Performance of a novel vertical flow constructed wetland for greywater treatment in rural areas in Jordan.
Jordan is facing severe challenges in terms of water scarcity and wastewater management. Thus, there is a growing need for adopting innovative approaches to overcome these challenges. Within the framework of this study, a pilot project was implemented to treat household greywater in rural areas in Jordan with a purpose of reuse for irrigation. The project consists of designing and developing four vertical flow constructed wetland (VFCW) systems located in different sites and integrating them in a decentralized treatment system. The project work aims particularly to present a model of an innovative, compact and effective modified VFCW system. The performance of the systems was assessed by analyzing the quality of the influent and effluent streams through testing 19 water quality parameters. The results revealed that the design was adequate and efficient in treating greywater as exemplified by removal efficiencies of 90%, 90% and 92% for BOD, COD and TSS respectively. Moreover, the other physico-chemical parameters (T-N, T-P, N-NO3-, Turbidity, Ca, Mg, SO4-, and heavy metals) measured in the effluent streams complied all with the Jordanian standards for unrestricted irrigation. Therefore, the outcomes of the current study can be invested to support the use of constructed wetlands in Jordan as a sustainable technology to improve the wastewater management practices and reinforce the decentralized wastewater treatment approach in rural areas.


Clopidogrel-induced Eosinophilia with Hypercalcemia.
There are few cases describing the association of eosinophilia with hypercalcemia, and drug-induced eosinophilia with hypercalcemia has not been reported. A 74-year-old man had been diagnosed with asthma 4 months earlier. He was admitted due to eosinophilia with hypercalcemia. Chest computed tomography showed a nodule in the left lung and mediastinal lymphadenopathy. By obtaining a detailed medical history, clopidogrel was suspected as the prime cause of eosinophilia. After the discontinuation of clopidogrel, the eosinophilia with hypercalcemia, lung nodule and mediastinal lymphadenopathy improved. Clopidogrel-induced eosinophilia can potentially cause hypercalcemia. Obtaining a detailed clinical history is important in diagnosing the cause of eosinophilia.


Do you like me? Neural correlates of social evaluation and developmental trajectories.
Social acceptance is of key importance for healthy functioning. We used functional magnetic resonance imaging (fMRI) to examine age-related changes in the neural correlates of social acceptance and rejection processing. Participants from four age groups participated in the study: pre-pubertal children (8-10 years), early adolescents (12-14 years), older adolescents (16-17 years) and young adults (19-25 years). During the experiment, participants were presented with unfamiliar faces of peers and were asked to predict whether they expected to be liked or disliked by the other person, followed by feedback indicating acceptance or rejection. Results showed that activation in the ventral mPFC and striatum to social feedback was context-dependent; there was increased activation when participants had positive expectations about social evaluation, and increased activation following social acceptance feedback. Age-related comparisons revealed a linear increase in activity with age in these brain regions for positive expectations of social evaluation. Similarly, a linear increase with age was found for activation in the striatum, ventral mPFC, OFC, and lateral PFC for rejection feedback. No age-related differences in neural activation were shown for social acceptance feedback. Together, these results provide important insights in the developmental trajectories of brain regions implicated in social and affective behavior.


[Extract of Herba Siegesbeckiae on mouse rheumatoid arthritis induced by anthrogen-CIA monoclonal antibody].
To investigate the anti-inflammatory effect of Herba Siegesbeckiae extracts on mouse rheumatoid arthritis induced by arthrogen-CIA monoclonal antibody. The rheumatoid arthritis was induced by arthrogen-CIA arthritogenic monoclonal antibody in mice. The sandwich enzyme-linked immunosorbent assay was used to determine the concentration of IL-1βin mouse serum,and the content of IL-6,IL-17 and MMP-3 in supernatant of tissue homogenate of hind limb below the stifle of mice. One-way ANOVA was used for data analysis. The toe swelling was attenuated in Siegesbeckiae group than that in model group [(0.218 ± 0.0307)cm(3) compared with (0.2545 ± 0.0179)cm(3), P<0.05]. The serum IL-1β level in Siegesbeckiae group was lower than that in model group [(63.74 ± 21.74)pg/ml compared with (104.96 ± 31.22)pg/ml, P<0.01]. The contents of IL-6, IL-17 and MMP-3 in tissue supernatants of Siegesbeckiae group were all lower than those of model group [(171.10 ± 48.35)pg/ml compared with (249.64 ± 75.08)pg/ml, P<0.05; (115.42 ± 56.52)pg/ml compared with (208.40 ± 88.54)pg/ml, P<0.05;(3660.31 ± 1680.99) pg/ml compared with (5420.79 ± 1201.43)pg/ml, P<0.05, respectively]. The extract of Herba Siegesbeckiae has anti-inflammatory effect on mouse rheumatoid arthritis induced by mixed arthrogen monoclonal antibody.


Alcohol consumption and the gastrointestinal tract.
Alcohol is one of the most commonly abused drugs, with a per capita consumption of approximately 10 L pure ethanol per year in the United States and even higher in Spain and France. In terms of mortality, the effect of alcohol on the liver and the pancreas is probably more significant than on the tubular gastrointestinal tract. However, alcohol is a very important cause of morbidity in the tubular gastrointestinal tract. Alcohol influences the motility in the esophagus, stomach and small bowel and has direct effects on the mucosa of the upper tract. While the stimulation of gastric acid secretion is inversely correlated with the alcohol concentration of the beverage, a direct pathogenetic role in peptic ulcer disease has not been demonstrated. Some alcohols, like red wine, have been shown to possess an anti-Helicobacter pylori effect. Alcohol also has a role in the development of tumors of the gastrointestinal tract.


Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data.
Cytochrome P4502D6 (CYP2D6) is a highly polymorphic gene locus with > 50 variant alleles which lead to a wide range in enzymatic activity. So called poor metabolizers are carriers of any two non-functional alleles of the CYP2D6 gene. CYP2D6 genotyping is cumbersome and the question of how much genotyping is necessary for an accurate phenotype prediction is still debated. The goal of this study was to determine the optimum amount of genotyping required to accurately predict the phenotype at a reasonable cost in a white North American population. To address this issue, we designed a polymerase chain reaction (PCR)/restriction fragment length polymorphism-based genotyping strategy to detect 'key' mutations linked to extensive metabolizer or poor metabolizer associated alleles in combination with extra-long PCR (XL-PCR). All mutations with the exception of gene deletions and duplications are detectable by simple restriction digestion analysis and agarose gel electrophoresis. In addition, we utilized a genotyping algorithm based on our own and published allele frequency data and phenotype analysis to calculate the probability of a correct genotype (and thus, phenotype) assignment. As little as one XL-PCR reaction followed by a maximum of six reamplification reactions allows an accurate prediction of an individual's genotype to 99.15%. As few as four reamplification reactions identify 97.9% of poor metabolizer individuals. We evaluated our model in 208 white North Americans by testing for the presence of 'key' mutations linked to CYP2D6*2, *3, *4, *6, *7, *8, *9, *10, *11, *12, *15, *17 and *18 alleles and the *5, *13 and *16 gene deletions. For all individuals, the correct phenotype has been predicted. Discordant phenotype assignment occurred in only two individuals which subsequently was attributed to CYP2D6 inhibition by concomitant drug therapy.


[Aneurysm of the anterior mitral leaflet - echocardiographic description].
Aneurysm of the anterior mitral leaflet is a rare complication of infective aortic valve endocarditis. The natural history of which is generally its rupture, with subsequent acute and severe mitral regurgitation. We describe a 78 years-old man without history of endocarditis, in whom transthoracic echocardiography was sufficient and transesophageal echocardiography was essential for the diagnosis of this lesion.


Three-Dimensional Bone Block Planning for Mandibular Sagittal Bone Defect Reconstruction.
Bone defects seen in severe sagittal discrepancies between the maxilla and mandible do not solely qualify for orthodontic treatment. An interdisciplinary approach with the aid of a surgical, orthodontic, and periodontal team should be implemented in the treatment of such cases. Despite the use of standard treatment methods, the therapy is always planned and carried out individually for each patient. The surgical treatment of bone defects in the area of the jawbones is associated with a number of potential complications. Regenerative medicine, which has already been practiced in reconstructive surgery, is now gradually receiving more attention in the treatment of orthognathic defects. We developed a method for the reconstruction of the alveolar bone in the sagittal dimension using 3D allogenic graft blocks, as a preparing feature in the orthodontic treatment of borderline cases or as a treatment option for complications arising during general orthodontic treatment.


Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel-Crafts-Type 1,4-Addition.
The highly enantioselective organocatalytic construction of spiroindanes containing an all-carbon quaternary stereocenter by intramolecular Friedel-Crafts-type 1,4-addition is described. The reaction was catalyzed by a cinchonidine-based primary amine and accelerated by water and p-bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (-)-cannabispirenones A and B.


Mental health assessment/mental status examination.
More than one-half of primary care patients have mental health symptoms or disorders. As health insurers are forced to cover mental disorders on parity with physical illness, the number of patients with mental health complaints will increase. Nurse practitioners must increase their skills in assessing, diagnosing, and treating mental disorders. This article provides a framework for mental health assessment, especially mental status examination. A method for improving mental health assessment skill is suggested.


The E-screen assay: a comparison of different MCF7 cell stocks.
MCF7 human breast cancer cells have been studied extensively as a model for hormonal effects on breast cancer cell growth and specific protein synthesis. Because the proliferative effect of natural estrogen is considered the hallmark of estrogen action, it was proposed that this property be used to determine whether a substance is an estrogen. The E-screen assay, developed for this purpose, is based on the ability of MCF7 cells to proliferate in the presence of estrogens. The aim of our study was to characterize the response of four MCF7 cell stocks (BUS, ATCC, BB, and BB104) and determine which of them performed best in the E-screen test. The four stocks assayed were distinguishable by their biological behavior. In the absence of estrogen, MCF7 BUS cells stopped proliferating and accumulated in the G0/G1 phase of the cell cycle; estrogen receptors increased, progesterone receptors decreased, and small amounts of pS2 protein were secreted. Of all the MCF7 stocks tested, MCF7 BUS cells showed the highest proliferative response to estradiol-17 beta: cell yields increased up to sixfold over those of nontreated cells in a 144-hr period. The differences between estrogen-supplemented and nonsupplemented MCF7 BUS cells were due mostly to G0/G1 proliferative arrest mediated by charcoal dextran-stripped serum. MCF7 BUS cell stocks and others showing a similar proliferative pattern should be chosen for use in the E-screen test, or whenever a proliferative effect of estrogen is to be demonstrated.


Hepatitis B Virus DNA Integration: In Vitro Models for Investigating Viral Pathogenesis and Persistence.
Hepatitis B Virus (HBV) is a globally-distributed pathogen and is a major cause of liver disease. HBV (or closely-related animal hepadnaviruses) can integrate into the host genome, but (unlike retroviruses) this integrated form is replication-defective. The specific role(s) of the integrated HBV DNA has been a long-standing topic of debate. Novel in vitro models of HBV infection combined with sensitive molecular assays now enable researchers to investigate this under-characterised phenomenon with greater ease and precision. This review covers the contributions these systems have made to understanding how HBV DNA integration induces liver cancer and facilitates viral persistence. We summarise the current findings into a working model of chronic HBV infection and discuss the clinical implications of this hypothetical framework on the upcoming therapeutic strategies used to curb HBV-associated pathogenesis.


Inorganic-Organic Interpenetrating Network Hydrogels as Tissue-Integrating Luminescent Implants: Physicochemical Characterization and Preclinical Evaluation.
Sensors capable of accurate, continuous monitoring of biochemistry are crucial to the realization of personalized medicine on a large scale. Great strides have been made to enhance tissue compatibility of long-term in vivo biosensors using biomaterials strategies such as tissue-integrating hydrogels. However, the low level of oxygen in tissue presents a challenge for implanted devices, especially when the biosensing function relies on oxygen as a measure-either as a primary analyte or as an indirect marker to transduce levels of other biomolecules. This work presents a method of fabricating inorganic-organic interpenetrating network (IPN) hydrogels to optimize the oxygen transport through injectable biosensors. Capitalizing on the synergy between the two networks, various physicochemical properties (e.g., swelling, glass transition temperature, and mechanical properties) are shown to be independently adjustable while maintaining a 250% increase in oxygen permeability relative to poly(2-hydroxyethyl methacrylate) controls. Finally, these gels, when functionalized with a Pd(II) benzoporphyrin phosphor, track tissue oxygen in real time for 76 days as subcutaneous implants in a porcine model while promoting tissue ingrowth and minimizing fibrosis around the implant. These findings support IPN networks for fine-tuned design of implantable biomaterials in personalized medicine and other biomedical applications.


Associative encoding in posterior piriform cortex during odor discrimination and reversal learning.
Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex and basolateral amygdala (ABL). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. We recently reported that neurons in anterior piriform cortex (APC) in rats exhibited significant plasticity in their responses to odor cues during associative learning. Here, we have repeated this study, recording from neurons in posterior piriform cortex (PPC), a region of piriform cortex that receives much stronger input from ABL. If associative encoding in piriform cortex is driven by inputs from ABL, then we should see more plasticity in PPC neurons than we observed in APC. Consistent with this hypothesis, we found that PPC neurons were highly associative and appeared to be somewhat more likely than neurons recorded in APC to alter their responses to the odor cues after reversal of the odor-outcome associations in the task. Further, odor-selective PPC populations exhibited markedly different firing patterns based on the valence of the odor cue. These results suggest associative encoding in piriform cortex is represented in a topographical fashion, reflecting the stronger and more specific input from olfactory bulb concerning the sensory features of odors in anterior regions and stronger input from ABL concerning the meaning of odors in posterior regions.


Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip.
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner. Moreover, the mRNA level of Scinderin (Scin) considerably increased. We established lentivirus-SCIN(GV144-SCIN) to transfect hBMSCs, which were treated with different Ccs levels (0.25 Hz*5 cm, 0.5 Hz*5 cm, and 1 Hz*10 cm); the result showed that overexpression of Scin upregulated osteogenesis and osteoclastogenesis. By contrast, expression of chondrocyte-specific genes, including ACAN, COL-2A, and Sox9, decreased. Further molecular investigation demonstrated that Scin promoted osteogenesis and osteoclastogenesis through activation of the p-Smad1/5/8, NF-κB, and MAPK P38 signaling pathways, as well as stimulated the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Moreover, Scin-induced osteogenesis outweighed osteoclastogenesis in defective femur in vivo. The results of the analysis of Micro-CT confirmed these findings. Overall, Ccs influenced the development of DDH by promoting osteogenesis and cartilage degradation. In addition, Scin played a vital role in the development of DDH.


Plant Fragrances Are Like Music for Our Senses: A Scoping Review of Aromatherapy in Gynecologic Cancers and Breast Cancer Care.
Introduction: Essential oil (EO) applications via inhalation and/or absorption through the skin-often referred to as aromatherapy-have particular relevance as complementary to cancer treatment and follow-up care. Aromatherapy is of particular interest for controlling symptoms and enhancing the general well-being of people with cancer. This is indicated by the increasing number of empirical studies on this topic. Although numerous reviews have summarized the extensive primary research about aromatherapy and cancer, no review on aromatherapy use targeting women with gynecologic and breast cancers currently exists. Our scoping review aims at giving an overview of the state of research about aromatherapy in this specific target group. By summarizing and describing study characteristics, based on methodological decisions and content, we intend to offer implications for future research, focused on the use of EO in women with gynecologic and breast cancers. Methods: A systematic scoping review was conducted, based on the literature, and using the extension of the PRISMA statement for scoping reviews (PRISMA-ScR). The databases PubMed and CINHAHL were searched in a multi-stage, iterative process taking the most relevant terms under consideration, given our research interest and Boolean operators. The included studies were analyzed and summarized through (1) a table matrix including categories of interest and (2) qualitative content analysis. Results: One hundred seventy studies were examined, and 10 were included in this review. They show high heterogeneity in how the term aromatherapy is defined, in content, research design, EO used, application, and outcomes. However, all 10 studies exclusively targeted women with breast cancer in different states of cancer treatment. Conclusions: Challenges of research within this field point to the heterogeneous use and classification of the term aromatherapy, the differentiation of the principle of action of EO, the lack of transparency in how EO are reported and described (e.g., botanical names, company, dosage, mixing ratios), and the need to include subjective perceptions. Ten implications for future research based on these challenges are given.


Tc-99m methoxyisobutylisonitrile parathyroid scintigraphy: the value of adding a whole-body scan.
The aim of this study was to estimate the frequency of incidental findings on Tc-99m-methoxyisobutylisonitrile (MIBI) scan performed for suspected parathyroid adenoma and to evaluate the benefit of additional whole-body scan. A total of 109 patients (37 men and 72 women; age range, 16-96 years; mean, 58.42 years) with clinically suspected parathyroid adenoma underwent Tc-99m MIBI whole-body scans and single-photon emission computed tomography of the base of the skull, the neck, and the thorax. Each case with suspected abnormal tracer accumulation was analyzed and correlated with clinical information. MIBI single-photon emission computed tomography of the base of the skull, the neck, and the thorax and whole-body scans of 109 patients were assessed. A total of five incidental findings were detected. The anatomical distribution of the incidental findings was as follows: two (40%) were located in the head and neck areas and three (60%) were in the abdomen and pelvis. Two (40%) were detected in standard acquisition view, which includes the base of the skull, the neck, and the thorax. Three (60%) incidentalomas were detected in whole-body scan. In addition, we found 23 cases of abnormal tracer distribution that were correlated with known clinical history of patients. Three (13%) were located in the head and neck areas, 10 (43.6%) in the thoracic region, six (26%) in the abdomen and pelvis, and four (17.4%) in the extremities. Whole-body imaging in patients with suspected parathyroid adenoma who underwent MIBI scans does not alter patient management in most cases.


Prediction of passing probability and risk evaluation along undivided road under heterogeneous traffic.
This study focuses on the safety part of the passing manoeuvre. Passing is considered as one of the most complex, unavoidable and challenging manoeuvres on two lane roads. A binary logistic regression model was developed to determine the probability of passing or aborting based on field data. The result shows that the probability of passing is affected by the factors such as speed of passing vehicle, speed of overtaken vehicle, speed of opposing vehicle, clearance time, and the total passing time. Risk assessment is an important aspect which should be addressed while assessing the passing operations. In the present study, a risk chart was developed based on clearance time and vehicle interaction. An overall risk table was developed for all possible combinations of risk. The study revealed that the selected road stretch along NH-66 in Kerala, India is more susceptible to passing crashes due to insufficient clearance time. This paper brings out a rational methodology for calculating a safety measure in terms of risk index factor which could be used in simulation softwares for adequate passing sight distance operational analysis.


[Vesicouterine fistula as a complication after previous cesarean section 18 years earlier].
A case of vesicouterine fistula diagnosed in 40-year old woman who underwent cesarean section 18 years earlier was presented. The clinical features, etiologic factors, diagnostic procedures and treatment modalities were discussed in relation to the case and others reported in the literature. The gift of contrast by catheter to bladder allowed to visualize the fistula.


BRASH Syndrome with Hyperkalemia: An Under-Recognized Clinical Condition.
BRASH syndrome is characterized by bradycardia, renal failure, use of an atrioventricular nodal blocker (AVNB), shock, and hyperkalemia. These symptoms represent an ongoing vicious cycle in a patient with a low glomerular filtration rate taking an AVNB. Decreased clearance of the medication and hyperkalemia associated with renal failure synergize to cause bradycardia and hypoperfusion. This reaction causes renal function to worsen, thereby perpetuating the cycle of BRASH syndrome.


Damage to the corneal endothelium from anterior chamber intraocular lenses in phakic myopic eyes.
The use of minus power anterior chamber intraocular lenses to correct myopia in phakic eyes has been demonstrated previously to produce a more accurate and predictable correction than corneal refractive surgery techniques. We have examined 15 such eyes by specular microscopy and 10 such eyes by Scheimpflug slit-lamp micrography. One year after surgery, in 5 (36.3%) eyes, there was a decrease of more than 20% in the central endothelial density. Paracentral endothelial damage was present in 13 eyes (86.6%). On the specular micrograph, this damage appeared as an overall decrease in the number of the cells, abnormal cell shape with marked pleomorphism, dark zones, and acellular zones that corresponded to endothelial defects. The slit-lamp anterior segment measurements showed a distance between the edges of the IOL optic and the endothelium which ranged from 0.71 to 1.50 mm. We discuss the criteria for intraocular lens removal.


Evaluation of the dermal subchronic toxicity of diphenyl ether in the rat.
Diphenyl ether (DPE) was investigated to determine the dermal absorption parameters and subchronic toxicity of this fragrance ingredient. For the absorption, distribution and elimination study, Sprague-Dawley rats received a dermal application of [14C]DPE under a semi-occlusive dressing for 6 h. DPE was diluted in diethyl phthalate (DEP) to administer a total application volume of 2 ml/kg and concentrations of 0.5, 5 and 50% (approximately equal to 10, 100 and 1000 mg DPE/kg body weight). Approximately 17.7% of the administered dose was eliminated in the urine, with small amounts also found in the feces (1.18-3.79%). At 72 h post-dosing, approximately 0.2% of the applied dose was retained in the body with low levels also measured in the liver, kidney and gastrointestinal tract (approximately equal to 0.04, 0.02 and 0.3%, respectively). The 13-week subchronic toxicity study was performed with groups of 12 Sprague-Dawley rats/sex/dose that received semi-occluded daily dermal applications of DPE for 6 h/day. All groups were dosed at a constant 2 ml/kg body weight volume of DPE in the DEP vehicle at concentrations to administer 0, 100, 300 or 1000 mg DPE/kg body weight/day. At the high dose level, there was a slight reduction in body weight gain in males (13%), increase in albumin (5-6%) and phosphate (10-15%) levels in both sexes, a reduction of cholesterol in females (14%), an increase in kidney (17%) and brain (8%) weights in males, and an increase in liver weight (18-19%) in both sexes. No histopathological lesions were seen in any organ examined. At 300 mg/kg body weight/day, the only notable findings were an increase in liver weight (10%) in both sexes and a slight increase in albumin (5%) in females. In addition, skin irritation reactions at the site of application were observed in all DPE dose groups. The systemic no-observed-effect level (NOEL) in this study is 100 mg/kg body weight/day. Owing to mitigating factors, the systemic findings were judged to lack biological significance and the no-observed-adverse-effect level (NOAEL) was determined to be 1000 mg/kg body weight/day.


Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria.
Cerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM. Patients included in the study were admitted (2009-2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization. In this cohort of 94 patients, median age was 44 (interquartile range 29-62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44-56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45-9.35). Elevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.


Ketoconazole inhibits acetaminophen-induced hepatotoxicity in mice.
To investigate the effect of ketoconazole on acetaminophen (AAP)-induced hepatotoxicity in mice. Mice were given AAP intragastrically (300 mg/kg) and treated with ketoconazole (100 mg/kg intraperitoneally) or saline either 30 min before or 2-3 h after AAP administration. Mortality was recorded for 48 h, during which all mice given saline either died or recovered fully. Serum alanine and aspartate transaminase levels were determined 24 h after administration of AAP. Prostaglandin E2, thromboxane A2 and leukotriene C4 production was determined 6 h after AAP administration in the supernatants from the short-term culture of liver fragments by radioimmunoassay. Ketoconazole significantly decreased mortality and transaminase levels when given to mice either 30 min before or 2 h after AAP. Liver fragments from mice with AAP hepatitis produced greater quantities of prostaglandin E2, thromboxane A2 and leukotriene C4 than fragments from normal liver. Pretreatment of mice with ketoconazole or its addition to liver fragments ex vivo further increased the production of prostaglandin E2 and reduced the production of thromboxane A2. The effect of ketoconazole on leukotriene C4 synthesis was different in vivo (synthesis stimulation) from in vitro (synthesis inhibition). The protective effect of ketoconazole in AAP hepatitis is most probably mediated by modulation of eicosanoid synthesis by liver cells.


[Primary myringoplasties. Results after a 2 year follow-up period].
The goals of myringoplasty are closure of the perforation in the tympanic membrane and improvement in hearing levels, with varying results in the published literature. Our aim was to determine the results of this procedure at our centre and compare them with the literature. Retrospective analysis of 217 primary myringoplasties carried out in the Otorhinolaryngology Department of the Ramón y Cajal University Hospital between 1998 and 2003, describing the characteristics of the perforations, surgical technique and post-operative results (perforation closure and hearing improvement). The majority were adults with perforations secondary to recurrent middle ear infections (91%). Most were less than subtotal (64%) and did not involve the tympanic annulus (79%). Grafts were inserted using lateral (45%), mixed (29%) and medial (26%) techniques, using retroauricular (66%) and endaural (34%) approaches. Temporal muscle fascia was the graft most frequently used (87%). Perforation closure was achieved in between 78% and 91% of cases throughout the 24-month follow-up period, with an overall closure value of 78% after 2 years of follow-up. Hearing improvement, established as an air bone gap difference of less than 20 dB, was seen in approximately 56% of cases. At our centre, myringoplasty achieves anatomical (78%) and functional (56%) success comparable to the results described in the literature. We consider medium-term follow-up to be of the utmost importance because of reperforation phenomena, which may occur as much as 2 years or more after surgery.


Alternate Cyclization Cascade Initiated by Substrate Isomer in Multiproduct Terpene Synthase from Medicago truncatula.
Promiscuity of terpene synthases results in the enormous diversity of terpenes found in nature. Multiproduct sesquiterpene synthase MtTPS5 isolated from Medicago truncatula generates 27 optically pure products from its natural substrate (2E,6E)-farnesyl diphosphate (FDP). In order to study the promiscuity of MtTPS5, (2Z,6E)-FDP, an analogue of presumptive reaction intermediates from natural reaction cascade, was utilized as a substrate. This stereoisomer induced a novel cyclization pathway leading to sesquiterpenes based on humulane, amorphene, and himachalane skeletons. Interestingly, none of these products matched those observed on incubation of MtTPS5 with natural (2E,6E)-FDP. Further determination of the absolute configuration of each product helped rebuild the stereochemical route of the reaction cascade. Interestingly, the presence of only one enantiomer of each product was observed, indicating the highly stereospecific nature of the enzymatic reaction. Substrate promiscuity of terpene synthases provides organism access to novel chemical bouquets of high optical purity by utilizing existing enzymes. The presence of this mechanism was indicated by the presence of these alternate products in natural herbivore-induced volatiles of M. truncatula.


Strategies for Manipulating T Cells in Cancer Immunotherapy.
T cells are attractive targets for the development of immunotherapy to treat cancer due to their biological features, capacity of cytotoxicity, and antigen-specific binding of receptors. Novel strategies that can modulate T cell functions or receptor reactivity provide effective therapies, including checkpoint inhibitor, bispecific antibody, and adoptive transfer of T cells transduced with tumor antigen-specific receptors. T cell-based therapies have presented successful pre-clinical/clinical outcomes despite their common immune-related adverse effects. Ongoing studies will allow us to advance current T cell therapies and develop innovative personalized T cell therapies. This review summarizes immunotherapeutic approaches with a focus on T cells. Anti-cancer T cell therapies are also discussed regarding their biological perspectives, efficacy, toxicity, challenges, and opportunities.


Medicare program; payment adjustments for sole community hospitals--HCFA. Final rule with comment period.
This rule changes Medicare prospective payment regulations for inpatient hospital services in order to allow an adjustment to the payment amounts (if warranted) under the prospective payment system for sole community hospitals that experience a significant increase in inpatient operating costs attributable to the addition of new inpatient services or facilities. In addition, in accordance with section 9302(e)(4) of the Omnibus Budget Reconciliation Act of 1986, we are extending certain payment provisions for sole community hospitals.


[Hypoglycemia: diagnostic approach].
Hypoglycaemia can occur if the endogenous liver glucose output is lower than the glucose uptake in insulin-sensitive and insulin-insensitive tissues. The onset of hypoglycaemia induces the production of counterregulatory hormones such as glucagon, epinephrine, growth hormone and cortisol, and symptoms of neuroglycopenia. The correlation between biological hypoglycaemia and the symptoms associated with low blood sugar is particularly poor in diabetic patients and in patients with suspected postprandial hypoglycaemia. It is important to discriminate between fasting and postprandial hypoglycaemia. Idiopathic postprandial hypoglycaemia should be diagnosed clinically without further laboratory assessment, whereas the etiology of a fasting hypoglycaemia needs to be clarified further by laboratory testing, as it is potentially life-threatening.


[Related factor analysis of the degree of tinnitus in sudden sensorineural hearing loss patients].
To provide the theory basis for clinical diagnosis, treatment and prognosis of sudden deafness patients, we detected the relative factors of degree of tinnitus of the patients with sudden deafness. Prospective analysis was used to compare degree of tinnitus with sex, ears, age, degree of hearing lose, hearing curve type and curative effect of tinnitus and sudden deafness. Tinnitus was detected in 87.2% in the 70 patients who with sudden deafness, and the most and least degree of tinnitus patients was the degree 3 (32.9%) and the degree 5 and 6 (0). The total effective rate of sudden deafness and tinnitus was 66.2% and 74.3%, respectively. The statistical analysis shown the degree of tinnitus was not related to sex, ears, age, degree of hearing lose, auditory curve type and curative effect of tinnitus and sudden deafness (P > 0.05). There was a high rate of tinnitus occurrence in sudden deafness patients, and the moderate degree predominated. The curative effect of tinnitus was better than sudden deafness. There was no relationship between the degree of tinnitus and sex, ears, age, degree of hearing lose, auditory curve type and curative effect of tinnitus and sudden deafness.


Clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations affecting HBV e antigen expression in Taiwan.
To assess the prevalence and clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations in Taiwan, a cohort of 200 Taiwanese chronic hepatitis B patients was analyzed. The HBV genotypes and sequences of the precore and the core promoter regions were determined in 66 asymptomatic carriers and 134 patients who had liver biopsy-verified chronic hepatitis and liver cirrhosis. The HBV e-antigen (HBeAg)-negative patients had a higher frequency of mutations at core promoter nucleotides 1753 and 1773 and precore nucleotides 1846, 1896, and 1899 than HBeAg-positive patients. Among the 200 patients, the frequencies of genotype C, T1762 and A1764, C1753, T1766 and A1768, and A1896 mutations increased and the frequencies of T or G1752, T1773, G1799, and C1858 mutations decreased with advancing liver diseases. These factors were different between those with HBeAg-positive status and those with HBeAg-negative status. Based on multiple logistic regression analysis, the risk factors of liver cirrhosis for 200 patients were the presence of T1762 and A1764 mutations (odds ratio [OR] = 11.11; 95% confidence interval [CI] = 3.91 to 31.25; P < 0.001), age > or =35 years (OR = 3.42; 95% CI = 1.33 to 8.77; P = 0.011), and genotype C (OR = 2.87; 95% CI = 1.21 to 6.81; P = 0.017). Further categorical analysis found that 62.1% of patients with genotype C, T1762 and A1764 mutations and age > or =35 years had liver cirrhosis. None of the 55 patients infected with the genotype B, A1762 and G1764 wild type and age <35 years showed liver cirrhosis. In conclusion, our data suggest that pathogenic differences between HBeAg-positive and -negative patients may exist. In Taiwan, HBV genotype C and the T1762 and A1764 mutations may play a role in HBV-related liver cirrhosis, and these could serve as molecular markers for prediction of the clinical outcomes of chronic HBV patients.


Basic Properties of Calcined Underground Ant Nest Materials and Its Influence on the Compressive Strength of Concrete.
Underground ant nests are typically made of soil and rubble mixed with dead plant bodies, ant secretions, and other organic substances. The clay content is high, and the natural clay materials show pozzolanic activity after calcination. In this study, the underground ant nest materials of Iridomyrmex anceps, which is a common ant in the Shanghai area, are calcined and ground, and the material properties of calcined ant nest clay powder (CANCP) are characterized from six aspects: chemical composition, particle morphology, specific gravity, specific surface area, particle size distribution and pozzolanic activity index. The pozzolanic activity of CANCP is evaluated by the strength contribution rate of pozzolanic activity, revealing that CANCP is beneficial to the strength of the mortar system from an early age. The influence of CANCP on the compressive strength of concrete is analyzed using three aspects, namely, content, curing age and calcination temperature, and it is found that the three aspects of CANCP have a strong influence on the compressive strength of concrete.


The effects of milk removal or four-times-daily milking on mammary expression of genes involved in the insulin-like growth factor-I axis.
Frequent milking of dairy cows during early lactation elicits both an immediate increase in milk yield and a partial carryover effect that persists to the end of lactation. We hypothesized that the immediate response would be associated with a local increase in insulin-like growth factor (IGF)-I signaling and a consequent increase in mammary growth. Four multiparous cows were assigned at parturition to unilateral frequent milking [UFM; milking of the left udder half twice daily (2x; 0230 and 1430 h); milking of the right udder half 4 times daily (4x; 0230, 0530, 1430, and 1730 h)]. Mammary biopsies were obtained from both udder halves at 5 d in milk at 0530 h (immediately after 4x glands were milked). Incorporation of [3H]-thymidine into DNA and mammary cell apoptosis were not affected by UFM. Because biopsies were obtained when udder halves were at different postmilking intervals, our results reflected both the acute, transient mammary response to milking and the sustained mammary response to frequent milking treatment. We further hypothesized that the acute, transient response involves mechanisms distinct from those regulating the sustained response to frequent milking. To test that hypothesis, mammary biopsies were obtained from UFM cows (n=5) at 0500 h, when time postmilking was the same for both udder halves. Mammary cell apoptosis was not affected by UFM. Expression of genes involved in the IGF-I axis was analyzed to identify acute responses associated with milking, per se, versus sustained responses to frequent milking treatment. Removal of milk from 4x glands was associated with an acute increase in expression of IGF binding protein-1, -3, and -4 mRNA in 2x glands, whereas IGF-I expression was increased by frequent milking treatment. These effects, however, were significant only for expression of IGF binding protein-3. Expression of IGF-I receptor did not differ because of milking frequency but was higher in both udder halves immediately postmilking, indicating a systemic effect. We conclude that several genes of the IGF-I axis respond to milking, per se, or frequent milking treatment, via at least 3 distinct patterns. Increased milking frequency does not alter mammary cell proliferation or apoptosis at 5 d in milk; however, it may increase the bioavailability of IGF-I in the mammary gland. Moreover, the increase in local expression of IGF-I in 4x udder halves indicates a role for this gene in the immediate milk yield response to frequent milking during early lactation.


Evaluation of the Milling Accuracy of Zirconia-Reinforced Lithium Silicate Crowns Fabricated Using the Dental Medical Device System: A Three-Dimensional Analysis.
This study aimed to analyze the milling accuracy of lithium disilicate and zirconia-reinforced silicate crown fabricated using chairside computer-aided design/manufacturing (CAD/CAM) system. Mandibular left first premolar was selected for abutment. A master model was obtained for digital impression using an intraoral scanner, and crowns were designed using a CAD software design program. Amber Mill (AM), IPS e max CAD (IPS), and CELTRA DUO (CEL) were used in the CAD/CAM system, and a total 45 crowns (15 crowns each for AM, IPS, and CEL) was fabricated. Milling accuracy was analyzed with respect to trueness, measured by superimposing CAD design data and scan data through a three-dimensional program to compare the outer and inner surfaces and internal and external parts, thereby acquiring both quantitative and qualitative data. Data were analyzed using the non-parametric test and Kruskal-Wallis H test. In addition, the Mann-Whitney U test was used by applying the level of significance (0.05/3 = 0.016) adjusted by post-analysis Bonferroni correction. All the measured parts of the lithium disilicate and zirconia-reinforced silicate crowns showed statistically significant differences (p < 0.05). The lithium disilicate (AM and IPS) materials showed superior milling accuracy than the zirconia-reinforced lithium silicate (CEL) materials.


[Febrile infant and small child: what solution could be rational?].
Fever of infant and small child is one of the greatest parental concerns. Mostly the source of fever is viral infection, but sometimes it can be serious bacterial infection: meningitis, sepsis, osteomyelitis, urinary tract infection, pneumonia and enteritis. Non-identified bacterial infection may be a cause of disablement or even death. Infant and younger children up to 36 months of age are in the highest risk period for invasive bacterial infection. After the examination of febrile infant the practitioner has to take a wise decision, especially if febrile infant looks well enough and there is no focus of infection. It is not reasonable to admit all febrile infants and do tests to all of them or start empiric antibiotic therapy. In order to protect infants from no identification of serious bacterial infection it is important for a physician to know the evaluation and management tactics of febrile infants. Thus, the salient question for any physician is: "When can a febrile infant be safely discharged from the emergency room?" Most often proposed recommendations for the management of febrile infants in the literature come predominantly from Boston, Philadelphia and Rochester prospective studies. Criteria introduced in these recommendations demonstrate a safe and effective way of screening febrile infants for a serious bacterial infection. Each management strategy involves criteria such as child's age, temperature, clinical appearance, white blood cell count, urinalysis, cerebrospinal fluid test, stool screening, chest radiography. The purpose of this article is to review the data and to validate optimal recommendation regarding the management of febrile infant and child 3 to 36 months of age.


Minimal hepatic encephalopathy.
The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. Physician does generally not perceive cirrhosis complications, and neuropsychological tests and another especial measurement like evoked potentials and image studies like positron emission tomography can only make diagnosis. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.


Histotopographical characterization of the para-aortic lymph nodes in the area near the origin of the thoracic duct, and its relationship to nodal cancer metastasis.
Using 10 elderly cadavers without macroscopically evident tumors, we histologically examined 115 para-aortic lymph nodes located near the origin of the thoracic duct after preparation of en bloc specimens using a clearance method. The afferent and efferent sides of these nodes were usually not discriminated clearly because i) the superficial cortex (B-lymphocyte area) and deep cortex (T-lymphocyte area) were not clearly differentiated due to lack of a typical hilus, and both cortices were intermingled to form "nodular masses"; ii) each nodule with a lining of macrophages was surrounded by dilated intermediate and subcapsular sinuses; iii) the nodes were often surrounded by multiple tributaries of the thoracic duct. Moreover, the nodes sometimes involved these tributaries inside. Therefore, the nodal architecture seemed to accelerate intranodal shunt flow without filtration through the cortex. Valves of the lymphatic vessel tended to be restricted to an area immediately before drainage into the thoracic duct. Thus, lymph flow was likely to change along a network of tributaries around a node. These morphologies suggested very limited barrier function of the para-aortic node against cancer metastasis. However, we hypothesized that "better" or "worse" types of nodes are histologically identifiable when they are picked up surgically along with the surrounding tissues.


Probabilistic techniques for obtaining accurate patient counts in Clinical Data Warehouses.
Proposal and execution of clinical trials, computation of quality measures and discovery of correlation between medical phenomena are all applications where an accurate count of patients is needed. However, existing sources of this type of patient information, including Clinical Data Warehouses (CDWs) may be incomplete or inaccurate. This research explores applying probabilistic techniques, supported by the MayBMS probabilistic database, to obtain accurate patient counts from a Clinical Data Warehouse containing synthetic patient data. We present a synthetic Clinical Data Warehouse, and populate it with simulated data using a custom patient data generation engine. We then implement, evaluate and compare different techniques for obtaining patients counts. We model billing as a test for the presence of a condition. We compute billing's sensitivity and specificity both by conducting a "Simulated Expert Review" where a representative sample of records are reviewed and labeled by experts, and by obtaining the ground truth for every record. We compute the posterior probability of a patient having a condition through a "Bayesian Chain", using Bayes' Theorem to calculate the probability of a patient having a condition after each visit. The second method is a "one-shot" approach that computes the probability of a patient having a condition based on whether the patient is ever billed for the condition. Our results demonstrate the utility of probabilistic approaches, which improve on the accuracy of raw counts. In particular, the simulated review paired with a single application of Bayes' Theorem produces the best results, with an average error rate of 2.1% compared to 43.7% for the straightforward billing counts. Overall, this research demonstrates that Bayesian probabilistic approaches improve patient counts on simulated patient populations. We believe that total patient counts based on billing data are one of the many possible applications of our Bayesian framework. Use of these probabilistic techniques will enable more accurate patient counts and better results for applications requiring this metric.


Orthopedic wound infections. 182 cases after 8913 operations during an 8-year survey.
We performed a surveillance of postoperative wound infections at our department for a period of 8 years. The surveillance was based on forms completed by the surgeons at the department. Retrospectively, by scrutinizing the records of patients with recorded infections, the criteria for infections used by the surgeons were compared with the criteria recommended by the Centers for Disease Control, USA, for routine infection surveillance studies: 1) pus present in the wound, 2) bacteria isolated from the wound, 3) spontaneous wound breakdown or surgical intervention due to suspected infection; if culture is performed, it must be positive, 4) evidence of infection at reoperation or at radiologic or histopathologic examination (restricted to deep infections) or 5) diagnosis of infection by a surgeon. 182 infections were recorded; in 106 (58%) pus was present, drained either spontaneously or by surgical intervention, in 24 (13%) no pus was seen, but the culture was positive. In 116 cases, surgical intervention was performed or wounds spontaneously broke down; pus was found in 101 of these and culture of non-purulent material was positive in 13 and negative in 2. In 52 (29%) patients, only criterion 5 was fulfilled. In surveillance studies where the recordings are based on several observers, the subjective criterion 5 may, as in our study, give a falsely high number of infections, also preventing comparison between studies. We recommend that all suspected infections are cultured and that only criteria 1, 2 and 4 are used.


Food addiction: A key factor contributing to obesity?
People may develop addiction to hyperpalatable foods, which may be a cause of obesity. This study aimed to determine the prevalence of obesity among adolescents and the effect of food addiction on obesity. In this cross-sectional study, food addiction and obesity status of high school students were investigated. Among 17,000 10th and 11th grade students, assuming the design effect as 2.0, with obesity prevalence of 10%, with 3% error, and 95% confidence interval, at least 752 participants were included. Obesity was the dependent variable, whereas sociodemographic characteristics, body image, eating habits, and food addiction were the independent variables. Food addiction was assessed using the Yale Food Addiction Scale. Obesity was determined by age- and sex-specific body mass index (BMI) percentiles for adolescents < 18 years of age and BMI ≥ 30.0 for those aged ≥ 18. Data were collected through face-to-face interviews. Statistical analyses were performed using SPSS 25.0. After adjustment for age, sex, and other variables, the effect of food addiction on obesity was determined through logistic regression. P <0.05 was deemed statistically significant. Among adolescents (n = 874), 18.9% were food addict, 25.1% were overweight, and 12.1% were obese. After adjusted for age, sex, and other variables, food addiction significantly increased the risk of obesity (odds ratio: 1.9; 95% confidence interval: 1.167-3.335). Having a fragmented family, working mother, overweight father, and participants not knowing their weight correctly significantly increased obesity. While quarter of the adolescents had weight problems, one-fifth suffered from food addiction. After adjusting for confounders, food addiction significantly increased obesity. Identifying individuals with food addiction, providing treatment to overcome that, paying special attention to adolescents with obese parents or living in fragmented families, and providing support to both parents and adolescents could be useful in tackling obesity.


Nation-wide Salmonella enterica surveillance and control in Danish slaughter swine herds.
A nation-wide Salmonella enterica surveillance and control programme was initiated in Danish finishing herds over the first quarter of 1995. In Denmark, all swine for slaughter are identifiable by a unique herd code. For each herd code, and depending on the herd's annual kill, random samples ranging from four to more than 60 swine are obtained quarterly at the abattoir. A meat sample from each pig is frozen, and meat juice (harvested after thawing) is examined for specific antibodies against S. enterica using an indirect enzyme-linked immunosorbent assay (ELISA). The ELISA combines several S. enterica O-antigens, and allows detection of antibody response after a variety of different S. enterica serovar infections. Results are transferred to a central database, which each month (based on meat-juice tests obtained in the previous 13 weeks) assigns all herds into three S. enterica infection levels: Level 1, in which the S. enterica prevalence is deemed low and acceptable; Level 2, where there is a moderate prevalence of S. enterica seroreactors (from > 50% in the smallest to > 10% in the largest herds); Level 3, in which S. enterica seroreactor prevalence is clearly unsatisfactory (> 50% for most herd sizes). Irrespective of Salmonella level, all herds receive a monthly update on the current results of the S. enterica test results. If a herd is categorized in Level 2 or 3, it must receive an advisory visit by a practising veterinarian and a local swine extension specialist, and certain management hygiene precautions must be taken. If a herd is categorized in Level 3, the finishers from the herd must additionally be slaughtered under special hygiene precautions. This is supervised by the veterinary authorities. During 1995, 604000 samples were tested for S. enterica, corresponding to 3.0% of the total kill. In December 1995, 15522 herds (representing > 90% of the national production) were categorized into one of the three levels: 14551 herds (93.7%) in Level 1; 610 herds (3.9%) in Level 2; 361 herds (2.3%) in Level 3. The proportion of serologically positive meat-juice samples collected during 1995 ranged from a mean of 2.9% in smaller herds (101-200 swine slaughtered per year) to 6.1% in relatively large herds (more than 5000 swine slaughtered per year).


A comparative study of effects of isoproterenol and dihydroouabain on calcium transients and contraction in cultured rat ventricular cells.
We investigated the effects of isoproterenol, a beta-adrenergic agonist, and dihydroouabain, a Na+,K(+)-pump inhibitor, on Ca2+ transients and contraction of cultured rat ventricular cells and compared the effects with those of altered external ion concentrations, with special reference to the changes in diastolic intracellular free calcium concentration ([Ca2+]i). We measured [Ca2+]i of cultured cell aggregates, stimulated at 1.0 Hz, with the use of dual-wavelength microfluorometry of fura-2, at room temperature (24-26 degrees C). The contraction was measured as a shortening of the aggregates using a photodiode array placed on a video monitor. Isoproterenol increased the magnitude of contraction and the peak amplitude of the Ca2+ transient, in a concentration (10(-9)-10(-6) M)-dependent manner, but did not change the diastolic Ca2+ level. Isoproterenol at 10(-7) M or higher significantly shortened the duration of contraction and half decay time of a Ca2+ transient yet it did not change the time to peak. Dihydroouabain (10(-7)-10(-5) M) increased the contraction and elevated both systolic and diastolic calcium levels but it did not alter the duration of contraction, the time to peak and the half decay time. The effects of dihydroouabain on Ca2+ transients were mimicked by lowering [K+]o (0.4 mM), by lowering [Na+]o (74 mM) or by elevating [Ca2+]o (3.6 or 5.4 mM). Ryanodine (10(-5) M), by itself, decreased systolic Ca2+ transient amplitude, increased diastolic Ca2+ levels and prolonged the time to peak and the half decay time. In the presence of ryanodine, isoproterenol increased both systolic and diastolic [Ca2+]i. Thus, most procedures that increased the systolic Ca2+ transient amplitude increased the diastolic Ca2+ levels as well, and enhanced the contraction. The only exception was isoproterenol that markedly increased the systolic Ca2+ transient amplitude without affecting the diastolic Ca2+ level, a finding in keeping with the observation that isoproterenol stimulates Ca2+ uptake by the sarcoplasmic reticulum.


Verification of the role of PCP 4-monooxygenase in chlorine elimination from pentachlorophenol by Flavobacterium sp. strain ATCC 39723.
The bacterial enzyme PCP 4-monooxygenase from Flavobacterium sp. strain ATCC 39723 catalyzes the oxygenolytic removal of the first chlorine from pentachlorophenol. PCP 4-monooxygenase is an FAD binding, NADPH requiring oxygenase, with similar functional domains as other bacterial flavoprotein monooxygenases specific for phenolic substrates. However, the definitive proof for the singular role of an oxygenolytic elimination of the primary chlorine from pentachlorophenol by Flavobacterium sp. has awaited the development of a genetic system whereby targeted mutagenesis via allelic exchange could be carried out with the corresponding gene from PCP 4-monooxygenase, pcpB. We report the development of a genetic system for Flavobacterium sp. strain ATCC 39723, and its application in targeted mutagenesis of the pcpB allele for elimination of PCP 4-monooxygenase activity.


Diagnosis and management of gastrointestinal chemical burns and post-burn oesophageal stenosis.
Post-burn oesophageal stenosis occurs as a result of accidental or intentional ingestion of a corrosive substance. Global estimates indicate tens of thousands of acid or lye ingestion cases per year. In some cases patients in the early post-burn phase require urgent surgical intervention. Endoscopy, along with chest and abdominal computed tomography, form the basis of diagnosis. The need for emergency oesophageal or gastric resection is associated with a high mortality rate of up to 60%. Post-burn oesophageal stenosis is a challenging clinical problem that requires coordinated multispecialty treatment. The treatment of post-burn stenosis may be with endoscopic techniques or reconstructive surgery. Surgical reconstruction is performed once the scar has definitively formed. The extent of the injury, anatomical conditions, previous surgery and the team's expertise determine the optimum reconstructive method. In this article, we present the current knowledge on the diagnosis and treatment of oesophageal burns.


Increased accessibility of semantic concepts after (more or less) subtle activation of related concepts: support for the basic tenet of priming research.
Increasingly remote concepts and behaviors have been primed, which have come under increasing criticism. In this present experiment, we take a step back and try to strengthen the roots of priming research. In this experiment, we systematically varied the activation or priming of a concept in six experiments (N = 1285). We then measured accessibility for semantic concepts using a word stem completion task. Across the six experiments, our investigations showed that the activation of semantic concepts is possible through greater accessibility of semantically congruent words (with only one experiment failing to reach a conventional level of significance). These results provide a prerequisite for further investigation into behavioral priming. The present experiment showed that the basal priming mechanisms are robust effects. The meta-analytic integration showed that women reliably had access to more baby-related words. A possible explanation is that social role stereotypes associate women more with the reproductive sphere than men and that women, to a certain extent, internalize these societal views. Other explanations and potential future applications are discussed.


Emergent Diagnosis of a Flail Mitral Leaflet With Bedside Echocardiography.
Flail mitral leaflet (FML) with associated acute pulmonary edema and acute decompensated heart failure is an emergent condition requiring prompt recognition by the emergency physician (EP). Focused cardiac ultrasound (FOCUS) and lung ultrasound (LUS) have a vital role in the evaluation of FML in the emergency department. This case report describes the identification of a FML with EP-performed bedside echocardiography.


Molecular mechanics calculations on Rous sarcoma virus protease with peptide substrates.
Molecular models of Rous sarcoma virus (RSV) protease and 20 peptide substrates with single amino acid substitutions at positions from P4 to P3', where the scissile bond is between P1 and P1'. were built and compared with kinetic measurements. The unsubstituted peptide substrate. Pro-Ala-Val-Ser-Leu-Ala-Met-Thr, represents the NC-PR cleavage site of RSV protease. Models were built of two intermediates in the catalytic reaction, RSV protease with peptide substrate and with the tetrahedral intermediate. The energy minimization used an algorithm that increased the speed and eliminated a cutoff for nonbonded interactions. The calculated protease-substrate interaction energies showed correlation with the relative catalytic efficiency of peptide hydrolysis. The calculated interaction energies for the 8 RSV protease-substrate models with changes in P1 to P1' next to the scissile bond gave the highest correlation coefficient of 0.79 with the kinetic measurements, whereas all 20 substrates showed the lower, but still significant correlation of 0.46. Models of the tetrahedral reaction intermediates gave a correlation of 0.72 for the 8 substrates with changes next to the scissile bond, whereas a correlation coefficient of only 0.34 was observed for all 20 substrates. The differences between the energies calculated for the tetrahedral intermediate and the bound peptide gave the most significant correlation coefficients of 0.90 for models with changes in P1 and P1', and 0.56 for all substrates. These results are compared to those from similar calculations on HIV-1 protease and discussed in relation to the rate-limiting steps in the catalytic mechanism and the entropic contributions.


Preparation and characterization of monoclonal antibodies to substance P.
A series of mouse hybridomas that produced monoclonal antibodies reactive with Substance P was prepared in an attempt to find a surrogate NK-1 receptor. When the binding profile of one particular antibody, SubP14.36.1, was compared in a rank order plot with NK-1 receptors against various agonists and antagonists of Substance P, a high correlation was found between these two binding structures. In addition, this monoclonal antibody inhibited a functional assay for Substance P. This result indicated that the pharmacological effects of this peptide can be blocked by an antibody (Ab).


Aldosterone Induces Tissue Inhibitor of Metalloproteinases-1 Expression and Further Contributes to Collagen Accumulation: From Clinical to Bench Studies.
Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity.


Drawing Attention to the Measurement Uncertainty Arising from Sampling in Chemical and Physicochemical Analyses: An Overview.
Sometimes, analytical chemicals forget that the measurement process begins with the selection of the sample; thus, it must be understood that the measurement uncertainty is constituted by the association of the uncertainty arising from the sampling and the uncertainty arising from the traditional analytical process, that which is carried out in the laboratory. The analytical process is well-controlled, so its uncertainty is well defined; however, the uncertainty arising from sampling, for not having this controlled environment, is often not evident, so that there is still no culture to consider it for the calculation of measurement uncertainty. This study discusses the importance of the sampling uncertainty concerning the analytical uncertainty and details the current approaches available in the literature, such as the classical analysis of variance, the robust analysis of variance, and the range statistics. Moreover, this work highlights the recent manuscripts that are using these mentioned approaches, correlating them to the matrices, chemical and physical-chemical analytes, and analytical techniques. Finally, some case studies using the uncertainty information in compliance assessment show that the measurement uncertainty arising from sampling in chemical and physicochemical analyses cannot always be neglected.


Cosmetic outcome of scalp wound closure with staples in the pediatric emergency department: a prospective, randomized trial.
The purpose of this study is to compare the cosmetic outcome of scalp wound closure with staples to traditional skin sutures. A prospective, randomized trial was conducted using a convenience sample of children (aged 1-16 y) with simple scalp lacerations admitted to the pediatric emergency department. After parental consent was obtained, patients were randomly assigned to either a stapling or suturing procedure. A trained attending physician completed the procedure following a standard protocol. Based on previously published data, a sample size of 18 patients per group was calculated to give 85% power to detect a 10% difference on a visual analogue scale (VAS) score (two-sided alpha 0.05). Initial outcome of wound healing at 7 to 10 days and final cosmetic outcome after 6 to 18 months were estimated using a VAS. Cosmetic outcome was assessed by a physician blinded to the procedure. Data were analyzed using SPSS (Version 8.02; SPSS Inc., Chicago, IL). The VAS scores for the two treatment groups were compared using the two-tailed Student t test. Analysis of age, race, mode of injury, time interval, and size of the wound were performed to estimate the strength of the association of VAS score with the treatment, adjusted for the covariates. A total of 42 patients were enrolled. Of the 42, 38 (90.5%) finished the initial follow-up and 31 of those 38 (81.6%) finished the final follow-up. There were no significant demographic differences between groups at recruitment and first follow-up. Among those patients who completed the final follow-up, 15 underwent stapling, and 16 underwent suturing. There were no significant demographic or baseline differences between the groups. Procedure time was significantly lower in the stapling group (P = 0.001). Final follow-up evaluations were completed in 12 +/- 4 months. The mean VAS scores at first and final follow-up were 78.75 +/- 16.16 and 96.31 +/- 8.06 for the suturing group and 86.67 +/- 9.76 and 97 +/- 7.02 for the stapling group (P = 0.17). There remained no significant difference in the final follow-up VAS score between groups when adjusted for covariates. Stapling appears to be a fast and cosmetically acceptable alternative to suturing for simple scalp lacerations.


[Pathophysiological aspects and clinical indications for plasma exchange treatment].
After a rather long initial period fraught with difficulties, plasma exchange has become an adjunct to the treatment of numerous diseases in medicine, such as hyperviscosity syndrome, where it alleviates disease symptoms, hemophilia due to inhibitors to clotting factor VIII, thrombotic thrombocytopenic purpura, rapidly progressing and Goodpasture glomerulonephritis, myasthenia gravis and Guillain Barre syndrome. As yet there are no formal indications for plasmapheresis, i.e. randomized placebo controlled studies are rare and proof of efficacy is often based on clinical criteria only. Therefore this treatment may be a transient means of removing noxious substances from plasma, giving way to more specific apheresis procedures such as plasma filtration, cascade filtration or immunoadsorption over charcoal or over solid-phase bound antibodies against the substance it is desired to remove. The present study presents the various plasmapheresis techniques, outlines the pathophysiological background to this treatment and adopts the now standard classification of indications into hematological, nephrological, neurological and miscellaneous indications. The English speaking reader will find an updated reference list of work published mainly in that language.


[Thrichosanthin enhances cisplatin-induced laryngocarcinoma apoptosis through inhibiting transcription factor nuclear factor κB].
To investigate the combined effect of thrichosanthin (TCS) and cisplatin on Hep-2 and AMC-HN-8 cell proliferation. Hep-2 and AMC-HN-8 cells were treated with low (3 µg/ml) or high (10 µg/ml) concentration of cisplatin (10 µg/ml), TCS(5 µg/ml), or the combination TCS (5 µg/ml) and cisplatin (3 µg/ml), the cells no exposure to the drugs as control. Cell proliferation was detected by CCK-8. Toxicity of drugs to cells was evaluated by LDH assay. Flow cytometry was used to detect apoptosis. Western blot was performed to detect the expressions of JNK, phosphor-JNK, p38, phosphor-p38, NF-κB, inhibitor of κB (I-κB), and phospho-I-κB. Compared with TCS (5 µg/ml) or cisplatin (3 µg/ml) alone, the combination of them had more significant inhibitory effect on the proliferation of Hep-2 and AMC-HN-8 cells (P < 0.01), but with no significant increase in cytotoxicity (P > 0.05). Western blot showed the expression of p-JNK/SAPK significantly increased in the cells treated with 5 µg/ml TCS for 48 hours, while the expression of NF-κB and phospho-I-κB increased in the cells treated with 3 µg/ml cisplatin. However in the cells treated with 5 µg/ml TCS combined with 3 µg/ml cisplatin, the expression of p-JNK stayed at a high level and the expressions of NF-κB and phospho-I-κB decreased dramatically compared to the cells treated with 3 µg/ml cisplatin alone. TCS could enhance cisplatin-induced apoptosis in Hep-2 and AMC-HN-8, at least in part, by inhibiting the NF-κB signaling pathway and activating JNK/SAPK signaling pathway and thus strengthening the antitumor effects of cisplatin, which highlights the possibility of combined application of TCS and cisplatin in the treatment of laryngeal carcinoma.


A convergent synthesis of the tricyclic architecture of the guanacastepenes featuring a selective ring fragmentation.
[reaction: see text] This Letter describes a concise, diastereoselective synthesis of the tricyclic carbon framework of the guanacastepene family of natural products. An intermolecular Diels-Alder reaction established a remote stereochemical relationship and facilitated a synthesis of allylic acetate 3, which was subsequently joined with vinylstananne 9 via a Stille coupling. An intramolecular [2 + 2] photocycloaddition then afforded complex cyclobutyl ketone 19, which underwent a stereoelectronically controlled fragmentation to the guanacastepene architecture on treatment with samarium diiodide.


A rational framework for decision making by the National Institute For Clinical Excellence (NICE).
Regulatory and reimbursement authorities face uncertain choices when considering the adoption of health-care technologies. In this Viewpoint, we present an analytic framework that separates the issue of whether a technology should be adopted on the basis of existing evidence from whether more research should be demanded to support future decisions. We show the application of this framework to the assessment of heath-care technologies using a published analysis of a new drug treatment for Alzheimer's disease. The results of the analysis show that the amount and type of evidence required to support the adoption of a health technology will differ substantially between technologies with different characteristics. Additionally, the analysis can be used to aid the efficient design of research. We discuss the implications of adoption of this new framework for regulatory and reimbursement decisions.


Premenstrual syndrome research: using the NIMH guidelines.
The 1983 National Institute of Mental Health (NIMH) guidelines for a premenstrual syndrome (PMS) diagnosis were applied to Daily Rating Form (DRF) data in a prospective research study. The use of two sets of criteria, each consistent with the NIMH guidelines, resulted in prevalence rates of 44% and 17%. The authors discuss other problems in defining a "syndrome": symptom patterns and the relationship between PMS and the presence of a psychiatric disorder.


Chylothorax caused by Paragonimus westermani in a native Californian.
Paragonimiasis is a parasitic infection endemic in Asia but uncommon in the United States. It presents most frequently with cough and hemoptysis. Pleural effusions are common and can manifest occasionally as a pseudochylothorax, but a true chylothorax has, to our knowledge, never been reported. We report a case of a chylothorax from infection with Paragonimus westermani. The case is also unique because it occurred in a native Californian who had not traveled to Asia and was infected by eating raw crabs at a local sushi restaurant. The freshwater crabs had been imported from Asia.


Real-time observation of the effect of iron on receptor-mediated endocytosis of transferrin conjugated with quantum dots.
The optical properties of antiphotobleaching and the advantage of long-term fluorescence observation of quantum dots are fully adopted to study the effects of iron on the endocytosis of transferrin. Quantum dots are labeled for transferrin and endocytosis of transferrin in HeLa cells is observed under the normal state, iron overloading, and an iron-deficient state. In these three states, the fluorescence undergoes a gradual process of first dark, then light, and finally dark, indicating the endocytosis of transferrin. The fluorescence intensity analysis shows that a platform emerges when fluorescence changes to a certain degree in the three states. Experienced a same period of time after platform, the fluorescence strength of cells in the normal state is 1.2 times the first value, and the iron-deficiency state is 1.4 times, but the iron overloading state was 0.85 times. We also find that the average fluorescence intensity in cells detected by the spectrophotometer in the iron-deficiency state is almost 7 times than that in a high iron state. All this proves that iron overloading would slow the process, but iron deficiency would accelerate endocytosis. We advance a direct observational method that may contribute to further study of the relationship of iron and transferrin.


Quantification of carnitine and acylcarnitines in biological matrices by HPLC electrospray ionization-mass spectrometry.
Analysis of carnitine and acylcarnitines by tandem mass spectrometry (MS/MS) has limitations. First, preparation of butyl esters partially hydrolyzes acylcarnitines. Second, isobaric nonacylcarnitine compounds yield false-positive results in acylcarnitine tests. Third, acylcarnitine constitutional isomers cannot be distinguished. Carnitine and acylcarnitines were isolated by ion-exchange solid-phase extraction, derivatized with pentafluorophenacyl trifluoromethanesulfonate, separated by HPLC, and detected with an ion trap mass spectrometer. Carnitine was quantified with d(3)-carnitine as the internal standard. Acylcarnitines were quantified with 42 synthesized calibrators. The internal standards used were d(6)-acetyl-, d(3)-propionyl-, undecanoyl-, undecanedioyl-, and heptadecanoylcarnitine. Example recoveries [mean (SD)] were 69.4% (3.9%) for total carnitine, 83.1% (5.9%) for free carnitine, 102.2% (9.8%) for acetylcarnitine, and 107.2% (8.9%) for palmitoylcarnitine. Example imprecision results [mean (SD)] within runs (n = 6) and between runs (n = 18) were, respectively: total carnitine, 58.0 (0.9) and 57.4 (1.7) micromol/L; free carnitine, 44.6 (1.5) and 44.3 (1.2) micromol/L; acetylcarnitine, 7.74 (0.51) and 7.85 (0.69) micromol/L; and palmitoylcarnitine, 0.12 (0.01) and 0.11 (0.02) micromol/L. Standard-addition slopes and linear regression coefficients were 1.00 and 0.9998, respectively, for total carnitine added to plasma, 0.99 and 0.9997 for free carnitine added to plasma, 1.04 and 0.9972 for octanoylcarnitine added to skeletal muscle, and 1.05 and 0.9913 for palmitoylcarnitine added to skeletal muscle. Reference intervals for plasma, urine, and skeletal muscle are provided. This method for analysis of carnitine and acylcarnitines overcomes the observed limitations of MS/MS methods.


Leptin receptor transcripts are constitutively expressed in placenta and adipose tissue with advancing baboon pregnancy.
The baboon (Papio sp.) is an accepted nonhuman primate model for the study of the endocrinology of human pregnancy. To further characterize this model with regard to leptin function, messenger RNA transcripts for both long (Ob-RL) and short (Ob-RS) leptin receptor isoforms were identified in maternal tissues at various stages of gestation. Thus, placental villous, subcutaneous and omental adipose tissues were collected upon cesarean delivery at early (Days 60-62), mid (Days 98-102) and late (Days 159-164) pregnancy (term approximately 184 days). Additionally, amniochorion, decidua, and corpus luteum were collected in late gestation. Expression of Ob-RL and Ob-RS transcripts was determined in relation to constitutively expressed glyceraldehyde-3-phosphate dehydrogenase via reverse transcriptase-polymerase chain reaction, and transcripts were localized within specific placental cell types by in situ hybridization. Ob-RL and Ob-RS transcripts were present in amniochorion, decidua, and corpus luteum at term and appeared constitutively expressed throughout gestation in placenta and adipose tissues. Ob-RS was expressed in greater (P < 0.02) abundance than Ob-RL in all tissues. Within the placenta, receptor isoforms were localized predominantly to the syncytiotrophoblast. The expression of leptin receptor transcripts in maternal adipose tissues, as well as in the syncytiotrophoblast, amniochorion, decidua, and corpus luteum, suggests the potential for autocrine/paracrine roles for the polypeptide in the endocrinology of primate pregnancy. These are the first such observations in a nonhuman primate and support the use of the baboon as a model for the study of leptin in human pregnancy.


Learned helplessness: expanding on a goal-directed perspective.
This commentary reviews a novel model of learned helplessness proposed by Boddez et al. in this issue of Cognition and Emotion. Combining operant and goal-directed perspectives, Boddez et al. suggest that helplessness stems from a lack of reinforcement when striving toward a goal, with the degree of generalisation dependent on subjective perceptions of goal similarity. We begin by reviewing the theoretical model, describe possible expansions from a cognitive perspective, and discuss several considerations. We finish with a brief discussion of possible directions for future work.


BACCardI--a tool for the validation of genomic assemblies, assisting genome finishing and intergenome comparison.
We provide the graphical tool BACCardI for the construction of virtual clone maps from standard assembler output files or BLAST based sequence comparisons. This new tool has been applied to numerous genome projects to solve various problems including (a) validation of whole genome shotgun assemblies, (b) support for contig ordering in the finishing phase of a genome project, and (c) intergenome comparison between related strains when only one of the strains has been sequenced and a large insert library is available for the other. The BACCardI software can seamlessly interact with various sequence assembly packages. Genomic assemblies generated from sequence information need to be validated by independent methods such as physical maps. The time-consuming task of building physical maps can be circumvented by virtual clone maps derived from read pair information of large insert libraries.


Septal rupture with right ventricular wall dissecting haematoma communicating with left ventricle after inferior myocardial infarction.
We report the case of an 86-year-old man referred for abdominal pain and ECG signs of inferior myocardial infarction. Transthoracic, transoesophageal and contrast echocardiographs showed a septal intra-mural haematoma, dissecting the right ventricle wall and partially obliterating the right ventricle lumen. A patent communication with left ventricle with extensive wall thrombosis was present at Doppler examination within dissecting haematoma. Although the patient refused any surgical treatment, a 3-month follow-up was uneventful.


Functional variation in VEGF is not associated with type 2 diabetes in a United Kingdom Caucasian population.
Vascular endothelial growth factor (VEGF) is important for pancreatic beta cell development and function. Common variation in the VEGF gene is associated with altered serum concentrations of VEGF and with several diseases, but its role in type 2 diabetes is not known. The single nucleotide polymorphisms C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963) in the 5'-region of VEGF are associated with altered serum concentrations of the protein. We performed a large case-control and family-based study to test the hypothesis that these variants are associated with type 2 diabetes in a UK Caucasian population. We genotyped 1,969 cases, 1,625 controls and 530 families for the three single nucleotide polymorphisms. Allele and genotype frequencies were compared between cases and controls. Family-based analysis was used to test for over- or under-transmission of alleles to affected offspring. Despite good power (80%) to detect odds ratios of approximately 1.2, there were no significant associations between single alleles or genotypes and type 2 diabetes. Odds ratios (and 95% confidence intervals) comparing case and control allele frequencies for single nucleotide polymorphisms C-2578A, G-1154A and G-634C were 0.97 (0.88-1.07), 0.99 (0.90-1.09) and 0.97 (0.88-1.08), respectively. This is the first large-scale study to examine the association between common functional variation in VEGF and type 2 diabetes risk. We have found no evidence that these three single nucleotide polymorphisms, shown previously to alter VEGF concentrations, are risk factors for type 2 diabetes in a large UK Caucasian case-control and family-based study.


Polyphenol- and Caffeine-Rich Postfermented Pu-erh Tea Improves Diet-Induced Metabolic Syndrome by Remodeling Intestinal Homeostasis in Mice.
Postfermented Pu-erh tea (PE) protects against metabolic syndrome (MS), but little is known regarding its underlying mechanisms. Animal experiments were performed to determine whether the gut microbiota mediated the improvement in diet-induced MS by PE and its main active components (PEAC). We confirmed that PE altered the body composition and energy efficiency, attenuated metabolic endotoxemia and systemic and multiple-tissue inflammation, and improved the glucose and lipid metabolism disorder in high-fat diet (HFD)-fed mice via multiple pathways. Notably, PE promoted the lipid oxidation and browning of white adipose tissue (WAT) in HFD-fed mice. Polyphenols and caffeine (CAF) played critical roles in improving these parameters. Meanwhile, PE remodeled the disrupted intestinal homeostasis that was induced by the HFD. Many metabolic changes observed in the mice were significantly correlated with alterations in specific gut bacteria. Akkermansia muciniphila and Faecalibacterium prausnitzii were speculated to be the key gut bacterial links between the PEAC treatment and MS at the genus and species levels. Interestingly, A. muciniphila administration altered body composition and energy efficiency, promoted the browning of WAT, and improved the lipid and glucose metabolism disorder in the HFD-fed mice, whereas F. prausnitzii administration reduced the HFD-induced liver and intestinal inflammatory responses. In summary, polyphenol- and CAF-rich PE improved diet-induced MS, and this effect was associated with a remodeling of the gut microbiota.


Layers of quasi-horizontally oriented ice crystals in cirrus clouds observed by a two-wavelength polarization lidar.
Layers of quasi-horizontally oriented ice crystals in cirrus clouds are observed by a two-wavelength polarization lidar. These layers of thickness of several hundred meters are identified by three attributes: the backscatter reveals a sharp ridge while the depolarization ratio and color ratio become deep minima. These attributes have been justified by theoretical calculations of these quantities within the framework of the physical-optics approximation.


[The diagnosis and monitoring of transitional cell cancer of the urinary tract through nuclear matrix protein 22].
To evaluate the urinary nuclear matrix protein (NMP22) as an adjuvant diagnostic index for transitional cell carcinoma of urinary tract and monitoring the state of disease. Urinary samples were collected from 262 patients with transitional cell carcinoma, 198 non-transitional cell carcinoma of the urinary tract and 65 patients with benign diseases. Urinary NMP22 concentration was determined through enzyme linked immunosorbent assay (ELISA). The urinary NMP22 concentration had significant difference among the three groups (Kruskal Wallis, chi(2) = 197.17 P < 0.001). The detection sensitivity and specificity of urinary NMP22 to transitional cell carcinoma were 71.37% and 87.69% respectively. The NMP22 concentration showed significant difference among three groups divided according to the pathological grade (Kruskal-Wallis test, chi(2) = 34.06 P < 0.01). The NMP22 concentration was significant lower in the recovery patients after the operation than the peoples of pre-operation and recurrence (Kruskal-Wallis test, chi(2) = 37.53, P < 0.001). MP22 is a helpful tumor marker for the diagnosis of transitional cell carcinoma and monitoring the state of illness with increased efficacy.


[Analytical Method for Fipronil and Fipronil Sulfone in Livestock Products Using LC-MS/MS].
A rapid and sensitive method for the simultaneous determination of fipronil and fipronil sulfone (metabolite B) in livestock products was developed. The analytes were extracted from samples with acidic acetonitrile. The crude extracts were subjected to clean-up step using neutral alumina cartridge column. The HPLC separation was performed on a C18 column with isocratic elution of acetonitrile and ammonium formate solution. For the determination of the analytes, a tandem mass spectrometry with negative ion electrospray ionization was used. In the recovery tests using 6 livestock products fortified with MRLs levels of analytes, the truenesses for fipronil and fipronil sulfone were 95 to 115 and 94 to 101% with the repeatabilities of 0.8 to 4.1 and 0.9 to 5.1 RSD%, respectively. The limits of quantification for both analytes were estimated to be 0.001 mg/kg. The developed method is considered suitable for regulatory analysis of fipronil and fipronil sulfone.


Spiritual Care Intervention and Spiritual Well-Being.
This study explored the frequency of providing aspects of spiritual care intervention and its association with nurses' own spiritual well-being in a convenience sample of 355 Jordanian Arab Muslim nurses. The nurses were recruited from different hospitals, representing both public and private health care sectors in northern and central Jordan. A cross-sectional descriptive and correlational design was used. Results indicated that Jordanian Muslim nurses provided religious aspects of spiritual care intervention to their Muslim patients infrequently and that their own spiritual well-being was positively associated with the frequency of provision of spiritual care interventions. The study concluded that Jordanian Muslim nurses most frequently provided spiritual care interventions that were existential, not overtly religious, were commonly used, were more traditional, and did not require direct nurse involvement. Moreover, the findings revealed that spiritual well-being was important to those nurses, which has implications for improving the provision of spiritual care intervention. The study provides information that enables nurses, nursing managers, and nursing educators to evaluate the nurses' provision of various aspects of spiritual care to their Muslim patients, and to identify aspects of spiritual care intervention where nurses might receive training to become competent in providing this care.


In vitro measurement of silicone bleed from breast implants.
A method to measure gel bleed from intact silicone gel-filled breast implants was developed. This nondestructive technique permits accurate and reproducible serial measurements of silicone bleed from smooth wall breast implants (n=10) under simulated physiologic conditions in vitro. Gel bleed rates from new low bleed gel-filled implants and intact explants (unbarriered, low bleed, double lumen) were determined. These results demonstrate the reliability of this method to quantify silicone gel bleed and may permit a meaningful comparison of bleed rates from implants in the future.


Neuropilin receptors guide distinct phases of sensory and motor neuronal segmentation.
The segmented trunk peripheral nervous system is generated by ventrally migrating neural crest cells that exclusively invade the anterior sclerotome and differentiate into metameric dorsal root and sympathetic ganglia. Meanwhile, ventral spinal motor axons also project through the somites in a segmental fashion. How peripheral nervous system segmentation is generated is unknown. We previously showed that neuropilin 2 (Nrp2)/semaphorin 3F (Sema3F) signaling is required for segmental neural crest migration, but not for metameric dorsal root gangliogenesis. We now expand these results to show that Nrp2 patterns initial motor axon outgrowth as well. Later, Nrp1/Sema3A signaling is essential for segmental dorsal root gangliogenesis and motor axonal fasciculation into ventral roots. Strikingly, Nrp/Sema signaling is not required for sympathetic ganglia segmentation. These data show that Nrp2 and Nrp1 work together to produce segmentation of sensory and motor nerves, and that dorsal peripheral nervous system metamerism is generated in a stepwise, Nrp-dependent process.


[Analysis of tick-host parasitic specificity. Evaluation of the Madagascar situation and intense samplings].
Ticks are traditionally considered being host-specific parasites. The pattern of tick-host relationship was elucidated by exhaustive collection from a considerable number of potential hosts from numerous sites in the Malagasy mid-altitude forest. It can from the findings be concluded that the Malagasy ticks found on small mammals may be distinguished as either having a broad host-specificity or being highly host-specific. The results may provide important information in respect to phylogenetic studies with regards to the geological history of Madagascar and its endemic fauna.


Structural studies on phospho-CDK2/cyclin A bound to nitrate, a transition state analogue: implications for the protein kinase mechanism.
Eukaryotic protein kinases catalyze the phosphoryl transfer of the gamma-phosphate of ATP to the serine, threonine, or tyrosine residue of protein substrates. The catalytic mechanism of phospho-CDK2/cyclin A (pCDK2/cyclin A) has been probed with structural and kinetic studies using the trigonal NO(3)(-) ion, which can be viewed as a mimic of the metaphosphate transition state. The crystal structure of pCDK2/cyclin A in complex with Mg(2+)ADP, nitrate, and a heptapeptide substrate has been determined at 2.7 A. The nitrate ion is located between the beta-phosphate of ADP and the hydroxyl group of the serine residue of the substrate. In one molecule of the asymmetric unit, the nitrate is close to the beta-phosphate of ADP (distance from the nitrate nitrogen to the nearest beta-phosphate oxygen of 2.5 A), while in the other subunit, the nitrate is closer to the substrate serine (distance of 2.1 A). Kinetic studies demonstrate that nitrate is not an effective inhibitor of protein kinases, consistent with the structural results that show the nitrate ion makes few stabilizing interactions with CDK2 at the catalytic site. The binding of orthovanadate was also investigated as a mimic of a pentavalent phosphorane intermediate of an associative mechanism for phosphoryl transfer. No vanadate was observed bound in a 3.4 A resolution structure of pCDK2/cyclin A in the presence of Mg(2+)ADP, and vanadate did not inhibit the kinase reaction. The results support the notion that the protein kinase reaction proceeds through a mostly dissociative mechanism with a trigonal planar metaphosphate intermediate rather than an associative mechanism that involves a pentavalent phosphorane intermediate.


Effects of cyclic loading on selected post-and-core systems.
The purpose of this study was to evaluate the resistance of selected post-and-core systems to fatigue testing. A fatigue-testing machine and data acquisition software were developed for this in vitro test. Pulpless mandibular second premolars were treated with three different types of post-and-core system: (1) two different prefabricated posts with amalgam cores, (2) the same two prefabricated posts with resin composite cores, and (3) cast post and cores, which served as the control group. The fatigue-testing machine applied alternating buccal and lingual forces to the core until lateral movement of 0.0025 inches (63.5 microns) was detected by a transducer contacting the surface of the core. This criterion represented initial cement failure. Although groups using the resin composite core material exhibited a higher number of cycles prior to failure, there was no statistically significant difference between the different post-and-core systems. All of the post-and-core systems that were tested may be acceptable for restoring endodontically treated teeth.