Evaluating learning models with transitions of human interests based on objective rule evaluation indices.
This paper presents a method to support the evaluation procedure of a data mining process using human-system interaction. The post-processing of mined results is one of the key factors for successful data mining process. However, it is difficult for human experts to completely evaluate several thousands of rules from a large dataset containing noise. We have designed a method based on objective rule evaluation indices to support the rule evaluation procedure; the indices are calculated to evaluate each if-then rule mathematically. We have evaluated five representative learning algorithms to construct rule evaluation models of the actual data mining results from a chronic hepatitis data set. Further, we discuss the relationship between the transitions of the subjective criterion of a medical expert and the performances of the rule evaluation models.


Tissue-specific GATA factors are transcriptional effectors of the small GTPase RhoA.
Rho-like GTPases play a pivotal role in the orchestration of changes in the actin cytoskeleton in response to receptor stimulation, and have been implicated in transcriptional activation, cell growth regulation, and oncogenic transformation. Recently, a role for RhoA in the regulation of cardiac contractility and hypertrophic cardiomyocyte growth has been suggested but the mechanisms underlying RhoA function in the heart remain undefined. We now report that transcription factor GATA-4, a key regulator of cardiac genes, is a nuclear mediator of RhoA signaling and is involved in the control of sarcomere assembly in cardiomyocytes. Both RhoA and GATA-4 are essential for sarcomeric reorganization in response to hypertrophic growth stimuli and overexpression of either protein is sufficient to induce sarcomeric reorganization. Consistent with convergence of RhoA and GATA signaling, RhoA potentiates the transcriptional activity of GATA-4 via a p38 MAPK-dependent pathway that phosphorylates GATA-4 activation domains and GATA binding sites mediate RhoA activation of target cardiac promoters. Moreover, a dominant-negative GATA-4 protein abolishes RhoA-induced sarcomere reorganization. The identification of transcription factor GATA-4 as a RhoA mediator in sarcomere reorganization and cardiac gene regulation provides a link between RhoA effects on transcription and cell remodeling.


Cysteine: a conditionally essential amino acid in low-birth-weight preterm infants?
Cyst(e)ine can be synthesized de novo from methionine and serine and is, therefore, a nonessential amino acid in human adults. Several studies have suggested that cyst(e)ine might be a conditionally essential amino acid in preterm infants because of biochemical immaturity. No data are available on cyst(e)ine requirements in low-birth-weight (LBW) preterm infants. The aim was to determine cyst(e)ine requirements in LBW infants with gestational ages from 32 to 34 wk, measured 1 mo after birth with the use of the indicator amino acid oxidation technique. LBW infants were randomly assigned to 1 or 2 of the 5 formulas containing graded cystine concentrations (11, 22, 32, 43, or 65 mg cyst(e)ine/100 mL) and generous amounts of methionine. After 24-h adaptation, cyst(e)ine requirement was determined by (13)CO(2) release from [1-(13)C]phenylalanine in expired breath. (13)CO(2) enrichment was measured by isotopic ratio mass spectrometry. Cyst(e)ine requirement was determined in 25 LBW infants with a mean (+/-SD) gestational age of 33 +/- 1 wk and birth weight of 1.78 +/- 0.32 kg. Fractional oxidation of [1-(13)C]phenylalanine did not differ between the 5 groups. There is no evidence for limited endogenous cyst(e)ine synthesis in 4-wk-old LBW preterm infants born at gestational ages from 32 to 34 wk. It is safe to conclude that the cyst(e)ine requirement is <18 mg kg(-1) d(-1) providing generous amounts of methionine and that cyst(e)ine is probably not a conditionally essential amino acid in fully enterally fed LBW preterm infants born at 32-34 wk.


Biphasic kinetic profile for carbamazepine epoxide formation.
The formation of the stable 10,11-epoxide from carbamazepine by rat liver microsomes was studied. A biphasic activity-substrate profile was consistently found with microsomes from both control and phenobarbital pretreated rats. These data could either indicate epoxide formation by multiple catalytic sites with differential substrate affinity or a solvent effect on the enzyme or its environment.


Pseudodyssynergia (contraction of the external sphincter during voiding) misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a therapeutic option.
Chronic lower urinary tract symptoms in young men are often attributed to misdiagnosed chronic nonbacterial prostatitis. We analyzed contraction of the external urinary sphincter during voiding (pseudodyssynergia) as an etiology of voiding dysfunction in men with misdiagnosed chronic prostatitis. The video urodynamic studies of 43 men 23 to 50 years old with chronic voiding dysfunction secondary to pseudodyssynergia performed between January 1990 and June 1996 were retrospectively analyzed. Pseudodyssynergia was diagnosed based on several criteria, including electrical activity of the external sphincter during voiding in the absence of abdominal straining, and brief and intermittent closing of the membranous urethra during voiding detected by electromyography and fluoroscopy. Patients with bacterial infection or excessive leukocytes in expressed prostatic secretions were excluded from the study. Of the patients 39 (91%) were firstborn men. Duration of symptoms ranged from 17 to 146 months (mean 43.6). Average number of previous antibiotic days ranged from 53 to 186 (mean 67.6). In addition, empirical trials of alpha-blockers were unsuccessful. Mean American Urological Association symptom score plus or minus standard deviation was 17.5 +/- 3.7, mean maximum flow rate was 13.3 +/- 4.2 ml. per second, mean detrusor pressure at maximum flow was 46.3 +/- 13.7 cm. water and mean detrusor contraction duration was 132.8 +/- 27.7 seconds. Behavior modification and biofeedback were successful in decreasing symptoms in 35 patients (83%) at 6 months. These results indicate that some men who are categorized as having and empirically treated for chronic nonbacterial prostatitis are misdiagnosed and, in fact, have functional bladder outlet obstruction. Urodynamics are helpful in diagnosing and predicting success with behavior modification and biofeedback in these patients.


[Antiphospholipid syndrome (APS) primary (PAPS) and secondary (SAPS)].
During the last decade, a wide variety of clinical manifestations and serological disturbances have been described associated to APS. However the real prevalence of most clinical manifestations with several autoantibody-cofactor systems still needs precise epidemiological and clinical long-term study. Evaluation of frequency clinical and serological symptoms of SLE and APS in PAPS and SAPS pts. Two groups of pts were analyzed: 78 SAPS (76F+2M) and 43 PAPS (32F+11M). All pts met Sapporo criteria for APS and SAPS pts met ARA criteria for SLE. Epidemiological, clinical and serological data were collected during 1995-2005 in the Connective Tissue Disease, Institute of Rheumatology, Warsaw, Poland and modified in 2005 according to actual directive line. PAPS pts were younger at the onset of the disease compare to SAPS pts. Duration time of the disease to set up the diagnosis as well as observation time was shorter in PAPS pts. Separated PAPS pts showed no more than two ARA criteria for SLE. All clinical ARA criteria for SLE occurred more often in SAPS pts. Also recurrent miscarriages, livedo reticularis and anti AnnexinV abs occurred more often in these pts. Pulmonary embolism, deep venous thrombosis and IgM aCL, LAC, anti beta2GP1, oxyLDL abs occurred more often in PAPS pts. Arterial thrombosis, migraine, crural ulceration, thrombocytopenia, false positive VDRL and IgG aCL abs were detected in almost the same percentage in both groups of pts. Men are less affected with SAPS. Wide variety of clinical SLE symptoms and immunological disturbances are more frequent in SAPS pts. Also in these pts recurrent miscarriages, livedo reticularis and anti AnnexinV abs occur more often. However pulmonary embolism, deep venous thrombosis with LAC, anti beta2GP1, IgM aCl, anti oxyLDL occur in less frequency in SAPS pts. The presence of arterial thrombosis, migraine, crural ulceration, thrombocytopenia, false positive VDRL and aCL IgG were almost in the same percentage in both groups of pts. Precise determination of the link between clinical symptoms of the APS and antibody-cofactor system needs future study on a bigger sample of pts.


[The child, growth and high-level sports].
The hormonal response to a short but intense session of physical exercise should be distinguished from the endocrine adaptation to systematic physical conditioning. The normal child is perfectly equipped to handle stress situations such as those generated by leisure sport: the transient increase in stress hormones has no deleterious effect on growth and puberty. For highly trained children and adolescents, standardized dynamic testing will provide little information on the state of their endocrine system. In addition, the effects of training should be differentiated from those of various bias of selection. In young elite athletes, as for adult athletes, the alterations of the endocrine system result from an inappropriate physical conditioning programme for the individual level of tolerance. Whereas it has been shown that the gonadal function is predominantly affected (pubertal delay, menstrual dysfunction), alterations of growth hormone and cortisol productions have also been reported. Anomalies of pubertal growth should be searched for among elite adolescent athletes: there are data suggesting that their growth potential should probably not be affected below 15 weekly hours of training. However, children do not respond to stress in a uniform manner and one should be prepared to detect the occasional athlete with inadequate growth at lower training intensities. This seems to be the case when training starts before puberty as well as in physical activities associated with a strict weight control. When growth and/or puberal progression become inappropriate, the only logical therapy consists in reducing markedly or stopping training temporarily: in this situation, there is no medical justification whatsoever to initiate a substitutive therapy.


Accelerated Rehabilitation in Non-operative Management of Acute Achilles Tendon Ruptures: A Systematic Review and Meta-analysis.
The optimal treatment and rehabilitation strategy for Achilles tendon ruptures is still under debate. There is a paradigm shift toward early mobilization and weightbearing. We examined the treatment effect of accelerated functional rehabilitation in nonoperative management of acute Achilles tendon ruptures. A systematic search of PubMed, EMBASE, and Web of Science databases for articles comparing accelerated versus delayed rehabilitation in the nonoperative management of acute Achilles tendon rupture was performed. Outcomes of interest were Achilles tendon rupture score (ATRS) (standardized patient-reported instrument related to symptoms and physical activity after treatment of an acute Achilles tendon rupture), rerupture rate, strength, range of motion, return to work, and sports. A total of 2001 articles were identified using our search strategy. We included 6 randomized controlled trials of interest. Although the concept of accelerated rehabilitation has gained popularity in recent years, no statistically significant differences could be revealed in any of the outcomes of interest. We performed a meta-analysis on the following outcomes: ATRS (mean difference -0.93 95% confidence interval [CI] -6.01 to 4.14), Rerupture rate (odds ratio [OR] 0.97, 95% CI: 0.46-2.03), Return to sports (OR 1.31, 95% CI 0.76-2.25), Return to work (mean difference 5.24, 95% CI to -12.04 to 22.51). The treatment effect of accelerated rehabilitation in nonoperatively treated patients seems to be small. However, we recommend accelerated rehabilitation for all conservatively treated patients, because it is a safe option and no detrimental effects have been described in the literature. Furthermore, many patients prefer this type of rehabilitation to avoid the practical disadvantages of prolonged immobilization.


Effect of racial background on motor cortical function as measured by threshold tracking transcranial magnetic stimulation.
A previous study using traditional paired-pulse TMS methods (amplitude-tracking) has reported differences in resting motor threshold (RMT) and short-interval intracortical inhibition (SICI) between healthy subjects of Caucasian and Han Chinese backgrounds, probably due to differences in the skull shape. The amplitude-tracking method delivers stimuli with constant intensity and causes substantial variabilities in motor-evoked potential amplitudes. To overcome this variability, threshold tracking transcranial magnetic stimulation (TT-TMS) has been developed. The present study aimed to investigate whether racial differences in motor cortical function exist, using TT-TMS. A total of 83 healthy volunteers (30 Caucasians, 25 Han Chinese, and 28 Japanese) were included in the present series. In TT-TMS and nerve conduction studies, electrodes were placed on the dominant limb, with measures recorded from the abductor pollicis brevis muscle. Stimulations were delivered with a circular coil, directly above the primary motor cortex. There were no significant differences at all the SICI intervals between races. Similarly, there were no significant differences in other measures of excitability including mean RMT, intracortical facilitation, and cortical silent period. Contrary to traditional amplitude-tracking TMS, motor cortical excitability and thereby motor cortical function is minimally influenced by racial differences when measured by TT-TMS. Recent studies have disclosed that SICI measured by TT-TMS differentiates amyotrophic lateral sclerosis (ALS) from ALS mimic disorders, with high sensitivity and specificity, in Caucasians. This study suggested that TT-TMS can be applied for the ALS diagnosis in Asian patients, as well as Caucasians.NEW & NOTEWORTHY Threshold tracking transcranial magnetic stimulation (TT-TMS) was applied for Caucasians, Han Chinese, and Japanese. No significant differences were found in TMS excitability indexes among races. Recent studies have disclosed that TT-TMS indexes differentiate amyotrophic lateral sclerosis (ALS) from ALS mimic disorders, with high sensitivity and specificity, in Caucasians. This study suggested that TT-TMS can be applied for the ALS diagnosis in Asian patients, as well as Caucasians.


Single-cell gel electrophoresis (the comet assay): loops or fragments?
Single-cell gel electrophoresis, or the comet assay, is widely used to measure DNA damage and repair. Upon electrophoresis, the DNA of lysed, agarose-embedded cells known as nucleoids, extends towards the anode in a structure resembling a comet, the relative intensity of the tail reflecting the frequency of DNA breaks. The structural organization of the DNA within comet preparations is not fully understood. We have used fluorescent in situ hybridization with large-insert genomic probes and human Cot-I DNA to investigate whether the production of the comet tail is simply explained by the relaxation of supercoiled DNA loops. We find that, under neutral electrophoresis conditions, when the tail and head DNA are double-stranded, the probed sequence of DNA is seen as a linear array, consistent with extension from a fixed point on the nuclear core or matrix. After alkaline electrophoresis, the appearance of the fluorescent probes suggests that linear DNA has coalesced into a granular form.


Congenital heart disease patients' and parents' perception of disease-specific knowledge: Health and impairments in everyday life.
Children and adolescents with congenital heart disease (CHD) and their families require qualified combined medical and psychosocial information, care, and counseling. This study aimed to analyze CHD patients' and parents' perception of disease-specific knowledge, state of health, and impairments experienced in everyday life, as well as factors influencing these perceptions. Analyses were based on a survey among patients/parents recruited via the German National Register for Congenital Heart Defects (NRCHD). The total sample (N = 818) was divided into four groups: "Children" (176 patients), "Adolescents" (142 patients), "Adults" (269 patients), and "Parents" (231 parents). The patients were stratified into those with simple and those with complex CHD. Descriptive and univariate analyses were performed. Patients' age and CHD severity were related to self-assessed state of health (P = .04 and P = .02). In addition, CHD severity was associated with worse impairment in everyday life (P < .001). Psychosocial support was related to the self-assessed state of health (P = .01) and the reported impairment in everyday life (P < .001). Patients' age, CHD severity, and psychosocial support seem to be related to self-assessed state of health and impairments in everyday life. To evaluate causality beyond associations, the development of patients' and parents' assessments and quality of life during the phase of transition from childhood to adulthood could be investigated by prospective long-term studies.


Schwann cells express motor and sensory phenotypes that regulate axon regeneration.
Schwann cell phenotype is classified as either myelinating or nonmyelinating. Additional phenotypic specialization is suggested, however, by the preferential reinnervation of muscle pathways by motoneurons. To explore potential differences in growth factor expression between sensory and motor nerve, grafts of cutaneous nerve or ventral root were denervated, reinnervated with cutaneous axons, or reinnervated with motor axons. Competitive reverse transcription-PCR was performed on normal cutaneous nerve and ventral root and on graft preparations 5, 15, and 30 d after surgery. mRNA for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 was expressed vigorously by denervated and reinnervated cutaneous nerve but minimally by ventral root. In contrast, mRNA for pleiotrophin (PTN) and glial cell line-derived neurotrophic factor was upregulated to a greater degree in ventral root. ELISA confirmed that NGF and BDNF protein were significantly more abundant in denervated cutaneous nerve than in denervated ventral root, but that PTN protein was more abundant in denervated ventral root. The motor phenotype was not immutable and could be modified toward the sensory phenotype by prolonged reinnervation of ventral root by cutaneous axons. Retrograde labeling to quantify regenerating neurons demonstrated that cutaneous nerve preferentially supported cutaneous axon regeneration, whereas ventral root preferentially supported motor axon regeneration. Schwann cells thus express distinct sensory and motor phenotypes that are associated with the support of regeneration in a phenotype-specific manner. These findings suggest that current techniques of bridging gaps in motor and mixed nerve with cutaneous graft could be improved by matching axon and Schwann cell properties.


Cardiovascular tissue banking in Europe.
In the past 50 years, human cardiovascular tissue allografts, also called homografts, have been implanted into patients with different valvular diseases. The use of these allografts and the number of cardiovascular tissue banks and their respective techniques increased. We conducted a survey to establish the quantity of allografts processed, and issued by, European tissue banks. The survey also included the collection of other relevant statistics. In 2011, the Foundation of European Tissue Banks collected data from 19 different cardiovascular tissue banks in 11 European countries. From 2007 to 2010 the data show a decrease in the number of hearts received, from 1700 to 1640 in 18 tissue banks; the average number of hearts received for cardiovascular tissue processing decreased from 113 to 91. The number of heart valves issued for transplantation increased from 1272 in 2007 to 1486 in 2010. The average rate of discard because of microbiological contamination was 20.7%, while 4.2% of the grafts were not used because of positive serology. Half of the tissue banks issued arterial grafts, while 3 banks also issued veins and pericardium. An overview of decontamination methods shows considerable methodological differencesbetween 17 cardiovascular tissue banks. From the experience in Europe, it can be concluded that cardiovascular tissue banks have an established place in the domain of cardiovascular surgery. The statistics show fluctuating data concerning the demand for human cardiovascular allografts and methodological questions. There is room for growth and improvement with respect to validation of decontamination methods.


The effect of hepatocyte growth factor on the initiation phase of liver regeneration after cold ischemia in a rat model of small-for-size liver transplantation.
In this study, adenovirus carrying human HGF gene (Ad-HGF) was administered to investigate whether hepatocyte growth factor (HGF) can restore liver regeneration after prolonged cold ischemia, especially during the initiation phase, in a rat model of small-for-size liver transplantation. A rat model was established using 30% small-for-size liver grafts. Before hand, the grafts were preserved at 4°C for 45min, 2h, 6h and 10h in UW solution. A recombinant adenoviral vector carrying HGF and Ad-HGF or adenovirus encoding enhanced green fluorescent protein (Ad-EGFP) was administered to the 10h group. Survival rates, serum levels of alanine aminotransferase, recovery of the graft weight, hepatic architecture, proliferating cell nuclear antigen (PCNA), cell signaling pathways and several immediate early genes (e.g. jun-B, c-fos) were assessed. Injury to the grafts and extent of inflammation of the small grafts increased due to prolonged cold ischemia, while the number of PCNA- positive hepatocytes decreased and liver regeneration mechanism was affected. These factors resulted in low levels of interleukin (IL)-6, tumor necrosis factor receptor (TNFR)- α , and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in liver tissue. Ad-HGF administration markedly improved the survival rate, but it did not significantly affect the other parameters. Prolonged cold ischemia significantly impaired the regenerative ability of small grafts. Ad-HGF promoted liver regeneration but had no observable effect on the initiation phase of liver regeneration.


Complete mitochondrial genome of Papilio elwesi and its phylogenetic analyses with other swallowtail butterflies (Lepidoptera, Papilionidae).
The complete mitochondrial genome of Papilio elwesi was sequenced and annotated using high-throughput sequencing in the present study. The mitochondrial genome (mitogenome) is a circular molecule of 15,082 bp in length, containing 37 genes (13 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes) and a putative control region. We performed mitogenomic phylogenetic analyses of 34 swallowtail species employing methods of Bayesian inference and maximum-likelihood. Our results further confirm that P. elwesi is a member of the subgenus Pterourus in Papilio sensu lato.


Characterization of the animal by-product meal industry in Costa Rica: Manufacturing practices through the production chain and food safety.
Animal by-product rendering establishments are still relevant industries worldwide. Animal by-product meal safety is paramount to protect feed, animals, and the rest of the food chain from unwanted contamination. As microbiological contamination may arise from inadequate processing of slaughterhouse waste and deficiencies in good manufacturing practices within the rendering facilities, we conducted an overall establishment's inspection, including the product in several parts of the process.An evaluation of the Good Manufacturing Practices (GMP) was carried out, which included the location and access (i.e., admission) to the facilities, integrated pest management programs, physical condition of the facilities (e.g., infrastructure), equipments, vehicles and transportation, as well as critical control points (i.e., particle size and temperature set at 50 mm, 133°C at atmospheric pressure for 20 min, respectively) recommended by the OIE and the European Commission. The most sensitive points according to the evaluation are physical structure of the facilities (avg 42.2%), access to the facilities (avg 48.6%), and cleaning procedures (avg 51.4%).Also, indicator microorganisms (Salmonella spp., Clostridium spp., total coliforms, E. coli, E. coli O157:H7) were used to evaluate the safety in different parts of the animal meal production process. There was a prevalence of Salmonella spp. of 12.9, 14.3, and 33.3% in Meat and Bone Meal (MBM), poultry by-products, and fish meal, respectively. However, there were no significant differences (P = 0.73) in the prevalence between the different animal meals, according to the data collected.It was also observed that renderings associated with the poultry industry (i.e., 92.0%) obtained the best ratings overall, which reflects a satisfactory development of this sector and the integration of its production system as a whole.


The Relationship between Number of Supernumerary Blastocysts Cryopreserved and Probability of a Live Birth Outcome after Single Fresh Blastocyst Transfer: Analysis of over 10 Thousand Cycles.
The ability to predict the likelihood of a live birth after single fresh embryo transfer is an important part of fertility treatment. While past studies have examined the likelihood of live birth based on the number of oocytes retrieved and cleavage-stage embryos available, the odds of a live birth based on the number of supernumerary blastocysts cryopreserved following a fresh embryo transfer has not been rigorously studied. We performed a retrospective analysis, stratified by age, on patients undergoing their first fresh autologous single day 5 blastocyst transfer to assess relationship between the likelihood of a live birth and number of supernumerary blastocysts cryopreserved. In patients aged <35 years and 35-39 years old, the likelihood of a live birth increased linearly between 1 and 6 supplementary blastocysts and non-linearly if 10 or more blastocysts were cryopreserved. When aged 40 years and above, the likelihood of a live birth increased linearly up to 4 cryopreserved blastocysts and then non-linearly if 10 or more blastocysts were cryopreserved. The present study demonstrated a non-linear relationship between the number of supernumerary blastocysts cryopreserved and the likelihood of a live birth after single blastocyst transfer in the first autologous fresh IVF/ICSI cycle across different age groups.


Impact of the Step-by-Step on febrile infants.
To evaluate the impact of introducing the Step-by-Step approach on care quality in young febrile infants. Observational study including infants ≤90 days old with fever without source seen in a paediatric emergency department 5 years before (n=1222) and after (n=1151) its introduction. Quality of care was evaluated in terms of adherence to recommendations, resource use and safety. Adherence: percentages of infants undergoing both urine and blood tests and infants <15 days old receiving full sepsis evaluation increased (84.7% vs 91.0% and 23.9% vs 63.3%, respectively; p<0.01). Resource use: lumbar puncture and admission rates decreased (24.1% vs 18.7% and 43.6% vs 38.3%, respectively; p<0.01), while the rate of antibiotic therapy increased (30.2% vs 43.2%; p<0.01). the invasive bacterial infection rate among infants managed as outpatients was unchanged (0.7% vs 0.3%; p=0.24). The introduction of the Step-by-Step increased the quality of care provided to young febrile infants.


Mitral valve area in combined mitral stenosis and regurgitation.
Eight patients with mixed mitral stenosis and regurgitation underwent hemodynamic and angiographic study prior to mitral valve replacement. The stenotic orifice of the mitral valve was calculated employing the total left ventricular stroke volume by cineangiography as the numerator of the Gorlin Formula. Excellent agreement with the measured orifice of the mitral valve was obtained using a value of 37.9 (0.85 X 44.5) for the constant in the Gorlin formula as recommended by Cohen and Gorlin. Recalculation of this constant independently by our data yielded a value that was almost identical. Regurgitant flows and orifice sizes were calculated for each patient using the same constant as for calculation of the stenotic orifices.


Selective extraction of palladium(II) with theophylline derivatives.
Theophylline derivatives with some kinds of alkyl chains were synthesized and used in extraction experiments involving metal ions. Theophylline derivatives have exhibited a high selectivity for palladium over other precious metals and base metals. The extraction of palladium from acidic chloride media has been investigated using theophylline derivatives (= RN) as extractants. Palladium(II) was found to be extracted with 7-octyltheophylline according to the following reaction: PdCl2 + 2RN <==> PdCl2(RN)2. The extraction equilibrium constant was determined to be K = 2.67 x 10(8) ( moldm(-3))(-2). In addition, the stripping of palladium was performed to an extent of 100% by a single batchwise treatment with a 1.0 mol dm(-3) ammonia solution. The stoichiometric relation in the extraction of palladium was supported by an analysis using mass spectrometry.


Topics and features of academic medical library tutorials.
In a 2007 study, librarians at the University of South Carolina School of Medicine Library examined freely available online tutorials on academic medical library Web sites. The team identified tutorial topics, determined common design features, and assessed elements of active learning in library-created tutorials; the team also generated a list of third-party tutorials to which medical libraries link. This article updates the earlier study, describing changes and trends in tutorial content and design on medical libraries' Web sites; the project team plans to continue to track trends in tutorial development by repeating this study annually.


Expectancy violations promote learning in young children.
Children, including infants, have expectations about the world around them, and produce reliable responses when these expectations are violated. However, little is known about how such expectancy violations affect subsequent cognition. Here we tested the hypothesis that violations of expectation enhance children's learning. In four experiments we compared 3- to 6-year-old children's ability to learn novel words in situations that defied versus accorded with their core knowledge of object behavior. In Experiments 1 and 2 we taught children novel words following one of two types of events. One event violated expectations about the spatiotemporal or featural properties of objects (e.g., an object appeared to magically change locations). The other event was almost identical, but did not violate expectations (e.g., an object was visibly moved from one location to another). In both experiments we found that children robustly learned when taught after the surprising event, but not following the expected event. In Experiment 3 we ruled out two alternative explanations for our results. Finally, in Experiment 4, we asked whether surprise affects children's learning in a targeted or a diffuse way. We found that surprise only enhanced children's learning about the entity that had behaved surprisingly, and not about unrelated objects. Together, these experiments show that core knowledge - and violations of expectations generated by core knowledge - shapes new learning.


A review of substance abuse research in malaysia.
This is a review of research done in the area of substance abuse in Malaysia. There were 109 articles related to substance abuse found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Only 39 articles were reviewed, and case series, case report, reviews and reports were excluded. Research reviewed include the epidemiology of substance abuse, genetics, treatment and its relation to health behaviour, and health management. Studies have shown that more males than females use drugs. There was also a high prevalence of blood-bourne virus diseases and sexually transmitted diseases among drug users. Two studies showed some genetic polymorphism (Cyp 3a4 gene and FAAH Pro129Thr) among heroin and amphetamine users respectively that may contribute to drug dependence. Study on pharmacological treatment for substance abuse were limited to methadone and it was shown to improve the quality of life of heroin dependant patients. Alternative treatments such as acupunture and spiritual approach play a role in the management of substance abuse. Data also showed that treatment centres for substance abuse are lacking facilities for screening, assessment and treatment for medical illness related to substance use, e.g. Hepatitis C and tuberculosis. Studies on the effectiveness of current drug rehabilitation centres were inconclusive.


[Allogenic stem cell transplantation following dose-reduced conditioning in patients with hematologic systemic diseases or solid tumors].
Allogeneic stem cell transplantation is an established treatment modality for a variety of hematologic malignancies. However this allogeneic stem cell transplantation carries the risk of severe complications which are partly due to the intensity of the conditioning regimen. Therefore, allogeneic stem cell transplantation has been so far only performed in younger patients with good performance status. Dose-reduced or non-myeloablative conditioning regimen has been proposed as an alternative that would allow exploiting the graft versus leukemia effect of allogeneic stem cell transplantation without severe toxicity. Clinical studies have shown that dose-reduced conditioning followed by allogeneic stem cell transplantation allows stable engraftment with lower toxicities which can be associated with long-term disease control. Therefore, dose-reduced conditioning followed by allogeneic stem cell transplantation can be offered to older and more debilitated patients who were no candidates for standard allogeneic stem cell transplantation.


Feasibility of preoperative supervised home-based exercise in older adults undergoing colorectal cancer surgery - A randomized controlled design.
Preoperative physical exercise is emerging as a growing field of research globally. There are still challenges in recruiting vulnerable older people, and time constraints in preoperative cancer care to consider. We therefore evaluated the feasibility of short-term supervised home-based exercise in older people prior to colorectal cancer surgery. This feasibility study was conducted between September 2016 and June 2018. People ≥70 years scheduled for colorectal cancer surgery were recruited and randomized to an intervention group receiving supervised home-based physical exercise at a high level of estimated exertion or a standard care group following the standard preoperative path. The exercise (respiratory, strength, and aerobic) consisted of 2-3 supervised sessions a week in the participants' homes, for at least 2-3 weeks or until surgery, and a self-administered exercise program in between. The primary outcome was process feasibility, including aspects specifically related to recruitment rate, compliance to the intervention, and acceptability. The secondary outcome was scientific feasibility including treatment safety, description of dose level and response, and estimation of treatment results. Twenty-three participants were included (recruitment rate 35%). A median of 6 supervised sessions was conducted over a 17-day exercise period. Compliance with the supervised sessions was 97%, and participants found the intervention acceptable. Concerning the self-administered exercise, a median of 19 inspiratory muscle training, 6 functional strength, and 8.5 aerobic sessions were reported. Challenges reported by program instructors were time constraints and difficulties in achieving high exercise intensities on the Borg CR-10 scale. A statistically significant between-group difference was only found in inspiratory muscle strength, favoring the intervention group (p<0.01). A short-term preoperative supervised home-based physical exercise intervention can be conducted, with respect to compliance and acceptability, in older people with similar physical status as in this study prior to colorectal cancer surgery. However, modifications are warranted with respect to improving recruitment rates and achieving planned intensity levels prior to conducting a definitive trial.


Carbon nanotube inner phase chemistry: the Cl- exchange SN2 reaction.
Density functional calculations have been carried out to investigate the nature of the inner phase of a (6,6) carbon nanotube, using the Cl(-) exchange S(N)2 reaction as an indicator. Inside the carbon nanotube the classical barrier height increases by 6.6 kcal/mol due to the nanotube polarizability. This suggests that the inner phase environment can be considered a form of solid solvation, offering the possibility of obtaining altered guest properties and reactivity through dielectric stabilization.


Th1 cytokines sensitize HER-expressing breast cancer cells to lapatinib.
The HER family of receptor tyrosine kinases has been linked to deregulation of growth and proliferation for multiple types of cancer. Members have therefore become thefocus of many drug and immune-based therapy innovations. The targeted anti-cancer agent, lapatinib, is a small molecule inhibitor that directly interferes with EGFR (HER-1)and HER-2 signaling, and indirectly reduces HER-3 signaling, thus suppressing important downstream events. A recently-developed dendritic cell-based vaccine against early breast cancer (ductal carcinoma in situ; DCIS) that generates strong Th1-dominated immunity against HER-2 has induced pathologic complete response in about one-third of immunized individuals. In vitro studies suggested cytokines secreted by Th1 cells could be major contributors to the vaccine effects including induction of apoptosis and suppression of HER expression. With a view toward improving complete response rates, we investigated whether the principle Th1 cytokines (IFN-γ and TNF-α) could act in concert with lapatinib to suppress activity of breast cancer lines in vitro. Lapatinib-sensitive SKBR3, MDA-MB-468 and BT474 cells were incubated with Th1 cytokines, lapatinib, or both. It was found that combined treatment maximized metabolic suppression(Alamar Blue assay), as well as cell death (Trypan Blue) and apoptosis(Annexin V/Propidium Iodide and TMRE staining). Combined drug plus cytokine treatment also maximized suppression of both total and phosphorylated forms of HER-2 and HER-3. Interestingly, when lapatinib resistant lines MDA-MB-453 and JIMT-1 were tested, it was found that the presence of Th1 cytokines appeared to enhance sensitivity for lapatinib-induced metabolic suppression and induction of apoptotic cell death, nearly abrogating drug resistance. These studies provide pre-clinical data suggesting the possibility that targeted drug therapy may be combined with vaccination to enhance anti-cancer effects, and furthermore that robust immunity in the form of secreted Th1 cytokines may have the capacity to mitigate resistance to targeted drugs.


[Intention, attitude, subjective norms and perception of control in Spanish adolescents about using Double Dutch].
With adolescence, boys and girls reach their sexual maturity and initiate their sexual encounters. They very frequently adopt risk behaviors as they tend not to use any contraceptive methods. Today's trend in relation to contraceptive methods is to recommend the combined utilization of condom and pill. In comparison to other methods, this last one, known as the Double Dutch (DD) method, has the advantage of preventing pregnancy and STD's, at the same time it increases the efficiency of contraception. Using the Theory of Planned Behavior the purpose of the study was to measure the intention, attitude, subjective norm and perceived behavioral control towards the utilization of the DD method among 15-16 year-old Spanish students and to determine the relationships among these variables. The results indicate that adolescents show favorable intention, attitude and subjective norm toward the utilization of the DD method. They seem to be more worried about pregnancy prevention than about STDs'prevention. Parents seem to be the most important reference people for adolescents, followed by their friends; the results show that at this age, adolescents tend to take into consideration these reference people's opinion.


Endoluminal Sphincter Augmentation with the MUSE™ System and GERDX™ System in the Treatment of Gastroesophageal Reflux Disease: A New Impact?
To bridge the gap between the long-term intake of proton pump inhibitors (PPIs) and the potential risks of laparoscopic fundoplication, a number of endoscopic procedures for the treatment of gastro-esophageal reflux disease (GERD) have been developed over the past 30 years. Because of the minimally invasive approach, short operative time, and efficacy in selected patients, endoluminal sphincter augmentation appears to be highly attractive. However, most early devices have proven to be unsafe or failed to provide long-term symptom relief. Accordingly, products for endoluminal sphincter augmentation have undergone several modifications to achieve an increased lower esophageal sphincter (LES) baseline pressure to re-establish the LES as an efficacious anti-reflux barrier. This paper reviews and discusses the two latest products for endoluminal sphincter augmentation, the MUSE™ device (Medigus, Ltd., Omer, Israel) and the GERDX™ system (G-SURG GmbH, Seeon-Seebruck, Germany). While the currently available literature has proven their effectiveness in principle, long-term results are lacking. Further studies and developments are necessary to determine whether these two new devices will truly impact GERD therapy.


Office diagnosis of sinus disorders: the role of ultrasound scanning.
The accurate diagnosis of sinus disorders has traditionally depended on history-taking, physical examination, and sinus radiographs. Other helpful tools include transillumination, sinus irrigation, and direct sinoscopy. Ultrasound scanning to define and follow the course of sinus disorders, although used for years in Europe, has only recently been introduced in this country. It is characterized as an inexpensive, non-invasive diagnostic aid which does not carry the risk of ionizing radiation. This paper discusses the use of ultrasound scanning in the management of sinus disorders commonly seen in office otolaryngologic practice, comparing it to other diagnostic modalities, and pointing out its advantages and shortcomings.


Prevalence of Periodontitis and Soft Tissue Lesions among Human Immunodeficiency Virus-positive Patients on Antiretroviral Therapy in Raichur Taluk, Karnataka, India.
In countries where human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is widespread and highly active antiretroviral therapy (HAART) medications are too expensive, or patients are failing HAART, oral disease management and risk remain an important issue. The aim of the study was to evaluate the prevalence of oral mucosal lesions and periodontitis among the HIV-positive adult patients and assess the association of these lesions with age, sex, duration of HIV, time on ART, dietary habits, and oral hygiene habits. Sample size was 170. Demographic data of the patients along with community periodontal index (CPI) and loss of attachment (LA) were recorded. Oral soft tissue lesions, such as ulcerations, sores, erosions, and fissures were also recorded. The study was carried out in Raichur Taluk, Karnataka, India. Convenience sampling design was followed. Statistical Package for the Social Sciences (SPSS) version 20.0 (Chicago, USA) was used for data analysis. Chi-square test was carried out; p < 0.05 was considered to be statistically significant. There was no association between the oral mucosal conditions and the age and the adverse habits, such as tobacco and alcohol, CD4 count, and the time duration of HIV and ART among these patients. A higher percentage of people with 4 to 5 mm of pockets was seen with those who cleaned their teeth with a finger, which was statistically significant. The present study highlights the poor condition of the oral health of these patients and their unmet dental needs.


Virginia Bioethics Network.
The Virginia Bioethics Network (VBN), a self-governing, self-supporting organization of Virginia healthcare institutions and other interested groups and individuals, was officially incorporated in the state of Virginia in December 1993.... The mission of the VBN is to advance the knowledge of biomedical ethics within Virginia healthcare institutions and their communities and to support the development of local institutional ethics programs and regional ethics networks throughout the state. The ultimate goal is enhancement of ethical decision making in the clinical setting with all pertinent factors, including community values, being given due consideration during the decision-making process....


Exploring analytical proteomics platforms toward the definition of human cardiac stem cells receptome.
Human cardiac stem cells (hCSC) express a portfolio of plasma membrane receptors that are involved in the regulatory auto/paracrine feedback loop mechanism of activation of these cells, and consequently contribute to myocardial regeneration. In order to attain a comprehensive description of hCSC receptome and overcoming the inability demonstrated by other technologies applied in receptor identification, mainly due to the transmembrane nature, high hydrophobic character and relative low concentration of these proteins, we have exploited and improved a proteomics workflow. This approach was based on the enrichment of hCSC plasma membrane fraction and addition of prefractionation steps prior to MS analysis. More than 100 plasma membrane receptors were identified. The data reported herein constitute a valuable source of information to further understand cardiac stem cells activation mechanisms and the subsequent cardiac repair process. All MS data have been deposited in the ProteomeXchange with identifier PXD001117 (http://proteomecentral.proteomexchange.org/dataset/PXD001117).


[Cytomegalovirus infection in the adult].
Aim of this report is to review the epidemiological and clinical features of HCMV infection in the adult. In all geographical areas high diffusion of HCMV infection involving all socioeconomic groups is observed; significant most elevated seroprevalence in North African and Asian ethnic groups is compared to Western populations is pointed out; besides, HCMV is absolutely the virus most frequently transmitted in the perinatal period. In the immunocompetent host, the HCMV infection is symptomless in the great majority of cases; in the symptomatic cases it shows the clinical features of a self-limited mononucleosis-like syndrome. In the immunocompromised patients, either in subjects infected with HIV or in onco-hematologic patients or recipients of solid organ or bone marrow transplants patients, HCMV infection leads to serious illness. The most frequent clinical pictures are: pneumonia, retinitis, hepatitis, polyradiculopathy, encephalitis, gastrointestinal tract disease, adrenal involvement; cases of myocarditis, pancreatitis, genitourinary localizations are less frequent. The clinical pictures are different in the different clinical groups: retinitis, in subjects with HIV infection and pneumonia in recipients of transplants, are respectively the main clinical manifestations; the mechanisms of such differences are not clearly defined. A to the diagnosis, the serological tests (evidence of IgM activity, IgG avidity) are useful in the immunocompetent host; whereas, in the immunocompromised host cytological detection (demonstration of typical cytological aspects and positive immunohistology for HCMV antigens) and/or virological detection (isolation of virus or evidence of viral antigens or viral DNA) are needed. The most used therapeutical choices are ganciclovir, foscarnet and cidofovir; these three drugs have similar antiviral effectiveness, but they show different outlines of toxicity and praticality of use.


PM1.0-Nitrite Heterogeneous Formation Demonstrated via a Modified Versatile Aerosol Concentration Enrichment System Coupled with Ion Chromatography.
Particulate nitrite is a critical source of hydroxyl radicals; however, it lacks high-resolution methods due to its low abundance and stability to explore its formation mechanism. In this study, a modified versatile aerosol concentration enrichment system (VACES) coupled with ion chromatography (IC) was used to measure particulate NO2- hourly online and achieve a lowered detection limit of 10-3 μg m-3. VACES-IC was used to observe a high- and low-concentration events of PM1.0-NO2- in Shanghai, corresponding to the ambient-level concentrations of 0.34 and 0.05 μg m-3, respectively. The morning peak concentrations of NO2- even exceeded 3σ (standard deviation) in the high-concentration event due to the reduction of NO2 by aerosol SO32- based on kinetics and regression analysis. This implies that controlling SO2 emissions would be an effective strategy to decrease morning NO2- concentrations, correspondingly reducing the kinetic formation of SO42- by 20.8-34.8%. However, after sunrise, NO2- formation was primarily attributed to NO2 hydrolysis at pH 4.97-6.14. In the low-concentration event, NO2 hydrolysis also accounted for an overwhelming proportion (∼90%) of NO2- formation. This work estimates the contribution of different paths to particulate NO2- formation based on newly established high-resolution measurements.


Intra- and interobserver agreement on radiographic phenotype in the diagnosis of canine hip dysplasia.
To investigate the repeatability and reproducibility of the presence of a circumferential femoral head osteophyte (CFHO), a curvilinear caudolateral osteophyte (CCO), osteosclerosis of the cranial acetabular edge (Scler CrAE), degenerative joint disease (DJD), and the diagnosis of suspected canine hip dysplasia (CHD) in different groups of experienced observers. Cross-sectional study. Standard hip extended radiographs (n = 50). Nine experienced observers were divided into 3 groups: surgeons (DECVS), radiologists (DECVDI), and non-board certified observers (NBC) and 2 subgroups (academics and non-academics). Cohen's kappa (κ) was calculated for CFHO, CCO, Scler CrAE, DJD, and suspected CHD, and weighted κ was calculated for DJD score to determine inter- and intraobserver agreement. Intraobserver agreement on CFHO, CCO, Scler CrAE, DJD, and suspected CHD ranged from slight to almost perfect, but was not significantly different between NBC, DECVS, and DECVDI. Radiologists and non-board certified observers had a more uniform scoring than surgeons on the overall DJD score, as did academics versus non-academics. Interobserver agreement for NBC was more uniform than that of radiologists and surgeons on CCO and DJD. NBC and radiologists scored more uniformly than surgeons on CFHO, and radiologists scored more uniformly than NBC and surgeons on Scler CrAE. Academics scored more uniformly than non-academics, but only significantly for Scler CrAE. Recognition of specific radiographic markers is only fairly reliable within and between experienced observers. Therefore, care must be taken to apply these traits in official screening, surgical decision-making and scientific research.


Treatment of manifest and impending pathologic fractures of the femoral neck by cemented hemiarthroplasty.
Thirty-four patients with manifest or impending pathologic fractures of the femoral neck were treated between 1971 and 1987. Breast carcinoma was the primary tumor in the majority of patients. All patients were treated with cemented hemiarthroplasty. Twenty-seven patients (79%) could walk at an average of nine days postoperatively. All patients experienced relief of pain. Two superficial wound dehiscences, one loosening of the prosthesis, and two prosthetic dislocations were encountered. Mean survival was 17.6 months overall (12 months for manifest fractures and 40 months for impending fractures). These results indicate that cemented hemiarthroplasty for pathologic fractures is a safe procedure resulting in long-lasting palliation without necessitating postoperative irradiation. The importance of tumor excochleation and the advantages of bone cement are emphasized.


Combined 677CC/1298AC genotypes of methylenetetrahydrofolate reductase (MTHFR ) reduce susceptibility to precursor B lymphoblastic leukemia in a Chinese population.
The methylenetetrahydrofolate reductase (MTHFR) encodes a major enzyme in folate metabolism. It has been suggested that two MTHFR polymorphisms, 677C>T and 1298A>C, influence risk of acute lymphoblastic leukemia (ALL). Most studies on relation of MTHFR polymorphisms to ALL susceptibility have been in pediatric populations because ALL is relatively rare in adults. Here, we report a case-control study of 127 Chinese patients with adult precursor B lymphoblastic leukemia (B-ALL) to examine correlation between the MTHFR polymorphisms and B-ALL susceptibility in adults. Our data show that although the prevalence of genotype 1298CC was significantly higher in the female patients than in the controls (P = 0.04), the differences in distributions of combined genotypes of 1298CC with either 677CC or 677CT between the cases and the controls were statistically insignificant. Haplotype analysis revealed no significant difference between the cases and the controls. The prevalence for joint MTHFR genotypes 677CC/1298AC was significantly lower in the female B-ALL cases than in the controls [odds ratio (OR) = 0.06, 95% CI = 0.00-0.53, P = 0.0033] and no differences among the men [OR = 0.71, 95% CI = 0.20-2.53, P = 0.55], suggesting that protective effects of combined MTHFR 677CC/1298AC genotypes on susceptibility of adult B-ALL are gender bias toward women with 677CC/1298AC women being at a 17-fold reduced odds to develop B-ALL.


Differences in the blast cells sensitivity to cytostatic drugs in various acute leukemia types and their clinical implications.
In 80 patients with AML, ALL, BC-CML and other proliferative blood diseases, the sensitivity of blast cells to cytostatics (vincristine, cytosine arabinoside, daunorubicin, l-asparaginase, hydrocortisone) was determined. The studies were made with the use of liquid scintillation measuring the inhibition of 3HTdR incorporation induced by the cytostatics tested. It has been shown that the method makes it possible to demonstrate individual reactivity of acute leukemia blasts to cytostatics. Variations in the individual sensitivity to cytostatics were mostly seen in acute myeloblastic leukemia, blastic crisis of chronic myelocytic leukemia, less often in acute lymphocytic leukemia.


Nucleotide sequence of the Mycobacterium leprae katG region.
Synthetic oligonucleotide primers based on the DNA sequence data of the Escherichia coli, Mycobacterium tuberculosis, and Mycobacterium intracellulare katG genes encoding the heme-containing enzyme catalase-peroxidase were used to amplify and analyze the Mycobacterium leprae katG region by PCR. A 1.6-kb DNA fragment, which hybridized to an M. tuberculosis katG probe, was obtained from an M. leprae DNA template. Southern hybridization analysis with a probe derived from the PCR-amplified fragment showed that the M. leprae chromosome contains only one copy of the putative katG sequence in a 3.4-kb EcoRI-BamHI DNA segment. Although the nucleotide sequence of the katG region of M. leprae was approximately 70% identical to that of the M. tuberculosis katG gene, no open reading frame encoding a catalase-peroxidase was detectable in the whole sequence. Moreover, two DNA deletions of approximately 100 and 110 bp were found in the M. leprae katG region, and they seemed to be present in all seven M. leprae isolates tested. These results strongly suggest that M. leprae lacks a functional katG gene and catalase-peroxidase activity.


[Cellular density of the femur head cartilage in relation to age].
The authors studied the cell density in samples of cartilage taken from the superior and inferior poles of the femoral heads of 65 subjects between 16 and 100 years of age. This study showed that the average cell density of the cartilage decreased significantly with age and that the decrease was proportionally identical in the two poles of the femoral head. In absolute values, the decrease in superficial cell densty is much greater in the inferior than in the superior pole. The relation between the decrease in cell density with age, cartilaginous lesions of senescence, and arthrosis are discussed.


Oligonucleotide microarray analysis of estrogen receptor alpha-positive postmenopausal breast carcinomas: identification of HRPAP20 and TIMELESS as outstanding candidate markers to predict the response to tamoxifen.
The estrogen receptor alpha (ER alpha) status of breast tumors is used to identify patients who may respond to endocrine agents such as tamoxifen. However, ER alpha status alone is not perfectly predictive, and there is a pressing need for more reliable markers of endocrine responsiveness. In this aim, we used a two-step strategy. We first screened genes of interest by a pangenomic 44 K oligonucleotide microarray in a series of ten ER alpha-positive tumors from five tamoxifen-treated postmenopausal patients who relapsed (distant metastasis) and five tamoxifen-treated postmenopausal patients who did not relapse, matched with respect to age, Scarff-Bloom-Richardson grade, lymph node status, and macroscopic tumor size. Genes of interest (n=24) were then investigated in an independent well-characterized series of ER alpha-positive unilateral invasive primary breast tumors from postmenopausal women who received tamoxifen alone as adjuvant hormone therapy after primary surgery. We identified four genes (HRPAP20, TIMELESS, PTPLB, and MGC29814) for which high mRNA levels were significantly associated with shorter relapse-free survival (log-rank test). We also showed that hormone-regulated proliferation-associated 20 kDa protein (HRPAP20) and TIMELESS are 17beta-estradiol-regulated in vitro and are ectopically expressed in OH-Tam-resistant cell lines. In conclusion, these findings point to HRPAP20 and TIMELESS as promising markers of tamoxifen resistance in women with ER alpha-positive breast tumors.


Thienopyrimidine ureas as novel and potent multitargeted receptor tyrosine kinase inhibitors.
A series of novel thienopyrimidine-based receptor tyrosine kinase inhibitors has been discovered. Investigation of structure-activity relationships at the 5- and 6-positions of the thienopyrimidine nucleus led to a series of N,N'-diaryl ureas that potently inhibit all of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. A kinase insert domain-containing receptor (KDR) homology model suggests that these compounds bind to the "inactive conformation" of the enzyme with the urea portion extending into the back hydrophobic pocket adjacent to the adenosine 5'-triphosphate (ATP) binding site. A number of compounds have been identified as displaying excellent in vivo potency. In particular, compounds 28 and 76 possess favorable pharmacokinetic (PK) profiles and demonstrate potent antitumor efficacy against the HT1080 human fibrosarcoma xenograft tumor growth model (tumor growth inhibition (TGI) = 75% at 25 mg/kg.day, per os (po)).


Effects of reactant heterogeneity and mixing on catabolite repression in cultures of Saccharomyces cerevisiae.
An experimental study was conducted into the effect of reactant heterogeneity on glucose-fed continuous cultures of S. cerevisiae, The heterogeneity was altered by varying mixing intensity in the nutrient entry region within a static mixing device. Experimental results confirm simulation predictions based upon a simple growth model, showing that mixing in the entry region can govern macroscopic culture behavior. Specifically, at high dilution rates, the biomass concentration was reduced by mixing patterns that increased the size of regions where glucose exceeded the threshold for catabolite repression. Because the size of such repressive regions is not uniquely determined by reactant segregation, the authors argue that in biological systems (and others involving a threshold response) an alternative measure of mixing quality should be used. Conclusions are drawn concerning the simulation of biological reactors for design purposes, and the importance of nutrient delivery systems to reactor performance.


How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion.
One approach to experimental science involves creating hypotheses, then testing them by varying one or more independent variables, and assessing the effects of this variation on the processes of interest. We use this strategy to compare the intellectual status and available evidence for two models or views of mechanisms of transmembrane drug transport into intact biological cells. One (BDII) asserts that lipoidal phospholipid Bilayer Diffusion Is Important, while a second (PBIN) proposes that in normal intact cells Phospholipid Bilayer diffusion Is Negligible (i.e., may be neglected quantitatively), because evolution selected against it, and with transmembrane drug transport being effected by genetically encoded proteinaceous carriers or pores, whose "natural" biological roles, and substrates are based in intermediary metabolism. Despite a recent review elsewhere, we can find no evidence able to support BDII as we can find no experiments in intact cells in which phospholipid bilayer diffusion was either varied independently or measured directly (although there are many papers where it was inferred by seeing a covariation of other dependent variables). By contrast, we find an abundance of evidence showing cases in which changes in the activities of named and genetically identified transporters led to measurable changes in the rate or extent of drug uptake. PBIN also has considerable predictive power, and accounts readily for the large differences in drug uptake between tissues, cells and species, in accounting for the metabolite-likeness of marketed drugs, in pharmacogenomics, and in providing a straightforward explanation for the late-stage appearance of toxicity and of lack of efficacy during drug discovery programmes despite macroscopically adequate pharmacokinetics. Consequently, the view that Phospholipid Bilayer diffusion Is Negligible (PBIN) provides a starting hypothesis for assessing cellular drug uptake that is much better supported by the available evidence, and is both more productive and more predictive.


Right ventricular involution: What can we learn from nature's model of compensated hypertrophy?
Right ventricular (RV) failure (RVF) is a vexing problem facing patients with various disease processes and carries a high mortality. RVF is a poorly understood phenomenon with limited treatment options. In mammalian fetal circulation, the right ventricle is the systemic ventricle. In neonates, however, the left ventricle assumes that role and gradually thickens compared with the right ventricle. This process, known as right ventricular involution (RVI), is poorly understood. We sought to define the time course and identify mechanisms involved in RVI. Wild-type mice were bred and sacrificed on day of life (DOL) 1, 4, 8, 16, and 30 to evaluate left ventricular (LV) and RV wall thickness and apoptosis. A terminal deoxynucleotidyl transferase nick-end labeling assay and RNA sequencing were performed to measure changes during RVI. Morphometric analysis demonstrated the changes in RV and LV wall thickness occurring between DOL 1 and DOL 16 (RV:LV, 0.53:0.44; P = .03). In addition, apoptosis was most active early, with the highest percentage of apoptotic cells on DOL 1 (1.0%) and a significant decrease by DOL 30 (0.23%) (P = .02). Similarly, expression of the proapoptotic genes BCL2l11 and Pawr were increased at DOL 1, and the antiapoptotic genes Nol3 and Naip2 were significantly increased at DOL 30. RVI is a misnomer, but significant changes occur early (by DOL 16) in neonatal mouse hearts. Apoptosis plays a role in RVI, but whether manipulation of apoptotic pathways can prevent or reverse RVI is unknown and warrants further investigation.


Assessment of Hospital Readmissions From the Emergency Department After Implementation of Medicare's Hospital Readmissions Reduction Program.
The Medicare Hospital Readmissions Reduction Program (HRRP) is associated with reduced readmission rates, but it is unknown how this decrease occurred. To examine whether the HRRP was associated with changes in the probability of readmission at emergency department (ED) visits after hospital discharge (ED revisits) overall and depending on whether admission is typically indicated for the patient's condition at the ED revisit. This retrospective cohort study used hospital and ED discharge data from California, Florida, and New York from January 1, 2010, to December 31, 2014. A difference-in-differences analysis examined change in readmission probability at ED revisits for recently discharged patients; ED revisits with clinical presentations for which admission is typically indicated vs those for which admission is more variable (ie, discretionary) were examined separately. Inclusion criteria were Medicare patients 65 years and older who revisited an ED within 30 days of inpatient discharge. Data were analyzed from December 18, 2018, to September 11, 2019. Before and after HRRP implementation among patients initially hospitalized for targeted vs nontargeted conditions. Thirty-day unplanned hospital readmissions at the ED revisit. A total of 9 914 068 index hospitalizations were identified in California, Florida, and New York from 2010 to 2014. Of 2 052 096 discharges in 2010, 1 168 126 (56.9%) discharges were women and 566 957 discharges (27.6%) were among patients older than 85 years. Among 1 421 407 patients with an unplanned readmission within 30 days of discharge, 1 266 107 patients (89.1%) were admitted through the ED. A total of 1 906 498 ED revisits were identified. After adjusting for patient demographic and clinical characteristics from the index hospitalization, HRRP implementation was associated with fewer readmissions from the ED, with a difference-in-difference estimate of -0.9 (95% CI, -1.4 to -0.4) percentage points (P < .001), or a 1.4% relative decrease from the 65.8% pre-HRRP readmission rates. Implementation of the HRRP was associated with fewer readmissions at the ED revisit involving clinical presentations for which admission is typically indicated (difference-in-differences estimate, -1.1 [95% CI, -1.6 to -0.6] percentage points; P < .001), or a 1.2% relative decrease from the 93.6% pre-HRRP rate. These results appear to be associated with patients presenting at the ED revisit with congestive heart failure (difference-in-difference estimate, -1.2 [95% CI, -2.0 to -0.4] percentage points; P = .003). These findings suggest that implementation of the HRRP was associated with a lower likelihood of readmission for recently discharged patients presenting to the ED, specifically for congestive heart failure. This highlights the critical role of the ED in readmission reduction under the HRRP and suggests that patient outcomes after HRRP implementation should be further studied.


Right heart thrombus-in-transit in a patient with Evans syndrome: A case report.
Right heart free-floating thrombus in the absence of structural heart disease or atrial fibrillation is rare. When it travels to the heart into the lung, called thrombus-in-transit, may cause cardiopulmonary collapse and sudden death. The clinical presentation varies from mild respiratory symptoms to sudden death; however, there are few clinical case reports of giant, free-floating thrombus in the right heart in an asymptomatic patient, and the optimal management options have not been established. A 36-year-old Asian woman presented to the emergency department with complaints of worsening swelling of the left lower extremity over 12 hours. Left leg deep vein thrombosis accompanied by an asymptomatic giant right atrial thrombus and pulmonary embolism with a rare autoimmune disease of Evans syndrome. Emergent surgical thrombectomy under cardiopulmonary bypass for right atrial thrombus. The postoperative course was uneventful, and she was discharged on the eighth postoperative day with normal heart function and mild tricuspid regurgitation. An additional diagnostic workup in cases of deep vein thrombosis is necessary for the rapid diagnosis of right heart thrombus and pulmonary embolism without delay. This case report illustrates that early recognition of venous thromboembolism and emergent thrombectomy of right heart thrombus-in-transit is crucial to prevent mortality.


In vitro determination of the mechanical and chemical properties of a fibre orthodontic retainer.
The aim of this study was to analyse, in vitro, the chemical and mechanical properties of a new fibre retainer, Everstick, comparing its characteristics with the requirements for an orthodontic retainer. Chemical analysis was used to examine seven fibre bundles exposed to a photocuring lamp and then to different acids and resistance to corrosion by artificial saliva fortified with plaque acids. The mechanical properties examined were tensile strength and resistance to flexural force. Ten fibre samples were tested for each mechanical analysis and the mean value and standard deviation were calculated. Wilcoxon signed rank test was used to evaluate change in weight after treatment in each group. To determine changes over time between the groups for each acid considered separately, both repeated measures analysis of variance (ANOVA) on original data and on rank transformed data were used. If the results were different, ANOVA on rank-transformed data was considered. Acetic acid was found to be the most corrosive and caused the most substance loss: both pure and at the salivary pH value. Hydrofluoric acid was the most damaging. For all acids analysed in both groups (lactic, formic, acetic, propionic), changes after treatment were statistically different between two groups (P < 0.001 for lactic, acetic, propionic; P = 0.004 for formic acid).The mean Young's modulus value was 68 510 MPa. Deformation before the fibre separated into its constituent elements (glass fibre and composite) was 3.9 per cent, stress to rupture was 1546 MPa, and resistance to bending was 534 MPa. The deflection produced over a length of 12 mm was 1.4 mm. The fibre bundle was attacked by acids potentially present in the oral cavity; the degree of aggressiveness depending on the acid concentration. To preserve fibre bundles long term, careful plaque control is necessary, especially in the interproximal spaces, to avoid acid formation. The tested product was found to be sufficiently strong to oppose flexural and occlusal forces.


Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience.
In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features. We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells. In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive. The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.


High-attenuation recent thrombus of the portal vein: CT demonstration and clinical significance.
Attenuation characteristics of portal vein thrombi on nonenhanced computed tomographic (CT) scans were assessed in 122 patients with proved portal vein thrombosis. Portal vein thrombi of high attenuation were found in four patients with hepatocellular carcinoma. From pathologic and radiologic studies, it was concluded that the high attenuation was caused by blood clots of recent onset formed at the tip of tumor thrombus. Differentiation from choledocholithiasis, hematobilia, and calcification of thrombi could be easily made by means of ultrasonography (US). Although plain CT is usually considered noncontributory in the diagnosis of venous thrombosis, it enabled the differentiation of recent thrombus in these four patients. Tumor thrombus in the major branches or main trunk of the portal vein is indicative of poor prognosis. When hepatic mass and high-attenuation portal vein thrombi are demonstrated with plain CT and substantiated by US, enhanced CT and angiography may be unnecessary for treatment of patients with advanced hepatocellular carcinoma.


A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse.
The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.


FSM-F: Finite State Machine Based Framework for Denial of Service and Intrusion Detection in MANET.
Due to the continuous advancements in wireless communication in terms of quality of communication and affordability of the technology, the application area of Mobile Adhoc Networks (MANETs) significantly growing particularly in military and disaster management. Considering the sensitivity of the application areas, security in terms of detection of Denial of Service (DoS) and intrusion has become prime concern in research and development in the area. The security systems suggested in the past has state recognition problem where the system is not able to accurately identify the actual state of the network nodes due to the absence of clear definition of states of the nodes. In this context, this paper proposes a framework based on Finite State Machine (FSM) for denial of service and intrusion detection in MANETs. In particular, an Interruption Detection system for Adhoc On-demand Distance Vector (ID-AODV) protocol is presented based on finite state machine. The packet dropping and sequence number attacks are closely investigated and detection systems for both types of attacks are designed. The major functional modules of ID-AODV includes network monitoring system, finite state machine and attack detection model. Simulations are carried out in network simulator NS-2 to evaluate the performance of the proposed framework. A comparative evaluation of the performance is also performed with the state-of-the-art techniques: RIDAN and AODV. The performance evaluations attest the benefits of proposed framework in terms of providing better security for denial of service and intrusion detection attacks.


In vitro synergistic activity of diketopiperazines alone and in combination with amphotericin B or clotrimazole against Candida albicans.
The synergistic anticandidal activity of three diketopiperazines [cyclo-(L-Pro-L-Leu) (1), cyclo-(D-Pro-L-Leu) (2), and cyclo-(D-Pro-L-Tyr) (3)] purified from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) in combination with amphotericin B and clotrimazole was investigated using the macrodilution method. The minimum inhibitory concentration and minimum fungicidal concentration of the diketopiperazines was compared with that of the standard antibiotics. The synergistic anticandidal activities of diketopiperazines with amphotericin B or clotrimazole were assessed using the checkerboard and time-kill methods. The results of the present study showed that the combined effects of diketopiperazines with amphotericin B or clotrimazole predominantly recorded synergistic (<0.5). Time-kill study showed that the growth of the Candida was completely attenuated after 12-24 h of treatment with 50:50 ratios of diketopiperazines and antibiotics. These results suggest that diketopiperazines combined with antibiotics may be microbiologically beneficial and not antagonistic. These findings have potential implications in delaying the development of resistance as the anticandidal effect is achieved with lower concentrations of both drugs (diketopiperazines and antibiotics). The cytotoxicity of diketopiperazines was also tested against two normal human cell lines (L231 lung epithelial and FS normal fibroblast) and no cytotoxicity was recorded for diketopiperazines up to 200 μg/mL. The in vitro synergistic activity of diketopiperazines with antibiotics against Candida albicans is reported here for the first time.


Treatment of von Willebrand's disease and hypofibrinogenemia with single donor cryoprecipitate from plasma exchange donation.
Conventional replacement therapy for hypofibrinogenemia and von Willebrand's disease requires multiple donor exposures and a correspondingly high risk of blood-borne infection. We describe the collection and successful use of cryoprecipitate derived from a single donor by plasma exchange donation to support such patients through major hemostatic stresses. The father of an epileptic patient with von Willebrand's disease produced cryoprecipitate containing 23,546 units of von Willebrand factor (vWF) in nine desmopressin-stimulated donations; this provided total factor replacement for neurosurgery to remove a seizure focus. The average yield was 2,616 units per donation and the average VWF concentration in cryoprecipitate was 17.7 units/ml. The husband of a hypofibrinogenemic patient with a history of postpartum hemorrhage provided cryoprecipitate containing 13.4 g of fibrinogen in five donations; this supported his wife through parturition without recourse to other blood products. The average yield was 2.7 g per donation, and the average fibrinogen concentration was 15.3 g/liter. Plasma exchange donation is a practical alternative source for cryoprecipitate. It can provide vWF and fibrinogen that carry a reduced risk of infectious disease transmission.


Endometrial Immune Profiling: A Method to Design Personalized Care in Assisted Reproductive Medicine.
Objective: To assess the efficiency of the endometrial immune profiling as a method to design personalized care to enhance the pregnancy rate in a large heterogeneous infertile population. We hypothesized that some reproductive failures could be induced by a uterine immune dysregulation which could be identified and corrected with a targeted plan. Design: Prospective cohort study. Setting: Multicentric study. Intervention(s) and Main outcome measure(s): One thousand and seven hundred thirty-eight infertile patients had an immune profiling on a timed endometrial biopsy between 2012 and 2018. This test documented the absence or the presence of an endometrial immune dysregulation and identified its type. In case of dysregulation, a targeted personalized plan was suggested to the treating clinician aiming to supply the anomaly. One year after the test, the clinician was contacted to provide the outcome of the subsequent embryo transfer with the applied suggested plan. Result(s): After testing, 16.5% of the patients showed no endometrial immune dysregulation, 28% had a local immune under-activation, 45% had a local immune over-activation, and 10.5% had a mixed endometrial immune profile. In patients with a history of repeated implantation failures (RIF) or recurrent miscarriages (RM), the pregnancy rate was significantly higher if an endometrial dysregulation was found and the personalized plan applied, compared to the patients with an apparent balanced immune profile (respectively 37.7 and 56% vs. 26.9 and 24%, p < 0.001). In contrast, in good prognosis IVF (in vitro fertilization) subgroup and patients using donor eggs, this difference was not significant between dysregulated and balanced subgroups, but higher pregnancy rates were observed in absence of dysregulation. For patients with immune over-activation, pregnancy rates were significantly higher for patients who had a test of sensitivity, regarding the type of immunotherapy introduced, when compared to the ones who did not (51 vs. 39.9%, p = 0.012). Conclusion(s): Local endometrial immunity appears to be a new and important parameter able to influence the prognosis of pregnancy. Targeted medical care in case of local immune dysregulation resulted in significantly higher pregnancy rates in RIF and RM patients.


Photophysics and photochemistry of horseradish peroxidase A2 upon ultraviolet illumination.
Detailed analysis of the effects of ultraviolet (UV) and blue light illumination of horseradish peroxidase A2, a heme-containing enzyme that reduces H(2)O(2) to oxidize organic and inorganic compounds, is presented. The effects of increasing illumination time on the protein's enzymatic activity, Reinheitzahl value, fluorescence emission, fluorescence lifetime distribution, fluorescence mean lifetime, and heme absorption are reported. UV illumination leads to an exponential decay of the enzyme activity followed by changes in heme group absorption. Longer UV illumination time leads to lower T(m) values as well as helical content loss. Prolonged UV illumination and heme irradiation at 403 nm has a pronounced effect on the fluorescence quantum yield correlated with changes in the prosthetic group pocket, leading to a pronounced decrease in the heme's Soret absorbance band. Analysis of the picosecond-resolved fluorescence emission of horseradish peroxidase A2 with streak camera shows that UV illumination induces an exponential change in the preexponential factors distribution associated to the protein's fluorescence lifetimes, leading to an exponential increase of the mean fluorescence lifetime. Illumination of aromatic residues and of the heme group leads to changes indicative of heme leaving the molecule and/or that photoinduced chemical changes occur in the heme moiety. Our studies bring new insight into light-induced reactions in proteins. We show how streak camera technology can be of outstanding value to follow such ultrafast processes and how streak camera data can be correlated with protein structural changes.


Cognitive Training Sustainably Improves Executive Functioning in Middle-Aged Industry Workers Assessed by Task Switching: A Randomized Controlled ERP Study.
Recently, we reported results of a cross-sectional study investigating executive functions in dependence of aging and type of work. That study showed deficits in performance and electrophysiological activity in middle-aged workers with long-term repetitive and unchallenging work. Based on these findings, we conducted a longitudinal study that aimed at ameliorating these cognitive deficits by means of a trainer-guided cognitive training (CT) in 57 further middle-aged workers with repetitive type of work from the same factory. This study was designed as a randomized controlled trail with pre- (t1), post- (t2), and a 3-month follow-up (t3) measure. The waiting control group was trained between t2 and t3. The training lasted 3 months (20 sessions) and was evaluated with the same task switching paradigm used in the previous cross-sectional study. The CT improved performance in accuracy at the behavioral level and affected the electrophysiological correlates of retrieval of stimulus-response sets (P2), response selection (N2), and error detection (Ne), thus unveiling the neuronal background of the behavioral effects. The same training effects were observed in the waiting control group after CT at t3. Moreover, at t3, most of the behavioral and electrophysiological training-induced changes were found stable. Hence, CT appears to be an important intervention for compensating cognitive deficits in executive functions in middle-aged employees with cognitively unchallenging work.


Pseudo-obstruction of the biliary tract associated with a traumatic biliary fistula.
Documentation of a biliary fistula as a complication of hepatic trauma may be made simply and noninvasively using radionuclide cholescintigraphy. This report describes the utility of this approach in the evaluation of the pathophysiology underlying apparent biliary obstruction in a patient with a large traumatic biliary fistula.


Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.
Stem cell lines that faithfully maintain the regional identity and developmental potency of progenitors in the human brain would create new opportunities in developmental neurobiology and provide a resource for generating specialized human neurons. However, to date, neural progenitor cultures derived from the human brain have either been short-lived or exhibit restricted, predominantly glial, differentiation capacity. Pluripotent stem cells are an alternative source, but to ascertain definitively the identity and fidelity of cell types generated solely in vitro is problematic. Here, we show that hindbrain neuroepithelial stem (hbNES) cells can be derived and massively expanded from early human embryos (week 5-7, Carnegie stage 15-17). These cell lines are propagated in adherent culture in the presence of EGF and FGF2 and retain progenitor characteristics, including SOX1 expression, formation of rosette-like structures, and high neurogenic capacity. They generate GABAergic, glutamatergic and, at lower frequency, serotonergic neurons. Importantly, hbNES cells stably maintain hindbrain specification and generate upper rhombic lip derivatives on exposure to bone morphogenetic protein (BMP). When grafted into neonatal rat brain, they show potential for integration into cerebellar development and produce cerebellar granule-like cells, albeit at low frequency. hbNES cells offer a new system to study human cerebellar specification and development and to model diseases of the hindbrain. They also provide a benchmark for the production of similar long-term neuroepithelial-like stem cells (lt-NES) from pluripotent cell lines. To our knowledge, hbNES cells are the first demonstration of highly expandable neuroepithelial stem cells derived from the human embryo without genetic immortalization.


CT characteristics and diagnostic value of COVID-19 in pregnancy.
To investigate the computed tomography (CT) characteristics and diagnostic value of novel coronavirus pneumonia (NCP or COVID-19) in pregnancy. This study included ten pregnant women infected with COVID-19, treated in the Zhongnan Hospital of Wuhan University from January 20, 2020 to February 6, 2020. Clinical and chest CT data were collected and clinical symptoms, laboratory indicators, and CT images were analyzed to explore CT characteristics and diagnostic value for COVID-19 during pregnancy. Laboratory examination showed that white blood cell count was normal in nine patients, and slightly higher in one patient (10.23 × 109). The lymphocyte ratio decreased in two patients by 12% and 14%, respectively. The levels of C-reactive protein was elevated in seven patients (range, 21.16-60.3 mg/L) and the levels of D-dimer was increased in eight patients (range, 507-2141 ng/mL). Six patients had low levels of total protein (range, 35.3-56.5 mg/L). Two patients showed small patchy ground glass opacity (GGO) involving single lung, while eight patients showed multilobe GGO in both the lungs, with partial consolidation. Peripheral and non-peripheral lesion distributions were seen in ten (100%) and four (40%) patients, respectively. There were four patients who had signs of intra-bronchial air-bronchogram, six patients had small bilateral pleural effusions, while none had lymphadenopathy. Dynamic observations were performed in four patients after COVID-19 treatment. Among these four patients, one patient showed normal on the initial examination, and new lesions were observed after 3 days; 1 patient showed progression after 7 days of treatment, with expansion of the lesion area; and the other 2 patients showed improvement after 14 days of treatment, with reduction in the density and area of lesions and appearance of linear opacity. The CT characteristics of COVID-19 in pregnancy were mainly observed in early and progressive stages, and multiple new lesions were common. And there were consolidations of varying sizes and degrees within the lesion. Moreover, the original ground glass lesions could be fused or partially absorbed. Six patients had small bilateral pleural effusion. In summary, CT scans can play an important role in early screening, dynamic observation, and efficacy evaluation of suspected or confirmed cases of pregnant women with COVID-19.


Recurrent carotid artery stenosis following endarterectomy.
Spectral analysis was used to examine 257 carotid arteries in 227 patients who had undergone carotid endarterectomy at 1, 3, 6, and 12 months after surgery and annually thereafter. Routine intraoperative completion angiography ensured that the operations were technically satisfactory. Postoperative restenoses were identified in 38 patients (15%). In 23 arteries (9%), the restenosis exceeded a 50% diameter reduction while in 15 arteries (6%) the stenosis was less than 50% of the diameter. Restenosis developed in 24/96 women (25%) and 14/161 men (9%). Twenty-nine (70%) stenotic lesions occurred within 12 months. In three patients early lesions regressed. Reoperation with patch angio-plasty was required in six patients. When the 219 carotid arteries that remained widely patent were compared to the 38 that restenosed , no differences were noted for age, diabetes mellitus, hypertension, smoking, or degree of preoperative stenosis. Early stenotic lesions appear to be due to myointimal hyperplasia, which is probably platelet mediated. The predominant female sex distribution may be explained by differences in platelet responsiveness in men and women.


[Controlled clinical study on the efficacy of tiropramide hydrochloride in the treatment of irritable colon: comparison with octylonium bromide].
The effectiveness of a new calmodulin-independent spasmolytic, tiropramide hydrochloride, and octylonium bromide, an antispasmodic calmodulin-antagonist drug, was compared in a controlled trial performed in 60 patients with irritable bowel syndrome with spastic pattern. The effect of treatments was assessed according to the score reduction of following symptoms: abdominal pain, constipation, bloating and dyspepsia. Tiropramide hydrochloride administered at the daily dose of 300 mg for 30 days induced a faster and higher improvement than that observed during the administration of 120 mg daily of octylonium bromide. On 3rd and 5th day, treatment with tiropramide induced the relief of abdominal pain in a significantly greater percentage of patients (p less than 0.05). Besides, in the group of subjects treated with this drug the "pain" score was more markedly decreased. Furthermore, at the end of the study 88% of subjects treated with tiropramide and 47% with octylonium bromide had normal bowel habits. This difference was statistically significant (p less than 0.05). Both treatments are effective in reducing dyspeptic symptoms and bloating. We can conclude that tiropramide--having a significant antispasmodic effect combined with a regulating effect on bowel habits--besides eliminating spasm, would act by synchronizing and therefore normalizing the intestinal motility.


Comparative transcriptomic analysis of genes involved in stem lignin biosynthesis in woody and herbaceous Paeonia species.
Paeonia is recognized globally due to its ornamental value. However, the mechanisms behind the formation of distinct levels of lignification in Paeonia stems remain largely unknown. In this study, we selected three representative Paeonia species, namely P. ostii (shrub), P. lactiflora (herb), and P. × 'Hexie' (semi-shrub), to evaluate and contrast their respective anatomical structure, phytochemical composition and transcriptomic profile. Our results showed that the degree of lignin deposition on the cell wall, along with the total amount of lignin and its monomers (especially G-lignin) were higher in P. ostii stems compared to the other two species at almost all development stages except 80 days after flowering. Furthermore, we estimated a total number of unigenes of 60,238 in P. ostii, 43,563 in P. × 'Hexie', and 40,212 in P. lactiflora from stem transcriptome. We then built a co-expression network of 25 transcription factors and 21 enzyme genes involved in lignin biosynthesis and identified nine key candidate genes. The expression patterns of these genes were positively correlated with the transcription levels of PAL, C4H, 4CL2, CCR, and COMT, as well as lignin content. Moreover, the highest relative expression levels of CCR, 4CL2, and C4H were found in P. ostii. This study provides an explanation for the observed differences in lignification between woody and herbaceous Paeonia stems, and constitutes a novel reference for molecular studies of stem-specific lignification process and lignin biosynthesis that can impact the ornamental industry.


Promoting autonomy of the client with persistent mental illness: a challenge for occupational therapists from The Netherlands, Germany and Belgium.
The aim of this study was to determine how occupational therapists from The Netherlands, Germany and Belgium promote the autonomy of clients with persistent mental illness. Sixty occupational therapists working in psychosocial mental health completed two semi-structured questionnaires. Data were analysed by applying the constant comparative method. The results of the study show the importance of handling motivation in relation to personal autonomy and the different strategies occupational therapists use in promoting autonomy. In conclusion, enhancing clients' personal autonomy will empower and help them to discover meaningful occupations. More in-depth information could have been obtained using an interview in combination with observations. Further research is needed to evaluate the effectiveness of strategies used by occupational therapists in promoting clients' autonomy.


PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway.
Protein phosphatase 1 (PP1) inhibitors play a role in tumor progression through different mechanisms. Protein phosphatase 1 regulatory subunit 14D (PPP1R14D) is an inhibitor of PP1. However, the role of PPP1R14D in tumors and its mechanism of action are largely unknown. The purpose of the present study was to investigate the expression, function and mechanism of PPP1R14D in lung adenocarcinoma (LUAD). In the present study, GEPIA database analysis and immunohistochemistry demonstrated that PPP1R14D was highly expressed in LUAD tissues and that the expression of PPP1R14D in LUAD was negatively correlated with the age of patients and positively correlated with the 8th American Joint Committee on Cancer staging among patients. In addition, Kaplan‑Meier Plotter database analysis showed that PPP1R14D expression was associated with lower survival rates in patients with LUAD. PPP1R14D knockdown significantly inhibited LUAD cell proliferation, migration and invasion and induced LUAD cell arrest at the G1 phase of the cell cycle. Mechanistic analyses revealed that PPP1R14D knockdown may inhibit cell proliferation, migration and invasion by inactivating PKCα/BRAF/MEK/ERK pathway signaling and its downstream key proteins c‑Myc/Cyclin E1‑CDK2 and MMP2/MMP9/Vimentin. Moreover, knockdown of PPP1R14D suppressed tumor growth in vivo. All these results showed that PPP1R14D plays an important role in LUAD tumorigenesis and may serve as a potential prognostic factor and therapeutic target in LUAD.