Possible active components of tan-shen (Salvia miltiorrhiza) for protection of the myocardium against ischemia-induced derangements.
Extract of Tan-Shen (Salvia miltiorrhiza, Labiatae), a Chinese traditional crude drug, was reported to show beneficial activity for heart disease. Chemical examination on the extract was performed on the basis of screening for protective action on the ischemic myocardium. Isolated hearts were subjected to hypoxic perfusion for 20 min, followed by 45 min reoxygenation, and the recovery of cardiac contractile force and changes in UV absorbance of the perfusate were examined. Among the components isolated, tanshinone I, cryptotanshinone, and tanshinone VI elicited a significant enhanced recovery of the contractile force upon reoxygenation. This was associated with a decrease in the increase in UV absorbance of the perfusate, suggesting the preservation of ATP metabolites in the myocardium. This, in turn, may enhance the restoration of ATP upon oxygen-replenishment. The results suggest that tanshinone I, cryptotanshinone, and tanshinone VI can protect the myocardium against ischemia-induced derangements.


Parental acceptance toward behavior guidance techniques for pediatric dental visits: a meta-analysis.
This study aimed to answer the following question: What is the proportion of acceptance reported by parents toward pediatric behavior guidance techniques (BGTs)? Observational studies that evaluated parental acceptance of BGTs during pediatric dental visits among parents of non-special health care need (non-SHCN) and SHCN children were included. A search of the Cochrane Library, Latin American and Caribbean Health Sciences (LILACS), MedLine/PubMed, PsycINFO, Scopus, and Web of Science databases, in addition to gray literature, was performed until October 2021. The Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used for quality assessment. The certainty of evidence was assessed using the Recommendation, Assessment, Development, and Evaluation (Grade). Fifty-three studies with 4868 participants were included, and 42 were retained for the random-effects proportion meta-analysis. The methodological quality varied from low to high. The agreement with the BGTs varied from 85.6% (95%CI: 77.5-92.1; p < 0.001; I 2 = 93.6%; 16 studies; n = 1399) for tell-show-do to 25.7% (95%CI: 17.8-34.4; p < 0.001; I 2 = 90.4%; 12 studies; n = 1129) for passive protective stabilization among non-SHCN children's parents; meanwhile, among the parents of SHCN children, it varied from 89.1% (95%CI: 56.1-99.7; p < 0.001; I 2 = 95.7%; 3 studies; n = 454) for tell-show-do to 29.1% (95%CI: 11.8-50.0; p = 0.001; I 2 = 84.8%; 3 studies; n = 263) for general anesthesia. The effect estimates varied greatly, as substantial heterogeneity across studies was observed, thus limiting the confidence in the results. Parents were more likely to agree with basic BGTs over advanced BGTs, with very low certainty of evidence. Dentists should discuss BGT options with parents. Protocol registration: PROSPERO CRD42018103834.


Molecular analysis of PML-RAR alpha fusion mRNA detected by reverse transcription-polymerase chain reaction assay in long-term disease-free acute promyelocytic leukaemia patients.
By use of RT-PCR of PML/RAR alpha, we evaluated bone marrow aspirates in 10 patients with APL in long-term disease-free status after induction chemotherapy and consolidation (median 54 months: range 33-101 months from complete remission). All patients were in clinical and cytogenetic remission at the time of molecular evaluation (range 32-96 months from CR). All patients but one were found to be RT-PCR negative at the molecular level for the expression of PML-RAR alpha transcript, confirming that the majority of the patients with long-term survival of APL are characterized by the eradication of the neoplastic clone.


Variability in determination of point of needle insertion in peripheral nerve blocks: a comparison of experienced and inexperienced anaesthetists.
Accurate identification of surface landmarks is essential for the successful performance of peripheral nerve blocks. The variability between experienced and inexperienced practitioners in identifying anatomical landmarks has not been studied previously. Anaesthetists were asked to identify the point of needle insertion for posterior lumbar plexus and sciatic nerve blocks on a volunteer using a standard textbook description. The chosen point for needle insertion was described in terms of X and Y co-ordinates, measured in millimetres, from a zero reference point marked on a volunteer's back. Fifteen experienced and 22 inexperienced anaesthetists took part in the study. The lumbar plexus block mean [range] values for the X, Y co-ordinates were 80 [62-108], 66 [46-86] and 92 [49-150], 62 [0-131] in the experienced and inexperienced groups, respectively. The sciatic nerve block X, Y co-ordinates were 77 [62-99], 70 [49-89] and 68 [29-116], 62 [26-93] in the experienced and inexperienced groups, respectively. The variance for the point of needle insertion was significantly greater in the inexperienced group (p <0.01) for both the lumbar plexus and sciatic nerve blocks. We conclude that with increasing experience, there is decreased variability in determining the point of needle insertion using anatomical landmarks.


An overview on ZnO-based sonophotocatalytic mitigation of aqueous phase pollutants.
Over the past several decades, the increase in industrialization provoked the discharge of harmful pollutants into the environment, affecting human beings and ecosystems. ZnO-based photocatalysts seem to be the most promising photocatalysts for treating harmful pollutants. However, fast charge carrier recombination, photo corrosion, and long reaction time are the significant factors that reduce the photoactivity of ZnO-based photocatalysts. In order to enhance the photoactivity of such photocatalysts, a combined process i.e., sonocatalysis + photocatalysis = sonophotocatalysis was used. Sonophotocatalysis is one of several different AOP methods that have recently drawn considerable interest, as it produces high reactive oxygen species (ROS) which helps in the oxidation of pollutants by acoustic cavitation. This combined technique enhanced the overall efficiency of the individual method by overcoming its limiting factors. The current review aims to present the theoretical and fundamental aspects of sonocatalysis and photocatalysis along with a detailed discussion on the benefits that can be obtained by the combined process i.e., US + UV (sonophotocatalysis). Also, we have provided a comparison of the excellent performance of ZnO to that of the other metal oxides. The purpose of this study is to discuss the literature concerning the potential applications of ZnO-based sonophotocatalysts for the degradation of pollutants i.e., dyes, antibiotics, pesticides, phenols, etc. That are carried out for future developments. The role of the produced ROS under light and ultrasound stimulation and the degradation mechanisms that are based on published literature are also discussed. In the end, future perspectives are suggested, that are helpful in the development of the sonophotocatalysis process for the remediation of wastewater containing various pollutants.


Erratum: Clinical Utility of Olaparib in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review of Current Evidence and Patient Selection [Corrigendum].
[This corrects the article DOI: 10.2147/OTT.S315170.].


Percutaneous intervention versus coronary bypass surgery for patients older than 70 years of age with high-risk unstable angina.
The Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) study was a multicenter Veterans Affairs randomized trial and registry that compared long-term survival of percutaneous coronary intervention with coronary artery bypass graft surgery for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for an adverse outcome with bypass. Both the randomized trial and the registry demonstrated comparable 3-year survival. The purpose of this study was to compare bypass and percutaneous intervention survival of AWESOME patients who were older than 70 years of age. Over a 5-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of the following five risk factors (prior heart surgery, myocardial infarction within 7 days, left ventricular ejection fraction less than 35%, age > 70 years, intraaortic balloon pump requirement to stabilize) were identified. Of these patients, 1,278 were older than 70 years of age. Eight hundred, seventy-one patients were turned down by at least one physician, 407 were acceptable to both physician and surgeon for randomization, and 236 (60%) consented to randomization. Of the 1,042 eligible patients who were not randomized, 871 had their revascularization directed by a physician who was not involved in the study. One hundred, seventy-one patients who were acceptable for randomization by both the interventional cardiologist and the cardiac surgeon refused consent. Bypass and percutaneous intervention survival were compared using Kaplan-Meier curves and log rank tests. Bypass and percutaneous intervention 36-month survival rates for patients older than 70 years of age were 76% and 75%, respectively, among the eligible patients. Survival was 71% and 78% among those patients who were randomized and 76% and 67% in the physician-directed subgroup. Of those patients who chose their revascularization techniques, the survivals were 79% and 85%, respectively. The survival differences are not large, and none of the global log rank tests of bypass compared with percutaneous intervention survival showed a statistically significant difference over 5 years. Both the randomized and registry subgroups of patients who were older than 70 years of age support the trial conclusions that either bypass or percutaneous intervention effectively relieves medically refractory ischemia among high-risk unstable angina patients whose age was greater than 70 years.


DIAG: a computer-assisted dermatologic diagnostic system--clinical experience and insight.
Over the past few decades, the computer has been utilized in various ways to assist physicians in formulating their differential diagnoses, usually on an experimental basis. Following a review of the three major technics employed in computer-assisted diagnosis, statistical pattern classification, production rules, and cognitive models, a new system (DIAG) is described. The sole function of DIAG is to assist in the formulation of the differential diagnosis of skin diseases. At the beginning of the fourth year of development, the accuracy of the program in reaching diagnoses has been shown, on many occasions, to be comparable to its expert counterparts. However, it has been demonstrated that the system is not utilized within the dermatology clinic routinely. In response to this, aspects of DIAG have been modified in order to improve its clinical acceptability. Until this acceptance is achieved, these tools will not fulfill their potential to affect patient care.


Recent advances in direct current electrokinetic manipulation of particles for microfluidic applications.
Microfluidic devices have been extensively used to achieve precise transport and placement of a variety of particles for numerous applications. A range of force fields have thus far been demonstrated to control the motion of particles in microchannels. Among them, electric field-driven particle manipulation may be the most popular and versatile technique because of its general applicability and adaptability as well as the ease of operation and integration into lab-on-a-chip systems. This article is aimed to review the recent advances in direct current (DC) (and as well DC-biased alternating current) electrokinetic manipulation of particles for microfluidic applications. The electric voltages are applied through electrodes that are positioned into the distant channel-end reservoirs for a concurrent transport of the suspending fluid and manipulation of the suspended particles. The focus of this review is upon the cross-stream nonlinear electrokinetic motions of particles in the linear electroosmotic flow of fluids, which enable the diverse control of particle transport in microchannels via the wall-induced electrical lift and/or the insulating structure-induced dielectrophoretic force.


Specific inhibition of hamster prion protein translocation by the dodecadepsipeptide valinomycin.
Regulating the entry of secretory and membrane proteins into the ER is shown to be an important physiological process, in terms of controlling quantity, localization and therefore function of target proteins. However, few small molecule modulators are available to pharmacologically regulate translocation of a specific protein. Here, we identified a small molecule that specifically inhibits pathogenic PrP biosynthesis using a highly sensitive and reproducible assay based on the fluorogenic substrate reporter PrP. This molecule specifically destabilized the signal peptide of PrP, leading to cotranslational rerouting of a significant amount of nascent PrP to proteasome-dependent degradation pathway in the cytosol. This study suggests that regulating differential translocation efficiency attributable to sequence diversity in signal peptides of disease-causing secretory and membrane proteins using cell-permeable small molecules may be a potential therapeutic approach for diseases associated with impaired protein biogenesis.


Formic acid as a milder alternative to trifluoroacetic acid and phosphoric acid in two-dimensional peptide mapping.
In reversed-phase chromatography of peptides, formic acid has been shown to successfully replace the stronger traditional trifluoroacetic and phosphoric acids. Detection of non-aromatic peptide at lower wavelength is not impaired and being volatile the acid is easily removed, enabling further studies of the peptides. Also in ion-exchange chromatography (the first step of a two-dimensional approach) formic acid works well with a sulphonic acid ion-exchange resin.


Antibiotic Stewardship in Food-producing Animals: Challenges, Progress, and Opportunities.
Approximately two thirds of the tonnage of antibiotics sold in the United States are intended for use in food production, and global use is projected to increase. This review summarizes the rationale for antibiotic use in animal agriculture, therapeutic classes used, risks from antibiotic-resistant organisms, and limits of existing regulation. In addition, opportunities for improved surveillance, stewardship, and advocacy will be highlighted. A transdisciplinary narrative review of drivers of antibiotics in food production was conducted, including concepts from population health, infectious diseases, veterinary medicine, and consumer advocacy. Globally, antibiotics of many important classes in human medicine are given to animals for the treatment of a diagnosed illness, disease control and prevention, and growth promotion. Extensive antibiotic use on farms drives the emergence of antibiotic-resistant organisms in food-producing animals, which can be transmitted to people and the environment. Antibiotic stewardship in food production has been associated with decreased rates of resistance in both animals and humans, without reducing farm productivity. Multiple European nations have successfully implemented stewardship strategies, including banning uses for disease prevention, benchmarking antibiotic utilization, and setting national reduction targets. In the United States, medically important antibiotics are no longer permitted for growth promotion; however, antibiotics may be prescribed for other indications with limited veterinary oversight and requirements for reporting. Marked reductions in use have been achieved in the poultry industry, although use in the pork and beef industries remain high. Despite some progress, significant challenges in surveillance and regulatory oversight remain to prevent the overuse of antibiotics in food production. Consumers remain a potent force via market pressure on grocery stores, restaurants, suppliers, and farmers. Improved, verified labelling is important for informing consumer choices. Numerous public health agencies, consumer groups, and professional societies have called for judicious antibiotic use, but increased direct advocacy from health care professionals is needed.


Application of plasma clearance of iohexol in evaluating renal function in chinese children with chronic kidney disease.
To evaluate the accuracy of plasma clearance of iohexol (PCio) for glomerular filtration rate (GFR) measurement in Chinese children with chronic kidney disease (CKD) and assess the feasibility of single-blood-sample method or dried capillary blood spots in determining the PCio. Totally 45 CKD children were included,in whom the (99m) Technetium-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) plasma clearance and iohexol plasma clearance were simultaneously determined. Blood samples were obtained 2,4,and 5 hours after injection. In addition, we also evaluated the efficacy of single blood sample method and dried blood spots method in iohexol plasma clearance. Forty-five CKD children completed the iohexol plasma clearance and thirty-six children completed the (99m)Tc-DTPA plasma clearance at the same time among them. Thirteen children finished the iohexol dried blood spot clearance. The correlation coefficient between (99m)Tc-DTPA plasma clearance and iohexol plasma clearance was 0.941 and the bias was (6.53 ± 11.6) ml/ (min·1.73 m²), and the intraclass correlation coefficient (ICC) was high (ICC=0.947). The correlation between iohexol single-sample plasma clearance and double samples was also strong (r=0.958), with the bias being (4.26 ± 9.06)ml/(min·1.73 m²) and the ICC being 0.970. The iohexol clearance by dried blood spots showed a good correlation with the serum iohexol clearance (r=0.950), with the bias still being small [(0.48 ± 10.89)ml/(min·1.73 m²)]. Iohexol plasma clearance has satisfactory agreement with (99m)Tc-DTPA plasma clearance and can be used as an ideal method to measure GFR in CKD children. The single-sample method and dried blood spots method make iohexol plasma clearance more convenient and practical.


Risk of depressive disorder among patients with head and neck cancer: A nationwide population-based study.
The purpose of this study was to assess the incidence and risk of depressive disorder among patients with head and neck cancer. We identified 48 548 patients from the National Health Insurance Research Database (NHIRD) in Taiwan who were newly diagnosed with head and neck cancer between 2000 and 2010. Each patient was randomly frequency-matched with an individual without head and neck cancer, based on index year, sex, age, occupation category, urbanization level, monthly income, and comorbidities. The Cox proportional Registry of Catastrophic Illnesses Patient Database regression analysis was performed to estimate the effect of head and neck cancer on the risk of depressive disorder. Patients with head and neck cancer had a significantly higher risk of depressive disorder than the matched cohort (adjusted hazard ratio [HR] 3.32; 95% confidence interval [CI] 3.05-3.61), with the highest risk seen in the hypopharynx and oropharynx. Patients with head and neck cancer had >3 times the incidence of depressive disorder, relative to the comparison group. Psychological evaluation and support are essential in head and neck cancer survivors.


Deregulated expression of polycomb repressive complex 2 target genes in a NF1 patient with microdeletion generating the RNF135-SUZ12 chimeric gene.
Neurofibromatosis type I (NF1) microdeletion syndrome, accounting for 5-11% of NF1 patients, is caused by the heterozygous deletion of NF1 and a variable number of flanking genes in the 17q11.2 region. This syndrome is characterized by more severe symptoms than those shown by patients with intragenic NF1 mutation and by variable expressivity, which is not fully explained by the haploinsufficiency of the genes included in the deletions. We here reevaluate an 8-year-old NF1 patient, who carries an atypical deletion generating the RNF135-SUZ12 chimeric gene, previously described when he was 3 years old. As the patient has developed multiple cutaneous/subcutaneous neurofibromas over the past 5 years, we hypothesized a role of RNF135-SUZ12 chimeric gene in the onset of the patient's tumor phenotype. Interestingly, SUZ12 is generally lost or disrupted in NF1 microdeletion syndrome and frequently associated to cancer as RNF135. Expression analysis confirmed the presence of the chimeric gene transcript and revealed hypo-expression of five out of the seven analyzed target genes of the polycomb repressive complex 2 (PRC2), to which SUZ12 belongs, in the patient's peripheral blood, indicating a higher transcriptional repression activity mediated by PRC2. Furthermore, decreased expression of tumor suppressor gene TP53, which is targeted by RNF135, was detected. These results suggest that RNF135-SUZ12 chimera may acquire a gain of function, compared with SUZ12 wild type in the PRC2 complex, and a loss of function relative to RNF135 wild type. Both events may have a role in the early onset of the patient's neurofibromas.


Multi-State Transition Kinetics of Intracellular Signaling Molecules by Single-Molecule Imaging Analysis.
The chemotactic signaling of eukaryotic cells is based on a chain of interactions between signaling molecules diffusing on the cell membrane and those shuttling between the membrane and cytoplasm. In this chapter, we describe methods to quantify lateral diffusion and reaction kinetics on the cell membrane. By the direct visualization and statistic analyses of molecular Brownian movement achieved by single-molecule imaging techniques, multiple states of membrane-bound molecules are successfully revealed with state transition kinetics. Using PTEN, a phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) 3'-phosphatase, in Dictyostelium discoideum undergoing chemotaxis as a model, each process of the analysis is described in detail. The identified multiple state kinetics provides an essential clue to elucidating the molecular mechanism of chemoattractant-induced dynamic redistribution of the signaling molecule asymmetrically on the cell membrane. Quantitative parameters for molecular reactions and diffusion complement a conventional view of the chemotactic signaling system, where changing a static network of molecules connected by causal relationships into a spatiotemporally dynamic one permits a mathematical description of stochastic migration of the cell along a shallow chemoattractant gradient.


Lipid and water suppression by selective 1H homonuclear polarization transfer.
A pulse sequence is presented which uses Polarization Transfer by a Selective Homonuclear Technique (POTSHOT) to retain all resonances, in phase, from a selected coupled spin system while suppressing all other peaks, from both coupled and noncoupled spins. This technique, which is a selective form of Homonuclear Polarization Transfer (HPT), has been used in a 1.5-T whole-body system to generate edited 1H lactate spectra from lactate/oil phantoms and from excised dog hearts.


In vivo therapeutic potential of combination thiol depletion and alkylating chemotherapy.
The effect of administering the thiol modulating agent buthionine sulfoximine (BSO) in conjunction with alkylating chemotherapy was investigated in vivo in the mouse KHT sarcomas and bone marrow stem cells. Tumour response to treatment was assessed by an in vivo to in vitro excision assay and bone marrow survival was determined in vitro by CFU-GM. Glutathione (GSH) depletion and recovery kinetics were determined at various times after treatment using high performance liquid chromatography (HPLC) techniques. Following a single 2.5 mmol kg-1 dose of BSO, tumour GSH reached a nadir of approximately 40% of control 12-16 h after treatment. Bone marrow GSH was depleted to approximately 45% of control 4-8 h after treatment but recovered to normal by 16 h. When a range of doses of CCNU, mitomycin C, cyclophosphamide or melphalan (MEL) were given 16 h after mice were exposed to a 2.5 mmol kg-1 dose of BSO, only the antitumour efficacy of MEL was effectively enhanced (by a factor of approximately 1.4). This BSO-MEL combination appeared to be selective for the tumour as the bone marrow toxicity was not increased beyond that seen for MEL alone. Since increasing the administered dose of BSO neither increased the extent of thiol depletion in the tumour nor enhanced the antitumour efficacy of MEL, three other protocols for delivering the thiol depletor were explored. BSO was given either as multiple 2.5 mmol kg-1 doses administered at 6 or 16 h intervals or continuously at a concentration of 30 mM supplied in the animals' drinking water. Both multi-dose BSO pretreatments were found to increase both the antitumour efficacy and normal tissue toxicity of MEL such that no advantage compared to the single dose combination was achieved. In contrast, maintaining the thiol depletor in the drinking water led to an approximately 1.7-fold increase in the antitumour efficacy of MEL without any corresponding increase in bone marrow stem cell toxicity. For the various pretreatment strategies it was possible, in all cases, to account for the presence or absence of a net therapeutic benefit on the basis of the tumour and bone marrow GSH depletion and recovery kinetics.


Effect of toothbrushing on titanium surface: an approach to understanding surface properties of brushed titanium.
This in vitro study aimed to characterize the surface morphology and composition of tooth-brushed titanium casting and thereby to elucidate interactions between the metal and abrasive material in dentifrice. Specimens were cast from CP Ti ingots and then mirror-finished. Two fluoride-free toothpastes containing crystalline CaHPO4.2H2O and amorphous SiO2 particles as abrasive were slurried with distilled water (15 g/30 mL). While toothbrushes were reciprocated at 120 strokes/min for 350,400 strokes, the specimens were brushed with the respective slurries under a load of 2.45 N. The brushed and non-brushed surfaces were characterized by means of SPM, EPMA, and XPS. SPM data were analyzed using one-way ANOVA, followed by post hoc Tukey test (p<0.01). Irrespective of toothpastes, toothbrushing had a significant influence on surface roughness. The CaHPO4.2H2O-containing paste produced much rougher surface than the SiO2-containing paste. Both the surfaces were chemically altered due to reactions with the respective abrasive materials. Abrading chips had dimensions of micron to submicron order. A number of chips were attached to abrasive particles. The alterations of surface morphology and composition may affect biological responses of titanium in the oral environment. Dentifrice with lower abrasivity might be advisable for daily oral hygiene practice of patients with dental titanium devices.


Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models.
Glycogen Synthase Kinase 3beta is one of the important targets in the treatment of type II diabetes and Alzheimer's disease. Currently this target is in pursuit for type II diabetes and a few GSK-3beta inhibitors have been now advanced to Phases I and II of clinical trials. The best validated HypoGen model consists of four pharmacophore features; 1) two hydrogen bond acceptors, 2) one hydrogen bond donor and 3) one hydrophobic. This pharmacophore model correlates well with the docking model, one hydrogen bond acceptor is necessary for the H-bond interaction with VAL135, and second hydrogen bond acceptor is important for the H-bond interactions with ARG141 and the hydrophobic feature may be required for the weak H-bond interactions with ASP133. The comparative model was developed from analogue and structure-based models like Catalyst, Glide SP & XP, Gold Fitness & ChemScore and Ligand Fit using multiple linear regression analysis. A virtual library of 10,000 molecules was generated employing fragment and knowledge-based approach and the comparative model was used to predict the activities of these molecules. The H-bond with ARG141 appears to be unique to GSK-3beta and explains the high GSK-3beta selectivity observed for 1H-Quinazolin-4-ones and Benzo[e][1,3]oxazin-4-ones. This understanding of protein-ligand interactions and molecular recognition increases the rapid development of potent and selective inhibitors, and also helps to eliminate the increase in number of false positives and negatives.


Oxidative stress mediates dibutyl phthalateinduced anxiety-like behavior in Kunming mice.
Among all phthalate esters, dibutyl phthalate (DBP) is only second to di-(2-ethylhexyl) phthalate (DEHP) in terms of adverse health outcomes, and its potential cerebral neurotoxicity has raised concern in recent years. DBP exposure has been reported to be responsible for neurobehavioral effects and related neurological diseases. In this study, we found that neurobehavioral changes induced by DBP may be mediated by oxidative damage in the mouse brain, and that the co-administration of Mangiferin (MAG, 50mg/kg/day) may protect the brain against oxidative damage caused by DBP exposure. The results of ethological analysis (elevated plus maze test and open-field test), histopathological examination of the brain, and assessments of oxidative stress (OS) in the mouse brain showed that there is a link between oxidative stress and anxiety-like behavior produced by DBP at higher doses (25 or 125mg/kg/day). Biomarkers of oxidative stress encompass reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA) and DPC coefficients (DPC). MAG (50mg/kg/day),administered as an antioxidant,can attenuatetheanxiety-like behavior of the tested mice.


Solid Cancers in the Premature and the Newborn: Report of Three National Referral Centers.
Advances in multidisciplinary care for pediatric cancer have resulted in significant improvement in cure rates over the last decades; however, these advances have not been uniform across all age groups. Cancer is an important cause of perinatal mortality, yet the full spectrum of malignant neoplasms in newborns is not well defined. The authors have reviewed the clinical features and outcomes of 37 newborns with congenital malignant tumors treated at three referral centers in North, Central, and South Poland between 1980 and 2014. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier methods and compared using long-rank test and Cox models. Twenty-two patients were diagnosed prenatally. The most common diagnoses were neuroblastoma (48.7%), followed by malignant germ-cell tumor (16.2%), and Wilms' tumor (8.1%). Neuroblastoma was the most common malignancy among full-term infants, and malignant sacrococcygeal teratoma was the most common malignancy in premature infants. Thirty patients (81%) are alive with a median follow-up of 4.8 years from diagnosis. Patients with Wilms' tumor and malignant germ-cell tumors had the best outcomes (5-year OS 100% for both), whereas the worst prognosis was observed for sarcoma patients (5-year OS 72.92%). Premature infants had better outcome than full-term infants (5-year OS 92.8% vs. 72.58%, respectively). Although rare, neonatal cancers can present with an aggressive clinical behavior, but they have a generally good outcome. Early diagnosis and management by expert multidisciplinary teams that integrate perinatal medicine experts with pediatric and surgical oncologists are critical. Centralized care with clear referral pathways that facilitate early initiation of specialized treatment should be prioritized.


Predictors of course satisfaction and perceived course impact of addiction nurses undertaking a postgraduate diploma in addictive behaviour.
The effectiveness and impact of continuing education for specialist nurses working with drug and alcohol had been poorly documented and the purpose of this study was to enhance our understanding of this process. The aims of the study were to identify predictors of course satisfaction and perceived course impact and to examine students' satisfaction with modules' learning outcomes and their applications to practice. This study was a cross-sectional survey of 46 part-time students enrolled a Postgraduate Diploma in Addictive Behaviour. Three instruments were used to measure modules' satisfaction, post-course satisfaction (PCSQ-18) and on-the-job impact (CIQ-17). The findings provided some support on the effect and impact of an educational programme on the practice development of addiction nurses. Within the multilayered hypothesis, the results indicate that expectations on the Health Education and Prevention Module were the only significant predictor of course satisfaction and Expectation of the Special Population Module was the only significant predictor of course impact on professional practice. Clinical placements have had a significant impact on professional practice of addiction nurses. Further evaluative studies need to be undertaken to examine the impact of educational programmes on its applications to clinical practice and the quality of care provided.


A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD.
PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact of oxidative stress in the brain. This study aims to investigate the efficacy of adjuvant NAC in people with treatment-resistant PTSD. A multicentre, randomised, double-blind, placebo-controlled trial for adults with PTSD unresponsive to first-line treatment. The intervention was either oral NAC 2.7 g/day or placebo for 12 weeks. The primary outcome was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks compared with baseline. Secondary outcomes included depression and substance craving. Follow-up measures were obtained at 16 and 64-weeks. 133 patients were assessed, with 105 randomised; 81 participants completed the 12-week trial, 79 completed week-16 follow-up, and 21 completed week-64 follow-up. There were no significant differences between those taking NAC and those taking placebo in CAPS-5 scores at week 12, nor in secondary outcomes. Significant between-group differences were observed at week 64 in craving duration (Cohen's d = 1.61) and craving resistance (Cohen's d = 1.03), both in favour of NAC. This was the first multicentre, double-blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. No benefit of NAC was observed in this group beyond that provided by placebo at end of the trial. ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.


Bacteriophage PRD1 terminal protein: expression of gene VIII in Escherichia coli and purification of the functional P8 product.
The gene VIII coding for the bacteriophage PRD1 terminal protein P8 has been cloned under the control of the lambda pL promoter. The recombinant plasmid thus obtained (pUSH20) was able to complement a mutation in the phage terminal-protein gene VIII. High expression of the cloned gene from this plasmid could be obtained by raising the growth temperature from 28 to 42 degrees C. This heat induction resulted in an increased synthesis of a protein of 30 kDa, the size expected for the P8 protein. When complemented with an extract of cells carrying the PRD1 DNA polymerase gene, the extract from the cells harboring the plasmid pUSH20 was able to form the P8-dGMP replication initiation complex. The PRD1 replication initiation reaction was optimized and used to detect the biological activity of the expressed terminal protein. Subsequently, P8 protein was purified to almost homogeneity and shown to be biologically functional after the various purification steps.


Interpreting treatment trials in schizophrenia patients: lessons learned from EUFEST.
There are various procedures to account for missing values in clinical trials. Mixed Model and Last Observation Carried Forward (LOCF) analyses are commonly employed methods. We compared the two methods by reanalysing Positive and Negative Syndrome Scale (PANSS) scores from the European First Episode in Schizophrenia Trial (EUFEST). While the predefined Mixed Model analysis detected no differences between PANSS total score changes in first episode patients treated with haloperidol, amisulpride, quetiapine, olanzapine or ziprasidone over the course of a one year treatment trial, a LOCF analysis revealed significant differences in favor of the new generation antipsychotics over haloperidol. Implications for clinical trial design and the interpretation of such studies are discussed.


Isolated lymphadenitis due to Histoplasma capsulatum diagnosed by fine-needle aspiration biopsy and immunohistochemistry.
In the disseminated form of histoplasmosis, isolation and further identification of Histoplasma capsulatum can be performed by several methods, namely, bone marrow aspiration, blood culture, and liver biopsy. Lymph node disease usually is diagnosed by excisional biopsy. Although fungal stains can identify this fungus, detection of specific antigens by immunohistochemistry shows a higher specificity and sensitivity. This approach can use the cell block method when the material is not sent to fungal cultures or fresh staining.


Increased Expression of FGF19 Contributes to Tumor Progression and Cell Motility of Human Thyroid Cancer.
Numerous reports indicate a role for aberrant expression of fibroblast growth factor 19 (FGF19) in tumor development and progression, and several drugs have been developed to target it. The aim of this study was to investigate the clinical significance of FGF19 and examine whether it plays any roles in progression of thyroid cancer. Translation research. Navy General Hospital of Chinese PLA, China. Expression patterns of FGF19 protein in 100 paired formalin-fixed and paraffin-embedded cancerous and adjacent noncancerous tissues from patients with thyroid cancer were detected by immunohistochemistry. Then, in vitro migration and invasion assays of siRNA-targeted FGF19-transfected cells were performed. Positive immunostaining of FGF19 protein expression was localized in cytoplasm with or without membrane of malignant cells and was observed in 82 (82.0%) of 100 patients with thyroid cancer. Statistically, the expression level of FGF19 protein in thyroid cancer tissues was significantly higher than that in normal tissues. In addition, FGF19 overexpression was significantly associated with the advanced tumor node metastasis staging (P = .008), the presence of extrathyroidal invasion (P = .01), lymph nodes metastasis (P = .01), and distant metastasis (P = .02). Furthermore, knockdown of FGF19 by transfection of siRNA-FGF19 could efficiently suppress the migration and invasion abilities of thyroid cancer cells in vitro. Our data revealed that the increased expression of FGF19 might be involved in the malignant behaviors of thyroid cancer, highlighting its potential as a molecular marker for early diagnosis and as a possible target for therapeutic intervention of this disease.


The fate of the aortofemoral graft.
To determine the incidence and cause for reoperation following aortofemoral bypass surgery. This paper describes the results of all aortofemoral grafts performed in the years 1978-1991, 251 of these patients underwent an aortobifemoral graft (ABF) whilst the remaining 50 had an aortounifemoral graft (AUF). The aortofemoral bypass was the only operation performed in fewer than half of the patients. Sixteen per cent of ABF and 50% of the AUF patients had surgery before the index operation. Subsequently 33% of the ABF patients and 60% of the AUF group had one or more additional vascular procedures. Graft infections and false aneurysms continued to present in about 1% patients per year at least up to 10 years following surgery. The 5 year actuarial survival was 73% in the ABF group and 38% in the AUF patients. The primary patency at 5 years was 85% in the ABF patients and 81% in the AUF group. Amputation was performed in 6% of the ABF patients and in 20% of the AUF patients. The frequent need for later surgery (1:3 for the ABF patients) should be considered in the decision to undertake the initial aortofemoral operation when the patient presents with intermittent claudication.


Processing of sting pheromone and its components in the antennal lobe of the worker honeybee.
In the honeybee Apis mellifera, a sting pheromone produced by sting glands plays an important role in coordinating defensive behavior. This pheromone is a blend constituted by several components. Little is known about the neural substrates underlying sting pheromone processing in the bee brain. Here, we investigated the neural activity elicited by eight components (five acetates and three alcohols) of the sting pheromone, and by real bee stings at the level of the antennal lobe (AL) of worker honeybees. We used in vivo calcium imaging to record odor-induced neural activity of 22 identified glomeruli in the AL. We found that acetates mainly activated medial glomeruli while alcohols mainly activated lateral dorsal glomeruli. The sting preparation evoked a glomerular pattern that was clearly distinct from those of individual pheromone components. No particular region of the imaged AL was found to process sting pheromone or any of its components. Further analyses in a putative honeybee olfactory space showed that the neural activity elicited by sting preparation cannot be linearly predicted by those of pheromone components and that such components are not clearly separated from non-sting pheromone odors. We conclude that sting pheromone is processed in the worker honeybee AL following the same principles of general odors so that the chemical structure of odorants is the main determinant of glomerular activation, rather than their pheromonal values. We cannot exclude, however, that the distinctness of sting-pheromone representation with respect to that of its components constitutes a form of specialized neural processing strategy for this kind of substance.


The protective effect of natural phenolic compound on the functional and structural responses of inhibited catalase by a common azo food dye.
In this research retrieval effects of natural yellow (NY) on the performance of carmoisine (CAR) inhibited bovine liver catalase (BLC) was studied using multispectral and theoretical methods. Kinetic studies showed that CAR inhibited BLC through competitive inhibition (IC50 value of 2.24 × 10-6 M) while the addition of NY recover the activity of CAR-BLC up to 82% in comparison with the control enzyme. Circular dichroism data revealed that NY can repair the structural changes of BLC, affected by CAR. Furthermore, an equilibrium dialysis study indicated that NY could reduce the stability of the CAR-catalase complex. The surface plasmon resonance (SPR) data analysis indicated a high affinity of NY to BLC compared to CAR and the binding of NY led to a decrease in the affinity of the enzyme to the inhibitor. On the other hand, fluorescence and molecular docking studies showed that the quenching mechanism of BLC by CAR occurs through a static quenching process, and van der Waals forces and hydrogen bonding play a crucial role in the binding of CAR to BLC. MLSD data demonstrated that NY could increase the binding energy of CAR-BLC complex from -7.72 kJ mol-1 to -5.9 kJ mol-1, leading to complex instability and catalase activity salvage.


Bilateral angiomyolipomas and renal cell carcinoma in polycystic kidney.
A case is presented of a twenty-eight-year-old man in whom renal failure developed at age twenty-four from polycystic kidney disease known to be present since childhood. He also had cutaneous manifestations of the tuberous sclerosis complex. Intrarenal hemorrhage led to bilateral nephrectomy. Microscopic examination disclosed typical polycystic disease and multiple angiomyolipomas in each kidney. In addition several renal cell carcinomas of oncocytic, papillary, and clear cell type were found. Review of the literature disclosed the uncommon coexistence of any two of these lesions and did not uncover any reported case of the simultaneous existence of all three.


The mechanism of overcoming multidrug resistance (MDR) of fungi by amphotericin B and its derivatives.
Comparative studies were performed to determine the activity and cytotoxicity of amphotericin B (AmB) and its derivatives on standard strain of Saccharomyces cerevisiae and its transformants with cloned genes from Candida albicans encoding multidrug resistance (MDR) pumps of ATP-binding cassette and major facilitator superfamilies. The AmB derivatives: amphotericin B 3-dimethylaminopropyl amide and N-methyl-N-D-fructopyranosylamphotericin B methyl ester were shown to be fungistatic and fungicidal towards MDR strains, by membrane permeabilization mechanism. Antibiotic-cell interaction monitored by energy transfer method indicates similar membrane affinity in parent strain and its MDR transformants. Experiments with fungal cells loaded with rhodamine 6G point to lack of competition between this dye and AmB and its derivatives for efflux driven by CDR2p. It can be thus assumed that AmB and its derivatives overcome fungal MDR by not being substrates of the multidrug exporting pumps, presumably due to their large molecular volumes.


The Sternohyoid Flap for Facial Reanimation.
This article discusses the use of the sternohyoid muscle for facial reanimation. The report outlines the rationale for use, the technical aspects of flap harvest, and early clinical outcomes. The utility of the flap and its comparative attributes relative to the gracilis flap are discussed.


Incremental prognostic value of cardiac computed tomography angiography in asymptomatic aortic stenosis: significance of aortic valve calcium score.
Cardiac computed tomography angiography (CCTA) provides the simultaneous evaluation of the aortic valve, myocardium, and coronary arteries. In particular, aortic valve calcium score (AVCS) can be accurately measured on the same scanning sequence used to measure coronary artery calcification, with no additional cost or radiation exposure. We sought to evaluate the prognostic value of CCTA measures, including AVCS, in asymptomatic aortic stenosis (AS). Sixty-four initially asymptomatic patients with AS with a normal ejection fraction were prospectively enrolled and followed for median 29 (IQR=18-50) months. During follow-up, 27 (42%) patients experienced cardiac events, including five cardiac deaths, eleven aortic valve replacements. Multivariate Cox proportional hazards analysis identified three CCTA measures as significant predictors of cardiac events: aortic valve area (per 0.1cm(2) decrease; hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05-1.34); multi-vessel obstructive coronary artery disease (HR: 2.84, 95% CI: 1.10-7.32); and AVCS (per 100; HR: 1.09, 95% CI: 1.04-1.15). Kaplan-Meier analysis showed that patients with AVCS greater than or equal to the median value of 723 had significantly worse outcomes than those with AVCS less than 723 (p<0.0001). The C-statistic value for cardiac events substantially increased when these CCTA measures were added to clinical characteristics plus echocardiographic peak transaortic velocity (0.913 vs. 0.702, p<0.001). In patients with asymptomatic AS, CCTA measures of valve area, coronary stenosis, and calcification severity provide independent and incremental prognostic value after accounting for the echocardiographic severity of stenosis.


Cardiorespiratory effects of conventional and high frequency ventilation in rabbits with bilateral pneumothoraces and surfactant depleted lungs.
We compared high frequency ventilation (HFV) to conventional mechanical ventilation (CMV) under normoxic and normocapnic condition in surfactant depleted rabbits with bilateral pneumothoraces. We hypothesized that lower airway pressures would be required with HFV under these conditions. We applied CMV and HFV in 8 anaesthetized rabbits with a prototype ventilator at frequencies of 30, 100, 200, and 300 cycles/min. A positive end-expiratory pressure (PEEP) just below the pressure sufficient to open the air leak from the pneumothoraces was applied at all frequencies. Airway pressures, gas exchange, heart rate, and mean arterial pressure were recorded. Peak airway pressure decreased significantly from 2.50 to 2.10 kPa when the frequency of ventilation was increased from 30 to 300 cycles/min. There were no significant changes in mean airway pressure, PaO2, arterial pH, heart rate, and mean arterial pressure when HFV was compared to CMV. In conclusion, during HFV peak airway pressures measured at the mouth were decreased. Our ability to maintain adequate gas exchange in the face of ongoing pulmonary air leaks may reflect lower alveolar pressures.


An involvement and overtness measure for lesbians: its development and relation to anxiety and social zeitgeist.
The relationships among anxiety, degree of overtness in homosexuality, involvement in homosexuality, and occupational status were investigated to test prevalent hypotheses relating homosexuality and neuroticism. Sixty-three acknowledged lesbians completed the Manifest Anxiety and Defensiveness Scale (MAD), the Lesbian Degree of Involvement and Overtness Scales (DIOS), and a biographical data sheet. Reliability and validity indices for the DIOS are presented. Some findings were that anxiety was not related to degree of involvement in homosexuality, that anxiety was related to degree of overtness in low- but not in high-status lesbians, and that the social Zeitgeist at the time of first lesbian activity was related to degree of overtness but not to degree of involvement in homosexuality. The results are discussed in terms of the relationship between social desirability and a hostile society. Additionally, comparisons of anxiety levels in homosexual and heterosexual women are presented and discussed. The results are interpreted as lending support to the emerging view of the homosexual as nonneurotic.


Multiparametric mapping by cardiovascular magnetic resonance imaging in cardiac tumors.
There is a paucity of quantitative measurements of cardiac tumors and myocardium using parametric mapping techniques. This study aims to explore quantitative characteristics and diagnostic performance of native T1, T2, and extracellular volume (ECV) values of cardiac tumors and left ventricular (LV) myocardium. Patients with suspected cardiac tumors who underwent cardiovascular magnetic resonance (CMR) between November 2013 and March 2021 were prospectively enrolled. The diagnoses of primary benign or malignant tumors were based on pathologic findings if available, comprehensive medical history evaluations, imaging, and long-term follow-up data. Patients with pseudo-tumors, cardiac metastasis, primary cardiac diseases, and prior radiotherapy or chemotherapy were excluded. Multiparametric mapping values were measured on both cardiac tumors and the LV myocardium. Statistical analyses were performed using independent-samples t-test, receiver operating characteristic, and Bland-Altman analyses. A total of 80 patients diagnosed with benign (n = 54), or primary malignant cardiac tumors (n = 26), and 50 age and sex-matched healthy volunteers were included. Intergroup differences in the T1 and T2 values of cardiac tumors were not significant, however, patients with primary malignant cardiac tumors showed significantly higher mean myocardial T1 values (1360 ± 61.4 ms) compared with patients with benign tumors (1259.7 ± 46.2 ms), and normal controls (1206 ± 44.0 ms, all P < 0.05) at 3 T. Patients with primary malignant cardiac tumors also showed significantly higher mean ECV (34.6 ± 5.2%) compared with patients with benign (30.0 ± 2.5%) tumors, and normal controls (27.3 ± 3.0%, all P < 0.05). For the differentiation between primary malignant and benign cardiac tumors, the mean myocardial native T1 value showed the highest efficacy (AUC: 0.919, cutoff value: 1300 ms) compared with mean ECV (AUC: 0.817) and T2 (AUC: 0.619) values. Native T1 and T2 of cardiac tumors showed high heterogeneity, while myocardial native T1 values in primary malignant cardiac tumors were elevated compared to patients with benign cardiac tumors, which may serve as a new imaging marker for primary malignant cardiac tumors.


Improved Growth Performance of Elaeis guineensis Jacq. Through the Applications of Arbuscular Mycorrhizal (AM) Fungi and Endophytic Bacteria.
Agrochemical application in the oil palm industry has been estimated to be the largest component amounting to almost 30% of the operational costing. Therefore, there is a huge pressure in the oil palm cultivation to exercise sustainable practices, preferably using cheaper alternatives such as biofertilizers and organic substrates. This study investigates the effect of arbuscular mycorrhizal (AM) fungi and endophytic bacteria applied independently and in combination on oil palm growth and nutrient uptake. Greenhouse and field studies were conducted with plant responses assessed through growth parameters. Greenhouse plants were significantly stimulated by AM fungi, Rhizophagus intraradices UT126 (M1), through single microbe application. An increase of 36% in leaf area was noted in M1 plants while the calcium (Ca) uptake in leaves increased by 11%. There was no significant improvement in overall nitrogen, phosphate, and potassium (NPK) uptake but a significant improvement of Ca measurement in greenhouse and field was observed in the leaves. The predicted synergism between mixed inocula of M1 and R. clarus BR152B (M2) on vegetative growth was not observed, suggesting the probability of interspecies incompatibility that requires further investigation. Growth readings in plants treated with the combination of M1-M2 and Pseudomonas aeruginosa UPMP3 in the field were highest without a significant difference as compared to single application of M1. The difference in readings for field and greenhouse may have been influenced by other external factors such as soil type, rhizospheric microbial community, and climate, and therefore requires further elucidation. These findings suggest R. intraradices UT126 as a promising biostimulant candidate in sustainable agronomic practices especially in the nursery practices.


Delayed Postoperative Spinal Cord Ischemia After Posterior Spinal Fusion in a Pediatric Patient with Syrinx and Decompressed Chiari: A Case Report.
We present a case of delayed postoperative neurologic deficits 1 day after posterior spinal fusion in a pediatric patient with syrinx and previous Chiari decompression, which reversed with urgent rod removal. There is limited literature on delayed cord injury occurring after surgery in a patient with scoliosis of neuromuscular origin. Patients with syrinx and a history of Chiari decompression may have spinal cords more sensitive to injury including delayed ischemia after deformity treatment and should be paid extra perioperative attention including considering prolonged mean arterial pressure goals or more conservative deformity correction.


Characterization of electrodeposited undoped and doped thin ZnO passive films on zinc metal in alkaline HCO3 -/CO3 2- buffer solution.
Electrochemical characterization of anodically grown thin ZnO films on pure zinc metal was studied in pH 9.2 bicarbonate/carbonate buffer solution. The different undoped passive films were formed potentiostatically in pH 9.2 borate buffer solution at processing anodic voltage (V a) of -1.04, -1.02, -1.0 and -0.99 V (vs. Ag/AgCl). While, various doped ZnO films were fabricated by anodizing the metal at a fixed potential of -1.00 V in the same borate buffer solution containing different amounts of LiCl or InCl3. The electrochemical and semiconducting properties of all formed films were investigated using chronoamperometric measurements, EIS and Mott-Schottky analysis supported by scanning electron microscopy. The impedance results showed a direct correlation between V a and the value of either total resistance (R f) of undoped passive film or its thickness (δ f). It is evident that anodization can afford better conditions for forming thicker compact passive films with more advanced barrier properties. On the other hand, R f decreases with increasing Li-doping level in the oxide film, and increases in case of In-doping. Interestingly, R f values of the doped films are always lower when compared to its value for the undoped film grown at -1.00 V, likely due to possible change in the film microstructure upon doping. For both undoped and doped ZnO films, Mott-Schottky plots reveals unintentional n-type conductivity with high electron density. Moreover, with increasing dopant level in ZnO host materials, Mott-Schottky analysis revealed a parallel correlation between charge carrier donor concentration (N D) and the passive film thickness (δ f), where the trend of their values are to decrease for Li+-doped and to increase for In3+-doped films.


The roles of behavioral inhibition/activation systems and impulsivity in problematic smartphone use: A network analysis.
Behavioral inhibition/activation systems (BIS/BAS) and impulsivity are associated with problematic smartphone use (PSU). However, no studies to date have explored how the subdomains of BIS/BAS and the dimensions of impulsivity relate to the components of PSU in a joint framework. This study aimed to examine the relationships between the three constructs at a fine-grained level and identify the central nodes and bridge nodes of their relationships using network analysis. A regularized partial correlation network of PSU, BIS/BAS, and impulsivity communities was estimated to investigate the connections between variables and determine the expected influence and bridge expected influence for each variable based on data from 325 Chinese adults. PSU, BIS/BAS, and impulsivity were assessed using the Smartphone Application-Based Addiction Scale (SABAS), BIS/BAS scales, and Barratt Impulsiveness Scale-Version 11 (BIS-11), respectively. In addition to connections within each community, network analysis revealed that there were connections between different communities, especially connections to PSU. I2 "motor impulsivity" was strongly associated with PSU2 "conflict" and PSU6 "relapse"; BASR "BAS-reward responsiveness" was strongly associated with PSU5 "withdrawal." Nodes BASR "BAS-reward responsiveness" and PSU6 "relapse" were the most central variables, while nodes BASR "BAS-reward responsiveness" and I2 "motor impulsivity" were the strongest bridge variables. The connections between the subdomains of BIS/BAS and the components of PSU and between the dimensions of impulsivity and the components of PSU may be particularly important in the development and maintenance of PSU. The central variables identified here, along with the bridge variables, could be promising and effective targets for the prevention and intervention of PSU.


Denervation supersensitivity as a model for the neural control of muscle.
A review about the neural regulation of the membrane distribution of muscle acetylcholine receptors is presented on the basis of author's and literature data. The main evidence in support of the role of nerve impulses and of chemical factors ("trophic" factors, acetylcholine, nerve breakdown products) as neural signals involved in the origin of denervation supersensitivity, is concisely described and evaluated. The contribution of breakdown products of the nerve, their interaction with muscle inactivity are illustrated and a unifying hypothesis on the neural control of extrajunctional and junctional acetylcholine receptors is presented.


Arctic amplification modulated by Atlantic Multidecadal Oscillation and greenhouse forcing on multidecadal to century scales.
Enhanced warming in the Arctic (Arctic amplification, AA) in the last decades has been linked to several factors including sea ice and the Atlantic Multidecadal Oscillation (AMO). However, how these factors contributed to AA variations in a long-term perspective remains unclear. By reconstructing a millennial AA index combining climate model simulations with recently available proxy data, this work determines the important influences of the AMO and anthropogenic greenhouse gas forcing on AA variations in the last millennium, leading to identification of a significant downward trend of AA on top of a sustained strong AMO modulation at the multidecadal scales. The decreased AA during the industrial era was strongly associated with the anthropogenic forcing, proving the emerging role of the forcing in reducing the AA strength.


Dural Tuberculoma Mimicking Meningioma: A Clinicoradiologic Review of Dural En-Plaque Lesions.
Tuberculosis has long been a major health concern in developing countries and now has troubled developed world as well, owing to increase in patients with human immunodeficiency virus and immigration. Central nervous system tuberculosis accounts for approximately 1% of cases of tuberculosis. The pathologic presentation is varied, with intraparenchymal tuberculomas and pachymeningitis being the most common. Being a great mimicker, it simulates numerous diseases radiologically, and this is best realized when atypical forms are encountered. Here an atypical case of dural en-plaque tuberculoma is presented with comprehensive review of dural en-plaque lesions with their differentiating features. A 20-year-old man presented with features of increased intracranial pressure. On imaging, there was an enhancing dural-based lesion in the left frontoparietal region. In view of herniation syndrome, urgent surgical decompression of the lesion was performed. Histopathology showed features of tuberculosis. The patient is now asymptomatic with antitubercular therapy without any residual lesion at 6 months of follow-up. Tuberculoma en-plaque is an unusual entity characterized by a plaque-like meningitic process without exudation. It is easily confused with meningiomas as can other dural-based lesions comprising benign to malignant neoplastic, infectious, and granulomatous lesions. A preoperative diagnosis is imperative to differentiate it at least from neoplastic lesions, which are usually curable with surgical intervention in contrast to tuberculosis, which needs only optimal chemotherapy in most of the cases. Knowledge of differentiating imaging features, in corroboration with clinical history and high index of suspicion, helps in a proper preoperative diagnosis and optimal patient treatment.


Medicine management.
I have a patient who would benefit from a medicine not available on the NHS. Is there any advice I can give?


Independent transposition of multiple Ac elements in the same transgenic tomato cell.
To effectively use transposable elements for the genetic manipulation of plant species lacking well characterized endogenous elements, it is important to evaluate the behavior of known transposable elements following their introduction into heterologous host species. One critical parameter concerns the timing of transposition in relation to the development of the transgenic host since this will affect the frequency with which transposition events are captured in the gametes. In order to examine whether different elements in the same cell are differentially active during development, we used Southern hybridizations to assess the activity of Activator (Ac) elements in progeny plants derived from a tomato transformant carrying five Ac's at two loci. All of the elements at one locus transposed in the primary transformant at a developmental stage resulting in the transmission of newly transposed elements to the next generation. In contrast, one or more of the Ac's at the second locus were not active at this stage and were transmitted to the next generation at the original donor T-DNA insertion site. These elements were, however, transpositionally active in somatic tissue. These results demonstrated that individual transposable elements in the same transformed cell can be differentially activated during development.


A novel graphene oxide polymer gel platform for cardiac tissue engineering application.
In this study, we demonstrated a Reverse Thermal Gel (RTG), which is injectable and functionalized with GOs (GO-RTG) that changes at room temperature (24 °C) from a mixture to a three-dimensional (3D) matrix gel soon after approaching its body temperature (37 °C). We also presented investigational evidence, which represents that the system of 3D GO-RTG promotes MCs proliferation as well as alignment, supports in long-standing survival of MCs, and enhances the function of MCs when compared with typical 3D plain RTG system and 2D gelatin control groups. Thus, this system of injectable GO-RTG can be capable of using as a negligibly invasive device for engineering efforts of cardiac tissue.


Multi-proxy evidence for sea level fall at the onset of the Eocene-Oligocene transition.
Continental-scale expansion of the East Antarctic Ice Sheet during the Eocene-Oligocene Transition (EOT) is one of the largest non-linear events in Earth's climate history. Declining atmospheric carbon dioxide concentrations and orbital variability triggered glacial expansion and strong feedbacks in the climate system. Prominent among these feedbacks was the repartitioning of biogeochemical cycles between the continental shelves and the deep ocean with falling sea level. Here we present multiple proxies from a shallow shelf location that identify a marked regression and an elevated flux of continental-derived organic matter at the earliest stage of the EOT, a time of deep ocean carbonate dissolution and the extinction of oligotrophic phytoplankton groups. We link these observations using an Earth System model, whereby this first regression delivers a pulse of organic carbon to the oceans that could drive the observed patterns of deep ocean dissolution and acts as a transient negative feedback to climate cooling.


Thrombotic thrombocytopenic purpura in pulmonary-renal syndromes.
Thrombotic thrombocytopenic purpura pathologically consists of a thrombotic microangiopathy that classically spares lung tissues. We describe a case of TTP that presented as a pulmonary-renal syndrome. In reviewing the international literature, pulmonary involvement is not as rare as once was thought, and the diagnosis of TTP should be considered in the differential diagnosis of pulmonary-renal syndromes.


The CD19+ B-cell counts at peripheral blood stem cell mobilization determine different levels of tumour contamination and autograft purgability in low-grade lymphoma.
The tumour load of peripheral blood stem cell (PBSC) harvests and the outcome of ex vivo immunomagnetic B-cell purging was investigated in 19 patients with low-grade lymphoma. To quantify the tumour load, we combined fluorescence-activated cell sorting measurement of CD19+ B-cells and determination of the B-cell light chain ratio (LCR) with consensus complementarity-determining region III-polymerase chain reaction (CDRIII-PCR) and gene scan analysis. The number of tumour cells was calculated using B-cell extracts from the PBSCs. Two different patterns were distinguished. In eight patients (42%) with CD19+ B cells >1% in the apheresis product, a high tumour load was found, characterized by a monoclonal LCR, positive PCR in seven out of eight cases, >5 x 10(7) extracted lymphoma cells in six out of seven PCR-assessable cases, and the presence of residual lymphoma after purging in six of seven cases. In 11 patients (58%) with <1% CD19+ B-cells in the product, a low tumour load was indicated by a polyclonal LCR, positive PCR in only 4 out of 11 cases, >5 x 10(7) extracted lymphoma cells in zero out of four PCR-assessable cases, and the presence of residual lymphoma after purging in zero out of four of these cases. The level of residual lymphoma following purging largely depended on the level of tumour contamination. CD19+ B-cells >50/microl in the peripheral blood at mobilization predicted a high tumour load in the apheresis product.


Current aspects of mucosal immunology and its influence by nutrition.
A significant body of clinical literature demonstrates that enteral feeding significantly reduces the incidence of pneumonia compared to patients fed parenterally. An immunologic link between the gastrointestinal tract and respiratory tract is postulated via the common mucosal immune hypothesis. This hypothesis states that cells are sensitized within the Peyer's patches of the small intestine and are subsequently distributed to submucosal locations in both intestinal and extra intestinal sites. This system is exquisitely sensitive to route and type of nutrition. This review examines the laboratory data regarding cell numbers, cell phenotypes, cytokine profile, and immunologic function in both intestinal and extra intestinal sites in animals that have been administered either parenteral feeding or various types of enteral feeding. It also establishes links between a specific nutrient, glutamine, the enteric nervous system, by way of neuropeptides, and mucosal immunity. Progress in understanding relationships between nutrient availability, enteric nervous system stimulation, and nutrient delivery on mucosal immunity offers opportunities to explore immune systems previously not appreciated by clinicians and basic scientists. These opportunities offer new challenges to the physician scientist, basic scientist, and clinician to understand, manipulate, and apply these concepts to the critically ill patient population by favorably influencing immunologic barriers and the inflammatory response.


You Get a Modification, and You Get a Modification… Everyone Gets a Modification!
In this issue of Molecular Cell,Sun et al. (2020) identify ERK-mediated phosphorylation of the m6A methyltransferase complex as a regulatory mechanism for m6A and pluripotency and highlight the potential of this interaction as a target for cancer therapy.


Somatostatin-14 alters the thymus size and relation among the thymocyte subpopulations in peripubertal rats.
It is well known that somatostatin exerts a wide range of effects in the body, and acts as an autocrine or paracrine factor in the thymus. However, it has not been investigated yet whether somatostatin alters the thymus size and relation among the thymocyte subpopulations in the peripubertal rats. For this purpose, the peripubertal AO male rats were cannulated intracerebroventriculary and treated with repeated, low doses of somatostatin-14 (experimental group) or saline (control group). Twenty-four hours after the last treatment, we removed and prepared the thymuses for determination of thymocyte subpopulations by flow cytometry. After five days, animals were sacrificed and their thymuses taken for morphometrical analysis by stereological methods. We noticed that somatostatin-14 decreased volumes of thymus cortex and medulla, total number of thymocytes, number of thymocytes in the cortex and medulla and numerical density of thymocytes in deeper cortex. As a consequence of these changes, thymus size was also diminished. The phenotypic analysis of thymocyte subpopulations showed that somatostatin-14 decreased the percentage of CD4(+)CD8(+) cells with low level of TCR alphabeta expression, positively selected CD4(+)CD8(+)TCRalphabeta (high) cells and the most mature CD4(-)CD8(+)TCRalphabeta (high) cells, while the percentage of CD4(+)CD8(-)TCRalphabeta (high) thymocytes was slightly increased. Somatostatin-14 increased the relative proportion of the least mature CD4(-)CD8(-)TCRalphabeta (-/low), CD4(+)CD8(+)TCRalphabeta (-) cells and both of TCRalphabeta (-/low) single positive subpopulations. These results show that centrally applied somatostatin-14, induces hypotrophy of the thymus in peripubertal rats by changing the volumes and cellularities of the thymic compartments. Additionally, increased number of the least mature thymocytes and a deficiency of double positive cells indicate the involvement of somatostatin in the modulation of T cells maturation.


Influence of falling height on the excitability of the soleus H-reflex during drop-jumps.
The stretch-shortening cycle (SSC) is characterized by stretching of the target muscle (eccentric phase) prior to a subsequent shortening in the concentric phase. Stretch reflexes in the eccentric phase were argued to influence the performance of short lasting SSCs. In drop-jumps, the short latency component of the stretch reflex (SLR) was shown to increase with falling height. However, in jumps from excessive heights, the SLR was diminished. So far, it is unclear whether the modulation of the SLR relies on spinal mechanisms or on an altered fusimotor drive. The present study aimed to assess the spinal excitability of the soleus Ia afferent pathway at SLR during jumps from low height (LH - 31 cm) and excessive height (EH - 76 cm). In 20 healthy subjects (age 25 +/- 3 years), H-reflexes were timed to occur at the peak of the SLR during drop-jumps from LH and EH. H-reflexes were significantly smaller at EH than at LH (P < 0.05). Neither soleus and tibialis anterior background EMG nor the size of the maximum M-wave changed with falling height. Differences in the H-reflex between EH and LH indicate that spinal mechanisms are involved in the modulation of the SLR. A decreased excitability of the H-reflex pathway at EH compared with LH is argued to serve as a 'prevention strategy' to protect the tendomuscular system from potential injuries caused by the high load. It is argued that pre-synaptic inhibition of Ia afferents is most likely responsible for the change in H-reflex excitability between the two jump conditions.


Anaerobic biooxidation of Fe(II) by Dechlorosoma suillum.
Anaerobic microbial oxidation of Fe(II) was only recently discovered and very little is known about this metabolism. We recently demonstrated that several dissimilatory perchlorate-reducing bacteria could utilize Fe(II) as an electron donor under anaerobic conditions. Here we report on a more in-depth analysis of Fe(II) oxidation by one of these organisms, Dechlorosoma suillum. Similarly to most known nitrate-dependent Fe(II) oxidizers, D. suillum did not grow heterotrophically or lithoautotrophically by anaerobic Fe(II) oxidation. In the absence of a suitable organic carbon source, cells rapidly lysed even though nitrate-dependent Fe(II) oxidation was still occurring. The coupling of Fe(II) oxidation to a particular electron acceptor was dependent on the growth conditions of cells of D. suillum. As such, anaerobically grown cultures of D. suillum did not mediate Fe(II) oxidation with oxygen as the electron acceptor, while conversely, aerobically grown cultures did not mediate Fe(II) oxidation with nitrate as the electron acceptor. Anaerobic washed cell suspensions of D. suillum rapidly produced an orange/brown precipitate which X-ray diffraction analysis identified as amorphous ferric oxyhydroxide or ferrihydrite. This is similar to all other identified nitrate-dependent Fe(II) oxidizers but is in contrast to what is observed for growth cultures of D. suillum, which produced a mixed-valence Fe(II)-Fe(III) precipitate known as green rust. D. suillum rapidly oxidized the Fe(II) content of natural sediments. Although the form of ferrous iron in these sediments is unknown, it is probably a component of an insoluble mineral, as previous studies indicated that soluble Fe(II) is a relatively minor form of the total Fe(II) content of anoxic environments. The results of this study further enhance our knowledge of a poorly understood form of microbial metabolism and indicate that anaerobic Fe(II) oxidation by D. suillum is significantly different from previously described forms of nitrate-dependent microbial Fe(II) oxidation.


Increased low-grade inflammation and plasminogen-activator inhibitor-1 level in nondippers with sleep apnea syndrome.
Patients with sleep apnea syndrome have an increased risk of cardiovascular events and frequently show a nondipper pattern (blunted nocturnal decline <10%) of systolic blood pressure. We investigated neurohumoral activation and risk factors in relation to nocturnal blood pressure dipping pattern and sleep apnea syndrome. We conducted sleep polysomnography and ambulatory blood pressure monitoring and measured high-sensitivity C-reactive protein, tissue-type plasminogen activator inhibitor-1, and neurohumoral factors in 121 outpatients with suspected sleep apnea syndrome who were classified into four groups on the basis of the presence or the absence of dipping/nondipping and sleep apnea syndrome. Nondippers with sleep apnea syndrome had higher high-sensitivity C-reactive protein (overall P < 0.001), plasminogen activator inhibitor-1 (overall P = 0.004), and aldosterone levels (overall P = 0.010) than any of the other three groups. After adjustment for significant covariates such as age, sex, body mass index, waist circumference, smoking, alcohol drinking, aspirin use, presence of diabetes, and insulin, nondippers with sleep apnea syndrome still had a higher high-sensitivity C-reactive protein level than nondippers without sleep apnea syndrome (geometric mean: 1.47 vs. 0.37 mg/l, P = 0.001). In multiple linear regression analysis controlling for confounding factors related with sleep apnea syndrome, high-sensitivity C-reactive protein was significantly correlated with 3% oxygen desaturation index (P = 0.047). Plasminogen activator inhibitor-1 level was also highest in the nondippers with sleep apnea syndrome but not independent of obesity. Plasminogen activator inhibitor-1 level correlated with insulin (r = 0.32, P = 0.002) and high-sensitivity C-reactive protein levels (r = 0.26, P = 0.005). Nondipper status was associated with an increased high-sensitivity C-reactive protein level in patients who also had sleep apnea syndrome but not in those who did not. High-sensitivity C-reactive protein level was closely affected by the desaturation level. Plasminogen activator inhibitor-1 level is also increased in nondippers with sleep apnea syndrome and is related to insulin and high-sensitivity C-reactive protein levels.


Synthesis and properties of a neutral derivative of diethylenetriaminepentaacetic acid (DTPA).
A neutral bifunctional derivative of diethylenetriaminepentaacetic acid europium(III) (11) was synthesized and its suitability to dissociation-enhanced lanthanide fluorescence immunoassay was investigated.


Questionnaire-based assessment of behavioral problems in Japanese children with epilepsy.
Behavioral problems in Japanese children with epilepsy were investigated by means of a questionnaire for parents consisting of three checklists: the Child Behavior Checklist (CBCL)/4-18 Japanese Edition, the High-Functioning Autism Spectrum Screening Questionnaire (ASSQ), and the Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-IV (ADHD-RS) for parents. The participants were the parents of 108 children aged 6-18 years with apparently normal intelligence. The CBCL indicated abnormal behavior in 10.5 to 35.6% of the children, and T scores on both the internalizing and externalizing scales had a significant positive relation with scores on the ASSQ and ADHD-RS. It was revealed through multivariate logistic regression analysis that the persistence of seizures was significantly related with abnormality on the externalizing scale of the CBCL (p=0.010, odds ratio: 3.48, 95% confidence interval: 1.34-9.02). Future studies are needed to determine whether seizure freedom improves behavior in children with epilepsy.


Investigation of the feasibility of synthetic MRI in the differential diagnosis of non-keratinising nasopharyngeal carcinoma and benign hyperplasia using different contoured methods for delineation of the region of interest.
To assess the feasibility and preliminary diagnostic performances of relaxation times derived from synthetic magnetic resonance imaging (syMRI) for differentiating nasopharyngeal carcinoma from nasopharyngeal benign lymphoid hyperplasia, and to assess the influence of tissue segmentation method on relaxation estimates. Fifty participants with nasopharyngeal carcinoma (NPC) and 40 participants with benign hyperplasia (NPH) who underwent syMRI examination were enrolled prospectively. T1, T2, and proton density (PD) values were obtained from four different regions of interest (ROIs), namely, partial-section, single-section, three-sections, and whole-lesion. The metrics between NPC and NPH or among different ROIs were compared using Student's t-test or one-way ANOVA. The area under curve (AUC) was calculated to assess the performance of metrics obtained from different ROIs to differentiate NPC and NPH. The T1, T2, and PD values for NPH were significantly higher than those for NPC, regardless of the type of ROI used, except for the PD value obtained from the whole-lesion ROI. The T2 values obtained from the single-section ROI showed the highest diagnostic accuracy in distinguishing NPC from NPH, with an AUC of 0.894, sensitivity of 0.900, and specificity of 0.800. Additionally, the T1, T2, and PD values for nasopharyngeal lesions showed no statistical difference among different kinds of ROI, except for the difference in T1 value between partial-section and other methods. Quantitative analysis of syMRI has the potential to distinguish NPC from NPH. Moreover, different types of ROI showed limited influence on the relaxation time estimation for nasopharyngeal lesions.


Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects.
Plasma concentrations of desferrioxamine and ferrioxamine were measured following bolus injections of desferrioxamine and during 24 h infusions of the drug. [59Fe]ferrioxamine clearance and urinary iron excretion were also measured. Higher plasma ferrioxamine concentrations were found in iron loaded subjects and higher desferrioxamine concentrations in subjects with normal ironloads. There is a correlation between the circulating concentration of ferrioxamine during an infusion and the 48 h urinary iron excretion. The data suggests that the amount of iron chelated in vivo is related to an increase in the size of an intermediate chelatable pool rather than the total amount of the iron load. The well-recognized delay in urinary iron excretion appears to be related to active tubular reabsorption of ferrioxamine.


Survival of genetically engineered, adult-derived rat astrocytes grafted into the 6-hydroxydopamine lesioned adult rat striatum.
Astrocytes are potentially useful as vehicles for gene transfer into the CNS. As endogenous CNS cells, they possess secretory mechanisms and can be grown in vitro. We have developed an animal model of this system using autologous astrocyte grafts in Fischer 344 rats. Cultured cells were infected with an adenoviral vector containing the reporter gene lacZ in vitro and then grafted into the striatum of adult Fischer 344 rats previously lesioned with 6-OHDA. Survival of the cells and activity of the beta-galactosidase protein were followed for up to 21 days after injection. The grafted cells were shown to survive throughout the experimental period although the expression of transgene was reduced with time. If long-term expression of therapeutically active substances can be achieved, grafts of adult-derived astrocytes genetically engineered using recombinant adenoviral vectors could be employed in the treatment of Parkinson's disease and other neurological disorders.


Progesterone in vitro stimulates secretion of a specific protein by ovine epithelial endometrial cells.
Cultured ovine epithelial endometrial cells from oestrogen-treated ovariectomized ewes were treated in vitro with combinations of oestradiol-17 beta (E), progesterone (P) and the P-receptor antagonist RU486 (each 10(-6) to 10(-9) M), in the presence of [35S]methionine. Neither DNA content of dishes nor total protein were increased in treatment compared with control dishes. Incorporation of [35S] into secreted protein was lower from cells treated in vitro with P or E + P (10(-9) M) than from those treated with E (10(-9) M, P less than 0.01). Incorporation of [35S] into cellular protein was decreased by P (10(-9) M, P less than 0.025). SDS-PAGE analysis of secreted proteins enabled measurement of levels of a 46K protein which is secreted maximally following E + P administration in vivo. In vitro, P either alone or with E (each 10(-7) M) increased the abundance of the 46K protein in cell secretions by a factor of 1.5 +/- 0.1 (N = 9) or 1.8 +/- 0.3 (N = 10) respectively (P less than 0.01) compared with controls. The administration of E (10(-7) M) or either or both steroids at 10(-9) M, was without effect. RU486 alone (10(-6) to 10(-8) M) was also without effect but in the presence of E + P or P, blocked the increase in the 46K protein, suggesting this effect is mediated via binding of P to its receptor.


Manual muscle testing: does it meet the standards of an adequate screening test?
To describe the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of manual muscle testing. Secondary analysis of cross-sectional strength data. Acute rehabilitation unit. Convenience sample of 107 consecutive qualifying rehabilitation inpatients. Not applicable. Knee extension forces measured by manual muscle testing and hand-held dynamometry. The ability of manual muscle testing to detect 15, 20, 25 and 30% between-side differences and deficits in knee extension force was described. Although the specificity of manual muscle testing was acceptable (mostly > 80%), its sensitivity to differences between sides and to deficits relative to normal never exceeded 75%. Its diagnostic accuracy was never greater than 78%. The results of this study cast doubt on the suitability of manual muscle testing as a screening test for strength impairments.


Studies of antiproteolytic effects of glyburide on rat L6 myoblasts: comparisons with insulin.
Cultured L6 myoblasts afford considerable advantages for identifying and studying the insulin-like actions of test substances in a muscle-derived line. We have used this system to examine the interaction of the oral hypoglycemic sulfonylurea glyburide with bovine insulin on protein degradation and synthesis as well as on thymidine incorporation (as a measure of DNA synthesis) in these cells. Bovine insulin, at doses of 0.1 microgram/mL to 10 micrograms/mL, produced a dose-dependent inhibition of protein degradation (measured by release of trichloracetic acid (TCA)-soluble 14C-tyrosine from myoblasts into the culture medium) and increase in total protein content in the cultured myoblasts. At concentrations of 10 micrograms/mL, insulin achieved its maximal suppression of protein degradation (by nearly 50%) and increased cellular protein content (by 15%) over levels observed in the absence of added insulin. Glyburide, at concentrations at or above 1 microgram/mL, significantly suppressed protein degradation (up to 14%) and slightly augmented protein content of the cells. The effects of glyburide on protein degradation were additive with those of submaximally but not maximally effective concentrations of insulin, suggesting a common mechanism of action of the compounds. Both insulin and glyburide, at maximally effective doses, significantly depressed protein degradation as early as 2 to 6 hours after exposure. In addition, in a 24-hour labeling experiment, insulin stimulated tyrosine incorporation into TCA-insoluble protein and thymidine incorporation into DNA in the cells, whereas glyburide did not enhance these processes and, under certain conditions, inhibited them. These results demonstrate that glyburide, either alone or in concert with insulin, is capable of significantly inhibiting protein turnover in skeletal muscle-derived cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Determination of indomethacin in serum by an extractive alkylation technique and gas-liquid chromatography.
A method for determining indomethacin in serum has been developed, involving extractive alkylation, in which indomethacin is converted into its ethyl ester, and subsequent gas chromatographic determination of the ester. The method is specific and permits the determination of amounts down to 50 ng/ml in serum. The indomethacin concentration in serum was followed for 24 h after oral and rectal application and the results are compared with those reported in the literature.


Dendritic cell-targeted CD40 DNA vaccine suppresses Th17 and ameliorates progression of experimental autoimmune glomerulonephritis.
The CD40-CD40L costimulatory pathway is critical for T cell activation in autoimmune disease. We have previously found that blocking the CD40-CD40L pathway using a dendritic cell-targeted CD40 DNA (DEC-CD40) vaccine prevented the development of Heymann nephritis. In this study, we explored the effect of a DEC-CD40 vaccine in the treatment of experimental autoimmune glomerulonephritis (EAG), an animal model of human Goodpasture's disease induced by antigen α3IV-NC1. DEC-CD40 vaccine given at week 3 and week 6 after 3IV-NC1 injection reduced kidney structural and functional injury significantly in EAG. DEC-CD40 vaccination suppressed Th17 cell numbers and Th17 immune responses in kidney and spleen, but did not alter Th1 cells number and responses. Serum derived from rats with DEC-CD40 vaccination suppressed Th17 differentiation, but not Th1 differentiation in vitro. Furthermore, B cell activation, driven by Th17 cytokines, was suppressed by serum from rats vaccinated with DEC-CD40. A DNA vaccine encoding CD40 and targeting dendritic cell, ameliorates kidney injury in both early and late stages in EAG rats, indicating DEC-CD40 vaccination has a therapeutic role in EAG. Its effect is associated with the reduction of Th17 differentiation and Th17-mediated B cell activation.


Peripheral calcifying odontogenic cyst.
Calcifying odontogenic cyst (COC) is a rare lesion representing about 1% of jaw cysts. It may occur in a central (intraosseous) or peripheral (extraosseous) location. A case of peripheral COC located on the gingiva, appearing as a painless, circumscribed, pink nodule has been reported. Peripheral, in contrast to central, COC tends to affect older patients. Peripheral COC is a less aggressive lesion than the central counterpart, and a simple excision biopsy is curative. The histological finding of a keratinized epithelium rich in ghost cells has helped in making the diagnosis.


Further studies on the specificity of diacylglycerol for protein kinase C activation.
Specificity of 1,2-diacylglycerol for the activation of protein kinase C was investigated with various synthetic products. 1-Stearoyl-2-arachidonylglycerol, a major species of diacylglycerol derived from the receptor-mediated hydrolysis of inositol phospholipids, was most active, but many other diacylglycerols having naturally occurring fatty acids were almost equally active in this role. Hormone-sensitive lipase could produce potentially active diacylglycerols during lipolysis. The lack of the specificity may be reconciled with the possibility that the stearoyl-arachidonyl species is the diacylglycerol with which protein kinase C indeed comes in contact in the membrane when the receptor is stimulated, and that diacylglycerols from other sources are produced in distinct compartments and are not intercalated into the phospholipid bilayer.


Sensitivity of Escherichia coli O157:H7 to commercially available alkaline cleaners and subsequent resistance to heat and sanitizers.
The effects of seven commercially available alkaline cleaners used in the food processing industry, 0.025 M NaOH, and 0.025 M KOH on viability of wild-type (EDL 933) and rpoS-deficient (FRIK 816-3) strains of Escherichia coli O157:H7 in logarithmic and stationary phases of growth were determined. Cells were treated at 4 or 23 degrees C for 2, 10, or 30 min. Cleaners 2, 4, 6, and 7, which contained hypochlorite and <11% NaOH and/or KOH (pH 11.2 to 11.7), killed significantly higher numbers of cells than treatment with cleaner 3, containing sodium metasilicate (pH 11.4) and <10% KOH, and cleaner 5, containing ethylene glycol monobutyl ether (pH 10.4). There were no differences in the sensitivities of logarithmic and stationary-phase cells to the alkaline cleaners. Treatment with KOH or NaOH (pH 12.2) was not as effective as four out of seven commercial cleaners in killing E. coli O157:H7, indicating that chlorine and other cleaner components have bactericidal activity at high pH. Stationary-phase cells of strain EDL 933 that had been exposed to cleaner 7 at 4 or 23 degrees C and strain FRIK 816-3 exposed to cleaner 7 at 23 degrees C had significantly higher D(55 degrees C) (decimal reduction time, minutes at 55 degrees C) values than control cells or cells exposed to cleaner 5, indicating that exposure to cleaner 7 confers cross-protection to heat. Cells of EDL 933 treated with cleaner 7 at 12 degrees C showed significantly higher D(55 degrees C) values than cells of FRIK 816-3, indicating that rpoS may play a role in cross-protection. Stationary-phase cells treated with cleaner 5 or cleaner 7 at 4 or 12 degrees C were not cross-protected against subsequent exposure to sanitizers containing quaternary ammonium compounds or sodium hypochlorite, or to cetylpyridinium chloride and benzalkonium chloride.


Wrapping of solitary ruptured intracranial aneurysms, outcome at five years.
Previous follow up studies of patients who have had ruptured intracranial aneurysms treated by a wrapping technique have largely been in the pre-microsurgical era. Our objective was to ascertain whether wrapping aneurysms with the aid of the operating microscope provides protection against rebleeding in the short and long term. The study involved retrospective analysis of patients with ruptured aneurysms treated by wrapping over a six-year period. Twenty-nine patients were identified with wrapped aneurysms, of these 15 had wrapping of a solitary ruptured aneurysm, the remainder were excluded because of clip/wrap combination, multiple aneurysms, and unruptured aneurysms. Of the 15 patients who had a solitary ruptured aneurysm wrapped, none had rebled at one year follow up. One patient died of a myocardial infarction at 4 years, the remaining 14 patients had no episodes of rebleeding with all patients achieving Glasgow outcome scores of four or five at 5 years follow-up. Although surgical clipping of intracranial aneurysms is the definitive method of treatment, our findings suggest that wrapping of ruptured intracranial aneurysms with the aid of the operating microscope confers good protection against both early and late rebleeding in those cases considered 'unclippable'.


The long noncoding RNA TARID regulates the CXCL3/ERK/MAPK pathway in trophoblasts and is associated with preeclampsia.
The widely accepted explanation of preeclampsia (PE) pathogenesis is insufficient trophoblast invasion and impaired uterine spiral artery remodeling. However, the underlying molecular mechanism remains unclear. We performed transcriptome sequencing on placentas of normal and PE patients and identified 976 differentially expressed long noncoding RNAs (lncRNAs). TCF21 antisense RNA inducing demethylation (TARID) was one of the most significantly differentially expressed lncRNAs and was negatively correlated with the systolic and diastolic blood pressure in PE patients. Furthermore, we verified the effect of TARID on the biological behavior of trophoblasts and performed UID mRNA-seq to identify the effectors downstream of TARID. Then, co-transfection experiments were used to better illustrate the interaction between TARID and its downstream effector. We concluded that the downregulation of TARID expression may inhibit trophoblast infiltration and spiral artery remodeling through inhibition of cell migration, invasion, and tube formation mediated through the CXCL3/ERK/MAPK pathway. Overall, these findings suggested that TARID may be a therapeutic target for PE through the CXCL3/ERK/MAPK pathway.


Orientation to solar radiation in black wildebeest (Connochaetes gnou).
We recorded the body axis orientation of free-living black wildebeest relative to incident solar radiation and wind. Observations were made on three consecutive days, on six occasions over the course of 1 year, in a treeless, predominantly cloudless habitat. Frequency of orientation parallel to incident solar radiation increased, and perpendicular to incident solar radiation decreased, as ambient dry-bulb temperature or solar radiation intensity increased, or wind speed decreased. We believe these changes were mediated via their effect on skin temperature. Parallel orientation behavior was more prominent when the wildebeest were standing without feeding than it was when they were feeding. We calculate that a black wildebeest adopting parallel orientation throughout the diurnal period would absorb 30% less radiant heat than the same animal adopting perpendicular orientation. Parallel orientation was reduced at times when water was freely available, possibly reflecting a shift from behavioral to autonomic thermoregulatory mechanisms. The use of orientation behavior by black wildebeest is well developed and forms part of the suite of adaptations that help them to maintain heat balance while living in a shadeless, often hot, environment.


The Role of Aspirin for Preeclampsia Prevention in Women with Diabetes.
A diagnosis of type I or type 2 diabetes confers heightened risk for virtually every obstetric and perinatal complication, with the incidence of superimposed preeclampsia representing a particularly high-risk scenario. Over the past three decades, studies have investigated the role of aspirin in preeclampsia prevention, yielding some promising results for certain at-risk groups, yet unconvincing evidence of benefit among women with pre-pregnancy diabetes. The purpose of this review is to present the current evidence base for aspirin use in pregnancy as a means of mitigating preeclampsia risk in the setting of pregestational type I or type 2 diabetes. Meta-analysis data examining low-dose aspirin for preeclampsia prevention in at-risk and low-risk women has demonstrated modest benefit, but subanalyses of cohorts with diabetes have failed to demonstrate a beneficial effect. Evidence is emerging that indicates a benefit only among women who initiate aspirin therapy prior to 16 weeks' gestation, and uncertainty exists surrounding the effective dose. In light of equipoise surrounding the potential role of aspirin for prevention of preeclampsia in women with diabetes, current research is targeted at determining clinical efficacy of aspirin in this high-risk obstetric population.