A comparison of robotic-assisted and manual techniques in restricted kinematically aligned total knee arthroplasty: coronal alignment improvement with no significant clinical differences.
The purpose of this study was to compare radiographic and clinical outcomes of robotic-assisted and conventional manual techniques in restricted kinematically aligned TKA. Patients who underwent either manual or robotic-assisted restricted kinematically aligned TKA between 2019 and 2020 were included in this retrospective comparative study. Radiographic outcomes comprised coronal plane measurements performed through standing full-length anteroposterior radiographs. The Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford score, Visual Analog Scale pain and satisfaction score, and Forgotten Joint Score were used to determine the clinical outcome. The continuous data were compared by Student's t test according to the Kolmogorov‒Smirnov normality test. The manual group consisted of 46 patients (38 females, eight males) with a mean age of 68.1 years, and the robotic group consisted of 70 patients (58 females, 12 males) with a mean age of 65.7 years (n.s.). Preoperatively, no significant difference was observed between groups concerning demographic characteristics, radiographic measurements, and clinical scores except for the symptom and pain domains of the KOOS score, which was significantly worse in the manual group (p = 0.011 and 0.035, respectively). At the postoperative 2-year follow-up, we observed significant differences between groups with respect to the mean HKA angle, mMPTA, and mLDFA (p = 0.034, 0.041, and 0.005, respectively). A comparison of clinical scores at the postoperative 2-year follow-up demonstrated no significant differences between groups. The current study demonstrated that using robotic-assisted technique for restricted kinematically aligned total knee arthroplasty (TKA) resulted in significantly better outcomes compared to the conventional manual technique in achieving normal ranges of lower extremity coronal alignment measurements. While the robotic-assisted group demonstrated better clinical scores, there was no statistically significant difference in clinical outcomes between the robotic-assisted group and the control group at the two-year follow-up. Concerning clinical relevance, the restoration of original anatomy and coronal alignment, a crucial concern in restricted kinematically aligned TKA, may be better achieved by the robotic-assisted technique. Level III (Retrospective cohort study).


Microbial community development in tropical constructed wetland soils in Taiwan.
Constructed wetlands are widely used around the world as a low-cost wastewater treatment system that simultaneously provides various ecosystem services. Microorganisms in wetland soils serve as fundamental producers and decomposers that support wetland functions. However, few studies have documented the compositions of soil microorganisms in constructed wetland systems and even fewer have evaluated how soil microorganisms change after a wetland is constructed. In this study, soil samples were collected from four constructed wetlands of different ages and analyzed with a phospholipid fatty acid (PLFA) method to show how soil microbial communities change overtime. The results were that both the bacterial and fungal abundances increased with wetland age, and bacteria comprised about 90% of the soil microbial communities in all ages of constructed wetlands. Although the compositions of microbial communities remained similar among the wetlands, the stress indices showed that microbial stress may be affected by changes in the availability of in situ nutrients, e.g. ammonium, nitrate, soluble organic nitrogen and total dissolved nitrogen.


Civic Engagement in Neighbourhoods regarding serious illness, death and loss (CEIN): a study protocol for a convergent-parallel mixed-methods process and outcome evaluation that balances control and flexibility.
New public health approaches in palliative care attribute an active role to civic society in providing care for those who are seriously ill, caring, or bereaved. Accordingly, Civic Engagement In Neighbourhoods regarding serious illness, dying and loss (CEIN) are emerging worldwide. However, study protocols that advise on how to evaluate the impact and complex social change processes underlying these civic engagement initiatives are lacking. The main objective of this study is to describe the study protocol for the evaluation of civic engagement initiatives in serious illness, dying, and loss in two neighbourhoods in Flanders, Belgium. A convergent-parallel mixed-method process and outcome evaluation for the CEIN study. We look at the evaluation of CEIN through a critical realist lens, thereby including the social, political, and economic determinants of social change in CEIN, the mechanisms to achieve this social change, the outcomes, and the mutual connection between these three aspects. We will conduct a convergent-parallel mixed-method process and outcome evaluation in which qualitative (i.e. observations, interviews, group discussions, and ego network mapping) and quantitative data (i.e. a pre-post survey) are simultaneously but separately collected and analysed and in the last stage combined by narrative synthesis. This protocol illustrates the difficulty of operationalising the desired long-term impact of social changes regarding serious illness, dying, and loss into more manageable outcomes. We recommend a well-cogitated logic model that connects the outcomes of the study to its potential actions. Applying this protocol in practice is a constant exercise between providing sufficient flexibility to meet feasibility, desirability, and context-specific needs in the CEIN study and providing sufficient guidelines to structure and control the evaluation process.


How Qualitative Methods Can be Used to Inform Model Development.
Decision-analytic models play a key role in informing healthcare resource allocation decisions. However, there are ongoing concerns with the credibility of models. Modelling methods guidance can encourage good practice within model development, but its value is dependent on its ability to address the areas that modellers find most challenging. Further, it is important that modelling methods and related guidance are continually updated in light of any new approaches that could potentially enhance model credibility. The objective of this article was to highlight the ways in which qualitative methods have been used and recommended to inform decision-analytic model development and enhance modelling practices. With reference to the literature, the article discusses two key ways in which qualitative methods can be, and have been, applied. The first approach involves using qualitative methods to understand and inform general and future processes of model development, and the second, using qualitative techniques to directly inform the development of individual models. The literature suggests that qualitative methods can improve the validity and credibility of modelling processes by providing a means to understand existing modelling approaches that identifies where problems are occurring and further guidance is needed. It can also be applied within model development to facilitate the input of experts to structural development. We recommend that current and future model development would benefit from the greater integration of qualitative methods, specifically by studying 'real' modelling processes, and by developing recommendations around how qualitative methods can be adopted within everyday modelling practice.


DOPA-sparing strategy in the treatment of young onset Parkinson's disease.
Late onset Parkinson's disease (LOPD) is a neurodegenerative disorder afflicting individuals of ages 60 and older. However, 5-10% of cases can begin earlier between the ages 20 to 40, and are classified as young onset Parkinson disease (YOPD). In turn, this study aims to observe the trend in the choice of drug administered to patients with both YOPD and LOPD, with particular emphasis on this trend in its relation to the practice background of the neurologist. A cross-sectional study was conducted in a community based Parkinson's disease and movement disorder clinic. Using a retrospective chart review data was obtained and analysed. The results showed that 83% of general neurologists prescribed levodopa to their patients with YOPD, whereas movement-disorder specialists took a different approach altogether. They opted not to use levodopa and, in its stead, prescribed a mixture of alternate drugs.


Human-Pig Chimeric Organ in Organ Transplantation from Islamic Bioethics Perspectives.
The use of pig derivatives in medicine is forbidden in Islamic law texts, despite the fact that certain applications offer medical advantages. Pigs can be one of the best human organ hosts; therefore, using human-pig chimeras may generate beneficial impact in organ transplantation, particularly in xenotransplantation. In Islam, medical emergencies may allow some pig-based treatments and medical procedures to be employed therapeutically. However, depending on the sort of medical use, emergency situation might differ. Using Islamic legal maxim as bioethical framework, the purpose of this study is to examine the use of pigs for the purpose of human-pig chimeric transplant from the perspective of Islamic bioethics. According to the findings, chimeric organ transplantation using pigs should only be done in emergency situations.


Effects of acute on chronic respiratory failure on hypercapnia and 3-month survival.
There is a lack of information on respiratory function and mechanics after COPD exacerbations. To find their role in short-term survival and occurrence of chronic hypercapnia after these events. Seventy-three COPD patients recovering from a recent severe exacerbation underwent evaluation of breathing pattern, breathing mechanics, lung function, and arterial blood gas levels at the time of discharge from a respiratory ICU (RICU). The 3-month mortality rate after RICU discharge was 11%. The percent of ideal body weight (%IBW) [R = 6.04; p = 0.01] and occlusion pressure (R = 5.41; p = 0.02) provided significant distinction between deceased patients and survivors; the final discriminant equation showed that %IBW was able to predict patient death or survival with an accuracy of 90%. With decreasing order of power, the ratio of inspiratory time to total breathing cycle time (Ti/Ttot) [R = 8.87; p = 0.003], pressure-time product of the inspiratory muscles (R = 7.12; p = 0.009), maximal esophageal pressure (R = 6.00; p = 0.01), esophageal pressure (R = 5.50; p = 0.02), Pa(O2)/fraction of inspired oxygen (R = 4.72; p = 0.03), and pressure time index (PTI) [R = 4.57; p = 0.03] provided a significant distinction between hypercapnia and normocapnia at discharge. The discriminant equation, including Ti/Ttot and PTI, could correctly separate hypercapnic or normocapnic patients with an accuracy of 76%. In COPD patients who are recovering from a severe exacerbation, hypercapnia is strongly related to inspiratory muscle work, strength, and breathing pattern; and only body weight predicts short-term survival.


Structural analysis and reaction mechanism of the disproportionating enzyme (D-enzyme) from potato.
Starch produced by plants is a stored form of energy and is an important dietary source of calories for humans and domestic animals. Disproportionating enzyme (D-enzyme) catalyzes intramolecular and intermolecular transglycosylation reactions of α-1, 4-glucan. D-enzyme is essential in starch metabolism in the potato. We present the crystal structures of potato D-enzyme, including two different types of complex structures: a primary Michaelis complex (substrate binding mode) for 26-meric cycloamylose (CA26) and a covalent intermediate for acarbose. Our study revealed that the acarbose and CA26 reactions catalyzed by potato D-enzyme involve the formation of a covalent intermediate with the donor substrate. HPAEC of reaction substrates and products revealed the activity of the potato D-enzyme on acarbose and CA26 as donor substrates. The structural and chromatography analyses provide insight into the mechanism of the coupling reaction of CA and glucose catalyzed by the potato D-enzyme. The enzymatic reaction mechanism does not involve residual hydrolysis. This could be particularly useful in preventing unnecessary starch degradation leading to reduced crop productivity. Optimization of this mechanism would be important for improvements of starch storage and productivity in crops.


Diabetes and treatment with orally administrated corticosteroids negatively affect treatment outcome at follow-up after acute Achilles tendon rupture.
Studies investigating the influence of comorbidities on patient-reported outcomes after acute Achilles tendon ruptures (ATR) are lacking. In this study, the aim was to investigate the effect of comorbidity and medical treatment on the patient-reported outcome measure Achilles tendon total rupture score (ATRS). The study was performed as a registry study from the Danish Achilles tendon Database (DADB). In the DADB, ATRS was registered at baseline (prior to rupture), at 3-6 month, 1-year and 2-year follow-ups. The outcomes were ATRS at follow-up and the change in ATRS from baseline to follow-up. Variables of interest were diabetes, hypertension, rheumatic disease and treatment with orally administrated corticosteroids. Linear mixed-effects models including all follow-up time points in the same model were used adjusting for sex, age group, treatment (operative or non-operative) and the investigated comorbidities. Data were collected from 2012 to 2019. Two thousand and four patients with ATR were included. Patients with the investigated comorbidities and treatment with orally administrated corticosteroid scored 10.6-19.1 points lower in mean ATRS at baseline (prior to rupture) compared to patients without the respective disease or treatment. At follow-up, patients with diabetes (mean difference, [95% CI]) (- 6.2, [- 11.7; - 0.8]; P = 0.03) and patients in treatment with orally administrated corticosteroids (- 10.9, [- 16.2; - 5.7]; P < 0.01) had a statistically significantly worse ATRS than patients without the respective disease. However, change in ATRS from baseline to follow-up was not affected. Hypertension and rheumatic disease did not affect ATRS at follow-up but had a positive effect on change in ATRS (4.3, [0.5; 8.1]; P = 0.03) and (12.0, [5.0; 19.9]; P < 0.01), respectively. No other statistically significant differences were found. This study showed that patients with diabetes, hypertension, rheumatic disease and patients in treatment with orally administrated corticosteroids had a lower ATRS at baseline (prior to the rupture) when compared to patients without the respective disease or treatment. Diabetes and treatment with orally administrated corticosteroids did negatively affect ATRS at follow-up, but none of the investigated comorbidities or treatment with orally administrated corticosteroids did negatively affect change in ATRS from baseline to follow-up. Level III.


Influence of capsaicin-induced denervation on neurogenic and humoral control of arterial pressure.
(1) The influence of capsaicin-sensitive afferent neurones on the regulation of blood pressure by reflex noradrenergic responses and by activation of the renin-angiotensin system was investigated in the rat anaesthetized with pentobarbital. (2) Lowering the pressure in the carotid sinus through unilateral carotid occlusion caused a reflex rise in mean systemic blood pressure which was less marked in capsaicin-pretreated rats than in controls, although an equal drop in mean pressure in the carotid sinus region was observed in both groups. Occlusion of the second carotid artery caused an additional increase in mean systemic blood pressure which was identical in the two groups. (3) Pharmacological blockade of the renin-angiotensin-system with captopril induced a more pronounced hypotonia in capsaicin-pretreated than in control rats. Yet, this difference was based on the impaired noradrenergic counterregulation in capsaicin-pretreated rats, because both groups showed identical responses to captopril following guanethidine-induced adrenergic blockade. (4) Plasma renin activity was increased by a factor of 2 following guanethidine treatment of awake animals. It reached levels 5-7 times higher than those observed in awake animals during pentobarbital anaesthesia. This anaesthesia-induced increase in plasma renin activity was not altered by guanethidine pretreatment. There was no difference in plasma renin activity between controls and capsaicin-pretreated rats under all the conditions tested. (5) These results show that the immediate reflex adjustment of blood pressure is impaired in the capsaicin-pretreated rat, possibly because of an impairment of sensors for low perfusion pressure in the carotid sinus. On the other hand, the renin-angiotension-system remains unimpaired after neonatal capsaicin-pretreatment.


Primary central nervous system lymphoma: a clinicopathological study of 75 cases.
Pathological and clinical data in a large series of immunocompetent patients with primary lymphoma of the central nervous system (PCNSL) were analysed. We immunostained tumour specimens of 75 patients for CD3, CD4, CD5, CD8, CD10, CD20, CD30, CD79a, Bcl-2, Bcl-6, CD138, MUM1, TDT, PAX5, FOXP1 and Ki-67 and performed in situ hybridisation for Epstein-Barr virus (EBV) RNA. Eleven cases were investigated for rearrangements of BCL6, immunoglobulin heavy chain (IGH) and FOXP1 genes using fluorescent in situ hybridisation (FISH). Histologically, most cases were classified as diffuse large B-cell lymphoma (80.2%) predominantly of centroblastic type. Immunophenotypic profiling revealed that 96% and 4% of cases corresponded to non-germinal centre and germinal centre type, respectively. FISH analysis showed t(3;14)/IGH-BCL6 in 2/11 cases and trisomy 3 in 2/11 cases. FOXP1 rearrangements were not found. At survival analysis, Karnofsky index >80 and presence of Bcl-6 expression showed independent significant association with favourable patient outcome. PCNSL represents a histologically and immunophenotypically very homogeneous lymphoma type, probably derived from germinal centre exit B cells. The frequent overexpression of FOXP1 appears not to be related to FOXP1 gene rearrangement. Survival analyses disclosed Bcl-6 expression and high Karnofsky performance score as independent prognostic parameters associated with favourable outcome.


Inter-individual variability of the facial morphology during conscious smiling.
Since many simulation and animation procedures for mimicry are based on averaged values and do not take into account an individual's situation, the goal of this study was to investigate the intra- and inter-individual variability of conscious smiling. Twenty-three surface points were marked on the faces of 31 adult test individuals. Six photographs of each subject's face were then taken under standardized conditions, one with a neutral facial expression and five while the individual was asked to smile (conscious smile "on command"). After digital superposition of the individual images (neutral and smiling) the displacements were measured for every measurement point on each individual. All data underwent statistical evaluation after normalization in the vertical and horizontal directions. Evaluation of intra- and inter-individual variability was carried out by analyzing the corresponding coefficients of variation and the formation of confidence intervals (confidence level 95%). The repeated measurements upon conscious smiling showed a moderate intra-individual variability with coefficients of variation under 10%. In contrast, the inter-individual variability of the measured values was relatively high. Here variation coefficients were measured of between 28% and 60% depending on the localization of the measuring point. The displacements' absolute magnitude was greatest in the lower facial third. The two corners of the mouth, the upper lip in the philtrum area, the cheeks and the side wings of the nose revealed the highest displacements. Due to the high inter-individual variability, an analysis based on averaged values or a simulation of the conscious smile must be viewed with a certain amount of criticism.


Ovarian ageing and the general biology of senescence.
Ovarian ageing is not only of major importance in its own right but is also of interest for its relationship with the general biology of senescence. A key feature of ageing is the distinction in higher animals between the immortality of the germ-line and the mortality of somatic cells and tissues. The ovary contains the female germ cells, and it is through these cells that the female contribution to germ-line immortality is effected. It is abundantly clear that individual oocytes can and do age and that the ageing of the ovary plays a major role in initiating or accelerating a series of other senescent changes. To understand how ovarian ageing fits within the general biology of senescence, it is necessary to explain why ageing occurs at all, to examine the likely mechanisms of general ageing, and to ask whether there is anything special about ovarian ageing and its relationship with the human menopause. Research on ovarian ageing interacts with the our emerging understanding of the general biology of senescence at many levels, ranging from the evolution of the human life history to the biochemical and cellular mechanisms of ageing and longevity.


Efficacy and safety of percutaneous treatment of iatrogenic femoral artery pseudoaneurysm by biodegradable collagen injection.
OBJECTIVES; The goal of this study was to assess the safety and efficacy of femoral artery pseudoaneurysm (FAP) closure by collagen injection. BACKGROUND; The FAP is an infrequent but troublesome complication after percutaneous transfemoral catheter procedures. If ultrasound-guided compression repair (UGCR) fails, vascular surgery is indicated. We have developed a less invasive method to close FAPs percutaneously by injecting collagen and, thus, inducing clotting within the aneurysm. Via a 9F needle or 11F sheath, a biodegradable adhesive bovine collagen is injected percutaneously into the FAP, guided by angiography from the contralateral site. From 1993 to 2000, compression and UGCR had failed to obliterate 110 FAPs. These patients have been treated by collagen injection. Mean age of the patients was 65.6 +/- 10.2 years (range: 32 to 85 years), and 50% were women. Immediate closure of the FAP was achieved in 107/110 patients (97.3%) without any complication or adverse effect. In one patient the collagen could not be applied due to unfavorable anatomy. One patient needed a second session of collagen injection. In one patient too much collagen was inserted, which resulted in external compression of the artery, and surgical intervention was required. The overall success rate was 108/110 (98%, 95% confidence interval: 93.5% to 99.8%). Among the patients with successful procedures, there were no recurrences during six months follow-up. The percutaneous treatment of iatrogenic FAP, by injection with collagen, is an effective and safe strategy. This method provides an excellent therapeutic alternative to the traditional surgical management.


Global molecular evolution and phylogeographic analysis of barley yellow dwarf virus based on the cp and mp genes.
Barley yellow dwarf virus (BYDV) has caused considerable losses in the global production of grain crops such as wheat, barley and maize. We investigated the phylodynamics of the virus by analysing 379 and 485 nucleotide sequences of the genes encoding the coat protein and movement protein, respectively. The maximum clade credibility tree indicated that BYDV-GAV and BYDV-MAV, BYDV-PAV and BYDV-PAS share the same evolutionary lineage, respectively. The diversification of BYDV arises from its adaptability to vector insects and geography. Bayesian phylogenetic analyses showed that the mean substitution rates of the coat and movement proteins of BYDV ranged from 8.327 × 10- 4 (4.700 × 10- 4-1.228 × 10- 3) and 8.671 × 10- 4 (6.143 × 10- 4-1.130 × 10- 3) substitutions/site/year, respectively. The time since the most recent common BYDV ancestor was 1434 (1040-1766) CE (Common Era). The Bayesian skyline plot (BSP) showed that the BYDV population experienced dramatic expansions approximately 8 years into the 21st century, followed by a dramatic decline in less than 15 years. Our phylogeographic analysis showed that the BYDV population originating in the United States was subsequently introduced to Europe, South America, Australia and Asia. The migration pathways of BYDV suggest that the global spread of BYDV is associated with human activities.


The skeletal stability of Le Fort I downfracture osteotomies with rigid fixation.
Twenty subjects receiving Le Fort I downfracture osteotomies stabilized with rigid fixation were studied for relapse. The analysis was based on longitudinal cephalometric radiographs taken within 2 weeks presurgically, 1 week postsurgically, and after a minimum period of 6 months postsurgically. Vertical and sagittal changes in the maxilla were evaluated in reference to the Frankfort horizontal plane. It was found that the mean postsurgical relapse was minimal and not significant. It was smaller than that reported for patients who had received stabilization of the maxilla with intraosseous and maxillomandibular wiring. It was concluded that the rigid fixation technique is dependable and yields stable postsurgical results in the maxilla.


Reduced-intensity conditioning with Fludarabin, oral Busulfan, and thymoglobulin allows long-term disease control and low transplant-related mortality in patients with hematological malignancies.
The development of reduced-intensity conditioning regimens rather than myeloablative regimens for allogeneic stem cell transplantation has led to decreased treatment-related mortality and increased use of this treatment modality, especially in older patients with hematological malignancies. No randomized controlled trials have been performed resulting in determining effectiveness on phase II studies, which rarely report on long-term survival. In an attempt to address this limitation, we analyzed a single-center cohort of 100 consecutive patients with hematological malignancies undergoing allogeneic stem cell transplantation from a human leukocyte antigen-matched related donor with median follow-up of 60 months. The reduced-intensity conditioning regimen consisted of oral Busulfan, rabbit anti-thymocyte globulin, and Fludarabin. Median age was 50 years (range, 18-64 years). The incidences of acute and chronic graft-vs.-host disease were 43% and 81%, respectively. The probability of nonrelapse mortality at 1 and 5 years was 15% and 25%, respectively. Nonrelapse mortality was adversely associated with acute graft-vs.-host disease (hazard ratio = 6; p = 0.0002). Of the 52 patients with measurable disease, 37 (71%) achieved a response. Relapse/progression occurred at a median of 11 months (range 1-52 months) in 21 patients, for a cumulative incidence of 22%. The probability of overall survival and progression-free survival at 5 years were 60% and 54%, respectively. Overall survival and progression-free survival were favorably influenced by having had previous autologous stem cell transplantation and a low CD34(+) cell dose. Overall survival, progression-free survival, and nonrelapse mortality improved over time in this cohort of patients. These results are encouraging for populations different in term of age, diagnosis, and disease status.


A synthesis of α-amino acids via direct reductive carboxylation of imines with carbon dioxide.
A method for the synthesis of α-amino acids by direct reductive carboxylation of aromatic imines with CO2 is described. The protocol employs readily available commercial reagents and serves as a one-step alternative to the Strecker synthesis.


Prenatal ethanol exposure impairs temporal ordering behaviours in young adult rats.
Prenatal ethanol exposure (PNEE) causes significant deficits in functional (i.e., synaptic) plasticity in the dentate gyrus (DG) and cornu ammonis (CA) hippocampal sub-regions of young adult male rats. Previous research has shown that in the DG, these deficits are not apparent in age-matched PNEE females. This study aimed to expand these findings and determine if PNEE induces deficits in hippocampal-dependent behaviours in both male and female young adult rats (PND 60). The metric change behavioural test examines DG-dependent deficits by determining whether an animal can detect a metric change between two identical objects. The temporal order behavioural test is thought to rely in part on the CA sub-region of the hippocampus and determines whether an animal will spend more time exploring an object that it has not seen for a larger temporal window as compared to an object that it has seen more recently. Using the liquid diet model of FASD (where 6.6% (v/v) ethanol is provided through a liquid diet consumed ad libitum throughout the entire gestation), we found that PNEE causes a significant impairment in the temporal order task, while no deficits in the DG-dependent metric change task were observed. There were no significant differences between males and females for either task. These results indicate that behaviours relying partially on the CA-region may be more affected by PNEE than those that rely on the DG.


The selective progesterone receptor modulator, telapristone acetate, is a mixed antagonist/agonist in the human and mouse endometrium and inhibits pregnancy in mice.
To investigate the effect of the selective progesterone receptor modulator, telapristone acetate (CDB-4124), on endometrial biology and reproductive outcomes. Ovariectomized and hormone-treated CD1 female mice, CD1 female mice with xenotransplants of reconstructed human endometrial tissue, mated wildtype female mice, and cultured human endometrial stromal cells (hESCs) were treated with CDB-4124, followed by the assessment of endometrial cell deoxyribonucleic acid (DNA) proliferation, stromal decidual response, and embryo implantation. Experimental study. Academic research laboratory. Healthy volunteer women from the community were recruited for endometrial biopsies. CD1 out-bred mice (Charles River Laboratories) and nude mice, NU/J (Jackson Laboratories, Bar Harbor, ME). Treatment of mice and hESCs with CDB-4124. The effect of CDB-4124 on endometrial cell morphology and DNA synthesis, decidual response, and mouse embryo implantation. CDB-4124 inhibited estradiol-induced epithelial DNA synthesis in the mouse uterus and xenotransplanted human endometrium. This antiproliferative effect was less than that of progesterone (P4) and was observed when CDB-4124 was administered alone or concomitantly with P4. In the uterine epithelium, CDB-4124 acted as a P4 agonist and partial antagonist. In contrast, CDB-4124 acted as a complete P4 antagonist in the uterine stroma, where it blocked P4's action to induce a decidual response in the pseudopregnant mouse uterus and wildtype mouse uterus after copulation. In mated female mice, CDB-4124 impaired embryo implantation. Similarly, CDB-4124 inhibited the morphological and biochemical transformations of hESCs to decidual cells in vitro. CDB-4124 exerts mixed P4 antagonistic/agonistic effects in the human and mouse endometrium, which result in failed embryo implantation because of the absence of stromal decidualization.


MOCSS: Multi-omics data clustering and cancer subtyping via shared and specific representation learning.
Cancer is an extremely complex disease and each type of cancer usually has several different subtypes. Multi-omics data can provide more comprehensive biological information for identifying and discovering cancer subtypes. However, existing unsupervised cancer subtyping methods cannot effectively learn comprehensive shared and specific information of multi-omics data. Therefore, a novel method is proposed based on shared and specific representation learning. For each omics data, two autoencoders are applied to extract shared and specific information, respectively. To reduce redundancy and mutual interference, orthogonality constraint is introduced to separate shared and specific information. In addition, contrastive learning is applied to align the shared information and strengthen their consistency. Finally, the obtained shared and specific information for all samples are used for clustering tasks to achieve cancer subtyping. Experimental results demonstrate that the proposed method can effectively capture shared and specific information of multi-omics data and outperform other state-of-the-art methods on cancer subtyping.


Normal database of dopaminergic neurotransmission system in human brain measured by positron emission tomography.
The central dopaminergic system is of interest in the pathophysiology of schizophrenia and other neuropsychiatric disorders. Both pre- and postsynaptic dopaminergic functions can be estimated by positron emission tomography (PET) with different radiotracers. However, an integrated database of both pre- and postsynaptic dopaminergic neurotransmission components including receptors, transporter, and endogenous neurotransmitter synthesis has not yet been reported. In the present study, we constructed a normal database for the pre- and postsynaptic dopaminergic functions in the living human brain using PET. To measure striatal and extrastriatal dopamine D(1) and D(2) receptor bindings, dopamine transporter binding, and endogenous dopamine synthesis rate, PET scans were performed on healthy men after intravenous injection of [(11)C]SCH23390, [(11)C]raclopride, [(11)C]FLB457, [(11)C]PE2I, or L-[beta-(11)C]DOPA. All PET images were anatomically standardized using SPM2, and a database was built for each radiotracer. Gray matter images were segmented and extracted from all anatomically standardized magnetic resonance images using SPM2, and they were used for partial volume correction. These databases allow the comparison of regional distributions of striatal and extrastriatal dopamine D(1) and D(2) receptors, dopamine transporter, and endogenous dopamine synthesis capability. These distributions were in good agreement with those from human postmortem studies. This database can be used in various researches to understand the physiology of dopaminergic functions in the living human brain. This database could also be used to investigate regional abnormalities of dopaminergic neurotransmission in neuropsychiatric disorders.


New species of Edessa Fabricius, 1803 (Hemiptera: Pentatomidae) from Costa Rica.
The edessines from Costa Rica are little known; only 18 species have been registered or described from this country so far. Mainly based in a large sample from Instituto Nacional de Biodiverdidad (INBio), Costa Rica, we decided to update the information concerning Edessinae from Costa Rica. We present a list of species from Costa Rica raising the number of known species from Costa Rica to 65. We are also describing nine new species: Edessa bella Fernandes & Silva, E. bruneolineata Fernandes & Correia, E. curvata Fernandes & Nunes, E. lewisi Fernandes & Silva, E. nigroangulata Fernandes & Silva, E. osae Fernandes & Nunes, E. oxcarti Fernandes & Correia, E. pallidoangulata Fernandes & Nunes and E. puravida Fernandes & Correia. Species were described, illustrated and photographed. Distribution maps for the species are also provided.


Sorption behavior and mechanism of U(VI) on Tamusu clay in the presence of U(VI)-CO3 complexes.
The sorption behavior of U(VI) on Tamusu clay sampled from a pre-selected high-level radioactive waste (HLW) disposal site in Inner Mongolia (China) was studied systematically in the U(VI)-CO3 solution at pH 7.8 by batch experiments. The results demonstrated that the distribution coefficients (Kd) decreased with the increasing values of pHinitial, [U(VI)]initial, and ionic strength, but increased with the extended time and the rising temperature. The sorption was a pH-dependent, heterogeneous, spontaneous, and endothermic chemical process, which could be better described by Freundlich isothermal model and pseudo-second-order kinetic model. The presence of humic acid (HA) or fulvic acid (FA) significantly inhibited the U(VI) sorption, due to the enhanced electrostatic repulsion between the negatively charged HA/FA adsorbed on the clay surface and the negative U(VI) species, as well as the well dispersed HA/FA aggregates in solution wrapping the U(VI) species. The FTIR and XPS spectra indicated that the HCO3- groups on the surface of Tamusu clay after hydroxylation and the ‒OH groups in HA/FA were involved in the U(VI) sorption. The results reported here provide valuable insights into the further understanding of U(VI) migration in geological media.


Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance.
Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric &symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric &symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm(-2) &19.1 Wh Kg(-1) and 194 mF cm(-2) &4.5 Wh Kg(-1) (based on total mass loading of 6.25 &6.0 mg) respectively at current density of 1 mA cm(-2). The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices.


Microcarrier cultivation of bovine aortic endothelial cells in spinner vessels and a membrane stirred bioreactor.
Primary bovine aortic endothelial cells were cultivated in serum supplemented medium without any additional growth factors. The anchorage dependent cells were propagated on Dormacell(®) microcarriers with covalently bound dimeric DEAE-groups at the surface of the dextrane beads. Cultivations were performed in 200 ml spinner cultures containing 1 g l(-1) to 3 g l(-1) of microcarriers. Out of five types of Dormacell(®) microcarriers with different ion exchange capacities ranging from 0.30 up to 0.65 meq g(-1), corresponding to nitrogen contents from 1.2% to 2.9%, respectively, optimal attachment and growth of endothelial cells were obtained with beads of highest nitrogen content (2.9%). Cells were seeded withca. 5 viable cells per microcarrier being sufficient to achieve fully confluent microcarriers after 4 to 5 days. Glucose concentrations decreased from 21 mM to uppermost half of the original concentrations. 4 mM glutamine was rapidly consumed and virtually exhausted after the cells reached confluency. Lactate concentrations raised to a maximum of 7 mM in spinner cultures, but was found to be reutilized in the stationary phase after glutamine limitation occurred. Serine was found to be the second most prominent amino acid being almost exhausted at confluency whereas alanine was produced in noteworthy amounts. Considerable decrease was determined for threonine, lysine and arginine; low consumption rates were observed for leucine, phenylalanine and methionine. All other amino acids did not alter significantly throughout cultivation. These data support that bovine aortic endothelial cells are capable to utilize glucose and glutamine as well as lactic acid (after glutamine exhaustion) as energy and/or carbon source. Finally, batch cultures in a 2 liter membrane stirred bioreactor with bubble-free aeration were performed to produce large quantities of endothelial cells using microcarrier concentrations of 3 g l(-1).


Kinetic evaluation of new generation of column packed with 1.3 μm core-shell particles.
The goal of this study was to critically evaluate a new generation of columns packed with 1.3 μm core-shell particles. The practical possibilities and limitations of this column technology were assessed and performance was compared with other reference columns packed with 1.7, 2.6 and 5 μm core-shell particles. The column efficiency achieved with 1.3 μm core-shell particles was indeed impressive, Hmin value of only 1.95 μm was achieved, this would correspond to an efficiency of more than 500,000 plates/m. The separation impedance of this column was particularly low, Emin=2000, mostly due to a reduced plate height, h of 1.50. Comparing the kinetic performance of 1.3 μm core-shell particles to that of other particle dimensions tested in this study revealed that the 1.3 μm material could provide systematically the shortest analysis time in a range of below 30,000 theoretical plates (N<30,000).Despite its excellent chromatographic performance, it was evident that this column suffers from the limitations of current instrumentation in terms of upper pressure limit and extra-column band broadening: (1) even at 1,200 bar, it was not possible to reach an optimal linear velocity showing minimal plate height value, due to the low permeability of this column (Kv=1.7×10(-11)cm(2)), and (2) for these short narrow bore columns packed with 1.3 μm core shell particles, which is mandatory for performing fast-analysis and preventing the influence of frictional heat on column performance in UHPLC, it was observed that the extra-column band broadening could have a major impact on the apparent kinetic performance. In the present work, significant plate count loss was noticed for retention factors of less than 5, even with the best system on the market (σ(2)ec=2 μL(2)).


Disseminated lethal Encephalitozoon cuniculi (genotype III) infections in cotton-top tamarins (Oedipomidas oedipus)--a case report.
For the first time, Encephalitozoon (E.) cuniculi genotype III ('dog strain') was verified in two cotton-top tamarins (Oedipomidas oedipus) by light microscopy, immunohistochemistry, electron microscopy, PCR and sequencing. The animals had a disseminated lethal infection with this protist. In earlier reports, genotype III had been found only in domestic dogs, man, emperor tamarins (Saguinus imperator) and golden lion tamarins (Leontopithecus rosalia). This investigation establishes now that the 'dog strain' can occur in cotton-top tamarins too. This is further evidence for the zoonotic potential of E. cuniculi. Furthermore, free E. cuniculi spores were identified also in blood vessels of several tissues. These findings indicate that during a disseminated infection E. cuniculi spores can occur in peripheral blood, too. We propose that blood should also be included in the investigations for the detection of microsporidia, so that a possible disseminated course of an infection can be detected.


Opioid self-administration results in cell-type specific adaptations of striatal medium spiny neurons.
Medium-sized spiny neurons (MSNs), the predominant neuronal population of the striatum, are an integral component of the many cortical and limbic pathways associated with reward-related behaviors. A differential role of the D1 receptor-enriched (D1) MSNs of the striatonigral direct pathway, as compared with the D2 receptor-enriched (D2) MSNs of the striatopallidal indirect pathway, in mediating the addictive behaviors associated with cocaine is beginning to emerge. However, whether opioids, well-known analgesics with euphoric properties, similarly induce dissociable signaling adaptations in these neurons remains unclear. Transgenic mice expressing green fluorescent protein (GFP)-labeled D1 or D2 neurons were implanted with intravenous jugular catheters. Mice learned to self-administer 0.1mg/kg/infusion of the opioid remifentanil during 2h sessions over 13 contiguous days. Thereafter, the electrophysiological properties of D1- and D2-MSNs in the shell region of the nucleus accumbens (NAc) were assessed. We found that prior opioid exposure did not alter the basic membrane properties nor the kinetics or amplitude of miniature excitatory postsynaptic currents (mEPSCs). However, when challenged with the mu opioid receptor (μOR) agonist DAMGO, the characteristic inhibitory profile of this receptor was altered. DAMGO inhibited the frequency of mEPSCs in D1-MSNs from control mice receiving saline and in D2-MSNs from mice exposed to remifentanil or saline, but this inhibitory profile was reduced in D1-MSNs from mice receiving remifentanil. Remifentanil exposure also altered the probability of glutamate release onto D1-, but not D2-MSNs. Together these results suggest a D1-pathway specific effect associated with the acquisition of opioid-seeking behaviors.


Twist-to-bend ratio: an important selective factor for many rod-shaped biological structures.
Mechanical optimisation plays a key role in living beings either as an immediate response of individuals or as an evolutionary adaptation of populations to changing environmental conditions. Since biological structures are the result of multifunctional evolutionary constraints, the dimensionless twist-to-bend ratio is particularly meaningful because it provides information about the ratio of flexural rigidity to torsional rigidity determined by both material properties (bending and shear modulus) and morphometric parameters (axial and polar second moment of area). The determination of the mutual contributions of material properties and structural arrangements (geometry) or their ontogenetic alteration to the overall mechanical functionality of biological structures is difficult. Numerical methods in the form of gradient flows of phase field functionals offer a means of addressing this question and of analysing the influence of the cross-sectional shape of the main load-bearing structures on the mechanical functionality. Three phase field simulations were carried out showing good agreement with the cross-sections found in selected plants: (i) U-shaped cross-sections comparable with those of Musa sp. petioles, (ii) star-shaped cross-sections with deep grooves as can be found in the lianoid wood of Condylocarpon guianense stems, and (iii) flat elliptic cross-sections with one deep groove comparable with the cross-sections of the climbing ribbon-shaped stems of Bauhinia guianensis.


Contrasting behaviors of groundwater arsenic and fluoride in the lower reaches of the Yellow River basin, China: Geochemical and modeling evidences.
Genesis of the contrasting distributions of high arsenic (>10 μg/L) and fluoride (>1 mg/L) groundwater and their negative correlations remain poorly understood. We investigated spatial distributions of groundwater arsenic and fluoride concentrations in the lower reaches of the Yellow River basin, Henan Province, China, using bivariate statistical analyses and geochemical simulations. Results suggest that high arsenic and fluoride groundwater showed contrasting distributions with few overlapped area. Groundwater arsenic concentrations were significantly negatively correlated with oxidation-reduction potential (ORP) values and positively with NH4+ and Fe(II) concentrations, while the opposites were true for groundwater fluoride concentrations. These may suggest that high arsenic groundwater is related to stronger organic matter degradation and Fe(III) oxide reduction, while groundwater fluoride enrichment occurs with less extent of organic matter degradation. Geochemical calculations supported that groundwater fluoride enrichment was governed by extent of fluorite dissolution, which was constrained by varied saturation indices of fluorite in groundwater. However, groundwater arsenic mobility may be explained by different solubility of Fe(III) oxides. Higher Fe(III) oxide solubility corresponding to goethite and lepidocrocite was related to higher arsenic concentrations, while hematite was too low in solubility to produce high arsenic groundwater. The study presented both geochemical and modeling evidences for the contrasting behaviors of groundwater arsenic and fluoride concentrations in anoxic aquifers.


Novel circular RNA, hsa_circ_0025039 promotes cell growth, invasion and glucose metabolism in malignant melanoma via the miR-198/CDK4 axis.
Malignant melanoma, a tumor derived from melanocytes, shows severe drug resistance and prompt metastasis, causing a serious threat to human health. Circular RNAs (circRNAs) are widely expressed in mammals and have been indicated to play important roles in tumorigenesis. In the present study, we analyzed the variability of circRNAs in malignant melanoma by microarray and identified six differentially expressed circRNAs. In particular, we found that hsa_circ_0025039, which is formed by FOXM1 exons, is significantly upregulated in melanoma. In vitro, the knockdown of circ_0025039 inhibited cell proliferation, colony formation ability, invasion and glucose metabolism in melanoma cells. Additionally, we identified miR-198 as a direct target of hsa_circ_0025039. Furthermore, we demonstrated that hsa_circ_0025039 regulates CDK4 expression by sponging miR-198. In vivo study indicated that the silencing of hsa_circ_0025039 inhibits melanoma tumor formation and downregulates miR-198 and CDK4 expression. Taken together, our data showed that circ_0025039 promotes cell growth, invasion and glucose metabolism in malignant melanoma by sponging miR-198 and regulating CDK4.


A comparative study of the effect of oxantel-pyrantel suspension and mebendazole in mixed infections with Ascaris and Trichuris.
A comparative trial was carried out in 4 orphanges in Seoul, to compare the anthelminthic efficacy of oxantel-pyrantel suspension and mebendazole tablets against mixed infections of Ascaris lumbricoides and Trichuris trichiura. 40 patients were divided into 4 groups and received oxantel-pyrantel suspension at 15 or 20mg/kg once only or on 2 consecutive days. Another group of 20 patients was treated with 100mg of mebendazole twice a day for 3 days. Both drugs achieved a 100% cure rate for Ascaris infections. Against Trichuris infections, the average cure rate and egg reduction rate of oxantel-pyrantel treated groups was 87.5% and 92.3% respectively, and that for mebendazole was 65% and 89.1%. There were no side-effects. The results of the present study suggest that oxantel-pyrantel is more effective in the treatment of mixed infections of Ascaris and Trichuris, and was more acceptable to the patients, than mebendazole.


Lipids in bone: optimal conditions for tissue storage prior to lipid analyses.
Optimal conditions for storage of calcified tissues prior to lipid analysis were determined by comparing the lipid composition (total lipid, total phospholipid, triglyceride, free fatty acid, cholesterol, and complexed acidic phospholipid) of mature rabbit diaphyseal bone stored 1, 2, and 5 months after animal sacrifice to that observed in the bones from which the lipids were immediately extracted at the time of sacrifice. Storage of lyophilized or nonlyophilized tissues at -70 degrees, or lyophilized tissues at -20 degrees, were the only methods that did not yield significant changes in bone lipid composition with time.


Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts.
The pressure during hyperbaric oxygen treatment may increase oxygen toxicity via an augmented oxygen pressure in the gas. Nevertheless, only a few reports have been published on the effect of cells grown under 2 atmospheric absolute (ATA) pressure. To evaluate the effect of pressure on oxygen toxicity and to study effects in addition to oxygen toxicity, we designed an experiment to compare the effects of normobaric mild hyperoxia (NMH, 40% oxygen) and hyperbaric air condition (HA, air with 2 ATA) on human diploid fibroblasts (HDF) in a hyperbaric incubator. HDFs in both the NMH and the HA condition had a similar oxidative stress response and exhibited premature senescence. To investigate differences in gene profiling in cells grown in the NMH and HA conditions, samples from cells exposed to each condition were applied to microarrays. We found no expression difference in genes related to aging and deoxyribonucleic acid damage, but the expression of genes including cell adhesion, stress response, and transcription were significantly increased in fibroblasts that were responsive to pressure. Among 26 statistically reliable genes, the expression of apoptosis related genes such as ADAM22, Bax, BCL2L14, and UBD, as well as tumor suppressor-related genes like Axin2 and ATF, and also mitogen-activated protein kinase-related genes like mitogen-activated protein kinase kinase kinase 1, histamine receptor, and RAB24, were significantly changed in cells responsive to pressure-induced oxidative stress.


Verrucous trichoadenoma.
Two cases of verrucous trichoadenoma are reported. Clinically, both lesions were diagnosed as seborrheic keratoses, but histopathologically no areas of basaloid cell proliferation were seen in the numerous sections and there were many small, epidermoid cysts in the dermis which contained one or more vellous hairs. Some of these cysts expelled their horn material into the surface keratin layer in a "boiling pattern". We propose the term "verrucous trichoadenoma" for these tumors.


Effect of stress during labor on the concentration of cortisol and estriol in maternal plasma.
The effect of stress during labor on the plasma concentration of cortisol, unconjugated estriol, and human chorionic somatomammotropin was studied in 15 healthy primiparous women. According to the method of pain relief the parturients were divided into two groups. One group was given continuous epidural analgesia and the other group received pethidine, diazepam, and nitrous oxide/oxygen in response to pain. In the most stressed nonepidural group there was a significant rise in the cortisol level during labor and the estriol concentration fell significantly. In the epidural group no significant changes were observed with respect to the concentration of either cortisol or estriol. These results give further support to the hypothesis that severe maternal stress may lead to a reduced concentration of estriol in maternal plasma.


A feasibility study to inform the design of a randomized controlled trial to identify the most clinically and cost effective anticoagulation length with low molecular weight heparin in the treatment of cancer associated thrombosis (ALICAT): study protocol for a mixed-methods study.
Venous thromboembolism is common in patients with cancer and requires anticoagulation with low molecular weight heparin. Current data informs anticoagulation as far as six months, yet guidelines recommend anticoagulation beyond six months in patients who have locally advanced or metastatic cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. ALICAT (Anticoagulation Length in Cancer Associated Thrombosis) is a feasibility study to identify the most clinically and cost effective length of anticoagulation with low molecular weight heparin in the treatment of cancer associated thrombosis. ALICAT is a randomized multi-centre phase two mixed-methods study with three components: a randomized controlled trial, embedded qualitative study and a survey investigating pathways of care. The randomized controlled trial will compare ongoing low molecular weight heparin treatment for cancer-associated thrombosis versus cessation of low molecular weight heparin at six months treatment (current licensed practice) in patients with locally advanced or metastatic cancer. The embedded qualitative study will include focus groups with clinicians to investigate attitudes to recruiting to the study, identify the challenges of progressing to a full randomized controlled trial, and also semi-structured interviews with patients and relatives/carers to explore their attitudes towards participating in the study and potential barriers and concerns to participation. Finally, a UK wide survey exercise will be undertaken to develop a classification and enumeration system for the cancer associated thrombosis models and pathways of care. There is a lack of evidence determining the length of anticoagulation for patients with cancer associated thrombosis and subsequently treatment length varies. The ALICAT study will consider the feasibility of recruiting patients to a phase three trial. Current Controlled Trials ISRCTN37913976.


Vitamin D status after colorectal cancer diagnosis and patient survival according to immune response to tumour.
High-level plasma 25-hydroxyvitamin D [25(OH)D] has been associated with lower colorectal cancer incidence and mortality. Considering evidence indicating immunomodulatory effects of vitamin D, we hypothesised that survival benefits from high systemic vitamin D level might be stronger for colorectal carcinoma with lower immune response to tumour. Using 869 colon and rectal cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study, we assessed the prognostic association of postdiagnosis 25(OH)D score [derived from diet and lifestyle variables to predict plasma 25(OH)D level] in strata of levels of histopathologic lymphocytic reaction. The Cox proportional hazards regression model was adjusted for potential confounders, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, PTGS2 (cyclooxygenase-2) expression and KRAS, BRAF and PIK3CA mutations. The association of postdiagnosis 25(OH)D score with colorectal cancer-specific mortality differed by levels of peritumoural lymphocytic reaction (pinteraction = 0.001). Multivariable-adjusted mortality hazard ratios for a quintile-unit increase of 25(OH)D score were 0.69 [95% confidence interval (CI), 0.54-0.89] in cases with negative/low peritumoural lymphocytic reaction, 1.08 (95% CI, 0.93-1.26) in cases with intermediate peritumoural reaction and 1.25 (95% CI, 0.75-2.09) in cases with high peritumoural reaction. The survival association of the 25(OH)D score did not significantly differ by Crohn's-like lymphoid reaction, intratumoural periglandular reaction or tumour-infiltrating lymphocytes. The association between the 25(OH)D score and colorectal cancer survival is stronger for carcinomas with lower peritumoural lymphocytic reaction. Our results suggesting interactive effects of vitamin D and immune response may contribute to personalised dietary and lifestyle intervention strategies.


Development of dispersive liquid-liquid microextraction combined with gas chromatography-mass spectrometry as a simple, rapid and highly sensitive method for the determination of phthalate esters in water samples.
A simple, rapid and efficient method, the dispersive liquid-liquid microextraction (DLLME) in conjunction with gas chromatography-mass spectrometry (GC-MS), has been developed for the extraction and determination of phthalate esters (dimethyl phthalate, diallyl phthalate, di-n-butyl phthalate, benzyl butyl phthalate, dicyclohexyl phthalate and di-2-ethylhexyl phthalate) in water samples. Factors relevant to the microextraction efficiency, such as the kind of extraction, the disperser solvent and their volume, the salt effect and the extraction time were investigated and optimized. Under the optimized extraction conditions (extraction solvent: chlorobenzene, volume, 9.5microL; disperser solvent: acetone, volume, 0.50mL, without salt addition and extraction time below 5s), the figures of merit of the proposed method were evaluated. The values of the detection limit of the method were in the range of 0.002-0.008microgL(-1), while the RSD% value for the analysis of 1microgL(-1) of the analytes was below 6.8% (n=4). A good linearity (0.9962>/=r(2)>/=0.9901) and a broad linear range (0.02-100microgL(-1)) were obtained. The method exhibited enrichment factors and recoveries, ranging from 681 to 889 and 68.1 to 88.9%, respectively, at room temperature (25+/-1 degrees C). Finally, the proposed method was successfully utilized for the preconcentration and determination of the phthalate esters in different real water samples and satisfactory results were obtained.


Measurement of resting energy expenditure in a clinical setting.
In this study indirect calorimetry for the measurement of a patient's resting energy expenditure (REE) was assessed in clinical practice. REE measured early in the morning after an overnight fast was highly reproducible. REE measured in the afternoon, when patients had consumed their meals, was 15% higher than REE measured in the morning. REE measured at mid-morning was not different from that measured early in the morning, except for patients who had breakfast between the two measurements. Therefore, to avoid the effect of diet-induced thermogenesis in the measurement a patient must be measured in the morning in the post-absorptive state. Variations because of limited physical activities may be neglected, including a short travel from home to the hospital, which implies that REE may be measured on an out-patient basis. The effect of total parenteral nutrition (TPN) on energy expenditure (EE) was a 12% increase. The respiratory quotient (RQ) rose to almost 1.0. Nine days of enteral nutritional support showed only a 3% increase in REE, while RQ increased from 0.78 to 0.87, indicating restored glycogen stores.


Enzyme action in polymer and salt solutions. II. Activity of penicillin acylase in poly(ethylene glycol) and potassium phosphate solutions in relation to water activity.
Increasing concentrations of poly(ethylene glycol) and potassium phosphate solutions decreased the enzymatic activity of penicillin acylase (penicillin aminohydrolase, EC 184.108.40.206). Low molecular weight poly(ethylene glycol) reduced the penicillin acylase activity more than high molecular weight poly(ethylene glycol). The decrease in enzymatic activity seemed to be related to the decrease in water activity in solutions containing poly(ethylene glycol), irrespective of the molecular weight of the polymer. The decrease in enzymatic activity in potassium phosphate solutions was lower than in poly(ethylene glycol) solutions and did not fit the water activity relationship. The decreased enzymatic activity is discussed in relation to the enzyme stability in these solutions.


Hyperbaric oxygen attenuation of lipopolysaccharide-induced acute lung injury involves heme oxygenase-1.
Hyperbaric oxygen (HBO) attenuates lipopolysaccharide (LPS)-induced acute lung injury. This beneficial effect of HBO involves inhibition of inducible nitric oxide synthase (iNOS) expression and subsequent nitric oxide (NO) biosynthesis. We sought to investigate the role of heme oxygenase-1 (HO-1) on this HBO inhibition of iNOS induction and acute lung injury in septic rat lungs. Before the experiment, 72 rats were randomly allocated to receive HBO or air treatment. With or without HBO pre-treatment, the rats were further divided into the following subgroups (n = 6): (i) LPS injection, (ii) normal saline (N/S) injection, (iii) hemin (a HO-1 inducer) plus LPS, (iv) hemin alone, (v) tin protoporphyrin (SnPP; a HO-1 inhibitor) plus LPS, and (vi) SnPP alone. All rats were maintained for 6 h and then sacrificed with a high-dose pentobarbital injection. Lung injuries and relevant enzymes expression were thus assayed. Histological analysis, PMNs/alveoli ratio, and wet/dry weight ratio measurements demonstrated that LPS caused significant lung injury and HBO and/or hemin significantly attenuated this LPS-induced lung injury. Increased pulmonary iNOS expression and NO production were associated with lung injury. Induction of HO-1, by HBO and/or hemin, significantly attenuated this LPS-induced iNOS expression and acute lung injury. SnPP, on the contrary, offset the effects of HBO and worsened the LPS-induced lung injury. HBO may act through inhibiting pulmonary iNOS expression to attenuate LPS-induced acute lung injury in septic rats. Furthermore, this HBO attenuation of iNOS expression involves HO-1 induction.


Correction: Measuring the impact of an interdisciplinary learning project on nursing, architecture and landscape design students' empathy.
[This corrects the article DOI: 10.1371/journal.pone.0215795.].


Infection control and outpatient parenteral antibiotic therapy.
Outpatient procedures have become more complex, requiring outpatient providers to offer technical procedures in the home, office, and clinic. This shift in health care has brought about the need for staff members to become proficient in a variety of technical procedures that were once done only in the hospital setting. Outpatient i.v. therapy has caused home health care agencies, physicians' offices, and clinics to seek education and training regarding i.v. therapy and to develop basic infection-control guidelines and guidelines related to the insertion and maintenance of i.v. devices. The goals of the outpatient provider are to prevent i.v.-related complications and to provide quality patient care. These can be accomplished by strict adherence to sound infection-control guidelines and routine monitoring of procedure techniques and complications of care. Outpatient providers may wish to seek expertise and guidance from hospital infection-control personnel, infectious diseases specialists, or other infection-control consultants to meet the demands of the complexity of outpatient care.


Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors.
This corrects the article DOI: 10.1038/jhh.2016.78.


Sample size requirements for prospective studies, with examples for coronary heart disease.
Methods of determining the required number of disease cases for estimation of relative odds in prospective studies are evaluated, with examples from coronary heart disease. Data from a British prospective study of coronary heart disease are used in simulation exercises to assess the reliability of estimation formulae for both continuous and categorical risk factors. For continuous risk factors, a univariate formula based on estimation of the standardized relative odds (Whittemore A. S. JAMA 1981; 76: 27-32 [1]), gives reliable estimation of the required number of disease cases, provided the risk factor has a near normal distribution. An extension of the formula to adjustment for other risk factors, was less satisfactory, perhaps because of departures from multivariate normality. For categorical risk factors, an adaption of a univariate method for case control studies (Smith PG, Day NE. Int J Epidemiol 1984; 13: 356-365 [2]), gives reliable estimates of the number of cases required. However, this depends on approximate prior knowledge of the relative odds. In general, prospective studies of coronary heart disease risk factors should aim for at least 400 cases to enable sufficient accuracy of estimation.


Lyme disease in Canada with possible transmission by an insect.
The first documented case of Lyme disease to have originated in Canada is presented. A 51-year old French female nurse visited Quebec, Canada from 20 July to 5 August, 1984 and contracted Lyme disease. She reported an insect bite on 3 August 1984 on the back of her knee with erythema chronicum migrans appearing at the site of the bite on 5 August 1984. The patient presented with meningeal lymphocytic reaction near the end of September, 1984. Total Ig serum titers in indirect immunofluorescence tests on 1 October 1984, 10 October 1984, and 10 January 1985 were 1/512, 1/2048 and 1/16,384, respectively.


Relationships between leaf water status and transpiration of cowpea with progressive soil drying.
It was previously reported that leaf water status of cowpea (Vigna unguiculata) exhibited only small changes with progressive soil drying over extended periods of time. In these studies, under field conditions, it was demonstrated that when soil water was not limiting, xylem pressure potential (ψ x ) exhibited a linear relationship with transpirational flux density with no obvious hysteresis. With progressive soil drying, values of ψ x and transpiration rate fell below the regression line established for nonlimiting soil conditions. It is proposed that paired measurements of ψ x and transpirational flux density made between midday and sunset can provide a measure of the extent to which soil conditions are limiting water uptake. The relation between ψ x and transpiration exhibits a family of curves, with more negative slopes and decreases in maximum transpiration rate indicating progressive limitation due to soil drying.


Low risk of treatment resistance in Down syndrome with Kawasaki disease.
A Japanese nationwide survey has reported that Down syndrome (DS) is a less-frequently occurring comorbidity in Kawasaki disease (KD). Although altered immune responses are frequently observed in DS, no studies have focused on the treatment response and risk for coronary artery abnormalities (CAA) in DS patients with KD. The aim of this study was therefore to evaluate the clinical manifestations, treatment response and prevalence of CAA in DS with KD. We retrospectively reviewed the medical records of DS patients with KD from 2005 through 2012. The survey questionnaires were sent to facilities nationwide, and clinical data regarding KD in DS were collected. A control group consisted of non-DS patients with KD who were managed at Toho University. Of the 94 233 children diagnosed with acute KD from 2005 to 2012, 16 children with acute KD also had DS (0.017%). The DS-KD patients were significantly older than the non-DS patients (median, 8 years vs 1 year, P < 0.05, respectively). Half of the DS patients had incomplete KD. Although 50% of the DS children were at high risk of immunoglobulin resistance, all children responded to initial treatment and none had CAA. All DS-KD patients responded to initial i.v. immunoglobulin (IVIG) or aspirin despite having a high risk of IVIG resistance, and none of the DS patients had CAA. This suggests that the risk of treatment resistance and development of CAA may be not higher in DS patients with acute KD.


Dissection of tumor-necrosis factor-alpha inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early-but not late-phase LTP.
The pro-inflammatory cytokine tumor-necrosis factor-alpha (TNF-alpha) is elevated in several neuropathological states that are associated with learning and memory deficits. Previous work has reported that TNF-alpha inhibits the induction of LTP in areas CA1 [Neurosci Lett 146 (1992) 176] and dentate gyrus [Neurosci Lett 203 (1996) 17]. The mechanism(s) underlying this process of inhibition have not to date been addressed. Here, we show that perfusion of TNF-alpha prior to long-term potentiation (LTP) inducing stimuli inhibited LTP, and that in late-LTP (3 h post-tetanus) a depression in synaptic field recordings was observed (68 +/- 5%, n = 6 versus control 175 +/- 7%, n = 6, P < 0.001). We investigated the involvement of the mitogen-activated protein kinase (MAPK) p38 in the inhibition of LTP by TNF-alpha as p38 MAPK has previously been shown to be involved in interleukin-1beta inhibition of LTP in the dentate gyrus [Neuroscience 93 (1999b) 57]. Perfusion of TNF-alpha led to an increase in the levels of phosphorylated p38 MAPK detectable in the granule cells of the dentate gyrus. The p38 MAPK inhibitor SB 203580 (1 microM) was found by itself to have no significant effect on either early or late phase LTP in the dentate gyrus. SB 203580 was found to significantly reverse the inhibition of early LTP by TNF-alpha (SB/TNF-alpha 174 +/- 5%, n = 6 versus TNF-alpha 120 +/- 7%, n = 6, P < 0.001, 1 h post-tetanus) to values comparable to control LTP (control 175 +/- 7%, n = 6). Interestingly however, the depressive effects of TNF-alpha on late LTP (2-3 h) were clearly not attenuated by p38 MAPK inhibition (SB/TNF-alpha 132 +/- 5%, n = 6 versus control LTP 175 +/- 7%, n = 6, P < 0.001, 3 h post-tetanus). This work suggests that TNF-alpha inhibition of LTP represents a biphasic response, a p38 MAPK-dependent phase that coincides with the early phase of LTP and a p38 MAPK independent phase that temporally maps to late LTP.


Robot-assisted Versus Standard Laparoscopy for Simple Prostatectomy: Multicenter Comparative Outcomes.
To report a comparative analysis of laparoscopic simple prostatectomy (LSP) vs robot-assisted simple prostatectomy (RASP). Consecutive cases of LSP and RASP done between 2003 and 2014 at 3 participating institutions were included in this retrospective analysis. The effectiveness of the two procedures was determined by performing a paired analysis of main functional and surgical outcomes. A multivariate analysis was also conducted to determine the factors predictive of "trifecta" outcome (combination of International Prostate Symptom Score <8, Qmax > 15 mL/second, and no perioperative complications). A total of 319 patients underwent minimally invasive simple prostatectomy at the participating institutions over the study period. Total prostate volume was larger in the RASP group (median 118.5 mL vs 109 mL, P = .02). Median estimated blood loss tended to be higher for LSP (300 mL vs 350 mL, P = .07). There was no difference in terms of catheterization time (P = .3) and hospital stay (P = .42). A higher rate of overall postoperative complications was recorded in the RASP group (17.7% vs 5.3%), but rate of major complications was not significantly different between the two techniques (2.3 vs 2.1, P = .6). Subjective and objective parameters significantly improved for both LSP and RASP. On multivariable analysis, only two factors were associated with likelihood of obtaining a favorable (trifecta) outcome: age (odds ratio: 0.94; P = .03) and body mass index (odds ratio: 0.84; P = .03). Both LSP and RASP can be regarded as safe and effective minimally invasive surgical treatments for bladder outlet obstruction due to large prostate glands.


Retrospective analysis of commercial heterospermic and homospermic cooled boar semen: Effect of the season, sample type and shipping temperature on sperm quality.
We retrospectively analysed data from heterospermic and homospermic boar semen for motility and morphology during a 2-year period. Homospermic doses were also evaluated for viability, acrosome integrity, DNA fragmentation, osmolality and pH. Additionally, we investigated the effect of temperature upon arrival and the agreement between viability and motility as evaluating tool. We observed lower (p < .05) total motility (TM) and normal sperm morphology within summer and fall. Conversely, lower (p < .05) progressive motility (PM) was found at the beginning and end of each year. Viability and acrosome integrity were reduced (p < .05) in summer months but not exclusively, suggesting that samples could be compromised by transport temperature. Sperm DNA fragmentation was <6% with a small variation. Medium osmolality and pH slightly changed (p < .05). Sperm count was not source of variation on sperm parameters. Sample temperature upon arrival correlated with PM and VSL (p < .05), while motility was reduced <12°C (p < .05). Homospermic doses were less affected by season and arrival temperature, having better parameters (p < .05) than contemporaneous heterospermic samples but influenced by genetic line (p < .05). We found a high agreement between viable acrosome-intact sperm and TM, especially when TM was ≥80%. Our data verify the improvement of sperm quality during time as sperm count/dose does not affect quality, but season effect persists regardless of ejaculate selection at the stud. Homospermic doses exhibited better parameters than heterospermic doses, seemingly being more resilient to temperature variations, suggesting that selection for sperm quality within boars selected by growth traits can improve the product quality.


Air pollution and pediatric respiratory disease: croup.
The question of a causative interrelation between air pollution and croup has received considerable attention by the mass media. A series of epidemiological studies has tried to establish a scientific basis for these speculations. Some studies have compared the occurrence of croup with locally measured concentrations of pollutants, while others have observed differences in the incidence of croup between populations subjected to different levels of pollution. Results have so far remained contradictory, most studies have failed to control for other variables, and thus clear-cut evidence for the etiologic role of air pollution has yet not been established on an epidemiological basis. On the other hand, simple croup is caused by viral infection, while recurrent croup is associated with allergy and airway hyperreactivity. Animal studies have documented that air pollution can reduce resistance against viral infections, increase the risk of allergic sensibilization, and induce airway hyperreactivity. Conceivably, air pollution could thus have a supportive role in the development of croup, but this possibility requires further investigation.


Prognostic Factors and Survival Benefits of Antitumor Treatments for Advanced Non-Small Cell Lung Cancer Patients With Central Nervous System Metastasis With or Without Driver Genes: A Chinese Single-Center Cohort Study.
The prognosis of non-small cell lung cancer (NSCLC) patients with central nervous system (CNS) metastasis is poor. The treatment for CNS metastasis could prolong the overall survival of NSCLC patients. We aimed to investigate the prognostic factors of Chinese NSCLC patients with CNS metastasis and the survival benefits of various treatments for CNS metastasis in NSCLC patients with or without driver genes. Based on the CAPTRA-Lung database, NSCLC patients with CNS metastasis admitted at the Peking Union Medical College Hospital between January 2010 and October 2018 were enrolled in the study. The prognostic factors were analyzed using univariate and multivariate Cox regression analyses. Overall, 418 patients were enrolled in the study. A total of 206 patients (49.3%) had CNS metastasis with positive driver genes, while 97 patients (23.2%) had negative driver genes. The median survival time after CNS metastasis was 20.8 months. In the multivariable analysis, an Eastern Cooperative Oncology Group performance status of ≥2 (hazard ratio [HR]: 1.750, 95% confidence interval [CI]: 1.184-2.588, P=0.005), number of CNS metastases ≥5 (HR: 1.448, 95% CI: 1.084 -1.934, P=0.012), and CNS metastasis developed during treatment (HR: 1.619, 95% CI: 1.232-2.129, P=0.001) were independent risk factors for poor survival. Lung adenocarcinoma (HR: 0.490, 95% CI: 0.279-0.861, P=0.013) and driver gene positivity (HR: 0.464, 95% CI: 0.302-0.715, P=0.001) were independent predictors of prolonged survival. Radiotherapy for CNS metastasis showed a survival benefit in NSCLC patients in the entire groups (HR: 0.472, 95% CI: 0.360-0.619, P <0.001), and in patients with positive driver genes. Performance status, number of CNS metastases, timing of CNS metastasis, histological subtype, and driver gene status are prognostic factors for NSCLC patients with CNS metastasis. Furthermore, radiotherapy improved the survival in NSCLC patients with CNS metastasis.


VyUSPA3, a universal stress protein from the Chinese wild grape Vitis yeshanensis, confers drought tolerance to transgenic V. vinifera.
VyUSPA3 from the Chinese wild grape Vitis yeshanensis interacts with ERF105, PUB24 and NF-YB3, and overexpression of the VyUSPA3 gene in V. vinifera cv. 'Thompson Seedless' confers drought tolerance. Drought is a major abiotic stress factor that seriously affects the growth and yield of grapevine. Although many drought-related genes have been identified in Arabidopsis and other plants, the functions of only a few of their counterparts have been revealed in grape. Here, a universal stress protein (USP) A from the Chinese wild grape Vitis yeshanensis, VyUSPA3, was identified and its function was subsequently characterized by overexpressing or silencing the VyUSPA3 gene in V. vinifera cv. 'Thompson Seedless' via Agrobacterium-mediated genetic transformation. After 21 d of the drought treatment, most leaves of the untransformed (UT) 'Thompson Seedless' lines wilted, yet UT lines were less damaged compared to the RNAi-VyUSPA3 lines, nonetheless, the OE-VyUSPA3 lines were mostly unaffected. Meanwhile, OE-VyUSPA3 lines showed smaller stomatal aperture, more developed roots, higher leaf relative water content, proline content, and antioxidant enzyme activities, as well as lower malondialdehyde, H2O2 and O2•- accumulation than UT lines, but this response pattern was reversed in the RNAi-VyUSPA3 lines. Besides, the transcript levels of four drought-related genes (RD22, RD29B, DREB2A, and NCED1) in OE-VyUSPA3 lines were greater than those in the RNAi-VyUSPA3 and UT lines. In addition, a yeast two-hybrid assay and a bimolecular fluorescence complementation assay confirmed that VyUSPA3 interacted with ERF105, PUB24, and NF-YB3, respectively. This study revealed that VyUSPA3 improved drought tolerance in transgenic grapevines possibly through interaction with the hormone signaling, ubiquitination system, ethylene-responsive element binding factor and nuclear factors.


The macroeconomics of pandemics around the world: Lives versus livelihoods revisited.
The COVID-19 pandemic led governments around the world to impose unprecedented restrictions on economic activity. Were these restrictions equally justified in poorer countries with fewer demographic risk factors and less ability to weather economic shocks? We develop and estimate a fully specified model of the macroeconomy with epidemiological dynamics, incorporating subsistence constraints in consumption and allowing preferences over "lives versus livelihoods" to vary with income. Poorer countries' demography pushes them unambiguously toward laxer policies. But because both infected and susceptible agents near the subsistence constraint will remain economically active in the face of infection risk and even to some extent under government containment policies, optimal policy in poorer countries pushes in the opposite direction. Moreover, for reasonable income-elasticities of the value of a statistical life, the model can fully rationalize equally strict or stricter policies in poorer countries.


Ribosome recycling is coordinated by processive events in two asymmetric ATP sites of ABCE1.
Ribosome recycling orchestrated by ABCE1 is a fundamental process in protein translation and mRNA surveillance, connecting termination with initiation. Beyond the plenitude of well-studied translational GTPases, ABCE1 is the only essential factor energized by ATP, delivering the energy for ribosome splitting via two nucleotide-binding sites by a yet unknown mechanism. Here, we define how allosterically coupled ATP binding and hydrolysis events in ABCE1 empower ribosome recycling. ATP occlusion in the low-turnover control site II promotes formation of the pre-splitting complex and facilitates ATP engagement in the high-turnover site I, which in turn drives the structural re-organization required for ribosome splitting. ATP hydrolysis and ensuing release of ABCE1 from the small subunit terminate the post-splitting complex. Thus, ABCE1 runs through an allosterically coupled cycle of closure and opening at both sites consistent with a processive clamp model. This study delineates the inner mechanics of ABCE1 and reveals why various ABCE1 mutants lead to defects in cell homeostasis, growth, and differentiation.


Coherent surface plasmon polariton amplification via free-electron pumping.
Surface plasmonics with its unique confinement of light1,2 is expected to be a cornerstone for future compact radiation sources and integrated photonics devices. The energy transfer between light and matter is a defining aspect that underlies recent studies on optical surface-wave-mediated spontaneous emissions3-5. However, coherent stimulated emission of free electrons, which is essential for free-electron light sources, and its dynamical amplification process remain to be disclosed in a clear, unambiguous and calibrated manner. Here we present the coherent amplification of terahertz surface plasmon polaritons via free-electron-stimulated emission: a femtosecond optical pulse creates an in-phase free-electron pulse with an initial terahertz surface wave, and their ensuing interactions intensify the terahertz surface wave coherently. The underlying dynamics of the amplification, including a twofold redshift in the radiation frequency over a one-millimetre interaction length, are resolved as electromagnetic-field-profile evolutions using an optical pump-probe method. By extending the approach to a properly phase-matched electron bunch, our theoretical analysis predicts a super-radiant surface-wave growth, which lays the ground for a stimulated surface-wave light source and may facilitate capable means for matter manipulation, especially in the terahertz band.


Antitumor effect of the selective hypoxia-inducible factor-1 inhibitors echinomycin and PX-478 on uterine fibroids.
To investigate the antitumor effects of the selective hypoxia-inducible factor-1 (HIF-1) inhibitors echinomycin and PX-478 on uterine fibroids. Experimental study using in vitro primary culture systems and an in vivo mouse xenograft model. Academic university center. Women with uterine fibroids who underwent hysterectomy or myomectomy. Administration of the selective HIF-1 inhibitors echinomycin and PX-478 to the media of the primary cultured uterine fibroid cells and to nonobese diabetic/severe combined immunodeficient mice bearing fibroid xenografts consisting of the primary cultured fibroid cells and type Ⅰ collagen gels beneath the kidney capsule. Cell proliferation was measured by Cell Counting Kit-8 assay. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and by measuring caspase 3 and 7 activities. The xenografts were evaluated by gross appearance, surface area, and histology. The Ki-67 index was measured to evaluate proliferation of the xenografts. Both echinomycin and PX-478 inhibited cell proliferation and induced apoptosis in fibroid cells cultured under hypoxia and normoxia. Enlargement of the fibroid xenografts was significantly attenuated. The Ki-67 index significantly decreased after the administration of the HIF-1 inhibitors in the xenograft model. Eight of 27 xenografts treated with the HIF-1 inhibitors contained calcification and hyalinizing components from 3 days after the grafting to 2 weeks, suggesting that the HIF-inhibitors induce degeneration of the fibroid xenografts. The selective HIF-1 inhibitors echinomycin and PX-478 show antitumor effects against uterine fibroids both in vitro and in vivo. These findings support the potential use of HIF-1 inhibitors for the treatment of uterine fibroids.


The effects of Team-Based Learning on learning behaviors in the maternal-child nursing course.
The Team-Based Learning (TBL) method has been used as a teaching strategy in many disciplines. It is instructor-led, learner-centered learning with functions similar to those of problem-based learning, but it is more cost-effective. However, little is known about the application of TBL to nursing education. The objectives of the study are to employ the TBL approach in a Maternal-Child Nursing course and to evaluate its effects on learning outcomes. We present one-group pretest-posttest research design with the intervention of the TBL teaching strategy. The study was conducted in one of the nursing universities in Taiwan. One-hundred-four students in 2011 and 103 students in 2012 in an RN-to-BSN program who enrolled in the Maternal-Child Nursing course participated in this study. These students had graduated from a five-year nursing diploma program before enrolling in the RN-BSN program. Data were collected before and after the implementation of the TBL, which included active learning, in-class activities, and application exercises. The Class Engagement Survey (CES), Value of Teams (VTs), Self-Directed Learning Instrument (SDLI), and exam scores were used to measure students' learning outcomes. TBL significantly influenced the students' learning outcomes. Students who expressed that TBL increased their learning interests had a higher score on VT; and students who had high achievement from the current TBL course had higher scores on the CES, VT, and SDLI. The means of the group test scores and the final examination score were significantly higher than the individual scores from the in-class tests in both 2011, 2012, and the combination of 2011 and 2012. The TBL design requires out-of-class preparation before all classes, which requires active and self-directed learning. TBL provides opportunities to foster learner-to-learner interactions, which lead to more active engagement and teamwork among learners. It also promotes the students' class engagement and teamwork values, and it increases academic performance. The TBL is suggested to have a greater effect on academically weaker students.


Clinical presentation, management, and outcomes of angiographically documented early, late, and very late stent thrombosis.
The aim of this study was to describe differences in treatment and in-hospital mortality of early, late, and very late stent thrombosis (ST). Early, late, and very late ST may differ in clinical presentation, management, and in-hospital outcomes. We analyzed definite (angiographically documented) ST cases identified from February 2009 to June 2010 in the CathPCI Registry. We stratified events by timing of presentation: early (≤1 month), late (1 to 12 months), or very late (≥12 months) following stent implantation. Multivariable logistic regression modeling was performed to compare in-hospital mortality for each type of ST after adjusting for baseline comorbidities. During the study period, 7,315 ST events were identified in 7,079 of 401,662 patients (1.8%) presenting with acute coronary syndromes. This ST cohort consisted of 1,391 patients with early ST (19.6%), 1,370 with late ST (19.4%), and 4,318 with very late ST (61.0%). Subjects with early ST had a higher prevalence of black race and diabetes, whereas subjects with very late ST had a higher prevalence of white race and a lower prevalence of prior myocardial infarction or diabetes. In-hospital mortality was significantly higher in early ST (7.9%) compared with late (3.8%) and very late ST (3.6%, p<0.001). This lower mortality for late and very late ST persisted after multivariable adjustment (odds ratio: 0.53 [95% confidence interval (CI): 0.36 to 0.79] and 0.58 [95% CI: 0.43 to 0.79], respectively). Significant differences exist in the presentation and outcomes of early, late, and very late ST. Among patients with acute coronary syndromes who are undergoing percutaneous coronary intervention for angiographically documented ST, early ST is associated with the highest in-hospital mortality.


General Dual-Switched Dynamic Singlet Fission Channels in Solvents Governed Jointly by Chromophore Structural Dynamics and Solvent Impact: Singlet Prefission Energetics Analyses.
The singlet fission (SF) channels in many systems are controlled by the thermodynamic driving force (Switch-1) and kinetic barrier (Switch-2), both of which could be modulated by chromophore structure dynamics and solvent properties. Using ab initio molecular dynamics (AIMD), we here simulate how the structural dynamics and solvent jointly govern singlet prefission energetics, taking a covalent BODIPY dimer (di-BODIPY) in solvents as an example. We report a general dual-switched dynamic channel for intramolecular SF in solvents and suggest an effective AIMD sampling method to characterize the joint effect of chromophore structure dynamics and the solvent impact on SFs. Results reveal that the joint effect not only provides di-BODIPY more chances for meeting the SF thermodynamic requirement (Switch-1 ON) but also tunes the charge-transfer state toward removing the kinetic barrier (Switch-2 ON). Two factors jointly govern each switch in the dual-switched SF channel, and any one does not open the channel alone. We suggest a general principle for dynamically dual-switching the SF channel in solvents by utilizing the joint effect to tune the pre-SF energetics for photoexcitation and the opening of the subsequent channel. AIMD sampling is used for the first time to discover explicit solvent-solute interaction and dynamics information and thus their effect on excitation energetics. This work also shows the statistical information for an ensemble of SF chromophores in solvents, which can undergo different photoexcitations and possible SFs. The high agreement of the findings here with the experiments justifies our AIMD sampling-based pre-SF energetic prediction as a reliable way for exploring novel SF systems and their controllability.


Factorial validity and norm data comparison of the Short Form 12 in patients with inflammatory-rheumatic disease.
Measuring quality of life is increasingly considered as an outcome criterion in clinical studies. In order to assess quality of life, disease specific as well as generic instruments are used. Generic instruments make it possible to compare outcomes among different indications, but for this purpose a test of the factorial validity of the method in each indication is necessary. In this study, the generic short form 12 was administered to a sample survey of 545 patients with inflammatory-rheumatic disease. Patients data from three scientific rehabilitation research projects were pooled for the analysis. First the structure was tested using confirmatory structural equation modeling. In a second step age and gender specific values were calculated and compared to norm data from the German National Health Survey 1998. The questionnaire's structure is acceptable and comparable to international results. Confirmatory analyses support a model allowing covariations of error terms between items of the same subdimensions. The two latent dimension are highly correlated. Crossloadings of items from different subdimension does not improve the model fit significantly. Comparisons with the German norm data shows that the patients are impaired within their physical and mental dimension of subjective health. Higher impairment is evident especially on the physical sumscale. Women show higher impairment in both scales. However no effects of age can be detected. The SF-12 could be used with trust in the study of patients with inflammatory-rheumatic diseases. But physical and mental health can not be seen as independently.


Purine and pyrimidine transport in pathogenic protozoa: from biology to therapy.
Purine salvage is an essential function for all obligate parasitic protozoa studied to date and most are also capable of efficient uptake of preformed pyrimidines. Much progress has been made in the identification and characterisation of protozoan purine and pyrimidine transporters. While the genes encoding protozoan or metazoan pyrimidine transporters have yet to be identified, numerous purine transporters have now been cloned. All protozoan purine transporter-encoding genes characterised to date have been of the Equilibrative Nucleoside Transporter family conserved in a great variety of eukaryote organisms. However, these protozoan transporters have been shown to be sufficiently different from mammalian transporters to mediate selective uptake of therapeutic agents. Recent studies are increasingly addressing the structure and substrate recognition mechanisms of these vital transport proteins.


Synthesis, antidiabetic, antioxidant and anti-inflammatory activities of novel hydroxytriazenes based on sulpha drugs.
The present study is aimed to investigate the anti-inflammatory, antioxidant and antidiabetic activities of three series of hydroxytriazenes based on sulfa drugs viz; Sulphathiazole (ST), Sulfisoxazole (SF) and Sulphamethoxazole (SM). Antidiabetic activities of the synthesized hydroxytriazenes were investigated by α-glucosidase and α-amylase inhibition method and IC50 values were recorded. The compounds presented significant α-glucosidase and α-amylase inhibition effect with IC50 values ranging from 122 to 341 μg/mL. Anti-inflammatory activity was also investigated by carrageenan-induced paw edema (CPE) method, where % inhibition was up to 89% after 4 h of treatment and antioxidant properties of the similar compounds were assessed by DPPH and ABTS radical scavenging assays. Antioxidant capacity of all the hydroxytriazenes detected by ABTS assay, was significantly higher as compared to DPPH assay. The hydroxytriazenes having highest antioxidant capacity presented IC50 values for compound ST-1 and ST-6 are 488 μg/mL for DPPH, 54.12 μg/mL for ABTS and 858.5 μg/mL for DPPH, 48.0 μg/mL for ABTS, respectively. These results suggested that ABTS assay may be more useful than DPPH assay for synthetic antioxidants. The findings from the molecular docking experiments may also expand the formation of new potent sulpha drugs based hydroxytriazenes targeting towards the subunit of C-terminal of human maltase-glucoamylase for the treatment of diabetes metabolic disorder. Overall, highlight the multifunctional role of hydroxytriazenes as antidiabetic, antioxidant and anti-inflammatory agents.


The DTH effector response and IL-2 are unaffected by cyclosporine A in autoimmune B6D2F1 mice.
Delayed-type hypersensitivity (DTH) is classically defined as inflammation involving activated Th1 cells and cytokine production. DTH paw swelling, along with the cytokines IL-2, IFNγ, MCP-1 and TNFα, were inhibited in Balb/c mice by cyclosporine A (CsA). Surprisingly, the DTH response in the B6D2F1 mice was unaffected by CsA, despite a decrease in TNFα and IFNγ levels. IL-2 levels, however, were not decreased. To determine if the IL-2 production in the B6D2F1 strain is occurring through CD28-mediated costimulation, both CsA and CTLA-4Ig were administered. Paw swelling and IL-2 levels were decreased, indicating a role for costimulation. Co-administration of temsirolimus and CsA also reduced DTH and IL-2 levels in B6D2F1 mice, demonstrating involvement of the mTORC1 pathway. These results indicate that the cell activation pathways responsible for DTH differ with mouse strain. It is important to understand these differences in order to accurately interpret the results using potential therapeutic agents.