Cross-regulation between G-protein-mediated pathways. Acute activation of the inhibitory pathway of adenylylcyclase reduces beta 2-adrenergic receptor phosphorylation and increases beta-adrenergic responsiveness.
Cross-regulation from the stimulatory to the inhibitory adenylylcyclase pathways has been described (Hadcock, J. R., Ros, M., Watkins, D. C., and Malbon, C. C. (1990) J. Biol. Chem. 265, 14784-14790). More recently, persistent activation (48 h) of the inhibitory adenylylcyclase pathway has been shown to cross-regulate the stimulatory pathway (i) enhancing the maximal response of beta-adrenergic agonits, (ii) increasing the expression of beta-adrenergic receptor, and (iii) reducing the ED50 for the isoproterenol-stimulated response by 50-fold (Hadcock, J. R., Port, J. D., and Malbon, C. C. (1991) J. Biol. Chem. 266, 11915-11922). Here, we report that short term activation (60 min) of the inhibitory adenylylcyclase pathway of hamster smooth muscle DDT1MF-2 cells with the A1-adenosine receptor agonist N6-phenylisopropyladenosine (PIA) likewise enhances the stimulatory adenylylcyclase response to the beta-adrenergic agonist isoproterenol. The PIA effect was exerted at the level of the receptor, i.e., the beta-adrenergic receptor-mediated response was enhanced, whereas the guanosine 5'-O-(thiotriphosphate)- and forskolin-stimulated adenylylcyclase activities were largely unaffected. In contrast to longer term persistent activation of the inhibitory pathway, receptor number and affinity for 125I-labeled cyanopindolol were unaffected. Metabolic labeling of cells with [32P]orthophosphate and immuneprecipitation of beta-adrenergic receptors detected phosphorylation of the receptor in unstimulated cells and marked phosphorylation in cells challenged with epinephrine. When cells were challenged short term with PIA, the basal state of beta-adrenergic receptor phosphorylation was reduced by 75%. Treating cells with PIA in combination with the cAMP analog 8-(4-chlorophenylthio)adenosine cyclic AMP attenuated the enhanced receptor-mediated adenylylcyclase response observed in cells treated with PIA alone. These data suggest that short term cross-regulation from the inhibitory to stimulatory adenylylcyclase pathways results in the following: (i) decreased intracellular cAMP levels and protein kinase A activity, (ii) reduced phosphorylation of the beta 2-adrenergic receptor in the "basal" (i.e. unstimulated) state, and (iii) enhanced receptor-mediated activation of Gs.


A simple protocol for amino acid type selective isotope labeling in insect cells with improved yields and high reproducibility.
An easy to use and robust approach for amino acid type selective isotope labeling in insect cells is presented. It relies on inexpensive commercial media and can be implemented in laboratories without sophisticated infrastructure. In contrast to previous protocols, where either high protein amounts or high incorporation ratios were obtained, here we achieve both at the same time. By supplementing media with a well considered amount of yeast extract, similar protein amounts as with full media are obtained, without compromising on isotope incorporation. In single and dual amino acid labeling experiments incorporation ratios are consistently ≥90% for all amino acids tested. This enables NMR studies of eukaryotic proteins and their interactions even for proteins with low expression levels. We show applications with human kinases, where protein-ligand interactions are characterized by 2D [(15)N, (1)H]- and [(13)C, (1)H]-HSQC spectra.


Heat shock protein 90 enhances the electron transfer between the FMN and heme cofactors in neuronal nitric oxide synthase.
Heat shock protein 90 (Hsp90) is a key regulator of nitric oxide synthase (NOS) in vivo. Despite its functional importance, little is known about the underlying molecular mechanism. Here, purified dimeric human Hsp90α was used to investigate whether (and if so, how) Hsp90 affects the FMN-heme interdomain electron transfer (IET) step in NOS. Hsp90α increases the IET rate for rat neuronal NOS (nNOS) in a dose-saturable manner, and a single charge-neutralization mutation at conserved Hsp90 K585 abolishes the effect. The kinetic results with added Ficoll 70, a crowder, further indicate that Hsp90 enhances the FMN-heme IET through specific association with nNOS. The Hsp90-nNOS docking models provide hints on the putative role of Hsp90 in constraining the available conformational space for the FMN domain motions.


Detection and differentiation of pigeon paramyxovirus serotype-1 (PPMV-1) isolates by RT-PCR and restriction enzyme analysis.
Detection and pathotyping of Newcastle disease virus (NDV) is extremely important because the appearance of virulent virus has significant economic consequences. During 1981 to 1985, infections of racing and show pigeons with an avian paramyxovirus serotype-1 (APMV-1) hit worldwide, and a panzootic occurred due to a variant form of classical NDV. On the basis of pathogenicity and monoclonal antibody binding studies, the virus was termed 'pigeon PMV-1' (PPMV-1). In the past, number of Newcastle disease outbreaks in poultry and other birds has been attributed to PPMV-1. PPMV-1 viruses are known to present difficulty when assessed by conventional in vivo pathogenicity tests. In this study, the technique of reverse transcription-polymerase chain reaction (RT-PCR) and restriction enzyme (RE) analysis was used to detect and differentiate PPMV-1 isolates of Indian origin. Restriction enzyme digestion analysis of RT-PCR-amplified fusion protein (F) gene, encoding for the cleavage activation sites of fusion protein, was carried out with restriction enzymes BglI, HhaI, HaeIII, HinfI, MboI, MspI, PvuII and StyI. A set of only four enzymes HhaI, MspI or HaeIII, MboI and BglI alone were sufficient to differentially detect APMV-1 and PPMV-1 viruses and their pathotypes. In conclusion, RT-PCR followed by RE analysis proved to be useful for detection and differentiation of APMV-1 and PPMV-1 isolates at genomic level.


Challenges of biomolecular detection at the nanoscale: nanopores and microelectrodes.
The interest in analytical devices, which typically rely on the reactivity of a biological component for specificity, is growing rapidly. In this Perspective, we highlight current challenges in all-electrical biosensing as these systems shrink toward the nanoscale and enable the detection of analytes at the single-molecule level. We focus on two sensing principles: nanopores and amperometric microelectrode devices.


Surgical repair of inferior sinus venosus atrial septal defect.
A 9-year-old girl presented for cardiac evaluation with symptoms of dyspena, fatigue, and cyanosis with exercise. Cardiac catheterization demonstrated an atrial septal defect; an anomalous right superior pulmonary vein was suspected but not confirmed. Operation disclosed anomalous drainage of the right superior and inferior pulmonary veins into the right atrium, an intact fossa ovalis, and an inferior sinus venosus defect. Repair was accomplished by detaching the posterior edge of the atrial septum and suturing it to the right of the pulmonary veins, so that the defect was closed and all the pulmonary venous blood was directed to the left atrium.


Effectiveness comparison between blended learning of histology practical in flipped physical classrooms and flipped virtual classrooms for MBBS students.
The flipped classroom blended learning model has been proven effective in the teaching of undergraduate medical courses as shown by student acceptance and results. Since COVID-19 necessitated the application of online learning in Histology practical for MBBS students, the effectiveness of the blended learning model on teaching quality has required additional attention. A blended learning of histology practical was flipped in a virtual classroom (FVCR-BL) or in a physical classroom (FPCR-BL) in School of Medicine, Zhejiang University in China. Students were split into FVCR-BL group (n = 146) due to COVID-19 pandemic in 2020 or were randomly allocated into FPCR-BL group (n = 93) in 2021, and retrospectively, students with traditional learning in 2019 were allocated into traditional learning model in a physical classroom (PCR-TL) group (n = 89). Same learning requirements were given for 3 groups; all informative and summative scores of students were collected; a questionnaire of student satisfaction for blended learning activities were surveyed in 2021. Data of scores and scales were analyzed with Kruskal-Wallis test and Kolmogorov-Smirnov test in SPSS Statics software. The results clarified that FPCR-BL students obtained higher final exam scores and were more likely to engage in face-to-face interactions with instructors than FVCR-BL students. FPCR-BL and FVCR-BL students had higher classroom quiz scores than the PCR-TL students owing to the contribution of blended learning. The results of the questionnaire showed that participants of FPCR-BL positively rated the online learning and preview test, with a cumulative percentage of 68.31%, were more satisfying than other learning activities of blended learning. There were significant correlations (r = 0.581, P < 0.05) between online learning and the other three blended learning strategies. In the flipped classroom with a blended learning process of histology practical, enhancing the quality of online learning boosts student satisfaction and improves knowledge learning; peer-to-peer interactions and instructor-to-peer interactions in the physical classroom improved knowledge construction.


Giant extra-axial cerebellopontine angle/cavernous sinus ependymoma: case report.
The presentation, diagnosis, and treatment are described for a patient with a giant ependymoma involving the right cerebellopontine angle extending into the cavernous sinus. This case presents the unusual occurrence of a large extra-axial intracranial ependymoma and is the first reported case of cavernous sinus extension of this tumor. The patient was a 22-year-old woman who presented with a 3-day history of generalized headache and right-sided facial droop. Magnetic resonance imaging revealed a nonhomogeneously enhancing cystic mass that was primarily in the posterior fossa with significant supratentorial extension and no apparent intra-axial or intraventricular involvement. Gross total resection of this mass was achieved via two-staged resections using an initial presigmoid transpetrous, transtentorial approach and a subsequent pterional craniotomy. Pathological evaluation confirmed the diagnosis of ependymoma, and adjuvant radiation therapy to the resection bed was administered. Ependymomas can present as entirely extra-axial intracranial masses and rarely may involve the confines of the cavernous sinus.


Visual modulation of proprioceptive reflexes during movement.
Previous research has demonstrated that feedback circuits such as reflexes can be tuned by setting their gains prior to movement onset during both posture and movement tasks. However, such a control strategy requires that perturbation contingencies be predicted during movement planning and that task goals remain fixed. Here we test the hypothesis that feedforward regulation of reflex circuits also occurs during the course of movement in response to changes in task goals. Participants reached to a visual target that was occasionally jumped on movement initiation, thus changing task goals. Reflex responses were elicited through a mechanical perturbation on the same trial, 100 ms after the target jump. Impedance to the perturbation was tuned to the direction of the preceding jump: reflex responses increased or decreased depending on whether the perturbation opposed or was consistent with the target jump. This modulation, although sensitive to the direction of the jump, was insensitive to jump amplitude, as tested in a follow-up experiment. Our findings thus suggest that modulation of reflex circuits occurs online, and is sensitive to changes in visual target information. In addition, our results suggest a two-level model for visuo-motor control that reflects hierarchical neural organization.


Reproductive health perspectives of young women with perinatally and behaviourally acquired HIV: A qualitative study.
The aim of this study was to describe the sexual and reproductive goals of female adolescents with human immunodeficiency virus (HIV) in an urban cohort and decipher if they vary depending on the mode of HIV acquisition. We conducted in-depth qualitative interviews with 25 Black and/or Hispanic/Latinx female adolescents living with HIV (14 perinatally, 11 behaviourally acquired) aged 17-25 years who have access to care and antiretroviral therapy at an urban public hospitals (NYC, NY). Interviews were transcribed, coded and analysed using thematic analysis. Interviews demonstrated that access to antiretroviral therapy and HIV disclosure to a sexual partner were critical aspects of sexual health for the majority of participants. Persons with perinatal HIV defined motherhood as a source of self-validation and were confident that antiretroviral therapy prevents HIV transmission. Persons with behaviourally acquired HIV viewed their status as an insurmountable barrier that will prevent them from attaining sexual intimacy with a partner and expressed persistent concerns about HIV transmission during pregnancy despite reassurance from medical providers. Sexual and reproductive perspectives of adolescents/young women living with HIV are multifactorial, highly stigmatized, and likely influenced by the mode of HIV acquisition. This population may benefit from patient-centred care models, including sexual health counselling that addresses sexual agency, intimacy, parenting and transmission risk reduction.


Long-term clinical outcome after endoluminal reconstruction of diffusely degenerated saphenous vein grafts with less-shortening wallstents.
This study was designed to evaluate the immediate and long-term clinical results of patients undergoing endoluminal reconstruction in diffusely degenerated saphenous vein grafts (SVGs) with elective implantation of one or more less-shortening Wallstents. The optimal treatment strategy for patients with diffusely degenerated SVGs is controversial. Endoluminal reconstruction by stent implantation is one proposed strategy; however, there are few data regarding long-term clinical outcome. Between May 1995 and September 1998, 6,534 consecutive patients underwent angioplasty in our institution, including 440 who were treated for SVG lesions. Of these, 126 (115 men, 11 women, median age 69.5 years, range: 33-86 years) with old SVGs (mean age: 13+/-5 years) diffusely degenerated stenosed or occluded (mean lesion length: 27+/-12 mm) were treated electively with implantation of one or multiple (total 197) less-shortening Wallstents. Before discharge, 13 patients (10.3%) sustained at least one major cardiovascular event, including 4 deaths (3.2%), 11 myocardial infarctions (MI) (8.7%), and 3 repeat revascularizations (target vessel = 1, nontarget vessel = 2, 2.4%). Surviving patients were followed for 22+/-11 months: 13 patients (11.1%) died, 11 (9.4%) sustained an MI, 37 underwent angioplasty (31.6%), and 4 (3.4%) underwent bypass surgery. The estimated three-year event-free survival rates (freedom from death, and freedom from death/MI/target vessel revascularization) were (mean +/- SE) 81.1+/-7.8% and 43.2+/-18.5%, respectively. The long-term clinical outcome of patients undergoing endoluminal reconstruction in diffusely degenerated SVG is relatively poor, mainly because of a high incidence of death or MI and the frequent need for repeat angioplasty. It is unlikely that percutaneous intervention alone will provide a satisfactory or definitive solution for these patients.


Abnormal expression of WIF1 in hepatocellular carcinoma cells and its regulating effect on invasion and metastasis factors of TIMP-3 and caveolin-1 of hepatocellular carcinoma.
To discuss the abnormal expression of Wnt inhibitory factor (WIF1) in hepatocellular carcinoma cells and its regulating effect on the hepatocellular carcinoma invasion and metastasis factors of tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) and caveolin-1. RT-PCR and Western blot were employed to detect the expression of WIF1 in six hepatocellular carcinoma cell lines of HepG2, Hep3B, Huh7, PLC/PRF/5, SMMC-7721 and MHCC97 and the immortalized human liver cell line THLE-3. Besides, Lipofectamine 2000 was employed to transfect the eukaryotic expression vector pcDNA3.1-WIF1 and blank plasmid pcDNA3.1 into hepatocellular carcinoma cell lines. Transwell assay was used to detect the effect of WIF1 on the invasion ability of hepatocellular carcinoma cells; Western blot was used to detect the effect of WIF1 on the expression of TIMP-3 and caveolin-1 in hepatocellular carcinoma cells, it also discussed the effect on the expression of β-catenin. The expression of WIF1 in hepatocellular carcinoma cell lines was lower than that in the normal liver cell lines (P < 0.01); while there was basically no expression of WIF1 in the human highly metastatic cell line MHCC-97 and moderate expression in HepG2 and SMMC-7721. Therefore, HepG2 and SMMC-7721 were chosen as the further experimental cell lines. After transfecting the eukaryotic expression vector pcDNA3.1-WIF1 and blank plasmid pcDNA3.1 into hepatocellular carcinoma cell lines, compared with the blank plasmid group, the cell viability and invasion ability in the WIF1 group were all reduced (P < 0.01), the expression of TIMP-3, caveolin-1 and mRNA were all down-regulated (P < 0.01), and the expression of β-catenin was decreased (P < 0.01). Because of down-regulation or missing of expression of WIF1 in hepatocellular carcinoma cell lines, the up-regulation of WIF1 expression can significantly inhibit the invasion and metastasis of HepG2 and SMMC-7721 of hepatocellular carcinoma cell lines, which are related to the up-regulated expression of TIMP-3 and down-regulated expression of caveolin-1 and may be realized through the Wnt/β-catenin signaling pathway.


Three-dimensional direct laryngoscopy and bronchoscopy: enhanced visualization of the airway.
This is the first description of 3-dimensional (3D) pediatric airway endoscopy in the otolaryngology literature detailing the superior visualization with this technology. Ultimately, enhanced optics may further improve the treatment of airway pathology. To report the first case series examining the use of 3D direct laryngoscopy and bronchoscopy (DLB) in the diagnosis and management of laryngotracheal pathology. Case series. Tertiary care pediatric hospital. Three patients underwent both telescopic 2-dimensional (2D) and 3D DLB for comparison purposes: a 12-year-old boy for visualization of complete tracheal rings, a 23-year-old man for dilation of tracheal stenosis, and a 4-month-old boy for resection of subglottic cysts. Enhanced visualization of laryngotracheal pathology and facilitated endoscopic surgery. To our knowledge, this is the first case series in the otolaryngology literature examining the use of 3D DLB for the resection of subglottic cysts, dilation of tracheal stenosis, and visualization of complete tracheal rings. We believe that the 3D view offers qualitatively improved depth perception, accuracy of balloon placement, and appraisal of subglottic cyst resection margins. This emerging technology has vast potential for improving endoscopy, surgical precision in airway interventions, tissue preservation, and methods of teaching. More research is needed in this area regarding the benefits and advantages of 3D compared with 2D endoscopy.


Novel antimicrobial activity of protein produced by Streptomyces lividans TK24 against the phytopathogen Clavibacter michiganensis.
Antimicrobial proteins and peptides are an alternative to current antibiotics. Here, we report an antimicrobial activity in a low-molecular-weight protein secreted naturally by Streptomyces lividans TK24 when glucose or glycerol were used as carbon sources. The antimicrobial activity was demonstrated against Bacillus subtilis, Bacillus cereus, Kokuria rhizophila, Clostridium sporogenes and Clavibacter michiganensis, causal pathogen of tomato bacterial canker; one of the most destructive bacterial diseases of this crop. The protein fraction with antimicrobial activity was identified and quantified by LC-MS/MS. From a total of 155 proteins, 11 were found to be within the range of 11.3-13.9 kDa of which four proteins were selected by functional analysis as possibly responsible for the antimicrobial activity. Protein fractionation, correlation analysis between antimicrobial activity and abundance of selected proteins, as well as transcriptional expression analysis, indicate that 50S ribosomal protein L19 is the main candidate responsible for antimicrobial activity.


The ilvIH operon of Escherichia coli K-12. Identification of the gene products and recognition of the translational start by polypeptide microsequencing.
The ilvI and ilvH gene products were identified physically by electrophoretic analysis of in vivo-labelled polypeptides produced in minicells from plasmids carrying the wild-type ilvIH operon of Escherichia coli K-12 and derivatives of it. An analysis of the distribution of methionine residues in the amino-terminal portion of micro-quantities of the ilvI product eluted from gel showed that the translational start of the ilvI gene is the promoter-proximal one of three putative methionine codons predicted from the DNA sequence.


Bioavailability and antioxidant effect of epigallocatechin gallate administered in purified form versus as green tea extract in healthy individuals.
Tea polyphenols have strong in vitro antioxidant activity. Due to their limited bioavailability, however, their contribution to in vivo antioxidant activity may depend on the form of administration. A human intervention study was performed to evaluate the bioavailability and antioxidant capacity of (-)-epigallocatechin-3-gallate (EGCG) administered as a single large dose in the form of either purified EGCG or as green tea extract (Polyphenon E). Plasma concentrations of tea polyphenols were determined by high-performance liquid chromatography (HPLC) analysis combined with coulometric array electrochemical detection (ECD). We found no differences in plasma EGCG concentrations and trolox equivalents determined by the trolox equivalent antioxidant capacity assay after administration of either form of EGCG. However, we found that the plasma antioxidant activity was significantly affected by changes in the plasma urate concentration, which may have interfered with the effect of tea polyphenols on the antioxidant activity. In addition, lymphocyte 8-hydroxydeoxyguanosine to deoxyguanosine (8-OHdG/10(6)dG) ratios were determined by HPLC with ECD. The 8-OHdG/10(6)dG ratios did not change significantly during the 24 h following both EGCG interventions but correlated significantly within individuals determined during the two interventions separated by 1 week. In summary, changes in plasma uric acid due to dietary intake were significantly correlated to the plasma antioxidant activity and exerted a stronger influence on the plasma antioxidant activity compared with the EGCG intervention. In future studies of dietary effects on the plasma antioxidant capacity, changes in plasma uric acid will need to be closely monitored.


An integrated fog and Artificial Intelligence smart health framework to predict and prevent COVID-19.
Nowadays, COVID-19 is spreading at a rapid rate in almost all the continents of the world. It has already affected many people who are further spreading it day by day. Hence, it is the most essential to alert nearby people to be aware of it due to its communicable behavior. Till May 2020, no vaccine is available for the treatment of this COVID-19, but the existing technologies can be used to minimize its effect. Cloud/fog computing could be used to monitor and control this rapidly spreading infection in a cost-effective and time-saving manner. To strengthen COVID-19 patient prediction, Artificial Intelligence(AI) can be integrated with cloud/fog computing for practical solutions. In this paper, fog assisted the internet of things based quality of service framework is presented to prevent and protect from COVID-19. It provides real-time processing of users' health data to predict the COVID-19 infection by observing their symptoms and immediately generates an emergency alert, medical reports, and significant precautions to the user, their guardian as well as doctors/experts. It collects sensitive information from the hospitals/quarantine shelters through the patient IoT devices for taking necessary actions/decisions. Further, it generates an alert message to the government health agencies for controlling the outbreak of chronic illness and for tanking quick and timely actions.


Closed-Loop Control of Tremor-Predominant Parkinsonian State Based on Parameter Estimation.
A significant feature of Parkinson's disease (PD) is the inability of the thalamus to respond faithfully to sensorimotor information from the cerebral cortex. This may be the result of abnormal oscillations in the basal ganglia (BG). Deep brain stimulation (DBS) is regarded as an effective method to modulate these pathological brain rhythmic activities. However, the selection of DBS parameters is challenging because the mechanism is not well understood. This work proposes the design of a closed-loop control strategy to automatically adjust the parameters of a DBS waveform based on a computational model. By estimating the synaptic input from BG to the thalamic neuron model as feedback variable, we designed and compared various control algorithms to counteract the effects of pathological oscillatory inputs. We then obtained optimal DBS parameters to modulate the tremor-predominant Parkinsonian state. We showed that even a simple proportional controller provides higher fidelity of thalamic relay of sensorimotor information and lower energy expenditure, as compared with classical open-loop DBS. Integral action further enhances DBS performance. Additionally, a positive bias voltage further improves the relay ability of the thalamus with decreased stimulation energy expenditure. These findings were conducive to the development of a more effective DBS to further improve the treatment of the PD.


Age- and gender-related differences in the use of secondary medical prevention after primary vascular surgery: a nationwide follow-up study.
This study examined the possible age- and gender-related differences in the use of secondary medical prevention following primary vascular reconstruction in a population-based long-term follow-up study. Using information from nationwide Danish registers, we identified all patients undergoing primary vascular reconstruction in-between 1996 and 2006 (n = 20,761). Data were obtained on all filled prescriptions 6 months and 3, 5 and 10 years after primary vascular reconstruction. Comparisons were made across age and gender groups, using men 40-60 years old as a reference. Compared to current guidelines the overall use of secondary medical prevention was moderate to low (e.g., lipid-lowering drugs 49.5%, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists (ACE/ATII) 43.4%, combination of lipid-lowering drugs and anti-platelet therapy and any anti-hypertensive therapy 44.7%). A decline was observed between 6 months and 3 years after surgery. Patients >80 years old were less likely to be prescribed lipid-lowering drugs and combination therapy (e.g.: adjusted risk ratio (RR) 5 years after surgery for men and women 0.63 (95% confidence interval (CI): 0.39-1.02) and 0.48 (95%CI: 0.31-0.75), respectively, whereas smaller and statistical non-significant gender-related differences were observed. The age- and gender-related differences appeared eliminated or substantially reduced in the latest part of the study period (2001-2007). We found moderate to low use of secondary medical prevention in Denmark compared with recommendations from clinical guidelines. However, the use has increased in recent years and age- and gender-related differences have been reduced or even eliminated.


Use of magnetic nanoparticles as nanosensors to probe for molecular interactions.
Biocompatible magnetic nanosensors have been designed to detect molecular interactions in biological media. Upon target binding, these nanosensors cause changes in the spin-spin relaxation times of neighboring water molecules, which can be detected by magnetic resonance (NMR/MRI) techniques. These magnetic nanosensors have been designed to detect specific mRNA, proteins, enzymatic activity, and pathogens (e.g., virus) with sensitivity in the low femtomole range (0.5-30 fmol).


Electrical burn with visceral injury.
A 37-year-old female patient suffered high voltage electrical injury with resultant exit wound on the left quadrant of the abdomen measuring 15 X 10 cm2 involving full thickness of the abdominal wall including the peritoneum. Early debridement and exploratory laparotomy was performed on the fifth post-burn day although the patient had no abdominal symptoms. All visceral organs were grossly normal. The peritoneum was closed and the wound covered with split thickness skin graft. On the twelfth post-burn day the anterior wall of the stomach sloughed and resulted in a 10 X 10 cm2 gastrocutaneous fistula. After 1 month of duodenostomy feeding via the fistula using a Foley catheter, the fistula was closed and was covered with greater omental flap and split thickness skin. Seventeen days later the patient was discharged following an uneventful recovery.


In vitro metabolism of 3-t-butyl-4-hydroxyanisole and its irreversible binding to proteins.
A method for the preparation of methyl-labelled 3-t-butyl-4-hydroxyanisole (BHA) is described. Metabolism of [14C]BHA using four different enzyme systems (liver microsomes + NADPH; liver microsomes + cumene hydroperoxide (CHP); sheep seminal vesicle (SSV) microsomes (as a source of prostaglandin synthetase) + arachidonic acid (AA); horseradish peroxidase (HRP) + hydrogen peroxide) was investigated. In all systems, BHA was oxidized to a variety of products including formaldehyde, a dimer di-BHA, polar and water soluble metabolites as well as a reactive intermediate(s) that binds irreversibly to proteins. With liver microsomes and NADPH, phenobarbital (PB) induction gave increased yields of all products while 3-methylcholanthrene (MC) induction specifically increased protein binding but decreased other metabolite formation. BHA addition effectively discharged the activated oxygen complex of cytochrome P-450 (liver microsomes) as well as Comp. I and Comp. II of HRP suggesting that it is a good one electron peroxidase donor. BHA addition also increased the net rate of NADPH oxidation in the presence of liver microsomes suggesting uncoupling. It is proposed that in all system investigated BHA is oxidized predominantly via a one electron oxidation process to yield first the BHA free radical which then dimerizes, forms more products or binds to proteins.


Tolerance induction in hypersensitivity reactions from drugs: a brief overview.
Drug hypersensitivity reactions can occur with many drugs, are unpredictable, may affect any organ system and range widely in clinical severity from mild pruritus to exanthems to anaphylaxis. In most cases, the suspected drug must be avoided in the future. However, for certain patients, the particular drug may be essential for an optimal therapy. Under these circumstances, desensitization may be performed.


Prevalence of antibody to Japanese encephalitis virus nonstructural 1 protein among racehorses in Japan: indication of natural infection and need for continuous vaccination.
Japanese encephalitis virus (JEV) causes fatal diseases in equines as well as humans. In Japan, racehorses are vaccinated with inactivated JE vaccine every year and no equine JE cases have been reported since 1986. However, the current reduction in JEV activity in nature has raised an argument against the requirement of continuous vaccination. Here, we studied natural infection rates in racehorses to address the issue. To identify naturally-infected individuals from vaccinated populations, we used an immunostaining method for detecting antibodies to JEV nonstructural 1 (NS1) protein. A total of 779 horses in eight nationwide locations showed NS1 antibody prevalences ranging from 15 to 73%. NS1 antibody prevalences among 2-year-old individuals that had spent one epizootic season in a particular location, therefore representing annual infection rates, were 15-67%. Individuals aged >/=3 years showed higher NS1 antibody titers than the 2-year-olds, suggesting that NS1 antibody levels were boosted by repeated exposures to JEV antigen over >/=2 epizootic seasons. These results indicate that horses in Japan are exposed to natural JEV infections, confirming the need for continuous vaccination for protecting horses from JE.


Lumbar puncture in the management of adults with suspected bacterial meningitis--a survey of practice.
Assess the use of lumbar puncture (LP) in the management of suspected community acquired bacterial meningitis in adults. A questionnaire was sent to secondary care clinicians (excluding junior house officers) in general internal and emergency medicine at three acute NHS healthcare trusts in the south west of England. The questionnaire recorded the experience of the clinician and asked questions related to case scenarios representing common presentations of bacterial meningitis or meningococcal disease. The response rate was 42% (108/260). Nearly all of the respondents (91%) reported regularly managing patients with suspected meningitis. Most respondents considered that (i) brain computerised tomography (CT) was necessary prior to undertaking LP (78%, 60/77), (ii) LP was a useful first line investigation in a patient with meningococcal shock.(80%, 84/105), (iii) LP could be performed safely in a man with a falling level of consciousness if the CT brain was normal (89/106, 84%). Early antibiotic administration was considered important, other management priorities such as oxygen therapy, volume resuscitation, and critical care involvement were not emphasised. Reported clinical practice in the investigation and management of meningitis in adults is not in line with current published guidance. Efforts to target interventions that promote consensus in practice are needed.


Target enzymes in serine-glycine-one-carbon metabolic pathway for cancer therapy.
Cancer cells selectively take up exogenous serine or synthesize serine via the serine synthesis pathway for conversion into intracellular glycine and one-carbon units for nucleotide biosynthesis. In this process, serine-glycine metabolism and the one-carbon cycle play vital roles, which is named serine-glycine-one-carbon metabolism (SGOC). The SGOC pathway is a metabolic network crucial for tumorigenesis with unexpected complexity and clinical importance. Accumulating evidence has demonstrated that metabolic enzymes in SGOC metabolism play key roles in tumorigenesis, metastasis and resistance to therapies. In this review, we focus on the involvement of serine and glycine in the folate-mediated one-carbon pathway during cancer progression and highlight the pathways through which cancer cells acquire and use one-carbon units. In addition, we discuss the recently elucidated effects of SGOC (folate cycle) metabolic enzymes in the occurrence and development of tumors and their links to drug resistance. Inhibitors of target enzymes in the SGOC pathway display promise as investigational new drug candidates for the treatment of tumors.


Key concepts relevant to quality of complex and shared decision-making in health care: a literature review.
High-quality provider-patient decision-making is key to quality care for complex conditions. We performed an analysis of key elements relevant to quality and complex, shared medical decision-making. Based on a search of electronic databases, including Medline and the Cochrane Library, as well as relevant articles' reference lists, reviews of tools, and annotated bibliographies, we developed a list of key concepts and applied them to a decision-making example. Key concepts identified included provider competence, trustworthiness, and cultural competence; communication with patients and families; information quality; patient/surrogate competence; and roles and involvement. We applied this concept list to a case example, shared decision-making for live donor kidney transplantation, and identified the likely most important concepts as provider and cultural competence, information quality, and communication with patients and families. This concept list may be useful for conceptualizing the quality of complex shared decision-making and in guiding research in this area.


Bone minerals in beta-thalassemia minor.
Homozygous beta-thalassemia is a severe hereditary disorder associated with osteopenia. Recently it was suggested that thalassemia minor may be a risk factor for osteoporosis. The purpose of the present study was to investigate this suggestion. Bone mineral status was assessed in 22 premenopausal women and 21 men with beta-thalassemia minor. In vivo neutron activation analysis was applied to measure hand-bone phosphorus (HBP), single-photon absorptiometry to measure forearm bone mineral content (BMC), and dual-energy X-ray absorptiometry to measure spinal bone mineral density (BMD). Comparison of the HBP, BMC, and BMD values with those of sex- and age-matched healthy subjects without the beta-thalassemia trait failed to indicate a statistically significant difference for either sex group. Concerning the biochemical markers of bone metabolism that were studied (serum calcium, phosphate, alkaline phosphatase, osteocalcin, and parathyroid hormone, and 3-h fasting urine calcium-to-urine creatinine ratio) no difference was observed between the study subjects and matched controls. In conclusion, the present study showed that subjects with beta-thalassemia minor are not at risk for osteoporosis.


Weight Bias, Shame, and Self-Compassion: Risk/Protective Mechanisms of Depression and Anxiety in Prebariatic Surgery Patients.
Psychopathology in bariatric surgery patients may contribute to adverse postoperative sequelae, including weight regain, substance use, and self-harm. This cross-sectional study aimed to advance the understanding of the risk and protective paths through which weight bias associates with depressive and anxiety symptoms in bariatric surgery candidates (BSC). BSC recruited from a surgical clinic (N = 213, 82.2% women, 43 [SD 12] years, mean BMI: 49 [SD 9] kg/m2 ) completed measures of experienced weight bias (EWB), internalized weight bias (IWB), body and internalized shame, and self-compassion; anxiety and depression screeners were accessed from medical charts. Multiple regression and PROCESS bootstrapping estimates tested our hypothesized mediation model as follows: EWB→IWB→body shame→shame→self-compassion→symptoms. After accounting for EWB and IWB, internalized shame accounted for greater variance in both end points than body shame. EWB was associated with greater anxiety through risk paths implicating IWB, body shame, and/or internalized shame. Protective paths associated EWB with fewer depressive and anxiety symptoms among those with higher self-compassion. The findings suggest a potentially important role for weight bias and shame in psychological health among BSC and implicate self-compassion, a trainable affect-regulation strategy, as a protective factor that may confer some resiliency. Future research using longitudinal and causal designs is warranted.


Trans-Pacific Partnership Provisions in Intellectual Property, Transparency, and Investment Chapters Threaten Access to Medicines in the US and Elsewhere.
Brook Baker describes the potential harms to global health from the Trans Pacific Partnership Agreement and its failure to balance the interests of patients and the public with those of industry.


Mediation of exciton concentration on magnetic field effects in NPB : Alq3-based heterojunction OLEDs.
Organic light-emitting diodes (OLEDs) are considered one of the most promising new display technologies owing to their advantages, such as all-solid-state, high color gamut, and wide viewing angle. However, in terms of special fields, the brightness, lifetime, and stability of the devices need further improvement. Therefore, heterojunction devices with different concentrations were prepared to regulate device brightness. The brightness of the bulk heterojunction device is enhanced by 9740 cd m-2, with a growth rate of about 26.8%. The impact of various temperatures and various exciton concentrations on the device magneto-conductance (MC) and magneto-electroluminescence (MEL) was investigated. Experimental results demonstrate that the exciton concentration inside the device can be tuned to improve optoelectronic properties and organic magnetic effects. The complex spin mixing process inside the bulk heterojunction device is deeply investigated, which provides a reliable basis for the design of bulk heterojunction devices.


Pharmacokinetics and effects of aminorex in horses.
To investigate the pharmacokinetics and behavioral effects of aminorex administered IV and PO in horses. 7 Thoroughbreds. In a cross-over design, aminorex (0.03 mg/kg) was administered IV or PO. Plasma and urinary aminorex concentrations were determined via liquid chromatography- mass spectrometry. Decrease of aminorex from plasma following IV administration was described by a 3-compartment pharmacokinetic model. Median (range) values of alpha, beta, and gamma half-lives were 0.04 (0.01 to 0.28), 2.30 (1.23 to 3.09), and 18.82 (8.13 to 46.64) hours, respectively. Total body and renal clearance, the area under the plasma time curve, and initial volume of distribution were 37.26 (28.61 to 56.24) mL x min/kg, 1.25 (0.85 to 2.05) mL x min/kg, 13.39 (8.82 to 17.37) ng x h/mL, and 1.44 (0.10 to 3.64) L/kg, respectively. Oral administration was described by a 2-compartment model with first-order absorption, elimination from the central compartment, and distribution into peripheral compartments. The absorption half-life was 0.29 (0.12 to 1.07) hours, whereas the beta and gamma elimination phases were 1.93 (1.01 to 3.17) and 23.57 (15.16 to 47.45) hours, respectively. The area under the curve for PO administration was 10.38 (4.85 to 13.40) ng.h/mL and the fractional absorption was 81.8% (33.8% to 86.9%). Aminorex administered IV had a large volume of distribution, initial rapid decrease, and an extended terminal elimination. Following PO administration, there was rapid absorption, rapid initial decrease, and an extended terminal elimination. At a dose of 0.03 mg/kg, the only effects detected were transient and central in origin and were observed only following IV administration.


A highly sensitive, mixed-phase assay for chloramphenicol acetyltransferase activity in transfected cells.
We describe a simple, rapid yet extremely sensitive assay for chloramphenicol acetyltransferase (CAT) activity in extracts from transfected eukaryotic cells. Using our modified reaction conditions and the mixed-phase assay, less than 0.000010 unit of CAT activity in transfected cells can be reliably detected. The mixed-phase assay is based on the inability of the polar [3H]-acetyl-Coenzyme A (CoA) substrate to partition out of a urea containing aqueous phase into the nonpolar scintillation fluor, while the [3H]chloramphenicol reaction products partition into the toluene scintillation fluor and are quantitated by scintillation counting. The increased sensitivity of this assay is due to the optimization of the acetyl-CoA concentration, to a urea-containing aqueous phase which lowers the assay background, and to the use of extract blanks. The mixed-phase assay is simpler, is quantitative, uses less costly substrates, and is far more sensitive than the most widely used CAT assays, which require solvent extraction followed by thin-layer chromatography to separate the unreacted substrate from product.


Silver staining of histones in Triton-acid-urea gels.
A reliable method for silver staining histones in Triton-acid-urea gels was developed. Optimum staining is achieved by treating the gels either with amido black or a colorless, water-soluble analog of amido black, 2,7-naphthalenedisulfonic acid, prior to staining with ammoniacal silver. Staining of purified calf thymus histones H2A, H2B, H3, and H4 by this method is 30 times more sensitive than staining with amido black alone, allowing the detection of each histone and its modified forms down to the nanogram level. The use of 2,7-naphthalenedisulfonic acid dramatically shortens the procedure permitting histone patterns to be visualized within 5 h.


Telomere shortening in T lymphocytes of older individuals with Down syndrome and dementia.
Telomere shortening has been recently correlated with Alzheimer's disease status. Therefore, we hypothesized that a possible association might exist for adults with Down syndrome (DS). Using blind, quantitative telomere protein nucleic acid FISH analyses of metaphase and interphase preparations from 18 age-matched trisomy 21 female study participants with and without dementia, we have observed increased telomere shortening in adults with DS and dementia (p < .01). From this initial study, we conclude that telomere shortening is associated with dementia in this high-risk population and suggest that additional research may show that telomere shortening may be a biological marker of dementia status.


miR-185-5p / ATG101 axis alleviated intestinal barrier damage in intestinal ischemia reperfusion through autophagy.
Intestinal ischemia-reperfusion (II/R) is a common pathological injury in clinic, and the systemic inflammatory response it causes will lead to multiple organ damage and functional failure. miR-185-5p has been reported to be a regulator of inflammatory response and autophagy, but whether it participates in the regulation of autophagy in II/R is still unclear. Therefore, we aimed to explore the mechanism of miR-185-5p regulating intestinal barrier injury in (II/R). Caco-2 cells was induced by oxygen-glucose deprivation/reoxygenation (OGD/R) to establish II/R model. The superior mesenteric artery of C57BL/6 mice was clamped for 45 min and then subjected to reperfusion for 4 h for the establishment of II/R mice model. miR-185-5p mimic, miR-185-5p inhibitor, pcDNA-autophagy-related 101 (ATG101) were respectively transfected into Caco-2 cells. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to assess miR-185-5p expression. Western blot detected the level of ATG101 and tight junction-associated proteins ZO1, Occludin, E-cadherin, β-catenin, as well as autophagy markers ATG5, ATG12, LC3Ⅰ/Ⅱ, Beclin1 and SQSTM1. Transepithelial electrical resistance (TEER) values was detected by a resistance meter. FITC-Dextran was performed to measure cell permeability. 5-ethynyl-2'-deoxyuridine (EDU) staining measured cell proliferation. Transmission electron microscope was conducted to observe autophagosomes. Hematoxylin & eosin (H&E) staining observed the damage of mice intestinal. Immunohistochemistry (IHC) measured the percentage of ki67 positive cells. TdT-mediated dUTP nick-end labeling (TUNEL) assay assessed cell apoptosis in intestinal tissues of II/R. Dual-luciferase assay verified the targeting relationship between miR-185-5p and ATG101.Results miR-185-5p was overexpressed in OGD/R-induced Caco-2 cells and intestinal tissues of II/R mice. Knocking down miR-185-5p markedly promoted autophagy and TEER values, reduced cell permeability, and alleviated intestinal barrier damage. ATG101 was a target of miR-185-5p, and overexpression of ATG101 promoted autophagy and dampened OGD/R-induced intestinal barrier damage. Overexpression of miR-185-5p reversed the effect of overexpressed ATG101 on OGD/R-induced Caco-2 cells. Knockdown of miR-185-5p enhanced autophagy and alleviated II/R intestinal barrier damage by targeting ATG101.


Restriction sites containing CpG show a higher frequency of polymorphism in human DNA.
Unique loci in the human genome were examined with restriction enzymes in order to detect restriction fragment length polymorphisms (RFLPs). Of 31 arbitrary loci, nine were detectably polymorphic, reflecting ten polymorphic restriction sites. Nine of the ten polymorphic sites were revealed with two restriction enzymes, Msp I and Taq I, whose recognition sequences have in common the dimer sequence CpG. The cytosines in the CpG sequence are known to be frequently methylated in mammals, and the occurrence of significant variation in Msp I and Taq I sites supports the view that methylated cytosine residues are hotspots for mutation in mammalian DNA.


Breast Implant-Associated Anaplastic Large Cell Lymphoma: Defining Future Research Priorities.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that is exclusively associated with textured-surface breast implants. This clinical review provides an update on the diagnosis and management of BIA-ALCL with an emphasis on major advances. The epidemiology and pathophysiology of the disease are also reviewed, focusing on current paradigm shifts and highlighting current controversies related to disease classification and risk mitigation. Finally, the authors conclude by discussing medicolegal and ethical issues surrounding BIA-ALCL while establishing a future basic science and clinical research agenda that is central to improving patient safety.


Radiofrequency ablation for subcapsular hepatocellular carcinoma.
Limited data from recent studies suggested an increased risk of bleeding complications, needle-track seeding, and local recurrence after radiofrequency ablation (RFA) of subcapsular hepatocellular carcinoma (HCC). Between May 2001 and October 2002, 80 patients underwent RFA of 104 HCC nodules. Forty-eight patients had subcapsular HCC (group I), whereas the other 32 patients did not have subcapsular HCC (group II). RFA was performed via celiotomy, laparoscopy, or a percutaneous approach. Subcapsular HCCs were ablated by indirect puncture through nontumorous liver, and the needle track was thermocoagulated. There were no significant differences between groups in treatment morbidity (14.6% vs. 15.6%; P =.898), mortality (2.1% vs. 0%; P = 1.000), complete ablation rate after a single session (89.4% vs. 96.9%; P =.392), local recurrence rate (4.3% vs. 12.5%; P =.216), recurrence-free survival (1 year: 60.9% vs. 49.2%; P =.258), or overall survival (1 year: 88.3% vs. 79.4%; P =.441). After a median follow-up of 13 months, no needle-track seeding or intraperitoneal metastasis was observed. This study shows that the results of RFA for subcapsular HCCs are comparable to those of RFA for nonsubcapsular HCCs. Subcapsular HCC should not be considered a contraindication for RFA treatment.


Evaluation of the white matter integrity in morbidly obese patients before and after bariatric surgery; a diffusion tensor imaging study.
To investigate the difference in FA (Fractional anisotropy), ADC (Apparent diffusion coefficient), RD (Radial diffusivity) and AD (axial diffusivity) values of white matter (WM) tracts in morbidly obese subjects before and after bariatric surgery (BS). A group of thirty-nine morbidly obese subjects are evaluated before and 4-6 months after BS. ADC, FA, RD and AD values of 17 distinct neuroanatomic localizations are measured and DTI parameters are analyzed. Following the BS, the patients' mean BMI decreased from 47.665.21 to 31.723.97. A significant difference is displayed between the pre-surgery and post-surgery FA values of SLF, SFOF, ALIC, fornix, ILF, CST, MCP (p = 0.010, p < 0.001, p = 0.048, p = 0.014, p = 0.012, p = 0.012, p = 0.040 respectively). Following BS, decrease in FA values in the mentioned areas are detected. ADC values obtained from MCP are significantly lower in the post-BS period compared to pre-BS period (p = 0.018). There was a statistically significant difference between the pre-surgery and post-surgery AD values of SLF, SFOF, ILF, ALIC, EC, CST, and MCP (p = 0.001, p = 0.022, p = 0.001, p = 0.011, p = 0.001, p = 0.000, p = 0.000, respectively). Following the BS, AD values of the SLF, SFOF, ILF, ALIC, EC, CST, and MCP are decreased. RD values measured from GCC are significantly lower in the post-BS period compared to pre-BS period (p = 0.008). Our study supported the hypothesis of the BS-induced reversibility of the low-grade inflammation in WM tracts in the morbidly obese group following BS. Our DTI results may represent the subacute period findings of the reversal of low-grade inflammation after BS.


Retrospective assessment of patterns of recurrence relative to radiotherapy volumes for adjuvant conformal chemoradiotherapy in gastric cancer.
Since the Intergroup 0116 study was published in 2000, adjuvant postoperative chemoradiotherapy using CT-planned and 3D conformal/intensity-modulated radiotherapy has been offered routinely to fit patients with resected gastric cancer at Princess Margaret Hospital .The objective of this study was to analyze patterns of disease recurrence with respect to the radiotherapy volumes. For the date and site (local, locoregional, or distant) of the first recurrence, medical records were reviewed for all patients treated at Princess Margaret Hospital with adjuvant chemoradiotherapy for resected gastric adenocarcinoma (January 1, 2000 to November 30, 2009). Patients whose recurrences were limited to local and/or regional sites were selected for further analysis. Available diagnostic imaging of the recurrence site was registered to the original planning radiotherapy dataset for contouring. If necessary to respect changes in anatomy, the contour was translocated on the basis of anatomic descriptors. The center of mass for each recurrence was identified as a point and its location was categorized according to the isodose encompassing it; in field (90 % or more), marginal (50-89 %), or out of field (less than 50 %). Of all 197 patients, 14 (7 %) had isolated locoregional failure, constituting 20 % of all 71 patients with a recurrence. Successful fusions were feasible in five cases. Of these recurrences, four were in field and one was marginal. In a further four cases, visual inspection was used, showing one in-field recurrence, one marginal recurrence, and two out-of-field recurrences. In five patients, either a useable original dataset or diagnostic imaging of the recurrence was not available. The rates of isolated local/locoregional tumor recurrence in this study were low. Of the small number of recurrences available for analysis, most (five of nine) were in field. Further studies involving a larger cohort of patients might allow a more meaningful analysis of trends in the recurrence site with evolving radiotherapy techniques.


Dentinal fluid dynamics in human teeth, in vivo.
Cavities were prepared in human premolars scheduled for extraction for orthodontic reasons. The smear layer was removed from the dentin surface by acid etching, and the cavity was sealed using a hollow chamber. The chamber was filled with sterile saline solution and connected via tubing to a hydraulic circuit featuring an adjustable pressure reservoir and a device that measures fluid movement across dentin. In the absence of any exogenous pressure, all cavities exhibited an outward fluid flow rate of 0.36 microliters min-1 cm-2. As exogenous pressure was applied to the cavity, the outward flow slowed. The exogenous pressure that stopped outward fluid flow was taken to be equal to normal pulpal tissue pressure. The mean value was 14.1 cm H2O in five teeth. This simple method permits measurement of dentinal fluid flux, the hydraulic conductance of dentin, and estimates pulpal tissue pressure.


Minimal sequence requirement of thrombin receptor agonist peptide.
A site-specific proteolytically generated neoamino terminus of the thrombin receptor having a sequence SFLLRNPNDKYEPF- has been reported to be a functional ligand of the receptor. This discovery raises question on the precise structural requirements of the "tethered ligand" responsible for receptor activation and signal transduction. By examining the agonist activity of a panel of synthetic sequence analogues of thrombin receptor agonist peptides (TRAP) on human platelet aggregation, we determined that the minimal sequence of the human platelet thrombin receptor ligand is SFLL-amide (TRAP1-4, EC50 = 300 uM). An extension of TRAP1-4 by an additional Arg-Asn segment yielded the most potent agonist among the series (TRAP1-6, EC50 = 1.3 microM). Based on the structure-activity relationships, we hypothesized a model of the ligand-binding site of the human platelet thrombin receptor that accommodates a hexapeptide structure. TRAP1-6, when administered intravenously, induced marked intravascular platelet aggregation in the anesthetized guinea pigs.


Possibility of microorganism elimination from the blood using modified coal hemosorbents.
We studied the possibility of using coal hemosorbents for elimination gram-positive and gram-negative microorganisms from the blood. After hemosorption, the number of S. aureus and K. pneumoniae pneumoniae colony-forming units significantly decreased. The obtained results indicate that coal sorbents can bind and probably eliminate gram-positive and gram-negative bacteria from the blood.


Respiratory drive and pattern during inertially-loaded CO2 rebreathing: implications for models of respiratory mechanics in obesity.
Chest wall inertance (Iw) constitutes a mechanical load which is small in normal individuals, but increases in the morbidly obese. The effect of increased Iw on respiratory drive and pattern has not previously been investigated. We studied this effect by measuring rebreathing CO2 response in 10 normal subjects with and without a 45.5 kg inertial load. Changes in inspiratory occlusion pressure (P0.1), ventilation, respiratory rate, mean inspiratory flow (VT/TI) duty cycle (TI/TT), inspiratory and expiratory times, and [P0.1/(VT/TI)] were assessed. The P0.1 vs. PETCO2 response shifted to the left during inertial loading, while the slope remained unchanged (x-intercept = 36.7 +/- 4.9 mm Hg unloaded vs. 32.7 +/- 7.5 mm Hg loaded, P less than 0.05), increasing P0.1 from 18.5 +/- 8.0 to 21.0 +/- 7.6 cm H2O at PETCO2 = 6.5 mm Hg (P less than 0.005). Respiratory pattern was unchanged with the inertial load except for a slight decrease in tidal volume. The inspiratory transfer characteristic [P0.1/(VT/TI)] at PETCO2 = 65 mm Hg increased significantly (8.3 +/- 2.0 to 10.5 +/- 2.9 cm H2O.(L.sec-1)-1, P less than 0.025) illustrating the strategy of maintaining similar ventilation by increasing inspiratory force against the load.


Development of rat pancreatic islet cells in vitro.
Islet cell lines were produced by retroviral transduction of SV-40 T antigen to monolayer cultures of neonatal rat islets. One line, RN0-11, showed evolution of phenotypes in vitro. It evolved from a non-hormone secreting cell line to an insulin secreting line. It further developed glucagon producing capability before it lost all hormone producing phenotypes. At passage 8, RN0-11 cells secreted a small amount of insulin 25 ng/10(6) cells/24 hours. They were unresponsive to glucose and secreted 1.7-1.9 ng of insulin/10(6) cells/2 hours under various levels of glucose. At passage 16, they secreted 2,577 ng of insulin/10(6) cells/24 hours and responded to glucose stimulation in static incubation. The insulin secreted by these cells at 0, 2.8, 5.5, 11.1, 16.7, and 27.7 mM of glucose was 6.46 +/- 2.56, 17.74 +/- 2.66, 32.24 +/- 0.58, 30.66 +/- 1.59, 33.55 +/- 4.83, and 20.95 +/- 2.17 ng/10(6) cells/2 hours respectively. The responsiveness to glucose and the ability to secrete insulin diminished as cells were passaged in culture, and by passage 35 no insulin was detectable in medium under any level of glucose tested. Northern blot analyses also showed corresponding changes of insulin expression in these cells at different passages. In addition, glucagon was detectable at passage 14 by immunocytochemistry and at passage 16 by Northern blot analysis. By passage 35, no insulin or glucagon expression was detectable by Northern blot analysis or immunocytochemistry. Immunocytochemical staining of these cells at passage 14 showed insulin-positive and glucagon-positive cells and cells positive for both insulin and glucagon. Presence of insulin and glucagon in the same cells suggests single clonality of the cell line. The evolution of RN0-11 cells in vitro provides an opportunity to study the development of islet cells.


Primary psoas abscess three years after ipsilateral nephrectomy.
We report an unusual case of primary, right psoas abscess caused by Proteus mirabilis which developed three years after ipsilateral nephrectomy. The diagnosis was established by computer tomography, recommended today as superior to other diagnostic methods of demonstration for the retroperitoneum.


Evaluation of oral tissue response and blood levels of mercury released from dental amalgam in rats.
Dental amalgam is the most common restorative material used in dentistry. It was reported that amalgam might constitute potential toxic hazards to pregnant patients and foetuses through mercury release and absorption. The present study aimed to investigate the vital tissue response in contact to dental amalgam plus determination of blood mercury levels in mother and offspring Wistar strain albino rats. Pregnant mothers were divided into two main groups each had dental amalgam implanted into either an oral mucosa incision or a bony socket following extraction. Third and fourth groups included the offspring rats of mothers from the first and second groups, respectively. The blood mercury levels and histopathology of oral tissues were analyzed in mothers at one and six months post-implantation and in offspring rats one day after birth. The blood mercury levels of mothers increased significantly at six months (P<0.01) as compared to levels at one month. However, blood mercury levels were not significant (P>0.05) when the two offspring (third and fourth) groups were compared. Histopathology results from mothers showed inflammatory response at the bottom of the socket, one month after amalgam implantation. At six months, teeth germs showed vacuolation of the abnormal odontoblasts with globular dentine formation. Degenerated periodontal fibres and thin trabeculae forming the bony sockets with large marrow spaces were evident. A fibrous connective tissue capsule surrounded the amalgam mass inside the mucosa of mothers at one month and was evident also at 6 months with a huge inflammatory cell infiltrate. Teeth germs showed elongated odontoblasts with intercellular oedema, thinner dentine and bony trabeculae with wider marrow spaces. Offspring rats showed comparable oral tissue response. There is a positive correlation between blood mercury levels and oral tissue response in mothers, however, the negative impact of mercury on oral tissues of offspring rats was due to high mercury levels in their mothers' blood during pregnancy. We would recommend that women should - as far as possible - postpone having dental amalgam filling placed or removed during pregnancy to avoid its harmful effect on the foetus. Further clinical studies are recommended to test our findings in man.


Extension of the liquid chromatography/quantitative structure-property relationship method to assess the lipophilicity of neutral, acidic, basic and amphotheric drugs.
A reported chromatographic method to determine the 1-octanol/water partition coefficient (logP(o/w)) has been used to estimate the lipophilicity of 33 drugs with diverse structures and functionalities, including neutral, acid, basic, and amphoteric compounds. The applicability of the chromatographic method has been extended to the UHPLC technique, and the results obtained were compared to those obtained from conventional HPLC. No significant difference between the results obtained by both techniques is noticed. Thus, the suitability of UHPLC, which involves shorter run times, for lipophilicity assessment is demonstrated. In order to show the consistency of this chromatographic method, the logP(o/w) values of those drugs which have acid-base properties have been also determined by potentiometry, and the final results have been compared with both values derived from the chromatographic method and the ones from the literature.


Neurovascular Complications in Forty-Nine Cases Elbow Arthroscopy and Review Literatures.
An elbow arthroscopic surgery is a minimally invasive surgery. There were several international publications report neurovascular complications in elbow arthroscopic surgery. But there was no study which was conducted in Thailand To report the result of elbow arthroscopic surgery which focus on the neurovascular complications. A retrospective review of elbow arthroscopic surgery between April 2011 to May 2014 at HRH Princess Maha Chakri Sirindhorn Medical Center Srinakharinwirot University in Nakhon Nayok province was performed. The data of complications were collected since immediately after surgery until 6 weeks after procedure. Forty-nine elbow arthroscopic surgeries were performed in 44 patients. The authors found total complications occurred in 2 cases (4%) which were minor complications. One case was transient cutaneous nerve injury (2%) and another case was cellulitis around a portal site (2%). No serious or permanent complication was detected. Elbow arthroscopic surgery is considered a safe operation, because only one minor neurological complication was observed and no major neurovascular complications were detected.


Triggering through NOD-2 Differentiates Bone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity.
Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naïve T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-αβ signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens.


Robotic right colectomy using the Da Vinci Single-Site® platform: case report.
While single-port laparoscopy for abdominal surgery is technically challenging, the Da Vinci Single-Site® robotic surgery platform may help to overcome some of the difficulties of this rapidly evolving technique. The authors of this article present a case of single-incision, robotic right colectomy using this device. A 74-year-old female with malignant polyp of caecum was operated on with a single-site approach using the Da Vinci Single-Site® robotic surgery device. Resection and anastomosis were performed extra-corporeally after undocking the robot. The procedure was successfully completed in 200 min. No surgical complications occurred during the intervention and the post-operative stay and no conversion to laparotomy or additional trocars were required. To the best of our knowledge, this is the first case of right colectomy using the Da Vinci Single-Site® robotic surgery platform to be reported. The procedure is feasible and safe and its main advantages are restoration of triangulation and reduced instrument clashes.


[Cystic teratoma of the caecum, demonstrating as an ovarian tumor: case report and literature review].
Benign cystic teratoma of the caecum of 24 year woman interpreted as an ovarian tumor. Rare case that can contribute to the gynecology theory, practice and diagnostic.


DNA denaturation kinetics in CHO cells exposed to different X-ray doses and after different repair intervals using the alkaline unwinding technique.
The kinetics of DNA denaturation in alkaline solution (pH 12.2) was studied in CHO cells using the alkaline unwinding technique. After X-ray doses of 0, 3, 5 and 9 Gy, the kinetics of alkaline denaturation was found to be independent of the number of induced strand breaks confirming earlier studies on this subject. In addition, the denaturation kinetics measured in cells exposed to 9 Gy were found to be identical for different repair intervals. This result shows that for the three different classes of DNA strand breaks described previously (Dikomey and Franzke 1986a) strand separation in alkaline solution occurs at the same kinetics. As a consequence, the relationship between the numbers of strand breaks and the fraction of remaining double-stranded DNA is considered the same for the three different classes.


[Spontaneous splenic rupture. Case report and literature review].
Spontaneous splenic rupture is often life threatening due to delay in diagnosis and treatment. Abdominal pain, Kehr's sign, nausea, bloating, altered consciousness, and intestinal obstruction may be present. In larger splenic lesions, signs of peritonitis and hypovolemic shock are present. Contrast-enhanced computed tomography is the election study. Diagnosis is confirmed by negative viral serology and normal spleen on gross and histopathologic inspection. The most frequent treatment in splenectomy. A 30-year-old male with no medical history presented with generalized abdominal pain accompanied by Kehr's sign. He is diagnosed with ruptured spleen by contrast-enhanced computed tomography and successfully treated with splenectomy. He was discharged 6 days after surgery. Spontaneous rupture of the spleen is uncommon, but with high morbidity and mortality. It must be a differential diagnosis in the face of abdominal and/or chest pain, and the corresponding imaging studies should be carried out if the patient's conditions allow it, or their search during an exploratory laparotomy.


Cellular internalization of human calcitonin derived peptides in MDCK monolayers: a comparative study with Tat(47-57) and penetratin(43-58).
The objective of this study was to evaluate key motif requirements of human calcitonin (hCT)-derived peptides for the permeation through the plasma membrane of MDCK monolayers, as epithelial model. Truncated and sequence-modified fluorescent-labeled hCT-derived peptides were synthesized through Fmoc chemistry. Peptide uptake by confluent MDCK was observed by confocal laser scanning microscopy. The cytotoxic effect of the peptides on cellular integrity was followed by LDH release. For direct comparison we covered the cellular uptake of established cell penetrating peptides, Tat(47-57) and penetratin(43-58). Truncated sequences of hCT, from hCT(9-32) to hCT(18-32), penetrated the plasma membrane and demonstrated a sectoral, punctuated cytoplasmic distribution. The uptake process appeared to be temperature-, time- and concentration-dependent. Amino acid modifications of hCT(18-32) indicated that both the proline in position 23 and the positive charge of lysine in position 18 are crucial for peptide uptake. The reverse sequence hCT(32-18) did not penetrate the membrane, indicating the importance of sequence orientation. Tat(47-57) and penetratin(43-58) showed a similar punctuated cytoplasmic distribution in MDCK and HeLa cell lines. No relevant toxicity was observed. Selected hCT-derived peptides have cell penetrating properties. The uptake mechanism seems to involve an endocytic pathway.


Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression.
Hippocampal N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic depression (LTD) is associated with a persistent dephosphorylation of the GluR1 subunit of AMPA receptors at a site (Ser-845) phosphorylated by cAMP-dependent protein kinase (PKA). In the present study, we show that dephosphorylation of a postsynaptic PKA substrate may be crucial for LTD expression. PKA activators inhibited both AMPA receptor dephosphorylation and LTD. Injection of a cAMP analog into postsynaptic neurons prevented LTD induction and reversed previously established homosynaptic LTD without affecting baseline synaptic transmission. Moreover, infusing a PKA inhibitor into postsynaptic cells produced synaptic depression that occluded homosynaptic LTD. These findings suggest that dephosphorylation of a PKA site on AMPA receptors may be one mechanism for NMDA receptor-dependent homosynaptic LTD expression.


Is PostureScreen® Mobile app an accurate tool for dentists to evaluate the correlation between malocclusion and posture?
To determine whether PostureScreen® Mobile app is a useful, simple tool that is accessible for dentists to evaluate the correlation between malocclusion and posture. Twenty-nine subjects underwent static and dynamic dental occlusion examinations and a postural exam with PostureScreen® Mobile app, a photographic method. The subjects were divided into groups depending on their static and dynamic occlusion features. The postural parameters were then compared between these groups. Statistically significant differences (p < 0.05) for some postural parameters were obtained for Angle Class 1 vs. 2 and 3 and for the passive interference group and active premature contacts group during left lateral movement. There were no statistically significant differences regarding protrusion and right lateral movement. Dental occlusion anomalies and posture pathological modifications can be inter-related. PostureScreen® Mobile app might represent a useful tool in the early diagnosis of dental occlusion pathology.


Creative thinking and interests of eleven- and twelve-year-olds.
Scores on What I Like To Do were not shown practical for predicting creative thinking in 100 11- and 12-year-olds from low-income backgrounds. Interests did account for a significant proportion of the variance (36%) in common with Torrance's total creative thinking score in the 50 girls. Suggestions for research are offered.


Status of free-radical oxidation and proliferation processes in patients with atopic dermatitis and lichen planus.
We studied the status of proliferation processes (by Ki-67 expression) and biogenesis of free radicals (by chemiluminescence method) in skin biopsy specimens from patients with atopic dermatitis and lichen planus. The index of Ki-67-positive nuclei significantly (p<0.05) increased to 28.40±2.00% in patients with dermatitis and to 32.6±1.9% in patients with lichen planus vs. 8.65±1.31% in the reference sample. Decompensated accumulation of free-radical oxidation products and inhibition of detoxification systems in skin biopsy specimens indicate the development of local oxidative stress. After therapy consisting of two 10-day courses of thymodepressin injections (0.1%, 1.0 ml) over 30 days, normalization of epidermis proliferation was observed. Labeling index in atopic dermatitis and lichen planus significantly decreased (p<0.05) to 17.00±1.87 and 10.9±1.1%, respectively. The role of free radicals in the development of hyperregeneratory processes during dermatoses is discussed.


Impurity analysis of pure aldrin using heart-cut multi-dimensional gas chromatography-mass spectrometry.
Identification and quantification of related-structure impurity is a research focus in the purity assessment of organic compounds. Determination of the purity value and uncertainty assessment are also important in the metrological research. A method for the determination of related-structure impurity in pure aldrin sample has been developed by using heart-cut multi-dimensional gas chromatography-mass spectrometry (MDGC/MS). Compared to the traditional one-dimensional (1-D) GC system, the two separated columns in the MDGC/MS system can effectively reduce co-elution, enhance separation capability, and thus improve detectability of the trace-level impurities. In addition, MDGC/MS system was simultaneously equipped with flame ionization detector (FID) or electron capture detector (ECD) in the first GC unit and mass spectrometry (MS) detector in the second GC unit. Therefore, accurate quantitative results of the trace-level impurities can be easily achieved by isolation of principal component to the second dimension column using "heart-cut" process. The mass fraction of related-structure impurities in aldrin samples obtained using MDGC/MS system ranged from 6.8×10⁻³ mg g⁻¹ to 26.47 mg g⁻¹ with five orders of magnitude, which is hard to be realized by mean of the 1-D GC. Excellent linearity with correlation coefficients of above 0.999 was achieved for each impurity analysis over a wide range of concentrations. Limits of quantification (LOQ) varied from 250 ng g⁻¹ to 330 ng g⁻¹ for FID, and from 1.0 ng g⁻¹ to 2.0 ng g⁻¹ detected by ECD. The combined standard uncertainty (u(c)) was lower than 0.37 mg g⁻¹ and 0.040 mg g⁻¹ detected using FID and ECD, respectively. Therefore, performance characterization of MDGC/MS used in the study is fit for quantification analysis of trace-level impurity. These results demonstrate that the MDGC/MS is extremely suitable for the purity assessment of organic compounds with medium structural complexity and low polarity.


Synthesis and antimicrobial properties of 2-(benzylidene-amino)-benzo[d]isothiazol-3-ones.
The in vitro antimicrobial activity of 2-amino-benzo[d]isothiazol-3-one and of several 2-arylideneamino derivatives carrying in the second position a substituted or unsubstituted aromatic ring or an arylalkenylidene moiety was determined by the broth dilution method against several strains selected to define their spectrum and potency. All the compounds demonstrated good antibacterial properties against Bacillus subtilis, streptococci, enterococci and staphylococci including penicillin-resistant clinical isolates. Several compounds showed excellent inhibitory properties against Streptococcus pyogenes, which is the most sensitive microorganism tested. Many benzisothiazolones exhibited good activity against Gram-negative Haemophilus influenzae. As regards antifungal activity, several of the tested compounds inhibited Saccharomyces cerevisiae at concentrations of 3-6 microg ml-1. In all cases the parent 2-amino-benzo[d]isothiazol-3-one was the most effective agent, with minimum inhibitory concentration (MIC) values ranging from 0.07 to 6 microg ml-1. The results obtained indicate that most of these compounds are wide-spectrum antimicrobial substances and promising agents against penicillin-resistant staphylococci.


Acteoside (Verbascoside): A Prospective Therapeutic Alternative against Hepatocellular Carcinoma by Inhibiting the Expression of AXL, FGFR, BRAF, TIE2 and RAF1 Targets.
Hepatocellular carcinoma (HCC) is the world's second leading cause of cancerrelated mortality and the fifth most prevalent cancer overall. Several synthetic and plant-based remedies are in practice to treat diverse liver disorders. Because of their minimal side effects and protective characteristics, plant phenolics have the potential to become alternative therapeutics, replacing currently existing HCC medications. The present study identifies the plant phenolics as having the capacity to inhibit HCC with low side effects and cost efficiency. Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality, despite the proven effectiveness of screening programs for at-risk individuals, the majority of patients have disease progression or tumor characteristics that preclude curative therapies at the time of diagnosis. Acteoside (Verbascoside) is a naturally occurring phenylethanoid glycoside found throughout the plant kingdom. Acteoside is a physiologically active chemical with the number of pharmacological and protective effects against various liver illnesses. Currently used HCC medications have a variety of side effects. Plant-based chemicals offer the possibility of treating HCC with minimal side effects. The work is targeted to find the best phytochemical (plant phenolic) lead molecule for future drug development research against Hepatocellular carcinoma. The targets were selected based on an analysis of relevant literature, and the 3D structures of the selected receptors were obtained in. pdb format from the RCSB-Protein data bank (PDB, http://www.rscb.org/pdb). Based on a review of the literature, sixty plant secondary metabolites, or plant phenolics, were selected. The ligand structures were obtained and downloaded in.sdf format from the NCBI PubChem chemicals database (https://pubchem.ncbi.nlm.nih.gov/). Molecular docking between the receptor and ligands was accomplished using the Molegro Virtual Docker 6.0 (MVD) software. The target RAF1, BRAF chain 1, TIE2 chain 2 FGFR1, FGFR2, AXL, and FGFR4 showed the best binding effectiveness with acteoside compared to their respective positive control. RET chain 1 and BRAF chain 2 acteoside showed prominent binding efficacy after Curcumin, and Epigallocatechingallate, respectively, against positive control. Present findings clearly point towards the potentiality of acteoside in inhibiting various HCC targets. Acteoside may be used as a prominent lead molecule in the future treatment of hepatic cancer with its multifaceted binding efficiencies against various target proteins.


Analysis of the "NIMA effect" in renal transplantation. Collaborative Transplant Study.
In an analysis of 5,000 parent-to-child kidney transplants performed from 1983 to 1989, we found no evidence that maternal donor grafts had a better outcome than grafts from paternal donors. We conclude that a "NIMA effect" does not exist in renal transplantation.


High yield post-thermal treatment of bulk graphitic carbon nitride with tunable band structure for enhanced deNOx photocatalysis.
The bulk graphitic carbon nitride (CN) suffers from low specific surface area, which limits its practical application for air purification. Here, we reported a facile post-thermal treatment to break bulk CN into nanosheets whose specific surface areas increased from 13.6 m2 g-1 to 68.0 m2 g-1. The yield of CN nanosheets reached up to 67%, and its photocatalytic decomposition of NOx activity was about 3.0 times higher than that of bulk CN. Moreover, the CN nanosheets obtained at 550 °C with higher specific surface area (113.9 m2 g-1) displayed lower photocatalytic activity than that obtained at 500 °C with lower specific surface area (68.0 m2 g-1), which was attributed to its lower valence band. This study illustrates that many factors including specific surface area and band structure could affect the performance of photocatalysts so that it is necessary to take account of various factors. Moreover, the facile and high yield thermal treatment provides the foundation for further large-scale industrial applications.


Specific allelic loss of p16 (INK4A) tumor suppressor gene after weeks of iron-mediated oxidative damage during rat renal carcinogenesis.
Oxidative tissue damage has been shown to be associated with carcinogenesis. In human cancers p16(INK4A) is one of the most frequently mutated tumor suppressor genes. The present study used the ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model to determine whether oxidative damage can cause specific allelic loss of p16 (INK4A). By the use of fluorescent in situ hybridization in combination with imprint cytology at single-cell resolution, we found that the number of renal tubular cells with aneuploidy (1 or 3 signals) at the p16(INK4A) locus was significantly and specifically increased (1 week, 37.2 +/- 2.3%; 3 weeks, 37.8 +/- 1.3% vs control, 22.5 +/- 1.9%; mean +/- SE, N = 8; P < 0.001 and P < 0.0001, respectively) after repeated intraperitoneal administration of 5 to10 mg of iron/kg in the form of Fe-NTA for 3 weeks. No increase in aneuploidy was observed at the loci of either the p53 or vhl tumor suppressor gene. Furthermore, the increase in the cells with 3 signals was followed by a continuous increase in those with 1 signal. Therefore, the p16 (INK4A) locus is specifically vulnerable to oxidative damage, leading to its allelic loss within weeks, presumably due to a deficiency in the replication of both the alleles.


"Saying one thing and doing another": examining the impact of event order on hypocrisy judgments of others.
This study investigated whether the temporal order of people's expressed statements and their behaviors affected others' judgments of hypocrisy, and why. It was proposed that hypocrisy would be greater when a statement establishing a personal standard preceded a behavior violating that standard as opposed to the reverse order. This order effect occurred in three studies, generalizing across two topic areas (healthy living and safe sex) and for both normative and non-normative statements (pro/anti-safe sex). Mediation analyses indicated that the reverse order mitigated against hypocrisy because the target's inconsistency was attributed to dispositional change. The discussion addresses additional variables likely to affect hypocrisy and the relationship of this research to hypocrisy paradigms in dissonance.


Termination of pregnancy following prenatally diagnosed central nervous system malformations.
To analyze fetal cerebral malformations with late termination of pregnancy (TOP) and to evaluate the rate of cases that could have been detected earlier using international recommended requirements of sonographic examination of the fetal central nervous system (CNS). Cases of singleton pregnancies above 18 + 0 weeks of gestation ending in late TOP due to fetal CNS malformations between 2002 and 2011 were retrospectively reviewed. The cases were divided into isolated and non-isolated cerebral malformations. Prevalence and timing of TOP were assessed relative to the identified malformations. During this 10-year period, 212 (20.8%) out of 1017 late TOPs were performed in pregnancies with fetal cerebral malformations. 59 cases were excluded because of chromosomal anomalies. 86 (56.2%) of the remaining 153 cases were isolated cerebral malformations while 67 (43.8%) were non-isolated. TOP after viability (≥ 24 + 0 weeks of gestation) was performed in 61.4% (94/153). Substantial morbidity (n = 80; 52.3%) and mental retardation (n = 33, 38.4%) made up the leading prognostic groups. In about 80% of detectable anomalies, diagnosis of CNS malformation could have been made earlier by following international guidelines of fetal CNS examination at second trimester scan. General implementation of ultrasound screening in maternity care can significantly reduce the number of late TOPs in Germany.


Perceiving and naming actions and objects.
Neuropsychological studies have suggested differences in the cortical representations of verbs and nouns. Assessment of word-class specific deficits often relies on picture naming with different sets of images used for action and object naming. Such a setup may be problematic in neuroimaging studies, as the perception of the image and the actual differences in retrieving verbs or nouns become intertwined. To address this issue, we investigated how different sets of images affect the pattern of activation in action and object naming. In the present fMRI experiment, healthy volunteers silently performed both action and object naming from action images, and object naming from object-only images. A similar network of cortical areas was activated in all three conditions, including bilateral occipitotemporal and parietal regions, and left frontal cortex. With action images, noun retrieval enhanced activation in bilateral parietal and right frontal cortex, areas previously associated with visual search and attention. Increased activation in the left posterior parietal cortex during this condition also suggests that naming an object in the context of action emphasizes motor-based properties of objects. Action images, regardless of whether verbs or nouns were named, evoked stronger activation than object-only images in the posterior middle temporal cortex bilaterally, the left temporo-parietal junction, and the left frontal cortex, a network previously identified in processing of action knowledge. The strong influence of perceptual input on neural activation associated with noun vs. verb naming can in part explain discrepancies in previous lesion and functional neuroimaging studies on the processing of nouns and verbs.


Visualization of Nuclear and Cytoplasmic Long Noncoding RNAs at Single-Cell Level by RNA-FISH.
The RNA fluorescence in situ hybridization (RNA-FISH) methodology offers an attractive strategy to deepen our knowledge on the long noncoding RNA biology. In this chapter, we provide a comprehensive overview of the current RNA-FISH protocols available for imaging nuclear and cytoplasmic lncRNAs within cells or tissues. We describe a multicolor approach optimized for the simultaneous visualization of these transcripts with their specific molecular interactors, such as proteins or DNA sequences. Common challenges faced by this methodology such as cell-type specific permeabilization, target accessibility, image acquisition, and post-acquisition analyses are also discussed.


TRPMs and neuronal cell death.
Death of CNS neurons during acute injury occurs as a result of a complex combination of excitotoxicity, necrosis, apoptosis, oedema and inflammatory reactions. Neuroprotection via glutamate receptor blockade or antioxidant or anti-inflammatory therapy have not proven effective in the clinical treatment of brain damage due to narrow therapeutic windows, poor pharmacokinetics or blockade of the signalling essential for normal excitatory neurotransmission and neuronal survival. Recent work in neuronal biochemistry, genomics and proteomics has increased understanding of the molecular organization of the excitatory synapse and the neuronal postsynaptic density. Transient receptor potential (TRP) channels are an exciting new family of cation channels that are highly expressed in the brain. Several members can be induced by oxidative stress and oxygen free radicals, both of which play important roles in neurodegeneration. Recent work has indicated that members of the melastatin subfamily (TRPM) of TRP proteins, particularly TRPM7 and TRPM2, may play key roles in neuronal death that is activated by oxidative stress and downstream from excitotoxic signal pathways. This discovery provides an exiting new avenue for research into the pathophysiology and treatment of acute neurodegeneration.


Antioxidant effect of nondigestible levan and its impact on cardiovascular disease and atherosclerosis.
Levan polysaccharide, a type of fructan, has been shown to favorably affect diabetes type 2 and hypercholesterolemia. Recent reports have indicated that excessive oxidative stress contributes to the development of atherosclerosis linked metabolic syndrome. The objective of this current study was to investigate the possible protection against oxidative stress linked atherosclerosis. A group of twenty four male rats was divided into four subgroups; a normal diet group (Control), normal rats received levan (L), a high-cholesterol diet group (Chol) and a high-cholesterol diet with 5% (w/w) levan group. After the treatment period, the plasma antioxidant enzymes and lipid profiles were determined. Our results show that treatment with levan positively changed plasma antioxidant enzyme activities by increasing superoxide dismutase (SOD) and catalase (CAT) by 40% and 28%, respectively, in heart. Similarly, the treatment of Chol fed groups with levan positively changed lipid profiles by decreasing total cholesterol, triglycerides and LDL-cholesterol by 50%, 38.33% and 64%, respectively. Thus may have potential antioxidant effects and could protect against oxidative stress linked atherosclerosis.


Laparoscopic surgical access in morbidly obese women undergoing endometrial cancer surgery: Repurposing the left upper quadrant approach.
The study purpose was to report the outcomes of patients undergoing endometrial cancer surgical staging with laparoscopic abdominal access entry using a left upper quadrant (LUQ) access technique. This was a retrospective cohort study conducted from 1 January 2013 to 1 January 2018. The setting was an academic, single institution gynecologic oncology service with a high volume of minimally invasive surgery (MIS). The patient cohort included obese (defined as BMI > 30 kg/m2) or morbidly obese (BMI > 40 kg/m2) women undergoing MIS for endometrial cancer staging. All patients underwent laparoscopic abdominal access via a 5-mm or 10-mm optical trocar system using a LUQ technique. In total, 317 patients were included with a median age of 54 years (range, 24-79) and median BMI 42.5 kg/m2 (range, 32-70); 60 % morbidly obese. Successful LUQ access was achieved in 98.1 %. Of those with a failed LUQ approach, two had undergone previous LUQ surgery and 4 had ≥1 previous midline vertical incisions. There was one LUQ trocar-related visceral injury (0.3 %) and no vascular injuries during the study period. A LUQ abdominal technique is a safe and reliable method of laparoscopic access in morbidly obese women undergoing MIS for endometrial cancer staging. This may be the preferred method of laparoscopic access for women with a panniculus or central adiposity, given the caudal displacement of the umbilicus and poor correlation with intraperitoneal anatomic landmarks in this setting.


HIV-1 integrase drug-resistance mutations in Iranian treatment-experienced HIV-1-infected patients.
The latest class of antiretrovirals (ARVs), including integrase strand transfer inhibitors (INSTIs), has been demonstrated to be effective for antiretroviral therapy (ART). Despite all the distinguishing characteristics of these drugs, including a high genetic barrier to resistance and lower toxicity than other ARVs, unfortunately, INSTI drug resistance mutations (DRMs) have occasionally been observed. The aim of this study was to investigate the presence of DRMs associated with INSTIs among treatment-experienced HIV-1-infected patients. From June 2012 to December 2018, a total of 655 treatment-experienced HIV-1-infected patients enrolled in this cross-sectional survey. Following amplification and sequencing of the HIV-1 integrase region of the pol gene, DRM and phylogenetic analysis were successfully carried out on the plasma samples of patients who had a viral load over 1,000 IU/ml after at least 6 months of ART. Out of the 655 patients evaluated, 62 (9.5%) had a viral load higher than 1,000 IU/ml after at least 6 months of ART. Phylogenetic analysis showed that all of the 62 HIV-1 patients experiencing treatment failure were infected with CRF35_AD, and one of these patients (1.6%) was infected with HIV-1 variants with DRMs. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. This survey shows that DRMs belonging to the INSTI class were detected in an Iranian HIV patient who has experienced treatment failure. Therefore, regarding the presence of DRMs to INSTIs in ART-experienced patients, it seems better to perform drug resistance mutation testing in HIV patients experiencing treatment failure before changing the ART regimen and prescribing this class of medication.


The effect of SH-SS transition in the structural organization of mitotic chromosomes.
Human lymphoid cell cultures were treated with 2,2'-dithiodipyridine, a thiol reacting agent which produces SS bridges inside the living cells. After 1 to 4 h treatment chromosome preparations were made. The chromosomes acquired a peculiar segmentation along the chromatids. The results suggest that the alteration might arise from a direct reaction of the agent with special chromosomal proteins. The resistance of treated chromosomes to alkali-heat treatment used in C-banding technique was different from that of untreated chromosomes. This prefixational procedure seems to be advantageous in analysing both the chromosome organization and the banding mechanism.


[Acute cystitis].
The management of uncomplicated lower urinary tract infections (UTI) implicate to look for risk factors and complications. Bacterial or radiological exams are not recommanded and short course of antibiotic is effective for treating uncomplicated UTI. Complicated UTI needs clinical, bacteriological and radiological exams, longer treatments are recommanded. Recurrent UTI definition is precised in these guidelines.


Multifaceted pediatric congenital hand reconstruction.
The management of a variety of complex congenital hand deformities is presented. The importance of early parental education by the surgeon and the rehabilitation team is stressed so that staged reconstruction can be planned and executed. New surgical techniques are demonstrated that provide the patient with the ability to perform normal bimanual activities at an early age.