Etanercept treatment for children with refractory juvenile idiopathic arthritis.
Etanercept has been shown to be an effective treatment for juvenile idiopathic arthritis (JIA). In this study, we evaluated the effectiveness of etanercept therapy in the treatment of refractory JIA. This was a retrospective analysis of 11 patients with refractory JIA (polyarticular type n=7; pauciarticular type, n=2; systemic type, n=2) who received treatment with etanercept during the period 2005-2009 in a medical center. The indications for etanercept treatment included persistent fever, arthritis/arthralgia, or elevated levels of inflammatory mediators after treatment with methotrexate and/or prednisolone for more than 6 months. The patients were treated with etanercept (0.4 mg/kg, with maximal 25mg, subcutaneously, twice a week) for a total of 12 months. The degree of arthritis/arthralgia improved (range of motion and painful sensation of involved joints), and the levels of inflammatory markers (C-reactive protein and erythrocyte sedimentation rate) decreased progressively in 10 of the 11 patients (p<0.05) at 1-, 3-, 5-, and 12-month follow-up after treatment with etanercept. Mean hemoglobin levels significantly increased, whereas mean platelet counts decreased after etanercept treatment (p<0.05). Only one patient with systemic type of JIA failed to respond to the treatment after 6 weeks of etanercept therapy. Methotrexate, prednisolone, and other immunosuppressive drugs were successfully discontinued after a mean of 2.5 months (range, 1-5 months) of etanercept therapy in the 10 patients who responded to etanercept treatment. Etanercept is beneficial for patients with polyarticular and pauciarticular type of JIA that is refractory to conventional treatment but less beneficial for systemic type of JIA.


Fever produced in the rat by intracerebral E. coli endotoxin.
E. coli endotoxin introduced into the brain ventricles or into various brain areas raises the body temperature of conscious rats. Endotoxin-sensitive sites were found within the anterior hypothalamus and the lower brainstem. The increase in temperature (delta T) after microinjection of endotoxin into the anterior hypothalamic nucleus was dose-dependent. Endotoxin injected into the ventricles produced monophasic hyperthermia, but microinjections into the anterior hypothalamus produced monophasic or biphasic types of hyperthermia. The second and third microinjections of endotoxin into the anterior hypothalamic nucleus subsequently caused higher responses in delta T, but not in the rate of temperature change. The effects of the fourth and furter microinjections were the same as those of the third, and no tolerance developed for 24 days. The observations of behaviour, vegetative reactions, skin temperature, and carbon dioxide production indicated that the rise in the rat body temperature induced by endotoxin represents fever and that the heat is gained, at an ambient temperature of 22 degrees C, mainly through skin vessel vasoconstriction. Aspirin abolished and reversed fever induced by endotoxin, while hydrocortisone was without effect.


Behavioral avoidance test for obsessive compulsive disorder.
Few treatment outcome studies of Obsessive Compulsive Disorder (OCD) have employed Behavioral Avoidance Tests (BATs) to assess changes in symptomatology, probably because of the difficulty of constructing such tests for a disorder which has widely varying symptoms. The few studies that have examined the psychometric properties of BATs for OCD have found mixed evidence for validity but good treatment sensitivity. The present study presents psychometric findings for a multi-step/multi-task BAT that assessed percentage of steps completed, subjective anxiety, global avoidance, and rituals. This measure was used with 50 clients diagnosed with OCD whose symptoms varied widely. The BAT demonstrated good convergent and divergent validity, as well as treatment sensitivity according to effect size calculations. A composite score combining steps, anxiety level, avoidance and rituals also performed well in psychometric tests. Strategies to reduce the complexity of scoring are presented, along with examples of several BAT tasks to enable researchers to employ this behavioral measure.


Autoantibodies against pituitary peptides in sera from patients with multiple sclerosis.
Autoantibodies against pituitary peptides were demonstrated in sera from multiple sclerosis (MS) patients. Ten patients with lupus erythematosus disseminatus (SLE) and 97 healthy blood donors served as controls. The sera were used as primary antibodies in the indirect immuno-enzyme cytochemical (IEC) method, with fixed, paraffin-embedded rat brains and rat and hog pituitaries as antigen substrates. Eleven of the 33 MS sera reacted with peptides in the neural lobe/hypothalamic nuclei or distal lobe. The MS had a significantly higher incidence of peptide antibodies than sera from controls (11/33 vs 9/97). The mean antibody titers were significantly different (1577 vs 333). Comparison with rabbit reference antibodies specific to each of the 6 distal lobe hormones showed that the 9 distal lobe-positive MS sera reacted with cells harboring peptides of the somatotropin family. The presence of peptide autoantibodies was not related to clinical status or medical treatment. No antibodies against pituitary peptides were found in the SLE sera. One of the 11 positive MS sera showed antibodies against gastric parietal cells. None of the 11 sera showed antibodies against muscle, mitochondria, thyroid, adrenal, or parotid antigens. We propose that in a proportion of patients with MS, these autoantibodies might be involved in the demyelinization process by interfering with the peptide/receptor interplay, thus placing MS as a disease in analogy with myasthenia gravis. Alternatively, these autoantibodies might be involved in the altered immunoregulation of MS or be secondary to the disease.


Estimation of exposure from spilled glutaraldehyde solutions in a hospital setting.
Glutaraldehyde is commonly used in hospitals for cold disinfection of instruments which may be damaged by autoclaving. The increased use of automatic washer/disinfection machines has resulted in a greater risk of spills than with manual methods. A series of experiments was conducted to answer two related research questions: what was the likely range of airborne concentrations when glutaraldehyde is spilled, and are commonly used personal protective equipment ensembles effective and practicable in use? Objective measurements using three sampling methods (two pumped methods based on OSHA 64, one using treated filters and the other based on adsorbent tubes, and a Glutaraldemeter direct reading instrument) were conducted with spills of various surface areas of both 2 and 50% solutions of glutaraldehyde. Results ranged between < 0.01 and 1.4 ppm. Two personal protective equipment ensembles were tested. One was based on a half-facepiece respirator with gas-tight goggles, while the other comprised a full-facepiece cartridge respirator. Both ensembles gave adequate protection against irritation, although in use the half-facepiece respirator and goggles tended to interfere with each other. The direct reading instrument generally underestimated the glutaraldehyde concentrations, although there was a significant association with the results obtained using the method based on adsorbent tubes.


Visualizing BDSM and AIDS Activism: Archiving Pleasures, Sanitizing History.
The visual archive of AIDS and fetish activism is a rich resource for studying interlinkages between art and science, activism and public health, politics and medicine, pleasure and sexual health prevention. This article explores AIDS and fetish activism imagery from the first two decades of the Norwegian AIDS crisis. Interrogating the materiality and visual context of images - photographs, posters, flyers, and safer sex instructions - it maps out visualization practices in leather, BDSM and AIDS activism. AIDS and fetish imagery made some bodies, pleasures, and political goals visible - and rendered others unseen. The article explores the materiality of images and their visual, social, and historical context of production, and traces their social biographies and afterlives. Fetish images were vehicles for change and actors co-producing history. They took part in destigmatizing BDSM, challenging psychiatric classification, and creating infrastructure and networks between subcultures, communities, and authorities. The visualization of fetish activism was as much about communication strategies as it was about aesthetic, style, and motive. The politics of visibility in Norwegian fetish activism point to the vulnerable project of fighting for acceptance through "respectability," while preserving the individuality and "otherness" of leather and fetish culture.


Potassium hydroxide-mediated novel rearrangement of 2-alkyl-sulfonyl-2-arylsulfonyl-1-phenylethanones to 1-aryl-2-(arylsulfonylmethanesulfonyl)ethanones.
Treatment of a solution of a mixture of 1-aryl-2-arylsulfonylethanones 9 and alkylsulfonyl chlorides (1.5-2.0 equiv) in THF at 0 degree C with potassium hydroxide (8 equiv) for 10 min gave a rearrangement product, i.e., 1-aryl-2-(arylsulfonylmethanesulfonyl)ethanones 8, in excellent yields. Regiospecific methyl- and ethylation at the methylene carbon sandwiched between two sulfonyl groups of 8 could be achieved by the reactions of 7i-j with LDA (1 equiv) in THF at room temperature, respectively.


Purification and characterization of a periplasmic Thiosulfate dehydrogenase from the obligately autotrophic Thiobacillus sp. W5.
A periplasmic thiosulfate dehydrogenase (EC 126.96.36.199) was purified to homogeneity from the neutrophilic, obligately chemolithoautotrophic Thiobacillus sp. W5. A five-step procedure resulted in an approximately 2,300-fold purification. The purified protein had a molecular mass of 120 +/- 3 kDa, as determined by gel filtration. It is probably a tetramer containing two different subunits with molecular masses of 33 +/- 1 kDa and 27 +/- 0.5 kDa, as determined by SDS-PAGE. UV/visible spectroscopy revealed that the enzyme contained haem c; haem staining showed that both subunits contained haem c. A haem c content of 4 mol per mol of enzyme was calculated using the pyridine haemochrome test. The pH optimum of the enzyme was 5.5. At pH 7.5, the Km and Vmax were 120 +/- 10 microM and 1,160 +/- 30 U mg-1, respectively. The absence of 2-heptyl-4-hydroquinoline-N-oxide (HQNO) inhibition for the oxidation of thiosulfate by whole cells suggested that the electrons enter the respiratory chain at the level of cytochrome c. Comparison with thiosulfate dehydrogenases from other Thiobacillus species showed that the enzyme was structurally similar to the thiosulfate dehydrogenase of the acidophilic, facultatively chemolithoautotrophic Thiobacillus acidophilus, but not to the thiosulfate dehydrogenases published for the obligately chemolithoautotrophic Thiobacillus tepidarius and Thiobacillus thioparus.


Neuropsychological and neuroimaging characteristics of classical superficial siderosis.
To define the neuropsychological and neuroimaging characteristics of classical infratentorial superficial siderosis (iSS), a rare but disabling disorder defined by hemosiderin deposition affecting the superficial layers of the cerebellum, brainstem and spinal cord, usually associated with a slowly progressive neurological syndrome of deafness, ataxia and myelopathy. We present the detailed neuropsychological and neuroimaging findings in 16 patients with iSS (mean age 57 years; 6 female). Cognitive impairment was present in 8/16 (50%) of patients: executive dysfunction was the most prevalent (44%), followed by impairment of visual recognition memory (27%); other cognitive domains were largely spared. Disease symptom duration was significantly correlated with the number of cognitive domains impaired (r = 0.59, p = 0.011). Mood disorders were also common (anxiety 62%, depression 38%, both 69%) but not associated with disease symptom duration. MRI findings revealed siderosis was not only in infratentorial brain regions, but also in characteristic widespread symmetrical supratentorial brain regions, independent of disease duration and degree of cognitive impairment. The presence of small vessel disease markers was very low and did not account for the cognitive impairment observed. Neuropsychological disturbances are common in iSS and need to be routinely investigated. The lack of association between the anatomical extent of hemosiderin and cognitive impairment or disease duration suggests that hemosiderin itself is not directly neurotoxic. Additional biomarkers of iSS disease severity and progression are needed for future research and clinical trials.


Sumatriptan-induced saphenous venoconstriction in the anaesthetized dog through 5-HT1-like receptor activation.
1. The role of vasoconstrictor 5-HT1-like receptors in the control of vascular reactivity in vivo has been relatively little studied, particularly with regards to venous function. Using an anaesthetized dog model, we have investigated the haemodynamic profile of the selective 5-HT1-like agonist, sumatriptan, focussing on the reactivity of the saphenous venous bed. The key feature of our experimental model was the implantation of ultrasonic crystals on the adventitial surface of the lateral saphenous vein to provide direct and continuous measurement of drug-induced changes in vein diameter. Saphenous vein pressure was measured simultaneously via a proximal branch. 2. Sumatriptan 1-30 micrograms kg-1, i.v., produced pronounced dose-related reductions in saphenous vein diameter which reached congruent to 40% at the highest dose tested. Sumatriptan also produced modest increases in mean blood pressure, total peripheral resistance and left ventricular end diastolic pressure but had little or no effect on cardiac output, heart rate, cardiac contractility or saphenous venous pressure. Sumatriptan-induced reductions in saphenous vein diameter were strongly antagonized by the 5-HT1-receptor antagonist, methiothepin (0.3 mg kg-1, i.v.) but were unaffected by the 5-HT2 antagonist, ketanserin (0.3 mg kg-1, i.v.). 3. Hence, 5-HT1-like receptor stimulation in vivo can result in a powerful local venoconstrictor effect.


Antibacterial mechanisms of clove essential oil against Staphylococcus aureus and its application in pork.
Clove essential oil (CEO) has been widely used in the processing of meat products due to its potent antibacterial activity and special aroma. However, studies on the antibacterial mechanism of CEO are still not detailed enough. The aims of this study were to investigate the antibacterial mechanisms of action of CEO against Staphylococcus aureus in detail and evaluate its efficacy in pork preservation. The Staphylococcus aureus cells treated with CEO were morphologically damaged and had significant leakage of intracellular components. At the metabolic level, CEO significantly inhibited the respiratory metabolism of Staphylococcus aureus by inhibiting the tricarboxylic acid cycle pathway and the total inhibition rate was found to be 31.23 %. Molecular biology experiments showed that CEO could interact with Staphylococcus aureus DNA molecules and affect the accessory gene regulator (Agr) system, which resulted in a significant decrease in the expression levels of Staphylococcus aureus virulence genes so that the expression of sea and hla decreased by 82.97 % and 77.27 %, respectively. Molecular docking results indicated that the interaction between eugenol, the main active ingredient in CEO, and the key phosphorylase Agr C in the Agr system may be one of the main reasons for the inhibition. The application results showed that CEO had a good antibacterial effect in pork for 7 days without affecting the texture of pork. The results obtained in this study provide a reference for an in-depth study of the detailed antibacterial mechanism of natural food antibacterial agents.


Factors associated with rapidly repeated acute poisoning by substances of abuse: a prospective observational cohort study.
We have previously found that 9% of patients treated for acute poisoning by substances of abuse in a primary care emergency outpatient setting presented with a new poisoning within a week. We now identify factors associated with rapidly repeated acute poisoning by substances of abuse. In 169/1952 (9%) cases of acute poisoning by substances of abuse included consecutively from October 2011 through September 2012 at a primary care emergency outpatient clinic in Oslo, Norway, the patient re-presented within a week with a new poisoning. Homeless patients were more likely to re-present, adjusted odds ratio (AOR) 2.0 (95% confidence interval (CI) 1.3-3.2, p = 0.003), as were self-discharging patients, AOR 1.7 (95% CI 1.2-2.4, p = 0.007), and patients with an opioid as main toxic agent, AOR 1.5 (95% CI 1.0-2.3, p = 0.028). There was no statistically significant association between rapid re-presentation and severe mental illness or suicidal intention.


A Feasibility Study to Evaluate Changes in Urinary Metabolites after OnabotulinumtoxinA Injection for Refractory Overactive Bladder.
Metabolomics analysis of urine before and after overactive bladder (OAB) treatment may demonstrate a unique molecular profile, allowing predictions of responses to treatment. This feasibility study aimed to correlate changes in urinary metabolome with changes in OAB symptoms after intravesical onabotulinumtoxinA (BTX-A) injections for refractory OAB. Women 18 years or older with non-neurogenic refractory OAB were recruited to complete OAB-V8 questionnaires and submit urine samples before and after 100 units intravesical BTX-A injection. Samples were submitted to CE-TOFMS metabolomics profiling. Data were expressed as percent of change from pre-treatment and were correlated with OAB-V8 score improvement. Urinary metabolite changes in the OAB-V8 groups were compared using the Kruskal-Wallis test, and associations between metabolites and OAB-V8 scores were examined using quantile regression analysis. Of 61 urinary metabolites commonly detected before and after BTX-A, there was a statistically significant decrease in adenosine and an increase in N8-acetylspermidine and guanidinoacetic acid levels associated with OAB score improvement, suggesting that intravesical BTX-A injection modifies the urinary metabolome. These urinary metabolites could provide insight into OAB pathophysiology and help identify patients who would benefit most from chemodenervation.


Impacts of highly active antiretroviral therapy (HAART) on metabolic status of patients with AIDS: What happens from the initiation of AIDS to the initiation of treatment?
Our study aimed to determine if alteration of metabolic parameters is associated with the severity of human immunodeficiency virus (HIV) infection, progress to acquired immunodeficiency syndrome (AIDS), or with the type of antiretroviral treatment (ART). In a cross-sectional study among 114 HIV infected patients, we measured hematological and biochemical parameters to assess metabolic alterations according to the disease process and anti-retroviral treatment. Of 114 HIV-positive patients, there were 82 AIDS patients receiving ART and 32 HIV patients without treatment. Alkaline phosphatase and parathyroid hormone (PTH) had lower serum levels in HIV patients with CD4(+) cell count ≤250 (P < 0.01). CD4(+) cell count was higher in patients receiving Protease Inhibitors (PI) and Nucleoside Reverse Transcriptase Inhibitors (NRTI) regimen compared with those treated with Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) and NRTI or NRTI alone. Calcium (Ca) serum level was lower in patients with only NRTI regimen while Phosphorus (P) serum level was higher in patients on NNRTI and NRTI (P < 0.05). CD4(+) cell count ≤250 cells/μl in HIV-positive patients is associated with decreased level of triglyceride and PTH. Moreover, patients receiving NRTI regimen alone have lower Ca level while this regimen in combination with NNRTI or PI has a positive correlation with P serum level.


Clinical Outcome Assessments in Pediatric Patients With Ulcerative Colitis and Crohn's Disease Receiving Biologics: A Retrospective Cohort Study.
To assess disease activity, steroid-free remission, and other clinical outcome assessments among pediatric patients with ulcerative colitis (UC) and Crohn's disease (CD) in the ImproveCareNow (ICN) registry. Patients aged 2-17 years diagnosed with UC or CD between June 1, 2013 and December 31, 2019 were enrolled if they initiated a biologic after enrollment in the ICN registry and completed at least 12 months follow-up after first maintenance dose. Baseline (at biologic initiation) demographics were summarized using descriptive statistics. Pediatric UC Activity Index (PUCAI), partial Mayo score, and Physician Global Assessment (PGA) were assessed for UC; and the Short Pediatric Crohn's Disease Activity Index (sPCDAI) and PGA were assessed for CD at first maintenance dose, 1- and 3-year time points. Kappa coefficients were used to assess the level of agreement between the outcome measures. A total of 1887 patients (UC = 350; CD = 1537) were included. Baseline demographics were similar across groups. For UC patients, mean PUCAI scores decreased and the proportion of patients in steroid-free remission, quiescent state based on PGA, and remission based on partial Mayo score increased from first maintenance dose to 1 and 3 years. For CD patients, mean sPCDAI score of CD patients decreased and the proportion of patients in steroid-free remission by sPCDAI and in quiescent state based on PGA increased from first maintenance dose to 1 and 3 years. Kappa coefficients showed only modest correlation between disease activity assessments. Disease activity scores improved over time, with more pediatric patients with UC and CD achieving steroid-free remission at 1 and 3 years after first biologic maintenance dose.


Use of volatile agents for sedation in the intensive care unit: A national survey in France.
Current intensive care unit (ICU) sedation guidelines recommend strategies using non-benzodiazepine sedatives. This survey was undertaken to explore inhaled ICU sedation practice in France. In this national survey, medical directors of French adult ICUs were contacted by phone or email between July and August 2019. ICU medical directors were questioned about the characteristics of their department, their knowledge on inhaled sedation, and practical aspects of inhaled sedation use in their department. Among the 374 ICUs contacted, 187 provided responses (50%). Most ICU directors (73%) knew about the use of inhaled ICU sedation and 21% used inhaled sedation in their unit, mostly with the Anaesthetic Conserving Device (AnaConDa, Sedana Medical). Most respondents had used volatile agents for sedation for <5 years (63%) and in <20 patients per year (75%), with their main indications being: failure of intravenous sedation, severe asthma or bronchial obstruction, and acute respiratory distress syndrome. Sevoflurane and isoflurane were mainly used (88% and 20%, respectively). The main reasons for not using inhaled ICU sedation were: "device not available" (40%), "lack of medical interest" (37%), "lack of familiarity or knowledge about the technique" (35%) and "elevated cost" (21%). Most respondents (80%) were overall satisfied with the use of inhaled sedation. Almost 75% stated that inhaled sedation was a seducing alternative to intravenous sedation. This survey highlights the widespread knowledge about inhaled ICU sedation in France but shows its limited use to date. Differences in education and knowledge, as well as the recent and relatively scarce literature on the use of volatile agents in the ICU, might explain the diverse practices that were observed. The low rate of mild adverse effects, as perceived by respondents, and the users' satisfaction, are promising for this potentially important tool for ICU sedation.


Metal-free Transformations of Nitrogen-Oxyanions to Ammonia via Oxoammonium Salt.
Transformations of nitrogen-oxyanions (NOx- ) to ammonia impart pivotal roles in sustainable biogeochemical processes. While metal-mediated reductions of NOx- are relatively well known, this report illustrates proton-assisted transformations of NOx- anions in the presence of electron-rich aromatics such as 1,3,5-trimethoxybenzene (TMB-H, 1 a) leading to the formation of diaryl oxoammonium salt [(TMB)2 N+ =O][NO3- ] (2 a) via the intermediacy of nitrosonium cation (NO+ ). Detailed characterizations including UV/Vis, multinuclear NMR, FT-IR, HRMS, X-ray analyses on a set of closely related metastable diaryl oxoammonium [Ar2 N+ =O] species disclose unambiguous structural and spectroscopic signatures. Oxoammonium salt 2 a exhibits 2 e- oxidative reactivity in the presence of oxidizable substrates such as benzylamine, thiol, and ferrocene. Intriguingly, reaction of 2 a with water affords ammonia. Perhaps of broader significance, this work reveals a new metal-free route germane to the conversion of NOx to NH3 .


Transient alternating hemichorea as presenting sign of progressive supranuclear palsy.
We report the case of a man who developed unilateral alternating chorea four years before presenting a typical clinical form of Steele-Richardson-Olszewski syndrome. It is known that choreic dyskinesias may occur during the course of this syndrome but this is the first account of choreas presenting sign of the syndrome.


Persister cells as a possible cause of antibiotic therapy failure in Helicobacter pylori.
Due to the failure of antibiotic treatment and recurrence of infection in patients with Helicobacter pylori, this study was designed to find the possible cause of treatment failure and recurrence of the H. pylori infections in Ilam, Iran. One hundred patients with specific symptoms of H. pylori infection were selected, and after taking a biopsy specimen, identification of H. pylori, antibiotic susceptibility assay, and persister cell assay were performed. In addition, after treatment, patients with persister cells were followed for possible recurrence of infection. Furthermore, an antibiotic susceptibility assay was performed. Our results demonstrated that, among 100 patients, 50% (n = 50) showed positive results for the existence of H. pylori. Among the susceptible isolates, 18% (n = 9) were persister cells that were sensitive to clarithromycin as confirmed by a 5 folds higher than the Minimal Inhibitory Concentration (MIC) of clarithromycin. The data were confirmed by following up the suspected patients. Our results demonstrated that persister cells in H. pylori infections may be responsible to recurrent infection and antibiotic treatment failure. However, more research is needed to obtain more information in this area.


Inhibition of GPX4 or mTOR overcomes resistance to Lapatinib via promoting ferroptosis in NSCLC cells.
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase and mutations in EGFR is a major driver force of lung cancer. EGFR tyrosine kinase inhibitors (TKIs) are group of promising agents to treat cancer patients with EGFR mutations. However, the application of TKIs is often hampered by the development of drug-resistance. In the present study, we studied the role of Glutathione peroxidase 4 (GPX4) and mammalian target of rapamycin (mTOR) in regulation of lung cancer cells response to Lapatinib (Lap). Lap resistant NSCLC cells A549/Lap and H1944/Lap were created and GPX4 was knockdown by lentivirus shGPX4. Change of cell viabilities and cell death were measured by MTT and flow cytometry, respectively. ROS, MDA, GSH and Fe2+ were detected by commercial kits. Xenograft mice was used to assay the in vivo effects of GPX4 on the sensitivity of Lap. We found that GPX4 and mTORC1 signalling was upregulated in Lap resistant NSCLC cells when compared to Lap sensitive NSCLC cells. Mechanistically, upregulation of GPX4 was due to enhanced activation of mTORC1 in Lap resistant NSCLC cells. Inhibition of mTORC1 led to the downregulation of GPX4 which promoted Lap induced ferroptosis as evidenced by increase of ROS, MDA, Fe 2+ and decrease of GSH. Rescue experiments confirmed the role of GPX4 in regulation of Lap induced ferroptosis. In vivo experiments also indicated that silencing of GPX4 enhanced the anticancer effect of Lap via promoting ferroptosis. Overall, targeting GPX4 might be a potential strategy to enhance antitumor effects of Lap.


Contribution of guanine nucleotide regulatory proteins to prostaglandin hyperalgesia in the rat.
The contribution of the stimulatory guanine nucleotide regulatory protein (Gs) to prostaglandin E2 (PGE2)-induced hyperalgesia was investigated in the hairy skin of the rat hindpaw using the Randall-Selitto paw-withdrawal test. Although without effect alone, guanosine-5'-[gamma-thio]triphosphate (GTP gamma S) and cholera toxin--which activate Gs--both increased, while guanosine-5'-[beta-thio] diphosphate (GDP beta S)--which prevents the activation of Gs--decreased the hyperalgesia induced by PGE2. These data support the hypothesis that the action of PGE2 on primary afferent nociceptors leading to decreases in paw-withdrawal threshold is Gs-mediated.


Transfection of lymphoblastoid cells using DNA-loaded reconstituted Sendai virus envelopes: expression of transfected DNA and selection of transfected cells.
The American Burkitt's lymphoma cell line Loukes was cotransfected with cloned BamHI K fragment of EBV DNA and a vector pSV2neo. Reconstituted Sendai virus envelopes (RSVE) loaded with DNA were used for efficient gene transfer. Two cell lines have been obtained following culture in the presence of geneticin sulfate (G-418). Messenger RNA from both transfected DNAs was expressed during the whole period of observation, 42 days after transfection. This method provides a relatively simple and efficient means for selection of lymphoblastoid cells expressing a transfected gene.


Role of 2,6-dideoxy-2,6-diaminoglucose in activation of a eukaryotic phospholipase C by aminoglycoside antibiotics.
Recent emergence of microbial resistance to aminoglycoside antibiotics, and the documented cytotoxicity associated with their use, calls for sustained efforts at understanding the effects of the compounds on eukaryotic cells. Using a glycosyl phosphatidylinositol (GPI)-phospholipase C (GPI-PLC) from the protozoan parasite Trypanosoma brucei, we demonstrate that a eukaryotic PLC can be activated 6-fold by aminoglycosides. Neomycin B protected GPI-PLC from a reduction in activity at pH 6.5, and increased the turnover number (kcat) of the enzyme. In structure-activity studies with the neomycin group, 2-deoxy-streptamine was mildly stimulatory; the concentration required to activate GPI-PLC 2-fold (SC200) was 310 microM. Neamine was 150-fold more active (SC200 = 2 microM) than 2-deoxy-streptamine, indicating that a 2,6-dideoxy-2, 6-diaminoglucose substituent at the 4-position of 2-deoxystreptamine plays an important role in activation of GPI-PLC. Ribostamycin and neomycin B also had SC200's of 2 microM, implying that the ribose group in ribostamycin is not involved in activation of GPI-PLC. These conclusions were affirmed in studies with Bacillus thuringiensis phosphatidylinositol-specific phospholipase C. A 2, 6-dideoxy-2,6-diaminoglucose substitution at the 4-OH of 2-deoxystreptamine activates the enzyme 17-fold, while a second 2, 6-dideoxy-2,6-diaminoglucose moiety on the ribose ring of ribostamycin provides an additional 3.5-fold stimulation. Possible implications of these observations for the effects of aminoglycosides on eukaryote cells are discussed.


Prognostic impact of early adjunctive corticosteroid therapy in non-HIV oncology or haematology patients with Pneumocystis jirovecii pneumonia: A propensity score analysis.
While early adjunctive corticosteroid therapy (EACST) has been proven effective in HIV patients with Pneumocystis Jirovecii Pneumonia (PJP), data remains controversial concerning non-HIV oncology or haematology patients. This retrospective study included cancer patients without HIV and with diagnosis of PJP admitted in a cancer referral centre, from January-1-2010 to March-31-2017. We compared 30-day and 1-year mortality rate, change in the respiratory item of the Sequential Organ Failure Assessment score(SOFA-resp worsening), use of tracheal intubation between day-1 and day-5 of anti-pneumocystis therapy and occurrence of coinfections between patients with EACST and those with no or late corticosteroid therapy, using an inverse probability weighting propensity score-based (IPW) analysis. 133 non-HIV oncology or haematology PJP patients were included (EACST n = 58, others n = 75). The main underlying conditions were haematological malignancies (n = 107, 80,5%), solid tumour (n = 27, 20,3%) and allogeneic stem cell transplantation (n = 17, 12,8%). Overall 30-day and 1-year mortality rate was 24,1% and 56,4%, respectively. IPW analysis found no difference on 30-day (HR = 1.45, 95% CI [0.7-3.04], p = 0.321) and 1-year (HR = 1.25, CI 95% [0.75-2.09], p = 0.39) mortality rate between groups. No difference in SOFA-resp worsening, tracheal intubation and coinfections was found between groups. Combination of EACST with anti-pneumocystis therapy in non-HIV onco-haematology PJP-patients was not associated with clinical improvement.


Combining an optimized mRNA template with a double purification process allows strong expression of in vitro transcribed mRNA.
mRNA is a blooming technology for vaccination and has gained global attention during the SARS-CoV-2 pandemic. However, the recent clinical trials have highlighted increased reactogenicity when using high mRNA doses. Intending to increase the potency of mRNA therapeutics and to decrease the therapeutic dose, we designed a mRNA backbone and optimized the mRNA purification process. We used the enhanced green fluorescent protein (eGFP) reporter gene flanked by one 5' untranslated region (UTR) and two 3' UTRs of the human β-globin as a reference mRNA and identified the most promising mRNA sequence using in vitro and in vivo models. First, we assessed the impact of different poly(A) sizes on translation and selected the most optimal sequence. Then, we selected the best 5' UTR among synthetic sequences displaying a high ribosome loading. Finally, we evaluated the transfection efficiency of our standard mRNA template after two capping strategies and purification using either double-stranded RNA (dsRNA) depletion or dephosphorylation of 5'PPP RNA or both combined. Double purification was shown to give the best results. Altogether, the use of a newly defined 5' UTR coupled to post-transcriptional treatments will be of great interest in the mRNA vaccine field, by limiting the amount of the antigen-coding transcript and subsequently the formulation components needed for an efficient vaccination.


An insight into the removal of fluoroquinolones in activated sludge process: Sorption and biodegradation characteristics.
The detailed sorption steps and biodegradation characteristics of fluoroquinolones (FQs) including ciprofloxacin, enrofloxacin, lomefloxacin, norfloxacin, and ofloxacin were investigated through batch experiments. The results indicate that FQs at a total concentration of 500μg/L caused little inhibition of sludge bioactivity. Sorption was the primary removal pathway of FQs in the activated sludge process, followed by biodegradation, while hydrolysis and volatilization were negligible. FQ sorption on activated sludge was a reversible process governed by surface reaction. Henry and Freundlich models could describe the FQ sorption isotherms well in the concentration range of 100-300μg/L. Thermodynamic parameters revealed that FQ sorption on activated sludge is spontaneous, exothermic, and enthalpy-driven. Hydrophobicity-independent mechanisms determined the FQ sorption affinity with activated sludge. The zwitterion of FQs had the strongest sorption affinity, followed by cation and anion, and aerobic condition facilitated FQ sorption. FQs were slowly biodegradable, with long half-lives (>100hr). FQ biodegradation was enhanced with increasing temperature and under aerobic condition, and thus was possibly achieved through co-metabolism during nitrification. This study provides an insight into the removal kinetics and mechanism of FQs in the activated sludge process, but also helps assess the environmental risks of FQs resulting from sludge disposal.


Tetrahymena thermophila: analysis of phospholipids and phosphonolipids by high-field 1H-NMR.
The phospholipids of control and lipid-modified Tetrahymena thermophila were identified and quantified, using 1-D and 2-D COSY proton NMR spectroscopy on intact lipids, before and after HPLC separation. The results are comparable to those obtained using classical lipid analytical techniques. The results indicate that the study of enzyme pathways and other metabolic processes involving phospholipids in Tetrahymena and related protozoa can be carried out using proton NMR spectroscopy as the investigating technique.


Student experiences in an academic support program to diversify the nursing workforce.
The current demographic of the Nursing workforce in the United States suggests a need to increase the percentage of minority nurses in practice. Diversifying the nursing workforce may change patient perceptions and improve the quality of care received by underserved patients. A college of nursing created the Nursing Endeavor Program to support first generation, low income, and/or underrepresented students from the point of acceptance in the nursing program to graduation. Nursing Endeavor students are guaranteed acceptance into the nursing major upon successful completion of these preliminary nursing courses. Despite application of some Jeffreys interventions, only 50% of Nursing Endeavor students enrolled in the preliminary nursing courses qualified to enter the major and graduated. One hundred percent of all Nursing Endeavor students who successfully transitioned into the final two years of the major had graduated. Therefore, this study focused on the efficacy of NEP interventions to support students in the first two years. The aim of this study was to analyze student perspectives of the efficacy of interventions in the Nurse Endeavor Program designed to facilitate successful completion of the first two years of preliminary courses in the nursing major, which equates to a successful transition to student nurse. This study used a Qualitative Phenomenographic research design. Individual interviews were conducted in the Principal Investigator's office in a Midwestern United States Research Universities' College of Nursing. Eleven students who continued in the Nursing Endeavor Program to graduation, and eight former Nursing Endeavor students who withdrew from the nursing major during preliminary nursing courses. Meleis transitions theory guided the study design. Institutional Review Board approval for study 17.272, and participant consent were obtained. Face-to-face interviews were conducted in the Principal Investigator's office and were transcribed verbatim. Phenomenographic methods were used for narrative analysis. Students reported nine interventions facilitated transition from preliminary nursing courses to the nursing major. Students reported three factors hindered transition: academic rigor, isolation, and living at home. Attendance at professional events was not mentioned. Students credited Jeffreys' interventions for successful transitions. Additional factors influencing transition identified by students merit further study.


Probes of inhibition of Escherichia coli F(1)-ATPase by 7-chloro-4-nitrobenz-2-oxa-1,3-diazole in the presence of MgADP and MgATP support a bi-site mechanism of ATP hydrolysis by the enzyme.
Binding of MgADP and MgATP to Escherichia coli F(1)-ATPase (EcF(1)) has been assessed by their effects on extent of the enzyme inhibition by 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl). MgADP at low concentrations (K(d) 1.3 microM) promotes the inhibition, whereas at higher concentrations (K(d) 0.7 mM) EcF(1) is protected from inhibition. The mutant betaY331W-EcF(1) requires much higher MgADP, K(d) of about 10 mM, for protection. Such MgADP binding was not revealed by fluorescence quenching measurements. MgATP partially protects EcF(1) from inactivation by NBD-Cl, but the enzyme remains sensitive to NBD-Cl in the presence of MgATP at concentrations as high as 10 mM. The activating anion selenite in the absence of MgATP partially protects EcF(1) from inhibition by NBD-Cl. A complete protection of EcF(1) from inhibition by NBD-Cl has been observed in the presence of both MgATP and selenite. The results support a bi-site catalytic mechanism for MgATP hydrolysis by F(1)-ATPases and suggest that stimulation of the enzyme activity by activating anions is due to the anion binding to a catalytic site that remains unoccupied at saturating substrate concentration.


Dual-ligand and hard-soft-acid-base strategies to optimize metal-organic framework nanocrystals for stable electrochemical cycling performance.
Most metal-organic frameworks (MOFs) hardly maintain their physical and chemical properties after exposure to acidic, neutral, or alkaline aqueous solutions, resulting in insufficient stability, therefore limiting their applications. Thus, the design and synthesis of stable size/morphology-controlled MOF nanocrystals is critical but challenging. In this study, dual-ligand and hard-soft-acid-base strategies were used to fabricate a variety of 3D pillared-layer [Ni(thiophene-2,5-dicarboxylate)(4,4'-bipyridine)]n MOF nanocrystals (1D nanofibers, 2D nanosheets and 3D aggregates) with controllable morphology by varying the concentration of 4,4'-bipyridine and thus controlling the crystal growth direction. Owing to the shorter ion diffusion length, enhanced electron/ion transfer and strong interactions between thiophene-2,5-dicarboxylate and 4,4'-bipyridine, the 2D nanosheets showed much larger specific capacitance than 1D nanofibers and 3D aggregates. A single device with an output voltage as high as 3.0 V and exceptional cycling performance (95% of retention after 5000 cycles at 3 mA cm-2) was realized by configuring two aqueous asymmetric supercapacitive devices in series. The excellent cycling property and charge-discharge mechanism are consistent with the hard-soft-acid-base theory.


Nucleoside triphosphatase activity associated with the N-terminal domain of mammalian tryptophanyl-tRNA synthetase.
Bovine tryptophanyl-tRNA synthetase (EC 126.96.36.199) deprived of Zn2+ by chelation with the phosphonate analog of Ap4A hydrolyzed ATP(GTP) to ADP(GDP) although its ability to form tryptophanyl adenylate was impaired. This hydrolytic activity is stimulated by Mg2+ and Mn2+ ions and inhibited by Zn2+. Monoclonal antibody Am1 against the N-terminal domain of the enzyme completely abolished ATP(GTP)ase activity. The core peptide generated after proteolytic splitting of the N-domain lacks this activity. We suggest that the nucleotide binding site(s) different from ATP sites involved in aminoacylation reaction reside(s) at the N-terminal domain(s) of the enzyme.


Fusobacterium nucleatum bacteremia with pneumopathy in a patient receiving eculizumab: A case report.
Fusobacterium nucleatum is a common oral commensal bacterium capable of severe invasive infections. We report a case of a diffuse bilateral pneumopathy with F. nucleatum-positive blood culture successfully treated by common antibiotics in a patient receiving eculizumab for a drug-induced thrombotic microangiopathy (TMA). It is the first described case of a severe F. nucleatum-associated infection in a patient undergoing terminal complement inhibitor therapy. We suggest providing preventive dental care before eculizumab initiation.


Routine clotting screen has no role in the management of epistaxis: reiterating the point.
Objective of the study is to investigate the role of clotting screen in adult patients presenting with epistaxis. The study is a prospective case series done in a teaching hospital in the Northeast of Scotland. Prospective data was collected for 100 consecutive patients with epistaxis admitted to the Department of Otolaryngology over 1 year (2006-2007 August). The demographics, co-morbidities, long-term medications and blood test results were noted for these patients. A retrospective audit of all patients attending the Emergency Department (ED) with epistaxis during the same study period was also performed. The following were measured: frequency of clotting screen performed in patients with epistaxis; the treatment modifying effect of clotting screen results. Of the 100 admitted patients, 45 were male and 55 were female. The majority of them had more than two co-morbidities such as hypertension, ischaemic heart disease and atrial fibrillation. Forty-seven patients were on aspirin, 19 on warfarin and 12 patients on clopidogrel. A clotting screen was done for 80 patients but only 2 patients (2.5%) had an abnormal INR. A total of 356 patients presented to the ED with epistaxis. Of 356 patients, 138 (39%) had their clotting screen checked. Of 138 patients, 42 (30%) were on warfarin. Only 7 patients (7/138 = 5%) had an abnormal result. Our data suggests that routine clotting screen check does not alter the epistaxis management in patients with no risk factors or with stable warfarin dosage. Therefore, routine clotting screen in patients with epistaxis without relevant risk factors is not an evidence-based practice.


Tetrahydroaminoacridine and lecithin in the treatment of Alzheimer's disease. Effect on cognition, functioning in daily life, behavioural disturbances and burden experienced by the carers.
In 12 ambulant patients with a clinical diagnosis of probable Alzheimer's disease, a 12-week, double-blind, placebo-controlled study with 100 mg/day tetrahydroaminoacridine (THA) and 10 g/day lecithin is reported. The aim of the study was to find whether treatment would result in an improvement of cognition, of functioning in daily life, decrease of behavioural disturbances, and decrease in burden experienced by the carers. Two of the six THA-treated patients demonstrated an increase on cognitive test scores with a moderate increase in the other outcome measurements. There was, however, no difference between the two groups in any outcome measurement after treatment. In addition, we found a reversible rise of liver transaminases in 4 of 6 patients in the treated group. This pilot study is too small to draw definite conclusions on the use of THA alone or in combination with lecithin. Our results suggest, however, that semi-structured interviews with the carers may be of value in the evaluation of treatment effects in patients with Alzheimer's disease.


The antinociceptive effect of acetaminophen in a rat model of neuropathic pain.
Acetaminophen is one of the most popular and widely used analgesics for the treatment of pain and fever but few studies have evaluated its effects on neuropathic pain. This study examined the effect of acetaminophen on thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain. Male Sprague-Dawley rats were prepared by tightly ligating the left L5 and L6 spinal nerves to produce a model of neuropathic pain. Sixty neuropathic rats were assigned randomly into six groups. Normal saline and acetaminophen (25, 50, 100, 200 and 300 mg/kg) were administered intraperitoneally to these individual groups. Thermal hyperalgesia, mechanical and cold allodynia were examined at preadministration and at 15, 30, 60, 90, 120, 180, 240 and 360 min after administering the drug. Mechanical allodynia was quantified by measuring the paw withdrawal threshold to stimuli with von Frey filaments. Cold allodynia was quantified by measuring the frequency of foot lift after applying 100% acetone. Thermal hyperalgesia was quantified by measuring the thermal withdrawal threshold. The rotarod performance was measured to detect any drug-induced adverse effects, such as drowsiness. The hepatic and renal adverse effect was also assessed by measuring the serum levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine. The paw withdrawal thresholds to mechanical stimuli and the thermal withdrawal threshold were increased significantly and withdrawal frequencies to cold stimuli were reduced by acetaminophen administration in a dose-dependent manner. Acetaminophen reduces thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain, and might be useful for managing neuropathic pain.


'Autistic person' or 'person with autism'? Person-first language preference in Dutch adults with autism and parents.
There are different words to describe people with an autism diagnosis. For instance, we can put the person before autism (e.g. 'person with autism'), or we can put autism before the person (e.g. 'autistic person'). Previous research showed that autistic adults in English-speaking countries generally liked it better when autism is placed before the person. Yet, people also greatly differ in the words they like and dislike. In this study, we examined word preference in Dutch autistic adults (n = 1026; 16-84 years; 57% women) and parents of autistic children (n = 286). Via an online questionnaire, we asked our participants to select one term for autistic people that they liked best. The results showed that most adults with autism (68.3%) and parents (82.5%) preferred to put the person before autism. Younger adults, with a higher intelligence, and with more autistic traits, were a bit more likely to put autism before the person. We conclude that there are large differences in the words that people prefer. Because we found different results in our Dutch participants compared to participants in English-speaking countries, we think that the Dutch language or culture may also play a role in word preference. For now, we advise autism researchers to use both person-first and autism-first language.


Editorial Commentary: Proximal Hamstring Tendon Injuries: Is the Research Hamstrung by the Use of Poor Outcome Measures?
Proximal hamstring tendon injuries are uncommon injuries, and there are few high-quality studies of surgical procedures in the literature. Increasing standardization of outcome measures with the use of validated, injury-specific, patient-reported outcome measures will improve research in this area. This will allow better assessment of novel surgical techniques.


On the radiotoxic 210Po in coffee beans worldwide and the impact of roasting and brewing on its extraction into beverages: from the experiments to 210Po content prediction.
We determined radiotoxic 210Po in roasted coffee beans from different regions worldwide, the beverages, and tried to create the prediction model of 210Po content based on its growth location. Additionally, the experiments on 210Po losses and extraction were performed to describe the actual exposure to 210Po. 210Po concentrations in coffee beans and brews tuned out low (maximally of 0.20 Bq∙kg-1 and 2.31 Bq∙L-1, respectively). We assessed the impact of the roasting process on 210Po content and its losses at a maximum of 56.7%. During infusion experiments, we estimated the extraction of 210Po to the coffee brew at a maximum of 40.6%. The amount of 210Po in the coffee brew depended on the infusion style and water type. We calculated the effective radiation doses from the coffee drink ingestion. Coffee drinking does not contribute significantly to the annual effective radiation dose worldwide.


Predicting the potential of sludge dewatering liquors to recover nutrients as struvite biominerals.
Phosphorus and nutrient recovery from wastewater as mineral salts can support local replenishment of fertilisers and reduce mining, contributing to the circular economy. Wastewater and related streams are rich in nutrients, however; there is need to develop bio-based processes to recover them. This study investigates the fractions of phosphorus (P) used by Brevibacterium antiquum to form struvite biominerals (bio-struvite) in wastewater sludge dewatering liquors. After 72h of incubation, 25.6 mg P/L were recovered as bio-struvite from 12.4 mg P/L organic plus condensed P and 13.2 mg P/L of ortho-phosphate. The potential of sludge dewatering liquors to recover nutrients as struvite was investigated by characterising ten types of sludge liquors (originating from primary, secondary sludge, feed to anaerobic digester and digestate, from 3 types of wastewater treatment plants) for their P fractions together with other parameters relevant for B. antiquum growth. Results indicated that liquors obtained from primary sludge, feed to anaerobic digesters and digestate were the most suitable to produce bio-struvite, as these were found to frequently have a high content of organic and condensed P, between to 276-732 mg P/L. Liquors, from all the investigated sites, presented a higher potential for bio-struvite production than with conventional struvite precipitation. This study demonstrated that B. antiquum could convert organic and condensed P into bio-struvite, and this opens up a completely new way to recover forms of phosphorus that are not typically available for nutrient recovery in a single process.


Morphological and biochemical analyses of trichloroethylene hepatotoxicity: differences in ethanol- and phenobarbital-pretreated rats.
The histological and biochemical differences between ethanol- and phenobarbital (PB)-potentiated hepatotoxicity of trichloroethylene (TRI) in Wistar strain male rats were investigated. Both ethanol (2 g in daily liquid diet for 3 weeks) and PB (80 mg/kg/day for 4 days, ip) pretreatments enhanced TRI (inhalation exposures of 500 ppm for 8 hr, 2000 ppm for 2 or 8 hr, and 8000 ppm for 2 hr)-induced hepatic damage as judged by increases in plasma transaminase activities. Livers from PB-treated rats exposed to TRI displayed centrilobular necrosis, whereas livers from ethanol-treated rats exposed to TRI were characterized by ballooning degeneration mainly in midzonal areas. TRI exposure decreased the in vitro metabolism of TRI, high-Km benzene aromatic hydroxylase (BAH) activity, and cytochrome P450 content in livers of PB-treated rats with severe hepatic damage. In ethanol-treated rats, TRI exposure increased both the in vitro metabolism of TRI and the low-Km BAH activity but did not cause an apparent decrease in cytochrome P450 content even in animals with severe hepatic damage. These results suggest that TRI caused necrosis of centrilobular hepatocytes in PB-pretreated rats, which was accompanied by loss of xenobiotic metabolizing functions, whereas ballooning degeneration of hepatocytes mainly in midzonal areas occurred in ethanol-pretreated rats without loss of xenobiotic metabolizing functions.


A new linear regression-like residual for survival analysis, with application to genome wide association studies of time-to-event data.
In linear regression, a residual measures how far a subject's observation is from expectation; in survival analysis, a subject's Martingale or deviance residual is sometimes interpreted similarly. Here we consider ways in which a linear regression-like interpretation is not appropriate for Martingale and deviance residuals, and we develop a novel time-to-event residual which does have a linear regression-like interpretation. We illustrate the utility of this new residual via simulation of a time-to-event genome-wide association study, motivated by a real study seeking genetic modifiers of Duchenne Muscular Dystrophy. By virtue of its linear regression-like characteristics, our new residual may prove useful in other contexts as well.


The association of adiponectin and low-grade inflammation with the course of metabolic syndrome.
Metabolic syndrome (MetS) is associated with low-grade inflammation. The connections of adiponectin and inflammatory cytokines with the course of MetS are not well-known. The aim of this study was to investigate the relation of adiponectin and low-grade inflammation with the development or resolution of MetS. In the town of Pieksämäki, Finland, five complete age groups (n = 1.294) were invited for health check-ups in 1997-1998 for the first time and in 2003-2004 for the second time. The final study population included 284 men and 396 women. MetS was defined according to the National Cholesterol Education Program criteria in the beginning and at the end of the 6-year research period, and adiponectin, high-sensitivity C-reactive protein (hs-CRP), interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1 beta (IL-1β) levels were determined from baseline samples. Both male and female study subjects were divided into four groups according to the diagnosis of MetS in the two check-ups: not diagnosed at either check-up (No MetS), diagnosed only at the second check-up (Incident MetS), diagnosed only at the first check-up (Resolute MetS), and diagnosed at both check-ups (Persistent MetS). Baseline adiponectin, IL-1Ra and IL-1β levels and IL-1β/IL-1Ra -ratio were found to predict Incident MetS, when adjusted for the change in BMI, age, smoking status and physical activity. Our data also suggested that a high adiponectin level and low hs-CRP and IL-1Ra levels predict the resolution of MetS. Adiponectin and inflammatory markers can predict the course of MetS.


Gender Differences in Self-Regulated Online Learning During the COVID-19 Lockdown.
Due to the spread of the epidemic around the world, online learning has received greater attention. Self-regulated learning (SRL) is an important factor for students to achieve academic success. This study investigated the gender differences in SRL and three sub-constructs of SRL in the context of online learning, that is the preparatory, performance, and appraisal phases. A total of 400 high school students (males = 125, females = 275) from China participated in this study. In order to identify whether there were gender differences in their self-regulated online learning (SROL), independent sample t-test was performed. The results showed that there were significant gender differences in the SROL (t = -3.334, p = 0.001 < 0.01, d = -0.410) and the three sub-constructs of SROL (preparatory: t = -0.702, p = 0.008 < 0.01, d = 0.018; performance: t = -3.801, p = 0.000 < 0.01, d = 0.456; appraisal: t = -3.120, p = 0.002 < 0.01, d = 0.361). The findings indicated that females performed better than males in all three dimensions of learners' online self-regulated learning.


Intestinal perforation involving the Dacron cuff of nephrostomy tubes following subcutaneous ureteral bypass system implantation for ureteral obstructions in two cats.
This case report describes two cats that had subcutaneous ureteral bypass (SUB) systems implanted and subsequently developed duodenal perforations and septic peritonitis associated with the Dacron cuff of the nephrostomy tube. One cat recovered following surgical explantation of the SUB system with intestinal resection and anastomosis of the perforated small intestine, and - at the time of writing - is still alive. The other cat was humanely euthanased intraoperatively at the owner's request owing to its perceived prognosis. To our knowledge this is the first time this complication has been reported following SUB device placement.


A novel classification system of lumbar disc degeneration.
The Pfirrmann and modified Pfirrmann grading systems are currently used to classify lumbar disc degeneration. These systems, however, do not incorporate variables that have been associated with lumbar disc degeneration, including Modic changes, a high intensity zone, and a significant reduction in disc height. A system that incorporates these variables that is easy to apply may be useful for research and clinical purposes. A grading system was developed that incorporates disc structure and brightness, presence or absence of Modic changes, presence or absence of a high intensity zone, and reduction in disc height (disc height less than 5mm). MRI of 300 lumbar discs in 60 patients were analyzed twice by two neurosurgeons. Intra and inter-observer reliabilities were assessed by calculating Cohen's κ values. There were 156 grade zero ("normal"), 50 grade one, 57 grade two, 26 grade three, 10 grade four, and one grade five ("worst") discs. Inter-observer reliability was substantial (κ = 0.66 to 0.77) for disc brightness/structure, Modic changes, and disc height. Inter-observer reliability was moderate (κ = 0.41) for high intensity zone. Intra-observer reliability was moderate to excellent (κ = 0.53 to 0.94) in all categories. Agreement on the total grade between reviewers occurred 71% of the time and a difference of one grade occurred in an additional 25% of cases. Lumbar disc degeneration can be graded reliably by this novel system. The advantage of this system is that it incorporates disc brightness/structure, Modic changes, high intensity zone, and a rigid definition of loss of disc height. This system might be useful in research studies evaluating disc degeneration. Further studies are required to demonstrate possible clinical utility in predicting outcomes after spinal treatments such as fusion.


An index to predict outcome of surgery for reflux esophagitis based on the AFP classification.
Fifteen patients with reflux esophagitis were treated surgically from July 1990 to April 1994. We evaluated these patients using the anatomic-functional-pathologic (AFP) classification both prior to and following the operation. An objective index for surgical outcome was devised. By using the grades Ai, Fj, and Pk, the i2 + j2 + k2 score was determined. The scores ranged from 3 to 22 (mean 9.1 +/- 5.4) prior to the operation. Postoperatively, 12 (80%) of 15 patients showed a complete recovery with a numerical score of 0, and their symptoms also disappeared. The scores of these 12 patients prior to the operation ranged between 3 and 11. However, the other 3 patients did not exhibit a complete recovery. Their scores prior to the operation ranged between 17 and 22, and the symptoms in 2 of these 3 patients persisted following the operation. These results suggest that surgical treatment for reflux esophagitis can be expected to be successful if the preoperative AFP score is less than 11.


Acceptability and Feasibility of the Transfer of Face-to-Face Group Therapy to Online Group Chats in a Psychiatric Outpatient Setting During the COVID-19 Pandemic: Longitudinal Observational Study.
At the height of the COVID-19 pandemic, several mental health care providers were obliged to shut down outpatient services, including group therapy and psychoeducational sessions. The lockdown in many countries is a serious threat to people's mental well-being, especially for individuals with severe mental illnesses. Discontinued outpatient treatments and disruption of daily routines are considered to be risk factors for destabilization of patients with mental illness. The aim of this study was to evaluate the acceptability, usability, and feasibility of a group chat program to replace cancelled face-to-face group sessions in an outpatient psychiatric department. Participants (N=33) were recruited in the outpatient department of a large university medical center in Leipzig, Germany. Former face-to-face group participants were invited to take part in a therapist-guided group-chat for 4 weeks (8 sessions) and were asked to evaluate the program via self-administered standardized questionnaires at baseline (T0, preintervention), after every chat session (T1), and posttreatment (T2, after 4-6 weeks). The chat groups were specific to the following mental disorder diagnoses and based on the same therapeutic principles and techniques as the former face-to-face groups: anxiety, depression, obsessive-compulsive disorder, and adult attention-deficit/hyperactivity disorder (ADHD). Sociodemographic measures, attitudes toward the COVID-19 pandemic, depressive symptoms (Patient Health Questionnaire-9), quality of life (abbreviated World Health Organization Quality of Life assessment), treatment credibility/expectancy (Credibility Expectancy Questionnaire), and participants' satisfaction (Client Satisfaction Questionnaire-8 [ZUF-8]) were measured. Participants joined an average of 5 out of 8 offered chat sessions. Participation rates in the respective groups were highest in the ADHD group (8.6/11, 78%) and lowest in the anxiety group (3.7/9, 41%). The overall preintervention level of depressive symptoms was moderate and showed a slight, nonsignificant improvement at posttreatment (T0: mean 10.7, SD 5.5; T2: mean 10.2, SD 5.5). A similar result was observed regarding quality of life (T0: median 41.7-68.8; T2: median 50-70.3). Treatment credibility and expectancy scores were medium-high (T0: meancredibility 18.1, SD 3.8; meanexpectancy 11.2, SD 5.1; T2: meancredibility 17.1, SD 4.8; meanexpectancy 10.3, SD 5.8). Further, significant correlations were detected between posttreatment expectancy score and posttreatment PHQ-9 score (r=-0.41, P=.02), posttreatment physical quality of life (r=0.54, P=.001), and posttreatment psychological quality of life (r=0.53, P=.002). Overall, participants' satisfaction with the program was very high, both after chat sessions and at posttreatment (ZUF-8: mean score 20.6, SD 1.0). Of all participants, a majority (27/31, 87%) rated the program as excellent/good and indicated they would recommend the group chat program to a friend in need of similar help (23/31, 74%). A therapist-guided group chat program to substitute outpatient group setting treatment during the COVID-19 lockdown was shown to be feasible, usable, and highly acceptable for participants. Web-based programs such as this one provide an easy-to-implement tool to successfully stabilize participants during a difficult time, such as the COVID-19 pandemic. German Clinical Trials Register DRKS00021527; https://tinyurl.com/3btyxc2r.


Boron neutron capture therapy (BNCT) for the treatment of spontaneous nasal planum squamous cell carcinoma in felines.
Recently, Boron neutron capture therapy (BNCT) was successfully applied to treat experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa, with no damage to normal tissue. It was also shown that treating spontaneous nasal planum SCC in terminal feline patients with low dose BNCT is safe and feasible. In an extension of this work, the present study aimed at evaluation of the response of tumor and dose-limiting normal tissues to potentially therapeutic BNCT doses. Biodistribution studies with (10)B-boronophenylalanine (BPA enriched in (10)B) as a (10)B carrier were performed on three felines that showed advanced nasal planum SCC without any standard therapeutic option. Following the biodistribution studies, BNCT mediated by (10)BPA was done using the thermalized epithermal neutron beam at the RA-6 Nuclear Reactor. Follow-up included clinical evaluation, assessment of macroscopic tumor and normal tissue response and biopsies for histopathological analysis. The treated animals did not show any apparent radiation-induced toxicity. All three animals exhibited partial tumor control and an improvement in clinical condition. Enhanced therapeutic efficacy was associated with a high (10)B content of the tumor and a small tumor size. BNCT is therefore believed to be potentially effective in the treatment of spontaneous SCC. However, improvement in targeting (10)B into all tumor cells and delivering a sufficient dose at a greater depth are still required for the treatment of deep-seated, large tumors. Future studies are needed to evaluate the potential efficacy of the dual mode cellular (e.g. BPA-BNCT) and vascular (e.g. GB-10-BNCT) targeting protocol in a preclinical scenario, employing combinations of (10)B compounds with different properties and complementary uptake mechanisms.


Stabilization training versus equilibrium training in karate athletes with deafness.
The aim of this study is to compare the effect of stabilization and equilibrium training on hip muscle strength and balance performance of karate athletes with deafness. Twenty-seven athletes from the National Deaf Karate Team (18 males, nine females) with an average age of 24.53±3.62 (18-43) years were included in this study. The athletes were randomly assigned to either stabilization or equilibrium training group. Both training programs lasted 6 weeks with once per day and 5 days per week sessions. The assessment of muscle strength and balance performance was done before and after the training. The muscle strength and balance have improved in both training groups (P<0.05), but while there was no difference in the results of muscle strength between the groups (P>0.05), balance performance was better in the equilibrium training group (P<0.05). In conclusion, stabilization and equilibrium training have helped the karate athletes with deafness to improve their muscle strength and balance performance.


Periodontal healing after impacted lower third molar surgery in adolescents and adults. A prospective study.
The effects of impacted lower 3rd molar surgery on periodontal tissues in the adjacent 2nd molar area have been investigated in a prospective study comprising 176 cases from 2 age groups: less than or equal to 20 years (n = 93) and greater than or equal to 30 years (n = 83), respectively. The preoperative and 1-year postoperative examinations included both clinical and radiographic variables. All patients were subjected to a standardized surgical procedure and optimal plaque control pre-, intra- and postoperatively. Early removal of impacted lower 3rd molars with large angulation and close positional relationship to the adjacent 2nd molar proved to have a beneficial effect on periodontal health.


ISG15 protects human Tregs from interferon alpha-induced contraction in a cell-intrinsic fashion.
Type I interferons (IFNs) inhibit regulatory T-cell (Treg) expansion and activation, making them beneficial in antiviral responses, but detrimental in autoimmune diseases. Herein, we investigate the role of ISG15 in human Tregs in the context of refractoriness to type I IFN stimulation. ISG15 expression and Treg dynamics were analysed in vitro and ex vivo from patients with chronic hepatitis C, with lupus and ISG15 deficiency. ISG15 is expressed at high levels in human Tregs, renders them refractory to the IFN-STAT1 signal, and protects them from IFN-driven contraction. In vitro, Tregs from healthy controls upregulate ISG15 upon activation to higher levels than conventional CD4 T cells, and ISG15-silenced Tregs are more susceptible to IFNα-induced contraction. In human ISG15 deficiency, patient Tregs display an elevated IFN signature relative to Tregs from healthy control. In vivo, in patients with chronic hepatitis C, 2 days after starting pegIFN/ribavirin therapy, a stronger ISG15 inducibility correlates with a milder Treg depletion. Ex vivo, in systemic lupus erythematosus patients, higher levels of ISG15 are associated to reduced STAT1 phosphorylation in response to IFNα, and also to increased frequencies of Tregs, characterising active disease. Our results reveal a Treg-intrinsic role of ISG15 in dictating their refractoriness to the IFN signal, thus preserving the Treg population under inflammatory conditions.


Genome-wide survey of the dehydrin genes in bread wheat (Triticum aestivum L.) and its relatives: identification, evolution and expression profiling under various abiotic stresses.
Bread wheat (Triticum aestivum) is an important staple cereal grain worldwide. The ever-increasing environmental stress makes it very important to mine stress-resistant genes for wheat breeding programs. Therefore, dehydrin (DHN) genes can be considered primary candidates for such programs, since they respond to multiple stressors. In this study, we performed a genome-wide analysis of the DHN gene family in the genomes of wheat and its three relatives. We found 55 DHN genes in T. aestivum, 31 in T. dicoccoides, 15 in T. urartu, and 16 in Aegilops tauschii. The phylogenetic, synteny, and sequence analyses showed we can divide the DHN genes into five groups. Genes in the same group shared similar conserved motifs and potential function. The tandem TaDHN genes responded strongly to drought, cold, and high salinity stresses, while the non-tandem genes respond poorly to all stress conditions. According to the interaction network analysis, the cooperation of multiple DHN proteins was vital for plants in combating abiotic stress. Conserved, duplicated DHN genes may be important for wheat being adaptable to a different stress conditions, thus contributing to its worldwide distribution as a staple food. This study not only highlights the role of DHN genes help the Triticeae species against abiotic stresses, but also provides vital information for the future functional studies in these crops.


[Further investigations into the effectiveness of gentamicin and other antibiotics against urinary tract infection organisms (author's transl)].
In continuance of our investigations from 1968 to 1972, we isolated 32939 microorganisms from urinary tract infections and subjected them to routine sensitivity tests against six antibiotics from 1973 to August 1975. All organisms except enterococci and proteus proved to be sensitive to gentamicin at a level exceeding 90% during the study period of two and a half years. A loss of activity of gentamicin worth mentioning was not detected during the studies. So this antibiotic must further be considered as one of the drugs of first choice in the treatment of urinary tract infections.


Studies on degradation of reactive textile dyes solution by electrochemical method.
The indirect electrochemical degradation of industrial effluents has become an attractive method in recent years. This paper deals with the electrochemical degradation of Novacron Deep Red C-D (NDRCD) and Novacron Orange C-RN (NOCRN) reactive azo dyes from aqueous solution using graphite carbon electrodes. The results indicated that initial pH, current density and supporting electrolytes were played an important role in the degradation of dyes. Electrochemical behavior of reactive azo dyes has been studied with cyclic voltammetry in acidic medium using pencil graphite as working electrode. The potentials selected for the two dyes were in the range +1.0 to -0.4V and +0.5 to -0.2V, respectively. The CV, UV-Vis and chemical oxygen demand (COD) studies were selected to evaluate the degradation efficiency. The maximum colour removal efficiency of 99% and 97% and chemical oxygen demand (COD) removal efficiency of 88% and 82% could be achieved for CDRCD and COCRN, respectively at 7 g L(-1) of NaCl concentration. The LC-MS study revealed the degradation of both the dyes and confirmed that the azo groups and aromatic rings were destroyed. The results revealed the suitability of the present process for the effective degradation of dye effluents.


Identification of a novel heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) ligand that disrupts HnRNPA2B1/nucleic acid interactions to inhibit the MDMX-p53 axis in gastric cancer.
Gastric carcinoma is a highly malignant tumor that still lacks effective molecular targets. Heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is an essential oncogenic driver overexpressed in various cancers. The potential role of hnRNPA2B1 in oncotherapy has not been revealed because of the absence of active chemical molecules. In this study, we identified the pseudourea derivative XI-011 as a novel hnRNPA2B1 ligand using chemical proteomics. An interaction study indicated that XI-011 could bind the nucleotide-binding domain to disrupt the recruitment of hnRNPA2B1 to the promoter and untranslated region of the murine double minute X (MDMX) gene, thereby inhibiting its transcription. In addition, chemical targeting of hnRNPA2B1 recovered inactivated p53 and enhanced the therapeutic efficacy of apatinib in vivo. This work presented a novel strategy to restore p53 activity for the treatment of gastric cancers via chemically targeting hnRNPA2B1.


Oral status and homebound status: A 6-year bidirectional exploratory prospective cohort study.
Little is known about the association between oral status and homebound status, and there is a possibility of a bidirectional relationship between them. In this exploratory prospective cohort study, we examined the association between four oral status measurements and being homebound bidirectionally. We used 2010-2016 panel data gathered from the Japan Gerontological Evaluation Study. All functionally independent participants aged 65 years or older (n = 26,579) were included in this study. Multiple imputation and Poisson regression were used for analyses. We adjusted for age, sex, education, comorbidity, and depressive symptoms. In the fully adjusted model, the prevalence ratio (PR) of being homebound at follow-up was 1.42 for having <20 remaining teeth, 1.28 for having chewing difficulty, 0.99 for having choking experience, and 0.94 for having dry mouth at baseline. Reversely, being homebound at baseline predicted having chewing difficulty at follow-up (PR = 1.17), while no significant association was demonstrated with having <20 teeth (PR = 1.00), choking experience (PR = 1.06), and dry mouth (PR = 1.02). Chewing difficulty and having <20 remaining teeth predicted homebound status after 6 years. Reversely, homebound status at baseline only predicted having chewing difficulty at follow-up. These findings may help to determine the oral frailty assessment measures for older people.


Recombinant granulocyte-macrophage colony stimulating factor followed by immunosuppressive therapy for aplastic anaemia.
Seventeen patients with aplastic anaemia were treated with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) for 14 d. Nonresponding patients were then treated with anti-human thymocyte globulin (ATG), methylprednisolone and oxymetholone. Side-effects of rhGM-CSF included fever, nausea and vomiting, diarrhoea, bone pain, headache and chills. Two patients had sustained trilineage haemopoietic recovery after receiving only rhGM-CSF. Of 11 patients who received immunosuppressive therapy, there was one complete response, two partial responses, one minimal response, and seven nonresponses. Actuarial survival at 2 years is 64%. Early administration of rhGM-CSF had no apparent effect on subsequent response to immunosuppressive therapy.


Activation and regulation of chemokines in allergic airway inflammation.
Allergic airway inflammation is characterized by peribronchial eosinophil accumulation with the submucosa surrounding the airway. The initial induction of immunoglobulin E (IgE)-mediated mast cell degranulation, up-regulation of adhesion molecules, and the production of inflammatory and chemotactic cytokines, leading to the infiltration of specific leukocyte subsets, is orchestrated in a sequential manner. The activation and degranulation of local mast cell populations is an immediate airway response mediated both by antigen-specific, surface bound IgE and by cytokine-induced activational pathways. Subsequently the infiltration and activation of effector leukocytes (neutrophils and eosinophils) mediated by the persistent activation of allergen-specific T cells leads to pathological manifestations within the lung and airway. The development of appropriate animal models to dissect the critical mechanisms involved in antigen-induced airway pathology is crucial for the development of efficacious therapies. We have utilized a model of allergic airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg antigen in presensitized mice. This model has proven useful in the assessment of eosinophil recruitment and has identified key cytokines involved in leukocyte elicitation. These cytokines include interleukin-4 and elicitation. These cytokines include interleukin-4 and tumor necrosis factor, which appear to act as early response mediators, as well as C-C chemokines, macrophage inflammatory protein-1a, and RANTES, which act directly on eosinophil recruitment. In addition, we have found that both C-X-C and C-C chemokines are expressed in pulmonary-derived mast cells, suggesting an important contribution to leukocyte responses in the allergic airway.


Progression of coronary atherosclerotic disease assessed by cinevideodensitometry: relation to clinical risk factors.
Progression of coronary artery stenosis was measured using a quantitative, computer-assisted cinevideodensitometric method in 144 arterial segments in 44 subjects undergoing coronary arteriography on two separate occasions at least 6 months apart. Projected coronary arteriograms were digitized into 512 X 512 pixel mode and percent stenosis was calculated by comparing background-corrected videodensitometric values over stenotic and normal segments. Subjects underwent repeat coronary arteriography because of worsening symptoms of angina or heart failure; subjects with renal failure, coronary artery bypass grafts or cardiac transplant were excluded. Clinical variables determined at the time of the first arteriogram included age, sex, serum cholesterol, systolic blood pressure and presence or absence of cigarette smoking, diabetes mellitus and left ventricular hypertrophy. The mean interval between arteriograms was 29.3 months. Overall progression of coronary stenosis was observed in 40 of the 44 subjects; the mean progression at 24 months was 39% (90% confidence interval, 33 to 45%) and at 36 months was 48% (40 to 56%). The degree of overall progression was related to the length of time between arteriograms (F = 5.81, p less than 0.05) and to serum cholesterol level (F = 4.37, p less than 0.05). These data indicate that using an accurate, quantitative method, it is possible to measure progression of coronary artery atherosclerosis within 2 to 3 years of the initial arteriogram. Serum cholesterol appears to be an important determinant of disease progression.


Magnesium levels and outcome after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.
Low intake of magnesium has been associated with the occurrence of lymphomas and decreased magnesium levels suppress the cytotoxic function of T cells and natural killer cells in patients with "X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia" (XMEN) syndrome. These cell types are also important mediators of immune-mediated effects after allogeneic hematopoietic stem cell transplantation. Here, we show that high posttransplant magnesium levels independently associate with a lower incidence of relapse, a higher risk of acute graft-versus-host disease, and a higher non-relapse mortality in 368 patients with acute myeloid leukemia from our center. Magnesium serum levels might impact on donor-cell-mediated immune responses in acute myeloid leukemia.


Is There a Role for Alcohol Septal Ablation in Young Patients with Medically Refractory Hypertrophic Obstructive Cardiomyopathy?
Surgical myectomy is recommended for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) after optimal pharmacological therapy. Percutaneous transluminal septal myocardial ablation (PTSMA) is reserved for high-risk adults. Symptomatic patients below 25 years underwent either surgery or PTSMA after heart-team discussion and informed consent. Echocardiography assessed gradients in surgical group. PTSMA group underwent invasive transseptal hemodynamic assessment, selective coronary angiography and super-selective cannulation of septal perforators using microcatheters. Contrast echocardiography through the microcatheter identified the myocardial target for PTSMA. Hemodynamic and electrocardiographic monitoring guided alcohol injection. Both groups were continued on beta-blockers. Symptoms, echocardiographic gradients and Brain natriuretic peptide (NTproBNP) measurements were assessed on follow-up. Twelve patients aged 5-23 years (11-98 kg) formed the study group. Indications for PTSMA in 8 patients included abnormal mitral valve anatomy warranting replacement (n = 3), Jehovah's witness (n = 2), severe neurodevelopmental and growth retardation (n = 1) and refusal of surgery (n = 2). PTSMA targeted first perforator (n = 5), second perforator (n = 2) and anomalous septal artery from left main trunk (n = 1). Outflow gradient reduced from 92.5 ± 19.7 to 33.1 ± 13.5 mmHg. At a median follow-up of 38 months (range 3-120 weeks), the peak instantaneous echocardiographic gradient was 32 ± 16.5 mmHg. Gradient reduced in four surgical patients from 86.5 ± 16.3 mmHg to 42 ± 14.7 mm Hg. All patients were in NYHA class I/II on follow-up. The mean NTproBNP in PTSMA group reduced from 6084 ± 3628 pg/ml to 3081 ± 2019 pg/ml; it was 1396 and 1795 pg/ml in surgery. PTSMA may be considered in medically refractory high-risk young patients. It relieves symptoms and reduces gradient. Though surgery is preferred in young patients, PTSMA may have a role in selected patients.


Protection of mitochondria during cold storage of liver and following transplantation: comparison of the two solutions, University of Wisconsin and Eurocollins.
Injury to allografts during ischaemia/reperfusion contribute to the development of graft failure following transplantation with significant morbidity and mortality to patients. The development of University of Wisconsin solution has significantly improved the quality of graft preservation and transplant outcome relative to formerly used solutions such as Eurocollins. The aim of this study was to further characterize mitochondrial structural and functional alterations occurring in rat livers following cold storage and transplantation. Mitochondrial impairment after prolonged storage in Eurocollins included decreased cyt. c+c1, cyt. b and cyt. a+a3 concentration and dramatic falls in the activities of the respiratory chain enzymes ubiquinol-cyt. c oxidoreductase and cytochrome oxidase. Under the same conditions the highest hydroperoxide but lowest vitamin E concentrations were also found. Although both the Eurocollins and University of Wisconsin preservation solutions have limitations in preventing oxidative injuries following cold storage and reperfusion, our data indicate that mitochondrial impairment was higher in Eurocollins- than in University of Wisconsin-stored livers. Further improvements are necessary in maintaining the stability of mitochondria in order to optimize preservations solutions used in transplantations.


Impact of high-load resistance training on bone mineral density in osteoporosis and osteopenia: a meta-analysis.
This study aimed to examine the effect of high-load resistance training (HLRT) on bone mineral density (BMD) in patients with osteoporosis and osteopenia using a meta-analysis. We searched for randomized controlled trials (RCTs) on HLRT in patients with osteoporosis and osteopenia from medical databases. Our meta-analysis was performed with the primary endpoints being the standardized mean difference (SMD) of the change in BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH). The robustness of the results was assessed by subgroup analysis. Heterogeneity factors were examined by meta-regression. Publication bias was evaluated using a funnel plot. We selected nine RCTs, with 259 patients in the HLRT group (women, 55.2%) and 236 patients in the control group (women, 62.7%). The HLRT group showed a significant increase in BMD in the LS [SMD = 1.40, 95% confidence interval (CI) = 0.68-2.12, p < 0.001, I2 = 90%], the FN (SMD = 0.86, 95% CI = 0.05-1.67, p = 0.04, I2 = 92%), and the TH (SMD = 1.26, 95% CI = 0.45-2.08, p = 0.002, I2 = 91%). Subgroup analysis confirmed the robustness of the results only in LS. Total sessions and a high risk of bias were identified as the factors of heterogeneity in FN and TH (p < 0.05). The funnel plot showed asymmetry in all measurement sites. This study suggested that HLRT can be effective in increasing BMD, mainly of LS, in patients with osteoporosis and osteopenia. However, due to high heterogeneity and publication bias, additional studies with a low risk of bias should be conducted to generalize our findings.


The inotropic action of tolbutamide and glyburide.
The effect of glyburide on myocardial function in human beings is not known. We divided 37 normal male volunteers into five groups. Each group received either intravenous saline solution; 10 mg propranolol by intravenous push followed by 0.1 mg/min; 5 micrograms/kg/min dobutamine; 1000 mg or 1250 mg oral tolbutamide; or 5 mg glyburide. Comparable therapeutic blood levels were obtained. Myocardial function was assessed by measurement of work product (WP, systolic pressure times heart rate) and ejection fraction (EF) by means of radionucleotide ventriculography. There was no change in EF or WP after administration of saline solution and tolbutamide; propranolol decreased EF and WP; dobutamine and glyburide increased EF and WP. In summary, tolbutamide had no effect on myocardial contractility, whereas glyburide increased myocardial contractility as measured by ejection fraction.


Indications for surgical replacement of the mitral valve. With particular reference to common and uncommon causes of mitral regurgitation.
Mitral valve replacement is considered when there is severe mitral stenosis, severe mitral insufficiency or a combination of the two. Ordinarily, surgical replacement is considered only for patients who are in functional classes III or IV and do not respond to medical management. Patients with symptomatic mitral stenosis should be treated with mitral commissurotomy whenever possible. Patients selected for commissurotomy should have a pliable valve, no other major valve dysfunction, sinus rhythm, no systemic embolism and good left ventricular function. Early operation is not ordinarily required. Mitral insufficiency may require mitral valve replacement in six rather common settings: rheumatic disease, rupture of mitral chordae tendineae, postinfarction rupture of a papillary muscle, intractable infective endocarditis, floppy mitral valve and malfunction of a prosthetic valve. Rupture of mitral chordae tendineae can usually be recognized from the history, physical examination, echocardiogram and angiocardiogram. Severe left ventricular papillary muscle dysfunction is usually due to cardiac infarction, and occurs within the first 9 days of infarction. When only a papillary muscle tip is ruptured the patient may survive long enough for a mitral valve replacement. In infective endocarditis, operation is more often needed because of congestive heart failure than because of refractory infection. Evidence of mitral stenosis or insufficiency in a patient with a previously implanted prosthetic valve usually indicates an urgent need for study and early operation. Uncommon causes of mitral incompetence that may require valve replacement are endocardial fibroelastosis, Marfan's syndrome, calcified mitral anulus, osteogenesis imperfecta, methysergide-induced heart disease and carcinoid heart disease.


Sleep-wake changes and cognition in neurodegenerative disease.
With the increasing aging population, neurodegenerative disorders will become more common in clinical practice. These disorders involve multiple pathophysiological mechanisms that differentially affect cognition, mood, and physical functions. Possibly due to the involvement of common underlying neurobiological circuits, sleep and/or circadian (sleep-wake) changes are also common in this disease group. Of significance, sleep-wake changes are often a prodromal feature and are predictive of cognitive decline, psychiatric symptoms, quality of life, need for institutional care, and caregiver burden. Unfortunately, in neurodegenerative disease, few studies have included detailed polysomnography or neuropsychological assessments although some data indicate that sleep and neurocognitive features are related. Further studies are also required to address the effects of pharmacological and nonpharmacological treatments on cognitive functioning. Such research will hopefully lead to targeted early intervention approaches for cognitive decline in older people.


The effect of inlet waveforms on computational hemodynamics of patient-specific intracranial aneurysms.
Due to the lack of patient-specific inlet flow waveform measurements, most computational fluid dynamics (CFD) simulations of intracranial aneurysms usually employ waveforms that are not patient-specific as inlet boundary conditions for the computational model. The current study examined how this assumption affects the predicted hemodynamics in patient-specific aneurysm geometries. We examined wall shear stress (WSS) and oscillatory shear index (OSI), the two most widely studied hemodynamic quantities that have been shown to predict aneurysm rupture, as well as maximal WSS (MWSS), energy loss (EL) and pressure loss coefficient (PLc). Sixteen pulsatile CFD simulations were carried out on four typical saccular aneurysms using 4 different waveforms and an identical inflow rate as inlet boundary conditions. Our results demonstrated that under the same mean inflow rate, different waveforms produced almost identical WSS distributions and WSS magnitudes, similar OSI distributions but drastically different OSI magnitudes. The OSI magnitude is correlated with the pulsatility index of the waveform. Furthermore, there is a linear relationship between aneurysm-averaged OSI values calculated from one waveform and those calculated from another waveform. In addition, different waveforms produced similar MWSS, EL and PLc in each aneurysm. In conclusion, inlet waveform has minimal effects on WSS, OSI distribution, MWSS, EL and PLc and a strong effect on OSI magnitude, but aneurysm-averaged OSI from different waveforms has a strong linear correlation with each other across different aneurysms, indicating that for the same aneurysm cohort, different waveforms can consistently stratify (rank) OSI of aneurysms.


Reliability and clinical correlates of the Astrand-Rhyming sub-maximal exercise test in patients with schizophrenia or schizoaffective disorder.
Cardiovascular fitness is reduced in people with schizophrenia and is related to an increased morbidity and mortality. There is mounting interest in the accurate measurement of cardiovascular fitness in schizophrenia, yet existing measures used in the general population have not been tested on validity and reliability in this high-risk group. Therefore, we examined the reproducibility and feasibility of the Astrand-Rhyming sub-maximal exercise test in patients with schizophrenia or schizoaffective disorder. Secondary aims were to assess minimal detectable changes, practice effects and the presence of clinical symptoms that are associated with cardio-respiratory fitness (expressed as estimated oxygen uptake). From 47 patients with schizophrenia or schizoaffective disorder two trials of the Astrand-Rhyming test, administered within three days, were analysed. The intraclass correlation coefficient for the estimated oxygen uptake between the two tests was 0.92 (95% confidence interval: 0.85-0.95). The minimal detectable change was 6.5mlO2/min/kg. No practice effect could be detected. A backward regression analysis demonstrated that illness duration, negative symptoms and level of physical activity explained 63.0% of the variance in estimated oxygen uptake. The current study demonstrates that the Astrand-Rhyming test can be recommended for evaluating the aerobic fitness in patients with schizophrenia or schizoaffective disorder.


A multicenter trial of sulindac in osteoarthritis of the hip.
Sulindac (cis-5-fluoro-2-methyl-l-[(p-methyl sulfinyl)-benzylidene]-indene-3-acetic acid) is a new nonsteroidal antirheumatic drug recently evaluated in a double-blind trial of 91 patients with hip osteoarthritis. Consecutive patients with documented flare following previous drug withdrawal were randomly assigned to one of 3 treatment groups: (1) sulindac given twice daily, (2) sulindac given 4 times daily, and (3) placebo. The dosage of sulindac, 100 to 300 mg daily, was adjusted according to patient global response and tolerance at 3- to 7-day intervals over 3 wk. Of 15 efficacy measurements evalulated, there was no difference between sulindac given 2 or 4 times daily, but differences were disclosed between one or both sulindac treatment groups and placebo in 11 of the 15 efficacy measurements (p less than 0.05, less than 0.01). The frequency of adverse reactions was of the same order for each treatment group. These included gastrointestinal upset, rash, and dizziness, usually transient and mild to moderate in severity. Serial laboratory studies revealed no evidence of renal, hepatic, or hematopoietic toxicity.


Synthesis, Spectroscopic Characterization, Catalytic and Biological Activity of Oxidovanadium(V) Complexes with Chiral Tetradentate Schiff Bases.
New oxidovanadium(V) complexes, VOL1-VOL10, with chiral tetradentate Schiff bases obtained by monocondensation reaction of salicylaldehyde derivatives with 1S,2S-(+)-2-amino-1-(4-nitrophenyl)-1,3-propanediol. All complexes have been characterized using different spectroscopic methods, viz. IR, UV-Vis, circular dichroism, one- (1H, 51V) and two-dimensional (COSY, NOESY) NMR spectroscopy, and elemental analysis. Furthermore, the catalytic ability of all compounds in the epoxidation of styrene, cyclohexene, and its naturally occurring monoterpene derivatives, i.e., S(-)-limonene and (-)-α-pinene has also been studied, using two different oxidants, i.e., aqueous 30% H2O2 or tert-butyl hydroperoxide (TBHP). In addition, the biological properties of these chiral oxidovanadium(V) compounds, but also cis-dioxidomolybdenum(VI) complexes with the same chiral Schiff bases, were studied. Their cytotoxic and cytoprotective activity studies with the HT-22 hippocampal neuronal cells revealed a concentration-dependent effect in the range of 10-100 μM. Moreover, vanadium(V) complexes, in contrast to cis-dioxidomolybdenum(VI) compounds, demonstrated higher cytotoxicity and lack of cytoprotective ability against H2O2-induced cytotoxicity.