Body weight-supported treadmill training in chronic incomplete spinal cord injury: a pilot study evaluating functional health status and quality of life.
A controlled single-case design: A1 (baseline: 6 weeks), B (intervention: 12 weeks of treadmill training (TT), maximally five times a week/30 min a day), A2 (wash-out: 6 weeks), follow-up measurement: 6 months. To investigate the effects of TT on functional health status (FHS) and quality of life (QoL) in subjects with a chronic incomplete spinal cord injury (ISCI). Rehabilitation Department, University Medical Centre Utrecht, The Netherlands. Three male subjects with a stable (>48 months postinjury) ISCI, American Spinal Injury Association (ASIA) class C (n=2) and D (n=1). Performance-based walking, subject's perception concerning quality of life (SEIQoL) and activities of daily living Canadian Occupational Performance Measure (COPM). The results of the three subjects were variable. Changes in QoL were relatively small and diverse. After 6 months' follow-up, QoL was unchanged in subjects 1 and 2, and improved in subject 3. In subject 2, performance of activities of daily living (ADL) was significantly improved, consistent with his perception of improvement (P<0.05), and this improvement was sustained throughout the follow-up period. Walking ability improved in subject 3 (P<0.05) but performance of other activities remained stable. Performance of ADL decreased slightly in subject 1 whereas his walking speed and Get up and Go performance improved (P<0.05). This study demonstrates positive effects of TT on FHS. A randomised clinical trial should be executed before definite conclusions about the effect of TT on FHS and QoL can be drawn. KF Hein Foundation and Rehabilitation Centre De Hoogstraat Scientific Foundation.


Potential of copper-tolerant grasses to implement phytostabilisation strategies on polluted soils in South D. R. Congo : Poaceae candidates for phytostabilisation.
Phytostabilisation (i.e. using plants to immobilise contaminants) represents a well-known technology to hamper heavy metal spread across landscapes. Southeastern D.R. Congo, Microchloa altera, a tolerant grass from the copper hills, was recently identified as a candidate species to stabilise copper in the soil. More than 50 grasses compose this flora, which may be studied to implement phytostabilisation strategies. However, little is known about their phenology, tolerance, reproductive strategy or demography. The present study aims to characterize the Poaceae that may be used in phytostabilisation purposes based on the following criteria: their ecological distribution, seed production at two times, abundance, soil coverage and the germination percentage of their seeds. We selected seven perennial Poaceae that occur on the copper hills. Their ecological distributions (i.e. species response curves) have been modelled along copper or cobalt gradients with generalised additive models using logic link based on 172 presence-absence samples on three sites. For other variables, a total of 69 quadrats (1 m(2)) were randomly placed across three sites and habitats. For each species, we compared the number of inflorescence-bearing stems (IBS) by plot, the percentage of cover, the number of seeds by IBS and the estimated number of seeds by plot between sites and habitat. Three species (Andropogon schirensis, Eragrostis racemosa and Loudetia simplex) were very interesting for phytostabilisation programs. They produced a large quantity of seeds and had the highest percentage of cover. However, A. schirensis and L. simplex presented significant variations in the number of seeds and the percentage of cover according to site.


Molecular typing techniques to characterize the development of a lactic acid bacteria community on vacuum-packaged beef.
The development of a community of lactic acid bacteria from vacuum-packaged beef was investigated during a 6-week storage trial at 2 degrees C. The lactic acid bacteria population was monitored by using molecular techniques to identify a random sample of isolates at biweekly intervals during the storage trial. The polymerase chain reaction and a randomly amplified polymorphic DNA technique were used to identify and distinguish populations of lactic acid bacteria that developed during the storage trial. At week 0, the population of lactic acid bacteria was 3.5 log cfu/120 cm2 and by week 6, the population reached a maximum of 7.6 log cfu/120 cm2. A sampling from the week 0 population indicated a mixed community of Lactobacillus curvatus, Lactobacillus sakei and Leuconostoc spp. However, the sampling from week 6 indicated the population composition had changed to one where a single Leuconostoc strain predominated. This strain demonstrated antagonism towards the growth of other lactic acid bacteria isolated during the study. Additionally, the strain inhibited the growth of foodborne pathogens Escherichia coli O157:H7 and Listeria monocytogenes. DNA sequence data from the 16S rRNA gene suggested that the isolate may be a Leuconostoc gelidum strain.


Exhaustive screens for disease susceptibility loci incorporating statistical interaction of genotypes: a comparison of likelihood-ratio-based and Akaike and Bayesian information criteria-based methods.
Several recent papers have suggested that two-locus tests of association that incorporate gene x gene interaction can be more powerful than marginal, single-locus tests across a broad range of multilocus interaction models, even after conservative correction for multiple testing. However, because these two-locus tests are sensitive to marginal associations with either marker, they can be difficult to interpret, and it is not immediately clear how to use them to select a list of the most promising markers worthy of further study. Here we apply single- and two-locus tests to 29 single-nucleotide polymorphisms (SNPs) selected from the dense marker map in the simulated Genetic Analysis Workshop 15 data spanning several candidate regions (the HLA region, the four SNPs flanking "Locus D," and two regions on the q-arm of chromosome 6). We compare the proposed two-locus likelihood ratio tests (LRT) to Akaike and Bayesian Information Criteria (AIC and BIC) for model selection, as well as AIC- and BIC-weighted measures of "SNP importance." The latter provide summary measures of evidence for association between each SNP and disease - including potential interactions with one or more other SNPs - by summing over all one- and two-SNP models. Our results suggest that the LRT using conservative p-value criteria were sensitive (but not specific) in identifying associated markers. Standard AIC and BIC criteria were similarly sensitive but not specific. On the other hand, the AIC- and BIC-weighted importance measures yielded a specific but not very sensitive rule for SNP selection. Algorithms incorporating gene x gene interaction to prioritize markers for follow-up will require further development.


Individual differences and asymmetry effects in memory for unfamiliar faces.
Visual field effects for recognition of unfamiliar faces was investigated using memory intervals of 0, 10, and 20 sec. and 8 stimuli in a same-different comparison paradigm. In Experiment I, 24 male and 24 female familial righthanders, half of whom had high and the other half, low Block Design (BD) scaled scores participated. Faces were recognized significantly more often in the LVF. A visual field x memory interval interaction resulted from reliable LVF superiorities with the 0 and 10 sec. memory intervals and a non-significant RVF superiority with the 20 sec. memory interval. Performance decreased significantly as the duration of the memory interval increased. No sex differences were found. Subjects with high and low BD scores performed similarly. In Experiment II, 16 stimuli were employed and the task repeated. Twenty-four male and 24 female familial righthanderds were given the BD and Vocabulary subtests of the WAIS as well as a brightness discrimination task. Field effects were non-significant. Performance decreased with longer memory intervals. For males, field effects for the 0 sec. memory interval were positively related to brightness discrimination scores.


Acute inactivation of tryptophan hydroxylase by amphetamine analogs involves the oxidation of sulfhydryl sites.
The activity of rat hippocampal tryptophan hydroxylase was reduced from 30-60% 3 h after the administration of a 10-15 mg/kg dose of either fenfluramine, methamphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Tryptophan hydroxylase inactivated by these drug treatments could be reconstituted by a prolonged anaerobic incubation in the presence of 5 mM dithiothreitol and 50 microM Fe2+. Drug-inactivated enzyme obtained from rats killed 18 h after multiple doses of either D(+)- or L(-)-MDMA could not be similarly restored. These observations suggest that the rapid decrease in central tryptophan hydroxylase activity induced by amphetamine analogs results from the reversible oxidation of a sulfhydryl site(s) within the enzyme molecule, whereas the irreversible decrease in enzymatic activity measured 18 h after multiple-dose MDMA treatment may reflect serotonergic toxicity.


[Poverty and assistance in Rio de Janeiro under the First Republic].
In the 1910s, some of Rio de Janeiro's most renowned intellectuals and philanthropists, known as the reformers, launched proposals for offering assistance to the poor, drawn in part from the debate then underway in Europe about alternative ways of fighting poverty. This analysis explores how these reformers received ideas proposed or implemented in Europe and how they adapted them to Brazilian reality, advocating measures intended to ameliorate problems related to Brazil's socalled social question.


Estrogen receptor 1 gene polymorphisms are associated with metabolic syndrome in postmenopausal women in China.
Metabolic syndrome (MetS) includes obesity, diabetes, dyslipidemia and hypertension. Its incidence is rapidly increasing worldwide, particularly in postmenopausal women. Estrogens regulate glucose homeostasis and lipid metabolism via estrogen receptors 1 (ESR1) and 2 (ESR2). The current study aimed to elucidate associations of MetS with ESR1 and ESR2 gene polymorphisms in postmenopausal Chinese women. This case-control study included 304 postmenopausal women (154 and 150 control and MetS patients, respectively). Clinical indicators related to MetS were assessed. Two ESR1 (PvuII and XbaI) and two ESR2 (RsaI and AluI) polymorphisms were evaluated by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. ESR1 polymorphisms were significantly different between MetS patients and healthy controls. G allele frequency for the XbaI polymorphism was significantly higher in patients than in control patients (p = 0.004, OR = 1.610, 95%CI 1.169-2.18). The haplotypes A-T (p = 0.015) and G-C (p = 0.024) showed significant differences. The minor alleles of the XbaI and PvuII gene polymorphisms in both homozygous and heterozygous forms showed associations with elevated waist circumference, fasting serum insulin and HOMA-IR. The minor G allele in homozygous and heterozygous forms of the RsaI and AluI gene polymorphisms showed associations with elevated total cholesterol and LDL-C. In postmenopausal Chinese women, ESR1 polymorphism and the haplotypes A-T and G-C of XbaI-PvuII are associated with MetS, unlike ESR2 polymorphisms. Patients harboring the G allele of XbaI have elevated BMI, waist circumference, systolic and diastolic BP, FBG, HOMA-IR, total cholesterol, TG, LDL-C and NAFLD (%), and reduced HDL-C.


Cardiopulmonary bypass established via a sutured vascular graft in the presence of extraanatomic bypass.
Cardiopulmonary bypass (CPB) was established via a sutured collagen sealed knitted Dacron graft in two patients who had undergone extraanatomic bypasses for lower limb ischemia, whose ascending aorta was not suitable for cannulation. One patient, with a history of femorofemoral bypass, underwent surgery for a ruptured aortic arch aneurysm (AAA) and the other patient, with a history of axillobifemoral bypass for chronic dissection involving the aortic arch and descending aorta, had unstable angina and underwent coronary artery bypass grafting. This technique of perfusion was found to be safe and effective for patients with an impaired ascending aorta who have undergone an extraanatomic bypass for the lower limb.


Cystathionine gamma-synthase and threonine synthase operate in concert to regulate carbon flow towards methionine in plants.
The sulfur-containing amino acid methionine is a nutritionally important essential amino acid and is the precursor of several metabolites that regulate plant growth and responses to the environment. Methionine production is largely regulated by cystathionine gamma-synthase, the first specific enzyme for its synthesis. This enzyme competes in a complex manner with threonine synthase, the last enzyme in threonine biosynthesis, for their common substrate O-phosphohomoserine. New genetic and molecular data suggest that methionine synthesis and catabolism are coordinately regulated by novel post-transcriptional and post-translational mechanisms that are associated with a regulatory part within the N-terminal part of cystathionine gamma-synthase.


Distortion product otoacoustic emission and auditory brain stem response measures of pediatric sensorineural hearing loss with islands of normal sensitivity.
To assess the accuracy of: 1) distortion product otoacoustic emission (DPOAE) measures for the identification of frequencies at which auditory sensitivity is normal or near normal; and 2) click and nonmasked tone burst-evoked auditory brain stem response (ABR) thresholds for behavioral threshold estimation for children with sensorineural hearing loss characterized by islands of normal sensitivity. DPOAEs and ABRs were recorded from five hearing-impaired and eight normal-hearing pediatric ears. The accuracy with which DPOAEs permitted identification of frequencies at which elevated hearing thresholds were present was examined. ABR and pure-tone threshold differences for the impaired ears were calculated. For three of the five hearing-impaired ears, significant impairments would have been missed based on click-evoked ABR thresholds. One of those hearing-impaired ears provided an essentially normal 500 Hz tone burst-evoked ABR threshold as well. Four of the hearing-impaired ears provided a 500 Hz tone burst-evoked ABR threshold within 10 dB of the respective pure-tone threshold. However, click-evoked ABR and 500 Hz tone burst-evoked ABR threshold data did not adequately delineate the hearing loss configuration for hearing aid frequency response selection. DPOAEs were present at three out of four frequencies from 1000 to 4000 Hz at which sensitivity was normal or near normal (< or =25 dB HL) and absent at 10 out of 11 frequencies at which sensitivity was impaired. The use of DPOAEs to identify frequencies at which sensitivity was normal and the use of tone burst ABR thresholds at frequencies where DPOAEs were absent provided a better estimate of these pure-tone audiograms than was provided by click-evoked and 500 Hz tone burst-evoked ABR thresholds.


Ethylene glycol monomethyl ether-induced testicular oxidative stress and time-dependent up-regulation of apoptotic, pro-inflammatory, and oncogenic markers in rats.
Ethylene glycol monomethyl ether (EGME) is a major component of paints, lacquers, inks, and automobile brake fluids. As a result, exposures to humans are inevitable. We therefore, investigated in this study, its effect on testicular cells in a time-course manner in male Wistar rats. Animals were orally administered 50 mg/kg body weight of EGME for duration of 7, 14, and 21 days. Following 7 days of the administration, levels of NO and GSH were significantly reduced, while levels of c-Myc, K-Ras, caspase-3, IL-6, TNF-α, and IL-1β were significantly increased compared with control. At the end of 14 days exposure, GPx, and SOD activities, as well as IL-10 level were significantly decreased, while levels of c-Myc, K-Ras, p53, Bax, caspase-3, IL-6, TNF-α, IL-1β, and GST activity were significantly elevated compared with control. After 21 days of EGME administration, Bcl-2, IL-10, and NO levels were significantly decreased, while levels of c-Myc, K-Ras, p53, Bax, caspase-3, IL-6, TNF-α, IL-1β, MDA and GST activity were significantly increased compared with control. After 7, 14, and 21 days of EGME administrations, testis histopathology showed severe loss of seminiferous tubules, the seminiferous epithelium revealed very few spermatocytes, spermatids, spermatogonia, spermatozoa, and Sertoli cells, while the interstitial tissue is eroded, with scanty abnormal Leydig cells, compared with the control that appeared normal. We therefore, concluded that EGME-induced testicular toxicity as a result of EGME administration could be via the disorganization of the endogenous antioxidant systems as well as up-regulation of pro-inflammatory, apoptotic and oncogenic mediators in rats.


Dietary lipids modulate methylmercury toxicity in Atlantic salmon.
This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as MeHg) for three months. The dietary lipid composition affected the fatty acid composition in the tissues, especially in liver and white muscle. After 84 days of exposure, the liver accumulated three times as much MeHg as the brain and white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1 transcriptional levels all showed significant effects of MeHg exposure in the liver. TBARS, α-tocopherol, γ-tocopherol, and the transcriptional levels of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of dietary lipid composition in liver tissue. Effects of dietary lipids were observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects between MeHg exposure and dietary lipid composition were observed in all tissues. Our data suggest that dietary fats have modulating effects on MeHg toxicity in Atlantic salmon.


Emissions of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) to air from waste incinerators and high thermal processes in India.
This study investigated dioxins and dioxin-like polychlorinated biphenyls in gasses emitted from waste incinerators and thermal processes in central and western parts of India. The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/DFs) ranged from 0.0070 to 26.8140 ng toxicity equivalent (TEQ)/Nm(3), and those of dioxin-like polychlorinated biphenyls (PCBs) ranged from 0.0001 × 10(-1) to 0.0295 ng TEQ/Nm(3). The characteristics of mean PCDD/F I-TEQ concentration and congener profiles were studied over all the samples of air. In particular, a pattern consisting of a low proportion of dioxin-like PCBs and high proportion of PCDDs/DFs was common for all the samples from incinerators and high-temperature processes.


Semi-automatic boundary detection to improve reporting of regional left ventricular function.
The reporting of regional left ventricular function is based on subjective assessment of endocardial motion and thickening and has a significant learning curve. We hypothesized that the use of an semi-automatic boundary detection system generating images with superimposed moving endocardial borders and a fixed end-diastolic reference border could improve the reporting of regional function. We obtained 58 resting contrast images of 15 patients and using a new boundary detection system (Quamus), generated images with superimposed endocardial borders. The contrast images, images with additional Quamus borders and Quamus borders alone were assessed by two level 1 and two level 2 echocardiographers. They scored regional function and results were compared to two level 3 experienced stress echocardiography readers. The addition of borders improved the agreement of level 1 echocardiographers (weighted Kappa increased from 0.55 to 0.64) but did not change for level 2 echocardiographers (0.63 to 0.64) and has the potential to be a useful training tool.


Controlled hypotension with sodium nitroprusside: anesthesiologist versus computer.
Computer systems developed for the automatic control of blood pressure have been previously shown to induce hypotension with sodium nitroprusside more rapidly and accurately than can be done with manual control. We compared the performance of a computer controller with performances by 10 anesthesiologists during challenges to homeostasis similar (or analogous) to those occurring during a surgical procedure. Hypotension was induced in 10 mongrel dogs and maintained for 2 hours, either by an anesthesiologist or by the computer controller. Challenges to homeostasis were given during the 2-hour period. The computer brought the mean arterial pressure to the desired value in an average of 4.1 minutes compared with 6.3 minutes for the anesthesiologists, but this difference was not statistically significant. There was no statistically significant difference between the computer and the anesthesiologists for 25 performance criteria. The anesthesiologists performed better during two imposed hypertensive perturbations by turning off the sodium nitroprusside sooner when the pressure rapidly decreased. In general, the computer controller performed as well as experienced anesthesiologists who devoted full attention to the control of blood pressure.


Racial and Ethnic Disparities in Barriers to Care in Patients with Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is a leading cause of death in patients with cirrhosis and has a rising mortality rate in the United States.1 Racial and ethnic minorities experience a disproportionate burden of HCC, including higher incidence rates, more late-stage diagnoses, and worse survival.2,3 These disparities are complex in nature and can be attributed to many proximal, intermediate, and distal determinants, such as health literacy and behaviors, social support, social needs, social determinants of health, and access to health care.4 Prior studies have identified racial and ethnic differences in clinical factors, including receipt of HCC surveillance and tumor stage5; however, few studies have examined differences in patient-reported barriers that may partly explain observed disparities. Understanding these data is essential to inform interventions to address and mitigate disparities. Therefore, we described patient-reported barriers to medical care and examined differences in barriers by race and ethnicity in a large, diverse population of patients newly diagnosed with HCC.


The iscom antigen-presenting system.
The immunostimulating complex, or iscom, provides an effective means of presenting antigens to the immune system. Vaccines for influenza, hepatitis B and AIDS are in the offing.


A novel SREBP-1 splice variant: tissue abundance and transactivation potency.
Sterol regulatory element binding proteins (SREBPs) belong to the family of basic helix-loop-helix-leucine zipper transcription factors. The SREBP-1 gene encodes two different isoforms, SREBP-1a and -1c, that are expressed at varying levels in different tissues and cultured cells and exhibit common and distinct functions. We identified an additional SREBP-1 isoform, termed SREBP-1ac, and determined its mRNA abundance in different human tissues and cell lines. SREBP-1ac mRNA was detectable in all tissues studied, although at lower levels than the major SREBP-1a and -1c isoforms. Transcription of the novel SREBP isoform was not induced by insulin or cholesterol depletion. SREBP-1ac did not transactivate the human LDLR and UCP2 promoters but robustly attenuated the transactivation capacity of SREBP-1a, -1c and -2 in cotransfection experiments.


Sensitivity of in vitro diagnostic dipstick tests to urinary protein.
Two commonly used brands of reagent strip (dipsticks) were evlauated for their sensitivity to Bence-Jones and seven other urinary proteins. Both brands showed significant differences in sensitivity to albumin, glycoprotein, ribonuclease and lysozyme; both were most sensitive to albumin and least sensitive to globulin. Furthermore, their comparative sensitivities to these proteins also differed markedly. These differences in sensitivity could lead to underestimation of protein content in urine specimens. Tests on urines from patients with multiple myeloma showed that a negative urinary dipstick test result did not rule out the presence of the disease.


Reversible opisthotonus following intracranial pressure changes in Chiari malformation.
A shunted myelodysplastic child with Chiari II malformation presented with shunt malfunction and opisthotonus. Correction of a distal obstruction lead to an initial improvement followed by overdrainage of cerebrospinal fluid and repetition of an opisthotonic posture. The possible mechanisms which unmask lower brainstem dysfunction in Chiari malformation when intracranial hyper- or hypotension exist, are discussed.


Image analysis for the detection of increased erythrocyte, leukocyte and platelet adhesiveness/aggregation in the peripheral blood of patients with diabetes mellitus.
Increased erythrocyte, leukocyte, and platelet adhesiveness and aggregation may contribute to the development of ischemic vascular conditions in diabetic patients. They have been described by using different diagnostic systems and following various ex vivo manipulations. We have adopted a simple slide test and image analysis to reveal the adhesiveness and aggregation of the three cellular elements in a picture that is obtained from one single citrated venous blood sample presented on a glass slide. A significant increment in the degree of adhesiveness/aggregation of erythrocytes, leukocytes and platelets was noted in 29 patients with diabetes mellitus as opposed to age- and gender-matched healthy controls. It is feasible to look at the increased state of adhesiveness/aggregation of erythrocytes, leukocytes and platelets present in their native milieu and following minimal manipulation by using an almost real time and low cost procedure.


Parapharyngeal hematoma following transesophageal echo in a patient with hemophilia A.
Hemophilia A is an X-linked disorder caused by deficiency of Factor VIII. Postoperative patients with mild hemophilia A, or those requiring intensive factor replacement, should be proactively screened for factor inhibitor development. This is a major complication of factor replacement that can induce severe factor resistant coagulopathy and life-threatening bleeding.


Thalamic network under wakefulness after sleep onset and its coupling with daytime fatigue in insomnia disorder: An EEG-fMRI study.
Fatigue is the most common daytime impairment of insomnia disorder (ID). Thalamus is acknowledged as the key brain region closely associated with fatigue. However, the thalamus-based neurobiological mechanisms of fatigue in patients with ID remain unknown. Forty-two ID patients and twenty-eight well-matched healthy controls (HCs) underwent simultaneous electroencephalography--functional magnetic resonance imaging. We calculated the functional connectivity (FC) between the thalamic seed and each voxel across the whole brain in two conditions of wakefulness--after sleep onset (WASO) and before sleep onset. A linear mixed effect model was used to determine the condition effect of the thalamic FC. The correlation between daytime fatigue and the thalamic connectivity was explored. After sleep onset, the connectivity with the bilateral thalamus was increased in the cerebellar and cortical regions. Compared with HCs, ID patients showed significantly lower FC between left thalamus and left cerebellum under the WASO condition. Furthermore, thalamic connectivity with cerebellum under the WASO condition was negatively correlated with Fatigue Severity Scale scores in the pooled sample. These findings contribute to an emerging framework that reveals the link between insomnia-related daytime fatigue and the altered thalamic network after sleep onset, further highlighting the possibility that this neural pathway is a therapeutic target for meaningfully mitigating fatigue.


Effect of carp gonadotropin (cGTH) and a fraction unabsorbed on concanavalin A-Sepharose obtained from cGTH on vitellogenesis in the hypophysectomized marine teleost Gobius niger.
To investigate whether a differential potency on vitellogenesis exists between the carp gonadotropin (cGTH) and fraction I-cGTH (proteins from cGTH unbound on concanavalin A-Sepharose, which represent 5% of cGTH in weight), hypophysectomized Gobius niger were treated with the two hormonal preparations at the same level. Vitellogenesis was checked for synthesis of vitellogenin and yolk incorporation in the ovary by means of immunological studies and histological techniques (light and electron microscopy). In addition, increased synthesis of vitellogenin was induced by injection of estradiol 17 beta together with each gonadotropin to assess the action of the two hormonal preparations on vitellogenin incorporation. Oogenesis was enhanced by cGTH and fraction I-cGTH, and at the same dose levels both treatments produced a similar pattern of stimulation of vitellogenesis. Vitellogenin was found in all the blood samples of animals treated by the hormones (cGTH and fraction I-cGTH) alone. Vesicles of pinocytosis were detected by electron microscopy up to Stage IIIa of oogenesis. When a high synthesis of vitellogenin was induced by exogeneous estradiol 17 beta injections, the two gonadotropic preparations had similar effects in yolk incorporation. cGTH was not less potent than fraction I-cGTH in these processes even though the cGTH preparation contains only 5% of fraction I-cGTH. The contamination of cGTH by a small amount of material unbound on concanavalin cannot be solely responsible for the vitellogenic activity of cGTH which consists of 95% glycoproteins.


Large Scalp Defect Repair with Flap Reconstruction Using Tissue Expander After Combined Bypass in Case of Moyamoya Disease.
Combined revascularization is the preferred surgical management of adult Moyamoya disease. However, postoperative flap necrosis of the scalp is not an uncommon complication. We investigated the role of scalp incision design on the basis of the course of the superficial temporal artery (STA) to prevent postoperative scalp necrosis. The utility of tissue expander in wide scalp defect repair is explored. A 13-year-old female patient underwent STA-to-middle cerebral artery anastomosis and encephaloduroarteriosynangiosis due to ischemic symptoms. However, she suffered from wide scalp necrosis measuring 10.5 × 10 cm after bypass surgery. Conventional rotational scalp flap reconstruction was impossible due to the wide defect, and therefore split thickness skin graft was considered. However, aesthetic compromise or hair loss is a psychologic burden in an adolescent female. Two tissue expanders were inserted under the contralateral normal scalp, and a gradual expansion was achieved by saline infusion for 3 months. Finally, a wide scalp flap, which covered the large defect, was obtained using this procedure. The patient underwent rotational flap advancement and was discharged without any hair loss wound. Miserable scalp flap design results in a large scalp defect during combined bypass surgery. However, tissue expanders aided the reconstruction of a large scalp defect. Reconstruction using tissue expanders and advancement of local rotation flap is recommended in case of large scalp necrosis. The procedure yields cosmetically superior outcomes due to scalp hair conservation and concealment of postoperative scar behind the hair line.


Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease.
Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid-resistant cGVHD. Thirty-five patients who developed GVHD after day 100 post-transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count > or = 100 x 10(9)/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD-free survival are warranted.


Age-related dissociation of N400 effect and lexical priming.
The use of contextual information is an important capability to facilitate language comprehension. This can be shown by studying behavioral and neurophysiological measures of accelerated word recognition when semantically or phonemically related information is provided in advance, resulting in accompanying attenuation of the respective event-related potential, i.e. the N400 effect. Against the background of age-dependent changes in a broad variety of lexical capacities, we aimed to study whether word priming is accomplished differently in elderly compared to young persons. 19 young (29.9 ± 5.6 years) and 15 older (69.0 ± 7.2 years) healthy adults participated in a primed lexical decision task that required the classification of target stimuli (words or pseudo-words) following related or unrelated prime words. We assessed reaction time, task accuracy and N400 responses. Acceleration of word recognition by semantic and phonemic priming was significant in both groups, but resulted in overall larger priming effects in the older participants. Compared with young adults, the older participants were slower and less accurate in responding to unrelated word-pairs. The expected N400 effect was smaller in older than young adults, particularly during phonemic word and pseudo-word priming, with a rather similar N400 amplitude reduction by semantic relatedness. The observed pattern of results is consistent with preserved or even enhanced lexical context sensitivity in older compared to young adults. This, however, appears to involve compensatory cognitive strategies with higher lexical processing costs during phonological processing in particular, suggested by a reduced N400 effect in the elderly.


The (pro)renin receptors.
Two (pro)renin receptors have been characterized so far, the mannose-6-phosphate receptor (M6P-R) and a specific receptor called (P)RR for (pro)renin receptor. Each receptor controls a different aspect of renin and prorenin metabolism. The M6P-R is a clearance receptor, whereas (P)RR mediates their cellular effects by activating intracellular signaling and up-regulating gene expression. Moreover, binding to (P)RR increases renin enzymatic activity and fully activates prorenin, the inactive proenzyme form of renin. Experimental models suggest that increased (P)RR synthesis and/or activation may be relevant to diseases, especially to high blood pressure, to cardiac fibrosis associated with hypertension, and to diabetic nephropathy.


Mechanical characterization of matrix-induced autologous chondrocyte implantation (MACI®) grafts in an equine model at 53 weeks.
There has been much interest in using autologous chondrocytes in combination with scaffold materials to aid in cartilage repair. In the present study, a total of 27 animals were used to compare the performance of matrix-assisted chondrocyte implantation (MACI®) using a collagen sponge as a chondrocyte delivery vehicle, the sponge membrane alone, and empty controls. A total of three distinct types of mechanical analyses were performed on repaired cartilage harvested from horses after 53 weeks of implantation: (1) compressive behavior of samples to measure aggregate modulus (HA) and hydraulic permeability (k) in confined compression; (2) local and global shear modulus using confocal strain mapping; and (3) boundary friction coefficient using a custom-built tribometer. Cartilage defects receiving MACI® implants had equilibrium modulus values that were 70% of normal cartilage, and were not statistically different than normal tissue. Defects filled with Maix™ membrane alone or left empty were only 46% and 51-63% of control, respectively. The shear modulus of tissue from all groups of cartilage defects were between 4 and 10 times lower than control tissue, and range from 0.2 to 0.4 MPa. The average values of boundary mode friction coefficients of control tissue from all groups ranged from 0.42 to 0.52. This study represents an extensive characterization of the mechanical performance of the MACI® grafts implant in a large animal model at 53 weeks. Collectively, these data demonstrate a range of implant performance, revealing similar compressive and frictional properties to native tissue, with inferior shear properties.


Cyclododecane shaping, sublimation rate and residue analysis for the extraction of painting micro-samples from resin cross-sections.
Cross-section preparation of painting micro-samples is part of their routine analysis. This type of preparation can be used for several analytical techniques, such as scanning electron microscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, and optical microscopy. These techniques offer high-resolution imaging and/or elemental information, providing access to technical and material data important for the interpretation, preservation, and restoration of painted artworks. However, it also means that the material from the sample embedded in the resin becomes unreachable for further analysis, except for the polished surface of the cross-section. Degradation of the embedding medium can also occur over time, which can lead to misinterpretation, loss of information, or even complete destruction of the embedded sample. In the field of cultural heritage, cyclododecane (CDD) is commonly used for the consolidation and protection of objects, and is used in the preparation of cross-sections to prevent contamination of the sample by the embedding medium. This study enhanced the existing preparation process by shaping the CDD layer to enable extraction of the micro-sample from the resin if needed, without compromising the integrity of the sample. Moreover, the purity, the sublimation rate in a normal environment and a vacuum, and the impact of CDD on three different types of samples (historical painting on a canvas, wall painting fragment, model sample) were examined.


Facile construction of a highly sensitive DNA biosensor by in-situ assembly of electro-active tags on hairpin-structured probe fragment.
An ultrasensitive DNA biosensor has been developed through in-situ labeling of electroactive melamine-Cu(2+) complex (Mel-Cu(2+)) on the end of hairpin-like probe using gold nanoparticles (AuNPs) as the signal amplification platform. The 3'-thiolated hairpin-like probe was first immobilized to the gold electrode surface by the Au-S bond. The AuNPs were then tethered on the free 5'-end of the immobilized probe via the special affinity between Au and the modified -NH2. Followed by, the Mel and Cu(2+) were assembled on the AuNPs surface through Au-N bond and Cu(2+)-N bond, respectively. Due to the surface area and electrocatalytic effects of the AuNPs, the loading amount and electron transfer kinetic of the Mel-Cu(2+) were enhanced greatly, resulting in significantly enhanced electrochemical response of the developed biosensor. Compared with the synthesis process of conventional electroactive probe DNA accomplished by homogeneous method, the method presented in this work is more reagent- and time-saving. The proposed biosensor showed high selectivity, wide linear range and low detection limit. This novel strategy could also be extended to the other bioanalysis platforms such as immunosensors and aptasensors.


A comparison of subject room dust with home vacuum dust for evaluation of dust-borne aeroallergens.
Assessment of indoor allergen is valuable in exposure research and evaluation of allergic individuals. Collection methods range from grab vacuum samples to filtration devices located in the breathing range of an individual. For practical purposes, many research studies use analysis of collected house dust to evaluate allergen reservoirs. To test the hypothesis that house dust collected from the family vacuum is equivalent to house dust collected by a technician following standard protocol. Homes from a healthy homes demonstration project (n = 41) were sampled using a specific Department of Housing and Urban Development-suggested protocol in the bedroom of the child with asthma and a simple grab procedure from the family vacuum. Samples were evaluated for the presence of 5 allergens, Bla g2, Can f1, Der f1, and Der p1 combined as total mite, Fel d1, and Mus m1. Samples were also evaluated for total antigenic protein from 4 fungal taxa, including Alternaria, Aspergillus, Cladosporium, and Penicillium. All of the allergens and antigens tested showed good correlation between the 2 collection methods. Fungal antigens ranged up to 92,651 nanograms per gram of dust for Aspergillus, and allergens ranged up to 17,928 nanograms per gram of dust for Can f1. The best correlation was for Cladosporium (r = 0.91), and the weakest was for dust mite (r = 0.34). Allergens and antigens tested from samples collected by protocol and by grab sampling from the home vacuum were highly positively correlated. Grab samples taken from the family vacuum may be a good surrogate for evaluating home allergen exposure.


A method for provoking EEG abnormalities by administration of nialamide.
Nialamide, a kind of monoamine oxydase inhibitor, was used for provoking centrencephalic EEG abnormalities and 6-14 Hz positive spikes. It was assumed that these EEG abnormalities have close relationship with dysfunctions of the brainstem which is rich in monoamines and monoamine oxydase. The nialamide provocation was carried out on 49 inpatients who had centrencephalic discharges in their EEG reports. These patients consisted of four cases of epilepsy, one case of anorexia nervosa, two cases of narcolepsy and 42 cases of diencephalosis. Another series of 22 patients suffering from other diseases, in whome EEG no centrencephalic EEG abnormallities were detected, were examined with nialamide. Out of the 49 patients, 35 cases (71.4+) showed increased EEG abnormalities following the administration of nialamide. It was noteworthy that this drug had provocative effect not only for EEG abnormalities, but also for the symptoms from which patients were suffering. In 26 out of 49 patients, both EEG abnormalities and clinical symptoms were provoked by nialamide. And the nialamide administration resulted in negative on all 22 patients who did not register centrencephalic EEG abnormalities. The mechanism and characteristics of this provocative procedure by the use of nialamide were evaluated.


Evaluation of Etest for testing antimicrobial susceptibilities of Neisseria gonorrhoeae isolates with different growth media.
The MICs for 101 isolates of Neisseria gonorrhoeae obtained by Etest (AB-Biodisk, Solna, Sweden) and the agar dilution method on GC medium base supplemented with 1% Kellog's defined supplement (GCMB) were compared. The overall percent agreement (within 1 log2 dilution) between methods was greater than 97.9. The Pearson's correlation coefficients for penicillin, tetracycline, erythromycin, and ceftriaxone for the two methods were 0.98, 0.97, 0.93, and 0.93 (P = 0.001), respectively, for comparisons on GCMB. The overall percent agreement was lower when hemoglobin-supplemented GCMB was used. Etest is an attractive alternative to the agar dilution method for gonococcal antimicrobial susceptibility testing and should be further analyzed in multicenter studies.


Día de los Muertos: Learning About Death Through Observing and Pitching In.
The chapter explores how young children in the state of Puebla, Mexico are socialized with respect to death by observing and pitching in during the annual celebration for día de los muertos. This chapter focuses on observations made of children's participation in practices related to día de los muertos and their experiences with death as explored through ethnographic interviews of preschool children and adults from the cities of Cholula and Puebla. We found that children were included in all aspects of día de los muertos and participated by hanging out, observing, pitching in, and listening. Parents (and grandparents) viewed this active participation as crucial for children to acquire the skills and traditions necessary to be responsible adults in their culture. The current research provides new perspectives regarding the study of children and death within the field of developmental psychology by focusing on how multiple modes of participation are an integral part of young children's socialization with death.


Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine as a heterologous booster.
To overcome the increased risk of SARS-CoV-2 reinfection or post-vaccination infection caused by the Omicron variant, Omicron-specific vaccines were considered a potential strategy. We reported the increased magnitude and breadth of antibody response against VOCs elicited by post-vaccination Delta and Omicron infection, compared to WT infection without vaccination. Then, in mouse models, three doses of Omicron-RBD immunization elicited comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, a heterologous Omicron-RBD booster following two doses of WT-RBD immunization increased the NAb titers against Omicron by 9-folds than the homologous WT-RBD booster. Moreover, it retains neutralization against both WT and current VOCs. Results suggest that Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs and that SARS-CoV-2 vaccines including two or more virus lineages might improve the NAb response.


Left-censored dementia incidences in estimating cohort effects.
We estimate the dementia incidence hazard in Germany for the birth cohorts 1900 until 1954 from a simple sample of Germany's largest health insurance company. Followed from 2004 to 2012, 36,000 uncensored dementia incidences are observed and further 200,000 right-censored insurants included. From a multiplicative hazard model we find a positive and linear trend in the dementia hazard over the cohorts. The main focus of the study is on 11,000 left-censored persons who have already suffered from the disease in 2004. After including the left-censored observations, the slope of the trend declines markedly due to Simpson's paradox, left-censored persons are imbalanced between the cohorts. When including left-censoring, the dementia hazard increases differently for different ages, we consider omitted covariates to be the reason. For the standard errors from large sample theory, left-censoring requires an adjustment to the conditional information matrix equality.


Co-existence of distinct prion types enables conformational evolution of human PrPSc by competitive selection.
The unique phenotypic characteristics of mammalian prions are thought to be encoded in the conformation of pathogenic prion proteins (PrP(Sc)). The molecular mechanism responsible for the adaptation, mutation, and evolution of prions observed in cloned cells and upon crossing the species barrier remains unsolved. Using biophysical techniques and conformation-dependent immunoassays in tandem, we isolated two distinct populations of PrP(Sc) particles with different conformational stabilities and aggregate sizes, which frequently co-exist in the most common human prion disease, sporadic Creutzfeldt-Jakob disease. The protein misfolding cyclic amplification replicates each of the PrP(Sc) particle types independently and leads to the competitive selection of those with lower initial conformational stability. In serial propagation with a nonglycosylated mutant PrP(C) substrate, the dominant PrP(Sc) conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to its lowest stability. Cumulatively, the data show that sporadic Creutzfeldt-Jakob disease PrP(Sc) is not a single conformational entity but a dynamic collection of two distinct populations of particles. This implies the co-existence of different prions, whose adaptation and evolution are governed by the selection of progressively less stable, faster replicating PrP(Sc) conformers.


Important parasites of dover sole (Solea solea L.) kept under mariculture conditions.
Dover sole (Solea solea L.) were examined for parasites at the White Fish Authority (WFA) fish farm at Hunterston, Ayrshire, Scotland. The most important parasites appeared to be the two blood-feeding ectoparasites Lernaeocera sp., a copepod, and Hemibdella soleae, an ichthyobdellid leech, and the haematoprotozoan Haemogregarina simondi. The anaemia and general malaise of the sole investigated was attributed partly to general stress and the debilitating effects of transfer from the wild into an aquaculture system and partly to the impact of the parasites observed.


[Diagnosis of hemophilia and von Willebrand-Jürgens syndrome. 3. Results of studies on patients with vWJS, heterozygotes of vWJS and patients with Glanzmann-Naegeli thrombasthenia].
By means of genealogical and laboratory-diagnostic examinations in the district of Magdeburg 59 patients with a von-Willebrand-Jürgens-syndrome and 2 patients with thrombasthenia were detected. On the basis of the laboratory data and the severity of the inclination to haemorrhage in patients with von-Willebrand-Jürgens-syndrome a subdivision into type I (severe from), type I (easy form) and type II was made. The diagnosis was rendered difficult by the appearance of clinically asymptomatic carriers of signs. The experiences hitherto made in the dispensary care and the use of the laboratory programme are estimated.


Breast-conserving surgery after tumor downstaging by neoadjuvant chemotherapy is oncologically safe for stage III breast cancer patients.
We conducted a retrospective study to evaluate the local recurrence (LR) rate depending on the use of neoadjuvant chemotherapy (NCT) and to determine the oncologic safety of breast-conserving surgery (BCS) after NCT by comparing LR between patients treated with BCS and mastectomy in clinical stage III breast cancer patients. Between 2004 and 2007, 166 patients underwent BCS or mastectomy after NCT (NCT group) and 193 patients underwent surgery first (surgery group) in clinical stage III breast cancer patients. Patients whose tumor size became ≤4 cm after NCT, 57 patients underwent mastectomy (mastectomy group) 39 patients underwent preplanned BCS (preplanned BCS group), and 33 patients underwent downstaged BCS (downstaged BCS group). The recurrence rates between the groups and risk factors for LR were analyzed. The 5-year LR-free survival rates were 93.6 % in the NCT group and 95.9 % in the surgery group (P = 0.108). In the NCT group, the 5-year LR-free survival rates were 96.3 % in the mastectomy group, 94.7 % in the preplanned BCS group and 90.9 % in the downstaged BCS group (P = 0.669). High expression of Ki-67 was a predictor of LR in patients in three groups (Hazard ratio 8.300, P = 0.049). Our findings suggest that BCS after NCT in clinical stage III patients is oncologically safe in terms of LR if breast tumor size is ≤4 cm after NCT and Ki-67 is a predictor of LR after NCT.


Morphological modification of nanostructured ultrathin-layer chromatography stationary phases.
Ultrathin-layer chromatography (UTLC) provides the high sensitivities and rapid separations over short distances desirable in many analytical applications. The dependence of these performance benefits on UTLC layer microstructure motivates continued stationary phase engineering efforts. A new method of modifying the elution behaviours of nanostructured thin film UTLC stationary phases is investigated in this report. Macroporous normal phase silica thin films ∼5 μm thick were fabricated using glancing angle deposition (GLAD). Reactive ion etching (RIE) and a subsequent annealing treatment modified stationary phase morphology to tune migration velocity, analyte retention, and overall separation performance. Combining this technique with a RIE shadow mask enabled fabrication of adjacent concentration and separation zones with markedly different elution properties. Although produced using an entirely new approach, GLAD UTLC concentration zone media behaved in a manner consistent with traditional thin-layer chromatography (TLC) and high-performance TLC (HPTLC) concentration zone plates. In particular, these new media focused large volume, low concentration dye mixture spots into narrow bands to achieve high-quality separations. The described approach to modifying the morphology and resultant elution behaviours of nanostructured stationary phases expands the capabilities of the GLAD UTLC technique.


Polymerization stress related to radiant exposure and its effect on microleakage of composite restorations.
Verify the influence of radiant exposure (dose) on polymerization stress and microleakage of composite restorations using two adhesive systems. An experimental composite (1BisGMA:1TEGDMA, 75wt.% filler) was subjected to 3, 6, 12 or 24J/cm(2) under 500mW/cm(2). Stress was measured in 1-mm height specimens placed between two glass rods (Ø=5mm) attached to a testing machine. Microleakage was assessed in cylindrical restorations (Ø=5mm, h=2mm) with enamel margins, using Adper Single Bond 2 (SB) or Adper Prompt (PR). After storage, specimens were subjected to dye penetration (50% AgNO(3)) and sectioned twice, perpendicularly. Microleakage of the 8tooth/composite interfaces was recorded in millimeters. KHN was measured at both surfaces of cylindrical specimens (Ø=5mm, 1 or 2mm height). ANOVA/Tukey test were used (alpha=0.05). KHN top and bottom were compared using paired t-tests. Stress increased significantly with dose (3J/cm(2): 1.4+/-0.3(c); 6J/cm(2): 4.3+/-0.5(b); 12J/cm(2): 9.3+/-0.6(a); 24J/cm(2): 9.9+/-0.7(a), in MPa). For both average and maximum microleakage, interactions were not statistically significant (p>0.05). Tooth average microleakage was influenced by the adhesive system (SB<PR) and increased with dose (3J/cm(2)<6J/cm(2)=12J/cm(2)=24J/cm(2)). Tooth maximum microleakage was influenced by dose only (3J/cm(2)<6J/cm(2)=12J/cm(2)=24J/cm(2)). A direct association between stress and microleakage was suggested with SB, while with PR showed severe dye penetration at all doses evaluated. KHN showed significant differences among all groups, except at bottom of 2mm specimens cured with 3 and 6J/cm(2). Differences between top and bottom were found for 2mm specimens cured with 3 and 6J/cm(2). Stress and microleakage increased significantly with the applied radiant exposure.


Screening computed tomography: will it result in overdiagnosis of renal carcinoma?
Despite uncertain benefits and harms, screening computed tomography (CT) is being marketed to consumers in the U.S. One plausible harm is the detection and treatment of renal carcinoma cases that otherwise would have remained clinically silent during the patient's lifetime. After estimating the prevalence of preclinical renal carcinoma using meta-analysis of five series of asymptomatic, middle-aged Americans who received CT screening, the authors divided the prevalence by U.S. incidence rates of clinical renal carcinoma among persons of similar age. This calculation would estimate the mean duration of the detectable preclinical period (the "sojourn time") of renal carcinoma if the incidence of preclinical and clinical renal carcinoma were equivalent. The 5 series included 16,174 screenees (mean age range, 58-64 years; 61% male). The prevalence of asymptomatic renal carcinoma ranged from 0.11% to 0.76%; the pooled prevalence was 0.21% (95% confidence interval, 0.14-0.28%). The estimated mean sojourn time for renal carcinoma was between 3.7 years and 5.8 years among middle-aged Americans. Because most renal carcinomas grow slowly during the preclinical period, the authors' estimated mean sojourn time did not seem unduly long. Therefore, the incidence rate of clinical renal carcinoma most likely is a reasonable surrogate for the incidence rate of preclinical renal carcinoma, implying that most renal carcinomas detected by CT screening among middle-aged Americans are likely to progress to clinical diagnosis.


Elastic registration based on particle filter in radiotherapy images with brain deformations.
This paper presents the evaluation of the accuracy of an elastic registration algorithm, based on the particle filter and an optical flow process. The algorithm is applied in brain CT and MRI simulated image datasets, and MRI images from a real clinical radiotherapy case. To validate registration accuracy, standard indices for registration accuracy assessment were calculated: the dice similarity coefficient (DICE), the average symmetric distance (ASD) and the maximal distance between pixels (Dmax). The results showed that this registration process has good accuracy, both qualitatively and quantitatively, suggesting that this method may be considered as a good new option for radiotherapy applications like patient's follow up treatment.


Cognitive functioning in compulsive hoarding.
The aim of this study is to determine whether neurocognitive performance distinguishes individuals with compulsive hoarding (CH) from those with obsessive-compulsive disorder (OCD). Compared to control subjects, OCD patients and CHs scored significantly worse on the Serial Reaction Time Task suggesting disturbed implicit memory in both patient groups. On the Iowa Gambling Task, an overall learning progression difference over time was found between the CHs, OCD group, and control subjects, suggesting differences in decision-making between the groups. The groups did not differ in performance on the Stop Signal Reaction Time Task (motor inhibition). This study found evidence for impaired implicit memory in CHs, but also in OCD patients, albeit less severe. There was evidence that OCD patients learned more slowly on a decision-making task than CHs and control subjects. This latter finding provides some evidence to suggest that CH and OCD have, at least on this one measure, differing cognitive substrates.


Localization of ectopic pheochromocytomas by magnetic resonance imaging.
Magnetic resonance imaging (MRI) was utilized to localize ectopic pheochromocytomas in two patients. In both cases, MRI proved superior to computed tomography. Differentiation from surrounding tissue was excellent. MRI permits spatial localization and by assessment of signal contrast intensity provides a suggestion as to the characteristics of the tumor without the use of invasive procedures or intravenous injections. MRI should be considered as an alternative to computed tomography when evaluating patients with a suspected pheochromocytoma.


Microbial influences on urinary polyamine excretion.
We determined diamines, polyamines, their monoacetylated conjugates and some of their catabolites in urines of healthy persons during decontamination of the gastrointestinal tract and patients with urinary tract infections. The compounds were also measured after in vitro incubation of urines from healthy persons and patients. During decontamination the urinary excretion of total putrescine decreased by a small amount. This fall was for the greater part accountable to monoacetylated putrescine. Free putrescine levels were increased in urines of patients with urinary tract infections, decreased after therapy, and increased after incubation of the pretherapeutical samples. Total cadaverine decreased during decontamination and increased during recontamination. The changes were partly accountable to monoacetylated cadaverine. Free cadaverine levels of patients with urinary tract infections were normal and did not change after therapy. These data show that, under normal conditions, a small part of monoacetylated putrescine and a considerable part of monoacetylated cadaverine originate from the gastrointestinal tract, and that urinary tract infections lead to an increase of free putrescine. The microbial synthesis of putrescine in the gastrointestinal- and urinary tracts, should therefore be taken into account for the interpretation of urinary putrescine levels as a parameter for body cell turnover.


The effects of fibromyalgia syndrome on female sexuality: a controlled study.
Fibromyalgia may have negative effects on sexual function in women. To evaluate the sexuality of women with fibromyalgia and healthy control subjects, and to investigate the relation between sexuality and clinical parameters of fibromyalgia. Female Sexual Function Index (FSFI), Tender Points Count (TPC), Beck Depression Inventory (BDI), Fibromyalgia Impact Questionnaire (FIQ), and Visual Analog Scale (VAS). Clinical evaluation and surveys were done with 126 women with fibromyalgia and 132 healthy women. Patients with fibromyalgia had higher BDI scores and lower frequency of sexual intercourse than control subjects. The mean FSFI scores (total and all domains) were significantly lower in patients with fibromyalgia than control subjects. Mean FSFI scores (total and most domains) were significantly lower in patients with fibromyalgia who had BDI score≥17 than those who had BDI score<17. In women with fibromyalgia, a significant negative correlation was noted between total FSFI score, and both FIQ and BDI scores. Fibromyalgia has negative effects on female sexual function that are aggravated by depression.


Preparation and characterization of recombinant human growth hormone-Zn2+-dextran nanoparticles using aqueous phase-aqueous phase emulsion.
An effective and simple method was developed to prepare spherical and uniform-sized recombinant human growth hormone (rhGH)-Zn(2+)-dextran nanoparticles (NPs) for a variety of delivery applications of the delicate protein. The results showed that the prepared rhGH-Zn(2+)-dextran particles were spherical, glassy, and uniform in size. rhGH recovered from the NPs maintained its structural integrity and its bioactivity well, as suggested by the Nb(2)-11 cell proliferation assay. Using polyethylene glycol and polysaccharide to mediate Zn(2+)-induced precipitation has proved to be a promising method to prepare spherical protein-loaded NPs with desired sizes and preserved protein stability. This basic science paper discusses a simple yet effective method to prepare spherical and uniform-sized recombinant human growth hormone (rhGH)-Zn(2+)-dextran nanoparticles for a variety of delivery applications.


Efficient, rapid and simple adsorption method by polydopamine polystyrene nanofibers mat for removal of multi-class antibiotic residues in environmental water.
Polydopamine polystyrene nanofibers mat (PDA-PS NFsM) was prepared as an adsorbent for the simultaneous removal of multiple antibiotic residues in environmental water for the first time. PDA-PS NFsM can directly be used to adsorb 18 antibiotic residues belonging to 8 classes without any pretreatment of water samples. The adsorption process was completed within 5 min. All antibiotics could be removed at the same time, and the removal rate of each target was above 85%. Moreover, the used PDA-PS NFsM can be easily separated from the environmental water by taking out directly, and can be reused for 10 times after simple regeneration. The thermodynamic and kinetic properties of PDA-PS NFsM adsorption of antibiotic residues were further investigated consequently. It was found that the adsorptions of PDA-PS NFsM to the targets were spontaneous and endothermic process (ΔG<0, ΔH>0, ΔS>0). The results of adsorption kinetic experiments illustrated that the adsorption process was rapid, the adsorption equilibrium of which can be reached in 5 min. Adsorption isotherm experiments proved that the adsorption process of PDA-PS NFsM was consistent with Langmuir adsorption (R2 > 0.994), and the maximum adsorption capacity of PDA-PS NFsM towards all targets were 123.76 mg g-1. The developed method is rapid and simple, and can efficiently adsorb and remove a variety of antibiotics in environmental water, which has good practical application prospect.


Conservative management of pelvi-ureteric junction obstruction (PUJO): is it appropriate and if so what duration of follow-up is needed?
• To establish whether it is safe to manage minimally symptomatic and asymptomatic pelvi-ureteric junction obstruction (PUJO) conservatively. • In all, 50 patients with PUJO diagnosed with dynamic renography, and monitored with at least two renograms. • In all, 19 patients were totally asymptomatic, while 31 patients had minimal symptoms at time of diagnosis. • The mean follow-up was 53 months. • During the course of follow-up 10 of the 50 patients deteriorated. • All patients who had asymptomatic renographic deterioration, deteriorated within 2 years of diagnosis. • Eight of the 10 patients that deteriorated needed pyeloplasty and two nephrectomy. • Conservative management of patients with minimally symptomatic and asymptomatic PUJO is safe. • Discharging patients could be considered at 2 years from diagnosis, if they remain renographically stable and asymptomatic or minimally symptomatic.


Enhancement of the anti-tumor effect of melphalan in experimental mice by some vaso-active agents.
A comparison is made between the vaso-active agents hydralazine, nifedipine, and verapamil for their ability to increase the anti-tumor effectiveness of melphalan. Treatment of mice with hydralazine (5 mg/kg) 15 mins after melphalan increases by a factor of approximately 2.5 melphalan-induced delay in growth of either the RIF-1 or KHT tumors. Similar enhancements are obtained when measurement is made of the surviving fraction of tumor cells in vitro following treatment in vivo with hydralazine and melphalan. Further, tumor cell kill is also increased when nifedipine is administered with melphalan compared with the effect of melphalan alone. These enhanced effects are observed if the vaso-active agents are given before or after melphalan. Hydralazine (5 mg/kg) induces close to 100% radiobiological hypoxia in the RIF-1 and KHT tumors. In contrast, Nifedipine has no effect on tumor hypoxic fraction at a dose of 10 mg/kg although the anti-tumor effectiveness of melphalan is substantially increased. However, a higher dose of 50 mg/kg nifedipine causes a large increase in tumor hypoxic fraction, an effect that persists for several hours. Verapamil causes no change in the fraction of hypoxic cells in the KHT tumor and increases, only slightly, the anti-tumor effect of melphalan.


LAN-1: a human neuroblastoma cell line with M1 and M3 muscarinic receptor subtypes coupled to intracellular Ca2+ elevation and lacking Ca2+ channels activated by membrane depolarization.
The LAN-1 clone, a cell line derived from a human neuroblastoma, possesses muscarinic receptors. The stimulation of these receptors with increasing concentrations of carbachol (CCh; 1-1,000 microM) caused a dose-dependent increase of the intracellular free Ca2+ concentration ([Ca2+]i). This increase was characterized by an early peak phase (10 s) and a late plateau phase. The removal of extracellular Ca2+ reduced the magnitude of the peak phase to approximately 70% but completely abolished the plateau phase. The muscarinic-activated Ca2+ channel was gadolinium (Gd3+) blockade and nimodipine and omega-conotoxin insensitive. In addition, membrane depolarization did not cause any increase in [Ca2+]i. The CCh-induced [Ca2+]i elevation was concentration-dependently inhibited by pirenzepine and 4-diphenylacetoxy-N-methylpiperidine methiodide, two rather selective antagonists of M1 and M3 muscarinic receptor subtypes, respectively, whereas methoctramine, an M2 antagonist, was ineffective. The coupling of M1 and M3 receptor activation with [Ca2+]i elevation does not seem to be mediated by a pertussis toxin-sensitive guanine nucleotide-binding protein or by the diacylglycerol-protein kinase C system. The mobilization of [Ca2+]i elicited by M1 and M3 muscarinic receptor stimulation seems to be dependent on an inositol trisphosphate-sensitive intracellular store. In addition, ryanodine did not prevent CCh-induced [Ca2+]i mobilization, and, finally, LAN-1 cells appear to lack caffeine-sensitive Ca2+ stores, because the methylxanthine was unable to elicit intracellular Ca2+ mobilization, under basal conditions, after a subthreshold concentration of CCh (0.3 microM), or after thapsigargin.


Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation.
Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair growth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.


Cromakalim suppresses hypertonic saline-induced renal vasoconstriction in anaesthetized dogs.
1. Intrarenal arterial infusion of hypertonic saline (HS) transiently increased and then gradually reduced renal blood flow (RBF) in anaesthetized dogs. Glomerular filtration rate (GFR) but not filtration fraction decreased at the end of the infusion. 2. In the presence of a potassium channel opener cromakalim (0.3 microgram/kg per min), HS infusion failed to reduce RBF; the initial increase in RBF was maintained throughout the infusion. Since cromakalim also prevented the decrease in GFR, HS infusion lowered filtration fraction. 3. The results suggest that cromakalim inhibits both pre-and postglomerular vasoconstriction induced by HS infusion.


A novel multi-attribute decision-making for ranking mobile payment services using online consumer reviews.
The onset of the COVID-19 pandemic has changed consumer usage behavior towards mobile payment (m-payment) services. Consumer usage behavior towards m-payment services continues to increase due to access to usage experiences shared through online consumer reviews (OCRs). The proliferation of massive OCRs, coupled with quick and effective decisions concerning the evaluation and selection of m-payment services, is a practical issue for research. This paper develops a novel decision evaluation model that integrates OCRs and multi-attribute decision-making (MADM) with probabilistic linguistic information to identify m-payment usage attributes and utilize these attributes to evaluate and rank m-payment services. First and foremost, the attributes of m-payment usage discussed by consumers in OCRs are extracted using the Latent Dirichlet Allocation (LDA) topic modeling approach. These key attributes are used as the evaluation scales in the MADM. Based on an unsupervised sentiment algorithm, the sentiment scores of the text reviews regarding the attributes are calculated. We convert the sentiment scores into probabilistic linguistic elements based on the probabilistic linguistic term set (PLTS) theory and statistical analysis. Furthermore, we construct a novel technique known as probabilistic linguistic indifference threshold-based attribute ratio analysis (PL-ITARA) to discover the weight importance of the usage attributes. Subsequently, the positive and negative ideal-based PL-ELECTRE I methodology is proposed to evaluate and rank m-payment services. Finally, a case study on selecting appropriate m-payment services in Ghana is examined to authenticate the validity and applicability of our proposed decision evaluation methodology.


[Endoscopic management of complications after laparoscopic sleeve gastrectomy].
Laparoscopic sleeve gastrectomy (SG) is currently the most commonly performed standalone bariatric procedure worldwide. Gastric staple line leakage is the feared immanent complication of the operation, which is difficult to treat and often persists. This article presents the endoscopic treatment options for complications after laparoscopic SG, particularly the treatment of gastric staple line leakage. Most important for a successful treatment is the understanding of the underlying pathophysiological causes, the exact surgical comprehension of the procedure and advanced endoscopic skills. The choice of endoscopic intervention depends on the available strategies as well as on the skills of the executing endoscopist. Currently, internal drainage seems to be the most expedient method.


Solute distribution and stability in emulsion-based delivery systems: an EPR study.
Oil-in-water emulsions and related systems are often used to deliver hydrophobic solutes in foods, personal care products, and pharmaceuticals. Recent work has considered the use of crystalline lipid carrier particles (i.e., solid lipid nanoparticles, SLN) to control the availability of the solute; however, there is little direct evidence for the localization of small molecules in these systems. Alkanes (10 wt.% tetradecane or eicosane) containing the spin probe 4-phenyl-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl (PTMIO, 200 ppm) were homogenized into sodium caseinate solution (1 wt.%) to produce fine or coarse droplets (0.2 μm or 1.3 μm, respectively) and cooled to 21.5 °C where eicosane is crystalline and tetradecane is liquid. Analysis of the resulting EPR spectra revealed populations of probe in two discrete environments (i.e., aqueous and lipid). PTMIO is largely hydrophobic with 77% and 70% present in the coarse and fine liquid lipid droplets (i.e., tetradecane droplets), respectively. In the solid droplets (i.e., eicosane), all of the probe was excluded from the droplets into the aqueous environment. In all cases, the mobility of the probe in both lipid and aqueous environments was affected by the droplet surface; thus, we hypothesize that the majority of the probe molecules are associated with the droplet interface. The PTMIO was reduced to an EPR-silent form by the addition of iron/ascorbate to the aqueous phase, and the apparent rate constant of the reaction was proportional to the fraction of the spin probe in the aqueous phase. Based on these findings, we propose that droplet crystallization excludes solute molecules from the droplet core to the aqueous environment where they interact with the droplet surface.


Lipase-catalyzed esterification of conjugated linoleic acid with sorbitol: a kinetic study.
The kinetics of esterification of conjugated linoleic acid (CLA) with sorbitol in acetone was investigated. An immobilized lipase from Candida antarctica (Chirazyme L-2) was used as the biocatalyst. A 2(2) x 3 factorial design was employed to find an experimental region in which one obtains a high rate of formation of the diester product. Best results were obtained at 10 degrees C using a CLA to sorbitol molar ratio of 5 and a biocatalyst loading of 150 mg/mL of acetone. Under these conditions, in 72 h one obtains a nearly quantitative yield (ca. 98%) of the diester of sorbitol with CLA. To minimize formation of products with degrees of esterification greater than two, the reaction should be carried out at 10 degrees C. A kinetic model developed using the King-Altman method was employed to fit the data. Use of the steady-state approximation for the monoester and an assumption that the concentration of sorbitol was constant and equal to its solubility limit permit one to minimize the number of parameters necessary to model the reaction network. Nonlinear regression analysis based on either two or three parameters provides very good fits of the multiresponse data in the presence or absence of triesters, respectively.


Melanocytic Nevi with Site-related Atypia: A Case Series and Characterization of their Immunohistochemical Profile.
Nevi of special sites (NOSS) are benign melanocytic lesions that occur at particular sites. Although the histological features of NOSS have been described, their immunophenotypic features have not been fully characterized. To present the clinicopathological characteristics of a case series of NOSS and to characterize their immunohistochemical profile. Thirty-five NOSS were assessed using immunoperoxidase staining techniques for the melanocytic (S100, Melan-A, and HMB45) and proliferation (Ki-67) markers RESULTS: All of the cases of NOSS showed concerning architectural changes (prominent lentiginous melanocytic proliferation, irregularities, crowdedness, and dyhesiveness of the nests), and cytological atypia (large nevomelanocytes with vesicular nuclei, clear cytoplasm, and dusty melanin pigment) that can lead to a misdiagnosis of atypical nevi or even melanomas. All of the cases of NOSS showed diffuse expression of S100 and Melan-A proteins. Ki-67 labeling index of the nevomelanocytes was extremely low. HMB45 protein expression was limited to the junctional and superficial dermal nevomelanocytes. NOSS can show histological features that can easily mimic atypical nevi or melanomas and this diagnostic consideration should be kept in mind to avoid their misdiagnosis. The expression of HMB45 protein in NOSS indicates that their nevomelanocytic cells have an activated phenotype. The decreased HMB45 protein expression following a gradient from junctional to deeper dermal localization in NOSS is indicative of their immunohistochemical maturation.


Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate therapy days for neonatal abstinence syndrome. A prospective randomized clinical trial.
To compare the efficacy of clonidine versus phenobarbital in reducing morphine sulfate treatment days for neonatal abstinence syndrome (NAS). Prospective, non-blinded, block randomized trial at a single level III NICU (Neonatal Intensive Care Unit). Eligible infants were treated with a combination of medications as per protocol. Primary outcome was treatment days with morphine sulfate. Secondary outcomes were the mean total morphine sulfate dose, outpatient phenobarbital days, adverse events and treatment failures. A total of 82 infants were eligible, of which 68 were randomized with 34 infants in each study group. Adjusting for covariates phenobarbital as compared with clonidine had shorter morphine sulfate treatment days (-4.6, 95% confidence interval (CI): -0.3, -8.9; P=0.037) with no difference in average morphine sulfate total dose (1.1 mg kg(-1), 95% CI: -0.1, 2.4; P=0.069). Post-discharge phenobarbital was continued for an average of 3.8 months (range 1 to 8 months). No other significant differences were noted. Phenobarbital as adjunct had clinically nonsignificant shorter inpatient but significant overall longer therapy time as compared with clonidine.


Differential proteomics profiling of the ova between healthy and Rice stripe virus-infected female insects of Laodelphax striatellus.
Rice stripe virus-infected females of the small brown planthopper (SBPH, Laodelphax striatellus) usually lay fewer eggs with a longer hatch period, low hatchability, malformation and retarded or defective development compared with healthy females. To explore the molecular mechanism of those phenomena, we analyzed the differential proteomics profiling of the ova between viruliferous and healthy female insects using an isobaric tag for relative and absolute quantitation (iTRAQ) approach. We obtained 147 differentially accumulated proteins: 98 (66.7%) proteins increased, but 49 (33.3%) decreased in the ova of the viruliferous females. RT-qPCR was used to verify the 12 differential expressed proteins from iTRAQ, finding that trends in the transcriptional change for the 12 genes were consistent with those at the proteomic level. Differentially expressed proteins that were associated with meiosis (serine/threonine-protein phosphatase 2B and cyclin B3) and mitosis (cyclin B3 and dynein heavy chain) in viruliferous ova may contribute to low hatchability and defective or retarded development. Alterations in the abundance of proteins involved in the respiratory chain and nutrition metabolism may affect embryonic development. Our study begins to explain macroscopical developmental phenomena and explore the mechanisms by which Rice stripe virus impacts the development of SBPH.


A case of unusual histology of infantile lipoblastoma confirmed by PLAG1 rearrangement.
Lipoblastoma, a relatively rare benign adipose neoplasm, predominantly affects children younger than 3 years of age. We herein report the case of a 7-month-old girl with an unusual myxomatous histology of lipoblastoma. A rapidly growing mass was detected in the subcutaneous area of the left buttock. Histologically, the tumor consisted of abundant myxoid stroma exhibiting cellular atypia and a high mitotic activity. Although the histological findings were unusual, the tumor was diagnosed as a lipoblastoma according to both PLAG1 immunohistochemistry and the presence of PLAG1 rearrangement on fluorescence in situ hybridization.


Synthesis and purification of a toxin-linked conjugate targeting epidermal growth factor receptor in Escherichia coli.
Aberrant epidermal growth factor receptor (EGFR) signaling is a common feature of multiple tumor types, including glioblastoma (GBM). As such, EGFR has emerged as an attractive target for antitumor therapy. In the present study, we sought to develop an immunotoxin capable of specifically targeting EGFR-expressing cells and mediating inhibition of cell growth and cell killing. The Luffin P1 (LP1) ribosome inactivating protein was chosen to generate a fusion protein, antiEGFR/LP1, based upon its potent protein synthesis inhibition and small size (5 kDa). LP1 was fused to the C-terminus of an anti-EGFR single-chain antibody (scFv). The recombinant antiEGFR/LP1 protein was expressed in Escherichia coli, and refolded and purified on an immobilized Ni(2+)-affinity chromatography column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting analysis revealed that antiEGFR/LP1 was sufficiently expressed. Confocal microscopy and flow cytometry demonstrated that antiEGFR/LP1 bound specifically to EGFR-positive cells (U251), as almost no binding to EGFR-negative (Jurkat cells) was observed under identical time and dosage conditions. Finally, the MTT cell viability assay showed that antiEGFR/LP1 elicited obvious cytotoxicity toward EGFR-positive tumor cells. Collectively, these results suggest that antiEGFR/LP1 is biologically active and specific toward EGFR-positive tumor cells and may represent an effective EGFR-targeted cancer therapy.


Impact of Proactive Integrated Care on Chronic Obstructive Pulmonary Disease.
Up to 50% of chronic obstructive pulmonary disease (COPD) patients do not receive recommended care for COPD. To address this issue, we developed Proactive Integrated Care (Proactive iCare), a health care delivery model that couples integrated care with remote monitoring. We conducted a prospective, quasi-randomized clinical trial in 511 patients with advanced COPD or a recent COPD exacerbation, to test whether Proactive iCare impacts patient-centered outcomes and health care utilization. Patients were allocated to Proactive iCare (n=352) or Usual Care ( =159) and were examined for changes in quality of life using the St George's Respiratory Questionnaire (SGRQ), symptoms, guideline-based care, and health care utilization. Proactive iCare improved total SGRQ by 7-9 units (p < 0.0001), symptom SGRQ by 9 units (p<0.0001), activity SGRQ by 6-7 units (p<0.001) and impact SGRQ by 7-11 units (p<0.0001) at 3, 6 and 9 months compared with Usual Care. Proactive iCare increased the 6-minute walk distance by 40 m (p<0.001), reduced annual COPD-related urgent office visits by 76 visits per 100 participants (p<0.0001), identified unreported exacerbations, and decreased smoking (p=0.01). Proactive iCare also improved symptoms, the body mass index-airway obstruction-dyspnea-exercise tolerance (BODE) index and oxygen titration (p<0.05). Mortality in the Proactive iCare group (1.1%) was not significantly different than mortality in the Usual Care group (3.8%; p=0.08). Linking integrated care with remote monitoring improves the lives of people with advanced COPD, findings that may have been made more relevant by the coronavirus 2019 (COVID-19) pandemic.


Association of cognitive enhancers and incident seizure risk in dementia: a population-based study.
Although individuals with dementia have a high risk of developing seizures, whether seizures are associated with cholinesterase inhibitors, which are commonly prescribed to treat individuals with dementia, remains unknown. This study investigated the risk of incident seizure following cholinesterase inhibitor use in patients with dementia. A nationwide, nested case-control study was conducted using data from the Korean Health Insurance Review and Assessment Service (HIRA) from 2014 through 2018. A total of 13,767 participants aged 65-95 years who experienced incident seizure were propensity score-matched for medical comorbidities and drug exposure at a 1:3 ratio with a control group of 39,084 participants. The study examined the incidence of seizures in patients diagnosed with dementia within one year after receiving cognitive enhancers. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for seizure incidence according to cholinesterase inhibitor use were analyzed using a multivariable conditional logistic regression model. There was no statistically significant association between duration of cholinesterase inhibitors use and seizure risk. Although there was slight increased seizure risk in patient after receiving donepezil for 1 year compared to memantine, subgroup analyses stratified age and sex did not reveal any significant association between cholinesterase inhibitors use and late-onset seizure. Our findings suggest no immediate increase in seizure risk is associated with cholinesterase inhibitor use, although the risk of seizure in patients with dementia did increase after one year of continued medication intake. Further study is required to obtain confirmatory results on the seizure-related safety of cognitive enhancers in patients with dementia.


Mortality in the first year after coronary artery bypass surgery. Irish Cardiac Surgery Register.
In the three years 1983-1985 the Irish Cardiac Surgery Register (ICSR) recorded details on 1,534 patients who underwent primary isolated coronary artery bypass grafting (CABG). This unselected series of patients accounted for all such operations in the Republic of Ireland during this period and provides information on a wide spectrum of clinical subgroups of patients with ischaemic heart disease. There were 52 operative deaths (3.4%). At one year the number of deaths had risen to 75 (4.9%). Factors related to operative mortality were female sex, age greater than 60, left ventricular failure, history of myocardial infarction in the six weeks prior to surgery, poor left ventricular function and extensive disease of vessels to be grafted. All of the above factors except female sex were related to one year mortality. Analysis of late deaths (1.5%) separately showed evidence of pre-operative impaired left ventricular function to be an important prognostic indicator.


Adsorption and desorption of malachite green by using chitosan-deep eutectic solvents beads.
Chitosan-deep eutectic solvent (DES) beads were prepared from chitosan and DESs. The DESs used were choline chloride-urea (DES A) and choline chloride-glycerol (DES B). Both chitosan-DES beads were used to remove malachite green (MG) dye from an aqueous solution. The optimum pH for chitosan-DES A was recorded at pH 8.0 while optimum pH for chitosan-DES B was pH 9.0. The maximum adsorption capacity obtained for chitosan-DES A and chitosan-DES B were 6.54 mg/g and 8.64 mg/g, respectively. The optimum conditions for both chitosan-DES beads to remove MG were 0.08 g of adsorbent and 20 min of agitation time. Five kinetic models were applied to analyse the data and the results showed that the pseudo-second-order and intraparticle diffusion model fitted best with R2 > 0.999. For the adsorption capacity, results show that the Freundlich and Langmuir adsorption isotherms fitted well with chitosan-DES A and chitosan-DES B, respectively. The maximum adsorption capacities (qmax) obtained from chitosan-DES A and chitosan-DES B were 1.43 mg/g and 17.86 mg/g, respectively. Desorption indicated good performance in practical applications.


[Unusual cause of macrohematuria in a 29-year-old woman].
We report on the case of a young women presenting with macrohaematuria, petechiae and strong headaches. Laboratory showed a thrombotic microangiopathy with helmet cells, increased LDH levels (>600 U/l), and thrombocytopenia (<40,000/μl). Due to strong haemolytic activity and headache with blurred vision, immediate plasma separation with fresh frozen plasma was commenced. Markedly decreased ADAMTS13 activity and detection of anti-ADAMTS13 antibodies were consistent with the diagnosis of idiopathic thrombotic thrombocytopenic purpura. In total, 11 plasma separations were required to stop disease activity. In parallel, immunosuppressive therapy using glucocorticoids was initiated. The patient was discharged from the hospital in a good general condition and with normalized laboratory findings 26 days after hospitalization. All patients with anemia and thrombocytopenia should be tested for haemolysis and helmet cells. An early diagnosis and initiation of necessary therapy are determining for the clinical outcome.


Activity and isoforms of peroxidases, lignin and anatomy, during adventitious rooting in cuttings of Ebenus cretica L.
Adventitious rooting of Ebenus cretica cuttings was studied in order to examine a) the rooting ability of different genotypes in relation to electrophoretic patterns of peroxidases. b) the activity and electrophoretic patterns of soluble and wall ionically bound peroxidases, the lignin content and anatomical changes in the control and IBA treated cuttings of <rooting> and <non-rooting> genotypes in the course of adventitious root formation. In addition, a fraction of soluble cationic peroxidases was separated by gel filtration chromatography from the total soluble peroxidases of a <rooting> genotype. No rooting occurred in cuttings without IBA-treatment. In both genotypes, electrophoretic patterns of soluble anionic peroxidases revealed two common peroxidase isoforms, while a fast-migrating anionic peroxidase isoform (A3) appeared only in <rooting> genotypes. Both genotypes showed similar patterns of soluble, as well as wall ionically bound cationic peroxidase isoforms. The number of isoforms was unchanged during the rooting process (induction, initiation and expression phase) but an increase in peroxidase activity (initiation phase) followed by decrease has been found in IBA-treated cuttings. During initiation phase the lignin content was almost similar to that on day 0 in <rooting> genotype while it was reduced at by about 50% in <non-rooting> genotype at the respective time. Microscopic observations revealed anatomical differences between genotypes. According to this study, the <rooting> and <non-rooting> genotypes display differences in anatomy, lignin content, activity of soluble peroxidases and the electrophoretic patterns of soluble anionic peroxidase isoforms. The A3-anionic peroxidase isoform could be used as biochemical marker to distinguish <rooting> and <non-rooting> genotypes of E. cretica and seems to be correlated to lignin synthesis in rooting process.


Exposure-response analysis for nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma (CheckMate 040).
This analysis was conducted to inform dose selection of a combination of nivolumab plus ipilimumab for the treatment of sorafenib-experienced patients with hepatocellular carcinoma (HCC). CheckMate 040 is an open-label, multicohort, phase I/II trial in adults with advanced HCC that evaluated nivolumab monotherapy (0.1-10 mg/kg once every 2 weeks [q2w]) and the following three combinations of nivolumab plus ipilimumab: (1) nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (q3w) for four doses, followed by nivolumab monotherapy 240 mg q2w (arm A); (2) nivolumab 3 mg/kg plus ipilimumab 1 mg/kg q3w for four doses, followed by nivolumab monotherapy 240 mg q2w (arm B); and (3) nivolumab 3 mg/kg q2w plus ipilimumab 1 mg/kg every 6 weeks continuously (arm C). Exposure-response relationships (efficacy and safety) were characterized using nivolumab and ipilimumab concentrations after the first dose (Cavg1) as the exposure measure. Objective tumor response (OTR) and overall survival (OS) improvements were associated with increased ipilimumab exposure (OTR: odds ratio 1.45, 95% confidence interval [CI], 1.13-1.86; OS: hazard ratio 0.86, 95% CI 0.75-0.98), but not nivolumab exposure (OTR: odds ratio 0.99, 95% CI 0.97-1.02; OS: hazard ratio 1.08, 95% CI 0.89-1.32). Hepatic treatment-related and immune-mediated adverse events were more common in arm A than in arms B or C. Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg q3w for four doses, followed by nivolumab monotherapy 240 mg q2w had the most favorable benefit:risk profile in patients with advanced HCC.


Photo-excited carrier relaxation dynamics in two-dimensional InSe flakes.
Carrier relaxation dynamics of InSe flakes is investigated by using time-resolved pump-probe reflectivity measurement. The photocarriers associated with the P xy orbital band-edge transition at 2.40 eV, which is coupled to the in-plane polarized light, is observed to possess a lifetime of ∼19 ps at room temperature and ∼99 ps at 10 K. The temperature and power dependent carrier lifetime suggests that Shockley-Read-Hall process is the dominant nonradiative recombination mechanism responsible for the carrier relaxation. In addition, the electron scattering with a 14.5 meV optical phonon plays an active role in the carrier relaxation with increasing temperatures. A broad absorption around 1.65-1.90 eV is observed. The photocarriers associated with this broad transition show a long lifetime of ∼200 ps that is nearly independent of temperature and photon energy. This is indicative of bound carriers by defects. Our experimental results provide essential information for the characteristics of carrier dynamics and defects in InSe flakes. The experimental findings are fundamentally important for further development of microelectronics and optoelectronics based on InSe.


pH-dependent complexation of hydroxypropyl-beta-cyclodextrin with chlorin e6: effect on solubility and aggregation in relation to photodynamic efficacy.
The activity of chlorin e6 (Ce6) in photodynamic therapy of cancers is significantly reduced by its propensity to form aggregates. It was postulated that disaggregation of Ce6 could be achieved with the use of hydroxypropyl-beta-cyclodextrin (HP-β-CD) through solubility enhancement. An initial phase solubility study of Ce6 was conducted with various concentrations of HP-β-CD at three different pH conditions, i.e. pH 3, pH 5 and pH 7. Solubility-induced disaggregation of Ce6 was illustrated by fluorescence spectroscopy and singlet oxygen generation studies. Interaction between Ce6 and HP-β-CD was further demonstrated by solid-state characterization techniques. Inclusion complex formulations were tested for improved efficacy on squamous cancer cell lines. Increase in Ce6 solubility was observed, especially at pH 7, indicating the formation of inclusion complex between Ce6 and HP-β-CD. This resulted in disaggregation of Ce6 aggregates illustrated by fluorescence spectroscopy. The mode of binding was predominated by H-bonding supported by temperature-dependent binding studies and molecular simulation work. The inclusion complex demonstrated improved photodynamic efficacy through enhanced singlet oxygen generation and phototoxicity on human oral squamous carcinoma cells. pH-dependent complexation between Ce6- and HP-β-CD-induced disaggregation of Ce6 aggregates and the resultant formulations facilitated improved PDT efficacy on tested cancer cell lines.