Validity and reliability of the glottal function index.
To evaluate a symptom-focused vocal impairment instrument for the evaluation of patients with voice disorders. Prospective, nonrandomized study of patients with voice disorders undergoing treatment with validation of a new symptom index, the Glottal Function Index (GFI). Voice disorders clinic at an academic tertiary care hospital. Consecutive patients undergoing therapy for glottal insufficiency, adductor spasmodic dysphonia, nodules, and granuloma (40 patients in each group) and 40 control patients. The Pearson correlation coefficient was used to evaluate GFI reproducibility and to compare it with the Voice Handicap Index (VHI). The paired-samples t test was used to compare pretherapy and posttherapy GFI values. Correlation of GFI with VHI; comparison of the GFI in normals, and in pretherapy and posttherapy GFI and VHI scores. The mean +/- SD normative GFI score was 0.87 +/- 1.32. The correlation coefficient for GFI between independent pretherapy measurements was 0.56 (P<.001). The correlation coefficient between total GFI and total VHI scores was 0.61 (P<.001). The mean posttherapy GFI scores improved among all groups as follows: glottal insufficiency: presenting GFI score, 12.7 +/- 4.1; posttherapy GFI score, 6.8 +/- 5.4; nodules: presenting GFI score, 12.9 +/- 4.2; posttherapy GFI score, 8.9 +/- 4.6; adductor spasmodic dysphonia: presenting GFI score, 13.2 +/- 4.1; posttherapy GFI score, 8.9 +/- 4.9; and granuloma: presenting GFI score, 7.8 +/- 4.6; posttherapy GFI score, 3.8 +/- 2.1. Relative to controls, the GFI score at presentation was significantly elevated and demonstrated significant reduction following treatment across each of these entities (P<.05). The GFI is a reliable, reproducible, 4-item, self-administered symptom index with excellent criterion-based and construct validity. Its advantages over existing indexes include brevity and ease of administration. The GFI is a useful adjunct in the evaluation and treatment of patients with glottal dysfunction.


Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases.
Discovery of circulating miRNAs in maternal blood has not only facilitated the understanding of their role in normal pregnancy, but also paved new avenues for biomarker discovery to detect pregnancy-associated complications, such as preeclampsia, ectopic pregnancy, gestational diabetes mellitus, fetal growth restriction, recurrent pregnancy loss, and preterm delivery. In this review, we summarize the studies to date of miRNAs in maternal circulation and placental tissue in human. This brief review does not cover all aspects of this intriguing field but focuses on some new and interesting findings of diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases.


Local Unfolding of Fatty Acid Binding Protein to Allow Ligand Entry for Binding.
Fatty acid binding proteins are responsible for the transportation of fatty acids in biology. Despite intensive studies, the molecular mechanism of fatty acid entry to and exit from the protein cavity is still unclear. Here a cap-closed variant of human intestinal fatty acid binding protein was generated by mutagenesis, in which the helical cap is locked to the β-barrel by a disulfide linkage. Structure determination shows that this variant adopts a closed conformation, but still uptakes fatty acids. Stopped-flow experiments indicate that a rate-limiting step exists before the ligand association and this step corresponds to the conversion of the closed form to the open one. NMR relaxation dispersion and H-D exchange data demonstrate the presence of two excited states: one is native-like, but the other adopts a locally unfolded structure. Local unfolding of helix 2 generates an opening for ligands to enter the protein cavity, and thus controls the ligand association rate.


Synergistic effects of cAMP-dependent protein kinase A and AMP-activated protein kinase on lipolysis in kinsenoside-treated C3H10T1/2 adipocytes.
We previously showed that 3-O-β-D-glucopyranosyl-(3R)-hydroxybutanolide (kinsenoside), a major compound of Anoectochilus formosanus, increased lipolysis through an AMP-activated protein kinase (AMPK)-dependent pathway. To extend our previous finding, we investigated the in vivo and in vitro effects of kinsenoside on lipolysis and the involvement of cyclic AMP (cAMP)-dependent protein kinase A (PKA) and AMPK in kinsenoside-mediated lipolysis. Mice were fed a high-fat diet for six weeks to induce lipid deposition and then treated with 50 and 100 mg/kg kinsenoside for two weeks. The coordination of PKA and AMPK activation in lipolysis in C3H10T1/2 adipocytes was evaluated in vitro by using PKA and AMPK's corresponding inhibitors, oil-red O staining, a glycerol production assay, and Western blot analysis. Kinsenoside reduced body weight, fat pad mass, and hepatic lipid accumulation in obese mice, and concurrently increased the induction and activation of hormone-sensitive lipase (HSL), perilipin, adipose triglyceride lipase (ATGL), and carnitine palmitoyltransferase I (CPT1). Kinsenoside concentration-dependently increased PKA activation by increasing the phosphorylation of Ser/Thr-PKA substrates in vitro. These increases were accompanied by a reduction in fat accumulation. Using H89 and Rp-8-Br-cAMPs to inhibit PKA reduced the release of glycerol but did not alter the activation of peroxisome proliferator-activated receptor alpha or the expression of CPT1 or ATGL. By contrast, compound C, an AMPK inhibitor, inhibited CPT1 and ATGL expression in kinsenoside-treated C3H10T1/2 adipocytes. In addition, H89 caused the reactivation of AMPK downstream targets by increasing the levels of the active form of pAMPK-Thr172, suggesting that PKA negatively modulates AMPK activity. Kinsenoside increased HSL activation through PKA-mediated phosphorylation at Ser660/563 and concomitantly increased perilipin activation in lipolysis. These lipolytic effects of kinsenoside were validated using 6-Bnz-cAMPs, a PKA agonist. In this study, we demonstrated that in addition to AMPK, PKA also plays a crucial role in kinsenoside-mediated lipolysis.


Industry funding was associated with increased use of core outcome sets.
The objective of this study was to assess the uptake of the rheumatoid arthritis core outcome set (RA-COS) using data from multiple data providers, and to investigate factors that may influence this uptake. An observational review was carried out on all clinical trials of rheumatoid arthritis that were indexed on the World Health Organization-International Clinical Trials Registry Platform (WHO-ICTRP). Various measures of COS uptake were calculated from information presented in the trial registries and trial publications. Logistic regression was conducted to investigate factors thought to be associated with planned COS uptake. A total of 341 trials were eligible for the evaluation of RA-COS uptake. In the decade leading up to 2019, the assessment of uptake based on published results was maintained at just over 80%. Trials that were not commercially funded were much less likely to plan to measure the RA-COS than those with industry funding (60% vs. 80%; adjusted OR 0.18, 95% CI 0.11 to 0.32; P < 0.001). This study has demonstrated that the use of the WHO-ICTRP can identify a large and geographically diverse range of trials to include in the evaluation of COS uptake.


Effect of folate deficiency on local cerebral glucose utilization in the rat.
There is considerable debate on the role of folate in CNS function. Recent work indicates that folate deficiency may affect CNS serotonin metabolism, and clinical studies describe many consequences of such a deficiency. On the other hand some workers maintain that folate deficiency alone causes CNS abnormalities. We maintained rats, through dietary deprivation, at folate levels below 4 ng/ml for more than 6 weeks and showed that at that time both their liver and brain folate levels were significantly reduced. We then studied their local cerebral glucose utilization (LCGU) using the [14C]deoxyglucose technique. This method assesses cerebral function by measuring regional metabolic activity. We also determined LCGU in rats given the same diet but replenished with folate (folate control) and in others given free access to commercially available food (normal controls). Our results show that this degree of folate deficiency has no effect on cerebral function. This contrasts with the focal suppression of LCGU we previously reported in a model of vitamin B12 deficiency.


Coating gigaporous polystyrene microspheres with cross-linked poly(vinyl alcohol) hydrogel as a rapid protein chromatography matrix.
Gigaporous polystyrene (PS) microspheres were hydrophilized by in situ polymerization to give a stable cross-linked poly(vinyl alcohol) (PVA) hydrogel coating, which can shield proteins from the hydrophobic PS surface underneath. The amination of microspheres (PS-NH2) was first carried out through acetylization, oximation and reduction, and then 4,4'-azobis (4-cyanovaleric acid) (ACV), a polymerization initiator, was covalently immobilized on PS-NH2 through amide bond formation, and the cross-linked poly(vinyl acetate) (PVAc) was prepared by radical polymerization at the surfaces of ACV-immobilized PS microspheres (PS-ACV). Finally, the cross-linked PVA hydrogel coated gigaporous PS microspheres (PS-PVA) was easily achieved through alcoholysis of PVAc. Results suggested that the PS microspheres were effectively coated with cross-linked PVA hydrogel, where the gigaporrous structure remained under optimal conditions. After hydrophilic modification (PS-PVA), the protein-resistant ability of microspheres was greatly improved. The hydroxyl-rich PS-PVA surface can be easily derivatized by classical chemical methods. Performance advantages of the PS-PVA column in flow experiment include good permeability, low backpressure, and mechanical stability. These results indicated that PS-PVA should be promising in rapid protein chromatography.


Neuromechanics of muscle synergies during cycling.
Muscle synergies have been proposed as building blocks that could simplify the construction of motor behaviors. However, the muscles within synergistic groups may have different architectures, mechanical linkages to the skeleton, and biochemical properties, and these put competing demands on the most appropriate way to activate them for different mechanical tasks. This study identifies the extent to which synergistic patterns of muscle activity vary when the mechanical demands on a limb were altered, and additionally identifies how consistent the spectral profiles of the electromyographic (EMG) intensities were across the different movement tasks. The muscle activities were measured with surface EMG across 10 muscles in the leg during cycling at a range of loads and velocities. The EMGs were quantified by their intensities in time-frequency space using wavelet analysis; the instantaneous patterns of activity identified using principal component analysis, statistically compared and further visualized using the varimax rotation. Variability (35.7%) in the patterns of activity between the muscles were correlated with the torque and velocity of the pedal crank. Anatomic groups of muscles share a common mechanical action across a joint; uncoupling between such muscles was identified in 68.8% of the varimax patterns that encompassed all 10 muscles and 20.8-29.5% of the activity patterns when the anatomic groups were analyzed separately. The EMG spectra showed greatest heterogeneity for the gastrocnemii. These results show that the activity of muscles within anatomic groups is partially uncoupled in response to altered mechanical demands on the limb.


Characterization of adsorption of humic acid onto alumina using quartz crystal microbalance with dissipation.
In this paper, a quartz crystal microbalance with dissipation monitoring (QCM-D) is used to investigate humic acid (HA) adsorption onto alumina (Al(2)O(3)). The amount of adsorption and layer structures of HA were determined by the real-time monitoring of resonance frequency and energy dissipation changes (Δf and ΔD). The effect of HA concentration, HA molecular characteristics (molecular weight and polarity), and pH on HA adsorption onto Al(2)O(3) were investigated. The mass of HA adsorption increases as the concentration of HA increases. The masses are about 24, 60, and 87 ng cm(-2) as the concentration of DOC is 1.0, 4.85, and 92.0 mg L(-1), respectively. The adsorbed layer of HA is more nonrigid, and the mass of HA adsorption is higher at weakly acidic pH values. It was 20, 80, 65, and 45 ng cm(-2) at pH values of 4.5, 5.5, 6.5, and 8.0, respectively. This reveals that efficient HA removal by coagulation at weakly acidic pH values is not just due to the hydrolysis of Al ions as previously presumed. The adsorbed layer of hydrophobic HA is more nonrigid than hydrophobic HA (fractionated by Amberlite XAD-8 resin), and the mass adsorption for the hydrophobic fraction is about four times higher than the hydrophilic fraction (120 ng cm(-2) and 30 ng cm(-2)). The method is of value in the research to establish a quantified calculation model for the coagulation process.


Improved thin-layer chromatographic determination of phospholipids in gastric aspirate from newborns, for assessment of lung maturity.
This one-dimensional thin-layer chromatographic method is used for assay of phospholipids in the gastric aspirate of newborns. The solvent mixture (chloroform/hexane/methanol/glacial acetic acid/water, 12/7/4/3/0.3 by vol) completely resolves lecithin, sphingomyelin, phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine, and phosphatidylglycerol. The method is simple, precise, inexpensive, and rapid (chromatographic development takes less than 25 min) and gives high chromatographic resolution. We used this method to determine the lecithin/sphingomyelin densitometric ratio (L/S ratio) and the phosphatidylglycerol percentage in 200 samples of gastric aspirate and found an L/S ratio of 2.5 to be a satisfactory cutoff value for distinguishing fetal lung maturity and immaturity. We confirmed that the presence of phosphatidylglycerol excluded the possibility of respiratory distress.


[Vibrio vulnificus in Mexico: a case report and review of the literature].
Vibrio vulnificus is an etiologic agent of septicemia and skin lesions. Patients with chronic diseases, and more frequently chronic liver disease, are specially susceptible to this infection. The main risk factor is shellfish ingestion. In this report we present a patient with chronic liver disease who suffered fulminant sepsis and necro-hemorrhagic bullaes secondary to a V. vulnificus infection. The patient had ingested shrimps two days before. A review of the recent literature on the subject is also presented.


Oxidative Stress Induced by Cigarette Smoke Extracts in Human Brain Cells (T98G) and Human Brain Microvascular Endothelial Cells (HBMEC) in Mono- and Co-Culture.
The objective of the current study was to examine oxidative stress induced by cigarette smoke extract (CSE) or cigarette smoke condensate (CSC) in human brain cells (T98G) and human brain microvascular endothelial cells (HBMEC) in mono- and co-culture systems. Cell viability of T98G cells exposed to CSC (0.05-4 mg/ml) was significantly decreased compared to CSE (0.025-20%). There were no marked differences between quantities of reactive oxygen species (ROS) generation by either CSE (2, 4, and 10%) or CSC (0.2, 0.4, and 0.8 mg/ml) treatment compared to control. However, a significant effect was noted in ROS generation following CSC incubation at 4mg/ml. Cellular integrity of HBMEC decreased to 74 and 64% within 120 h of exposure at the IC50 value of CSE and CSC, respectively. This study suggests that chronic exposure to cigarette smoking might initiate damage to the blood-brain barrier.


Therapeutic potential and strategies against leukocyte-platelet interaction in atherosclerosis.
Leukocyte rolling, adhesion, transmigration and activation are features of vascular inflammation leading to atherosclerosis. In particular the interaction between platelets and leukocytes is a key process for adhesion of inflammatory cells to the vascular wall. The various mechanisms of the specific platelet-leukocyte interaction may provide a powerful target to prevent initiation and/or progression of atherosclerotic lesions.


The cutaneous porphyrias.
The porphyrias are a group of mainly inherited disorders of heme biosynthesis where accumulation of porphyrins and/or porphyrin precursors gives rise to 2 types of clinical presentation: cutaneous photosensitivity and/or acute neurovisceral attacks. The cutaneous porphyrias present with either bullous skin fragility or nonbullous acute photosensitivity. This review discusses the epidemiology, pathogenesis, clinical presentation, laboratory diagnosis, complications, and current approach to porphyria management. Although focusing mainly on their dermatological aspects, the article also covers the management of acute porphyria, which by virtue of its association with variegate porphyria and hereditary coproporphyria, may become the responsibility of the clinical dermatologist.


Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3.
The activation of caspase-8, a crucial upstream mediator of death receptor signaling, was investigated in epirubicin- and Taxol-induced apoptosis of B-lymphoma cells. This study was performed because the CD95/Fas receptor-ligand interaction, recruitment of the Fas-associated death domain (FADD) adaptor protein, and subsequent activation of procaspase-8 have been implicated in the execution of drug-induced apoptosis in other cell types. Indeed, active caspase-8 was readily detected after treatment of mature and immature B-lymphoid cells with epirubicin or Taxol. However, neither constitutive nor drug-induced expression of the CD95/Fas ligand was detectable in B-lymphoma cells. Furthermore, overexpression of a dominant-negative FADD mutant (FADDdn) did not block caspase-8 processing and subsequent DNA fragmentation, indicating that drug-induced caspase-8 activation was mediated by a CD95/Fas-independent mechanism. Instead, caspase-8 cleavage was slightly preceded by activation of caspase-3, suggesting that drug-induced caspase-8 activation in B-lymphoma cells is a downstream event mediated by other caspases. This assumption was confirmed in 2 experimental systems-zDEVD-fmk, a cell-permeable inhibitor of caspase-3-like activity, blocked drug-induced caspase-8 cleavage, and depletion of caspase-3 from cell extracts impaired caspase-8 cleavage after in vitro activation with dATP and cytochrome c. Thus, these data indicate that drug-induced caspase-8 activation in B-lymphoma cells is independent of death receptor signaling and is mediated by postmitochondrial caspase-3 activation.


[Dehydration--a risk factor for the decompression-accident in diving].
We report on a decompression-accident with neurological manifestation in an experienced recreational diver. As no obvious omission against the prescribed rules of decompression could be observed, dehydration due to intense jogging prior to the dive was identified as a risk-factor. Hyperbaric treatment resulted in a complete restitution. The physiological aspects are discussed and recommendations for the fluid-intake before diving are given.


Characteristics and incidence of large eggs in Trichuris muris.
The production of small numbers of large eggs among the standard-sized eggs of Trichuris trichiura is well known. Large eggs have also been observed in Trichuris muris, but they have not been studied previously. This paper compares the characteristics of the large eggs (LEs, ≥74.5 μm long) and standard-sized eggs (SEs, <74.5 μm long) in cultures of T. muris. Among 112,554 cultured eggs, LEs occurred at very low frequency (0.03 %, i.e., about three large eggs per 10(4) cultured eggs). Embryonated eggs represented 93.72 % of SEs, but only 25.00 % of LEs were embryonated. Embryonated LEs and SEs contained fully matured larvae. An atypical category of unembryonated egg, which contained an incompletely developed larva, an abnormal larva, or granular components, was common among the LEs. However, similar atypical unembryonated SEs were rarely observed. These observations suggest that the LEs that occur very infrequently in T. muris result from an abnormality of embryonation (larval development).


Cancer clinical trial enrollment of diverse and underserved patients within an urban safety net hospital.
Enrollment rates onto cancer clinical trials are low and reflect a small subset of the population of which even fewer participants come from populations of racial or ethnic diversity or low socioeconomic status. There is a need to increase enrollment onto cancer clinical trials with a focus on recruitment of a diverse, underrepresented patient population. To use the electronic medical record (EMR) to understand the eligibility and enrollment rates for all available cancer trials in the ambulatory care setting at an urban safety net hospital to identify specific strategies for enhanced accrual onto cancer clinical trials of diverse and underserved patients. A clinical trial screening note was created for the EMR by the clinical trials office at an urban safety net hospital. 847 cancer clinical trial screening notes were extracted from the EMR between January 1, 2010 and December 31, 2010. During that time, 99 cancer trials were registered for accrual, including clinical treatment, survey, data repository, imaging, and symptom management trials. Data on eligibility, enrollment status, and relationship to sociodemographic status were compared. This is a single-institution and retrospective study. The findings demonstrate that a formal process of tracking cancer clinical trial screens using an EMR can document baseline rates of institution-specific accrual patterns and identify targeted strategies for increasing cancer clinical trial enrollment among a vulnerable patient population. Offering nontreatment trials may be an important and strategic method of engaging this vulnerable population in clinical research.


Bistable dynamic coordination polymer showing reversible structural and functional transformations.
A bistable dynamic coordination polymer [Ni(pca)(bdc)(0.5)(H(2)O)(2)] having a two-dimensional (2D) zigzag sheet structure is synthesized solvothermally. Topological analysis revealed that the frameworks have an hcb type of uninodal net. The compound exhibits guest specific reversible structural transformations accompanying reversible changes in physical properties driven by inherent flexibility and transformability.


Comparative tissue distribution of metals in birds in Sweden using ICP-MS and laser ablation ICP-MS.
Cadmium, copper, lead, palladium, platinum, rhodium, and zinc profiles were investigated along feather shafts of raptor and other bird species by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The distribution of external versus internal metal contamination of feathers was investigated. The species examined were peregrine falcon (Falco peregrinus), sparrowhawk ( Accipiter nisus), willow grouse (Lagopus lagopus), and house sparrow (Passer domesticus) in Sweden. For habitat comparisons, total Cu, Pb, Zn, and Cd concentrations were analyzed by ICP-MS in feathers of the examined species as well as captive peregrine falcon. For investigation of metal distribution and correlation in different biological materials of raptors, total concentrations of Cu, Pb, Cd, and Zn were also investigated by ICP-MS in feathers, eggs, blood, feces, liver, and kidney of wild peregrine falcon from southwestern Sweden. Laser ablation of feathers revealed that Pb contamination is both external and internal, Zn contamination is internal, and Cd and Cu contamination is predominantly internal, with a few externally attached particles of high concentration. Pb, Cu, and Cd signal intensities were highest in urban habitats and contamination was mainly external in feathers. The background signal intensity of Zn was also higher in birds from urban habitats. The laser ablation profile of PGE (Pt, Pd, Rh) demonstrated that PGE contamination of feathers consists almost exclusively of externally attached PGE-containing particles, with little evidence of internally deposited PGE.Generally, total metal concentrations in feathers were highest in sparrowhawk and house sparrow due to their urban habitat. Total Cu, Zn, and Cd concentrations were highest in liver and kidney due to binding to metallothionein, while the total Pb concentration was highest in feces due to the high excretion rate of Pb. A decreasing temporal trend for Pb in feathers, showing that Pb levels in feathers have decreased since the introduction of nonleaded petrol, is also discussed.


A rapid screening method to detect nonsense and frameshift mutations: identification of disease-causing APC alleles.
A functional screen for nonsense and frameshift mutations has been devised that allows genes of interest to be scanned in segments. This assay is based on the cloning of these segments in-frame with a colorimetric marker gene (lacZ) followed by screening for the level of functional activity from the marker polypeptide (beta-galactosidase). Individuals at risk for any one of a number of genetic diseases, in particular familial adenomatous polyposis coli (APC), can be quickly screened for chain-terminating mutations introduced by stops and frameshifts. At present, scanning of the APC gene for mutation requires significant effort because it is a large gene and most APC mutations are unique. Therefore, this assay offers a powerful option for the diagnosis of this and other genetic diseases, as well as great potential for the development of a similar rapid screen to detect APC mutations in colorectal adenomas and carcinomas.


Color and translucency of in vivo natural central incisors.
The range of shades in shade guides is not consistent with natural teeth, and there is no information on the color and translucency of the natural tooth for all age groups. Therefore, it is important to obtain a database of the characteristics of the natural tooth from a wide age group. This study obtained information on color and translucency of natural teeth for all age groups, and attempted to clarify the difference of the color and translucency between natural teeth and VITA Lumin Vacuum shade guide. Natural central incisors of 87 subjects (42 men and 45 women; age range from 13 to 84 years) and 16 shades of VITA Lumin Vacuum shade guide were evaluated. Color and translucency of 5 sites, each 1.0 mm in diameter, on the surfaces of individual teeth were measured for L*, a*, and b*, using a color computer according to CIELAB color spaces. At the center site, negative correlation was found between age and L*, with positive correlation between age and b*. Both a* and b* of the natural tooth increased when moving in the direction of the cervical site, but translucency decreased in the direction of the root. The a* value for the natural tooth was significantly higher than those for VITA Lumin Vacuum shade guide. This study found that the older the subject, the darker and more yellow the color at the center site of the natural tooth. Both reddish and yellowish colors of natural teeth tend to increase from the incisal to cervical, whereas translucency decreases. Red-green chromaticity of VITA Lumin Vacuum shade guide was not distributed to cover the natural tooth.


Highlights from Faraday Discussion 301: Nanolithography of Biointerfaces, London, UK, July 3-5 2019.
The 2019 Faraday Discussion on the Nanolithography of Biointerfaces brought together a diverse set of interdisciplinary scientists involved in the seemingly disparate fields of materials science, nanolithography and glycoscience. The setting and format of this meeting renders the experience unique, and anyone in the audience is instantly engaged in the debate. This Faraday Discussion attracted about sixty delegates, ranging from graduate students and early career researchers to full professors. The meeting was a reflection on how far lithography techniques, tissue engineering and glycoscience have come, with the aid of scientists working at the realm of the nanoscale. True to its name, this gathering was also a discussion on what the outstanding questions in glycobiology are and how nanolithography can be appropriately applied to answer them. In this report, we will give an overview of the topics and discussions covered during the meeting and highlight the content of each session.


Does box model training improve surgical dexterity and economy of movement during virtual reality laparoscopy? A randomised trial.
Laparoscopic box model trainers have been used in training curricula for a long time, however data on their impact on skills acquisition is still limited. Our aim was to validate a low cost box model trainer as a tool for the training of skills relevant to laparoscopic surgery. Randomised, controlled trial (Canadian Task Force Classification I). University Hospital. Sixteen gynaecologic residents with limited laparoscopic experience were randomised to a group that received a structured box model training curriculum, and a control group. Performance before and after the training was assessed in a virtual reality laparoscopic trainer (LapSim and was based on objective parameters, registered by the computer system (time, error, and economy of motion scores). Group A showed significantly greater improvement in all performance parameters compared with the control group: economy of movement (p=0.001), time (p=0.001) and tissue damage (p=0.036), confirming the positive impact of box-trainer curriculum on laparoscopic skills acquisition. Structured laparoscopic skill training on a low cost box model trainer improves performance as assessed using the VR system. Trainees who used the box model trainer showed significant improvement compared to the control group. Box model trainers are valid tools for laparoscopic skills training and should be implemented in the comprehensive training curricula in gynaecology.


Anti-TNF agents in patients with inflammatory bowel disease and malignant melanoma--challenges in management.
The inflammatory bowel diseases (IBD) are chronic immune-mediated inflammatory diseases of the gut that occur in genetically predisposed individuals exposed to environmental triggers. Several immunosuppressive agents have been successfully used for induction and maintenance treatment in inflammatory bowel disease. These include steroids, thiopurines, methotrexate, anti-tumor necrosis factor (anti-TNF) alpha agents, anti-alpha 4 integrins, and anti-IL-12/23 agent to name a few. There are also limited data on novel approaches including thalidomide and stem cell transplant. In spite of the significant successes associated with these agents, numerous malignancies have been associated with their use. Lymphomas including hepatosplenic T cell lymphomas, non-melanoma skin cancers and, more recently, melanoma have been described, specifically with anti-TNF. We reviewed the available published literature on melanoma in IBD, melanoma associated with anti-TNF, and the data on other treatment options in patients with IBD. In addition, we also reviewed the limited data on the gut specific integrin-vedolizumab. This may provide an additional option in the management of the subset of patients with IBD and melanoma. Options for treatment of IBD should be based on the stage of melanoma, control of IBD, and patient preferences. It should involve shared decision-making and close interdisciplinary follow-up between the IBD physician and the dermatologist, preferably with expertise in the management of melanoma. Treatment choices in patients with IBD and melanoma are challenging. There is very limited data providing guidance in this subset of patients. As such, treatment and follow-up should be individualized, extensively discussed with patients and their families as appropriate, and done in conjunction with a close follow-up by gastroenterologist and dermatologist.


Joint replacement surgery in patients under thirty.
Forty-five patients, twenty-six of them with juvenile rheumatoid arthritis, had sixty-seven total hip arthroplasties. The patients' ages ranged from twelve to twenty-nine years. An over-all good result was demonstrated in 93 per cent of the patients had a poor result, in 6.9 per cent. The average follow-up period was 32.5 months. Careful planning in severely dysplastic joints should be done.


Desperately seeking...something.
Published online this week in Structure, Wisely et al. present a high-resolution X-ray crystallographic structure of the ligand binding domain of human hepatocyte nuclear factor 4 gamma (HNF4gamma). They find fatty acids filling the ligand binding pocket of this receptor long considered an orphan, but these "ligands" appear to be locked into the protein and not readily amenable to exchange. Not only does this present a new paradigm for nuclear receptors but it also provides new insights into their evolutionary origins.


Appearance of angiotensin II expression in non-basal epithelial cells is an early feature of malignant change in human prostate.
Despite increasing interest in the renin-angiotensin system in cancer, little is known about angiotensin II (Ang II) expression in human prostate tumors. Using immunohistochemistry, we examined Ang II expression in prostate cancer (Gleason grades 2-5), benign prostatic hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HGPIN). Ang II was present in proliferating neoplastic cells in HGPIN, in malignant cells in all grades of prostate cancer examined, in basal but not luminal epithelial cells in BPH, and in the cytoplasm of LNCaP, DU145, and PC3 prostate cancer cells. The data establishes the presence of Ang II in pre-malignant and malignant prostate cells, suggests Ang II staining in non-basal epithelial cells is an early sign of malignant change, and supports suggestions that HGPIN and malignant prostate cells both arise from transformed basal cells. Using immunohistochemistry we examined Ang II expression in proliferative disorders of the prostate and concluded that Ang II staining in non-basal epithelial cells is evidence of early malignant change.


[A case of intussusception due to intestinal metastasis of renal carcinoma].
Adult intussusceptions due to metastatic intestinal-tumor are very rare. A 71-year-old man with an intussusception due to intestinal metastasis of renal carcinoma is reported. To our knowledge, this is the third such patient in the Japanese literature. The patient was suffered from an intestinal obstruction six months after his renal carcinoma was detected. Laparotomy was performed, revealing that he had developed a jejunojejunal intussusception due to metastasis of renal carcinoma. The early diagnosis of metastatic intestinal tumor is difficult. It is important to bear in mind that patients with malignant tumor may already have metastasis.


She's always a woman: Butch lesbian trans women in the lesbian community.
While the visibility and acceptance of trans women have grown globally in recent years, this progress has primarily been within a traditional, heteronormative narrative. But a growing number of trans women identify as butch lesbians and challenge this heteronormative narrative. The existence of butch trans women has created a debate on where they fit within queer and lesbian communities and how their gender performance fits within traditional butch/femme understandings of lesbian or queer relationships. This article seeks to explore the intersections of gender identity and sexual orientation that butch trans women experience when they engage with lesbian and trans communities.


Cadmium solubility in paddy soils: effects of soil oxidation, metal sulfides and competitive ions.
Cadmium (Cd) is a non-essential element for human nutrition and is an agricultural soil contaminant. Cadmium solubility in paddy soils affects Cd accumulation in the grain of rice. This is a human health risk, exacerbated by the fact that rice grains are deficient in iron (Fe) and zinc (Zn) for human nutrition. To find ways of limiting this potential risk, we investigated factors influencing Cd solubility relative to Fe and Zn during pre-harvest drainage of paddy soils, in which soil oxidation is accompanied by the grain-filling stage of rice growth. This was simulated in temperature-controlled "reaction cell" experiments by first excluding oxygen to incubate soil suspensions anaerobically, then inducing aerobic conditions. In treatments without sulfur addition, the ratios of Cd:Fe and Cd:Zn in solution increased during the aerobic phase while Cd concentrations were unaffected and the Fe and Zn concentrations decreased. However, in treatments with added sulfur (as sulfate), up to 34 % of sulfur (S) was precipitated as sulfide minerals during the anaerobic phase and the Cd:Fe and Cd:Zn ratios in solution during the aerobic phase were lower than for treatments without S addition. When S was added, Cd solubility decreased whereas Fe and Zn were unaffected. When soil was spiked with Zn the Cd:Zn ratio was lower in solution during the aerobic phase, due to higher Zn concentrations. Decreased Cd:Fe and Cd:Zn ratios during the grain filling stage could potentially limit Cd enrichment in paddy rice grain due to competitive ion effects for root uptake.


Optimization of selenylation conditions for Chinese angelica polysaccharide based on immune-enhancing activity.
Chinese angelica polysaccharide (CAP) was extracted by water decoction and ethanol precipitation, purified through eliminating protein by Sevage method and column chromatography of Sephadex G-200, then selenizingly modified by nitric acid-sodium selenite method according to L(9)(3(4)) orthogonal design of three-factors, the usage amount of sodium selenite, reaction temperature and reaction time, at three level to obtain nine selenizing CAPs, sCAP(1)-sCAP(9). Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay taking the non-modified CAP as control. The results showed that selenylation modification could significantly enhance the immune-enhancing activity of CAP, sCAP(2) presented best effect and the optimal modification conditions were 200mg of sodium selenite for 500 mg of CAP, the reaction temperature of 70 °C and the reaction time of 6 h.


Ischemic stroke in Jordan 2000 to 2002: a two-year, hospital-based study.
A total of 200 consecutive patients with first ischemic stroke seen at Jordan University Hospital in Amman, Jordan, during a 2-year period were studied retrospectively. Mean age was 61.2 years (range: 29-95 years). The most common stroke subtype was lacunar infarct (51%), but the frequency of cardioembolic strokes was low (8%). Hypertension, diabetes mellitus, coronary artery disease, and smoking were the most common risk factors for atherosclerotic noncardioembolic strokes. Chronic atrial fibrillation was the most common risk factor for cardioembolic strokes. No patient had significant (>50%) extracranial carotid or vertebral artery stenosis. The outcome was relatively good; 85% of patients were discharged home, the majority with only mild neurologic deficit. The favorable outcome is most likely because of the relatively young mean age and the predominance of lacunar infarcts.


Systematic review of transversus abdominis release in complex abdominal wall reconstruction.
Transversus abdominis release (TAR), as a type of posterior component separation, is a new myofascial release technique in complex ventral hernia repair. TAR preserves rectus muscle innervation, creates an immense retromuscular plane and allows bilaminar ingrowth of the mesh. The place of the TAR within the range of established anterior component separation techniques (CST) is unclear. Aim of this systematic literature review is to estimate the position of the TAR in the scope of ventral hernia repair techniques. MEDLINE, Embase, Pubmed and the Cochrane controlled trials register and Science citation index were searched using the following terms: 'posterior component separation', 'transversus abdominis release', 'ventral hernia repair', 'complex abdominal wall reconstruction'. To prevent duplication bias, only studies with a unique cohort of patients who underwent transversus abdominis release for complex abdominal wall reconstruction were eligible. Postoperative complications and recurrences had to be registered adequately. The rate of surgical site occurrences and recurrences of the TAR were compared with those after anterior CST, published earlier in two meta-analyses. Five articles met our strict inclusion criteria, describing 646 TAR patients. Methodological quality per study was good. Mean hernia surface was 509 cm2 and 88% of the hernias were located in the midline. Preoperative risk stratification was distributed in low risk (10%), co-morbid (55%), potentially contaminated (32%) and infected (3%). Pooled calculations demonstrated a mean SSO rate of 15% after TAR (20-35% after anterior CST) and a mean 2-year hernia recurrence rate of 4% (13% after anterior CST). Mean hernia surface was 300 cm2 in anterior component separation studies. This review demonstrates that the transversus abdominis release is a good alternative for anterior CST in terms of SSO and recurrence, especially in very large midline ventral hernias.


Vaccination against Paediatric Respiratory Pathogens.
Acute respiratory infections (ARIs) are extremely common in children, especially those under 5 years old. They can lead to complications, super-infection, respiratory failure, and even compromised respiratory function in adulthood. For some of the responsible pathogens, vaccines are available. This review reports current issues about vaccines against the main respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease. The optimal use of influenza, pneumococcal, pertussis and measles vaccines is required in order to reduce ARI burden. Vaccination coverage rates must be improved to achieve the full benefits of these vaccines. Recently, advances in the knowledge of respiratory syncytial virus structural biology and immunology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines even against this harmful pathogen.


Forskolin potentiates calcium-dependent amylase secretion from rat pancreatic acinar cells.
The cellular and molecular effects of forskolin, a direct, nonhormonal activator of adenylate cyclase, were assessed on the enzyme secretory process in dispersed rat pancreatic acinar cells. Forskolin stimulated adenylate cyclase activity in the absence of guanyl nucleotide. It promoted a rapid and marked increase in cellular accumulation of cyclic AMP alone or in combination with vasoactive intestinal peptide (VIP) but was itself a weak pancreatic agonist and did not increase the secretory response to VIP or other cyclic AMP dependent agonists. Somatostatin was a partial antagonist of forskolin stimulated cyclic AMP synthesis and forskolin plus cholecystokinin-octapeptide (CCK-OP) induced amylase release. Forskolin potentiated amylase secretion in response to calcium-dependent agonists such as CCK-OP, carbachol and A-23187, but did not affect the ability of CCK-OP and (or) carbachol to mobilize 45Ca from isotope preloaded cells; forskolin alone did not stimulate 45Ca release. In calcium-poor media, the secretory response to forskolin and CCK-OP was reduced in a both absolute and relative manner. The data suggests that calcium plays the primary role as intracellular mediator of enzyme secretion and that the role of cyclic AMP may be to modulate the efficiency of calcium utilization.


Model-guided ligation strategy for optimal assembly of DNA libraries.
DNA ligation is essential to many molecular biology manipulations, but this reaction is often carried out by following generic guidelines or by trial and error. Maximizing the desired ligation product is especially important in DNA library construction for directed evolution experiments since library diversity is directly affected by ligation efficiency. Here, we suggest that display vectors that rely on Type IIP restriction sites for cloning should be redesigned to utilize Type IIS restriction sites instead because ligation yield is significantly improved: we observed up to 15- and 2.6-fold increases in desired products for circular and linear ligation reactions, respectively. To guide ligation optimization more rationally, we developed an easily parameterized thermodynamic model that predicts product distributions based on input DNA concentrations and free energies of the ligation events. We applied this model to study ligation reactions using a ribosome display vector redesigned with Type IIS restriction sites (pRDV2). We computationally predicted and experimentally validated the relative abundance of various products in three-piece linear ligations as well as the extent of transformation from vector-insert circular ligations. Based on our results, we provide general insights into ligation and we outline guidelines for optimizing this reaction for both in vivo and in vitro display methodologies.


Formation of lipid-bound oligosaccharides in yeast.
Incubation of a membrane fraction from Saccharomyces cerevisiae with UDP-N-acetyl [14C]glucosamine catalyzes the transfer of N-acetylglucosamine to an endogenous lipid fraction as well as a methanol-insoluble polymer. The glycolipid was shown to separate into three compounds by thin-layer chromatography. The biosynthesis of two of them could clearly be stimuated by the addition of dolichol monophosphate to the incubation mixture. Evidence is presented that the substances are dolichol pyrophosphate derivatives: dolichol pyrophosphate N-acetylglucosamine and dolichol pyrophosphate di-N-acetylchitobiose. The formation of the chitobiose-containing lipid was increased by reincubation of the glycolipid with non-radioactive UDP-N-acetylglucosamine. The same particulate preparation transferred mannose from GDPmannose to dolichol pyrophosphate di-N-acetylchitobiose, giving rise to a lipid-bound oligosaccharide. Molecular weight determination of the oligosaccharide moiety gave a value of 780, which is consistent with a tetrasaccharide containing two mannose subunits attached to di-N-acetylchitobiose. The methanol-insoluble radioactive product obtained in the presence of UDP-N-acetyl[14C]glucosamine was transformed by pronase treatment to a large extent into dialyzable material. It is suggested that the glycolipids described serve as intermediates in the glycosylation of yeast mannoproteins.


[Research on problem of exogenous pollution of Chinese medicine resources from perspective of circular economy].
Based on the in-depth analysis of the current situation of the exogenous pollution of Chinese medicine resources, this research mainly discusses the intrinsic link and practical significance between the development of circular economy in Chinese medicine resources and the control of the problem of the exogenous pollution from the perspective of circular economy, and proposes some suggestions to develop the recycling economy of Chinese medicine resources from the establishment of legal system, mechanism of development, production norms, industry standards and regulatory system of the recycling of Chinese medicine resources.


Application of 2D-TOCSY NMR to the measurement of specific(13C-enrichments in complex mixtures of 13C-labeled metabolites.
A 2D-NMR method based on zero-quantum filtered (ZQF-) TOtal Correlation SpectroscopY (TOCSY) was applied to measure 13C-enrichments in complex mixtures of 13C-labeled metabolites generated in carbon-labeling experiments. Using ZQF-TOCSY, more than 30 13C-enrichments could be potentially measured from the analysis of a biomass hydrolyzate prepared from Escherichia coli cells grown on a mixture of 20% [U-13C]-glucose and 80% [1-13C]-glucose, without need for separation of metabolites. The method is applicable to biomass hydrolyzates, cell extracts, and other complex biological samples. It is also applicable to any combination of labeled substrates and provides a basis for examining non-steady-state conditions.


[Diagnosis and follow-up study of human papillomavirus infection in benign epithelium and mild dysplasia of the uterine cervix].
In this study, we evaluated the sensitivity of cytology, colposcopy and the dot blot method (Vira Pap, Vira Type) for the screening of HPV infection in benign epithelium and mild dysplasia of the uterine cervix, and then investigated subsequent changes in HPV DNA in the lesion. The HPV infection detection rates for cytology, colposcopy and the dot blot method were 14/46 (30.4%), 30/46 (65.2%) and 35/46 (76.1%), respectively. Cases where HPV DNA was negative with the dot blot method but HPV infection was suspected with cytologic and colposcopic examination were 3/6 (50.0%) in the undigestive type except for HPV types 6, 11, 16, 18, 31, 33 and 35. HPV DNA disappeared after 3-6 months in persistent cases with histologically benign epithelium in the one year follow-up. In persistent cases of mild dysplasia followed up histologically for one year from the time of the first visit showed differences between negative and positive cases of HPV DNA after 1 year. In 2 progressive cases (HPV 31 and 16 types) HPV DNA in the cervix was detected continuously. We consider that the dot blot technique is a valuable method for identifying human papillomavirus infection. However, detection of undigestive HPV types by the dot blot method was poor. Therefore, the joint use of cytology, colposcopy and the dot blot method seems to be a valuable screening technique. Individual variations in the clinical course of the high risk group appear to reflect profound differences in the effectiveness of host responses. Therefore, cases where continuous HPV DNA was observed in the high risk groups should be followed up for a long period.


Growth impairment and adrenal suppression on low-dose inhaled beclomethasone.
Growth impairment and adrenal suppression secondary to inhaled corticosteroids (ICS) is a well-recognised phenomenon. We report a 13-year-old boy, treated long-term for asthma, who presented with short stature while on low-dose inhaled corticosteroid (beclomethasone 200 microg/d). Investigations revealed evidence of severe adrenal suppression. Weaning off the steroid treatment resulted in recovery of adrenal activity and rapid growth. While low-dose ICS are normally considered to have few side effects, this case illustrates the extreme variability of individual sensitivity and the need for careful surveillance of all children treated with long-term steroids.


The correlation between the loss of chromosome 14q with histologic tumor grade, pathologic stage, and outcome of patients with nonpapillary renal cell carcinoma.
Conventional pathologic classifications of human renal cell carcinoma (RCC) give little insight into oncogenesis and little assistance in predicting the clinical behavior of this disease. Identification of specific genetic alterations involved in the development of RCC using fluorescence in situ hybridization (FISH) however, may help provide foundations for classification, prognosis, and clinical management of the patients. Archival, paraffin embedded tissue sections from 30 human non-papillary RCCs were examined with a dual color FISH technique for loss of chromosomes 3p and 14q. Telomeric DNA probes from 3p or 14q and an internal ploidy control probe, centromeric probe of chromosome 2, were applied directly to the tumor sections. The correlations between loss of 3p or 14q, and tumor ploidy, with tumor grade, pathologic stage, and patient outcome were assessed. Ninety percent of the patients (27) lost chromosome 3p, and 36.7% of the patients (11) had chromosome 14q deletions. The loss of 3p in the samples tested was unrelated to patient age, gender, outcome, tumor stage, or histologic grade. However, the deletion of 14q was significantly correlated with higher stage (P = 0.01), histologic grade (P = 0.01), and patient outcome (P < 10(-4)). The close correlation of 14q loss with higher stage, higher histologic grade, and poorer outcome for patients with nonpapillary RCC indicates that it may be a promising prognostic marker.


The meaning and significance of the equilibrium phase in enhanced computed tomography of the liver.
The "equilibrium phase" (EP) in liver contrast enhancement in CT is generally held to be a potential pitfall by way of loss of intrinsic lesion conspicuity. Unfortunately, the definitions extant in the literature are not firmly rooted in a pharmacokinetic basis. Such a basis is developed in this article and a method is described for estimating the time of onset of the EP. It is shown that this may be, effectively, as early as 120 s or so after the beginning of a typical infusion of contrast agent. This means that incremental scanning protocols are likely to result in later slices being acquired in the EP. It is further shown that the pharmacokinetic model does predict a danger of loss of lesion conspicuity in EP scanning. Fortunately, rapid helical/spiral scanning makes it a danger that is easily avoided.


Syringe loading introduces macromolecules into living mammalian cell cytosol.
We describe a simple, efficient, gentle and inexpensive technique for the introduction of normally impermeant macromolecules into the cytosol of living mammalian cells growing in suspension or attached to the culturing substratum. Loading is achieved by the production of transient, survivable plasma membrane disruptions as cells are passed back and forth through a standard syringe needle or similar narrow orifice. The loading volume required, which contains cells and the macromolecule to be loaded, can be as little as 5 microliters, thus minimizing the use of valuable reagents. In addition, we report that the surfactant molecule, Pluronic F-68, is capable of altering the physical properties of the plasma membrane in such a way as to increase loading efficiency and the long-term survivability of cells loaded by this and other mechanically based cell-loading techniques.


A systematic review of the adoption and acceptance of eHealth in Saudi Arabia: Views of multiple stakeholders.
eHealth is defined as "the use of information and communication technology for health". Adoption and acceptance are key concepts to measure the level of eHealth impact. The aim of this systematic review was to critically appraise, synthesise and present evidence of the status of eHealth adoption and acceptance in Saudi Arabia from the perspectives of multiple stakeholders. Based on a Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guided protocol published with the international prospective register of systematic reviews (Prospero), five databases were searched for articles published between 1993 and 2017. Inclusion and exclusion criteria of studies were applied in which only peer-reviewed, full-text primary research articles in English language were included. One reviewer performed the searches; two reviewers independently screened the titles then abstracts followed by full articles. Studies excluded were recorded with reasons. Critical appraisal tools appropriate to study design were applied. Eleven items from every study were extracted for further synthesis. After duplicates were removed, 110 papers were screened, and 15 studies met the inclusion criteria. Studies were generally of good quality. Thirty-nine factors were identified as influences affecting the adoption and acceptance of eHealth in Saudi Arabia. Lack of eHealth studies from the perspective of health managers and the limitation of studies to few geographical areas were identified as knowledge gaps. eHealth field in Saudi Arabia showed evidence of continual growth in both publications and awareness of significance. Therefore, findings from this review may help key professionals to address the current challenges and barriers and prioritise the main areas for improvement.


Zombie bugs? Manipulation of kissing bug behavior by the parasite Trypanosoma cruzi.
The parasite manipulation hypothesis states that the parasite modifies host's behavior thereby increasing the probability that the parasite will pass from an intermediate host to its final host. We used the kissing bugs Triatoma pallidipennis and T. longipennis and two isolates of the Trypanosoma cruzi parasite (Chilpancingo and Morelos) to test these ideas. These insects are intermediate hosts of this parasite, which is the causal agent of Chagas disease. The Chilpancingo isolate is more pathogenic than the Morelos isolate, in the bugs. We expected that infected bugs would be more active and likely at detecting human-like odors. Given the differences in pathogenicity between isolates, we expected the Chilpancingo isolate to induce these effects more strongly and lead to higher parasite number than the Morelos isolate. Finally, infected bugs would gain less mass (a mechanism thought to increase bite rate, and thus transmission) than non-infected bugs. Having determined that both isolate haplotypes belong to the Tc1a group, we found that: (a) young instars of both species were more active and likely to detect human odor when they were infected, regardless of the isolate; (b) there was no difference in parasite abundance depending on isolate; and, (c) infected bugs did not end up with less weight than uninfected bugs. These results suggest that T. cruzi can manipulate the bugs, which implies a higher risk to contract Chagas disease than previously thought.


Medicines management in care homes for older people: the nurse's role.
Increasing attention is being paid to the inappropriate use of medicines in UK care homes for older people. While polypharmacy may sometimes be necessary, older people can be particularly sensitive to the effects of medicines due to physiological chances, while the effect of a mixture of medicines is often unknown. The harmful consequences of inappropriate prescribing for older people unnecessarily add to overall health-care expenditure and the workload of staff. Community nurses can play an important role in attenuating some of these problems while enhancing the quality of life of older people in care homes. The growing population of older people and burgeoning health-care expenditure on medicines demands that greater attention is given to medicine management among older people so that the efficacy of therapeutic regimes are maximized.


[Psoriatic synovitis: pathogenic and therapeutic implications].
Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune disease characterized by arthritis and psoriasis of the skin. It is classified within the spondyloarthropathies (SpA) group. The wide clinical heterogeneity of PsA has hampered research into its pathogenesis and the performance of large randomized clinical trials with disease-modifying anti-rheumatic drugs. The success of biologic agents in PsA has stimulated wide interest in this disease as well as in its clinical classification and underlying pathogenic mechanisms. Several recent articles on the pathogenesis of PsA are reviewed, focussing on the potential of synovial angiogenesis as a therapeutic target and on synovial expression of macrophages and p53 protein related to joint damage in rheumatoid arthritis (RA) and PsA. Finally, the question of whether the polyarticular variant of PsA shares immunohistochemical features with RA or SpA is also discussed. Although the success of tumor necrosis factor-alpha antagonists in both RA and PsA supports a similar pathogenesis in both disorders, these and other studies suggest that there are differences in the synovial expression and pathogenic significance of certain cells and molecules. If confirmed, this phenomenon could open new avenues in specific therapy for PsA.


Video-Based Intervention in Teaching Fraction Problem-Solving to Students with Autism Spectrum Disorder.
The purpose of this study was to determine the effectiveness of a point-of-view video modeling intervention to teach mathematics problem-solving when working on word problems involving subtracting mixed fractions with uncommon denominators. Using a multiple-probe across students design of single-case methodology, three high school students with ASD completed the study. All three students demonstrated greater accuracy in solving fraction word problems and maintained accuracy levels at a 1-week follow-up.


Comparison of the mouse bioassay and enzyme-linked immunosorbent assay procedures for the detection of type A botulinal toxin in food.
Samples of chili linked to a foodborne illness outbreak of type A botulism were examined for preformed type A botulinal toxin using two enzyme-linked immunosorbent assay (ELISA) procedures and the mouse bioassay. One of the samples was positive for type A botulinal toxin and three of the samples were negative for type A, B, E, and F botulinal toxins using the three methods. The mouse bioassay indicated that type A toxin was present at the 10,000 minimal lethal dose per gram (MLD per g) of product. The ELISA tests indicated a toxicity of 7,650 MLD per g with one method and 8,350 MLD per g with the other method. The sample toxicity determined by the ELISA was estimated by comparing samples to a standard curve generated with standard type A neurotoxin in casein buffer. The ELISA methods are more rapid than the mouse bioassay, since the toxin type can be determined in 1 day. The mouse bioassay is more sensitive than the ELISA but usually requires multiple assays to obtain the toxin type and toxicity. Type A culture isolates from the sample were also verified using one ELISA method.


[Thyroid malignant tumor with flare up glottic paralysis for first symptom].
To approach clinical feature of thyroid malignant tumor with Flare up glottic paralysis for first symptom, and analysis that should be avoided missed diagnosis and misdiagnosis during diagnosis and treatment. Retrospective research five cases of thyroid malignant tumor with flare up glottic paralysis papillary adenocarcinoma of thyroid by pathology. Four cases had one side glottic paralysis, the same side thyroid were moved after dissecting the recurrent laryngeal nerve. Three cases of them recovered normal vocal cord function, the function of one case was compensated by another side vocal cord. The last one had right gliotic paralysis first, then both cricoarytenoid joint had been fixed, hoarse voice was worse and developed to dyspnea since the tumor invaded in larynx one year later. We only did cut the right thyroid and right half larynx, but the tumor came back again in larynx in three months, then had to removal whole larynx without recurrence follow up two years. For the flare up glottic paralysis with same side tiny thyroid tumor, we suggest that the thyroid must be made operation research if no other reasons, dissecting and protecting the recurrent laryngeal nerve during operation, and cut reasonable thyroid and others according to fast pathologic diagnosis.


Obsessions of infanticide and imminent psychosis.
In young mothers an obsession of infanticide, that is, fear that they may murder their children, may be coupled with an obsession of imminent psychosis, that is, fear that the first obsession is a sign of approaching insanity. Sixteen mothers with this clinical picture were evaluated in interviews. Seven of them entered psychotherapy and improved. The causative factors in childhood and adolescence wich led to the later development of these obsessive difficulties are analyzed. Even when psychotherapy was not possible, as was the case in nine patients, they should be strongly reassured and explanations should be given about the nature of the problem, for such encouragement and clarification helps them to improve to a significant extent. The prognosis of patients who have systematic psychoterapy is good.


Prostaglandin in calcium and bone metabolism.
The effect of prostaglandins on bone resorption and formation is reviewed. The prostaglandins probably play a role in pathological changes in bone, e.g., those occurring in immune responses and neoplastic disease. Their physiological role is unknown.


Prevalence of risk factors and risk of mortality in relation to occupational group.
The aims of this study were to examine the prevalence of risk factors in different occupational groups of Kaunas men and women aged 35-64 years, and to assess the prognostic value of occupation on all-cause and cardiovascular mortality risk. The four random samples of Kaunas men and women (3,293 men and 3,561 women) aged 35-64 years from the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study (1983-2002) were examined using the standard epidemiological methods. The participants of the first three surveys were followed-up, in terms the end points reached, from the beginning of each survey until January 1, 2004. A multivariate Cox model was used for the analysis. In 1983-1984, the proportion of manual workers was greater than proportion of non-manual workers among both men and women. Twenty years later, the proportion of female manual workers decreased twice to 26.2%. The prevalence of majority risk factors showed no difference in manual and non-manual workers among both men and women. The risk of death from cardiovascular diseases among manual workers was 1.5 times greater than among non-manual workers. The different prognostic value of various variables has been determined on all-cause mortality risk in groups of manual and non-manual workers.


Monitoring glutamate and ascorbate in the extracellular space of brain tissue with electrochemical microsensors.
This paper describes electrochemical microsensors for the in vivo measurement of glutamate and ascorbate in the extracellular space of brain tissue. To prepare glutamate microsensors, carbon fiber microelectrodes (10 microns in diameter and 300-400 microns long) were modified with a cross-linked redox polymer film containing enzymes. The microsensors were coated with a thin Nafion film before use. The glutamate microsensors were both selective and sensitive toward glutamate, with detection limits in the low micromolar range. Physiologically relevant concentrations of several electroactive compounds found in brain tissue produced no response at the glutamate microsensors and also did not affect their glutamate response, the only exception being glutamine, for which a small response was observed in the absence, but not in the presence, of glutamate. The ascorbate microsensors were used in conjunction with cyclic voltammetry. They were sensitive and selective toward ascorbate, but did exhibit a small sensitivity toward the dopamine metabolite, dihydroxyphenylacetic acid. The in vivo measurements performed establish the ability of the glutamate microsensors to monitor the component of the basal extracellular glutamate level that is derived from the neuronal activity of brain tissue.


[Guideline principle and technical requirement for preparing traditional Chinese medicine reference drug].
Traditional Chinese medicine (TCM) reference drug is a new form of TCM standard reference substance. The purpose of this guideline is to guide the establishment of the reference drug and standardize its investigation and application in national drug standards. Definition of TCM reference drug was specified and relating guideline and technical requirement were introduced in this paper. Its application in quality control of TCM was analyzed and the developing train was proposed. There is a wide prospect for the application of reference drug in quality control of TCM. Thus it has practical significance to explore and conduct the quality evaluation system by using TCM reference drug as the reference substance.


Bioaccumulation of polycyclic aromatic hydrocarbons by marine organisms.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the marine environment, occurring at their highest environmental concentrations around urban centers. While they can occur naturally, the highest concentrations are mainly from human activities, and the primary sources are combustion products and petroleum. Two factors, lipid and organic carbon, control to a large extent the partitioning behavior of PAHs in sediment, water, and tissue; the more hydrophobic a compound, the greater the partitioning to these phases. These two factors, along with the octanol-water partition coefficient, are the best predictors of this partitioning and can be used to determine PAH behavior and its bioavailability in the environment. It is well known that the lipid of organisms contains the highest levels of hydrophobic compounds such as PAHs, and that organic carbon associated with sediment or dissolved in water can have the greatest influence on PAH bioavailability. Partitioning of combustion-derived PAHs between water and sediment may be much less than predicted, possibly because associations with particles are much stronger than expected. This reduced partitioning may produce erroneous results in predicting bioaccumulation where uptake from water is important. Accumulation of PAHs occurs in all marine organisms; however, there is a wide range in tissue concentrations from variable environmental concentrations, level and time of exposure, and species ability to metabolize these compounds. PAHs generally partition into lipid-rich tissues, and their metabolites can be found in most tissues. In fish, liver and bile accumulate the highest levels of parent PAH and metabolites; hence, these are the best tissues to analyze when determining PAH exposure. In invertebrates, the highest concentrations can be found in the internal organs, such as the hepatopancreas, and tissue concentrations appear to follow seasonal cycles, which may be related to variations in lipid content or spawning cycles. The major route of uptake for PAHs has been debated for years. For the more water-soluble PAHs, it is believed that the main route of uptake is through ventilated water and that the more hydrophobic compounds are taken in mainly through ingestion of food or sediment. There are many variables, such as chemical hydrophobicity, uptake efficiency, feeding rate, and ventilatory volume, which may affect the outcome. The route of uptake may be an important issue for short-term events; however, under long-term exposure and equilibrium conditions between water, prey, and sediment, the route of uptake may be immaterial because the same tissue burdens will be achieved regardless of uptake routes.(ABSTRACT TRUNCATED AT 400 WORDS)


[The long-run development of mortality in Germany].
The paper deals with the long-run development in mortality at individual ages in Germany by using a relative index of change in probabilities to die. The mortality at early childhood ages diminished to about one percent of what it was in the first German life table of 1871/81. Changes in infant mortality alone were responsible for 25 percent of the total increase in "life expectancy at birth" in the observation period. Changes in mortality at ages below 10 accounted for roughly 50 percent of change in life expectancy at birth. In the second part of the paper the measurement concept is used to evaluate assumptions about the future course of mortality in Germany. The most recent official forecast by the German Statistical Office is used to demonstrate the principle. The official assumptions about the future mortality proof to be unrealistically conservative. At ages below 20 the latest available data on mortality are more favorable than what is assumed for the year 2050.


NFKB1 -94 insertion/deletion ATTG polymorphism contributes to risk of systemic lupus erythematosus.
Growing evidence has shown that nuclear factor-κB (NF-κB) plays a key role in the initiation and progression of systemic lupus erythematosus (SLE) pathogenesis. A common polymorphism (-94 insertion/deletion ATTG, rs28362491) in the promoter region of NFKB1 gene was identified as functional. The -94del ATTG allele exhibited loss of binding to nuclear proteins and resulted in reduced promoter activity. We investigated the association between NFKB1 -94 insertion/deletion ATTG polymorphism and risk of SLE. A total of 224 SLE patients and 256 control subjects were genotyped using a polymerase chain reaction-polyacrylamide gel electrophoresis strategy and DNA sequencing. We found that the ATTG(1)/ATTG(2) genotype was associated with a significantly decreased risk of SLE (odds ratio=0.52, 95% confidence interval: 0.32-0.87, p=0.012). This finding indicates that the -94 insertion/deletion ATTG polymorphism may play pivotal roles in the development of SLE in the Chinese population. Further studies with larger sample size are warranted to confirm this finding, especially in different populations.


Robust charge transport in DNA double crossover assemblies.
Multiple-stranded DNA assemblies, encoded by sequence, have been constructed in an effort to self-assemble nanodevices of defined molecular architecture. Double-helical DNA has been probed also as a molecular medium for charge transport. Conductivity studies suggest that DNA displays semiconductor properties, whereas biochemical studies have shown that oxidative damage to B-DNA at the 5'-G of a 5'-GG-3' doublet can occur by charge transport through DNA up to 20 nm from a photo-excited metallointercalator. The possible application of DNA assemblies, in particular double crossover (DX) molecules, in electrical nanodevices prompted the design of a DNA DX assembly with oxidatively sensitive guanine moieties and a tethered rhodium photo-oxidant strategically placed to probe charge transport. DX assemblies support long-range charge transport selectively down the base stack bearing the intercalated photo-oxidant. Despite tight packing, no electron transfer (ET) crossover to the adjacent base stack is observed. Moreover, the base stack of a DX assembly is well-coupled and less susceptible than duplex DNA to stacking perturbations. Introducing a double mismatch along the path for charge transport entirely disrupts long-range ET in duplex DNA, but only marginally decreases it in the analogous stack within DX molecules. The path for charge transport in a DX DNA assembly is determined directly by base stacking. As a result, the two closely packed stacks within this assembly are electronically insulated from one another. Therefore, DX DNA assemblies may serve as robust, insulated conduits for charge transport in nanoscale devices.


Early generation yield testing versus visual selection in chickpea (Cicer arietinum L.).
Four F3 populations of chickpea (Cicer arietinum L.) were simultaneously evaluated for yield in an F3 yield trial and in single plant progeny rows. Ten high yielding, 10 low yielding and 10 randomly sampled lines, along with 10 lines visually selected for yield from the progeny rows, were retained for further evaluation. The lines from each of the four selection groups in each population were bulked and evaluated in a replicated yield trial at three locations and four environments. The bulk of visually selected lines was not superior in yield to the bulk of randomly sampled lines at all locations. The present results indicate that an early generation yield testing selection procedure is more efficient than visual selection for yield improvements in chickpea.


Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats.
Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO2 nanoparticle group (IR+ CeO2). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft failure.


[Controlled hypotension].
Induced hypotension is defined as a reduction in mean arterial blood pressure to 50-60 mm Hg in normotensive subjects. The aim of induced hypotension is to decrease intraoperative blood loss, decrease the need for blood transfusions and improve operating conditions. Most studies indicate that induced hypotension can decrease intraoperative blood loss by 50% in many surgical procedures; however, some studies report that blood loss is not significantly reduced. Current methods of induced hypotension are based on the use of rapid and short-acting vasodilators as primary agents (nitroprusside, nitroglycerine, urapidil), supplemented by volatile anesthetics (isoflurane) and/or beta-blockers (esmolol) to improve effect, reduce dosage and prevent side effects (reflex tachycardia, tachyphylaxis, rebound hypertension). Proper positioning of the patient and controlled ventilation aid in reducing blood loss. Major risks of induced hypotension are a reduction in blood flow (i.e. ischaemia) of vital organs (brain, myocardium) and elevation of intracranial pressure in neurosurgical patients. Thus, major contraindications of induced hypotension are severe coronary artery disease, hypertension combined with arteriosclerosis of cerebral vessels and increased intracranial pressure in patients with cerebral disease. Complications are rare in otherwise healthy patients, but may be higher in elderly patients and those with underlying organ dysfunction. Therefore, careful assessment and selection of patients, together with consideration of the potential complications, appropriate choice of drugs and invasive beat-by-beat monitoring, are essential for the safe practice of induced hypotension.


Diffuse esophageal leiomyomatosis: A case report with surgical correlation.
A 15 year old female with a history only significant for long standing dysphagia and intermittent chest pain underwent a screening chest radiograph. Findings of a large mass prompted cross sectional imaging where extensive and marked diffuse esophageal thickening was demonstrated. The patient ultimately underwent biopsy and surgical resection for diffuse esophageal leiomyomatosis. Diffuse leiomyomatosis of the esophagus has been described in the literature for about 100 years with increasing recognition in more recent times. There is a known association with inherited syndromes such as Alport and Esophageal-Vulvar syndrome, though some cases are sporadic. This case report will demonstrate the imaging features of diffuse esophageal leiomyomatosis utilizing multiple modalities including radiography, fluoroscopy, CT, and MRI, with surgical and pathologic correlation.


Wound botulism after traumatic open fracture in Italy.
Seventeen days after a traumatic open fracture, a Clostridium botulinum wound infection was diagnosed, with self-limiting symptoms. This is the first report of wound botulism in Italy and the authors discuss the possible role of aerosolized contamination of the wound prior to hospital admission.


Intrauterine latent herpes simplex virus infection: II. Latent neonatal infection.
Herpes simplex virus (HSV, probably type 2) antigen has been detected in endometria and abortion tissue (companion paper) and in placentae, umbilical cords, and fetal and neonatal organs by avidin-biotin complex immunohistochemical studies. HSV cytologic abnormalities were not detected in any of the 12 normal and 64 abnormal cases analyzed, nor was HSV detected by culture or electron microscopy in selected cases. Antigen was present in single epithelial and, rarely, mesenchymal cells of various organs. Clinically unexplained fetal or neonatal problems associated with HSV antigen positivity included intrauterine death, fetal growth retardation, cystic brain degeneration, hydrops, interstitial pneumonitis, necrotizing enterocolitis, hepatitis, encephalitis, myocarditis, and renal failure. Maternal floor infarct of placenta and calcifying funisitis are the manifestations of intrauterine HSV infection in most cases. Maternal history of HSV infection was uncommon. It is concluded that intrauterine HSV infection may persist in the fetus and neonate in a latent fashion without cytologic abnormalities or detectable virus. This latent infection may be associated with intrauterine and neonatal death, organ damage, and neonatal disease.


[Investigation and evaluation on the harmfulness of partial vibration and the contact vibration time].
The harmfulness from partial vibration with extended contact vibration time was studied by investigating into the symptoms and signs of workers with local vibration disease in Taiyuan Iron & Steel Company. The sense of hand, the function of nerve ending and the microcirculation of fingernail wrinkles of 321 workers working on local vibration operations were examined and observed. The indexes examined are worse with the increase of contact time and are better in low contact group. A positive correlation between the abnormal of microcirculation, the pain and numbness of hand was observed. It is concluded that the degree of harmfulness on hands and upper limbs of whom working on local vibration operation is related to the time of contact vibration. The function of nerve ending and the ending circulation were injured at the same time.


Safety and Biodistribution Evaluation of rAAV2tYF-CB-hRS1, a Recombinant Adeno-Associated Virus Vector Expressing Retinoschisin, in RS1-Deficient Mice.
Applied Genetic Technologies Corporation is developing a recombinant adeno-associated virus (rAAV) vector for treatment of X-linked retinoschisis (XLRS), an inherited retinal disease characterized by splitting (schisis) of the layers of the retina, which causes poor vision. We report here results of a study evaluating the safety and biodistribution of rAAV2tYF-CB-hRS1 in RS1-deficient mice. Three groups of male RS1-deficient mice received an intravitreal injection in one eye of either vehicle, or rAAV2tYF-CB-hRS1 at one of two dose levels (1 × 10(9) or 4 × 10(9) vg/eye) and were sacrificed 30 or 90 days later. The intravitreal injection procedure was well tolerated in all groups, with no test article-related changes in ophthalmic examinations. Two low-dose vector-treated animals had minimally to mildly higher white blood cell counts at day 90. There were no other intergroup differences in hematology or clinical chemistry analyses and no test article-related gross necropsy observations. Microscopic pathology results demonstrated minimal to slight mononuclear cell infiltrates in 80% of vector-injected eyes at day 30 and 20% of vector-injected eyes at day 90. Immunohistochemistry studies showed RS1 labeling of the retina in all vector-treated eyes. At the day 90 sacrifice, there was a decrease in the severity of splitting/disorganization of the inner nuclear layer of the retina in high-dose vector-treated eyes. Biodistribution studies demonstrated vector DNA in vector-injected eyes but not in any nonocular tissue. These results support the use of rAAV2tYF-CB-hRS1 in clinical studies in patients with XLRS.


An update on the safety of amlodipine.
A previous article on the safety of amlodipine reviewed data from over 4,000 subjects who participated in clinical trials sponsored by Pfizer Central Research. Once-daily amlodipine was shown to be a well-tolerated treatment of hypertension and myocardial ischemia. Although amlodipine is a potent vasodilator, there was a low incidence of side effects such as headache, flushing, and dizziness. Amlodipine was not associated with adverse effects on hematologic or biochemical safety parameters nor on serum cholesterol or triglyceride levels. Amlodipine did not alter electrical conduction in the heart. Amlodipine had a favorable safety profile in comparative trials vs. beta-blockers. The data base of comparative trials vs. other calcium antagonists was small but the toleration of amlodipine was similar to that of verapamil and diltiazem. No data from comparative trials vs. another calcium antagonist of the dihydropyridine class have been available. This article reviews data from recently completed trials vs. nitrendipine and from trials in which amlodipine was used in combination with other agents. Amlodipine was better tolerated than nitrendipine and had a much lower incidence of side effects usually related to vasodilatation. This difference in side-effect profile was especially marked during the first days of treatment. Amlodipine was well tolerated when used in combination with beta-blockers, diuretics, ACE inhibitors, and nitrates. The gradual onset of action and relatively long half-life of amlodipine are the probable cause for the improved toleration in comparison with other dihydropyridines. Besides the low incidence of trivial side effects, increasing clinical experience with amlodipine provides no evidence that amlodipine is a cause of rare but serious adverse effects. It is concluded that amlodipine is an antihypertensive and anti-ischemic agent that has the combined advantages of a good safety profile with once-daily dosage and a smooth onset and long duration of action.


[Fibrotic fraction and myocardial cell diameter in latent cardiomyopathy].
100 left-ventricular endomyocardial biopsies of 32 patients were studied by means of morphometric and histological methods. No differences were found between patients with normal left ventricular end-diastolic pressure (LVEDP) and with increased LVEDP in the mean diameter of heart muscle cells, the distribution parameters coefficient of variation and kurtosis, and the volume density of the connective tissue. These patients did not show pathological findings of the other functional parameters and the coronary arteries. Statistically significant differences had been proved between patients with different histological diagnosis (post-myocarditic state, chronic-ischemic heart disease) with respect to the mean diameter of the myocytes (p less than 0.001) and the kurtosis of the distribution of myocytes' diameter (p less than 0.05).


Immunity to Brugia pahangi in athymic nude and normal mice: eosinophilia, antibody and hypersensitivity responses.
Congenitally athymic nude (nu/nu) mice, immunologically reconstituted by thymus grafting before inoculation with infective larvae, and mice heterozygous for the nu gene (nu/+), mounted potent protective humoral and cellular immune responses to Brugia pahangi. Although responses were not identical, both groups of mice produced IgM, IgG and IgE antibodies specific for adult worm antigen (S-Ag) present in a crude aqueous extract, made immediate and delayed hypersensitivity footpad swelling responses when challenged with S-Ag and eliminated their infection in the early larval stages. Heterozygotes also exhibited a marked eosinophilia which peaked coincident with larval killing. In contrast, thymus grafting of patent nudes had no effect upon microfilaraemias or adult worm burdens and did not completely protect against a challenge larval inoculum although antibodies specific for S-Ag were produced. With the occasional exceptions of moderate immediate footpad swelling and very low titres of IgM specific for S-Ag, no specific immune responses to B. pahangi were found in ungrafted nude mice which allowed full development of adult worms and supported patent infections.


Glutamate and cysteinylglycine effects on NMDA receptors: inhibition by ethanol.
Glutamate, the endogenous neurotransmitter at the NMDA receptor, and cysteinylglycine are formed as byproducts of glutathione (GSH) metabolism by gamma-glutamyltranspeptidase. Glutamate and cysteinylglycine were investigated in Fura-2-loaded whole-brain neonatal (< 24 h) dissociated neurons to determine 1) if cysteinylglycine might act as a glycine site coagonist, 2) the inhibitory effects of ethanol on glutamate-stimulated increases in cytosolic calcium concentration (Glu-[Ca2+]i), and 3) the effects of cysteinylglycine on ethanol's inhibition of Glu-[Ca2+]i. Glu-[Ca2+]i (EC50 = 0.7 microM) in these cells was highly specific for NMDA receptor-operated calcium channels as they were dependent on extracellular calcium, enhanced by glycine, and blocked by magnesium, APV, and ethanol. However, because cysteinylglycine did not potentiate Glu-[Ca2+]i nor reverse ethanol inhibition of Glu-[Ca2+]i, it does not appear to act as a glycine coagonist or change the inhibitory sensitivity of ethanol to Glu-[Ca2+]i.


Role of apical caspases and glucocorticoid-regulated genes in glucocorticoid-induced apoptosis of pre-B leukemic cells.
Glucocorticoid (GC) sensitivity in hematopoietic cells requires the activation and nuclear translocation of the glucocorticoid receptor (GR) and the subsequent activation of caspases. To gain insight into the caspase cascade responsible for the execution phase of GC-induced apoptosis, 697 pre-B leukemic cells were stably transfected with dominant negative forms of caspase-8, caspase-9, or caspase-10 and the caspase-8 inhibitor CrmA. We observed that inhibition of caspase-9 or caspase-10 activity, but not caspase-8, caused partial resistance of 697 cells to GC-induced apoptosis. Inhibition of multiple caspases through the use of specific peptide inhibitors had an additive effect and caused complete resistance. To identify GR-regulated genes upstream of caspase activation in 697 cells, we performed DNA microarray analysis. 113 genes were identified, which were induced or repressed at least 3-fold by GC. Surprisingly, mitogen-activated protein kinase phosphatase-1 (MKP-1), a GR-induced gene in other cell types, was repressed 3-fold and correlated with an induction of JNK activity. These results suggest the involvement of mitogen activated protein kinases and apical caspase-9 and caspase-10 in the GC-induced apoptosis of pre-B lymphocytes.


Dual-Phase 18F-FP-CIT PET in Corticobasal Syndrome.
Corticobasal syndrome is the most common phenotype of corticobasal degeneration (CBD). F-FP-CIT PET and MRI are not helpful in distinguishing CBD from idiopathic Parkinson disease. Dual-phase F-FP-CIT PET is a recently developed imaging that shows regional cerebral perfusion in the early phase and dopamine transporter density in the late phase. We investigated the usefulness of dual-phase F-FP-CIT PET imaging in 3 patients with corticobasal syndrome. This image highlights that the early phases of F-FP-CIT PET may reflect regional cerebral perfusion with a pattern very similar to that of regional glucose metabolism in CBD.


Campylobacter enteritis mimicking acute abdominal emergency.
Among 81 hospitalized patients with enteritis due to Campylobacter fetus ssp. jejuni, abdominal pain was found to be an outstanding symptom, being observed in half the patients on admission. In 16 patients pain was the main reason for admission and in 5 prompted laparotomy. In 4 cases appendicitis was suspected, but in only 2 was slight inflammation seen; in 1 of these, however, the inflammation could not be verified by microscopic examination. One patient was operated on because of intestinal occlusion, presumably due to Campylobacter enteritis. In 10 further cases a surgeon was consulted because the abdominal pains were at first suspected to be due to cholecystitis, pancreatitis or other abdominal emergencies. Thus, acute phase of Campylobacter infection may mimick acute abdominal emergency. The diagnosis is sometimes hampered by the late onset of diarrhoea or even by its total absence, as well as by the usual presence of abdominal tenderness and severe abdominal pains.


Health-Related Quality of Life, Anxiety, and Depression in Bariatric Surgery Candidates Compared to Patients from a Psychosomatic Inpatient Hospital.
Past research indicated high psychiatric comorbidity and poor health-related quality of life (HRQOL) in patients seeking surgical treatment for obesity. This study investigated if preoperative bariatric surgery patients perceive equally poor HRQOL and increased levels of anxiety and depression as mentally ill patients. The study included four groups: 192 bariatric surgery candidates (PRE, 71% women, BMI 48.35 ± 8.98 kg/m2), 96 psychotherapy inpatients with mental disorders (PSY, 77% women, BMI 27.12 ± 9.17 kg/m2), 103 postoperative bariatric surgery patients (POST, 78% women, BMI 30.38 ± 2.88 kg/m2), and a convenience sample of 96 non-clinical volunteers with pre-obesity or obesity grade 1 (CG, 52% women, BMI 29.22 ± 2.64 kg/m2). HRQOL was measured using the 12-item short form health survey (SF-12), and psychopathology was assessed with the hospital anxiety and depression scale (HADS). The PRE group exhibited the lowest physical HRQOL, and the PSY group the lowest mental HRQOL. The highest mental/physical HRQOL was reported by the POST group and the CG, without significant differences between these two groups. While the PSY group scored higher on HADS-anxiety scale than the PRE group, neither group differed with regards to symptoms of depression. The lowest levels of HADS-depression were found in the POST group and the CG. The present findings suggest that bariatric surgery candidates may suffer from equally high levels of depression as psychotherapy inpatients, but they perceive better mental well-being. Routine mental health evaluation should incorporate assessments for both psychopathology and HRQOL. DRKS00009901.


Ca(v)1.2, Ca(v)1.3, and Ca(v)2.1 in the mouse hippocampus during and after pilocarpine-induced status epilepticus.
Calcium binding proteins are well known to be expressed by different groups of hippocampal interneurons; however, whether voltage-dependent calcium channels (Ca(v)) are also localized in these neurons, changed during and after status epilepticus (SE), and involved in epileptic activity have not been reported. In the present study, we showed the colocalization of three subtypes of voltage-gated calcium channels (Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1) with different calcium binding proteins such as calbindin (CB), calretinin (CR), and parvalbumin (PV). At early stages during and after pilocarpine-induced status epilepticus (PISE), significant changes of expression of Ca(v)1.2, Ca(v)1.3 (L-type), and Ca(v)2.1 (P/Q-type) were found in different groups of hippocampal neurons. Induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes was shown at 1 week and 2 months after PISE. At the latter time point, higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunoposivie neurons were observed in gliotic CA1 area. We therefore conclude that voltage-gated calcium channels are expressed by different groups of hippocampal interneurons in the mouse. At acute stages during and after PISE, up- or down-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in functionally different groups of interneurons in CA1 area may be related to the changes of their plasticity. Up-regulation of Ca(v)1.2, Ca(v)1.3, or Ca(v)2.1 in granule cells may be directly related to the occurrence of SE. The induced expression of Ca(v)1.3 or Ca(v)2.1 in reactive astrocytes at 1 week and 2 months after PISE suggests that Ca(v)1.3 or Ca(v)2.1-related calcium signaling in reactive astrocytes may be involved in initiation, maintenance or spread of seizure activity. In gliotic CA1 area at chronic stage (i.e., 2 months after PISE), the occurrence of higher percentages of colocalization of PV and Ca(v)1.2, CB, or PV and Ca(v)1.3 or Ca(v)2.1, lower percentages of CR and Ca(v)1.3 or Ca(v)2.1 immunopositive neurons may suggest that such colocalizations may be linked to the survival or loss of particular group of hippocampal neurons.


Surgical approach to atrial septal defect in the female. Right thoracotomy versus sternotomy.
Repair of atrial septal defect (ASD) remains a high-benefit, low-risk procedure due to technologic improvements. From July 1981 to December 1986, 35 females (age, 7 months to 28 years) had repair of ASD; 20 by right thoracotomy and aortic cannulation (group 1) and fifteen by median sternotomy (group 2). In general, right thoracotomy was applied to patients with secundum ASD two years or older and without associated lesions, while median sternotomy was applied to patients with ostium primum lesions and/or associated lesions. Patients or their families perceived the cosmetic results superior to the right thoracotomy approach over the median sternotomy. We feel that a right thoracotomy and aortic cannulation is effective in females (2 years and older) with secundum ASD for a superior cosmetic result over median sternotomy. However, females with ostium primum and/or associated lesions should undergo median sternotomy for better cardiac access and safety.