Methotrexate in rheumatoid arthritis: a quarter century of development.
Methotrexate (MTX) is now the most popular drug worldwide for the treatment of rheumatoid arthritis. Low-dose, weekly MTX (10 to 25 mg/wk) used as either monotherapy or in combination with other drugs has a superior efficacy profile as defined in placebo-controlled trials and comparable efficacy to other drugs including anti-TNF therapy. At 1 year, one third of patients on MTX have no radiographic progression and even greater effects are seen when combined with targeted biological therapies. MTX is well tolerated; gastrointestinal toxicity is the most common toxicity with rarely bone marrow, lung, or liver toxicity. MTX therapy has been a major advance in the treatment of rheumatoid arthritis and is now the cornerstone of therapy.


Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial.
Single-drug checkpoint inhibition has shown efficacy in patients with recurrent malignant pleural mesothelioma. Here, we assessed the safety and efficacy of the combination of nivolumab, an anti-programmed cell death 1 antibody, plus ipilimumab, an anti-cytotoxic T-lymphocyte protein 4 antibody, in patients with previously treated and relapsed malignant pleural mesothelioma. INITIATE was a prospective single-centre, single arm, phase 2 trial. Patients with malignant pleural mesothelioma who progressed after at least one line of platinum-containing chemotherapy were enrolled. Key eligibility criteria were measurable disease according to the modified Response Evaluation Criteria in Solid Tumours for mesotheliomas, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received intravenous nivolumab (240 mg every 2 weeks) plus intravenous ipilimumab (1 mg/kg every 6 weeks up to four times). Treatment was continued for up to 2 years or until confirmed progression or unacceptable toxicity. The primary endpoint was disease control at 12 weeks. All patients who received at least one dose of therapy were included in safety analysis and all patients who received one dose of therapy and at least one radiological assessment were included in the primary analysis. This trial is registered at ClinicalTrials.gov, number NCT03048474. Between Oct 5, 2016, and Aug 3, 2017, 38 patients were enrolled in the study, of which two patients were excluded because they were not eligible for a biopsy. Of 36 eligible patients, one deteriorated before the start of the study so was not included in any analyses and one withdrew consent after one treatment cycle before radiological assessment so was included in the safety population only. 34 patients were evaluable for response assessment at 12 weeks. Of these, ten (29%) patients had a partial response and 13 (38%) patients had stable disease; thus, disease control was achieved by 23 (68%, 95% CI 50-83) of 34 patients. Treatment-related adverse events were reported in 33 (94%) patients. The most common adverse events were infusion-related reactions, skin disorders, and fatigue. Grade 3 treatment-related adverse events were reported in 12 (34%) of 35 patients. In this single-centre phase 2 trial, the combination of nivolumab plus ipilimumab showed marked efficacy in patients with recurrent malignant pleural mesothelioma. The safety profile was consistent with known data on the combination regimen. Our results warrant further investigation of this combination in a phase 3 trial. Bristol-Myers Squibb.


Double-blind comparison of acute bronchial and cardiovascular effects of oral terbutaline and ephedrine.
Acute effects of oral terbutaline (5 mg), ephedrine (25 mg) and placebo on bronchial dynamics, heart rate, systolic and diastolic pressure and arterial blood gases at rest were compared over a period of 7 hours in 20 subjects with bronchial asthma using a double-blind crossover technique. Both terbutaline and ephedrine caused significant bronchodilation, but the effect of terbutaline on specific airway conductance (SGA) was significantly greater (peak mean increase in SGA 0.069 vs 0.027 L/sec/cm H2O/L), had an earlier onset (30 minutes vs 1 hour) and lasted longer (7 hours vs 4 hours) than that of ephedrine. Slight but significant increases in arterial Po2 were noted following institution of both ephedrine and terbutaline, suggesting improvement in ventilation-perfusion relationships. Both drugs caused modest but statistically significant increases in heart rate of 8.4-10.9 beats/min and the mean peak increase following terbutaline (8.4 beats/min) was comparable to that following ephedrine. In constrast to ephedrine, terbutaline caused significant, although slight, increases in systolic pressure and decreases in diastolic pressure, indicating that this drug, in the dose recommended for clinical use, is not free of cardiovascular effects.


Subjective symptoms among female workers and winter working conditions in a consumer cooperative.
Subjective musculoskeletal symptoms are more frequently complained about in cold store work and in related conditions than in normal temperature work. This cross sectional study was undertaken (a) to explore the prevalence of subjective symptoms in winter among a group of female workers engaged in classification of cold storage goods, and in a group of female checkers in several supermarkets of a large consumer cooperative; and (b) to give recommendations for improving the winter working conditions of these workers. The subjects consisted of 46 workers engaged in classification of cold storage goods, 56 checkers operating a laser scanner in supermarkets and 59 office workers (control group). Work loads for the three groups were estimated according to the recommended criteria. A self-administered questionnaire covering age, occupational career, smoking, alcohol drinking and physical exercise, present or past history of diseases, individual protective measures against cold, and subjective symptoms (54 items) was used. The air temperature of the working site at the opening time for classification workers was 4.8 degrees C which was significantly lower than those measured for the other two work places (12.1 degrees C and 15.8 degrees C). About 70 to 80% of classification workers complained of cold sensation in different body regions, as well as shoulder stiffness, and problems related to the back. The supermarket checkers and office workers had a high prevalence of cold sensation in their feet. The frequencies of using warm clothes and foot heaters, as an individual measure to work comfortably in winter among the classification workers and the checkers were significantly higher than that among the office workers. We concluded that work difficulty due to moderate cold exposure among workers in the consumer cooperative could be reduced by some physical activity as well as proper clothes.


A morphology based key to the genera of the tribe Nemoriini (Lepidoptera: Geometridae, Geometrinae).
A diagrammatic key to the genera of the Nemoriini tribe (Lepidoptera, Geometridae) is presented and illustrated. The genera studied exhibit two main character sets, corresponding to the Nemoria lineage and the Phrudocentra lineage. The spatulate type of uncus is associated with multicolor wing markings on both hemispheres. A rod-shaped uncus, often slightly bulbed at its tip, is common in the Neotropics, the genera involved having their wing markings reduced to white lines or brown-grey vein marks on a plain green ground color.


Tyrosine sulfation of the glycoprotein Ib-IX complex: identification of sulfated residues and effect on ligand binding.
Here, we present evidence that glycoprotein (GP) Ib alpha, one of three polypeptides that make up the GP Ib--IX complex--the receptor for von Willebrand factor (vWf) on the surface of unactivated platelets--is modified by sulfation of tyrosine residues. Only GP Ib alpha was found to incorporate 35S when the GP Ib--IX complex was immunoprecipitated from [35S]sulfate metabolically labeled L and CHO cells that express the recombinant complex. The occurrence of sulfation on tyrosine residues of the polypeptide backbone was determined by removing O- and N-linked oligosaccharides. Limited proteolytic digestion of metabolically labeled GP Ib alpha revealed that sulfated tyrosine residues are located in the 45-kDa globular region containing the vWf binding site. By mutating potentially sulfated tyrosine residues to phenylalanine and comparing the stoichiometry of sulfate incorporation of these mutants to the incorporation in wild-type GP Ib alpha, three clustered tyrosine residues--Tyr-276, Tyr-278, and Tyr-279-were identified that undergo the modification. Culturing cells in sulfate-depleted medium containing sodium chlorate and guaiacol completely inhibited GP Ib alpha sulfation but did not decrease GP Ib-IX expression on the cell surface. Similarly, transiently transfected CHO cells expressed the mutant GP Ib alpha polypeptide on their surfaces at the same levels as they expressed wild-type GP Ib alpha. These results suggest that tyrosine sulfation of GP Ib alpha has little or no effect on the synthesis, assembly, and surface expression of the GP Ib-IX complex. Nevertheless, inhibiting sulfation of GP Ib alpha reduced the binding of 125I-labeled vWf in the presence of ristocetin by up to 37%.(ABSTRACT TRUNCATED AT 250 WORDS)


Separation of Palladium from Alkaline Cyanide Solutions through Microemulsion Extraction Using Imidazolium Ionic Liquids.
In this paper, three imidazolium-based ionic liquids, viz., 1-butyl-3-undecyl imidazolium bromide ([BUIm]Br), 1-butyl-3-octyl imidazolium bromide ([BOIm]Br), and 1-butyl-3-hexadecyl imidazolium bromide ([BCIm]Br), were synthesized. Three novel microemulsions systems were constructed and then were used to recover Pd (II) from cyanide media. Key extraction parameters such as the concentration of ionic liquids (ILs), equilibration time, phase ratio (RA/O), and pH were evaluated. The [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system exhibited a higher extraction percentage of Pd (II) than the [BOIm]Br/n-heptane/n-pentanol/sodium chloride and [BCIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion systems. Under the optimal conditions (equilibrium time of 10 min and pH 10), the extraction percentages of these metals were all higher than 98.5% when using the [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system. Pd(CN)42- was separated through a two-step stripping procedure, in which Fe (III) and Co (III) were first separated using KCl solution, then Pd(CN)42- was stripped using KSCN solution (separation factors of Pd from Fe and Co exceeded 103). After five extraction-recovery experiments, the recovery of Pd (II) through the microemulsion system remained over 90%. The Pd (II) extraction mechanism of the ionic liquid [BUIm]Br was determined to occur via anion exchange, as shown by spectral analysis (UV, FTIR), Job's method, and DFT calculations. The proposed process has potential applications for the comprehensive treatment of cyanide metallurgical wastewater.


Crystal structure of 2-cyano-3,3-bis-(ethyl-sulfan-yl)-N-o-tolyl-acryl-amide.
In the mol-ecule of the title compound, C15H18N2OS2, the central S2C=C(CN)C moiety is planar (r.m.s. deviation = 0.029 Å). The C=O and C-CN groups are trans to each other across their common C-C bond. In the crystal, one classical and two 'weak' hydrogen bonds combine with borderline N⋯N and S⋯S contacts to form layers parallel to (10-2). One ethyl group is disordered over two positions with relative occupancy 0.721/0.279 (7).


L-Carnitine transport in human placental brush-border membranes is mediated by the sodium-dependent organic cation transporter OCTN2.
Maternofetal transport of l-carnitine, a molecule that shuttles long-chain fatty acids to the mitochondria for oxidation, is thought to be important in preparing the fetus for its lipid-rich postnatal milk diet. Using brush-border membrane (BBM) vesicles from human term placentas, we showed that l-carnitine uptake was sodium and temperature dependent, showed high affinity for carnitine (apparent K(m) = 11.09 +/- 1.32 microM; V(max) = 41.75 +/- 0.94 pmol.mg protein(-1).min(-1)), and was unchanged over the pH range from 5.5 to 8.5. l-Carnitine uptake was inhibited in BBM vesicles by valproate, verapamil, tetraethylammonium, and pyrilamine and by structural analogs of l-carnitine, including d-carnitine, acetyl-d,l-carnitine, and propionyl-, butyryl-, octanoyl-, isovaleryl-, and palmitoyl-l-carnitine. Western blot analysis revealed that OCTN2, a high-affinity, Na(+)-dependent carnitine transporter, was present in placental BBM but not in isolated basal plasma membrane vesicles. The reported properties of OCTN2 resemble those observed for l-carnitine uptake in placental BBM vesicles, suggesting that OCTN2 may mediate most maternofetal carnitine transport in humans.


Enhanced DNA Damages of Human Prostate Cancer Cells Induced by Radiofrequency Capacitive Hyperthermia Pre- and Post X-rays: 6 MV versus 15 MV.
This study aimed to determine the effect of 13.56 MHz radiofrequency (RF) capacitive hyperthermia (HT) on radiosensivity of human prostate cancer cells pre and post X-ray radiation treatment (RT). In this experimental study, the human prostate cancer cell line DU145 was cultured as 300 µm diameter spheroids. We divided the spheroids into group I: control, group II: HT at 43˚C for 30 minutes (HT), group III: 4 Gy irradiation with 6 MV X-ray [RT (6 MV)], group IV: 4 Gy irradiation with 15 MV X-ray [RT (15 MV)], group V: HT+RT (6 MV), group VI: HT+RT (15 MV), group VII: RT (6 MV)+HT, and group VIII: RT (15 MV)+HT. The alkaline comet assay was used to assess DNA damages in terms of tail moment (TM). Thermal enhancement factor (TEF) was obtained for the different treatment combinations. Mean TM increased with increasing photon energy. Group II had significantly greater TM compared to group I. Groups III and IV also had significantly higher TM compared to group I. Significant differences in TM existed between groups V, VII, and III (P<0.05). We observed significant differences in TM between groups VI, VIII, and IV. TEF values demonstrated that enhanced response to radiation was more pronounced in group V compared to the other combined treatments. Our results suggest that HT applied before RT leads to higher radiosensivity compared to after RT. HT at 43˚C for 30 minutes added to 6 MV X-ray causes higher enhancement of radiation compared to 15 MV X-ray.


Glutamate transporter studies reveal the pruning of metabotropic glutamate receptors and absence of AMPA receptor desensitization at mature calyx of Held synapses.
We examined the effect of glutamate transporter blockade at the calyx of Held synapse. In immature synapses [defined as postnatal day 8 (P8) to P10 rats], transporter blockade causes tonic activation of NMDA receptors and strong inhibition of the AMPA receptor-mediated EPSC amplitude. EPSC inhibition was blocked with a metabotropic glutamate receptor (mGluR) antagonist [1 microm LY341495 (2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoic acid)], suggesting that elevated resting glutamate concentration specifically activates group II and group III mGluRs. Using mGluR subtype-specific agonists and antagonists, we determined that increased glutamate activates presynaptic mGluR2/3 and mGluR8 receptors but not mGluR4, although this receptor is present. Surprisingly, in older animals (P16-P18), transporter blockade had no effect on EPSC amplitude because of a developmental downregulation of group II/III mGluR activation in rats and mice. In contrast to other CNS synapses, we observed no effect of transporter blockade on EPSC decay kinetics, although expression of glutamate transporters was strong in nearby glial processes at both P9 and P17. Finally, using a low-affinity AMPA receptor antagonist (gamma-D-glutamylglycine), we show that desensitization occurs at P8-P10 but is absent at P16-P18, even during trains of high-frequency (100-300 Hz) stimulation. We suggest that diffusion and transporter activation are insufficient to clear synaptically released glutamate at immature calyces, resulting in significant desensitization. Thus, mGluRs may be expressed in the immature calyx to help limit glutamate release. In the more mature calyx, there is a far smaller diffusional barrier attributable to the highly fenestrated synaptic terminal morphology, so AMPA receptor desensitization is avoided and mGluR-mediated inhibition is not necessary.


Role of macrophage glycosaminoglycans in the cellular catabolism of oxidized LDL by macrophages.
Macrophage binding sites for oxidized LDL (Ox-LDL) include class A scavenger receptors (SR-As), the CD-36 molecule, and an additional but hitherto unidentified binding site. Because cell-surface glycosaminoglycans (GAGs) were previously shown to be involved in the cellular uptake of native LDL and lipoprotein(a), several strategies to assess the participation of heparan sulfate (HS) and chondroitin sulfate (CS) in macrophage catabolism of Ox-LDL were used. First, incubation of J-774 A.1 macrophage-like cells with either heparinase or chondroitinase, or with both enzymes together, reduced the binding, uptake, and degradation of 125I-Ox-LDL by 20% to 45%, in comparison with control nontreated cells, while catabolism of 125I-labeled acetylated LDL (Ac-LDL) and native LDL were unaffected. Second, the proteoglycan (PG) cellular content was increased by cell enrichment with exogenous GAGs or by using human monocyte-derived macrophages from two patients with Sanfilippo mucopolysaccharidosis, which are characterized by cellular HS accumulation. In these macrophages, cellular uptake of 125I-Ox-LDL increased, while catabolism of 125I-Ac-LDL and native LDL were unaffected. Experiments using conditioned media from control, heparinase-digested, or chondroitinase-digested macrophages indicated that neither secreted GAGs nor released digestion products played any role in Ox-LDL catabolism. To evaluate potential interactions between cell-surface GAGs and known receptors for Ox-LDL, we used excess unlabeled Ac-LDL to block SR-As or anti-CD-36 antibodies to block CD-36, and then examined the catabolism of 125I-Ox-LDL by GAG-enriched or -depleted macrophages. Both excess unlabeled Ac-LDL and anti-CD-36 antibodies reduced 125I-Ox-LDL catabolism, but only excess unlabeled Ac-LDL completely abolished the increase in 125I-Ox-LDL catabolism on GAG enrichment of the cells, indicating a cooperation between exogenous GAGs and cell-surface SR-As in the catabolism of OX-LDL. Moreover, the addition of GAGases to macrophages that were preincubated with anti-CD-36 antibodies and excess Ac-LDL further reduced macrophage degradation of Ox-LDL in comparison with cells that were pretreated only with anti-CD-36 antibodies and Ac-LDL, indicating a more complex role for endogenous GAGs. Overall, these studies demonstrate a substantial contribution of macrophage-associated GAGs in the catabolism of Ox-LDL, which is mediated in part by a cooperation between GAGs and cell-surface SR-As.


[Confusional states in advanced age--a current review of the literature].
Delirium--a state of acute or subacute confusion--is a common organic mental syndrome occurring predominantly in old age. The disorder is highly prevalent in psychiatric institutions, in general hospitals and nursing homes. Patients affected by delirium carry an increased mortality-risk and will become dependent on nursing care in a high percentage. In this paper, diagnostic criteria, symptomatology, and pathogenesis of delirious states are reviewed. The wide variety of etiologic factors is illustrated by case histories. The present state of diagnostic and therapeutic management is discussed. A review of recent publications indicates that substantial advances in knowledge on epidemiology, operationalized diagnosis, risk factors, and course of delirium have been attained. There are, however, important aspects--e.g. the evaluation of prophylactic and therapeutic measures--which have been neglected. With regard to the high prevalence of delirium and the inderdisciplinary relevance of this syndrome scientific activities on this field should be increased as well as refreshment of knowledge of medical and nursing staff should be aimed at.


Effects of frusemide and captopril on the relationship between biologically and immunologically active renin in human plasma.
1. The plasma renin concentration (PRC) and active renin concentration determined by radioimmunometric assay (ARC) were measured before and after administration of frusemide or captopril to normal volunteers. 2. Injection of 40 mg of frusemide followed by 1 h in the upright position significantly increased both PRC (P less than 0.001) and ARC (P less than 0.001). Oral administration of 50 mg of captopril also increased PRC (P less than 0.05) and ARC (P less than 0.05). 3. ARC and PRC were linearly correlated in the basal supine position [y = 0.635x - 0.048 (y = PRC, x = ARC), r = 0.958, P less than 0.001], after frusemide injection and standing (y = 0.800x + 0.359, r = 0.793, P less than 0.02) and after captopril administration in the supine position (y = 0.938x - 0.555, r = 0.998, P less than 0.001). 4. A cross-calibration study in which pure human renin was added to pooled plasma and PRC and ARC were measured showed linearity between the values obtained by the two methods. 5. The regression line for values of PRC and ARC in the supine position after captopril administration had a significantly greater slope (P less than 0.001) and that for values after frusemide injection and standing was significantly elevated (P less than 0.001) compared with the regression line for basal values in the supine position. 6. These results show that the biological activity of renin may be increased by various acute stimulations of renin to inappropriately high levels compared with the immunological activity.(ABSTRACT TRUNCATED AT 250 WORDS)


High-risk population and factors of stroke has changed among middle-aged and elderly Chinese-Evidence from 1989 to 2015.
Stroke is an acute cerebrovascular disease with high mortality and disability. This study aimed to investigate the trend of stroke prevalence from 1989 to 2015 in China, explore the transition of high-risk population and high-risk factors, and provide some evidence to develop more targeted stroke intervention strategies. We derived the baseline data from China Health and Nutrition Survey (CHNS). Participants responded to face-to-face interviews and examinations containing demographic information, behavioral health information, disease history, and physical examination. We applied chi-square test, shapley value decomposition model, and decision tree model to evaluate the changes of high-risk population and high-risk factors of stroke. Across 42,419 middle-aged and elderly residents, the prevalence of stroke was decreasing from 1989 to 2015. Hypertension was the leading risk factor of stroke, while its contribution rate was weakened with the increasing of medicine taking rate. As the second risk factor of stroke, the contribution of age decreased either. Meanwhile, the contribution rate of historical health factors, lifestyle factors, and regional factors, such as body mass index, diabetes, and living area to the impact of stroke was increasing. In addition, the first high-risk population of stroke changed from hypertension patients aged 75 years and above to without spouse residents living in stroke belt such as Beijing and Liaoning. The second risk population of stroke transformed from male hypertensive patients under 75 years old into male hypertensive patients living in urban. The third high-risk group turned from the elderly aged 75 and above into the female patients with hypertension and diabetes. This study demonstrated that the high-risk population and high-risk factors of stroke changed in China and revealed the direction and internal mechanism of transition of stroke. Targeted stroke intervention strategies should be renewed. Health education for the high-risk population of stroke should be carried out, healthy living habits need be advocated, and the use of antihypertensive drugs for the hypertensive patients should be standardized.


Update on clinical imaging of coronary plaque in acute coronary syndrome.
Current evidence suggests that understanding coronary artery disease extends beyond identifying and treating traditional risk factors. Progression of coronary plaque contributes to the development of acute coronary syndrome (ACS). In this article, we reviewed current literature for modalities to image coronary plaque as well as discussed the role of emerging techniques that can improve our understanding of the pathophysiology of ACS.


312-fs pulse generation from a passive C-band InAs/InP quantum dot mode-locked laser.
For the first time, we report femtosecond pulses from a passive single-section InAs/InP quantum-dot (QD) mode-locked laser (MLL) with the active length of 456 microm and ridge width of 2.5 microm at the C-band wavelength range. Without any external pulse compression, the transform-limited Gaussian-pulses are generated at the 92 GHz repetition rate with the 312 fs pulse duration, which is the shortest pulse from any directly electric-pumping semiconductor MLLs to our best knowledge. The lasing threshold injection current and external differential quantum efficiency are 17.2 mA and 38%, respectively. We have also investigated the working principles of the proposed QD MLLs.


[The usefulness and limitations of the radioallergosorbent test in diagnosing food allergy in atopic dermatitis].
To clarify the diagnostic value of the radioallergosorbent test (RAST), the relationship between RAST and the oral food challenge test was evaluated. 263 children with atopic dermatitis were challenged by egg, cow's milk or soy bean after their skin manifestations had been improved by elimination diet and environmental control. Of 200 cases with negative RAST results for egg white, 108 cases (54.0%) showed no reaction in egg challenge tests. However, 65 cases (31.5%) had non-immediate reactions, while 29 cases (14.5%) had immediate reactions (within 2 hours of challenge). Of 16 cases with RAST score of 1 for egg white, 11 cases (68.8%) had non-immediate reactions and 2 cases (12.5%) had immediate reactions in egg challenge tests. Of 19 cases with RAST scores of 2 for egg white, 2 cases (10.5%) had no reaction, 6 cases (31.6%) had non-immediate reactions and 11 cases (57.9%) had immediate reactions in egg challenge tests. Of 21 cases with RAST scores of 3 for egg white, 1 case (4.8%) had no reaction, 3 cases (14.3%) had non-immediate reactions and 17 cases (81.0%) had immediate reactions in egg challenge tests. All 7 cases with RAST scores of 4 for egg white had immediate reactions in egg challenge tests. Almost the same relationship between RAST and challenge tests were found in test using cow's milk or soy bean. In conclusion, false negative results were seen in 46.0% of RAST for egg white, 51.7% of RAST for cow's milk and 26.9% of RAST for soy bean.(ABSTRACT TRUNCATED AT 250 WORDS)


Mitral valve replacement in infancy: haemodynamic factors.
Severe mitral valve regurgitation necessitated the insertion of a prosthetic valve (Björk-Shiley no. 21) in a girl 10 months of age. Control studies after the baby had doubled her body weight showed normal haemodynamic data. It is estimated that a valve of this size should allow the expected cardiac output for a patient of 9-12 years of age. Thrombosis and tissue overgrowth may result in "recurrent" mitral stenosis long before this date. Repeated haemodynamic studies at intervals of 2-3 years are therefore indicated, since clinical signs fail to show recurrent valve stenosis; should the latter develop there is the risk of irreversible pulmonary vascular resistance.


Effect of triazole fungicides on lipid metabolism of Saccharomyces cerevisiae.
The triazole fungicide (Flusilazole) modified the sterol content of Saccharomyces cerevisiae. The plasma membrane fluidity was altered by the presence of methyl sterol which increased with the flusilazole concentration. On the other hand, the short free fatty acids (C6 to C14) and the unsaturated free fatty acids increased in the cells, while the short free fatty acids decreased in the medium.


Persistent infection caused by Hobi-like pestivirus.
A calf persistently infected by Hobi-like pestivirus was monitored for about 6 months, displaying clinical signs typical of bovine viral diarrhea virus persistent infection and shedding the virus through all body secretions, with maximal titers detected in urine. This report provides new insights into the pathogenesis of the emerging pestivirus.


Autophosphorylation-dependent inactivation of plant chimeric calcium/calmodulin-dependent protein kinase.
Chimeric calcium/calmodulin dependent protein kinase (CCaMK) is characterized by the presence of a visinin-like Ca(2+)-binding domain unlike other known calmodulin- dependent kinases. Ca(2+)-Binding to the visinin-like domain leads to autophosphorylation and changes in the affinity for calmodulin [Sathyanarayanan P.V., Cremo C.R. & Poovaiah B.W. (2000) J. Biol. Chem. 275, 30417-30422]. Here, we report that the Ca(2+)-stimulated autophosphorylation of CCaMK results in time-dependent loss of enzyme activity. This time-dependent loss of activity or self-inactivation due to autophosphorylation is also dependent on reaction pH and ATP concentration. Inactivation of the enzyme resulted in the formation of a sedimentable enzyme due to self-association. Specifically, autophosphorylation in the presence of 200 microm ATP at pH 7.5 resulted in the formation of a sedimentable enzyme with a 33% loss in enzyme activity. Under similar conditions at pH 6.5, the enzyme lost 67% of its activity and at pH 8.5, 84% enzyme activity was lost. Furthermore, autophosphorylation at either acidic or alkaline reaction pH lead to the formation of a sedimentable enzyme. Transmission electron microscopic studies on autophosphorylated kinase revealed particles that clustered into branched complexes. The autophosphorylation of wild-type kinase in the presence of AMP-PNP (an unhydrolyzable ATP analog) or the autophosphorylation-site mutant, T267A, did not show formation of branched complexes under the electron microscope. Autophosphorylation- dependent self-inactivation may be a mechanism of modulating the signal transduction pathway mediated by CCaMK.


EVOLUTION OF DISPERSAL RATES IN METAPOPULATION MODELS: BRANCHING AND CYCLIC DYNAMICS IN PHENOTYPE SPACE.
We study the evolution of dispersal rates in a two patch metapopulation model. The local dynamics in each patch are given by difference equations, which, together with the rate of dispersal between the patches, determine the ecological dynamics of the metapopulation. We assume that phenotypes are given by their dispersal rate. The evolutionary dynamics in phenotype space are determined by invasion exponents, which describe whether a mutant can invade a given resident population. If the resident metapopulation is at a stable equilibrium, then selection on dispersal rates is neutral if the population sizes in the two patches are the same, while selection drives dispersal rates to zero if the local abundances are different. With non-equilibrium metapopulation dynamics, non-zero dispersal rates can be maintained by selection. In this case, and if the patches are ecologically identical, dispersal rates always evolve to values which induce synchronized metapopulation dynamics. If the patches are ecologically different, evolutionary branching into two coexisting dispersal phenotypes can be observed. Such branching can happen repeatedly, leading to polymorphisms with more than two phenotypes. If there is a cost to dispersal, evolutionary cycling in phenotype space can occur due to the dependence of selection pressures on the ecological attractor of the resident population, or because phenotypic branching alternates with the extinction of one of the branches. Our results extend those of Holt and McPeek (1996), and suggest that phenotypic branching is an important evolutionary process. This process may be relevant for sympatric speciation.


The diagnostic yield of advanced imaging in dogs with Horner's syndrome presenting with and without additional clinical signs: A retrospective study of 120 cases (2000-2018).
To evaluate the diagnostic yield of advanced imaging in dogs with Horner's syndrome (HS) both with and without additional clinical signs. Retrospective review of clinical records from a UK referral hospital (2000-2018). Cases were excluded if HS was trauma- or surgery-related and if no advanced imaging with MRI or CT was performed. Imaging findings were assessed as well as any additional investigations performed. One hundred twenty cases met the inclusion criteria; 88 with additional clinical signs and 32 with isolated HS. MRI or CT of head and neck was performed in 115 cases and/or thoracic CT in eight cases. Causative lesions were identified in 98% (86/88) of cases with additional clinical signs and 3% (1/32) of cases with isolated HS. This was statistically significant (p < .001). Pharmacological localization using phenylephrine (0.1%-10%) was accurate in predicting the site of a causative lesion in 79% (19/24) of tested cases. Overall, 28% (33/120) of cases were idiopathic, of which 49% (16/33) were golden retrievers. When compared to the overall hospital population, and UK Kennel Club records, this confirmed a significant predisposition in this breed (p < .001). No associations between idiopathic HS and concurrent systemic disease were identified. This is the first study to evaluate the diagnostic yield of advanced imaging in dogs with HS. Isolated HS is significantly more likely to be idiopathic than cases presenting with additional clinical signs; this could guide decision-making regarding further investigations performed in a clinical setting. Idiopathic HS is over-represented in the golden retriever.


Don't make cache too complex: A simple probability-based cache management scheme for SSDs.
Solid-state drives (SSDs) have recently become a common storage component in computer systems, and they are fueled by continued bit cost reductions achieved with smaller feature sizes and multiple-level cell technologies. However, as the flash memory stores more bits per cell, the performance and reliability of the flash memory degrade substantially. To solve this problem, a fast non-volatile memory (NVM-)based cache has been employed within SSDs to reduce the long latency required to write data. Absorbing small writes in a fast NVM cache can also reduce the number of flash memory erase operations. To maximize the benefits of an NVM cache, it is important to increase the NVM cache utilization. In this paper, we propose and study ProCache, a simple NVM cache management scheme, that makes cache-entrance decisions based on random probability testing. Our scheme is motivated by the observation that frequently written hot data will eventually enter the cache with a high probability, and that infrequently accessed cold data will not enter the cache easily. Owing to its simplicity, ProCache is easy to implement at a substantially smaller cost than similar previously studied techniques. We evaluate ProCache and conclude that it achieves comparable performance compared to a more complex reference counter-based cache-management scheme.


Inhibition of fibrinolytic system by liquoid (polyanetholesulfonate). A contributing factor in the liquoid-induced renal cortical necrosis.
Liquoid induces microvascular thrombosis and renal cortical necrosis in experimental animals. We hypothesized that thrombosis and renal cortical necrosis may, at least in part, result from the inhibition of the fibrinolytic system by liquoid. Effects of liquoid on plasminogen activation by rat kidney, purified human tissue plasminogen activator (TPA), urokinase, streptokinase, and on the amidolytic activities of TPA, urokinase, and plasmin were studied using chromogenic substrates and clot lysis. Liquoid had a strong inhibitory effect on the fibrinolytic system in vivo and in vitro. The inhibition was most effective at the plasminogen activation level, with activation by streptokinase being most susceptible. The demonstrated stoichiometric binding between liquoid and plasminogen, and to a lesser degree the direct inactivation of plasminogen activators and plasmin, is probably responsible for the reduction of plasminogen activation in circulation and in the kidneys.


[A case of Fitz-Hugh-Curtis syndrome in a male].
Fitz-Hugh-Curtis syndrome has been described as focal perihepatitis accompanying pelvic inflammatory disease caused by Neisseria gonorrhea and Chlamydia trachomatis. The highest incidence occurs in young, sexually active females. However, the syndrome has been reported to occur infrequently in males, according to the foreign literature. The predominant symptoms are right upper quadrant pain and tenderness, and pleuritic right sided chest pain. The clinical presentation is similar in men and women. In women, the spread of infection to liver capsule is thought to occur directly from infected fallopian tube via the right paracolic gutter. In men, hematogenous and lymphatic spread is thought to be postulated. Recently, we experienced a case of Fitz-Hugh-Curtis syndrome occurred in a man. As far as we know, it is the first report in Korea, and we report a case with a review of the literature.


Use of Oral Empagliflozin to Obtain Optimal Blood Sugar Levels for Conducting 18 F-FDG PET-CT in Patients with Hyperglycemia-A Pilot Study.
Background Flourine-18 fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET-CT) is a well-established imaging modality for the evaluation of patients with oncological and nononcological conditions. The underlying principle of imaging is the preferentially increased glucose consumption by cancer cells, due to overexpression of glucose type 1 receptors that are insulin independent. Thus, one of the factors that leads to decreased sensitivity of an 18 F-FDG PET-CT is elevated blood sugar levels, leading to decreased glucose uptake by cancer cells due to competitive inhibition. A significant percentage of patients scheduled for PET-CT scan has diabetes mellitus type II as a comorbid condition and often has elevated random blood sugar (RBS) precluding an upfront PET-CT evaluation. Such cases must be rescheduled. This causes delay in the evaluation and management of such patients. Empagliflozin is a novel sodium glucose type 2 inhibitor that prevents tubular reabsorption of glucose and increases renal glycosuria resulting in decreased blood sugar. This drug does not cause significant hypoglycemia or increase endogenous insulin secretion. This study was undertaken to evaluate a potential role for empagliflozin in facilitating optimal blood sugar control in patients with hyperglycemia on the day of the scheduled PET scan. Methods This is an interventional prospective study and patients detected to have RBS more than 200 mg/dL on the day of the scheduled scan were included in the study. The patients were administered two tablets of 10 mg empagliflozin and kept under observation. Samples for RBS were taken at approximately 2nd and 4th hour post administration by bedside method. These patients underwent scan on the same day after adequate sugar control and when an RBS of less than 200 mg/dL was achieved. The primary outcome studied was change in RBS values in the patient cohort and evaluation of PET SUV (standardized uptake value) compared with the rest of the patients scheduled on the same day. Secondary outcome was assessment of any side effects in the patients. Results Total of 10 patients were found to have elevated blood sugar (RBS > 200 mg/dL; irrespective of being on medication) and did not meet the evaluation criteria for a PET-CT scan on the scheduled day. Following administration of the drug, all 10 patients were able to attain blood sugar levels and fulfill the criteria for undergoing a PET-CT scan. No obvious side effect was noted in any of the patient. The SUV values of the patient cohort were comparable with the rest of the patient scanned on the day. Conclusion In this pilot study, 20 mg of empagliflozin (2 tablets of 10 mg) appears to be a safe and effective method for achieving optimal decrease in the RBS without causing hypoglycemia or hyperinsulinemia. It can be safely employed in the subset of population with RBS between 201 and 300 mg/dL to adequately bring the sugar levels at acceptable levels RBS less than 200 mg/dl and fulfill the FDG PET-CT criteria as per European Association of Nuclear Medicine (EANM) norms.


Role of RP11-83J16.1, a novel long non-coding RNA, in rheumatoid arthritis.
This study aimed to explore the effects of long non-coding RNA (lncRNA) expression on rheumatoid arthritis (RA). LncRNA expression profiles were obtained from the synovial tissues of five RA patients and five age-/gender-matched controls by RNA-Seq. Six candidate lncRNAs were then chosen and their levels in synovial fluid further examined in 25 RA patients and 25 health controls using RT-qPCR. The effects of lncRNA RP11-83J16.1 overexpression and knockdown on RA fibroblast-like synoviocytes (RA-FLS) function, inflammation state, and URI1, FRAT1, and β-catenin levels were assessed. After RNA-Seq, lncRNA expression profiles clearly distinguished RA patients from controls, and 190 upregulated lncRNAs and 131 downregulated lncRNAs were identified, which were mainly enriched in proliferative/immune/inflammatory pathways. Results of RT-qPCR showed that the levels of lncRNAs MTCO2P12, KCNQ5-IT1 and RP11-83J16.1 were increased, whereas lncRNAs LINC00570, RP11-342M1.6, and REXO1L4P were decreased in RA patients compared to controls. Notably, lncRNA RP11-83J16.1 correlated with increased inflammation and disease activity in RA patients. Additionally, lncRNA RP11-83J16.1 promoted cell proliferation, migration, invasion and inflammation, reduced apoptosis, and positively regulates cellular URI1, FRAT1 and β-catenin expression in RA-FLS. Rescue experiments revealed that URI1 overexpression compensated for the regulatory effects of lncRNA RP11-83J16.1 knockdown in RA-FLS. In conclusion, lncRNA RP11-83J16.1, a novel lncRNA identified by RNA-Seq, correlates with increased risk and disease activity of RA, and promotes RA-FLS proliferation, migration, invasion and inflammation by regulating URI1 and downstream β-catenin pathway components.


Clinical factors affecting salivary transferrin level, a marker of blood contamination in salivary analysis.
Diagnostic value of whole saliva may be compromised when blood contamination is present in saliva samples. Measuring transferrin level in saliva samples has been used for detecting the level of blood contamination in saliva. The aim of this study was to investigate the validity of transferrin as a proper biomarker for blood contamination in whole saliva. Thirty younger (mean age: 25.9 ± 2.1 years) and twenty older (mean age: 65.1 ± 9.0 years) females were included. The index reflecting overall gingival inflammation (total gingival index), salivary flow rate, and salivary concentration and secretion rate of transferrin of each subject were analyzed. Salivary transferrin concentrations and secretion rates were higher in the younger females than in the older ones despite a lower total gingival index in the younger females. The total gingival index showed no significant correlations with the concentration or secretion rate of transferrin in either unstimulated or stimulated whole saliva of younger and older subjects. The salivary concentration of transferrin showed negative correlations with the flow rate of saliva in both the younger and older groups. There were significant positive correlations between the salivary concentrations and secretion rates of transferrin in both the younger and older groups. Salivary transferrin levels could be affected by other factors as well as the level of blood contamination. The influences of age, gonadal hormones, salivary flow rate, and chewing performance need to be considered when using the salivary level of transferrin as a blood contamination marker.


A Practical, Evidence-informed Approach to Managing Stimulant-Refractory Attention Deficit Hyperactivity Disorder (ADHD).
Stimulants (methylphenidate or amphetamines) are the recommended first-line option for the pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD). However, some patients with ADHD will not respond optimally to stimulants. Here, we discuss strategies to manage stimulant-refractory ADHD, based on the recommendations advanced in clinical guidelines, knowledge of expert practice in the field, and our own clinical recommendations, informed by a comprehensive literature search in PubMed, PsycInfo, EMBASE + EMBASE classic, OVID Medline, and Web of Science (up to 30 March 2021). We first highlight the importance of stimulant optimization as an effective strategy to increase response. We then discuss a series of factors that should be considered before using alternative pharmacological strategies for ADHD, including poor adherence, time action properties of stimulants (and wearing-off of effects), poor tolerability (that prevents the use of higher, more effective doses), excessive focus on or confounding from presence of comorbid non-ADHD symptoms, and tolerance. Finally, we consider the role of non-stimulants and combined pharmacological approaches. While the choice of medication for ADHD is still to a large extent based on a trial-and-error process, there are reasonably accepted data and guidelines to aid in clinical decision-making. It is hoped that advances in precision psychiatry in the years ahead will further guide prescribers to tailor medication choice to the specific characteristics of the patient.


Identical characteristics of the patient populations with pineal region tumors in Japan and in Korea and therapeutic modalities.
The therapeutic modalities used for tumors of the pineal region in Western countries differ from those in Japan, mainly because of the different patient populations. An extensive survey was conducted to delineate the racial differences in Japan and in Korea in the epidemiology and recent therapeutic modalities for this tumor group. Among the members of International Society for Pediatric Neurosurgery (ISPN), 15 from Japan and 5 from Korea reported their recent findings in 118 (1-25 years of age, mean 7.38-year period) and 125 (1-12 years of age, mean 6.69-year period) histologically verified cases, respectively. The patient populations in the two countries were found to be almost identical, with an extremely high incidence of germ cell tumors representing 71.2% (in Japan) and 80.0% (in Korea) of all pineal region tumors and neuroectodermal tumors representing only 15.2% and 16.8%, respectively. The most common type of pineal region tumor was germinoma (46.6% in Japan and 47.2% in Korea). The majority of tumors were radio- and/or chemosensitive, and adjuvant therapy rather than extensive surgery played the major role in the treatment in both countries. Radical resection of the tumor was recommended as the initial procedure by only 22.2% of neurosurgeons in Japan and 16.6% in Korea. Biopsy was recommended by 38.9% and 50.0%, and radiation therapy by 38.9% and 37.5%, respectively. A minimally invasive procedure, by either a neuroendoscopic (33.3% of biopsies in Japan) or a stereotactic approach (33.3% of biopsies in Korea), was considered to be appropriate as the initial procedure. The study disclosed the almost identical epidemiology of this brain tumor in Japan and in Korea and clarified the consequent therapeutic modalities. The authors emphasize that minimally invasive tissue diagnosis with or without tumor debulking should be considered as the initial step for the treatment planning of the pineal region tumor, followed by the most commonly indicated major procedures, including radiation therapy, chemotherapy and/or radical resection with various methodologies.


[Microbiological and immunodiagnostic studies in experimental erysipeloid].
The use of the passive hemagglutination test with a set of antigenic and antibody erythrocytic diagnostic reagents made it possible to detect antibodies to Erysipelothrix rhusiopathiae specific and type specific antigens in the blood serum of infected mice and to reveal the presence of these antigens in the internal organs of the animals. After a considerable increase of the infective dose a higher level of contamination and the retention of the antigens in the internal organs were observed, while the activity of specific antibodies in the blood serum decreased.


Ion temperature and rotation fluctuation measurements with ultra-fast charge exchange recombination spectroscopy (UF-CHERS) in the DIII-D tokamak.
An upgraded detector and several optimizations have significantly improved the Ultra-Fast Charge Exchange Recombination Spectroscopy (UF-CHERS) diagnostic sensitivity to ion temperature and parallel velocity fluctuations at turbulence relevant spatio-temporal scales. Normalized broadband ion temperature and parallel velocity fluctuations down to x̃x∼1% (x = Ti, v∥) and up to ∼450 kHz have been measured in a variety of plasmas. The multi-field nature of the CHERS technique also allows measurements of the cross-phase angles of the fluctuating fields. UF-CHERS is optimized to observe emissions from the electron exchange reaction between intrinsic C6+ and hydrogenic neutral beam injected particles near 529 nm. UF-CHERS consists of two chords separated by ∼1 cm radially, less than the turbulence correlation length in DIII-D plasmas, which enables correlated measurements to suppress incoherent electronic and photon noise. The optical components of the spectrometer include a volume-phase-holographic grating with >90% transmission between 528 and 530 nm and f/2 200-mm lenses, selected to maximize the optical efficiency and photon flux. Diffracted light from each chord is collected in eight spectral bins, each with a bandwidth of ∼0.25 nm, and detected and amplified by chilled avalanche photodiodes and custom high-gain, wide bandwidth low-noise preamplifiers to achieve the optimal signal-to-noise ratio. The resulting signals are digitized at 1 MHz, 103-104× faster than the conventional CHERS diagnostics. Spatial coverage is achieved by repositioning a motorized fiber tray between plasmas. UF-CHERS measurements will advance the understanding of turbulent ion transport and contribute to the validation of transport models and simulations.


A novel technique for tumor localization and targeted lymphatic mapping in early-stage lung cancer.
To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-infrared (NIR) localization of small, ill-defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non-small cell lung cancer (NSCLC). Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB-guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured. Ex vivo confirmation of NIR+ SLNs and adverse events were recorded. Twelve patients underwent NB-guided marking with indocyanine green of lung lesions ranging in size from 0.4 to 2.2 cm and located 0.1 to 3 cm from the pleural surface. An NIR+ "tattoo" was identified in all cases. Ten patients were diagnosed with NSCLC and 9 SLNs were identified in 8 of the 10 patients, resulting in an 80% SLN detection rate. SLN pathologic status was 100% sensitive and specific for overall nodal status with no false-negative results. Despite previous nodal sampling, one patient was found to have metastatic disease in the SLN alone, a 12.5% rate of disease upstaging with NIR SLN mapping. SLN were detectable for up to 3 hours, allowing time for obtaining a tissue diagnosis and surgical resection. There were no adverse events associated with NB-labeling or indocyanine green dye itself. NB-guided NIR lesion localization and SLN identification was safe and feasible. This minimally invasive image-guided technique may permit the accurate localization and nodal staging of early stage lung cancers.


Noncontact laser microdissection and pressure catapulting: sample preparation for genomic, transcriptomic, and proteomic analysis.
The understanding of the molecular mechanisms of cellular metabolism and proliferation necessitates accurate identification, isolation, and finally characterization of a specific cell or a population of cells and subsequently their subsets of biomolecules. For the simultaneous analysis of thousands of molecular parameters within a single experiment, as realized by DNA, RNA, and protein microarray technologies, a defined number of homogeneous cells derived from a distinct morphological origin is required. Sample preparation is therefore a very crucial step for high-resolution downstream applications. Laser microdissection and laser pressure catapulting (LMPC) enables such pure and homogeneous sample preparation, resulting in an eminent increase in the specificity of molecular analyses. For microdissection, the force of focused laser light is used to excise selected cells or large tissue areas from object slides or from living cell culture down to a resolution of individual single cells and subcellular components like organelles or chromosomes, respectively. After microdissection this sample is directly catapulted into an appropriate collection device. As the entire process works without any mechanical contact, it enables pure sample retrieval from morphologically defined origin without cross contamination. Wherever homogenous samples are required for subsequent analysis of, e.g., cell areas, single cells, or chromosomes, the PALM MicroBeam system is an indispensable tool. The integration of image analysis platforms fully automates screening, identification, and finally subsequent high-throughput sample handling. These samples can be directly linked into versatile downstream applications, such as single-cell mRNA-extraction, different PCR methods, microarray techniques, and many others. Acceleration in sample generation vastly increases the throughput in molecular laboratories and leads to an increasing knowledge about differentially regulated mRNAs and expressed proteins, providing new insights into cellular mechanisms and therefore enabling the development of systems for tumor biomarker identification, early detection of disease-causing alterations, therapeutic targeting and/or patient-tailored therapy.


The lack of correlation between radiographic findings and cartilage integrity.
Total knee arthroplasty is a common treatment of osteoarthritis, although unicompartmental knee arthroplasties are frequently used to retain unaffected compartments. Joint space width (JSW) is a major factor in determining treatment. We examined the relationship between JSW and cartilage quality in 60 patients undergoing total knee arthroplasty to assess its accuracy in representing cartilage degradation. Radiographic JSW was recorded, whereas the unaffected compartment of each tibial plateau was examined postoperatively using Collins, Mankin, and Kellgren and Lawrence scores. No correlation was seen between visual or histologic grading and JSW. Histology more accurately represented cartilage quality, yet it is impractical to obtain preoperatively; thus, JSW is the main mode of assessment. However, using JSW solely to indicate unicompartmental knee arthroplasty may overlook disease in apparently unaffected compartments.


Risk factors for child and adolescent maltreatment: a longitudinal investigation of a cohort of inner-city youth.
This study investigates associations between individual, family, and extrafamilial factors and the likelihood of subsequent childhood and adolescent maltreatment. The authors analyzed 1,411 participants in the Chicago Longitudinal Study whose maltreatment records were verified from administrative data. Findings suggest that maternal age at the child's birth was a robust predictor of maltreatment outcomes. Receipt of public assistance and single-parent family status were significantly associated with select outcomes. Among school-age indicators examined, parent participation in school was negatively associated with most maltreatment outcomes. Participation in the Chicago Child-Parent Center program was negatively associated with maltreatment, although effects varied by type and timing of maltreatment. In separate analyses, several factors were associated with neglect, but only maternal age at the child's birth was associated with physical abuse. Findings suggest that prevention programs may need to target select populations and specific mechanisms associated with different types of maltreatment to maximize effectiveness.


Water Adsorption and Its Pore Structure Dependence in Shale Gas Reservoirs.
Investigating the occurrence characteristics of water molecules in shale is of great resource, economic, and environmental significance. In this work, the adsorption behavior of water vapor on Longmaxi shale samples is tested, and several isothermal adsorption models are employed to fit the experimental data and primary and secondary adsorption processes. Furthermore, the influence of organic matter content, mineralogical composition, and pore structure on the adsorption process is discussed, and their special combination relationship is revealed correspondingly. The results indicate that the Dent model is suitable for the experimental data with excellent goodness of fit, and the Langmuir and Freundlich models are suitable for the primary and secondary adsorption processes, respectively. The adsorption of water vapor is controlled by the pore volume and specific surface area (SSA) of shale. Mesopore structure parameters mostly determine the water adsorption amount. Massive micropores developed in organic matter with a huge SSA contribute strongly to the primary adsorption process. In general, the combination of organic matter and clay minerals controls the pore structure of shale, which further controls the primary and secondary adsorption processes of water vapor. These findings contribute to a better understanding of water adsorption in different adsorption carriers and in microscopic pores of different sizes occurring in shale gas reservoirs.


Defining HIV-1 Envelope N-Glycan Microdomains through Site-Specific Heterogeneity Profiles.
The HIV-1 envelope (Env) glycans shield the surface of Env from the immune system and form integral interactions important for a functional Env. To understand how individual N-glycosylation sites (NGS) coordinate to form a dynamic shield and evade the immune system through mutations, we tracked 20 NGS in Env from HIV-transmitted/founder (T/F) and immune escape variants and their mutants involving the N262 glycan. NGS were profiled in a site-specific manner using a high-resolution mass spectrometry (MS)-based workflow. Using this site-specific quantitative heterogeneity profiling, we empirically characterized the interdependent NGS of a microdomain in the high-mannose patch (HMP). The changes (shifts) in NGS heterogeneity between the T/F and immune escape variants defined a range of NGS that we further probed for exclusive combinations of sequons in the HMP microdomain using the Los Alamos National Laboratory HIV sequence database. The resultant sequon combinations, including the highly conserved NGS N262, N448, and N301, created an immune escape map of the conserved and variable sequons in the HMP microdomain. This report provides details on how some clustered NGS form microdomains that can be identified and tracked across Env variants. These microdomains have a limited number of N-glycan-sequon combinations that may allow the anticipation of immune escape variants.IMPORTANCE The Env protein of HIV is highly glycosylated, and the sites of glycosylation can change as the virus mutates during immune evasion. Due to these changes, the glycan location and heterogeneity of surrounding N-glycosylation sites can be altered, resulting in exposure of different glycan or proteoglycan surfaces while still producing a viable HIV variant. These changes present a need for vaccine developers to identify Env variants with epitopes most likely to induce durable protective responses. Here we describe a means of anticipating HIV-1 immune evasion by dividing Env into N-glycan microdomains that have a limited number of N-glycan sequon combinations.


Chinese herbal prescriptions for COVID-19 management: Special reference to Taiwan Chingguan Yihau (NRICM101).
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. As at June 2022, increasing numbers of newly diagnosed COVID-19-associated pneumonia cases worldwide have attracted close attention from the international community. The present review analyzes and summarizes the treatment of COVID-19 with traditional Chinese medicine (TCM). A systematic analysis of the efficacies and benefits of TCM for the treatment of COVID-19 was performed, and the mechanisms underlying such treatment are summarized. This analysis of the literature highlights the potential of TCM to prevent and treat COVID-19 via antiviral, anti-inflammatory and immunomodulatory activities, with evidence showing that many TCM components act upon multiple targets and pathways. Famous TCM formulas include Qing-Fei-Pai-Du-Tang (QFPDT), Lianhuaqingwen Capsule (LHC), Taiwan Chingguan Yihau (NRICM101), and Jing Si herbal drink (JSHD). In particular, the botanical preparation NRICM101 was developed in 2020 for use in viral respiratory tract infections and is recommended for treating non-severe and mild COVID-19 infections. NRICM101 has been adopted for use in Taiwan for the clinical treatment of COVID-19. The common components and active ingredients of 10 TCM preparations have been analyzed for the most promising substances. This review aims to provide reliable evidence demonstrating the therapeutic efficacy of TCM substances in support of their further development against novel coronavirus infectious diseases in Taiwan.


Antiarrhythmic effect of chronic oral amiodarone treatment in dogs with myocardial infarction and reproducibly inducible sustained ventricular arrhythmias.
The antiarrhythmic effect of an 8-week oral amiodarone regimen was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Eighteen dogs were randomly assigned to receive either amiodarone, 40 mg/kg/day for 10 days, followed by 30 mg/kg/day for 4 days and then 20 mg/kg/day for 6 weeks (N = 9), or placebo (N = 9). Programmed electrical stimulation was conducted weekly in the two treatment groups. Plasma concentrations of amiodarone and desethylamiodarone were determined weekly, and their myocardial concentrations in the noninfarcted and infarcted regions of the left ventricle were measured at the end of the study. Suppression of inducible arrhythmias was observed at weeks 1,3-7, and 8 in the amiodarone-treated dogs, whereas no suppression occurred in the placebo-treated group. Plasma amiodarone concentration was maximal at 2.5 +/- 1.4 micrograms/ml at week 2, decreased to 1.9 +/- 1.1 micrograms/ml at week 3, and remained steady thereafter. Plasma desethylamiodarone concentrations were in the range of 0.2 +/- 0.1 to 0.4 +/- 0.2 microgram/ml from weeks 1 through 8. Myocardial amiodarone and desethylamiodarone concentrations in the noninfarcted region of the left ventricle were 34.0 +/- 15.8 and 20.8 +/- 7.8 micrograms/g, respectively, at the end of the study. The lack of antiarrhythmic effect of amiodarone at week 2 coincided with the highest plasma amiodarone concentration. The data indicate that this dog model of ventricular arrhythmias is useful for studying the antiarrhythmic action of amiodarone.


Electronic structure and local atomic arrangement of transition metal ions in nanoporous iron-substituted nickel phosphates, VSB-1 and VSB-5.
The electronic structure and local atomic arrangement of transition metal ions in nanoporous iron-substituted nickel phosphates VSB-1 and VSB-5 have been investigated using X-ray absorption near-edge structure (XANES) spectroscopy at Fe K- and Ni K-edges. The Fe K-edge XANES study clearly demonstrated that substituted iron ions were stabilized in octahedral nickel sites of nanoporous nickel phosphate lattice. A comparison with several Fe-references revealed that the substituted irons have mixed Fe2+/Fe3+ oxidation state with the average valence of +2.8-3.0. According to the Ni K-edge XANES analysis, the aliovalent substitution of Ni2+ with Fe2+/Fe3+ induced a slight reduction of divalent nickel ions in VSB-5 to meet a charge balance. On the contrary, Fe substitution for the VSB-1 phase did not cause notable decrease in the oxidation state of nickel ions, which would be related either to the accompanying decrease of pentavalent phosphorus cations or to the increase of oxygen anions. In conclusion, the present findings clearly demonstrated that the nanoporous lattice of nickel phosphate can accommodate effectively iron ions in its octahedral nickel sites.


Construction and characterization of Pseudomonas aeruginosa algB mutants: role of algB in high-level production of alginate.
The algB gene, which is involved in the production of alginate in Pseudomonas aeruginosa, was localized to approximately 2.2 kilobases of DNA from strain FRD by using transposon Tn501 insertion mutagenesis, subcloning, and complementation techniques. The previously reported alg-50(Ts) mutation, which confers the phenotype of temperature-sensitive alginate production, was here designated as an algB allele. A transduction-mediated gene replacement technique was used for site-directed mutagenesis to isolate and characterize algB::Tn501 mutants of P. aeruginosa FRD. Although algB::Tn501 mutants had a nonmucoid phenotype (indicating an alginate deficiency), they still produced about 1 to 5% of wild-type levels of alginate in most growth media and up to 16% in very rich media. The algB::Tn501 mutations had no apparent effect on growth rate or growth requirements. Using another gene replacement technique called excision marker rescue, we constructed a chromosomal algB deletion (delta algB) mutant of P. aeruginosa FRD. The delta algB mutant also produced low levels of alginate as did the algB::Tn501 mutants. The alginate produced by algB::Tn501 mutants resembled wild-type alginate by all criteria studied: molecular weight, acetylation, and proportion of mannuronic and guluronic acids. Thus, the algB gene product is apparently involved in the high-level production of alginate by P. aeruginosa and is not directly involved in the pathway leading to its biosynthesis. Chromosomal mapping of an algB::Tn501 insertion showed linkage to the trp-2 marker on the FRD chromosome as does the algB50(Ts) mutation. The excision marker rescue technique was also used to place the algB::Tn501 marker on the chromosome of characterized strains of P. aeruginosa PAO. The algB::Tn501 mutation mapped near 21 min on the PAO chromosome.


Heidelberg Neuro-Music Therapy Enhances Task-Negative Activity in Tinnitus Patients.
Background: Suffering from tinnitus causes mental distress in most patients. Recent findings point toward a diminished activity of the brain's default-mode network (DMN) in subjects with mental disorders including depression or anxiety and also recently in subjects with tinnitus-related distress. We recently developed a therapeutic intervention, namely the Heidelberg Neuro-Music Therapy (HNMT), which shows an effective reduction of tinnitus-related distress following a 1-week short-term treatment. This approach offers the possibility to evaluate the neural changes associated with the improvements in tinnitus distress. We previously reported gray matter (GM) reorganization in DMN regions and in primary auditory areas following HNMT in cases of recent-onset tinnitus. Here we evaluate on the same patient group, using functional MRI (fMRI), the activity of the DMN following the improvements tinnitus-related distress related to the HNMT intervention. Methods: The DMN activity was estimated by the task-negative activation (TNA) during long inter-trial intervals in a word recognition task. The level of TNA was evaluated twice, before and after the 1-week study period, in 18 treated tinnitus patients ("treatment group," TG), 21 passive tinnitus controls (PTC), and 22 active healthy controls (AC). During the study, the participants in TG and AC groups were treated with HNMT, whereas PTC patients did not receive any tinnitus-specific treatment. Therapy-related effects on DMN activity were assessed by comparing the pairs of fMRI records from the TG and PTC groups. Results: Treatment of the TG group with HNMT resulted in an augmented DMN activity in the PCC by 2.5% whereas no change was found in AC and PTC groups. This enhancement of PCC activity correlated with a reduction in tinnitus distress (Spearman Rho: -0.5; p < 0.005). Conclusion: Our findings show that an increased DMN activity, especially in the PCC, underlies the improvements in tinnitus-related distress triggered by HNMT and identify the DMN as an important network involved in therapeutic improvements.


Immunological changes of T helper cells in flow cytometer-sorted CD4+ T cells from patients with Hashimoto's thyroiditis.
Recent incidence rates for Hashimoto's thyroiditis (HT) and hypothyroidism are higher than those of previous studies. Previous studies indicated that T helper cells may have a major role in the pathogenesis and development of HT, but there is no consensus in the literature. The aim of the present study was to explore the peripheral T helper cell response in the different stages of HT. In this cross-sectional study, we performed flow cytometry analysis to determine the various T cell subsets of 389 patients with HT (34 patients with HT who developed overt hypothyroidism, and 148 patients with HT who developed subclinical hypothyroidism), as well as 51 healthy controls. Anti-thyroid antibodies, and thyroid function were measured. The findings demonstrated that the proportion of peripheral Th1 cells was significantly lower in patients with HT than in healthy euthyroid controls (P<0.001), and the proportion of peripheral Th2, Treg cells was significantly higher in patients with HT than in healthy euthyroid controls (P<0.001). Therefore the Th1/Th2 ratio was significantly lower in HT patients than in healthy euthyroid controls (P<0.001). The Th17/Treg ratio in HT patients was significantly lower than that control subjects (P<0.001). Th1 proportions in patients with overt hypothyroidism HT were significantly higher than in subclinical hypothyroidism HT patients (P=0.031). In conclusion, the findings of the present study demonstrated that there is an increased immune deviation of Th1 lymphocytes and compensatory accelerating activity of Treg cells in HT, and the peripheral Th1 cells from the HT patients correlated to the developmental stage of hypothyroidism.


Comparison of Clinical and Radiological Results according to Glenosphere Position in Reverse Total Shoulder Arthroplasty: A Short-term Follow-up Study.
In a previous biomechanical study, eccentric glenospheres with more inferior position of the center of rotation were shown to improve range of motion and reduce the incidence of scapular notching after reverse total shoulder arthroplasty (RSA). The purpose of this study was to compare the clinical and radiological results of RSA using an eccentric glenosphere to those using a concentric glenosphere and to determine the usefulness of the eccentric glenosphere. From 2009 to 2015, we performed a retrospective review of 20 consecutive patients who underwent RSA using a deltopectoral approach. Nine patients underwent RSA using a concentric glenosphere (group A) while 11 had an eccentric glenosphere (group B). The average follow-up period was 13.9 months (range, 12 to 18 months). All glenoid components were placed with 15° of inferior tilt. Clinical results were assessed using the visual analog pain scale score (VAS), the American Shoulder and Elbow Surgeon (ASES) score, the Korean shoulder scoring system (KSS), and the Constant score. On radiological evaluation, prosthesisscapular neck angle (PSNA), peg-glenoid rim distance (PGRD), scapular neck-inferior glenoshere rim distance (inferior glenoshpere overhang), acromion-greater tuberosity (AT) distance, glenoid-greater tuberosity (GT) distance, and severity of notching according to the Nerot-Sirveaux classification were assessed. The clinical results improved significantly in both groups, but there was no statistically significant difference between the two groups. A significant intergroup difference was observed with regard to PGRD (24.8 ± 1.6 mm for group A vs. 22.2 ± 1.9 mm for group B; p = 0.002) and inferior glenosphere overhang (2.0 ± 1.7 mm for group A vs. 5.8 ± 1.6 mm for group B; p = 0.000). Seven of 9 patients in group A developed notching compared with 2 of 11 patients in group B (p = 0.022). The other radiological parameters such as inferior tilt and AT and GT distances were not significantly different between two groups. Complications such as loosening and scapular fractures did not occur. The eccentric glenosphere in RSA was more effective in reducing the rate of notching than the concentric glenosphere although clinical outcomes were not significantly different in the short-term follow-up.


Social identity and community effects on contraceptive use and intentions in southern Ethiopia.
In this study, data gathered in southern Ethiopia are used to explain how ethnic and religious identities affect current or intended contraceptive use. The only compositionalfactors that increase the likelihood of birth limitation are having a member of the family with a higher level of education and community access to health services. Compositional factors by themselves do not explain Muslim and ethnic variations in contraceptive use and intentions. Village health and economic crises do not promote birth limitation. One normative economic factor--the practice of sons' inheritance of land from their fathers--considerably reduces the likelihood of contraceptive use, but does not account for religious and ethnic differentials. No evidence is found of a minority-status effect on contraception. Exposure to ethnic and religious diversity in the community of residence substantially increases the likelihood of emergent birth limitation, especially among the predominant Muslim Silte population.


A web-based survey on self-management for patients with inflammatory bowel disease in Japan.
Self-management (SMN) is a recognized component of care for chronic conditions, yet its importance in the context of inflammatory bowel disease (IBD) is unclear. This study evaluates the status of SMN and its relationship with quality of life (QOL) in Japanese patients with IBD. A web-based survey was conducted among adult (≥20 years old) Japanese patients with ulcerative colitis (UC) or Crohn's disease (CD). Registered members of an online IBD information platform completed a 45-item survey covering demographics, diet, treatment, physical condition, stress management, financial concerns, support services, and QOL. SMN was operationally defined by dietary and lifestyle behaviours, and contingency analysis was used to test for associated factors. Individual-level contributions to SMN were identified with logistic regression. There were 372 responses to the survey (211 with UC, 161 with CD). Approximately 60% of participants practiced SMN and these patients were 4-24% more likely to report positive QOL than those who did not. SMN was more common in patients with CD than those with UC. SMN practice was also associated with IBD-related hospitalisation/surgery and consultation with others about IBD (e.g. physicians, nurses, patients). The results of this study suggest an association between the practice of SMN and positive QOL in patients with IBD in Japan.


Value of pleural lactate in the differential diagnosis between empyema and non-bacterial pleural effusions.
Lactate concentrations in the pleural fluid of 50 patients were determined by the Monotest Lactate Kit. Lactate values were found higher in bacterial pleural infections than in cases of hydrothorax. Elevated levels were also found in most cases of histologically confirmed cases of pleural neoplasms and in some cases of non-bacterial pleuritis exsudativa . The highest levels were found in cases of empyema, but there was considerable overlapping between the groups. Pleural lactate thus appears to have little diagnostic value in the differential diagnosis between empyema and non-bacterial pleural effusions.


Transient global amnesia: neuropsychological findings after single and multiple attacks.
We examined by neuropsychological tests 41 patients who had presented attacks of transient global amnesia (TGA; 31 had single and 10 multiple episodes), comparing them with 41 matched normal controls. Patients with single attacks showed only two impaired memory tasks with respect to controls (immediate and long-term verbal memory), while patients with multiple attacks showed more impaired tasks in memory and visuoperceptual ability. These data confirm that TGA is a benign syndrome, but could leave a few subclinical memory deficits probably exacerbated by repeated attacks.


Impact of Reticulated Platelets on Platelet Reactivity in Neonates.
Neonatal megakaryopoiesis and platelet turnover form a developmentally unique pattern by generating a pool of newly released reticulated platelets from the bone marrow into the circulation. Reticulated platelets are more reactive and hyperaggregable compared to mature platelets, due to their high residual mRNA content, large size, increased expression of platelet surface receptors, and degranulation. The proportion of reticulated platelets in neonates is higher compared to that in adults. Due to the emergence of an uninhibited platelet subpopulation, the newly formed reticulated platelet pool is inherently hyporesponsive to antiplatelets. An elevated population of reticulated platelets is often associated with increased platelet reactivity and is inversely related to high on-treatment platelet reactivity, which can contribute to ischemia. Measurements of the reticulated platelet subpopulation could be a useful indicator of increased tendency for platelet aggregation. Future research is anticipated to define the distinct functional properties of newly formed reticulated or immature platelets in neonates, as well as determine the impact of enhanced platelet turnover and high residual platelet reactivity on the response to antiplatelet agents.


Cavitation and bubble dynamics: the Kelvin impulse and its applications.
Cavitation and bubble dynamics have a wide range of practical applications in a range of disciplines, including hydraulic, mechanical and naval engineering, oil exploration, clinical medicine and sonochemistry. However, this paper focuses on how a fundamental concept, the Kelvin impulse, can provide practical insights into engineering and industrial design problems. The pathway is provided through physical insight, idealized experiments and enhancing the accuracy and interpretation of the computation. In 1966, Benjamin and Ellis made a number of important statements relating to the use of the Kelvin impulse in cavitation and bubble dynamics, one of these being 'One should always reason in terms of the Kelvin impulse, not in terms of the fluid momentum…'. We revisit part of this paper, developing the Kelvin impulse from first principles, using it, not only as a check on advanced computations (for which it was first used!), but also to provide greater physical insights into cavitation bubble dynamics near boundaries (rigid, potential free surface, two-fluid interface, flexible surface and axisymmetric stagnation point flow) and to provide predictions on different types of bubble collapse behaviour, later compared against experiments. The paper concludes with two recent studies involving (i) the direction of the jet formation in a cavitation bubble close to a rigid boundary in the presence of high-intensity ultrasound propagated parallel to the surface and (ii) the study of a 'paradigm bubble model' for the collapse of a translating spherical bubble, sometimes leading to a constant velocity high-speed jet, known as the Longuet-Higgins jet.


Chromium supplements for glycemic control in type 2 diabetes: limited evidence of effectiveness.
Some adults with type 2 diabetes mellitus (T2DM) believe that chromium-containing supplements will help control their disease, but the evidence is mixed. This narrative review examines the efficacy of chromium supplements for improving glycemic control as measured by decreases in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c). Using systematic search criteria, 20 randomized controlled trials of chromium supplementation in T2DM patients were identified. Clinically meaningful treatment goals were defined as an FPG of ≤7.2 mmol/dL, a decline in HbA1c to ≤7%, or a decrease of ≥0.5% in HbA1c. In only a few randomized controlled trials did FPG (5 of 20), HbA1c (3 of 14), or both (1 of 14) reach the treatment goals with chromium supplementation. HbA1c declined by ≥0.5% in 5 of 14 studies. On the basis of the low strength of existing evidence, chromium supplements have limited effectiveness, and there is little rationale to recommend their use for glycemic control in patients with existing T2DM. Future meta-analyses should include only high-quality studies with similar forms of chromium and comparable inclusion/exclusion criteria to provide scientifically sound recommendations for clinicians.


Noninvasive Assessment of Elimination and Retention using CT-FMT and Kinetic Whole-body Modeling.
Fluorescence-mediated tomography (FMT) is a quantitative three-dimensional imaging technique for preclinical research applications. The combination with micro-computed tomography (µCT) enables improved reconstruction and analysis. The aim of this study is to assess the potential of µCT-FMT and kinetic modeling to determine elimination and retention of typical model drugs and drug delivery systems. We selected four fluorescent probes with different but well-known biodistribution and elimination routes: Indocyanine green (ICG), hydroxyapatite-binding OsteoSense (OS), biodegradable nanogels (NG) and microbubbles (MB). µCT-FMT scans were performed in twenty BALB/c nude mice (5 per group) at 0.25, 2, 4, 8, 24, 48 and 72 h after intravenous injection. Longitudinal organ curves were determined using interactive organ segmentation software and a pharmacokinetic whole-body model was implemented and applied to compute physiological parameters describing elimination and retention. ICG demonstrated high initial hepatic uptake which decreased rapidly while intestinal accumulation appeared for around 8 hours which is in line with the known direct uptake by hepatocytes followed by hepatobiliary elimination. Complete clearance from the body was observed at 48 h. NG showed similar but slower hepatobiliary elimination because these nanoparticles require degradation before elimination can take place. OS was strongly located in the bones in addition to high signal in the bladder at 0.25 h indicating fast renal excretion. MB showed longest retention in liver and spleen and low signal in the kidneys likely caused by renal elimination or retention of fragments. Furthermore, probe retention was found in liver (MB, NG and OS), spleen (MB) and kidneys (MB and NG) at 72 h which was confirmed by ex vivo data. The kinetic model enabled robust extraction of physiological parameters from the organ curves. In summary, µCT-FMT and kinetic modeling enable differentiation of hepatobiliary and renal elimination routes and allow for the noninvasive assessment of retention sites in relevant organs including liver, kidney, bone and spleen.


Characterization of esterase activity in Geobacillus sp. HBB-4.
A thermophilic esterase producing bacterium (Bacillus sp. 4), recently isolated from Alangüllü thermal spring in Aydin (Turkey), was analyzed using 16S rRNA and classified as Geobacillus sp. HBB-4, most closely related to Bacillus sp. BGSC W9A59 (0.70% sequence divergence) which belongs to the newly described genus Geobacillus. The effects of several chemicals on the activity of thermostable esterase from Geobacillus sp. HBB-4 were examined. Among the various metal ions tested, esterase activity was enhanced by Mn(+2) and Ni(+2), but was inhibited by Hg(+2) and Cu(+2), whereas Ca(+2), Mg(+2) and Co(+2) had no effect. In addition, other metal ions studied have caused a slight inhibition on the esterase activity. EDTA partially inhibited the HBB-4 esterase. The activator metal ions, Mn(+2) and Ni(+2) have restored partial inhibition of EDTA. The activity of HBB-4 esterase was inhibited by ionic detergents while non-ionic detergents activated the enzyme. However, a zwitterionic detergent, CHAPS, has caused a slight inhibition in the enzyme activity. HBB-4 esterase activity was inhibited at the high concentrations of all the organic solvents tested in the present study. However, 50% final concentration of DMSO increased the enzyme activity about 7%. The HBB-4 esterase has shown more than about 50% of activity in the presence of ethanol and methanol solutions. These characteristics of the enzyme along with its significant thermostability make the Geobacillus sp. HBB-4 esterase a potent candidate for future industrial applications.


The Pertinence of Microwave Irradiated Coconut Shell Bio-Sorbent for Wastewater Decolourization: Structural Morphology and Adsorption Optimization Using the Response Surface Method (RSM).
Palm oil mill effluent contains carcinogenic coloured compounds that are difficult to separate due to their aromatic structure. Though colour treatment using adsorption processes at lower pH (<4) have been reported effectual, due to its acidity the remediated effluent poses an environmental hazard as a result. Thus, the current study focused on achieving decolourization at neutral pH by enhancing the morphology of the coconut shell activated carbon (CSAC) using N₂ as activating-agent with microwave irradiation heating. The microwave pretreated and non-pretreated CSAC were characterized using scanned electron microscopy (SEM), energy dispersive X-ray (EDX) and Brunauer-Emmett-Teller (BET) analysis. A significant modification in the porous structure with a 66.62% increase in the specific surface area was achieved after the pretreatment. The adsorption experimental matrix was developed using the central composite design to investigate the colour adsorption performance under varied pH (6⁻7), dosage (2⁻6 g) and contact time (10⁻100 min). At optimum conditions of neutral pH (7), 3.208 g dosage and contact time of 35 min, the percentage of colour removal was 96.29% with negligible differences compared with the predicted value, 95.855%. The adsorption equilibrium capacity of 1430.1 ADMI × mL/g was attained at the initial colour concentration of 2025 ADMI at 27 °C. The experimental data fitted better with the Freundlich isotherm model with R² 0.9851.


Impact of early coronary angiography on the survival to discharge after out-of-hospital cardiac arrest.
Acute myocardial infarction is a major cause of out-of-hospital cardiac arrest (OHCA). Coronary angiography (CAG) enables diagnostic confirmation of coronary artery disease and subsequent revascularization, which might improve the prognosis of OHCA survivors. Non-randomized data has shown a favorable impact of CAG on prognosis for this population. However, the optimal timing of CAG has been debated. The clinical outcomes of 607 OHCA patients registered in CAPTURES (Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance), a nationwide multicenter registry performed in 27 hospitals, were analyzed. Early CAG was defined as CAG performed within 24 hours of emergency department admission. The primary outcome was survival to discharge, with neurologically favorable status defined by cerebral performance category scores ≤2. Compared to patients without CAG (n=469), patients who underwent early CAG (n=138) were younger, more likely to be male, and more likely to have received bystander cardiopulmonary resuscitation, pre-hospital defibrillation, and revascularization (P<0.01 for all). Analysis of 115 propensity score-matched pairs showed that early CAG is associated with a 2.3-fold increase in survival to discharge with neurologically favorable status (P<0.001, all). Survival to discharge increased consistently according to the time interval between emergency department visit and CAG (P<0.05). Early CAG of OHCA patients was associated with better survival and favorable neurologic outcomes at discharge. However, there was no clear time threshold for CAG that predicted survival to discharge.


Differentiating mass-forming intrahepatic cholangiocarcinoma from atypical hepatocellular carcinoma using Gd-EOB-DTPA-enhanced magnetic resonance imaging combined with serum markers in at-risk patients with hepatitis B virus.
The precise differentiation of intrahepatic cholangiocarcinoma (ICC) from atypical hepatocellular carcinoma (HCC) is vital for treatment strategy and prognostic prediction. In clinical practice, nearly 40% of HCCs demonstrate atypical manifestations, particularly HCCs with rim arterial phase hyperenhancement (APHE), which is challenging to differentiate from mass-forming ICC. Thus, we aimed to develop a diagnostic regimen of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) contrast-enhanced magnetic resonance imaging (MRI) combined with serum tumor markers in differentiating mass-forming ICC from atypical HCC in at-risk patients with the hepatitis B virus (HBV). This study enrolled 129 patients with pathologically proven mass-forming ICCs (n=53) and atypical HCCs (n=76) who had undergone preoperative Gd-EOB-DTPA contrast-enhanced MRI. The clinical data and imaging findings were analyzed. Univariate and multivariate logistic analyses were performed to identify the independent predictors for differentiating mass-forming ICCs from atypical HCCs. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curves, and DeLong test was used to compare the areas under curves of all independent predictors. Univariate logistic regression analysis revealed normal alpha fetoprotein (AFP), elevated carbohydrate antigen 19-9 (CA19-9) level, elevated carcinoma embryonic antigen (CEA) level, central hyperintensity on T2-weighted imaging (T2WI), central hypointensity on T2WI, and targetoid sign on hepatobiliary phase (HBP) and targetoid restriction on diffusion-weighted imaging (DWI) were more likely to be significant predictors favoring mass-forming ICCs (all P values <0.05). In contrast, multifocal hyperintensity on T2WI and capsule sign were more frequently seen in patients with atypical HCC (all P values <0.05). Multivariate analysis revealed normal AFP, elevated CA19-9 level, targetoid sign on HBP, and targetoid restriction on DWI (all P=0.001) were independent predictors for differentiating mass-forming ICCs from atypical HCCs; DeLong test showed that the area under curve (AUC) increased to 0.949 when the above predictors were combined (all P values <0.05), and the sensitivity, specificity, and accuracy of the combined independent predictors were 88.7%, 93.4%, and 91.5%, respectively. A diagnostic regimen integrating tumor markers (AFP, CA19-9) and imaging biomarkers (targetoid restriction on DWI and/or targetoid sign on HBP) using Gd-EOB-DTPA-enhanced MRI could help to differentiate mass-forming ICCs from atypical HCCs and achieve high diagnostic performance of mass-forming ICCs in at-risk patients with the HBV. Mass-forming intrahepatic cholangiocarcinoma (mass-forming ICC); atypical hepatocellular carcinoma (atypical HCC); magnetic resonance imaging (MRI); gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA); hepatobiliary phase (HBP).


[Work conditions, quality of life, and voice disorders in teachers].
Voice disorders are common among teachers, with adverse consequences for their work and quality of life. This study focuses on factors associated with voice-related quality of life among female teachers in the municipal school system in Belo Horizonte, Southeast Brazil. A cross-sectional study with 2,133 female teachers was conducted, using the Voice-Related Quality of Life (VRQL) questionnaire, which has two domains: socio-emotional and physical. Teachers were grouped into quartiles based on the distribution of the final score in each domain. Those in the lowest quartile were then compared with all the others for a number of factors, using multiple logistic regression analysis. Less creativity at work and poor relationship with pupils were associated with worse voice-related quality of life in both domains. Mental disorders (GHQ12 > 4) were associated with worse voice-related quality of life in the socio-emotional domain, and intra-class noise with worse voice-related quality of life in the physical domain. Improvements in working conditions are key factors for achieving better voice-related quality of life among teachers.


[Intestinal transplantation in children].
A long period of experimental work has allowed to study successively hypothermic preservation of the small bowel, autotransplantation and finally allotransplantation. After this initial phase of experimental surgery, a certain number of intestinal transplantations in humans could be attempted as cyclosporine became available. Following a brief of report of 3 intestinal transplantations recently performed by the group of the hôpital des Enfants-Malades in Paris, indications for intestinal transplantation are provided. Subtotal resections of the small bowel in children or adolescents and extensive resections in neonates account for most of the indications. Despite significant progress, further advances in intestinal transplantation need to be made, because the small bowel poses unique problems in that it seems to represent a compendium of all the particularities and difficulties of other organ transplantations.


Use of phosphorus release batch tests for modelling an EBPR pilot plant.
The aim of this study was to evaluate how routinely performed phosphorus release tests could be used when modelling enhanced biological phosphorus removal (EBPR) using activated sludge models such as ASM2d. A pilot plant with an extensive analysis programme was used as basis for the simulations. Without any calibration the prediction of phosphorus removal was poor and the initial release rates from the simulations were not similar to those found from the laboratory tests. A period with low organic loading was chosen as a calibration period. In this period averages of daily influent measurements were used as influent parameters. First, calibration was performed in order to fit effluent COD and MLVSS in the sludge. Next, the phosphorus content in the sludge was decreased to the measured level by decreasing the fermentation rate. Finally, the initial phosphorus release rate was calculated from a simulated batch test and the PHA uptake rate was increased to fit this release rate with the average initial rates from laboratory batch tests performed during the period. The calibrated model was verified with data from the subsequent period where acetate was dosed.


[The effects of tobacco on children].
Smoking remains an important topic. It is estimated that at present half the children born in France have been, or will be, exposed to the toxic effects of passive smoking. This paper aims to review the evidence of the effects of passive smoking, both intra and extra-uterine. Extra-uterine passive smoking is implicated in numerous respiratory (asthma, allergy, infections...) and non respiratory diseases (neoplastic, dental, ophthalmic, digestive, cardio-vascular and infective). Intra-uterine exposure is even more dangerous and leads to abnormalities of the pregnancy (placental abnormalities, prematurity...), of the foetus (behavioural problems, malformations) and long term problems for the unborn child. Passive smoking is responsible for pulmonary morphological abnormalities (pulmonary hypoplasia, reduction in elasticity, increased deposition of collagen and alteration of alveolar structure) and functional disorders (reduced compliance, increased airways resistance, bronchial hyperreactivity). Finally it causes a disturbance of respiratory control, promoting all the factors responsible for sudden cot death. The ill effects of passive smoking fully justify efforts to inform and persuade the medical profession of its duty to fight this scourge.


Prevalence of H pylori associated "high risk gastritis" for development of gastric cancer in patients with normal endoscopic findings.
To investigate the prevalence of H pylori associated corpus-predominant gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM) in patients without any significant abnormal findings during upper-GI endoscopy. Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System. Eight hundred and forty-five patients (mean age 54.8 +/- 2.8 years) with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scoring systems. The prevalence of severe H pylori associated changes like pangastritis, CPG, IM, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years. The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk for gastric cancer development--only a proper follow-up can provide this information.