Characterization, Molecular Docking, and In Vitro Dissolution Studies of Solid Dispersions of 20(S)-Protopanaxadiol.
In this study, we prepared solid dispersions (SDs) of 20(S)-protopanaxadiol (PPD) using a melting-solvent method with different polymers, in order to improve the solubility and dissolution performance of drugs with poor water solubility. The SDs were characterized via differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and molecular docking and dynamics study. DSC and PXRD results indicated that PPD crystallinity in SDs was significantly reduced, and that the majority of PPD is amorphous. No interaction was observed between PPD and polymers on FTIR and NMR spectra. Molecular docking and dynamic calculations indicated that the PPD molecule localized to the interpolated charged surface, rather than within the amorphous polymer chain network, which might help prevent PPD crystallization, consequently enhancing the PPD dispersion in polymers. An in vitro dissolution study revealed that the SDs considerably improved the PPD dissolution performance in distilled water containing 0.35% Tween-80 (T-80). Furthermore, among three PPD-SDs formulations, Poloxamer188 (F68) was the most effective in improving the PPD solubility and was even superior to the mixed polymers. Therefore, the SD prepared with F68 as a hydrophilic polymer carrier might be a promising strategy for improving solubility and in vitro dissolution performance. F68-based SD, containing PPD with a melting-solvent preparation method, can be used as a promising, nontoxic, quick-release, and effective intermediate for other pharmaceutical formulations, in order to achieve a more effective drug delivery.


MAGI-3 regulates LPA-induced activation of Erk and RhoA.
Lysophosphatidic acids (LPA) exert multiple biological effects through specific G protein-coupled receptors. The LPA-activated receptor subtype LPA(2) contains a carboxyl-terminal motif that allows interaction with PDZ domain-containing proteins, such as NHERF2 and PDZ-RhoGEF. To identify additional interacting partners of LPA(2), the LPA(2) carboxyl-terminus was used to screen a proteomic array of PDZ domains. In addition to the previously identified NHERF2, several additional LPA(2)-interacting PDZ domains were found. These included MAGI-2, MAGI-3 and neurabin. In the present work, we demonstrate the specific interaction between LPA(2) and MAGI-3, and the effects of MAGI-3 in colon cancer cells using SW480 as a cell model. MAGI-3 specifically bound to LPA(2), but not to LPA(1) and LPA(3). This interaction was mediated via the fifth PDZ domain of MAGI-3 interacting with the carboxyl-terminal 4 amino acids of LPA(2), and mutational alteration of the carboxyl-terminal sequences of LPA(2) severely attenuated its ability to bind MAGI-3. LPA(2) also associated with MAGI-3 in cells as determined by co-affinity purification. Overexpression of MAGI-3 in SW480 cells showed no apparent effect on LPA-induced activation of Erk and Akt. In contrast, silencing of MAGI-3 expression by siRNA drastically inhibited LPA-induced Erk activation, suggesting that the lack of an effect by overexpression was due to the high endogenous MAGI-3 level in these cells. Previous studies have shown that the cellular signaling elicited by LPA results in activation of the small GTPase RhoA by Galpha(12/13) - as well as Galpha(q)-dependent pathways. Overexpression of MAGI-3 stimulated LPA-induced RhoA activation, whereas silencing of MAGI-3 by siRNA resulted in a small but statistically significant decrease in RhoA activation. These results demonstrate that MAGI-3 interacts directly with LPA(2) and regulates the ability of LPA(2) to activate Erk and RhoA.


Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial.
There is a lack of effective pharmacotherapy for prolonged grief disorder (PGD). Evidence suggests that the neurobiology of PGD involves the same circuitry as the reward pathway. Based upon this evidence, we hypothesize that PGD can be conceptualized as a disorder of addiction and therefore could benefit from being treated with medications that are currently used to treat such disorders. One such medication is naltrexone, which is currently used to treat alcohol and opioid dependence. Oral naltrexone was chosen for its mechanism of action, safety, and convenience. The primary aim of this study is to establish the efficacy of using oral naltrexone as a pharmacological treatment for PGD. Specifically, we hypothesize that participants receiving naltrexone will demonstrate reduced PGD symptoms when compared to placebo. This is a randomized, placebo-controlled, triple-blinded (to healthcare professionals/study staff, participants, and data analysts) study in which we propose to enroll 48 participants who meet criteria for Prolonged Grief Disorder (PGD). Participants will be randomly assigned to the naltrexone 50 mg oral arm or placebo arm; medications will be over-encapsulated to appear identical. Participants will take their assigned medication for 8 weeks, with clinic visits every 4 weeks to assess symptom severity, social closeness, and adverse reactions. Weekly surveys of Prolonged Grief-13-Revised (PG-13-R) will be used to relate naltrexone use to changes in PGD symptom severity. Follow-up 4 weeks after their last visit will assess the longevity of treatment, as well as any lingering adverse reactions. This study is the first to investigate the use of oral naltrexone as pharmacological treatment for PGD. The acute and debilitating nature of the disorder, in addition to the increased risk of comorbidities, highlights the need for pharmacological treatment like naltrexone that can act more rapidly, may help those for whom psychotherapy may not be effective, and/or may augment psychotherapy to promote PGD symptom grief resolution. ClinicalTrials.gov NCT04547985 . Registered on 8/31/2020.


Incidence, risk factors, and clinical outcomes of atrial fibrillation and atrial flutter after heart transplantation.
Atrial fibrillation (AF) and atrial flutter (AFL) after heart transplantation (HT) has been associated with increased mortality. Diverse incidence rates have been reported to date, with no clear classification according to the time of onset of such arrhythmias. We determined the incidence of AF/AFL using the time of onset after HT and analyzed the associated risk factors and outcomes. We performed a retrospective study of 228 HT recipients (March 1996 to July 2007), including donor and recipient demographics, gender mismatch, ischemia time, surgical anastomosis, time of onset of AF/AFL, acute cellular rejection, left ventricular systolic function, and all-cause mortality. The mean age of the donors (81% men) was 30 +/- 12 years and of the recipients (78% men) was 53 +/- 11 years. AF/AFL occurred in 45 patients (20%): 24 (11%) in the first 30 days, 10 (4%) within the 31 days to 1 year, and 11 (5%) after 1 year. When the patients with AF/AFL were compared to those with sinus rhythm, the significant difference was the older mean age of the donors (p = 0.001) and the recipients (p = 0.02). The all-cause mortality rate was 43% for those with AF/AFL compared to 23% for those with sinus rhythm (hazard ratio 2.45; 95% confidence interval 1.2 to 4.8), mostly driven by the greater mortality in the later-onset AF/AFL group (>30 days after HT). In conclusion, AF and AFL have an incidence of 20% after HT and are associated with increased overall mortality compared to that in patients in sinus rhythm. AF/AFL is more common within the first 30 days of HT, with an overall incidence of 20%. Older donor and recipient age is a risk factor associated with AF/AFL.


Community-based outbreaks in vulnerable populations of invasive infections caused by Streptococcus pneumoniae serotypes 5 and 8 in Calgary, Canada.
Outbreaks of invasive pneumococcal disease (IPD) typically occur within institutions. Beginning in 2005, we detected an increase in serotype (ST) 5 and ST8 IPD cases, predominantly in homeless persons living in an open community. CASPER (Calgary Area S. pneumoniae Epidemiology Research) surveillance study of all IPD (sterile site isolates) in our region (pop ~1,100,000). Interviews and chart reviews of all cases and all isolates phenotypically analyzed and selected isolated tested by multi-locus sequence typing (MLST). During 2005-2007, 162 cases of ST5 IPD and 45 cases of ST8 IPD were identified. The isolates demonstrated phenotypic and genotypic clonality. The ST5 isolates were sequence type (ST) 289 and demonstrated intermediate susceptibility to TMP-SMX. The ST8 isolates were predominantly ST1268, with a susceptible antimicrobial susceptibility profile. Individuals with ST5 IPD were more likely to be middle aged (OR 2.6), homeless (OR 4.4), using illicit drugs(OR 4.8), and asthmatic(OR 2.6). Those with ST8 were more likely to be male (OR 4.4), homeless (OR 2.6), aboriginal (OR7.3), and a current smoker (OR 2.5). Overlapping outbreaks of ST5 and ST8 IPD occurred in an open community in Calgary, Canada and homelessness was a predominant risk factor. Homelessness represents a unique community in which pneumococcal outbreaks can occur.


Tubularized incised plate repair in circumcised adults.
In this study, the experience of tubularized incised plate repair in circumcised adults in terms of functional, cosmetic, and satisfactory results is reported. Tubularized incised plate repair urethroplasty (TIPU) was performed to 27 circumcised adult patients between 2008- 2010; 19 (70.4%) had distal penile hypospadias and eight (29.6%) had midshaft hypospadias. All patients were operated by a single surgeon and were asked to fill out a questionnaire to asses functional and cosmetic results of the surgery. The mean age of patients was 22.0 years. All patients were controlled in urology office seven days after the removal of urethral catheter. They were controlled in the 3rd, 6th, and 12th month after the operation and they filled out the questionnaire in the 6th month after the operation in the TIP. The mean follow up was 13 months. Three (11.1%) patients had meatus stenosis and two (7.4%) urethral fistula as a complication. Twenty-four (88.8%) patients reported that they were satisfied about penile length, 26 (96.2%) about the appearance of the meatus, 25 (92.5%) about the appearance of the glans penis, 22 (81.4%) about the appearance of the foreskin, 23 (85.1%) about the straightness of the penis with erection, and 24 (88.8%) about the overall appearance of the penis. All patients were satisfied about the urinary flow and seven (100%) patients who were sexually active reported that they were satisfied with vaginal penetration and sexual satisfaction. Tubularized incised plate repair technique reveals good functional and cosmetic results even in adults who were circumcised.


Eosinophilic hepatitis after ingestion of choline magnesium trisalicylate.
Choline magnesium trisalicylate is a non-acetylated salicylate used widely as a nonsteroidal anti-inflammatory drug. Although mild transient hepatotoxicity associated with aspirin and other salicylates has been well documented, most commonly with high-dose treatment for rheumatologic disorders 112), we report a case of severe hypersensitivity hepatitis with striking tissue and peripheral eosinophilia after ingestion of choline magnesium trisalicylate.


[Role of benzodiazepine receptors in realizing the anxiolytic effect of compounds on intact rats and on animals with a physical dependence ethanol].
Anxiolytic activity of DSIP, sodium hydroxybutyrate, nicotinoyl-GABA, mebicar, some derivatives of aminoandrostane and beta-carboline was not, like in the case of diazepam and beta C-3CEE, related to benzodiazepine receptors. The degree of the decrease in anxiolytic activity of these compounds did not correspond to increasing Ki binding of 3H diazepam in alcoholic rats.


Subcellular localization of cadmium and cadmium-binding peptides in tobacco leaves : implication of a transport function for cadmium-binding peptides.
The synthesis of Cd-binding peptides (CdBPs) was induced upon addition of 20 micromolar CdCl(2) (nonphytotoxic level) to the nutrient solution of hydroponically grown tobacco seedlings (Nicotiana rustica var Pavonii). Amino acid analysis showed that the main components were gamma-(Glu-Cys)(3)-Gly and gamma-(Glu-Cys)(4)-Gly. Seedlings exposed to the metal for 1 week contained similar glutathione levels as found in the controls (about 0.18 micromole per gram fresh weight). If, as has been proposed, CdBPs are involved in Cd-detoxification by chelation, both metal and ligand must be localized in the same cellular compartment. To directly determine the localization of Cd and CdBPs, protoplasts and vacuoles were isolated from leaves of Cd-exposed seedlings. Purified vacuoles contained virtually all of the CdBPs and Cd found in protoplasts (104% +/- 8 and 110% +/- 8, respectively). CdBPs were associated with the vacuolar sap and not with the tonoplast membrane. Glutathione was observed in leaves and protoplasts but not in vacuoles. The probability that CdBPs are synthesized extravacuolarly and our finding that they and Cd are predominantly located in the vacuole suggest that these molecules might be involved in transport of Cd to the vacuole. Our results also suggest that a simple cytoplasmic chelator role for CdBPs in Cd tolerance cannot be assumed.


A novel multiphoton microscopy images segmentation method based on superpixel and watershed.
Multiphoton microscopy (MPM) imaging technique based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) shows fantastic performance for biological imaging. The automatic segmentation of cellular architectural properties for biomedical diagnosis based on MPM images is still a challenging issue. A novel multiphoton microscopy images segmentation method based on superpixels and watershed (MSW) is presented here to provide good segmentation results for MPM images. The proposed method uses SLIC superpixels instead of pixels to analyze MPM images for the first time. The superpixels segmentation based on a new distance metric combined with spatial, CIE Lab color space and phase congruency features, divides the images into patches which keep the details of the cell boundaries. Then the superpixels are used to reconstruct new images by defining an average value of superpixels as image pixels intensity level. Finally, the marker-controlled watershed is utilized to segment the cell boundaries from the reconstructed images. Experimental results show that cellular boundaries can be extracted from MPM images by MSW with higher accuracy and robustness.


Exercise training from late middle age until senescence does not attenuate the declines in skeletal muscle aerobic function.
We previously showed that 7 wk of treadmill exercise training in late-middle-aged rats can reverse the modest reductions in skeletal muscle aerobic function and enzyme activity relative to values in young adult rats (Exp Physiol 93: 863-871, 2008). The purpose of the present study was to determine whether extending this training program into senescence would attenuate the accelerated decline in the muscle aerobic machinery normally seen at this advanced age. For this purpose, 29-mo-old Fisher 344 Brown-Norway rats underwent 5 or 7 mo of treadmill exercise training. Training resulted in greater exercise capacity during an incremental treadmill exercise test and reduced percent body fat in 34- and 36-mo-old rats and improved survival. Despite these benefits at the whole body level, in situ muscle aerobic capacity and muscle mass were not greater in the trained groups at 34 mo or 36 mo of age. Similarly, the trained groups did not have higher activities of citrate synthase (CS) or Complex IV in homogenates of either the plantaris (fast twitch) or the soleus (slow twitch) muscles at either age. Finally, protein expression of CS (a marker of mitochondrial content) and peroxisome proliferator-activated receptor-gamma coactivator-1 (relating to the drive on mitochondrial biogenesis) were not higher in the trained groups. Therefore, although treadmill training from late middle age into senescence had significant benefits on running capacity, survival, and body fat, it did not prevent the declines in muscle mass, muscle aerobic capacity, or mitochondrial enzyme activities normally seen across this age, revealing a markedly diminished plasticity of the aerobic machinery in response to endurance exercise at advanced age.


Photofragmentation at 263 nm of small peptides containing tyrosine: the role of the charge transfer on CO.
The photofragmentation pathways at 263 nm of several small peptides containing tyrosine as the UV chromophore have been characterized using a multi-coincidence technique. A detailed study of the fragmentation dynamics of protonated Glycine-Tyrosine (GYH(+)), Tyrosine-Glycine (YGH(+)), Glycine-Tyrosine-Glycine (GYGH(+)), Alanine-Tyrosine (AYH(+)) and Tyrosine-Alanine (YAH(+)) is presented in this paper. Fragmentations occurring or initiated in an excited state are distinguished from those occurring after internal conversion to the ground electronic state by their rapid fragmentation times and binary nature. For the studied systems, it is shown that fragmentations occurring after internal conversion to the ground state are the dominant processes compared to fragmentations occurring in the excited state. The low abundances associated with the observed UV photospecific channels, i.e. Cα-Cβ bond breakage in YGH(+) and YAH(+) and direct z-type bond breakage in GYGH(+), respectively, can be rationalized upon consideration of charge transfer states accessible after absorption of one UV photon. Indeed, excited state calculations performed at the RI-CC2 level of theory indicate that charge transfer on the active CO group is a prerequisite for photospecific bond ruptures. The fragmentation mechanisms and the localization of the charge on the side chain after fragmentation are discussed in terms of ionization energies of the fragments.


Role of serum sodium in assessing hospital mortality in cancer patients with spontaneous tumour lysis syndrome inducing acute uric acid nephropathy.
Spontaneous tumour lysis syndrome (STLS) inducing acute uric acid nephropathy, a rare and neglected disease, presents more insidiously than conventional post-treatment tumour lysis syndrome. Although STLS is a serious and potentially fatal complication in patients with neoplastic disorders, few investigations have addressed the relevance of clinical and laboratory features in assessing prognosis. A retrospective study was conducted, reviewing the records of all patients who developed acute renal failure (ARF) at Chang Gung memorial hospital between 1 July 1999 and 30 June 2003. STLS-induced acute uric acid nephropathy was identified in 12 of 1072 ARF patients (1.1%) during the study period. All patients had advanced stage tumours with large tumour burden, and 66.7% of cases had abdominal organ involvement. All 12 hyperuricemic patients became oliguric despite conservative therapy, and remained hyperuricemic (21.6 +/- 5.2 mg/dl) before dialysis therapy. Diuresis developed in eight patients (66.7%), with associated resolution of hyperuricemia, azotemia and metabolic derangements following dialysis initiation. Overall hospital mortality was 58.3%. Death in most patients was related to hyponatremia and hypoalbuminemia on admission. The serum sodium was found to have the best Youden index (0.86) and highest overall prediction accuracy (93%). Moreover, serum sodium and serum albumin for individual patients were significantly and positively correlated (r = 0.617, p = 0.032). This investigation confirms a grave prognosis for cancer patients with STLS inducing acute uric acid nephropathy. Hyponatremia and hypoalbuminemia on the first day of admission indicate poor prognosis in such patients.


[High-resolution computerized tomography in interstitial lung diseases: experiences with over 100 patients].
The report covers experience made with high-resolution computerized tomography in examining more than 100 patients with interstitial lung disease. Small bullous lesions, tiny linear bands in fibrosis and thickening of the bronchovascular bundle can easily be demonstrated by this method. Another advantage is the early detection of ground glass opacities. Although no truly pathognomonic patterns exist, this technique significantly reduces the spectrum of differential diagnosis, especially due to its ability to detect the anatomical relationship between pathological changes and substructures of the lung.


Development of Sphere-Polymer Brush Hierarchical Nanostructure Substrates for Fabricating Microarrays with High Performance.
In this work, a sphere-polymer brush hierarchical nanostructure-modified glass slide has been developed for fabricating high-performance microarrays. The substrate consists of a uniform 160 nm silica particle-self-assembled monolayer on a glass slide with a postcoated poly(glycidyl methacrylate) (PGMA) brush layer (termed PGMA@3D(160) substrate), which can provide three-dimensional (3D) polymer brushes containing abundant epoxy groups for directly immobilizing various biomolecules. As a typical example, the interactions of three monosaccharides (4-aminophenyl β-d-galactopyranoside, 4-aminophenyl β-d-glucopyranoside, and 4-aminophenyl α-d-mannopyranoside) with two lectins (biotinylated ricinus communis agglutinin 120 and biotinylated concanavalin A from Canavalia ensiformis) have been assessed by PGMA@3D(160) substrate-based carbohydrate microarrays. The carbohydrate microarrays show good selectivity, strong multivalent interaction, and low limit of detection (LOD) in the picomolar range without any signal amplification. Furthermore, the proposed sphere-polymer brush hierarchical nanostructure substrates can be easily extended to fabricate other types of microarrays for DNA and protein detection. PGMA@3D(160) substrate-based microarrays exhibit higher reaction efficiencies and lower LODs (by at least 1 order of magnitude) in comparison to those of two-dimensional microarrays, which are fabricated on planar epoxy substrates, making it a promising platform for bioanalytical and biomedical applications.


Primary angioplasty in patients > or = 75 years old with ST-elevation myocardial infarction - one-year follow-up results.
Efficacy and safety of primary percutaneous coronary angioplasty (PCI) in elderly patients with acute ST-elevation myocardial infarction (STEMI) have not yet been definitely established because these patients were usually excluded from large randomised trials. To evaluate in-hospital and one-year outcome after primary PCI in elderly patients, and to assess clinical characteristics of this group. The study population included 1061 consecutive STEMI patients, mean age 60.6+/-17 years, treated with primary PCI. Clinical characteristics and results of 127 patients aged > or = 75 years were compared to the younger group. Elderly patients were more frequently female (48.4 vs. 23.6%, p <0.005) and diabetics (22.2 vs. 12.1%, p <0.02) and more frequently had renal and/or left ventricular failure (22.3 vs. 9.1%, and 9.1 vs. 4.5%, p <0.005, respectively). In older patients less frequently stents were implanted and TIMI flow 3 was restored (65.1 vs. 78.8%, p <0.05 and 74.6 vs. 84.7%, p <0.03). In-hospital mortality in older versus younger patients was 11.8 vs. 3.0%, p <0.005. The incidence of in-hospital complications (stroke, major bleeding and reinfarction) was similar in both groups. The one-year mortality and MACE rates were higher in older patients (21.3 vs. 6.0% and 24.9 vs. 11.0%, p <0.0005). In multivariate analysis Killip class II-IV (OR 6.73; 95% CI 1.75-25.97, p=0.006) and heart rate (OR 1.04; 95% CI 1.01-1.07, p=0.03) were independent predictors of one-year mortality in patients aged > or = 75 years. Primary PCI in older STEMI patients is associated with a favourable in-hospital and one-year outcome, although inferior to that seen in younger patients. The in-hospital complication rate is similar in the elderly and in younger patients.


Culture-independent exploration of the teat apex microbiota of dairy cows reveals a wide bacterial species diversity.
Due to their close proximity to the mammary gland tissue, the bacterial communities lining the teat apex of the udders from lactating cows influence udder health. Denaturing gradient gel electrophoresis of the amplified V3 variable region of the 16S rRNA gene was used as a culture-independent method to reveal the bacterial composition of 48 samples originating from the teat apices of twelve Friesian-Holstein dairy cows suffering from clinical mastitis in one quarter. The microbiota belonged to four bacterial phyla: the Actinobacteria (32% of all genera), the Bacteroidetes (1%), the Firmicutes (42%), and the Proteobacteria (25%), encompassing 17 bacterial genera. Some differences in occurrence of these genera were seen when comparing quarters that were non-infected (n=22), subclinically infected (n=14), or clinically infected (n=12). Besides commensal skin-associated bacteria, opportunistic pathogenic bacteria, and mastitis-causing pathogens were found as well. The species diversity varied considerably among the most prevalent bacterial genera. While Corynebacterium and Staphylococcus displayed a large diversity among the recovered sequences, indicating the possible presence of a variety of different species, only a single bacterial species (represented by one sequence) was obtained for the genera Aerococcus, Acinetobacter, and Psychrobacter. In conclusion, introducing culture-independent analysis of teat apical skin swabs in mastitis research revealed an unexpected wide bacterial diversity, with variations between quarters with a different clinical status. In addition to potential mastitis-causing pathogens, it exposed the yet poorly mapped presence of skin-associated and other bacteria residing in close proximity to the mammary gland tissue. PCR-DGGE may thus be considered as a useful tool for the entanglement of animal skin microbiota, in casu the teat apices of dairy cows.


[Construction of Chinese genomic cosmid library].
A Chinese genomic library has been constructed using SuperCos1 cosmid vector. 6.09 x 10(5) clones were obtained with an everage insert size of 40 kb ranging from 32 to 45 kb, which cover approximately 8.12 fold human genomic DNA. DNA pools prepared from the total library were screened with 6 known markers distributed on different chromosomes, which all were tested positive.


Structure and function of human jun-D.
A jun related cDNA and its corresponding genomic fragment were cloned from human cells and sequenced. Polymerase chain reaction analysis showed that this gene is the human homologue of the mouse jun-D gene despite the fact that the degree of amino acid sequence conservation between the two is much poorer (77.3%) than that found between the homologues of c-jun and jun-B (95-98%). The product of this gene binds an AP-1 site and upon cotransfection stimulates the activity of a promoter that bears an AP-1 site. The level of activation is comparable to that of v-jun and the activity of both is further stimulated by v-fos. Deletion mutants of the gene that lack the best conserved region in the activating domain are poorly active. However, our data suggest that the activating domain is not confined exclusively to the conserved regions. Interestingly, at high concentrations human jun-D displays decreased activity which cannot be explained by a simple self squelching model.


The effects of bifemelane hydrochloride on depressive illness of the elderly.
The therapeutic efficacy, utility and safety of bifemelane hydrochloride were studied in 52 elderly depressive patients. The drug was administered as a tablet containing 50 mg orally three times daily for 8 consecutive weeks. The final global improvement rating and global utility rating were respectively 80.8 and 73.1 percent for all patients. The improvement rates on the Hamilton depression rating scale (HAM-D) were more than 60% for depressed mood, guilt, suicide, middle insomnia, delayed insomnia, psychotic anxiety, gastro-intestinal symptom, hypochondriasis, depersonalization and derealization. The rates regarding global symptoms evaluated by the Psychoneurotic rating scale for doctor's use were more than 60% for tension, agitation, irritability and excitement, phobia, depression, hypochondria and nocturnal delirium in psychotic symptoms, and insomnia in addition to palpitation in somatic symptoms. A significant decrease was also observed in the symptoms covered by the Self-rating depression scale of Zung after treatment with this drug. There were no instances of side-effects, nor any abnormalities in laboratory tests, encountered throughout the trial. Therefore, bifemelane hydrochloride is of value for the treatment of geriatric depression.


Lipopolysaccharide From E. coli Increases Glutamate-Induced Disturbances of Calcium Homeostasis, the Functional State of Mitochondria, and the Death of Cultured Cortical Neurons.
Lipopolysaccharide (LPS), a fragment of the bacterial cell wall, specifically interacting with protein complexes on the cell surface, can induce the production of pro-inflammatory and apoptotic signaling molecules, leading to the damage and death of brain cells. Similar effects have been noted in stroke and traumatic brain injury, when the leading factor of death is glutamate (Glu) excitotoxicity too. But being an amphiphilic molecule with a significant hydrophobic moiety and a large hydrophilic region, LPS can also non-specifically bind to the plasma membrane, altering its properties. In the present work, we studied the effect of LPS from Escherichia coli alone and in combination with the hyperstimulation of Glu-receptors on the functional state of mitochondria and Ca2+ homeostasis, oxygen consumption and the cell survival in primary cultures from the rats brain cerebellum and cortex. In both types of cultures, LPS (0.1-10 μg/ml) did not change the intracellular free Ca2+ concentration ([Ca2+]i) in resting neurons but slowed down the median of the decrease in [Ca2+]i on 14% and recovery of the mitochondrial potential (ΔΨm) after Glu removal. LPS did not affect the basal oxygen consumption rate (OCR) of cortical neurons; however, it did decrease the acute OCR during Glu and LPS coapplication. Evaluation of the cell culture survival using vital dyes and the MTT assay showed that LPS (10 μg/ml) and Glu (33 μM) reduced jointly and separately the proportion of live cortical neurons, but there was no synergism or additive action. LPS-effects was dependent on the type of culture, that may be related to both the properties of neurons and the different ratio between neurons and glial cells in cultures. The rapid manifestation of these effects may be the consequence of the direct effect of LPS on the rheological properties of the cell membrane.


Treatment of infected tibial nonunion with tobramycin-impregnated calcium sulfate: report of two cases.
The treatment of infected tibial nonunion usually includes a staged reconstruction protocol. We present 2 patients with tibial nonunion and plate loosening with oxacillin-resistant Staphylococcus aureus infection. The patients were treated using the removal of the plate, radical debridement, and implantation of gentamycin-impregnated cement beads during the first stage. During the second stage, plate fixation was performed and tobramycin-impregnated calcium sulfate (Osteoset T) was used as a bone graft substitute. Neither an autogenous bone graft nor an allograft was used. At 3 years of follow-up, each tibia showed good union, and there was no recurrence of infection. We consider tobramycin-impregnated calcium sulfate to be an alternative method of bone grafting to treat infected tibial nonunion.


Ethylene Production by Albedo Tissue of Satsuma Mandarin (Citrus unshiu Marc.) Fruit.
Isolated albedo tissue of Satsuma mandarin (Citrus unshiu Marcovitch, cv. Owari) fruit produced a large quantity of ethylene during incubation at 26 C in the dark. When sliced, albedo tissue began producing ethylene at an increasing rate until a maximum was reached after incubation for about 30 hours. Aged albedo discs which were capable of producing ethylene, actively converted l-[U-(14)C]methionine into both ethylene and carbon dioxide. In fresh tissue, almost no measurable conversion of radioactive methionine into ethylene took place. Conversion of labeled l-methionine into ethylene was totally inhibited by the addition of nonradioactive l-methionine or l-ethionine. It appears possible, from these findings, that methionine is a precursor of ethylene in the aged albedo discs. Ethylene synthesis in the aged albedo tissue was markedly reduced in the presence of cycloheximide, suggesting that there may be a rapid turnover of the ethylene-producing system, and that its formation involves protein synthesis. Actinomycin D exerted no effect.


Precise localization of silicone-based intercranial planar electrodes in magnetic resonance imaging.
Intercranial planar electrodes enable neural recordings with high spatial resolution in diagnosis as well as for treatments. The value of the measurements increases with the precision of localization of the electrodes related to the individual anatomy. In this context, post-implantation MRI provides excellent soft tissue contrast, but the accurate localization of electrodes is impaired by magnetic susceptibility artifacts. We have addressed this problem without adding a substantial burden to the electrode fabrication process. Simple silicone reference structures were strategically placed on the implant surface to visualize the electrodes position in MRI. These reference structures allowed high precision electrode localization independently of electrode imaging artifacts. This implant manufacturing approach could prove extremely useful in combination with existing image processing pipelines.


Regional Dysfunction After Myocardial Infarction in Rats.
Detailed understanding of regional function after myocardial infarction (MI) is currently incomplete. We aimed at investigating regional myocardial strain and work in post-MI rats with and without heart failure. Six weeks after induction of MI, 62 male Wistar-Hannover rats with a range of infarct sizes, plus 14 sham-operated rats, were examined by cine and phase-contrast magnetic resonance imaging. After magnetic resonance imaging, the rats were catheterized, and left ventricular pressures were recorded. Regional strain and work were calculated from the magnetic resonance imaging and pressure data. On the basis of end-diastolic left ventricular pressure, 34 MI rats were classified as nonfailing (MINF) and 28 MI rats as failing (MICHF). In the region remote to the infarct, the MINF rats exhibited preserved strain and increased work compared with sham, whereas MICHF had reduced longitudinal strain and no increase in work in this region. In the noninfarcted region adjacent to the infarct, MICHF demonstrated substantially reduced work because of high levels of negative work. We have demonstrated a distinct difference in regional work between nonfailing and failing hearts after MI and offer novel insight into the relation between regional function and presence of congestion. Work analysis provided significant added value over strain analysis alone.


[Treatment of multiple myeloma--present status and perspectives].
Multiple myeloma (MM) remains incurable. Despite many chemotherapy programs for large numbers of patients, there has been little improvement in outcome during the past 25 years. For many years, intermittent courses of melphalan and prednisone have represented the standard chemotherapy for newly diagnosed symptomatic MM. Many other drug combinations have been assessed, including regimens using multiple alkylating agents, and programs with vincristine, or an anthracycline, and have failed to show any superiority to melphalan-prednisone. Interferon alpha (IFN alpha) inhibits plasma cell growth and has induced responses in approximately 15% of previously untreated patients. This cytokine may have a role when used in those patients who have reached a good "plateau phase" with low tumor burden at the end of a chemotherapeutic program or after a transplantation procedure. The results of myeloablative therapy with allogenic or autologous marrow transplantation are promising and suggest possibility of a cure in some patients. Important problem in the management of MM patients is the treatment of complications, especially bone destruction, hypercalcemia, anemia and infections. Experimental modalities, especially immunotherapy, hold promise for use in humans and may also provide further insights into the pathogenesis of MM.


The role of the methyl group in stabilising the weak N-H...pi hydrogen bond in the 4-fluorotoluene-ammonia complex.
The 4-fluorotoluene-ammonia van der Waals complex has been studied using a combination of resonant two-photon ionisation (R2PI) spectroscopy, ab initio molecular orbital calculations and multidimensional Franck-Condon analysis. The R2PI spectrum shows two sets of features assignable to two distinct conformers: one in which the ammonia binds between the hydrogen meta to the methyl group and the fluorine atom in a planar configuration and the other a pi-bound structure involving one bond between an ammonia hydrogen and the pi-system and another between the ammonia lone pair and the slightly acidic hydrogens on the methyl group. Ground state estimated CCSD(T) interaction energies were computed at the basis-set limit: these calculations yielded very similar interaction energies for the two conformers, whilst zero point energy correction yielded a zero point binding energy for the pi-complex about 10% larger than that of the in-plane, sigma-complex. The results of multidimensional Franck-Condon simulations based on ab initio ground and excited state geometry optimisations and vibrational frequency calculations showed good agreement with experiment, with further improvements achieved using a fitting procedure. The observation of a pi-complex in addition to a sigma-complex supports the intuitive expectation that electron-donating groups should help to increase pi-density and hence stabilise pi-proton acceptor complex formation. In this case, this occurs in spite of the presence of a strongly electron-withdrawing fluorine atom.


Phantosmia and dysgeusia as the first presentation of glioblastoma.
Glioblastoma is the most common and aggressive primary brain tumor in adults and has an extremely poor prognosis. It is rare for a high-grade glioma, or any brain tumor, to have an initial presentation of gastrointestinal symptoms. We present a rare case of a healthy 70-year-old woman who presented with symptoms of phantosmia and dysgeusia with magnetic resonance imaging findings of a brain mass confirmed via brain biopsy to be glioblastoma. Through a rare presentation, we aim to elucidate the importance of recognizing the association of phantosmia and dysgeusia to seizure auras and the critical need for diagnostic imaging to rule out organic causes such as infection and neoplasms.


Isoproterenol Increases RANKL Expression in a ATF4/NFATc1-Dependent Manner in Mouse Osteoblastic Cells.
Sympathetic nervous system stimulation-induced β-adrenergic signal transduction is known to induce bone loss and increase of osteoclast activity. Although isoproterenol, a nonspecific β-adrenergic receptor agonist, has been shown to increase receptor activator of NF-κB ligand (RANKL), the details of the regulatory mechanisms remain unclear. In the present study, we investigated the role of the nuclear factor of activated T-cells (NFAT) in isoproterenol-induced RANKL expression in C2C12 and in primary cultured mouse calvarial cells. Isoproterenol increased nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and RANKL expressions at both mRNA and protein levels and increased NFAT reporter activity. NFATc1 knockdown blocked isoproterenol-mediated RANKL expression. Isoproterenol also promoted cAMP response element-binding protein 1 (CREB1) and activating transcription factor 4 (ATF4) phosphorylation. Isoproterenol-mediated transcriptional activation of NFAT was blocked by protein kinase A (PKA) inhibitor H89. Isoproterenol-induced CREB1, ATF4, NFATc1, and RANKL expressions were suppressed by H89. Mutations in cAMP response element-like or NFAT-binding element suppressed isoproterenol-induced RANKL promoter activity. Chromatin immunoprecipitation analysis demonstrated that isoproterenol increased NFAT-binding and ATF4-binding activities on the mouse RANKL promoter, but did not increase CREB1-binding activity. Association of NFATc1 and ATF4 was not observed in a co-immunoprecipitation study. ATF4 knockdown suppressed isoproterenol-induced NFAT binding to the RANKL promoter, whereas NFATc1 knockdown did not suppress isoproterenol-induced ATF4 binding to the RANKL promoter. ATF4 knockdown suppressed isoproterenol-induced expressions of NFATc1 and RANKL. These results suggest that isoproterenol increases RANKL expression in an ATF4/NFATc1-dependent manner.


Acetylcholinesterase inhibitory activity of some Amaryllidaceae alkaloids and Narcissus extracts.
Amaryllidaceous plants produce pharmacologically active alkaloids, galanthamine being the most interesting for its use in the treatment of Alzheimer's disease as a cholinesterase inhibitor. The aim of this work was to test 23 pure Amaryllidaceae alkaloids and 26 extracts from different species of the genus Narcissus for their acetylcholinesterase inhibitory activity using galanthamine as a reference. Only seven alkaloids, belonging to the galanthamine and lycorine skeleton types, exhibited such an effect, sanguinine being the most active, even more than galanthamine. All the extracts with the highest acetylcholinesterase inhibitory activity contained galanthamine except that of N. assoanus, a lycorine type alkaloid-bearing species.


The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells.
Fanconi Anemia (FA) is a disease characterized by bone marrow (BM) failure and aplastic anemia. In addition to a defective DNA repair system, other mechanisms are involved in its pathogenesis, such as defective mitochondrial metabolism, accumulation of lipids, and increment of oxidative stress production. To better understand the role of these metabolic alterations in the process of HSC maturation in FA, we evaluated several biochemical and cellular parameters on mononuclear cells isolated from the bone marrow of FA patients or healthy donors. To mimic the cellular residence in the BM niche or their exit from the BM niche to the bloodstream, cells have been grown in hypoxic or normoxic conditions, respectively. The data show that, in normoxic conditions, a switch from anaerobic to aerobic metabolism occurs both in healthy and in pathological samples. However, in FA cells this change is associated with altered oxidative phosphorylation, the increment of oxidative stress production, no activation of the endogenous antioxidant defenses and arrest in the G2M phase of the cell cycle. By contrast, FA cells grown in hypoxic conditions do not show cell cycle and metabolic alterations in comparison to the healthy control, maintaining both an anaerobic flux. The data reported herein suggests that the passage from the BM niche to the bloodstream represents a crucial point in the FA pathogenesis associated with mitochondrial dysfunction.


Recent changes in trends of opioid overdose deaths in North America.
As several regulatory and environmental changes have occurred in North America, trends in overdose deaths were examined in the United States (US), Ontario and British Columbia (BC), including changes in consumption levels of prescription opioids (PO) and overdose deaths, changes in correlations between consumption levels of PO and overdose deaths and modeled differences between observed and predicted overdose deaths if no changes had occurred. Consumption levels of PO included defined daily doses for statistical purposes per million inhabitants per day for the US and Canada (2001-2015). Overdose deaths included opioid overdose deaths for the US (2001-2017) and Ontario (2003-2017) and illicit drug overdose deaths for BC (2001-2017). The analytic techniques included structural break point analyses, Pearson product-moment correlations and multivariate Gaussian state space modeling. Consumption levels of PO changed in the US in 2010 and in Canada in 2012. Overdose deaths changed in the US in 2014 and in Ontario and BC in 2015. Prior to the observed changes in consumption levels of PO, there were positive correlations between consumption levels of PO and overdose deaths in the US (r = 0.99, p < 0.001) and Ontario (r = 0.92, p = 0.003). After the observed changes in consumption levels of PO, there was a negative correlation between consumption levels of PO and overdose deaths in the US (r = - 0.99, p = 0.002). Observed overdose deaths exceeded predicted overdose deaths by 5.7 (95% Confidence Interval [CI]: 4.8-6.6), 3.5 (95% CI: 3.2-3.8) and 21.8 (95% CI: 18.6-24.9) deaths per 100,000 people in the US, Ontario and BC, respectively in 2017. These excess deaths corresponded to 37.7% (95% CI: 31.9-43.6), 39.2% (95% CI: 36.3-42.1) and 72.2% (95% CI: 61.8-82.6) of observed overdose deaths in the US, Ontario and BC, respectively in 2017. The opioid crisis has evolved in North America, as a sizeable proportion of overdose deaths are now attributable to the several regulatory and environmental changes. These findings necessitate substance use policies to be conceptualized more broadly as well as the continued expansion of harm reduction services and types of pharmacotherapy interventions.


Parent-Child Attunement Moderates the Prospective Link between Parental Overcontrol and Adolescent Adjustment.
Parental overcontrol (OC), behavior that intrusively or dominantly restricts child autonomy, has been identified as a transdiagnostic risk factor for youth. However, it is as yet unknown whether the association between parental OC and child maladjustment remains even when OC is exerted infrequently or by attuned parents. Rather, the selective use of OC might steer children away from danger. Taking a developmental psychopathology approach, this study focuses on the larger parent-child relationship context, testing whether either the dose at which parents demonstrate OC or the degree to which children perceive their parents as attuned determines whether OC is risky or protective for adolescents' adjustment. Among a community sample of 114 families of children followed from the ages of 12-18, we examine whether OC, behaviorally coded from triadic mother-father-child discussions in middle childhood, is associated with later risky behavior and anxiety symptoms in adolescence. Overcontrol exerted by either mothers or fathers had a curvilinear effect on adolescent risky behaviors, and this effect was moderated by children's perceived attunement. Although OC generally was associated with increased risky behaviors, low doses of OC or OC exerted by highly attuned parents protected against engagement in risky behaviors. No main effect of OC was observed on adolescent anxiety; however, mothers' OC interacted with perceived parental attunement, such that OC exerted by less attuned parents predicted greater anxiety. Results underscore that the effect of parenting behaviors depends on the larger parent-child relationship context.


[Genetics of insulin-dependent juvenile diabetes].
Since the works of Singal and al. and Nerup and al., an increase in B 8, B 15 and B 18 antigens has been found in Insulin Dependent Diabetes. Thomson and al., Rubinstein and al. and the authors of this paper have shown an stronger association with DRw 3 and DRw 4 antigens. We investigated the genetic predisposition to juvenile diabetes in 22 families of 48 cases and 96 members. The study of one affected child in each family showed that DRw 3 was found in 63,63% and DRw 4 in 59,59% (healthy 16,22%)--RR = 9,0 and 7,49. The hypothesis of overdominance proposed by Nerup can be confirmed by our data, when I.D.D.M. share two different alleles (DRw 3 and DRw 4). 3 particular haplotypes with linkage imbalance are therefore observed in our series: B 8-Bf S-DRw 3, B 15-Bf F-DRw 4 and B 8-Bf F 1-DRw 3. Our date show a excessive transmission of the diabetic haplotype by parents who are either diabetics or carriers of the gene.


Basilar Artery Fenestration Versus Hypoglycemia-Induced Vertebrobasilar Insufficiency: A Case Report.
Vertebrobasilar insufficiency (VBI) is a common transient neurological condition related to posterior circulation hemodynamic insufficiency. However, it is rarely seen as an initial presentation in basilar artery (BA) fenestration or hypoglycemia. We present this case to further clarify the association between BA fenestration and hypoglycemia-induced VBI, as well as the difficulty in diagnosis, especially in acute clinical settings. Herein, we report a case with BA fenestration, in which the patient suffered from transient episodes of focal neurological deficits, including dysarthria, focal limbs weakness, and ataxia with subsequent total recovery. Apart from hypoglycemia, no other abnormal laboratory surveys were found. This concurrent finding of hypoglycemia with transient focal neurological deficit poses a difficulty in differentiating between hypoglycemia-induced VBI and true acute ischemic stroke in the clinical setting. Subsequent brain imaging studies revealed no evidence of acute infarction and no evidence of atherosclerosis changes in vessels but BA fenestration was observed. We prescribed antiplatelets for the prevention of future strokes. However, currently, no consensus exists regarding the prevention of cerebral ischemia with BA fenestration. BA fenestration-induced VBI and hypoglycemia-induced VBI are rarely reported and their mechanisms of action remain uncertain and controversial. However, BA fenestration-induced VBI may pose a risk for future cerebral ischemic events and warrants further investigations.


The cell biology of antigen processing and presentation.
Histocompatibility molecules are peptide-binding proteins and present antigenic peptides to T cells. In spite of similarity in structure and peptide specificity, class-I and class-II histocompatibility molecules present peptides at different intracellular locations. Class-I molecules present peptides derived from endogenous proteins, but class-II molecules can present peptides from endocytosed (exogenous) antigen as well as endogenous antigen. Binding of antigenic peptides by histocompatibility molecules is a function of their assembly, intracellular trafficking, and endocytosis. For class-I molecules, assembly appears to be the most important step for peptide acquisition, while all three processes can potentially influence class-II antigen presentation. The versatility of peptide binding by class-II MHC molecules is due to its association with the invariant chain which blocks peptide binding during the initial stages of class-II assembly and export and contributes to the endosomal targeting of class-II molecules. Once invariant chain dissociates, class-II molecules become competent to bind peptides and are released to the cell surface. The location in which a particular antigenic peptide is produced is a function both of its route of introduction into the cell and its susceptibility to degradation. These factors contribute significantly to whether an antigen will be presented by class-I or class-II molecules and should be taken into account in the design and development of vaccines.


Emergence of BCR-ABL-specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term imatinib mesylate treatment.
Imatinib mesylate has been demonstrated to allow the emergence of T cells directed against chronic myeloid leukemia cells. A total of 10 Philadelphia chromosome-positive acute lymphoblastic leukemia patients receiving high-dose imatinib mesylate maintenance underwent long-term immunological monitoring (range, 2-65 months) of (p190)BCR-ABL-specific T cells in the bone marrow and peripheral blood. (p190)BCR-ABL-specific T lymphocytes were detected in all patients, more frequently in bone marrow than in peripheral blood samples (67% vs 25%, P < .01) and resulted significantly associated with lower minimal residual disease values (P < .001), whereas absent at leukemia relapse. Specific T cells were mainly effector memory CD8(+) and CD4(+) T cells, producing interferon-gamma, tumor necrosis factor-alpha, and interleukin-2 (median percentage of positive cells: 3.34, 3.04, and 3.58, respectively). Cytotoxic subsets able to lyse BCR-ABL-positive leukemia blasts also were detectable. Whether these autologous (p190)BCR-ABL-specific T cells may be detectable under other tyrosine-kinase inhibitors, expanded ex vivo, and exploited for immunotherapy remains to be addressed.


Epithelial-Cell-Derived Cytokines in Patients with Obesity before and after Bariatric Surgery.
Abstract/Purpose: Epithelial signals such as interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) are stimulators of group 2 innate lymphoid cells (ILCs2) that are integral regulators of adipose tissue type 2 immunity. The purpose of this study was to assess cytokines activating ILCs2 in the serum of patients with obesity and the effect of bariatric surgery on these parameters. In a single-center prospective study, serum IL-25, IL-33, TSLP, and ST2L levels were assayed at the baseline and at 6 months after bariatric surgery and correlated with anthropometric changes and metabolism parameters. Mean age and median of body mass index (BMI) of study participants were 41.9 years ± 11 and 45.6 kg/m2 (range 36.3-56.3), respectively. Six months after surgery, excess weight loss percentage was 43.1 ± 10.2%. Serum TSLP was significantly lower in patients with obesity both before and after surgery than in healthy controls. TSLP values before operation were significantly correlated to glycated hemoglobin percentage and BMI. Serum IL-25, IL-33, and ST2L levels were comparable to controls both before and after operation. Decreased serum levels of TSLP may be a characteristic trait for obesity however nonmodifiable by body mass surgical reduction in short time observation. Low serum levels of TSLP are related to disturbances in glucose metabolism and BMI.


Optimal timing for removal of abdominal drainage after liver resection for hepatocellular carcinoma.
The aim of this study was to retrospectively assess the optimal timing for removal of abdominal drainage after liver resection for hepatocellular carcinoma (HCC). A total of 148 patients were divided into 2 groups. In Group I, drains were removed according to the judgment of the surgeon. In Group II, drains were removed on postoperative day (POD) 2, except in cases of bile leakage, purulent ascites, or hemorrhage. Postoperative complications were compared between the 2 groups. Postoperative hospital stay was shorter in Group II than in Group I. Six patients required drain reinsertion for abdominal abscess and massive ascites. The risk factor for drain reinsertion was volume of drain discharge greater than 450 mL on POD 2. Early removal of the drain is desirable after surgical treatment of HCC. Moreover, it seems preferable to determine the necessity of drain removal based on assessment of the volume and nature of drain discharge on POD 2.


Induction of non-apoptotic cell death by sodium 5,6-benzylidene-L-ascorbate in a human salivary gland tumor cell line.
We investigated whether sodium 5,6-benzylidene-L-ascorbate (SBA) induces apoptotic cell death in a human salivary gland tumor cell line HSG, using two different cytochemical methods. Millimolar concentrations of SBA dose-dependently reduced the viable cell number of HSG cells, accompanied by the detachment of dying cells from the culture plates. The nuclei of the dying cells were not stained with TUNEL reagent, indicating the lack of DNA nicks or fragments. On the other hand, the nuclei of epigallocatechin gallate (EGCG)-treated cells (positive control) were TUNEL-positive, demonstrating the production of DNA nicks or fragments. Furthermore, the cytoplasms of SBA-treated cells were not stained with M30 monoclonal antibody, which reacts with the degradation products of cytokeratin 18 by the activated caspases, in contrast to those of EGCG-treated cells. These results suggest that SBA induces non-apoptotic cell death, possibly necrosis, in HSG cells.


[The influence of Mozart's and Beethoven's music on reverse mnemonic recall tasks].
The aim of this paper is to investigate one of the most well-known phenomena in the field of music psychology: the influence of Mozart's music (Mozart effect). Today the Mozart effect is generally related to every kind of short-term or long-term positive influence of music on men and animals. Here it is examined in relation to cognitive tasks and par ticularly in relation to reverse mnemonic recall tasks. Twenty-four volunteers, aged 50-55 participated in all 3 ten-minute conditions of the experiment which were Mozart's Allegro con spirito K.448, Beethoven's Rondo-Allegro opus 61 and ten minutes of silence without any recorded acoustic stimulus. The individuals were randomly separated in six groups. The examination material were three improvised groups of series consisted of one-digit numbers from 2 to 9 digits, which were read in a rate of one digit per second. Results indicated that the majority of the participants did not show any increase in the number of digits that they could recall due to the listening of Mozart's piece. Also, no statistically significant difference was found between the three conditions associated with listening to a morphologically similar excerpt by Beethoven. What was however found was that individuals who strongly preferred the Mozart condition scored better than the others (p=0,005). Finally, it seems that participants who had attended even basic music studies remembered more digits in all three conditions of the experiment than the others who had never studied music before (p=0,000).


A Re-evaluation of Soybean Leaf Photorespiration.
Recalculations of soybean photorespiration indicate that mean rates are closer to 16.1 than 5.6 milligrams of CO(2) per square decimeter per hour as previously reported. Photorespiration of soybean thus amounts to at least a 30% carbon turnover of light-saturated photosynthesis. Photorespiration showed no significant relationship to net photosynthesis. Negative correlations were found between CO(2) efflux and stomatal resistance as well as between corrected photorespiration and residual intracellular resistance of the leaf to CO(2) uptake.


The role of super-diversity in shaping the perception of and services for older migrants.
Population ageing and international migration are on the rise. The common denominator between these two phenomena is the older migrant population, which has been steadily increasing in Northern America and Western Europe. The emergence of this population has been challenging institutional practices and services due to a growth in heterogeneity. Against this background, the paper aims to answer two questions: (1) does super-diversity in the older native population have an impact on the ways in which practitioners regard and refer to older migrants? and (2) what kind of service responses does the recognition of super-diversity as a characteristic of the older population, both native and migrant, lead to? The empirical analysis focuses on Switzerland, a highly relevant case for two reasons: first due to the heterogeneity within the native population, given its three linguistic regions, and second due to the large proportion of (older) migrants. Based on 33 in-depth interviews with representatives of local institutions dealing with older persons including migrants in Switzerland; the conclusion of the paper is that super-diversity in the majority population can potentially lead to a recognition and acceptance of super-diversity in other populations, and in this case older migrants. Yet, at an institutional level super-diversity can translate in over-individualized tailored services, which can unintentionally contribute to inequality.


Incidence of primary bone tumours and tumour like lesions in and around Dakshina Kannada district of Karnataka.
A total of 523 cases of primary bone tumours and tumour like lesions in and around Dakshina Kannada district of Karnataka were diagnosed over a period of 36 years. About 39% of these tumours were malignant and the remaining benign. Among the malignant tumours the highest incidence was of osteosarcoma (45.7%) followed by Ewing's sarcoma (19.4%). Osteochondroma was the most frequent in the benign tumour category (30.3%). Peak incidence of tumour was in the 2nd and 3rd decade of life with a male preponderance. The most commonly affected bones were femur, tibia and humerus in that order. Results indicate a significantly higher incidence of primary bone tumours in this part of India.


Exophthalmos as a first manifestation of small cell lung cancer: a long-term follow-up.
Small cell lung cancer is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic therapy, until now treatments have failed to control or cure this disease in most patients. Orbital metastases are a rare manifestation of systemic malignancies. Breast and lung cancers represent more than two thirds of the primary cancer sites. Metastases to the eye and orbit develop in approximately 0.7-12% of patients with lung cancer. Here, we report a rare case of exophthalmos as the first manifestation of a metastatic carcinoma due to small cell lung cancer, and a 6-months follow-up with complete exophthalmic response to chemotherapy.


Developmental assessment of human vitrified-warmed blastocysts based on oxygen consumption.
In this study, we aimed to develop a model for embryo selection based on oxygen consumption following cryopreservation, the relationship between the developmental competence of blastocysts and their oxygen consumption was assessed. Oxygen consumption of vitrified-warmed human blastocysts was measured at 0, 1.5, 3, 4.5, 6, 7.5, 9 and 24 h after warming using scanning electrochemical microscopy. On the basis of their developmental stage at 24 h, blastocysts were classified into four groups (hatched, hatching, arrested and degenerated). Moreover, cytochrome c oxidase (CCO) activity in vitrified-warmed blastocysts was assessed at 0 and 24 h. The oxygen consumption rate of blastocysts just after warming was significantly lower than that of non-vitrified blastocysts (P< 0.05). The oxygen consumption rate of blastocysts was significantly higher in the hatched group than in the arrested and the degenerated groups after 1.5 h (P< 0.05) and than in the hatching group (P< 0.05) at 7.5 and 9 h. Moreover, CCO activity was absent in vitrified-warmed blastocysts at 0 h, but was detected at 24 h. The respiratory rate of vitrified blastocysts after warming was significantly lower than non-cryopreserved blastocysts. Oxygen consumption of blastocysts with high developmental potential was restored earlier than that of blastocysts with low developmental potential. The results of this study suggest that it is possible to select vitrified-warmed blastocysts with high developmental potential based on their respiratory activity.


Reactions of the immune system in epilepsy.
Epilepsy may present as a symptom of many neurological disorders and often an etiological explanation cannot be identified. There is growing evidence that autoimmune mechanisms might have a role in some patients. The evidence for immunological mechanisms in epilepsy can be examined within the following three main areas: the childhood epilepsy syndromes, epilepsy associated with other immunologically mediated diseases, and the more common unselected groups of patients with epilepsy. Autoimmunity was recently suspected to be involved in the pathology of certain human epilepsies. This includes numerous reports of the detection of theoretically relevant serum autoantibodies, experimental data showing that antibodies can be epileptogenic, and a response of some epilepsy syndromes to immunomodulation. The high prevalence of epilepsies in specific immune diseases suggests that immune system may play a role in the pathogenesis of epilepsy or might be associated with it. There is some evidence that immune mechanisms play a role in the pathogenesis of some epilepsy syndromes.


Cdk7: a kinase at the core of transcription and in the crosshairs of cancer drug discovery.
The transcription cycle of RNA polymerase II (Pol II) is regulated by a set of cyclin-dependent kinases (CDKs). Cdk7, associated with the transcription initiation factor TFIIH, is both an effector CDK that phosphorylates Pol II and other targets within the transcriptional machinery, and a CDK-activating kinase (CAK) for at least one other essential CDK involved in transcription. Recent studies have illuminated Cdk7 functions that are executed throughout the Pol II transcription cycle, from promoter clearance and promoter-proximal pausing, to co-transcriptional chromatin modification in gene bodies, to mRNA 3´-end formation and termination. Cdk7 has also emerged as a target of small-molecule inhibitors that show promise in the treatment of cancer and inflammation. The challenges now are to identify the relevant targets of Cdk7 at each step of the transcription cycle, and to understand how heightened dependence on an essential CDK emerges in cancer, and might be exploited therapeutically.


Posterior Reversible Encephalopathy Syndrome in a Patient With Microscopic Polyangiitis: A Case Report and Literature Review.
Central nervous system (CNS) is rarely involved in microscopic polyangiitis (MPA). Here, we report a 14-year-old girl with MPA who developed new-onset seizures with deterioration of renal function. Her brain CT scan and MRI showed concurrent complications of intracerebral hemorrhage and posterior reversible encephalopathy syndrome (PRES). She got remission with combinations of methylprednisolone pulse, plasma exchange, regular hemodialysis, antiseizure and antihypertension medications. Furthermore, it is crucial to exclude the adverse effect of medications such as corticosteroid and biological therapy. We searched the literatures, retrieved 6 cases of MPA with PRES and summarized their clinical characteristics.


All-trans retinoic acid-induced focal myositis, synovitis, and mononeuritis.
All-trans retinoic acid has revolutionized the treatment of acute promyelocytic leukemia, but this therapy is often complicated by the all-trans retinoic acid syndrome. Here we report a patient with newly diagnosed acute promyelocytic leukemia who developed acute focal myositis, synovitis, and possible vasculitis, after receiving all-trans retinoic acid therapy. We review the existing literature on this rare clinical entity, all-trans retinoic acid-induced myositis. This condition can manifest as fever, myalgia, arthralgia, and Sweet syndrome, accompanied by distinct magnetic resonance findings involving the lower extremity musculature. Treatment consists of discontinuation of the offending drug and often high dose corticosteroids.


Addressing women's non-maternal healthcare financing in developing countries: what can we learn from the experiences of rural Indian women?
This paper focuses on the inadequate attention on women's non-maternal healthcare in low- and middle-income countries. The study assessed the purchase of and financial access to non-maternal healthcare. It also scoped for mainstreaming household financial resources in this regard to suggest for alternatives. A household survey through multi-stage stratified sampling in the state of Orissa interviewed rural women above 15 years who were neither pregnant nor had any pregnancy-related outcome six weeks preceding the survey. The questions explored on the processes, determinants and outcomes of health seeking for non-maternal ailments. The outcome measures were healthcare access, cost of care and financial access. The independent variables for bivariate and multivariate analyses were contextual factors, health seeking and financing pattern. The survey obtained a response rate of 98.64% and among 800 women, 43.8% had no schooling and 51% were above 60 years. Each woman reported at least one episode of non-maternal ailment; financial constraints prevented 68% from receiving timely and complete care. Distress coping measures (e.g. borrowings) dominated the financing source (67.9%) followed by community-based measures (32.1%). Only 6% had financial risk-protection; financial risk of not obtaining care doubled for women aged over 60 years (OR 2.00, 95% CI 0.84-4.80), seeking outpatient consultation (OR 2.01, 95% CI 0.89-4.81), facing unfavourable household response (OR 2.04, 95% CI 1.09-3.83), and lacking other financial alternatives (OR 2.13, 95% CI 1.11-4.07). When it comes to timely mobilization of funds and healthcare seeking, 90% (714) of the households preferred maternal care to non-maternal healthcare. The existing financing options enable sub-optimal purchase of women's non-maternal healthcare. Though dominant, household economy extends inadequate attention in this regard owing to its unfavourable approach towards non-maternal healthcare and limited financial capacity and support from other financial resources.


[Stability of HDTMA modified montmorillonite].
In order to probe the stability of organic montmorillonite, the nature montmorillonite was modified with hexadeeyltrimethylammonium (HDTMA) in different cation exchange capacity (CEC). The results of experiments showed that the stability of modified montmorillonite declined as its CEC was big and HDTMA was desorbed from 1.0 CEC modified montmorillonite. HDTMA bound to the montmorillonite surface was resistant to temperature(70 degrees C) and instable to strong ultrasonic and to vibrational intensity(180 r/min). The result also indicated that the stability of modified montmorillonite increased to NaCl(1.8 mol/L) but decreased to CaCl2 (1.8 mol/L) and modified montmorillonite was more stable in high-pH environment(12.00) than in low-pH environment(2.06). On the basis of the results of these studies, low CEC modified montmorillonite appeared suitable as a sorbent for wastewater chemical treatment and as carrier for wastewater biotreatment in low stir environment.


Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.
Protein acetyltransferases and deacetylases have been implicated in oncogenesis, apoptosis and cell cycle regulation. Most of the protein acetyltransferases described acetylate epsilon-amino groups of lysine residues within proteins. Mouse ARD1 (homologue of yeast Ard1p, where Ard1p stands for arrest defective 1 protein) is the only known protein acetyltransferase catalysing acetylation of proteins at both alpha-(N-terminus) and epsilon-amino groups. Yeast Ard1p interacts with Nat1p (N-acetyltransferase 1 protein) to form a functional NAT (N-acetyltransferase). We now describe the human homologue of Nat1p, NATH (NAT human), as the partner of the hARD1 (human ARD1) protein. Included in the characterization of the NATH and hARD1 proteins is the following: (i) endogenous NATH and hARD1 proteins are expressed in human epithelial, glioma and promyelocytic cell lines; (ii) NATH and hARD1 form a stable complex, as investigated by reciprocal immunoprecipitations followed by MS analysis; (iii) NATH-hARD1 complex expresses N-terminal acetylation activity; (iv) NATH and hARD1 interact with ribosomal subunits, indicating a co-translational acetyltransferase function; (v) NATH is localized in the cytoplasm, whereas hARD1 localizes both to the cytoplasm and nucleus; (vi) hARD1 partially co-localizes in nuclear spots with the transcription factor HIF-1alpha (hypoxia-inducible factor 1alpha), a known epsilon-amino substrate of ARD1; (vii) NATH and hARD1 are cleaved during apoptosis, resulting in a decreased NAT activity. This study identifies the human homologues of the yeast Ard1p and Nat1p proteins and presents new aspects of the NATH and hARD1 proteins relative to their yeast homologues.


Defining progression of ovarian carcinoma during follow-up according to CA 125: a North Thames Ovary Group Study.
Many studies have shown that CA 125 levels frequently rise prior to clinical evidence of progression of ovarian cancer. For clinical trials an accepted definition of progression according to CA 125 is required. We therefore determined what change in CA 125 level was the most accurate predictor of relapse in patients on follow up after therapy for ovarian cancer. Serial CA 125 levels were studied from 255 patients entering the North Thames Ovary Trial of 5 versus 8 courses of chemotherapy. An initial analysis was made 2 months after closure of the trial, a more detailed analysis was made after 81 confirmed relapses among evaluable patients and a final analysis was made one year later with longer follow-up. On the basis of the results from the interim analyses and the cut-off level of 22-35 U/ml used by different laboratories, 30 U/ml was chosen as the upper limit of normal. In the final analysis a doubling of CA 125 from the upper limit of normal was defined as progression. Using this method sensitivity was 85.9%, specificity 91.3%, positive predictive value 94.8%, and negative predictive value was 77.8%. Insisting on a confirmatory elevated CA 125 level reduced the false positive rate to < 2% with a sensitivity of 83.9%. The median lead-time prior to clinical progression was 63 days. A confirmed rise of serum CA 125 level to more than twice the upper limit of normal during follow up after first line chemotherapy accurately predicts tumour relapse.


Thin wetted film cylindrical flow photo reactor for the degradation of Procion blue H-B dye over TiO2 and ZnO.
A thin wetted film cylindrical flow reactor was fabricated for photocatalytic oxidation of Procion blue H-B dye in textile washwater with the suspensions of TiO2 and ZnO. The disappearance of colour and organic reduction were studied in terms of the removal of colour and chemical oxygen demand (COD). Operating parameters such as effect of pH, UV irradiation with and without catalyst, initial concentration of dye and effect of flow rate were studied and kinetics of Procion blue H-B dye has been studied over TiO2 and ZnO surfaces. Since adsorption is the prerequisite condition for decolorization/degradation of dye molecules in the presence of heterogeneous catalysis, the Langmuir and Freundlich isotherms were examined to verify the adsorption intensity. The results clearly demonstrated that, the optimum loading of the photocatalyst was found to be 300 and 400 mg/L of TiO2 and ZnO, respectively. The maximum COD reduction efficiency was 68% for TiO2 and 58% for ZnO. On the other hand, the colour removal efficiency was found to be 74% and 69%, respectively for TiO2- and ZnO-assisted systems under optimum conditions. Conclusively, these two semiconductors could degrade Procion blue H-B dye at different time intervals and both isotherms fit well.


Optimizing the hospital management of leg ulcers.
Leg ulcers are common and are often the cause of a long hospital admission. However, little information is available on the efficacy and efficiency of inpatient leg ulcer management. The inpatient management of leg ulceration was examined and areas for improvement were sought. The management of patients admitted to a teaching hospital with a primary diagnosis of leg ulceration was examined, the costs estimated and areas for improvement identified. A retrospective analysis of 174 admissions to Heidelberg Repatriation Hospital between 1 January 1991 and 31 December 1992 was performed. Of 119 patients, 61 had ulcers due to arterial disease and 34 due to venous disease. Over 2 years, leg ulcers accounted for 5259 inpatient bed days, a mean of 44.2 days per patient. The estimated cost exceeded $2,750,000, averaging over $12,000 per admission. Thirty-three percent of patients had no recorded investigations into the cause of their ulcer and fewer than 50% had documented improvement at discharge. Leg ulcers are costly due to their extended treatment on an inpatient basis. Unfortunately, hospital admission does not guarantee optimal wound healing rates. A leg ulcer protocol is proposed to minimize inpatient stay and improve investigation and management in an outpatient or community setting.


Treating the patients in the 'grey-zone' with aortic valve disease: a comparison among conventional surgery, sutureless valves and transcatheter aortic valve replacement.
Although the use of transcatheter aortic valve replacement (TAVR) has recently become an attractive strategy in extremely high-risk patients undergoing aortic valve replacement (AVR), the most appropriate treatment option in patients with an intermediate- to high-risk profile with conventional surgery (sAVR), TAVR or novel options, such as sutureless valves, has been widely debated. One hundred and sixty-three consecutive patients with intermediate to high risk were prospectively enrolled and selected to undergo sAVR (Group 1: G1, n = 55), sutureless valve implantation (Group 2: G2, n = 53) or TAVR (Group 3: G3, n = 55) following a multidisciplinary evaluation including frailty, anatomy and degree of atherosclerotic disease of the aorta/peripheral vessels. The mean logistic EuroSCORE (G1 = 21.3 ± 12.7 vs G2 = 16 ± 11.7 vs G3 = 20.4 ± 12.7, P = 0.06) and preoperative demographics, such as age, gender and left ventricular ejection fraction, were similar: of note, chronic obstructive pulmonary disease was more frequent in TAVI patients (G1 = 27.2% vs G2 = 15.1% vs G3 = 47%; P <0.01). The Perceval S sutureless valve was used in Group 2, whereas TAVR was performed with a Corevalve prosthesis. Post-procedural pacemaker implantation (G1 = 1.8% vs G2 = 2% vs G3 = 25.5%, P <0.001) and peripheral vascular complications (G1 = 0% vs G2 = 0% vs G3 = 14.5%, P <0.001) occurred more frequently in patients undergoing TAVR. Hospital mortality was similar among the groups (G1 = 0% vs G2 = 0% vs G3 = 1.8%, P = NS). At the 24-month follow-up, overall survival free from major adverse cardiac and cerebrovascular events and prosthetic regurgitation was better in patients who had undergone sAVR and sutureless valves than those who had undergone TAVR (G1 = 95.2 ± 3.3% vs G2 = 91.6 ± 3.8% vs G3 = 70.5 ± 7.6%; P = 0.015). This preliminary study suggests that the use of TAVR in patients with an intermediate- to high-risk profile is associated with a higher rate of perioperative complications and decreased survival at the 24-month follow-up compared with the use of conventional surgery or sutureless valves.


Target therapy of ovarian carcinoma by monoclonal antibodies bearing chemical drugs entrapped in liposomes.
Monoclonal antibody COC166-9 against ovarian carcinoma was conjugated with adriamycin or cisplatinum entraped in liposomes as immunochemical liposomes MLA and MLP respectively. MLA was shown to have the highest effect than adriamycin or other groups on SKOV3 (ovarian cancer cell line) growth inhibition. MLA was also used in target therapy on nude mice bearing human ovarian carcinoma by xenograft of SKOV3 cells. The observations of tumor volumes revealed that this target therapy other than the controls presents a significantly better result which gives a hopeful clue to ovarian carcinoma treatment.


[Complex role of the FA proteins in providing genome stability].
FA is a rare genetic disorder characterized by developmental abnormalities, bone marrow failure and cancer susceptibility. Cells that are derived from patients with FA display spontaneous chromosomal instability and hypersensitivity to DNA crosslinking agents that is used in FA clinical diagnostics. FA is genetically heterogeneous and caused by mutations in at least 11 distinct genes, FANCA, FANCA, B, C, D1, D2, E, F, G, I, J and L. FA proteins interact with various proteins involved in DNA damage response and cell cycle checkpoint regulation, such as: RAD51, BRCA1, BRCA2, ATM or NBS1. Moreover, BRCA2 that plays a crucial role in homologous recombination is one of FA proteins. Collectively, all these data indicate, that the FA pathway is involved in different molecular processes that prevent DNA and control genomic stability, although its precise role still remains undefined.


Paediatric dental care during and post-COVID-19 era: Changes and challenges ahead.
COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus is transmitted through respiratory droplets and by physical contact from contaminated surfaces to the mucosa. Its route of transmission has caused a significant challenge in medical and dental healthcare. This article aims to review the literature and information available on the provision of paediatric dental treatment during and post-pandemic and to provide specific recommendations on the safe provision of paediatric dental care. Children infected by SARS-CoV-2 have no or milder COVID-19 symptoms and are potential vectors in spreading the disease. Routine dental treatment is suspended in many countries because of the increased risk of cross-infection in dental practices. Only emergency dental care is provided for urgent conditions. It is necessary to gradually reinstate regular dental care to paediatric patients and maintain their good oral health. To control the disease transmission and maintain the oral health of the population, minimally intervention techniques that minimise or eliminate aerosol generation, plus comprehensive oral health preventive measures should be practised to safeguard safety at dental practices in this unprecedented time. Robust infection control guidelines should be implemented in dental clinics to minimise the risk of infection and to ensure the safety of patients and staff during the pandemic. Three levels of preventive care should be practised to prevent oral diseases and improve children's oral health in this COVID-19 era. Treatment should be prioritized to patients in urgent needs and aerosol-generating procedures should be minimized.


Periodate-mediated glycosaminoglycan stabilization in bioprosthetic heart valves.
Bioprosthetic heart valves (BPHVs) derived from glutaraldehyde-crosslinked porcine aortic valves are frequently used in heart valve replacement surgeries. However, the majority of bioprostheses fail clinically because of calcification and degeneration. We have recently shown that glycosaminoglycan (GAG) loss may be in part responsible for degeneration of glutaraldehyde-crosslinked bioprostheses. In the present studies, we used a mild reaction of periodate-mediated crosslinking to stabilize glycosaminoglycans in the bioprosthetic tissue. We demonstrate the feasibility of periodate reaction by crosslinking major components of extracellular matrix of bioprosthetic heart valve tissue, namely type I collagen and hyaluronic acid (HA). Uronic acid assay of periodate-fixed HA-collagen matrices showed 48% of HA disaccharides were bound to collagen. Furthermore, we show that such reactions are also feasible to fix glycosaminoglycans present in the middle spongiosa layer of bioprosthetic heart valves. The periodate reactions were compatible with conventional glutaraldehyde crosslinking and showed adequate stabilization of extracellular matrix as demonstrated by thermal denaturation temperature and collagenase assays. Moreover, uronic acid assays of periodate-fixed BPHV cusps showed 36% reduction in the amount of unbound GAG disaccharides as compared with glutaraldehyde-crosslinked cusps. We also demonstrate that calcification of BPHV cusps was significantly reduced in the periodate-fixed group as compared with the glutaraldehyde-fixed group in 21-day rat subdermal calcification studies (periodate-fixed tissue Ca 72.01 +/- 5.97 microg/mg, glutaraldehyde-fixed tissue Ca 107.25 +/- 6.56 microg/mg). We conclude that periodate-mediated GAG fixation could reduce structural degeneration of BPHVs and may therefore increase the useful lifetime of these devices.


C3: Java-based medical record system for cardiology.
This paper describes a system for electronic medical record (EMR) we have developed for use in our health care institution, mainly dealing with diagnosis and treatment of cardiovascular pathologies. This activity is part of the project SPERIGEST, supported by Health Ministry of Italy, for the management of health care delivery, as concerns both clinical and administrative aspects. A networked computer-based information system was realized to integrate the different heterogeneous sources of patient information. Both clinical and administrative patient relevant data are provided from the various systems and stored into a central database. The EMR system was designed using World Wide Web (WWW) technology (Java, HTML). The system is currently under clinical evaluation.


[The use of continuous subcutaneous insulin infusion (CSII) with personal insulin pumps in the treatment of children and adolescents with diabetes type 1].
This paper sums up recently published researches on the continuous subcutaneous insulin infusion (CSII) with the use of insulin pump in children and adolescents with diabetes type 1. Obtaining a balance in the organism metabolism in childhood and adolescence diabetology is nowadays one of the most important rules of the diabetes management in children. One of the modern ways to achieve that goal is the intensive insulin therapy model with use of the insulin pump. In this paper the advantages and disadvantages as well as the indications and contraindications for the CSII in children and adolescents with diabetes are widely discussed.


The Dynamic Aging Mind: Revelations From Functional Neuroimaging Research.
The conception of the aging mind that emerged from behavioral and structural imaging studies portrayed the mind as a victim of passive deterioration and decline with age, with a few domains of preserved function. The advent of functional neuroimaging has demonstrated that the aging brain is an adaptive and plastic structure that responds dynamically to cognitive challenge and structural deterioration-thus, fundamentally changing views of cognitive aging. In addition, a neural theory of the aging mind based on behavioral data-the dedifferentiation view of cognitive aging-was largely confirmed when neuroimaging technology became available to test it. We argue that functional neuroimaging has advanced cognitive aging theories by creating a stronger emphasis on compensatory mechanisms related to brain plasticity and potential reorganization as evidenced by the resurgence of interest and research in cognitive training research designed to improve cognition through enhancement of neural structures or reorganization of functional circuitry.


A note of caution about the "Moral Judgment Test in Physical Education" (MJT-PE).
A new test, the Moral Judgment Test-PE (MJT-PE), has good validity but scores on Competence should be used with great care. These scores will differ from those of the original Moral Judgment Test (MJT) because the single dilemma is targeted to the specific population of interest, physical educators. This reduces the variance in such a way that scores on the new test cannot be compared with or interpreted in the same way as scores on the original MJT. Careful research would be needed to develop norms for the MJT-PE; in the meantime, the two tests should be used together so that the C-scores can be interpreted with confidence.


[Determination of phthalate esters in Baiyangdian Lake by solid phase microextraction and gas chromatography].
A simple method based on solid-phase microextraction (SPME) coupled with gas chromatography-flame ionization detection (GC-FID) was developed for the determination of trace amounts of phthalate esters (PAEs) in environment water samples. In this method, polydimethylsilane (PDMS) fiber was chosen to enrich the PAEs. The PAEs were extracted for 60 min using the PDMS fiber under stirring with a magnetic stir bar, after that the fiber was introduced into the GC injector port and the extract was desorbed at 250 degrees C for 4 min. Under the optimized conditions, 13 PAEs can be extracted completely and separated well. The limits of detection (LOD) were from 0.02 to 0. 83 microg/L (S/N = 3). The water samples collected from Baiyangdian lake were successfully analyzed using the proposed method, phthalic acid, bis-isobutyl ester (DIBP), phthalic acid, bis-butyl ester (DBP) and phthalic acid, bis-2-ethylhexyl ester (DEHP) were detected in all the samples. The spiked (2.5 microg/L and 5.0 microg/L) recoveries were in the range of 75.3-111.0% and the relative standard deviations (RSDs) were between 2.1% and 8.0% (n=3). The results showed that this would be a valuable method for PAEs analysis in environmental water samples.


Recurrent laryngeal nerve injury following single- and multiple-level anterior cervical discectomy and fusion: a meta-analysis.
Recurrent laryngeal nerve (RLN) palsy is a common and potentially debilitating complication of anterior cervical discectomy and fusion (ACDF). The relationship between the risk of RLN palsy and the number of operated levels remains unclear, and no previous studies address potential differences between short- and long-term RLN injury following ACDF. Electronic searches of PubMed, Cochrane, ScienceDirect and Google Scholar were performed from database inception to June 2019. Relevant studies reporting the rate of RLN palsy for patients undergoing ACDF for cervical spine pathology were identified according to predetermined inclusion and exclusion criteria. Statistical analysis was performed using fixed effects and random effects modelling. I2 and Q statistics were used to explore heterogeneity. Five studies with a total of 3,514 patients were included in the meta-analysis. The incidence of RLN palsy was found to be 1.2%. There were no statistically significant differences in the rate of RLN palsy between multiple- and single-level ACDF [odds ratio (OR) 1.04; 95% CI: 0.56-1.95; P=0.891, I2=0%]. There were similarly no statistically significant differences in RLN palsy rates for multiple- and single-level ACDF when patients were stratified based on length of follow-up of less than or greater than 12 months. This analysis suggests that there is no statistically significant association between the number of ACDF operative levels and the risk of short- or long-term RLN palsy.


Schizophrenic Diblock-Copolymer-Functionalized Nanoparticles as Temperature-Responsive Pickering Emulsifiers.
Stimuli-responsive pickering emulsions have received considerable attention in recent years, and the utilization of temperature as a stimulus has been of particular interest. Previous efforts have led to responsive systems that enable the formation of stable emulsions at room temperature, which can subsequently be triggered to destabilize with an increase in temperature. The development of a thermoresponsive system that exhibits the opposite response, however, i.e., one that can be triggered to form stable emulsions at elevated temperatures and subsequently be induced to phase separate at lower temperatures, has so far been lacking. Here, we describe a system that accomplishes this goal by leveraging a schizophrenic diblock copolymer that exhibits both an upper and a lower critical solution temperature. The diblock copolymer was conjugated to 20 nm silica nanoparticles, which were subsequently demonstrated to stabilize O/W emulsions at 65 °C and trigger phase separation upon cooling to 25 °C. The effects of particle concentration, electrolyte concentration, and polymer architecture were investigated, and facile control of emulsion stability was demonstrated for multiple oil types. Our approach is likely to be broadly adaptable to other schizophrenic diblock copolymers and find significant utility in applications such as enhanced oil recovery and liquid-phase heterogeneous catalysis, where stable emulsions are desired only at elevated temperatures.


Reversed dorsal metatarsal artery flap for reconstruction of a soft tissue defect of the big toe.
Soft tissue defects of the great toe that include exposed tendon and bone present a reconstructive challenge for plastic surgeons. A distally based dorsalis pedis island flap based on the first dorsal metatarsal artery, which has been successfully used to cover the soft tissue defect following wide excision of melanoma of the big toe, is reported.


Bound states of string networks and D-branes.
We show the existence of nonthreshold bound states of (p,q) string networks and D3-branes, preserving 1/4 of the full type-IIB supersymmetry, interpreted as string networks "dissolved" in D3-branes. We also explicitly write down the expression for the mass density of the system and discuss the extension of the construction to other Dp-branes. Differences in our construction of string networks with the ones interpreted as dyons in N = 4 gauge theories are also pointed out.


Racial/ethnic matching of clients and therapists in mental health services: a meta-analytic review of preferences, perceptions, and outcomes.
Across several decades the effects of matching clients with therapists of the same race/ethnicity have been explored using a variety of approaches. We conducted a meta-analysis of 3 variables frequently used in research on racial/ethnic matching: individuals' preferences for a therapist of their own race/ethnicity, clients' perceptions of therapists across racial/ethnic match, and therapeutic outcomes across racial/ethnic match. Across 52 studies of preferences, the average effect size (Cohen's d) was 0.63, indicating a moderately strong preference for a therapist of one's own race/ethnicity. Across 81 studies of individuals' perceptions of therapists, the average effect size was 0.32, indicating a tendency to perceive therapists of one's own race/ethnicity somewhat more positively than other therapists. Across 53 studies of client outcomes in mental health treatment, the average effect size was 0.09, indicating almost no benefit to treatment outcomes from racial/ethnic matching of clients with therapists. These 3 averaged effect sizes were characterized by substantial heterogeneity: The effects of racial/ethnic matching are highly variable. Studies involving African American participants demonstrated the highest effect sizes across all 3 types of evaluations: preferences, perceptions, and outcomes.


Delayed treatment of bladder outlet obstruction after sling surgery: association with irreversible bladder dysfunction.
Our urethrolysis cohort demonstrated an unusual delay time to surgical treatment of bladder outlet obstruction. We determined whether urethrolysis outcomes, ie persistent bladder symptoms, were associated with time between sling and urethrolysis surgeries. Retrospective analysis of all patients who underwent urethrolysis for post-sling voiding dysfunction between June 1997 and June 2002 was performed. We excluded from study 6 patients with a known history of overactive bladder symptoms, neurogenic bladder dysfunction and use of anticholinergic pharmacotherapy before stress incontinence surgery. The remaining 15 patients were stratified into 2 outcomes groups based upon the absence or presence of post-urethrolysis bladder storage symptoms. Patients (7) in group 1 have no current bladder symptoms. Patients (8) in group 2 still require anticholinergic drug therapy for significant bladder symptoms of frequency and urgency. Data collected for the 2 groups included mean age, existence of urinary retention before urethrolysis, mean time to urethrolysis in months, urethrolysis outcome based upon subjective bladder symptoms and followup duration. For comparison of mean age between groups the standard t test was used. Fisher's exact test was used to compare frequency of urinary retention before urethrolysis between groups. Lastly the Mann-Whitney U test was conducted to compare time to urethrolysis between groups. All statistical analyses were conducted using the SPSS software package (SPSS, Inc., Chicago, Illinois). There was no statistically significant difference between the groups with respect to age or frequency of urinary retention before urethrolysis. Time to urethrolysis for the whole cohort ranged from 2 to 66 months. Mean followup after urethrolysis was 17.3 +/- 22.9 months. Comparison of mean time between incontinence and urethrolysis surgeries between group 1 (9.0 +/- 10.1 months) and group 2 (31.25 +/- 21.9 months) demonstrated a statistically significant difference (p = 0.01). This urethrolysis population demonstrated an unusual delay time to surgical treatment of bladder outlet obstruction. We categorized the cohort according to absence or presence of persistent bladder storage symptoms, and found a strong association between persistent bladder symptoms and greater delay to urethrolysis.