Psychiatry and the nursing home.
In the last two decades, nursing homes have become major providers of health services for the frail elderly. Despite ample evidence of need for specialized psychiatric services in the nursing home setting, the majority of patients who could benefit from such care do not receive it. The authors propose a fourfold role for the psychiatrist, encompassing clinical care, consultation, teaching, and research. Features of this role can be adapted to fee-for-service, community mental health center, and academic models of psychiatric practice.


Epidural injections of bupivacaine, morphine, fentanyl, lofentanil, and DADL in chronically implanted rats: a pharmacologic and pathologic study.
A new technique of epidural catheterization in rats is described. The pharmacologic characterizations of the model were established after epidural injection of bupivacaine, morphine, fentanyl, lofentanil, and D-Ala2-D-Leu5-enkephalin (DADL) on hot plate (HP) and tail flick (TF). In addition, rostral spread, motor function, behavior, and reproducibility of the effects over time were assessed. The time-response curves showed an almost immediate onset of action for bupivacaine, fentanyl, and lofentanil and a delayed onset for morphine and DADL. Morphine and lofentanil displayed a significantly longer duration of action than bupivacaine, fentanyl, and DADL. The dose-response curves were monotonic and the slopes were log-linear. Based on the ED50 values, the following rank order of potency was obtained 1 day after catheterization for both HP and TF: lofentanil much greater than fentanyl greater than morphine much greater than DADL greater than bupivacaine. Intraperitoneal (IP) administration of naloxone antagonizes the agonist effects of epidural morphine, fentanyl, and lofentanil. To assess the role in analgesia played by epidural vascular uptake after epidural administration of morphine, fentanyl, and lofentanil, the lowest maximally effective epidural dose of these agents was given intravenously. After iv fentanyl and lofentanil, the analgesic and behavioral effects were not different from the values obtained after epidural administration. By contrast, the effects were negligible after iv morphine when compared with the epidural route. Epidural vascular uptake is thought to be low for morphine and high for fentanyl and lofentanil. The reproducibility of the analgesic and behavioral effects over time was assessed by epidurally injecting the lowest maximally effective dose of bupivacaine, morphine, fentanyl, and lofentanil 1 day and 10 days after catheterization. After 10 days, a significant reduction of analgesic and behavioral effects was noted and was thought to be due to a complete fibrotic sheath surrounding the epidural catheter.


The N-end rule adaptor protein ClpS from Plasmodium falciparum exhibits broad substrate specificity.
The N-end rule is a conserved protein degradation pathway that relates the metabolic stability of a protein to the identity of its N-terminal residue. Proteins bearing a destabilising N-terminal residue (N-degron) are recognised by specialised components of the pathway (N-recognins) and degraded by cellular proteases. In bacteria, the N-recognin ClpS is responsible for the specific recognition of proteins bearing an N-terminal destabilising residue such as leucine, phenylalanine, tyrosine or tryptophan. In this study, we show that the putative apicoplast N-recognin from Plasmodium falciparum (PfClpS), in contrast to its bacterial homologues, exhibits an expanded substrate specificity that includes recognition of the branched chain amino acid isoleucine.


Sequence analysis of the gene encoding the major outer membrane protein rOmp B of Rickettsia japonica.
The complete nucleotide sequence of the gene encoding rOmp B (ompB), one of the two major outer membrane antigen proteins, of Rickettsia japonica was determined and compared to those of the other spotted fever group and typhus group rickettsiae. Open reading frame of the ompB gene of R. japonica consisted of 4,968 nucleotides coding for a putative precursor protein with 1,656 amino acids (aa) in which the N-terminal 1,363 aa and the C-terminal 293 aa encode 135-kilodalton rOmp B and 32-kilodalton beta-peptide, respectively. Putative promoter and terminator sequences for transcription were present in the upstream region of the ATG start codon and downstream of the TAA stop codon. Overall sequences of the ompB genes were well conserved beyond the group, especially in the beta-peptide regions.


Feelings of Usefulness to Others Predict Active Coping With Osteoarthritis Knee Pain.
To investigate associations of perceived usefulness to other people with active versus passive coping strategies among adults with knee osteoarthritis (OA). Additional aims explored contributions of personality variables to this dynamic. 199 persons (70.3 years ± 10.4) with knee OA reported personality, coping, and psychosocial data using the Big Five Inventory, subscales from the Social Provisions Scale, and the Coping With Illness measure. Regression analyses identified predictors of perceived usefulness and its independent and interactive associations with active versus passive coping and personality variables. Better subjective health predicted perceived usefulness. Older adults with higher reported perceived usefulness employed more active than passive pain coping strategies. Passive coping was associated with neuroticism and greater functional disability. Usefulness predicted active OA pain coping, suggesting that it may promote well-being among persons with chronic pain. Further study investigating perceived usefulness in promoting positive health behaviors is needed.


Microphotometric analysis of cytochrome P-450 in periportal, midzonal, and perivenular hepatocytes of mice treated with phenobarbital.
To obtain detailed information on the increase of cytochrome P-450 (P-450) content in periportal, midzonal, and perivenular hepatocytes after phenobarbital (PB) administration, and to study the mechanism of increased P-450 in the endoplasmic reticulum (ER), we estimated microphotometrically the P-450 content and morphometrically the area of ER in hepatocytes of three zones from mice injected with 35, 50, 100, or 150 mg/kg of PB for 3 days. The amount of P-450 per unit cytoplasmic volume and the number of P-450 molecules per unit ER area (P-450 number) were increased by injection of 50, 100, or 150 mg/kg, and the ER area per unit cytoplasmic volume was increased by injection of 100 or 150 mg/kg, in hepatocytes from all three zones. Thus, the amount of P-450 in hepatocytes appeared in general to increase multiplicatively by simultaneous increases in both the P-450 number and the ER area. Furthermore, we could recognize two general types of relationship in the P-450 number and ER area between the patterns of change and the increasing doses: (a) increase in the P-450 number without ER proliferation (active type) in periportal and perivenular hepatocytes after injection of low doses; and (b) increase in ER proliferation without increase in the P-450 number (passive type) in hepatocytes of all three zones after injection of high doses.


Inhibitory action of cyclosporin A on the early events of T cell activation: effects on T cell-independent production of IL1 and on IL1-dependent expression of reactivity to IL2.
Cyclosporin A (CsA) has a selective immunosuppressive effect on T cell functions, but its mode of action on IL1 activities and production remain unclear and controversial. While it has been documented that CsA has a profound effect on the ability of IL1 to promote IL2 production, its effects on the ability of IL1 to promote IL2-responsiveness are not known. Macrophage-depleted nylon wool non-adherent thymocytes (NATs) were preincubated for 6 h with or without IL1 in the presence of a wide range of concentrations of CsA (1 ng/ml-1 microgram/ml), washed and then pulsed with Con A. After washings in medium with alpha-MM, the capacity of NATs to proliferate in response to IL2 was determined. Both background and IL1-dependent acquisition of IL2-reactivity were inhibited by concentrations of CsA as low as 5 ng/ml. The effects of CsA (1 ng/ml-1 microgram/ml) on T cell-independent production of IL1 by irradiated, carrageenan-stimulated peritoneal macrophages were also examined. Up to 50 ng/ml CsA had no effect on IL1 production but higher concentrations produced a dose-dependent inhibition that was complete at 1 microgram/ml. These results show that CsA inhibits both T cell-independent production of IL1 and IL1-dependent expression of reactivity to IL2.


Feeding modality evolution in traumatic brain injury patients with severe alteration of consciousness: A observational study.
The aim of this study was to compare feeding modalities and the level of consciousness in patients with a severe brain injury during reeducation and rehabilitation. The clinical data of vegetative state or minimal conscious state due to severe traumatic brain injury hospitalized in a coma arousal unit were collected from 2012 to 2019. Feeding modalities were evaluated clinically and with functional endoscopy evaluation of swallowing or video fluoroscopy and functional oral intake scale. Evolution of consciousness was evaluated using Wessex Head Injury Matrix scale (WHIM). Comparison between WHIM score and feeding modalities were performed at admission and at discharge of the arousal unit. Of the 93 patients considered, 33 were included corresponding to inclusion criteria (traumatic brain injury, disorder of consciousness and age > 18 years). The mean age was 44.8 ± 16.8 years, and there were 6 females for 27 males. At admission, all patients were fed by gastrostomy (n = 25) or by nasogastric tube (n = 8) and 27 had a tracheostomy. At discharge, 10 patients keep an exclusive alimentation by gastrostomy (Group 1, G1) as 23 had exclusive oral feeding (Group 2, G2). The score of the WHIM at admission was identical in both groups (21.7 ± 10.9 (G1) vs. 21.0 ± 15.33 (G2) (ns)). At discharge, WHIM increased to 38.3 ± 15.4 in G1 and to 49.8 ± 9.7 in G2 (P < .05). WHIM score was significantly higher in G2 than in G1 (P < .05). There was a positive correlation between functional oral intake scale and WHIM at discharge. Our results demonstrated that recovery of oral feeding in patients with a severe traumatic brain injury appeared in those who had the better improvement of consciousness level.


Mechanical Allodynia Predicts Better Outcome of Surgical Decompression for Painful Diabetic Peripheral Neuropathy.
To determine the role of mechanical allodynia (MA) in predicting good surgical outcome for painful diabetic peripheral neuropathy (DPN). Data of 192 patients with painful DPN were collected in this study, with 148 surgical patients and 44 patients in the control group. Both groups were further divided into subgroups based on the presence of MA on admission. Clinical evaluations including the visual analog scale (VAS), the Hospital Anxiety and Depression Scale (HADS), nerve conduction velocity (NCV), and high-resolution ultrasonography (cross-sectional area, CSA) were performed preoperatively and postoperatively. The levels of VAS and HADS and the results of NCV and CSA were improved in the surgical group (p < 0.05). In the surgical subgroups, pain reduction, psychiatric amelioration, improvement in NCVs, and the restoration of the CSA were observed in patients with signs of MA (p < 0.05), whereas only pain reduction, psychiatric amelioration, and restoration of the CSA were noted in patients without signs of MA (p > 0.05). Furthermore, better pain reduction was achieved in patients with MA when compared with those without MA (p < 0.05). MA is proved to be a reliable predictor of good surgical outcome for painful DPN.


New and improved tools for in utero electroporation studies of developing cerebral cortex.
In utero electroporation (IUE) has become a method of choice for rapid gain and loss of function studies in embryonic cerebral cortex. In this review we highlight some of the proven and recent advances in IUE technology that make it applicable to an increasingly wide array of experiments requiring spatial and temporal control of gene expression. Recently, cell-type-specific promoters and tamoxifen-gated cre-recombinase have been shown to work effectively with IUE. Experiments can now be designed and carried out to test whether and which cell-type-specific mechanisms operate within defined periods of neuronal migration and maturation. We have recently adapted this conditional expression approach to implement conditional rescue experiments. In conditional rescue, expression of an RNA interference (RNAi) target is restored by tamoxifen-induced cre-mediated recombination. An initial disruption in migration, and resultant malformation, caused by DCX RNAi was reversed by delayed re-expression of Dcx. In the future, combinations of spatially directed, cell-type-specific, and tamoxifen-gated transgene expression can be used to address the complex mechanisms likely to operate during development of cerebral cortex.


Change of left ventricular geometric pattern after 1 year of antihypertensive treatment: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.
Patients with hypertension have different types of left ventricular (LV) geometry, but the impact of blood pressure (BP) reduction on LV geometry change during antihypertensive treatment remains unclear. Two-dimensional and M-mode echocardiograms were recorded at baseline in 853 unmedicated patients with stage II to III hypertension and LV hypertrophy determined by electrocardiography (Cornell voltage duration > or =2440 mV x ms or modified Sokolow-Lyon criteria: SV1 + RV5/RV6 >38 mV) after 14 days of placebo treatment. Follow-up echocardiography was done after 1 year of blinded treatment with either losartan or atenolol, in some cases supplemented with thiazide and calcium antagonist to reach target a BP of 140/90 mm Hg. Baseline systolic/diastolic BP were reduced from 174 +/- 20/95 +/- 11 to 151 +/- 19/84 +/- 11 mm Hg. LV mass was reduced from 234 +/- 56 to 207 +/- 51 g and relative wall thickness from 0.41 +/- 0.07 to 0.38 +/- 0.06 (all P <.001). Prevalence of concentric LV hypertrophy decreased from 24% to 6%, eccentric LV hypertrophy from 46% to 37%, and concentric LV remodeling from 10% to 6%; normal geometry increased from 20% to 51%. A shift toward lower LV mass and relative wall thickness was found, as approximately 73% of those with concentric LV remodeling at baseline shifted to normal geometric pattern, whereas only 7% of those with normal pattern at baseline shifted to concentric LV remodeling. Of patients with concentric LV hypertrophy at baseline, 34% shifted to eccentric LV hypertrophy, whereas only 3% with eccentric LV hypertrophy at baseline had concentric LV hypertrophy. Furthermore, multiple regression analysis showed that Doppler stroke volume reduction was a significant correlate of LV mass reduction (beta = 0.108, P <.001) independent of BP, heart rate change, and assigned drug treatment. Antihypertensive treatment reduces LV mass and decreases the prevalence of LV hypertrophy and concentric LV remodeling. Additional control of Doppler stroke volume potentiates the effect of BP reduction on LV mass regression independent of the BP reduction per se.


Perceived Risk of Job Instability and Unethical Organizational Behaviour Amid the COVID-19 Pandemic: The Role of Family Financial Pressure and Distributive Injustice in the Tourism Industry.
The economic disaster precipitated by the pandemic of COVID-19 changed people's perceptions of ordinary job stability and elevated it to an ultimate high level. To avoid being laid off, employees who are concerned about job stability may engage in unethical activities in the name of their employer. In this study, the influence of job instability on unethical organizational behaviour (UOB) was investigated through the mediating role of family financial pressure and distributive injustice. Perceptions of 830 employees working in hotels (5-star and 4-star) and travel agencies (Category A) were explored and further analyzed using structural equation modelling. The results asserted that family financial pressure and distributive injustice partially mediated the effects of job insecurity on UOB. Important insights on theoretical and practical implications were further deliberated towards the end of this study.


Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex.
Human MOF (MYST1), a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs), is the human ortholog of the Drosophila males absent on the first (MOF) protein. MOF is the catalytic subunit of the male-specific lethal (MSL) HAT complex, which plays a key role in dosage compensation in the fly and is responsible for a large fraction of histone H4 lysine 16 (H4K16) acetylation in vivo. MOF was recently reported to be a component of a second HAT complex, designated the non-specific lethal (NSL) complex (Mendjan, S., Taipale, M., Kind, J., Holz, H., Gebhardt, P., Schelder, M., Vermeulen, M., Buscaino, A., Duncan, K., Mueller, J., Wilm, M., Stunnenberg, H. G., Saumweber, H., and Akhtar, A. (2006) Mol. Cell 21, 811-823). Here we report an analysis of the subunit composition and substrate specificity of the NSL complex. Proteomic analyses of complexes purified through multiple candidate subunits reveal that NSL is composed of nine subunits. Two of its subunits, WD repeat domain 5 (WDR5) and host cell factor 1 (HCF1), are shared with members of the MLL/SET family of histone H3 lysine 4 (H3K4) methyltransferase complexes, and a third subunit, MCRS1, is shared with the human INO80 chromatin-remodeling complex. In addition, we show that assembly of the MOF HAT into MSL or NSL complexes controls its substrate specificity. Although MSL-associated MOF acetylates nucleosomal histone H4 almost exclusively on lysine 16, NSL-associated MOF exhibits a relaxed specificity and also acetylates nucleosomal histone H4 on lysines 5 and 8.


An innovative protein expression system using RNA polymerase I for large-scale screening of high-nucleic-acid content Saccharomyces cerevisiae strains.
Saccharomyces cerevisiae is the preferred source of RNA derivatives, which are widely used as supplements for foods and pharmaceuticals. As the most abundant RNAs, the ribosomal RNAs (rRNAs) transcribed by RNA polymerase I (Pol I) have no 5' caps, thus cannot be translated to proteins. To screen high-nucleic-acid content yeasts more efficiently, a cap-independent protein expression system mediated by Pol I has been designed and established to monitor the regulatory changes of rRNA synthesis by observing the variation in the reporter genes expression. The elements including Pol I-recognized rDNA promoter, the internal ribosome entry site from cricket paralytic virus which can recruit ribosomes internally, reporter genes (URA3 and yEGFP3), oligo-dT and an rDNA terminator were ligated to a yeast episomal plasmid. This system based on the URA3 gene worked well by observing the growth phenotype and did not require the disruption of cap-dependent initiation factors. The fluorescence intensity of strains expressing the yEGFP3 gene increased and drifted after mutagenesis. Combined with flow cytometry, cells with higher GFP level were sorted out. A strain showed 58% improvement in RNA content and exhibited no sequence alteration in the whole expression cassette introduced. This study provides a novel strategy for breeding high-nucleic-acid content yeasts.


Analysis of membrane proteins by two-dimensional electrophoresis: comparison of the proteins extracted from normal or Plasmodium falciparum-infected erythrocyte ghosts.
Parasite-encoded membrane proteins translocated to the surface of infected erythrocytes or in specialized vesicles underneath (Maurer's clefts) play a key role in the asexual life cycle of Plasmodium falciparum (a malaria-causing protozoan), by mediating key steps such as red blood cell invasion, sequestration of infected cells in microcapillaries, and red blood cell rupture. A large-scale analysis of these membrane proteins would therefore be of great help to gain knowledge of the different stages of the Plasmodium falciparum life cycle. In order to be able to detect and identify parasite-encoded proteins directed to the red blood cell membrane, we first defined the conditions required for optimal extraction and separation of normal red blood cell ghost proteins by two-dimensional gel electrophoresis. These conditions included the use of urea, thiourea and new zwitterionic detergents in the extraction and isoelectric focusing media. The optimized conditions were then applied to analyze normal and P. falciparum-infected red blood cell ghosts. Several protein spots were found only in infected ghosts and are expected to represent parasite-encoded proteins. These proteins are currently under investigation.


Determination of alkylphenols and 17beta-estradiol in fish homogenate. Extraction and clean-up strategies.
The determination of target analytes such as nonyl- and octylphenols and 17beta-estradiol in fish homogenate require of solid-liquid extraction step. In this work microwave-assisted extraction (MAE) and focused-ultrasound liquid extraction (FUSLE) were studied as two different alternatives for extraction of the target compounds in zebrafish (Danio rerio) homogenate. In this work solid phase extraction (SPE) using 5-g and 10-g Florisil cartridges and gel permeation chromatography (GPC) were studied for the clean-up of the MAE and FUSLE extracts due to the non-selective extraction step. Although good recoveries were obtained both for SPE (106% and 126% range) and GPC (79% and 100% range) clean-up procedures, cleaner chromatograms were obtained after SPE and finally 5-g Florisil cartridges were tested since no improvement was observed when 10-g Florisil cartridges were used. Under optimized clean-up conditions, MAE and FUSLE provided comparable results for 4nOP and NP, while more accurate results were obtained for 4tOP and E2 after FUSLE. Finally, the method was applied to the determination of alkylphenols and 17beta-estradiol in zebrafish homogenate that had been exposed to known concentrations of the target analytes. In the case of alkylphenols two different isomers of nonyl- and octylphenol (4-(3',6'-dimethyl-3'-hepthyl)phenol, 363-NP, and 4-(3'-methyl-3'-hepthyl)phenol, 33-OP) were studied.


Lack of extracellular matrix switches TGF-β induced apoptosis of endometrial cells to epithelial to mesenchymal transition.
The extracellular matrix and the correct establishment of epithelial cell polarity plays a critical role in epithelial cell homeostasis and cell polarity. In addition, loss of tissue structure is a hallmark of carcinogenesis. In this study, we have addressed the role of extracellular matrix in the cellular responses to TGF-β. It is well known that TGF-β is a double-edged sword: it acts as a tumor suppressor in normal epithelial cells, but conversely has tumor-promoting effects in tumoral cells. However, the factors that determine cellular outcome in response to TGF-β remain controversial. Here, we have demonstrated that the lack of extracellular matrix and consequent loss of cell polarity inhibits TGF-β-induced apoptosis, observed when endometrial epithelial cells are polarized in presence of extracellular matrix. Rather, in absence of extracellular matrix, TGF-β-treated endometrial epithelial cells display features of epithelial-to-mesenchymal transition. We have also investigated the molecular mechanism of such a switch in cellular response. On the one hand, we found that the lack of Matrigel results in increased AKT signaling which is sufficient to inhibit TGF-β-induced apoptosis. On the other hand, we demonstrate that TGF-β-induced epithelial-to-mesenchymal transition requires ERK and SMAD2/3 activation. In summary, we demonstrate that loss of cell polarity changes the pro-apoptotic function of TGF-β to tumor-associated phenotype such as epithelial-to-mesenchymal transition. These results may be important for understanding the dual role of TGF-β in normal versus tumoral cells.


Lichens as biomonitors of air quality around a diamond mine, northwest territories, Canada.
Lichens are known to be bioaccumulators of atmospheric pollutants and are abundant in the Canadian arctic. Mining in this region may negatively impact the tundra communities and these impacts may be detected by increased accumulation of heavy metals, greenhouse gas constituents, and organic compounds in lichen tissue. The effect of sampling direction and distance from a diamond mine on bioaccumulation in three lichen species, Flavocetraria nivalis, Flavocetraria cucullata, and Cladina arbuscula, was investigated. Eight sample sites were located immediately adjacent to a diamond mine, one in each cardinal and ordinal direction, and six sample sites each were located 30 and 60 km from the mine (cardinal, NE, and SE). Thirty-three major and trace elements, sulfate (SO(4)), nitrate (NO(3)), ammonium (NH(4)), polycyclic aromatic hydrocarbons (PAH), and phthalates were analyzed in lichen tissue and soil. A significant interaction occurred between distance and direction from the mine. Highest concentrations of Al, Cr, Cu, Fe, Ni, Ti, and V in lichen were at the mine site regardless of direction. Highest concentrations for all other elements were at the mine in at least two directions. Although present in lichen tissue, there was no significant difference among sites for Hg, Mn, S, and three phthalates. PAHs were below detection limits in lichen tissue. The effect of direction was dependent on element and species, although concentrations of most elements were greatest east or southeast of the mine site. At distance from the mine, direction had less of an effect on concentrations. Elevated concentrations in tissue did not negatively impact lichen or plant cover or lichen richness. This research strongly suggests selection of sample sites and species can impact results and interpretation of data from air quality monitoring programs that use lichens as biomonitors.


The Clinical Impact of Using 18F-FDG-PET/CT in the Diagnosis of Suspected Vasculitis: The Effect of Dose and Timing of Glucocorticoid Treatment.
18F-Fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) with computed tomography (CT) is effective for diagnosing large vessel vasculitis, but its usefulness in accurately diagnosing suspected, unselected vasculitis remains unknown. We evaluated the feasibility of 18F-FDG-PET/CT in real-life cohort of patients with suspicion of vasculitis. The effect of the dose and the timing of glucocorticoid (GC) medication on imaging findings were in special interest. 82 patients with suspected vasculitis were evaluated by whole-body 18F-FDG-PET/CT. GC treatment as prednisolone equivalent doses at the scanning moment and before imaging was evaluated. 38/82 patients were diagnosed with vasculitis. Twenty-one out of 38 patients had increased 18F-FDG accumulation in blood vessel walls indicating vasculitis in various sized vessels. Vasculitis patients with a positive vasculitis finding in 18F-FDG-PET/CT had a significantly shorter duration of GC use (median = 4.0 vs 7.0 days, P=0.034), and they used lower GC dose during the PET scan (median dose = 15.0 mg/day vs 40.0 mg/day, p=0.004) compared to 18F-FDG-PET/CT-negative patients. Vasculitis patients with a positive 18F-FDG-PET/CT result had significantly higher C-reactive protein (CRP) than patients with a negative 18F-FDG-PET/CT finding (mean value = 154.5 vs 90.4 mg/L, p=0.018). We found that 18F-FDG-PET/CT positivity was significantly associated with a lower dose and shorter duration of GC medication and higher CRP level in vasculitis patients. 18F-FDG-PET/CT revealed clinically significant information in over half of the patients and was effective in confirming the final diagnosis.


[Comparison of Clinical Performance and Safety between Domestic New Pull-type Triple-lumen Sphincterotome and Conventional Sphincterotome: A Prospective Multicenter Trial].
Sphincterotomes are essential for endoscopic sphincterotomy (EST) and can also be used for cannulation in ERCP. A domestic new pull-type sphincterotome (Optimos™, Taewoong, Goyang, Korea) provides acceptable technical feasibility and safety, but there are no comparison results. Thus, this study compared the clinical performance and safety of Optimos™ sphincterotome to a conventional sphincterotome (CleverCut3™, Olympus, Tokyo, Japan) in patients who underwent ERCP. From April 2021 to July 2021, a randomized prospective comparative study was conducted on 104 consecutive patients who underwent ERCP in three medical centers. The primary endpoint was the clinical performance and safety of sphincterotomes during ERCP. One hundred and four patients were assigned randomly to the Optimos™ group (n=51) or CleverCut3™ group (n=53). All demographic characteristics did not differ between the groups except the BMI. The technical success rate for cannulation, performance of EST, and total procedure time were similar in the two groups. The adverse events did not differ, even though two cases of post-ERCP pancreatitis occurred in CleverCut3™. On the other hand, in questionnaire analysis, CleverCut™ showed a better user's convenience (median [interquartile range] 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.013) and manipulability (median [interquartile range], 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.039) than Optimos™, even though the other profiles did not reveal any differences. New domestic pull-type sphincterotome can offer comparable clinical performance and safety profiles to conventional sphincterotome, but it needs refinements to increase the user's convenience and manipulability. Further improvement and innovation will be required to advance domestic medical devices.


Highly Effective Protein Converting Strategy for Ultrasensitive Electrochemical Assay of Cystatin C.
In this work, a highly effective protein converting strategy based on immunoreaction-induced DNA strand displacement and T7 Exonuclease (T7 Exo)-assisted protein cyclic enzymatic amplification for ultrasensitive detection of cystatin C was described. Herein, Au@Fe3O4 as magnetic separator was labeled by antibody 1-conjungated DNA (DNA1) and the DNA substrate of T7 Exo (DNA3) which initially hybridized with output DNA (S1) to form a stable S1/DNA1 duplex (S1/DNA3). Antibody 2 was labeled by competing DNA (DNA 2). In the presence of cystatin C, sandwich immunoreaction would induce proximity hybridization between DNA2 and DNA3 and thus displace S1 from the S1/DNA3 duplex with formation of a stable DNA2/DNA3 duplex, realizing the conversion of input target cystatin C into output S1. To enhance the conversion ratio, the DNA2/DNA3 duplex was then digested by T7 Exo with release of DNA2 which could act as competing DNA again to displace S1 from the S1/DNA3 duplex in adjacent locations and initiate another cleavage reaction. Through such a cyclic process, each input cystatin C could induce more than one output S1, enhancing detection sensitivity. A hairpin DNA modified electrode was used to capture the output S1, and then, a hybridization chain reaction is triggered on the biosensor surface. Then, thionine as electron mediator was embedded into the dsDNA polymers to produce a detection signal. The electrochemical biosensor exhibited a much wider linear range of 0.01 pg mL(-1) to 30 ng mL(-1) with low detection limit of 3 fg mL(-1). Moreover, this method introduced protein unrelated to nucleic acids into the realm of potential inputs for translation, which might create a new immunoassay method for sensitive detection of protein.


[Well-being in call centres: a multidisciplinary approach to research and evaluation].
The topics of stress and well-being in call centres are the focus of many different disciplines. This article presents the definition and start-up phases of the "Well-being in Telecom Italia Call Centres" project, which was coordinated and supervised by an interdisciplinary scientific committee composed of members from different universities. To address the topic of individual well-being in the organizational context means considering all the main factors that can affect wellbeing. For this reason, the study assessed the topic from three different view-points (psychological/sociological/cultural, physical/chemical/biological, organizational/technological/work-related) in order to obtain an accurate as possible picture of the complex well-being dynamics. The study plan shows that merging qualitative methods (interviews, observations, focus-groups) and quantitative methods (questionnaires, physiological response to perceived stress) was a central concern for the research team. The collected data highlighted important differences between psychological and physical well-being and discomfort according to the different kinds of call centre, the respondents'gender and working hours. This method enabled us to define the specific features of call centre environments, leading to a definition of work in the centres as an activity with high psychological uncertainty, where rigid rules coexist with demands of high levels of flexibility and competence, and suggesting the importance of specific organizational measures in order to improve well-being.


Effect of osteoporosis on fixation of osseointegrated implants in rats.
The effect of osteoporosis on implant osseointegration has been widely investigated, whereas osteoporosis may also newly occur in patient with previously osseointegrated implant. This study was designed to investigate the effect of osteoporosis on implant fixation in rats after successful osseointegration had been obtained. Seventy female Sprague-Dawley rats were included, and each animal received two titanium implants in the distal metaphysis of femur bilaterally. Eight weeks later, ten rats were sacrificed to confirm the establishment of implant osseointegration. All left rats were randomly subjected to bilateral ovariectomy (OVX) or sham operation. Three, six, and twelve weeks later, implant osseointegration, peri-implant bone tissue, and biomechanical properties of implant were analyzed. Right femurs with implants were used for micro-CT and histological analysis, and left femurs with implants were used for biomechanical test. Micro-CT, histology, and biomechanical test confirmed the destructive effect of OVX on previously osseointegrated implant in rats; when compared to sham-operated rats, peri-implant bone volume, trabecular architecture, bone-to-implant contact ratio, as well as biomechanical parameters decreased progressively within 12 weeks. Results also indicated that the effect of OVX on undisturbed bone (proximal tibiae) was much stronger than that on peri-implant bone. Osteoporosis produced a progressive negative effect on previously osseointegrated implant in distal femora of rats during 12 weeks. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2426-2432, 2017.


Mesothelioma, asbestos, and reported history of cancer in first-degree relatives.
Although malignant mesothelioma is known to be strongly related to asbestos exposure, its relationship to familial factors is unclear. We compared reported histories of cancer in first-degree relatives, obtained from telephone interviews with the next-of-kin of 196 patients who had a pathologic diagnosis of mesothelioma, and with those from 511 decreased controls. Among men exposed to asbestos, we found a statistically significant twofold elevation in the risk of mesothelioma for patients reporting cancer in two or more first-degree relatives. We found no significant elevation in women or among the small number of men without asbestos exposure. The next-of-kin of three patients (but no controls) reported a possible mesothelioma in a first-degree relative; asbestos exposure could not be ruled out in those relatives. Associations of asbestos with pleural mesothelioma were stronger among men with a reported family history of cancer than men without, although no statistical evidence of an interaction was detected. These results provide suggestive, but limited, evidence that a family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma given asbestos exposure.


Expression of the Escherichia coli pcnB gene is translationally limited using an inefficient start codon: a second chromosomal example of translation initiated at AUU.
Expression of the gene pcnB, encoding the dispensable Escherichia coli poly(A) polymerase (PAPI), which is toxic when overproduced, was investigated. Its promoter was identified and found to be moderately strong when used to express a beta-galactosidase reporter. Expression levels were not affected by increasing or decreasing PcnB concentration. Translation of pcnB was found to initiate from the non-canonical initiation codon AUU. The only other coli gene reported to use AUU as initiation codon is infC, which encodes the initiation factor IF-3. AUU, in common with other rarely used initiation codons, is discriminated against by IF-3, resulting in the aborting of most AUU-promoted initiation events. This enables AUU to form part of an autoregulatory circuit controlling IF-3 production. We show that InfC discrimination reduces PcnB production fivefold. This is the first instance of this mechanism being used to limit severely the production of a potentially toxic product.


Pharmacotherapy for treatment of attention deficits after non-progressive acquired brain injury. A systematic review.
To systematically review the effectiveness of medications used to improve attention in people with non-progressive acquired brain injury. A systematic review. MEDLINE, EMBASE, CINALH, PUBMED and PsychINFO databases were used to identify studies published between 1987 and 2008 meeting the following criteria: studies with subjects older than 18 years; diagnosis of new onset or previous acquired brain injury; medication given to improve attention and use of outcome to measure attention. Studies involving subjects in low arousal states or with neurogenerative conditions were excluded. The studies were categorized into three evidence levels: I - Randomized controlled trials; II - Prospective studies, controlled trials with methodological limitations; and III - Retrospective studies, clinical case series. Forty-seven articles were identified on initial search. Twenty-six met the pre-specified criteria. Five articles were assessed as meeting the level I evidence criteria, 12 were level II studies and 9 were level III studies. Methylphenidate can improve information processing speed but not all attention aspects in some people after traumatic brain injury. There is weak evidence for use of dopamine agonists to improve neglect/inattention after stroke. There is little evidence on the frequency of adverse effects and long-term functional benefits. Although there is lack of robust evidence to recommend the routine use of medication to improve attention after traumatic brain injury and stroke, the existing evidence indicates potential for benefit in some patents and therefore further research is warranted.


A rare case of arteriosclerosis obliterans without prominent risk factors complicated by idiopathic thrombocytopenic purpura. A case report.
An eighty-four-year-old man was admitted to the hospital because of pain at rest in the lower extremities. On physical examination, trophic changes of the skin and petechiae in the limbs were observed. Computed tomographic scan of the abdomen showed focal renal infarctions and calcification of the descending aorta. Moreover, radionuclide imaging of the arterial system revealed complete obstructions of the two right iliac arteries and the left external iliac artery, where collateral flows were observed. Laboratory examination showed a severe thrombocytopenia caused by immunoglobulin G (IgG)-type autoantibody against platelets. He was diagnosed as having arteriosclerosis obliterans complicated by idiopathic thrombocytopenic purpura, although no known risk factors promoting atherosclerosis other than age were evident. In such a case with hemorrhagic diathesis, a hemorheologic agent and the vasodilator prostaglandin could confer advantages in relieving and controlling the ischemic leg pain without hemorrhagic complications. Moreover, small doses of the initial prednisolone therapy for ITP might also be recommended to avoid thrombus formations in the atherosclerotic lesions.


Tissue engineering of small-diameter vascular grafts: a literature review.
For the treatment of cardiovascular disease, functional arterial blood vessel prostheses with an inner diameter less than 6 mm are needed. This article gives an overview of the preparation of such vascular grafts by means of tissue engineering.


[Dental hygienist in financial independent practice: an established institute?].
The purpose of this article was to describe the development and actual status of the financial independent dental hygienist in The Netherlands. In 15 years nearly 100 dental hygienists started in financial independent practice after a few years of experience. In a survey (response: 80%, N = 58) respondents reported that especially patients with advanced periodontal diseases were treated in their practice. A majority of the respondents also works for a dentist employer. Compensation by insurance companies makes the treatment by independent dental hygienists approachable for more patients and is therefore advisable.


Specialty intentions of 1995 U.S. medical school graduates and patterns of generalist career choice and decision making.
The authors report on the specialty intentions that graduating students declared on the 1995 AAMC Medical School Graduation Questionnaire (GQ) and compare the pattern of career choices in 1995 with that in 1992. Family practice was the leading choice of graduates in 1995, followed by internal medicine subspecialties and general internal medicine. These choices represented significant gains over those made in these specialties in 1992 and were at the expense of declines in the interest of 1995 graduates for internal medicine specialties, radiology, anesthesiology, obstetrics-gynecology subspecialties, and some other fields. In 1992, 14.6% of graduating students declared plans to pursue careers in one of the generalist specialties; in 1995, 27.6% declared such plans. In 1992, no school graduated 50% or more students with generalist intentions, and only one school reached 40%; in 1995, five schools graduated more than 50%, and another 15 graduated more than 40% who favored generalist careers. Medical schools with significant GQ response rates (110 out of 125) were aggregated by level of generalist production (top 25%, middle 50%, and bottom 25%) according to the percentages of their 1995 graduates selecting careers in the individual generalist specialties of family practice, general internal medicine, and general pediatrics, and in these generalist specialties in toto. Within these groups, the linking of GQ responses to declarations given by the same students on the Matriculating Student Questionnaire (MSQ) made it possible to determine the extent to which graduates' specialty choices represented early interests that were retained or interests acquired later during medical school.(ABSTRACT TRUNCATED AT 250 WORDS)


Morphological and Photosynthetic Properties of Digitonin-treated Chloroplast Membranes from the Wild-type and ac-5 Strains of Chlamydomonas reinhardi.
Chloroplast membranes of wild-type Chlamydomonas reinhardi, treated with digitonin, yield photosystem II-rich and photosystem I-rich fractions; this fractionation is accompanied by a separation of stacked (grana) lamella from unstacked (stroma) lamellae. Poor fractionation of the photosystems occurs when the treated chloroplast membranes derive from the ac-5 strain grown mixotrophically, whereas good fractionation occurs with ac-5 cells grown phototrophically; the mixotrophic cells possess only unstacked membranes, whereas the phototrophic cells possess stacked membranes. We concluded that digitonin fractionation is dependent on the stacked membrane configuration.


Bile Formation: a Concerted Action of Membrane Transporters in Hepatocytes and Cholangiocytes.
A large number of membrane transport mechanisms in hepatocytes and cholangiocytes serves for the secretion of bile acids, various other organic anions, organic cations, lipids, and electrolytes. After their functional characterization, some of these mechanisms' individual transport molecules are now identified, allowing better understanding of inherited and acquired disorders of bile formation.


Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia.
Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1) plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF) is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF) secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24) cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.


Learning disabilities and adolescent suicide.
To investigate the hypothesis that learning disabilities (LD) play a part in adolescent suicide, all available suicide notes (n = 27) from 267 consecutive adolescent suicides were analyzed for spelling and handwriting errors. The suicide notes were dictated to adolescents with LD and adolescent non-LD controls. The results showed that 89% of the 27 adolescents who committed suicide had significant deficits in spelling and handwriting that were similar to those of the adolescents with LD, and they were significantly more impaired than the non-LD adolescents and older adults (65 and older) who had committed suicide in the same time period and in the same geographical area.


Hypoxaemia in children with severe pneumonia in Papua New Guinea.
To investigate the severity and duration of hypoxaemia in 703 children with severe or very severe pneumonia presenting to Goroka Hospital in the Papua New Guinea highlands; to study the predictive value of clinical signs for the severity of hypoxaemia, the predictive value of transcutaneous oxygen saturation (SpO2) and other variables for mortality. Prospective evaluation of children with severe or very severe pneumonia. SpO2 was measured at the time of presentation and every day until hypoxaemia resolved. Children with a SpO2 less than 85% received supplemental oxygen. By comparing with a retrospective control group for whom oxygen administration was guided by clinical signs, we evaluated whether there was a survival advantage from using a protocol for the administration of oxygen based on pulse oximetry. We determined normal values for oxygen saturation in children living in the highlands. In 151 well, normal highland children, the mean SpO2 was 95.7% (SD 2.7%). The median SpO2 among children with severe or very severe pneumonia was 70% (56-77); 376 (53.5%) had moderate hypoxaemia (SpO2 70-84%); 202 (28.7%) had severe hypoxaemia (SpO2 50-69%); and 125 (17.8%) had very severe hypoxaemia (SpO2 < 50%). Longer duration of cough or the presence of hepatomegaly or cyanosis predicted more severe degrees of hypoxaemia. After 10, 20 and 30 days from the beginning of treatment, respectively 102 (14.5%), 38 (5.4%) and 19 (2.7%) of children had persistent hypoxaemia; 46 children (6.5%) died. Predictors of death were low SpO2 on presentation, severe malnutrition, measles and history of cough for more than 7 days. The mortality risk ratio between the 703 children managed whose oxygen administration was guided by the use of pulse oximetry and the retrospective control group who received supplemental oxygen based on clinical signs was 0.65 (95%CI 0.41-1.02, two-sided Fisher's exact test, P = 0.07). There is a need to increase the availability of supplemental oxygen in smaller health facilities in developing countries, and to train health workers to recognise the clinical signs and risk factors for hypoxaemia. In moderate sized hospitals a protocol for the administration of oxygen based on pulse oximetry may improve survival.


Predicting Physical Activity Outcomes During Episodes of Academic Goal Conflict: The Differential Role of Action Planning and Coping Planning.
The moderating role of academic goal conflict in the relations between action planning (AP) and coping planning (CP) with physical activity was tested using samples of university students concurrently pursuing an academic and a physical activity goal. In Study 1 (N = 317), AP was found to positively relate to physical activity goal progress at low, but not at high, levels of goal conflict. CP trended toward being positively related to goal progress at high, but not at low levels of goal conflict. Study 2 (N = 97), using a 1-week daily diary design and measures of self-reported physical activity behavior and goal progress, showed that daily AP positively related to daily physical activity outcomes on days when students experienced lower, but not higher, levels of goal conflict relative to their average. Conversely, CP positively related to daily physical activity outcomes on days when students experienced higher, but not lower, levels of goal conflict.


Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events.
We compared patients who received an internal-mammary-artery graft to the anterior descending coronary artery alone or combined with one or more saphenous-vein grafts (n = 2306) with patients who had only saphenous-vein bypass grafts (n = 3625). The 10-year actuarial survival rate among the group receiving the internal-mammary-artery graft, as compared with the group who received the vein grafts (exclusive of hospital deaths), was 93.4 percent versus 88.0 percent (P = 0.05) for those with one-vessel disease; 90.0 percent versus 79.5 percent (P less than 0.0001) for those with two-vessel disease; and 82.6 percent versus 71.0 percent (P less than 0.0001) for those with three-vessel disease. After an adjustment for demographic and clinical differences by Cox multivariate analysis, we found that patients who had only vein grafts had a 1.61 times greater risk of death throughout the 10 years, as compared with those who received an internal-mammary-artery graft. In addition, patients who received only vein grafts had 1.41 times the risk of late myocardial infarction (P less than 0.0001), 1.25 times the risk of hospitalization for cardiac events (P less than 0.0001), 2.00 times the risk of cardiac reoperation (P less than 0.0001), and 1.27 times the risk of all late cardiac events (P less than 0.0001), as compared with patients who received internal-mammary-artery grafts. Internal-mammary-artery grafting for lesions of the anterior descending coronary artery is preferable whenever indicated and technically feasible.


Postural sway and joint kinematics during quiet standing are affected by lumbar extensor fatigue.
The purpose of this study was to investigate changes in postural sway and strategy elicited by lumbar extensor muscle fatigue. Specifically, changes in center of mass (COM), center of pressure (COP), and joint kinematics during quiet standing were determined, as well as selected cross correlations between these variables that are indicative of movement strategy. Twelve healthy male participants stood quietly both before and after exercises that fatigued the lumbar extensors. Whole-body movement and ground reaction force data were recorded and used to calculate mean body posture and variability of COM, COP, and joint kinematics during quiet standing. Three main findings emerged. First, participants adopted a slight forward lean post-fatigue as evidenced by an anterior shift of the COM and COP. Second, post-fatigue increases in joint angle variability were observed at multiple joints including joints distal to the fatigued musculature. Despite these increases, anterior-posterior (AP) ankle angle correlated well with AP COM position, suggesting the body still behaved similar to an inverted pendulum. Third, global measures of sway based on COM and COP were not necessarily indicative of changes in individual joint kinematics. Thus, in trying to advance our understanding of how localized fatigue affects movement patterns and the postural control system, it appears that joint kinematics and/or multivariate measures of postural sway are necessary.


[Estimation of Surface Ozone Concentration and Health Impact Assessment in China].
Within the context of PM2.5 concentrations decreasing annually, ozone concentrations have increased instead of decreased, and ozone has become one of the main pollutants in the warm season in China. Based on the idea of big data association analysis, the extreme gradient boosting (XGBoost) ozone concentration estimation model was constructed and developed to estimate the maximum daily 8 h average ozone concentration (O3_8h) in China in 2019 for human exposure assessment. The model input ground monitoring station data, high-resolution remote-sensing satellite data, meteorological data, emission inventory data, digital elevation model (DEM) data, and population data were used to capture the temporal and spatial variation of O3_8h. In this study, ten-fold cross-validation was used to evaluate the estimation performance of the model (R2=0.871, RMSE=11.7 μg·m-3). Compared to those with the random forest (RF) model and kernel ridge regression (KRR) model, due to the improvement in the algorithm itself and the advancement of parallel processing, the estimation results of the XGBoost model showed higher accuracy (RF:R2=0.864, RMSE=12.387 μg·m-3). The KRR model was as follows:R2=0.582, RMSE=23.1 μg·m-3, and the computational efficiency of the model was significantly improved. At the same time, the level of ozone exposure and the relative risk of death due to chronic obstructive pulmonary disease (COPD) in China's provinces and cities were evaluated. The results showed that the top five number of days exceeding the standard occurred in Shandong Province, Henan Province, Hebei Province, Anhui Province, and the Ningxia Hui Autonomous Region. In terms of exposure intensity, Hebei Province, Shandong Province, Shanxi Province, Tianjin City, and Jiangsu Province ranked the top five in terms of population weighted ozone concentration. In terms of health effects, the relative risk of COPD death showed seasonal changes, with the highest in summer and the lowest in winter.


[A case of pituitary adenoma and hyperplasia with primary hypothyroidism].
A 23 year-old woman was admitted to our hospital, complaining of sterility and obesity. Her serum TSH and Prolactin were abnormally high, and her serum T3, T4 were low. Contrast-enhanced computerized tomographic (CT) scan revealed a round mass in the sella and suprasellar region. A transsphenoidal operation was then performed. The intrasellar mass was composed of a soft liquid-like part and a solid part. Only the soft liquid-like part of the mass was removed. Histological examination showed the typical appearance of chromophobe adenoma, Reticulin stain of the specimen revealed no reticular network. The remnant of the mass was considered to be hyperplasia because the size of the mass decreased on serial CT scan after thyroid hormonal replacement. Sometimes it may be difficult to distinguish between hyperplasia and adenoma. The application of reticulin stains is considered to be useful for differentiation between hyperplasia and adenoma.


Acylglycerol and fatty acid components of pulp, seed, and whole olive fruit oils. Their use to characterize fruit variety by chemometrics.
The contents of triacylglycerols and diacylglycerols in three kinds of olive fruit oils (pulp, seed, and whole fruit) were determined. The fatty acid composition and the quality ratios 1,2-diacylglycerols/1,3-diacylglycerols and 1,2-diacylglycerols/total diacylglycerols were also assessed. Seven major Italian olive varieties were considered. Results of univariate statistical analyses indicated that the above analytical parameters (glyceridic ratios excepted) were effective in discriminating between pulp and seed oils. The seed oil fraction did not determine any change in the glyceridic indices and the acylglycerol or fatty acid composition concerning the whole fruit oil (mixture of pulp and seed oil fractions), the weight (%) of seed ( approximately 2%) being by far lower than the weight (%) of pulp ( approximately 85%) (fruit weight basis). Based on the data of triacylglycerol or fatty acid composition, and using appropriate parametric or nonparametric multivariate statistics, the genetic origins (olive variety) of the three fruit oil kinds were characterized.


Moyamoya syndrome associated with Graves' disease: a case series study.
The aim of this study was to describe the clinical and radiological findings of patients with moyamoya syndrome and Graves' disease. Possible mechanisms predisposing these individuals to ischemic stroke are discussed. We retrospectively analyzed 12 consecutive patients with both moyamoya syndrome and Graves' disease. Moyamoya vasculopathy was diagnosed by digital subtract angiography or magnetic resonance angiography (MRA). The clinical characteristics, laboratory data, vascular radiological characteristics and outcome were reported. All patients were female and mean age was 33.33±12.65 years. Stenosis or occlusion of bilateral terminal internal carotid artery and/or proximal anterior/middle cerebral arteries was found in nine patients. Among them, three patients displayed asymmetrical stenosis. In addition, there were three patients with probable unilateral moamoya syndrome. Eleven patients presented with ischemic stroke and/or transient ischemic attack (TIA) and one with dizziness. Thyroid function tests demonstrated elevated thyroid hormone levels and suppressed thyroid stimulating hormone levels in all the patients with ischemic events. All patients received anti-thyroid therapy and two had recurrent ischemic attack after drug withdrawal. Moyamoya syndrome associated Graves' disease often presented with asymmetric stenosis or occlusion. We hypothesize cerebrovascular hemodynamic changes due to thyrotoxicosis contribute to the ischemic events.


Three-dimensional image analysis of the temporal bone in patients with unilateral attic cholesteatoma.
We determined temporal bone anatomy in patients with unilateral attic cholesteatoma. We compared the affected and normal ears of ten patients with unilateral attic cholesteatoma using three-dimensionally reconstructed high-resolution computed tomography images of the temporal bone. We determined the eustachian tube angle, eustachian tube length, sizes of the tympanic orifice of the eustachian tube, the pars flaccida, and the mastoid cavity, and distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. No significant differences were found between the normal and affected ears with regard to the size of the eustachian tube orifice, eustachian tube length or distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. By contrast, the mastoid cavity and the eustachian tube angle were significantly larger in the normal ears than in the affected ears [mean, 6.99 cm(3) (S.D.,4.9 cm(3)) vs. 1.28 cm(3) (0.81 cm(3)) and 16.7° (4.12°) vs. 13.89° (5.30°), respectively]. The pars flaccida was significantly smaller in the normal ears [1.07 cm (0.31 cm)] than in the affected ears [2.19 cm (0.77 cm)]. The inherent anatomy of the eustachian tube may be particularly important in the formation of attic cholesteatomas.


Howard Florey, Alexander Fleming and the fairy tale of penicillin.
The public myth of the discovery of penicillin is an archetypal "quest story" of the type common to every human culture. But the real story of the discovery, testing and refinement of penicillin is a complex tale of accident, serendipity, oversight, conflict, the pressure of war, idiosyncratic personalities and even--the invention of history.


Successful treatment of lipoid pneumonia associated with bowel obstruction by Ascaris lumbricoides.
Partial bowel obstruction is a serious complication of ascariasis infestation generally treated with mineral oil. This prospective study aimed to evaluate the efficacy of multiple bronchoalveolar lavages (BAL) as a therapeutic strategy for reducing lung inflammation of lipoid pneumonia associated with ascariasis. The study included five children (mean age 25 months) with partial small-bowel obstruction by Ascaris lumbricoides, who underwent diagnostic bronchoalveolar lavage for assessment of refractory pneumonia. Routine biochemical, microbiological and cytological analysis were carried out in the BAL. Protein, lactate dehydrogenase and tumor necrosis factor-alpha (TNF-α) cytokine levels were determined in the serum before and after treatment. At admission, children consistently had respiratory symptoms, altered hematological function, increased immunoglobulin E serum level and peripheral blood eosinophilia. Chest tomography showed consolidation with air bronchogram (4/4), ground-glass infiltration (3/4) and decreased attenuation in the consolidation areas (2/4). Presence of marked pleocytosis with Sudan positive foamy alveolar macrophages, high protein and lactate dehydrogenase levels in the BAL indicated presence of mixed alveolitis. One child with extensive consolidation and air bronchogram in both lungs died before treatment. Multiple bronchoalveolar lavages efficiently removed alveolar oil deposits, restored BAL cellularity, improved clinical symptoms, radiological parameters and further reduced inflammatory reaction evidenced by marked decrease of the inflammatory cytokine, TNF-α. This study presents a therapeutic strategy for management of lung complications caused by mineral oil administration to treat intestinal bowel obstruction associated with ascariasis.


Superior Cervical Sympathetic Ganglion: Normal Imaging Appearance on 3T-MRI.
To identify superior cervical sympathetic ganglion (SCSG) and describe their characteristic MR appearance using 3T-MRI. In this prospective study, we recruited 53 consecutive patients without history of head and neck irradiation. Using anatomic location based on literature review, both sides of the neck were evaluated to identify SCSGs in consensus. SCSGs were divided into definite (medial to internal carotid artery [ICA] and lateral to longus capitis muscle [LCM]) and probable SCSGs based on relative location to ICA and LCM. Two readers evaluated signal characteristics including intraganglionic hypointensity of all SCSGs and relative location of probable SCSGs. Interrater and intrarater agreements were quantified using unweighted kappa. Ninety-one neck sites in 53 patients were evaluated after exclusion of 15 neck sites with pathology. Definite SCSGs were identified at 66 (73%) sites, and probable SCSGs were found in 25 (27%). Probable SCSGs were located anterior to LCM in 16 (18%), lateral to ICA in 6 (7%), and posterior to ICA in 3 (3%). Intraganglionic hypointensity was identified in 82 (90%) on contrast-enhanced fat-suppressed T1-weighted images. There was no statistical difference in the relative location between definite and probable SCSGs of the right and left sides with intragnalionic hypointensity on difference pulse sequences. Interrater and intrarater agreements on the location and intraganglionic hypointensity were excellent (κ-value, 0.749-1.000). 3T-MRI identified definite SCSGs at 73% of neck sites and varied location of the remaining SCSGs. Intraganglionic hypointensity was a characteristic feature of SCSGs.


Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer.
The tetraspan protein epithelial membrane protein-2 (EMP2) has been shown to regulate the surface display and signaling from select integrin pairs, and it was recently identified as a prognostic biomarker in human endometrial cancer. In this study, we assessed the role of EMP2 in human ovarian cancer. We examined the expression of EMP2 within a population of women with ovarian cancer using tissue microarray assay technology. We evaluated the efficacy of EMP2-directed antibody therapy using a fully human recombinant bivalent antibody fragment (diabody) in vitro and ovarian cancer xenograft models in vivo. EMP2 was found to be highly expressed in >70% of serous and endometrioid ovarian tumors compared with nonmalignant ovarian epithelium using a human ovarian cancer tissue microarray. Using anti-EMP2 diabody, we evaluated the in vitro response of nine human ovarian cancer cell lines with detectable EMP2 expression. Treatment of human ovarian cancer cell lines with anti-EMP2 diabodies induced cell death and retarded cell growth, and these response rates correlated with cellular EMP2 expression. We next assessed the effects of anti-EMP2 diabodies in mice bearing xenografts from the ovarian endometrioid carcinoma cell line OVCAR5. Anti-EMP2 diabodies significantly suppressed tumor growth and induced cell death in OVCAR5 xenografts. These findings indicate that EMP2 is expressed in the majority of ovarian tumors and may be a feasible target in vivo.


Biofortified Diets Containing Algae and Selenised Yeast: Effects on Growth Performance, Nutrient Utilization, and Tissue Composition of Gilthead Seabream (Sparus aurata).
Efforts have been made to find natural, highly nutritious alternatives to replace fish meal (FM) and fish oil (FO), which can simultaneously promote fish health and improve the nutritional quality of filets for human consumption. This study evaluated the impact of biofortified diets containing microalgae (as replacement for FM and FO), macroalgae (as natural source of iodine) and selenised yeast (organic source of selenium) on gilthead seabream growth, nutrient utilization, tissue composition and gene expression. A control diet (CTRL) with 15% FM and 5.5% FO was compared with three experimental diets (AD1, AD2, and AD3), where a microalgae blend (Chlorella sp., Tetraselmis sp., and DHA-rich Schizochytrium sp.) replaced 33% of FM. Diet AD1 contained 20% less FO. Diets were supplemented with Laminaria digitata (0.4% AD1 and AD2; 0.8% AD3) and selenised yeast (0.02% AD1 and AD2; 0.04% AD3). After feeding the experimental diets for 12 weeks, growth was similar in fish fed AD1, AD2, and CTRL, indicating that microalgae meal can partially replace both FM and FO in diets for seabream. But AD3 suppressed fish growth, suggesting that L. digitata and selenised yeast supplementation should be kept under 0.8 and 0.04%, respectively. Despite lower lipid intake and decreased PUFAs bioavailability in fish fed AD3, compared to CTRL, hepatic elovl5 was upregulated resulting in a significant increase of muscle EPA + DHA. Indeed, filets of fish fed AD2 and AD3 provided the highest EPA + DHA contents (0.7 g 100 g-1), that are well above the minimum recommended values for human consumption. Fish consuming the AD diets had a higher retention and gain of selenium, while iodine gain remained similar among diets. Upregulation of selenoproteins (gpx1, selk, and dio2) was observed in liver of fish fed AD1, but diets had limited impact on fish antioxidant status. Overall, results indicate that the tested microalgae are good sources of protein and lipids, with their LC-PUFAs being effectively accumulated in seabream muscle. Selenised yeast is a good fortification vehicle to increase selenium levels in fish, but efforts should be placed to find new strategies to fortify fish in iodine.


Decreased Serum Hepatocyte Growth Factor (HGF) in Individuals with Depression Correlates with Severity of Disease.
To assess serum Hepatocyte Growth Factor (HGF) levels in individuals with depression and to test the hypothesis that there is a relationship between severity of depression and HGF concentration. Serum from 26 clinically depressed individuals and 19 controls were tested for serum HGF using ELISAs. Correlation was established between HGF concentration and disease severity. Depressed individuals had significantly lower serum levels of HGF compared to controls (P < 0.0001). HGF concentration correlated with overall depressive behavior (P = 0.03) and specifically depression (P = 0.02), but not anxiety (P = 0.36). These results suggest an association between HGF serum levels and clinically depressed individuals and demonstrate a correlation between severity of depression and HGF levels. Further studies of the predictive strength of HGF as a biomarker for depression may be warranted.


Polygalacturonase from Rhizopus stolonifer, an Elicitor of Casbene Synthetase Activity in Castor Bean (Ricinus communis L.) Seedlings.
Apparently homogeneous polygalacturonase-elicitor purified from the filtrates of Rhizopus stolonifer cultures stimulates germinating castor bean seedlings to produce greatly increased levels of casbene synthetase activity. The purification procedure involved gel-filtration chromatography on Sephadex G-25 and G-75 columns followed by cation-exchange chromatography on a Sephadex CM C-50 column. Homogeneity of the purified preparation was indicated by the results of cationic polyacrylamide disc gel electrophoresis and isoelectric focusing (pI = 8.0). The identity of the casbene elicitor activity and polygalacturonase were indicated by the coincidence of the two activities at all stages of purification, the coincidence of both activities with the single protein-staining band detected on a cationic polyacrylamide disc gel and an isoelectric focusing gel, and the identical behavior of both activities on an agarose gel affinity column. The purified polygalacturonase-elicitor is a glycoprotein with approximately 20% carbohydrate content and an estimated molecular weight of 32,000 by polyacrylamide disc gel electrophoresis.


Distribution of Lectins in Tissues, Derived Callus, and Roots of Psophocarpus tetragonolobus (Winged Bean).
The distribution of lectin in parental tissues, roots formed de novo from parental stem tissue, and derived callus cells of Psophocarpus tetragonolobus has been measured by hemagglutinating activity and radioimmunoassay. The antisera used for the radioimmunoassay was raised in rabbits to lectin isolated from seeds by affinity chromatography using insolubilized hog gastric mucin. The distribution of lectin in buffer extracts of the tissues (or cells) and the extracellular medium favors the tissues for in vitro grown roots, regardless of the culture conditions used. The lectin content of the extracellular medium is more significant for callus, regardless of its conditions of culture. The lectin activity of extracts of in vitro grown roots was higher than that of mature roots from whole plants. Differences in relative levels of lectin activity measured by hemagglutination and by radioimmunoassay, and differences in saccharide inhibition of hemagglutination, suggest the presence of multiple lectins in extracts of different tissues.


Urate as a physiological substrate for myeloperoxidase: implications for hyperuricemia and inflammation.
Urate and myeloperoxidase (MPO) are associated with adverse outcomes in cardiovascular disease. In this study, we assessed whether urate is a likely physiological substrate for MPO and if the products of their interaction have the potential to exacerbate inflammation. Urate was readily oxidized by MPO and hydrogen peroxide to 5-hydroxyisourate, which decayed to predominantly allantoin. The redox intermediates of MPO were reduced by urate with rate constants of 4.6 × 10(5) M(-1) s(-1) for compound I and 1.7 × 10(4) M(-1) s(-1) for compound II. Urate competed with chloride for oxidation by MPO and at hyperuricemic levels is expected to be a substantive substrate for the enzyme. Oxidation of urate promoted super-stoichiometric consumption of glutathione, which indicates that it is converted to a free radical intermediate. In combination with superoxide and hydrogen peroxide, MPO oxidized urate to a reactive hydroperoxide. This would form by addition of superoxide to the urate radical. Urate also enhanced MPO-dependent consumption of nitric oxide. In human plasma, stimulated neutrophils produced allantoin in a reaction dependent on the NADPH oxidase, MPO and superoxide. We propose that urate is a physiological substrate for MPO that is oxidized to the urate radical. The reactions of this radical with superoxide and nitric oxide provide a plausible link between urate and MPO in cardiovascular disease.


Causal-explanatory pluralism: How intentions, functions, and mechanisms influence causal ascriptions.
Both philosophers and psychologists have argued for the existence of distinct kinds of explanations, including teleological explanations that cite functions or goals, and mechanistic explanations that cite causal mechanisms. Theories of causation, in contrast, have generally been unitary, with dominant theories focusing either on counterfactual dependence or on physical connections. This paper argues that both approaches to causation are psychologically real, with different modes of explanation promoting judgments more or less consistent with each approach. Two sets of experiments isolate the contributions of counterfactual dependence and physical connections in causal ascriptions involving events with people, artifacts, or biological traits, and manipulate whether the events are construed teleologically or mechanistically. The findings suggest that when events are construed teleologically, causal ascriptions are sensitive to counterfactual dependence and relatively insensitive to the presence of physical connections, but when events are construed mechanistically, causal ascriptions are sensitive to both counterfactual dependence and physical connections. The conclusion introduces an account of causation, an "exportable dependence theory," that provides a way to understand the contributions of physical connections and teleology in terms of the functions of causal ascriptions.


[Hyaluronan and CD44 in maternal serum in pre-eclampsia].
Pre-eclampsia is associated with serum factors which can activate blood vessel endothelial cells. Hyaluronan (HYA) and its specific receptor CD44 play a central role in cell activation processes. Our study focussed on the behavior of serum concentrations of HYA and the soluble standard form of CD44 (sCD44std) in the maternal serum from normotensive and pre-eclamptic pregnancies. Serum was collected from normotensive pregnant women (n = 10) and from pregnant women with a severe pre-eclampsia (n = 10). HYA-serum concentrations were measured with a radioimmunoassay while sCD44std were measured with an ELISA. The pre-eclampsia group shows a significant (p < 0.001, Mann and Whitney u-test) increased HYA serum concentration (median 79 ng/ml, range 53-165 ng/ml) when compared to the normotensive group (n = 10, median 32 ng/ml, range 19-59 ng/ml). sCD44std-serumconcentration in the pre-eclampsia group (328.3 +/- 68.3 ng/ml) was weakly higher but not statistically significant (p > 0.05) when compared to the normotensive group (292.9 +/- 74.0 ng/ml). There exist no correlations between the HYA and sCD44std serum concentrations in both pre-eclamptic and normotensive groups. The increased HYA-serumconcentration may indicate a pathophysiological role of the HYA/CD44-signal transduction system in pre-eclampsia. The existing overlap of HYA serum levels in the pre-eclampsia group with HYA serum levels in the normotensive control group limits the diagnostic precision of HYA serum concentration as a diagnostic parameter in pre-eclampsia. According CD44 it is not excluded that serum concentration of other soluble CD44-isoforms is increased in pre-eclampsia.


Role of lymphadenectomy for invasive bladder cancer.
Radical cystectomy with lymph node dissection remains the standard of care in the treatment of muscle-invasive and refractory non-invasive bladder cancer. Over the past decade, the extent of lymphadenectomy has varied to include dissection up to the common iliac vessels and aortic bifurcation proximally (may also extend up to the level of the inferior mesenteric artery), the genitofemoral nerve laterally, the circumflex iliac vein and lymph node of Cloquet distally, and the hypogastric vessels posteriorly (obturator fossa, presciatic nodes bilaterally and the presacral lymph nodes over the sacral promontory). Evidence supports the role of lymphadenectomy as both a therapeutic and prognostic variable in patients with invasive bladder cancer. We review the literature regarding the role and extent of lymphadenectomy, as well as its impact on patient outcomes.


Asynchronous decoding of finger position and of EMG during precision grip using CM cell activity: application to robot control.
Recent brain-machine interfaces (BMI) have demonstrated the use of intracortical signals for the kinematic control of robotic arms. However, for potential restoration of manual dexterity, two issues remain to be addressed: (1) Can hand and digit movements for dexterous manipulation be controlled in a similar way to arm movements? (2) Can the potentially large signal space for decoding of the many degrees of freedom (dof) of hand and digit movements be minimized? The first question addresses BMI control of dexterous prosthetic devices, while the second addresses the problem of whether few, but identified, neurons might provide adequate decoding. Asynchronous decoding of precision grip finger movement kinematics from identified corticomotoneuronal (CM) cell activity was performed with an artificial neural network (ANN). After training over a given session, the ANNs successfully decoded trial-by-trial movement kinematics. Average accuracy over sessions was in the order of 80% and 50% for data sets of two monkeys respectively. Decoding accuracy increased as a function of (1) number of simultaneously recorded CM cells used for prediction, and (2) size of the sliding input window. Subsequently, a robot digit actuated by pneumatic artificial muscles, fed with the predicted trajectory, mimicked the recorded movement offline. Furthermore, CM cell signals were used for decoding of time-varying hand muscle EMG activity. The performance of EMG prediction tended to increase if CM cells that facilitated this particular muscle (compared to CM cells that facilitated other muscles) were used. These results provide evidence that an anthropomorphic robot finger can be controlled offline by spike trains recorded from identified corticospinal neurons. This represents a step towards neuroprosthetic devices for dexterous hand movements.


Estrogen receptor beta expression in human prostate tissue.
Estrogen receptor subtype beta (ERbeta) is highly expressed in rat prostate epithelium, but its presence in human prostate needs to be confirmed. Here we investigated the expression of ERbeta in five benign (normal and/or hyperplastic) and 10 malignant (Gleasons' score 2-7) prostate tissue specimens using immunohistochemistry. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections, using a commercially available ERbeta polyclonal antibody developed against the C-terminal amino acid residue. Nuclear ERbeta expression was found in the nuclei of glandular epithelium of benign prostate tissue specimens; faint nuclear ERbeta positivity was also present in a few stromal cells around normal epithelium. Nuclear ERbeta specific immunostaining was undetectable in all prostate cancer sections.


Transomental titanium plates for sternal osteomyelitis in cardiac surgery.
Wound infection is a devastating complication resulting in a high mortality rate from 7% to 80%. The risk of recurrences depends on the depth and the extension of the infection. We present our experience of omentoplasty using transomental sternal plates. Five patients (two females, mean age 61.2 ± 8.3 years) had severe osteomyelitis requiring radical sternectomy and omental flap transposition. In three cases (60%), the sternal manubrium was completely removed: in case of upper sternectomy, chest wall stability was achieved without metallic bars; in two cases chest wall stability required the use of three metallic plates for each patient (STRATOS SYSTEM) fixed on the second, third, and fourth ribs. The plates were passed through the omental flap to obtain a partial cover of the devices. No patient had abdominal complications. One patient had postoperative dehiscence of the superficial wound that was treated by VAC therapy for 30 days. The length of hospital stay was 65.2 ± 45.2 days. All patients had complete wound healing and are alive after 24.0 ± 21.4 months. Omental flap transposition represents a good option in the treatment of sternal osteomyelitis. Partial or total sternal manubrium preservation and fixation are essential for the restoration of sternal stability. The use of transomental titanium plates provides chest wall stabilization when extensive sternal resection is required.


Effect of maternal dietary hexachlorocyclohexane exposure on pup survival and growth in albino rats.
In adult albino rats, maternal dietary beta- and gamma-hexachlorocyclohexane (HCH) intake during gestation upto 400 ppm level did not affect the number of litters produced. But about 50 and 100% pup mortality was found in 200 and 400 ppm beta-HCH group within 5 days of birth. Maternal mortality was observed in 800 ppm beta-HCH group during third week of gestation. The effect of maternal dietary intake of HCH isomers at 50 and 250 ppm level during gestation and/or lactation on perinatal development was also studied. The body weights and sizes of the newborn litters of mother rats exposed to dietary HCH isomers did not differ from controls. Similarly, the growth and development of the litters of HCH exposed mother rats that survived 28 day lactation period were found to be comparable to controls as evidenced by the body weight and weight of vital organs. However, liver weight increases were found in the 28 days weaned litters wherever the mothers had been exposed to HCH isomers during lactation. Lowered kidney weight was seen in litters of mother rats fed 250 ppm gamma-HCH during gestation and lactation. The brain and testis weights were not affected in the litters of any experimental groups.


Posttreatment cut-off levels of squamous cell carcinoma antigen as a prognostic factor in patients with locally advanced cervical cancer treated with radiotherapy.
The aim of the present study was to assess prognostic factors for patients with locally advanced cervical cancer treated with radiotherapy as the primary treatment and to assess the posttreatment cut-off levels of squamous cell carcinoma antigen (SCC-Ag) to predict three-year overall survival (OS) rates. One hundred and twenty-eight patients with cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage IIB-IVA) treated using radiotherapy or concurrent chemoradiotherapy were identified. Of these patients, 116 who had SCC-Ag levels >1.5 ng/mL prior to treatment were analyzed retrospectively. Median age was 68 years (range, 27 to 79 years). The complete response rate was 70.7% and the three-year OS rate was 61.1%. The median levels of pretreatment and posttreatment SCC-Ag were 11.5 ng/mL (range, 1.6 to 310.0 ng/mL) and 0.9 ng/mL (range, 0.4 to 41.0 ng/mL), respectively. Multivariate analysis showed that pretreatment anemia (p=0.041), pelvic lymph node metastasis (p=0.016) and posttreatment SCC-Ag levels (p=0.001) were independent prognostic factors for three-year OS. The SCC-Ag level cut-off point for three-year OS rates, calculated using a receiver operating characteristic curve, was 1.15 ng/mL (sensitivity, 80.0%; specificity, 74.0%). Pretreatment anemia and pelvic lymph node metastasis are poor prognostic factors in locally advanced cervical cancer. Furthermore, posttreatment SCC-Ag levels <1.15 ng/mL predicted better three-year OS rates.


IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor.
We have identified and purified a factor that inhibits the production of IL-1 beta and TNF by stimulated human mononuclear cells. The activity is produced by the T cell lines Hut-78 and Mo constitutively under serum-free conditions. Crude conditioned media have titers of up to 100 U/ml (one unit defined as the reciprocal of the dilution producing 50% inhibition). The activity resides mainly in a single size peak of 30 to 35 kDa and an isoelectric point around 8. Other cytokines in this size range that have been reported to be inhibitory for IL-1 and TNF production include TGF-beta, IL-4, and IL-6; these factors were excluded by lack of detection, neutralizing antibody, and low activity compared with our factor. Another factor with these size and charge properties is IL-10, which inhibits T cell cytokine production. By polymerase chain reaction analysis, Mo and HuT-78 lines contain IL-10 transcripts whereas JURKAT is negative; this correlates with inhibitor bioactivity from the three lines. Use of mAb specifically showed the inhibitor to be IL-10.


On-line concentration and separation of cationic and anionic neurochemicals by capillary electrophoresis with UV absorption detection.
This paper presents on-line simultaneous concentration and separation of cationic and anionic neurochemicals by capillary electrophoresis (CE) with UV absorbance spectroscopy. Neurochemical stacking exploits differences in local electric field and viscosity between the sample zone and the background electrolyte (BGE). To achieve these discontinuous conditions for CE, neurochemicals were prepared in a solution containing 1mM formic acid and 20% (v/v) acetonitrile (ACN). The capillary was filled with a solution of 500 mM Tris-borate (TB) and 10% (v/v) glycerol. The buffer vial contained 500 mM TB and 0.5% (v/v) polyethylene oxide (PEO). After injecting a large sample volume, PEO enters the capillary by electro-osmotic flow (EOF). Anionic neurochemicals stacked at the sample zone and PEO-containing BGE boundary. Simultaneously, cationic neurochemicals were concentrated at the boundary between the sample zone and the glycerol-containing BGE. The concentrated cationic neurochemicals were baseline separated in the presence of glycerol, mainly due to hydrogen bonding interactions between glycerol hydroxyl groups and the neurochemical's hydroxyl and amino groups. Under optimal stacking conditions, we observed the following: (a) the maximum sample injection volume was 720 nL; (b) the limit of detection for signal-to-noise ratio of 3 ranged from 14.7 to 313.4 nM; and (c) sensitivity enhancements compared to normal injection (15 nL) ranged from 116 to 281-fold. We evaluated the proposed method by the determination of neurochemicals in urine samples.


Rapid progression of aortic stenosis after initiation of teriparatide treatment: a case report.
Teriparatide, a recombinant formulation of endogenous PTH, is indicated for the treatment of osteoporosis in patients at high risk for fracture including postmenopausal women, men with primary or hypogonadal osteoporosis and patients with glucocorticoid-induced osteoporosis. A 64-year-old Jewish osteoporotic woman initiated use of Teriparatide (FORTEOTM, 250 µg per 1 ml subcutaneously per day) in April 2018. Prior to therapy initiation, the patient has undergone eight echocardiograms with an aortic valve pressure gradient ranging between 29 and 39 mmHg, defined as mild aortic stenosis (AS), with no clear trend of progression. In two subsequent echo tests conducted 4 and 7 months after treatment initiation, there was a rapid progression of AS with gradient pressures of 55 and 58 mmHg, respectively. Intermittent exposure to PTH analogues may be one of the causes of rapid progression of AS. Studies with sizeable populations are required to assess causal relationship between PTH analogues use and progression of AS.


Predicting clinical instability of older patients in post-acute care units: a nationwide cohort study.
Although patients admitted to post-acute care (PAC) units are usually clinically stable, unexpected medical conditions requiring acute ward readmissions still occur and can jeopardize the clinical effectiveness of PAC services. The main purpose of the present study was to evaluate predictive factors for clinical instability of patients in PAC units to improve the quality of PAC services. This was a nationwide multicenter cohort study that recruited patients from five PAC units in Taiwan between July 2007 and June 2009. All patients received the comprehensive geriatric assessment (CGA) within 72 h of PAC unit admissions. Conditions requiring acute ward re-admissions from PAC units were defined as clinical instability. Causes of clinical instability for all patients and data of CGA were collected for analysis. Of 918 enrolled participants, 119 (12.9%) experienced acute ward readmissions, including 106 (89.1%) admissions related to medical conditions and 13 (10.9%) for surgical causes. Common conditions included diseases of the respiratory system (n = 32, 26.9%), genitourinary system (n = 24, 20.2%) and digestive system (n = 14, 11.8%). Surgical conditions, mainly fractures and dislocation of upper limbs, were significantly more likely to occur later (P = 0.05) in the PAC unit admissions than medical conditions. Compared with the non-readmission group, the readmission group was leaner (mean body mass index 21.1 ± 2.8 vs 22.0 ± 3.8 kg/m(2) , P = 0.007), having poorer functional status (mean Barthel Index 41.0 ± 19.4 vs 45.4 ± 20.3, P = 0.02; mean IADL: 1.3 ± 1.6 vs 1.7 ± 1.8, P = 0.016), poorer cognitive function (mean Mini-Mental State Examination: 16.8 ± 6.4 vs 18.3 ± 6.4, P = 0.022), poorer ambulation (mean Timed Up & Go test 32.7 ± 18.7 vs 26.6 ± 11.7 s, P = 0.039) and poorer nutritional status (mean Mini-Nutrition Assessment 13.3 ± 5.7 vs 15.4 ± 5.8, P < 0.001), but similar in depression status (mean Geriatric Depression Score 3.7 ± 3.3 vs 3.4 ± 2.8, P = 0.247). In multivariate logistical regression model, lower Mini-Mental State Examination score was the only independent predictor for clinical instability (odds ratio 3.8, 95% confidence interval 1.348-10.870, P = 0.012). Approximately 13% of PAC patients might experience acute ward readmissions, and nearly 90% of them are caused by medical conditions. Poor cognitive function is a significant predictive factor for clinical instability in PAC, which deserves more clinical attention for all PAC patients.


Zinc absorption in experimental osmotic diarrhea: effect of long-chain fatty acids.
The effect of free fatty acids on zinc absorption was studied in a rat model of chronic osmotic diarrhea induced with magnesium citrate and phenolphthalein. In vivo rates of zinc removal from the lumen and analysis of tissue for zinc uptake and metallothionein alterations were monitored. One mmol/L stearate enhanced zinc absorption in rats with or without diarrhea, from 207 +/- 22 and 353 +/- 13 pmol/min x cm to 676 +/- 34 and 610 +/- 26 pmol/min x cm, respectively. Palmitate was only effective in normal rats. Zinc absorption inversely correlated with mucosal zinc content in the perfused intestinal segments, in both type of rats. Hepatic metallothionein was enhanced by zinc and even more by oleate plus zinc in both groups; kidney metallothionein in animals with diarrhea was normalized by either oleate or zinc. The data support previous reports on the effect of long-chain fatty acids on the enhancement of zinc absorption: saturation and a longer chain appear to be positive factors. A membrane modification role of long-chain fatty acids could have nutritional implications in the formulation of special diets.


Homologous Recombination Deficiency in Patients With Pancreatic Ductal Adenocarcinoma and Response to Chemotherapy.
Mutations or copy number abnormalities of genes involved in homologous recombination (HR) occur in pancreatic ductal adenocarcinoma (PDAC). DNA-based measures of HR deficiency (HRD) have been developed and may help identify tumors with better response to DNA-damaging agents. This study aimed to describe the HR pathway mutations and HRD status and determine their association with treatment response and outcome in patients with PDAC. We performed a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PDAC. Patients were included if they received gemcitabine plus nanoparticle albumin-bound paclitaxel (control) or fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX) and had adequate follow-up to assess survival and response to therapy. Tumor analysis generated a three-biomarker HRD score and mutation data for 44 genes. Ninety-one samples met inclusion criteria, and 78 samples (formalin-fixed paraffin-embedded, n = 15; fine-needle aspiration, n = 63) generated mutation data. HRD analysis was successful for 57 samples (HRD score: median, 18; range, 5 to 61); the primary cause of failure was low tumor cellularity. Six BRCA1/2 mutations were detected, four with HRD scores in the top decile (P = .011). There was no statistically significant correlation between HRD score and radiographic response (odds ratio per interquartile range, 1.40; P = .32 adjusted for treatment) in either treatment group. In patients treated with FOLFIRINOX, HRD score dichotomized at the median was not associated with progression-free survival (median, 5.3 v 9.4 months for low v high HRD score, respectively; P = .083) or overall survival (median, 11.9 v 10.7 months for low v high HRD score, respectively; P = .76). Mutations in DNA repair genes occur in PDAC, and HRD scores can be generated in the majority of patients. The HRD score was not significantly associated with higher response rate or prolonged survival in patients treated with FOLFIRINOX.


Two-dimensional magnetization exchange spectroscopy of Anabaena 7120 ferredoxin. Nuclear Overhauser effect and electron self-exchange cross peaks from amino acid residues surrounding the 2Fe-2S* cluster.
Hyperfine 1H NMR signals of the 2Fe-2S* vegetative ferredoxin from Anabaena 7120 have been studied by two-dimensional (2D) magnetization exchange spectroscopy. The rapid longitudinal relaxation rates of these signals required the use of very short nuclear Overhauser effect (NOE) mixing times (0.5-20 ms). The resulting pattern of NOE cross-relaxation peaks when combined with previous 1D NOE results [Dugad, L. B., La Mar, G. N., Banci, L., & Bertini, I. (1990) Biochemistry 29, 2263-2271] led to elucidation of the carbon-bound proton spin systems from each of the four cysteines ligated to the 2Fe-2S* cluster in the reduced ferredoxin. Additional NOE cross peaks were observed that provide information about other amino acid residues that interact with the iron-sulfur cluster. NOE cross peaks were assigned tentatively to Leu27, Arg42, and Ala43 on the basis of the X-ray coordinates of oxidized Anabaena 7120 ferredoxin [Rypniewski, W.R., Breiter, D.R., Benning, M.M., Wesenberg, G., Oh, B.-H., Markley, J.L., Rayment, I., & Holden, H. M. (1991) Biochemistry 30, 4126-4131]. Three chemical exchange cross peaks were detected in magnetization exchange spectra of half-reduced ferredoxin and assigned to the 1H alpha protons of Cys49 and Cys79 [both of whose sulfur atoms are ligated to Fe(III)] and Arg42 (whose amide nitrogen is hydrogen-bonded to one of the inorganic sulfurs of the 2Fe-2S* cluster). The chemical exchange cross peaks provide a means of extending assignments in the spectrum of reduced ferredoxin to assignments in the spectrum of the oxidized protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Studies on the Secretion of Maize Root Cap Slime: II. Localization of Slime Production.
The distribution of fucose-containing polysaccharides in apical 1-cm sections of corn (Zea mays cv. SX-17) root tips was analyzed. Fucose-containing polysaccharides were localized predominantly in the apical 1 mm of the root, i.e., in the apical initials and root cap. An analysis of the distribution of incorporated radioactive label from l-fucose[(3)H] gave similar results. After a 2-hr incubation with fucose[(3)H], label was found principally in two components, namely a water-soluble slime fraction and hemicellulose. The incorporation of fucose into the water-soluble, ethanol-insoluble fraction was primarily in the apical 1 mm of the root, whereas incorporation into a water-insoluble, potassium hydroxide-soluble fraction was in the region 2 to 5 mm behind the root cap. Addition of sucrose to the incubation medium during fucose[(3)H] incorporation reduces label uptake but increases the amount of label in the fucose-rich secreted polysaccharide. The utility of fucose as a marker for the secreted polysaccharide was confirmed by demonstrating that no appreciable metabolism of this sugar occurs.