomyces cerevisiae. The social amoeba Dictyostelium discoideum contains at least 17 members of this kinase family, 13 from the germinal center kinase (GCK) subgroup and 4 p21-activated kinases (PAK). Here, we describe the kinase Krs1 which is encoded by the gene krsA, and phylogenetic analysis groups it into subfamily GCK-II together with human MST2 and MST1 or Hippo from Drosophila melanogaster. Significant similarities are found especially in the catalytic domain and in a short regulatory region (SARAH) which is thought to be important for protein/protein interactions. Northern blot analysis showed a single krsA transcript throughout development with an upregulation at 12h after the onset of starvation. The protein levels as detected with anti-Krs1 polyclonal antibodies revealed a similar pattern. Gel filtration experiments suggested that AX2 wild-type cells harbored multimeric forms of Krs1. In vitro phosphorylation assays with recombinant protein showed that the kinase exhibits autophosphorylation and accepts myelin basic protein and D. discoideum severin as substrates. A series of C-terminal deletions of Krs1 indicated that the regulatory domain in the C-terminal half contains inhibitory elements, and highlighted the importance of two predicted alpha-helices following subdomain XI of the classical catalytic domain. GFP-Krs1-overexpressing wild-type cells showed an enrichment of the kinase in the cortex, and motility of these cells during aggregation was reduced. Krs1 knockout strains exhibited only subtle differences to wild-type cells which suggests a certain redundancy among Ste20-like kinases in D. discoideum.


Effectiveness of cevimeline to improve oral health in patients with postradiation xerostomia.
We assessed the effectiveness of cevimeline 30 mg 3 times daily in patient-reported oral health (Oral Health Impact Profile [OHIP-49]) and quality of life (QOL) in patients with xerostomia. In our investigator-initiated, multicenter, randomized, double-blind, placebo-controlled study, patients who received >40 Gy of radiation therapy to the head and neck including at least 3 major salivary glands were randomized to cevimeline 30 mg or placebo orally 3 times daily for 6 weeks. Patients had to have grade 1 or 2 xerostomia and be >16 weeks posttreatment. Clinical data were collected and questionnaires administered at baseline and week 6. The primary outcome was change in OHIP-49 total score from baseline to week 6. No statistically significant differences in oral health or QOL were observed. During the 6 weeks of the study, the severity of xerostomia decreased from baseline. Xerostomia is a significant sequela of treatment of head and neck cancer that may improve with time. The role of oral parasympathetic muscarinic secretogogues in alleviating patient symptoms and complaints remains unclear.


A case of myocarditis after COVID-19 vaccination: incidental or consequential?
Vaccination represents one of the fundamentals in the fight against SARS-CoV-2. Myocarditis has been reported as a rare but possible adverse consequence of different vaccines, and its clinical presentation can range from mild symptoms to acute heart failure. We report a case of a 29-year-old man who presented with fever and retrosternal pain after receiving SARS-CoV-2 vaccine. Cardiac magnetic resonance imaging and laboratory data revealed typical findings of acute myocarditis.


Head direction cell firing properties and behavioural performance in 3-D space.
Previous studies have identified a population of neurons in the rat brain that discharge as a function of the animal's directional heading in the horizontal plane, independent of their location and on-going behaviour. Most studies on head direction (HD) cells have explored how they respond in two-dimensional environments within the horizontal plane. Many animals, however, live and locomote in a three-dimensional world. This paper reviews how HD cells respond when the animal locomotes on a vertical surface or inverted on a ceiling. We found that HD cells fire in a normal, direction-dependent manner when the rat is in the vertical plane, but not when the animal is inverted. Recent behavioural studies reported that rats are capable of accurately performing a navigational task when inverted, but only when the task was simple and started from not more than one or two entry points. Probe trials found that they did not have a flexible, map-like representation of space when inverted. The loss of the directional signal when the animal is in an inverted orientation may account for the absence of the map-like representation. Taken together, these findings indicate that a normal otolith signal contributes an important role to HD cell discharge.


Cerebral blood flow autoregulation and transcranial Doppler sonography in patients with cirrhosis.
Impairment of cerebral blood flow (CBF) autoregulation may have serious implications for patients with cirrhosis if arterial hypotension occurs during coma, anesthesia, bleeding, or sepsis. In this study, CBF autoregulation was investigated in patients with cirrhosis with no or mild encephalopathy. Ten patients (median age, 45 years; range, 30 to 61 years) and six healthy volunteers (median age, 30 years; range 21 to 61 years) were included. Catheters were placed in a radial artery and in the internal jugular veins. Baseline CBF was measured using single-photon emission computed tomography (SPECT) with concomitant measurements of cerebral arteriovenous oxygen content differences (AVDO2). CBF autoregulation was evaluated using the AVDO2 method and changes in mean flow velocity in the middle cerebral artery (Vmean) as determined by transcranial Doppler (TCD). Mean arterial pressure (MAP) was increased by 30 mm Hg by intravenous norepinephrine, and subsequently decreased by a combination of lower body negative pressure and ganglion blockade, whereas AVDO2 and Vmean were measured at each 5 mm Hg change in MAP. CBF was 61 (range, 45 to 78) mL 100 g-1 min-1 in patients with cirrhosis and 65 (range < 53 to 88) mL 100 g-1 min-1 in volunteers (not significant [NS]). There were no regional differences in CBF between the two groups. Arterial carbon dioxide tension was 31 (23 to 35) mm Hg in patients with cirrhosis and lower, compared with 36 (range, 34 to 47) mm Hg in the volunteers (P < .01). For evaluation of autoregulation, MAP was raised to 116 (range, 100 to 145) and then decreased to 39 (range, 34 to 50) mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum high-density lipoprotein (HDL) inhibits in vitro enterohemolysin (EHly) activity produced by enteropathogenic Escherichia coli.
Enterohemolysin (EHly) produced by Escherichia coli shows hemolytic activity towards washed erythrocytes from different animal species on blood agar plates. It has been shown recently that EHly activity is inhibited by normal mammalian serum and by cholesterol in vitro. Plasma lipoproteins can interact with bacterial toxins, such as endotoxin, to reduce their toxicity. In this work, we examine the ability of human purified chylomicrons, very low-density lipoproteins, intermediate-density, low-density and high-density lipoproteins, to inhibit the hemolytic activity of EHly. Our results show that these lipoproteins are hemolysin inactivators, and that high-density lipoprotein is the most potent inhibitor of enterohemolytic activity.


Quality of life implications of inadequate protein nutrition among hemodialysis patients.
To determine the quality of life implications of inadequate protein nutrition among hemodialysis patients. Cross-sectional study. All 22 chronic hemodialysis units in northeast Ohio. There were 289 randomly selected patients. Interview and chart abstraction. Six quality of life subscales related to general health, physical function, social function, symptoms, burden of kidney disease, and employment status. Low albumin levels were independently associated with decreased physical function, social function, and burden of kidney disease scores after adjustment for patient age, race, gender, health insurance, cause of renal failure, years on dialysis, and number of comorbid conditions. Low protein catabolic rate was independently associated with decreased physical function scores and with being retired or disabled. Inadequate protein nutrition is independently associated with poor quality of life. Further study is needed to develop interventions to overcome barriers to protein nutrition and to determine the effect of such interventions on protein nutrition and patient quality of life.


Racial disparities in treatment of ruptured abdominal aortic aneurysms.
The Society for Vascular Surgery has recommended immediate transfer of patients with ruptured abdominal aortic aneurysms (rAAAs) to a regional center when feasible. However, Black patients might be less likely to be transferred and more likely to be turned down for repair. We, therefore, examined the transfer rates, turndown rates, and outcomes for Black vs White patients presenting with rAAAs in two large databases. We examined all rAAA repairs in the Vascular Quality Initiative from 2003 to 2020 to evaluate the transfer rates and outcomes for Black vs White patients. We used the National Inpatient Sample from 2004 to 2015 to examine the turndown rates. Mixed effects logistic regression, Cox regression, and marginal effects modeling were used to study the interaction between race, insurance status, surgery type (open repair vs endovascular aortic aneurysm repair), and hospital volume. We identified 4935 patients with rAAAs in the Vascular Quality Initiative (6.2% Black) and 48,489 in the National Inpatient Sample (6.0% Black). The rates of transfer were high; however, Black patients were significantly less likely to undergo transfer before repair compared with White patients (49% Black vs 62% White; P = .002). The result was consistent in both crude and adjusted analyses when considering only stable patients and was not modified by insurance status, surgery type, or hospital volume. No significant differences were found in perioperative mortality (22% vs 26%; P = .098) or complications (52% vs 52%; P = .64). However, Black patients were significantly more likely to be turned down for repair (37% vs 28%; odds ratio, 1.5; 95% confidence interval, 1.2-1.9; P < .001). A significant interaction was found between race and insurance status with respect to turndown. Patients with private insurance had undergone surgery at a similar rate, regardless of race. However, among patients with Medicare or Medicaid/self-pay, Black patients were less likely than were White patients to undergo repair (Medicare, 64% vs 72%; P = .001; Medicaid/self-pay, 43% vs 61%; P = .031). Patients with Medicaid/self-pay were also less likely to undergo repair than were patients of the same race with either Medicare or private insurance (P < .05). We found that Black patients with rAAAs are poorly served by the current systems of interhospital transfer in the United States, because they less often undergo transfer before repair. Although the postoperative outcomes appeared similar, this finding could be falsely optimistic, because Black patients, especially the underinsured, were turned down for repair more often even after adjustment. Significant work is needed to better understand the reasons underlying these disparities and identify the targets to improve the care of Black patients with rAAAs.


The effects of calcium channel blocker benidipine and calmodulin antagonist W7 on GDP-binding capacity of brown adipose tissue in mice.
It has been suggested that increased dietary calcium intake can attenuate obesity. Calcium antagonists, such as benidipine, also have been shown to have an anti-obesity effect. However, the mechanism for calcium-related anti-obesity effect has not yet been established. A defective brown adipose tissue thermogenesis has been shown in obese rodents. This study was designed to examine the direct effects of calcium channel blocker benidipine and calmodulin antagonist W7 administration on the adaptive thermogenesis in brown adipose tissue taken from the genetically obese mice and their lean controls. The GDP binding to brown-fat cell mitochondria was used as a brown adipose tissue thermogenic index. The results show that benidipine treatment had no marked effect on brown-fat cell GDP-binding capacities in both obese and lean mice. However, GDP-binding capacities were significantly reduced in both obese and lean mice after the W7 administration. The results of this study support the previous finding that benidipine did not have direct thermogenic effect on brown adipose tissue and suggest that the change in intracellular calmodulin availability might contribute to the adaptive thermogenesis in brown adipose tissue.


Erratum: COUP-TFII promotes colorectal carcinoma resistance to doxorubicin involving inhibition of epithelial-mesenchymal transition.
[This corrects the article on p. 3921 in vol. 8, PMID: 27725871.].


A causal link between mental imagery and affect-laden perception of climate change related risks.
Previous studies have shed light on the importance of affect in risk perception and the role of mental imagery in generating affect. In the current study, we explore the causal relationship between mental imagery, affect, and risk perception by systematically varying the level of mental imagery in three levels (i.e., enhanced, spontaneous, or prevented). In light of the increasing environmental risk of adverse events caused by climate change, we operationalize risk as participants' perceived risk of climate change. One-thousand-fifty-five participants were recruited online and randomized to one of three levels of mental imagery. As predicted, we found a causal link between the level of mental imagery, affective experience, and perceived risk of climate change, in that enhanced mental imagery caused a larger decrease in positive affective valence and a larger increase in perceived risk of climate change. We argue that mental imagery enhances the negative affect associated with the risk event by creating a perceptual experience that mimics seeing the environmental risk events.


Factors Associated with Smoking Relapse in the Early Postpartum Period: A Prospective Longitudinal Study in Spain.
A high proportion of women who quit smoking during pregnancy relapse during the postpartum period. However, research on smoking relapse in the early postpartum period is scarce. The aims of this study were to estimate rates of smoking relapse at 2 months postpartum and to analyze the factors (sociodemographic, psychological and pregnancy- and tobacco-related variables) involved in relapse and maintenance of abstinence. Eight hundred and fifty-three pregnant women in Spain were interviewed in the first and third trimesters of pregnancy and 2 months postpartum. Assessment included administration of an ad hoc questionnaire, to obtain socio-demographic and obstetric data and determine tobacco consumption status, the State Anxiety Inventory and the Edinburgh Postnatal Depression Scale. Biochemical tests were used to confirm smoking abstinence at each assessment. The study sample consisted of 125 women who smoked before becoming pregnant and who had spontaneously quit smoking during pregnancy. At 2 months postpartum, 17.6% of the sample had relapsed. Stepwise logistic regression analysis showed that the women significantly most likely to relapse in the early postpartum period were those who quit smoking later than the first month of pregnancy (OR = 18.51), those with high levels of anxiety (OR = 6.15) and those who smoked more cigarettes before pregnancy (OR = 4.91). The moment of smoking cessation during pregnancy, the level of consumption prior to pregnancy and anxiety levels should be considered in interventions aimed at maintaining smoking abstinence in pregnant women and preventing postpartum relapse.


Methotrexate hepatotoxicity in children with leukemia.
Percutaneous liver biopsy was performed on seven children with acute lymphocytic leukemia who had received maintanance chemotherapy with high-dose intravenous methotrexate for 1 1/2 to 2 1/2 years. Portal fibrosis was found in four of the seven children and in an additional patient treated with oral methotrexate. Serial tests of liver function and 99mtechnetium-sulfur-colloid scans did not accurately identify children with hepatic fibrosis. Clinical evidence of liver disease was not seen.


Expression of functional N-methyl-D-aspartate receptors during development of chick embryo retina cells: in vitro versus in vivo studies.
The N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors were studied in retina cells developing in chick embryos and in retina cells cultured as retinospheroids, at the same stages of development. In the retinospheroids, the activity of the NMDA receptors was followed by monitoring the changes in the intracellular free calcium concentration ([Ca2+](i)), in response to NMDA or to L-glutamate. The expression of the subunits NMDAR1, NMDAR2A/B and NMDAR2C in the retinospheroids and in chick retinas were determined by Western blot analyses. The changes in [Ca2+](i) in response to 400 microM NMDA increased from 5 h in vitro to 3 days in vitro (DIV) and remained constant until 14 DIV, whereas the [Ca2+](i) response to 500 microM L-glutamate increased from 5 h in vitro to 3 DIV and decreased slightly until 14 DIV. In the retinospheroids, the expression of the NMDAR1 and NMDAR2A/B subunits increased from 5 h in vitro until 14 DIV, whereas the NMDAR2C subunit increased from 5 h in vitro until 10 DIV and remained constant until 14 DIV. In the retinas, the expression of NMDAR1 increased from embryonic day 8 (E8) until E15, decreased until E18, and increased again until day 22 (post-hatched 1, PH1). The NMDAR2A/B increased from E8 until E18 and decreased slightly until PH1, whereas the NMDAR2C subunit increased from E8 until E15, remained constant until E18, and increased again until PH1. The results suggest that NMDA receptors are expressed and functionally active at early embryonic stages in the retina and in retinospheroids, before synapse formation (E12). However, the calcium responses to NMDA were relatively constant from 3 DIV until 14 DIV, showing no correlation with the increase in the expression of the studied NMDA receptor subunit during the same period. Also, the patterns of NMDA receptor subunits expressed in chick embryo retina cells cultured in vitro and in retina cells developing in vivo were similar.


Controlled release of metronidazole from composite poly-ε-caprolactone/alginate (PCL/alginate) rings for dental implants.
Dental implants provide support for dental crowns and bridges by serving as abutments for the replacement of missing teeth. To prevent bacterial accumulation and growth at the site of implantation, solutions such as systemic antibiotics and localized delivery of bactericidal agents are often employed. The objective of this study was to demonstrate a novel method of controlled localized delivery of antibacterial agents to an implant site using a biodegradable custom fabricated ring. The study involved incorporating a model antibacterial agent (metronidazole) into custom designed poly-ε-caprolactone/alginate (PCL/alginate) composite rings to produce the intended controlled release profile. The rings can be designed to fit around the body of any root form dental implants of various diameters, shapes and sizes. In vitro release studies indicate that pure (100%) alginate rings exhibited an expected burst release of metronidazole in the first few hours, whereas Alginate/PCL composite rings produced a medium burst release followed by a sustained release for a period greater than 4 weeks. By varying the PCL/alginate weight ratios, we have shown that we can control the amount of antibacterial agents released to provide the minimal inhibitory concentration (MIC) needed for adequate protection. The fabricated composite rings have achieved a 50% antibacterial agent release profile over the first 48 h and the remaining amount slowly released over the remainder of the study period. The PCL/alginate agent release characteristic fits the Ritger-Peppas model indicating a diffusion-based mechanism during the 30-day study period. The developed system demonstrates a controllable drug release profile and the potential for the ring to inhibit bacterial biofilm growth for the prevention of diseases such as peri-implantitis resulting from bacterial infection at the implant site.


Controversy and consensus regarding myosin II function at the immunological synapse.
Regulated actin dynamics play a central role in modulating signaling events at the immunological synapse (IS). Polymerization of actin filaments at the periphery of the IS, coupled to depolymerization near the center, generates a centripetal flow of the actin network and associated movement of signaling molecules. A recent flurry of papers addresses the role of myosin II in facilitating these events. Investigators agree that myosin II is present at the IS, where it forms actomyosin arcs within the peripheral supramolecular activation cluster, a region corresponding to the lamellum of migrating cells. However, there is substantial disagreement about the extent to which myosin II drives IS formation and signaling events leading to T cell activation.


Retracted: Correlations of Ezrin Expression with Pathological Characteristics and Prognosis of Osteosarcoma: A Meta-Analysis.
[This retracts the article DOI: 10.1155/2014/837543.].


VAR2CSA binding phenotype has ancient origin and arose before Plasmodium falciparum crossed to humans: implications in placental malaria vaccine design.
VAR2CSA is a leading candidate for developing a placental malaria (PM) vaccine that would protect pregnant women living in malaria endemic areas against placental infections and improve birth outcomes. Two VAR2CSA-based PM vaccines are currently under clinical trials, but it is still unclear if the use of a single VAR2CSA variant will be sufficient to induce a broad enough humoral response in humans to cross-react with genetically diverse parasite populations. Additional immuno-focusing vaccine strategies may therefore be required to identify functionally conserved antibody epitopes in VAR2CSA. We explored the possibility that conserved epitopes could exist between VAR2CSA from the chimpanzee parasite Plasmodium reichenowi and Plasmodium falciparum sequences. Making use of VAR2CSA recombinant proteins originating from both species, we showed that VAR2CSA from P. reichenowi (Pr-VAR2CSA) binds to the placental receptor CSA with high specificity and affinity. Antibodies raised against Pr-VAR2CSA were able to recognize native VAR2CSA from different P. falciparum genotypes and to inhibit the interaction between CSA and P. falciparum-infected erythrocytes expressing different VAR2CSA variants. Our work revealed the existence of cross-species inhibitory epitopes in VAR2CSA and calls for pre-clinical studies assessing the efficacy of novel VAR2CSA-based cross-species boosting regimens.


Right atrial aneurysm with downward displacement of the anterior leaflet that resembled Ebstein's anomaly.
A 13-year-old boy presented with right atrial aneurysm and downward displacement of the anterior leaflet in the tricuspid valve into the right ventricle, without tricuspid valve regurgitation. Paroxysmal atrial flutter was caused by an abnormal electrical re-entry circuit, which could not be treated using catheter radiofrequency ablation. Therefore, the patient underwent surgical ablation and resection of the enlarged right atrial wall. The anterior leaflet of the tricuspid valve was plastered and displaced downward into the right ventricle, which resembled Ebstein's anomaly. Pathological evaluation revealed a thin wall that contained fibrous tissue with lipomatous degeneration and few muscular elements. No postoperative arrhythmia was observed.


Testosterone aromatization and cognition in women: a randomized, placebo-controlled trial.
To explore whether inhibition of the conversion of testosterone to estradiol modifies the effects of testosterone on cognition in 61 healthy, estrogen-treated postmenopausal women. Seventy-six postmenopausal women using transdermal estrogen for at least 8 weeks, with a serum total testosterone less than 1.2 nmol/L participated in a single-center, double-blind, randomized, placebo-controlled study. All participants received transdermal testosterone, 400 muL of a 0.5% testosterone gel, daily and were randomized to receive either letrozole 2.5 mg/day or an identical placebo tablet. The main outcome measure was cognition, evaluated using a comprehensive battery of standardized neuropsychological tests, at baseline and week 16. Thirty women in each group completed the study. Free testosterone increased from baseline in both groups, with no difference between groups. Free testosterone levels achieved were below the 90th centile for young women in 80% of the participants at week 16. Serum estradiol and sex hormone-binding globulin levels did not differ from baseline or between groups during the study. No clinically significant effects of testosterone treatment were seen for attention and working memory, psychomotor speed, or executive function. Significant improvements were seen for immediate and delayed visual and verbal memory and for simple concentration with testosterone therapy, all of which were unaffected by the aromatase inhibitor. We did not observe any effects of aromatase inhibition on cognition in healthy, estrogen-treated postmenopausal women treated with testosterone. This may be due to insufficient study power or a true lack of effect. However, our findings highlight that the detection of subtle changes in cognition in well women require the development of sensitive instruments and large randomized, controlled trials.


Deep hypothermia terminates status epilepticus--an experimental study.
In search for novel treatment approaches in status epilepticus, the anticonvulsant effect of moderate and deep hypothermia was assessed in a rodent model. Self-sustaining status epilepticus (SSSE) characterized by spontaneous high-amplitude discharges recorded from the dentate gyrus was induced in male adult rats by electrical stimulation of the perforant path. After the end of stimulation, rats underwent cooling to 30 °C (n=7) and 20 °C (n=10) for 120 min and rewarming to 37 °C for another 60 min. Control SSSE animals (n=6) remained untreated for 180 min. Frequency of epileptiform discharges was assessed every 10 min. At the target temperature of 20 °C, SSSE was completely suppressed in four rats, this effect was not observed in any animal of the other two groups (p=0.043). On rewarming, seizure activity did not reoccur. Discharge frequency was significantly lower in the 20 °C group at most time points after 60 min of cooling. Following deep hypothermia, eight animals were rewarmed, all survived and moved spontaneously at 37 °C. These experimental data indicate the strong and enduring anticonvulsant and obviously safe properties of cooling down to 20 °C. Patients with status epilepticus refractory to first- and second-line anticonvulsants may benefit from deep cooling as an effective non-pharmacological adjunct to anesthetic anticonvulsants.


Stereoselective synthesis and immunogenic activity of the C-analogue of sulfatide.
[Structure: see text] The C-sulfatide 1b was synthesized through a [2,3]-Wittig sigmatropic rearrangement and a Horner-Wadsworth-Emmons olefination as the key steps. The C-analogue 1b is less immunogenic than natural sulfatide 1a, but induces a preferential secretion of the proinflammatory cytokine IFN-gamma.


Modern tools for identification of nucleic acid-binding proteins.
Numerous biological mechanisms depend on nucleic acid--protein interactions. The first step to the understanding of these mechanisms is to identify interacting molecules. Knowing one partner, the identification of other associated molecular species can be carried out using affinity-based purification procedures. When the nucleic acid-binding protein is known, the nucleic acid can be isolated and identified by sensitive techniques such as polymerase chain reaction followed by DNA sequencing or hybridization on chips. The reverse identification procedure is less straightforward in part because interesting nucleic acid-binding proteins are generally of low abundance and there are no methods to amplify amino acid sequences. In this article, we will review the strategies that have been developed to identify nucleic acid-binding proteins. We will focus on methods permitting the identification of these proteins without a priori knowledge of protein candidates.


Left ventricular free-wall rupture in acute myocardial infarction : a blow-out type case.
One of the most serious complications following acute myocardial infarction is left ventricular free-wall rupture (LVFWR). There are two different types of anatomical-pathological rupture: (i) the 'oozing' type, characterized by perforation, which allows enough time for diagnosis and surgery; and (ii) the blow-out type characterized by rapid, irreversible, electromechanical dissociation, shock and death within a few minutes due to massive haemorrhages into the pericardial cavity. Consequently, the prevention of LVFWR could save more lives than treatment, and early recognition and diagnosis could be more beneficial than potentially life-saving therapeutic intervention. A better understanding of the pathogenesis of LVFWR could improve the survival rate of patients with LVFWR. This article reports a blow-out type case of LVFWR, together with a review of the literature including risk factors, pathophysiology, clinical manifestation, diagnosis, surgical treatment and adjunctive therapies.


A critical appraisal of clinical practice guidelines on surgical treatments for spinal cord injury.
Spinal cord injury (SCI) is a global health problem with a heavy economic burden. Surgery is considered as the cornerstone of SCI treatment. Although various organizations have formulated different guidelines on surgical treatment for SCI, the methodological quality of these guidelines has still not been critically appraised. We aim to systematically review and appraise the current guidelines on surgical treatments of SCI and summarize the related recommendations with the quality evaluation of supporting evidence. Systematic review. Medline, Cochrane library, Web of Science, Embase, Google Scholar, and online guideline databases were searched from January 2000 to January 2022. The most updated and recent guidelines containing evidence-based or consensus-based recommendations and established by authoritative associations were included. The Appraisal of Guidelines for Research and Evaluation, 2nd edition instrument containing 6 domains (eg, applicability) was used to appraise the included guidelines. An evidence-grading scale (ie, level of evidence, LOE) was utilized to evaluate the quality of supporting evidence. The supporting evidence was categorized as A (the best quality), B, C, and D (the worst quality). Ten guidelines from 2008 to 2020 were included, however, all of them acquired the lowest scores in the domain of applicability among all the six domains. Fourteen recommendations (eight evidence-based recommendations and six consensus-based recommendations) were totally involved. The SCI types of the population and timing of surgery were studied. Regarding the SCI types of the population, eight guidelines (8/10, 80%), two guidelines (2/10, 20%), and three guidelines (3/10, 30%) recommended surgical treatment for patients with SCI without further clarification of characteristics, incomplete SCI, and traumatic central cord syndrome (TCCS), respectively. Besides, one guideline (1/10, 10%) recommended against surgery for patients with SCI without radiographic abnormality. Regarding the timing of surgery, there were eight guidelines (8/10, 80%), two guidelines (2/10, 20%), and two guidelines (2/10, 20%) with recommendations for patients with SCI without further clarification of characteristics, incomplete SCI, and TCCS, respectively. For patients with SCI without further clarification of characteristics, all eight guidelines (8/8, 100%) recommended for early surgery and five guidelines (5/8, 62.5%) recommended for the specific timing, which ranged from within 8 hours to within 48 hours. For patients with incomplete SCI, two guidelines (2/2, 100%) recommended for early surgery, without specific time thresholds. For patients with TCCS, one guideline (1/2, 50%) recommended for surgery within 24 hours, and another guideline (1/2, 50%) simply recommended for early surgery. The LOE was B in eight recommendations, C in three recommendations, and D in three recommendations. We remind the reader that even the highest quality guidelines often have significant flaws (eg, poor applicability), and some of the conclusions are based on consensus recommendations which is certainly less than ideal. With these caveats, we found most included guidelines (8/10, 80%) recommended early surgical treatment for patients after SCI, which was consistent between evidence-based recommendations and consensus-based recommendations. Regarding the specific timing of surgery, the recommended time threshold did vary, but it was usually within 8 to 48 hours, where the LOE was B to D.


A novel robot for imposing perturbations during overground walking: mechanism, control and normative stepping responses.
The most common approach to studying dynamic balance during walking is by applying perturbations. Previous studies that investigated dynamic balance responses predominantly focused on applying perturbations in frontal plane while walking on treadmill. The goal of our work was to develop balance assessment robot (BAR) that can be used during overground walking and to assess normative balance responses to perturbations in transversal plane in a group of neurologically healthy individuals. BAR provides three passive degrees of freedom (DoF) and three actuated DoF in pelvis that are admittance-controlled in such a way that the natural movement of pelvis is not significantly affected. In this study BAR was used to assess normative balance responses in neurologically healthy individuals by applying linear perturbations in frontal and sagittal planes and angular perturbations in transversal plane of pelvis. One way repeated measure ANOVA was used to statistically evaluate the effect of selected perturbations on stepping responses. Standard deviations of assessed responses were similar in unperturbed and perturbed walking. Perturbations in frontal direction evoked substantial pelvis displacement and caused statistically significant effect on step length, step width and step time. Likewise, perturbations in sagittal plane also caused statistically significant effect on step length, step width and step time but with less explicit impact on pelvis movement in frontal plane. On the other hand, except from substantial pelvis rotation angular perturbations did not have substantial effect on pelvis movement in frontal and sagittal planes while statistically significant effect was noted only in step length and step width after perturbation in clockwise direction. Results indicate that the proposed device can repeatedly reproduce similar experimental conditions. Results also suggest that "stepping strategy" is the dominant strategy for coping with perturbations in frontal plane, perturbations in sagittal plane are to greater extent handled by "ankle strategy" while angular perturbations in transversal plane do not pose substantial challenge for balance. Results also show that specific perturbation in general elicits responses that extend also to other planes of movement that are not directly associated with plane of perturbation as well as to spatio temporal parameters of gait.


Exhaled breath temperature in NSCLC: could be a new non-invasive marker?
The exhaled breath temperature (EBT) has been proven to be the expression of airways inflammation as well as of the increased vascularity. Although both these conditions characterize lung cancer pathogenesis, this is the first study where the EBT has been analysed in patients affected by non-small-cell lung cancer. The aim of this study was to verify whether and how the lung cancer being examined influences the EBT for possible future clinical implications. Eighty-two consecutive subjects with a radiological suspicion of lung cancer were enrolled and underwent standard diagnostic and staging procedures for cancer. EBT was measured in all the subjects at the enrolment with the X-Halo device. Forty patients resulted as affected by lung cancer while 42 as false-positive (controls). We found a higher EBT in NSCLC patients compared to healthy subjects. The EBT was correlated with number of packs/year and associated with the stage of lung cancer. We identified a cut-off value for the EBT that is able to screen patients with lung cancer with a high sensitivity and specificity. Our results suggest that lung cancer causes an increase in the EBT, which, whether confirmed and validated, could become a new non-invasive clinical tool in the screening and monitoring of this disease.


DNA polymorphisms at the lipoprotein lipase gene are associated with macroangiopathy in type 2 (non-insulin-dependent) diabetes mellitus.
We studied the effect of variation at the lipoprotein lipase (LPL) gene locus on the susceptibility of individuals with Type 2 diabetes mellitus to atherosclerotic vascular disease in a population of 126 male and 114 female patients. The prevalence of any evidence of coronary heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial infarction) was low in the patients who were homozygous for the presence of the PvuII restriction site (genotype 2-2) (40.9%) compared with those who were heterozygous (genotype 1-2) (57.9%; P = 0.05) or homozygous for the absence of it (genotype 1-1) (61.9%; P < 0.04). In men, a clear gene dosage effect on CHD was seen, the genotype 2-2 patients having the lowest (39.1%), the 1-2 patients an intermediate (49.3%) and the 1-1 patients the highest (61.1%) frequency of coronary disease. Patients with the genotype 2-2 of the HindIII polymorphism (absence of the restriction site) had the highest prevalence of any evidence of CHD (90.0%) compared with the genotype 1-2 (heterozygotes for the presence of the restriction site) (55.4%) or 1-1 (presence of the restriction site) (54.6%; P < 0.03). Stepwise discriminant analysis revealed that in the whole diabetic population the PvuII genotype of the LPL gene was independently and significantly associated with CHD but its effect decreased when the plasma lipids were taken into account. Overall, this study demonstrates the role of the PvuII polymorphism in the LPL gene to modulate the risk for diabetic macroangiopathy in patients with Type 2 diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)