[Conservative treatment of hepatic trauma].
Liver trauma has increased over the past few years. In haemodynamically stable patients with hepatic injuries a conservative approach is possible, mainly as a result of the reliability of the diagnostic tools available which allow accurate monitoring of the patients. Computed tomography (CT) of the abdomen is extremely useful for documenting the extent of the damage. Of 16 patients treated for blunt hepatic injury, 10 were managed non-operatively. In this group of patients there were no deaths or delayed laparotomies. Total hospital stay and transfusion requirements were lower. The advantages of non-operative therapy include a lower incidence of abdominal septic complications. All patients managed non-operatively were monitored until their CT scans showed complete resolution. The authors conclude that non-operative management of hepatic injury is a safe technique applicable to haemodynamically stable patients.


Balneophototherapy in small plaque parapsoriasis--four case reports.
Four patients suffering from small plaque parapsoriasis were treated successfully with balneophototherapy. Within 4 weeks salt-water baths and UV irradiation resulted in clinical clearing of more than 90% of lesions with a duration of total clinical response between 8 and 12 weeks without further maintenance treatment.


A single-arm study of systemic and sub-Tenon chemotherapy for Groups C and D intraocular retinoblastoma: A Children's Oncology Group study (ARET 0231).
Eyes with Group D intraocular retinoblastoma have low salvage rates. A pilot study showed safety and efficacy of sub-Tenon's fascia carboplatin with systemic chemotherapy supporting further study. Children with newly diagnosed bilateral intraocular retinoblastoma with at least one remaining Group C or D eye were treated with six courses of carboplatin/etoposide/vincristine (CEV) with sub-Tenon's fascia carboplatin for Group C/D eyes during courses 2-4. Local ophthalmic therapy started at course 3. The primary study objective was to determine the 1-year failure rate of Group D eyes. The study closed prematurely due to poor accrual and 22 of 30 patients were evaluable for failure rate, contributing 25 Group D and four Group C eyes. Among the 25 Group D eyes, there were 13 failures within the first year of study enrollment including eight needing external beam radiotherapy (EBR) and five needing enucleation, resulting in 1-year failure rate of 52%. The failure rate was significantly lower than the historical rate of 70% (P = .039). The 1-year eye preservation rate for Group D eyes was 80% (20/25). One-year failure rate for Group C eyes was 25% (1/4); 1-year preservation rate was 100% without need for EBR. Systemic toxicity included Grade 3 hearing loss in two subjects, infections, neutropenia, and thrombocytopenia. Ocular toxicities included periorbital fat atrophy (13/29 = 45% eyes), optic nerve atrophy (1/29 = 3% eyes), and restrictive fibrosis (1/29 = 3% eyes). Sub-Tenon's fascia carboplatin plus CEV was partially effective in Group D intraocular retinoblastoma but had unacceptable ocular toxicities.


Our roles are not at ease: The work of engaging a youth advisory council in a mental health services delivery organization.
There is growing policy impetus for including youth voices in health services research and health system reform. This article examines the perspectives of professionals in a mental healthcare organization charged with engaging young people as advisors in service transformation. An institutional ethnography of a youth mental health services organization in Ontario, Canada, was conducted. Fieldwork consisted of twelve months of observation of meetings, interviews with youth advisors and adult service providers, with subsequent text analysis of engagement training and policy materials. The present article reports data from six adult professionals and related field observations. Service providers' efforts to engage youth were observed in three areas: a) supporting youth's development as advisors, b) retaining and deepening youth participation while waiting for organizational change and c) embedding relationships between youth and adults at various levels within the system of care. This work denotes existing tensions between the values and ideals of youth engagement and the everyday demands of services delivery. In this setting, a fundamental dimension of this work consisted of negotiating tensions between the policy enthusiasm for engagement and its realization in a health services context. In describing these contextual challenges, we outline implications for consideration by other youth mental health services. Engagement efforts that are authentic and sustained require resources and flexibility, and leadership commitment to instil service users' perspectives throughout multiple levels within the organization.


Impact of Aeromonas and diarrheagenic Escherichia coli screening in patients with diarrhea in Paraná, southern Brazil.
A wide diversity of bacterial agents may cause diarrhea, presenting challenges to clinical laboratories to define a diagnosis. Considering that most stool cultures are negative, we screened stool samples from patients with diarrhea for the presence of 14 bacterial enteropathogens, aiming to establish which of them should be included in routine stool analysis. Stool samples from 400 patients with diarrhea were analyzed for the presence of Salmonella, Shigella, Campylobacter, Aeromonas, Plesiomonas shigelloides, Vibrio, Yersinia enterocolitica, and diarrheagenic Escherichia coli using conventional microbiological methods and PCR. Two distinct samples were studied; one included predominantly patients involved in outbreaks, and the other patients of low socioeconomic status presenting sporadic cases of diarrhea. In total, 86 cultures (21.5%) were positive. Mixed infections were found in five patients, leading to recovery of 91 strains of enteropathogenic bacteria: Salmonella Enteritidis (9.2%), Aeromonas (7.2%), diarrheagenic E. coli (5.2%), and C. jejuni (1%). However, Salmonella predominated, with 11.5% frequency in diarrhea outbreaks, while Aeromonas predominated among patients of low socioeconomic status, with 14.6% frequency. Aeromonas and diarrheagenic E. coli, which are not routinely screened for, deserve to be included in laboratory screening panels.


Chitotriosidase activity in pleural effusions.
Chitotriosidase (ChT) is mainly secreted by monocyte-derived macrophages, and is considered a useful marker of macrophage activation. Macrophages represent the first line of defence against Mycobacterium tuberculosis, and consequently the study of ChT activity in pleural effusions (PE) would be of clinical value in the laboratory characterization of tuberculous pleurisy. ChT and adenosine deaminase (ADA) activities were determined in 12 tuberculous PE, 26 non-tuberculous lymphocytic PE and 25 neutrophilic PE. The enzyme heterogeneity study for ChT was made by thermal inactivation at 60 degrees C according to Wajner et al. (Clin Biochem 2004;37:893). ChT activity was significantly higher in the group of tuberculous PE than in the non-tuberculous lymphocytic PE group (p < 0.01), although no significant difference was found with respect to neutrophilic PE. The correlation between ChT and ADA was statistically significant, although in the partial correlation keeping the protein concentration constant, statistical significance was only achieved in tuberculous and non-tuberculous lymphocytic PE (r = 0.358, p < 0.05). In lymphocytic PE, a ChT activity greater than 40 mmol/h/mL has a sensitivity of 92%, specificity of 72%, and efficiency of 78% for the biochemical characterization of tuberculous pleurisy. Residual activities obtained for ChT by heat inactivation did not make it possible to differentiate the enzyme isoforms in PE presumably secreted by macrophages and polymorphonuclear leukocytes.


Influence of adhesive application duration on dentin bond strength of single-application bonding systems.
This study examined the relationship between the bond agent application duration and the dentin bond strength of several single-application bonding systems. The restorative material/ bonding systems used were Reactmer, with its single-application bonding system Reactmer Bond (RB, Shofu Inc, Kyoto, Japan); Palfique Estelite, with its single-application bonding system One-Up Bond F (OU, Tokuyama Co, Tokyo, Japan) and F2000 Compomer, with its bonding system Primer/Adhesive in Clicker (F2,3M Dental Products, St Paul, MN 55144, USA). Bovine mandibular incisors were mounted in self-curing resin and wet ground with #600 SiC to expose labial dentin. Adhesives were applied for 5, 10, 20, 30 and 60 seconds, and restorative materials were condensed into a Teflon mold (04 x 2 mm) on the dentin and light activated. Fifteen samples per test group were stored in 37 degrees C water for 24 hours, then shear tested at a crosshead speed of 1.0 mm/min. One-way ANOVA followed by Duncan test (p = 0.05) was done. SEM observations of the treated dentin surface were also conducted. The dentin bond strength ranged from 6.9 +/- 2.4 to 11.2 +/- 2.8 MPa for RB, 8.9 +/- 2.2 to 12.2 +/- 1.9 MPa for OU, and 7.8 +/- 3.1 to 11.4 +/- 2.6 MPa for F2. No significant differences were found among the 10-60 second application duration groups for the systems used. From the SEM observations, demineralization of the dentin surface was more pronounced with longer application duration. The data suggest that the duration of single-application bonding systems was not a crucial factor for determining dentin bond strength, even though morphological changes were observed on the dentin surface.


Linear indices of the "molecular pseudograph's atom adjacency matrix": definition, significance-interpretation, and application to QSAR analysis of flavone derivatives as HIV-1 integrase inhibitors.
This report describes a new set of molecular descriptors of relevance to QSAR/QSPR studies and drug design, atom linear indices fk(xi). These atomic level chemical descriptors are based on the calculation of linear maps on Rn[fk(xi): Rn--> Rn] in canonical basis. In this context, the kth power of the molecular pseudograph's atom adjacency matrix [Mk(G)] denotes the matrix of fk(xi) with respect to the canonical basis. In addition, a local-fragment (atom-type) formalism was developed. The kth atom-type linear indices are calculated by summing the kth atom linear indices of all atoms of the same atom type in the molecules. Moreover, total (whole-molecule) linear indices are also proposed. This descriptor is a linear functional (linear form) on Rn. That is, the kth total linear indices is a linear map from Rn to the scalar R[ fk(x): Rn --> R]. Thus, the kth total linear indices are calculated by summing the atom linear indices of all atoms in the molecule. The features of the kth total and local linear indices are illustrated by examples of various types of molecular structures, including chain-lengthening, branching, heteroatoms-content, and multiple bonds. Additionally, the linear independence of the local linear indices to other 0D, 1D, 2D, and 3D molecular descriptors is demonstrated by using principal component analysis for 42 very heterogeneous molecules. Much redundancy and overlapping was found among total linear indices and most of the other structural indices presently in use in the QSPR/QSAR practice. On the contrary, the information carried by atom-type linear indices was strikingly different from that codified in most of the 229 0D-3D molecular descriptors used in this study. It is concluded that the local linear indices are an independent indices containing important structural information to be used in QSPR/QSAR and drug design studies. In this sense, atom, atom-type, and total linear indices were used for the prediction of pIC50 values for the cleavage process of a set of flavone derivatives inhibitors of HIV-1 integrase. Quantitative models found are significant from a statistical point of view (R of 0.965, 0.902, and 0.927, respectively) and permit a clear interpretation of the studied properties in terms of the structural features of molecules. A LOO cross-validation procedure revealed that the regression models had a fairly good predictability (q2 of 0.679, 0.543, and 0.721, respectively). The comparison with other approaches reveals good behavior of the method proposed. The approach described in this paper appears to be an excellent alternative or guides for discovery and optimization of new lead compounds.


The Positive Impact of Combining Motor Imagery, Action Observation and Coach's Feedback on Archery Accuracy of Young Athletes.
In recent years, learning and motor control researchers have examined, in diverse ways, the practical strategies that enhance motor skill acquisition in sport. In this study we investigated the impact of combining Motor Imagery (MI), Feedback (F), and Action Observation (AO) on the quality of archery longbow shooting at a 10-meter target. We randomly assigned 60 young athletes to (a) a Control group (Control), (b) a Feedback and Motor Imagery group (F + MI), and (c) a Feedback, Motor Imagery, and Action Observation group (F + MI + AO). Over an 8-week intervention period athletes performed two training sessions per week. During each session, all participants engaged in two blocks of ten effective shots. Performance improvement was significantly greater in the F + MI + AO group than in the two other groups, confirming the beneficial impact of combining all three methods of improving archery accuracy. These findings suggest practical recommendations for athletes and trainers for delivering optimal mental training to improve shooting accuracy for these archers.


Transient inositol 1,4,5-trisphosphate-induced Ca2+ release: a model based on regulatory Ca(2+)-binding sites along the permeation pathway.
A remarkable property of Ca2+ fluxes through the inositol 1,4,5-trisphosphate (InsP3)-gated Ca2+ channel is that successive increments of InsP3 induce repeated transient release of accumulated Ca2+. The initial aim of this study was to propose a model, based on hypotheses compatible with the current description of this Ca2+ channel, which could account for such experimental observations. The key feature of the model was the assumption that the Ca(2+)-binding sites on the receptor, whose occupancy leads to immediate channel activation but to subsequent slow channel desensitization, were located somewhere along the permeation pathway and were therefore sensitive to the flux of Ca2+ rather than the cytosolic or luminal Ca2+ concentration per se. Simulation showed that, provided Ca2+ bound to both activating and inhibitory sites with adequate cooperativity, addition of submaximal concentrations InsP3 resulted in transient opening well above the stationary state. The model also rationalized the documented existence of a threshold for InsP3 action, the puzzling control of channel sensitivity to InsP3 by luminal and cytosolic Ca2+, as well as the functional heterogeneity of the Ca2+ pools.


Axial eye-length measurement by wavelength-shift interferometry.
A simplified noncontact measuring technique for axial eye length was developed. According to this method, the wavelength shift of a single-mode laser-diode beam that is irradiated onto the eyeball causes a phase shift in the interference fringes of reflections from the retina and the cornea. Then the optical distance between the cornea and the retina is obtained from the phase-shift measurement. High-speed axial eye-length measurements can be performed by using a laser diode on a pulse-modulation drive and signals from the reference light path as an analog-to-digital-conversion trigger. Compared with the technique that uses partially coherent light, this technique is inferior in terms of measurement accuracy but superior in its wide, measurable range of 16-32 mm. The results of measurements of 21 adults showed that 2 standard deviations of measurement was 2 sigma = +/- 0.11 mm.


Are Structural Changes in Polish Rural Areas Fostering Leisure-Time Physical Activity?
Background: In this study, we analyze the determinants of leisure-time physical activity (LTPA) of farmers and non-farmers living in rural areas. Methods: We use statistical analysis to describe urban and rural populations, as well as econometric techniques (Heckman regressions and propensity score matching) to assess the role of rural lifestyle in physical activity. Results: World Health Organization (WHO) pro-health PA (physical activity) recommendations are not met by 66% of farmers and 49% of other dwellers in rural areas. Approximately two thirds of them are completely inactive. Farmers enjoy vigorous PA (VPA), cycling and recreational walking less than their non-farming counterparts and are 46% less likely to be active than them; however the difference disappears when they take up an activity. The amount of PA is negatively correlated with age, but tends to increase for older people compared to those in middle age. Women are 6%-7% less active than men, yet the odds of being active at all are higher for women than for men. Household size is negatively correlated with LTPA. Conclusion: Considering the structural changes, rural area dwellers, especially farmers, require public intervention aimed at increasing their awareness of the advantages of LTPA.


Direct comparison of liquid-based and conventional cytology in a South African screening trial.
Our study directly compares the performance of liquid-based (LBC) and conventional cytology for detecting high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) in high-risk, previously unscreened women. As part of a larger randomized clinical trial assessing the efficacy and safety of a "screen and treat" program for cervical cancer prevention, 5,652 South African women, aged 35 to 65 years, were screened using either ThinPrep or conventional Papanicolaou cytology. The cytology method used (i.e., ThinPrep or conventional) was rotated on a 6-month basis for the duration of the study. Directly following collection of the cytology specimen, all women underwent colposcopy with endocervical curettage and biopsy of all colposcopic abnormalities. Assessment of cytology and histology results was blinded and results were compared using histology-confirmed CIN as the "gold standard." The accuracy of LBC and conventional cytology was statistically equivalent, although the sensitivity of conventional cytology was at least 5 percentage points higher at all cutoff levels. For example, at a cytology cutoff level of low-grade squamous intraepithelial lesion, the sensitivity of LBC was 60.3% for CIN2+ vs. 69.1% for conventional cytology and specificity was 94.1% and 94.5%, respectively. LBC specimens were significantly less likely to be "satisfactory-but-limited-by" (6.5% vs. 27.9%) but significantly more likely to be unsatisfactory (2.2% vs. 0.8%). Thus, in this high-risk population, the sensitivity of LBC is no greater than the sensitivity of conventional cytology. Because of the higher unit cost of LBC, low resource settings should carefully consider the potential benefits and drawbacks of LBC before adopting this new technology.


Different protective and reparative effects of olmesartan in stroke according to time of administration and withdrawal.
Angiotensin type 1 receptor blockers (ARBs) have induced improved functional recovery and reduced infarct volume in experimental animal models of stroke. Clinical data have indicated a positive correlation between prestroke treatment with ARBs and reduced stroke severity and better outcomes; however, the mechanisms of these beneficial effects are not yet well understood. This study compares the protective and possible reparative effects of continuous oral treatment with olmesartan (OLM) with OLM pretreatment and withdrawal after permanent middle cerebral artery occlusion (pMCAO) in rats. Fifty-two Sprague-Dawley rats were randomly assigned to five groups: MCAO(-/OLM) (OLM 10 mg/kg/day for 14 days after infarct), MCAO(OLM/OLM) (OLM 10 mg/kg/day for 7 days before and 14 days after infarct), MCAO(OLM/-) (OLM 10 mg/kg/day for 7 days before infarct), sham, and control. We analyzed functional recovery; lesion size; cell death; expression of the pro-oxidant enzyme NADPH oxidase 4 (NOX-4); isolectin-B4; and repair markers such as glial fibrillary acidic protein, vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF). All of the OLM-treated groups showed significantly better functional scores and reduced infarct sizes and cell death compared with the control group 14 days after pMCAO. Levels of NOX-4, VEGF, and BDNF were significantly lower in the brains of the MCAO(OLM/OLM) and sham groups compared with the other groups. OLM treatment improved functional recovery and reduced lesion size and cell death after cerebral ischemia. Only the continuous administration of OLM before and after stroke reduced oxidative stress levels, with better tissue preservation, without triggering brain repair marker activation.


Transdisciplinary teams: very important leadership stuff.
As the health care delivery system continues to evolve in terms of increased provider accountability for costs and clinical care outcomes, leaders are pushing for greater productivity and yield from all disciplines. As a result of their unique perspective of the roles of clinicians and the processes of care, nurse managers are strategically positioned to lead clinical knowledge-based teams. And they are being called on to do so. However, the skill set needed for this leadership role is quite different than that of patient-care unit leadership and management. In addition, the role and functions of senior leadership are critical to the success of both the team and its leader. This article discusses the needed competencies for both leadership entities and describes the interplay between the two.


Recognizing and treating deep neck infection.
Deep neck infection has ominous implications if not detected and treated in an early stage. The anatomic relationships of head and neck spaces encourage spread of infection. Immediate hospitalization and constant monitoring of the patient after diagnosis are mandatory.


Diagnostic value of four-dimensional CT angiography in arterial erectile dysfunction using 320-detector row dynamic volume CT.
The present study aims to evaluate the diagnostic value of four-dimensional CT angiography (4D-CTA) in the diagnosis of arterial erectile dysfunction (ED) using 320-detector row dynamic volume CT. Arterial ED patients attributed to arterial insufficiency were enrolled. To induce penile erection, an intracavernous injection (ICI) of corpus cavernosum with a vasoactive drug was administered. Patients were assigned into the erection hardness score (EHS) 1/2 group or EHS 3/4 group. Color duplex Doppler ultrasound (CDDU) was used to analyze blood flow spectrum. Each patient was examined using 4D-CTA. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of 4D-CTA in arterial ED. According to Irwin Goldstein, the EHS 3/4 group (n=38) had a shorter course of ED and low proportion with history of hypertension, hyperlipidemia, and diabetes than the EHS 1/2 group (n=35). The peak systolic velocity (PSV), end diastolic velocity (EDV), and resistant index (RI) in the EHS 3/4 group were lower than those of the EHS 1/2 group. 4D-CTA showed there were a total of 35 cases in the EHS 1/2 group (two cases missed) and 38 cases in the EHS 3/4 group (seven cases misdiagnosed). Using 4D-CTA to diagnose arterial ED, the area under the ROC curve yielded a value of 0.879, with a specificity of 93.9% and a sensitivity of 82.5%. These findings indicated that 4D-CTA using 320-detector row dynamic volume CT is a promising and reliable utility in diagnosing arterial ED.


The perfection of mimicry: an information approach.
We consider why imperfect deceptive mimics can persist when it appears to be in the predator's interest to discriminate finely between mimics and their models. One theory is that a receiver will accept being duped if the model and mimic overlap in appearance and the relative costs of attacking the model are high. However, a more fundamental explanation for the difficulty of discrimination is not based on perceptual uncertainty, but simply based on a lack of information. In particular, predators in the process of learning may cease sampling imperfect mimics entirely because the immediate pay-off and future value of information is low, allowing such mimics to persist. This outcome will be particularly likely when the model is relatively costly to attack and/or the discriminative rules the predator has to learn are complex. Information limitations neatly explain why predators tend to adopt discriminative rules based on single traits (such as stripe colour), rather than on combinations of traits (such as stripe order). They also explain why predators utilize certain salient discriminative traits while ignoring equally informative ones (a phenomenon known as overshadowing), and why imperfect mimics may be more common in phenotypically diverse prey communities.This article is part of the themed issue 'Animal coloration: production, perception, function and application'.


Reversible striatal hypermetabolism in a case of Sydenham's chorea.
We studied a 10-year-old girl with Sydenham's chorea (SC) using positron emission tomography (PET) with fluorodeoxyglucose (FDG). Choreic movements involved the head and the left side of her body. PET showed increased glucose metabolism in the right caudate nucleus and putamen. Three months after complete recovery, striatal glucose metabolism had returned to normal in the caudate nucleus. In the right putamen, glucose metabolism had decreased compared to that in the first study but remained elevated compared to that of normal young adults. We propose that the transient striatal hypermetabolism may have been due to increased afferent inputs to the striatum as a consequence of striatal or subthalamic nucleus dysfunction.


Future imaging techniques in aortic pathologies and clinical implications.
Future imaging techniques in aortic pathology will be used to detect early subclinical pathological changes and to identify patients who would benefit from early surgical intervention. Current imaging for aortic pathology is mainly computed tomography (CT). This modality produces static images which are used as the basis to decide which patients require intervention. Subclinical disease can be detected experimentally by novel magnetic resonance (MR) techniques such as molecular imaging: measurement of the amount of elastin in the aortic wall has the potential to identify patients with low levels of elastin at risk of aortic dilatation. These patients could then be monitored in a more intensive aneurysm surveillance programme. Endothelial dysfunction can also be detected experimentally by MR techniques. Measurement of endothelial permeability will be used to tailor preventative medical treatment to individual patients. Aortic diameter is the main indication for treatment in both aortic aneurysms and chronic aortic dissection but may be prone to error. False lumen thrombosis detected on first-pass imaging is used as an outcome measure in randomized controlled trials. Blood pool contrast agent imaging is flow independent and is not subject to the significant error associated with current imaging methods. Four-dimensional phase contrast magnetic resonance (4D PC-MR) imaging can quantify flow in both the true and false lumens of aortic dissection. The amount and pattern of flow in the false lumen is related to the rate of aortic expansion. 4D PC-MR can demonstrate entry tears between the true and false lumens and this information can be used to guide endovascular treatment. Hybrid imaging techniques such as positron emission tomography (PET) combined with CT (PET-CT) can give information about the degree of inflammation in the aortic wall, and preliminary studies have shown that a positive scan can predict patients with dissection who are likely to have a poor outcome. These new techniques combine anatomical and functional data in a single acquisition. The richness of the data allows a greater understanding of the pathophysiology in each individual patient which will result in improved clinical outcomes.


A single purification procedure for the major resident proteins of the ER lumen: endoplasmin, BiP, calreticulin and protein disulfide isomerase.
We have developed a single purification procedure for the four major resident endoplasmic reticulum (ER) proteins: protein disulfide isomerase (PDI), BiP, endoplasmin, and calreticulin. Three of these proteins are thought to play a role in protein folding in vivo, whereas calreticulin is thought to be the major calcium binding protein in the ER. The proteins were purified from fresh bovine liver by taking advantage of individual characteristics of the proteins. Liver microsomes were prepared and then premeabilized to release the lumenal contents. After ammonium sulfate precipitation, the proteins were purified by chromatography; BiP was purified by affinity chromatography on ATP-agarose, and both endoplasmin and calreticulin were purified by affinity chromatography on Con A-Sepharose. PDI was purified by anionic ion exchange chromatography.


Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? There Is Only One True Winner.
The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1. It is also possible that chimeric structure does not present the correct virion conformation permitting the development of protective neutralizing antibodies. A premonitory signal shared by the Sanofi Pasteur and the Takeda vaccines was the failure of fully immunized subhuman primates to prevent low-level viremia and/or anamnestic antibody responses to live DENV challenge. The vaccine developed by the National Institute of Allergy and Infectious Diseases (National Institutes of Health [NIH]) has met virtually all of the goals needed to demonstrate preclinical efficacy and safety for humans. Each monovalent vaccine was comprehensively studied for reactogenicity and immunogenicity in human volunteers. Protective immunity in subjects receiving tetravalent candidate vaccines was evidenced by the fact that when vaccinated subjects were given further doses of vaccine or different strains of DENV the result was "solid immunity," a nonviremic and nonanamnestic immune response.


[Sudden death of a 16-year-old girl with WPW syndrome: a case report].
The Wolff-Parkinson-White syndrome is a usually benign heart disease with accessory pathways. Circling excitations arise between atria and ventricles which can lead to cardiac arrhythmias. Cases of sudden cardiac death are rare (0.2 %). Risk factors for sudden cardiac death in patients with WPW syndrome are old age, several accessory pathways, male sex and previous syncopes. A 16-year-old girl was found lying dead in her bed. The evening before, she didn't feel well and complained about abdominal pain. The girl had known epilepsy and Wolff- Parkinson-White syndrome. The macroscopic and histological findings are presented and discussed with reference to the pertinent literature.


A huge omental lymphangioma with extension into labia majorae: a case report.
Abdominal cystic lymphangiomas are uncommon congenital benign tumors. We present a case of a 4 year old female child with a cystic lymphangioma arising from greater omentum and occupying whole of the abdomen and protruding through labia mejora. Ultrasonography and CT scan confirmed the diagnosis. Complete excision of the cyst along with omentectomy done with no clinical or radiological evidence of recurrence till 6 months. Due to variable presentation of abdominal lymphangiomas, extensive imaging studies are necessary for evaluation and diagnosis. Complete surgical resection is a treatment of choice.


Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study.
Preterm infants are at increased risk for vitamin D deficiency (VDD). We aimed to assess the adequacy of standardized vitamin D supplementation protocol in very low birth weight (VLBW) infants. Additionally, vitamin D status of mother/infant couples and the associations between vitamin D status at birth and morbidities of the infants were investigated. In this single-center, prospective cohort study blood samples were collected from 55 mothers just before delivery and from their infants at birth and on the 30th day of life (DOL) for 25 hydroxy vitamin D (25OHD) measurements. Vitamin D was initiated in dose of 160 IU/kg by parenteral nutrition on the first DOL and oral vitamin D supplementation (400 IU/day) was administered when enteral feedings reached 50% of total intake or on the 15th DOL. The median 25OHD levels of the infants were 16.12 (9.14-20.50) in cord blood and 36.32 (31.10-44.44) in venous blood on the 30th DOL (p<0.01). In 98% of the VLBW infants 25OHD reached sufficient levels on the 30th DOL. None of the mothers had sufficient vitamin D levels (25OHD >30 ng/mL). Maternal 25OHD levels were correlated with the 25OHD levels of the infants in cord blood (r=0.665, p<0.001). There was a significant difference in mean cord 25OHD levels between winter (13.65 ± 5.69 ng/mL) and summer seasons (19.58 ± 11.67 ng/mL) (p=0.021). No association was found between neonatal morbidity and vitamin D status. The results clearly show that by utilizing the current supplementation protocol, the majority of VLBW infants with deficient/insufficient serum 25OHD levels reached sufficient levels on the 30th DOL. Furthermore, vitamin D levels in mother/infant couples were found to be highly correlated.


Cardiac fibroma presenting as sudden death in a six-month-old infant.
Cardiac fibroma is a rare benign tumour which occurs predominantly in infancy and childhood. We present the case of a six-month-old female infant who died suddenly at home and was found at autopsy to have a large cardiac fibroma in the ventricular septum. The tumour was apparently asymptomatic although there was evidence of mild cardiac failure. Death was thought to be due to a fatal arrhythmia.


Antihistone antibodies in systemic lupus erythematosus: assay dependency and effects of ubiquitination and serum DNA.
Antihistone antibodies occur in systemic lupus erythematosus (SLE) but there are many discrepancies in their reported prevalence, isotype, specificity and correlation with disease symptoms. We examined the role of the assay and the influence of serum DNA as possible causes of these discrepancies. In addition, we sought to confirm the presence of antibodies to ubiquitin and ubiquitinated H2A (uH2A). Western blot and enzyme linked immunosorbent assay (ELISA). Sera displayed substantial differences between ELISA and Western blot in reactivity to individual histones when all reagents were nearly identical, indicating that subtle differences in the solid phase adsorbents have pronounced effect on histone antigenicity. No uniform pattern of antibody reactivity with the 5 histones was apparent with either assay. For most sera, digestion with DNase caused only minor decrease in binding to histones and no histone class showed particular sensitivity to this treatment. In agreement with most other studies, no significant correlation between histone binding and symptoms was found. Just 2 of 40 sera showed detectable binding to ubiquitin or uH2A. Although IgG antihistone antibodies were detected in 53-55% of patients with SLE with active disease, the sensitivity of antibody activity to assay conditions, patient variability, and lack of correlation with symptoms compromise the clinical utility of measuring antihistone antibodies by Western blot or ELISA: We were also unable to confirm that ubiquitin and uH2A are major antigens recognized by antibodies in SLE.


MicroRNA-149 Suppresses Inflammation in Nucleus Pulposus Cells of Intervertebral Discs by Regulating MyD88.
BACKGROUND Intervertebral disc degeneration (IDD) is associated with low back and neck pain, but the mechanisms underlying its pathogenesis are unclear. In this study, we explored the function of microRNA-149 (miR-149) in inflammatory response mediated by lipopolysaccharide (LPS) in nucleus pulposus (NP) cells. MATERIAL AND METHODS Quantitative real-time PCR was used to detect miRNA and mRNA levels, while Western blotting was utilized to determine protein levels. ELISA was used to examine chemokine production. The correlation between miR-149 and MyD88 was assessed by reporter assay. Apoptosis was examined by flow cytometry. RESULTS miR-149 expression was significantly decreased after LPS exposure in NP cells. Overexpression of miR-149 reversed LPS-induced inhibition in aggrecan and collagen II expression and attenuated LPS-mediated promotion in the levels of MMP3, ADAMTS4, and inflammatory cytokines. Moreover, we found that miR-149 exerted its function by targeting MyD88 in NP cells. CONCLUSIONS miR-149 can inhibit the inflammatory response mediated by LPS in NP cells, and might be a potential target for the treatment of IDD.


Mirror image proteins.
Proteins composed entirely of unnatural d-amino acids and the achiral amino acid glycine are mirror image forms of their native l-protein counterparts. Recent advances in chemical protein synthesis afford unique and facile synthetic access to domain-sized mirror image d-proteins, enabling protein research to be conducted through 'the looking glass' and in a way previously unattainable. d-Proteins can facilitate structure determination of their native l-forms that are difficult to crystallize (racemic X-ray crystallography); d-proteins can serve as the bait for library screening to ultimately yield pharmacologically superior d-peptide/d-protein therapeutics (mirror-image phage display); d-proteins can also be used as a powerful mechanistic tool for probing molecular events in biology. This review examines recent progress in the application of mirror image proteins to structural biology, drug discovery, and immunology.


Interferon-beta induction through toll-like receptor 3 depends on double-stranded RNA structure.
Type I interferons (IFN-alpha/beta) play an essential role in both innate and adaptive antiviral immune responses. IFN- beta is produced by fibroblasts and myeloid dendritic cells (DCs) upon viral infection or in response to doublestranded RNA (dsRNA). Several intracellular molecules having a dsRNA-binding motif such as dsRNA-dependent protein kinase recognize dsRNA in a sequence-independent manner and induce antiviral innate responses. Toll-like receptor (TLR) 3, a member of TLR family proteins, recognizes extracellular dsRNA and activates NF- kappaB and the IFN-beta promoter leading to the induction of IFN-beta production. Here we analyzed the dsRNA structure capable of inducing TLR3-mediated IFN-beta production using various synthetic RNA duplexes. In contrast to the recognition of dsRNA by intracellular molecules, TLR3 preferentially recognizes polyriboinocinic:polyribocytidylic acid (poly(I:C)) rather than synthetic virus-derived dsRNAs. 2'-O-methyl or 2'-fluoro modification of cytidylic acid abolished the IFN-beta-inducing ability of the poly(I:C) duplex, and these modified dsRNAs inhibited poly(I:C)-induced TLR3-mediated IFN-beta production by fibroblasts and DCs. In addition, poly(dI:dC), a non-IFN inducer, also blocked poly(I:C)-induced IFN-beta induction. Since TLR3 is localized in the intracellular compartment of DCs where signaling occurs, modified dsRNAs may compete with poly(I:C) for binding to the cell-surface receptor that transfers dsRNA into TLR3-enriched vesicles. Thus, TLR3 recognizes a unique dsRNA structure that largely differs from those recognized by other dsRNA-binding proteins.


Composites of perfectionism and inauthenticity in relation to controlled motivation, performance anxiety and exhaustion among elite junior performers.
The present study identified profiles of perfectionism and inauthenticity at baseline and tested whether they differed in the maladaptive outcomes of controlled motivation, performance anxiety, and exhaustion after a nine-month period. We purposefully selected elite junior performers (NT1 = 219; NT2 = 156), 16-19 years of age, from Norwegian talent development schools in sports and performing arts. The participants completed questionnaires to report their perceptions of the study variables. The results of the latent profile analysis indicated a multidimensionality of perfectionism, thereby identifying four profiles. Although our identified profiles are in line with the 2 × 2 model of perfectionism; however, the results of the mean differences between the identified profiles did not align with the 2 × 2 model's hypotheses. The elite junior performers who displayed non-perfectionism demonstrated to be the most adaptive profile. They reported the lowest level of inauthenticity and the maladaptive outcomes of controlled motivation, performance anxiety, and exhaustion. The mixed perfectionism profile, displaying high levels of perfectionistic concerns (PC) and perfectionistic strivings (PS), demonstrated to be the least adaptive profile. This profile reported higher levels of inauthenticity and was even more maladaptive than the PC dominated profile contrary to the proposed hypotheses. Findings showed that a heightened vulnerability of perfectionism seems evident in PC, independent of the reported PS levels. Because only one out of five elite junior performers were distributed in the non-perfectionism profile, the vulnerability of perfectionism might be an important risk factor to note in talent development settings.


Preparation of GM1 ganglioside with sialidase-producing marine bacteria as a microbial biocatalyst.
This paper describes the preparation of monosialoganglioside GM1 with sialidase-producing marine bacteria as a microbial biocatalyst. A new sialidase-producing bacterium, identified tentatively as Pseudomonas sp. strain YF-2, was isolated from seawater by enrichment culture with ganglioside as the sole source of carbon. When YF-2 was cultured in a synthetic medium containing crude bovine brain gangliosides at 25 degrees C for 3 days, 80 to 90% of the gangliosides were converted to GM1. GM1 was then purified from the supernatant of YF-2 culture by C18 reverse-phased chromatography, followed by DEAE-Sephadex A25 anion-exchange chromatography. In a typical experiment, 178 mg of highly purified GM1 was obtained from 500 mg of the crude ganglioside fraction. The GM1 induced neurite outgrowth of neuroblastoma Neuro2a cells at a concentration of 33 to 100 microM in the presence of fetal calf serum. Sialidase was purified 33-fold with 13.3% recovery from the culture supernatant of YF-2. The purified enzyme hydrolyzed polysialogangliosides to produce GM1 but did not act on GM1. It was therefore concluded that polysialogangliosides in the culture of strain YF-2 were converted to GM1 by this sialidase.


Transgenic chickens expressing beta-galactosidase hydrolyze lactose in the intestine.
Chickens do not possess the necessary enzymes to efficiently hydrolyze lactose into glucose and galactose. The bacterial enzyme beta-galactosidase can convert lactose into glucose and galactose. Transgenic chickens that carry the E. coli lacZ gene and express beta-galactosidase could potentially utilize lactose as an energy source. The objective of this study was to determine the ability of the transgenic chicken small intestinal mucosa to hydrolyze lactose into glucose and galactose. Lactase activity was examined in the intestinal muscosa from wild-type chickens and two lines of chickens that carry the lacZ gene and express beta-galactosidase. Lactase activity was significantly higher in both transgenic lines compared with wild-type birds (P < 0.05). The presence of the beta-galactosidase enzyme was revealed by X-gal staining in the intestine of transgenic chickens, whereas it was not present in the wild-type chickens. Overall, it appears that inserting the lacZ gene, which encodes beta-galactosidase, has resulted in a chicken that can utilize lactose as an energy source. This study demonstrates that transgenic technology can be used to modify nutrient utilization in domestic poultry.


Engineering porous membranes mimicking in vivo basement membrane for organ-on-chips applications.
Porous membrane-based microfluidic chips are frequently used for developing in vitro tissue-barrier models, the so-called tissue barriers-on-chips (TBoCs). The porous membrane in a TBoC plays a crucial role as an alternative to an in vivo basement membrane (BM). To improve the physiological relevance of an artificial porous membrane, it should possess complex BM-like characteristics from both biophysical and biochemical perspectives. For practical use, artificial membranes should have high mechanical robustness, and their fabrication processes should be conducive to mass production. There have been numerous approaches to accomplishing these requirements in BM-like porous membranes. Extracellular matrix (ECM) hydrogels have emerged as physiologically relevant materials for developing artificial BMs; they remarkably improve the phenotypes and functions of both cells and their layers when compared to previous synthetic porous membranes. However, for practical use, the poor mechanical robustness of ECM membranes needs to be improved. Recently, an advanced ECM membrane reinforced with a nanofiber scaffold has been introduced that possesses both BM-like characteristics and practical applicability. This advanced ECM membrane is expected to promote not only in vivo-like cellular functions but also cellular responses to drugs, which in turn further facilitates the practical applications of TBoCs.


Pressure-interval relationship characterizes left ventricular irregular beat contractilities and their mean level during atrial fibrillation.
How left ventricular (LV) contractility relates to irregular RR intervals during atrial fibrillation (AF) is still unclear. We investigated the relationship between the LV contractility (Emax) of individual beats and their preceding RR intervals during AF in isovolumic contractions is excised cross-circulated canine hearts, and additionally in ejecting contractions in in situ canine hearts. Atrial high-frequency electrical stimulation induced AF. We recorded a LV electrocardiogram, volume and pressure, and calculated the Emax of every arrhythmic beat. Multiple linear regression analysis between Emax and the six preceding RR intervals of all arrhythmic beats during 1 min AF showed the preceding RR interval (RR1) and the pre-preceding interval (RR2) to be the predominant predictors of Emax. The Emax-RR1/RR2 scattergram was closely fitted by a linear regression line. We found Emax at RR1/RR2 = 1 on the regression line to be virtually identical with both mean Emax during AF and stable Emax obtained during irregular atrial pacing at the same intervals as the mean RR interval during AF. These results newly indicate that the pressure-interval relationship predominantly characterizes LV irregular beat contractilities and their mean level during AF.


Emerging technologies for point-of-care management of HIV infection.
The global HIV/AIDS pandemic has resulted in 39 million deaths to date, and there are currently more than 35 million people living with HIV worldwide. Prevention, screening, and treatment strategies have led to major progress in addressing this disease globally. Diagnostics is critical for HIV prevention, screening and disease staging, and monitoring antiretroviral therapy (ART). Currently available diagnostic assays, which include polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and western blot (WB), are complex, expensive, and time consuming. These diagnostic technologies are ill suited for use in low- and middle-income countries, where the challenge of the HIV/AIDS pandemic is most severe. Therefore, innovative, inexpensive, disposable, and rapid diagnostic platform technologies are urgently needed. In this review, we discuss challenges associated with HIV management in resource-constrained settings and review the state-of-the-art HIV diagnostic technologies for CD4(+) T lymphocyte count, viral load measurement, and drug resistance testing.


Qualea grandiflora, a Brazilian "Cerrado" medicinal plant presents an important antiulcer activity.
Qualea grandiflora is one of the species widely used in folk medicine to treat gastric ulcers in Cerrado of the central region of Brazil. The hydroalcoholic extract of bark (HE) of Qualea grandiflora was investigated for their ability to prevent and heal lesions in the gastric mucosa. The oral administration of HE exhibited antiulcer activity decreasing the ulcerative index induced by HCl/ethanol solution, indomethacin/bethanechol and stress. In the Shay model, results showed that HE (p.o.) only reduced the severity of gastric lesions without effects on pH, gastric acidity or volume. When given by intraduodenal route, HE changed the pH, but did not modify the other parameters of the gastric juice. These data were in accordance with those obtained when HE was administered orally for 14 days after gastric ulcers were induced by acetic acid in rats. HE presented healing process in subacute gastric ulcer induced by acetic acid in rats. Moreover, histological examinations showed the simple columnar epithelium, lamina propria with simple branched tubular glandules with dilated lumen and large amounts of mucus secretion. Phytochemical investigation of HE led to the detection of terpenes, steroids, saponins, phenolic compounds and tannins in this extract, which may be involved in the observed activity.


Current Perspective in the Discovery of Anti-aging Agents from Natural Products.
Aging is a process characterized by accumulating degenerative damages, resulting in the death of an organism ultimately. The main goal of aging research is to develop therapies that delay age-related diseases in human. Since signaling pathways in aging of Caenorhabditis elegans (C. elegans), fruit flies and mice are evolutionarily conserved, compounds extending lifespan of them by intervening pathways of aging may be useful in treating age-related diseases in human. Natural products have special resource advantage and with few side effect. Recently, many compounds or extracts from natural products slowing aging and extending lifespan have been reported. Here we summarized these compounds or extracts and their mechanisms in increasing longevity of C. elegans or other species, and the prospect in developing anti-aging medicine from natural products.


Sex differences in tail-flick latency of non-stressed and stressed rats.
The present study was conducted to assess whether there are sex differences between male and female subjects in their response to noxious stimuli under non-stressed and stressed conditions. Tail-flick latency assay was used as an experimental tool on 12 adult male and 12 adult female Sprague-Dawley rats before immobilization (i.e., non-stressed condition) and after 30, 120, 240, and 360 min of continuous immobilization (i.e., stressed conditions). It was found that the non-stressed female rats exhibited significantly longer response latency to noxious thermal stimuli than the non-stressed male rats. Stressed conditions caused by immobilization of the animal inside a ventilated restrainer significantly prolonged the tail-flick latency thresholds of both sexes. Female and male rats did not develop any adaptation after 120, 240, and 360 min of immobilization compared to their 30 min of immobilization, as demonstrated by the tail-flick assay. Moreover, the difference in the tail-flick latency between male and female rats was reduced as the duration of immobilization in the restrainer lengthened. At 30 min of immobilization, the significant difference between the sexes reduced to p < .05 compared to p < .01 before immobilization, and to statistically non-significant differences after 120, 240, and 360 min of immobilization. Results from this study suggested that female rats had longer tail-flick latency than male rats in non-stressed environment, and the difference in tail-flick latency after immobilization between the sexes became less significant with time. In addition, 360 min of immobilization was not enough to adapt to the restrainer, as shown by the tail-flick assay.


A dual-mode surface display system for the maturation and production of monoclonal antibodies in glyco-engineered Pichia pastoris.
State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface display techniques in prokaryotic and eukaryotic cells require multiple steps of reformatting and switching of hosts to transition from display to expression. This results in a separation between antibody affinity maturation and full-length mAb production platforms. Here, we report for the first time, a method in Glyco-engineered Pichiapastoris that enables simultaneous surface display and secretion of full-length mAb molecules with human-like N-glycans using the same yeast cell. This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG molecule to a surface-anchored "bait" Fc, which results in targeting functional "half" IgGs to the cell wall of Pichiapastoris without interfering with the secretion of full length mAb. We show the utility of this method in isolating high affinity, well-expressed anti-PCSK9 leads from a designed library that was created by mating yeasts containing either light chain or heavy chain IgG libraries. Coupled with Glyco-engineered Pichiapastoris, this method provides a powerful tool for the discovery and production of therapeutic human mAbs in the same host thus improving drug developability and potentially shortening the discovery time cycle.


Ordering mechanisms in epitaxial SiGe nanoislands.
We investigate and elucidate the surprising observation of atomically ordered domains in dome-shaped SiGe nanoislands. We show, through atomistic Monte Carlo simulations, that this ordering is a surface-related phenomenon, and that is driven by surface equilibrium rather than by surface kinetics. The ordering depends on facet orientation. The main source of ordering is the {15 3 23} facet, while the {105} and {113} facets contribute less. Subsurface ordered configurations self-organize under this facet and are frozen-in and buried during island growth, giving rise to the ordered domains. Ordering mechanisms based on constrained surface kinetics, requiring step-mediated segregation at the island facets, are shown to be much less likely.


Intermittent and sustained periodic windows in networked chaotic Rössler oscillators.
Route to chaos (or periodicity) in dynamical systems is one of fundamental problems. Here, dynamical behaviors of coupled chaotic Rössler oscillators on complex networks are investigated and two different types of periodic windows with the variation of coupling strength are found. Under a moderate coupling, the periodic window is intermittent, and the attractors within the window extremely sensitively depend on the initial conditions, coupling parameter, and topology of the network. Therefore, after adding or removing one edge of network, the periodic attractor can be destroyed and substituted by a chaotic one, or vice versa. In contrast, under an extremely weak coupling, another type of periodic window appears, which insensitively depends on the initial conditions, coupling parameter, and network. It is sustained and unchanged for different types of network structure. It is also found that the phase differences of the oscillators are almost discrete and randomly distributed except that directly linked oscillators more likely have different phases. These dynamical behaviors have also been generally observed in other networked chaotic oscillators.


[Pulmonary arterial hypertension in pediatric age].
Pulmonary arterial hypertension (PAH) is serious and a progressive disease with relatively poor prognosis if not identified and treated early in children. In pediatric age group, the transition of the pulmonary circulation from fetal life to neonatal period plays a pivotal role to maintain the pulmonary vascular resistance to be low. In children with iPAH, acute drug response to vasodilator is more prominent than that in adult. But, prognosis is relatively poor. Recently, phosphodiesterase (PDE) 5 inhibitor (sildenafil, Viagra) and endothelin receptor antagonist (bosentan, Tracleer) in addition to prostacyclin used as a combination therapy can be used for this age population. The 5-year survival has been improved to > 80%. In this chapter, we focus on pathophysiological aspects and treatment strategy of idiopathic PAH, familial PAH, and PAH in the neonate (ex. PPHN).


Wall shear stress and near-wall flows in the stenosed femoral artery.
Stenotic artery hemodynamics are often characertised by metrics including oscillatory shear index (OSI) and residence time (RT). This analysis was conducted to clarify the link between the near-wall flow behaviour and these resultant flow metrics. A computational simulation was conducted of a stenosed femoral artery, with an idealised representative geometry and a physiologically realistic inlet profile. The overall flow behaviour was characterised through consideration of the axial flow, which was non-dimensionalised against mean flow velocity. The OSI and RT metrics, which are a useful indicator of likely atherosclerotic sites, were explained through a discussion of the WSS values at different time points, the velocity behaviour and velocity profiles, with a particular focus on the near-wall behaviour which influences wall shear stress and the transient evolution of the wall shear stress. While, the stenosis throat experiences high values of wall shear stress, the smooth flow through this contracted region results in low variation in wall shear stress vectors and limited opportunity for any particle stasis. However, regions were noted distal and proximal (though to a lesser extent), where the change in recirculation zones over the cycle created highly elevated regions of both OSI and RT.


Identification of characteristic gene modules of osteosarcoma using bioinformatics analysis indicates the possible molecular pathogenesis.
The aim of the present study was to investigate the possible pathogenesis of osteosarcoma using bioinformatics analysis to examine gene‑gene interactions. A total of three datasets associated with osteosarcoma were downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were identified using the significance analysis of microarrays method, which then were subjected to the Human Protein Reference Database to identify the protein‑protein interaction (PPI) pairs and to construct a PPI network of the DEGs. Subsequent multilevel community analysis was applied to mine the modules in the network, followed by screening of the differential expression module using the GlobalAncova package. The genes in the differential expression modules were verified in the valid datasets. The verified genes underwent functional and pathway enrichment analysis. A total of 616 DEGs were selected to construct the PPI network, which included 5,808 osteosarcoma‑specific interaction pairs and 8,012 normal‑specific pairs. Tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1) and estrogen receptor 1 (ESR1) were identified the most important osteosarcoma‑associated genes, with the highest levels of topological properties. Neurogenic locus notch homolog protein 3 (NOTCH3) and caspase 1 (CASP1) were identified as the osteosarcoma‑specific interaction pairs. Among all 23 mined modules, three were identified as differential expression modules, which were verified in the other two datasets. The genes in these modules were predominantly enriched in the FGFR, MAPK and Notch signaling pathways. Therefore, TP53, MAPK1, ESR1, NOTCH3 and CASP1 may be important in the development of osteosarcoma, and provides valuable clues to investigate the pathogenesis of osteosarcoma using the three differential expression modules.


Comparison of Ovarian volume and Antral follicle count with Endocrine tests for prediction of responsiveness in ovulation induction protocols.
The aim of this study was to determine if the basal antral follicle number and ovarian volume contributes to the prediction of responsiveness in ovulation induction protocol and comparison of it with hormonal tests. 52 irregularly-menstruating patients, aged 18-46 years, participated in this prospective study. All the patients underwent a transvaginal sonography to measure the basal ovarian volume and the basal antral follicles count (AFC). Clomiphene citrate challenge test was measured by summation of measurements of FSH on day 2 and 10. All the women received clomiphene citrate from day 2 to 6. Ovarian responsiveness was measured 1 week after termination of clomiphene citrate and was used as gold standard. Multiple regression analysis revealed that AFC was the only significant factor for ovarian responsiveness prediction. The area under the curve for AFC to discriminate responder ovaries was 0.66 (95% confidence interval, 0.87-0.99). The cutoff value for predicting ovarian responsiveness was 15.5. AFC can contribute to the prediction of responsiveness in ovulation induction protocol better than ovarian volume and hormonal tests.


Capillary electrophoresis integrated immobilized enzyme reactor for kinetic and inhibition assays of β-secretase as the Alzheimer's disease drug target.
Capillary electrophoresis integrated immobilized enzyme reactors are becoming an increasingly popular alternative for enzyme kinetic and inhibition assays thanks to their unique set of features including cost effectiveness, repeated use of the enzyme, minuscule sample consumption, rapid analysis time and easy automation. In this work we present the development and application of a capillary electrophoresis integrated immobilized enzyme reactor based on magnetic particles for kinetic and inhibition studies of β-secretase, a key enzyme in the development of Alzheimer's disease and a promising drug target. We document the optimization of the immobilization procedure, characterization of immobilized β-secretase, optimization of a mutually compatible incubation protocol and separation method as well as the production of the capillary electrophoresis integrated immobilized enzyme reactor. The applicability of the capillary electrophoresis integrated immobilized enzyme reactor was demonstrated by kinetic assay with an unlabelled substrate and by inhibition assays using three structurally different reference inhibitors. The resulting kinetic and inhibition parameters clearly support the applicability of the herein presented method as well as document the fundamental phenomena which need to be taken in account when comparing the results to other methods.


Waterproofing EMG Instrumentation.
While still experimental, measurement of external uterine electromyographic (EMG) activity is a more sensitive and noninvasive method for measuring uterine contractility in human labor than the methods currently used in clinical practice. Hydrotherapy is purported to improve contractility in labor, yet there have been no reports of abdominal uterine EMG activity measured during immersion. To test telemetric EMG equipment and different waterproofing techniques under dry and immersed conditions, the authors recorded surface EMG activity from the abdominal muscles of 11 healthy, nonpregnant women, 22 to 51 years of age. After attaching one pair of electrodes to the skin on either side of the umbilicus and applying the waterproofing material, the authors tested the signal by asking participants to perform a short series of leg lifts while seated in a chair to evoke abdominal muscle contractions. They were then immersed to the chest in a hydrotherapy tub while performing two to three leg lifts over 60 s every 5 min for 60 min with 20 lb of weight suspended from their ankles to counteract the buoyancy effect of water. EMG activity was continuously recorded. They then repeated the dry-measures sequence. While waterproofing remained intact, EMG signals were essentially unchanged between dry and wet conditions. Of the 11 waterproofing applications tested, 10 failed at some point. In the data from the successful application, EMG signals in both channels exhibited stable baselines throughout and an absence of low-frequency artifact. The development of this technique allows for the recording of external uterine EMG activity during hydrotherapy. The authors have begun using it to investigate the effects of hydrotherapy on uterine contractility during human labor.


Population structure of an endangered species living in contrasted habitats: Parnassia palustris (Saxifragaceae).
In endangered species, it is critical to analyse the level at which populations interact (i.e. dispersal) as well as the levels of inbreeding and local adaptation to set up conservation policies. These parameters were investigated in the endangered species Parnassia palustris living in contrasted habitats. We analysed population structure in 14 populations of northern France for isozymes, cpDNA markers and phenotypic traits related to fitness. Within population genetic diversity and inbreeding coefficients were not correlated to population size. Populations seem not to have undergone severe recent bottleneck. Conversely to pollen migration, seed migration seems limited at a regional scale, which could prevent colonization of new sites even if suitable habitats appear. Finally, the habitat type affects neither within-population genetic diversity nor genetic and phenotypic differentiation among populations. Thus, even if unnoticed local adaptation to habitats exists, it does not influence gene flow between populations.


Macrophage Migration Inhibitory Factor - A Favorable Marker in Inflammatory Diseases?
Macrophage migration inhibitory factor (MIF) was firstly described in the 1960s as a pleiotropic cytokine affecting a variety of immune cells. Different physiological functions mainly involving inflammatory reactions such as chemokine-like function and regulating systemic stress responses have been reported. In several clinical studies the use of MIF as a biomarker has been investigated promising support for diseases with an inflammatory aspect such as sepsis, systemic infections and autoimmune diseases. This article in detail reviews clinical data and evaluates the function as biomarker focusing on inflammatory and autoimmune diseases. Recent studies suggest MIF to be a marker for different inflammatory diseases and might serve as therapeutic target in the future.


Brain distribution and molecular cloning of the bovine GABA rho1 receptor.
GABA(C) receptors were originally found in the mammalian retina and recent evidence shows that they are also expressed in several areas of the brain, including caudate nucleus, brain stem, pons and corpus callosum. In this study, plasma membranes from the caudate nucleus were microinjected into X. laevis oocytes. This led the oocyte plasma membrane to incorporate functional bicuculline-resistant, Cl(-) conducting bovine GABA receptors, similar to those of the retina. Immunolocalization of the GABA rho1 subunit revealed its expression in bovine neurons in the head of the caudate as well as in the olive, cuneiform and reticular nuclei of the brain stem. The same antibodies failed to show expression in the callosum and pons, where the GABA rho1 mRNA was previously detected. The cloned GABA rho1 sequence predicts a protein with 473 amino acids and 74-93% similarity to other GABA rho1 subunits. Oocytes injected with the cDNA express a non-desensitizing, homomeric receptor with a GABA EC(50)=6.0 microM and a Hill coefficient of 1.8. The results confirm the presence of GABA(C) receptor mRNAs in several areas of the mammalian brain and show that some of these areas express functional GABA rho1 receptors that have the classic GABA(C) receptor characteristics.


Influence of transforming growth factor-beta1 gene polymorphism at codon 10 on the development of cirrhosis in chronic hepatitis B virus carriers.
Transforming growth factor (TGF)-beta1 is a key cytokine producing extracellular matrix. We evaluated the effect of TGF-beta1 gene polymorphism at codon 10 on the development of cirrhosis in patients with chronic hepatitis B. One hundred seventy eight patients with chronic hepatitis (CH, n=57) or liver cirrhosis (LC, n=121), who had HBsAg and were over 50 yr old, were enrolled. The genotypes were determined by single strand conformation polymorphism. There were no significant differences in age and sex ratio between CH and LC groups. HBeAg positivity and detection rate of HBV DNA were higher in LC than in CH groups (P=0.055 and P=0.003, respectively). There were three types of TGF-beta1 gene polymorphism at codon 10: proline homozygous (P/P), proline/leucine heterozygous (P/L), and leucine homozygous (L/L) genotype. In CH group, the proportions of P/P, P/L, and L/L genotype were 32%, 51%, and 17%, respectively. In LC group, the proportions of those genotypes were 20%, 47%, and 33%, respectively. The L/L genotype was presented more frequently in LC than in CH groups (P=0.017). Multivariate logistic regression analysis confirms that detectable HBV DNA (odds ratio [OR]: 3.037, 95% confidence interval [CI]: 1.504-6.133, P=0.002) and L/L genotype (OR: 3.408, 95% CI: 1.279-9.085, P=0.014) are risk factors for cirrhosis.


The influence of plant age on tolerance of rice to injury by the rice water weevil, Lissorhoptrus oryzophilus (Coleoptera: Curculionidae).
For most plant species, tolerance to many types of herbivory increases as plants age, but the applicability of this pattern to root herbivory has not been tested. Injury to roots of rice plants by larvae of the rice water weevil, Lissorhoptrus oryzophilus Kuschel, causes severe reductions in yields in the United States. It is generally thought that young rice plants, because their root systems are smaller, are less tolerant than older plants of root feeding by L. oryzophilus. Field experiments were conducted to test this hypothesis. Plots of rice (4.7 to 6.5 m2) were established and subjected to natural infestations of L. oryzophilus larvae. A soil insecticide was applied to plots at different times during the tillering phase of rice in order to manipulate the timing of weevil infestation. The impact of these treatments (timings of insecticide applications) was assessed by comparing relationships between yield loss and larval pressure for each treatment using analysis of covariance. Yield losses ranged from 13% to over 40% in plots not treated with insecticide. Patterns of yield losses from plots treated with insecticide at different times were best explained by the hypothesis that yield loss is determined both by the age of plants infested and by the size of larvae infesting plants. Young plants appear to be less tolerant than older plants, and feeding by large larvae appears to be more deleterious than feeding by smaller larvae. Management practices that delay infestation of rice by L. oryzophilus until plants are older may be an important component of management programmes for this pest.


Cyclic nucleotide regulation of store-operated Ca2+ influx in airway smooth muscle.
Sarcoplasmic reticulum (SR) Ca2+ release and plasma membrane Ca2+ influx are key to intracellular Ca2+ ([Ca2+]i) regulation in airway smooth muscle (ASM). SR Ca2+ depletion triggers influx via store-operated Ca2+ channels (SOCC) for SR replenishment. Several clinically relevant bronchodilators mediate their effect via cyclic nucleotides (cAMP, cGMP). We examined the effect of cyclic nucleotides on SOCC-mediated Ca2+ influx in enzymatically dissociated porcine ASM cells. SR Ca2+ was depleted by 1 microM cyclopiazonic acid in 0 extracellular Ca2+ ([Ca2+]o), nifedipine, and KCl (preventing Ca2+ influx through L-type and SOCC channels). SOCC was then activated by reintroduction of [Ca2+]o and characterized by several techniques. We examined cAMP effects on SOCC by activating SOCC in the presence of 1 microM isoproterenol or 100 microM dibutryl cAMP (cell-permeant cAMP analog), whereas we examined cGMP effects using 1 microM (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO nitric oxide donor) or 100 microM 8-bromoguanosine 3',5'-cyclic monophosphate (cell-permeant cGMP analog). The role of protein kinases A and G was examined by preexposure to 100 nM KT-5720 and 500 nM KT-5823, respectively. SOCC-mediated Ca2+ influx was dependent on the extent of SR Ca2+ depletion, sensitive to Ni2+ and La3+, but not inhibitors of voltage-gated influx channels. cAMP as well as cGMP potently inhibited Ca2+ influx, predominantly via their respective protein kinases. Additionally, cAMP cross-activation of protein kinase G contributed to SOCC inhibition. These data demonstrate that a Ni2+/La3+-sensitive Ca2+ influx in ASM triggered by SR Ca2+ depletion is inhibited by cAMP and cGMP via a protein kinase mechanism. Such inhibition may play a role in the bronchodilatory response of ASM to clinically relevant drugs (e.g., beta-agonists vs. nitric oxide).


Adolescent Gynecologic Emergencies.
Adolescent females frequently present to the ED with complaints that may be caused by a gynecologic emergency. Differentiating and excluding some of the common and most serious gynecologic emergencies reviewed in this article are critical. Timely and effective treatment of these conditions, once diagnosed, can result in better health outcomes.


In Search of Lost Springs: A Protocol for Locating Active and Inactive Springs.
Groundwater springs are significant landscape features for humans and the biota that occupies their habitat. Many springs become inactive where groundwater exploitation by humans has lowered the water table or artesian pressure. In order to assess this impact, it is important to identify and locate active, and with more difficulty, inactive springs. Using a variety of archival, environmental and field-based data, this study presents a protocol for the determination of the location and status of springs across the Great Artesian Basin of Australia. This protocol underpins a database of springs, which is not only important for the assessment of spring ecosystems, but also contributes to understand groundwater extraction impacts and hydrogeological processes. The database indicates that 30.0% of discharge (artesian) springs in the Great Artesian Basin are entirely inactive and another 11.8% are partially inactive. For the outcrop (gravity) springs of the Basin, only 1.9% are entirely inactive and 7.4% partially inactive, and for the outcrop springs in the Tertiary sandstone overlying the Basin 30.9% are inactive and 18.2% are partially inactive.


Isolation of lesbian, gay, bisexual and transgender youth: a dimensional concept analysis.
To present the findings of a dimensional analysis of isolation in the context, and from the perspective, of lesbian, gay, bisexual and transgender youth. Lesbian, gay, bisexual and transgender youth are often at greater risk for negative health outcomes compared with heterosexual youth. Isolation is one risk factor cited throughout the literature; however, the concept is complicated and has many uses and thus warrants clarification. Concept Analysis. Sources comprise 35 English language research articles retrieved from CINAHL and EBSCOHost (1987-2012). A dimensional concept analysis was undertaken to analyse how the concept, isolation, is socially constructed. This dimensional analysis revealed five socially constructed dimensions and four sub-dimensions. These findings indicate that there is substantial variability in the concept of isolation. These differences and variations are most notably observed in the 20 articles (57%) that had more than one dimension. Although some of these articles were explicit with the different meanings and use of the concept, most of the papers had wide variability in the use and meaning of the concept. The disproportionately greater physical and mental health disparities between lesbian, gay, bisexual and transgender and heterosexual youth are a signal to conduct more research to clarify the concept of isolation, to develop instrumentation to identify at-risk youth and to explore predictors and consequences of isolation. Nurses and others can lead the way in translating this knowledge into strategies that will improve the health and lives of these young people.


A comparison of prenatal muscle transcriptome and proteome profiles between pigs with divergent growth phenotypes.
The growth of pigs is an important economic trait that involves multiple genes and coordinated regulatory mechanisms. The growth rate and potential of skeletal muscles are largely decided by embryonic myofiber development. Tibetan pig (TP) that is a mini-type breed has a divergent phenotype in growth rate and adult body weight with Wujin pig (WJ) and large White pig (LW). In the current study, the transcriptome (using RNA-seq) and proteome (using the isobaric tag for relative and absolute quantification [iTRAQ]) data from the prenatal muscle tissues were analyzed to identify the genes related to postnatal growth rate and growth potential in pigs. In the RNA-seq experiment, 19 626 genes were detected in the embryonic muscle tissues, and 3626 unique differentially expressed genes (DEGs) were identified in TP in comparison to that in LW and WJ. In the iTRAQ experiment, 2474 proteins were detected, and 735 unique differentially expressed proteins (DEPs) were identified in TP in comparison to that in LW and WJ. Combining the DEGs and DEPs, 209 genes were found to be differentially expressed, consistently at both the messenger RNA and protein levels, between TP and the other two breeds; these are mainly involved in 2-oxocarboxylic acid metabolism, citrate cycle, and biosynthesis of amino acids. Of these, 20 genes that were related to myoblast differentiation and muscle fiber formation might have important roles in determining the postnatal growth rate and potential body weight in pigs. Our results provide new candidate genes and insights into the molecular mechanisms involved muscle growth traits in pigs.


Cell cycle and gene expression in the insulin producing pancreatic cell line beta TC1.
The pancreatic cell line beta TC1, established from insulinomas of transgenic mice carrying a hybrid insulin-promoted large T antigen gene, has retained several characteristics of normal cells, including the insulin content and inducibility of insulin secreting by glucose. We show here that the growth of beta TC1 cells is arrested in low serum-concentration medium. Cells exposed for three days to 0.25% fetal calf serum ceased to incorporate [3H]thymidine but were still able to resume the cell division cycle upon addition of serum. In this cell line, we have determined by cytofluorometry the cell cycle kinetic parameters to be of 21 h, 10 h 30 min and 12 h for the G1, S and G2/M phases, respectively. Quiescent beta TC1 cells constitutively expressed the protooncogene c-jun that codes for the transcriptional factor AP1, as well as cdc2, another cell cycle-related gene. A large transient increase in the expression of the c-fos gene was obtained rapidly, 30 min after addition of serum and a similar increase in c-jun expression after one hour. Expression of the cdc2 gene was also enhanced to a lesser extent. The same effects were also observed in the presence of cycloheximide, thus proving that the expression of these three genes is directly stimulated by serum growth factors. Consequently, quiescent beta TC1 cells provide a good model for studying the short- and long-term effects of growth factors on Beta-cell proliferation.


[Comparative morphological studies on the kinetoplast of various species of trypanosomes, with special reference to trypanosoma cruzi (author's transl)].
Comparative electron microscope studies on the morphology of the kinetoplast DNA (K-DNA) of the epimastigotes in many trypanosome species were carried out under standardized conditions. The K-DNA shows a morphological variation during the cell cycle of culture forms of the trypanosome species under study. In longitudinal sections of the kinetoplast, the K-DNA of T. cruzi appears as a compact trabecular structure; as a relatively disaggregated unit, with a central band or in a transitional stage between these forms. The conspicuous central band of the K-DNA which occurs at the beginning of cell division when the basal body is duplicated, could be demonstrated in all the 8 T. cruzi isolates studied. This has been found in the human-pathogen strains as well as in the T. cruzi-like trypanosomes of wild animals. In contrast, in comparable developmental stages of T. conorhini, T. rangeli and two strains of T. lewisi, this structural configuration of the K-DNA could not be observed. Based on these results, the extent to which the central band of K-DNA may be used in differentiating between trypanosomes is discussed. These findings may also reflect the present state of knowledge, as based on the study of 12 trypanosome isolates, so that corrections or additions may be lateron possible.


Isochoric heating of solid-density matter with an ultrafast proton beam.
A new technique is described for the isochoric heating (i.e., heating at constant volume) of matter to high energy-density plasma states (>10(5) J/g) on a picosecond time scale (10(-12)sec). An intense, collimated, ultrashort-pulse beam of protons--generated by a high-intensity laser pulse--is used to isochorically heat a solid density material to a temperature of several eV. The duration of heating is shorter than the time scale for significant hydrodynamic expansion to occur; hence the material is heated to a solid density warm dense plasma state. Using spherically shaped laser targets, a focused proton beam is produced and used to heat a smaller volume to over 20 eV. The technique described of ultrafast proton heating provides a unique method for creating isochorically heated high-energy density plasma states.


[Study on apoptosis mechanism of H9c2 cardiomyocytes induced by N, N-dimethylformamide].
Objective: To observe the change levels of nuclear factor-kappa B (NF-κB) p65 protein in cytoplasm and nuclear, phosphorylation of inhibitor of kappa B (p-IκB) protein and cytochrome C (Cyt-c) , cleaved cysteinyl aspartate specific proteinase-3 (Cleaved caspase-3) , B-cell lymphoma/leukemia-2 (Bcl-2) in cytoplasm in the process of N, N-dimethylformamide (DMF) -induced apoptosis in H9c2 cardiomyocytes, and explore the tentative mechanism of apoptosis. Methods: H9c2 cardiomyocytes were exposed to 200 mmol/L DMF. Western blotting was used to detect the protein expression levels of p65 in cytoplasm and nuclear, p-IκB after exposure for 0, 2, 4, 6, 8, 12 h, and the protein expression levels of Cyt-c, Cleaved caspase-3, Bcl-2 in cytoplasm after exposure for 0, 2, 4, 8, 12, 24 h. Immunofluorescencecytochemistry (IFC) was used to observe the location of Cyt-c after 200 mmol/L DMF exposure for different times. Results: The levels of p65 in cytoplasm and nuclear and p-IκB among groups were statistically significant (F were 7.79, 33.11, 90.25, respectively, all P<0.01) . Compared with the control group, the levels of p65 in cytoplasm of 2, 4, 6 h group were significantly decreased (all P<0.01) ; the levels of p65 in nuclear of 2, 4, 6, 8 h were significantly increased (all P<0.01) ; the levels of p-IκB of 2, 4, 6 h group were significantly increased (all P<0.01) . The levels of Cyt-c, Cleaved caspase-3 and Bcl-2 among groups were statistically significant (F were 51.42, 503.68, 73.37, respectively, all P<0.01) . Compared with the control group, the levels of Cyt-c of 8, 12 h group were significantly increased (both P<0.01) ; the levels of Cleaved caspase-3 of 2, 4, 8, 12, 24 h were significantly increased (all P<0.01) ; the levels of Bcl-2 of 2, 4, 8, 12, 24 h group were significantly decreased (all P<0.01) . IFC showed that Cyt-c was released from the mitochondria to the cytoplasm gradually as the extension of the exposure time. Conclusion: NF-κB signaling pathway and mitochondrial pathway are involved in the mechanism of DMF-induced apoptosis in H9c2 cardiomyocytes.


Open versus endovascular abdominal aortic aneurysm repair in Medicare beneficiaries.
Abdominal aortic aneurysms are relatively common and often life-threatening, with especially high mortality after aneurysm rupture. The introduction of endovascular aneurysm repair, a minimally invasive alternative to traditional open repair, led to decreased mortality and morbidity in randomized controlled trials, but these trials were conducted in highly selected patients and providers and were underpowered to detect differences in rare adverse events throughout follow-up. With observational studies of Medicare beneficiaries, we demonstrate that the randomized trial results are generalizable to the majority of patients undergoing abdominal aortic aneurysm repair in the United States. Additionally, with a larger cohort, comparative analyses evaluating rare, previously unstudied late outcomes such as laparotomy-related complications, late reinterventions, mortality with reinterventions, and late rupture could be conducted. Furthermore, trends in management over time and relationships between surgeon and hospital volume and outcomes can be studied. The goal of this review was to summarize the existing literature regarding abdominal aortic aneurysms among Medicare beneficiaries and to evaluate the benefits and limitations of administrative claims data in comparative effectiveness research.


Traditional fish intake and fatty acid composition in fish consuming and non-fish consuming populations.
To evaluate the validity of habitual marine fish intake, the relation between fatty acid composition of serum phospholipids and dietary patterns were investigated. Dietary intake and serum fatty acid concentrations were measured in healthy subjects of coastal fish consuming and non-fish consuming populations. Amongst fish consumers, the intake of total energy (p<0.01) and carbohydrate (p<0.05) is significantly lower and protein intake higher than in non-fish consumers. The mean percentages of saturated and monounsaturated fatty acids do not show significant variation. However, in the ω-6 fatty acid series, the percent of linoleic acid, 22:4 ω-6 and 22:5 ω-6 is significantly lower in fish consumers, whereas dihomo-gamma linolenic acid is higher than in the non-fish consumers. The percentage of w-3 fatty acids in fish consumers, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid are significantly greater (p<0.01) than those in non-fish consumers probably attributable to differences in fish intake. These differences in fatty acid profiles, particularly in the long-chain ω-3 series, are highlighted with the consumption of fish being a possible explanation between fish consuming and non-fish populations. The findings of this study suggest that the therapeutic efficacy of fish consumption is worthy of further study.


Narrow linewidth, 100 W cw Yb3+-doped silica fiber laser with a point-by-point Bragg grating inscribed directly into the active core.
We report on the power scaling to 103 W of a 1.1 microm continuous-wave Yb(3+)-doped silica fiber laser incorporating a point-by-point (PbP) fiber-Bragg grating inscribed directly into the active core using 800 nm femtosecond laser pulses. The spectrum of the laser exhibited a narrow linewidth that broadened to 260 pm at 103 W. The output was frequency doubled using an 11 mm long periodically poled MgO:LiNbO3 crystal to generate 2.1 W of green with an internal conversion efficiency of 10% at high power and 0.81%/W at low power.


Enantioseparation and chiral recognition of α-cyclohexylmandelic acid and methyl α-cyclohexylmandelate on hydroxypropyl-β-cyclodextrin as chiral selector: HPLC and molecular modeling.
Enantioseparations of (R/S)-α-cyclohexylmandelic acid [(R/S)-CHMA] and methyl (R/S)-α-cyclohexylmandelate [(R/S)-MCHMA] were performed on an achiral column (ODS) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral mobile phase additive. The influences of chromatographic conditions on the retention behavior of (R/S)-CHMA and (R/S)-MCHMA were studied in detail. Meanwhile, the thermodynamics parameters of enantioseparations for (R/S)-CHMA and (R/S)-MCHMA were determined to discuss driven power in the enantioseparation process. The inclusion complexation of HP-β-CD with each enantiomer for (R/S)-CHMA and (R/S)-MCHMA was simulated by molecular docking to understand the chiral recognition mechanism of (R/S)-CHMA and (R/S)-MCHMA on HP-β-CD. The results showed that the chiral recognition ability of enantiometers of (R/S)-CHMA and (R/S)-MCHMA on HP-β-CD is better than α-CD, β-CD, γ-CD and DM-β-CD. Under the selected chromatographic conditions, baseline separations of enantiomers of (R/S)-CHMA and (R/S)-MCHMA were achieved. It is proved that the stoichiometry for (R/S)-CHMA-HP-β-CD and (R/S)-MCHMA-HP-β-CD complexes is 1:1. However, the results of thermodynamics parameters analysis and molecular modeling show that the enantioseparations of CHMA and MCHMA on HP-β-CD are enthalpy-driven processes and the primary driving forces responsible for chiral recognition are hydrophobic forces, dipole-dipole interaction, charge-transfer and hydrophobic interaction.


[Effect of mouse interferons on the development of Ehrlich ascitic carcinoma].
Intraperitoneal injection of various preparations of mouse interferons (L cell tissue culture interferons, concentrated or partly purified, and also serum interferon) significantly inhibited the development of Ehrlich's ascites carcinoma in randombred mice. In view of comparatively low activity of serum interferon, the effect of normal mouse serum on the tumour development and its action on L cell tissue culture interferon was investigated. It was shown that normal mouse serum inhibits the action of L cell tissue culture interferon and promotes the development of Ehrlich's ascites carcinoma.


[Acute erythermalgia: look for mushrooms!].
To describe the first European observation of erythromelalgia due to mushroom poisoning. Seven cases observed and followed over 4 years are reported. All ill patients had eaten the same mushroom species, gathered in the same French alpine valley. Clinical features of erythromelalgia were observed. This syndrome was first described in Japan after Clitocybe acromelalga ingestion. It had never been observed in Europe before. Clitocybe acromelalga does not grow in Europe. Clitocybe amoenolens was identified as the possible cause of poisoning in our cases. This species can be confused with an edible mushroom, Lepista inversa. Even in Europe, recent mushroom poisoning is a possible cause of erythromelalgia.


Analysis of protein expression and compartmentalization in retinal neurons using serial tangential sectioning of the retina.
The progress in understanding visual signal transduction in vertebrate photoreceptors, arguably the best studied G protein-mediated signal transduction cascade in modern biology, was facilitated by the unique anatomy of rod photoreceptors. Held only by thin connected cilia, rod outer segments can be readily separated from the rest of the retina simply by shaking, and then purified by gradient centrifugation. The availability of such an efficient procedure of rod outer segment purification not only previously facilitated the identification of many principal visual signaling proteins located in this cellular compartment, but it is also currently being exploited in proteomics studies. In this paper, we describe a simple and inexpensive technique that allows for the quantitative analysis of protein expression within different subcellular compartments of photoreceptors, and could also be used for studying protein expression in the secondary retinal neurons. This technique is based on the Western blot analysis of the protein content of serial sections obtained by tangential sectioning of flat-mounted frozen retinas from mouse and rat, and it could serve as a way to validate proteomic data, similar to the way the quantitative RT-PCR technique is used for validation of gene-microarray data. To demonstrate the utility of this technique, we have determined the expression profiles in normal mouse retina of several signaling, energy-producing, and chaperone proteins, which were recently identified in bovine rod photoreceptors by mass spectrometry.


Assay of protein-bound lipoic acid in tissues by a new enzymatic method.
A new enzymatic method for the determination of protein-bound lipoic acid was established. Bound lipoyl groups were liberated in the form of lipoyllysine by protease digestion and assayed by lipoamide dehydrogenase (NADH:lipoamide oxidoreductase, EC 18.104.22.168)-mediated NADH oxidation. NADH oxidation was coupled to reduction of the lipoyl disulfide group. Fluorescence kinetics of NADH oxidation were markedly enhanced by the addition of glutathione disulfide, recycling the enzyme-mediated lipoyl/dihydrolipoyl conversion. In the presence of a large excess of glutathione disulfide, NADH oxidation follows pseudo-first-order kinetics in terms of lipoyllysine concentration. A good linear correlation is obtained between the oxidation rate and lipoyllysine concentration up to 5 microM and the calibration curve indicates that the detection limit could be 100 nM lipoyllysine. The method was applied to protease lysates of bovine, rat, and rabbit tissues to determine lipoyllysine levels. Kidney and liver were found to have the highest content of lipoyllysine in the range of 3.9 to 4.6 nmol/g rat or rabbit wet tissue or 11.6 to 13.1 nmol/g bovine acetone powder.


An overview of policies for managing polybrominated diphenyl ethers (PBDEs) in the Great Lakes basin.
The Great Lakes are an important environmental and economic resource for Canada and the United States. The ecological integrity of the Great Lakes, however, is becoming increasingly threatened by a number of persistent, bio-accumulative and harmful chemicals that enter the Great Lakes ecosystem through fluvial and atmospheric deposition. Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardant, are among such chemicals, whose concentration in the Great Lakes has greatly increased in recent years. Despite growing concern over the possible health and environmental effects of these compounds, only four of the eight Great Lakes states have enacted regulations to ban/restrict the use of PBDE while the two Canadian Great Lakes provinces are yet to endorse any regulation. Of the three main commercial PBDE mixtures (pentaBDE, octaBDE and decaBDE), penta- and octaBDE are no longer manufactured or imported into the United States and Canada. DecaBDE, however, still finds use in a variety of products. In the present paper, the authors review the current regulations and policies for managing PBDEs in the Great Lakes jurisdictions and briefly review commercially available non-bromine chemical alternatives to PBDE. As these alternatives are comparatively more expensive than PBDE, future adoption of more eco-friendly flame retardants by the polymer industry will likely depend on stricter legislation regulating the use of PBDE and/or an increased public demand for PBDE-free products.


Conidia of black aspergilli as new biological adsorbents for ochratoxin A in grape juices and musts.
Biological removal of ochratoxin A (OTA) by living and heat-treated dead conidia of black Aspergillus isolates representing the species Aspergillus niger, Aspergillus carbonarius, and Aspergillus japonicus in synthetic and natural grape juices was found to be a two-stage phenomenon. Several lines of evidence suggest that the first observed stage was passive, metabolism was not required, and OTA adsorption on conidia of black aspergilli could be involved. This removal was fast, without delay just after conidial inoculation both in synthetic and natural grape juices. Moreover, even nonviable, heat-treated conidia were capable of removing OTA. Finally, no OTA degradation products were detected. In the second observed stage, removal of OTA was linked to degradation by live conidia only. Ochratoxin alpha, a degradation product of OTA, was detected in the medium after incubation for 30 and 14 h for biseriate (A. niger and A. carbonarius) and uniseriate (A. japonicus) black aspergilli, respectively, when well-developed mycelium appeared. Comparisons between the three black Aspergillus isolates tested showed that A. carbonarius detoxified grape juice most effectively. However, this species often produces OTA. A. niger and A. japonicus isolates were also effective and because those species are not systematically OTA producers, they could be interesting for further OTA detoxification processes in grape juices and musts.


2020: Association for Nursing Professional Development's Year of Resources and Resilience.
The coronavirus pandemic has undoubtedly challenged the nursing professional development community to adeptly navigate unchartered territory to meet the needs of frontline staff. To ease the struggles of its membership, the Association for Nursing Professional Development conducted, summarized, and provided meaningful environmental scanning and just-in-time resources. Numerous resources were created to ensure nursing professional development practitioners were equipped to navigate the challenges presented throughout 2020.